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[ { "answer_id": 23583, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 3, "selected": true, "text": "<p>The term \"general immunity\" is not used all that often nowadays, but <a href=\"https://europepmc.org/article/med/6830015\" rel=\"nofollow noreferrer\">it seems</a> to stand in opposition to \"local immunity\" which are more specialized immune responses in some regions of the body but not others. \nA 1923 (!) <a href=\"https://www.jimmunol.org/content/8/1/1.short\" rel=\"nofollow noreferrer\">paper</a> on this contrast mentions \"Metchnikoff's phagocytic theory of immunity\"... and in <a href=\"https://www.sciencedirect.com/science/article/pii/S0092867416310686\" rel=\"nofollow noreferrer\">more recent publications</a> Metchnikoff is called \"the father of innate immunity\"; this latter paper doesn't use the term \"general immunity\" at all. So possibly, the terms \"general immunity\" and \"<a href=\"https://en.wikipedia.org/wiki/Innate_immune_system\" rel=\"nofollow noreferrer\">innate immunity</a>\" are used interchangeably in some quarters.</p>\n\n<p>Now, why would [innate] immunity be lower in Yemen and comparably disadvantaged populations? In general, from (at least) <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996946/\" rel=\"nofollow noreferrer\">animal studies</a> the innate immune system was shown to be modulated by starvation, and so presumably by poor nutrition too. And the innate immune system has a few general mechanisms that e.g. in response to type I interferon trigger some specific <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441850/\" rel=\"nofollow noreferrer\">mechanisms</a> that slow or inhibit viral replication: Dicer, PARP 13 etc. Now viruses themselves are in an arms race with the innate immune system and some viruses have acquired ways of disrupting it.</p>\n\n<p>A <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889773/\" rel=\"nofollow noreferrer\">2016 review</a> on human immunity issues resulting from malnutrition notes that:</p>\n\n<blockquote>\n <p>Characterization of immunodeficiency was limited by a lack of longitudinal studies, particularly for mild and moderate malnutrition. The precise nature of immunodeficiency in undernutrition therefore remains uncertain; however, the consensus from the available evidence is that both innate and adaptive immunity are impaired by malnutrition. Defects in innate immune function include impaired epithelial barrier function of the skin and gut, reduced granulocyte microbicidal activity, fewer circulating dendritic cells, and reduced complement proteins, but preserved leukocyte numbers and acute phase response. </p>\n</blockquote>\n\n<p>(The same review notes that interestingly overnutrition, e.g. resulting in obesity also seems to impair some immune functions. On that [aside] angle, there has been a bit of <a href=\"https://www.wired.com/story/covid-19-does-not-discriminate-by-body-weight/\" rel=\"nofollow noreferrer\">controversy</a> whether (higher) BMI is risk factor for Covid-19, if all other associated problems like diabetes etc. are factored out.)</p>\n" }, { "answer_id": 23585, "author": "Graham Chiu", "author_id": 3414, "author_profile": "https://health.stackexchange.com/users/3414", "pm_score": 0, "selected": false, "text": "<p>I think they're just pointing out that Yemen has a very poorly functioning public health system with generalised poor nutrition so that the individuals of the population have little reserve to fight infection.</p>\n\n<blockquote>\n <p>More than 80% of Yemen's population lacks food, fuel, drinking water and access to health care services, which makes it particularly vulnerable to diseases that can generally be cured or eradicated elsewhere in the world. The health care system has been decimated by years of unrelenting war in Yemen.</p>\n</blockquote>\n\n<p>They also suffered terribly from cholera which is a treatable disease.</p>\n\n<blockquote>\n <p>Despite being a completely treatable disease, thousands of people have died from the outbreak of cholera unleashed in Yemen in 2017. </p>\n</blockquote>\n\n<p><a href=\"https://www.icrc.org/en/where-we-work/middle-east/yemen/health-crisis-yemen\" rel=\"nofollow noreferrer\">https://www.icrc.org/en/where-we-work/middle-east/yemen/health-crisis-yemen</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/23582", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19529/" ]

[ { "answer_id": 23588, "author": "Marinos An", "author_id": 17794, "author_profile": "https://health.stackexchange.com/users/17794", "pm_score": 2, "selected": false, "text": "<h2>There are guidelines actually:</h2>\n\n<h3>In the <a href=\"http://www.emro.who.int/noncommunicable-diseases/campaigns/campaigns.html\" rel=\"nofollow noreferrer\">Campains</a> section there are the following links:</h3>\n\n<p><strong><a href=\"http://www.emro.who.int/noncommunicable-diseases/campaigns/feeding-babies-and-young-children-during-the-covid-19-outbreak.html\" rel=\"nofollow noreferrer\">Feeding babies and young children during the COVID-19 outbreak\nApril 2020</a></strong></p>\n\n<blockquote>\n <p>Proper nutrition is vital in the first two years of a child's life. It helps to:\n - ensure healthy growth<br>\n - <strong>strengthen the immune system</strong><br>\n - improve cognitive development<br>\n - Reduce the risk of getting ill with infectious and chronic<br>\n deseases.</p>\n</blockquote>\n\n<p><strong><a href=\"http://www.emro.who.int/noncommunicable-diseases/campaigns/breastfeeding-advice-during-the-covid-19-outbreak.html\" rel=\"nofollow noreferrer\">Breastfeeding advice during COVID-19\nMarch 2020</a></strong></p>\n\n<blockquote>\n <p>[...] Breastfeeding is particularly effective against infectious deseases because <strong>it strengthens the immune system</strong> by transfering atibodies from you</p>\n</blockquote>\n\n<p><strong><a href=\"http://www.emro.who.int/noncommunicable-diseases/campaigns/nutrition-for-adults-during-covid-19.html\" rel=\"nofollow noreferrer\">Nutrition for adults during COVID-19\nMarch 2020</a></strong></p>\n\n<blockquote>\n <p>Eat a well-balenced diet everyday to get the vitamins, minerals, dietary fibre, protein and antioxidants your body needs to be healthier with a <strong>stronger immune system</strong> and to lower your risk of chronic illnesses and infectious deseases.</p>\n</blockquote>\n\n<h3>In the <a href=\"http://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/technical-guidance\" rel=\"nofollow noreferrer\">technical guidance</a> section also:</h3>\n\n<p><strong><a href=\"http://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/technical-guidance/food-and-nutrition-tips-during-self-quarantine2\" rel=\"nofollow noreferrer\">Food and nutrition tips during self-quarantine</a></strong></p>\n\n<blockquote>\n <p>[...]Good nutrition is crucial for health, particularly in times when <strong>the immune system might need to fight back</strong>\n [...]Alcohol is not only a mind-altering and dependence-producing substance, harmful at any level consumed, but it also <strong>weakens the immune system</strong></p>\n</blockquote>\n\n<p><strong><a href=\"http://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/technical-guidance/stay-physically-active-during-self-quarantine2\" rel=\"nofollow noreferrer\">Stay physically active during self-quarantine</a></strong></p>\n\n<blockquote>\n <p>[...]Staying at home for prolonged periods of time can pose a significant challenge for remaining physically active. Sedentary behaviour and <strong>low levels of physical activity can have negative effects on the health</strong>, well-being and quality of life of individuals. Self-quarantine can also cause additional stress and challenge the mental health of citizens. <strong>Physical activity and relaxation techniques can be valuable tools to help you remain calm and continue to protect your health during this time.</strong></p>\n \n <p>WHO recommends 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity physical activity per week, or a combination of both.[...]</p>\n</blockquote>\n" }, { "answer_id": 23809, "author": "PGC1-alpha", "author_id": 19754, "author_profile": "https://health.stackexchange.com/users/19754", "pm_score": 1, "selected": false, "text": "<p>Not sure about the WHO, but this article might help in Sports Medicine</p>\n\n<p><a href=\"https://link.springer.com/article/10.1007/s40279-020-01295-8\" rel=\"nofollow noreferrer\">The Challenge of Maintaining Metabolic Health During a Global Pandemic</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/23587", "https://health.stackexchange.com", "https://health.stackexchange.com/users/17794/" ]

[ { "answer_id": 23626, "author": "Marcus D", "author_id": 19626, "author_profile": "https://health.stackexchange.com/users/19626", "pm_score": -1, "selected": false, "text": "<p>I can't comment on rt-PCR.</p>\n\n<p>Recent findings (which can be listened to in this <a href=\"https://www.youtube.com/watch?v=y5QJ5O3ldE0\" rel=\"nofollow noreferrer\">MedCram Youtube clip, by Roger Seheult, MD</a> on Covid-19 diagnosis), in summary says</p>\n\n<blockquote>\n <p>Lung ultrasound rivals CT imaging for fast and accurate bedside diagnosis and monitoring of coronavirus infection</p>\n</blockquote>\n" }, { "answer_id": 23634, "author": "Graham Chiu", "author_id": 3414, "author_profile": "https://health.stackexchange.com/users/3414", "pm_score": 1, "selected": false, "text": "<p>This is an emerging area of advice. It really depends on the pre-test probability of COVID-19 in your region, and the urgency of surgery.</p>\n<p>The Royal College of Surgeons, Edinburgh make the following recommendation</p>\n<p>9th April 2020</p>\n<blockquote>\n<p>Patients who present as abdominal emergencies who have an abdominal CT in their diagnostic investigations should also have a Chest CT scan (ref ––Updated General Surgery Guidance on Covid-19 – Intercollegiate / ASGBI 5th April 2020).</p>\n<p>Due to its low sensitivity and the low pre-test probability of disease (Scotland), computed tomography should only be deployed in very specific circumstances</p>\n</blockquote>\n<p>Your pre-test probability may be much higher which might justify CT chest if you don't have time to do rtPCR, and antibody studies.</p>\n<p><a href=\"https://www.rcsed.ac.uk/news-public-affairs/news/2020/april/intercollegiate-guidance-for-pre-operative-chest-ct-imaging-for-elective-cancer-surgery-during-the-covid-19-pandemic\" rel=\"nofollow noreferrer\">https://www.rcsed.ac.uk/news-public-affairs/news/2020/april/intercollegiate-guidance-for-pre-operative-chest-ct-imaging-for-elective-cancer-surgery-during-the-covid-19-pandemic</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/23624", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19117/" ]

[ { "answer_id": 23839, "author": "gotwo", "author_id": 17963, "author_profile": "https://health.stackexchange.com/users/17963", "pm_score": 1, "selected": false, "text": "<p><a href=\"https://www.medrxiv.org/content/10.1101/2020.04.04.20053058v1\" rel=\"nofollow noreferrer\">There</a> are described any infections on supermarkets in China. </p>\n\n<p>Ten workers became infected in <strong>Liaocheng</strong>. As a result, there were at least 6 secondary infections.</p>\n\n<p>There were 17 cases in <strong>Wenzhou</strong>. The patient with the earliest symptoms was a female cleaner. As a result, more than 100,000 people were traced.</p>\n\n<p>In <strong>Tianjin</strong>, 6 shop workers and 9 customers were infected.</p>\n\n<p>An other outbreak is described <a href=\"https://www.nytimes.com/2020/04/15/us/politics/coronavirus-grocery-workers-washington.html\" rel=\"nofollow noreferrer\">here</a>, in a Whole Foods market in the near of <strong>Washington</strong>. There was 16 employees infected. However, there is no information about infections outside the market.</p>\n" }, { "answer_id": 23862, "author": "lordy", "author_id": 19718, "author_profile": "https://health.stackexchange.com/users/19718", "pm_score": 0, "selected": false, "text": "<p>I dont know about supermarkets but there were clusters based on postal service centers in Austria (at least 72 infected this way):</p>\n\n<ul>\n<li><a href=\"https://www.wienerzeitung.at/nachrichten/chronik/wien/2062276-Covid-19-Fall-im-Briefzentrum.html\" rel=\"nofollow noreferrer\">https://www.wienerzeitung.at/nachrichten/chronik/wien/2062276-Covid-19-Fall-im-Briefzentrum.html</a></li>\n<li><a href=\"https://kurier.at/politik/inland/corona-krise-bei-der-post-wie-es-dazu-kommen-konnte/400844573\" rel=\"nofollow noreferrer\">https://kurier.at/politik/inland/corona-krise-bei-der-post-wie-es-dazu-kommen-konnte/400844573</a></li>\n</ul>\n" } ]

[ "https://health.stackexchange.com/questions/23667", "https://health.stackexchange.com", "https://health.stackexchange.com/users/10980/" ]

[ { "answer_id": 23839, "author": "gotwo", "author_id": 17963, "author_profile": "https://health.stackexchange.com/users/17963", "pm_score": 1, "selected": false, "text": "<p><a href=\"https://www.medrxiv.org/content/10.1101/2020.04.04.20053058v1\" rel=\"nofollow noreferrer\">There</a> are described any infections on supermarkets in China. </p>\n\n<p>Ten workers became infected in <strong>Liaocheng</strong>. As a result, there were at least 6 secondary infections.</p>\n\n<p>There were 17 cases in <strong>Wenzhou</strong>. The patient with the earliest symptoms was a female cleaner. As a result, more than 100,000 people were traced.</p>\n\n<p>In <strong>Tianjin</strong>, 6 shop workers and 9 customers were infected.</p>\n\n<p>An other outbreak is described <a href=\"https://www.nytimes.com/2020/04/15/us/politics/coronavirus-grocery-workers-washington.html\" rel=\"nofollow noreferrer\">here</a>, in a Whole Foods market in the near of <strong>Washington</strong>. There was 16 employees infected. However, there is no information about infections outside the market.</p>\n" }, { "answer_id": 23862, "author": "lordy", "author_id": 19718, "author_profile": "https://health.stackexchange.com/users/19718", "pm_score": 0, "selected": false, "text": "<p>I dont know about supermarkets but there were clusters based on postal service centers in Austria (at least 72 infected this way):</p>\n\n<ul>\n<li><a href=\"https://www.wienerzeitung.at/nachrichten/chronik/wien/2062276-Covid-19-Fall-im-Briefzentrum.html\" rel=\"nofollow noreferrer\">https://www.wienerzeitung.at/nachrichten/chronik/wien/2062276-Covid-19-Fall-im-Briefzentrum.html</a></li>\n<li><a href=\"https://kurier.at/politik/inland/corona-krise-bei-der-post-wie-es-dazu-kommen-konnte/400844573\" rel=\"nofollow noreferrer\">https://kurier.at/politik/inland/corona-krise-bei-der-post-wie-es-dazu-kommen-konnte/400844573</a></li>\n</ul>\n" } ]

[ "https://health.stackexchange.com/questions/23672", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19653/" ]

[ { "answer_id": 23839, "author": "gotwo", "author_id": 17963, "author_profile": "https://health.stackexchange.com/users/17963", "pm_score": 1, "selected": false, "text": "<p><a href=\"https://www.medrxiv.org/content/10.1101/2020.04.04.20053058v1\" rel=\"nofollow noreferrer\">There</a> are described any infections on supermarkets in China. </p>\n\n<p>Ten workers became infected in <strong>Liaocheng</strong>. As a result, there were at least 6 secondary infections.</p>\n\n<p>There were 17 cases in <strong>Wenzhou</strong>. The patient with the earliest symptoms was a female cleaner. As a result, more than 100,000 people were traced.</p>\n\n<p>In <strong>Tianjin</strong>, 6 shop workers and 9 customers were infected.</p>\n\n<p>An other outbreak is described <a href=\"https://www.nytimes.com/2020/04/15/us/politics/coronavirus-grocery-workers-washington.html\" rel=\"nofollow noreferrer\">here</a>, in a Whole Foods market in the near of <strong>Washington</strong>. There was 16 employees infected. However, there is no information about infections outside the market.</p>\n" }, { "answer_id": 23862, "author": "lordy", "author_id": 19718, "author_profile": "https://health.stackexchange.com/users/19718", "pm_score": 0, "selected": false, "text": "<p>I dont know about supermarkets but there were clusters based on postal service centers in Austria (at least 72 infected this way):</p>\n\n<ul>\n<li><a href=\"https://www.wienerzeitung.at/nachrichten/chronik/wien/2062276-Covid-19-Fall-im-Briefzentrum.html\" rel=\"nofollow noreferrer\">https://www.wienerzeitung.at/nachrichten/chronik/wien/2062276-Covid-19-Fall-im-Briefzentrum.html</a></li>\n<li><a href=\"https://kurier.at/politik/inland/corona-krise-bei-der-post-wie-es-dazu-kommen-konnte/400844573\" rel=\"nofollow noreferrer\">https://kurier.at/politik/inland/corona-krise-bei-der-post-wie-es-dazu-kommen-konnte/400844573</a></li>\n</ul>\n" } ]

[ "https://health.stackexchange.com/questions/23674", "https://health.stackexchange.com", "https://health.stackexchange.com/users/17847/" ]

[ { "answer_id": 23713, "author": "Jan", "author_id": 3002, "author_profile": "https://health.stackexchange.com/users/3002", "pm_score": 3, "selected": true, "text": "<p>Muscle twitches (fasciculations) caused by malnutrition are usually (not always) associated with muscle cramps.</p>\n\n<p>Malnutrition-related causes of twitches include severely insufficient nutrient intake (fasting, anorexia nervosa...) or malabsorption (Crohn or celiac disease...):</p>\n\n<ul>\n<li><strong>dehydration,</strong> especially if associated with exercise (<a href=\"https://books.google.com/books?id=R0dvDwAAQBAJ&amp;pg=PA356&amp;lpg=PA356&amp;dq=dehydration%20fasciculations&amp;source=bl&amp;ots=CZmidvgCOX&amp;sig=ACfU3U0jHdHjNd_v7d_KSnLYkxzJX0kdSQ&amp;hl=en&amp;sa=X&amp;ved=2ahUKEwiQpPGyr8fpAhVRzoUKHTRzChMQ6AEwEXoECAkQAQ#v=onepage&amp;q=dehydration%20fasciculations&amp;f=false\" rel=\"nofollow noreferrer\">Managing the Side Effects of Psychotropic Medications, JF Goldberg, CL Erns</a>)</li>\n<li>moderate <a href=\"https://www.uofmhealth.org/health-library/aa20831\" rel=\"nofollow noreferrer\">hypoglycaemia</a>, which may develop in some people during prolonged starvation or in others after large meals (reactive hypoglycaemia) </li>\n<li>severe hypokalemia (<a href=\"https://www.msdmanuals.com/en-au/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypokalemia\" rel=\"nofollow noreferrer\">MSD Manual</a>)</li>\n<li>hypomagnesemia (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062555/\" rel=\"nofollow noreferrer\">PubMed Central</a>)</li>\n<li>vitamin D deficiency, if associated with hypocalcemia (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413335/\" rel=\"nofollow noreferrer\">BMJ, 2008</a>)</li>\n</ul>\n\n<p>Prolonged exercise or certain sitting or sleeping positions, tiredness, hypothermia, certain drugs (diuretics...) and other triggers mentioned in the question can aggravate malnutrition-related twitching.</p>\n\n<p>In conclusion, dehydration and, maybe, hypoglycemia seem to be the most common causes of \"food- related\" twitching. Eating disorders and unbalanced vegans diets may also be risk factors. </p>\n" }, { "answer_id": 23738, "author": "Sohrab T", "author_id": 19659, "author_profile": "https://health.stackexchange.com/users/19659", "pm_score": 1, "selected": false, "text": "<p>Apparently twitching can indeed be caused by low sugar (hypoglycemia), but this is more in line with having diabetes than being malnourished.\nSee \"Symptoms of moderate low blood sugar\" in <a href=\"https://www.healthlinkbc.ca/health-topics/aa20831\" rel=\"nofollow noreferrer\">https://www.healthlinkbc.ca/health-topics/aa20831</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/23709", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7951/" ]

[ { "answer_id": 23713, "author": "Jan", "author_id": 3002, "author_profile": "https://health.stackexchange.com/users/3002", "pm_score": 3, "selected": true, "text": "<p>Muscle twitches (fasciculations) caused by malnutrition are usually (not always) associated with muscle cramps.</p>\n\n<p>Malnutrition-related causes of twitches include severely insufficient nutrient intake (fasting, anorexia nervosa...) or malabsorption (Crohn or celiac disease...):</p>\n\n<ul>\n<li><strong>dehydration,</strong> especially if associated with exercise (<a href=\"https://books.google.com/books?id=R0dvDwAAQBAJ&amp;pg=PA356&amp;lpg=PA356&amp;dq=dehydration%20fasciculations&amp;source=bl&amp;ots=CZmidvgCOX&amp;sig=ACfU3U0jHdHjNd_v7d_KSnLYkxzJX0kdSQ&amp;hl=en&amp;sa=X&amp;ved=2ahUKEwiQpPGyr8fpAhVRzoUKHTRzChMQ6AEwEXoECAkQAQ#v=onepage&amp;q=dehydration%20fasciculations&amp;f=false\" rel=\"nofollow noreferrer\">Managing the Side Effects of Psychotropic Medications, JF Goldberg, CL Erns</a>)</li>\n<li>moderate <a href=\"https://www.uofmhealth.org/health-library/aa20831\" rel=\"nofollow noreferrer\">hypoglycaemia</a>, which may develop in some people during prolonged starvation or in others after large meals (reactive hypoglycaemia) </li>\n<li>severe hypokalemia (<a href=\"https://www.msdmanuals.com/en-au/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypokalemia\" rel=\"nofollow noreferrer\">MSD Manual</a>)</li>\n<li>hypomagnesemia (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062555/\" rel=\"nofollow noreferrer\">PubMed Central</a>)</li>\n<li>vitamin D deficiency, if associated with hypocalcemia (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413335/\" rel=\"nofollow noreferrer\">BMJ, 2008</a>)</li>\n</ul>\n\n<p>Prolonged exercise or certain sitting or sleeping positions, tiredness, hypothermia, certain drugs (diuretics...) and other triggers mentioned in the question can aggravate malnutrition-related twitching.</p>\n\n<p>In conclusion, dehydration and, maybe, hypoglycemia seem to be the most common causes of \"food- related\" twitching. Eating disorders and unbalanced vegans diets may also be risk factors. </p>\n" }, { "answer_id": 23738, "author": "Sohrab T", "author_id": 19659, "author_profile": "https://health.stackexchange.com/users/19659", "pm_score": 1, "selected": false, "text": "<p>Apparently twitching can indeed be caused by low sugar (hypoglycemia), but this is more in line with having diabetes than being malnourished.\nSee \"Symptoms of moderate low blood sugar\" in <a href=\"https://www.healthlinkbc.ca/health-topics/aa20831\" rel=\"nofollow noreferrer\">https://www.healthlinkbc.ca/health-topics/aa20831</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/23719", "https://health.stackexchange.com", "https://health.stackexchange.com/users/17760/" ]

[ { "answer_id": 23713, "author": "Jan", "author_id": 3002, "author_profile": "https://health.stackexchange.com/users/3002", "pm_score": 3, "selected": true, "text": "<p>Muscle twitches (fasciculations) caused by malnutrition are usually (not always) associated with muscle cramps.</p>\n\n<p>Malnutrition-related causes of twitches include severely insufficient nutrient intake (fasting, anorexia nervosa...) or malabsorption (Crohn or celiac disease...):</p>\n\n<ul>\n<li><strong>dehydration,</strong> especially if associated with exercise (<a href=\"https://books.google.com/books?id=R0dvDwAAQBAJ&amp;pg=PA356&amp;lpg=PA356&amp;dq=dehydration%20fasciculations&amp;source=bl&amp;ots=CZmidvgCOX&amp;sig=ACfU3U0jHdHjNd_v7d_KSnLYkxzJX0kdSQ&amp;hl=en&amp;sa=X&amp;ved=2ahUKEwiQpPGyr8fpAhVRzoUKHTRzChMQ6AEwEXoECAkQAQ#v=onepage&amp;q=dehydration%20fasciculations&amp;f=false\" rel=\"nofollow noreferrer\">Managing the Side Effects of Psychotropic Medications, JF Goldberg, CL Erns</a>)</li>\n<li>moderate <a href=\"https://www.uofmhealth.org/health-library/aa20831\" rel=\"nofollow noreferrer\">hypoglycaemia</a>, which may develop in some people during prolonged starvation or in others after large meals (reactive hypoglycaemia) </li>\n<li>severe hypokalemia (<a href=\"https://www.msdmanuals.com/en-au/professional/endocrine-and-metabolic-disorders/electrolyte-disorders/hypokalemia\" rel=\"nofollow noreferrer\">MSD Manual</a>)</li>\n<li>hypomagnesemia (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062555/\" rel=\"nofollow noreferrer\">PubMed Central</a>)</li>\n<li>vitamin D deficiency, if associated with hypocalcemia (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413335/\" rel=\"nofollow noreferrer\">BMJ, 2008</a>)</li>\n</ul>\n\n<p>Prolonged exercise or certain sitting or sleeping positions, tiredness, hypothermia, certain drugs (diuretics...) and other triggers mentioned in the question can aggravate malnutrition-related twitching.</p>\n\n<p>In conclusion, dehydration and, maybe, hypoglycemia seem to be the most common causes of \"food- related\" twitching. Eating disorders and unbalanced vegans diets may also be risk factors. </p>\n" }, { "answer_id": 23738, "author": "Sohrab T", "author_id": 19659, "author_profile": "https://health.stackexchange.com/users/19659", "pm_score": 1, "selected": false, "text": "<p>Apparently twitching can indeed be caused by low sugar (hypoglycemia), but this is more in line with having diabetes than being malnourished.\nSee \"Symptoms of moderate low blood sugar\" in <a href=\"https://www.healthlinkbc.ca/health-topics/aa20831\" rel=\"nofollow noreferrer\">https://www.healthlinkbc.ca/health-topics/aa20831</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/23724", "https://health.stackexchange.com", "https://health.stackexchange.com/users/10980/" ]

[ { "answer_id": 23772, "author": "JMP", "author_id": 97, "author_profile": "https://health.stackexchange.com/users/97", "pm_score": 3, "selected": false, "text": "<p><a href=\"https://www.nature.com/articles/ncomms5212\" rel=\"nofollow noreferrer\">Nature Communications</a> have such a database.</p>\n<blockquote>\n<p><strong>Human symptoms–disease network</strong></p>\n<p><em>XueZhong Zhou, Jörg Menche, Albert-László Barabási &amp; Amitabh Sharma</em></p>\n<p>Published: 26 June 2014</p>\n</blockquote>\n<p>They count the number of times a disease and a symptom keywords both appear on the same <a href=\"https://pubmed.ncbi.nlm.nih.gov/\" rel=\"nofollow noreferrer\">PudMed</a> article, and assign a <a href=\"https://en.wikipedia.org/wiki/Tf%E2%80%93idf\" rel=\"nofollow noreferrer\">TF-IDF</a> value to each pair.</p>\n<p>In their words:</p>\n<blockquote>\n<p><strong>Acquisition of symptom and disease relationships</strong></p>\n<p>The association between symptoms and diseases were then quantified using term co-occurrence (number of PubMed identifiers in which two terms appear together;</p>\n</blockquote>\n<p>Link to the database:</p>\n<blockquote>\n<p><a href=\"https://static-content.springer.com/esm/art%3A10.1038%2Fncomms5212/MediaObjects/41467_2014_BFncomms5212_MOESM1045_ESM.txt\" rel=\"nofollow noreferrer\">https://static-content.springer.com/esm/art%3A10.1038%2Fncomms5212/MediaObjects/41467_2014_BFncomms5212_MOESM1045_ESM.txt</a></p>\n</blockquote>\n<p>(<a href=\"https://www.nature.com/articles/ncomms5212#Sec18\" rel=\"nofollow noreferrer\">Supplementary Data 3</a> from the article)</p>\n" }, { "answer_id": 23855, "author": "Graham Chiu", "author_id": 3414, "author_profile": "https://health.stackexchange.com/users/3414", "pm_score": 2, "selected": false, "text": "<p>What you're looking for is used by AI or Bayesian networks for online diagnosis. These databases are commercially sensitive and likely only accessible by API rather than raw data. For example, ISABEL, has been around for 20 years </p>\n\n<p><a href=\"https://www.isabelhealthcare.com/products/integration\" rel=\"nofollow noreferrer\">https://www.isabelhealthcare.com/products/integration</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/23764", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19718/" ]

[ { "answer_id": 23791, "author": "Brian", "author_id": 19203, "author_profile": "https://health.stackexchange.com/users/19203", "pm_score": 2, "selected": false, "text": "<p>I had trouble finding any specific estimates for your question after various searches, but given the common cold is much milder than the flu, one can presume it is significantly less than the CFR of the flu.</p>\n\n<p>The issue with the common cold isn't the virus itself, but instead the complications that patients can get after the virus, which can rarely but potentially become dangerous. For instance, a bacterial sinus infection can develop -- in children, <a href=\"https://pubmed.ncbi.nlm.nih.gov/11533355/\" rel=\"nofollow noreferrer\">5-13% of bacterial sinus infections have a preceding viral infection</a>. Serious but rare neurological diseases, like <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991291/\" rel=\"nofollow noreferrer\">Guillain-Barre Syndrome</a>, can also occur after a common cold.</p>\n\n<p>The common cold can also <a href=\"https://www.sciencedirect.com/science/article/pii/S0012369215353794?casa_token=sYuwlTkcj9UAAAAA:cfxpxmeoiWCNRRkzz0MdhxsbSxGwkk_zspZmtglVcrn4N6mwVGLTyNtuRQRcx97JnwKYdATbzw\" rel=\"nofollow noreferrer\">exacerbate the symptoms</a> one has from other health conditions, such as COPD, which is a common cause for hospitalization among adults with COPD. </p>\n" }, { "answer_id": 23794, "author": "Jan", "author_id": 3002, "author_profile": "https://health.stackexchange.com/users/3002", "pm_score": 4, "selected": true, "text": "<p>SARS-Cov-2 is a distinct virus that causes a distinct disease: COVID-19.</p>\n\n<p>Virus influenzae is a distinct virus (or a term for a small group of similar viruses) that causes a distinct disease: seasonal influenza or \"flu.\"</p>\n\n<p>This is why you can compare death rates of SARS-Cov-2 and influenza virus, or COVID-19 and flu.</p>\n\n<p>\"<a href=\"https://www.medicinenet.com/common_cold/article.htm\" rel=\"nofollow noreferrer\">Common cold</a>\" refers to a group of various viral infections of the nose and throat, which can be caused by at least 200 different viruses. This means you can't compare death rates of a diverse group of diseases called common cold and a single disease, such as COVID-19 or flu.</p>\n\n<p>When a common cold extends to the lower respiratory tract, it is, by definition, no longer called common cold, but laryngitis, bronchitis or pneumonia, for example. </p>\n\n<p>When a person gets a common cold that becomes complicated as pneumonia and dies from it, the cause of death is recorded as pneumonia not as a common cold.</p>\n\n<p>If you stick with a definition of common cold linked above:</p>\n\n<blockquote>\n <p>Common cold is a <em>self-limited</em> contagious disease that can be caused by a\n number of different types of viruses. The common cold is medically\n referred to as a viral upper respiratory tract infection.</p>\n</blockquote>\n\n<p>...then you can't even say that common cold is deadly.</p>\n" } ]

[ "https://health.stackexchange.com/questions/23777", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19730/" ]

[ { "answer_id": 23791, "author": "Brian", "author_id": 19203, "author_profile": "https://health.stackexchange.com/users/19203", "pm_score": 2, "selected": false, "text": "<p>I had trouble finding any specific estimates for your question after various searches, but given the common cold is much milder than the flu, one can presume it is significantly less than the CFR of the flu.</p>\n\n<p>The issue with the common cold isn't the virus itself, but instead the complications that patients can get after the virus, which can rarely but potentially become dangerous. For instance, a bacterial sinus infection can develop -- in children, <a href=\"https://pubmed.ncbi.nlm.nih.gov/11533355/\" rel=\"nofollow noreferrer\">5-13% of bacterial sinus infections have a preceding viral infection</a>. Serious but rare neurological diseases, like <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991291/\" rel=\"nofollow noreferrer\">Guillain-Barre Syndrome</a>, can also occur after a common cold.</p>\n\n<p>The common cold can also <a href=\"https://www.sciencedirect.com/science/article/pii/S0012369215353794?casa_token=sYuwlTkcj9UAAAAA:cfxpxmeoiWCNRRkzz0MdhxsbSxGwkk_zspZmtglVcrn4N6mwVGLTyNtuRQRcx97JnwKYdATbzw\" rel=\"nofollow noreferrer\">exacerbate the symptoms</a> one has from other health conditions, such as COPD, which is a common cause for hospitalization among adults with COPD. </p>\n" }, { "answer_id": 23794, "author": "Jan", "author_id": 3002, "author_profile": "https://health.stackexchange.com/users/3002", "pm_score": 4, "selected": true, "text": "<p>SARS-Cov-2 is a distinct virus that causes a distinct disease: COVID-19.</p>\n\n<p>Virus influenzae is a distinct virus (or a term for a small group of similar viruses) that causes a distinct disease: seasonal influenza or \"flu.\"</p>\n\n<p>This is why you can compare death rates of SARS-Cov-2 and influenza virus, or COVID-19 and flu.</p>\n\n<p>\"<a href=\"https://www.medicinenet.com/common_cold/article.htm\" rel=\"nofollow noreferrer\">Common cold</a>\" refers to a group of various viral infections of the nose and throat, which can be caused by at least 200 different viruses. This means you can't compare death rates of a diverse group of diseases called common cold and a single disease, such as COVID-19 or flu.</p>\n\n<p>When a common cold extends to the lower respiratory tract, it is, by definition, no longer called common cold, but laryngitis, bronchitis or pneumonia, for example. </p>\n\n<p>When a person gets a common cold that becomes complicated as pneumonia and dies from it, the cause of death is recorded as pneumonia not as a common cold.</p>\n\n<p>If you stick with a definition of common cold linked above:</p>\n\n<blockquote>\n <p>Common cold is a <em>self-limited</em> contagious disease that can be caused by a\n number of different types of viruses. The common cold is medically\n referred to as a viral upper respiratory tract infection.</p>\n</blockquote>\n\n<p>...then you can't even say that common cold is deadly.</p>\n" } ]

[ "https://health.stackexchange.com/questions/23903", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19827/" ]

[ { "answer_id": 23919, "author": "anongoodnurse", "author_id": 169, "author_profile": "https://health.stackexchange.com/users/169", "pm_score": 2, "selected": true, "text": "<blockquote>\n <p>Can bacteria be present on Dry fruits/nuts?</p>\n</blockquote>\n\n<p>Absolutely. In fact, everything in your environment, including your food, is covered with bacteria, but most of them are harmless. In the good old days, we washed fruit and veggies to reduce possible contaminants, like insecticides used in their growth to keep them pretty, not to remove bacteria. But <a href=\"https://www.medicalnewstoday.com/articles/327028\" rel=\"nofollow noreferrer\">today it's different</a>.^*</p>\n\n<blockquote>\n <p>Is washing them before eating advisable?</p>\n</blockquote>\n\n<p>In this day of increased mass production, questionable preservatives, and increased litigation, the medical websites I looked at recommend washing dried fruit and nuts. :(</p>\n\n<blockquote>\n <p>What are the other possibilities of removing bacteria from dry fruits/nuts? </p>\n</blockquote>\n\n<p>Refrigeration keeps many bacteria from multiplying, but doesn't kill bacteria already present on food.</p>\n\n<p>I couldn't find anything other method of reducing bacteria on the surfaces of dried fruits and nuts. On the effects of pretreatment on bacteria before dehydrating, yes. But once dried, no.</p>\n\n<p>*_{I am old enough to remember this, and to remember the first big food-borne illness outbreaks. There were some outbreaks before then, of course, but many more probably occurred unnoticed. Looking into the origins of the Food and Drug Administrations is pretty informative and interesting reading.}</p>\n" }, { "answer_id": 23952, "author": "Arctiic", "author_id": 16504, "author_profile": "https://health.stackexchange.com/users/16504", "pm_score": 2, "selected": false, "text": "<p>There are different approaches to answering this question, but I will say as a pragmatic generalisation: no, that wouldn't be advisable.</p>\n<p>For one thing, the standard procedures that can be applied to the &quot;washing&quot; of food products varies greatly depending upon their physical, chemical. and other characteristics. Washing of dry ingredients involves rehydrating them, and from the safety standpoint you are introducing further risks of &quot;pulling in&quot; more contaminants in the process without any definitive benfits to gain by doing so (and the quality standpoint will generally suffer greatly without further processing involved). (See <a href=\"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-industry-guide-minimize-microbial-food-safety-hazards-fresh-cut-fruits-and-vegetables\" rel=\"nofollow noreferrer\">FDA Guidance</a>)</p>\n<p>A better solution is to simply learn more about the supply chain and purchase from a reputable facility or brand identity, such as ones with 3rd party audit certification, e.g., at the <a href=\"https://mygfsi.com/\" rel=\"nofollow noreferrer\">GFSI level</a> (<a href=\"https://www.sqfi.com/wp-content/uploads/2019/07/SQF-Code_Manufacturing-ed-8.1-FINAL.pdf\" rel=\"nofollow noreferrer\">SQF</a>, BRC, FSSC22000, etc.), or private retailer branded items (e.g., Trader Joe's brands, Aldi's Fusia brand line, etc). Also, learn the types of illnesses that result from adulterated food: there's infection, intoxication, and infection-mediated intoxication, etc (<a href=\"http://www.csun.edu/%7Ecjh78264/foodsafety/pages/fbi1.html\" rel=\"nofollow noreferrer\">source</a>). Simply achieving lethality does not necessarily render food safe for consumption, so beware to keep that in mind.</p>\n<p>EDIT: Please note that upon second thought, I'm not sure I'm able to disclose TJ's or Aldi's brand identity requirements guidance documentation as I'm not sure if it's covered under their NDA or not. To put it simply though, the reason why I bring them up is simply due to the nature of how contract manufacturing works in the retail food sector; they will not contract out to a manufacturer for an item packed under their own brand identity unless there is a certain level of assurance that no harm should come to their brand in the event of, e.g., recall or etc. Thus, anyone who is approved to manufacture under their branding has to meet a certain level of safety and quality standards, and the minimmum of which is benchmarked at the GFSI standard. Trader Joe's actually is even more stringent and has implemented their own standard as of last year, mediated by SAI Global. Therefor, even without the documentation, you can arrive to the same conclusion via common-sense.)</p>\n" } ]

[ "https://health.stackexchange.com/questions/23918", "https://health.stackexchange.com", "https://health.stackexchange.com/users/17196/" ]

[ { "answer_id": 23948, "author": "Jiminy Cricket.", "author_id": 15405, "author_profile": "https://health.stackexchange.com/users/15405", "pm_score": 1, "selected": false, "text": "<p>DI stands for <a href=\"https://www.medicinenet.com/script/main/art.asp?articlekey=2977\" rel=\"nofollow noreferrer\">diachronic</a>:</p>\n<blockquote>\n<p>Diachronic: Over a period of time. The opposite of synchronic.</p>\n</blockquote>\n<p>This would indicate that the medication is given in a drip, not as a bolus.</p>\n<p>D1 seems to not have any standard meaning, the conclusion this answerer draws is that D1 is a probable transcription substitution for DI.</p>\n" }, { "answer_id": 23986, "author": "Graham Chiu", "author_id": 3414, "author_profile": "https://health.stackexchange.com/users/3414", "pm_score": 3, "selected": true, "text": "<p>D1 means on day one of the three weekly cycles. DI is a typo.</p>\n<p><a href=\"https://oncologypro.esmo.org/meeting-resources/esmo-2016/Lurbinectedin-PM01183-administered-once-D1-every-3-weeks-q3w-in-combination-with-capecitabine-XEL-in-patients-pts-with-metastatic-breast-MBC-colorectal-CRC-or-pancreatic-PaC-cancer\" rel=\"nofollow noreferrer\">https://oncologypro.esmo.org/meeting-resources/esmo-2016/Lurbinectedin-PM01183-administered-once-D1-every-3-weeks-q3w-in-combination-with-capecitabine-XEL-in-patients-pts-with-metastatic-breast-MBC-colorectal-CRC-or-pancreatic-PaC-cancer</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/23947", "https://health.stackexchange.com", "https://health.stackexchange.com/users/2248/" ]

[ { "answer_id": 23948, "author": "Jiminy Cricket.", "author_id": 15405, "author_profile": "https://health.stackexchange.com/users/15405", "pm_score": 1, "selected": false, "text": "<p>DI stands for <a href=\"https://www.medicinenet.com/script/main/art.asp?articlekey=2977\" rel=\"nofollow noreferrer\">diachronic</a>:</p>\n<blockquote>\n<p>Diachronic: Over a period of time. The opposite of synchronic.</p>\n</blockquote>\n<p>This would indicate that the medication is given in a drip, not as a bolus.</p>\n<p>D1 seems to not have any standard meaning, the conclusion this answerer draws is that D1 is a probable transcription substitution for DI.</p>\n" }, { "answer_id": 23986, "author": "Graham Chiu", "author_id": 3414, "author_profile": "https://health.stackexchange.com/users/3414", "pm_score": 3, "selected": true, "text": "<p>D1 means on day one of the three weekly cycles. DI is a typo.</p>\n<p><a href=\"https://oncologypro.esmo.org/meeting-resources/esmo-2016/Lurbinectedin-PM01183-administered-once-D1-every-3-weeks-q3w-in-combination-with-capecitabine-XEL-in-patients-pts-with-metastatic-breast-MBC-colorectal-CRC-or-pancreatic-PaC-cancer\" rel=\"nofollow noreferrer\">https://oncologypro.esmo.org/meeting-resources/esmo-2016/Lurbinectedin-PM01183-administered-once-D1-every-3-weeks-q3w-in-combination-with-capecitabine-XEL-in-patients-pts-with-metastatic-breast-MBC-colorectal-CRC-or-pancreatic-PaC-cancer</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/23971", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19881/" ]

[ { "answer_id": 23995, "author": "anongoodnurse", "author_id": 169, "author_profile": "https://health.stackexchange.com/users/169", "pm_score": 2, "selected": false, "text": "<p>Edited to correct misunderstanding of the question (thank you, @Tobias Fritz.)</p>\n<p>According to the <a href=\"https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html\" rel=\"nofollow noreferrer\">CDC</a>, 2,886,267 people in the US have tested positive for SARS-CoV-2, of which 129,811 have died (which is likely a conservative number).</p>\n<p>That means that 4.5% of infected persons die from the infection (129811 is 4.4975395554188% of 2886267.)</p>\n<p>You ask</p>\n<blockquote>\n<p>...for what definition of &quot;significant&quot; is that quoted statement [that 99 percent of infected people have no significant illness from it] true?</p>\n</blockquote>\n<p>It would need to be <strong>more significant than death</strong> for that statement to be true, since the death rate exceeds 1% by about 4.5 times.</p>\n" }, { "answer_id": 30478, "author": "Matthew Christopher Bartsh", "author_id": 21794, "author_profile": "https://health.stackexchange.com/users/21794", "pm_score": -1, "selected": false, "text": "<p>It's an absurd statement, mainly because &quot;significant&quot; is extremely vague. Conceivably he meant &quot;life-threatening or resulting in serious permanent lung damage&quot;. It would be an odd meaning to attach to &quot;significant&quot;, but just about defensible.</p>\n<p>If he believes 99.9 percent of infections by covid are survived, arguable using <a href=\"https://en.wikipedia.org/wiki/Coronavirus_disease_2019#Infection_fatality_rate\" rel=\"nofollow noreferrer\">these figures --thanks for your comment @LangLangC</a> then he might figure that for every covid death, there were nine covid infections that nearly resulted in death, and/or resulted in serious permanent lung damage. I'm doing it now: what is &quot;serious&quot;?</p>\n" } ]

[ "https://health.stackexchange.com/questions/23993", "https://health.stackexchange.com", "https://health.stackexchange.com/users/10980/" ]

[ { "answer_id": 23999, "author": "Rodrigo de Azevedo", "author_id": 12704, "author_profile": "https://health.stackexchange.com/users/12704", "pm_score": 0, "selected": false, "text": "<p><a href=\"https://en.wikipedia.org/wiki/Group_testing\" rel=\"nofollow noreferrer\">Group testing</a> was introduced by <a href=\"https://en.wikipedia.org/wiki/Robert_Dorfman\" rel=\"nofollow noreferrer\">Robert Dorfman</a> during WWII to &quot;weed out all syphilitic men&quot;:</p>\n<ul>\n<li>Robert Dorfman, <a href=\"http://dx.doi.org/10.1214/aoms/1177731363\" rel=\"nofollow noreferrer\">The detection of defective members of large populations</a>, Annals of Mathematical Statistics, Volume 14, Number 4, 1943.</li>\n</ul>\n<hr />\n<p><a href=\"https://i.stack.imgur.com/MOr4i.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/MOr4i.png\" alt=\"The detection of defective members of large populations\" /></a></p>\n" }, { "answer_id": 24035, "author": "cbeleites unhappy with SX", "author_id": 11479, "author_profile": "https://health.stackexchange.com/users/11479", "pm_score": 2, "selected": false, "text": "<p>The principal goal of pooled testing is to rapidly clear <em>many</em> cases in <em>low prevalence</em> (or incidence) situations.</p>\n<hr />\n<p>Long version:</p>\n<p>Disclaimer: I'm analytical chemist, i.e. someone who could by profession be involved in developing such tests, but I'm not involved in SARS-CoV2 testing or SARS-CoV2 test development. What I write here is basically my general professional knowledge and what I read in newspapers.</p>\n<hr />\n<p>As you notice, <strong>pooling works only if the fraction of positive cases is sufficiently <em>low</em></strong>, otherwise all or nearly all pooled samples are positive and the procedure does not save tests*, time and money.</p>\n<p>I use &quot;tests*&quot; to denote the RT-PCR testing procedure done in the lab. For this question, we need to distinguish this &quot;lab test in the narrower sense&quot; (which I mark with a *) from the overall testing procedure in the wider sense that starts with swabbing and ends with reporting the results.</p>\n<p>If a pooled test* is positive, it is usually not necessary to redo the whole testing from sampling on: the lab sampling procedure has steps where diluted sample is prepared (or more precisely: aliquots of the sample are taken, i.e. a known volume that is smaller than the sample volume), and thus only a fraction of this solution actually goes into the PCR vial. So doing a second test* here means that another aliqot of the already prepared sample is taken, put into a 2nd PCR vial and goes into the next (or another) batch of PCR samples. This PCR procdure &quot;test*&quot; is in order of magnitude of an hour, whereas the overall testing procedure from swabbing the patient over shipping the samples, entering into the lab sample logistics, preparation, actual &quot;test*&quot;, signing of the results, getting the results back to health authorities and call the patient can take a few days. <strong>Doing the lab PCR analysis a 2nd time if the pooled sample was positive is quick compared to the overall time from swabbing to results are known to the patient</strong></p>\n<p>The pooling protocol can be adapted to the expected fraction of positive cases: the lower this fraction is, the more samples can be pooled.<br />\nFrom the 2nd diagram in <a href=\"https://medicalsciences.stackexchange.com/a/21562/11479\">my answer to a similar question</a> you can see that in your scenario of 10 % of the cases, pooling 4 cases would in the end save about 40 % of the tests*. Pooling 10 cases in that scenario would save about 25 % of the tests*</p>\n<p>But: 10 % positive cases for a workplace screening would be really high prevalence, in the order of magnitude of the current outbreaks in German meat plants. To put it into some context: the Tönnies meat plant that recently made news as the worst hotspot in the whole of Europe had 1500+ of 6500 workers positive, so 20 - 25 % (in the actual slaughtering part even 65 % positive). In another meat plant, Westfleisch, they apparently caught the outbreak earlier with 33 positive out of 1250 workers (2.5 %).<br />\nIn contrast, the general population in Germany now has about 3.5 positive tests per 100000 inhabitants and week, so &lt;0.01 %. At such low fractions of positive cases, always pooling 10 samples saves more than 90 % of the tests. In other words, within the same time, you can tell 9x as many people that they are negative, and still have only a slightly slower results for the remaining 10 % of tested people.</p>\n<hr />\n<p>Whether it makes sense to test at such low incidences if you do not have any indication of elevated risk, is a different question: <a href=\"https://www.instand-ev.de/en/news/detail/news/extra-instand-ringversuch-340-virusgenom-nachweis-sars-cov-2-april-2020-teilnahmedokumente-sin/?tx_news_pi1%5Bcontroller%5D=News&amp;tx_news_pi1%5Baction%5D=detail&amp;cHash=58a2c9186c54a6cf9661fabde8dbf6c7\" rel=\"nofollow noreferrer\">a recent ring trial found roughly 1.5 - 2 % of false positive tests* or 98 - 98.5 % specificity</a>. Testing a population with incidence &lt;&lt; (1 - specificity) means that almost all positives are false positives.<br />\n(I did not include false positive rate in the calculations above)</p>\n<hr />\n<ul>\n<li>A 2nd requirement is that the test* is sufficiently sensitive to detect a single positive sample in the pool. As I understand, this is less of a concern with the discussed pooling protocols for SARS-CoV2 since only few cases (10) are pooled, and I suspect that for the pooled tests* the sample material is diluted less than for single sample tests*.</li>\n</ul>\n<hr />\n<p>Update: <a href=\"https://dx.doi.org/10.1093/cid/ciaa531\" rel=\"nofollow noreferrer\">Yelin <em>et al.</em>: Evaluation of COVID-19 RT-qPCR Test in Multi-Sample Pools, Clin Infect Dis, 2020, DOI: 10.1093/cid/ciaa531</a> discuss a pooling protocol that uses the standard kits.<br />\nThey start by taking an aliquot of 130 μl of the swab transport buffer (typical volume: 1 ml) and add 270 μl of lysis buffer. As I understand, these 400 μl are a typical sample volume to go into the RT-qPCR machine.<br />\nNote that this already offers the possibility to take additional aliquots from the transport buffer, i.e. a solution optimized to keep the sample analyzable for much longer times and under less controlled conditions than sample storage in the lab to wait whether it needs to go into the next batch of tests*. They found that 1 positive in 32 samples could be identified 90 % of the time. Typical definition for lower limit of detection is getting a positive response 95 % of the time. Still, this looks as if pools of size 10 (the size I've seen discussed in the local media here) may work without or without too much adjustments to the standard test*ing procedure.</p>\n<hr />\n<p>Without knowing details, I'd expect that the &quot;analyze quickly after putting into test kit vial&quot; refers to such a lysis buffer.</p>\n" }, { "answer_id": 24036, "author": "chongman", "author_id": 19917, "author_profile": "https://health.stackexchange.com/users/19917", "pm_score": 2, "selected": false, "text": "<p>There are several use cases.</p>\n<p><em><strong>But the main reason is always to operate in a situation where the number of tests is a bottleneck or constraint.</strong></em> In the USA, this is usually because of limited test reagents or limited laboratory techs and machines to run the PCR.</p>\n<p>If you have unlimited testing, you would not use pooled testing.</p>\n<p>One use case is surveillance. You pool test 100 people. The amount of RNA copies may tell you roughly if there are 0, 1, 2 or N people in that group that are positive.</p>\n<p>Another is reopening. For schools, you could swab everyone on Friday, run the PCR, and say I'd you likely have 0 active carriers. If so, you open on Monday. If not, you close and do more testing and tracing.</p>\n<p>Another is to save on testing. (With a speed tradeoff). If you have 16 people, and your goal is to get a YES or NO answer for each, you can pool test all 16. Then, if it's positive, then test in sets of 4,4,4,4. Then 1,1,1,1. In the worst case, yes, you use more tests. But if the positive rate is lower than about 30%, this will save tests overall. But this technique takes 3x the time vs test everyone.</p>\n<p>SOURCES\nI've been working tangentially on this issue for 2 months. It's already in use in Germany and has been used at Stanford and in labs a few other places.</p>\n<p>See <a href=\"http://leakylockdown.com\" rel=\"nofollow noreferrer\">http://leakylockdown.com</a></p>\n<p>And <a href=\"http://tinyurl.com/batchPods\" rel=\"nofollow noreferrer\">http://tinyurl.com/batchPods</a></p>\n<p>Or the subReddit for CoronaVirusTesting. I'm u/chongman99</p>\n<p>A NYT article, a few research reports cited on there.</p>\n<h2>UPDATE 08/01/2020</h2>\n<p>See <a href=\"https://arxiv.org/pdf/2004.14934.pdf\" rel=\"nofollow noreferrer\">https://arxiv.org/pdf/2004.14934.pdf</a> for a detail of one procedure used in Uganda. Apparently, they devised a way to do the PCR's in parallel, which doesn't have the slowdown effect of sequential.</p>\n" } ]

[ "https://health.stackexchange.com/questions/23998", "https://health.stackexchange.com", "https://health.stackexchange.com/users/11421/" ]

[ { "answer_id": 23999, "author": "Rodrigo de Azevedo", "author_id": 12704, "author_profile": "https://health.stackexchange.com/users/12704", "pm_score": 0, "selected": false, "text": "<p><a href=\"https://en.wikipedia.org/wiki/Group_testing\" rel=\"nofollow noreferrer\">Group testing</a> was introduced by <a href=\"https://en.wikipedia.org/wiki/Robert_Dorfman\" rel=\"nofollow noreferrer\">Robert Dorfman</a> during WWII to &quot;weed out all syphilitic men&quot;:</p>\n<ul>\n<li>Robert Dorfman, <a href=\"http://dx.doi.org/10.1214/aoms/1177731363\" rel=\"nofollow noreferrer\">The detection of defective members of large populations</a>, Annals of Mathematical Statistics, Volume 14, Number 4, 1943.</li>\n</ul>\n<hr />\n<p><a href=\"https://i.stack.imgur.com/MOr4i.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/MOr4i.png\" alt=\"The detection of defective members of large populations\" /></a></p>\n" }, { "answer_id": 24035, "author": "cbeleites unhappy with SX", "author_id": 11479, "author_profile": "https://health.stackexchange.com/users/11479", "pm_score": 2, "selected": false, "text": "<p>The principal goal of pooled testing is to rapidly clear <em>many</em> cases in <em>low prevalence</em> (or incidence) situations.</p>\n<hr />\n<p>Long version:</p>\n<p>Disclaimer: I'm analytical chemist, i.e. someone who could by profession be involved in developing such tests, but I'm not involved in SARS-CoV2 testing or SARS-CoV2 test development. What I write here is basically my general professional knowledge and what I read in newspapers.</p>\n<hr />\n<p>As you notice, <strong>pooling works only if the fraction of positive cases is sufficiently <em>low</em></strong>, otherwise all or nearly all pooled samples are positive and the procedure does not save tests*, time and money.</p>\n<p>I use &quot;tests*&quot; to denote the RT-PCR testing procedure done in the lab. For this question, we need to distinguish this &quot;lab test in the narrower sense&quot; (which I mark with a *) from the overall testing procedure in the wider sense that starts with swabbing and ends with reporting the results.</p>\n<p>If a pooled test* is positive, it is usually not necessary to redo the whole testing from sampling on: the lab sampling procedure has steps where diluted sample is prepared (or more precisely: aliquots of the sample are taken, i.e. a known volume that is smaller than the sample volume), and thus only a fraction of this solution actually goes into the PCR vial. So doing a second test* here means that another aliqot of the already prepared sample is taken, put into a 2nd PCR vial and goes into the next (or another) batch of PCR samples. This PCR procdure &quot;test*&quot; is in order of magnitude of an hour, whereas the overall testing procedure from swabbing the patient over shipping the samples, entering into the lab sample logistics, preparation, actual &quot;test*&quot;, signing of the results, getting the results back to health authorities and call the patient can take a few days. <strong>Doing the lab PCR analysis a 2nd time if the pooled sample was positive is quick compared to the overall time from swabbing to results are known to the patient</strong></p>\n<p>The pooling protocol can be adapted to the expected fraction of positive cases: the lower this fraction is, the more samples can be pooled.<br />\nFrom the 2nd diagram in <a href=\"https://medicalsciences.stackexchange.com/a/21562/11479\">my answer to a similar question</a> you can see that in your scenario of 10 % of the cases, pooling 4 cases would in the end save about 40 % of the tests*. Pooling 10 cases in that scenario would save about 25 % of the tests*</p>\n<p>But: 10 % positive cases for a workplace screening would be really high prevalence, in the order of magnitude of the current outbreaks in German meat plants. To put it into some context: the Tönnies meat plant that recently made news as the worst hotspot in the whole of Europe had 1500+ of 6500 workers positive, so 20 - 25 % (in the actual slaughtering part even 65 % positive). In another meat plant, Westfleisch, they apparently caught the outbreak earlier with 33 positive out of 1250 workers (2.5 %).<br />\nIn contrast, the general population in Germany now has about 3.5 positive tests per 100000 inhabitants and week, so &lt;0.01 %. At such low fractions of positive cases, always pooling 10 samples saves more than 90 % of the tests. In other words, within the same time, you can tell 9x as many people that they are negative, and still have only a slightly slower results for the remaining 10 % of tested people.</p>\n<hr />\n<p>Whether it makes sense to test at such low incidences if you do not have any indication of elevated risk, is a different question: <a href=\"https://www.instand-ev.de/en/news/detail/news/extra-instand-ringversuch-340-virusgenom-nachweis-sars-cov-2-april-2020-teilnahmedokumente-sin/?tx_news_pi1%5Bcontroller%5D=News&amp;tx_news_pi1%5Baction%5D=detail&amp;cHash=58a2c9186c54a6cf9661fabde8dbf6c7\" rel=\"nofollow noreferrer\">a recent ring trial found roughly 1.5 - 2 % of false positive tests* or 98 - 98.5 % specificity</a>. Testing a population with incidence &lt;&lt; (1 - specificity) means that almost all positives are false positives.<br />\n(I did not include false positive rate in the calculations above)</p>\n<hr />\n<ul>\n<li>A 2nd requirement is that the test* is sufficiently sensitive to detect a single positive sample in the pool. As I understand, this is less of a concern with the discussed pooling protocols for SARS-CoV2 since only few cases (10) are pooled, and I suspect that for the pooled tests* the sample material is diluted less than for single sample tests*.</li>\n</ul>\n<hr />\n<p>Update: <a href=\"https://dx.doi.org/10.1093/cid/ciaa531\" rel=\"nofollow noreferrer\">Yelin <em>et al.</em>: Evaluation of COVID-19 RT-qPCR Test in Multi-Sample Pools, Clin Infect Dis, 2020, DOI: 10.1093/cid/ciaa531</a> discuss a pooling protocol that uses the standard kits.<br />\nThey start by taking an aliquot of 130 μl of the swab transport buffer (typical volume: 1 ml) and add 270 μl of lysis buffer. As I understand, these 400 μl are a typical sample volume to go into the RT-qPCR machine.<br />\nNote that this already offers the possibility to take additional aliquots from the transport buffer, i.e. a solution optimized to keep the sample analyzable for much longer times and under less controlled conditions than sample storage in the lab to wait whether it needs to go into the next batch of tests*. They found that 1 positive in 32 samples could be identified 90 % of the time. Typical definition for lower limit of detection is getting a positive response 95 % of the time. Still, this looks as if pools of size 10 (the size I've seen discussed in the local media here) may work without or without too much adjustments to the standard test*ing procedure.</p>\n<hr />\n<p>Without knowing details, I'd expect that the &quot;analyze quickly after putting into test kit vial&quot; refers to such a lysis buffer.</p>\n" }, { "answer_id": 24036, "author": "chongman", "author_id": 19917, "author_profile": "https://health.stackexchange.com/users/19917", "pm_score": 2, "selected": false, "text": "<p>There are several use cases.</p>\n<p><em><strong>But the main reason is always to operate in a situation where the number of tests is a bottleneck or constraint.</strong></em> In the USA, this is usually because of limited test reagents or limited laboratory techs and machines to run the PCR.</p>\n<p>If you have unlimited testing, you would not use pooled testing.</p>\n<p>One use case is surveillance. You pool test 100 people. The amount of RNA copies may tell you roughly if there are 0, 1, 2 or N people in that group that are positive.</p>\n<p>Another is reopening. For schools, you could swab everyone on Friday, run the PCR, and say I'd you likely have 0 active carriers. If so, you open on Monday. If not, you close and do more testing and tracing.</p>\n<p>Another is to save on testing. (With a speed tradeoff). If you have 16 people, and your goal is to get a YES or NO answer for each, you can pool test all 16. Then, if it's positive, then test in sets of 4,4,4,4. Then 1,1,1,1. In the worst case, yes, you use more tests. But if the positive rate is lower than about 30%, this will save tests overall. But this technique takes 3x the time vs test everyone.</p>\n<p>SOURCES\nI've been working tangentially on this issue for 2 months. It's already in use in Germany and has been used at Stanford and in labs a few other places.</p>\n<p>See <a href=\"http://leakylockdown.com\" rel=\"nofollow noreferrer\">http://leakylockdown.com</a></p>\n<p>And <a href=\"http://tinyurl.com/batchPods\" rel=\"nofollow noreferrer\">http://tinyurl.com/batchPods</a></p>\n<p>Or the subReddit for CoronaVirusTesting. I'm u/chongman99</p>\n<p>A NYT article, a few research reports cited on there.</p>\n<h2>UPDATE 08/01/2020</h2>\n<p>See <a href=\"https://arxiv.org/pdf/2004.14934.pdf\" rel=\"nofollow noreferrer\">https://arxiv.org/pdf/2004.14934.pdf</a> for a detail of one procedure used in Uganda. Apparently, they devised a way to do the PCR's in parallel, which doesn't have the slowdown effect of sequential.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24007", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19734/" ]

[ { "answer_id": 24073, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 6, "selected": true, "text": "<p>People could develop antibodies from natural exposure to the virus. The vaccine is trying to cause antibodies to exist in more people (and/or more strongly) than would express them naturally, therefore a good comparison group is a sample taken randomly in the same way as those getting the vaccine: a placebo group.</p>\n<p>At the same time, these trials tend to assess safety outcomes; again, to assess safety you want to know that effects are <em>no worse</em> than those in some comparison population. Comparing to placebo is typically a gold standard for this comparison.</p>\n<p>You're right that a placebo wouldn't be as necessary if we could prevent random exposure, but in the middle of a pandemic that isn't feasible.</p>\n" }, { "answer_id": 24074, "author": "wisdom_seeker", "author_id": 17314, "author_profile": "https://health.stackexchange.com/users/17314", "pm_score": 4, "selected": false, "text": "<p>Good question. A phase I trial normally has small numbers, is purely sized to test safety, and it would have no placebo arm.\nWith side effects and antibodies are end points, and a placebo group, this would more often be called a <strong>combined phase I/II trial</strong>.</p>\n<p>The purpose of the placebo should be to compare the proportion of side effects and antibodies in the vaccine arm and those in the placebo arm. However with only 20 people in each arm, this seems a bit, ehm, optimistic.</p>\n<p>Imagine if 4 of the vaccinated people report a sore arm, 2 a headache and sore throat, and 2 a fever, that might be unacceptable. But headache and sore throat are common, and as well as fever during winter-time, when colds and influenza are running around. So I expect the reason for the placebo group is to be able to partially compensate for influenza-like illnesses in the community, so they could suggest that some of the reported vaccine side effects aren't from the vaccine. (Note, you can't just subtract one from the other -- with that few people in each group, random variation will be high, so it may be that more of the &quot;placebo&quot; folks got unlucky... but the vaccine still causes fevers in 10% of the vaccinated folks).</p>\n<p>As far as antibodies, you're right -- assuming that in Adelaide, Australia the rates of COVID-19 are very low, then only the vaccinated volunteers could develop antibodies. But what if one of the vaccinated people gets a mild infection naturally? Then you'd better hope that 1-2 of the placebo volunteers do as well, so that you can know the antibody response isn't necessarily from the vaccine.</p>\n<p>Or what if the antibody test is not quite accurate? What if it has some false positives? Then some of the placebo volunteers might test positive as well, and be a flag to take the positive results with a grain of salt.</p>\n" }, { "answer_id": 24078, "author": "BlueRaja - Danny Pflughoeft", "author_id": 12680, "author_profile": "https://health.stackexchange.com/users/12680", "pm_score": 4, "selected": false, "text": "<p>People in the control group will behave differently if they know they're in the control group.</p>\n<p>For example, it's not unreasonable to expect people will do less social distancing once they're vaccinated. This will increase their chances of being exposed to the virus.</p>\n" }, { "answer_id": 24082, "author": "JeanV", "author_id": 19526, "author_profile": "https://health.stackexchange.com/users/19526", "pm_score": 2, "selected": false, "text": "<p>Antibodies only reflect one part of the immune response: the humoral immunity.</p>\n<p>There is another part of the immunity that can't be detected by dosing the antibodies: the <strong>cell-mediated immunity</strong>. It produces no antibodies. It only creates effector T-cells that can detect the presence of viruses (or some intra-cellular bacteria) inside body cells and destroy these cells or trigger apoptosis.</p>\n<p>This is one reason why checking the clinical outcomes of a vaccine is interesting. The results will be compared to antibody titers for interpretation.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24071", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19946/" ]

