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['PMC7467851'] | ['32520991'] | ['bib28', 'bib29', 'bib30', 'bib30'] | To evaluate the LBP, JLEQ and JOA were used. JLEQ is a self-administered, disease-specific measure for assessing the extent of LBP (28,29). It consists of the visual analog scale (VAS) for the degree of LBP, the JLEQ-I, and a total of 30 questions. These questions include 7 questions regarding LBP related to activities of daily living over the last several days (JLEQ-II), 17 questions regarding problems due to LBP over the last several days (JLEQ-III), and 6 questions regarding health and psychological condition in the last month (JLEQ-IV). These 30 questions in the latter 3 domains are each ranked on a 5-point scale from no impairment (0 points) to serious impairment (4 points) and then added to produce a total score (maximum 120 points). The total score and scores for each domain (JLEQ-I through -IV) were compared between the active and placebo groups. The JOA score is used to evaluate the therapeutic outcome of LBP. It is a disease-specific measure for assessing the intensity of LBP from the clinician's point of view (30). It consists of 14 questions with a 3–4-point scale, including 3 questions regarding subjective symptoms, 3 questions regarding objective responses, 7 questions regarding activities of daily living, and 1 question regarding bladder function. These 14 questions in the 4 domains are ranked on the 3–4-point scale and then added according to the designated method to produce a total score (maximum: 29 points; minimum: 6 points) (30). | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC7467851'] | ['32520991'] | ['bib31'] | To evaluate knee pain, JKOM was used. It is a self-administered, disease-specific measure for assessing the extent of knee pain and discomfort (31). It consists of a VAS for the degree of knee pain, JKOM-I, and a total of 25 questions. These questions include 8 questions regarding pain and stiffness in the knee over the last several days (JKOM-II), 10 questions regarding problems in daily life due to knee pain over the last several days (JKOM-III), 5 questions regarding usual activities in the last month (JKOM-IV), and 2 questions regarding general health status in the last month (JKOM-V). These 25 questions in the latter 4 domains are ranked on a 5-point scale from no impairment (0 points) to serious impairment (4 points) and then added to produce a total score (maximum 100 points). The total score and scores for each domain (JKOM-I through -V) were compared between the active and placebo groups. | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC7467851'] | ['32520991'] | ['bib32', 'bib34', 'bib35'] | The BPI was used to evaluate the intensity of the overall pain and the impact of the pain on daily life; it consists of 8 questions (32–34). These 8 questions are ranked on an 11-point scale from no impairment (0 points) to serious impairment (10 points). The EQ-5D-5L was used to evaluate health-related QOL, and consists of 5 questions. These 5 questions are ranked on a 5-point scale from no impairment (1 point) to serious impairment (5 points) and then analyzed according to the reported method (35). | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC7467851'] | ['32520991'] | [] | Systolic and diastolic blood pressure and pulse rate measurements were conducted at baseline and weeks 4, 8, and 12. At baseline and week 8, blood was collected under fasting conditions in the morning. The following blood parameters were measured: white blood cell (WBC) count, RBC count, hemoglobin (Hb), hematocrit (Ht), platelet count, total protein, albumin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, total bilirubin, alkaline phosphatase, γ-glutamyl transpeptidase, urea nitrogen, creatinine, uric acid, sodium, chlorine, potassium, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, fasting plasma glucose concentration (FPG), and glycated hemoglobin (HbA1c). The urine samples were obtained at baseline and week 8, and the following urine parameters were measured: urine protein, urine glucose, and urine occult blood. All plasma biochemical variables were measured by LSI Medience Corporation using automatic analyzer LST-008α (Hitachi High-Tech Corp) and JCA-BM8060 (JEOL Ltd) biochemistry analyzers with Sysmex, Nittobo Medical, and LSI Medience reagents using standardized procedures and fresh samples. FPG was determined using a glucose glucokinase assay (LSI Medience Corp) and HbA1c concentrations were measured by LSI Medience using an automated biochemical analyzer JCA-BM9130 and JCA-BM9030 (JEOL Ltd). WBC counts were determined by flow cytometry as part of a full blood count. RBC and platelet counts were determined by electrical resistance detection. Hb concentration was determined by the SLS-Hb method, and Ht was measured by erythrocyte pulse peak detection. A clinician evaluated the safety of the supplementation based on these results and adverse events. | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC7467851'] | ['32520991'] | ['bib36'] | Data are summarized as the means and SDs. Statistical significance of differences between thel-Ser + EPA group and the placebo group was assessed by ANCOVA using the initial scores at baseline as covariates at each time point, at a significance level of 5%. All statistical analyses were performed using IBM SPSS Statistics Ver. 24 or R version 3.5.0 (R Foundation) (36). The statistical analysis was predetermined before key opening. The primary decision was planned in advance to be conducted based on the total scores of JLEQ and JKOM at week 8, and these 2 outcomes were tested by a fixed sequence procedure; the statistical significance test for JKOM score was conducted only when a significant improvement in the JLEQ score was observed. Thus, the type I error was controlled under the α = 5% level regarding the primary outcome. For other outcome measures, such as JLEQ and JKOM scores at other time points, subdomains of JLEQ and JKOM, JOA score, BPI, and EQ-5D-5L, statistical multiplicity was not considered because these do not affect the primary decision. | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC7467851'] | ['32520991'] | ['fig1', 'tbl1'] | We enrolled 60 participants in both groups (Figure 1). There were no dropouts, and all participants completed the study protocol; thus, the full analysis set included all study participants. The compliance rate in this study was high, such that >95% of capsules were consumed throughout the study in both groups. Mean age, height, weight, BMI, JLEQ, JKOM, and JOA scores at baseline are listed inTable 1. Fifty-one participants (active compared with placebo: 22 compared with 29) had pain in multiple body sites, such as the neck and shoulders, in addition to LBP and knee pain. | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC7467851'] | ['32520991'] | ['fig3'] | Figure 3AandSupplemental Table 1show the JLEQ scores, evaluating the issues regarding LBP.Supplemental Table 2presents the prevalence of participants with each issue in the JLEQ questionnaire. JLEQ scores decreased in both groups at weeks 4, 8, and 12 compared with baseline. As a primary outcome, at week 8, ANCOVA using the baseline scores as a covariate demonstrated significantly lower scores in thel-Ser + EPA group compared with the placebo group. Additionally, at week 8, a significant decrease in all 4 domains (I: VAS for the degree of LBP; II: LBP related to activities of daily living over the last several days; III: problems due to LBP over the last several days; and IV: health and psychological condition in the last month) was detected in thel-Ser + EPA group compared with the placebo group. The JOA score was not significantly different between the 2 groups. | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC7467851'] | ['32520991'] | ['fig3', 'sup1'] | Figure 3BandSupplemental Table 1show the JKOM scores, evaluating issues regarding knee pain.Supplemental Table 3demonstrates the prevalence of participants with each issue in the JKOM questionnaire. Although JKOM scores decreased in both groups at weeks 4, 8, and 12 compared with baseline, ANCOVA using the baseline scores as a covariate demonstrated significantly lower scores in thel-Ser + EPA group compared with the placebo group at week 8 as the primary outcome. In addition, significantly lower scores in thel-Ser + EPA group compared with the placebo group were observed at weeks 4 and 12. Additionally, a significant decrease in the following 2 domains (I: VAS for the degree of knee pain; and II: pain and stiffness in the knee over the last several days) was detected in thel-Ser + EPA group compared with the placebo group at week 8. Interestingly, significant differences between these 2 groups were also detected in the posttreatment observation period at week 12 in the following domains: I: VAS for the degree of knee pain; II: pain and stiffness in the knee over the last several days; III: problems in daily life due to knee pain over the last several days; and IV and V: usual activities in the last month and general health status in the last month. | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC7467851'] | ['32520991'] | ['tbl2'] | On the BPI, which evaluates the intensity of overall pain and the impact of pain on daily life, both groups showed significant improvement in all parameters from baseline to weeks 4, 8, and 12 (Table 2). ANCOVA demonstrated significant improvement in thel-Ser + EPA group compared with the placebo group at week 4 on BPI1: pain at its worst in the last 24 h; BPI3: pain on average; and BPI5D: intensity of the pain on moving. Similarly, at week 8, the BPI1, BPI3, and BPI5D scores were significantly lower in thel-Ser + EPA group than in the placebo group. In the posttreatment observation period at week 12, significant differences in BPI1 and BPI3 were not detected, whereas a significant decrease in BPI5D remained.Supplemental Table 4shows the improvement in the health-related QOL based on EQ-5D-5L due tol-Ser + EPA supplementation, at week 8. To evaluate the effects ofl-Ser and EPA on multiple pain sites, an additional subgroup analysis was conducted on a study subset of 51 participants (active compared with placebo: 22 compared with 29) who had pain in multiple body sites, such as the neck and shoulders, in addition to LBP and knee pain. The results of the subgroup analysis of the 51 participants are shown inSupplemental Table 5. ANCOVA demonstrated a significant improvement in thel-Ser + EPA group compared with the placebo group at week 4 on BPI1: pain at its worst in the last 24 h; BPI3: pain at its worst in the last 24 h; BPI4: pain right now; BPI5B: intensity of pain when sitting; and BPI5D: intensity of pain when moving. Similarly, at week 8, the BPI1, BPI3, BPI4, BPI5B, and BPI5D scores were significantly lower in thel-Ser + EPA group than in the placebo group. | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC7467851'] | ['32520991'] | [] | No adverse events, including blood and urine laboratory test results, were observed. The assessment of safety was made through medical interviews with each participant, and no issues were reported.Supplemental Table 6shows the results of blood and urine laboratory tests. | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC7467851'] | ['32520991'] | ['bib2', 'bib37', 'bib38', 'bib39', 'bib40', 'bib41', 'bib43', 'bib44', 'bib45', 'bib25', 'bib46', 'bib47', 'bib12', 'bib11', 'bib20', 'bib22', 'fig4', 'tbl2', 'sup1', 'bib14'] | This randomized, double-blind, placebo-controlled, parallel-group study examined the effect of orall-Ser + EPA (594 mg and 149 mg daily, respectively) supplementation for 8 wk on back and knee pain intensity in healthy adults with LBP and knee pain. As the primary outcomes of the study, LBP, as assessed by JLEQ, and knee pain, as assessed by JKOM, were both significantly improved byl-Ser and EPA supplementation at week 8. The ANCOVA of JLEQ demonstrated significantly lower scores at week 8, assessed by both total scoring and scoring for each domain. The ANCOVA of JKOM demonstrated significantly lower scores at all time points: weeks 4, 8, and 12. The QOL related to pain was also significantly improved at all time points, as demonstrated by the BPI scores at weeks 4, 8, and 12. As demonstrated in a subgroup analysis of the 51 participants who had pain in multiple body sites, thel-Ser + EPA supplementation also relieved the symptoms of participants who had multiple-site pain. We also observed a very high compliance rate as well as study completion rate, and adverse events were not observed in either of the groups. These results suggest thatl-Ser and EPA supplementation is both safe and effective in improving pain and QOL in adults with chronic and nonspecific pain in multiple body sites, including LBP and knee pain. In this study, JOA was also used for the evaluation of LBP, but the scores were not significantly different between the 2 groups. Compared with JLEQ, which is a patient-reported outcome that focuses more on QOL aspects of pain, JOA is a physician-reported measure that has been widely used to evaluate the clinical results of various surgical and nonsurgical interventions performed on patients with LBP. Therefore, the characteristics of the healthy adult study population could have been related to the limitations in JOA results. LBP is considered chronic if it has been present for >3 mo. The etiology of chronic LBP is, in most cases (≤85%), unknown or nonspecific, whereas specific causes (specific spinal pathology and neuropathic/radicular disorders) are uncommon (2). Often, the condition or injury that triggered the pain can be healed and undetectable, but the pain can continue. Recent studies have investigated the potential relation between central sensitization and chronic pain disorders. Enhanced excitability in the central nervous system is an important phenomenon observed in people with chronic LBP (37,38) and also occurs in various other pain conditions (39,40). Given