[ { "answer_id": 24105, "author": "Thomas", "author_id": 19070, "author_profile": "https://health.stackexchange.com/users/19070", "pm_score": 2, "selected": false, "text": "<p>Its primary action is as NaSSA (a noradrenergic and specific serotonergic antidepressant), not as 5-HT3 inhibitor. If you have a look at e. g. the Wikipedia page (<a href=\"https://en.wikipedia.org/wiki/Mirtazapine#Pharmacodynamics\" rel=\"nofollow noreferrer\">https://en.wikipedia.org/wiki/Mirtazapine#Pharmacodynamics</a>), you will see that nausea is listed as side effect under &quot;discontinuation syndrome&quot;, i. e. sudden withdrawal from continuous 5-HT3 blocking.\nAs a side note, it also has H1-blocking effects, which are antiemetic as well.</p>\n<p>There are more withdrawal symptoms listed here: <a href=\"https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Mirtazapine-(Remeron)\" rel=\"nofollow noreferrer\">https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Mirtazapine-(Remeron)</a></p>\n" }, { "answer_id": 24129, "author": "kouty", "author_id": 19966, "author_profile": "https://health.stackexchange.com/users/19966", "pm_score": 1, "selected": false, "text": "<p>I was mistaken, the 5HT3 inhibitor of Vortioxetine is not responsible for the nausea, see <a href=\"https://www.google.com/search?client=firefox-b-d&amp;q=vortioxetine+nausea\" rel=\"nofollow noreferrer\">here</a></p>\n<blockquote>\n<p>Its additional antagonism of 5-HT3 receptors may partly counteract gastrointestinal adverse effects but nausea has an important role on drug discontinuation.</p>\n</blockquote>\n<p>His 5HTI agonist property contributes to Nausea.</p>\n<p>Its additional antagonism of 5-HT3 receptors may partly counteract gastrointestinal adverse effects but nausea has an important role on drug discontinuation.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24092", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19966/" ]

[ { "answer_id": 24105, "author": "Thomas", "author_id": 19070, "author_profile": "https://health.stackexchange.com/users/19070", "pm_score": 2, "selected": false, "text": "<p>Its primary action is as NaSSA (a noradrenergic and specific serotonergic antidepressant), not as 5-HT3 inhibitor. If you have a look at e. g. the Wikipedia page (<a href=\"https://en.wikipedia.org/wiki/Mirtazapine#Pharmacodynamics\" rel=\"nofollow noreferrer\">https://en.wikipedia.org/wiki/Mirtazapine#Pharmacodynamics</a>), you will see that nausea is listed as side effect under &quot;discontinuation syndrome&quot;, i. e. sudden withdrawal from continuous 5-HT3 blocking.\nAs a side note, it also has H1-blocking effects, which are antiemetic as well.</p>\n<p>There are more withdrawal symptoms listed here: <a href=\"https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Mirtazapine-(Remeron)\" rel=\"nofollow noreferrer\">https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Mirtazapine-(Remeron)</a></p>\n" }, { "answer_id": 24129, "author": "kouty", "author_id": 19966, "author_profile": "https://health.stackexchange.com/users/19966", "pm_score": 1, "selected": false, "text": "<p>I was mistaken, the 5HT3 inhibitor of Vortioxetine is not responsible for the nausea, see <a href=\"https://www.google.com/search?client=firefox-b-d&amp;q=vortioxetine+nausea\" rel=\"nofollow noreferrer\">here</a></p>\n<blockquote>\n<p>Its additional antagonism of 5-HT3 receptors may partly counteract gastrointestinal adverse effects but nausea has an important role on drug discontinuation.</p>\n</blockquote>\n<p>His 5HTI agonist property contributes to Nausea.</p>\n<p>Its additional antagonism of 5-HT3 receptors may partly counteract gastrointestinal adverse effects but nausea has an important role on drug discontinuation.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24156", "https://health.stackexchange.com", "https://health.stackexchange.com/users/15483/" ]

[ { "answer_id": 24179, "author": "Andrew", "author_id": 20025, "author_profile": "https://health.stackexchange.com/users/20025", "pm_score": 3, "selected": true, "text": "<p>Different cell lines exist for different reasons, depending on the cell type and their properties they are useful for different experiments.</p>\n<p><a href=\"https://en.wikipedia.org/wiki/HEK_293_cells\" rel=\"nofollow noreferrer\">HEK-293</a> - Embryonic Stem Cells - Female</p>\n<p><a href=\"https://en.wikipedia.org/wiki/WI-38\" rel=\"nofollow noreferrer\">WI-38</a> - Fibroblasts derived from lung tissue - 3 month old female</p>\n<p><a href=\"https://en.wikipedia.org/wiki/MRC-5\" rel=\"nofollow noreferrer\">MRC-5</a> - Fibroblasts derived from lung tissue - 14 week old male</p>\n<p>Embryonic stem cells are totipotent, meaning they have the ability to differentiate into any other cell type.</p>\n<p>Unfortunately to my knowledge we cannot yet generate totipotent cell lines. The cell line HEK-293 (or any embryonic stem cell line) are useful for studies that require the use of embryonic/totipotent stem cells.</p>\n<p>The other cell lines - WI-38 &amp; MRC-5 may be replaced by others quite easily however it may be the age of these cell lines that makes them attractive for scientific use. Scientists collaborate - when a cell line is able to 'do something' others may want to use it for their experiments too, and that is why particular cell lines are popular.</p>\n<p>The ethical quandary of aborted fetus stem cells or stem cells sources from non-aborted fetuses. Yes it is possible to get a type of stem cell from E.g. Cord Blood (Blood from the umbilical cord of a baby) or Amniocentesis. But not embryonic/totipotent stem cells.</p>\n<p>&quot;<a href=\"https://en.wikipedia.org/wiki/Cord_blood\" rel=\"nofollow noreferrer\">The stem cells found in cord blood are often confused with embryonic stem cells - unlike embryonic stem cells, cord blood stem cells are all types of adult stem cells, are lineage restricted and are not pluripotent.</a>&quot;</p>\n<p>To avoid ethical concerns <em><a href=\"https://en.wikipedia.org/wiki/Induced_pluripotent_stem_cell\" rel=\"nofollow noreferrer\">induced pluripotent stem cells (IPSCs)</a></em> may be used. IPSCs have the ability to differentiate into <em>almost</em> any other cell type, it is easy to generate a large number of cells, they are great for modeling disease &amp; have a huge\ntransplantation potential. IPSCs are pluripotent, not totipotent. The image below outlines how IPSCs are generated, how they avoid ethical concerns and, IPSCs potential to be transplanted back into the patient. <a href=\"https://geneticsperspective.blogspot.com/2020/06/genetic-disease-modeling-where-next.html\" rel=\"nofollow noreferrer\">More information on how and why IPSCs were discovered can be found here</a>.</p>\n<p><a href=\"https://i.stack.imgur.com/uwxVE.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/uwxVE.png\" alt=\"How to generate IPSCs and their uses.\" /></a></p>\n" }, { "answer_id": 24234, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 1, "selected": false, "text": "<p>In addition to @Andrew's answer about technical limitations, consider that searching for &quot;HEK-293&quot; for example on Google Scholar returns over 120,000 results.</p>\n<p>The thousands and thousands of studies using these cell lines provides an extensive institutional body of knowledge. There are many foundational studies done to understand these cell lines and there just isn't enough funding or motivation to redo them all. Cell lines are all unique, and any effort you make to create new ones have to create new research potential to be worth using.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24170", "https://health.stackexchange.com", "https://health.stackexchange.com/users/20031/" ]

[ { "answer_id": 24179, "author": "Andrew", "author_id": 20025, "author_profile": "https://health.stackexchange.com/users/20025", "pm_score": 3, "selected": true, "text": "<p>Different cell lines exist for different reasons, depending on the cell type and their properties they are useful for different experiments.</p>\n<p><a href=\"https://en.wikipedia.org/wiki/HEK_293_cells\" rel=\"nofollow noreferrer\">HEK-293</a> - Embryonic Stem Cells - Female</p>\n<p><a href=\"https://en.wikipedia.org/wiki/WI-38\" rel=\"nofollow noreferrer\">WI-38</a> - Fibroblasts derived from lung tissue - 3 month old female</p>\n<p><a href=\"https://en.wikipedia.org/wiki/MRC-5\" rel=\"nofollow noreferrer\">MRC-5</a> - Fibroblasts derived from lung tissue - 14 week old male</p>\n<p>Embryonic stem cells are totipotent, meaning they have the ability to differentiate into any other cell type.</p>\n<p>Unfortunately to my knowledge we cannot yet generate totipotent cell lines. The cell line HEK-293 (or any embryonic stem cell line) are useful for studies that require the use of embryonic/totipotent stem cells.</p>\n<p>The other cell lines - WI-38 &amp; MRC-5 may be replaced by others quite easily however it may be the age of these cell lines that makes them attractive for scientific use. Scientists collaborate - when a cell line is able to 'do something' others may want to use it for their experiments too, and that is why particular cell lines are popular.</p>\n<p>The ethical quandary of aborted fetus stem cells or stem cells sources from non-aborted fetuses. Yes it is possible to get a type of stem cell from E.g. Cord Blood (Blood from the umbilical cord of a baby) or Amniocentesis. But not embryonic/totipotent stem cells.</p>\n<p>&quot;<a href=\"https://en.wikipedia.org/wiki/Cord_blood\" rel=\"nofollow noreferrer\">The stem cells found in cord blood are often confused with embryonic stem cells - unlike embryonic stem cells, cord blood stem cells are all types of adult stem cells, are lineage restricted and are not pluripotent.</a>&quot;</p>\n<p>To avoid ethical concerns <em><a href=\"https://en.wikipedia.org/wiki/Induced_pluripotent_stem_cell\" rel=\"nofollow noreferrer\">induced pluripotent stem cells (IPSCs)</a></em> may be used. IPSCs have the ability to differentiate into <em>almost</em> any other cell type, it is easy to generate a large number of cells, they are great for modeling disease &amp; have a huge\ntransplantation potential. IPSCs are pluripotent, not totipotent. The image below outlines how IPSCs are generated, how they avoid ethical concerns and, IPSCs potential to be transplanted back into the patient. <a href=\"https://geneticsperspective.blogspot.com/2020/06/genetic-disease-modeling-where-next.html\" rel=\"nofollow noreferrer\">More information on how and why IPSCs were discovered can be found here</a>.</p>\n<p><a href=\"https://i.stack.imgur.com/uwxVE.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/uwxVE.png\" alt=\"How to generate IPSCs and their uses.\" /></a></p>\n" }, { "answer_id": 24234, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 1, "selected": false, "text": "<p>In addition to @Andrew's answer about technical limitations, consider that searching for &quot;HEK-293&quot; for example on Google Scholar returns over 120,000 results.</p>\n<p>The thousands and thousands of studies using these cell lines provides an extensive institutional body of knowledge. There are many foundational studies done to understand these cell lines and there just isn't enough funding or motivation to redo them all. Cell lines are all unique, and any effort you make to create new ones have to create new research potential to be worth using.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24214", "https://health.stackexchange.com", "https://health.stackexchange.com/users/20071/" ]

[ { "answer_id": 24279, "author": "program", "author_id": 20058, "author_profile": "https://health.stackexchange.com/users/20058", "pm_score": 2, "selected": false, "text": "<p>As you have already described, the hypothalamus regulate the set point at which the body temperature is maintained. This set point is elevated in fever, reflecting an infection, or resulting from tissue damage, inflammation, etc. These conditions all enhance formation of cytokines such as IL-1beta, IL-6, TNF-alfa, and interferons, which act as endogenous pyrogens; this first phase is mediated by ceramide release in neurons of the preoptic area in the anterior hypothalamus. The second phase is mediated by coordinate induction of COX-2 and formation of PGE2 which (by a cascade of reactions) will trigger the hypothalamus to elevate body temperature by promoting an increase in heat generation and decrease in heat loss.</p>\n<p>NSAID's (Nonsteroidal Anti-Inflammatory Drug) supress this response by inhibiting COX-2 and thus as well as the synthesis of PGE2. This is the fundamental therapeutic effect of this class of drugs - inhibit prostaglandin (PG).</p>\n<p>Now regarding your question specifically, NSAID's reduce fever in most situations, but not the circadian variation in temperature or the rise in response to exercise or increased ambient temperature. Normal body temperature in healthy humans is not affected by NSAID's because there are no PG's triggering the hypothalamus in normal conditions.</p>\n<p>There is a danger however... and that is due to toxicological effects specially with paracetamol (acetaminophen) which may cause liver injury with unintentional overdose; and if the drug has too much affinity for COX-2 enzymes (some companies were very well sued for that)</p>\n<p><strong>References</strong></p>\n<p>Rang &amp; Dale's Pharmacology</p>\n<p>Sorry, I misread your whole question.. the question was if it is good or not to have fever, you can remove the upvote if you like.</p>\n<p>I've found this <a href=\"https://pubmed.ncbi.nlm.nih.gov/26436473/\" rel=\"nofollow noreferrer\">article</a> which concludes that</p>\n<blockquote>\n<p>Early administration of acetaminophen to treat fever due to probable infection did not affect the number of ICU-free days</p>\n</blockquote>\n<p>That is a true dilemma, in one hand it is relatively safe to not take any antipyretic medication for minor illnesses, and let the system defend itself, on the other as some studies reveal it does not affect or worsen the outcomes.</p>\n" }, { "answer_id": 24292, "author": "Sikander", "author_id": 15514, "author_profile": "https://health.stackexchange.com/users/15514", "pm_score": 3, "selected": true, "text": "<p>In normal patients fever can reduce our efficiency or <a href=\"https://pubmed.ncbi.nlm.nih.gov/21357332/\" rel=\"nofollow noreferrer\">comfort</a> for doing work. For mild infections one may wait for the fever to get over and let our immune response do their job.</p>\n<p>For <strong>early and effective</strong> treatment we prefer antibiotics with antipyretics as antibiotics can do their job alone and fever might not be necessary here. It will give early response than giving antipyretic alone or letting fever be alone.<br />\nThe other point is that, we prefer antibiotics with antipyretics because the organism inflicting it may cause more damage to our body before getting killed by immune system and thus increasing morbidity and mortality.</p>\n<p>Fever is not the only mechanism to fight infection, some people take antipyretics alone which reduces fever and provides comfort but our immune system alone is effective enough to curb some mild infections, so people who take antipyretics alone are not in too much danger but it may <a href=\"https://clinicaltrials.gov/ct2/show/NCT01891084\" rel=\"nofollow noreferrer\">prolong the illness</a> in some cases. It is not the general prescribed method and antipyretics <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145646/#:%7E:text=Antipyretics%20should%20be%20used%20with,or%20not%20is%20still%20controversial\" rel=\"nofollow noreferrer\">should be used with indications like other drugs and not for fever per se</a> (though this reference is for the pediatric population but in general practice, antipyretics are generally not given alone for infections and the same argument can be applied)</p>\n<p>For some common viral fevers only conservative treatment is required. Antipyretics are given if temperature is too high because in that case its benifit can outweigh the effects of having fever, otherwise we must let fever to happen recognising the fact that <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145646/#:%7E:text=Antipyretics%20should%20be%20used%20with,or%20not%20is%20still%20controversial\" rel=\"nofollow noreferrer\">fever is beneficial or not is still controversial</a> (considering the fact that fever in this case can be benificial.)</p>\n<p>Finally, there can be many other indications for the use of antipyretic to reduce fever, not just considering a simple argument that it can enhance the immune response eg. paracetamol is given in dengue fever or antipyretics are given to prevent febrile seizures. So I recommend taking antipyretics under the prescription of the concerned medical professional only.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24277", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19856/" ]

[ { "answer_id": 24286, "author": "Franck Dernoncourt", "author_id": 43, "author_profile": "https://health.stackexchange.com/users/43", "pm_score": -1, "selected": false, "text": "<p>The 2020 study {1} found that dogs can detect COVID-19 with a sensitivity of 82.63% and a specificity of 96.35%:</p>\n<blockquote>\n<p>The dogs were able to discriminate between samples of infected (positive) and non-infected (negative) individuals with average diagnostic sensitivity of 82.63% (95% confidence interval [CI]: 82.02–83.24%) and specificity of 96.35% (95% CI: 96.31–96.39%). During the presentation of 1012 randomised samples, the dogs achieved an overall average detection rate of 94% (±3.4%) with 157 correct indications of positive, 792 correct rejections of negative, 33 incorrect indications of negative or incorrect rejections of 30 positive sample presentations.</p>\n</blockquote>\n<p>Sample size: 8 dogs, 1012 samples. Note that, as expected, there is variability between dogs in terms of sensitivity and specificity, as shown in <a href=\"https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05281-3/tables/2\" rel=\"nofollow noreferrer\">Table 2</a>.</p>\n<p>YouTube video from the authors: <a href=\"https://youtu.be/lzDYsZfd-fY\" rel=\"nofollow noreferrer\">https://youtu.be/lzDYsZfd-fY</a></p>\n<p>Reddit thread commenting on that study and its caveats: <a href=\"https://redd.it/hz3d9m\" rel=\"nofollow noreferrer\">https://redd.it/hz3d9m</a> (<a href=\"http://archive.is/7srdm\" rel=\"nofollow noreferrer\">mirror</a>).</p>\n<hr />\n<p>References:</p>\n<ul>\n<li>{1} Jendrny, Paula, Claudia Schulz, Friederike Twele, Sebastian Meller, Maren von Köckritz-Blickwede, Albertus Dominicus Marcellinus Erasmus Osterhaus, Janek Ebbers et al. &quot;Scent dog identification of samples from COVID-19 patients–a pilot study.&quot; BMC Infectious Diseases 20, no. 1 (2020): 1-7. <a href=\"https://doi.org/10.1186/s12879-020-05281-3\" rel=\"nofollow noreferrer\">https://doi.org/10.1186/s12879-020-05281-3</a></li>\n</ul>\n" }, { "answer_id": 25752, "author": "Gonçalo Peres", "author_id": 8861, "author_profile": "https://health.stackexchange.com/users/8861", "pm_score": 3, "selected": true, "text": "<p>I wouldn't be surprised if dogs could detect COVID-19, as they can help detect <a href=\"https://www.sciencedaily.com/releases/2019/01/190115144053.htm\" rel=\"nofollow noreferrer\">hypoglycaemia in diabetics</a>, warn people who are about to have an <a href=\"https://epilepsyfoundation.org.au/understanding-epilepsy/epilepsy-and-seizure-management-tools/seizure-alert-dogs/\" rel=\"nofollow noreferrer\">epileptic seizure</a> and have been used to <a href=\"https://www.medicalnewstoday.com/articles/323620\" rel=\"nofollow noreferrer\">sniff out some cancers</a>.</p>\n<p><a href=\"https://www.nature.com/articles/d41586-020-03149-9\" rel=\"nofollow noreferrer\">This article on Nature's website</a> (23 November 2020) has the following</p>\n<blockquote>\n<p>Canines seem to detect coronavirus infections with remarkable\naccuracy, but researchers say large-scale studies are needed before\nthe approach is scaled up.</p>\n</blockquote>\n" } ]

[ "https://health.stackexchange.com/questions/24285", "https://health.stackexchange.com", "https://health.stackexchange.com/users/43/" ]

[ { "answer_id": 24306, "author": "chongman", "author_id": 19917, "author_profile": "https://health.stackexchange.com/users/19917", "pm_score": 0, "selected": false, "text": "<p>A potential &quot;ideal&quot; experiment is a small, non-ventilated room. A known infected person is in that room for an hour or two. That person leaves and 5 minutes later a susceptible person (or persons) enter and stay in the room for several hours.</p>\n<p>(This is not ethical, since it's not okay to knowingly make someone sick. It'd be nice to say CDC says <code>it's mainly droplets</code> and you won't get infected, but this won't pass ethics review.)</p>\n<p>You'd also have to isolate that person for the incubation period (5-14 days, for example) to make sure they didn't accidentally get the virus from fomites or large droplets.</p>\n<ul>\n<li><p>And that's the trouble... the ideal treatment+control experiment isn't ethical.</p>\n</li>\n<li><p>It's also hard to rule out &quot;other explanations&quot; if one uses observational data.</p>\n</li>\n<li><p>The &quot;observation studies&quot; of HVAC and cruises or Skagit choir have potential confounds (you can't prove they didn't get it from the cookies/snacks).</p>\n</li>\n</ul>\n<p>===</p>\n<p>With regards to prevalence, I use the Jose Jimenez tool and the Wells-Riley model</p>\n<p><a href=\"https://docs.google.com/spreadsheets/d/16K1OQkLD4BjgBdO8ePj6ytf-RpPMlJ6aXFg3PrIQBbQ/edit#gid=519189277\" rel=\"nofollow noreferrer\">https://docs.google.com/spreadsheets/d/16K1OQkLD4BjgBdO8ePj6ytf-RpPMlJ6aXFg3PrIQBbQ/edit#gid=519189277</a></p>\n<p>This gives estimates of the quanta and a numerical probability of infection <em>from aerosol</em>. If there were a numerical probability of <em>from droplet</em> then the prevalance would simply be the ratio of the two.</p>\n" }, { "answer_id": 25905, "author": "slew123", "author_id": 21575, "author_profile": "https://health.stackexchange.com/users/21575", "pm_score": 3, "selected": true, "text": "<p>You can use Particle Image Velocimetry (PIV) (camera and laser sheet) to get a 2D image of velocity vector fields which show the velocity of plastic microbeads (whose size is known beforehand) to measure how long they remain suspended in the air. You can set up the experiment to measure the settling times for different sized microparticles. You cannot use (PIV) to measure the size of the particulates because the laser sheet used during the experiments has a Gaussian profile and finite thickness so you cannot easily provide a link between the intensity of light emitted by the particulates (and exposed to a camera) as they enter the sheet and the size of the particulate.</p>\n<p>You can also use Phase Doppler Anemometry (PDA) to measure simultaneously the size and velocity of the droplets but this is a 1D point measurement system so you would need to apply the technique at several locations. Laser Doppler works under the same principle with the exception it only provides velocity measurements.</p>\n<p>There are other more advanced techniques but these are the most common to measure velocity. Both techniques can be used to measure the background air flow conditions in both quiescent and turbulent flows, but there are technical and practical difficulties in setting up experiments which can measure both the continuous phase (air) and dispersed phase (particulates) simultaneously. If you don't introduce too many particulates in the air flow, then their presence does not adversely affect the background air flow (we call this &quot;one way coupling&quot;) and therefore it would be reasonable to measure the air flow first and then measure the particulate velocities separately.</p>\n<p>You can use basic imaging techniques with natural light rather than a laser to obtain estimates of the size of the particulates, but the light source would need to be powerful enough to illuminate the very small droplets or it would need to be very close to the source which may not make it practical.</p>\n<p>You can find more information in common journals like Physics of Fluids, Journal of Fluid Mechanics and Experiments in Fluids. Numerous experiments have been carried out in fields such as combustion, drying, cloud physics etc.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24305", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19917/" ]

[ { "answer_id": 24329, "author": "Sikander", "author_id": 15514, "author_profile": "https://health.stackexchange.com/users/15514", "pm_score": 4, "selected": true, "text": "<blockquote>\n<p>Although serum levels of the acute‐phase reactant C‐reactive protein (CRP) usually parallel disease activity in inflammatory states, it is widely believed that systemic lupus erythematosus (SLE) is an exception.</p>\n</blockquote>\n<p><a href=\"https://onlinelibrary.wiley.com/doi/full/10.1002/art.24316\" rel=\"nofollow noreferrer\">https://onlinelibrary.wiley.com/doi/full/10.1002/art.24316</a>.</p>\n<p>Well, since it is an exception we cannot say CRP levels are not reliable indicators of inflammation. The explanation for the relatively low levels of CRP in many patients with SLE has remained unclear despite many years of study. Another such exception is of systemic sclerosis.</p>\n<blockquote>\n<p><strong>Your question</strong><br />\n1.Is it possible that a person with an autoimmune disease (e. g. autoimmune hemolytic anemia) and without an impaired CRP production has a non-detectable level of C-reactive protein in their blood serum (0,0 mg/l)?<br />\n2.can there be no C-reactive protein in blood serum of a patient with an autoimmune disease?</p>\n</blockquote>\n<p>I don't really understand why do you say '0' or 'no' levels of CRP level when a normal healthy person do have some CRP level. Less than 0.3mg/dl is normal range seen in most healthy individuals. But if you question that:- Can a person with autoimmune disorder have CRP levels within the normal range, I will say Yes!</p>\n<blockquote>\n<p>CRP levels within normal limits do not mean there is no disease progression. In 10% of RA cases with active disease acute phase reaction(APR) levels may be within normal limits.</p>\n</blockquote>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366934/#!po=15.2174\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366934/#!po=15.2174</a>.</p>\n<blockquote>\n<p>Inflammatory marker such as ESR or C- reactive protein(CRP) are normal in about 60% of patients with early RA.</p>\n</blockquote>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1079582\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1079582</a>.</p>\n" }, { "answer_id": 24332, "author": "Debbie Yates", "author_id": 20152, "author_profile": "https://health.stackexchange.com/users/20152", "pm_score": 1, "selected": false, "text": "<p>I have a auto immune inflammatory arthritis and Vietnam time my crp was elevated was xinhua chest infection. They measure my c3 and c 4 which are elected and I'm Told more accurate markers.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24322", "https://health.stackexchange.com", "https://health.stackexchange.com/users/15516/" ]

[ { "answer_id": 24362, "author": "DrDee", "author_id": 20172, "author_profile": "https://health.stackexchange.com/users/20172", "pm_score": 2, "selected": false, "text": "<p>Definitive manuals, or textbooks for drug interactions tend not to be published on their own any longer, due to their need to be constantly updated, and having been superseded by better ways to search for the information required, in a digital format. OR - they are tremendously expensive, like <a href=\"https://www.pharmpress.com/product/9780857113474/stockley\" rel=\"nofollow noreferrer\">this</a>. Otherwise, drug interactions and adverse reactions are integrated into clinical pharmacology textbooks such as Rang and Dale.</p>\n<p>Other study books, such as <a href=\"https://www.amazon.co.uk/Top-100-Drugs-Pharmacology-Prescribing/dp/070207442X/ref=sr_1_1?dchild=1&amp;keywords=prescribing&amp;qid=1596656972&amp;sr=8-1\" rel=\"nofollow noreferrer\">this</a>, do have commonly prescribed drugs with major interactions listed per each drugs.</p>\n<p>In the United Kingdom, we tend to use the British National Formulary (BNF) which is given to all doctors in a paper-copy, but is also online - <a href=\"https://bnf.nice.org.uk/\" rel=\"nofollow noreferrer\">here</a> which has a fully searchable interactions section. It can be bought in paper copy <a href=\"https://www.amazon.co.uk/British-National-Formulary-September-2020/dp/0857113690/ref=sr_1_1?dchild=1&amp;keywords=formulary&amp;qid=1596657102&amp;sr=8-1\" rel=\"nofollow noreferrer\">here</a> - but it's not a good study book, it's a reference for working prescribers.</p>\n<p><a href=\"https://www.drugs.com/\" rel=\"nofollow noreferrer\">https://www.drugs.com/</a> is reliable, an USA-based, with an interactions - but is again a website.</p>\n<p>If you want to let us know what specifically you are revising for, or what you need it for - perhaps we'll be able to point you to a more specific book. :)</p>\n" }, { "answer_id": 24366, "author": "Don_S", "author_id": 7166, "author_profile": "https://health.stackexchange.com/users/7166", "pm_score": 1, "selected": false, "text": "<p>One of the most well-known books dedicated to drug interactions and serving as a comprehensive reference for this topic specifically is <a href=\"https://www.pharmpress.com/product/9780857113474/stockley\" rel=\"nofollow noreferrer\">Stockley's Drug Interactions</a>. You can find a sample chapter <a href=\"https://www.pharmpress.com/files/docs/Stockleys_Drug_Interactions_11_Sample.pdf\" rel=\"nofollow noreferrer\">here</a>.</p>\n<p>Highly recommended!</p>\n" } ]

[ "https://health.stackexchange.com/questions/24359", "https://health.stackexchange.com", "https://health.stackexchange.com/users/20169/" ]

[ { "answer_id": 24394, "author": "BobE", "author_id": 11421, "author_profile": "https://health.stackexchange.com/users/11421", "pm_score": 4, "selected": true, "text": "<p>In the US, in order for a mask to be labeled &quot;medical&quot;, that mask must be approved by the FDA as a medical device. With so many new people manufacturing masks coupled with the public demand for masks, it is likely not profitable to delay to seek FDA approval. The FDA also is unlikely to approve a new manufacturer's mask without ASTM testing.</p>\n<p>Thus, it is possible that these KN95 masks are a functional equivalent to N95 masks approved for medical use, but have not yet been approved by FDA.</p>\n<p>Keep in mind that that coronavirus particles (fancy scientific name “virions”) are spheres with diameters of approximately 0.125 microns (125 nm). The smallest particles are 0.06 microns, and the largest are 0.14 microns. (Lancet)</p>\n<p>The <a href=\"https://smartairfilters.com/en/blog/can-masks-capture-coronavirus/\" rel=\"nofollow noreferrer\">article here</a> may be useful to help you sort through the efficiency of masks.</p>\n" }, { "answer_id": 24397, "author": "Brayton", "author_id": 20191, "author_profile": "https://health.stackexchange.com/users/20191", "pm_score": 2, "selected": false, "text": "<p>Typically for an N95 mask to be considered &quot;medical grade&quot; it must be compatible with a sterile environment, such as by filtering both inhaled and exhaled air.</p>\n<p>Surgical masks provide some filtration of exhaled air, which is why they're useful in surgury (e.g. keep saliva off an operating region).\nI have an N95 mask advertised for environments with dust and smoke (e.g. to wear while working with soil to <a href=\"https://worksafe.govt.nz/topic-and-industry/legionnaires-disease/legionnaires-disease-and-legionellosis/\" rel=\"nofollow noreferrer\">prevent Legionnaires' disease</a>). In these environments there's no need to filter air on the exhale; such filter would add to cost and increase the effort to exhale. For this reason &quot;medical grade&quot; N95 masks may be more expensive and more humid than those with a valve for exhaling air.</p>\n<p>Unless there's a significant difference in how the filters are manufactured, then these masks are effectively the same for filtration of inhaled air. If medical grade masks were able to filter 99% of particles within a given size range then they would be N99 masks, not N95 masks.</p>\n<p>However as @BobE mentioned &quot;medical grade&quot; likely must pass further tests and conform to other regulations (and perhaps requiring more expensive quality control measures) which would drive up the prices and could delay a product from reaching market.</p>\n" }, { "answer_id": 24399, "author": "gatorback", "author_id": 7446, "author_profile": "https://health.stackexchange.com/users/7446", "pm_score": 1, "selected": false, "text": "<p>The mask protects people from <strong>the person wearing the mask</strong>. In surgery, my colleagues and I wear a mask to protect the patient's open wound from me. Do not make the mistake of thinking that you, as the mask wearer, are conferring a degree of protection that provides safety.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24391", "https://health.stackexchange.com", "https://health.stackexchange.com/users/17725/" ]

[ { "answer_id": 24407, "author": "Chris Rogers", "author_id": 7951, "author_profile": "https://health.stackexchange.com/users/7951", "pm_score": 2, "selected": false, "text": "<p>Topical products are applied directly to a part of the body, whereas other products are administered in other (more specific) ways. For example, oral products are used in or around the mouth.</p>\n<p>Snuff is a smokeless tobacco made from ground or pulverised tobacco leaves. Snuff is dry and usually consumed via the nasal route (via the nose) by sniffing it. In the case presented, the snuff is used topically (in hamster cheek pouches), probably in the form of <a href=\"https://en.wikipedia.org/wiki/Snus\" rel=\"nofollow noreferrer\">snus</a> or <a href=\"https://en.wikipedia.org/wiki/Dipping_tobacco\" rel=\"nofollow noreferrer\">dipping tobacco</a>, both of which are wet powdered smokeless tobacco products.</p>\n" }, { "answer_id": 24408, "author": "Ojasvi", "author_id": 19734, "author_profile": "https://health.stackexchange.com/users/19734", "pm_score": 2, "selected": false, "text": "<p>I think it is a form of tobacco. Since the main etiology for squamous cell carcinoma is tobacco consumption.</p>\n<blockquote>\n<p>Tobacco and alcohol are the two most important known risk factors for the development of oral cancer.\n<a href=\"http://www.indianjcancer.com/article.asp?issn=0019-509X;year=2006;volume=43;issue=2;spage=60;epage=66;aulast=Mehrotra\" rel=\"nofollow noreferrer\">Reference</a></p>\n</blockquote>\n<p>Here is an <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028589/\" rel=\"nofollow noreferrer\">article</a></p>\n<blockquote>\n<p>Herpes simplex virus (HSV) may enhance the development of oral carcinoma in individuals who are already at increased risk of the disease because of tobacco consumption and cigarette smoking and so must be considered as a possible etiologic agent in oral cancer and precancer.</p>\n</blockquote>\n<p>So yeah, the snuff should be a form of tobacco only.</p>\n<p>Also interestingly I found that study which the Burket's is referring to-\n<a href=\"https://www.sciencedirect.com/topics/medicine-and-dentistry/cheek-pouch\" rel=\"nofollow noreferrer\">Hamster study</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/24405", "https://health.stackexchange.com", "https://health.stackexchange.com/users/17742/" ]

[ { "answer_id": 24421, "author": "JMP", "author_id": 97, "author_profile": "https://health.stackexchange.com/users/97", "pm_score": 1, "selected": false, "text": "<p>The first one is a Treatment Schedule from the Acute Myeloid Leukemia - Berlin–Frankfurt–Munster Study of 2004.</p>\n<p>The image can be found on page 39 of the article found here:</p>\n<blockquote>\n<p><a href=\"https://ashpublications.org/blood/article/122/1/37/31565/Randomized-trial-comparing-liposomal-daunorubicin?utm_source=TrendMD&amp;utm_medium=cpc&amp;utm_campaign=Blood_TrendMD_0\" rel=\"nofollow noreferrer\">Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004</a></p>\n</blockquote>\n<blockquote>\n<p>Ursula Creutzig, Martin Zimmermann, Jean-Pierre Bourquin, Michael N. Dworzak, Gudrun Fleischhack, Norbert Graf, Thomas Klingebiel, Bernhard Kremens, Thomas Lehrnbecher, Christine von Neuhoff, Jörg Ritter, Annette Sander, André Schrauder, Arend von Stackelberg, Jan Starý, Dirk Reinhardt</p>\n</blockquote>\n<p>or specifically:</p>\n<blockquote>\n<p><a href=\"https://watermark.silverchair.com/37.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAA64wggOqBgkqhkiG9w0BBwagggObMIIDlwIBADCCA5AGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM_VrH0Rf70gZuw5T2AgEQgIIDYcOWIhs0Lv4vYlV5FjgJfhQAXHxWUq6cQq0XZPbONpLtfap7lV1a5yR-JMDV04eAiqYbO9vBq5P5JX-H2qGRiJUiMWH6HXD2zREnwoaZhKbIEhiwCgKa5kdnA9-n6Z0smWy_6CQa7iLiAeF6PEivK4YPhL1dInvX6BdQrGOliHu6ZQn_ihYgoO-M6GRkf7QC9rWYQHoHOE3g5WUHat56Cxn907eQwIlnS1kl-bW932J6oNJL3bEyPCXanXFarEwCY9tKXYaQFoJkcu2mCWUBuZCBA1jZZwqZ3VBUPAsdboCGsFsN4lba6Zgl3s0c5hzSImXdRP3FkZ0n2UzsaPPjke4gMRz5DQOkvcwraSBWwoBRy0GRFtiBKYzkrp6LxyD3B5TsaSOnCgSpPwN33c-hdy2nbMkT_eLB-uaGtGB-n-9sDiJ2hjHKtbVBVH54iWpX4DtDuye2uBf8lBGin4PbT_SqimqcNLA6eNmZA-obAAG6Tr3Jo1M9AlSOgpx9Rt7glaxgJCnJXsoApu_HpprOZWi8s2_ElFkSXOJ5s3O2C3pFoagaZxN3RYGlxRxwidzd3hUUeHNYTrOdVx5PRxrBbADGzMy0PskqbmB3XIjx5xx3jU9CLvHCmktXIpZKGTp4r1E-OXwPAH5ztovyIfQY5QXENzn_YmziDHTP_3zN1cf9AfLXz3YwN2ZEOKfH1OthIKKxbnjqq0YD6hCp1Ch7QsPzoDI2N171a2TQhxvgvWvX143mpbN17s96zlfgAAb-ik9pEZ0g8Odr41f9GQkP-xdPrsRyPPEiuY11DaIC3OTsQmUXhS_tGwoDrzL3aevOe7X2af5hyT6eGaJHKJLeSy1b1Ogt5JxiJNQBHNRiMb2nHEfaB6lO_uPV27bP7rBZf1SLm4GH5paKMvhnAfersBPq-mnW1xELmbdS1C9K2zXOYQDbmXmy_IYPYJqP7-vP_cPdMJ9yTmhFbEGfDeBzs9t8zzsU9VpXI8LvCtHBQ9tYtM-psve3hnHNeNVtDZ2S9vm8wZybtIZ8rd8a7Vmxkz79J-33dYYrl3xjNygHz1obZeoKi4nMzq_nL1ELQ-LHELuoh87j__U8msbVTBCE5bixFa96LsyK-EcmP9CrK6sDWol91wAefyj_C8rqcGdas0M\" rel=\"nofollow noreferrer\">BLOOD, 4 JULY 2013 x VOLUME 122, NUMBER 1</a></p>\n</blockquote>\n" }, { "answer_id": 24440, "author": "Diana Petitti", "author_id": 20133, "author_profile": "https://health.stackexchange.com/users/20133", "pm_score": 1, "selected": false, "text": "<p>As indicated in the first answer, the first figure is for a clinical trial. This kind of figure is often called a &quot;Clinical Trial Design Schematic&quot; or simply a &quot;Schematic for a Clinical Trial.&quot;</p>\n<p>Here are some other examples of trials that present such figures and label them as “clinical trial design schematic” or “schematic.”</p>\n<p><a href=\"https://www.researchgate.net/figure/Schematic-design-of-the-clinical-study_fig1_260005337\" rel=\"nofollow noreferrer\">https://www.researchgate.net/figure/Schematic-design-of-the-clinical-study_fig1_260005337</a></p>\n<p><a href=\"https://www.researchgate.net/figure/MAGELLAN-1-part-1-clinical-trial-design-schematic-In-part-1-of-the-MAGELLAN-1-study_fig1_313022113\" rel=\"nofollow noreferrer\">https://www.researchgate.net/figure/MAGELLAN-1-part-1-clinical-trial-design-schematic-In-part-1-of-the-MAGELLAN-1-study_fig1_313022113</a></p>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/books/NBK533357/figure/cl3.f2/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/books/NBK533357/figure/cl3.f2/</a></p>\n<p>There appear to be no rules for creating this kind of figure for a trial. Time is consistently on the x-axis.</p>\n<p>The second two figures appear to be &quot;schematics&quot; that show the overall treatment plan for patients with cancer. There does not appear to be a specific name for this kind of graphic presentation of a treatment plan. There do not appear to be official rules for how these graphics are drawn. Time is consistently on the x-axis.</p>\n<p>Oncology treatment plans are often shown graphically as &quot;algorithms.&quot; This is a figure that shows the &quot;algorithm&quot; for treatment of acute lymphoblastic leukemia in 2013 from the Leukemia and Bone Marrow Transplant Program of British Columbia.</p>\n<p>These (roughly) follow &quot;rules&quot; for flow charts as they are described in widely accessible public documents (WIKIPEDIA).</p>\n<p><a href=\"https://en.wikipedia.org/wiki/Flowchart\" rel=\"nofollow noreferrer\">https://en.wikipedia.org/wiki/Flowchart</a></p>\n<p><a href=\"http://www.leukemiabmtprogram.com/healthcare_professionals/cancer_management_guidelines/ALL.html\" rel=\"nofollow noreferrer\">http://www.leukemiabmtprogram.com/healthcare_professionals/cancer_management_guidelines/ALL.html</a></p>\n<p><a href=\"https://i.stack.imgur.com/0AFRs.jpg\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/0AFRs.jpg\" alt=\"Algorithm for Acute Lymphoblastic Leukemia Treatment\" /></a></p>\n" }, { "answer_id": 24514, "author": "supercoco", "author_id": 20201, "author_profile": "https://health.stackexchange.com/users/20201", "pm_score": 0, "selected": false, "text": "<p>It seems the first two diagrams are general treatment plans. You could also say it is a general view of the clinical pathway to follow for those two different cancer diagnosis.</p>\n<p>The third image is a detailed pharmacological treatment that comes if you &quot;zoom in&quot; or &quot;double click&quot; a box in the first two diagrams. It shows what drugs must be taken in certain days.</p>\n<p>I have found no formal definitions or documentation for this type of notation though I have seen these notations in english, spanish and german documents. So I still think that someone invented it and must have some sort of consensus on the elements of the notation.</p>\n<p>There seems to be an effort to document clinical pathways using BPMN, CMMN, and DMN. (<a href=\"https://www.bpm-plus.org/healthcare-and-bpmn.htm\" rel=\"nofollow noreferrer\">https://www.bpm-plus.org/healthcare-and-bpmn.htm</a>).</p>\n" } ]

[ "https://health.stackexchange.com/questions/24414", "https://health.stackexchange.com", "https://health.stackexchange.com/users/20201/" ]

[ { "answer_id": 24454, "author": "Physicsapproval", "author_id": 15648, "author_profile": "https://health.stackexchange.com/users/15648", "pm_score": 1, "selected": false, "text": "<p>Loss of intracellular free water because of increased plasma osmolality, this causes water to move out of cell.</p>\n<p>After this, potassium concentration has increased inside cell, so this causes extracellular movement of potassium (secondary to increased intracellular potassium concentration)</p>\n<p>Similar mechanism happens at level of kidney tubules and interstitium.</p>\n<p>Source: Uworld step 1 qbank( Q Id 985) (may not be accessible)</p>\n" }, { "answer_id": 30605, "author": "Brian Ó Maoláin", "author_id": 24505, "author_profile": "https://health.stackexchange.com/users/24505", "pm_score": 2, "selected": false, "text": "<p>As another answer has noted, increased tonicity of the blood increases the tonicity of the extracellular fluid causing water to flow out of cells into the extracellular space and subsequently the intravascular space. This is the mechanism of action for hypertonic mannitol infusion. <a href=\"https://www.ncbi.nlm.nih.gov/books/NBK470392/\" rel=\"nofollow noreferrer\">1</a></p>\n<p>However this is not the end of the story. Increased intravascular volume subsequently causes increased renal blood flow. This has two consequences. Firstly, the glomerular filtration rate is increased, this means that the total amount of fluid filtered by the glomerulus into the nephron is increased. Second there is increased perfusion of the renal medulla. This collapses the normal concentration gradients of electrolytes which impairs the ability of the nephron to concentrate urine. There is a net loss of electrolytes as a result with the production of increased volumes of urine. Total body potassium is decreased (although because it is being removed from a large intracellular reservoir perhaps the serum potassium will not fall). <a href=\"https://pubmed.ncbi.nlm.nih.gov/3133729/\" rel=\"nofollow noreferrer\">2</a></p>\n<p>In fact it is relatively common for serum potassium to be normal and there are case reports of <a href=\"https://academic.oup.com/ndt/article/18/1/198/1809186\" rel=\"nofollow noreferrer\">hyperkalaemia associated with DKA.</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/24453", "https://health.stackexchange.com", "https://health.stackexchange.com/users/15648/" ]

[ { "answer_id": 24616, "author": "Diana Petitti", "author_id": 20133, "author_profile": "https://health.stackexchange.com/users/20133", "pm_score": 2, "selected": false, "text": "<p>Two case reports of hyponatremia in infants fed exclusively with almond, nut, chestnut and soy milk or a homemade sesame seed emulsion were identified. These cases appear to be due to inadequate sodium in the diet.</p>\n<p>Fourreau D, Peretti N, Hengy B, et al. Complications carentielles suite à l'utilisation de « laits » végétaux, chez des nourrissons de deux mois et demi à 14 mois (quatre cas) [Pediatric nutrition: Severe deficiency complications by using vegetable beverages, four cases report]. Presse Med. 2013;42(2):e37-43. French. doi: 10.1016/j.lpm.2012.05.029. Epub 2012 Sep 28. PMID: 23021957.</p>\n<p>Shohat M, Levy I, Levy Y, Nitzan M. Nutritional complications in an infant fed exclusively on homemade sesame seed emulsion. J Am Coll Nutr. 1989;8:167-9. doi: 10.1080/07315724.1989.10720291. PMID: 2708731.</p>\n<p>According to Sterns, hyponatremia is not a disease but rather a pathophysiologic process indicating disturbed water homeostasis.</p>\n<p>Sterns RH. Disorders of plasma sodium--causes, consequences, and correction. N Engl J Med. 2015;372:55-65. doi: 10.1056/NEJMra1404489. PMID:25551526.</p>\n<p>Sterns states:</p>\n<blockquote>\n<p>Maximal dilution of urine prevents hyponatremia unless water intake is\nextraordinarily large (&gt;1 liter per hour) (e.g., in patients with\nschizophrenia who drink water compulsively) or the rate of urinary\nsolute excretion is extremely low (e.g., in beer drinkers who eat very\nlittle).</p>\n</blockquote>\n<p>There are numerous case reports of a condition called “beer potomania”—excessive consumption of beer—which is characterized by hyponatremia. Lodhi et al. explain “beer potomania” as follows:</p>\n<blockquote>\n<p>Beer potomania, a unique syndrome of hyponatremia, was first reported\nin 1972. It is described as the excessive intake of alcohol,\nparticularly beer, together with poor dietary solute intake that leads\nto fatigue, dizziness, and muscular weakness. The low solute content\nof beer, and suppressive effect of alcohol on proteolysis result in\nreduced solute delivery to the kidney. The presence of inadequate\nsolute in the kidney eventually causes dilutional hyponatremia\nsecondary to reduced clearance of excess fluid from the body.</p>\n</blockquote>\n<p>Lodhi MU, Saleem TS, Kuzel AR, et al. &quot;Beer Potomania&quot; - A Syndrome of Severe Hyponatremia with Unique Pathophysiology: Case Studies and Literature Review. Cureus. 2017;9(12):e2000. doi: 10.7759/cureus.2000. PMID: 29507848; PMCID: PMC5832394.</p>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832394/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832394/</a></p>\n<p>Published case reports of beer potomania up to 2018 are cited in Joshi and Chou, who also explain the pathophysiology.</p>\n<p>Joshi R, Chou S. Beer Potomania: A View on the Dynamic Process of Developing Hyponatremia. Cureus 2018;10(7): e3024. DOI 10.7759/cureus.3024</p>\n<p><a href=\"https://pubmed.ncbi.nlm.nih.gov/30254813/\" rel=\"nofollow noreferrer\">https://pubmed.ncbi.nlm.nih.gov/30254813/</a></p>\n<p>Pica is a condition in which patients crave and chew substances with no nutritional value. Ice pica (pagophagia) is seen in patients with iron deficiency. A case report of hyponatremia due to excessive consumption of water because of ice pica (pagophagia) was identified.</p>\n<p>Bedanie G, Tikue A, Thongtan T, et al. Pica/Pagophagia-Associated Hyponatremia: Patient Presenting With Seizure. Cureus 2020;12(7): e9330. DOI 10.7759/cureus.9330\n<a href=\"https://pubmed.ncbi.nlm.nih.gov/32742885/\" rel=\"nofollow noreferrer\">https://pubmed.ncbi.nlm.nih.gov/32742885/</a></p>\n" }, { "answer_id": 24636, "author": "D.Tan", "author_id": 13163, "author_profile": "https://health.stackexchange.com/users/13163", "pm_score": 1, "selected": false, "text": "<p><a href=\"https://en.wikipedia.org/wiki/Tea_and_toast_syndrome\" rel=\"nofollow noreferrer\">Tea and Toast syndrome</a> is a well-known cause of hyponatremia due to a diet with restricted salt/protein intake but abundant fluids (&quot;tea and toast&quot;), usually occurring among elderly who are unable to cook or feed themselves properly. This is especially dangerous when taking other salt-wasting medication such as diuretics.</p>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694198/\" rel=\"nofollow noreferrer\">Symptoms of hyponatremia</a>:</p>\n<blockquote>\n<p>symptomatology of acute hyponatremia (developed in &lt;48 h) such as <strong>nausea, vomiting, headache, stupor, coma and seizures</strong>, as well as manifestations (even mild) associated with chronic hyponatremia, such as <strong>fatigue, cognitive impairment, gait deficits, falls, adverse effects on bone quality (eg, osteoporosis) and fractures</strong>, are more frequent and severe in elderly patients</p>\n</blockquote>\n<p>Source:</p>\n<p>Filippatos TD, Makri A, Elisaf MS, Liamis G. Hyponatremia in the elderly: challenges and solutions. Clin Interv Aging. 2017;12:1957-1965. Published 2017 Nov 14. doi:10.2147/CIA.S138535</p>\n" } ]

[ "https://health.stackexchange.com/questions/24578", "https://health.stackexchange.com", "https://health.stackexchange.com/users/14522/" ]

[ { "answer_id": 24601, "author": "Community", "author_id": -1, "author_profile": "https://health.stackexchange.com/users/-1", "pm_score": 1, "selected": false, "text": "<p>It is now in the third testing stage, which would end at the start of 2021. Announcing and readiness are quite different things.</p>\n<p>Direct quote from <a href=\"https://www.forbes.com/sites/kenrapoza/2020/08/11/putin-says-russian-covid-19-vaccine-ready-to-go-january-1-2021/#21d5088a15c7\" rel=\"nofollow noreferrer\">Forbes</a>:</p>\n<blockquote>\n<p>Vladimir Putin said on Tuesday that the country registered its vaccine and that after passing phase trials for emergency use <strong>it will be made available by January 1, 2021 for regular patients</strong> if all goes well in final tests.</p>\n</blockquote>\n" }, { "answer_id": 24604, "author": "Allure", "author_id": 12423, "author_profile": "https://health.stackexchange.com/users/12423", "pm_score": 4, "selected": false, "text": "<p>Answering my own question since I believe I've found the answer.</p>\n<p>According to <a href=\"https://www.rt.com/russia/497360-russia-first-covid19-vaccine/\" rel=\"noreferrer\">this</a> source,</p>\n<blockquote>\n<p>The senior minister at the department, Mikhail Murashko, announced last week that a nationwide mass vaccination program is planned to begin in October. Murashko added that all expenses will be covered by the government.</p>\n</blockquote>\n<p>Therefore right now (September) the vaccine hasn't been deployed yet, and therefore we should not expect to see a reduction in cases or deaths.</p>\n" }, { "answer_id": 24607, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 5, "selected": true, "text": "<p>The initial Russian announcement was bluster. From the <a href=\"https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html\" rel=\"noreferrer\">NYT's vaccine tracker</a>:</p>\n<blockquote>\n<p>On Aug. 11, President Vladimir V. Putin announced that a Russian health care regulator had approved the vaccine, renamed Sputnik V, before Phase 3 trials had even begun. Vaccine experts decried the move as risky, and Russia later walked back the announcement, saying that the approval was a “conditional registration certificate,” which would depend on positive results from Phase 3 trials</p>\n</blockquote>\n<p>In other words, the Russian vaccine approval was basically just a statement that &quot;we're starting Phase 3 trials and will use the vaccine if those trials are successful&quot;. Several other vaccine candidates are also in Phase 3 trials, so nothing is particularly special about the Russian progress. Perhaps they will start distributing it before the phase 3 results are in, but that hasn't happened yet.</p>\n" }, { "answer_id": 24624, "author": "user1271772", "author_id": 16670, "author_profile": "https://health.stackexchange.com/users/16670", "pm_score": 0, "selected": false, "text": "<p>The other answers have said (correctly) that the vaccine hasn't yet been distributed as it is still in Phase 3 of testing.</p>\n<p>But even if it was distributed, it takes <em><strong>time</strong></em> before the number of cases/day goes down. People that were first infected by SARS-CoV-2 three weeks ago might only have started to develop a fever one week ago, and a confirmed positive test completed today. Therefore today's &quot;cases/day&quot; includes people that were infected 3 weeks ago. To think that a vaccine announced on August 11th would have an impact on the number of cases/day at the beginning of September is a bit extreme (even if it <em><strong>was</strong></em> actually done Phase 3 testing and was deployed to people by now).</p>\n" }, { "answer_id": 24639, "author": "Timur Shtatland", "author_id": 17046, "author_profile": "https://health.stackexchange.com/users/17046", "pm_score": 1, "selected": false, "text": "<p>The answer to this question is: &quot;we don't know&quot;. This is because <strong>COVID-19 statistics reported by Russia may be highly questionable</strong>. This alone makes its interpretation hard, whether or not the vaccine is widely available by the time the data are published. Even by the time the vaccine is distributed widely, and regardless of its effect on COVID-19 statistics, the serious questions about the data will remain.</p>\n<p>Some refer to the COVID-19 statistics currently coming from the official Russian sources as <a href=\"https://www.rferl.org/a/russian-demographer-questioned-government-covid-numbers-fire/30724158.html\" rel=\"nofollow noreferrer\"><strong>&quot;almost completely handcrafted and manipulated&quot;</strong></a>, and having <a href=\"https://www.themoscowtimes.com/2020/08/11/six-months-into-the-coronavirus-outbreak-russias-statistics-still-provide-more-questions-than-answers-a71069\" rel=\"nofollow noreferrer\"><strong>&quot;nothing to do with reality at all&quot;</strong></a></p>\n<p><strong>SEE ALSO:</strong></p>\n<p><a href=\"https://stats.stackexchange.com/q/467704/\">A chart of daily cases of COVID-19 in a Russian region looks suspiciously level to me - is this so from the statistics viewpoint?</a>. The answers note that &quot;[The chart] is decidedly out of the ordinary&quot;, and that other charts from Russia show similar &quot;underdispersion&quot;.</p>\n<p><strong>REFERENCES:</strong></p>\n<blockquote>\n<p>For health demographers like Aleksei Raksha, employed by the state\nstatistics agency Rosstat, something hasn't been right for months, and\nin May, he spoke out publicly: The low death toll wasn't due to a\nsuperior state response, he said, it was due to how coronavirus\nstatistics were being counted.</p>\n<p>In other words, Russia has been misclassifying COVID-19 deaths.</p>\n<p>Two months after speaking out, Raksha received what may be official\nacknowledgment of his contribution to Russia's national discussion\nabout the government's response: He was fired from his job, he said. ...</p>\n<p>&quot;In general, the statistics on the Stopcoronavirus.ru website raise a\nlot of questions, I don't trust them, and it's obvious to any\nspecialist that they've all been drawn, forged, fitted, brushed,\ncropped, aligned and almost completely handcrafted and manipulated,&quot;\nhe said.</p>\n<p>&quot;But we have nothing else, so you need to somehow take [this data],\ndecode it, think it out, and make a guess. Unfortunately, it is very\ndifficult to draw conclusions based on it,&quot; he said. ...</p>\n<p>Rosstat itself has come under fire over the past year, with\nallegations that its otherwise reputable number collection and\nrecord-keeping on many socioeconomic indicators were being manipulated\nfor political purposes.</p>\n</blockquote>\n<p><em>Mark Krutov, Timur Olevsky. &quot;Russian Demographer Questioned Government COVID-19 Numbers. He Was Fired Earlier This Month.&quot; Radio Free Europe/Radio Liberty (RFE/RL). July 13, 2020: <a href=\"https://www.rferl.org/a/russian-demographer-questioned-government-covid-numbers-fire/30724158.html\" rel=\"nofollow noreferrer\">https://www.rferl.org/a/russian-demographer-questioned-government-covid-numbers-fire/30724158.html</a></em></p>\n<hr />\n<blockquote>\n<p>“In many regions, the statistics have nothing to do with reality at\nall,” said Tatiana Mikhailova, a statistician who has been tracking\nthe virus outbreak since the beginning and regularly raises concerns\nabout data. ...</p>\n<p>But Mikhailova told The Moscow Times that the quality is so poor, “it\nmakes no sense to draw medical, virological, or epidemiological\nconclusions from them.” ...</p>\n<p>New more detailed information on deaths being published by regional\nregistry offices — with a significant delay — is now starting to show\njust how wrong Russia’s original fatality count is.</p>\n<p>The data shows that Russia saw 26,360 excess fatalities in May and\nJune, compared with the average death tally over the previous five\nyears, while Russia’s coronavirus task force reported just 9,303\nfatalities from Covid-19 over the same period. ...</p>\n<p>“Essentially all Russian regions are doing their best to artificially\nsuppress the headline death count,” said Mikhail Tamm, a statistician\nat the Higher School of Economics (HSE). ...</p>\n<p>In a policy which runs counter to World Health Organization guidelines\n— which says all deaths related to Covid-19 should be counted as such\n“unless there is a clear alternative cause of death that cannot be\nrelated to Covid-19 disease (e.g. trauma)” — Russian authorities only\ncount deaths assigned to the first two categories [out of four total]\nas specifically resulting from the coronavirus. ...</p>\n<p>The broader interpretation of coronavirus-related deaths would have\nsent Russia’s overall mortality rate at the end of June up from the\n1.4% reported by the task force to 4.2%.</p>\n<p>Once again, in many regions, the discrepancy is significantly starker,\nand further complicates understanding the regional aspects of Russia’s\ncoronavirus spread, which was already showing major discrepancies. ...</p>\n<p>In fact, including all deaths would have more than tripled the\nheadline mortality rates in 19 of the worst-affected regions.</p>\n</blockquote>\n<p><em>Jake Cordell. &quot;Six Months Into the Coronavirus Outbreak, Russia’s Statistics Still Provide More Questions Than Answers.&quot; The Moscow Times. Updated: Aug. 13, 2020: <a href=\"https://www.themoscowtimes.com/2020/08/11/six-months-into-the-coronavirus-outbreak-russias-statistics-still-provide-more-questions-than-answers-a71069\" rel=\"nofollow noreferrer\">https://www.themoscowtimes.com/2020/08/11/six-months-into-the-coronavirus-outbreak-russias-statistics-still-provide-more-questions-than-answers-a71069</a></em></p>\n" } ]

[ "https://health.stackexchange.com/questions/24600", "https://health.stackexchange.com", "https://health.stackexchange.com/users/12423/" ]

[ { "answer_id": 24672, "author": "Chukwuyem Obiazi", "author_id": 20377, "author_profile": "https://health.stackexchange.com/users/20377", "pm_score": 0, "selected": false, "text": "<p>There is no &quot;yes&quot; or &quot;no&quot; answer to your question as far as the use of both terms are concerned.</p>\n" }, { "answer_id": 25520, "author": "program", "author_id": 20058, "author_profile": "https://health.stackexchange.com/users/20058", "pm_score": 2, "selected": true, "text": "<p>Regarding one of the topics of this subject: <em>Why can’t painkillers be both safe and effective?</em></p>\n<p><a href=\"https://www.nature.com/articles/s41598-020-71804-2\" rel=\"nofollow noreferrer\">It should be duly noted that,</a></p>\n<p>One of the most problematic conditions when using opioids in clinic is the respiratory depression that they can cause</p>\n<blockquote>\n<p>The most common cause of opioid overdose and death is opioid-induced respiratory depression (OIRD)</p>\n</blockquote>\n<p>essentially due to a neuronal malfunction at the brainstem level</p>\n<blockquote>\n<p>Opioids such as morphine depress the hypoxic ventilatory response in the brainstem by affecting the chemosensitive cells that respond to changes in the partial pressures of carbon dioxide and oxygen in the blood</p>\n</blockquote>\n<p>The difficulty to treat an overdose and the <a href=\"https://pubmed.ncbi.nlm.nih.gov/30640650/\" rel=\"nofollow noreferrer\">narrow therapeutic window that opioids are known for</a>, make them drugs that need to be monitored very well and thus not much &quot;<strong>safe</strong>&quot;; <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1312206/pdf/bumc0013-0007.pdf\" rel=\"nofollow noreferrer\">although there are a lot being made to counter that effect with the new development of drugs, such as Fentanyl or Remifentanil</a></p>\n<blockquote>\n<p>Conventional µ receptor opioids have a narrow therapeutic window in part because of their mechanism of action</p>\n</blockquote>\n<p><a href=\"https://www.frontiersin.org/articles/10.3389/fphar.2014.00280/full\" rel=\"nofollow noreferrer\">The opioid receptor desensitization is also a problem,</a> that diminish their effectiveness, being also a cause of dependency and overdose.</p>\n<p>Now, regarding your question: <em><strong>Are opioids just dependency inducing or are they actually addictive to a majority of patients?</strong></em></p>\n<p>The answer is both. Opioids are in fact addictive to the majority of patients due to their ability to desensitize quickly.</p>\n<blockquote>\n<p>Opioids are required in ever-increasing doses as you develop a tolerance to them. In other words, the dose you used to take to relive your pain will eventually not work as well, which means you’ll need more of the opioid to get the same effect</p>\n</blockquote>\n<blockquote>\n<p>From a clinical standpoint, opioid withdrawal is one of the most powerful factors driving opioid <strong>dependence and addictive behaviors</strong>. Treatment of the patient’s withdrawal symptoms is based on understanding how withdrawal is related to the brain’s adjustment to opioids</p>\n</blockquote>\n<p>From a psychological point of view</p>\n<blockquote>\n<p>Other areas of the brain create a lasting record or memory that associates these good feelings with the circumstances and environment in which they occur. These memories, called conditioned associations, often lead to the craving for drugs when the abuser reencounters those persons, places, or things, and they drive abusers to seek out more drugs in spite of many obstacles</p>\n</blockquote>\n<p>And also they induce dependency essentially with the <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851054/pdf/spp-01-1-13.pdf\" rel=\"nofollow noreferrer\">release of endorphins</a>.\nWith the definition being stated on the article that you have provided such that <em><strong>Dependence is characterized by the symptoms of tolerance and withdrawal</strong></em>.</p>\n<blockquote>\n<p>One of the brain circuits that is activated by opioids is the mesolimbic (midbrain) reward system. This system generates signals in a part of the brain called the ventral tegmental area (VTA) that result in the release of the chemical dopamine (DA) in another part of the brain, the nucleus accumbens (NAc). This release of DA into the NAc causes feelings of pleasure. Other areas of the brain create a lasting record or memory that associates these good feelings with the circumstances and environment in which they occur.</p>\n</blockquote>\n<blockquote>\n<p>Two clinically important results of this alteration are <strong>opioid tolerance</strong> (the need to take higher and higher dosages of drugs to achieve the same opioid effect) <strong>and drug dependence</strong> (susceptibility to withdrawal symptoms).</p>\n</blockquote>\n<p>By all those reasons chronic pain is thus a very difficult condition to treat and is usually regarded according to the principle of the <em>gate control theory of pain</em> which leads to a <em><strong>broad spectrum analgesia</strong></em> therapy.</p>\n<hr />\n<p>Regarding the fact that\n<em><strong>If the cause(s) of the chronic pain are removed and the patient is being weaned off the opioids, do the damaging behaviours associated with addiction appear in a large proportion of these patients?</strong></em></p>\n<p>Naturally a high intake for a longer duration is associated with more severe withdrawal and to better grasp this concept there is a psychological scale that enable us to measure that (Clinical Opiate Withdrawal Scale - COWS) by quantifying the severity of opiate withdrawal symptoms,</p>\n<p><a href=\"https://www.asam.org/docs/default-source/education-docs/cows_induction_flow_sheet.pdf?sfvrsn=b577fc2_2\" rel=\"nofollow noreferrer\">article</a></p>\n<blockquote>\n<p>Patients who score between 5-12 are classified as mild withdrawal, 13-24 as moderate, 25-36 as moderately severe, and over 36 as severe withdrawal</p>\n</blockquote>\n<p>On the other hand, sometimes the chronic use of opioids can lead to brain abnormalities (dependce/addiction abnormalities) and here we have a clear difference about dependence and addiction, because it will lead to different ends.</p>\n<blockquote>\n<p>The abnormalities that produce dependence, well understood by science, appear to resolve after detoxification, within days or weeks after opioid use stops.</p>\n</blockquote>\n<blockquote>\n<p>The abnormalities that produce addiction, however, are more wide-ranging, complex, and long-lasting. [...] Such abnormalities can produce craving that leads to relapse months or years after the individual is no longer opioid dependent.</p>\n</blockquote>\n" } ]