the increasing evidence supporting the clinical significance of central sensitization in chronic pain, effective methods designed to normalize pain physiology are required. There have been several clinical studies regarding the oral administration ofl-Ser. Orall-Ser administration has shown effectiveness in patients with hereditary sensory autonomic neuropathy type I, who suffer a debilitating, progressive disorder of peripheral nerves that results in sensory loss and neuropathic pain (41–43). Additionally, an exploratory study suggested thatl-Ser can slow disease progression in patients with amyotrophic lateral sclerosis (44,45). Kiya et al. (25) reported that the administration ofl-Ser improved peripheral hyperalgesia in a paclitaxel-induced hyperalgesia model, especially focusing on the function ofl-Ser in the DRG. In vitro studies have also demonstrated thatl-Ser is essential for maintaining normal functions of the nervous system. Savoca et al. (46) demonstrated thatl-Ser is an important factor for the morphological differentiation of neurons in vitro through the observation of marked effects on dendritogenesis and axon length whenl-Ser was added to developing neurons. Additionally, a study conducted in an animal model of brain injury revealed thatl-Ser plays a role in inducing the proliferation and differentiation of neural stem cells and promoting the repair of nerve injury (47). Additionally, whereas demyelination contributes to the development of neuropathic pain by disrupting the molecular and structural features of nerve fibers (12),l-Ser is an important component for neural cell membrane and myelin formation (11). These findings indicate thatl-Ser is an essential factor for neural cells to function properly. EPA competes with arachidonic acid, thereby suppressing the production of eicosanoids and inflammation. It has also been reported that the anti-inflammatory lipid mediator resolvin E1 is produced from EPA via an intracellular biosynthetic pathway when activated neutrophils adhere to vascular endothelial cells in local inflammation. In addition to its anti-inflammatory properties, resolvin E1 suppresses NMDA hyperfunction caused by transient activity of receptor potential cation channel subfamily V member 1 and TNF-α by inhibiting extracellular signal-regulated kinase signaling in spinal dorsal horn neurons. Through this mechanism, pain and hyperalgesia in response to heat and mechanical stimuli are alleviated (20–22). These reports suggest that EPA is useful for the treatment of neuropathic pain triggered by inflammation. l-Ser could support neuronal function in damaged nerve fibers by providing essential components required for normal neuronal function. EPA could exert anti-inflammatory properties and reduce local inflammation, thereby suppressing pain signals from neuronal fibers (Figure 4).Table 2demonstrates thatl-Ser and EPA supplementation alleviated overall pain, andSupplemental Table 5demonstrates that thel-Ser + EPA supplementation also relieved the symptoms of participants who had multiple-site pain such as the neck and shoulders, in addition to LBP and knee pain, suggesting thatl-Ser and EPA might act on similar pathways in these multiple sites and improve neuropathic pain.l-Ser and EPA might synergistically work in the DRG, by providing necessary components for nerve function and mitigating local inflammation. Additional studies in the future are necessary to clarify the detailed mechanism. The results from the posttreatment observation period in the current study demonstrated a significant difference in the degree of knee pain between thel-Ser + EPA group and the placebo group, indicating thatl-Ser and EPA provide continued effects even after supplementation has ceased. Compared with other pain management methods that are often used for temporary pain relief,l-Ser and EPA could have the potential to provide more lasting effects. There were several limitations in this study. Firstly, evaluation during thel-Ser and EPA ingestion period was performed only at weeks 4 and 8. We do not have data regarding effects on the pain scores with shorter-term and longer-term ingestion. Secondly, only a limited subgroup analysis was conducted in this study to examine the relation between background information and improvement in outcome scores. In particular, because thel-Ser concentration decreases with aging (14), stratification analysis using biomarkers for efficacy prediction is also important. Thirdly, we did not collect dietary records in this study. In the future, dietary intake should be assessed for potential deficiencies or excess intake of nutrients such asl-Ser and EPA, which could provide additional insight to the mechanistic rationale. In conclusion, this randomized, double-blind, placebo-controlled, parallel-group study demonstrated that supplementation withl-Ser and EPA improved the pain scores of a generally healthy adult population with pain in at least the low back and knee for ≥3 mo. The compliance rate was high throughout the study, and no adverse events (including abnormal blood and urine laboratory test results) were observed. To our knowledge, this is the first study to report beneficial effects of the combinatory administration ofl-Ser and EPA in improving such pain. Although further research is needed to clarify the underlying mechanism related to this effect,l-Ser and EPA supplementation could provide effective pain management and improve QOL in people with chronic LBP and knee pain. | PMC7467851 | Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions; AcademicSubjects/MED00060; AcademicSubjects/SCI00960 | null | 32,520,991 | l-Serine and EPA Relieve Chronic Low-Back and Knee Pain in Adults: A Randomized, Double-Blind, Placebo-Controlled Trial | Sasahara I, Yamamoto A, Takeshita M, Suga Y, Suzuki K, Nishikata N, Takada M, Hashimoto M, Mine T, Kobuna Y, Nagao K. | J Nutr. 2020 Sep 1;150(9):2278-2286. doi: 10.1093/jn/nxaa156. | Sasahara I | J Nutr | 2,020 | 2020/06/11 | PMC7467851 | null | 10.1093/jn/nxaa156 | oa_comm/txt/all/PMC7467851.txt | 8798468a796a3705683c5a50abe04f80 | J Nutr. 2020 Jun 10; 150(9):2278-2286 | 2021-06-19 06:05:55 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.ref001', 'pone.0194027.ref002', 'pone.0194027.ref005', 'pone.0194027.ref006', 'pone.0194027.ref002', 'pone.0194027.ref004', 'pone.0194027.ref003', 'pone.0194027.ref004', 'pone.0194027.ref005', 'pone.0194027.ref002', 'pone.0194027.ref006', 'pone.0194027.ref007'] | Illness Management and Recovery (IMR) is a curriculum-based rehabilitation program developed to help people with severe mental illness improve their illness self-management and to obtain a decreasing severity of symptoms, increase level of functioning, and achieve prolonged remission [1]. Previously, five randomized trials, investigating IMR have been conducted with varying sizes and design, among others four randomized on an individual level [2–5], whereas one used a cluster randomization design [6]. The findings from four of these trials