[ "https://health.stackexchange.com/questions/24655", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7951/" ]

[ { "answer_id": 24701, "author": "BobE", "author_id": 11421, "author_profile": "https://health.stackexchange.com/users/11421", "pm_score": 0, "selected": false, "text": "<p>Finally found at least the Moderna Trial at <a href=\"https://clinicaltrials.gov/ct2/show/NCT04470427\" rel=\"nofollow noreferrer\">ClinicalTrials website</a>, still searching for others.</p>\n<p>This study description makes no mention of ethnicity targets, but Moderna's website (as of Sept 11 2020) has a graph of enrollees by ethnicity. Also states that as of Sept 11 2020 had not yet arrived at enrollment goal (24,000 of planned 30,000) <a href=\"https://www.modernatx.com/cove-study\" rel=\"nofollow noreferrer\">Moderna website</a></p>\n" }, { "answer_id": 27448, "author": "Farzan", "author_id": 22191, "author_profile": "https://health.stackexchange.com/users/22191", "pm_score": 2, "selected": false, "text": "<p>For the results you are interested in you need the full text of the publications.</p>\n<p>For Pfizer/BioNTech vaccine (BNT162b2 mRNA):</p>\n<ul>\n<li><p>N Engl J Med 2020; 383:2603-2615</p>\n<p>DOI: <a href=\"https://doi.org/10.1056/NEJMoa2034577\" rel=\"nofollow noreferrer\">10.1056/NEJMoa2034577</a></p>\n<p>Clinical Trial: <a href=\"https://clinicaltrials.gov/ct2/show/NCT04368728\" rel=\"nofollow noreferrer\">NCT04368728</a></p>\n</li>\n</ul>\n<p>For Moderna vaccine (mRNA-1273):</p>\n<ul>\n<li><p>N Engl J Med 2020; 383:1920-1931</p>\n<p>DOI: <a href=\"https://doi.org/10.1056/NEJMoa2022483\" rel=\"nofollow noreferrer\">10.1056/NEJMoa2022483</a></p>\n<p>Clinical Trial: <a href=\"https://clinicaltrials.gov/ct2/show/NCT04283461\" rel=\"nofollow noreferrer\">NCT04283461</a></p>\n</li>\n</ul>\n<p>For Astra Zeneca vaccine (ChAdOx1 nCoV-19/AZD1222):</p>\n<ul>\n<li><p>Lancet. 2020 Aug 15;396(10249):467-478</p>\n<p>doi: <a href=\"https://doi.org/10.1016/S0140-6736(20)31604-4\" rel=\"nofollow noreferrer\">10.1016/S0140-6736(20)31604-4</a></p>\n<p>Clinical Trial: <a href=\"https://clinicaltrials.gov/ct2/show/NCT04324606\" rel=\"nofollow noreferrer\">NCT04324606</a></p>\n</li>\n</ul>\n<p>For Janssen vaccine (Ad26.COV2.S):</p>\n<ul>\n<li><p>N Engl J Med. 2021 Jun 10;384(23):2187-2201</p>\n<p>doi: <a href=\"https://doi.org/10.1056/NEJMoa2101544\" rel=\"nofollow noreferrer\">10.1056/NEJMoa2101544</a></p>\n<p>Clinical Trial: <a href=\"https://clinicaltrials.gov/ct2/show/NCT04505722\" rel=\"nofollow noreferrer\">NCT04505722</a></p>\n</li>\n</ul>\n" } ]

[ "https://health.stackexchange.com/questions/24671", "https://health.stackexchange.com", "https://health.stackexchange.com/users/11421/" ]

[ { "answer_id": 24708, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 1, "selected": false, "text": "<p>I don't think he's referring to anything specific. &quot;May be&quot; is not a definitive statement, it just seems he is suggesting that it is plausible that a vaccine could be less protective than regular mask wearing. &quot;I might even go so far&quot; couches it even more.</p>\n<p>I think that's probably not a great statement to make, either, a better one might be to suggest that &quot;because a vaccine is not effective in everyone that gets it, mask-wearing may continue to be important even with a vaccine&quot;, but not every quote in front of the media is ever ideal. Really, the rest of his statement:</p>\n<blockquote>\n<p>if I don't get an immune response, the vaccine is not going to protect me. This face mask will</p>\n</blockquote>\n<p>seems like the part to focus on.</p>\n<p>For comparisons to influenza, this page talks about the annual flu vaccine efficiacy:</p>\n<p><a href=\"https://www.cdc.gov/flu/professionals/acip/immunogenicity.htm\" rel=\"nofollow noreferrer\">https://www.cdc.gov/flu/professionals/acip/immunogenicity.htm</a></p>\n<p>A quote, emphasis mine:</p>\n<blockquote>\n<p>IIV3 provided statistically significant protection against both the included B lineage (<strong>66%</strong>; 95%CI 58, 73) and the non-included B lineage (<strong>51%</strong>; 95%CI 36, 63) during the 2012– 13 season</p>\n</blockquote>\n<p>Another paper,</p>\n<p><em>Tricco, A. C., Chit, A., Soobiah, C., Hallett, D., Meier, G., Chen, M. H., ... &amp; Loeb, M. (2013). Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis. BMC medicine, 11(1), 153.</em></p>\n<p>is a meta-analysis of flu vaccine efficacy in children. They write, quote, with emphasis mine:</p>\n<blockquote>\n<p>The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, <strong>VE 54%</strong>, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, <strong>VE 83%</strong>, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months</p>\n</blockquote>\n<blockquote>\n<p>VE was calculated using the following formula: (1 - relative risk × 100%)</p>\n</blockquote>\n<p>So it seems that 70% would be in the ballpark of the annual flu vaccine against the included strain. Obviously the 2019 coronavirus is not influenza, but we have no solid long-term efficacy data yet, and I think it's reasonable to expect that even a very useful vaccine (on par with the annual flu vaccine given to millions) would not approach 100% efficacy. Even with a vaccine, it will probably be important to continue basic public health protocols intended to limit virus spread, especially before many people are immunized.</p>\n<p>There's some mixing here between &quot;immune response&quot; and &quot;efficiacy&quot; but I think it would be fair to say that if someone gets sick, then whatever measured immune response they may have had was not effective, so we might as well consider it not an immune response for this purpose. Rewriting a paraphrased version of the quote, I would say:</p>\n<blockquote>\n<p>&quot;If the Covid vaccine provides similar protection to the annual influenza vaccine, the immunogenicity could be around 70%. If I don't get an immune response, the vaccine is not going to protect me but a face mask will still provide some protection.&quot;</p>\n</blockquote>\n" }, { "answer_id": 24709, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 1, "selected": false, "text": "<p>From a <a href=\"https://europepmc.org/article/med/32591466\" rel=\"nofollow noreferrer\">recent review</a> of &quot;Warp Speed&quot; vaccine candidates</p>\n<blockquote>\n<p>General experience, combined with emerging data, suggests that the most rapidly produced vaccines (i.e., nucleic acids and virus vectors) may also be the least capable of eliciting high titers of antibodies and NAbs to the S-protein.</p>\n</blockquote>\n<p>So, it's probably a safe bet to limit discussion to those for now... The review also says that</p>\n<blockquote>\n<p>it is unknown whether the results obtained in small animals will be matched in humans. The immunogenicity of mRNA and DNA vaccines is generally far stronger in small animals than in macaques, and more so in humans.</p>\n</blockquote>\n<p>And for the latter it cites <a href=\"https://europepmc.org/article/PMC/7185789\" rel=\"nofollow noreferrer\">a paper</a> on a MERS DNA vaccine, which interestingly happens to mention something like those ~70% numbers....</p>\n<blockquote>\n<p>T-cell responses were detected in 47 (71%) of 66 participants after two vaccinations and in 44 (76%) of 58 participants after three vaccinations. [...] At week 60, vaccine-induced humoral and cellular responses were detected in 51 (77%) of 66 participants and 42 (64%) of 66, respectively.</p>\n</blockquote>\n<p>There's also been a bit of a debate as to what measure(s) of immunity are most relevant. Most of the (short-term) Covid-19 vaccine data published so far, itself on the order of one-month, seems to have been mainly anti-bodies (e.g. a <a href=\"https://www.medrxiv.org/content/10.1101/2020.06.30.20142570v1.full.pdf\" rel=\"nofollow noreferrer\">recent study</a> on one of the mRNA vaccines found average levels exceeding convalescence), but some researchers <a href=\"https://news.berkeley.edu/2020/09/09/for-an-effective-covid-vaccine-look-beyond-antibodies-to-t-cells/\" rel=\"nofollow noreferrer\">disagree</a> this is the most relevant measure, pointing to T-cells response as more relevant. Actually the T-cells measure was reported for that vaccine candidate too, in a <a href=\"https://www.medrxiv.org/content/10.1101/2020.07.17.20140533v1\" rel=\"nofollow noreferrer\">separate</a> publication/preprint; it was on the order of 80% response [29/36 participants] for CD8+ T cells. And that <a href=\"https://www.evaluate.com/vantage/articles/news/trial-results/covid-19-vaccine-contest-turns-t-cell-responses\" rel=\"nofollow noreferrer\">seems</a> to be as good as it gets in terms of Covid-19 phase-1 published data.</p>\n<p>I guess there's some &quot;fudge factor&quot; to consider here given that phase I trials tend to select healthy volunteers in the 18-55 age range etc.</p>\n" }, { "answer_id": 24742, "author": "BobE", "author_id": 11421, "author_profile": "https://health.stackexchange.com/users/11421", "pm_score": 0, "selected": false, "text": "<p>Without questioning the CDC director specifically we are left to speculate why he said 70% as contrasted with 60% or 80%.\nHowever, the <a href=\"https://pfe-pfizercom-d8-prod.s3.amazonaws.com/2020-09/C4591001_Clinical_Protocol_0.pdf\" rel=\"nofollow noreferrer\">protocol</a> released by Pfizer may give some clue. The clinical trial for their candidate vaccine will last approximately two years, however they will be conducting Interim Analysis for Vaccine Efficacy at several points during that two year period.</p>\n<p>Pfizer will consider the vaccine an <strong>interim</strong> success, if after 32 persons contract Covid19, only 6 of those people were injected with the trial vaccine. That calculates to an efficacy of 77%.(see page 102 of protocol)</p>\n<p>Subsequent interim analysis the last being after 164 persons contract Covid-19. If, of the 164 persons only 53 were injected with the trial vaccine, that would also be deemed a success. That calculates to an efficacy of 52%. (same page)</p>\n<p>So from the Pfizer protocol we see efficacy targets for success of 52% or greater.</p>\n<p>However, Efficacy (the extent to which a vaccine provides a beneficial result) is not synonymous with Immunogenicity (the ability of a vaccine to provoke an immune response creating antibodies). Having antibodies (naturally or provoked) against COVID19 is clearly better than having no antibodies, but there is no assurance that any of the trial vaccines will produce antibodies in <strong>every single</strong> person (100% immunogenicity). As a practical matter the immunogenicity will likely be less than 100%, but 70% would be considered a great success, particularity if the antibodies are constantly being produced and renewed. For those who do not develop antibodies, or that their bodies do not continue to produce &quot;fresh&quot; antibodies they will have to rely on other protective means - such as masks.</p>\n<p>The Pfizer protocol is silent on the immunogenicity criteria for success.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24707", "https://health.stackexchange.com", "https://health.stackexchange.com/users/10980/" ]

[ { "answer_id": 24718, "author": "Carey Gregory", "author_id": 805, "author_profile": "https://health.stackexchange.com/users/805", "pm_score": 2, "selected": false, "text": "<p>Yes, activated Charcoal (AC) can be given rectally. Although this is a veterinary journal, I doubt the principles are different and according to <a href=\"https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/enema\" rel=\"nofollow noreferrer\">this article</a> it's given in a liquid slurry, much like oral administration:</p>\n<blockquote>\n<p>Enemas also have been used to decrease the colonic bacterial numbers\nand substrates. The following types of enemas have been recommended:</p>\n<p>• Warm water enemas at 10 ml/kg q4-6h until signs improve, lactulose\nenemas at 1 to 3 ml/10 kg BW diluted 1 : 1 to 1 : 3 with warm water\nq6-8h</p>\n<p>• Neomycin enemas at 15 to 20 ml of 1% solution q8-12h</p>\n<p>• Metronidazole enemas at 7.5 mg/kg (systemic dose) mixed with water\nq12h</p>\n<p>• Betadine enemas given by diluting 1 : 10 with warm water and giving\n10 ml/kg q8h and flushing out with warm water after 10 to 15 minutes</p>\n<p><strong>• Activated charcoal enemas using the liquid suspension q8h</strong></p>\n<p>• Vinegar enemas made by diluting the vinegar 1 : 4 with warm water\nand administering at 10 ml/kg q8h</p>\n</blockquote>\n<p>This is substantiated by the following human clinical trial involving the treatment of anal fistulas. Although I can't find historical evidence that rectal administration was a common practice in the past, it received new attention in 2017 with <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355500/#:%7E:text=Rectal%20application%20of%20high%2Dpurity,may%20additionally%20preserve%20sphincter%20function.\" rel=\"nofollow noreferrer\">this study</a>:</p>\n<h2><strong>An open prospective study evaluating efficacy and safety of a new medical device for rectal application of activated carbon in the treatment of chronic, uncomplicated perianal fistulas</strong>.</h2>\n<blockquote>\n<p>The aim of this study was to evaluate the clinical effects on\nnon-Crohn’s disease perianal fistula healing, and the safety and\ntolerability of a new medical device that applies high-purity,\nhigh-activity granular activated carbon locally into the rectum twice\ndaily of patients with perianal fistulas without any concomitant\nmedication.</p>\n</blockquote>\n<p>It appeared to be moderately successful:</p>\n<blockquote>\n<p>Of 28 patients included, 10 patients (35.7%) showed complete fistula\nhealing (closed, no discharge on palpation) after 8 weeks; seven of\nthese patients, corresponding to 25% of the enrolled patients,\nremained in remission for up to 31 weeks.</p>\n</blockquote>\n<p>As I said before, I couldn't find historical evidence of rectal administration being used, but I did find an article from 1964 that seems to hint that it could have been administered other than orally in some cases. Unfortunately, the full text of the article is behind a pay wall. <a href=\"https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1532-5415.1964.tb05735.x\" rel=\"nofollow noreferrer\">Here</a> is what's freely available:</p>\n<p><a href=\"https://i.stack.imgur.com/O0Zoz.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/O0Zoz.png\" alt=\"https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1532-5415.1964.tb05735.x\" /></a></p>\n" }, { "answer_id": 24741, "author": "Chris Chung", "author_id": 20437, "author_profile": "https://health.stackexchange.com/users/20437", "pm_score": 0, "selected": false, "text": "<p>Yes absolutely. There was a hemorrhoid treatment made of activated charcoal called <a href=\"https://charcoalremedies.com/2019/06/05/hemorrhoids/\" rel=\"nofollow noreferrer\">Freedhem</a> that was applied rectally. It is no longer available on the market. Also, for <a href=\"https://charcoalremedies.com/2019/06/05/prostatitis/\" rel=\"nofollow noreferrer\">prostatitis</a>, <a href=\"https://charcoalremedies.com/2019/06/05/drs_thrash_md/\" rel=\"nofollow noreferrer\">Dr. Thrash</a>, former medical examiner of the state of Georgia, used an activated charcoal enema with success.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24717", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7166/" ]

[ { "answer_id": 24840, "author": "πάντα ῥεῖ", "author_id": 13674, "author_profile": "https://health.stackexchange.com/users/13674", "pm_score": 1, "selected": false, "text": "<p>Seems I found the answer about the correlation of <em>gram negative</em> test and high resistance against antibiotics.</p>\n<p>From Wikipedia <strong><a href=\"https://en.wikipedia.org/wiki/Gram-negative_bacteria\" rel=\"nofollow noreferrer\">Gram-negative bacteria</a></strong> (emphasis mine):</p>\n<blockquote>\n<p>Gram-negative bacteria are found everywhere, in virtually all\nenvironments on Earth that support life. The gram-negative bacteria\ninclude the model organism Escherichia coli, as well as many\npathogenic bacteria, such as Pseudomonas aeruginosa, Chlamydia\ntrachomatis, and Yersinia pestis. <strong>They are an important medical\nchallenge, as their outer membrane protects them from many antibiotics\n(including penicillin); detergents that would normally damage the\npeptidoglycans of the (inner) cell membrane; and lysozyme, an\nantimicrobial enzyme produced by animals that forms part of the innate\nimmune system. Additionally, the outer leaflet of this membrane\ncomprises a complex lipopolysaccharide (LPS) whose lipid A component\ncan cause a toxic reaction when these bacteria are lysed by immune\ncells.</strong> This toxic reaction can include fever, an increased respiratory\nrate, and low blood pressure — a life-threatening condition known as\nseptic shock.</p>\n</blockquote>\n<p>Now it's clear for me, why <em>gram-negative</em> was mentioned by my dermatologist in 1st place.<br />\nIt is a general indication of antibiotic resistance of bacteria strains.</p>\n" }, { "answer_id": 24841, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 2, "selected": false, "text": "<p><a href=\"https://en.wikipedia.org/wiki/Gram_stain\" rel=\"nofollow noreferrer\">Gram positivity/negativity</a> is sort of a historical classification that comes down to an ability to separate bacteria types without knowing what that separation really meant physically.</p>\n<p>Of course, what really matters isn't whether or not a bacterial species takes up a particular stain, but rather that the reason that they stain well or poorly is because they have a different type of outer coat. <a href=\"https://en.wikipedia.org/wiki/Gram-positive_bacteria\" rel=\"nofollow noreferrer\">Gram-positive</a> bacteria have a thick peptidoglycan (sugars+amino acids) wall. <a href=\"https://en.wikipedia.org/wiki/Gram-negative_bacteria\" rel=\"nofollow noreferrer\">Gram-negative bacteria</a> have a second membrane on the outside, and typically a thinner peptidoglycan layer in the middle.</p>\n<p>There is some complexity in this because not all bacteria necessarily follow the same staining &quot;rule&quot; by their coat, but it works as a rough characterization for many species and is quick and cheap.</p>\n<p>Some antibiotics target the peptidoglycan wall, so they are most effective against Gram-positive bacteria (<a href=\"https://en.wikipedia.org/wiki/Penicillin\" rel=\"nofollow noreferrer\">penicillin</a> is an example).</p>\n<p>However, there is nothing that says a Gram-positive bacteria can't also have antibiotic resistance. <em>Staphylococcus</em> are a common Gram-positive pathogenic strain, and you may have heard of <a href=\"https://en.wikipedia.org/wiki/Methicillin-resistant_Staphylococcus_aureus\" rel=\"nofollow noreferrer\">MRSA</a>, a particularly troublesome antibiotic-resistant Staph strain.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24838", "https://health.stackexchange.com", "https://health.stackexchange.com/users/13674/" ]

[ { "answer_id": 24840, "author": "πάντα ῥεῖ", "author_id": 13674, "author_profile": "https://health.stackexchange.com/users/13674", "pm_score": 1, "selected": false, "text": "<p>Seems I found the answer about the correlation of <em>gram negative</em> test and high resistance against antibiotics.</p>\n<p>From Wikipedia <strong><a href=\"https://en.wikipedia.org/wiki/Gram-negative_bacteria\" rel=\"nofollow noreferrer\">Gram-negative bacteria</a></strong> (emphasis mine):</p>\n<blockquote>\n<p>Gram-negative bacteria are found everywhere, in virtually all\nenvironments on Earth that support life. The gram-negative bacteria\ninclude the model organism Escherichia coli, as well as many\npathogenic bacteria, such as Pseudomonas aeruginosa, Chlamydia\ntrachomatis, and Yersinia pestis. <strong>They are an important medical\nchallenge, as their outer membrane protects them from many antibiotics\n(including penicillin); detergents that would normally damage the\npeptidoglycans of the (inner) cell membrane; and lysozyme, an\nantimicrobial enzyme produced by animals that forms part of the innate\nimmune system. Additionally, the outer leaflet of this membrane\ncomprises a complex lipopolysaccharide (LPS) whose lipid A component\ncan cause a toxic reaction when these bacteria are lysed by immune\ncells.</strong> This toxic reaction can include fever, an increased respiratory\nrate, and low blood pressure — a life-threatening condition known as\nseptic shock.</p>\n</blockquote>\n<p>Now it's clear for me, why <em>gram-negative</em> was mentioned by my dermatologist in 1st place.<br />\nIt is a general indication of antibiotic resistance of bacteria strains.</p>\n" }, { "answer_id": 24841, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 2, "selected": false, "text": "<p><a href=\"https://en.wikipedia.org/wiki/Gram_stain\" rel=\"nofollow noreferrer\">Gram positivity/negativity</a> is sort of a historical classification that comes down to an ability to separate bacteria types without knowing what that separation really meant physically.</p>\n<p>Of course, what really matters isn't whether or not a bacterial species takes up a particular stain, but rather that the reason that they stain well or poorly is because they have a different type of outer coat. <a href=\"https://en.wikipedia.org/wiki/Gram-positive_bacteria\" rel=\"nofollow noreferrer\">Gram-positive</a> bacteria have a thick peptidoglycan (sugars+amino acids) wall. <a href=\"https://en.wikipedia.org/wiki/Gram-negative_bacteria\" rel=\"nofollow noreferrer\">Gram-negative bacteria</a> have a second membrane on the outside, and typically a thinner peptidoglycan layer in the middle.</p>\n<p>There is some complexity in this because not all bacteria necessarily follow the same staining &quot;rule&quot; by their coat, but it works as a rough characterization for many species and is quick and cheap.</p>\n<p>Some antibiotics target the peptidoglycan wall, so they are most effective against Gram-positive bacteria (<a href=\"https://en.wikipedia.org/wiki/Penicillin\" rel=\"nofollow noreferrer\">penicillin</a> is an example).</p>\n<p>However, there is nothing that says a Gram-positive bacteria can't also have antibiotic resistance. <em>Staphylococcus</em> are a common Gram-positive pathogenic strain, and you may have heard of <a href=\"https://en.wikipedia.org/wiki/Methicillin-resistant_Staphylococcus_aureus\" rel=\"nofollow noreferrer\">MRSA</a>, a particularly troublesome antibiotic-resistant Staph strain.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24839", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7949/" ]

[ { "answer_id": 24840, "author": "πάντα ῥεῖ", "author_id": 13674, "author_profile": "https://health.stackexchange.com/users/13674", "pm_score": 1, "selected": false, "text": "<p>Seems I found the answer about the correlation of <em>gram negative</em> test and high resistance against antibiotics.</p>\n<p>From Wikipedia <strong><a href=\"https://en.wikipedia.org/wiki/Gram-negative_bacteria\" rel=\"nofollow noreferrer\">Gram-negative bacteria</a></strong> (emphasis mine):</p>\n<blockquote>\n<p>Gram-negative bacteria are found everywhere, in virtually all\nenvironments on Earth that support life. The gram-negative bacteria\ninclude the model organism Escherichia coli, as well as many\npathogenic bacteria, such as Pseudomonas aeruginosa, Chlamydia\ntrachomatis, and Yersinia pestis. <strong>They are an important medical\nchallenge, as their outer membrane protects them from many antibiotics\n(including penicillin); detergents that would normally damage the\npeptidoglycans of the (inner) cell membrane; and lysozyme, an\nantimicrobial enzyme produced by animals that forms part of the innate\nimmune system. Additionally, the outer leaflet of this membrane\ncomprises a complex lipopolysaccharide (LPS) whose lipid A component\ncan cause a toxic reaction when these bacteria are lysed by immune\ncells.</strong> This toxic reaction can include fever, an increased respiratory\nrate, and low blood pressure — a life-threatening condition known as\nseptic shock.</p>\n</blockquote>\n<p>Now it's clear for me, why <em>gram-negative</em> was mentioned by my dermatologist in 1st place.<br />\nIt is a general indication of antibiotic resistance of bacteria strains.</p>\n" }, { "answer_id": 24841, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 2, "selected": false, "text": "<p><a href=\"https://en.wikipedia.org/wiki/Gram_stain\" rel=\"nofollow noreferrer\">Gram positivity/negativity</a> is sort of a historical classification that comes down to an ability to separate bacteria types without knowing what that separation really meant physically.</p>\n<p>Of course, what really matters isn't whether or not a bacterial species takes up a particular stain, but rather that the reason that they stain well or poorly is because they have a different type of outer coat. <a href=\"https://en.wikipedia.org/wiki/Gram-positive_bacteria\" rel=\"nofollow noreferrer\">Gram-positive</a> bacteria have a thick peptidoglycan (sugars+amino acids) wall. <a href=\"https://en.wikipedia.org/wiki/Gram-negative_bacteria\" rel=\"nofollow noreferrer\">Gram-negative bacteria</a> have a second membrane on the outside, and typically a thinner peptidoglycan layer in the middle.</p>\n<p>There is some complexity in this because not all bacteria necessarily follow the same staining &quot;rule&quot; by their coat, but it works as a rough characterization for many species and is quick and cheap.</p>\n<p>Some antibiotics target the peptidoglycan wall, so they are most effective against Gram-positive bacteria (<a href=\"https://en.wikipedia.org/wiki/Penicillin\" rel=\"nofollow noreferrer\">penicillin</a> is an example).</p>\n<p>However, there is nothing that says a Gram-positive bacteria can't also have antibiotic resistance. <em>Staphylococcus</em> are a common Gram-positive pathogenic strain, and you may have heard of <a href=\"https://en.wikipedia.org/wiki/Methicillin-resistant_Staphylococcus_aureus\" rel=\"nofollow noreferrer\">MRSA</a>, a particularly troublesome antibiotic-resistant Staph strain.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24864", "https://health.stackexchange.com", "https://health.stackexchange.com/users/15516/" ]

[ { "answer_id": 24871, "author": "Community", "author_id": -1, "author_profile": "https://health.stackexchange.com/users/-1", "pm_score": 4, "selected": true, "text": "<p>As far as I can tell the most relevant CDC guidelines are the <a href=\"https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html\" rel=\"noreferrer\">&quot;Discontinuation of Transmission-Based Precautions and Disposition of Patients with COVID-19 in Healthcare Settings (Interim Guidance)&quot;</a></p>\n<blockquote>\n<p>Patients with mild to moderate illness who are not severely\nimmunocompromised:</p>\n<ul>\n<li>At least 10 days have passed since symptoms first appeared and</li>\n<li>At least 24 hours have passed since last fever without the use of fever-reducing medications and</li>\n<li>Symptoms (e.g., cough, shortness of breath) have improved</li>\n</ul>\n<p>Note: For patients who are not severely immunocompromised1 and who\nwere asymptomatic throughout their infection, Transmission-Based\nPrecautions may be discontinued when at least 10 days have passed\nsince the date of their first positive viral diagnostic test.</p>\n<p>Patients with severe to critical illness or who are severely\nimmunocompromised1:</p>\n<ul>\n<li>At least 10 days and up to 20 days have passed since symptoms first appeared and</li>\n<li>At least 24 hours have passed since last fever without the use of fever-reducing medications and</li>\n<li>Symptoms (e.g., cough, shortness of breath) have improved</li>\n<li>Consider consultation with infection control experts</li>\n</ul>\n</blockquote>\n<p>The document also notes</p>\n<blockquote>\n<p>A test-based strategy is no longer recommended (except as noted below) because, in the majority of cases, it results in prolonged isolation of patients who continue to shed detectable SARS-CoV-2 RNA but are no longer infectious.</p>\n</blockquote>\n<p>So it appears that a mostly time-based decision is supported by the CDC guidelines. But there are some important conditions here that are not based on the duration of the illness alone, but on the symptoms and the severeness of the illness.</p>\n<p>In the case of Donald Trump we simply don't have all the information that is necessary to apply these guidelines.</p>\n" }, { "answer_id": 24875, "author": "BobE", "author_id": 11421, "author_profile": "https://health.stackexchange.com/users/11421", "pm_score": 3, "selected": false, "text": "<p>Here is a nice graphic that aggregates data from CDC &amp; WHO that demonstrates the stages of Covid19 progression.</p>\n<p>Notice that the contagious/infectious period tends to begin 3 days after exposure, reaches a peak about 5 or 6 days after exposure and gradually diminishes over the period of 10/11 after initial exposure. By the 16th day after exposure the anticipated infectionness is near zero.</p>\n<p>Note, however the persons may continue to test positive well after infectiousness ends (up to three months).</p>\n<p>As it applies to Trump, we do not know when he was exposed, nor do we know when his last negative test occurred prior to his first positive test. Similarly, we do not know if he has tested negative since returning from Walter Reed (although I would be very surprised if he has had a PCR negative result yet).</p>\n<p><a href=\"https://i.stack.imgur.com/P1vmk.jpg\" rel=\"noreferrer\"><img src=\"https://i.stack.imgur.com/P1vmk.jpg\" alt=\"Link\" /></a></p>\n" } ]

[ "https://health.stackexchange.com/questions/24870", "https://health.stackexchange.com", "https://health.stackexchange.com/users/2523/" ]

[ { "answer_id": 24969, "author": "Diana Petitti", "author_id": 20133, "author_profile": "https://health.stackexchange.com/users/20133", "pm_score": 2, "selected": false, "text": "<p>The question of the efficacy of stem cell treatments is a topic of great current (October 2020) interest with randomized clinical trials on-going or planned for a variety of conditions.</p>\n<p>This 2020 publication is a systematic review of studies of mesenchymal stromal cell-based therapies for the treatment of osteoarthritis.</p>\n<p>Maleitzke T, Elazaly H, Festbaum C, et al. Mesenchymal Stromal Cell-Based Therapy-An Alternative to Arthroplasty for the Treatment of Osteoarthritis? A State of the Art Review of Clinical Trials. J Clin Med. 2020;9(7):2062. Published 2020 Jun 30. doi:10.3390/jcm9072062\n<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409016/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409016/</a></p>\n<p>The review provides a description of studies of mesenchymal stromal cell-based therapies for treatment of osteoarthritis that are registered at ClinicalTrials.gov and are currently recruiting along with their registration numbers. Review of these registered and recruiting trials gives an idea of the scope of interest in these therapies for one condition—osteoarthritis—as well as the diversity of approaches.</p>\n<p>The review identified published randomized placebo-controlled trials of mesenchymal stromal cell treatments for osteoarthritis as well as randomized trials with an active treatment comparison and non-randomized studies (sometimes called trials but not really trials). These are described in Table 2 of the cited publication.</p>\n<p>The authors do not try to meta-analyze data from these published studies. Nor do they draw conclusions about whether mesenchymal stromal cell treatments should or should not be used to treat osteoarthritis.</p>\n<p>Two studies cited in this review (reference 83 and 103) seem to address the question of whether there are any randomized trials that show benefits of mesenchymal cell-based therapies for any condition. There are.</p>\n<p><strong>FREITAG, BATES, WICKHAM et al.</strong></p>\n<p>Reference 83 is a reference to a study of adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis.</p>\n<p>Freitag J, Bates D, Wickham J, et a. Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regen Med. 2019;14:213-230. doi: 10.2217/rme-2018-0161. Epub 2019 Feb 14. PMID: 30762487.</p>\n<p>The article is available in full-text form for free. The link is accessed from PubMed.</p>\n<p>The trial was registered on the Australian and New Zealand Clinic Trial Registry (Trial ID: ACTRN12614000814673).</p>\n<p>There were 30 patients in the trial. They were randomized to three groups with 10 patients in each group—a single intra-articular injection of 108 (100 million) mesenchymal cells, two injections of 108 (100 million) mesenchymal cells six months apart, and a control (ongoing conventional conservative management only). The mesenchymal cells were autologous—derived from the treated persons own adipose tissue. The participants were not blinded to their treatment assignment. Randomization was “prepared in advance using a random number generator.” However, researchers with direct involvement in participant recruitment and treatment were blinded to the randomization process.</p>\n<p>In spite of random assignment, participants in the control group had a lower body mass index than participants in the treatment groups (25.2 for control compared with 31.6 in the group given 1 injection and 30.4 in the group given two injections).</p>\n<p>Follow-up was done at 1, 3, 6 and 12 months.</p>\n<p>Main results for pain and function were as follows:</p>\n<blockquote>\n<p>“Pain, as measured by the NPRS [Numeric Pain Rating Scale], in the\none-injection group and two-injection group improved from a mean\n(standard deviation) of 6.7 (1.7) and 6.5 (1.4) to 2.6 (1.8) and 2.3\n(2) respectively at completion of the study. Within group improvement\nwhen compared with baseline was statistically significant (&lt; 0.05)\nthroughout all time points in both the single and two injection\nprotocol treatment groups. Similarly, between group differences\nrevealed that both the one-injection and two-injection groups had\nsignificantly less pain at 12 months compared with the Control group.\nNo significant differences were found between the two treatment\ngroups.”</p>\n<p>“KOOS [Knee Injury and Osteoarthritis Outcome Score] subscale analysis\nshowed consistent improvement in all subscales during follow-up and\nthis was maintained until completion of follow-up at 12 months. There\nwas no significant difference at 12 months in all subscales between\nthe two treatment groups. All subscales displayed statistically\nsignificant improvement against control at 12 months of follow-up. The\none-injection group had more consistent improvement against Control\nthroughout the follow-up period.”</p>\n</blockquote>\n<p><strong>MATAS, ORREGO, AMENABAR et al.</strong></p>\n<p>Reference 103 is a reference to a study of adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis.</p>\n<p>Matas J, Orrego M, Amenabar D, et al. Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial. Stem Cells Transl Med. 2019;8(3):215-224. doi:10.1002/sctm.18-0053</p>\n<p>The full-text can be accessed on PMC.\n<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392367/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392367/</a></p>\n<p>The study was registered at Clinical Trials.gov (NCT02589695). It was a randomized, double-blind study of a single versus repeated (two) injections of umbilical-derived mesenchymal stromal cells compared with compared with standard therapy--repeated (two) injections of intra‐articular hyaluronic acid—in patients with knee OA.</p>\n<p>There were 29 patients in the trial. They were randomized to three groups—10 were allocated to receive a single intra-articular injection of 20 x 106 (20 million) umbilical-derived mesenchymal cells at baseline and a plasma/saline placebo injection at six month; 10 were allocated to receive a baseline intra-articular injection of 20 x 106 (20 million) umbilical-cord mesenchymal cells and another injection of 20 x 106 (20 million) cells at six months; 9 were allocated to receive two intra-articular injections of hyaluronic acid--one at baseline and another at six months. There was 1 drop-out in each of the three groups leaving 9 patients in the single injection group, 9 in the two injection group, and 8 in active treatment comparator.</p>\n<p>The mesenchymal cells were allogenic—derived from the umbilical cords obtained from full‐term human placentas by cesarean section after informed consent.</p>\n<p>The investigators and the participants were blinded to their treatment assignment. Randomization was described as being “by electronic data entry system.”</p>\n<p>Follow-up was done at 1, 4, 8, 12, 24, 36, and 52 weeks.</p>\n<p>Pain and function outcomes were assessed using a number of instruments-- the Western Ontario and Mc Master Universities Arthritis Index (WOMAC), the Pain Visual Analog scale (VAS), the Short‐form 36 (SF‐36) questionnaire, the Patient Global Assessment, and the Outcome Measures in Rheumatology Committee (OMERACT)‐Osteoarthritis Research Society International (OARSI) Responder Index Criteria .</p>\n<p>Results were reported for the Western Ontario McMaster Universities Arthritis Index, the Pain Visual Analogue Scale, the SF-36, and Outcomes Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARS) Responder Index.</p>\n<p>Results were as follows:</p>\n<p>At 12 months follow‐up, scores on the pain subscale of the WOMAC‐A were statistically lower [better] in the group treated with 2 mesenchymal stromal cell injections (1.1 ± 1.3) compared with the group treated with hyaluronic acid (4.3 ± 3.5). (Table 3) (p = 0.04 after correction for multiple comparison)</p>\n<p>Considering the total WOMAC, at 12 months, the group treated with 2 mesenchymal stromal cell injections also had statistically significantly lower [better] scores than the group with hyaluronic acid at 12 months (4.2 ± 3.9 vs. 15.2 ± 11). (Table 3) (p = .05 after correction for multiple comparisons).</p>\n<p>At 12 months, scores on the pain VAS were statistically significantly lower [better] in the group treated with two mesenchymal stromal cell injections compared with group treated with hyaluronic acid (2.4 ± 2.1 vs. 22.1 ± 9.8). (Table 3) (p = .03 after correction for multiple comparison).</p>\n<p>There were no statistically significant differences between the three groups on functional component of the WOMAC or the SF-36.</p>\n<p>The authors also reported that:</p>\n<blockquote>\n<p>“When comparing how often patients in the trial would achieve\nresponder status at study endpoint, as defined by the OMERACT‐OARSI\nresponder index criteria, all individuals in the repeated MSC (two\ninjections of mesenchymal stromal cell) group were found to be\nresponders as opposed to 62.5% of patients in the control HA group, a\ntendency that did not reach significance (p = .08; Figure 3D).”</p>\n</blockquote>\n<p>So the answer to your question is yes, there are randomized controlled trials—with one being blinded--that report benefits of mesenchymal stromal cell (stem cell) treatment for knee osteoarthritis.</p>\n<p>Given the small number of patients in these two trials and the findings in other randomized trials, these findings should <strong>NOT</strong> be used as evidence that the treatments studied in these two trials, or any other stem cell treatment, are recommended for any patient with knee osteoarthritis (or any other condition).</p>\n" }, { "answer_id": 24997, "author": "Blue Various", "author_id": 16820, "author_profile": "https://health.stackexchange.com/users/16820", "pm_score": 1, "selected": false, "text": "<p>Is your question focused on the clinical trial on the spine, rather than arthritis in general? If so, the following articles will be helpful.</p>\n<p><strong>As for the PRPs,</strong> how about this <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394242/\" rel=\"nofollow noreferrer\">review</a>?</p>\n<p>They conclude that;</p>\n<blockquote>\n<p>Clinical studies for evaluating the effects of the injection of PRP into degenerated IVDs for patients with discogenic LBP have been reviewed. Although there was only one double-blind randomized controlled trial, all the studies reported that PRP was safe and effective in reducing back pain. While the clinical evidence of tissue repair of IVDs by PRP treatment is currently lacking, there is a great possibility that the application of PRP has the potential to lead to a feasible intradiscal therapy for the treatment of degenerative disc diseases. Further large-scale studies may be required to confirm the clinical evidence of PRP for the treatment of discogenic LBP.</p>\n</blockquote>\n<p>They say they need larger-scale trials, but remember that any small difference can be made statistically significant by increasing the sample size.</p>\n<p><strong>As for the MSCs</strong>, how about this <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711491/\" rel=\"nofollow noreferrer\">review</a>?\nThey conclude that;</p>\n<blockquote>\n<p>Treatment of LBP by implantation of MSCs is unlikely to effect a significant repair or relieve pain. ＜＜omission of middle part＞＞ <br>\nIn addition clinical studies suggesting MSC injections as a possible treatment for LBP, all lack high patient numbers and long‐term results. As not all of them have controls, they are not able to rule out that the positive results reported could arise from a placebo effect. ＜＜omission of middle part＞＞<br>\nHence the treatment of the illustrated case through injection of MSCs cannot thus be recommended. MSC implantation is very unlikely to effect a clinically relevant repair and even if it could, it is unclear whether the patient would benefit from repair of her disc.</p>\n</blockquote>\n<p>Note that, as you can see from other <a href=\"https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/sctm.19-0202\" rel=\"nofollow noreferrer\">review</a> review the spine is not a major target of the MSCs; you can see how many clinical trials on MSC are registered on <a href=\"https://clinicaltrials.gov/\" rel=\"nofollow noreferrer\">clinicaltrials.gov</a>.</p>\n<p>From the above reviews, in general, one <strong>should conclude that the benefits of MSCs and PRP for arthritis or similar diseases on the spine have not been proven to be worth the cost</strong>. No credible evidence has yet been found to establish their effectiveness. Conducting larger sample size trials may lead to statistically significant differences in some surrogates, but I don't think that dramatic treatment exists as an extension of the current MSC and PRP;I think we need a radically improved MSC or PRP.</p>\n<p>Recently, Mesoblast Group appears to have an MSC-based pipeline, MPC-25-Osteo, for the spine. There appears to be a Phase 3 clinical trial underway, so I suspect we'll know more about it when the results come in. (See this <a href=\"https://www.mesoblast.com/product-candidates/spine-orthopedic-disorders/spinal-fusion\" rel=\"nofollow noreferrer\">site</a>). However, <a href=\"https://www.youtube.com/watch?v=Zvwdxn93kMU&amp;feature=youtu.be&amp;t=9m00s\" rel=\"nofollow noreferrer\">they say</a> their target is opioid substitution; in other words, the goal might be pain relief rather than a cure for the root cause.</p>\n" } ]

[ "https://health.stackexchange.com/questions/24951", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19551/" ]

[ { "answer_id": 25623, "author": "Dale C", "author_id": 21286, "author_profile": "https://health.stackexchange.com/users/21286", "pm_score": 0, "selected": false, "text": "<blockquote>\n<p>Are there other ways of supplementing? Are there supplements that are not contraindicated?</p>\n</blockquote>\n<p>Yes. There are ways to deliver vitamins directly to the cell without needing to be passed by the intestinal system.</p>\n<p>E.g. Vitamin B12, one of the most commonly deficient vitamins observed in IBD and crohn's patients as uptake is mainly oral and the main site of oral absorption being in the ileum, can be delivered intramuscularly via injection. [<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112015/\" rel=\"nofollow noreferrer\">1</a>]</p>\n<p>Oral Vitamin D supplements also tend to be less effective in IBD patients with active inflammation in the small bowel as that is where most absorption takes place. And can be supplemented through natural biosynthesis by the keratinocytes in the epidermis when in the presence of UV light.</p>\n" }, { "answer_id": 25635, "author": "tintenfisch", "author_id": 21296, "author_profile": "https://health.stackexchange.com/users/21296", "pm_score": 1, "selected": false, "text": "<p>Supplementation of vitamins and minerals in the context of Inflammatory Bowel Disease (IBD) should be <strong>specific to existing deficiencies</strong> in each patient (<a href=\"https://scholar.google.com/scholar_lookup?title=Nutritional+management+of+inflammatory+bowel+diseases:+a+comprehensive+guide&amp;publication_year=2016&amp;\" rel=\"nofollow noreferrer\">1</a>).</p>\n<p>There is little evidence in this context for blind ingestion of over the counter supplements without a diagnostic correlate for, or at least reasonable clinical suspicion of a particular deficiency.</p>\n<blockquote>\n<p>Do guidelines exist for how people with Inflammatory Bowel Disorder should supplement with multiminerals and not risk a flare?</p>\n</blockquote>\n<p>Guidelines exist for management of IBD including treatment of deficiency (for example: <a href=\"https://academic.oup.com/ecco-jcc/article/13/2/144/5078195#130780346\" rel=\"nofollow noreferrer\">2</a>, <a href=\"https://www.gesa.org.au/public/13/files/Education%20%26%20Resources/Clinical%20Practice%20Resources/IBD/2018_IBD_Clinical_Update_May_update.pdf\" rel=\"nofollow noreferrer\">3</a>). The intended audience is physicians. Informational resources for patients are also available (for instance: <a href=\"http://www.gesa.org.au/public/13/files/Education%20%26%20Resources/Patient%20Resources/Diet%20in%20IBD/Diet_in_IBD_Final_2018.pdf\" rel=\"nofollow noreferrer\">4</a>, <a href=\"https://www.gesa.org.au/public/13/files/Education%20%26%20Resources/Patient%20Resources/IBD/IBD_Crohns_Colitis_Factsheet.pdf\" rel=\"nofollow noreferrer\">5</a>). Patients should consult with their physicians to determine the necessity of taking supplements.</p>\n<blockquote>\n<p>...as their gut is already compromised such conventional supplements are contraindicated.</p>\n</blockquote>\n<p>IBDs are variable in their severity: the function of the gut is not necessarily <em>continuously</em> compromised and different sections of the gut can be affected. As such the choice of supplement and method of administration must be tailored to the individual situation: disease activity, patient tolerance, degree of deficiency and success or failure of a given supplement are relevant factors.</p>\n<blockquote>\n<p>Are there other ways of supplementing?</p>\n</blockquote>\n<p>Application methods depend on the substance. The most common deficiencies in the context of IBD are Iron, Vitamin D, Vitamin B12, Zinc and Calcium (<a href=\"https://academic.oup.com/ibdjournal/article/18/10/1961/4608026\" rel=\"nofollow noreferrer\">6</a>). All of these can be administered per os or intravenously (1, 6). As pointed out elsewhere, Vitamin B12 and Vitamin D can be administered under the skin or in the muscle (<a href=\"https://onlinelibrary.wiley.com/doi/full/10.1111/jgh.13359\" rel=\"nofollow noreferrer\">7</a>).</p>\n" } ]

[ "https://health.stackexchange.com/questions/24960", "https://health.stackexchange.com", "https://health.stackexchange.com/users/-1/" ]

[ { "answer_id": 25039, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 1, "selected": false, "text": "<p>The FDA's <a href=\"https://www.fda.gov/files/food/published/Food-Labeling-Guide-%28PDF%29.pdf\" rel=\"nofollow noreferrer\">food labeling guide</a> is a more complete reference.</p>\n<p>Importantly, these labels are not precise to any scientific standard. Fat quantities are rounded to the nearest gram or half gram, fat quantities &lt;0.5g are reported as zero, only saturated and trans fats must be labeled separate from total fat (if &gt;0.5g per serving) and others are up to the manufacturer. These are meant to provide general information to consumers, not to be an exact representation.</p>\n<p><a href=\"https://en.wikipedia.org/wiki/Omega-3_fatty_acid\" rel=\"nofollow noreferrer\">Omega-3</a> fats are a particular category of polyunsaturated fat. Manufacturers can add information about unsaturated fat as a whole or in categories, often separated into polyunsaturated and monounsaturated fats, but they don't have to. Often when they do it's because they are attempting to make some sort of health claim, so this is a form of allowed marketing rather than a government standard.</p>\n" }, { "answer_id": 25052, "author": "Mark", "author_id": 333, "author_profile": "https://health.stackexchange.com/users/333", "pm_score": 2, "selected": false, "text": "<p>There are many different ways of <a href=\"https://en.wikipedia.org/wiki/Fat#Classification\" rel=\"nofollow noreferrer\">classifying fats</a>, including:</p>\n<ul>\n<li>Chain length of the constituent fatty acids. This is mostly of interest in determining if the fat will be solid or liquid at room temperature, so it doesn't show up on nutrition labels.</li>\n<li>Presence of carbon-carbon double bonds in the constituent fatty acids. Saturated fats don't have any double bonds, while unsaturated fats do. (Monounsaturated fats have one double bond per fatty acid, while polyunsaturated fats have multiple double bonds.)</li>\n<li>The arrangement of atoms around any carbon-carbon double bonds. <em>Cis</em>-fatty acids have a &quot;C&quot; shape, while <em>trans</em>-fatty acids have a zig-zag shape.</li>\n</ul>\n<p>The nutrition label you show lists only some of the constituent fats of the product: the saturated fats, and those unsaturated fats with a <em>trans</em> arrangement. <em>Cis</em>-unsaturated fats aren't listed.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25035", "https://health.stackexchange.com", "https://health.stackexchange.com/users/16352/" ]

[ { "answer_id": 25189, "author": "Wrzlprmft", "author_id": 1409, "author_profile": "https://health.stackexchange.com/users/1409", "pm_score": 2, "selected": false, "text": "<p>Two major reasons and one minor:</p>\n<ul>\n<li><p><strong><a href=\"https://en.wikipedia.org/wiki/Herd_immunity\" rel=\"nofollow noreferrer\">Herd immunity</a></strong>: The 95% for which the vaccine works are not only spared from the disease, but they also do not infect others and thus do not contribute to spreading the virus. In absence of hygienic countermeasures, an average person infected with Covid-19 infects about 3 others on average (<a href=\"https://en.wikipedia.org/wiki/Basic_reproduction_number\" rel=\"nofollow noreferrer\">basic reproductive rate</a>). As this number is bigger than 1, the virus can spread; otherwise it would die out. Now, if 95% of those 3 would be immune thanks to the vaccine, only 0.15 people would get infected on average, which is far less than 1 (and it gets even better with hygiene). If the entire population were vaccinated instantly (with 95% success rate), Covid-19 would die out in a few weeks, simply because it could not spread anymore.</p>\n</li>\n<li><p><strong>Independence of probabilities:</strong> There is no reason to expect that the vaccine works exclusively for people who would also survive an infection. For a simple calculation, let’s assume that the vaccine is equally likely to work for everybody, i.e., independent of their chances to survive an infection¹. In that case the vaccine saves 95% of the 2.5% that would be killed by the virus and only 0.125% would die (0.05·0.025 = 0.00125).</p>\n</li>\n<li><p><strong>It’s not only about deaths</strong>. Survivors of Covid-19 can still suffer from severe long-lasting or permanent damage. This is also something you want to avoid.</p>\n</li>\n</ul>\n<hr />\n^{\n¹ This is a simplifying assumption, because whether the vaccine works for you depends on your immune system, which also influences whether you survive corona. However, probably nobody knows yet how strong this correlation is and what its direction is, i.e., whether the vaccine works better or worse for corona-sensitive people (this would also depend on the individual vaccine). The assumption is certainly closer to the truth than that the vaccine only works for those who would survive anyway.\n}\n" }, { "answer_id": 25191, "author": "Nuclear Hoagie", "author_id": 1050, "author_profile": "https://health.stackexchange.com/users/1050", "pm_score": 3, "selected": false, "text": "<p><strong>You seem to have misunderstood efficacy.</strong></p>\n<p>The 95% efficacy figure is a derived from a ratio of the number of cases in the control group (no vaccine) to the number of cases in the vaccine group. So, if both groups have 1000 people, perhaps 100 people in the control group become infected, while only 5 people in the vaccine group become infected. The vaccine efficacy is 95%, since the number of cases in the vaccine group is 95% lower than what you saw in the no-vaccine group (note that these numbers are illustrative and not actual figures).</p>\n<p>A 95% efficacy does not mean that 5% of people will die from the disease. It doesn't even mean that 5% of people will become infected. It means that 95% of people <em>who would have otherwise been infected</em> will not be. If everyone was magically vaccinated today, you would expect the number of cases to drop by 95%, and the number of deaths from the disease to drop by a similar amount. Instead of 2.5% of the population dying, it might be more like 0.13%.</p>\n<p>Note that there will be major downstream effects since viruses spread in an exponential manner - an important number you may have heard of is called R0, which represents the average number of new people an infected person will infect. A vaccine can cause R0 to drop below 1, meaning that the number of cases will dwindle over time. It's not just the case that a vaccine will prevent infection in 95% of people who would have otherwise gotten the disease, it also drastically lowers the number of people who &quot;would have otherwise gotten the disease&quot;, since 95% of vaccinated individuals won't spread the disease.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25188", "https://health.stackexchange.com", "https://health.stackexchange.com/users/20826/" ]

[ { "answer_id": 25218, "author": "Don_S", "author_id": 7166, "author_profile": "https://health.stackexchange.com/users/7166", "pm_score": 3, "selected": true, "text": "<p>There is a historical and obsolete term in English called <a href=\"https://en.wikipedia.org/wiki/Benign_hypertension\" rel=\"nofollow noreferrer\">Benign hypertension</a>. According to the <a href=\"https://en.wikipedia.org/wiki/History_of_hypertension\" rel=\"nofollow noreferrer\">History of hypertension</a> article in Wikipedia:</p>\n<blockquote>\n<p>... hypertension was often classified into &quot;malignant&quot; and &quot;benign&quot; ... Charles Friedberg's 1949 classic textbook &quot;Diseases of the Heart&quot;,[17] stated that &quot;people with 'mild benign' hypertension ... [defined as blood pressures up to levels of 210/100 mm Hg] ... need not be treated&quot;.[15] However, the tide of medical opinion was turning: it was increasingly recognised in the 1950s that <strong>&quot;benign&quot; hypertension was not harmless</strong>.[18] Over the next decade increasing evidence accumulated from actuarial reports[2][19] and longitudinal studies, such as the Framingham Heart Study,[20] that &quot;benign&quot; hypertension increased death and cardiovascular disease.</p>\n</blockquote>\n" }, { "answer_id": 25219, "author": "CowperKettle", "author_id": 2248, "author_profile": "https://health.stackexchange.com/users/2248", "pm_score": 0, "selected": false, "text": "<p>I also found this expression: <strong>habitual blood pressure</strong>. I don't know how common it is.</p>\n<p>An excerpt from <em><a href=\"https://www.cambridge.org/core/journals/amg-acta-geneticae-medicae-et-gemellologiae-twin-research/article/constitutional-disorders-of-homeostasis-the-genetic-aspect-of-diabetes-mellitus-essential-hypertension-and-obesity/F191D93B196EB0E00B234A0AC851DEB7\" rel=\"nofollow noreferrer\">Constitutional disorders of homeostasis. The genetic aspect of diabetes mellitus, essential hypertension and obesity</a></em> by Julius Bauer:</p>\n<p><a href=\"https://i.stack.imgur.com/gYHVB.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/gYHVB.png\" alt=\"enter image description here\" /></a></p>\n" } ]

[ "https://health.stackexchange.com/questions/25209", "https://health.stackexchange.com", "https://health.stackexchange.com/users/2248/" ]

[ { "answer_id": 25233, "author": "Franck Dernoncourt", "author_id": 43, "author_profile": "https://health.stackexchange.com/users/43", "pm_score": -1, "selected": false, "text": "<blockquote>\n<p>Are there vaccines which work for humans of one ethnicity, but have a lesser efficacy for humans of a different efficacy?</p>\n</blockquote>\n<p>Yes, e.g. influenza vaccine {1,2}. One reason is that some genes influence the anti-influenza antibody response, and some of these genes are correlated to the ethnicities. E.g., from {2}:</p>\n<blockquote>\n<p>In addition, we analyzed ethnically diverse individuals within the 1000 genomes project and discovered marked variations in F- and L- genotypes and CN among the various ethnic groups that may impact HV1-69-sBnAb responses. These results have immediate implications for understanding HV1-69-sBnAb responses at the individual and population level and for the design and implementation of “universal” influenza vaccine.</p>\n</blockquote>\n<hr />\n<p>References:</p>\n<ul>\n<li>{1} Watson, Corey T., Jacob Glanville, and Wayne A. Marasco. &quot;The individual and population genetics of antibody immunity.&quot; Trends in immunology 38, no. 7 (2017): 459-470. <a href=\"https://doi.org/10.1016/j.it.2017.04.003\" rel=\"nofollow noreferrer\">https://doi.org/10.1016/j.it.2017.04.003</a></li>\n<li>{2} Avnir, Yuval, Corey T. Watson, Jacob Glanville, Eric C. Peterson, Aimee S. Tallarico, Andrew S. Bennett, Kun Qin et al. &quot;IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity.&quot; Scientific Reports 6 (2016). <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754645/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754645/</a></li>\n</ul>\n" }, { "answer_id": 25254, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 3, "selected": true, "text": "<p>Some differences have been observed in certain studies, although most reviews nowadays seem focused on the genetics angle in variations to vaccine response. One such <a href=\"https://royalsocietypublishing.org/doi/pdf/10.1098/rstb.2014.0341\" rel=\"nofollow noreferrer\">(2015) review</a> cites (somewhat in passing) as evidence for known variation in ethnically linked response a <a href=\"https://pubmed.ncbi.nlm.nih.gov/8651234/\" rel=\"nofollow noreferrer\">study in Taiwan</a> that found response variation for some vaccines but not for others (the groups involved being aboriginals vs Han Chinese):</p>\n<blockquote>\n<p>children whose parents were both aborigines had lower anti-HBs [hepatitis B] mean titer than did children whose parents were both ethnic Han Chinese. Children of mixed parental origins had intermediate mean titer of anti-HBs. Serologic responses to Japanese encephalitis virus and diphtheria vaccines did not show such correlation with ethnic groups, indicating that the determinant for HBV hyporesponsiveness among the aboriginal children is distinct from that of other childhood vaccines. It was therefore concluded that host factors pertaining to ethnic origin might be responsible for the hyporesponsiveness to HBV vaccine in the aboriginal populations</p>\n</blockquote>\n<p>Such differences in the immediately quantifiable immune response were observed in other studies, <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980440/\" rel=\"nofollow noreferrer\">e.g.</a>, one in the US (on response to rubella vaccine in African-Americans vs others):</p>\n<blockquote>\n<p>individuals of African descent have significantly higher rubella-specific neutralizing antibody levels compared to individuals of European descent and/or Hispanic ethnicity</p>\n<p>Our study provides consistent evidence for racial/ethnic differences in humoral immune response following rubella vaccination.</p>\n</blockquote>\n<p>However, in the conclusion section, the authors note that some caution may be required in interpreting such results from the angle of clinical relevance:</p>\n<blockquote>\n<p>although it would be difficult to interpret our findings [...] in terms of possible protection from infection [... we] speculate that the higher neutralizing antibody levels observed for African-Americans (compared to Caucasians and/or Hispanics) in our study may potentially denote genetic and racial differences in the long-term immunity and protection following vaccination</p>\n</blockquote>\n<p>A <a href=\"https://www.jstor.org/stable/26679592\" rel=\"nofollow noreferrer\">2007 review</a> (also on genetic variations) mentions two studies for observed ethnic differences in vaccine response; both studies found differences in the response to measles vaccine <a href=\"https://pubmed.ncbi.nlm.nih.gov/15358652/\" rel=\"nofollow noreferrer\">one</a> on Bedouin vs Jewish Israelis response (to the MMR combo):</p>\n<blockquote>\n<p>Seroconversion to measles was 99% in Bedouin and 79% in Jewish children (P &lt; 0.01), and that to mumps and rubella was 92 to 100% in both groups [For the latter two presumably not a statistically significant difference; P not reported in the abstract.] Measles neutralizing antibody titers were higher in Bedouin (333 +/- 39 mIU/ml) than Jewish (122 +/- 60 mIU/ml) children (P &lt; 0.002). [...] It is not known whether genetic differences or environmental exposure accounts for these differences.</p>\n</blockquote>\n<p>the <a href=\"https://pubmed.ncbi.nlm.nih.gov/10195789\" rel=\"nofollow noreferrer\">other</a> on Inuit/Inuit vs Caucasian:</p>\n<blockquote>\n<p>Native (Innu and Inuit) schoolchildren (n = 253) had a significantly higher seropositive rate (83%) after a single dose of measles vaccine compared to Caucasian (n = 353) children (76%; p = 0.025),</p>\n</blockquote>\n<p>One interesting result to highlight perhaps is that a <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325335/\" rel=\"nofollow noreferrer\">2016 study</a> on influenza vaccine (components) found that the ethnic/race differences were mainly found in the younger groups:</p>\n<blockquote>\n<p>Race-related differences were caused by samples from younger African Americans, while results obtained with samples of aged African Americans were similar to those of aged Caucasians.</p>\n</blockquote>\n" } ]

[ "https://health.stackexchange.com/questions/25232", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7314/" ]

[ { "answer_id": 25245, "author": "Chris Rogers", "author_id": 7951, "author_profile": "https://health.stackexchange.com/users/7951", "pm_score": 1, "selected": false, "text": "<p>The article you linked has the following citation in APA format when clicking &quot;cite&quot;.</p>\n<blockquote>\n<p>Goldman, A. S., Chheda, S., Keeney, S. E., Schmalstieg, F. C., &amp; Schanler, R. J. (1994). Immunologic protection of the premature newborn by human milk. <em>Seminars in perinatology, 18</em>(6), 495–501.</p>\n</blockquote>\n<p>Google searching for the journal <em>Seminars in perinatology</em> comes up with <a href=\"https://www.sciencedirect.com/journal/seminars-in-perinatology\" rel=\"nofollow noreferrer\">https://www.sciencedirect.com/journal/seminars-in-perinatology</a></p>\n<p>Searching for the volume and issue numbers seems to indicate that the journal website <a href=\"https://www.sciencedirect.com/journal/seminars-in-perinatology/issues?page=2\" rel=\"nofollow noreferrer\">only goes back as far as Volume 19 (1995)</a> — 1 year before the article you wish to read.</p>\n<p>I would suggest that the only way you are going to get hold of a copy of this article is by <a href=\"https://service.elsevier.com/app/contact/supporthub/sciencedirect/\" rel=\"nofollow noreferrer\">contacting Elsevier</a>.</p>\n" }, { "answer_id": 25251, "author": "Franck Dernoncourt", "author_id": 43, "author_profile": "https://health.stackexchange.com/users/43", "pm_score": 0, "selected": false, "text": "<blockquote>\n<p>How do I know where to find full articles in cases such as the one I linked? Or how do I know who to contact to find a way to obtain it?</p>\n</blockquote>\n<p>If you can't find the research article via Google, you can always try to contact the authors of the article and ask for a copy of it.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25244", "https://health.stackexchange.com", "https://health.stackexchange.com/users/20888/" ]

[ { "answer_id": 25391, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 4, "selected": true, "text": "<p>We don't know, and may never know or won't know for a long time.</p>\n<p>The reason we think the recently approved mRNA vaccines are effective is due to randomized controlled trials. You take a population of people who haven't previously gotten COVID-19, give half the vaccine and half the placebo, and determine efficacy based on the ratio of subsequent infections in both groups.</p>\n<p>To answer your question, whether there is a benefit to vaccination after having COVID-19, you'd have to repeat the same trial in people who were already infected. That's...probably not going to happen. For one, any protection that prior infection provides is going to mean the &quot;control&quot; group in such a trial has a lower infection rate. This means that the overall <em>power</em> of the study will be lower for the same vaccine protection, so they trial may need to be <em>much much larger</em> to show an effect. Trials are expensive, and there's little reason to do this trial so little chance anyone will want to fund it. Companies manufacturing the vaccine want to show it works in the uninfected population, because most people still remain uninfected. Secondly, to answer conclusively that the vaccine has <strong>no</strong> benefit in people previously infected is even more difficult; it's actually statistically impossible to demonstrate this so it's necessary to set a threshold&gt;0 to compare to. It's very unusual to design trials like this for anything but safety.</p>\n<p>Overall, it's likely that people who have had COVID-19 before will still be recommended to get vaccinated. We won't have sufficient data to recommend against it, and can't be certain those people won't benefit from the vaccine. Prior knowledge of other coronaviruses causing &quot;common cold&quot; illnesses suggests that coronavirus immunity is not long-lasting; the worry is that people with generally cold-like symptoms will only get cold-like immunity to the virus, and hope that the vaccines will elicit a stronger immune response. We still don't know exactly how long vaccine protection will last (because the vaccines are still so new), but it's far more likely for us to understand the extent of vaccine protection than to understand the effect of natural infection since the former is possible in a controlled study setting.</p>\n" }, { "answer_id": 25417, "author": "gatorback", "author_id": 7446, "author_profile": "https://health.stackexchange.com/users/7446", "pm_score": 1, "selected": false, "text": "<p>As I understand the matter:</p>\n<ul>\n<li>there are case of C19 where the same person is <a href=\"https://www.cdc.gov/coronavirus/2019-ncov/your-health/reinfection.html\" rel=\"nofollow noreferrer\">re-infected after recovery</a></li>\n<li>Moderna / Pfizer vaccines tout <a href=\"https://lmgtfy.app/?q=covid%2019%20vaccine%20efficacy%20rate\" rel=\"nofollow noreferrer\">90%+ efficacy</a>.</li>\n</ul>\n<p>If this is the case and 90%+ efficacy holds for recovered patients, then it follows that yes, it is reasonable to expect a benefit of a COVID-19 vaccination if one had COVID-19.</p>\n" }, { "answer_id": 25719, "author": "ZachB", "author_id": 12748, "author_profile": "https://health.stackexchange.com/users/12748", "pm_score": 1, "selected": false, "text": "<p>There's now more data supporting a <strong>yes</strong> answer: Moderna just published results of a phase 2 trial that found that vaccinated individuals had higher antibody responses than people who had symptomatic COVID-19. See Figure 3 of <a href=\"https://www.sciencedirect.com/science/article/pii/S0264410X21001535\" rel=\"nofollow noreferrer\">Chu 2021</a>. While antibody levels aren't a direct measure of protection from disease, those two things generally correlate very well.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25390", "https://health.stackexchange.com", "https://health.stackexchange.com/users/2445/" ]

[ { "answer_id": 25393, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 3, "selected": false, "text": "<p>Roman Zieliński seems to be intentionally misleading you by making an implausible circumstance that is technically possible sound like a likely outcome. This strategy is not unusual among people who argue against vaccination, because they have very little actual science to argue based on.</p>\n<p>The Central Dogma as stated by Crick says nothing about RNA vs DNA. It does not say that RNA must enter DNA, or anything like that. It only says that information in protein sequence does not become information in nucleic acid sequence, and that information in nucleic acid sequence <em>does</em> become information in protein sequence. The historical basis of this is that there was a time in which people thought protein might be the hereditary material. We know now this is not the case, and Crick was trying to make a special point of it by giving it this &quot;central dogma&quot; name.</p>\n<p><a href=\"https://en.wikipedia.org/wiki/Telomerase\" rel=\"noreferrer\">Telomerase</a> is a special reverse transcriptase that adds a &quot;cap&quot; to human chromosomes by replicating a specific RNA it holds. It does not copy random sequences of RNA to DNA or put DNA anywhere else.</p>\n<p>Reverse transcriptase of viral origin comes from <a href=\"https://en.wikipedia.org/wiki/Retrovirus\" rel=\"noreferrer\">retroviruses</a>. You don't have these reverse transcriptases present unless you are infected with such a virus, like HIV. These viruses do not insert all RNA into the genome, they use another protein called <a href=\"https://en.wikipedia.org/wiki/Integrase#In_HIV\" rel=\"noreferrer\">integrase</a> that specifically inserts virus-derived double-stranded DNA copies into the genome. Even if this process were less specific, the only affected cells would be those already infected with HIV.</p>\n<p>Similarly, he might be making reference to <a href=\"https://en.wikipedia.org/wiki/Endogenous_retrovirus\" rel=\"noreferrer\">endogenous retroviruses</a> but these do not incorporate random RNA into the genome as he implies.</p>\n<p>If random RNA present in cells regularly inserted itself into the genome, we would have a huge huge problem <strong>all the time</strong>, not just when adding some exogenous RNA. Human cells are full of all sorts of mRNA, and if it was inserted back into the DNA genome we'd have multiple extra copies of all sorts of genes. They'd be in the wrong places, getting transcribed under the wrong promoters, ending up in the middle of other genes, etc.</p>\n" }, { "answer_id": 25397, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 3, "selected": false, "text": "<p>To supplement Bryan's answer (although I'm not going to say anything fundamentally different here), according to their proponents, mRNA vaccines are considered the safest genetic vaccines (in this integration regard) because mRNA transcription (&quot;<a href=\"https://en.wikipedia.org/wiki/Transfection\" rel=\"noreferrer\">transfection</a>&quot;) to proteins happens outside the nucleus. Quoting from a <a href=\"https://www.frontiersin.org/articles/10.3389/fimmu.2018.01963/full\" rel=\"noreferrer\">review</a></p>\n<blockquote>\n<p>mRNA vaccines do not interact with the host-cell DNA, they avoid the potential risk of genomic integration posed by DNA-based vaccines.</p>\n</blockquote>\n<p>On other hand, if you're really curious about this, DNA vaccines have also been proposed and even tried in clinical studies, and regulators are a bit more concerned about integration effects with these, even just at the local, administration-site level.</p>\n<blockquote>\n<p>employing DNA as a basis for vaccination also implicates some disadvantages. A concern in this context is the long-term persistence of DNA plasmids upon injection. Indeed, DNA persistence was shown in various preclinical studies that demonstrated the presence of plasmid DNA for up to 2 years upon IM injection with low but detectable expression and immunogenicity in a mouse model. According to the FDA, DNA persistence is not generally evident at ectopic sites in biodistribution and persistence studies, but remains detectable at the injection sites for periods exceeding 60 days. Especially in the context of this long-term persistence, the presence of foreign genetic information in the nucleus of transfected cells poses the additional risk of genomic integration into the host's chromosomes and the resulting threat of mutagenesis and oncogenesis. Despite negative results in several studies focusing on detection of DNA integration events upon IM injection in small animal models, genomic integration events were detectable following electroporation in mice demonstrating that integration represents a small risk that nevertheless needs to be considered in systems with enhanced DNA uptake. The FDA recommends integration studies to be included whenever plasmid DNA exceeding 30,000 copies per μg of host DNA persists in any tissue by study termination. The WHO advises integration studies as part of the preclinical safety program of DNA vaccines.</p>\n</blockquote>\n<p>If you read that carefully, the regulators are concerned about DNA vaccines giving the patient some form of cancer, and so they require tests showing low integration effects, however this [integration] is generally regarded as a remote risk. Note that this kind of concern didn't stop DNA vaccine from proceeding to clinical trials, e.g.</p>\n<blockquote>\n<p>DNA based vaccines were among the first to proceed to clinical trials upon the Zika crisis in 2016.</p>\n</blockquote>\n<p>In general, DNA vaccines have proven to be less effective in clinical trials in part because they need to cross two membranes (cell and then nucleus) to actually have their desired transfection effect. mRNA vaccines have required quite a bit of engineering just to achieve the former (i.e. cell entry) well enough--the whole liquid nanoparticles thing is about that.</p>\n<blockquote>\n<p>vaccination with a DNA vector alone generally leads to relatively low immunogenicity, especially in large animal models and humans. A factor that may play a role is the need for DNA vaccines to cross two cellular membranes, i.e., the plasma, as well as the nuclear membrane, in order to achieve protein expression. Of note, this does not hold true for RNA vaccines, which are translated upon crossing the plasma or endosomal membrane, respectively.</p>\n</blockquote>\n<p>On the other hand, DNA vaccine proponents <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631684/\" rel=\"noreferrer\">point out</a> that even for these the risk of integration has been overblown, and that even DNA vaccines are <em>not</em> considered <a href=\"https://en.wikipedia.org/wiki/Gene_therapy\" rel=\"noreferrer\">gene therapy</a> (i.e. host-DNA modification):</p>\n<blockquote>\n<p>DNA vaccines did not need to be evaluated by the US National Institutes of Health (NIH) Recombinant Advisory Committee prior to human clinical trials, unlike viral vectors for gene therapy. Nevertheless, significant safety studies were initially required to evaluate the possibility of integration of the plasmid DNA into the host genome. As a result of these studies for both human vaccines and for the licensed DNA vaccines for fish, as well as the many human studies with DNA vaccines that have demonstrated safety, little concern now exists regarding integration. Comparisons have stated that mRNA offers an advantage because RNA itself cannot integrate into genomic DNA without the presence of the viral elements in a retrovirus that enable such integration (reverse transcriptase and integrase). However, HERVs (human endogenous retroviruses) whose remnants are now permanent parts of human genomes as retrovirus-like sequences comprise up to 8% of the human genome. In addition, some recipients of mRNA drugs or vaccines may be already infected with a retrovirus (e.g., HIV), thus providing a theoretical means for provision of the proteins needed for integration. Nevertheless, the risk of integration remains, at this point, extremely unlikely for mRNA, even from a theoretical standpoint, nor is it any longer a significant concern for plasmid DNA. This means that mRNA does not offer any clear advantage compared to plasmid DNA in this regard. From a regulatory perspective, mRNA prophylactic vaccines appear to not be considered gene therapy products, similar to DNA vaccines before them.</p>\n</blockquote>\n<p>In other words (as Bryan said and you can see reflected in the quote above), the only (theoretically) known means by which such integration of mRNA into cell-host DNA could happen is co-infection with a retrovirus, which is regarded as an unlikely coincidence/risk. There don't seem to be any experiments that have actually tried to even demonstrate this risk, i.e. that mRNA (particularly one from a vaccine) could be integrated in the host in the presence of e.g. HIV.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25392", "https://health.stackexchange.com", "https://health.stackexchange.com/users/6604/" ]

[ { "answer_id": 25402, "author": "BrenBarn", "author_id": 17847, "author_profile": "https://health.stackexchange.com/users/17847", "pm_score": 4, "selected": true, "text": "<p><a href=\"https://elemental.medium.com/every-covid-19-vaccine-question-youll-ever-have-answered-9a0eeb334ded\" rel=\"noreferrer\">An article</a> on Medium had a Q&amp;A with various medical and public policy experts about the vaccine and its rollout. One of the questions was exactly what you asked. The answer is basically &quot;probably not but it might help against SARS and the research could lead to multi-coronavirus vaccines later.&quot; Here is the main part of the response:</p>\n<blockquote>\n<p>“We do not expect any cross-protection against other coronavirus infections since the vaccines trigger an immune response to the SARS-CoV-2 spike protein,” Belongia said. “The immune system sees this as distinct from other human coronaviruses with little or no cross-reactivity. Seasonal coronaviruses cause mild upper respiratory illness, and the focus of vaccine development has been to prevent serious illness due to Covid-19.”</p>\n</blockquote>\n<blockquote>\n<p>But we can’t completely rule out cross-strain protection against a new coronavirus that comes along later, or even SARS-CoV (which causes SARS) if it returns, said Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine and co-director of Texas Children’s Hospital Center for Vaccine Development.</p>\n</blockquote>\n<blockquote>\n<p>“There is evidence, for instance, that because of the genetic similarity between SARS-CoV and SARS-CoV-2, antibodies generated from SARS vaccines or SARS-2 vaccines can cross neutralize both viruses,” Bottazzi said. “This provides initial evidence for the development of multivalent vaccines or possibly universal coronavirus vaccines. This will be the new research moving forward.”</p>\n</blockquote>\n<p>Bottazzi's credentials are mentioned there. Belongia's are given elsewhere in the Q&amp;A piece:</p>\n<blockquote>\n<p>Edward Belongia, MD, director of the Center for Clinical Epidemiology &amp; Population Health at Marshfield Clinic Research Institute, Marshfield, Wisconsin</p>\n</blockquote>\n" }, { "answer_id": 25414, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 2, "selected": false, "text": "<blockquote>\n<p>Don't all coronaviruses share this same spike protein?</p>\n</blockquote>\n<p>No they don't, although the spikes do share a &quot;shaft&quot; fragment &quot;S2&quot; that is recognized by some anti-bodies across several coronavirues. This cross-reactivity <a href=\"https://www.cidrap.umn.edu/news-perspective/2020/11/prepandemic-coronavirus-antibodies-may-react-covid-19\" rel=\"nofollow noreferrer\">was</a> even in blood samples collected as far back as 2011, but it was at low levels.</p>\n<blockquote>\n<p>Two preliminary retrospective studies in the United Kingdom, sub-Sahara Africa, and the United States suggest that some people who were never infected with the virus that causes COVID-19 have cross-reactive antibodies against it—perhaps from previous exposure to similar human coronaviruses.</p>\n<p>[...]</p>\n<p>the researchers analyzed more than 300 blood samples collected from 2011 to 2018. While almost all samples had antibodies against coronaviruses that cause the common cold, 16 of 302 adults (5.3%) had antibodies that would recognize SARS-CoV-2—regardless of whether they had recently had a cold</p>\n</blockquote>\n<p>And in slightly more technical <a href=\"https://science.sciencemag.org/content/370/6522/1339\" rel=\"nofollow noreferrer\">detail</a>, which explains these findings, a sub-unit of the spike is indeed shared between SARS-CoV-2 and &quot;common cold&quot; coronavirues [hCov], but not all of the spike:</p>\n<blockquote>\n<p>Ng et al. report that in a cohort of 350 SARS-CoV-2–uninfected individuals, a small proportion had circulating immunoglobulin G (IgG) antibodies that could cross-react with the S2 subunit of the SARS-CoV-2 spike protein [...] By contrast, COVID-19 patients generated IgA, IgG, and IgM antibodies that recognized both the S1 and S2 subunits. The anti-S2 antibodies from SARS-CoV-2–uninfected patients showed specific neutralizing activity against both SARS-CoV-2 and SARS-CoV-2 S pseudotypes. A much higher percentage of SARS-CoV-2–uninfected children and adolescents were positive for these antibodies compared with adults. This pattern may be due to the fact that children and adolescents generally have higher hCoV infection rates and a more diverse antibody repertoire, which may explain the age distribution of COVID-19 susceptibility.</p>\n</blockquote>\n<p>(In case you wonder, from the paper's supplementary <a href=\"https://science.sciencemag.org/content/sci/suppl/2020/11/05/science.abe1107.DC1/abe1107-Ng-SM.pdf\" rel=\"nofollow noreferrer\">materials</a>, the <a href=\"https://en.wikipedia.org/wiki/Pseudotyping\" rel=\"nofollow noreferrer\">pseudotyping</a> involved &quot;Lentiviral particles pseudotyped with either SARS-CoV-2 S or Vesicular Stomatitis\nVirus glycoprotein (VSVg)&quot;; the latter was basically the control.)</p>\n<p>Diagrammatically, the S2 unit is the &quot;shaft&quot; (or the &quot;stalk&quot;) of the spike, not its tip (aka &quot;bulbous head&quot;); <a href=\"https://www.nature.com/articles/s41401-020-0485-4\" rel=\"nofollow noreferrer\">shown</a> below for SARS-CoV-2. And it is the tip (S1) that actually provides specificity to the receptor (ACE2 in the case of SARS-CoV-2, but that receptor is also targeted by the original SARS virus, albeit with a spike that is only ~75% similar to the one in SARS-CoV-2, at the genome level).</p>\n<p><a href=\"https://i.stack.imgur.com/IGnu3.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/IGnu3.png\" alt=\"enter image description here\" /></a></p>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604128/#sec3title\" rel=\"nofollow noreferrer\">In general</a></p>\n<blockquote>\n<p>Among HCoVs, the S1 subunit varies in length and amino acid sequence, while the S2 subunits share relatively high sequence homology</p>\n</blockquote>\n<p>Another <a href=\"https://www.nature.com/articles/s41598-020-78506-9\" rel=\"nofollow noreferrer\">study</a> published this December even found some cross-reactivity to the S1 &quot;tip&quot; part of the spike between antibodies for HCoV-NL63 (which also targets ACE2 like SARS-CoV1 &amp; 2, although by a spike that is very substantially genetically dissimilar). Again this cross-reactivity was slight (and actually HCoV-OC43 which targets a different receptor with its S1 has somewhat higher cross-reactivity with SARS-CoV-2 on S1):</p>\n<p><a href=\"https://i.stack.imgur.com/qOd7z.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/qOd7z.png\" alt=\"enter image description here\" /></a></p>\n<p>It's even less clear how much protection one can expect &quot;in reverse&quot; i.e. to hCoV while having SARS-CoV-2 antibodies, because this basically was not studied, as far as I can tell... (understandably since the risk of severe disease from &quot;common cold&quot; HCoVs is extremely rare, although <a href=\"https://pubmed.ncbi.nlm.nih.gov/31996093/\" rel=\"nofollow noreferrer\">not totally</a> inexistent.)</p>\n" } ]

[ "https://health.stackexchange.com/questions/25400", "https://health.stackexchange.com", "https://health.stackexchange.com/users/21045/" ]

[ { "answer_id": 25443, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 3, "selected": false, "text": "<p>The paper itself describes how this is calculated (see the Methods section), but also see this Q&amp;A at Biology.SE talking more broadly about how efficacy has been defined in these vaccine trials:</p>\n<p><a href=\"https://biology.stackexchange.com/q/96941/27148\">https://biology.stackexchange.com/q/96941/27148</a></p>\n<p>They define efficacy as the fraction of infected in the vaccine compared to placebo categories, normalized for observation time (the integral of time by number observed). Quoting from the paper you linked:</p>\n<blockquote>\n<p>Vaccine efficacy was estimated by 100×(1−IRR), where IRR is the calculated ratio of confirmed cases of Covid-19 illness per 1000 person-years of follow-up in the active vaccine group to the corresponding illness rate in the placebo group</p>\n</blockquote>\n<p>giving the equations</p>\n<p>IRR = (VaccineInfections/VaccinePersonYears/1000)/(PlaceboInfections/PlaceboPersonYears/1000)</p>\n<p>VE = 100 * (1 - IRR)</p>\n<p>If VaccinePersonYears and PlaceboPersonYears are equal, then IRR reduces to:</p>\n<p>IRR = VaccineInfections/PlaceboInfections= 39/82 = 0.48</p>\n<p>100 * (1-0.48) = 52% effective</p>\n<p>So yes, this is algebraically equivalent to the equation you give, but it's originally calculated based on the actual data, not the simplified formula. It's just likely that VaccinePersonYears and PlaceboPersonYears are sufficiently similar (remember, they're giving the vaccine and placebo 50:50 to people in the same time frame), and it's a large study with thousands of participants so drop outs and such are likely to even out statistically and reduce to the simplified form you give.</p>\n" }, { "answer_id": 25444, "author": "Chris", "author_id": 14056, "author_profile": "https://health.stackexchange.com/users/14056", "pm_score": 3, "selected": false, "text": "<p>The formula used for vaccine efficacy is as follows:</p>\n<pre><code>VE = (ARU - ARV) / ARU\n\n(VE: vaccine efficacy, ARU: attack rate in unvaccinated participants, ARV: attack rate in vaccinated participants)\n</code></pre>\n<p>This is equivalent to:</p>\n<pre><code>VE = 1 - RR\n\n(RR: Relative risk)\n</code></pre>\n<p>The attack rate is simply the number of new cases divided by the total group size.</p>\n<pre><code>ARV = 39 / 21,314 = 0.00182978\n\nARU = 82 / 21,258 = 0.00385737\n\nVE = 0.5256 which is approximately 52%\n</code></pre>\n<p>These numbers are from figure three in the linked paper, showing the number of cases in each group between the first dose and the second dose (i.e. ignoring the effect of a second dose). The vaccine efficacy rose to approximately 95% by seven days after the second dose.</p>\n<p>Your calculation produced a similar result due to the very similar group sizes (21,314 and 21,258).</p>\n<p>Importantly, the authors note:</p>\n<blockquote>\n<p>The study was not designed to assess the efficacy of a single-dose regimen.</p>\n</blockquote>\n<p>This places caveats on the conclusions that can be drawn from this study with regard to a single-dose regimen of this vaccine.</p>\n<hr />\n<p>The Wikipedia page on <a href=\"https://en.wikipedia.org/wiki/Vaccine_efficacy\" rel=\"noreferrer\">vaccine efficacy</a> provides a good summary of the measure and the associated caveats.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25442", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7166/" ]

[ { "answer_id": 25443, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 3, "selected": false, "text": "<p>The paper itself describes how this is calculated (see the Methods section), but also see this Q&amp;A at Biology.SE talking more broadly about how efficacy has been defined in these vaccine trials:</p>\n<p><a href=\"https://biology.stackexchange.com/q/96941/27148\">https://biology.stackexchange.com/q/96941/27148</a></p>\n<p>They define efficacy as the fraction of infected in the vaccine compared to placebo categories, normalized for observation time (the integral of time by number observed). Quoting from the paper you linked:</p>\n<blockquote>\n<p>Vaccine efficacy was estimated by 100×(1−IRR), where IRR is the calculated ratio of confirmed cases of Covid-19 illness per 1000 person-years of follow-up in the active vaccine group to the corresponding illness rate in the placebo group</p>\n</blockquote>\n<p>giving the equations</p>\n<p>IRR = (VaccineInfections/VaccinePersonYears/1000)/(PlaceboInfections/PlaceboPersonYears/1000)</p>\n<p>VE = 100 * (1 - IRR)</p>\n<p>If VaccinePersonYears and PlaceboPersonYears are equal, then IRR reduces to:</p>\n<p>IRR = VaccineInfections/PlaceboInfections= 39/82 = 0.48</p>\n<p>100 * (1-0.48) = 52% effective</p>\n<p>So yes, this is algebraically equivalent to the equation you give, but it's originally calculated based on the actual data, not the simplified formula. It's just likely that VaccinePersonYears and PlaceboPersonYears are sufficiently similar (remember, they're giving the vaccine and placebo 50:50 to people in the same time frame), and it's a large study with thousands of participants so drop outs and such are likely to even out statistically and reduce to the simplified form you give.</p>\n" }, { "answer_id": 25444, "author": "Chris", "author_id": 14056, "author_profile": "https://health.stackexchange.com/users/14056", "pm_score": 3, "selected": false, "text": "<p>The formula used for vaccine efficacy is as follows:</p>\n<pre><code>VE = (ARU - ARV) / ARU\n\n(VE: vaccine efficacy, ARU: attack rate in unvaccinated participants, ARV: attack rate in vaccinated participants)\n</code></pre>\n<p>This is equivalent to:</p>\n<pre><code>VE = 1 - RR\n\n(RR: Relative risk)\n</code></pre>\n<p>The attack rate is simply the number of new cases divided by the total group size.</p>\n<pre><code>ARV = 39 / 21,314 = 0.00182978\n\nARU = 82 / 21,258 = 0.00385737\n\nVE = 0.5256 which is approximately 52%\n</code></pre>\n<p>These numbers are from figure three in the linked paper, showing the number of cases in each group between the first dose and the second dose (i.e. ignoring the effect of a second dose). The vaccine efficacy rose to approximately 95% by seven days after the second dose.</p>\n<p>Your calculation produced a similar result due to the very similar group sizes (21,314 and 21,258).</p>\n<p>Importantly, the authors note:</p>\n<blockquote>\n<p>The study was not designed to assess the efficacy of a single-dose regimen.</p>\n</blockquote>\n<p>This places caveats on the conclusions that can be drawn from this study with regard to a single-dose regimen of this vaccine.</p>\n<hr />\n<p>The Wikipedia page on <a href=\"https://en.wikipedia.org/wiki/Vaccine_efficacy\" rel=\"noreferrer\">vaccine efficacy</a> provides a good summary of the measure and the associated caveats.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25453", "https://health.stackexchange.com", "https://health.stackexchange.com/users/21082/" ]

[ { "answer_id": 25531, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 2, "selected": false, "text": "<p>Summary:</p>\n<p>To answer the bounty question</p>\n<blockquote>\n<p>I am looking for a simple and straightforward answer which describes in a few sentences the mechanism by which the adaptive immune system, informed by a vaccine, would prevent infection of the epithelia of the respiratory system by a virus.</p>\n</blockquote>\n<p><em>a</em> (not <em>the</em>) mechanism by which the adaptive immune system affects respiratory viruses before cell entry is antibodies presence in mucus, which does seem to have a noticeable [counter]effect on <em>viral particle mobility</em> in mucus <em>for the specific viruses against which the host has antibodies</em>. (See last section of this answer for details.)</p>\n<p>However, I'll also that (adaptive) humoral immune system response in the mucus is hardly the end of the adaptive immune system relevance to the epithelium, as avoiding cellular infection <em>altogether</em> cannot be <em>guaranteed</em> by mucus (even with antibodies in it). The epithelium is also &quot;guarded&quot; by adaptive cellular mechanisms (e.g. T cells) that preferentially attack [epithelium] cells infected with specific viruses, as &quot;bits&quot; of these viruses are exposed on infected cells' surface via MHC I.</p>\n<hr />\n<p>Basically, the immune system <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197993/\" rel=\"nofollow noreferrer\">does function in the respiratory epithelium</a> contra to your theory, and the usual cascade of innate mechanisms triggering the adaptive ones also works in the epithelium:</p>\n<blockquote>\n<p>Several immune cell populations are resident in epithelium including CD103+ CD8+ T cells and CD103+ conventional dendritic cell populations which act as sentinel cells. Other immune cell populations including innate lymphoid cells (ILCs), mucosal associated invariant T cell (MAIT), natural killer cells (NKT) and γδ T cells are in close proximity to the epithelium. [...]</p>\n<p>The airway epithelium utilizes structural and barrier defence provided by the mucociliary escalator and their incumbent anti-microbial proteins, and intra- or epithelial-associated immune cells like resident dendritic cells, invariant natural killer T (iNKT) cells, γδ T cells and intra-epithelial lymphocytes.</p>\n</blockquote>\n<p>You're correct that respiratory viruses often have the epithelium as their preferred/evolved target, but this is also where they are usually &quot;defeated&quot; (in fact if they're not defeated there, the host is usually in big trouble). Furthermore, experimentally interfering with this signalling cascade results in much worse outcomes--see emphasized part on dendritic cells further below.</p>\n<blockquote>\n<p>Upon binding sialic acid receptors on the epithelial cell surface, IAV are internalised via receptor-mediated endocytosis [...] The host cell begins sensing IAV as soon as it is internalised, utilising pathogen recognition receptors (PRRs), primarily the Toll-like receptors (TLRs) and RNA-sensing RIG-I–like receptors (RLRs), such as retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA-5) [...]</p>\n</blockquote>\n<p>Those (TLRs, RLRs etc.) are indeed part of the innate immune system, but that's not the end of the story:</p>\n<blockquote>\n<p>Activation of type I interferons is the key consequence of intracellular recognition of IAV infection by TLRs and RLRs. These cytokines bind to the IFN-α/β receptor (IFNAR) on infected as well as neighbouring cells and induces the transcription of a large group of genes (interferon stimulated genes or ISG) whose main task is to limit spread of infection. [...] In epithelial cells, type I IFN has the additional task of acting as an early warning system, communicating viral threat between infected and uninfected cells. [...]</p>\n</blockquote>\n<p>But epithelial cells also signal &quot;the invasion&quot; through a more specific mechanism: type III interferons (IFN-λ). In any case:</p>\n<blockquote>\n<p>Activation of both type I and III IFN results in induction of hundreds of ISGs. ISGs trigger apoptosis, shut down protein synthesis and activate key components of the innate and adaptive immune systems, including antigen presentation and production of cytokines involved in activation of T, B, and natural killer (NK) cells.</p>\n</blockquote>\n<p>So, thanks to interferons the adaptive immune system does get triggered, even in the epithelium. Furthermore</p>\n<blockquote>\n<p>There is substantial cross-talk between epithelial and immune cells sequestered in the epithelium. CD103+cDCs continuously sample the airway via extended dendrites and respond to chemokines and cytokines (including type I and III IFNs) and DAMPs secreted by IAV- infected epithelial cells</p>\n<p><strong>Intra-epithelial dendritic cells are essential to generate protective IAV-specific CD8+ T cells; mice lacking this DC subset succumb to severe disease and impaired viral clearance.</strong></p>\n</blockquote>\n<p>Basically, not having the adaptive immune system active/functional in the epithelium is usually fatal for the host, even in relation to &quot;mere&quot; influenza infection. <a href=\"https://en.wikipedia.org/wiki/Dendritic_cell\" rel=\"nofollow noreferrer\">DCs</a> &quot;act as messengers between the innate and the adaptive immune systems.&quot;</p>\n<p>Also, at least the epithelium of the lungs has additional defenses (iNKT cells). If you look at <a href=\"https://en.wikipedia.org/wiki/Natural_killer_T_cell\" rel=\"nofollow noreferrer\">their Wikipedia page</a>, the NKT cells are somewhat of a hybrid of adaptive (T cells) and innate (NK cells) immune system; they in turn release a plethora of signalling molecules &quot;large quantities of interferon gamma, IL-4, and granulocyte-macrophage colony-stimulating factor, as well as multiple other cytokines and chemokines (such as IL-2, IL-13, IL-17, IL-21, and TNF-alpha)&quot; that activate the adaptive immune system, although I think NKTs mostly respond to bacterial rather than viral infections. (I could be wrong though on this.) But if they do &quot;get triggered&quot;, e.g. in a co-infection scenario (not uncommon in pneumonias), NKTs seem to help with the viral [part of the] infection as well (going back to quoting from the review paper [1st link]):</p>\n<blockquote>\n<p>In the mouse, presence, and exogenous activation, of lung iNKT cells by α-GalCer, protects against lethal H1N1 and H3N2 influenza in prophylactic settings.</p>\n</blockquote>\n<p>But to reiterate again the more common mechanisms:</p>\n<blockquote>\n<p>The epithelial cells’ attempt to clear IAV results in inevitable tissue injury, in part because of collateral damage from the accompanying innate immune response and direct induction of apoptosis by IAV, <strong>but also because cytotoxic T cells will eventually kill cells with IAV peptides presented on their MHC class I molecules</strong>. If epithelial cells are not killed they undergo apoptosis or de-differentiation. If IAV reaches the alveolar epithelium, various injurious events can occur. [...]</p>\n</blockquote>\n<p>Speaking of that last (emphasized) issue, the influenza viruses <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548845/\" rel=\"nofollow noreferrer\">&quot;try pretty hard&quot;</a> to make themselves invisible to the MHC I pathway.</p>\n<blockquote>\n<p>we showed that infection of several cell types, including epithelial A549 cells, with a panel of IAV and IBV viruses downregulated the surface MHC-I expression on IAV/IBV-infected cells during the late stages of influenza virus infection in vitro. [...] Importantly, the two viruses utilized two distinct mechanisms for MHC-I downregulation.</p>\n</blockquote>\n<p>If MHC I (triggering T cells) wasn't a problem for them, why would they have evolved these camouflage/countermeasures?</p>\n<hr />\n<p>Since you confusion (or argument) seems to be whether Cytotoxic CD8+ T cells are or aren't part of the adaptive immune system (they are), let's side-step such categorization discussion and simply <a href=\"https://www.nature.com/articles/s41586-020-2814-7\" rel=\"nofollow noreferrer\">observe</a> that a Covid-19 mRNA vaccine trains them so that significant fraction recognize the virus bits:</p>\n<blockquote>\n<p>Fractions of RBD-specific IFNγ+ CD8+ T cells reached up to several per cent of total peripheral blood CD8+ T cells in immunized individuals</p>\n</blockquote>\n<p>RBD here means the receptor binding domain (protein) of the specific virus (SARS-CoV-2 in this case).</p>\n<p>(The same is true for vaccines that target the full spike protein, which are the ones actually approved by regulators, although the corresponding <a href=\"https://www.medrxiv.org/content/10.1101/2020.12.09.20245175v1.full\" rel=\"nofollow noreferrer\">paper(s)</a> still seem to be in the preprint stage. The latter paper speaks of &quot;S-specific CD8+&quot;, meaning SARS-CoV-2 spike-specific.)</p>\n<hr />\n<p>Now, if you want to focus/ask only what happens <em>before any cell entry</em>, the humoral immune system is present in mucus. It (also) has innate (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752725/\" rel=\"nofollow noreferrer\">e.g.</a> mucins, lactoferrin) and adaptive components; antibodies <em>are</em> present in the mucus.</p>\n<p>Antibodies importance (relative to innate mechanism) in mucus has been less studied, but their presence in mucus has surely been (commonly) observed, and some studies comparing viral movement speeds in mucus do suggest that specific antibodies slow down the corresponding viruses in mucus <a href=\"https://erj.ersjournals.com/content/49/1/1601709\" rel=\"nofollow noreferrer\">e.g.</a>:</p>\n<blockquote>\n<p>To investigate whether trapping of influenza in airway mucus can be attributed primarily to haemagglutinin binding to mucin-associated sialic acid, we prepared VLPs fluorescently labelled internally using HIV-1 GAG-mCherry capsid proteins in the core, and expressing both neuraminidase and haemagglutinin from H1N1 (influenza A/PR/8/34) (WT-Inf), or the same neuraminidase and haemagglutinin that has the sialic acid-binding domain deleted (ΔSAB-Inf) and hence cannot bind directly to mucins. Interestingly, both WT-Inf and ΔSAB-Inf were trapped in airway mucus to a similar extent as H1N1 and H3N2, with roughly 98% of WT-Inf and 97% of ΔSAB-Inf immobilised in airway mucus and average diffusivities ∼1700- and ∼1100-fold lower than expected speeds in buffer, respectively (figure 1b, online supplementary movies S4 and S5). [...]</p>\n<p>Using whole-virus ELISA assays, we detected substantial quantities of endogenous IgG and IgA against influenza in airway mucus (data not shown), as well as against both WT-Inf and ΔSAB-Inf VLPs. [...] This leaves open the possibility that influenza-specific antibodies in airway mucus may immobilise virions by cross-linking the antibody–virus complex to mucus constituents, such as mucins. We sought to measure virus and VLP mobility in airway mucus devoid of antibodies; however, we were not able to adequately remove Ig by dialysis, possibly due to membrane clogging, and mucus secretions isolated from air–liquid interface cultures of bronchial epithelial cells did not produce a sufficiently rigid matrix to immobilise mucoadhesive latex nanoparticles. We also attempted to “saturate” the mucus–antibody barrier by mixing &gt;20-fold more unlabelled than labelled influenza viruses into airway mucus prior to adding labelled viruses, and still observed no discernible difference in the trapping of the labelled influenza viruses. Therefore, <strong>we investigated whether the lack of binding antibodies in mucus correlates to greater virus mobility by tracking HIV VLPs that were prepared similarly to the influenza VLP, but expressing HIV YU2 gp160. We found no detectable HIV-binding IgG or IgA in airway mucus (figure 1d, e), and HIV VLPs exhibited markedly greater diffusivity in airway mucus (figure 1b, online supplementary movie S6; p&lt;0.05), with &gt;45% of HIV VLPs classified as mobile and ∼10-fold higher ensemble effective diffusity than WT-Inf and ΔSAB-Inf. HIV VLP mobility was similar to that of PS-PEG in the same airway mucus samples (data not shown).</strong></p>\n<p>Together, these results demonstrate that influenza virus can be trapped in human airway mucus without binding to sialic acids on mucins, in good agreement with the evidence that human influenza viruses possess haemagglutinin that preferentially binds α2,6-linked sialic acids on the airway epithelium rather than α2,3-linked sialic acids on mucins. Trapping of influenza in human airway mucus can probably be attributed to the presence of influenza-binding antibodies that can cross-link individual virions to the mucus mesh network. <strong>Importantly, adhesive interactions between the array of pathogen-bound antibodies and mucus gel provide a universal strategy that enables the otherwise relatively nonadaptive and nonspecific biochemistry and microstructure of mucus secretions across different mucosal surfaces to be fortified with adaptive antibodies against an ever-changing spectrum of pathogens.</strong></p>\n<p><a href=\"https://i.stack.imgur.com/fIgYe.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/fIgYe.png\" alt=\"enter image description here\" /></a></p>\n</blockquote>\n<p>But before you get too excited about this finding, remember that the immune systems is &quot;defense in depth&quot;, some virus particles will make it through the mucus, even if you do have specific antibodies against them there; this is when\nthe cellular mechanisms kick in. There's no one mechanism that is going to be 100% foolproof.</p>\n" }, { "answer_id": 30768, "author": "Peter Bernhard", "author_id": 21148, "author_profile": "https://health.stackexchange.com/users/21148", "pm_score": 1, "selected": false, "text": "<p>Trying to understand your question:</p>\n<p>a. Can vaccination, by inducing antibodies, prevent infection, i.e. shield off the virus before it enters any cell, in locations that seem to be inaccessible for antibodies and lymphocytes?</p>\n<p>b. If innate immunity successfully hinders infection and renders vaccination superfluous and redundant can the latter be considered effective?</p>\n<p>c. Considering vaccination being able to prevent symptomatic or severe illness but not infectivity and epidemic spread what is the role of innate versus adaptive immunity in both, prevention of disease and epidemic spread?</p>\n<p>If c. were correct understanding one prospective answer might be: Whereas, indeed, innate immunity prevents the spread of the virus, adaptive immunity prevents symptomatic disease. Another intricacy: In case innate immunity cannot prevent infection and epidemic spread, why doesn't vaccine/adaptive immunity come in stopping the spread - if it successfully prevents symptomatic disease? I see that point to your question and that's why I am out to publish my personal view, see inverted text at the end.</p>\n<p>Answering:</p>\n<p>According to not very basic textbook knowledge antibodies/immunoglobulins are able to cross the blood tissue barrier. Immunoglobulins' sizes permit the evasion from blood and the invasion of interstitium/tissue/epithelia. IgE is a known example of specialized immunoglobulins that take care of outer epithelia. There do exist local lymphocytes, <a href=\"https://en.wikipedia.org/wiki/Langerhans_cell\" rel=\"nofollow noreferrer\">Langerhans cells</a>, that make it across the vessel wall under regular circumstances, no inflammation or infection needed beforehand; they are in place.</p>\n<p>In fact, not IgE, but IgA seems tailored for mucosa.</p>\n<p>&quot;IgA is the 2nd most common serum Ig. IgA is the major class of Ig in secretions - tears, saliva, colostrum, mucus. Since it is found in secretions secretory IgA is important in local (mucosal) immunity. Normally IgA does not fix complement, unless aggregated. IgA can bind(...) to some cells - PMN's and some lymphocytes.&quot;\n<a href=\"http://www.microbiologybook.org/mayer/IgStruct2000.htm\" rel=\"nofollow noreferrer\">http://www.microbiologybook.org/mayer/IgStruct2000.htm</a></p>\n<p>While the question whether antibodies not only cross the blood-epithelial barrier but the blood-air-barrier as well is to be answered to the affirmative, there is a debate about the extent to which this holds for the fencing off of respiratory at the blood-air-barrier (not blood-tissue barrier), which makes your question non-trivial:</p>\n<p>&quot;...Translocation of large serum proteins (e.g., albumin, IgG) via paracellular routes by restricted passive diffusion does not appear to be the primary route, although under pathological conditions such passive diffusion may become the main route of protein leak.&quot; <a href=\"https://journals.physiology.org/doi/pdf/10.1152/ajplung.00235.2002\" rel=\"nofollow noreferrer\">Protein transport across the lung epithelial barrier\nKim/Malik, 2003</a></p>\n<p>As the quote above might suggstest the response of the adaptive immune system might seem late or reluctant, in accordance with the intention of your question I assume. Adaptive immunity might set in when infective spread has already happened. Even if antibodies have not waned they do not seem to be very willing to fit in where or when needed, in the mucosa.</p>\n<p>On the other hand, imagine just one single epithelial cell the infection of which adaptive immunity could not prevent. If any shedding of virions from that one cell will encounter antibodies, and any lysis of that one cell will immunize local lymphocytes in between infected single cells of the epithelial you may consider vaccination/adaptive immunity effective.</p>\n<p>Effectiveness of adaptive immunity may not being perturbed if it allows the transfection of one single cell as this signal of invasion is needed to trigger defence cascade.</p>\n<p>Antibodies in between cells of epithelia and local lymphocytes, &quot;Langerhans cells&quot;, may not be able to &quot;prevent infection&quot;, however in principle, these elements of the adaptive immune response are able to prevent any further spreading.</p>\n<p>Regarding the argument that there are no antibodies in the mucus, on the outside to prevent any &quot;one cell&quot; being invaded by virus one must admit that, in principle, this goes for the innate immune system as well as far as it is based on cell signaling, too.\nIn other words: adaptive immunity needs initiating infection to start a signaling cascade and does not prevent such infection; it would logically stop itself from starting. However, same applies to the interferon system of innate immune system that needs infection to start the interferon cascade.</p>\n<p>*The following is my personal opinion that tries to answer your question &quot;in deep&quot;.\n&quot;How can vaccines be effective against respiratory viruses when it is the innate immune system that is the primary response to such pathogens?&quot;</p>\n<p>Yes, you are right in some way. Indeed, there seem to be many variants or even species of respiratory viruses where vaccines are able to prevent symptomatic disease, however are not able to restrict viruses in replication sufficiently in order to prevent epidemic spread and non-symptomatic infection.</p>\n<p>For instance, he Omicron variant of the Corona virus CoV-19, arguably a new serotype, may well illustrate a yet non-accepted principle of mutational viral evolution that pertains to balancing the innate and the adaptive immune system, assuming that the virus renders itself, paradoxically, more vulnerable to the innate system or other factors of the non-adaptive innate immunity, thereby not contacting the adaptive immune system and circumventing it, not even causing &quot;much&quot; immunity. This principle of escape from immunitiy is different from the strategy of hiding away by turning silent, especially by integrating, as retro viridae do, into the genome. My point is that from a single cell, compare the above, there might leak out into the air, lung a very large amount for infectious virus particle, so there is no latency at all. There is only a restriction by the innate immunity, that, in the intention of your question, is &quot;just&quot; not strong enough to stop infectivity and shedding of infectious virus by isolated cells.</p>\n<p>Counterintuitively mutations turn out to be successful that render the virus less pathogenic and/or less infectious because the virus refrains from defending itself against the innate response as it is rewarded by non-immunizing and non-coping with existing adaptive immunity. It is the price the adaptive defence pays out to the virus for the virus weakening itself to a point of being beaten in first line by the innate immune system. In that mutational to and fro there are limits: for the virus there is a minimum of infectivity that must be &quot;left over&quot;. Otherwise there will be some remake of the weakened.</p>\n<p>Thus, vaccines may tend not to prevent the infectious spread. This is no trivial posting: the adaptive immune systeme accepts infectivity that is not pathogenic, not intrusive enough for to be bothered. The being late and the ineffectiveness is the price mutations certain respiratory viruses are being awarded if they let themselves be restricted to no invasiveness of the body, thus, in principle, harmlessness, paired with high incidental rates and epidemic spread. If there is hiding away of retro viruses, there is retreat of certain respiratory viruses.</p>\n<p>The principle of evolution I hereby postulate thus pertains to the selective advantage for the virus that lies in not inducing immunity by not encountering antibodies and/or antigen presenting cells. Stated principle is that adaptive immunity, hence vaccination, by evolutionary art, does not fill the gap of infectiousness, epidemic infectivity, that innate immunity may or may not open.</p>\n<p>It is the selective advantage viral evolution must have: the spread. Let me explain the spread. To spread is the reward adaptive immunity does not take away. Only then viral mutations find succes in letting the viruses being dampened, at the verge of extinction, by the interferon system of innate immnity. Thus vaccination, by principle, in many cases can only prevent disease, not infection.</p>\n<p>Known mechanisms of adaptive immunity seen anew show that adaptive immunity &quot;comes late&quot;:</p>\n<ol>\n<li><p>Antigen presenting cells take up antigens that are derived from already infected, then succumbed, lysed cells.</p>\n</li>\n<li><p>T-cytotoxic cells await the apoptotic signal of already infected cells - most important, as an argument: specific T-Killer cells are known to become &quot;anergic&quot; when encountering their target, they have to wait until they get primed in lymph nodes, they come very late</p>\n</li>\n<li><p>The only defense of the adaptive system seems to be &quot;neutralizing&quot; antibodies that throw themselve in between the virus and the cell, theoretically. But then: they wane very quickly, and in my opinion, this regular waning fast of antibodies is coherent with the stated principle of reluctancy of the adaptive response.</p>\n</li>\n</ol>\n<p>What regards the viral turning itself either more or less exposed to the innate system of immunity I name two mechanisms, there may be more:</p>\n<ol>\n<li><p>Syncytialization</p>\n</li>\n<li><p>Interferon signalling</p>\n</li>\n</ol>\n<p>Respiratory Syncytial Virus by its name exemplifies: like Corona-Viridae this respiratory virus induces syncytialisation, i.e. fusion of one infected cell with others that surround it. While this is considered circumventing the adaptive immune system as far as more and more cells are infected without virus entering the interstitial or humoural space in between cells it is - in terms of my arguing - a mechanism of balancing and modulation: known are viral mutations that change binding of viral factors to syncytialization promoters of the host cell thus changing the degree of pushing back the entry of adaptive immune response.</p>\n<p>As far as respiratory virus mentioned in your question use the way of syncytialization of infection one can say vaccines will be dampened. Vaccination sets in only as soon as there is lysis of syncytia (for the APS to uptake antigen, after &quot;persistence ended&quot; and/or MHC-presentation by syncytia with preexisting immunity).</p>\n<p>Very intriguing in the context of your question is the barely popular fact of the placenta more or less being a syncytia that prevents the adaptive system of immunity from working, as it is said to block contacting the father's foreign antigens. Viral genes in the humane genome are held responsible. Analogy permitted, the pneumocytes type II, target cells of CoV, are very extended in form and appear as large extended shields. It is rare knowledge that CoV induces their syncytialisation, and if the latter is considered &quot;infection&quot;, it is hidden and cannot be coped with by adaptive response nor vaccination. Thus, if induced by viral infection, syncytia of the lung cells can not only be seen as hideaways from the adaptive immune system but also as,in principle, fencing off a separate room - the mucosal room - which antibodies and lymphocytes cannot enter, which refers to your question.</p>\n<p>Some references:</p>\n<p>[Liangyu Lin et al. 2021],1<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114657/\" rel=\"nofollow noreferrer\">4</a>Syncytia formation during SARS-CoV-2 lung infection: a disastrous unity to eliminate lymphocytes</p>\n<p><a href=\"https://medicalsciences.stackexchange.com/posts/30768/edit\">Cattin-Ortolá et al.</a><a href=\"https://pubmed.ncbi.nlm.nih.gov/34504087/\" rel=\"nofollow noreferrer\">https://pubmed.ncbi.nlm.nih.gov/34504087/</a>\nSequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation*</p>\n<p>&quot;Placental transfer - IgG is the only class of Ig that crosses the placenta. Transfer is mediated by a receptor on placental cells for the Fc region of IgG.&quot;</p>\n<p>The Omikron variant of Cov might be an example of a presumably highly infectious, (in many cases) but non-symptomatic disease that still manages to cause the formation of antibodies. According to my reasoning and in the intention of your question I assume their building up might be weak, which, in result, has already be confirmed by re-infection with Omicron - within same season - being reported in Great Britan. Even if there were adapted vaccination against a respiratory virus variant, according to my reasoning, it should &quot;not work well&quot; against infectivity, non-pathgenicity only following suit the non-contacting of the realms of adaptive immunity, to affirmatively answer your question and putting my reasoning up for test in the near future, hopefully.</p>\n<p>I will reference all this by tomorrow if allowed to.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25514", "https://health.stackexchange.com", "https://health.stackexchange.com/users/5371/" ]

[ { "answer_id": 25531, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 2, "selected": false, "text": "<p>Summary:</p>\n<p>To answer the bounty question</p>\n<blockquote>\n<p>I am looking for a simple and straightforward answer which describes in a few sentences the mechanism by which the adaptive immune system, informed by a vaccine, would prevent infection of the epithelia of the respiratory system by a virus.</p>\n</blockquote>\n<p><em>a</em> (not <em>the</em>) mechanism by which the adaptive immune system affects respiratory viruses before cell entry is antibodies presence in mucus, which does seem to have a noticeable [counter]effect on <em>viral particle mobility</em> in mucus <em>for the specific viruses against which the host has antibodies</em>. (See last section of this answer for details.)</p>\n<p>However, I'll also that (adaptive) humoral immune system response in the mucus is hardly the end of the adaptive immune system relevance to the epithelium, as avoiding cellular infection <em>altogether</em> cannot be <em>guaranteed</em> by mucus (even with antibodies in it). The epithelium is also &quot;guarded&quot; by adaptive cellular mechanisms (e.g. T cells) that preferentially attack [epithelium] cells infected with specific viruses, as &quot;bits&quot; of these viruses are exposed on infected cells' surface via MHC I.</p>\n<hr />\n<p>Basically, the immune system <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197993/\" rel=\"nofollow noreferrer\">does function in the respiratory epithelium</a> contra to your theory, and the usual cascade of innate mechanisms triggering the adaptive ones also works in the epithelium:</p>\n<blockquote>\n<p>Several immune cell populations are resident in epithelium including CD103+ CD8+ T cells and CD103+ conventional dendritic cell populations which act as sentinel cells. Other immune cell populations including innate lymphoid cells (ILCs), mucosal associated invariant T cell (MAIT), natural killer cells (NKT) and γδ T cells are in close proximity to the epithelium. [...]</p>\n<p>The airway epithelium utilizes structural and barrier defence provided by the mucociliary escalator and their incumbent anti-microbial proteins, and intra- or epithelial-associated immune cells like resident dendritic cells, invariant natural killer T (iNKT) cells, γδ T cells and intra-epithelial lymphocytes.</p>\n</blockquote>\n<p>You're correct that respiratory viruses often have the epithelium as their preferred/evolved target, but this is also where they are usually &quot;defeated&quot; (in fact if they're not defeated there, the host is usually in big trouble). Furthermore, experimentally interfering with this signalling cascade results in much worse outcomes--see emphasized part on dendritic cells further below.</p>\n<blockquote>\n<p>Upon binding sialic acid receptors on the epithelial cell surface, IAV are internalised via receptor-mediated endocytosis [...] The host cell begins sensing IAV as soon as it is internalised, utilising pathogen recognition receptors (PRRs), primarily the Toll-like receptors (TLRs) and RNA-sensing RIG-I–like receptors (RLRs), such as retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA-5) [...]</p>\n</blockquote>\n<p>Those (TLRs, RLRs etc.) are indeed part of the innate immune system, but that's not the end of the story:</p>\n<blockquote>\n<p>Activation of type I interferons is the key consequence of intracellular recognition of IAV infection by TLRs and RLRs. These cytokines bind to the IFN-α/β receptor (IFNAR) on infected as well as neighbouring cells and induces the transcription of a large group of genes (interferon stimulated genes or ISG) whose main task is to limit spread of infection. [...] In epithelial cells, type I IFN has the additional task of acting as an early warning system, communicating viral threat between infected and uninfected cells. [...]</p>\n</blockquote>\n<p>But epithelial cells also signal &quot;the invasion&quot; through a more specific mechanism: type III interferons (IFN-λ). In any case:</p>\n<blockquote>\n<p>Activation of both type I and III IFN results in induction of hundreds of ISGs. ISGs trigger apoptosis, shut down protein synthesis and activate key components of the innate and adaptive immune systems, including antigen presentation and production of cytokines involved in activation of T, B, and natural killer (NK) cells.</p>\n</blockquote>\n<p>So, thanks to interferons the adaptive immune system does get triggered, even in the epithelium. Furthermore</p>\n<blockquote>\n<p>There is substantial cross-talk between epithelial and immune cells sequestered in the epithelium. CD103+cDCs continuously sample the airway via extended dendrites and respond to chemokines and cytokines (including type I and III IFNs) and DAMPs secreted by IAV- infected epithelial cells</p>\n<p><strong>Intra-epithelial dendritic cells are essential to generate protective IAV-specific CD8+ T cells; mice lacking this DC subset succumb to severe disease and impaired viral clearance.</strong></p>\n</blockquote>\n<p>Basically, not having the adaptive immune system active/functional in the epithelium is usually fatal for the host, even in relation to &quot;mere&quot; influenza infection. <a href=\"https://en.wikipedia.org/wiki/Dendritic_cell\" rel=\"nofollow noreferrer\">DCs</a> &quot;act as messengers between the innate and the adaptive immune systems.&quot;</p>\n<p>Also, at least the epithelium of the lungs has additional defenses (iNKT cells). If you look at <a href=\"https://en.wikipedia.org/wiki/Natural_killer_T_cell\" rel=\"nofollow noreferrer\">their Wikipedia page</a>, the NKT cells are somewhat of a hybrid of adaptive (T cells) and innate (NK cells) immune system; they in turn release a plethora of signalling molecules &quot;large quantities of interferon gamma, IL-4, and granulocyte-macrophage colony-stimulating factor, as well as multiple other cytokines and chemokines (such as IL-2, IL-13, IL-17, IL-21, and TNF-alpha)&quot; that activate the adaptive immune system, although I think NKTs mostly respond to bacterial rather than viral infections. (I could be wrong though on this.) But if they do &quot;get triggered&quot;, e.g. in a co-infection scenario (not uncommon in pneumonias), NKTs seem to help with the viral [part of the] infection as well (going back to quoting from the review paper [1st link]):</p>\n<blockquote>\n<p>In the mouse, presence, and exogenous activation, of lung iNKT cells by α-GalCer, protects against lethal H1N1 and H3N2 influenza in prophylactic settings.</p>\n</blockquote>\n<p>But to reiterate again the more common mechanisms:</p>\n<blockquote>\n<p>The epithelial cells’ attempt to clear IAV results in inevitable tissue injury, in part because of collateral damage from the accompanying innate immune response and direct induction of apoptosis by IAV, <strong>but also because cytotoxic T cells will eventually kill cells with IAV peptides presented on their MHC class I molecules</strong>. If epithelial cells are not killed they undergo apoptosis or de-differentiation. If IAV reaches the alveolar epithelium, various injurious events can occur. [...]</p>\n</blockquote>\n<p>Speaking of that last (emphasized) issue, the influenza viruses <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548845/\" rel=\"nofollow noreferrer\">&quot;try pretty hard&quot;</a> to make themselves invisible to the MHC I pathway.</p>\n<blockquote>\n<p>we showed that infection of several cell types, including epithelial A549 cells, with a panel of IAV and IBV viruses downregulated the surface MHC-I expression on IAV/IBV-infected cells during the late stages of influenza virus infection in vitro. [...] Importantly, the two viruses utilized two distinct mechanisms for MHC-I downregulation.</p>\n</blockquote>\n<p>If MHC I (triggering T cells) wasn't a problem for them, why would they have evolved these camouflage/countermeasures?</p>\n<hr />\n<p>Since you confusion (or argument) seems to be whether Cytotoxic CD8+ T cells are or aren't part of the adaptive immune system (they are), let's side-step such categorization discussion and simply <a href=\"https://www.nature.com/articles/s41586-020-2814-7\" rel=\"nofollow noreferrer\">observe</a> that a Covid-19 mRNA vaccine trains them so that significant fraction recognize the virus bits:</p>\n<blockquote>\n<p>Fractions of RBD-specific IFNγ+ CD8+ T cells reached up to several per cent of total peripheral blood CD8+ T cells in immunized individuals</p>\n</blockquote>\n<p>RBD here means the receptor binding domain (protein) of the specific virus (SARS-CoV-2 in this case).</p>\n<p>(The same is true for vaccines that target the full spike protein, which are the ones actually approved by regulators, although the corresponding <a href=\"https://www.medrxiv.org/content/10.1101/2020.12.09.20245175v1.full\" rel=\"nofollow noreferrer\">paper(s)</a> still seem to be in the preprint stage. The latter paper speaks of &quot;S-specific CD8+&quot;, meaning SARS-CoV-2 spike-specific.)</p>\n<hr />\n<p>Now, if you want to focus/ask only what happens <em>before any cell entry</em>, the humoral immune system is present in mucus. It (also) has innate (<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752725/\" rel=\"nofollow noreferrer\">e.g.</a> mucins, lactoferrin) and adaptive components; antibodies <em>are</em> present in the mucus.</p>\n<p>Antibodies importance (relative to innate mechanism) in mucus has been less studied, but their presence in mucus has surely been (commonly) observed, and some studies comparing viral movement speeds in mucus do suggest that specific antibodies slow down the corresponding viruses in mucus <a href=\"https://erj.ersjournals.com/content/49/1/1601709\" rel=\"nofollow noreferrer\">e.g.</a>:</p>\n<blockquote>\n<p>To investigate whether trapping of influenza in airway mucus can be attributed primarily to haemagglutinin binding to mucin-associated sialic acid, we prepared VLPs fluorescently labelled internally using HIV-1 GAG-mCherry capsid proteins in the core, and expressing both neuraminidase and haemagglutinin from H1N1 (influenza A/PR/8/34) (WT-Inf), or the same neuraminidase and haemagglutinin that has the sialic acid-binding domain deleted (ΔSAB-Inf) and hence cannot bind directly to mucins. Interestingly, both WT-Inf and ΔSAB-Inf were trapped in airway mucus to a similar extent as H1N1 and H3N2, with roughly 98% of WT-Inf and 97% of ΔSAB-Inf immobilised in airway mucus and average diffusivities ∼1700- and ∼1100-fold lower than expected speeds in buffer, respectively (figure 1b, online supplementary movies S4 and S5). [...]</p>\n<p>Using whole-virus ELISA assays, we detected substantial quantities of endogenous IgG and IgA against influenza in airway mucus (data not shown), as well as against both WT-Inf and ΔSAB-Inf VLPs. [...] This leaves open the possibility that influenza-specific antibodies in airway mucus may immobilise virions by cross-linking the antibody–virus complex to mucus constituents, such as mucins. We sought to measure virus and VLP mobility in airway mucus devoid of antibodies; however, we were not able to adequately remove Ig by dialysis, possibly due to membrane clogging, and mucus secretions isolated from air–liquid interface cultures of bronchial epithelial cells did not produce a sufficiently rigid matrix to immobilise mucoadhesive latex nanoparticles. We also attempted to “saturate” the mucus–antibody barrier by mixing &gt;20-fold more unlabelled than labelled influenza viruses into airway mucus prior to adding labelled viruses, and still observed no discernible difference in the trapping of the labelled influenza viruses. Therefore, <strong>we investigated whether the lack of binding antibodies in mucus correlates to greater virus mobility by tracking HIV VLPs that were prepared similarly to the influenza VLP, but expressing HIV YU2 gp160. We found no detectable HIV-binding IgG or IgA in airway mucus (figure 1d, e), and HIV VLPs exhibited markedly greater diffusivity in airway mucus (figure 1b, online supplementary movie S6; p&lt;0.05), with &gt;45% of HIV VLPs classified as mobile and ∼10-fold higher ensemble effective diffusity than WT-Inf and ΔSAB-Inf. HIV VLP mobility was similar to that of PS-PEG in the same airway mucus samples (data not shown).</strong></p>\n<p>Together, these results demonstrate that influenza virus can be trapped in human airway mucus without binding to sialic acids on mucins, in good agreement with the evidence that human influenza viruses possess haemagglutinin that preferentially binds α2,6-linked sialic acids on the airway epithelium rather than α2,3-linked sialic acids on mucins. Trapping of influenza in human airway mucus can probably be attributed to the presence of influenza-binding antibodies that can cross-link individual virions to the mucus mesh network. <strong>Importantly, adhesive interactions between the array of pathogen-bound antibodies and mucus gel provide a universal strategy that enables the otherwise relatively nonadaptive and nonspecific biochemistry and microstructure of mucus secretions across different mucosal surfaces to be fortified with adaptive antibodies against an ever-changing spectrum of pathogens.</strong></p>\n<p><a href=\"https://i.stack.imgur.com/fIgYe.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/fIgYe.png\" alt=\"enter image description here\" /></a></p>\n</blockquote>\n<p>But before you get too excited about this finding, remember that the immune systems is &quot;defense in depth&quot;, some virus particles will make it through the mucus, even if you do have specific antibodies against them there; this is when\nthe cellular mechanisms kick in. There's no one mechanism that is going to be 100% foolproof.</p>\n" }, { "answer_id": 30768, "author": "Peter Bernhard", "author_id": 21148, "author_profile": "https://health.stackexchange.com/users/21148", "pm_score": 1, "selected": false, "text": "<p>Trying to understand your question:</p>\n<p>a. Can vaccination, by inducing antibodies, prevent infection, i.e. shield off the virus before it enters any cell, in locations that seem to be inaccessible for antibodies and lymphocytes?</p>\n<p>b. If innate immunity successfully hinders infection and renders vaccination superfluous and redundant can the latter be considered effective?</p>\n<p>c. Considering vaccination being able to prevent symptomatic or severe illness but not infectivity and epidemic spread what is the role of innate versus adaptive immunity in both, prevention of disease and epidemic spread?</p>\n<p>If c. were correct understanding one prospective answer might be: Whereas, indeed, innate immunity prevents the spread of the virus, adaptive immunity prevents symptomatic disease. Another intricacy: In case innate immunity cannot prevent infection and epidemic spread, why doesn't vaccine/adaptive immunity come in stopping the spread - if it successfully prevents symptomatic disease? I see that point to your question and that's why I am out to publish my personal view, see inverted text at the end.</p>\n<p>Answering:</p>\n<p>According to not very basic textbook knowledge antibodies/immunoglobulins are able to cross the blood tissue barrier. Immunoglobulins' sizes permit the evasion from blood and the invasion of interstitium/tissue/epithelia. IgE is a known example of specialized immunoglobulins that take care of outer epithelia. There do exist local lymphocytes, <a href=\"https://en.wikipedia.org/wiki/Langerhans_cell\" rel=\"nofollow noreferrer\">Langerhans cells</a>, that make it across the vessel wall under regular circumstances, no inflammation or infection needed beforehand; they are in place.</p>\n<p>In fact, not IgE, but IgA seems tailored for mucosa.</p>\n<p>&quot;IgA is the 2nd most common serum Ig. IgA is the major class of Ig in secretions - tears, saliva, colostrum, mucus. Since it is found in secretions secretory IgA is important in local (mucosal) immunity. Normally IgA does not fix complement, unless aggregated. IgA can bind(...) to some cells - PMN's and some lymphocytes.&quot;\n<a href=\"http://www.microbiologybook.org/mayer/IgStruct2000.htm\" rel=\"nofollow noreferrer\">http://www.microbiologybook.org/mayer/IgStruct2000.htm</a></p>\n<p>While the question whether antibodies not only cross the blood-epithelial barrier but the blood-air-barrier as well is to be answered to the affirmative, there is a debate about the extent to which this holds for the fencing off of respiratory at the blood-air-barrier (not blood-tissue barrier), which makes your question non-trivial:</p>\n<p>&quot;...Translocation of large serum proteins (e.g., albumin, IgG) via paracellular routes by restricted passive diffusion does not appear to be the primary route, although under pathological conditions such passive diffusion may become the main route of protein leak.&quot; <a href=\"https://journals.physiology.org/doi/pdf/10.1152/ajplung.00235.2002\" rel=\"nofollow noreferrer\">Protein transport across the lung epithelial barrier\nKim/Malik, 2003</a></p>\n<p>As the quote above might suggstest the response of the adaptive immune system might seem late or reluctant, in accordance with the intention of your question I assume. Adaptive immunity might set in when infective spread has already happened. Even if antibodies have not waned they do not seem to be very willing to fit in where or when needed, in the mucosa.</p>\n<p>On the other hand, imagine just one single epithelial cell the infection of which adaptive immunity could not prevent. If any shedding of virions from that one cell will encounter antibodies, and any lysis of that one cell will immunize local lymphocytes in between infected single cells of the epithelial you may consider vaccination/adaptive immunity effective.</p>\n<p>Effectiveness of adaptive immunity may not being perturbed if it allows the transfection of one single cell as this signal of invasion is needed to trigger defence cascade.</p>\n<p>Antibodies in between cells of epithelia and local lymphocytes, &quot;Langerhans cells&quot;, may not be able to &quot;prevent infection&quot;, however in principle, these elements of the adaptive immune response are able to prevent any further spreading.</p>\n<p>Regarding the argument that there are no antibodies in the mucus, on the outside to prevent any &quot;one cell&quot; being invaded by virus one must admit that, in principle, this goes for the innate immune system as well as far as it is based on cell signaling, too.\nIn other words: adaptive immunity needs initiating infection to start a signaling cascade and does not prevent such infection; it would logically stop itself from starting. However, same applies to the interferon system of innate immune system that needs infection to start the interferon cascade.</p>\n<p>*The following is my personal opinion that tries to answer your question &quot;in deep&quot;.\n&quot;How can vaccines be effective against respiratory viruses when it is the innate immune system that is the primary response to such pathogens?&quot;</p>\n<p>Yes, you are right in some way. Indeed, there seem to be many variants or even species of respiratory viruses where vaccines are able to prevent symptomatic disease, however are not able to restrict viruses in replication sufficiently in order to prevent epidemic spread and non-symptomatic infection.</p>\n<p>For instance, he Omicron variant of the Corona virus CoV-19, arguably a new serotype, may well illustrate a yet non-accepted principle of mutational viral evolution that pertains to balancing the innate and the adaptive immune system, assuming that the virus renders itself, paradoxically, more vulnerable to the innate system or other factors of the non-adaptive innate immunity, thereby not contacting the adaptive immune system and circumventing it, not even causing &quot;much&quot; immunity. This principle of escape from immunitiy is different from the strategy of hiding away by turning silent, especially by integrating, as retro viridae do, into the genome. My point is that from a single cell, compare the above, there might leak out into the air, lung a very large amount for infectious virus particle, so there is no latency at all. There is only a restriction by the innate immunity, that, in the intention of your question, is &quot;just&quot; not strong enough to stop infectivity and shedding of infectious virus by isolated cells.</p>\n<p>Counterintuitively mutations turn out to be successful that render the virus less pathogenic and/or less infectious because the virus refrains from defending itself against the innate response as it is rewarded by non-immunizing and non-coping with existing adaptive immunity. It is the price the adaptive defence pays out to the virus for the virus weakening itself to a point of being beaten in first line by the innate immune system. In that mutational to and fro there are limits: for the virus there is a minimum of infectivity that must be &quot;left over&quot;. Otherwise there will be some remake of the weakened.</p>\n<p>Thus, vaccines may tend not to prevent the infectious spread. This is no trivial posting: the adaptive immune systeme accepts infectivity that is not pathogenic, not intrusive enough for to be bothered. The being late and the ineffectiveness is the price mutations certain respiratory viruses are being awarded if they let themselves be restricted to no invasiveness of the body, thus, in principle, harmlessness, paired with high incidental rates and epidemic spread. If there is hiding away of retro viruses, there is retreat of certain respiratory viruses.</p>\n<p>The principle of evolution I hereby postulate thus pertains to the selective advantage for the virus that lies in not inducing immunity by not encountering antibodies and/or antigen presenting cells. Stated principle is that adaptive immunity, hence vaccination, by evolutionary art, does not fill the gap of infectiousness, epidemic infectivity, that innate immunity may or may not open.</p>\n<p>It is the selective advantage viral evolution must have: the spread. Let me explain the spread. To spread is the reward adaptive immunity does not take away. Only then viral mutations find succes in letting the viruses being dampened, at the verge of extinction, by the interferon system of innate immnity. Thus vaccination, by principle, in many cases can only prevent disease, not infection.</p>\n<p>Known mechanisms of adaptive immunity seen anew show that adaptive immunity &quot;comes late&quot;:</p>\n<ol>\n<li><p>Antigen presenting cells take up antigens that are derived from already infected, then succumbed, lysed cells.</p>\n</li>\n<li><p>T-cytotoxic cells await the apoptotic signal of already infected cells - most important, as an argument: specific T-Killer cells are known to become &quot;anergic&quot; when encountering their target, they have to wait until they get primed in lymph nodes, they come very late</p>\n</li>\n<li><p>The only defense of the adaptive system seems to be &quot;neutralizing&quot; antibodies that throw themselve in between the virus and the cell, theoretically. But then: they wane very quickly, and in my opinion, this regular waning fast of antibodies is coherent with the stated principle of reluctancy of the adaptive response.</p>\n</li>\n</ol>\n<p>What regards the viral turning itself either more or less exposed to the innate system of immunity I name two mechanisms, there may be more:</p>\n<ol>\n<li><p>Syncytialization</p>\n</li>\n<li><p>Interferon signalling</p>\n</li>\n</ol>\n<p>Respiratory Syncytial Virus by its name exemplifies: like Corona-Viridae this respiratory virus induces syncytialisation, i.e. fusion of one infected cell with others that surround it. While this is considered circumventing the adaptive immune system as far as more and more cells are infected without virus entering the interstitial or humoural space in between cells it is - in terms of my arguing - a mechanism of balancing and modulation: known are viral mutations that change binding of viral factors to syncytialization promoters of the host cell thus changing the degree of pushing back the entry of adaptive immune response.</p>\n<p>As far as respiratory virus mentioned in your question use the way of syncytialization of infection one can say vaccines will be dampened. Vaccination sets in only as soon as there is lysis of syncytia (for the APS to uptake antigen, after &quot;persistence ended&quot; and/or MHC-presentation by syncytia with preexisting immunity).</p>\n<p>Very intriguing in the context of your question is the barely popular fact of the placenta more or less being a syncytia that prevents the adaptive system of immunity from working, as it is said to block contacting the father's foreign antigens. Viral genes in the humane genome are held responsible. Analogy permitted, the pneumocytes type II, target cells of CoV, are very extended in form and appear as large extended shields. It is rare knowledge that CoV induces their syncytialisation, and if the latter is considered &quot;infection&quot;, it is hidden and cannot be coped with by adaptive response nor vaccination. Thus, if induced by viral infection, syncytia of the lung cells can not only be seen as hideaways from the adaptive immune system but also as,in principle, fencing off a separate room - the mucosal room - which antibodies and lymphocytes cannot enter, which refers to your question.</p>\n<p>Some references:</p>\n<p>[Liangyu Lin et al. 2021],1<a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114657/\" rel=\"nofollow noreferrer\">4</a>Syncytia formation during SARS-CoV-2 lung infection: a disastrous unity to eliminate lymphocytes</p>\n<p><a href=\"https://medicalsciences.stackexchange.com/posts/30768/edit\">Cattin-Ortolá et al.</a><a href=\"https://pubmed.ncbi.nlm.nih.gov/34504087/\" rel=\"nofollow noreferrer\">https://pubmed.ncbi.nlm.nih.gov/34504087/</a>\nSequences in the cytoplasmic tail of SARS-CoV-2 Spike facilitate expression at the cell surface and syncytia formation*</p>\n<p>&quot;Placental transfer - IgG is the only class of Ig that crosses the placenta. Transfer is mediated by a receptor on placental cells for the Fc region of IgG.&quot;</p>\n<p>The Omikron variant of Cov might be an example of a presumably highly infectious, (in many cases) but non-symptomatic disease that still manages to cause the formation of antibodies. According to my reasoning and in the intention of your question I assume their building up might be weak, which, in result, has already be confirmed by re-infection with Omicron - within same season - being reported in Great Britan. Even if there were adapted vaccination against a respiratory virus variant, according to my reasoning, it should &quot;not work well&quot; against infectivity, non-pathgenicity only following suit the non-contacting of the realms of adaptive immunity, to affirmatively answer your question and putting my reasoning up for test in the near future, hopefully.</p>\n<p>I will reference all this by tomorrow if allowed to.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25542", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7951/" ]