indicate that IMR is effective in terms of clinical recovery measures. Participants receiving IMR showed significant improvements in psychiatric symptoms, that is positive symptoms, negative symptoms, symptoms of depression [2,4], in coping with symptoms [3], in psychosocial functioning [4], reduced hospital use over time [5], and less suicidal ideation [2] compared with participants who receive treatment as usual. The latest published trial investigating IMR versus an active control group reported that IMR was not significantly different from the control group on symptoms, medication adherence, or service utilization, but there were very low rates of retention in both the IMR and control groups over the study period [6]. The results from these trials should, however, be interpreted with caution. All trials lack one or more desirable aspects of controlled clinical trials, such as power and sample size calculation, outcome assessment by blinded assessors, or systematic approach to handling missing data, resulting in an increased risk of bias. Consequently, the intention with this trial was to add knowledge to the existing evidence of the IMR program by meeting the highest standards of methods in a randomized clinical trial. The aim of this randomized trial was to investigate the effects of the IMR program compared with treatment as usual in Danish patients with schizophrenia or bipolar disorder. The following hypothesis was tested: Participants in the IMR program would score higher than participants receiving treatment as usual on the Global Assessment of Function scale (GAF-F) at the end of the 9 month intervention period. In this paper, the results on the clinical outcomes: functioning, symptom severity, social functioning, drug/alcohol abuse, and service utilization will be presented. Results regarding self-perceived recovery have been presented elsewhere [7]. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.ref008'] | The trial was designed as a randomized, assessor-blinded, multi-center, clinical trial of the IMR program compared with treatment as usual in community mental health centers in the Capital Region of Denmark with a post-intervention assessment and a one-year follow-up; see the trial protocol [8]. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | Participants were recruited from three community mental health centers (CMHC) in the Capital Region of Denmark. To increase the number of participants enrolled in the study an additional community mental health center was added to the original two. The project was planned in collaboration with the heads of management at the first two of the three CMHC, all of which had shown commitment to implement IMR. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.ref009'] | Eligible participants were at least 18 years old, receiving services from one of the CMHCs, diagnosed according to the ICD-10 criteria with schizophrenia or bipolar disorder, able to speak and understand Danish, and provided written informed consent. The Present State Examination [9] was used to verify the diagnosis prior entering the trial. Patients were excluded if they had a guardian or a forensic arrangement, or met the criteria for ICD-10 diagnosis of dementia or mental retardation, had an active substance use disorder, lived in a community residential home as treatment as usual is different for this group, or were involved in psychoeducation at the time of inclusion. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | After the baseline assessment, participants were randomly allocated to IMR plus treatment as usual or treatment as usual alone. To secure the concealment of the allocation sequence, the randomization was central and telephone-based through an administrative office unrelated to the research team. The allocation sequence was stratified by diagnosis and CMHC. The allocation sequence was computer-generated using permuted blocks varying in sizes of 6, 8 and 10. Randomization was done one at a time and on average the patients in the intervention group waited 87 days (SD 77) before the first group session was held and 62% of the patients waiting under 90 days before the first group session took place. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.ref008', 'pone.0194027.ref010'] | Patients randomized to the experimental intervention were offered group-based IMR plus treatment as usual (see below). IMR is a curriculum-based program organized in 11 modules which consist of: recovery strategies; practical facts about mental illness; the stress-vulnerability model; building social support; using medication effectively; drug and alcohol use; reducing relapses; healthy lifestyle; coping with stress; coping with problems and symptoms; and getting your needs met in the mental health system. IMR was provided in a group format with weekly one-hour sessions over a period of nine months. Ten patients were assigned to each group which was facilitated by two or three practitioners. IMR was conducted using a closed enrollment group format, such that once the group was started new participants were not enrolled into it (IMR has also been conducted using open group formats). Strategies such as motivational phone calls and in-hospital-sessions were employed to motivate participants to attend and to be engaged in the IMR program. A further description of the IMR program can be found elsewhere [8,10]. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | Participants randomized to the control group received treatment as usual only, which included individually adapted interdisciplinary treatment at the CMHC or in the patient’s own home. Treatment included medication, case management, group therapy (i.e. cognitive behavioral therapy), as well as unstandardized psycho-education. Staff members across the three CMHCs had comparable levels of education and years of experience working with people with severe mental illness. Every patient had a case manager who together with the patient planned the individualized treatment. The patient met with case manager at the CMHC or at home or attended other activities at the community mental health center approximately once a week. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.ref011', 'pone.0194027.ref013', 'pone.0194027.ref014', 'pone.0194027.ref015', 'pone.0194027.ref014', 'pone.0194027.ref016', 'pone.0194027.ref017', 'pone.0194027.ref018'] | Baseline assessments were conducted from February 2011 till December 2012 and follow-up assessments from March 2012 till December 2013. The primary outcome was global functioning post-intervention assessed by the Global Assessment of Functioning (GAF-F). The GAF scale can be divided into two scales GAF-F and GAF-S (one that focuses on functioning and one that focuses on symptoms) [11–13]. In this trial the focus of the primary outcome was functioning which is why the GAF-F scale was used. The secondary outcomes were symptom severity on Positive and Negative Syndrome Scale (PANSS) [14] and social functioning on Personal and Social Performance Scale (PSP) [15]. The PANSS has been validated in Danish [14] but not the PSP scale. Exploratory outcomes were symptoms on the GAF-S, depression on the Hamilton Rating Scale for Depression (HAM-6) [16,17], mania on Young Mania Rating Scale (YMRS) [18], substance abuse (assessed by the case manager), and service utilization based on hospital records. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.ref010'] | The IMR Fidelity Scale [10] was used to assess fidelity to the IMR in all the groups. A multiple data approach was used including interviews, observation of the IMR group, an audit of the patient service records as well as audits of the IMR notes of progress. The fidelity assessments were made half-way through the program (after 4 months) and at the end of the intervention for each IMR group (9 months). | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.ref019', 'pone.0194027.ref020', 'pone.0194027.ref021', 'pone.0194027.ref022', 'pone.0194027.ref008'] | Prior to recruitment a sample size of 200 participants was estimated sufficient for detecting a true difference in the IMR and control group of at least 6 points on the GAF-F. The few previous studies using IMR or elements of IMR, where the effectiveness has been assessed by using the total GAF score, have showed a difference from 6 to 10 points [19,20]. Based on this knowledge we conservatively estimated the true difference in the experimental and control group means to be 6 points on the GAF-F score. The sample size calculation was furthermore based on a power of 80%, an alpha of 5% and a standard deviation (SD) of 15 points [21,22]. For the secondary outcomes it was determined that the sample size of 200 participants was sufficient to test minimal clinically relevant differences with an alpha of 5% and a power of 80%. See the trial protocol for more information on power and sample size calculation [8]. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.s003'] | Post intervention assessments were conducted by assessors who were blind to treatment allocation. Two different assessors performed the assessments, and therefore the assessors rated together to reach agreement before rating patients individually to ensure inter-rater reliability. Analysis of these data showed an acceptable inter-rater reliability (S1 Text). Participants as well as the staff were strongly inculcated not to disclose the allocation status of the participant at the follow up assessment. The statistical analyses were conducted with the two intervention groups coded as A and B, and the Steering Committee drew the conclusions with the blind still intact. In order to secure this blinding the analyses exploring the interactions between degree of participation in IMR and outcomes were carried out after all the other analyses were completed. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.ref023', 'pone.0194027.ref008', 'pone.0194027.ref024'] | The data analysis was based on the intention-to-treat principle. The analysis of difference between the two groups was conducted using analysis of covariance for the continuous primary and secondary outcome measures (GAF-F, GAF-S, PSP, and PANSS). This was estimated as marginal means adjusted for the baseline value of the variable in question [23]. Independent sample t-tests were conducted for the variables concerning substance use, service utilization, that is number and length of hospital admission and number of emergency service visits together with number of visit to the community mental health center (use of treatment as usual) and harm and adverse effect. As service utilization and harms and adverse effects were measured during the study period no baseline mean existed. As missing data is a potential source of bias a strategy of conducting an analysis using multiple imputations were decided beforehand [8]. An analysis of missing data was conducted for the primary and secondary variables GAF-F, PSP, and PANSS and it showed that up to 23% of all observations were incomplete. Therefore, multiple imputation with chained equations under the assumption of data missing at random (MAR) was conducted to enable intention-to-treat analyses. Post-treatment values were imputed for GAF-F, PSP, and PANSS, using baseline values of all three variables, sex, diagnosis, age, community mental health center and intervention group as covariates. The automatic procedure was used and 100 imputations estimated. Per-protocol analysis was performed to see if group attendance influenced the result as proposed in one trial [24]. An analysis using the continuous variable of group attendance for the participants randomized to IMR was made as well as an analysis using a dichotomous variable categorizing attendance into 0–10 sessions or ≥11 sessions. Subgroup analyses tested whether diagnosis or sex interacted with the primary and secondary outcomes. The level of significance for all statistical tests was 0.05. The IBM SPSS Statistics version 19 for Windows was used for statistical analysis and STATA /SE version 13.1 was used for multiple imputations. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | Patients were recruited from the involved community mental health centers in the Capital Region of Denmark by their case manager supported by a local IMR supervisor. The patients were informed about the on-going trial by a poster in the waiting room and verbally by their case manager. If they were interested in participating they received more information about the IMR program and what their role would be in the controlled trial both verbally and written. Interested participants provided consent verbally and in writing. The case managers were informed about the trial and how to provide information to the patients by the researchers, the local IMR supervisor and their management. The trial was approved by the Ethics Committee in the Capital Region of Denmark (H-1-2010-134) January 20th2011, before recruiting patients, reported to the Danish Data Protection Agency (RHP-2011-09) during 2011, and registered onwww.clinicaltrials.gov(NCT01361698). The authors confirm that all ongoing and related trials for this intervention are registered. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.g001', 'pone.0194027.t001'] | Fig 1shows the CONSORT diagram for the participants through the trial. 