[ { "answer_id": 25550, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 3, "selected": false, "text": "<p>Even if you just read a bit further in the article, there is a quote:</p>\n<blockquote>\n<p>“The Norwegian Medicines Agency has communicated, prior to the vaccination, that when vaccinating the oldest and sickest, it is expected that deaths will occur in a time-related context with vaccination. This does not mean that there is a causal link between vaccination and death. We have also, in connection with the reported deaths, conveyed that it is possible that common and known side effects of the vaccines may have been a contributing factor to a serious course or fatal outcome.”</p>\n</blockquote>\n<p>Some frail elderly people were vaccinated. These are the type of people that die all the time, they are frail and elderly. For just a thought experiment, imagine you vaccinate 10000 people that have a 1% likelihood to die this week. You'd expect 100 of them to die within a week of being vaccinated. It would be false to attribute causality to the vaccine in this circumstance, but it would still show up in the numbers discussed.</p>\n<p>As said in the article, so far we have no idea if the vaccine is causal in any of these deaths. Perhaps in a very frail person it could (we know in healthy people there are some mild side effects; sometimes mild effects are serious for the frail) so we shouldn't vaccinate those people, but no matter what it's important to realize that tens of thousands of people die every day around the world; if we vaccinate everyone we should expect thousands of deaths to occur post-vaccine even with no vaccine-related increase.</p>\n" }, { "answer_id": 25570, "author": "WHO's NoToOldRx4CovidIsMurder", "author_id": 17268, "author_profile": "https://health.stackexchange.com/users/17268", "pm_score": 2, "selected": false, "text": "<p>Yes, they're normal. No, these problems were not unexpected. In the big trial of one of the first two vaccines, 6 people died. <strong>Four who received placebo</strong> and two received the vaccine. <em>But none of the six died from something that the vaccine is believed likely to have caused or prevented</em>.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25547", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7049/" ]

[ { "answer_id": 25550, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 3, "selected": false, "text": "<p>Even if you just read a bit further in the article, there is a quote:</p>\n<blockquote>\n<p>“The Norwegian Medicines Agency has communicated, prior to the vaccination, that when vaccinating the oldest and sickest, it is expected that deaths will occur in a time-related context with vaccination. This does not mean that there is a causal link between vaccination and death. We have also, in connection with the reported deaths, conveyed that it is possible that common and known side effects of the vaccines may have been a contributing factor to a serious course or fatal outcome.”</p>\n</blockquote>\n<p>Some frail elderly people were vaccinated. These are the type of people that die all the time, they are frail and elderly. For just a thought experiment, imagine you vaccinate 10000 people that have a 1% likelihood to die this week. You'd expect 100 of them to die within a week of being vaccinated. It would be false to attribute causality to the vaccine in this circumstance, but it would still show up in the numbers discussed.</p>\n<p>As said in the article, so far we have no idea if the vaccine is causal in any of these deaths. Perhaps in a very frail person it could (we know in healthy people there are some mild side effects; sometimes mild effects are serious for the frail) so we shouldn't vaccinate those people, but no matter what it's important to realize that tens of thousands of people die every day around the world; if we vaccinate everyone we should expect thousands of deaths to occur post-vaccine even with no vaccine-related increase.</p>\n" }, { "answer_id": 25570, "author": "WHO's NoToOldRx4CovidIsMurder", "author_id": 17268, "author_profile": "https://health.stackexchange.com/users/17268", "pm_score": 2, "selected": false, "text": "<p>Yes, they're normal. No, these problems were not unexpected. In the big trial of one of the first two vaccines, 6 people died. <strong>Four who received placebo</strong> and two received the vaccine. <em>But none of the six died from something that the vaccine is believed likely to have caused or prevented</em>.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25608", "https://health.stackexchange.com", "https://health.stackexchange.com/users/1155/" ]

[ { "answer_id": 25630, "author": "BrenBarn", "author_id": 17847, "author_profile": "https://health.stackexchange.com/users/17847", "pm_score": 3, "selected": true, "text": "<p>The closest thing I have found to this is a tool called the <a href=\"https://docs.google.com/spreadsheets/d/16K1OQkLD4BjgBdO8ePj6ytf-RpPMlJ6aXFg3PrIQBbQ/edit#gid=519189277\" rel=\"nofollow noreferrer\">COVID-19 Airborne Transmission Estimator</a>. It is basically a spreadsheet on which you can tweak various parameters and get an estimate of the number of people infected at a given gathering. It was developed last summer by a professor at the University of Colorado; he is not a doctor but is a chemist who studies aerosols. Here is <a href=\"http://cires1.colorado.edu/jimenez/\" rel=\"nofollow noreferrer\">a page about his research group</a> and here is <a href=\"https://cires.colorado.edu/news/covid-19-airborne-transmission-tool-available\" rel=\"nofollow noreferrer\">a brief press release about the tool</a>. As far as I can tell there has been no peer review of this model and it seems to be still quite provisional.</p>\n<p>The Spanish newspaper El Pais wrote <a href=\"https://english.elpais.com/society/2020-10-28/a-room-a-bar-and-a-class-how-the-coronavirus-is-spread-through-the-air.html\" rel=\"nofollow noreferrer\">an article</a> which describes some examples of risk based on the model. National Geographic also did <a href=\"https://www.nationalgeographic.com/science/2020/08/how-to-measure-risk-airborne-coronavirus-your-office-classroom-bus-ride-cvd/\" rel=\"nofollow noreferrer\">an article</a> showing some graphs of risk in various situations based on the model.</p>\n<p>Those articles are useful because the spreadsheet itself can be somewhat overwhelming to use. The model requires values for certain parameters that the average person has no real knowledge about, such as the volume of air breathed in by a person in an hour and the rate at which the air in the space is replaced with fresh air from an external source; as well as parameters that are not definitively known or may be quite variable, such as the number of infectious doses of the virus exhaled per hour.</p>\n<p>Thus the model comes with a major &quot;garbage in, garbage out&quot; caveat. Also, of course, it is not so much an analysis of experimental data as a mathematical model, and it relies on many simplifying assumptions. For instance, it does not consider the details of airflow within the space, although there is evidence that that can be important. Nonetheless, it is the only model I've seen that attempts to push the numbers all the way through to direct estimates of infection. The author is quoted in the National Geographic article as saying, &quot;We do not have a ton of information, but we cannot afford to wait for a ton of information.&quot;</p>\n" }, { "answer_id": 28884, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 1, "selected": false, "text": "<p>I'll note that a more recent &quot;room simulation&quot; paper was published <a href=\"https://science.sciencemag.org/content/372/6549/1439\" rel=\"nofollow noreferrer\">in <em>Science</em></a> (a top journal). This paper was basically based on a Fangcang Hospital simulation (200 people in a 500m² x 10m high hall--see supplementary material) and lots of data on infectious dose estimates, mask filtration efficiency etc., but neither the authors of the paper nor the <em>Science</em> editors could conclude from it something &quot;in layperson's terms&quot; about some other setting like a restaurant, a bus etc. The editors' best attempt at summarizing the results were something like:</p>\n<blockquote>\n<p>In indoor settings, it is impossible to avoid breathing in air that someone else has exhaled, and in hospital situations where the virus concentration is the highest, even the best-performing masks used without other protective gear such as hazmat suits will not provide adequate protection.</p>\n</blockquote>\n<p>Meh. A slightly more daring simulation study (in terms of conclusions) was <a href=\"https://www.pnas.org/content/118/17/e2018995118/tab-figures-data\" rel=\"nofollow noreferrer\">published in PNAS</a>. They offered this summary graph for a classroom and respectively a nursing home:</p>\n<p><a href=\"https://i.stack.imgur.com/Bp7fw.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/Bp7fw.png\" alt=\"enter image description here\" /></a></p>\n<p>Basically such models are informed (by real-world parameter estimates) but not really calibrated, since you can't easily check their predictions conform to some experimental results.</p>\n<p>I'm personally pretty skeptical of the predictions in this latter (PNAS) study. It almost looks engineered to predict that a classroom is safe <em>without</em> masks at normal occupancy (6ft distance) and natural ventilation, for the duration of a fairly normal school day (6-7 hrs)... and with (cloth) masks, basically indefinitely. The paper's statement:</p>\n<blockquote>\n<p>For normal occupancy and without masks, the safe time after an infected individual enters the classroom is 1.2 h for natural ventilation and 7.2 h with mechanical ventilation, according to the transient bound, SI Appendix, Eq. S8. Even with cloth mask use (pm=0.3), these bounds are increased dramatically, to 8 and 80 h, respectively. Assuming 6 h of indoor time per day, a school group wearing masks with adequate ventilation would thus be safe for longer than the recovery time for COVID-19 (7 d to 14 d), and school transmissions would be rare. We stress, however, that our predictions are based on the assumption of a “quiet classroom”, where resting respiration (Cq=30) is the norm. Extended periods of physical activity, collective speech, or singing would lower the time limit by an order of magnitude (Fig. 2).</p>\n</blockquote>\n<p>But a recent <a href=\"https://www.cdc.gov/mmwr/volumes/70/wr/mm7035e2.htm\" rel=\"nofollow noreferrer\">CDC case study</a> found that a teacher who at least occasionally didn't wear a mask when lecturing very likely was the source of an outbreak, infecting (in two days) all the children in the front row, and some/fewer in the back, in a nearly similar setup, i.e. 6ft distance [supposedly] maintained, even though the children supposedly were wearing masks, and the windows were open; this is with the delta variant though.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25621", "https://health.stackexchange.com", "https://health.stackexchange.com/users/20619/" ]

[ { "answer_id": 25769, "author": "Blue Various", "author_id": 16820, "author_profile": "https://health.stackexchange.com/users/16820", "pm_score": 2, "selected": false, "text": "<p>First, we should focus on &quot;ivermectin plus covid19 or a virus that mimics covid19.\nFor now, the <a href=\"https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy\" rel=\"nofollow noreferrer\">FDA</a> recognizes ivermectin as an antiviral drug. Therefore, the comparison should be &quot;antiviral drug + covid19 or covid19-mimicking virus&quot;.</p>\n<p>The <a href=\"https://covid19criticalcare.com/\" rel=\"nofollow noreferrer\">FLCCC</a> may have a bit of a bias because they are enthusiastic proponents of ivermectin, but their <a href=\"https://covid19criticalcare.com/wp-content/uploads/2020/11/FLCCC-Ivermectin-in-the-prophylaxis-and-treatment-of-COVID-19.pdf\" rel=\"nofollow noreferrer\">report</a> has the following description;</p>\n<blockquote>\n<p>Arevalo et al investigated in a murine model infected with a type 2 family RNA coronavirus\nsimilar to SARS-CoV-2, (mouse hepatitis virus), the response to 500 mcg/kg of ivermectin vs.\nplacebo (Arevalo et al., 2020). The study included 40 infected mice, with 20 treated with ivermectin,\n20 with phosphate buffered saline, and then 16 uninfected control mice that were also given phosphate\nbuffered saline. At day 5, all the mice were euthanized to obtain tissues for examination and viral load\nassessment. The 20 non-ivermectin treated infected mice all showed severe hepatocellular necrosis\nsurrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic\nviral load (52,158 AU), while in the ivermectin treated mice a much lower viral load was measured\n(23,192 AU; p&lt;0.05), with only few livers in the ivermectin treated mice showing histopathological\ndamage such that the differences between the livers from the uninfected control mice were not\nstatistically significant. <br><br>\nDias De Melo and colleagues recently posted the results of a study they did with golden\nhamsters that were intranasally inoculated with SARS-CoV-2 virus, and at the time of the infection,\nthe animals also received a single subcutaneous injection of ivermectin at a dose of 0.4mg/kg on day 1\n(de Melo et al., 2020). Control animals received only the physiologic solution. They found the\nfollowing among the ivermectin treated hamsters; a dramatic reduction in anosmia (33.3% vs 83.3%,\np=.03) which was also sex-dependent in that the male hamsters exhibited a reduction in clinical score\nwhile the treated female hamsters failed to show any sign of anosmia. They also found significant\nreductions in cytokine concentrations in the nasal turbinate’s and lungs of the treated animals despite\nthe lack of apparent differences in viral titers</p>\n</blockquote>\n<p>Based on this statement, the following two papers seem to fit our purpose. However, it should be noted that these are preprints.</p>\n<ul>\n<li><a href=\"https://www.biorxiv.org/content/10.1101/2020.11.02.363242v1\" rel=\"nofollow noreferrer\">Arevalo et al</a></li>\n<li><a href=\"https://www.biorxiv.org/content/10.1101/2020.11.21.392639v1\" rel=\"nofollow noreferrer\">de Melo et al</a></li>\n</ul>\n<p>Arevalo et al has following description;</p>\n<blockquote>\n<p>However, experimental conditions with SARS-CoV2 are not easily available in research laboratories due to biosecurity reasons, thus having in vivo preclinical data is not always easy.</p>\n</blockquote>\n<p><strong>Isn't this description the answer to your question?</strong> If it is clinical research, there is no need to contain infected animals in a laboratory. It must be quite difficult to control a virus that is considered more dangerous than the flu. Also, in the case of influenza, the pharmaceutical companies are probably planning and conducting trials over a long period of time. In contrast, MSD does not seem to be active in the coronary indication of ivermectin.</p>\n" }, { "answer_id": 27478, "author": "WHO's NoToOldRx4CovidIsMurder", "author_id": 17268, "author_profile": "https://health.stackexchange.com/users/17268", "pm_score": -1, "selected": false, "text": "<p>Ivermectin is already FDA-approved, which means the FDA has decided it had been proven by MERCK to be safe and effective. But only some large cities and regions, smaller countries, and smaller institutions have ruled that it's appropriate or safe and effective <em>for CoViD-19</em>, plus India, which wavers. With around 10,000 people a day dying of CoViD-19, it makes sense to move research forward quickly, as is being done with the vaccines. And ivermectin investigators have moved quickly. There are already results from 96 ivermectin COVID-19 studies available, including 59 peer reviewed, and 59 clinical trials with results comparing treatment and control groups, in <em>homo sapiens</em>. Humans are animals. So reasons including those of Arevalo that @Blue-Various cites, plus the results from the many clinical trials that have run and are ongoing, explain the limited lab animal testing. However I do find 6 <em>lab animal</em> studies, which are identified as such in the 96 ivermectin v. COVID-19 studies I find in the preprint and main literature, which I have listed below, from most recent to oldest. (<a href=\"https://twitter.com/CovidAnalysis\" rel=\"nofollow noreferrer\">Fork of</a>; I included all papers/studies excepting the discredited/fraudulent Surgisphere/Desai and López-Medina ones.)</p>\n<p>4/29 Ahsan et al., Cureus, doi:10.7759/cureus.14761 (Peer Reviewed) death, ↓50.0%, p=0.03 Clinical Variants, Characteristics, and Outcomes Among COVID-19 Patients: A Case Series Analysis at a Tertiary Care Hospital in Karachi, Pakistan</p>\n<p>4/19 DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2021-001655 (Review) (Peer Reviewed) review Anti-inflammatory activity of ivermectin in late-stage COVID-19 may reflect activation of systemic glycine receptors</p>\n<p>4/17 Loue et al., J. Infectious Diseases and Epidemiology, doi:10.23937/2474-3658/1510202 (Peer Reviewed) death, ↓70.0%, p=0.34 Ivermectin and COVID-19 in Care Home: Case Report</p>\n<p>4/16 Morgenstern et al., medRxiv, doi:10.1101/2021.04.10.21255248 (Preprint) hosp., ↓80.0%, p=0.50 Retrospective cohort study of Ivermectin as a SARS-CoV-2 pre-exposure prophylactic method in Healthcare Workers</p>\n<p>4/14 Seet et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.04.035 (Peer Reviewed) severe case, ↓49.8%, p=0.01 Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial</p>\n<p>4/10 Bello et al., Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1911857 (Peer Reviewed) Elucidation of the inhibitory activity of ivermectin with host nuclear importin α and several SARS-CoV-2 targets</p>\n<p>4/3 Turkia, M., Research Gate (Review) (Preprint) review A timeline of ivermectin-related events in the COVID-19 pandemic</p>\n<p>4/1 Mourya et al., Int. J. Health and Clinical Research (Peer Reviewed) viral+, ↓89.4%, p&lt;0.0001 Comparative Analytical Study of Two Different Drug Regimens in Treatment of Covid 19 Positive Patients in Index Medical College Hospital and Research Center, Indore, India</p>\n<p>3/30 Wehbe et al., Front. Immunol., doi:10.3389/fimmu.2021.663586 (Review) (Peer Reviewed) review Repurposing Ivermectin for COVID-19: Molecular Aspects and Therapeutic Possibilities</p>\n<p>3/30 Chahla et al., Research Square, doi:10.21203/rs.3.rs-495945/v1 (original preprint 3/30) (Preprint) no disch., ↓86.9%, p=0.004 Cluster Randomised Trials - Ivermectin Repurposing For COVID-19 Treatment Of Outpatients With Mild Disease In Primary Health Care Centers</p>\n<p>3/29 Kow et al., Pharmacological Reports, doi:10.1007/s43440-021-00245-z (Peer Reviewed) (meta analysis) meta-analysis The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis</p>\n<p>3/26 Tanioka et al., medRxiv, doi:10.1101/2021.03.26.21254377 (Preprint) death, ↓88.2%, p=0.002 Why COVID-19 is not so spread in Africa: How does Ivermectin affect it?</p>\n<p>3/25 Udofia et al., Network Modeling Analysis in Health Informatics and Bioinformatics, doi:10.1007/s13721-021-00299-2 (Peer Reviewed) In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV</p>\n<p>3/25 Choudhury et al., Future Medicine, doi:10.2217/fvl-2020-0342 (Peer Reviewed) Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach</p>\n<p>3/25 Huvemek Press Release (Preprint) no improv., ↓31.6%, p=0.28 Kovid-19 - Huvemek® Phase 2 clinical trial</p>\n<p>3/24 Yagisawa et al., The Japanese Journal of Antibiotics, 74-1, Mar 2021 (Review) (Peer Reviewed) review Global trends in clinical studies of ivermectin in COVID-19</p>\n<p>3/21 Emmerich et al., Int. J. Environ. Res. Public Health, doi:10.3390/ijerph18073371 (Peer Reviewed) Comparisons between the Neighboring States of Amazonas and Pará in Brazil in the Second Wave of COVID-19 Outbreak and a Possible Role of Early Ambulatory Treatment</p>\n<p>3/18 Del Franco et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1008 (Peer Reviewed) Ivermectin in Long-Covid Patients: A Retrospective Study</p>\n<p>3/12 Roy et al., medRxiv, doi:10.1101/2021.03.08.21252883 (Preprint) recov. time, ↓5.6%, p=0.87 Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study</p>\n<p>3/11 Nardelli et al., Signa Vitae, doi:10.22514/sv.2021.043 (Peer Reviewed) (meta analysis) death, ↓79.5%, p&lt;0.0001 Crying wolf in time of Corona: the strange case of ivermectin and hydroxychloroquine. Is the fear of failure withholding potential life-saving treatment from clinical use?</p>\n<p>3/11 Scheim et al., OSF Preprints (Preprint) (meta analysis) meta-analysis Ivermectin sales in Valle del Cauca, Colombia, patterns of AEs, and other background re López-Medina et al. 2021</p>\n<p>3/11 Bryant et al., Research Square, doi:10.21203/rs.3.rs-317485/v1 (OSF preprints 3/11) (Preprint) (meta analysis) death, ↓68.0%, p=0.006 Ivermectin for prevention and treatment of COVID-19 infection: a systematic review and meta-analysis</p>\n<p>3/11 Scheim et al., OSF Preprints (Preprint) (meta analysis) meta-analysis Protocol violations in López-Medina et al.: 38 switched ivermectin (IVM) and placebo doses, failure of blinding, widespread IVM sales OTC in Cali, and nearly identical AEs for the IVM and control groups</p>\n<p>3/10 Yesilbag et al., Virus Research, doi:10.1016/j.virusres.2021.198384 (Peer Reviewed) (In Vitro) in vitro Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro</p>\n<p>3/9 Pott-Junior et al., Toxicology Reports, doi:10.1016/j.toxrep.2021.03.003 (Peer Reviewed) ventilation, ↓85.2%, p=0.25 Use of ivermectin in the treatment of Covid-19: a pilot trial</p>\n<p>3/8 Chamie-Quintero et al., OSF Preprints (Preprint) Ivermectin for COVID-19 in Peru: 14-fold reduction in nationwide excess deaths, p=.002 for effect by state, then 13-fold increase after ivermectin use restricted</p>\n<p>3/8 Guzman et al., medRxiv, doi:10.1101/2021.03.04.21252084 (Preprint) Factors associated with increased mortality in critically ill COVID-19 patients in a Mexican public hospital: the other faces of health system oversaturation</p>\n<p>3/8 Galan et al., Pathogens and Global Health, doi:10.1080/20477724.2021.1890887 (Peer Reviewed) Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection</p>\n<p>3/5 Descotes, J., ImmunoSafe Consultance (Preprint) safety analysis Medical Safety of Ivermectin</p>\n<p>3/1 Saha et al., Structural Chemistry, doi:10.1007/s11224-021-01776-0 (preprint 3/1) (Peer Reviewed) The Binding mechanism of ivermectin and levosalbutamol with spike protein of SARS-CoV-2</p>\n<p>2/23 Gonzalez et al., medRxiv, doi:10.1101/2021.02.18.21252037 (Peer Reviewed) death, ↓14.4%, p=1.00 Efficacy and safety of Ivermectin and Hydroxychloroquine in patients with severe COVID-19. A randomized controlled trial</p>\n<p>2/20 BIRD Meeting 20th February 2021 (News) news BIRD Meeting 20th February 2021</p>\n<p>2/16 Elalfy et al., J. Med. Virol., doi:10.1002/jmv.26880 (Peer Reviewed) viral+, ↓86.9%, p&lt;0.0001 Effect of a combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-1</p>\n<p>2/15 Behera et al., Research Square, doi:10.21203/rs.3.rs-208785/v1 (Preprint) cases, ↓83.0%, p&lt;0.001 Prophylactic role of ivermectin in SARS-CoV-2 infection among healthcare workers</p>\n<p>2/12 Biber et al., medRxiv, doi:10.1101/2021.05.31.21258081 (results 2/12/21) (Preprint) hosp., ↓70.2%, p=0.34 Favorable outcome on viral load and culture viability using Ivermectin in early treatment of non-hospitalized patients with mild COVID-19, A double-blind, randomized placebo-controlled trial</p>\n<p>2/10 Lima-Morales (Peer Reviewed) death, ↓77.7%, p&lt;0.001 Effectiveness of a multidrug therapy consisting of ivermectin, azithromycin, montelukast and acetylsalicylic acid to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico</p>\n<p>2/2 Mohan et al., Research Square, doi:10.21203/rs.3.rs-191648/v1 (Preprint) no recov., ↓62.5%, p=0.27 Ivermectin in mild and moderate COVID-19 (RIVET-COV): a randomized, placebo-controlled trial</p>\n<p>1/29 Cobos-Campos et al., Clin. Res. Trials, 2021, doi:10.15761/CRT.1000333 (Peer Reviewed) (meta analysis) meta-analysis Potential use of ivermectin for the treatment and profilaxis of SARS-CoV-2 infection: Efficacy of ivermectin for SARS-CoV-2</p>\n<p>1/27 Castaneda-Sabogal et al., medRxiv, doi:10.1101/2021.01.26.21250420 (Preprint) (meta analysis) meta-analysis Outcomes of Ivermectin in the treatment of COVID-19: a systematic review and meta-analysis</p>\n<p>1/25 Eweas et al., Frontiers in Microbiology, doi:10.3389/fmicb.2020.592908 (Peer Reviewed) Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2</p>\n<p>1/23 Errecalde et al., Journal of Pharmaceutical Sciences, doi:10.1016/j.xphs.2021.01.017 (Peer Reviewed) animal study Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model</p>\n<p>1/21 Chamie-Quintero et al., Preprint, doi:10.2139/ssrn.3765018 (Preprint) Sharp Reductions in COVID-19 Case Fatalities and Excess Deaths in Peru in Close Time Conjunction, State-By-State, with Ivermectin Treatments</p>\n<p>1/20 Mody et al., Communications Biology, doi:10.1038/s42003-020-01577-x (Peer Reviewed) (In Vitro) in vitro Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents</p>\n<p>1/19 Shahbaznejad et al., Clinical Therapeutics, doi:10.1016/j.clinthera.2021.04.007 (partial results available 1/19) (Peer Reviewed) death, ↑197.1%, p=1.00 Effect of ivermectin on COVID-19: A multicenter double-blind randomized controlled clinical trial</p>\n<p>1/19 Hill et al., Research Square, doi:10.21203/rs.3.rs-148845/v1 (Preprint) (meta analysis) death, ↓75.0%, p=0.0002 Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection</p>\n<p>1/16 Samaha et al., Viruses, doi:10.3390/v13060989 (results 1/16) (Peer Reviewed) hosp., ↓85.7%, p=0.24 Effects of a Single Dose of Ivermectin on Viral and Clinical Outcomes in Asymptomatic SARS-CoV-2 Infected Subjects: A Pilot Clinical Trial in Lebanon</p>\n<p>1/16 Bukhari et al., medRxiv, doi:10.1101/2021.02.02.21250840 (results 1/16) (Preprint) viral+, ↓82.4%, p&lt;0.0001 Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease</p>\n<p>1/13 Late, PrEP, PEP Kory et al., Frontiers in Pharmacology, doi:10.3389/fphar.2021.643369 (Review) (Peer Reviewed) review Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19</p>\n<p>1/12 Okumuş et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06104-9 (preprint 1/12) (Peer Reviewed) death, ↓33.3%, p=0.55 Evaluation of the Effectiveness and Safety of Adding Ivermectin to Treatment in Severe COVID-19 Patients</p>\n<p>1/11 Chahla et al., medRxiv, doi:10.1101/2021.03.26.21254398 (Preprint) cases, ↓95.2%, p=0.002 A randomized trial - intensive treatment based in ivermectin and iota-carrageenan as pre-exposure prophylaxis for COVID-19 in healthcare agents</p>\n<p>1/11 Bousquet-Melou et al., Preprint, doi:10.22541/au.161047848.80388481/v1 (Preprint) dosing study Large Impact of obesity on the disposition of ivermectin, moxidectin and eprinomectin in a canine model: relevance for COVID-19 patients</p>\n<p>1/10 Formiga et al., J. Control Release, doi:10.1016/j.jconrel.2020.10.009 (Review) (Peer Reviewed) review Ivermectin: an award-winning drug with expected antiviral activity against COVID-19</p>\n<p>1/9 Kirti et al., medRxiv, doi:10.1101/2021.01.05.21249310 (Preprint) death, ↓88.7%, p=0.12 Ivermectin as a potential treatment for mild to moderate COVID-19: A double blind randomized placebo-controlled trial</p>\n<p>1/8 Chamie, J. (News) news COVID-19 in Mexico</p>\n<p>1/6 Babalola et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcab035 (preprint 1/6) (Peer Reviewed) viral+, ↓63.9%, p=0.11 Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos</p>\n<p>1/6 Hirsch et al., Microbiology &amp; Infectious Diseases (Peer Reviewed) Ivermectin as Prophylaxis Against COVID-19 Retrospective Cases Evaluation</p>\n<p>1/3 Late, PrEP, PEP Lawrie et al., Preprint (Preprint) (meta analysis) death, ↓83.0%, p&lt;0.0001 Ivermectin reduces the risk of death from COVID-19 – a rapid review and meta-analysis in support of the recommendation of the Front Line COVID-19 Critical Care Alliance</p>\n<p>12/31 Wijaya et al., Cermin Dunia Kedokteran, 47:7 (Peer Reviewed) Ivermectin as a Potential Therapeutic Agent for COVID-19 – case studies</p>\n<p>12/31 Madrid et al., Heliyon, doi:10.1016/j.heliyon.2020.e05820 (Peer Reviewed) animal study Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation</p>\n<p>12/30 McCullough et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.264 (Review) (Peer Reviewed) review Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)</p>\n<p>12/30 Procter et al., Reviews in Cardiovascular Medicine, doi:10.31083/j.rcm.2020.04.260 (Peer Reviewed) Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection</p>\n<p>12/27 Hill, A., Preprint (Preprint) (meta analysis) meta-analysis Meta-analysis of clinical trials of ivermectin to treat COVID-19 infection</p>\n<p>12/24 Jeffreys et al., bioRxiv, doi:10.1101/2020.12.23.424232 (Preprint) (In Vitro) in vitro Remdesivir-Ivermectin combination displays synergistic interaction with improved in vitro antiviral activity against SARS-CoV-2</p>\n<p>12/20 Vallejos et al., Trials, doi:10.1186/s13063-020-04813-1 (Preprint) cases, ↓73.4%, p&lt;0.0001 Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19): a structured summary of a study protocol for a randomized controlled trial</p>\n<p>12/18 Late, PrEP, PEP Kory et al., FLCCC Alliance (Preprint) (meta analysis) death, ↓69.0%, p&lt;0.0001 Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19</p>\n<p>12/15 Alam et al., European Journal ofMedical and Health Sciences, doi:10.24018/ejmed.2020.2.6.599 (Peer Reviewed) cases, ↓90.6%, p&lt;0.0001 Ivermectin as Pre-exposure Prophylaxis for COVID-19 among Healthcare Providers in a Selected Tertiary Hospital in Dhaka – An Observational Study</p>\n<p>12/15 Afsar et al., SSRN (Preprint) symptoms, ↓92.2%, p=0.04 Ivermectin Use Associated with Reduced Duration of COVID-19 Febrile Illness in a Community Setting</p>\n<p>12/11 Hussain et al., International Journal of Molecular and Immuno Oncology, doi:10.25259/IJMIO_30_2020 (Peer Reviewed) Outcome of ivermectin and doxycycline in cancer patients with COVID-19: A positive experience in Bangladesh</p>\n<p>12/7 Chaccour et al., EClinicalMedicine, doi:10.1016/j.eclinm.2020.100720 (preprint 12/7) (Peer Reviewed) symp. prob., ↓52.9%, p&lt;0.05 The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial</p>\n<p>12/4 Kalfas et al., medRxiv, doi:10.1101/2020.11.30.20236570 (Preprint) meta-analysis The therapeutic potential of ivermectin for COVID-19: a systematic review of mechanisms and evidence</p>\n<p>12/4 Surnar et al., ACS Pharmacol. Transl. Sci., doi:10.1021/acsptsci.0c00179 (Peer Reviewed) (In Vitro) in vitro Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for COVID-19</p>\n<p>12/2 Ahmed et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.191 (Peer Reviewed) symptoms, ↓85.0%, p=0.09 A five day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness</p>\n<p>12/2 Chamie, J. (News) news The effect of using ivermectin to control COVID-19 in Chiapas</p>\n<p>12/1 Alonso et al., (Preprint) death, ↓91.8%, p=0.009 COVID-19: Uso de ivermectina</p>\n<p>11/28 Bernigaud et al., Annals of Dermatology and Venereology, doi:10.1016/j.annder.2020.09.231 (Peer Reviewed) death, ↓99.4%, p=0.08 Ivermectin benefit: from scabies to COVID-19, an example of serendipity</p>\n<p>11/28 Hellwig et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2020.106248 (Peer Reviewed) cases, ↓78.0%, p&lt;0.02 A COVID-19 Prophylaxis? Lower incidence associated with prophylactic administration of Ivermectin</p>\n<p>11/24 Niaee et al., Research Square, doi:10.21203/rs.3.rs-109670/v1 (Preprint) death, ↓81.8%, p=0.001 Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial</p>\n<p>11/22 de Melo et al., bioRxiv, doi:10.1101/2020.11.21.392639 (Preprint) animal study Anti-COVID-19 efficacy of ivermectin in the golden hamster</p>\n<p>11/18 Budhiraja et al., medRxiv, doi:10.1101/2020.11.16.20232223 (Preprint) death, ↓99.1%, p=0.04 Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience</p>\n<p>11/17 Carvallo et al., Journal of Biomedical Research and Clinical Investigation, doi:10.31546/2633-8653.1007 (Peer Reviewed) cases, ↓99.9%, p&lt;0.0001 Study of the Efficacy and Safety of Topical Ivermectin + Iota-Carrageenan in the Prophylaxis against COVID-19 in Health Personnel</p>\n<p>11/14 Spoorthi et al., IAIM, 2020, 7:10, 177-182 (Peer Reviewed) recov. time, ↓21.1%, p=0.03 Utility of Ivermectin and Doxycycline combination for the treatment of SARSCoV-2</p>\n<p>11/11 Camprubí et al., PLoS ONE, 15:11, doi:10.1371/journal.pone.0242184 (Peer Reviewed) ventilation, ↓40.0%, p=0.67 Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients</p>\n<p>11/10 Turkia, M., ResearchGate (Review) (Preprint) review FLCCC Alliance MATH+ ascorbic acid and I-MASK+ ivermectin protocols for COVID-19 — a brief review</p>\n<p>11/4 Cadegiani et al., medRxiv, doi:10.1101/2020.10.31.20223883 (Preprint) death, ↓78.3%, p=0.50 Early COVID-19 Therapy with Azithromycin Plus Nitazoxanide, Ivermectin or Hydroxychloroquine in Outpatient Settings Significantly Reduced Symptoms Compared to Known Outcomes in Untreated Patients</p>\n<p>11/3 Late Morgenstern et al., J. Clinical Trials (preprint 11/3) (Peer Reviewed) The Use of Compassionate Ivermectin in the Management of SymptomaticOutpatients and Hospitalized Patients with Clinical Diagnosis of Covid-19 at theCentro Medico Bournigal and at the Centro Medico Punta Cana, GrupoRescue, Dominican Republic, from May 1 to August 10, 2020</p>\n<p>11/3 Behera et al., PLoS ONE, doi:10.1371/journal.pone.0247163 (preprint 11/3) (Peer Reviewed) cases, ↓53.8%, p&lt;0.0001 Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study</p>\n<p>11/2 Arévalo et al., Scientific Reports, doi:10.1038/s41598-021-86679-0 (preprint 11/2/20) (Peer Reviewed) animal study Ivermectin reduces in vivo coronavirus infection in a mouse experimental model</p>\n<p>10/31 Chang et al., ResearchGate (Preprint) COVID-19: Effectiveness of pre-exposure prophylaxis with ivermectin in exposed persons</p>\n<p>10/31 Szente Fonseca et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101906 (Peer Reviewed) hosp., ↑13.9%, p=0.45 Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis</p>\n<p>10/26 Hashim et al., medRxiv, doi:10.1101/2020.10.26.20219345 (Preprint) death, ↓66.7%, p=0.27 Controlled randomized clinical trial on using Ivermectin with Doxycycline for treating COVID-19 patients in Baghdad, Iraq</p>\n<p>10/22 Guerrero et al., Colombia Médica, doi:10.25100/cm.v51i4.4613 (Peer Reviewed) COVID-19: The Ivermectin African Enigma</p>\n<p>10/19 Carvallo et al., NCT04425850 (Preprint) cases, ↓96.3%, p&lt;0.0001 Usefulness of Topic Ivermectin and Carrageenan to Prevent Contagion of Covid 19 (IVERCAR)</p>\n<p>10/13 Chaccour et al., Scientific Reports, doi:10.1038/s41598-020-74084-y (Peer Reviewed) animal study Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats</p>\n<p>10/13 Rajter et al., Chest, doi:10.1016/j.chest.2020.10.009 (Peer Reviewed) death, ↓46.0%, p=0.04 Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID-19 (ICON study)</p>\n<p>10/9 Mahmud et al., Journal of International Medical Research, doi:10.5061/dryad.qjq2bvqf6 (preprint 10/9/20) (Peer Reviewed) death, ↓85.7%, p=0.25 Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial</p>\n<p>10/8 Francés-Monerris et al., ChemRxiv, doi:10.26434/chemrxiv.12782258.v1 (Preprint) (Theory) theory Has Ivermectin Virus-Directed Effects against SARS-CoV-2? Rationalizing the Action of a Potential Multitarget Antiviral Agent</p>\n<p>10/8 Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066 (Preprint) death, ↓17.1%, p=0.01 Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru</p>\n<p>9/30 Chachar et al., International Journal of Sciences, 9:31-35, doi:10.18483/ijSci.2378 (Peer Reviewed) no recov., ↓10.0%, p=0.50 Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients</p>\n<p>9/24 Khan et al., Archivos de Bronconeumología, doi:10.1016/j.arbres.2020.08.007 (Letter) death, ↓87.0%, p&lt;0.05 Ivermectin treatment may improve the prognosis of patients with COVID-19</p>\n<p>9/22 Li et al., J. Cellular Physiology, doi:10.1002/jcp.30055 (Peer Reviewed) (In Vitro) in vitro Quantitative proteomics reveals a broad‐spectrum antiviral property of ivermectin, benefiting for COVID‐19 treatment</p>\n<p>9/15 Carvallo et al., medRxiv, doi:10.1101/2020.09.10.20191619 (Preprint) death, ↓87.9%, p=0.05 Safety and Efficacy of the combined use of ivermectin, dexamethasone, enoxaparin and aspirin against COVID-19</p>\n<p>9/15 Jans et al., Cells 2020, 9:9, 2100, doi:10.3390/cells9092100 (Review) (Letter) review Ivermectin as a Broad-Spectrum Host-Directed Antiviral: The Real Deal?</p>\n<p>9/6 DiNicolantonio et al., Open Heart, doi:10.1136/openhrt-2020-001350 (Review) (Peer Reviewed) review Ivermectin may be a clinically useful anti-inflammatory agent for late-stage COVID-19</p>\n<p>9/3 Podder et al., IMC J. Med. Science, 14:2, July 2020 (Peer Reviewed) recov. time, ↓16.1%, p=0.34 Outcome of ivermectin treated mild to moderate COVID-19 cases: a single-centre, open-label, randomised controlled study</p>\n<p>8/31 Kishoria et al., Paripex - Indian Journal of Research, doi:10.36106/paripex/4801859 (Peer Reviewed) no disch., ↑7.5%, p=1.00 Ivermectin as adjuvant to hydroxychloroquine in patients resistant to standard treatment for SARS-CoV-2: results of an open-label randomized clinical study</p>\n<p>8/28 Shouman et al., Journal of Clinical and Diagnostic Research, doi:10.7860/JCDR/2020/46795.0000 (Peer Reviewed) symp. case, ↓91.3%, p&lt;0.001 Use of Ivermectin as a Potential Chemoprophylaxis for COVID-19 in Egypt: A Randomised Clinical Trial</p>\n<p>8/15 Espitia-Hernandez et al., Biomedical Research, 31:5 (Peer Reviewed) viral+, ↓97.2%, p&lt;0.0001 Effects of Ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study</p>\n<p>8/14 Bhattacharya et al., Int. J. Scientific Research, doi:10.36106/ijsr/7232245 (Peer Reviewed) Observational Study on Clinical Features, Treatment and Outcome of COVID 19 in a tertiary care Centre in India- a retrospective case series</p>\n<p>7/31 Vora et al., Indian Journal of Tuberculosis, doi:10.1016/j.ijtb.2020.07.031 (Review) (Peer Reviewed) review White paper on Ivermectin as a potential therapy for COVID-19</p>\n<p>7/31 Chang et al., ResearchGate (Preprint) Post-acute or prolonged COVID-19: ivermectin treatment for patients with persistent symptoms or post-acute symptoms</p>\n<p>7/31 Chang et al., ResearchGate, doi:10.13140/RG.2.2.34561.48483/2 (Preprint) (Theory) theory COVID-19: Post-exposure prophylaxis with ivermectin in contacts. At Homes, Places of Work, Nursing Homes, Prisons, and Others</p>\n<p>7/31 Alam et al., Journal of Bangladesh College of Physicians and Surgeons, doi:10.3329/jbcps.v38i0.47512 (Peer Reviewed) A Case Series of 100 COVID-19 Positive Patients Treated with Combination of Ivermectin and Doxycycline</p>\n<p>7/31 Rahman et al., J. Bangladesh Coll. Phys. Surg. 38, 5-9, doi:10.3329/jbcps.v38i0 (Peer Reviewed) Comparison of Viral Clearance between Ivermectin with Doxycycline and Hydroxychloroquine with Azithromycin in COVID-19 Patients</p>\n<p>7/14 Chowdhury et al., Eurasian Journal of Medicine and Oncology, doi:10.14744/ejmo.2021.16263 (Peer Reviewed) hosp., ↓80.6%, p=0.23 A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients</p>\n<p>7/8 Gorial et al., medRxiv, doi:10.1101/2020.07.07.20145979 (Preprint) death, ↓71.0%, p=1.00 Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial)</p>\n<p>6/19 Lehrer et al., In Vivo, 34:5, 3023-3026, doi:10.21873/invivo.12134 (Theory) theory Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2</p>\n<p>6/16 Ramos et al., Preprint (Preprint) Intervención de la Ivermectina Pre-Hospitalaria para la Modificación de la Evolución del Covid19. Estudio realizado en Perú</p>\n<p>6/12 Heidary et al., The Journal of Antibiotics, 73, 593–602, doi:10.1038/s41429-020-0336-z (Review) (Peer Reviewed) review Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen</p>\n<p>5/2 Chang, G., Research Gate, doi:10.13140/RG.2.2.34689.48482/7 (Preprint) Inclusión de la ivermectina en la primera línea de acción terapéutica para COVID-19</p>\n<p>4/21 Bray et al., Antiviral Res., doi:10.1016/j.antiviral.2020.104805 (Review) (Preprint) review Ivermectin and COVID-19: A report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors' responses</p>\n<p>4/3 Caly et al., Antiviral Research, doi:10.1016/j.antiviral.2020.104787 (Peer Reviewed) (In Vitro) in vitro The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro</p>\n<p>2013 N/A Guzzo et al., J. Clinical Pharmacology, doi:10.1177/009127002237994 (Peer Reviewed) safety analysis Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects</p>\n" } ]

[ "https://health.stackexchange.com/questions/25687", "https://health.stackexchange.com", "https://health.stackexchange.com/users/10980/" ]

[ { "answer_id": 25823, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 2, "selected": false, "text": "<p>Even assuming the same ecological conditions, <a href=\"https://www.gavi.org/vaccineswork/what-difference-between-efficacy-and-effectiveness\" rel=\"nofollow noreferrer\">efficacy</a> of a vaccine is in a (<a href=\"https://apps.who.int/iris/rest/bitstreams/1324092/retrieve\" rel=\"nofollow noreferrer\">dose-dependent</a> trade-off with side effects. (This was e.g. easily <a href=\"https://www.sciencemag.org/news/2020/11/fever-aches-pfizer-moderna-jabs-aren-t-dangerous-may-be-intense-some\" rel=\"nofollow noreferrer\">shown</a> in the phase I/II <a href=\"https://www.nejm.org/doi/full/10.1056/nejmoa2022483\" rel=\"nofollow noreferrer\">trials</a> of Moderna's vaccine.) Even for the exact same tech/vaccine, manufacturers may choose different points along this curve.</p>\n<p>Furthermore, the amount of &quot;training&quot; and thus resulting levels of antibodies etc. depends on how long the injected vaccine lasts in your body. There are numerous factors that affect this, see e.g. <a href=\"https://medicalsciences.stackexchange.com/questions/25380/how-do-mrna-vaccines-work-and-what-are-their-advantages-over-traditional-vaccine\">prior discussion here</a> what affects that in mRNA vaccines alone.</p>\n<p>Changing the delivery vector to something more substantially different, e.g. from a lipid nanoparticle (LNP) to an adenovirus (Janssen, Astra-Zeneca, Sputnik) can have more substantial effects in both of the above regards; i.e. the side-effect vs efficacy profile may be on different curve; the technology that makes a pure mRNA vaccine persist long enough in your body is not the same as that using an adenovirus--by the way, the latter is a DNA virus, so the protein is coded in a slightly different substrate, with a different &quot;decay rate&quot;. You can also have prior immunity to some adenoviruses (and also develop it from the vaccine, I think).</p>\n<p>Furthermore, some other Covid-19 vaccines (e.g. Novavax) deliver the proteins themselves (in a LNP) rather then mRNA, so they are even more fundamentally different than mRNA/DNA based ones with respect to all of the above. The same mRNA molecule can <a href=\"https://medicalsciences.stackexchange.com/questions/25522/is-the-code-from-the-mrna-vaccine-executed-by-the-cells-as-a-one-off\">get reused</a> a good number times in a cell to produce (spike, in this case) proteins, but a protein is more or less of &quot;one use&quot; for the immune system. Generally speaking, protein vaccines (and this include's Novavax) <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423510/\" rel=\"nofollow noreferrer\">use</a> various adjuvants to get more immune response out of the same dose of proteins, which are fairly <a href=\"https://medicalsciences.stackexchange.com/questions/25469/for-fighting-covid19-why-we-give-the-body-the-rna-and-not-give-the-body-the-pro\">involved to manufacture</a>. (Such adjuvants <a href=\"https://www.idsociety.org/covid-19-real-time-learning-network/vaccines/vaccines-information--faq/\" rel=\"nofollow noreferrer\">aren't</a> used by current mRNA vaccines that have been approved, probably because they generate [translate to] more than enough proteins.)</p>\n<p>Of the vaccines you've listed, Pfizer/Biontech and Moderna <a href=\"https://asm.org/Articles/2020/December/COVID-19-Vaccine-FAQs\" rel=\"nofollow noreferrer\">are</a> the most similar to each other technology-wise (both mRNA in a PEGylated LNP--their actual formulation differences are somewhat obscure), so somewhat not surprisingly they produced the most similar results.</p>\n<hr />\n<p>Additionally, small changes have been made to the genetic sequence of the spike protein; <a href=\"https://www.nature.com/articles/s41577-020-00480-0/tables/1\" rel=\"nofollow noreferrer\">more specifically</a></p>\n<ul>\n<li>Astra-Zeneca &amp; Sputnik don't report any modifications</li>\n<li>Pfizer and Moderna (both) made the same proline substitutions</li>\n<li>Janssen additionally made two mutations at furin cleavage sites</li>\n<li>Novavax made three of those</li>\n</ul>\n<p>The <a href=\"https://science.sciencemag.org/content/369/6510/1501\" rel=\"nofollow noreferrer\">role</a> of proline substitutions is to keep the (produced) spike protein in the prefusion conformation for a longer time, thus effectively increasing yield. If you wonder how they both got this idea: it's because this was first\n<a href=\"https://www.pnas.org/content/114/35/E7348\" rel=\"nofollow noreferrer\">done</a> on a MERS vaccine.\nIt was observed that most of the naturally produced antibodies target the\nRBD, which is only exposed in the prefusion conformation.</p>\n<p>According to Janssen's pre-clinical <a href=\"https://www.nature.com/articles/s41541-020-00243-x\" rel=\"nofollow noreferrer\">research</a>, their furin mutations have an additional\nstabilizing effect and cause the host to produce a greater ratio of neutralizing to non-neutralizing antibodies (compared to the variant with the two proline substitutions only). Novavax basiscally <a href=\"https://www.nature.com/articles/s41467-020-20653-8\" rel=\"nofollow noreferrer\">did</a> the same thing but altered the cleavage site at three points RRAR→QQAQ.</p>\n" }, { "answer_id": 25846, "author": "BrenBarn", "author_id": 17847, "author_profile": "https://health.stackexchange.com/users/17847", "pm_score": 0, "selected": false, "text": "<p>As Fizz noted in a comment, from <a href=\"https://www.nature.com/articles/s41577-020-00480-0/tables/1\" rel=\"nofollow noreferrer\">what we know</a> about the vaccines, the Novavax and Janssen vaccines make slightly different modifications to the spike protein than the Moderna and Pfizer vaccines. In other words, they are not delivering the exact same instructions for recognizing the virus.</p>\n<p>We don't <em>know</em> if these small differences are what causes the difference in efficacy. But your assumption that the &quot;end result&quot; is the same is not necessarily valid. There may be differences in the nature or degree of the immune system's ability to recognize the virus because, in a manner of speaking, the different vaccines give slightly different instructions for doing so.</p>\n<p>It's also worth noting that the different vaccines were tested at different times and in different places. It's possible that differences in their measured efficacy reflect different COVID-19 variants that were prevalent in the populations where the trials took place.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25807", "https://health.stackexchange.com", "https://health.stackexchange.com/users/346/" ]

[ { "answer_id": 25827, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 2, "selected": false, "text": "<p><a href=\"https://en.wikipedia.org/wiki/Dry_heat_sterilization\" rel=\"nofollow noreferrer\">Dry heat sterilization</a> is fairly inefficient, time-wise, in general. According to Wikipedia, which cites the CDC for this:</p>\n<blockquote>\n<p>The proper time and temperature for dry heat sterilization is 160 °C (320 °F) for 2 hours or 170 °C (340 °F) for 1 hour or in the case of High Velocity Hot Air sterilisers 190°C (375°F) for 6 to 12 minutes.</p>\n</blockquote>\n<p>But this is for all mirco-organisms, which some of which are more hardy than coronaviruses. I'm not sure if there's a study just on the latter in re dry heat.</p>\n<p>Also this is not exactly what you're asking here, as you want to sterilize the air, but it is somewhat relevant if you're trying to do that by heat transfer from a surface, e.g. a hot plate, coil etc. Because of inefficiency relative to other methods, this way of sterilizing air it might not have been studied too much, <a href=\"https://www.sciencedirect.com/science/article/pii/S0065216408701321\" rel=\"nofollow noreferrer\">e.g.</a>:</p>\n<blockquote>\n<p>Many ways have been suggested for sterilizing air. These include destruction of microorganisms by: dry heat-gas fired or electrical; adiabatic compression; and irradiation or removal of microorganism. The removal of microorganisms involve: scrubbing, electrostatic precipitation, sieving, and filtration fibrous or granular beds. Of these, only adiabatic compression, filtration through beds of fibrous materials, and filtration through beds of granular materials have found widespread usage on an industrial scale.</p>\n</blockquote>\n<p>(Albeit that's a 1960's article, but physics didn't change much since...)</p>\n<p>The (1st) <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340062\" rel=\"nofollow noreferrer\">(2020) paper</a> you've linked to uses a <em>heated filter</em>, so it's really a combination method. (The filter had non-zero effect even without it being heated, if you look at their graphs--fig 3.) That paper also mentions the air flow rate at which they've tested their system. Which of course is a factor in heat transfer too; e.g. they quantified the observed temperature drop with increased air flow, albeit only at couple of points.</p>\n<p>See also <a href=\"https://en.wikipedia.org/wiki/Sterility_assurance_level\" rel=\"nofollow noreferrer\">sterility assurance level</a> for what professionals mean when they say something is sterilized. Basically, it's a statistical measure/guarantee, not an absolute one. In the 2020 paper you've linked to, they set/measured that at 99.8%.</p>\n" }, { "answer_id": 25830, "author": "Tyler Durden", "author_id": 5371, "author_profile": "https://health.stackexchange.com/users/5371", "pm_score": -1, "selected": false, "text": "<p>Viruses are not &quot;alive&quot; in the sense that larger organism is. They are like little machines. So, they do not &quot;die&quot;, they simply function at different levels of efficiency. So, for example, an increase in temperature may damage a virus and impair its function. Even if a virus is impaired and unable to reproduce by itself, it can still act in various ways, such as loaning its DNA to other viruses.</p>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807520/\" rel=\"nofollow noreferrer\">In a recent study of inactivation of various shellfish viruses</a>, it was found that a temperature of 80-degrees centigrade (176 Farenheit) for 12 seconds was sufficient to inactivate all the viruses under study and this appeared to be due to capsid disruption. Since SARS-COV2 and all coronaviridae have a similar capsid, they probably subject to the same rule.</p>\n<p>The study found that a lesser temperature of 62-degrees centigrade was sufficient to inactivate some viruses, if it was applied for as long as 30 minutes, but not all of the test viruses were completely inactivated.</p>\n<p>Note that the chemical behavior of a virus can differ depending on the media in which it exists. Respiratory viruses spend their lives adhering to various proteins in mucus. If they are removed from that environment in placed dry air or even water, they can become unstable and more fragile.</p>\n<p>Also, it is worth noting that even small variations in temperature can signficantly affect the efficiency of viral reproduction. For example, animals will often raise body temperature (a fever) to defend against an infection, and this change in temperature in the case of humans is only from 98 degrees Farenheit to 104 degrees, but even so it is enough to impair viral reproduction significantly.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25826", "https://health.stackexchange.com", "https://health.stackexchange.com/users/21511/" ]

[ { "answer_id": 25879, "author": "KHAN", "author_id": 21546, "author_profile": "https://health.stackexchange.com/users/21546", "pm_score": 0, "selected": false, "text": "<p>The covid vaccine is as an RNA vaccine which needs to be delivered to the cells via RNA delivery technologies like LNP.\nFrom what I understand, the reactions to some vaccines are not due to the actual viral component, but the 'medium' or molecular 'packaging' ITSELF, e.g. the lipid nano particles (LNP). Otherwise, your reasoning may be correct. However, please also keep in mind that the body's immune response may be modified depending on other factors as well.</p>\n" }, { "answer_id": 25882, "author": "Gerry Creager", "author_id": 21548, "author_profile": "https://health.stackexchange.com/users/21548", "pm_score": 2, "selected": false, "text": "<p>I've a couple of thoughts. I've been following and studying SARS-CoV-2 since before the first case was &quot;identified&quot; in the United States, and have amassed a reasonable library of medical literature about it, COVID-19 diagnosis and treatment, and now, the vaccines. No advice you receive online should replace competent medical advice from a healthcare provider you know (and hopefully see professionally), but I can offer some thoughts.</p>\n<p>In general, when I am asked this question, I respond that I can treat side effects and anaphylaxis successfully and fairly simply (of course, there are exceptions, but they are vanishingly few), but treating severe COVID-19 is much more questionable. The current vaccines (and I'm not sufficiently familiar with the data from Sinovax or Sputnic-V as their data are not readily available in a form I trust yet; this comment is thus limited to Pfizer/BioNTech, Moderna, Janssen/J+J, and AstraZenica) are either messenger RNA (mRNA) or recombinant DNA (rDNA) processes where proteins consistent with elements of the Spike protein are manually reproduced without culturing or utilizing live, attenuated or killed virus in the production. Thus, there is literally no way to contract COVID-19 from any of the vaccines.</p>\n<p>The mRNA vaccines are encased in a lipid layer preventing the host immune system from responding to and destroying the encoding mRNA but allowing the mRNA to pair with ribosomes and have the host create the elements of the Spike protein that are released and seen as foreign material by the host immune system allowing creation of antibodies to the elements of that particular protein complex that can subsequently neutralize the ability of the coronavirus to attach to the acetylcholinesterase-2 receptors that are common in the mouth, nose, nasopharynx and other elements of the airway, as well as other communicating passages including the tear (lacrymal) ducts and corneal surfaces. These receptors, if the virus attaches to them, allow entry of the viral RNA material into the cell, and subsequent viral reproduction will create millions of infectious viral particles.</p>\n<p>The primary mechanism of immunity seen so far, either by immunity conferred by infection or by vaccination, is that the antibodies prevent the Spike from attaching to the ACE2 receptor, usually by neutralizing the S1 protein. In addition, cellular immunity is recruited, where your innate immune system utilizes memory cells, CD4+ and CD8+ T lymphocytes, which respond to repeated exposure of antigens by initiating the predetermined immune response to the detected foreign material and initiating the response much faster than the first time one is exposed to the antigen naturally (or artificially with the vaccine).</p>\n<p>Most reactions to the vaccines are relatively mild, and are considerably less intense than the result of infection with COVID-19 if you have a symptomatic case. Some people are asymtomatic, perhaps the majority, but they are not completely free from later complications. I'm including personal experiences for myself and my wife, as we both had bouts of COVID-19 and have also completed a full regimen of the Moderna vaccine. With COVID-19, my symptoms were present but mild enough to allow me to think they were associated with the high level of airborne allergens at the time, up to the time I lost my sense of taste and smell. The other clue was that none of my normal antihistamine treatments provided any relief. My wife had was met the criteria for moderate-to-severe symptoms and would have been hospitalized had I not been available to care for her. My symptoms lasted for about 4.5 days; hers lasted 14 days and she was debilitated for nearly 3 months thereafter, and has x-ray evidence of lung scarring.</p>\n<p>By contrast, the side effects we had to the two shots of Moderna's mRNA vaccine were nearly identical: Lethargy for about 12 hours starting roughly 12 hours after the injection, and soreness at the injection site. I also experienced itching near the injection site for several days after the second injection. These are consistent with other vaccine injections such as influenza, shingles or pneumonia. Overall, significant reactions are rare and are on a level consistent with other vaccines. Quoting from <a href=\"https://jamanetwork.com/journals/jama/fullarticle/2777417\" rel=\"nofollow noreferrer\">https://jamanetwork.com/journals/jama/fullarticle/2777417</a>:</p>\n<blockquote>\n<p>Acute allergic reactions were reported by 2.10% overall, more frequently with the Moderna vaccine compared with Pfizer-BioNTech (2.20% [95% CI, 2.06%-2.35%] vs 1.95% [95% CI, 1.79%-2.13%]; P = .03). Anaphylaxis was confirmed in 0.025% (95% CI, 0.014%-0.040%): 0.027% from the Pfizer-BioNTech vaccine (95% CI, 0.011%-0.056%) and 0.023% from the Moderna vaccine (95% CI, 0.011%-0.044%) (P = .76).</p>\n</blockquote>\n<blockquote>\n<p>Individuals with anaphylaxis were a mean (SD) age of 41 (13) years, and 15 (94%) were female; 63% had a prior allergy history and 31% had an anaphylaxis history. Mean time to anaphylaxis onset was 17 minutes (SD, 28; range, 1-120). One patient was admitted to intensive care, 9 (56%) received intramuscular epinephrine, and all recovered. Three employees, with prior anaphylaxis history, did not seek care.</p>\n</blockquote>\n<p>The long-term effects of infection by SARS-CoV-2 are still being evaluated because the virus is relatively new, but have included long-term scarring to the lungs, clotting of peripheral vessels as well as clots migrating to the lung (pulmonary embolism) and increased clotting leading to stroke. In addition, cardiac anomalies have been seen including eosinophyllic infiltration of cardiac muscle, heart failure, shortness of breath, previously undiagnosed reactive airway disease, &quot;brain fog&quot;, and loss of stamina. I'm sure there are others but I'm still coffee-deficient and only briefly looked at my literature cache. The US Centers for Disease Control has some good information: <a href=\"https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html\" rel=\"nofollow noreferrer\">https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html</a>.</p>\n<p>An additional concern is the rise of viral variants. These variations are normal. Viruses, especially coronaviruses mutate &quot;all the time&quot;. The variants that do not promote virus genomic survival do not tend to survive: If the virus kills too many hosts then it can't replicate in additional hosts and that variant will die off with its hosts. On the other hand, a variant that is more infective, as we've been seeing with the so-called UK-, South African- Brazilian, and California-variants will tend to become more prevalent because they aren't killing a larger proportion of their victims but are recruiting new hosts.</p>\n<p>Some news has cited that the various vaccines have reduced efficacy against the recent variants, but the conventional wisdom of virologists, epidemiologists and vaccinologists is that the current set of vaccines remains sufficiently effective against the known variants. In addition, because of how the mRNA and rDNA vaccines are made, updating them requires relatively minor modifications to the workflow, and much smaller studies and datasets for approval because the heavy work of proving safety and efficacy has been done.</p>\n<p>About the only way to prevent another surge in cases involving the recognized (and over-hyped, in my opinion) variants is to increase the worldwide rate of vaccination, and to continue use of the simple and effective precautions including use of a 2-3 ply cloth mask (or even two masks), maintaining 2 meter social distancing, staying home if you don't feel completely well, and hand hygiene using soap and water or hand sanitizer based on 60% (ethanol) or higher sanitizers and the approved techniques for hand hygiene. Duration of handwashing or sanitizing matters. 20 seconds is the minimum to engage in effective hand cleaning, not the maximum.</p>\n<p>So, if you've read all of this, the short answer is: Vaccination has some exceedingly minor risks, and the side effects generally do NOT rise to the level of symptoms and risks of COVID-19. My recommendation is to get vaccinated as soon as you can. One benefit is that the fewer susceptible persons out there, the fewer variant strains will infect people. Don't quibble over which vaccine you want, get the first of the approved vaccines available to you.</p>\n<p>Vaccination\nMasking\nSocial Distancing\nHand hygiene\nSelf-isolate if you do not feel well</p>\n" }, { "answer_id": 25888, "author": "Gulzar", "author_id": 9125, "author_profile": "https://health.stackexchange.com/users/9125", "pm_score": 0, "selected": false, "text": "<p>I was vaccinated by the pfizer vaccine, as milions of others in Israel, twice.</p>\n<p>I also had the side effects that apply to a large percantage of those who got the vaccine.</p>\n<p>After the 1st dose- nothing.\nAfter the second one- i had a couple hours of fever and a day of wekness, and that was it.</p>\n<p>Those are the majority of people.</p>\n<p>If you get covid and get sick, you will have 10% chance of long covid, you will suffer much more, and you will be a danger to others, as the vaccine is already proven to also partially protect against non symptomatic contagiousness.</p>\n<p>The side effects are subjectively nothing, and objectively nothing as compared to real covid.</p>\n<p>The chances of dying from covid are around 1%, depending where you live, your age, ect. The chance to catch it sooner òr later is large. The chance to dye from the vaccine is nullable.</p>\n<p>Go get vaccinated.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25877", "https://health.stackexchange.com", "https://health.stackexchange.com/users/21545/" ]

[ { "answer_id": 25902, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 3, "selected": true, "text": "<p>The ratio of false positives to true positives (as well as overall &quot;accuracy&quot;) is a function of the underlying rate in the population.</p>\n<p>Let's imagine you have a test that has 95% <a href=\"https://en.wikipedia.org/wiki/Sensitivity_and_specificity\" rel=\"nofollow noreferrer\">specificity</a>. Specificity is the number of negatives that you correctly identify as negative. If you test 1000 negative samples with a 95% specificity test, you will find 95% of them correctly return negative, and the other 5% (=50 tests) return positive. In this case, because we've tested an entirely negative population, 100% of the positive tests are false positives. <strong>You will always get this result when you test an entirely negative population, even if your test is 99.999% specific: if you test on entirely negative samples, 100% of the positives are false positives by definition.</strong></p>\n<p>Let's instead consider testing a combined population of 500 positive and 500 negative. For simplicity let's assume the test is 100% sensitive while still being 95% specific. 100% of 500=500 positives will test positive, and 5% of 500=25 negatives will test positive. You have a total of 525 positive tests, and only 25/525 (&lt;5%) of these are false positive.</p>\n<hr />\n<p>Sensitivity and specificity are a trade-off according to your decision threshold, so if you want to have fewer false negatives it's going to cost you in more false positives. For antigen screening followed up by PCR, the goal is to set a threshold for the antigen test that results in few false negatives, to avoid infected people from spreading to their coworkers. However, you expect you are going to get a lot of false positives that way, which is why the strategy is to then follow up on these tests with PCR. A combined positive on the antigen test + follow-up PCR test is much less likely to be a false positive.</p>\n<p>The purpose of the antigen test here is less to identify true positive cases, and instead it is to add a rapid way to isolate potential positives and to make the most efficient use of the PCR test.</p>\n<p>You can use <a href=\"https://en.wikipedia.org/wiki/Bayesian_statistics\" rel=\"nofollow noreferrer\">Bayesian statistics</a> to better interpret results after a test if you start out with a prior understanding of expected ratios of positive to negative cases in the population you're testing.</p>\n" }, { "answer_id": 25940, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 1, "selected": false, "text": "<p>Bryan is correct, especially in his comment in the case of 0% true/prior prevalence</p>\n<blockquote>\n<p>40/1000 = 4% positive. 1-2/40 = 2.5-5%.</p>\n</blockquote>\n<p>But even in such a <em>conditioned</em> test scenario, in which the 2nd test is only applied to the positive-reporting sample of the first test, a decent test (e.g. 90% sensitivity, 95% specificity) will actually converge pretty quickly (i.e. &quot;disagree with itself&quot; a lot less).</p>\n<p>E.g. if the true prevalence is 1% (instead of 0%) instead of t2:t1 positive reports ratio of 1:20 (i.e. 5%), you'll actually get (in the 1% prevalence case) just a 1:5 (t2:t1) ratio (more precisely 18.85%). Also this t2:t1 positive report ratio further drops to just 1:3 (29.18%) on just 2% true prevalence.\nHere's a table of such calculations below, in which I assume the same test is repeated (as not to complicate this example with two sets of sensitivity/specificity.)</p>\n<p><a href=\"https://i.stack.imgur.com/AQ1CH.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/AQ1CH.png\" alt=\"enter image description here\" /></a></p>\n<p>Furthermore, for a highly specific test, i.e. 99% (instead of 95%) specificity, the convergence is even faster, e.g. for just 1% true prevalence, the t2:t1 positive report ratio is now almost 1:2 (43.86%; up from 18.85% when the specificity was just 95%).</p>\n<p><a href=\"https://i.stack.imgur.com/ht3xn.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/ht3xn.png\" alt=\"enter image description here\" /></a></p>\n<p>Ironically however, if the true prevalence is 0%, a more specific test (99% vs 95% specificity) will &quot;disagree with itself&quot; on a retest even more, i.e. 1:100 vs 1:20 concurrence.</p>\n<p>Considering the specificities and sensitivities of the tests known (which is alas a bit iffy in &quot;real world&quot; situations as opposed to lab settings) you can basically find out what the true prevalence is, e.g. assuming 60% sensitivity and 95% specificity for the antigen test and 95% sensitivity and 99% specificity for the (t2) PCR test, from a range of t2:t1 like you reported (2:20 to 1:40), you can get somewhere between 0.1% and 1% true prevalence in the starting population... which is still a fairly large range. (Of some note, this doesn't depend on the initial population size anymore, i.e. having two tests allows us to &quot;factor out&quot; that.)</p>\n<p><a href=\"https://i.stack.imgur.com/8bwdI.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/8bwdI.png\" alt=\"enter image description here\" /></a></p>\n<p>In reality (even for lab-settings tests) you only have confidence intervals for the sensitivity and specificity as opposed to their true number, which makes the above exercise a bit more involved... and as Bryan's numerical example showed, 0% (true) prevalence could well be in the solution interval. The specificity of the 2nd test (PCR) is actually critical in this regard, if you relax it to 95% (from 99%), then 0% true prevalence becomes a (realistic) solution.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25901", "https://health.stackexchange.com", "https://health.stackexchange.com/users/17384/" ]

[ { "answer_id": 25928, "author": "BrenBarn", "author_id": 17847, "author_profile": "https://health.stackexchange.com/users/17847", "pm_score": 3, "selected": false, "text": "<p><a href=\"https://www.chop.edu/news/long-term-side-effects-covid-19-vaccine\" rel=\"noreferrer\">This general-audience article</a> from Children's Hospital of Philadelphia gives a good overview of reasons to believe that long-term side effects are unlikely. To summarize its two main points:</p>\n<ul>\n<li>Previous vaccine research and development has found that most side effects occur within about two months. The FDA approval process for COVID vaccines required the trial to follow participants for eight weeks before submitting the vaccine for approval.</li>\n<li>Although the Pfizer and Moderna vaccines are the first mRNA vaccines in wide use, previous mRNA vaccines were developed and tested for Zika, influenza, and other diseases. Thus although the technology is &quot;new&quot; it is not as if this is the first time anyone has been injected with mRNA.</li>\n</ul>\n<p>In assessing long-term side effects, one problem is you have to wait a long time, but another problem is that the longer you wait, the more difficult it becomes to track the results and determine which events can be attributed to the vaccine. Answers to <a href=\"https://medicalsciences.stackexchange.com/questions/23094/was-there-ever-a-vaccine-candidate-that-showed-negative-side-effects-many-months\">this question</a> discuss such issues with the oral polio vaccine.</p>\n<p>There is no way to completely rule out the possibility of totally unexpected side effects that don't show up until much later. You can't really know what will happen in ten years until ten years have passed. However, all that is known from previous vaccines suggests it is unlikely that some catastrophic side effect will suddenly arise years later.</p>\n<p>Your last question is also relevant: any decision about the use of the vaccine has to take into account the risks of <em>not</em> using it. Given the massive public health crisis and other societal damage caused by COVID-19, there would probably need to be significant justification for waiting, say, an extra year &quot;just to be sure&quot; that no side effects emerged in that time. Also, preliminary data on &quot;long COVID&quot; mean that it is also possible there will be long-term &quot;side effects&quot; of COVID-19 itself, meaning that delaying the vaccine to avoid its possible side effects could just result in people suffering different long-term effects from the disease. So even if a catastrophic vaccine side effect <em>did</em> arise years later, that could still be better than not getting the vaccine. (Of course, we won't know the long-term effects of COVID until time passes, just as we won't know the long-term effects of the vaccine.)</p>\n<p>Another thing to remember is that people's subjective feelings about risk levels are often only vaguely connected to reality. I'm sure there are people out there who worry about the risk of the COVID vaccine but smoke a pack of cigarettes a day; three guesses which one of those is likely to pose a greater health risk. Some people worry about the risk of dying in a crash when they get on a commercial airline flight in the US, despite the fact that annual total deaths from such events rarely exceed zero. (<a href=\"https://scholarsbank.uoregon.edu/xmlui/bitstream/handle/1794/22549/Slovic_089.pdf\" rel=\"noreferrer\">Here</a> is one classic paper on risk perception.) Fear of long-term side effects is as likely to be due to the human tendency to exaggerate unfamiliar risks as it is to be due to any actual risk from the vaccine. In other words, even apart from the scientific evidence for the safety of this vaccine, there is a fair amount of scientific evidence that how safe you think something is may not be a good predictor of how safe it actually is.</p>\n" }, { "answer_id": 26213, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 2, "selected": true, "text": "<p>Since there are a number of vaccine technologies being used for Covid vaccines, a complete answer is complex.</p>\n<p>Perhaps the simplest situation is that of the mRNA vaccines (e.g. Pfizer and Moderna). With these, a short piece of mRNA (the genetic &quot;working instructions&quot; that direct the production of one or more proteins) is injected into a person, enters some of their cells, and directs them to make a slightly modified version of the Covid &quot;spike&quot; protein. Only the mRNA and some fatty molecules that coat the mRNA and protect it until it gets into the cell are injected.</p>\n<p>The fatty molecules are small and simple and quite safe. Although a very few people may have an allergic reaction to them, that shows up very quickly and is the reason for the post-shot 15-30 minute waiting period. We are confident that there will be no long-term effects from the tiny amount of fatty molecules.</p>\n<p>The mRNA is essentially a small snippet of the virus's mRNA. The spike protein it codes for is used by a full-blown intact virus to attach to a cell and &quot;inject&quot; a full virus mRNA into that cell as the first stage of infection. However, the vaccine mRNA snippet contains no instructions for the other viral proteins, so no infection results and no working viruses are produced. The spike protein that is made appears on the cell's surface, both whole and in pieces, and the body's immune system recognizes these as foreign molecules appearing on the body's own cells, triggering an immune response. What happens over the next few weeks is that out of the body's many antibody-producing cells (B cells), each recognizing a single semi-random shape, those that match the shape of part of the spike protein get activated, divide over and over, and produce lots of antibodies matching that shape. At the same time, T cells, also each recognizing a single semi-random shape, get activated and divide if they match the shape of part of the spike protein. Some of these T cells directly kill cells showing part of the spike protein on their surface (presumably, infected cells). Some of the T cells activate B cells matching the spike protein so they produce more antibodies, which circulate in the blood.</p>\n<p>Over a time span of months, the antibody levels slowly drop if no further spike protein is present, but a small number of the B cells and T cells continue to circulate for months or years. If they are again activated by the presence of spike protein, they quickly jump-start the reaction process to produce more B cells, antibodies and T cells in only a day or two instead of the few-week process from a first exposure. The 2nd shot of 2-dose vaccines triggers this second phase, which helps the &quot;memory&quot; effect last even longer and be more potent at the next exposure (i.e. when actually exposed to the real virus).</p>\n<p>The whole process triggered by the vaccine mRNA is a subset of that in the real viral infection -- the actual viral infection also involves more viral genes and additional attacks on immune system and other cells. Thus, any reaction that is due to the vaccine should also happen in an actual viral infection, so in theory there is nothing to be gained and much to lose by forgoing an mRNA vaccine and instead waiting to get an actual Covid virus infection.</p>\n<p>There is an additional danger in waiting to get vaccinated: the live Covid virus is mutating, and selection seems to be favoring &quot;variants&quot; that infect people much more easily and/or make people sicker once they are infected. Thus, the longer one waits to get a vaccine, the greater the chance of being infected by Covid once exposed, and the greater the chance of more serious illness once infected.</p>\n<p>The above analysis does not apply for other types of vaccines, such as those that use modified or crippled helper viruses to introduce parts of the Covid virus genetic material into cells, as the additional material introduced into cells is substantially more complex than just some fatty molecules.</p>\n<p>PS - In general, a vaccine just gives the body's immune response a &quot;preview&quot; of a likely future infectious agent, so that system is able to respond within hours or days instead of weeks once that agent infects the body, and clear it with little or no obvious illness symptoms. We are constantly exposed to infectious agents, triggering the specific immune system at some level probably daily. This immune response is so important to continued life that the system has been maintained and extended by evolution over hundreds of millions of years in vertebrate animals. That would likely not have been the case if it were easy to induce negative long-term consequences by triggering it (e.g. from vaccines). Thus, you can think of &quot;vaccines&quot; as essentially having a many-hundred-million year good safety record.</p>\n" } ]

[ "https://health.stackexchange.com/questions/25926", "https://health.stackexchange.com", "https://health.stackexchange.com/users/21566/" ]

[ { "answer_id": 26007, "author": "JMP", "author_id": 97, "author_profile": "https://health.stackexchange.com/users/97", "pm_score": 3, "selected": false, "text": "<p>The full details are quite complicated, but this nomenclature defines SARS-CoV-2 variants by a lineage depending on which variant they are descended from.</p>\n<blockquote>\n<p><a href=\"https://www.biorxiv.org/content/10.1101/2020.04.17.046086v1.full.pdf\" rel=\"noreferrer\">A dynamic nomenclature proposal for SARS-CoV-2 to assist genomic\nepidemiology</a></p>\n<p>Andrew Rambaut, Edward C. Holmes, Verity Hill, Áine O’Toole, JT McCrone, Chris Ruis, Louis du Plessis, Oliver G. Pybus</p>\n</blockquote>\n<p>This article can be found from <a href=\"https://pangolin.cog-uk.io/\" rel=\"noreferrer\">Pangolin</a> (<strong>P</strong>hylogenetic <strong>A</strong>ssignment of <strong>N</strong>amed <strong>G</strong>lobal <strong>O</strong>utbreak <strong>LIN</strong>eages, in case you were wondering!).</p>\n<p>which uses the above system in it's software.</p>\n<p>The concept is not unique however, for example <a href=\"https://nextstrain.org/\" rel=\"noreferrer\">NextStrain</a> use the following to name their COVID-19 clades.</p>\n<blockquote>\n<p><a href=\"https://docs.nextstrain.org/en/latest/tutorials/SARS-CoV-2/steps/naming_clades.html\" rel=\"noreferrer\">https://docs.nextstrain.org/en/latest/tutorials/SARS-CoV-2/steps/naming_clades.html</a></p>\n</blockquote>\n" }, { "answer_id": 26008, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 3, "selected": false, "text": "<p>Alas (Pangoling/COG-UK) base letterings don't stand for location. And neither do the numbers following them stand for directly identifiable mutations except for the &quot;with E484K&quot; designators. Those directly stand for specific mutations relative to the first-identified/original variant. As Wikipedia explains</p>\n<blockquote>\n<p>The name of the mutation, E484K, refers to an exchange whereby the glutamic acid (E) is replaced by lysine (K) at position 484. It is nicknamed &quot;Eeek&quot;.</p>\n</blockquote>\n<p>As for designations like B.1.1.7 those refer indirectly to mutations. The competing designation for that from Nextstrain <a href=\"https://en.wikipedia.org/wiki/Lineage_B.1.1.7\" rel=\"nofollow noreferrer\">is</a> 20I/501Y.V1 (formerly 20B/501Y.V1).</p>\n<p><a href=\"https://nextstrain.org/\" rel=\"nofollow noreferrer\">Nextstrain</a> is a US-Swiss endeavor, while Pangolin/COG-UK <a href=\"https://en.wikipedia.org/wiki/COVID-19_Genomics_UK_Consortium#Developments\" rel=\"nofollow noreferrer\">is</a> (somewhat evidently) UK based.</p>\n<p>As for the Pangolin naming, they started with two letter (A and B) but the first letter actually changes when the nesting gets too deep:</p>\n<blockquote>\n<p>We propose that major lineage labels begin with a letter. At the root of the phylogeny of SARS-CoV-2 are two lineages that we simply denote as lineages A and B. The earliest lineage A viruses, such as Wuhan/WH04/2020 (EPI_ISL_406801), sampled on 2020-01-05, share two nucleotides (positions 8782 in ORF1ab and 28144 in ORF8) with the closest known bat virus (RaTG13). Different nucleotides are present at those sites in viruses assigned to lineage B, of which Wuhan-Hu-1 (Genbank accession MN908947) sampled on 2019-12-26 is an early representative. Hence, although viruses from lineage B were sequenced and published first (Wu et al. 2020; Zhu et al. 2020; Lu et al. 2020), it is likely (based on current data) that lineage A viruses form the root of the SARS-CoV-2 pandemic phylogeny. At the time of writing, viruses from both lineages A and B are still circulating in many countries around the world [...]</p>\n<p>e then defined\nfurther SARS-CoV-2 lineages, each of which descends from either lineage A or B and is\nassigned a numerical value (e.g. lineage A.1, or lineage B.2). Lineage designations were made\nusing the following set of conditions: [...]</p>\n<p>Each descendent lineage should show phylogenetic evidence of emergence from an\nancestral lineage into another geographically distinct population, implying substantial\nonward transmission in that population. In the case of a rapidly expanding global lineage\nthe recipient “population” may comprise multiple countries. In the case of large and\npopulous countries it may represent a new region or province. [...]</p>\n<p>The iterative procedure in step II can proceed for a maximum of 3 sublevels (e.g. A.1.1.1) after which new descendent lineages are given a letter (in English alphabetical sequence from C - so A.1.1.1.1 would become C.1 and A.1.1.1.2 would become C.2.</p>\n</blockquote>\n<p>At the time that paper was written B.1.1.7 had not yet been identified, but its ancestors were:</p>\n<p><a href=\"https://i.stack.imgur.com/tnv0J.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/tnv0J.png\" alt=\"enter image description here\" /></a></p>\n<p>As you can see B.1.1 had spread to the UK, so the &quot;Kent&quot; variant discovered in late 2020 was assigned under B.1.1 for those reasons.</p>\n<p>Now the <a href=\"https://en.wikipedia.org/wiki/Lineage_P.1\" rel=\"nofollow noreferrer\">lineage P.1</a> for example</p>\n<blockquote>\n<p>has also been called 'B.1.1.28.1', although strictly only three sublevels are permitted in the PANGO Lineage system of nomenclature, hence the designation 'P.1'.</p>\n</blockquote>\n" } ]

[ "https://health.stackexchange.com/questions/26006", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7446/" ]

[ { "answer_id": 26037, "author": "Carey Gregory", "author_id": 805, "author_profile": "https://health.stackexchange.com/users/805", "pm_score": 3, "selected": false, "text": "<p>First off, my condolences on your loss.</p>\n<p>No one can tell you whether the person was alive when found or if more could be done because that would be pure speculation. We don't have sufficient information to even make an educated guess. But I can tell you that finding the fists clinched alone is not sufficient to conclude that they were still alive or that more could have been done.</p>\n<p>Normally, when cardiac arrest occurs, all the muscles in the body go limp immediately and stay that way until rigor sets in. However, what you've described fits the phenomenon known as <a href=\"https://en.wikipedia.org/wiki/Cadaveric_spasm\" rel=\"noreferrer\">Cadaveric Spasm</a> very closely, as you can see from <a href=\"https://www.ncbi.nlm.nih.gov/books/NBK539741/\" rel=\"noreferrer\">this description</a>:</p>\n<blockquote>\n<p>Cadaveric spasm is a condition in which a group of muscles that were\nused profusely just before death becomes stiff and rigid immediately\nafter death.[24] This ‘instantaneous rigor’ mostly involves hands,\nvery rarely, the entire body may undergo cadaveric spasm. It can occur\nin assaults involving a scuffle before death, in suicides, and cases\nof drowning, etc. In such scenario, the victim’s hand presents as\nrigid and clenched, holding/ grasping on to the clothing, buttons, or\nhair, etc. of the assailant (in assault), maybe holding the weapon\nused for committing suicide, or the weeds, gravel mud, etc. from the\nwater bed (in drowning). While rigor mortis provides information about\ntime since death, the cadaveric spasm is valuable in commenting on the\nmanner of death.</p>\n</blockquote>\n<p>Your description matches several key points in the description above:</p>\n<ul>\n<li>In a hanging death, it's quite likely the victim struggled and\nclutched at the rope in the final moments, thereby using their hand\nmuscles profusely.</li>\n<li>It was a suicide.</li>\n<li>&quot;the victim’s hand presents as rigid and clenched&quot; -- as did yours.</li>\n</ul>\n<p>So you can't base any conclusions on what the first arriving person found and what they should or should not have done based on the clinched fists.</p>\n<p>EDIT:</p>\n<p>Cadaveric spasm was <a href=\"https://jamanetwork.com/journals/jama/article-abstract/468552\" rel=\"noreferrer\">described in JAMA in 1898</a>.</p>\n" }, { "answer_id": 26040, "author": "Martin", "author_id": 21789, "author_profile": "https://health.stackexchange.com/users/21789", "pm_score": 1, "selected": false, "text": "<p>I lost a friend to a hanging suicide about 30 years ago, so I looked into this. I'm not medically trained, so the following is a summary of what I could discover; please check it before relying on it.</p>\n<p>Rigor, either of the whole body, or localized as spasm, is where myofiber (muscle) cells fully contract once they exhaust their internal energy reserves. These cells are relatively tolerant of anoxia, so this doesn't usually start until around 2 hours after respiration ceases, but may occur much sooner if the muscles have been exercising or heated.</p>\n<p>Many people who attempt suicide by hanging wrongly assume that it is an instantaneous method. However like any method that relies on depriving the brain of oxygen, loss of consciousness may take up to 15 seconds after blood flow to the brain stops, or several minutes if breathing is stopped but blood flow to the brain continues.</p>\n<p>Suicide by hanging often fails to break the neck, and fails to constrict the carotid artery, allowing for vigorous activity by the forearm muscles so that they may become both &quot;exercised&quot; and &quot;heated&quot;.</p>\n<p>The adrenal stress response increases metabolism within the brain, continuing to burn the small-and-now-depleted energy reserves in brain tissue even after consciousness is lost, which reduces the time during which they could potentially be revived.</p>\n<p>Unless the victim is (unusually) strong enough to lift their own weight and relax the asphyxia, and has the presence of mind to do so, they are unlikely to remain conscious long enough for muscular activity to make any appreciable difference to the length of time for whole-body rigor mortis to set in.</p>\n" } ]

[ "https://health.stackexchange.com/questions/26036", "https://health.stackexchange.com", "https://health.stackexchange.com/users/2244/" ]

[ { "answer_id": 26054, "author": "Carey Gregory", "author_id": 805, "author_profile": "https://health.stackexchange.com/users/805", "pm_score": 1, "selected": false, "text": "<p>Because it <em>may</em> be toxic.</p>\n<p><a href=\"http://www.ihcworld.com/royellis/ABCSafe/chemicals/orcein.htm\" rel=\"nofollow noreferrer\">http://www.ihcworld.com/royellis/ABCSafe/chemicals/orcein.htm</a></p>\n<blockquote>\n<p>HEALTH HAZARD DATA</p>\n<p>The toxicity of orcein has not been quantified but\nother dyes in this group are known to be highly toxic and mutagenic,\neg. thionine. Because of its chemical composition it is assumed to be\nan eye and possible skin irritant. Can be absorbed through the skin.</p>\n</blockquote>\n<p>As for how it was banned in Europe before the EU existed, I would imagine that's a bit of an overstatement. It was probably banned by one or more of the larger, more influential countries and others followed suit, but I would be very surprised to learn that all of Europe followed that lead, particularly the Soviet Union and Eastern Bloc. A detailed answer to that part of the question is better suited for History.SE.</p>\n" }, { "answer_id": 26055, "author": "JMP", "author_id": 97, "author_profile": "https://health.stackexchange.com/users/97", "pm_score": 2, "selected": false, "text": "<p>Searching for Orcein on the EU website:</p>\n<blockquote>\n<p><a href=\"https://op.europa.eu/en/\" rel=\"nofollow noreferrer\">https://op.europa.eu/en/</a></p>\n</blockquote>\n<p>returns this publication, amongst others:</p>\n<blockquote>\n<p>REPORTS OF THE SCIENTIFIC COMMITTEE FOR FOOD. First series. (European Commission).</p>\n</blockquote>\n<p>The article that discusses Orchil and Orcein (page 17)</p>\n<blockquote>\n<p>REPORT OF THE SCIENTIFIC COMMITTEE FOR FOOD ON THE REVISION OF THE DIRECTIVE ON COLOURING MATTERS AUTHORIZED FOR USE IN FOODSTUFFS INTENDED FOR HUMAN CONSUMPTION (1975)</p>\n</blockquote>\n<p>(<a href=\"https://op.europa.eu/en/publication-detail/-/publication/275edf96-6233-416c-952a-ca5ebc68ade6/language-en/format-PDF/source-199724795\" rel=\"nofollow noreferrer\">Link</a>)</p>\n<p>claims that an ADI (Acceptable Daily Intake) could not be found (bottom of page 18), and then proceeds to outline the case for banning it.</p>\n" } ]

[ "https://health.stackexchange.com/questions/26053", "https://health.stackexchange.com", "https://health.stackexchange.com/users/5371/" ]

[ { "answer_id": 26211, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 2, "selected": false, "text": "<p>While I realize this doesn't answer your question in the narrow way that you frame it (&quot;I do not believe that we can exclude accidental errors as a potential cause&quot; as you put it), I'm offering this as a frame challenge to the theory that accidental i.v. injection is the <em>main</em> reason why STT occurred in those patients.</p>\n<p>There's a 2020-published <a href=\"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/full/10.1002/jat.3941\" rel=\"nofollow noreferrer\">study</a> on the biodistribution of ChAd3 vaccine in rats. (The vaccine itself has already been administered in humans in some years prior.) In my non-expert opinion, the important point is that even after presumably-as-properly-as-I.M.-injection-can-be-done-in-a-lab-setting, there was systemic DNA circulation detected in the blood within 24 hours.</p>\n<p><a href=\"https://i.stack.imgur.com/9pXnM.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/9pXnM.png\" alt=\"enter image description here\" /></a></p>\n<blockquote>\n<p>In the biodistribution study, rats received a single intramuscular injection of\neither ChAd3-EBO-Z or saline\n[...] Blood was collected before necropsy from the abdominal aorta or\nvena cava of animals (under deep anesthesia)</p>\n</blockquote>\n<p>So while you seem to have a binary approach (i.v. accident/error vs totally proper I.M. injection), biology doesn't seem to work that way in practice.</p>\n<p>On the other hand, it's also true from <a href=\"https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1521-2254(199909/10)1:5%3C360::AID-JGM54%3E3.0.CO;2-Q\" rel=\"nofollow noreferrer\">older studies</a> (cited in that paper) that the level of such effects was (administration) dose-dependent, so very likely it's also dose-dependent on the amount of DNA that does get into the blood even after a as-proper-as-can-be-done I.M. injection.</p>\n<p>So, a more proper way to frame the problem would be to measure the amount of circulating viral DNA (even after a seemingly-totally-proper-I.M.-injection) and correlate <em>that</em> with the side effects of concern here. But I don't know of any study that has done that.</p>\n<hr />\n<p>Furthermore, one interesting, perhaps, angle here is that most of the papers cited in the (two) studies you've linked to were actually done on Ad5. Quoting from one of these (<a href=\"https://jvi.asm.org/content/81/9/4866\" rel=\"nofollow noreferrer\">Lieber et al. (2007)</a>):</p>\n<blockquote>\n<p>Adenovirus-Platelet Interaction in Blood Causes Virus Sequestration to the Reticuloendothelial System of the Liver [...]</p>\n<p>it is well documented that Ad5-based vectors induce thrombocytopenia after i.v. delivery (7, 37, 47, 50) [...]</p>\n</blockquote>\n<p>Lieber's study itself was done on Ad5.</p>\n<p>In the Ad26-related literature (relevant to J&amp;J's vaccine), and more generally in &quot;species D&quot; favoring literature (Ad5 is &quot;species C&quot;; Ad26 is &quot;species D&quot;), some effort is made claim that those Ad5-findings might not apply to them, at least to the same extent, <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762200/\" rel=\"nofollow noreferrer\">e.g.</a></p>\n<blockquote>\n<p>Biodistribution studies of Ad26 and Ad48 demonstrated no liver sequestration after intravenous delivery, in contrast to Ad5.</p>\n</blockquote>\n<p>The latter claim seem to rely on single 2008 paper (Baker et al.), which did look at the precise (Ad5) protein [hexon] involved; the gist of it is in its <a href=\"https://www.cell.com/cell/fulltext/S0092-8674(08)00116-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867408001165%3Fshowall%3Dtrue#fig7\" rel=\"nofollow noreferrer\">figure 7</a>. The Ad-26 treated mice literally glow in the dark less than the Ad5-treated ones, in the liver area. That Baker paper also dabbled with swapping out the precise Ad5 genes involved with ones from Ad48, creating a chimeric Ad5 that was more &quot;nicely behaved&quot; with respect to liver accumulation &amp; toxicity.</p>\n<p>So, Ad26-proponents (at least the Gamaleya press releases) thus seem to want to claim that Ad26-vectored therapeutics would be less susceptible to other kinds of side effects (besides lower liver toxicity) that were noted with &quot;stock&quot; Ad5. But I think the difference is rather insufficiently quantified otherwise; (insofar) I could not find comparative studies on how much the precise choice of Ad vector subtype matters for thrombocyte count or coagulation issues. (There is however a more in-depth <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762479/\" rel=\"nofollow noreferrer\">2012 study</a> on how Species C (Ad5) triggers coagulation.)</p>\n" }, { "answer_id": 29193, "author": "user21820", "author_id": 21912, "author_profile": "https://health.stackexchange.com/users/21912", "pm_score": 2, "selected": true, "text": "<p><strong>Yes</strong>. <a href=\"https://www.nature.com/articles/d41586-021-02291-2\" rel=\"nofollow noreferrer\">This recent Nature article</a> mentions a few potential hypotheses for vaccine-related blood clots, including the hypothesis in question here:</p>\n<blockquote>\n<p>One possible factor affecting the safety of adenoviral vaccines is how they are administered. The COVID-19 vaccines are given as injections into muscle, but if the needle happens to puncture a vein, the vaccine could enter the bloodstream directly. Leo Nicolai, a cardiologist at Ludwig Maximilian University of Munich, Germany, and his colleagues found in a mouse study that platelets clump together with adenovirus and become activated when the Oxford–AstraZeneca vaccine is injected into blood vessels, but not when it is injected into muscle.</p>\n</blockquote>\n<p>It cites <a href=\"https://www.biorxiv.org/content/10.1101/2021.06.29.450356v1.full\" rel=\"nofollow noreferrer\">Nicolai et al. (2021)</a>, which provided experimental support in mice models of thrombocytopenia due to the AstraZeneca vaccine after intravenous injection but not after intramuscular injection. It does state that animal models may not reproduce effects observed in humans, but it does provide evidence that vaccine-related blood clots could be due partly to injection technique.</p>\n" } ]

[ "https://health.stackexchange.com/questions/26146", "https://health.stackexchange.com", "https://health.stackexchange.com/users/21912/" ]

[ { "answer_id": 26242, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 3, "selected": true, "text": "<p>mRNA (messenger RNA) is the &quot;working copy&quot; of gene that the machinery in the cell's cytoplasm uses to direct synthesis of a protein (translation). Thus, if you can get a suitable-looking mRNA into the cytoplasm (e.g. by coating it with NLP), the cell will start translating it.</p>\n<p>DNA, on the other hand, first needs additional machinery to make an mRNA working copy from it (transcription), which process takes place in the cell's nucleus. It's much harder to get things into the nucleus from outside the cell. Adenoviruses are not only robust (hence their long shelf life under refrigeration), but as double-stranded DNA viruses they are already specialized to get their DNA contents into the nucleus and get it transcribed.</p>\n<p>It's all a matter of the right tool for the job.</p>\n<p>Edit: Regarding transport of the viral DNA into the nucleus, here's part of an abstract from a relevant paper: (&quot;Viral entry into the nucleus&quot; PMID: 11031249 DOI: 10.1146/annurev.cellbio.16.1.627)</p>\n<p>&quot;Because many viruses replicate in the nucleus of their host cells, they must have ways of transporting their genome and other components into and out of this compartment. For the incoming virus particle, nuclear entry is often one of the final steps in a complex transport and uncoating program. Typically, it involves recognition by importins (karyopherins), transport to the nucleus, and binding to nuclear pore complexes. Although all viruses take advantage of cellular signals and factors, viruses and viral capsids vary considerably in size, structure, and in how they interact with the nuclear import machinery. Influenza and adenoviruses undergo extensive disassembly prior to genome import&quot;</p>\n<p>Just injecting DNA into the cytoplasm won't do much of anything - a lot of machinery is needed to get it to and into the nucleus, some supplied by the virus and some supplied by the cell. NLPs have none of that.</p>\n" }, { "answer_id": 29262, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 0, "selected": false, "text": "<p><a href=\"https://www.nature.com/articles/s41598-020-65059-0\" rel=\"nofollow noreferrer\">There are</a> experimental vaccines that deliver DNA of interest (e.g. that would express spike protein) merely tied to a plasmid encapsulated in a LNP (liquid nano-particle). Some animal trials indicate that LNP-encapsulated plasmid-DNA vaccines would achieve approximately 10-20 times better delivery efficiency than &quot;naked&quot; plasmid-DNA injection, i.e. LNP encapsulation would lead to that 10-20 times less active substance (and possibly fewer booster doses as well).</p>\n<p>The recently approved (in India) ZyCoV-D, which is a plasmid-DNA vaccine (exact plasmid <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166516/\" rel=\"nofollow noreferrer\">used</a> is pVAX-1, which has been commercially available for at least a decade), doesn't seem use a LNP encapsulation though. ZyCoV-D requires <em>three</em> doses as the initial schedule, so delivery efficiency (via a jet injector) is probably not as good as what could achieve with additional LNP encapsulation.</p>\n<p>Basically, a plasmid is circular piece of DNA (typically found in bacteria) that if it makes it into the nucleus, results in mRNA being produced from a certain part of it--part which follows the promoter region/gene. pVAX-1 [for instance] uses the promoter from the cytomegalovirus (CMV). CREB binding sites in this promoter region <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705778/\" rel=\"nofollow noreferrer\">facilitate</a> movement to the nucleus, although that might not be whole story of how it achieves nuclear import. The current plasmid-based vaccines seem to rely on rather inefficient means of nuclear import. Something like 1-3% of plasmids injected into cytoplasm make it into the nucleus.(The full CMV appears substantially more complicated in this regard, with additional nuclear localization sites in other large proteins, only more recently <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648141/\" rel=\"nofollow noreferrer\">identified</a>.)</p>\n<p>LNP encapsulation is a fairly expensive procedure, which requires investing in highly specialized microfluidics equipment, so there's probably a commercial tradeoff between &quot;brute forcing&quot; the solution with more DNA vs. encapsulating in LNP.</p>\n<p>For mRNA the benefits of LNP encapsulation are perhaps even higher; <a href=\"https://link.springer.com/article/10.1007/s12195-020-00619-y\" rel=\"nofollow noreferrer\">one paper</a> reported 40-fold increase in expression with LNP encapsulation than without.</p>\n<p>I'm not totally sure about this, but currently it seems that plasmid-DNA vaccines cannot be made by the mostly synthetic route that mRNA vaccines use, i.e. plasmids still need to be grown in bacteria inside bioreactors, which makes them less attractive than mRNA-LNP vaccines in that regard.</p>\n<hr />\n<p>Adenovirus vectored vaccines (like Astra Zeneca's) are grown with the virus infecting actual cells, so you cannot easily replace the DNA inside this DNA-based virus (family) with RNA. The &quot;trick&quot; with an adenovirus-vectored vaccine is that it doesn't replicate in <em>most</em> cells, but it does replicate in the ones in which it is actually grown; these cells are themselves <a href=\"https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-021-00859-1\" rel=\"nofollow noreferrer\">modified</a> to actually supply the missing replication gene for the virus.</p>\n<blockquote>\n<p>Adenovirus-based vectors typically have two regions of the virus genome removed, known as E1 and E3. The E1 region contains early genes required to trigger a transcription cascade enabling viral replication; E1-deleted vectors therefore need to be grown in E1 trans-complementing cell lines such as HEK293 cells. HEK293 cells have a 4-kbp region of human adenovirus type 5 (HuAd5) integrated into the cellular genome that provides the E1 genes in trans enabling efficient virus vector replication and recombinant virus production. [...] Usually, the transgene to be expressed [e.g. spike] is inserted into the virus genome in place of the E1 region under the control of a highly active promoter.</p>\n</blockquote>\n<p>There is <a href=\"https://www.criver.com/eureka/viral-vector-quandary\" rel=\"nofollow noreferrer\">actually</a> a small risk that some of the viruses produced this way are replication\ncompetent, by including (via recombination events) the original E1 gene from the cell in which they are grown. One of the reasons for selecting a virus that is not adapted to humans <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842362/\" rel=\"nofollow noreferrer\">is to minimize</a> the chance of bad outcomes stemming from this risk. (The other/major reason is to limit the likelihood the immune response will react to the vector before it can deliver is transgene payload.)</p>\n<p>There are also some further similarities between the ZyCoV-D vaccine and the AZ vaccine: both use the CMV promoter to mark the start of the transgene, which is also terminated by the same BGH poly-A sequence. So, on this level, they rely on the same cookbook once in the nucleus.</p>\n<p>Finally, RNA viruses have also been <a href=\"https://doi.org/10.3390/genes10030189\" rel=\"nofollow noreferrer\">tried</a> as viral vectors. There were even some head-to-head comparisons with DNA vectored-vaccines; like between ChAd3 and rVSV viral vectors <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705229/\" rel=\"nofollow noreferrer\">for Ebola (2017)</a>; as far as I can tell, there wasn't much difference in either safety or effectiveness in that trial. The RNA-virus-vectored vaccine for Ebola was <a href=\"https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-ebola-virus-disease-marking-critical-milestone-public-health\" rel=\"nofollow noreferrer\">approved</a> by the FDA in 2020. There's also an <a href=\"https://www.nature.com/articles/s41467-020-20228-7\" rel=\"nofollow noreferrer\">experimental</a> Covid-19 vaccine based on the same rVSV platform. I'm not entirely sure why this was not pursued, but I suspect that it's because RNA-viral-vectored vaccines <a href=\"https://academic.oup.com/jid/article/217/suppl_1/S48/4999139\" rel=\"nofollow noreferrer\">need</a> -60 degrees C storage, so the DNA-based vaccines definitely have an advantage here.</p>\n" } ]

[ "https://health.stackexchange.com/questions/26241", "https://health.stackexchange.com", "https://health.stackexchange.com/users/-1/" ]

[ { "answer_id": 26270, "author": "aitía", "author_id": 1881, "author_profile": "https://health.stackexchange.com/users/1881", "pm_score": 1, "selected": false, "text": "<p>This is normal, anatomy is a complex subject to grasp at first. I can suggest the following to help you study more efficiently:</p>\n<p><strong>Learning Strategies</strong></p>\n<ul>\n<li>Begin by knowing all <a href=\"https://en.wikipedia.org/wiki/List_of_systems_of_the_human_body\" rel=\"nofollow noreferrer\">systems</a> of the human body\n(learn the skeletal system first and then the muscular system etc.)</li>\n<li>Focus on a particular system and <a href=\"https://human.biodigital.com\" rel=\"nofollow noreferrer\">visualize</a> its parts\n(learn the head and go down or start with fingers then limbs etc.)</li>\n</ul>\n<p><strong>Learning Approaches</strong></p>\n<ul>\n<li>Exercise your knowledge and ability to recollect using anatomy <a href=\"https://www.google.ca/books/edition/Anatomy_Flashcards/qbZNMQEACAAJ\" rel=\"nofollow noreferrer\">flashcards</a></li>\n<li>Actively engage in your learning (don't only read), <a href=\"https://www.google.ca/books/edition/The_Anatomy_Coloring_Book/x3eArHrj6x4C\" rel=\"nofollow noreferrer\">color</a> and explain relations</li>\n</ul>\n" }, { "answer_id": 26320, "author": "02q4u", "author_id": 22124, "author_profile": "https://health.stackexchange.com/users/22124", "pm_score": 0, "selected": false, "text": "<p>Aitía gave you good answers to start with in structuring your learning: If you sort into digestable chunks what is up for learning, you can feed your long term potentiation with the necessary repetition.</p>\n<p>A friend once told me that he started to learn the (peripheral) nervous system first, so he found it easier, later, to attach muscles, and then muscles to bones - this approach is a functional one, not a structural one, though.</p>\n<p>I happen to memorize things better - and research has shown that to be effective for the brain - when I imagine a patient case (a pathology) related to an anatomical structure. If that is what you like, books of functional anatomy (you can lay them out side to side with those of structural anatomy) tend to explain more clinical cases or &quot;why's&quot;. Find something that connects the content to your life, so that your brain thinks, &quot;aah, that is why that matters&quot;, for example, if you do fitness, think of how muscles stretch or contract when you make a movement or how ligaments limit a certain movement etcetera. Many books come with clinical cases (take, for example, golfer's elbow - you may palpate your own Epicondylus medialis when making a fist - this lets you remember where the flexor muscles have their origin). The sensory experience of palpating what you just &quot;learned&quot; turns theoretical knowledge into practical knowledge. &quot;Learning&quot; often meant to the brain that the two were apart, and this performative approach often meant fatigue, thus, the disappearance of joy, which is a central motivating factor in the physiological learning of children.</p>\n<p>You can also be rigorous and make a learning plan. That is suggested in an exam preparation book series (The GK Series by Thieme, referring to a forum for German medial students, medi-learn.de), here a summary in my free and brief simplification:</p>\n<ul>\n<li><p>reserve 6-8 hours / day for learning, 5 days a week</p>\n</li>\n<li><p>keep track of until when you want to (or &quot;have to&quot;) learn &quot;what&quot;</p>\n</li>\n<li><p>don't learn too much &quot;all new&quot; stuff on one day/session, repetition is okay</p>\n</li>\n<li><p>if it is too complicated, learn it in chunks</p>\n</li>\n<li><p>read/learn before noon on one day, what you check/ask yourself in the afternoon of the next day (you can connect the dots with Aitía's flashcard example here)</p>\n</li>\n<li><p>truly seek in yourself what you know already, before you look at the back of a flashcard too fast</p>\n</li>\n<li><p>Let me add: There are also flashcard learning systems that put aside those cards you either labeled &quot;I don't need to repeat THAT&quot;, &quot;I could repeat that&quot; and &quot;I should repeat that&quot;.</p>\n</li>\n</ul>\n<p>It may also be worth to note that learning benefit from healthy sleep, even only naps, if the brain becomes tired after learning (studies show that after sleep, long term potentiation is improved). Most probably, if you ask it, your brain tells you about the way it likes to digest certain types of information. The more neurons blink, the more connections you make because things and their interdependence become important to your growing understanding, the better the connection between them gets and long term potentiation is reinforced. Podcasts, for example, can be a medium to listen to in supermarkets or subways, still keeping your mind &quot;at it&quot; ... I also imagined me being very small and the structures of the body like roads I'd travel (the french series &quot;Il était une fois… la Vie&quot; may have stimulated that). There is also good 3D visualisation software out there, if you look for it.</p>\n<p>There are types of questions explicity linking the &quot;chunks&quot; of structural anatomy, like &quot;What nerve innervates this muscle/organ&quot;, &quot;what muscle sits on that part of this bone&quot;, &quot;which ligament restricts that joint movement&quot; - you see that my anatomy is more or less based on musculoskeletal needs, but you might want to take that as a metaphor. In school we had a guy whom I talked to about his learning, and he said: &quot;I don't <em>learn</em> muscle functions at all, I simply remember where they are and then imagine what happens when they contract&quot;. He was somehow already thinking like the body when I was still learning some thinking. (However, the full scope of some muscle function also can't be explained by just looking at a drawing of them, but he made an important point to my slightly overfocused and a little bit narrow minded brain at the time. I was so busy in attempting &quot;to get it all right&quot; that I lost the big picture, &quot;that I can, basically, grasp things&quot;, just not all at once).</p>\n<p>If you speak with a buddy (like with us, here), but maybe off-Internet, you get a taste of the personal depth their learning had. One of my other buddies was the son of a doctor. He had a serious love for the stuff. Man, that still inspires me today! It helps me to understand that whatever I understand, &quot;why do I have the feeling he'd understand it better&quot;? But through always knowing-or-feeling that, I always learn, and it never gets <em>really</em> boring ... :)</p>\n<p>In the end, I wish to you that you can make learning fun and sometimes think of the smiles of the people that are grateful, when you help them .. it is really the most rewarding thing. My greatest joy is in balancing mild leg length differences with marginal heel lifts and check the results of possibly symmetrically aligned zygapophysial joint movement (with palpation, while radiology hardly is there so far). Here, I desperately <em>need</em> functional anatomy :)! Hardly anyone does mild leg length difference compensation in such relative precision, it is very successful and people are so thankful. Really strange that there's not much more science about &quot;the hard problem of practical relevance&quot; for LLD/LLI, which is of course my favorite example for why learning matters and is fun. I wish you all the success you can have, and that you find your own &quot;favourite problem&quot; to work with! Go for it :) !</p>\n" } ]

[ "https://health.stackexchange.com/questions/26269", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19940/" ]

[ { "answer_id": 26292, "author": "chrishmorris", "author_id": 15829, "author_profile": "https://health.stackexchange.com/users/15829", "pm_score": 2, "selected": false, "text": "<p>Yes ... unless the fit person uses their advantage to kill and eat the other.</p>\n<p>This is probably the evolutionary cause of obesity: if you have an irregular food supply, it is sensible to build up a stock, either externally stored food or internally stored fat. This gave us physiology, and preferences, that work less well in rich countries, where you are surrounded 24/7 by a buffet.</p>\n" }, { "answer_id": 26293, "author": "Katie", "author_id": 22060, "author_profile": "https://health.stackexchange.com/users/22060", "pm_score": 4, "selected": true, "text": "<p>Assuming no underlying health problems and similar muscle stores, the obese person would survive significantly longer.</p>\n<p>When eating normally, the body gets most of its energy from free glucose and glycogen stores. After a day or two of no food intake, the body will switch to get most of its energy from the breakdown of fat tissue. Some cell types can't utilize energy from fat, so those cells will get energy from the breakdown of muscle protein which can be converted to glucose (<a href=\"https://www.ncbi.nlm.nih.gov/books/NBK22414/\" rel=\"noreferrer\">Biochemistry Textbook - 30.3.1</a>).</p>\n<p>Death from starvation can occur due to running out of fat tissue, or running out of muscle tissue that can be safely broken down. A person of average body weight would generally run out of fat tissue first, whereas an obese person would run out of muscle tissue first (<a href=\"https://watermark.silverchair.com/12.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAApYwggKSBgkqhkiG9w0BBwagggKDMIICfwIBADCCAngGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM7kXz8ihHKFkF-nGBAgEQgIICSRUCL3Zaqv4xt1DDaWoEP8PSFEFoyxsEhoYtpWDTS6XTn1d4R_TCafoYl9K-LuUtZmQ1btjnF5ld1DSatPQsaR2V2-KoAblzVq1CbymPtIYplz9C5elGh1DsLI1cp4cThIaVWdnYcWAmuj7-ZQ6EHUSy18PSMUjL1yVwDHjdZFhOmNolv_EIZCJGZAbuiHbYEveT00ElX7I60onRhTKWGKhkcCdqL-rEN7UKYv9jn3Go3ONI4eHHr7-H3tPVjgMPGREnj2amF-fzOIlWpnYp9yNn1OayfKQnc-WxU2ascwiAXeNdNm7PNL-QgSbav07uVfyWNE06UMBQx4Cno7uLDr5fxVPhaGf1Dbzp6yrMx5_Aif0uSMTvYBhwFFn53mO9DzICvlKuKMjuSDFAFUn0ZxQ22wIy33IIXtP0PTWMJxOAaZ1TAaCRwh9LjMBGjDNWIFLN94BF9-iWxCUooe8Vnk08scUS9RziNJO6Kx4UZ7VwjoapWg0aEcXARkJNyNqSZROcKmBL3e_t9fKvF_i03dqdcTV4UFt6ALbiXPA2ZYnumypDLxZNDyCaPzRVpmr3zQrx2y5XroU-L3iOH6RMqgqRiE-eX1KJDIymJGO2O-BGwUcRyDVk9xarN9daTIb1Y12_MpFZPmB7b7Mt2N4yWZe1OSFdcgYmSNdOnkfj8QKgm22kRDbIj6zWGrDu8SjUCkVd03YMFUYSyY2ghufwqA9dxig3uV0ZTYF_CKzIs5jcFJWwlozH4wkAGzsqYY3uT5UOI3B_c25YAw\" rel=\"noreferrer\">Review Article - see pg. 15</a>). Assuming they started with the same amount of muscle tissue, that means the obese person would survive longer.</p>\n<p>A caveat: The immune system is significantly weakened in starvation due to metabolic changes, making deadly infections common (<a href=\"https://www.who.int/emergencies/humanitarian-emergencies/famine/en/\" rel=\"noreferrer\">WHO</a>). An obese person would not have advantage against those infections.</p>\n<p>To answer your second framing:</p>\n<p>The average person can survive a long time without eating - about 1 to 3 months (<a href=\"https://www.ncbi.nlm.nih.gov/books/NBK22414/\" rel=\"noreferrer\">Biochemistry Textbook - 30.3.1</a>) (<b>NOTE: This does NOT mean a person can safely fast for more than a day or so at a time. After a few days there will be significant, often permanent damage to many organs</b>). That said, vitamin deficiencies take even longer to develop in most cases (<a href=\"https://www.betterhealth.vic.gov.au/health/healthyliving/vitamins-common-misconceptions#deficiencies-and-illness\" rel=\"noreferrer\">Victoria Dept. of Health</a>), so taking a multivitamin wouldn't help much.</p>\n" } ]

[ "https://health.stackexchange.com/questions/26285", "https://health.stackexchange.com", "https://health.stackexchange.com/users/13209/" ]

[ { "answer_id": 26369, "author": "JMP", "author_id": 97, "author_profile": "https://health.stackexchange.com/users/97", "pm_score": 0, "selected": false, "text": "<p>According to the 'History' link on the DICOM web site:</p>\n<blockquote>\n<ul>\n<li><a href=\"https://www.dicomstandard.org/history\" rel=\"nofollow noreferrer\">https://www.dicomstandard.org/history</a></li>\n</ul>\n</blockquote>\n<p>in 2013, <a href=\"https://www.dicomstandard.org/dicomweb/\" rel=\"nofollow noreferrer\">DICOMweb</a> was introduced, and this uses <a href=\"https://en.wikipedia.org/wiki/Representational_state_transfer\" rel=\"nofollow noreferrer\">RESTful</a> web services, which uses HTML, XML and JSON.</p>\n<blockquote>\n<p>Second generation RESTful web services defined to retrieve, store and query DICOM images. The suite of web services is re-branded as DICOMweb™, and is aligned with the upcoming HL7 FHIR web services:</p>\n</blockquote>\n" }, { "answer_id": 27392, "author": "Andrew Ho-Lee", "author_id": 22187, "author_profile": "https://health.stackexchange.com/users/22187", "pm_score": 2, "selected": false, "text": "<p>I would flip this question on its head and ask what you think the benefit would be to changing the underlying file format? There are a few points that I can think of that might help frame the context for you, but there is probably no &quot;correct answer&quot; in the SE-sense.</p>\n<p>Imagine if a new file format were to be developed in medical imaging which stored its data in JSON. There would still need to be a separate documented standard that exhaustively details how imaging data is coded in this new format. That already exists in the form of the DICOM standard, so why rewrite it when it will still need to be interpreted by any library using this new format?</p>\n<p>Secondly, remember that in clincial practice medical software is a diverse mix of vendors from all over the world, some large, some small. There is no unifying body that mandates how software companies design their products, and interoperability is already extremely challenging. Given the established nature of DICOM, there is little incentive for these vendors to invest money in creating / utilising a different standard. Even if they were to do so, hospitals are notorious for being stuck on legacy software. <a href=\"https://www.theguardian.com/technology/2010/jan/22/internet-explorer-nhs-vulnerability\" rel=\"nofollow noreferrer\">This article</a> from 2010 gives you an idea of the state of play. Even today, one of the pieces of software I use on a daily basis only works in Internet Explorer, not in Edge/Chrome.</p>\n<p>It is probably worth noting that DICOM is not the only medical imaging file format in use, although it is probably the most prevalent in the clincial setting. For example, the <a href=\"https://nifti.nimh.nih.gov/\" rel=\"nofollow noreferrer\">NifTI format</a> is widely used in the neuroimaging research space.</p>\n<p>Bear in mind, as well, that medical imaging data is very heterogeneous and so writing a new standard is not a small task. For example:</p>\n<ul>\n<li>A chest X-ray is a 2D grayscale image</li>\n<li>A CT scan is multiple stacked 2D images, sometimes with several series (i.e. several associated stacks) in a single scan</li>\n<li>A PETCT scan would include a co-registered map onto a CT displaying tracer avidity detected by the gamma camera</li>\n<li>A 4DCT would also incorporate a time element into this</li>\n<li>DICOM-RT objects could include information such as radiotherapy dose planned to a particular voxel, or the physical position of a radiotherapy field</li>\n</ul>\n<p>This is before you get into the metadata associated with it, which ranges from patient demographics, the field strength of the MRI scanner, the frame of reference of the scan and beyond.</p>\n<p>Finally, what do you mean when you say</p>\n<blockquote>\n<p>it would significantly decrease the amount of work needed&quot;?</p>\n</blockquote>\n<p>There exist already many libraries (e.g. <a href=\"https://pydicom.github.io/\" rel=\"nofollow noreferrer\">pydicom</a>) to work with DICOM, if there were a JSON-based format they would then need to be developed for that.</p>\n" } ]

[ "https://health.stackexchange.com/questions/26355", "https://health.stackexchange.com", "https://health.stackexchange.com/users/17183/" ]

[ { "answer_id": 26363, "author": "Kate Gregory", "author_id": 400, "author_profile": "https://health.stackexchange.com/users/400", "pm_score": 2, "selected": false, "text": "<p>Two facts you need: first, clinical trials have very strict rules for who can be in them. Second, some trials are &quot;drug A vs placebo&quot; while others are &quot;Drug A vs Drug B&quot; or &quot;Drug A vs Drugs A and B together&quot; not to mention variations in dose etc. It's not all a matter of &quot;we won't treat half the participants.&quot;</p>\n<p>I was in a trial for &quot;dose X1 of drug A and dose Y1 of drug B&quot; vs &quot;dose X2 of drug A and dose Y2 of drug B&quot;. Previous studies had shown that both of these had the same efficacy, and this study was to compare side effects. There were entrance rules like &quot;no brain metastases&quot; and on each day of treatment, rules about how ill you were allowed to be. I personally came very close to being too ill for the study so I learned quite a lot about that. Your hypothetical patient in very poor condition is more likely to be removed from the study, at which point they can only get the current treatment, not the intervention being studied. (In some cases their doctor can arrange for them to get the study drug outside the study; this depends on how medications are regulated where they live.)</p>\n<p>Clinical trials in the US are listed on clinicaltrials.gov. Here is the <a href=\"https://clinicaltrials.gov/ct2/show/NCT04482621\" rel=\"nofollow noreferrer\">record for one study</a> I chose at random, studying a possible Covid treatment. You can see that it makes clear what is being compared (this one is drug vs placebo, but explore the site and you'll find drug vs drug, dose vs dose and more), how many are in the study (12 at first, later a total of 40) and the eligibility criteria (quite a way down the page) ruling large sets of people out for being too ill. It doesn't say there that patients will be removed if they develop an exclusion criteria, but that is the practice.</p>\n<p>The matter of it being unethical to give someone a placebo is far more complicated than you think, and cannot be solved by giving the sickest people the drug on compassionate grounds. (For example, those people might die at a higher rate than others, making the drug look bad and causing less people to get the drug over the coming years.) Generally, people go into studies knowing they may not be saved by the study and have made peace with that. I can tell you that I did.</p>\n<p>As a third fact, in the majority of modern day trials nobody (not the patient, not the people administering the treatment, not the people assessing the subsequent health of the patient -- recovery and side effects) have any idea who is getting what. In my study, there was ONE PERSON I never met who actually put the drug in an IV bag with coded number stickers on it and delivered it to the chemo nurses who administered it. Everything was done the same no matter what arm of the study the patients happen to be in. In placebo studies this includes carefully infusing saline, giving people all the same process as if they were actually getting IV meds. THis would make it impossible for a doctor to do as you suggest even if it was a good idea (which it isn't.)</p>\n<p>Studies are sometimes stopped early when those assessing outcomes can see a strong partition into two groups. They ask for permission to &quot;unblind&quot; and if there is a strong and clear difference between drug and placebo, will stop early so as to be able to give the drug to everyone. Here is <a href=\"https://news.yahoo.com/gilead-leukemia-drug-trial-unblinded-early-due-success-165310387--finance.html\" rel=\"nofollow noreferrer\">one example from 2015</a> for a leukemia study. That article says:</p>\n<blockquote>\n<p>Independent safety monitors oversee blinded trials so that they can be halted or unblinded early in case it is determined that the drug is causing harm or if the benefit becomes clear so that the medicine can be offered to placebo patients. A trial can also be stopped for futility if monitors determine the study is doomed to fail.</p>\n</blockquote>\n<p>This is a rare thing and is not based on some participants being really ill.</p>\n" }, { "answer_id": 26385, "author": "Glen", "author_id": 19515, "author_profile": "https://health.stackexchange.com/users/19515", "pm_score": 2, "selected": false, "text": "<p>Two things:</p>\n<ul>\n<li>Clinical trials are generally double-blinded, meaning that neither the subjects nor the researchers know what the subject is receiving, and</li>\n<li>Potential ethical issues are considered ahead of time by both the researchers as well as Human Subject Review Committees who have to approve the research protocol.</li>\n</ul>\n" } ]

[ "https://health.stackexchange.com/questions/26362", "https://health.stackexchange.com", "https://health.stackexchange.com/users/22162/" ]

[ { "answer_id": 27389, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 0, "selected": false, "text": "<p>(I am a molecular biologist, not a doctor)</p>\n<p>(earlier text deleted as wrong)</p>\n<p>My naive reading is that a stroke (CVA) happened, and after a few weeks indirectly caused orthostatic pneumonia (apparently &quot;an older term that refers to pneumonia that develops because the patient is on prolonged bedrest&quot;), which rapidly led to congestive heart failure.</p>\n<p>PS - I think Ankylosing Spondilitis is more of an autoimmune arthritis of the bones of the spine</p>\n" }, { "answer_id": 27581, "author": "Diana Petitti", "author_id": 20133, "author_profile": "https://health.stackexchange.com/users/20133", "pm_score": 3, "selected": true, "text": "<p>Several folks working together (Chris Rogers, agoodnurse, Carey Gregory) come to a consensus about this certificate as follows.</p>\n<p>CVA is virtually certain to be &quot;Cerebrovascular Accident,&quot; which is an (acute) stroke.</p>\n<p>The term “ASDH” is likely a transposition of the last two letters of “ASHD,” and thus means &quot;Atherosclerotic Heart Disease”.</p>\n<p>Bad handwriting makes &quot;generalized&quot; look like &quot;serialized,&quot; which can be seen by blowing up the image and inspecting with a magnifier. A photo of the blown up image (courtesy of Carey Gregory) is here.\n<a href=\"https://drive.google.com/file/d/1YfmV3Q5_l_6AWEv1fO7OB9oI-ysDjKXE/view\" rel=\"nofollow noreferrer\">enter link description here</a></p>\n<p>AS is a recognized as abbreviation for &quot;Atherosclerosis.&quot;</p>\n<p>Thus, the whole phrase on the second line of the “Other Significant Conditions” box would be “Atherosclerotic Heart Disease with generalized Atherosclerosis.”</p>\n<p>The entire sequence of events appears to be “Acute Congestive Heart Failure” for a few hours and pneumonia for one day, with an acute stroke (CVA or cerebrovascular accident) leading up to the pneumonia and congestive heart failure. These events occurred in a person who had, for years, Parkinson’s Disease, atherosclerotic heart disease with generalized atherosclerosis, and chronic brain disease.</p>\n" } ]

[ "https://health.stackexchange.com/questions/27388", "https://health.stackexchange.com", "https://health.stackexchange.com/users/20850/" ]

[ { "answer_id": 27461, "author": "porton", "author_id": 15189, "author_profile": "https://health.stackexchange.com/users/15189", "pm_score": -1, "selected": false, "text": "<p><a href=\"https://www.aboutkidshealth.ca/article?contentid=472&amp;language=english\" rel=\"nofollow noreferrer\">Genetically determined metabolic disorders are rare conditions that affect about one in 2000 newborn babies. These conditions can cause serious illness, and may cause death.</a></p>\n<p><a href=\"https://www.genome.gov/human-genome-project/Completion-FAQ\" rel=\"nofollow noreferrer\">The size of human genome is 30000 genes.</a></p>\n<p>This means that the probability y of no common defects (due to no better data I could find, I calculate under the wrong assumption that all the fetuses in the study survive at least till birth) is calculated as 1-y = (1-p⁴)³⁰⁰⁰⁰ where p is the probability of a defect in a single gene, because there are 4 recombinations (I assume for simplicity the same probability for all genes and the same for men and women, I assume all people are from the same uniformly &quot;intermixed&quot; ethnos, and maximum one defect per gene).</p>\n<p>Probability (under the same assumptions) of a baby to have a defect is 1/2000 = 1 - (1-p²)³⁰⁰⁰⁰.</p>\n<p>It remains to do math. Sage code:</p>\n<pre><code>var('p y')\np = find_root(1/2000==1-((1-p^2)**30000), 0, 1); p\nfind_root(1-y==(1-(p^4))**30000, 0, 1)\n</code></pre>\n<p>We have p = 0.00012911558610889591, y = 10^-11 that is almost impossible.</p>\n" }, { "answer_id": 27470, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 3, "selected": true, "text": "<p>&quot;If a couple has no common defective gene, they can produce a big healthy population from just two people, right?&quot;</p>\n<p>No. As described in the review &quot;The genetic basis of disease&quot; Essays Biochem. 2018 Dec 3; 62(5): 643–723. Published online 2018 Dec 3. doi: 10.1042/EBC20170053\n&quot;we now know that, on average, each individual has several hundred variants that are either known, or predicted, to be damaging to gene function, including roughly 85 variants that lead to truncated (incomplete) protein products.&quot;</p>\n<p>Since a given 2nd generation offspring of a founding couple might have both their copies of a given gene be the exact same version from one grandparent, if that version is defective, both the offspring's copies will thus be defective. This is the consequence of inbreeding and is why for example conservation biologists try to preserve as many different individuals as possible as founders in a captive breeding program.</p>\n" } ]

[ "https://health.stackexchange.com/questions/27460", "https://health.stackexchange.com", "https://health.stackexchange.com/users/15189/" ]

[ { "answer_id": 27512, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 5, "selected": true, "text": "<p>They're an island that <a href=\"https://www.health.gov.au/news/health-alerts/novel-coronavirus-2019-ncov-health-alert/coronavirus-covid-19-restrictions/coronavirus-covid-19-advice-for-international-travellers\" rel=\"noreferrer\">tests and quarantines visitors from outside the island</a>, <a href=\"https://www.health.gov.au/resources/apps-and-tools/covidsafe-app\" rel=\"noreferrer\">traces contacts when infections occur</a>, and <a href=\"https://www.nsw.gov.au/media-releases/new-covid-19-restrictions-for-greater-sydney-23-june-2021\" rel=\"noreferrer\">implements mandatory public health measures like social distancing and capacity restrictions that vary in intensity according to the level of infections observed</a>.</p>\n<p>There are lots of lay press articles about Australia, I'll include just a sampling here:</p>\n<p><a href=\"https://www.theguardian.com/australia-news/2021/feb/15/australia-covid-19-lockdown-rules-coronavirus-restrictions-by-state-nsw-victoria-vic-queensland-qld-western-south-australia-wa-sa-nt-act-travel-border-social-distancing-masks\" rel=\"noreferrer\">https://www.theguardian.com/australia-news/2021/feb/15/australia-covid-19-lockdown-rules-coronavirus-restrictions-by-state-nsw-victoria-vic-queensland-qld-western-south-australia-wa-sa-nt-act-travel-border-social-distancing-masks</a></p>\n<p><a href=\"https://www.businessinsider.com/expert-explains-4-key-differences-between-us-australia-coronavirus-strategy-2020-5\" rel=\"noreferrer\">https://www.businessinsider.com/expert-explains-4-key-differences-between-us-australia-coronavirus-strategy-2020-5</a></p>\n<p><a href=\"https://www.forbes.com/sites/williamhaseltine/2021/03/24/what-can-we-learn-from-australias-covid-19-response\" rel=\"noreferrer\">https://www.forbes.com/sites/williamhaseltine/2021/03/24/what-can-we-learn-from-australias-covid-19-response</a></p>\n<p><a href=\"https://www.brookings.edu/research/policy-and-institutional-responses-to-covid-19-australia/\" rel=\"noreferrer\">https://www.brookings.edu/research/policy-and-institutional-responses-to-covid-19-australia/</a></p>\n<p><a href=\"https://www.abc.net.au/news/2020-10-18/contact-tracing-coronavirus-australia-five-hallmarks-succcess/12759068\" rel=\"noreferrer\">https://www.abc.net.au/news/2020-10-18/contact-tracing-coronavirus-australia-five-hallmarks-succcess/12759068</a></p>\n" }, { "answer_id": 27513, "author": "B-K", "author_id": 22344, "author_profile": "https://health.stackexchange.com/users/22344", "pm_score": 4, "selected": false, "text": "<h1>From an Australian perspective</h1>\n<h2>Policy</h2>\n<ul>\n<li>Restrictions\n<ul>\n<li>The governemnt, especially at a state level, is willing to halt the entire functions of the area, in the hope that restrictions don't have to be enforced for as long as a result</li>\n</ul>\n</li>\n<li>Border controls\n<ul>\n<li>As a result of our position on a (remote-ish) island, border restriction were applied earlier, and haven't been opened (except to New Zealand)</li>\n</ul>\n</li>\n<li>Quarantine\n<ul>\n<li>Quarantine for people coming to Australia, which is managed by the government, rather than just telling people to stay at home, using hotels temporarily converted to isolate potentially infected people for 2 weeks</li>\n<li>In addition, home quarantine is used, when people travel between some internal areas of the country, which helps in limiting spread</li>\n</ul>\n</li>\n</ul>\n<h2>Social/Not Policy</h2>\n<ul>\n<li>There is quite a high level of pride in being 'free of covid' here, and people are willing to make sacrifices to uphold that, and unlike other countries, mostly follow restrictions</li>\n<li>The population here is quite low, especially for the size of the landmass, and almost all of the major cities are spaced quite far apart</li>\n</ul>\n" }, { "answer_id": 27517, "author": "jcaron", "author_id": 19225, "author_profile": "https://health.stackexchange.com/users/19225", "pm_score": 3, "selected": false, "text": "<p>Australia, like other countries such as New Zealand, Singapore, and more (including China after the initial outbreak, but of course information from China is often unreliable), have applied a &quot;zero Covid&quot; strategy.</p>\n<p>The goal is to:</p>\n<ul>\n<li>prevent the virus from entering (this is really the key)</li>\n<li>whenever it still manages to enter, stop it very aggressively from spreading so that it disappears.</li>\n</ul>\n<p>The first part, for Australia and New Zealand, is made a lot easier by the fact that they are isolated islands/continents, relatively far away from other land masses, with limited continuous exchanges with neighbouring countries, and the ability to effectively cut off most travel in or out (which is <strong>very</strong> different from the UK for instance).</p>\n<p>So they applied very strict restrictions on entry into their territories, real quarantine (not &quot;please stay at home and please don't see anyone during your self isolation, or we will be very unpleased&quot;).</p>\n<p>It was also helped by the fact that during the initial spread of the virus throughout the world, before many of the important facts were known (human-to-human transmission, asymptomatic transmission, airborne transmission, fatality rate...), they were relatively spared, possibly thanks to the yet-to-be-fully-understood seasonal effect. So when they started isolating, there were few cases inside the countries, and those local clusters could be curtailed through the usual very restrictive measures which have been applied elsewhere (masks, social distancing, strict lockdowns...).</p>\n<p>At the opposite end of the spectrum, many other countries, especially in Europe and the Americas had already extensive numbers of infected people in many different places before anything could be understood, were in the middle of winter, faced significant difficulties in getting PPE when needed, and had to address varying policies and stages of the pandemic in different countries/regions/states which have extensive exchanges with them.</p>\n<p>Many European countries also faced the &quot;summer surprise&quot;: the virus seemingly vanished during the summer, only to return with a vengeance at fall, after the virus had spread out a lot more through asymptomatic cases.</p>\n<p>Once you get past a certain number of cases, you can only slow down propagation, it's a lot more difficult to really stamp out the fire. As soon as there's even a single person with the virus, the risk of it spreading to millions is still there. But getting back to 0 when you have had tens of thousands of cases per day is virtually impossible. Due to the exponential nature of contagion, it takes a lot of time, i.e. very very long lockdowns, and that is economically, psychologically, medically and politically devastating.</p>\n" }, { "answer_id": 27527, "author": "JonathanReez", "author_id": 7314, "author_profile": "https://health.stackexchange.com/users/7314", "pm_score": 3, "selected": false, "text": "<p>Australia's low COVID rates can be explained by three factors: always locking down until zero community cases are reached, having no land borders and enforcing a hardcore quarantine on all arrivals. Lets compare them to the UK to see why one failed to achieve while the other succeeded.</p>\n<h2 id=\"lock-down-until-zero-cases-dnox\">Lock down until zero cases</h2>\n<p>Australia's general modus operandi has been to clamp down on all in-person activity (<a href=\"https://www.bbc.com/news/world-australia-54139669\" rel=\"nofollow noreferrer\">including a ban on protesting</a> and <a href=\"https://www.independent.co.uk/life-style/coronavirus-australia-lockdown-fine-holiday-photos-a9463906.html\" rel=\"nofollow noreferrer\">harassment of people sharing family photos</a>) until <strong>zero</strong> community cases are reached. Not a &quot;low amount&quot;, not &quot;enough to relieve the hospitals&quot;, but zero. One single case can grow into thousands and then into millions (in fact, the original COVID infection probably happened to a single person) so you can't tolerate a single infection in the community without some hardcore measures. As a result, Melbourne <a href=\"https://www.washingtonpost.com/world/2020/10/28/melbourne-australia-coronavirus-lockdown-111-days/\" rel=\"nofollow noreferrer\">has been in lockdown for 111 days</a> during their &quot;second wave&quot; and then spent a couple of weeks in lockdown <a href=\"https://www.reuters.com/world/asia-pacific/covid-19-curbs-australias-melbourne-ease-after-low-cases-2021-06-09/\" rel=\"nofollow noreferrer\">recently</a> over a few local cases.</p>\n<p>To contrast this, the UK <strong>never</strong> reached zero cases since the initial wave started in March 2020. So essentially their lockdown was pretty much a waste of time, short of relieving some stress from their hospital system. Otherwise it merely delayed the inevitable as cases avoided in spring 2020 came back roaring in the winter.</p>\n<h2 id=\"no-land-borders-mbe3\">No land borders</h2>\n<p>Australia is a relatively remote island where everyone has to arrive either by ship or by plane. This makes border control a no-brainer as you just have to ensure quarantine protocols in your airports and sea ports. Obviously a rogue traveler could in theory charter a boat and land on a beach in the middle of nowhere but that's something out of reach for the vast majority of people.</p>\n<p>Now you might argue that the UK is likewise an island (along with Ireland) and that all sea crossings are controlled but there's one huge difference: <strong>truck drivers</strong>. As a general rule truck drivers take their goods from one country, drive straight into another country and then unload them at the destination. This is in contrast with ships or planes where the cargo is unloaded at the port and then carried on to the destination by local residents. So even if the UK was absolutely perfect in securing their borders, they would still have to contend with the problem of tens of thousands of foreigners coming in without quarantine. In theory you could build a system where all trucks unload their cargo in, say, Dover and then local truck drivers carry them on, but this would take many years if not decades to complete. Stopping trucks altogether is not an option as this would cause massive disruption in the supply chain.</p>\n<h2 id=\"hardcore-quarantine-inja\">Hardcore quarantine</h2>\n<p>Four types of border control were seen during the pandemic:</p>\n<ol>\n<li>&quot;Free for all&quot; - seen in Mexico, Turkey, Brazil and a few other nations. Anyone could come in with no quarantine, though sometimes a test was required for entry.</li>\n<li>&quot;Only locals&quot; - free entry with no quarantine if you're a citizen/resident, otherwise you're banned. Implemented by the US.</li>\n<li>&quot;Home quarantine&quot; - after entering the country travelers are legally obligated to stay at home for 7-14 days and sometimes obligated to get tested on arrival. Implemented by most countries in the world, including the UK.</li>\n<li>&quot;Hotel quarantine&quot; - armed men escort all arrivals into specially designated hotels with no one allowed to go out before they spend 14 days in isolation and get multiple tests. Implemented by China, Taiwan, Australia, New Zealand</li>\n</ol>\n<p>Is #3 as good as #4? No, definitely not. Lets evaluate each solution as to how well it can stop the virus:</p>\n<ol>\n<li>Allows for at least 1 infected person to interact with the general public upon arrival</li>\n<li>Allows for at least 1 infected person to interact with the general public upon arrival</li>\n<li>Allows for at least 1 infected person to interact with the general public upon arrival</li>\n<li>Does not allow any arrivals to interact with the general public</li>\n</ol>\n<p>Is it weird that 1-3 are all the same? No, because remember once again that <strong>one</strong> case can easily grow into millions. There's no such thing as &quot;good enough&quot; when it comes to international quarantine, it has to be all or nothing. And you definitely can't pretend that the locals are all virus-free while the foreigners are all infested with COVID, as the virus does not discriminate by ones citizenship.</p>\n<p>Australia took this one step further by <a href=\"https://apnews.com/article/asia-pacific-australia-lifestyle-travel-coronavirus-pandemic-a1d239e80be05c8cf393ec67d1b6cce2\" rel=\"nofollow noreferrer\">preventing citizens</a> from leaving the country, which reduced the number of international arrivals. They've also introduced a <a href=\"https://www.nytimes.com/2021/05/03/world/australia/covid-india-travel-ban.html\" rel=\"nofollow noreferrer\">complete ban</a> on travel from India for a few weeks, which applied even to citizens.</p>\n<hr />\n<p>As a final note, its important to distinguish between &quot;success in fighting COVID&quot; and &quot;long term success&quot;. It remains to be seen if Australia can reopen the border after their vaccination campaign is complete. Its possible that they will spend many more years with <a href=\"https://www.reuters.com/world/asia-pacific/australias-new-south-wales-reports-24-locally-acquired-covid-19-cases-2021-07-01/\" rel=\"nofollow noreferrer\">localized lockdowns</a> due to strong fear of the virus and its many variants. In contrast the UK is likely to fully reopen sometime this year and just carry on with life while accepting a certain number of COVID deaths per year as unavoidable. Which scenario is a better solution still remains to be seen.</p>\n<p><strong>Update:</strong> <a href=\"https://twitter.com/NSWHealth/status/1415113868183937026\" rel=\"nofollow noreferrer\">looks like</a> Sydney/NSW is now facing a major COVID wave and would likely spend several months in lockdown to stop it. Quite unlike the US which is currently living a maskless life with zero concern for whatever cases remain in the nation. As mentioned before, we'll only be able to judge the best strategy in the long run.</p>\n" } ]

[ "https://health.stackexchange.com/questions/27511", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7049/" ]

[ { "answer_id": 27557, "author": "Mark", "author_id": 333, "author_profile": "https://health.stackexchange.com/users/333", "pm_score": 4, "selected": true, "text": "<p>It's impossible to say based on the available data. The adverse-event reports merely show correlation, not causation.</p>\n<p>One common confounding factor is the population receiving the vaccine: the Pfizer and Moderna vaccines were the first ones approved, so people with elevated risk from COVID-19 tended to get these vaccines. Many of these risk factors are also risk factors for dying of things that are neither COVID-19 nor a COVID-19 vaccine. You need to compensate for the fact that these populations contain a higher proportion of 98-year-olds suffering from cancer, heart disease, and lung disease than the general population.</p>\n<p>Specific points from <a href=\"https://www.lareb.nl/coronameldingen\" rel=\"noreferrer\">the Dutch site</a> (via Google Translate):</p>\n<ul>\n<li>A reported side effect may not always be due to the vaccine . Complaints or disorders can also have arisen from another cause after the vaccination.</li>\n<li>The data below cannot be used to compare side effects per vaccine. The different corona vaccines are used in varying amounts and for different target groups.</li>\n</ul>\n" }, { "answer_id": 29234, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 2, "selected": false, "text": "<p>The Q is a bit apples to oranges, as the side-effect profiles are different. With the recombinant vaccines (AZ, J&amp;J) the main concern was with clots and bleeding, but with the mRNA ones, myocarditis has been the issue.</p>\n<p>Large enough studies have found a statistically significant risk differences <a href=\"https://www.nature.com/articles/s41591-021-01408-4\" rel=\"nofollow noreferrer\">e.g.</a> among the 2.53 million people that were vaccinated in Scotland at that point:</p>\n<blockquote>\n<p>Reports of ChAdOx1 vaccine–associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0–27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41–13.83), with an estimated incidence of 1.13 (0.62–1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29–3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12–1.34) 0–27 d after vaccination, with an SCCS RR of 0.97 (0.93–1.02). For hemorrhagic events 0–27 d after vaccination, the aRR was 1.48 (1.12–1.96), with an SCCS RR of 0.95 (0.82–1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.</p>\n</blockquote>\n<p>Further, the issue is that while that effect itself is quite rare, a large fraction of the unlucky few <a href=\"https://www.nejm.org/doi/full/10.1056/NEJMoa2109908\" rel=\"nofollow noreferrer\">have had</a> pretty bad outcomes (death).</p>\n<blockquote>\n<p>Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a new syndrome associated with the ChAdOx1 nCoV-19 adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2. [...] We conducted a prospective cohort study involving patients with suspected VITT who presented to hospitals in the United Kingdom between March 22 and June 6, 2021. ​[...] Among 294 patients who were evaluated, we identified 170 definite and 50 probable cases of VITT. All the patients had received the first dose of ChAdOx1 nCoV-19 vaccine and presented 5 to 48 days (median, 14) after vaccination. The age range was 18 to 79 years (median, 48), with no sex preponderance and no identifiable medical risk factors. Overall mortality was 22%.</p>\n</blockquote>\n<p>Whereas with <a href=\"https://www.nejm.org/doi/10.1056/NEJMoa2109730\" rel=\"nofollow noreferrer\">myocraditis after Pfizer</a> but alas from a country that didn't adminizer AZ (so no comparator like you want):</p>\n<blockquote>\n<p>Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance.</p>\n<p>Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal.</p>\n</blockquote>\n" } ]

[ "https://health.stackexchange.com/questions/27556", "https://health.stackexchange.com", "https://health.stackexchange.com/users/22339/" ]

[ { "answer_id": 27557, "author": "Mark", "author_id": 333, "author_profile": "https://health.stackexchange.com/users/333", "pm_score": 4, "selected": true, "text": "<p>It's impossible to say based on the available data. The adverse-event reports merely show correlation, not causation.</p>\n<p>One common confounding factor is the population receiving the vaccine: the Pfizer and Moderna vaccines were the first ones approved, so people with elevated risk from COVID-19 tended to get these vaccines. Many of these risk factors are also risk factors for dying of things that are neither COVID-19 nor a COVID-19 vaccine. You need to compensate for the fact that these populations contain a higher proportion of 98-year-olds suffering from cancer, heart disease, and lung disease than the general population.</p>\n<p>Specific points from <a href=\"https://www.lareb.nl/coronameldingen\" rel=\"noreferrer\">the Dutch site</a> (via Google Translate):</p>\n<ul>\n<li>A reported side effect may not always be due to the vaccine . Complaints or disorders can also have arisen from another cause after the vaccination.</li>\n<li>The data below cannot be used to compare side effects per vaccine. The different corona vaccines are used in varying amounts and for different target groups.</li>\n</ul>\n" }, { "answer_id": 29234, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 2, "selected": false, "text": "<p>The Q is a bit apples to oranges, as the side-effect profiles are different. With the recombinant vaccines (AZ, J&amp;J) the main concern was with clots and bleeding, but with the mRNA ones, myocarditis has been the issue.</p>\n<p>Large enough studies have found a statistically significant risk differences <a href=\"https://www.nature.com/articles/s41591-021-01408-4\" rel=\"nofollow noreferrer\">e.g.</a> among the 2.53 million people that were vaccinated in Scotland at that point:</p>\n<blockquote>\n<p>Reports of ChAdOx1 vaccine–associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0–27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41–13.83), with an estimated incidence of 1.13 (0.62–1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29–3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12–1.34) 0–27 d after vaccination, with an SCCS RR of 0.97 (0.93–1.02). For hemorrhagic events 0–27 d after vaccination, the aRR was 1.48 (1.12–1.96), with an SCCS RR of 0.95 (0.82–1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.</p>\n</blockquote>\n<p>Further, the issue is that while that effect itself is quite rare, a large fraction of the unlucky few <a href=\"https://www.nejm.org/doi/full/10.1056/NEJMoa2109908\" rel=\"nofollow noreferrer\">have had</a> pretty bad outcomes (death).</p>\n<blockquote>\n<p>Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a new syndrome associated with the ChAdOx1 nCoV-19 adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2. [...] We conducted a prospective cohort study involving patients with suspected VITT who presented to hospitals in the United Kingdom between March 22 and June 6, 2021. ​[...] Among 294 patients who were evaluated, we identified 170 definite and 50 probable cases of VITT. All the patients had received the first dose of ChAdOx1 nCoV-19 vaccine and presented 5 to 48 days (median, 14) after vaccination. The age range was 18 to 79 years (median, 48), with no sex preponderance and no identifiable medical risk factors. Overall mortality was 22%.</p>\n</blockquote>\n<p>Whereas with <a href=\"https://www.nejm.org/doi/10.1056/NEJMoa2109730\" rel=\"nofollow noreferrer\">myocraditis after Pfizer</a> but alas from a country that didn't adminizer AZ (so no comparator like you want):</p>\n<blockquote>\n<p>Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance.</p>\n<p>Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal.</p>\n</blockquote>\n" } ]

[ "https://health.stackexchange.com/questions/27558", "https://health.stackexchange.com", "https://health.stackexchange.com/users/15863/" ]

[ { "answer_id": 27577, "author": "NetServOps", "author_id": 22263, "author_profile": "https://health.stackexchange.com/users/22263", "pm_score": 2, "selected": false, "text": "<p>Its for a 'Red-Green duochrome test'.</p>\n<p>A primary task of the eye care professional is determining the refraction, or optical correction, of a patient. The duochrome red-green test is a standard tool for verification of the final refraction. Traditionally, it is recommended for use both prior to and subsequent to determining the cylindrical or astigmatic component of the refraction.</p>\n<p><a href=\"https://doi.org/10.1371/journal.pone.0118874\" rel=\"nofollow noreferrer\">Red-Green Duochrome testing</a></p>\n" }, { "answer_id": 31295, "author": "jlliagre", "author_id": 17838, "author_profile": "https://health.stackexchange.com/users/17838", "pm_score": 4, "selected": true, "text": "<p>These two lines can be used to detect color blindness in which red cannot be distinguished from green (deuteranopia). The person tested, often a child in that case, must be able to name the colors of the lines. (Reference: Ellen M. Chiocca, <em>Advanced Pediatric Assessment</em>, p 314):</p>\n<p>Otherwise, it is also certainly a convenience to allow the test taker to say which line they are comfortable with, e.g., <em>I can read the letters just above the red line but not the ones under it.</em></p>\n" } ]

[ "https://health.stackexchange.com/questions/27575", "https://health.stackexchange.com", "https://health.stackexchange.com/users/15863/" ]

[ { "answer_id": 27604, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 4, "selected": true, "text": "<p>Trivial in concept, sure, but not necessarily trivial in practice. It's not about just producing a handful of doses in a proof-of-concept; if you want to produce a different version of a vaccine at scale it means either building a bunch of new equipment or retooling a previous production line to make the whole vaccine. Since only a minority of people are vaccinated world-wide, it makes sense that the original vaccines continue to be manufactured since these are still effective against the variants that are being transmitted (maybe not as effective as they can be, of course). Right now, it's almost certainly more important to get <em>any</em> vaccine into arms rather than the ideal vaccine.</p>\n<p>That said, it would be false to state that vaccines to target variants are not in the pipeline. Pfizer <a href=\"https://www.cnbc.com/2021/07/08/pfizer-says-it-is-developing-a-covid-booster-shot-to-target-the-highly-transmissible-delta-variant.html\" rel=\"noreferrer\">announced today</a>, for example, that they are developing a booster to target the delta variant. Presumably other vaccine manufacturers are doing so as well - not everything in pharmaceutical research labs gets reported. Manufacturers have to make cost-benefit analyses about what variants to target. Had they prepared a variant booster a few months ago it might have targeted the alpha variant rather than delta variant, for example; today, it seems targeting the delta variant is more pressing.</p>\n<p>I'd also add that, as far as I know, no regulatory agency has declared that <em>no</em> clinical trials of an &quot;updated&quot; mRNA vaccine is necessary, or publicly specified what data are required, so I think that's just speculation so far, although well-informed. If descendants of COVID-19 become endemic like influenza, then it seems likely that a regulatory framework similar to that for the annual influenza vaccine would allow new formulations to be distributed without large-scale testing (like in this Q&amp;A: <a href=\"https://medicalsciences.stackexchange.com/questions/24637/\">Flu vaccine paradox</a>), but we aren't there yet.</p>\n" }, { "answer_id": 29338, "author": "herman", "author_id": 22456, "author_profile": "https://health.stackexchange.com/users/22456", "pm_score": -1, "selected": false, "text": "<p>Here is the best answer that I have found, from Dr. Katelyn Jetelina, MPH PhD, writing as <a href=\"https://yourlocalepidemiologist.substack.com\" rel=\"nofollow noreferrer\">Your Local Epidemiologist</a></p>\n<blockquote>\n<p>If we need another vaccine, we can do this incredibly quickly. Thanks\nto the new biotechnology, mRNA vaccines are really easy to alter. Once\nthe minor change is made, only 2 dozen people need to enroll in a\ntrial to make sure the updated vaccine works. Then it can be\ndistributed to arms. Because the change is small, an updated vaccine\ndoesn’t need Phase III trials and/or regularity approval. So, this\nwhole process should take a max of 6 weeks.</p>\n</blockquote>\n<p><a href=\"https://yourlocalepidemiologist.substack.com/p/new-concerning-variant-b11529\" rel=\"nofollow noreferrer\">Source</a></p>\n" } ]

[ "https://health.stackexchange.com/questions/27601", "https://health.stackexchange.com", "https://health.stackexchange.com/users/22456/" ]

[ { "answer_id": 27629, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 5, "selected": true, "text": "<p>The short answer is maybe, but rarely, and the whole Covid virus has never been seen to integrate into the cell's DNA intact. Any integration requires &quot;helper&quot; molecules not found in the Covid virus, and only very rarely found in a normal cell.</p>\n<p>It's been known for many decades that RNA in a cell can be converted into DNA and integrated into the cell's genomic DNA. This is extremely rare except under certain conditions. For example, a class of viruses (including HIV) called &quot;retroviruses&quot; carries an enzyme called reverse transcriptase or RT that the viruses use to convert their RNA genome into DNA and &quot;hide&quot; by splicing that into the cell's own DNA. Covid does NOT have such an enzyme.</p>\n<p>However, during evolution, our cells have picked up many small DNA elements (&quot;jumping genes&quot; or transposons), many of which &quot;hop&quot; by reverse-transcribing their transcript and inserting that new DNA somewhere in the cell's DNA. They continue to &quot;hop&quot; to this day, rarely. Occasionally, they make an error and convert some of the other mRNA in the cell into DNA and insert it into the genome. LINE1 elements in particular make up almost 20% of our cellular DNA, so the paper's authors tried to see if any LINE1 elements were able to (rarely) incorporate Covid fragments into a cell's DNA.</p>\n<p>Greatly simplified, the authors tried to answer the following questions:</p>\n<ol>\n<li><p>Can laboratory cells which have been engineered to make lots of the LINE1 transposase, then infected with Covid, end up with fragments of Covid virus in their DNA?</p>\n</li>\n<li><p>Can &quot;normal&quot;, non-engineered laboratory cells infected with Covid, end up with fragments of Covid virus in their DNA?</p>\n</li>\n<li><p>Do any patient samples from Covid-infected patients show any fragments of Covid virus in their cellular DNA?</p>\n</li>\n</ol>\n<p>The method the authors used to check this was to massively sequence mRNAs from cells, and look for any that had normal cellular gene sequences spliced onto Covid sequences. Their reasoning was that such chimeric transcripts must represent genes with reverse-transcribed Covid DNA spliced into the genomic DNA of the gene, and so appearing in the gene's RNA transcript. It turned out there was a big technical problem with this (hence the wishy washy conclusions of the paper) - the sequencing sample preparation process will also rarely splice two mRNA sequences together even if they were not spliced in the cell. However, that artificial process tends to almost always only splice two &quot;antisense&quot; strands, while the LINE1 process should have no preference between sense and antisense. Thus, the authors reasoned that if they were finding only antisense/antisense that could be an artifact, while significant amounts of antisense/sense splices would indicate real splices from the genomic DNA.</p>\n<p>The answers they inferred were roughly:</p>\n<ol>\n<li>Yes, artifcially expressing lots of LINE1 tranposase resulted in detectable integration of partial Covid virus sequences in the cellular DNA.</li>\n<li>With more normal laboratory cells, they found many fewer integrated Covid virus fragments, but still found some.</li>\n<li>With patient samples, there were many additional technical problems; they think they found some Covid fragments integrated in cells from 1 patient, but are not nearly as confident with that result as for (1) and (2).</li>\n</ol>\n<p>In any case, the integrated Covid sequences they found seem to be only fragments of the virus (although their techniques could not be fully sure on this); they never found a whole virus integrated into any cell.</p>\n<p>As a practical matter, the &quot;consensus&quot; is correct, but given billions of people and quadrillions of Covid viruses, there might be a few outliers.</p>\n<p>Paper ref:\nReverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues\nPNAS May 25, 2021 118 (21) e2105968118; <a href=\"https://doi.org/10.1073/pnas.2105968118\" rel=\"nofollow noreferrer\">https://doi.org/10.1073/pnas.2105968118</a></p>\n<p>LINE1 review: &quot;LINE-1 Elements in Structural Variation and Disease&quot;\nAnnu Rev Genomics Hum Genet. 2011; 12: 187–215.\ndoi: 10.1146/annurev-genom-082509-141802\nAuthor's manuscript freely downloadable from <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124830/pdf/nihms606127.pdf\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124830/pdf/nihms606127.pdf</a></p>\n<p><a href=\"https://biology.stackexchange.com/questions/107418/is-this-pfizer-related-paper-reliable\">Related Question explaining why another paper is NOT reliable</a>:\n&quot; Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line by Alden et al. ( Curr. Issues Mol. Biol. 2022, 44(3), 1115-1126; &quot;</p>\n<p><strong>Update Apr 2022</strong>: Here are two additional papers comments that are highly relevant:</p>\n<p><a href=\"https://journals.asm.org/doi/10.1128/JVI.00294-21\" rel=\"nofollow noreferrer\">journals.asm.org/doi/10.1128/JVI.00294-21</a>&quot;Host-Virus Chimeric Events in SARS-CoV-2-Infected Cells Are Infrequent and Artifactual&quot;</p>\n<p><a href=\"https://doi.org/10.1073/pnas.2109066118\" rel=\"nofollow noreferrer\">https://doi.org/10.1073/pnas.2109066118</a>&quot;No evidence of SARS-CoV-2 reverse transcription and integration as the origin of chimeric transcripts in patient tissues&quot;</p>\n" }, { "answer_id": 30960, "author": "Peter Bernhard", "author_id": 21148, "author_profile": "https://health.stackexchange.com/users/21148", "pm_score": 0, "selected": false, "text": "<p>Answering on</p>\n<p>&quot;If my understanding is true, why is there a consensus saying that mRNA cannot go into the DNA ?&quot;</p>\n<p>I highlighted several quotes from the paper's references that may answer your question:</p>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038843/\" rel=\"nofollow noreferrer\">Akira Shimizu, Characterisation of cytoplasmic DNA complementary to non-retroviral RNA viruses in human cells</a>, 2014:\n&quot;...Thus, the genetic information of the <em>non-retroviral RNA virus genome <strong>can flow into the DNA</strong></em> of mammalian cells expressing LINE-1-like elements.&quot; That study was on &quot;infection of various human cell lines and primary fibroblasts with the vesicular stomatitis virus (VSV)&quot;.</p>\n<p><a href=\"https://pubmed.ncbi.nlm.nih.gov/19150848/\" rel=\"nofollow noreferrer\">Geuking et al., Recombination of Retrotransposon and Exogenous RNA Virus Results in Nonretroviral cDNA Integration, 2009</a>:\n&quot;We found that <em><strong>illegitimate</strong></em> recombination between an exogenous <em>nonretroviral</em> RNA virus, lymphocytic choriomeningitis virus, and the endogenous intracisternal A-type particle (IAP) retrotransposon occurred and led to reverse transcription of exogenous viral RNA.&quot;</p>\n<p><a href=\"https://www.nature.com/articles/36740\" rel=\"nofollow noreferrer\">Weiss/Kellam, <em><strong>Illicit</strong></em> viral DNA</a>,, Nature volume 390, pages235–236 (1997):</p>\n<p>&quot;More than 20 years ago, the late Victor Zhdanov (...) claiming that complementary DNA copies of RNA viruses such as measles and polio occurred in retrovirus-infected cells. The observations raised eyebrows at the time, because promiscuous cDNA synthesis seemed to run counter to everything known about viral replication. But the data were neither confirmed nor refuted, and were soon forgotten.&quot;</p>\n<p>These quotes show that Crick's dogma - from DNA to RNA, with the exception of retro-viruses - still holds. The fact that the study you refer to was severely scrutinized and its validity questioned by peer review seems to lay proof that the dogma you speak of is valid even today.</p>\n<p>To sum up: Crick's dogma still holds (and will), and the study in question contradicts that rule in its results.</p>\n<p>Note:\nSee Geuking et al. in the context of the quote about distinguishing between retro-transcription and integration into the genome. These authors speak of, in particular, &quot;recombination&quot; between non-retro-virus and retro-transcriptional elements termed endogenous virus (virus-viral recombination). Crick's rule, in a restricted sense, may not cover integration of DNA into the genome, and, conversely, it may play down the role of non-genome DNA, external or episomal.</p>\n" } ]

[ "https://health.stackexchange.com/questions/27611", "https://health.stackexchange.com", "https://health.stackexchange.com/users/22469/" ]

[ { "answer_id": 27674, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 2, "selected": false, "text": "<p>From the links you've supplied, none of these other vaccines have gotten further than phase 2 trials yet. Most seem to only have phase 1 trials started or merely planned so far.</p>\n<p>These vaccines are not yet available because they have not completed clinical trials that demonstrate safety and efficacy.</p>\n" }, { "answer_id": 27675, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 4, "selected": true, "text": "<p>A few-year-old review that might be useful is:</p>\n<p>Pardi, N., Hogan, M., Porter, F. et al. mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov 17, 261–279 (2018). <a href=\"https://doi.org/10.1038/nrd.2017.243\" rel=\"noreferrer\">https://doi.org/10.1038/nrd.2017.243</a></p>\n<p>The tricky part of creating an mRNA vaccine once the &quot;platform&quot; has been developed remains exactly what mRNA sequence do you put into it? Remember, the virus sequence is selected for infection and replication; the sequence for the vaccine should NOT do that, but still should generate an immune response that will stop the actual virus (perhaps antibodies, perhaps cellular, perhaps both). And of course, you don't want something that accidentally causes a bad side effect like a misdirected immune response.</p>\n<p>For Covid, it turns out a key factor in creating successful vaccines has been pre-existing work to modify the spike protein so it holds a certain shape that normally is only transient: see <a href=\"https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38\" rel=\"noreferrer\">https://cen.acs.org/pharmaceuticals/vaccines/tiny-tweak-behind-COVID-19/98/i38</a></p>\n<p>In any case, you've still got to test your candidate to make sure it generates an effective immune response and doesn't have any major side effects.</p>\n" }, { "answer_id": 28876, "author": "WHO's NoToOldRx4CovidIsMurder", "author_id": 17268, "author_profile": "https://health.stackexchange.com/users/17268", "pm_score": -1, "selected": false, "text": "<p>I know at least one far more deadly rare disease <a href=\"https://www.massgeneral.org/neurology/treatments-and-services/about-mog-antibody-disease\" rel=\"nofollow noreferrer\">1</a> for which an mRNA vaccine has been developed and <a href=\"https://science.sciencemag.org/content/371/6525/145\" rel=\"nofollow noreferrer\">shown to work in the lab</a>. The treatment is likely to work for MOG antibody disease. Maybe the lack of a business model is a major factor in why phase 1 trials for this mRNA vaccine <a href=\"https://science.sciencemag.org/content/371/6525/145\" rel=\"nofollow noreferrer\">2</a> for that disease were <a href=\"https://www.youtube.com/watch?v=w2-X4c1fKio&amp;t=859s\" rel=\"nofollow noreferrer\">not even being discussed at all in this ~40 -minute YouTube presentation on it <strong>by two of the researchers who invented and tested it</strong>/demonstrated efficacy in several ways in the lab</a>.</p>\n<p>Maybe a trial is being discussed and will happen. But it is <em>common</em> for approval for and further testing of drugs which appear to be quite effective to not be <em>pursued</em> because of the lack of a business model.</p>\n<p>The US and EU <a href=\"https://www.fda.gov/industry/developing-products-rare-diseases-conditions\" rel=\"nofollow noreferrer\">orphan drug strategies</a> are an attempt to address this problem. (In my view, this created a two-tier system that is better than a one-tier system, but retains all the problems that caused the one-tier system to be modified. They're just a bit smaller, on average.)</p>\n<p>Also, and this is particularly relevant to the OP's question, there were (appropriate) shortcuts taken in development of the CoViD-19 vaccines. A lot of unnecessary work was eliminated, investment and decision making were sped up, manufacturing investments were made prior to the existence of clinical trial evidence. (<a href=\"https://www.youtube.com/watch?v=w2-X4c1fKio&amp;t=1200s\" rel=\"nofollow noreferrer\">6</a> ibid. ~ t=1200s) Re-reviewing the video, I note that Ugur Sahin suggests that perhaps some of these shortcuts are also appropriate specifically in situations of high medical need and standard development timeline of &gt; 10-years - like the one I document here. (<a href=\"https://www.youtube.com/watch?v=w2-X4c1fKio&amp;t=1340s\" rel=\"nofollow noreferrer\">5</a> ibid. ~ t=1340s)</p>\n<p>Compared to the way the disease is currently treated (broad suppression with prednisone long term, acutely with megadoses of prednisolone, indefinitely with rituximab, azathioprine, etc.) pinpoint immune system tolerization to self is likely to be much, much safer.</p>\n<p>Inventors of what's best known as the Pfizer mRNA vaccine and the MOG m1[PSI] mRNA vaccines -the esteemed scientists who have created these vaccines are not wrong to call them both &quot;vaccines&quot;. They have worked tirelessly in this research area for many years. Tolerizing mRNA vaccines are about as traditional as any other mRNA vaccines. They are hardly a new concept as they have been in development for many many years; certainly 7; probably ~3x more. Its analogous that we still use the term <code>atom</code>, even though the definition has changed radically over the centuries.</p>\n<p>There is more than one kind of EAE. Murine EAE is always caused by improper immune response against the self, but here it is specifically caused by an anti-MOG antibody induced by &quot;immunizing&quot; the mice, causing paralyssis. (14:40 in the presentation.) And the treatment used is MOG m1[PSI] mRNA.</p>\n<p>Again, notably, the people who created the MOG m1[PSI] mRNA vaccine and do call it a vaccine are largely the SAME experts that invented the particular famous &quot;mass-market same-for-all immune-stimulatory&quot; disease preventative injected into billions of arms manufactured by Pfizer.</p>\n" } ]

[ "https://health.stackexchange.com/questions/27670", "https://health.stackexchange.com", "https://health.stackexchange.com/users/16786/" ]

[ { "answer_id": 28696, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 2, "selected": false, "text": "<p>We have no real scientific data released yet, but here are some things to think about.</p>\n<ol>\n<li>Being infected, feeling sick and being contagious are three different things.</li>\n<li>Certainly, many fewer of the vaccinated are getting infected, even with the delta variant.</li>\n<li>Many fewer of the vaccinated are feeling sick even if they get infected, even with the delta variant.</li>\n<li>The CDC director apparently said they have some info that some subgroup of vaccinated people who get infected with the delta variant may be significantly contagious. Apparently at least some have significant levels of virus in their nose and throat.</li>\n</ol>\n<p>(4) above does not apply to all vaccinated people. We don't know which subgroup it applies to - perhaps only a small subset of vaccinated people who get infected and feel sick.</p>\n<p>Re: (4); The nose and throat are important regions for spreading the virus, because that's where your breath picks up virus particles to exhale and infect others. They are not significant regions for making you seriously ill (lungs and perhaps other internal organs are important there). Thus, this fits with the delta variant being easier to spread, but doesn't indicate much about how sick you will get.</p>\n" }, { "answer_id": 28724, "author": "WHO's NoToOldRx4CovidIsMurder", "author_id": 17268, "author_profile": "https://health.stackexchange.com/users/17268", "pm_score": 2, "selected": false, "text": "<p>The White House reports (<a href=\"https://www.whitehouse.gov/briefing-room/press-briefings/2021/08/02/press-briefing-by-white-house-covid-19-response-team-and-public-health-officials-47/\" rel=\"nofollow noreferrer\">1</a>) that several studies show that those with breakthrough infections of Delta had viral loads that were similar to people who were infected and unvaccinated, and that in this way, the Delta variant is different from prior strains.</p>\n<p>^{(I surmise SFist is just trying to communicate that SARS-CoV-2 is <em>much more</em> infectious in breakthrough infections of Delta vs breakthrough infections of other strains, not that the latter aren't at all infectious.)}</p>\n" }, { "answer_id": 28728, "author": "Meia", "author_id": 22519, "author_profile": "https://health.stackexchange.com/users/22519", "pm_score": 1, "selected": false, "text": "<p>Note that I am no virologist but am explaining to the best of my knowledge\nand for practical use from a variety of reports and my own understanding from my background in Nursing and Health Informatics. I think it is worth answering because the reasoning comes up a lot with skeptical friends and family who might question if it's even &quot;worth&quot; getting the vaccine, or &quot;worth&quot; maintaining measures to prevent infection spread.</p>\n<p>To answer your questions in a nutshell--the increased viral load of all variants can be infectious in both vaccinated and unvaccinated people (that is to say, it's not that 1 is infectious and 1 is not--any can be potentially infectious).</p>\n<p>My main takeaway from the <a href=\"https://sfist.com/2021/07/27/cdc-confirms-that-viral-loads-in-vaccinated-people-with-delta-are-indistinguishable-from-unvaccinated/\" rel=\"nofollow noreferrer\">article</a> you shared is that flip-flopping on policies regarding masks may contribute to further spread, since vaccinated folks can still contract/spread the Delta variant. While vaccinated folks are more likely to experience the more mild or asymptomatic symptoms of Delta COVID-19, the inconsistency of mask-enforcement makes infection spread pernicious.</p>\n<p>To further go into my answer for your questions--it is possible that what makes Delta a variant of concern is that it has mutated to replicate much <em>faster</em> than previous variants we've observed. A faster replication rate of SARS-CoV-2 in our cells contributes to a <strong>higher</strong> viral load in a <strong>shorter</strong> amount of time, giving the virus an exponentially greater opportunity to be shed.</p>\n<p>Per <a href=\"https://www.healthline.com/health-news/cdc-says-delta-variant-as-infectious-as-chickenpox-what-to-know-now#What-makes-Delta-so-contagious?\" rel=\"nofollow noreferrer\">Healthline</a>:</p>\n<blockquote>\n<p>With higher viral loads, it’s believed that people who contract SARS-CoV-2 shed more virus, making it easier to transmit the virus to those around them. “<strong>The individuals with Delta have higher viral loads, so the virus is not only more transmissible, but there is more of it in each cough or sneeze</strong> to try and get into your cells,” Nachman explained.</p>\n</blockquote>\n<p>From <a href=\"https://virological.org/t/viral-infection-and-transmission-in-a-large-well-traced-outbreak-caused-by-the-delta-sars-cov-2-variant/724\" rel=\"nofollow noreferrer\">this study</a>, it is suggested that Delta replicates faster based on the observation that the viral load from Delta was ~1000x higher than that of other strains by the time an infected subject tested positive:</p>\n<blockquote>\n<p>Compared to the 19A/19 B strains, the relative viral loads in the Delta variant infections (62 cases, Ct value 24.00 (IQR 19.00~29.00) for ORF1ab gene) were <strong>1260 times higher</strong> than the 19A/19B strains infections (63 cases, Ct value 34.31 (IQR 31.00~36.00) for ORF1ab gene) on the day when viruses were first detected. Considering the daily testing performed for the central isolated subjects since the beginning of quarantine, <strong>the higher within host growth rate of the Delta variant was proposed, which led to the higher viral loads on the time points when viral nucleotides excess the PCR detection threshold.</strong> [...] For the Delta variant infections, 80.65% samples contained &gt;6x105 copies/mL in oropharyngeal swabs when viruses were firstly detected compared to the 19.05% samples in 19A/19B infections. <strong>These data highlight that the Delta variant could be more infectious during the early stage of the infection.</strong></p>\n</blockquote>\n<p>There might be multiple factors as to what else makes Delta spread faster, and spread among both the vaccinated and unvaccinated--and while we have some idea why, we don't have all the pieces just yet.</p>\n<p>From an actual <a href=\"https://hub.jhu.edu/2021/07/19/andrew-pekosz-delta-variants/\" rel=\"nofollow noreferrer\">virologist</a>:</p>\n<blockquote>\n<p>We know that if we look at the spike protein, which is the protein the virus uses to attach to cells and start the infection process, we see that there are mutations that make that protein better at entering human cells. We can also look at the spike protein and see mutations that should reduce the ability of some of the antibodies generated by the vaccine to bind to the virus. So we think it's also finding ways to get around the immunity that we're generating in the population through vaccination.</p>\n</blockquote>\n<p>That said, it's important to emphasize that while some vaccinated folks can still spread infection, today's vaccines are still <a href=\"https://www.nejm.org/doi/full/10.1056/NEJMoa2108891\" rel=\"nofollow noreferrer\">substantially effective</a> in preventing more serious symptoms against both variants. While we're still gathering more numbers, we're <a href=\"https://www.cidrap.umn.edu/news-perspective/2021/07/study-2-covid-vaccine-doses-much-more-effective-1-against-delta\" rel=\"nofollow noreferrer\">seeing</a> vaccines offer a greater likelihood in effectiveness against variants such as Alpha, more than Delta, and an even greater likelihood in reducing serious symptoms leading to hospitalization, ongoing symptoms, or death related to COVID-19 in general.</p>\n<p>Per the same virologist above (<a href=\"https://hub.jhu.edu/2021/07/19/andrew-pekosz-delta-variants/\" rel=\"nofollow noreferrer\">Andrew Pekosz at Johns Hopkins U</a>):</p>\n<blockquote>\n<p>Say, for example, it's a one in a million chance that a mutation will\nbe advantageous to the virus. If you let the virus replicate itself\n900,000 times, odds are that the advantageous mutation will occur. But\nif you limit the overall replication of the virus to 1,000 times, then\nit's much less likely that the random advantageous mutation is going\nto occur. And that's where public health interventions really help us\na lot during this pandemic—by reducing the total amount of virus\nreplication and therefore reducing the chances that the virus can\nimprove or adapt.</p>\n</blockquote>\n<p>TLDR: More people getting vaccinated sooner rather than later substantially helps us in the race against further spread and mutation of SARS-CoV-2.</p>\n" } ]

[ "https://health.stackexchange.com/questions/27696", "https://health.stackexchange.com", "https://health.stackexchange.com/users/43/" ]

[ { "answer_id": 28718, "author": "Chris Rogers", "author_id": 7951, "author_profile": "https://health.stackexchange.com/users/7951", "pm_score": 1, "selected": false, "text": "<p>For the answer, you need to find the source of the mannose.</p>\n<p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252654/\" rel=\"nofollow noreferrer\">Sharma, et al (2014)</a> points out that</p>\n<blockquote>\n<p>Mannose occurs in microbes, plants and animals. Free mannose is found in small amounts in many fruits such as oranges, apples and peaches [12] and in mammalian plasma at 50–100 μM [13]. More often, mannose occurs in homo-or hetero-polymers such as yeast mannans (α-mannose) where it can account for nearly 16% of dry weight [14]</p>\n<p>[...]</p>\n<ol start=\"12\">\n<li><p>Herman RH. Mannose metabolism. I. Am J Clin Nutr. 1971;24:488–98. [<a href=\"https://www.ncbi.nlm.nih.gov/pubmed/4933108\" rel=\"nofollow noreferrer\">PubMed</a>] [<a href=\"https://scholar.google.com/scholar_lookup?journal=Am%20J%20Clin%20Nutr&amp;title=Mannose%20metabolism.%20I&amp;author=RH%20Herman&amp;volume=24&amp;publication_year=1971&amp;pages=488-98&amp;pmid=4933108&amp;\" rel=\"nofollow noreferrer\">Google Scholar</a>]</p>\n</li>\n<li><p>Alton G, Hasilik M, Niehues R, Panneerselvam K, Etchison JR, Fana F, et al. Direct utilization of mannose for mammalian glycoprotein biosynthesis. Glycobiology. 1998;8:285–95. [<a href=\"https://www.ncbi.nlm.nih.gov/pubmed/9451038\" rel=\"nofollow noreferrer\">PubMed</a>] [<a href=\"https://scholar.google.com/scholar_lookup?journal=Glycobiology&amp;title=Direct%20utilization%20of%20mannose%20for%20mammalian%20glycoprotein%20biosynthesis&amp;author=G%20Alton&amp;author=M%20Hasilik&amp;author=R%20Niehues&amp;author=K%20Panneerselvam&amp;author=JR%20Etchison&amp;volume=8&amp;publication_year=1998&amp;pages=285-95&amp;pmid=9451038&amp;\" rel=\"nofollow noreferrer\">Google Scholar</a>]</p>\n</li>\n<li><p>Falcone G, Nickerson WJ. Cell-wall mannan-protein of baker’s yeast. Science. 1956;124:272–3. [<a href=\"https://www.ncbi.nlm.nih.gov/pubmed/13351642\" rel=\"nofollow noreferrer\">PubMed</a>] [<a href=\"https://scholar.google.com/scholar_lookup?journal=Science&amp;title=Cell-wall%20mannan-protein%20of%20baker%E2%80%99s%20yeast&amp;author=G%20Falcone&amp;author=WJ%20Nickerson&amp;volume=124&amp;publication_year=1956&amp;pages=272-3&amp;pmid=13351642&amp;\" rel=\"nofollow noreferrer\">Google Scholar</a>]</p>\n</li>\n</ol>\n</blockquote>\n<p>So the mannose is actually coming from the <a href=\"https://www.cdc.gov/fungal/diseases/candidiasis/index.html\" rel=\"nofollow noreferrer\">candida</a> yeast infection being studied by <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC273987/\" rel=\"nofollow noreferrer\">Monson &amp; Wilkinson (1981)</a>.</p>\n<p>Sharma et al. also points out that mannose has good, bad or ugly outcomes depending on its steady state levels and metabolic flux and their review describes the role of mannose at cellular level and its impact on organisms.</p>\n<blockquote>\n<p>Mannose is a simple sugar with a complex life. It’s a welcome therapy for genetic and acquired human diseases, but it kills honeybees and blinds baby mice. It could cause diabetic complications. Mannose chemistry, metabolism, and metabolomics in cells, tissues and mammals can help explain these multiple systemic effects.</p>\n</blockquote>\n<h2>References</h2>\n<p>Monson, T. P., &amp; Wilkinson, K. P. (1981). Mannose in body fluids as an indicator of invasive candidiasis. Journal of clinical microbiology, 14(5), 557–562. <a href=\"https://doi.org/10.1128/jcm.14.5.557-562.1981\" rel=\"nofollow noreferrer\">https://doi.org/10.1128/jcm.14.5.557-562.1981</a> (Open access at <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC273987/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC273987/</a>)</p>\n<p>Sharma, V., Ichikawa, M., &amp; Freeze, H. H. (2014). Mannose metabolism: more than meets the eye. Biochemical and biophysical research communications, 453(2), 220-228. <a href=\"https://doi.org/10.1016/j.bbrc.2014.06.021\" rel=\"nofollow noreferrer\">https://doi.org/10.1016/j.bbrc.2014.06.021</a> (Open access at <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252654/\" rel=\"nofollow noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252654/</a>)</p>\n" }, { "answer_id": 28750, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 0, "selected": false, "text": "<p>TLDR: yeast (C. albicans) cell walls <a href=\"https://pubmed.ncbi.nlm.nih.gov/32858856/\" rel=\"nofollow noreferrer\">have</a> a &quot;hairy&quot; abundance of mannan as the outer layer, which is a polymer of mannose.</p>\n<p>Also of some note, there's an innate part of the human immune system (<a href=\"https://en.wikipedia.org/wiki/Mannan-binding_lectin\" rel=\"nofollow noreferrer\">MBL</a>) that detect and attacks these...</p>\n<p>Frankly detecting mannose as a yeast infection indicator seems a proposal that never really took off in clinical practice as detecting mannan and/or its antibodies <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219989/\" rel=\"nofollow noreferrer\">is fairly practical</a> and subject to fewer confounders. (You may want for instance to detect galactomannan for differential diagnosis from aspergillosis, etc.)</p>\n" } ]

[ "https://health.stackexchange.com/questions/28715", "https://health.stackexchange.com", "https://health.stackexchange.com/users/23604/" ]

[ { "answer_id": 28794, "author": "anongoodnurse", "author_id": 169, "author_profile": "https://health.stackexchange.com/users/169", "pm_score": 3, "selected": false, "text": "<blockquote>\n<p>My question is, statistically most cases are horses, but how do you find the zebras?</p>\n</blockquote>\n<p>The answer is... complicated. I will answer first from my experience as a (US) physician, and secondly, from a general standpoint in (US) Medicine.</p>\n<p>While we spend the vast amount of our time <em>as physicians</em> treating &quot;horses&quot; (as it were), we spend the vast amount of our training (medical school and some of Residency) learning about zebras.^* So, we know a lot about zebras, and the fear of missing a zebra is what keeps a lot of us on our toes. (There are lots of publications that feature a rare case in every issue or periodically.)</p>\n<p>Also, there is a not terribly well known and informal source of further assistance: online groups for physicians consisting of physicians where difficult cases are discussed in the hopes that a solution might be found.</p>\n<p>But, we can't recognize <em>all</em> the zebras, and this is where the line of referral comes in: a primary care physician or primary care provider refers to a specialist they think might help; if the specialist can't figure it out, they refer to a subspecialist, and on it goes up the chain. It may take time (in some cases, up to a decade), but eventually, one hopes the patient meets a specialist that has seen a zebra they have never forgotten and it is the zebra that the patient happens to have. A friend of mine finally got a diagnosis after 7 years of referrals. It's a long time, but it eventually got diagnosed. (Their condition is literally 1/1,000,000.)</p>\n<p>*_{I recall one lecture on Ewing sarcoma (2.9/1,000,000) where, at the end of the lecture, the professor said, &quot;But don't worry, you'll never see this in your entire lifetime.&quot; And as it so happened, I saw two.}</p>\n<p>_{Sometimes pure luck plays a roll. I saw a patient who had seen 4 specialists in the two weeks prior to his visit with me (a generalist). I performed a test that no one else had done, which led to a diagnosis that was so rare, only 5 people in the US had it before him.}</p>\n<p>_{In residency, our service had a patient with a fairly rare disease (1/100,000) which went undiagnosed, and the attending thought it was psychogenic, which led to embarrassingly atrocious care for the patient. Luckily there was a senior resident who researched the symptoms diligently and came up with the correct, physiologic diagnosis.}</p>\n" }, { "answer_id": 28799, "author": "Ian Campbell", "author_id": 22190, "author_profile": "https://health.stackexchange.com/users/22190", "pm_score": 2, "selected": false, "text": "<p>The UK National Health Service estimates that 80% of rare diseases have an underlying genetic etiology<a href=\"https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/260562/UK_Strategy_for_Rare_Diseases.pdf\" rel=\"nofollow noreferrer\">¹</a>. Thus, rare diseases diagnosis now and in the near future is mostly a function of:</p>\n<h3>Having a screening test with the appropriate sensitivity and specificity to consider multiple rare diseases simultaneously</h3>\n<p>There are probably more than 7000 such genetic diseases<a href=\"https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases\" rel=\"nofollow noreferrer\">²</a>, and no one clinician can possible be aware of all of them other than superficially. Thankfully, there is a screening test which accurately identifies the vast majority of known genetic diseases, exome sequencing. Moreover, exome sequencing has favorable sensitivity and specificity<a href=\"https://pubmed.ncbi.nlm.nih.gov/25492405/\" rel=\"nofollow noreferrer\">³</a>.</p>\n<p>Thus, it seems most likely that diagnosis of the great majority of rare diseases mostly relies on being evaluated by a clinician comfortable with the application of broad genetic testing.</p>\n" } ]

[ "https://health.stackexchange.com/questions/28792", "https://health.stackexchange.com", "https://health.stackexchange.com/users/11/" ]

[ { "answer_id": 28845, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 2, "selected": false, "text": "<p><a href=\"https://en.wikipedia.org/wiki/Absolute_risk\" rel=\"nofollow noreferrer\">Absolute risk</a> is just &quot;events/population&quot;. &quot;# of deaths in a population&quot; is an absolute risk. I don't see any other more complex way to define or describe it, it's one of the simplest summary measures there is. It differs from &quot;case&quot; or &quot;infections&quot; measures in that the denominator is the whole population. If you pluck a name out of a registry of UK children, what's the probability that the name you plucked belongs to someone who died: that's your absolute risk.</p>\n<p>Despite being simple, absolute risks can be both useful and misleading like any statistic, depending on how you phrase it and if you realize what is being said. To take something a bit less political, consider Ebola. The absolute risk of death from Ebola for someone in the UK is somewhere very close to zero. Something reasonable to take from this information might be &quot;if I'm living in the UK, Ebola shouldn't be causing me immediate worry that I'm going to drop dead&quot;. Taking a bunch of extra countermeasures to avoid getting Ebola would be a waste of time. Something <em>not</em> reasonable to take from this statistic would be &quot;Ebola is safe&quot; or &quot;if an Ebola outbreak occurs, we shouldn't try to prevent its spread&quot;.</p>\n<p>In the context of the Twitter discussion, the problem is that the news has mostly been talking about case or infection rates of death. It <em>sounds</em> like &quot;2 in a million&quot; refers to &quot;a million children with COVID&quot; rather than &quot;a million children in the population&quot;. It's only misleading by that implied (incorrect) context.</p>\n" }, { "answer_id": 28846, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 0, "selected": false, "text": "<p>The short Wikipedia article linked from Bryan Krause's answer seems not to get much google juice perhaps because it's verys short, but it does have a source:\n<em>A dictionary of epidemiology</em> (OUP), which says</p>\n<blockquote>\n<p>absolute risk (AR) The probability of an event (usually adverse, but it may also be\nbeneficial) in a closed population over a specified time interval. The number of events\nin a group divided by the total number of subjects in that group. This usage presumes\nthe population is a cohort. AR is not a synonym of attributable fraction, excess risk,\nor risk difference.</p>\n</blockquote>\n<p>(That OUP dictionary is also citing 5 previous works for the def.)</p>\n<p>So it seems reasonable that if &quot;death from covid&quot; is the event, the population in the denominator need not have Covid for AR purposes.</p>\n<p>Nature Scitable also <a href=\"https://www.nature.com/scitable/definition/absolute-risk-63/\" rel=\"nofollow noreferrer\">defines</a> AR as</p>\n<blockquote>\n<p>[...] the probability that an individual will develop a particular condition, such as a disease or some other outcome [...]</p>\n</blockquote>\n<p>Having said that, by looking at a few other sources (<a href=\"https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245381\" rel=\"nofollow noreferrer\">1</a> <a href=\"https://patient.info/news-and-features/calculating-absolute-risk-and-relative-risk\" rel=\"nofollow noreferrer\">2</a> <a href=\"https://www.healthknowledge.org.uk/public-health-textbook/research-methods/1a-epidemiology/numerators-denominators-populations\" rel=\"nofollow noreferrer\">3</a> <a href=\"https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/cancer/art-20044092\" rel=\"nofollow noreferrer\">4</a>), it seems that &quot;absolute risk&quot; is more commonly used to report just the probability of catching the disease rather than the combined event of catching <em>and</em> dying from it. To <a href=\"https://www.nap.edu/read/11340/chapter/7\" rel=\"nofollow noreferrer\">exemplify</a>,</p>\n<blockquote>\n<p><em>Absolute</em> risk is the simple rate of disease among a population (e.g., 75 per 100,000 population per year among the exposed or 25 per 100,000 per year among the nonexposed).</p>\n</blockquote>\n<p>On the other hand, there is <a href=\"https://www.cidrap.umn.edu/news-perspective/2021/03/death-rate-64-higher-b117-covid-variant-study-finds\" rel=\"nofollow noreferrer\">one other</a> UK study that reports absolute risk of death from a Covid variant, but also reported relative risk:</p>\n<blockquote>\n<p>The increased hazard ratio between 1.32 and 2.04, higher than for other variants, translates to a 32% to 104% increased risk of death, with the most probable hazard ratio estimate of 1.64, or a 64% increased risk of death. The absolute risk of death in this group of community identified participants, however, remains relatively low.</p>\n</blockquote>\n" } ]

[ "https://health.stackexchange.com/questions/28843", "https://health.stackexchange.com", "https://health.stackexchange.com/users/10980/" ]

[ { "answer_id": 28845, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 2, "selected": false, "text": "<p><a href=\"https://en.wikipedia.org/wiki/Absolute_risk\" rel=\"nofollow noreferrer\">Absolute risk</a> is just &quot;events/population&quot;. &quot;# of deaths in a population&quot; is an absolute risk. I don't see any other more complex way to define or describe it, it's one of the simplest summary measures there is. It differs from &quot;case&quot; or &quot;infections&quot; measures in that the denominator is the whole population. If you pluck a name out of a registry of UK children, what's the probability that the name you plucked belongs to someone who died: that's your absolute risk.</p>\n<p>Despite being simple, absolute risks can be both useful and misleading like any statistic, depending on how you phrase it and if you realize what is being said. To take something a bit less political, consider Ebola. The absolute risk of death from Ebola for someone in the UK is somewhere very close to zero. Something reasonable to take from this information might be &quot;if I'm living in the UK, Ebola shouldn't be causing me immediate worry that I'm going to drop dead&quot;. Taking a bunch of extra countermeasures to avoid getting Ebola would be a waste of time. Something <em>not</em> reasonable to take from this statistic would be &quot;Ebola is safe&quot; or &quot;if an Ebola outbreak occurs, we shouldn't try to prevent its spread&quot;.</p>\n<p>In the context of the Twitter discussion, the problem is that the news has mostly been talking about case or infection rates of death. It <em>sounds</em> like &quot;2 in a million&quot; refers to &quot;a million children with COVID&quot; rather than &quot;a million children in the population&quot;. It's only misleading by that implied (incorrect) context.</p>\n" }, { "answer_id": 28846, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 0, "selected": false, "text": "<p>The short Wikipedia article linked from Bryan Krause's answer seems not to get much google juice perhaps because it's verys short, but it does have a source:\n<em>A dictionary of epidemiology</em> (OUP), which says</p>\n<blockquote>\n<p>absolute risk (AR) The probability of an event (usually adverse, but it may also be\nbeneficial) in a closed population over a specified time interval. The number of events\nin a group divided by the total number of subjects in that group. This usage presumes\nthe population is a cohort. AR is not a synonym of attributable fraction, excess risk,\nor risk difference.</p>\n</blockquote>\n<p>(That OUP dictionary is also citing 5 previous works for the def.)</p>\n<p>So it seems reasonable that if &quot;death from covid&quot; is the event, the population in the denominator need not have Covid for AR purposes.</p>\n<p>Nature Scitable also <a href=\"https://www.nature.com/scitable/definition/absolute-risk-63/\" rel=\"nofollow noreferrer\">defines</a> AR as</p>\n<blockquote>\n<p>[...] the probability that an individual will develop a particular condition, such as a disease or some other outcome [...]</p>\n</blockquote>\n<p>Having said that, by looking at a few other sources (<a href=\"https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245381\" rel=\"nofollow noreferrer\">1</a> <a href=\"https://patient.info/news-and-features/calculating-absolute-risk-and-relative-risk\" rel=\"nofollow noreferrer\">2</a> <a href=\"https://www.healthknowledge.org.uk/public-health-textbook/research-methods/1a-epidemiology/numerators-denominators-populations\" rel=\"nofollow noreferrer\">3</a> <a href=\"https://www.mayoclinic.org/diseases-conditions/cancer/in-depth/cancer/art-20044092\" rel=\"nofollow noreferrer\">4</a>), it seems that &quot;absolute risk&quot; is more commonly used to report just the probability of catching the disease rather than the combined event of catching <em>and</em> dying from it. To <a href=\"https://www.nap.edu/read/11340/chapter/7\" rel=\"nofollow noreferrer\">exemplify</a>,</p>\n<blockquote>\n<p><em>Absolute</em> risk is the simple rate of disease among a population (e.g., 75 per 100,000 population per year among the exposed or 25 per 100,000 per year among the nonexposed).</p>\n</blockquote>\n<p>On the other hand, there is <a href=\"https://www.cidrap.umn.edu/news-perspective/2021/03/death-rate-64-higher-b117-covid-variant-study-finds\" rel=\"nofollow noreferrer\">one other</a> UK study that reports absolute risk of death from a Covid variant, but also reported relative risk:</p>\n<blockquote>\n<p>The increased hazard ratio between 1.32 and 2.04, higher than for other variants, translates to a 32% to 104% increased risk of death, with the most probable hazard ratio estimate of 1.64, or a 64% increased risk of death. The absolute risk of death in this group of community identified participants, however, remains relatively low.</p>\n</blockquote>\n" } ]

[ "https://health.stackexchange.com/questions/28880", "https://health.stackexchange.com", "https://health.stackexchange.com/users/23787/" ]

[ { "answer_id": 28899, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 2, "selected": false, "text": "<p>It's unclear to me what tissue you expect to be sampled. SARS-CoV-2 is a respiratory virus and <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494547/\" rel=\"nofollow noreferrer\">like</a> similar viruses it's (differentially) diagnosed by &quot;nasal&quot; (more accurately: nasopharyngeal) swabs and PCR or at most by doing the same (PCR) on the more invasive (to obtain) <a href=\"https://en.wikipedia.org/wiki/Bronchoalveolar_lavage\" rel=\"nofollow noreferrer\">BAL</a> samples, which are more commonly used in pneumonia cases. (The latter samples are also used to detect bacterial co-infections etc.)</p>\n<p>Actually, SARS-CoV-2 has some affinity for cells in the digestive tract as well, but while stool sampling <a href=\"https://virologyj.biomedcentral.com/articles/10.1186/s12985-020-01359-1\" rel=\"nofollow noreferrer\">can</a> detect it, I haven't heard of it this method being very common, in practice.\n(As far as determining the aforementioned affinity, some duodenal biopsies <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335412/\" rel=\"nofollow noreferrer\">were</a> performed, but that would be way overkill/invasive for regular diagnostics.)</p>\n<p>As for your question on the destruction of the spike protein from the vaccines... no that hasn't been tested at all in humans, as far as I know. During vaccine development, modified fluorescent proteins have been used <a href=\"https://www.sciencedirect.com/science/article/pii/S0264410X21006071#f0030\" rel=\"nofollow noreferrer\">in vitro</a> to determine how the protein spreads and how long it lasts. (For some other vaccines, I do recall seeing full-mouse fluorescent images, but I'm not sure such studies have been for SARS-CoV-2 vaccines in particular, due to the speed of development during the pandemic.) For a state-of-the-art paper on fluorescence tracking of mRNA during delivery see e.g. <a href=\"https://pubs.acs.org/doi/10.1021/jacs.1c00014\" rel=\"nofollow noreferrer\">https://pubs.acs.org/doi/10.1021/jacs.1c00014</a></p>\n<p>Below is what a &quot;kinetic biodistribution&quot; study looks like. <a href=\"https://www.nature.com/articles/s41392-021-00634-z\" rel=\"nofollow noreferrer\">This one</a> is for an experimental Chinese mRNA vaccine, using two different types on nanoparticles. (The point of the paper is to claim that their LPP is in some ways superior to &quot;traditional&quot; LNPs used in Western vaccines.)</p>\n<p><a href=\"https://i.stack.imgur.com/3Gmtw.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/3Gmtw.png\" alt=\"enter image description here\" /></a></p>\n<p>The time-graph (e) is pretty badly rendered; there's larger version <a href=\"https://www.nature.com/articles/s41392-021-00634-z/figures/2\" rel=\"nofollow noreferrer\">here</a>, but from I can see, they've only tracked up to 240 hours, after which the mRNA was mostly gone (except maybe from the lungs), so they stopped.</p>\n<p>These things are generally conducted for regulatory approval purposes, but not always published as papers in the academic press. For your purpose of knowing the trajectory of the spike protein rather than mRNA, a study like this on a protein subunit vaccine like Novavax's would be useful, but from their studies <a href=\"https://www.nature.com/articles/s41467-020-20653-8\" rel=\"nofollow noreferrer\">I know about</a>, they haven't published something like the above.</p>\n" }, { "answer_id": 29010, "author": "Dale", "author_id": 16005, "author_profile": "https://health.stackexchange.com/users/16005", "pm_score": 0, "selected": false, "text": "<p>Yes, there is a way to test for presence of the spike protein in organ samples. This may not be possible in human biopsies / tissue samples with the standard vaccine, but it was done by Pfizer while testing BNT162, PF-07302048, as indicated in their own test data*. Done in rats (Wistar Han strain).</p>\n<p><a href=\"https://i.stack.imgur.com/p68CD.jpg\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/p68CD.jpg\" alt=\"Mean total lipid concentration in rats over time, Pfizer Report 185350\" /></a></p>\n<ul>\n<li><a href=\"https://files.catbox.moe/0vwcmj.pdf\" rel=\"nofollow noreferrer\">Pfizer Report</a></li>\n</ul>\n<p>The highest concentrations were found in: Injection site 165, Liver 24.3, Spleen 23.4, Adrenal glands 18.2, Ovaries 12.3, Bone marrow 3.77, Small intestine 1.47, Lymph (mesenteric) 1.37, Large intestine 1.34, Lung 1.09, Thyroid 1 µg lipid equivalent/g.</p>\n" } ]

[ "https://health.stackexchange.com/questions/28897", "https://health.stackexchange.com", "https://health.stackexchange.com/users/16005/" ]

[ { "answer_id": 29023, "author": "timx", "author_id": 23915, "author_profile": "https://health.stackexchange.com/users/23915", "pm_score": 0, "selected": false, "text": "<p>JAMA has a randomized clinical trial in 2019: &quot;N95 Respirators vs Medical Masks for Preventing Influenza Among Health Care Personnel&quot;. The finding is &quot;there was no significant difference in the incidence of laboratory-confirmed influenza&quot;.</p>\n<p>Regarding Bavaria's N95/FFP2 respirator mandate, there's a graph of Bavaria vs Germany daily new cases in this article: <a href=\"https://swprs.org/face-masks-evidence/#development-of-cases-after-mask-mandates\" rel=\"nofollow noreferrer\">https://swprs.org/face-masks-evidence/#development-of-cases-after-mask-mandates</a></p>\n" }, { "answer_id": 29026, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 1, "selected": false, "text": "<p>Apparently no reports from that German experience, but recently researchers published a working paper with the results of &quot;<a href=\"https://www.poverty-action.org/sites/default/files/publications/Mask_RCT____Symptomatic_Seropositivity_083121.pdf\" rel=\"nofollow noreferrer\">A <strong>randomized-trial of community-level mask promotion</strong> in rural Bangladesh during COVID-19 shows that <strong>the intervention tripled mask usage and reduced symptomatic SARS-CoV-2 infections</strong> ...</a>&quot;\n<a href=\"https://www.poverty-action.org/publication/impact-community-masking-covid-19-cluster-randomized-trial-bangladesh\" rel=\"nofollow noreferrer\">https://www.poverty-action.org/publication/impact-community-masking-covid-19-cluster-randomized-trial-bangladesh</a></p>\n<p>It seems likely that this trial did not encounter much of the delta variant, as it seems that interventions were completed by April 2021 and delta seemed to hit Bangladesh in late June 2021.</p>\n<p>Note - this is not yet reviewed/published, but it does seem to be a proper paper with methodological details, results, etc.</p>\n<p>Here's the <a href=\"https://med.stanford.edu/news/all-news/2021/09/surgical-masks-covid-19.html\" rel=\"nofollow noreferrer\">Stanford press release</a> about the study.</p>\n" } ]

[ "https://health.stackexchange.com/questions/28911", "https://health.stackexchange.com", "https://health.stackexchange.com/users/10980/" ]

[ { "answer_id": 28915, "author": "Michael A", "author_id": 23819, "author_profile": "https://health.stackexchange.com/users/23819", "pm_score": 2, "selected": true, "text": "<p>There are several open access journals and collections that you can search.</p>\n<ul>\n<li>The <a href=\"https://jamanetwork.com/journals/jamanetworkopen\" rel=\"nofollow noreferrer\">Journal of the American Medical Association (JAMA) Open Access network</a>.</li>\n<li>The <a href=\"https://www.nejm.org/about-nejm/access-levels\" rel=\"nofollow noreferrer\">New England Journal of Medicine allows open access to certain articles</a>.</li>\n<li><a href=\"https://www.thelancet.com/open-access\" rel=\"nofollow noreferrer\">Several journals in the Lancet family are open access</a>.</li>\n<li>The British Medical Journal has an open access counterpart, <a href=\"https://bmjopen.bmj.com/\" rel=\"nofollow noreferrer\">BMJ Open</a>.</li>\n</ul>\n<p>Also, for many articles, the authors will happily share a copy with you if you email them and ask politely. Since they're busy, it might take a while for them to reply, but at least with academics, many are happy to share their work.</p>\n" }, { "answer_id": 28917, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 1, "selected": false, "text": "<p>It's often useful to search on a big database (like <a href=\"https://pubmed.ncbi.nlm.nih.gov/\" rel=\"nofollow noreferrer\">PubMed</a>) to find articles you're interested in, then next try to figure out how to access them.</p>\n" }, { "answer_id": 28937, "author": "Timur Shtatland", "author_id": 17046, "author_profile": "https://health.stackexchange.com/users/17046", "pm_score": 2, "selected": false, "text": "<ul>\n<li><a href=\"https://pubmed.ncbi.nlm.nih.gov/\" rel=\"nofollow noreferrer\"><strong>PubMed</strong></a> comprises more than 32 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full text content from PubMed Central and publisher web sites.</li>\n</ul>\n<p>After you search using the search box on the main web site, select in the left column this filter:\n<code>text availability: free full text</code>.</p>\n<ul>\n<li><a href=\"https://www.ncbi.nlm.nih.gov/pmc/\" rel=\"nofollow noreferrer\"><strong>PubMed Central</strong></a> (PMC) is a free <strong>full-text</strong> archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health's National Library of Medicine (NIH/NLM).</li>\n</ul>\n" }, { "answer_id": 28948, "author": "Franck Dernoncourt", "author_id": 43, "author_profile": "https://health.stackexchange.com/users/43", "pm_score": 0, "selected": false, "text": "<ul>\n<li><a href=\"http://scholar.google.com/\" rel=\"nofollow noreferrer\">Google Scholar</a> is another good place to try to find a freely available PDF for a given article.</li>\n<li><a href=\"https://www.medrxiv.org/\" rel=\"nofollow noreferrer\">https://www.medrxiv.org/</a>: preprints of medical papers</li>\n<li><a href=\"https://www.biorxiv.org/\" rel=\"nofollow noreferrer\">https://www.biorxiv.org/</a>: preprints of biology papers</li>\n<li><a href=\"https://connect.medrxiv.org/relate/content/181\" rel=\"nofollow noreferrer\">https://connect.medrxiv.org/relate/content/181</a>: COVID-specific articles.</li>\n</ul>\n" } ]

[ "https://health.stackexchange.com/questions/28913", "https://health.stackexchange.com", "https://health.stackexchange.com/users/23818/" ]

[ { "answer_id": 28915, "author": "Michael A", "author_id": 23819, "author_profile": "https://health.stackexchange.com/users/23819", "pm_score": 2, "selected": true, "text": "<p>There are several open access journals and collections that you can search.</p>\n<ul>\n<li>The <a href=\"https://jamanetwork.com/journals/jamanetworkopen\" rel=\"nofollow noreferrer\">Journal of the American Medical Association (JAMA) Open Access network</a>.</li>\n<li>The <a href=\"https://www.nejm.org/about-nejm/access-levels\" rel=\"nofollow noreferrer\">New England Journal of Medicine allows open access to certain articles</a>.</li>\n<li><a href=\"https://www.thelancet.com/open-access\" rel=\"nofollow noreferrer\">Several journals in the Lancet family are open access</a>.</li>\n<li>The British Medical Journal has an open access counterpart, <a href=\"https://bmjopen.bmj.com/\" rel=\"nofollow noreferrer\">BMJ Open</a>.</li>\n</ul>\n<p>Also, for many articles, the authors will happily share a copy with you if you email them and ask politely. Since they're busy, it might take a while for them to reply, but at least with academics, many are happy to share their work.</p>\n" }, { "answer_id": 28917, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 1, "selected": false, "text": "<p>It's often useful to search on a big database (like <a href=\"https://pubmed.ncbi.nlm.nih.gov/\" rel=\"nofollow noreferrer\">PubMed</a>) to find articles you're interested in, then next try to figure out how to access them.</p>\n" }, { "answer_id": 28937, "author": "Timur Shtatland", "author_id": 17046, "author_profile": "https://health.stackexchange.com/users/17046", "pm_score": 2, "selected": false, "text": "<ul>\n<li><a href=\"https://pubmed.ncbi.nlm.nih.gov/\" rel=\"nofollow noreferrer\"><strong>PubMed</strong></a> comprises more than 32 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full text content from PubMed Central and publisher web sites.</li>\n</ul>\n<p>After you search using the search box on the main web site, select in the left column this filter:\n<code>text availability: free full text</code>.</p>\n<ul>\n<li><a href=\"https://www.ncbi.nlm.nih.gov/pmc/\" rel=\"nofollow noreferrer\"><strong>PubMed Central</strong></a> (PMC) is a free <strong>full-text</strong> archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health's National Library of Medicine (NIH/NLM).</li>\n</ul>\n" }, { "answer_id": 28948, "author": "Franck Dernoncourt", "author_id": 43, "author_profile": "https://health.stackexchange.com/users/43", "pm_score": 0, "selected": false, "text": "<ul>\n<li><a href=\"http://scholar.google.com/\" rel=\"nofollow noreferrer\">Google Scholar</a> is another good place to try to find a freely available PDF for a given article.</li>\n<li><a href=\"https://www.medrxiv.org/\" rel=\"nofollow noreferrer\">https://www.medrxiv.org/</a>: preprints of medical papers</li>\n<li><a href=\"https://www.biorxiv.org/\" rel=\"nofollow noreferrer\">https://www.biorxiv.org/</a>: preprints of biology papers</li>\n<li><a href=\"https://connect.medrxiv.org/relate/content/181\" rel=\"nofollow noreferrer\">https://connect.medrxiv.org/relate/content/181</a>: COVID-specific articles.</li>\n</ul>\n" } ]

[ "https://health.stackexchange.com/questions/29052", "https://health.stackexchange.com", "https://health.stackexchange.com/users/23957/" ]

[ { "answer_id": 28915, "author": "Michael A", "author_id": 23819, "author_profile": "https://health.stackexchange.com/users/23819", "pm_score": 2, "selected": true, "text": "<p>There are several open access journals and collections that you can search.</p>\n<ul>\n<li>The <a href=\"https://jamanetwork.com/journals/jamanetworkopen\" rel=\"nofollow noreferrer\">Journal of the American Medical Association (JAMA) Open Access network</a>.</li>\n<li>The <a href=\"https://www.nejm.org/about-nejm/access-levels\" rel=\"nofollow noreferrer\">New England Journal of Medicine allows open access to certain articles</a>.</li>\n<li><a href=\"https://www.thelancet.com/open-access\" rel=\"nofollow noreferrer\">Several journals in the Lancet family are open access</a>.</li>\n<li>The British Medical Journal has an open access counterpart, <a href=\"https://bmjopen.bmj.com/\" rel=\"nofollow noreferrer\">BMJ Open</a>.</li>\n</ul>\n<p>Also, for many articles, the authors will happily share a copy with you if you email them and ask politely. Since they're busy, it might take a while for them to reply, but at least with academics, many are happy to share their work.</p>\n" }, { "answer_id": 28917, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 1, "selected": false, "text": "<p>It's often useful to search on a big database (like <a href=\"https://pubmed.ncbi.nlm.nih.gov/\" rel=\"nofollow noreferrer\">PubMed</a>) to find articles you're interested in, then next try to figure out how to access them.</p>\n" }, { "answer_id": 28937, "author": "Timur Shtatland", "author_id": 17046, "author_profile": "https://health.stackexchange.com/users/17046", "pm_score": 2, "selected": false, "text": "<ul>\n<li><a href=\"https://pubmed.ncbi.nlm.nih.gov/\" rel=\"nofollow noreferrer\"><strong>PubMed</strong></a> comprises more than 32 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full text content from PubMed Central and publisher web sites.</li>\n</ul>\n<p>After you search using the search box on the main web site, select in the left column this filter:\n<code>text availability: free full text</code>.</p>\n<ul>\n<li><a href=\"https://www.ncbi.nlm.nih.gov/pmc/\" rel=\"nofollow noreferrer\"><strong>PubMed Central</strong></a> (PMC) is a free <strong>full-text</strong> archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health's National Library of Medicine (NIH/NLM).</li>\n</ul>\n" }, { "answer_id": 28948, "author": "Franck Dernoncourt", "author_id": 43, "author_profile": "https://health.stackexchange.com/users/43", "pm_score": 0, "selected": false, "text": "<ul>\n<li><a href=\"http://scholar.google.com/\" rel=\"nofollow noreferrer\">Google Scholar</a> is another good place to try to find a freely available PDF for a given article.</li>\n<li><a href=\"https://www.medrxiv.org/\" rel=\"nofollow noreferrer\">https://www.medrxiv.org/</a>: preprints of medical papers</li>\n<li><a href=\"https://www.biorxiv.org/\" rel=\"nofollow noreferrer\">https://www.biorxiv.org/</a>: preprints of biology papers</li>\n<li><a href=\"https://connect.medrxiv.org/relate/content/181\" rel=\"nofollow noreferrer\">https://connect.medrxiv.org/relate/content/181</a>: COVID-specific articles.</li>\n</ul>\n" } ]

[ "https://health.stackexchange.com/questions/29064", "https://health.stackexchange.com", "https://health.stackexchange.com/users/23975/" ]

[ { "answer_id": 29183, "author": "Bryan Krause", "author_id": 8728, "author_profile": "https://health.stackexchange.com/users/8728", "pm_score": 7, "selected": true, "text": "<p><a href=\"https://vaers.hhs.gov/data/dataguide.html\" rel=\"noreferrer\">https://vaers.hhs.gov/data/dataguide.html</a> provides a useful guide for interpreting these data.</p>\n<p>VAERS deaths are not causal reports, they're just a report where someone (doctor, family member) decided to fill in a form. Most are likely to be coincidences. These links are posing the question &quot;well if these are just coincidences, why are so many the day after vaccination and so few weeks later?&quot;</p>\n<p>If someone dies of heart failure the day they get a vaccine, after struggling with heart failure for months, how likely do you think it is that someone would report to the vaccine surveillance database? After all, they just got the vaccine the day they died!</p>\n<p>Now imagine the same person dies 3 weeks after the vaccine. Who is going to think to report that as a vaccine-related death? They were probably very ill before the vaccine, very ill after, and very ill for the weeks until they eventually died.</p>\n<p>Same things go for old, boring, annual flu vaccine vs new, exciting COVID vaccines. Docs are instructed not to report deaths after a flu vaccine that are unlikely to be vaccine related since those vaccines have been given over many years without problem; the newer COVID vaccines don't come with this same guideline, so docs are likely to report deaths after the new vaccines, even if they have no reason to think they are related. They are reporting just to be safe, and it's silly to compare two vaccines reported under very different guidelines.</p>\n<p>These data are very hard to understand for these reasons, but certainly the interpretations given in those links seem very misinformed. It's crucial to know and understand where your data are coming from before reporting them. Since they clearly do not (or know and choose to mislead anyways), I don't think it's even worth investigating further. There are similar questions on Skeptics.SE if you want to find more misuse of VAERS data, just search VAERS there.</p>\n" }, { "answer_id": 29202, "author": "user3067860", "author_id": 10926, "author_profile": "https://health.stackexchange.com/users/10926", "pm_score": 3, "selected": false, "text": "<p>VAERS has a useful purpose, but in high profile situations such as this the data is often more reflective of data collection issues rather than actual effects of vaccination.</p>\n<p>In addition to the reasons mentioned in another answer (people are more diligent about reporting incidents after the COVID vaccines because they are new and notable), note that VAERS has a literal form on a webpage where any member of the public can submit a report with no real verification/validation. This form has a notice that it is <em>illegal</em> to deliberately submit false reports, but since it is a form on the internet of course people do anyway. (As well as probably a number of people who intend to submit a correct report but have accidentally entered something incorrectly, etc.)</p>\n<p>Looking at your source of OpenVaers, there is an item in their FAQ:</p>\n<blockquote>\n<p>We do not change, modify or vet data. We take the downloads, upload them to our server and put a different face on them so they are easier to browse and get quick accurate info from. There are mistakes in the data (impossible dates are usually the most obvious), clearly, but we leave it as we get it.</p>\n</blockquote>\n<p>And a very, very quick glance at their data confirms this: from an eyeball estimate, more than 7,500 people were reported as dying from the COVID vaccine between 1990 and 2019. Since the COVID vaccine didn't exist until 2020, this is a very easy example of the data quality and reliability of reporting here.</p>\n<p>Additionally, the actual VAERS has a disclaimer that you have to click &quot;I agree&quot; to in order to access the data which elaborates on this. It reads as follows (reproducing in entirety because it's important, also as it's US gov't work it is not copyrighted):</p>\n<blockquote>\n<p>VAERS accepts reports of adverse events and reactions that occur following vaccination. Healthcare providers, vaccine manufacturers, and the public can submit reports to VAERS. While very important in monitoring vaccine safety, VAERS reports alone cannot be used to determine if a vaccine caused or contributed to an adverse event or illness. The reports may contain information that is incomplete, inaccurate, coincidental, or unverifiable. Most reports to VAERS are voluntary, which means they are subject to biases. This creates specific limitations on how the data can be used scientifically. Data from VAERS reports should always be interpreted with these limitations in mind.</p>\n<p>The strengths of VAERS are that it is national in scope and can quickly provide an early warning of a safety problem with a vaccine.\nAs part of CDC and FDA's multi-system approach to post-licensure vaccine safety monitoring, VAERS is designed to rapidly detect unusual or unexpected patterns of adverse events, also known as &quot;safety signals.&quot; If a safety signal is found in VAERS, further studies can be done in safety systems such as the CDC's Vaccine Safety Datalink (VSD) or the Clinical Immunization Safety Assessment (CISA) project. These systems do not have the same limitations as VAERS, and can better assess health risks and possible connections between adverse events and a vaccine.</p>\n<p>Key considerations and limitations of VAERS data:</p>\n<ul>\n<li>Vaccine providers are encouraged to report any clinically significant health problem following vaccination to VAERS, whether or not they believe the vaccine was the cause.</li>\n<li>Reports may include incomplete, inaccurate, coincidental and unverified information.</li>\n<li>The number of reports alone cannot be interpreted or used to reach conclusions about the existence, severity, frequency, or rates of problems associated with vaccines.</li>\n<li>VAERS data are limited to vaccine adverse event reports received between 1990 and the most recent date for which data are available.</li>\n<li>VAERS data do not represent all known safety information for a vaccine and should be interpreted in the context of other scientific information.</li>\n</ul>\n<p>VAERS data available to the public include only the initial report data to VAERS. Updated data which contains data from medical records and corrections reported during follow up are used by the government for analysis. However, for numerous reasons including data consistency, these amended data are not available to the public.</p>\n</blockquote>\n" } ]

[ "https://health.stackexchange.com/questions/29181", "https://health.stackexchange.com", "https://health.stackexchange.com/users/24083/" ]

[ { "answer_id": 29207, "author": "bob1", "author_id": 24128, "author_profile": "https://health.stackexchange.com/users/24128", "pm_score": 2, "selected": false, "text": "<p>I am neither a medical professional nor a statistician, so <em>caveat emptor</em> and all that</p>\n<p>Short answer is no.</p>\n<p>This is because, in the article the authors state:</p>\n<blockquote>\n<p>A total of 1,736,832 persons were eligible for inclusion in the vaccination cohort...</p>\n</blockquote>\n<blockquote>\n<p>...The vaccination cohorts included a mean of 884,828 vaccinated persons, with a median age of 38 years</p>\n</blockquote>\n<p>If you compare these to the numbers of persons in the adverse events cohort column recorded for each category, then you can see that a sum total of persons (22,080,670, if my maths is correct) would be well in excess of the enrolled cohort. This means that each reported event is not independent and it is likely that a person who had one adverse event also had at least one other reported event.</p>\n<p>Thus, a simple sum of the excess events is not something that can be performed. Indeed, if this were the case, the authors would likely have done so in the paper, but they did not, leading to the conclusion that it is not a valid technique.</p>\n<p>Now we must consider that adverse event risk ratios are calculated for vaccines and other medicines, so there must be some methodology to do so, but what that methodology is, I don't know though I suspect an <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938757/\" rel=\"nofollow noreferrer\">odds-ratio</a> calculation of some sort.</p>\n<p>Note that the authors only considered some of these events to be a significant difference, even if the risk ratio or risk difference were higher than expected, so they excluded parathesia (tingling/prickling sensation) as well as vertigo (dizziness), but it looks like the excluded ones are all minor symptoms not associated with a general morbidity/mortality:</p>\n<blockquote>\n<p>The risk was substantially higher on either the multiplicative (risk ratio) or additive (risk difference) scales in the vaccinated group than in the unvaccinated group for myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2).</p>\n</blockquote>\n<p>They also note the risks associated with SARS-CoV-2 infection in general and in figures 3 and 4 of the paper comparing to the risk with vaccination:</p>\n<blockquote>\n<p>Infection substantially increased the risk of many different adverse events, including <strong>myocarditis</strong> (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8), acute kidney injury (risk ratio, 14.83; 95% CI, 9.24 to 28.75; risk difference, 125.4 events per 100,000 persons; 95% CI, 107.0 to 142.6), pulmonary embolism (risk ratio, 12.14; 95% CI, 6.89 to 29.20; risk difference, 61.7 events per 100,000 persons; 95% CI, 48.5 to 75.4), intracranial hemorrhage (risk ratio, 6.89; 95% CI, 1.90 to 19.16; risk difference, 7.6 events per 100,000 persons; 95% CI, 2.7 to 12.6), pericarditis (risk ratio, 5.39; 95% CI, 2.22 to 23.58; risk difference, 10.9 events per 100,000 persons; 95% CI, 4.9 to 16.9), myocardial infarction (risk ratio, 4.47; 95% CI, 2.47 to 9.95; risk difference, 25.1 events per 100,000 persons; 95% CI, 16.2 to 33.9), deep-vein thrombosis (risk ratio, 3.78; 95% CI, 2.50 to 6.59; risk difference, 43.0 events per 100,000 persons; 95% CI, 29.9 to 56.6), and arrhythmia (risk ratio, 3.83; 95% CI, 3.07 to 4.95; risk difference, 166.1 events per 100,000 persons; 95% CI, 139.6 to 193.2).</p>\n</blockquote>\n<p><strong>Figure 3</strong>\n<a href=\"https://i.stack.imgur.com/szNFl.jpg\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/szNFl.jpg\" alt=\"Figure 3\" /></a>\n<strong>Figure 4</strong>\n<a href=\"https://i.stack.imgur.com/E9okj.jpg\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/E9okj.jpg\" alt=\"Figure 4\" /></a></p>\n" }, { "answer_id": 29215, "author": "Fizz", "author_id": 10980, "author_profile": "https://health.stackexchange.com/users/10980", "pm_score": 2, "selected": false, "text": "<p>I think there's some missing the forest for the trees here, in the sense that adverse events (aka adverse effects) generally do not have a strict definition beyond something <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098080/\" rel=\"nofollow noreferrer\">like</a>:</p>\n<blockquote>\n<p>untoward medical occurrences after exposure. These endpoints, which are not necessarily causally related [to the treatment], are called adverse events (or sometimes adverse effects) (AEs)</p>\n</blockquote>\n<p>AEs are often enough protocol-defined. In this Israeli study:</p>\n<blockquote>\n<p>Adverse events were defined according to diagnostic codes and short free-text phrases that accompany diagnoses in the CHS database. A complete list of the study outcomes (adverse events) and their definitions is provided in Table S2.</p>\n</blockquote>\n<p>with the stated intent to capture &quot;a broad set of potential short- and medium-term adverse events among vaccinated persons&quot;.</p>\n<p>You'll note that the most common AE in table 2 (that you've included in your question) is lymphadenopathy (inflammation of the lymph nodes) which is a common but temporary (and most often <a href=\"https://edition.cnn.com/2021/10/08/health/covid-vaccine-swollen-lymph-nodes-wellness/index.html\" rel=\"nofollow noreferrer\">benign</a>) side effect of vaccines, but almost certainly not the most common side effect spontaneusly reported... as shown e.g. in this <a href=\"https://health-infobase.canada.ca/covid-19/vaccine-safety/\" rel=\"nofollow noreferrer\">Canadian database</a>, where lymphadenopathy is somewhere in the middle of the pack of the effects reported (and even below myocarditis in the Canadian database, even though that's much, much rarer in the Israeli study):</p>\n<p><a href=\"https://i.stack.imgur.com/JA92o.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/JA92o.png\" alt=\"enter image description here\" /></a></p>\n<p>So the &quot;broad set&quot; was perhaps not so broad in the Israeli study, as if clearly excluded the commonly reported vaccine side effects like headache etc. While you can definitely sum up AEs according to one study's particular definition(s) and even express that total as a ratio to the population under study... it's an not incredibly useful sum/conclusion beyond that study. Whereas specific AEs are in a sense &quot;portable&quot; between studies, assuming they used some reasonably common definition for the individual AEs. (Myocarditis is somewhat complicated as there are [Brighton Collaboration] levels for it. Also the Canadians reported it up to 92 days after vaccination, which is a longer time window than in the Israeli study.) This is almost certainly why the Israeli paper's abstract doesn't present some sum, but the individual AEs that they found statistically significant in the vaccine's direction:</p>\n<blockquote>\n<p>Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2).</p>\n</blockquote>\n<p>One has to wonder how herpes or appendicitis might be causally related to the vaccine, by the way. It could be simply behavioral like more kissing and going out to restaurants more often, although for appendicitis some connection via a higher likelihood of general inflammatory reaction can't be excluded. (For herpes zoster at least, reactivation from lymph nodes has been <a href=\"https://www.ijidonline.com/article/S1201-9712(21)00681-0/fulltext\" rel=\"nofollow noreferrer\">posited</a>.) The Israeli paper notes that the clinical trials have noted a trend for appendicitis too, but not statistically significant, perhaps due to undepowered sample to detect a small effect. So, it's somewhat clear that they tried do &quot;double check&quot; some such trends they noticed/suspected, useing their larger database, while excluding AEs they probably considered trivial or &quot;boring&quot;.</p>\n" } ]

[ "https://health.stackexchange.com/questions/29184", "https://health.stackexchange.com", "https://health.stackexchange.com/users/11724/" ]

[ { "answer_id": 30571, "author": "Brian Ó Maoláin", "author_id": 24505, "author_profile": "https://health.stackexchange.com/users/24505", "pm_score": 2, "selected": false, "text": "<p>This is a difficult question to answer because it is very broad. Your sources concern a number of different pathologies which have different mechanisms and different treatment approaches.</p>\n<p>It's important to differentiate between <a href=\"https://www.webmd.com/pain-management/features/types-pain\" rel=\"nofollow noreferrer\">acute and chronic pain</a> because chronic pain is not associated with continued damage to the tissues. This means that e.g. whether NSAIDs inhibit the immune system from contributing to healing may not be relevant to chronic pain where the initial insult has disappeared.</p>\n<p>Back pain can be an acute musculoskeletal injury or chronic pain which is no longer associated with damage. It may also be <a href=\"https://en.wikipedia.org/wiki/Musculoskeletal_disorder\" rel=\"nofollow noreferrer\">musculoskeletal</a> vs <a href=\"https://en.wikipedia.org/wiki/Neuropathic_pain\" rel=\"nofollow noreferrer\">neuropathic</a> which may have different management.</p>\n<p>Your sources move between several <a href=\"https://en.wikipedia.org/wiki/Hierarchy_of_evidence\" rel=\"nofollow noreferrer\">levels of evidence</a> from in vitro experiments to Cochrane reviews. In terms of evaluating the quality of evidence for current treatments it is probably better to stick to systematic reviews so I will use Cochrane from here. I will also restrict my answer to NSAIDs and paracetamol in reference to non-neuropathic back pain.</p>\n<p>The short answer is that the evidence for any treatment isn't great, and the results are contradictory even when taking large numbers of studies in aggregate.</p>\n<h2><a href=\"https://www.cochrane.org/CD000396/BACK_non-steroidal-anti-inflammatory-drugs-for-low-back-pain\" rel=\"nofollow noreferrer\">Non-steroidal anti-inflammatory drugs for low-back pain</a></h2>\n<blockquote>\n<p>The review authors conclude that NSAIDs are slightly effective for short-term symptomatic relief in patients with acute and chronic low-back pain without sciatica (pain and tingling radiating down the leg). In patients with acute sciatica, no difference in effect between NSAIDs and placebo was found.</p>\n</blockquote>\n<blockquote>\n<p>The review authors also found that NSAIDs are not more effective than other drugs (paracetamol/acetaminophen, narcotic analgesics, and muscle relaxants). Placebo and paracetamol/acetaminophen had fewer side effects than NSAIDs, though the latter has fewer side effects than muscle relaxants and narcotic analgesics.</p>\n</blockquote>\n<blockquote>\n<p>Only 42% of the studies were considered to be of high quality. Many of the studies had small numbers of patients, which limits the ability to detect differences between the NSAID and the control group. There are few data on long term results and long-term side effects.</p>\n</blockquote>\n<p>So, NSAIDs might help a bit in the short term.</p>\n<h2><a href=\"https://www.cochrane.org/CD012230/BACK_paracetamol-low-back-pain\" rel=\"nofollow noreferrer\">Paracetamol for low back pain</a></h2>\n<blockquote>\n<p>We found high-quality evidence that paracetamol (4 g per day) is no better than placebo for relieving acute LBP in either the short or longer term. It also worked no better than placebo on the other aspects studied, such as quality of life and sleep quality. About one in five people reported side effects, though few were serious, and there was no difference between intervention and control groups. As most of the participants studied were middle-aged, we cannot be sure that the findings would be the same for other age groups.</p>\n</blockquote>\n<p>So paracetamol (i.e. acetaminophen) is probably not ideal. This is confusing in relation to NSAIDs being found to be no better than paracetamol but still effective.</p>\n<h2>In practice</h2>\n<p>The current UK <a href=\"https://cks.nice.org.uk/topics/back-pain-low-without-radiculopathy/management/management/\" rel=\"nofollow noreferrer\">NICE guidelines for management of low back pain are basically:</a></p>\n<ol>\n<li>Rule out any &quot;red flag&quot; pathology</li>\n<li>Identify any underlying cause. If back pain is secondary to a treatable cause e.g. osteoporosis then that should be dealt with first.</li>\n<li><a href=\"https://backcare.org.uk/wp-content/uploads/2020/02/901-Exercises-for-back-pain.pdf\" rel=\"nofollow noreferrer\">Provide information on exercises for low back pain</a></li>\n<li>The current guidelines then suggest to offer NSAIDs, and if these are not tolerated to offer codeine. These are both given for the shortest possible time at the lowest dose that relieves symptoms.</li>\n</ol>\n<p>This is probably based on that on balance NSAIDs are probably the least worst choice although it would be fair to conclude we are still not very good at treating this condition.</p>\n" }, { "answer_id": 30579, "author": "asha verma", "author_id": 24543, "author_profile": "https://health.stackexchange.com/users/24543", "pm_score": -1, "selected": false, "text": "<p>Their are so many options you can select..\nBut first try to find out exact cause and treat them accordingly.\nTreatment as per condition is important .\nuse hot water fomentation .. rest .. analgesics , anti inflammatory ie NSAIDS....also precautions ..nd lumbar belt .. precautions like don't bend forward ..don't lift the weight on head nd use thick pillow of you have cervical ..and do flexibility andROM.and stretching exercises</p>\n" } ]

[ "https://health.stackexchange.com/questions/29191", "https://health.stackexchange.com", "https://health.stackexchange.com/users/24098/" ]

[ { "answer_id": 29253, "author": "Jiminy Cricket.", "author_id": 15405, "author_profile": "https://health.stackexchange.com/users/15405", "pm_score": 3, "selected": false, "text": "<p><strong>For the UK up to 27 October 2021:</strong></p>\n<p>All recipients were requested to wait 15 minutes before departing the point of vaccination.</p>\n<p>A history of anaphylactic reactions to any of the ingredients forbids taking the vaccine, but which dose (first or second) the listed reactions occurred after is not specified in the data.</p>\n<p>Estimated first/second doses - Vaccine Manufacturer - Anaphylaxis or anaphylactoid reactions.</p>\n<blockquote>\n<p>23.5/20.3 million doses - Pfizer/BioNTech vaccine - 517</p>\n</blockquote>\n<blockquote>\n<p>24.9/24.1 million doses - AstraZeneca - 834</p>\n</blockquote>\n<blockquote>\n<p>1.5/1.3 million doses - Moderna - 41</p>\n</blockquote>\n<p>From <a href=\"https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting\" rel=\"noreferrer\">UK Government website</a> 8th November 2021.</p>\n<p><strong>With reference to the total number of reactions reported:</strong></p>\n<p><a href=\"https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1031316/Pfizer_CORRECT.pdf\" rel=\"noreferrer\">Pfizer/BioNTech</a> - 357,084 (Anaphylactic data on page 31)</p>\n<p><a href=\"https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1031317/AZ_CORRECT.pdf\" rel=\"noreferrer\">Astra Zenica</a> - 836,957 (Anaphyl. data page 37)</p>\n<p><a href=\"https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1031318/Moderna.pdf\" rel=\"noreferrer\">Moderna</a> - 55,081 (Anaphyl. data page 18)</p>\n<p>A small number of reports from <a href=\"https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1031319/Unspecified.pdf\" rel=\"noreferrer\">unspecified vaccines</a> with 1 anaphylactoid reaction for 3,557 reports.</p>\n" }, { "answer_id": 29254, "author": "Carey Gregory", "author_id": 805, "author_profile": "https://health.stackexchange.com/users/805", "pm_score": 4, "selected": false, "text": "<p>The data on this aren't hard to find. Here are some more examples that specifically provide time frames to back up @A Rogue Ant's answer:</p>\n<p>For the <a href=\"https://www.cdc.gov/mmwr/volumes/70/wr/mm7002e1.htm\" rel=\"noreferrer\">Pfizer vaccine</a>:</p>\n<blockquote>\n<p>During December 14–23, 2020, monitoring by the Vaccine Adverse Event\nReporting System detected 21 cases of anaphylaxis after administration\nof a reported 1,893,360 first doses of the Pfizer-BioNTech COVID-19\nvaccine (11.1 cases per million doses); <strong>71% of these occurred within\n15 minutes of vaccination</strong>.</p>\n</blockquote>\n<p>And for <a href=\"https://www.cdc.gov/mmwr/volumes/70/wr/mm7004e1.htm\" rel=\"noreferrer\">Moderna</a>:</p>\n<blockquote>\n<p>During December 21, 2020–January 10, 2021, monitoring by the Vaccine\nAdverse Event Reporting System detected 10 cases of anaphylaxis after\nadministration of a reported 4,041,396 first doses of Moderna COVID-19\nvaccine (2.5 cases per million doses administered). <strong>In nine cases,\nonset occurred within 15 minutes of vaccination.</strong> No\nanaphylaxis-related deaths were reported.</p>\n</blockquote>\n<p>In both studies, 70-90% of anaphylactic reactions occurred within the first 15 minutes, hence the 15-minute protocol.</p>\n" }, { "answer_id": 29256, "author": "JonathanReez", "author_id": 7314, "author_profile": "https://health.stackexchange.com/users/7314", "pm_score": 4, "selected": false, "text": "<p>The most noteworthy complication, and most heard about in the news, is anaphylaxis.</p>\n<p>This article breaks down cases of anaphylaxis nicely: <a href=\"https://jamanetwork.com/journals/jama/fullarticle/2776557\" rel=\"nofollow noreferrer\">Reports of Anaphylaxis After Receipt of mRNA COVID-19 Vaccines in the US—December 14, 2020-January 18, 2021</a>. They provide a great table with a specification of whether the case happened during the 15-minute window:</p>\n<p><a href=\"https://i.stack.imgur.com/lqLsL.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/lqLsL.png\" alt=\"enter image description here\" /></a></p>\n<p>So for Pfizer specifically the numbers are:</p>\n<ul>\n<li>4.7 anaphylaxis cases per million in total</li>\n<li>3.6 cases per million if only the 15 minute window is considered</li>\n<li>1.1 per million for those without a prior allergic reaction to a drug or vaccine</li>\n</ul>\n<p>This doesn't account for non-anaphylaxis allergic reactions (more common, less severe), vasovagal syncope(fear of needles/injections), or any other, more rare conditions.</p>\n<p>To date data regarding medical attention received within 15 minutes of vaccination has been hard to come by. The data from the first week of Pfizer administration, covering some 1.8m patients <a href=\"https://www.cdc.gov/mmwr/volumes/70/wr/mm7002e1.htm\" rel=\"nofollow noreferrer\">shows that non-anaphylaxis allergic reactions were roughly 8 times more common</a> (and typically far less severe) than anaphylactic reactions.</p>\n<p>While we could attempt to extrapolate based on anaphylaxis cases and non over the year based on the first week's data, it'd be a relatively pointless exercise. The occurrences/million for anaphylaxis dropped from 11.1 to 4.7 in the time frame. We can't assume the reduction in case numbers to be proportionally identical, yet a simple extrapolation based only on time would be disingenuous.</p>\n<p>In short, reliable data on the topic outside anaphylaxis is hard to come by because other instances requiring medical attention are either less severe or less common.</p>\n" } ]

[ "https://health.stackexchange.com/questions/29252", "https://health.stackexchange.com", "https://health.stackexchange.com/users/7314/" ]

[ { "answer_id": 29280, "author": "Timur Shtatland", "author_id": 17046, "author_profile": "https://health.stackexchange.com/users/17046", "pm_score": 7, "selected": true, "text": "<p>Race and ethnicity are risk factors in many diseases. Examples include, but are not limited to, cystic fibrosis and spinal muscular atrophy.</p>\n<p>There is also an epidemiological purpose of collecting this information. It is important to know if some disease is affecting some races or some ethnicities disproportionately. This is how it was found out that race or ethnicity <strong>is</strong> a risk factor in certain diseases in the first place.</p>\n<p><strong>RFERENCES:</strong></p>\n<p><em>Sheets L, Johnson J, Todd T, Perkins T, Gu C, Rau M. Unsupported labeling of race as a risk factor for certain diseases in a widely used medical textbook. Acad Med. 2011 Oct;86(10):1300-3. doi: 10.1097/ACM.0b013e31822bbdb5. PMID: 21869670. : <a href=\"https://pubmed.ncbi.nlm.nih.gov/21869670/\" rel=\"noreferrer\">https://pubmed.ncbi.nlm.nih.gov/21869670/</a></em></p>\n<p><em>McGarry ME, Williams WA 2nd, McColley SA. The demographics of adverse outcomes in cystic fibrosis. Pediatr Pulmonol. 2019;54 Suppl 3(Suppl 3):S74-S83. doi:10.1002/ppul.24434 : <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857719/\" rel=\"noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857719/</a></em></p>\n<p><em>Hendrickson BC, Donohoe C, Akmaev VR, et al. Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 2009;46(9):641-644. doi:10.1136/jmg.2009.066969: <a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729371/\" rel=\"noreferrer\">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729371/</a></em></p>\n" }, { "answer_id": 29281, "author": "Anastasios Tsarouchas", "author_id": 24243, "author_profile": "https://health.stackexchange.com/users/24243", "pm_score": 4, "selected": false, "text": "<p>There's a myriad of adjustments that can improve patients' treatment if it's race-informed. As a very small but characteristic example, the 2021 European Society of Cardiology Guidelines for Heart Failure recommend considering hydralazine and isosorbide dinitrate <strong>only</strong> for patients self-identifying as Black.</p>\n<p><a href=\"https://i.stack.imgur.com/rgpgU.png\" rel=\"nofollow noreferrer\"><img src=\"https://i.stack.imgur.com/rgpgU.png\" alt=\"enter image description here\" /></a></p>\n<p>Reference: McDonagh TA et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368</p>\n" }, { "answer_id": 29282, "author": "Abraxas Yu", "author_id": 24244, "author_profile": "https://health.stackexchange.com/users/24244", "pm_score": 2, "selected": false, "text": "<p>On a scale from sledgehammer to scalpel, race, as recorded in medical data is closer to sledgehammer in terms of granularity, but hey, sometimes we need sledgehammers (e.g. for broad epidemiological surveys).</p>\n<p>In terms of precision medicine, the promised dream is of identification of genetic idiosyncrasies guiding treatment - for which race is a very rough approximation.</p>\n<p>A counterexample to the utility of race in medicine is the very recent overturning of the use of race in estimated glomerular filtration rate (eGFR) calculation. Recently (as in this year, 2021), the national kidney foundation formed a task force to reassess the inclusion of race in eGFR calculation and recommended NOT including race as a factor.</p>\n<p><a href=\"https://www.kidney.org/news/update-reassessing-inclusion-race-diagnosing-kidney-diseases\" rel=\"nofollow noreferrer\">https://www.kidney.org/news/update-reassessing-inclusion-race-diagnosing-kidney-diseases</a></p>\n" }, { "answer_id": 29285, "author": "Rsf", "author_id": 24254, "author_profile": "https://health.stackexchange.com/users/24254", "pm_score": 4, "selected": false, "text": "<p>Here are some random examples:</p>\n<p><a href=\"https://www.uofmhealth.org/health-library/tv7879\" rel=\"noreferrer\">Ashkenazi Jewish Genetic Diseases</a></p>\n<blockquote>\n<p>Bloom syndrome.</p>\n<p>Canavan disease.</p>\n<p>Cystic fibrosis. Th</p>\n<p>Familial dysautonomia (FD).</p>\n<p>Fanconi anemia.</p>\n<p>Gaucher disease.</p>\n<p>Mucolipidosis IV.</p>\n<p>Niemann-Pick disease (type A).</p>\n<p>Tay-Sachs disease.</p>\n<p>Torsion dystonia.</p>\n</blockquote>\n<p><a href=\"https://en.wikipedia.org/wiki/Medical_genetics_of_Jews#Sephardi_and_Mizrahi_diseases\" rel=\"noreferrer\">Sephardi and Mizrahi Jews diseases</a></p>\n<blockquote>\n<p>Oculocutaneous albinism</p>\n<p>Ataxia telangiectasia</p>\n<p>Creutzfeldt–Jakob disease</p>\n<p>Cerebrotendinous xanthomatosis</p>\n<p>Cystinuria</p>\n<p>Familial Mediterranean fever</p>\n<p>Glycogen storage disease III</p>\n<p>Limb girdle muscular dystrophy</p>\n<p>Tay–Sachs</p>\n<p>11-β-hydroxylase deficiency</p>\n</blockquote>\n<p><a href=\"https://intermountainhealthcare.org/blogs/topics/live-well/2017/07/lactose-intolerance/#:%7E:text=African%20American%20and%20Asian%20ethnicities,they%20need%20for%20the%20day.\" rel=\"noreferrer\">Lactose Intolerance: Millions of Americans Don't Know They Have It</a></p>\n<blockquote>\n<p>African American and Asian ethnicities see a 75% - 95% lactose intolerance rate, while northern Europeans have a lower rate at 18% - 26% lactose intolerance</p>\n</blockquote>\n<p><a href=\"https://pubmed.ncbi.nlm.nih.gov/22643754/\" rel=\"noreferrer\">High lactose tolerance in North Europeans</a></p>\n<blockquote>\n<p>Lactose tolerance is exceptionally widespread in Northern European countries such as Sweden and Finland, with tolerance levels of 74% and 82%, respectively</p>\n</blockquote>\n" }, { "answer_id": 29295, "author": "Turbo", "author_id": 24276, "author_profile": "https://health.stackexchange.com/users/24276", "pm_score": 2, "selected": false, "text": "<p>The answer to your question can come from many angles. I do not have clinical experience, but I do have regulatory reporting experience.</p>\n<p>In the United States, the CDC runs a program called &quot;Vaccines for Children&quot;. I've had to run reports on demographics of patients many times, specifically for the following VFC criteria located at the link below.</p>\n<p><a href=\"https://www.cdc.gov/vaccines/programs/vfc/providers/questions/qa-flyer-hcp.html\" rel=\"nofollow noreferrer\">https://www.cdc.gov/vaccines/programs/vfc/providers/questions/qa-flyer-hcp.html</a></p>\n<p><strong>VFC Eligibility</strong></p>\n<p>Patients are eligible until they turn 19, if they meet one or more of the following criteria:</p>\n<ul>\n<li>Medicaid-eligible</li>\n<li>Uninsured</li>\n<li><strong>American Indian or Alaska Native (AI/AN)</strong></li>\n<li>Underinsured (Underinsured\nchildren can only be vaccinated at a Federally Qualified Health\nCenter (FQHC) or Rural Health Center (RHC)</li>\n</ul>\n<p>The medical record system I use refers to this data as the patient &quot;Ethnic Group&quot;.</p>\n<p><strong>Below is the relevant CMS regulation that states this information should be collected for those on Medicaid and CHIP. Many organizations will simply ask everyone during registration. If you're uncomfortable, you can simply decline to answer.</strong></p>\n<p><a href=\"https://www.medicaid.gov/medicaid/quality-of-care/quality-improvement-initiatives/quality-of-care-health-disparities/index.html\" rel=\"nofollow noreferrer\">https://www.medicaid.gov/medicaid/quality-of-care/quality-improvement-initiatives/quality-of-care-health-disparities/index.html</a></p>\n<p>*The Affordable Care Act of 2010 (Section 4302) requires the secretary of the Department of Health ad Human Services (HHS) to establish data collection standards for race, ethnicity, sex, primary language, and disability status, and calls for these categories to be consistently collected and reported in all national population health surveys that rely on self-report. Section 4302(b)(1) requires the collection of data on these five demographic characteristics in Medicaid and CHIP, and requires that the collection of these data in Medicaid and CHIP adhere to the data-collection standards developed in 4302(a). *</p>\n" }, { "answer_id": 29297, "author": "Flydog57", "author_id": 19535, "author_profile": "https://health.stackexchange.com/users/19535", "pm_score": 2, "selected": false, "text": "<p>When you immigrate to the United States (as I did), one of the first things you notice is that you get asked about your race <em>all the time</em>. Want a loan from your bank, your race is recorded (if you decide not to disclose your race, the bank officer will take a best guess - really) <a href=\"https://www.fdic.gov/resources/bankers/fair-lending/\" rel=\"nofollow noreferrer\">https://www.fdic.gov/resources/bankers/fair-lending/</a>. Apply to university, expect questions about race and ethnicity (<a href=\"https://stanfordmag.org/contents/race-and-admissions\" rel=\"nofollow noreferrer\">https://stanfordmag.org/contents/race-and-admissions</a>). And so on. Much like @Servaes pointed out in the comments, the US questions about race are (at least to me) rare outside of the US.</p>\n<p>The US is burdened with the history of slavery, post-slavery <em>Jim Crow</em> policy and some level of post-Jim-Crow systemic racism. There are now many laws that address and try to correct these injustices. However, in order to do that, they need to measure what's going on. That's the source of many of these questions in the US.</p>\n<p>And, of course, there are the specifics of race as a contributor to the likelihood of genetic conditions that the other answers address (personal example: after my wife's third miscarriage, my wife's Middle Eastern heritage and my French Canadian background suggested a Tay–Sachs test - <a href=\"https://www.ninds.nih.gov/Disorders/All-Disorders/Tay-Sachs-Disease-Information-Page\" rel=\"nofollow noreferrer\">https://www.ninds.nih.gov/Disorders/All-Disorders/Tay-Sachs-Disease-Information-Page</a>).</p>\n" }, { "answer_id": 29301, "author": "Scott Seidman", "author_id": 24291, "author_profile": "https://health.stackexchange.com/users/24291", "pm_score": 2, "selected": false, "text": "<p>In addition to all the fine answers, there are even more clinical reasons for including race in your chart. For one, clinical lab norms and calculations based on the clinical lab values can differ by race. For example, the calculation for Glomerular Filtration Rate, an important indicator of renal function, uses a different formula for African American patients inside the US (<a href=\"https://www.kidney.org/atoz/content/race-and-egfr-what-controversy\" rel=\"nofollow noreferrer\">https://www.kidney.org/atoz/content/race-and-egfr-what-controversy</a>). Note that this is not without controversy, as discussed in the link.</p>\n<p>There are also known biases in the output of pulse oximeters by skin color (<a href=\"https://www.nejm.org/doi/full/10.1056/nejmc2029240\" rel=\"nofollow noreferrer\">https://www.nejm.org/doi/full/10.1056/nejmc2029240</a>). Perhaps a situation can arise where a clinician is making an important therapeutic choice based on the numbers -- like whether a patient needs to be on a ventilator or not -- but isn't at the bedside. It might be nice to have race in the chart to determine how reliable the pulse oximeter numbers may or may not be.</p>\n" } ]

[ "https://health.stackexchange.com/questions/29276", "https://health.stackexchange.com", "https://health.stackexchange.com/users/21715/" ]

[ { "answer_id": 30624, "author": "Gerry Creager", "author_id": 21548, "author_profile": "https://health.stackexchange.com/users/21548", "pm_score": 1, "selected": false, "text": "<p>In vitro research suggests that the multiple changes associated with the S- (Spike) protein and for that matter, the N- (nucleocapsid) protein attributed to omicron that has demonstrated some ability to evade current vaccine-induced immunity, but also, and more markedly, can evade infection-conferred immunity. Or, to put it another way, recent infection with the delta variant is little protection against a breakthrough infection with omicron. Recent prior infection appears to moderate the potential severity in some unvaccinated, but previously infected patients. Persons who have been fully vaccinated and boosted may also experience breakthrough infection but the majority are mild symptomatically,with a much lower predisposition toward requiring hospitalization. Persons previously infected and subsequently fully vaccinated, or fully vaccinated but who still experienced breakthrough infection are much less likely to contract a breakthrough infection and much more likely, if they are reinfected, to have asymptomatic or very mild disease.</p>\n<p>I'm not sure I've seen any research, peer-reviewed or preprint, that discusses the IgG binding affinity for the case you describe.</p>\n<p>(<a href=\"https://www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-49-Omicron/\" rel=\"nofollow noreferrer\">https://www.imperial.ac.uk/mrc-global-infectious-disease-analysis/covid-19/report-49-Omicron/</a>)</p>\n" }, { "answer_id": 30635, "author": "Armand", "author_id": 21994, "author_profile": "https://health.stackexchange.com/users/21994", "pm_score": 2, "selected": false, "text": "<p>There is no general answer to this question -- it depends on the viruses involved, the antibodies in question and the specific immune system gene versions of an infectee.</p>\n<p>Unlike with monoclonal antibodies, the population of antibodies to a given protein generated by a natural immune response is enormous. That population includes antibodies targeted to different parts of the protein, as the immune system chops up the protein into short (8-20 aa long) peptides in order to &quot;present&quot; those to the various antigen-recognizing immune cells. <a href=\"https://dx.doi.org/10.1186%2F1745-7580-4-6\" rel=\"nofollow noreferrer\">&quot;Peptide length significantly influences in vitro affinity for MHC class II molecules&quot; doi: 10.1186/1745-7580-4-6</a></p>\n<p>Any given change to the original target protein may directly or indirectly affect from just one to many of its recognized peptides. Thus, a given antibody may have an affinity for the new protein ranging from unchanged (if its target antigen region was unchanged) all the way to essentially no binding (if its target region was greatly changed or eliminated). An individual's overall Ab &quot;neutralizing titer&quot; against the new protein will depend both on the affinity of individual Abs to the new protein and on the number of each Ab present.</p>\n" } ]

[ "https://health.stackexchange.com/questions/29323", "https://health.stackexchange.com", "https://health.stackexchange.com/users/588/" ]

[ { "answer_id": 29347, "author": "Polyhat", "author_id": 24340, "author_profile": "https://health.stackexchange.com/users/24340", "pm_score": 4, "selected": false, "text": "<p>If you think about prosthetic devices, the answer will soon become clear. You would not wish to have your thigh bone extended by an extra six or eight inches (about the minimum distance that one could practically strap it to) and have the new joint that much lower than the natural knee of the other leg.</p>\n<p>Neither would it work well to extend the leg clear to the foot/ankle point without a knee joint at all.</p>\n<p>Cutting the bone roughly midway between joints is the most practical way of enabling the amputee to restore some function via a prosthesis.</p>\n" }, { "answer_id": 29353, "author": "Dylan Russell", "author_id": 12870, "author_profile": "https://health.stackexchange.com/users/12870", "pm_score": 3, "selected": false, "text": "<p>The bone cut must be proximal enough to perform a myodesis (anchoring the muscle through drill holes near the cut end of the bone) or myoplasty (suturing the fascia of antagonistic muscles together) and allow the flaps to cover the end of the femur without tension.</p>\n<p>The incision can not simply be moved lower to address the problem of flap coverage because now you are essentially trying to cover an above knee amputation with below knee amputation flaps. There is likely a good reason an above knee amputation was selected in the first place (perhaps inadequate below knee perfusion) and thus it would be unwise to rely on these poorly perfused flaps to adequately heal.</p>\n" }, { "answer_id": 29355, "author": "Criggie", "author_id": 12922, "author_profile": "https://health.stackexchange.com/users/12922", "pm_score": 2, "selected": false, "text": "<p>Because every piece of biological function that can be retained is one less act for the patient to re-learn and for a prosthetic to replicate.</p>\n<p>Removing a patient's knee and below means a more expensive artificial limb with more joints compared to foot removal only.</p>\n<p>By retaining the operating knee joint where possible allows the patient as much function as they can have to assist with recuperation, both physical and mental.</p>\n<p>Additionally, the knee is a weight bearing joint when assembled. The bare bottom end of the femur is not well-suited to taking loads when not mated with the rest of the knee.</p>\n<p>And there is less flesh in this area, so the blood supply is not conducive to growing healthy flesh over the stump either. When the leg is cut above the knee, the bone is cut a little higher and the thigh muscle/flesh is used to cover the stump. There is far less meat in the knee to close the hole.</p>\n<p>(source, my Grandad had a foot removed. He'd also had a steel knee installed earlier, which limited blood flow to the stump and it simply starved. So he had an above-knee amputation and could not adjust to a longer leg, ended up in a wheelchair for the rest of his life.)</p>\n" } ]

[ "https://health.stackexchange.com/questions/29345", "https://health.stackexchange.com", "https://health.stackexchange.com/users/19939/" ]