202 participants were included and randomized but four of them were excluded immediately after randomization: Two participants from the control group withdrew their informed consent, one participant from the control group did not meet the criteria for diagnosis after all, and one participant was assigned as the only participant in an IMR group, that was never conducted and therefore the research group decided to exclude this individual from the trial instead. Therefore, 198 participants entered the trial, 99 participants in each intervention group. The baseline characteristics of the 198 participants are listed inTable 1, showing an equally distributed in the two groups. A total of 26 participants from the IMR group and 11 from the control group did not participate in the follow-up assessments, a statistically significant difference (χ2 = 7.48, df = 1, p = 0.006). The reason for drop-out was that most patients in both groups simply did not want to continue participating with a higher percentage giving this answer in the intervention group compared to the control group (55% vs. 45%). | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.t002', 'pone.0194027.s001', 'pone.0194027.s002'] | The exposure to IMR in the intervention group is shown inTable 2. The exposure rate was 57.6%, as 57 of the 99 participants attended 10 or more IMR sessions. Among all the participants mean number of sessions were 16.4 (SD 13.3), compared to a mean of 26.1 (SD 8.1) among the 58, who participated in 10+ sessions. To explore if there were any differences between the non-exposed participants (attending 0–10 sessions) and the exposed participants (attending 10+ sessions) we did some post-hoc analyses to see, if there was a different in the time they had to wait from completion of baseline assessment to beginning the first IMR group as well as differences in baseline characteristics. There were no significant different in the mean waiting-time for the two groups (S1 Table). Furthermore, there were no significant differences in sex, age, housing, employment status, education, living status, diagnoses and substance abuse, but a significant difference in numbers in the two groups when we compared the three CMHCs (S2 Table). | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.t003'] | Multiple imputations were used to analyze data according to intention-to-treat principle (Table 3). IMR was not significantly different from treatment as usual regarding level of functioning assessed by GAF-F, mean difference: +2.5 points (95% confidence interval (CI): -1.4 points to +6.4points, t = 1.25, df = 1, p = 0.21). For the secondary outcomes, there were no group differences regarding PSP, mean difference: +3.7points (95% CI: -0.8points to +8.1points, t = 1.62, df = 1, p = 0.11), or PANSS, mean difference: -2.7points (95% CI: -8.3points to2.8 points, t = —0.4498, df = 1, p = 0.33). | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.t002'] | When analyzing data as complete cases, which are all cases where we had observed data on, similar results were found for GAF-F, PSP, and PANSS as in the intention-to-treat analyses, please seeTable 2. No differences between the two intervention groups were seen in any of the explorative assessments of GAF-S, HAM-D, and Young Mania Rating Scale. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.t003', 'pone.0194027.t002'] | Treatment as usual that is the number of visits to CMHC (treatment i.e. meetings with the case manager, meetings with a psychologist or a psychiatrist, or times participating in group activities) was the same for both groups, seeTable 3. IMR participants had a mean of 24.1 visits (SD = 23.8) and control group participants had a mean of 24.5 visits (SD = 20.2), respectively. This number covered a wide range where some participants in both groups had no visits and some had more than 130 visits during the follow-up period. Exposure to IMR in the intervention group is shown inTable 2. Participants in the IMR group had a mean number of days in the psychiatric hospital of 13.5 (SD = 71.1) whereas participants in the control group had a mean number of 12.5 days (SD = 46.3), there was no statistically significant difference. There were no significant differences in the number of times the psychiatric emergency service was used or in number of hospital admissions between the two groups. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.t004'] | The results of the three per-protocol subgroup analyses are listed inTable 4. There was no association between a higher number of sessions attended and the end of intervention GAF-F score (F = 5.7, df = 1, p = 0.49). Subgroup analyses showed no differences in the effect of IMR according to diagnosis or sex regarding the outcomes of GAF-F, PSP or PANSS. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.t003'] | InTable 3is an overview of harms and adverse effects. There were no significant differences between the two groups in suicide or deaths. Participants in IMR did not differ from participants in the control group in terms of misuse of alcohol or drugs (F = 1.46, df = 1, p = 0.57). Three participants died in the period of follow-up, one of suicide from the control group and two died of natural causes, one from each group. No relation between participating in the IMR trial and the deaths was detected. No further harms or life-threatening conditions were reported during the trial. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | Staff specially trained in IMR fidelity assessment from one participating community mental health center was conducting the assessments at the other community mental health centers’ groups and vice versa. The IMR Fidelity mean score across the three participating community mental health centers assessed half-way at 4 months was 4.2 (SD 0.3) indicating good fidelity and the mean score for the end assessment was 4.9 (0.2) indicating high fidelity. A total of 10 IMR groups started and 9 of them completed. One group ended before time because the participants could not come to sessions because of personal reasons (e.g., serious hospitalization, got a job in the day hours, recently had a baby). | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.ref005', 'pone.0194027.ref004', 'pone.0194027.ref004', 'pone.0194027.ref002', 'pone.0194027.ref004', 'pone.0194027.ref006', 'pone.0194027.ref002', 'pone.0194027.ref004', 'pone.0194027.ref005', 'pone.0194027.ref006', 'pone.0194027.ref025'] | This trial investigated the benefits and harms of the IMR program compared with treatment as usual. The trial was designed as an “add-on” study, and therefore patients in the intervention group received IMR as well as “treatment as usual”. Thereby potential difference between the two groups can only be explained by the effect of the IMR program. We found no effect on functioning, symptoms, substance abuse or service utilization. Two of the five earlier studies on IMR also examined the effect of IMR on functioning. One found no effect [5], but the other had a positive result [4]. Furthermore two of the five studies examined the effect on symptoms. Levitt et al. had a conflicting result, as they found a significant effect on a clinicians measured scale, mainly because of a reduction of the level of depression and anxiety, but no effect on a self-report scale [4], whereas Färdig had a positive result [2]. Two studies of the five studies measured IMR effect on substance abuse, and our result is consistent with these earlier results, as they found no effect [4,6]. Finally, four of the five studies measured the effect on service utilization, three with a result in line with ours, as they found no effect [2,4,5], but the last study had a positive result [6]. As the results of all five earlier trials have to be addressed with caution due to a high risk of bias, one might conclude in line with our study that IMR have no effect on functioning, symptoms, substance abuse or service utilization. However the present study also has some limitation, i.e. not as high an exposure to IMR as wanted. Therefore, in order to get a robust answer to whether IMR is an effective program or not, more research is needed, among others there is a need for collecting the evidence from randomized trials of IMR in a systematic review with a meta-analysis, which is under preparation [25]. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | ['pone.0194027.ref026', 'pone.0194027.ref028', 'pone.0194027.ref029', 'pone.0194027.ref030'] | This trial has several strengths. The trial was conducted with adequate generation of allocation sequence; adequate allocation concealment; adequate blinding wherever possible; adequate reporting of all relevant outcomes; intention-to-treat analyses; and no for-profit bias [26–28]. The Illness Management and Recovery Fidelity Score indicated that the implementation of the program was satisfactory. A strength of this trial is that prior beginning recruitment a sample size calculation was made. Furthermore, only patients with a validated diagnosis of schizophrenia or bipolar disorder were included in the trial. In the randomization process an external partner conducted the randomization and assured the concealment of sequence and allocation. It is also strength of the trial that most outcome assessments were conducted blinded, so that the knowledge of group status did not influenced the process. The external validity is high because the included participants represent the majority of patients with severe mental illnesses getting treatment in a community. However, this trial also has some limitations. It is a limitation that 23 percent of the observed data were incomplete because the attrition rate was high. The attrition from research was higher in the IMR group. Our results indicate that the difference in attrition rate mainly is because more participants in the intervention group simply just did not want to participate in the follow-up interview. As 50% of the participants who withdraw from the research in the intervention group had attended zero or only one IMR-group session, one can argue that the main reason for the higher attrition rate in the intervention group is that these patients were not motivated to participate in the study all together not the IMR-intervention or the research interview. To address attrition from research, intention-to-treat analyses were done with multiple imputation. This is the least biased way to deal with missing data [29]. We may also have been too optimistic when planning the present trial as we based the number of participants needed to include on a 6 points difference on the GAF-F scale. Due to this our sample size may be too small, whereby we do not have the power to state if the observed difference of 2.4 is in fact a true difference, but it is most likely not of ‘clinical’ relevance. A study performed after we have started our study, indicate that the minimum clinically important difference for GAF is 4 points [30]. Furthermore, the waiting-time from randomization to the first IMR group session was on average 87 days and this can have affected the results, since it is important to provide psychosocial treatment when a participant is interested and motivated for it, and this may not be the case in the present study as there was a significant delay from the time a participant said yes to the treatment until they started actually started. Therefore we did a post-hoc analysis to see if the ones attending from 0–10 sessions waited longer than the ones attending 10+ sessions had a longer waiting time, but this was not the case, indicating that the waiting time didn’t affect the motivation for participating in the IMR program. Moreover, only 57.6% were fully exposed to the IMR program and this may have influenced the outcome measure. Therefore we did a subgroup analyses to see if the degree of exposure to IMR affected the primary and secondary outcomes. This was not the case. Finally, it is also a limitation that the secondary outcome Personal and Social Performance scale was not validated in Danish. However, the scale has been validated in a number of other countries and seems reliable and valid. Overall IMR did not differ from treatment as usual in any of the analyzed outcomes. This means that IMR added to treatment as usual in a Danish context does not result in better or worse outcomes for the participants. A possible explanation is that the participants already received a sufficient high quality treatment as part of the usual treatment and perhaps mental health services and the intensity of it in Denmark is somewhat bigger compared to other countries, and that IMR in that context does not add anything further. Another possible explanation can be found in the theoretic framework for IMR. According to the theory of the IMR program clinical recovery outcomes such as functioning and symptoms remission are considered to be distal outcomes, therefore a longer follow-up period is needed to address the effectiveness of the IMR program properly. Improvements in functioning is supposed to be found after the participant has adapted the new illness management skills into his/hers life. Perhaps the reason why this trial did not find any difference between IMR and the treatment as usual is that the period of follow-up was too brief. Without setting an exact time frame for the IMR theory maybe this trial assessed a distal outcome in a proximal short-time perspective (post treatment). A longer follow-up assessment could perhaps show if IMR is effective according to global assessment of functioning and the other distal clinical recovery outcomes. The trial is therefore also designed to have a longer follow-up and a 12-month after post treatment follow-up is completed currently. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | IMR had no significant effect on the primary outcome GAF-F at the end of intervention (difference of 2.5 points in favor of IMR, P = 0.21). The 95% confidence interval (-1.4 point to +6.4points) makes the possibility of the hypothesized difference of 6 points favoring IMR unlikely. IMR was not significantly different from treatment as usual at end of intervention in terms of clinical outcomes such as level of functioning, symptoms severity, or service utilization. This randomized trial contributes to the evidence base of IMR by providing a methodological solid base for its conclusions; however the trial has some important limitations. More research is needed to get a firm answer on the effectiveness of the IMR. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | No conflicts of interest that have to be declared. | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | (DOCX) | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | (DOCX) | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | (DOC) | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | (DOC) | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC5886399'] | ['29621284'] | [] | (DOCX) | PMC5886399 | Research Article; Medicine and Health Sciences; Mental Health and Psychiatry; Medicine and Health Sciences; Mental Health and Psychiatry; Schizophrenia; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Bipolar Disorder; People and places; Geographical locations; Europe; European Union; Denmark; Medicine and Health Sciences; Mental Health and Psychiatry; Substance-Related Disorders; Substance Abuse; Medicine and Health Sciences; Public and Occupational Health; Substance-Related Disorders; Substance Abuse; People and Places; Population Groupings; Ethnicities; European People; Danish People; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Medicine and Health Sciences; Mental Health and Psychiatry; Suicide | null | 29,621,284 | Illness management and recovery: Clinical outcomes of a randomized clinical trial in community mental health centers | Dalum HS, Waldemar AK, Korsbek L, Hjorthøj C, Mikkelsen JH, Thomsen K, Kistrup K, Olander M, Lindschou J, Nordentoft M, Eplov LF. | PLoS One. 2018 Apr 5;13(4):e0194027. doi: 10.1371/journal.pone.0194027. eCollection 2018. | Dalum HS | PLoS One | 2,018 | 2018/04/06 | PMC5886399 | null | 10.1371/journal.pone.0194027 | oa_comm/txt/all/PMC5886399.txt | afa5378a6813fa9a05e421936765dcbb | PLoS One. 2018 Apr 5; 13(4):e0194027 | 2021-06-18 17:05:20 | CC BY | no |
['PMC7573404'] | ['32711440'] | [] | Leukemia is the most common malignancy in children with a prevalence of 30-40%. The incidence of leukemia reaches 2.76 / 100,000 in children aged 1-4 years with the most cases are acute lymphoblastic leukemia (ALL) (Permono et al., 2012). The highest overall incidence of oral mucositis in a study can reach 80-100% and 25 - 45% of them experience severe oral mucositis (stage 3 or 4). High-dose methotrexate in the ALL chemotherapy protocol has been shown to significantly increase the risk of oral mucositis which is a reactive process of interaction between environmental damage to the oral cavity, bone marrow suppression, infection and as a side effect of chemotherapy (Sukhotnik et al., 2014). Glutamine acts to accelerate the division of leukocytes along with macrophages in the immune system. Glutamine stimulates the synthesis of hexosamine as a mucin-forming material that lines the mucosa and as a barrier in preventing bacterial translocation. The use of glutamine in preventing oral mucositis in chidren with ALL after high-dose methotrexate chemotherapy is widely introduced but there is no agreement on the terms of prevention and treatment of oral mucositis (Naidu et al., 2004; Silverman 2007; Chang et al., 2017). Glutamine supplementation can reduce the incidence and severity of oral mucositis during treatment by repairing cell damage and cell recovery (Chang et al., 2017). However, other studies have not found definitive results, and show that more research with higher methodological consistency and validity is needed to find more solid evidence. Mucositis will affect nutrient intake, energy requirements, speech difficulties, and decrease or increase in saliva, ulcerations that cause systemic infections, delay chemotherapy, extend treatment days (treatment costs), affect quality of life and mortality (Sonis, 2004; Silverman, 2007; Vadhan-Raj, 2010). Glutamine appears to be appropriate and safe for preventing oral mucositis and can be considered in patients receiving high doses of methotrexate (Chang et al., 2017). However, to date there has been no definitive guidance in the management of oral mucositis after the administration of high-dose methotrexate in pediatric ALL chemotherapy. Therefore, research on the use of glutamine in the prevention of oral mucositis is very important to be done in children undergoing ALL chemotherapy with the administration of high doses of methotrexate. The aim of this study was to evaluate the incidence of oral mucositis, duration of treatment and cost of care in children with ALL who received high-dose methotrexate chemotherapy in the consolidation phase with glutamine administration at Dr. Soetomo General Academic Hospital, Surabaya. | PMC7573404 | Research Article | null | 32,711,440 | Efficacy Oral Glutamine to Prevent Oral Mucositis and Reduce Hospital Costs During Chemotherapy in Children with Acute Lymphoblastic Leukemia | Widjaja NA, Pratama A, Prihaningtyas R, Irawan R, Ugrasena I. | Asian Pac J Cancer Prev. 2020 Jul 1;21(7):2117-2121. doi: 10.31557/APJCP.2020.21.7.2117. | Widjaja NA | Asian Pac J Cancer Prev | 2,020 | 2020/07/27 | PMC7573404 | null | 10.31557/APJCP.2020.21.7.2117 | oa_comm/txt/all/PMC7573404.txt | 957df72e53dee96ed7af60faeb7e8949 | Asian Pac J Cancer Prev. 2020 Jul; 21(7):2117-2121 | 2021-06-19 06:23:11 | CC BY | no |
['PMC7573404'] | ['32711440'] | [] | The research design used was an experimental study with a randomized pre-post test controlled group trial. The researcher and the research subject (S) were blind fot the treatment (type of drug) given. Subjects grouped into two random groups (R) namely the control group (C) who received a placebo and the treatment group (T) who received oral glutamine. Researchers and research subjects did not know which preparations to be given were glutamine or placebo (double blind) (Figure 1). Subjects were children with ALL aged 1 to 18 years who underwent consolidation phase chemotherapy and received high-dose methotrexate according to the 2013 Indonesian ALL Chemotherapy Protocol and did not experience allergies. All subjects will receive ALL chemotherapy using the 2013 Indonesian ALL Chemotherapy Protocol for the Consolidation Phase of high-dose methotrexate. The study subjects were 48 children divided into two treatment groups: the control group, given a placebo (24 subjects) and the treatment group (24 subjects) were given glutamine at a dose of 400 mg/kg/day orally. Glutamine and placebo were started 24 hours before high-dose methotrexate chemotherapy was given according to protocol. Glutamine and placebo were given for 14 days. The incidence of mucositis and the degree of mucositis were evaluated using the WHO’s Oral Toxicity Scale on days 3, 4, 5, 6, 7 and 14 after administration of high-dose methotrexate (O1 and O2) by dental and oral specialists as shown in Figure 1. | PMC7573404 | Research Article | null | 32,711,440 | Efficacy Oral Glutamine to Prevent Oral Mucositis and Reduce Hospital Costs During Chemotherapy in Children with Acute Lymphoblastic Leukemia | Widjaja NA, Pratama A, Prihaningtyas R, Irawan R, Ugrasena I. | Asian Pac J Cancer Prev. 2020 Jul 1;21(7):2117-2121. doi: 10.31557/APJCP.2020.21.7.2117. | Widjaja NA | Asian Pac J Cancer Prev | 2,020 | 2020/07/27 | PMC7573404 | null | 10.31557/APJCP.2020.21.7.2117 | oa_comm/txt/all/PMC7573404.txt | 957df72e53dee96ed7af60faeb7e8949 | Asian Pac J Cancer Prev. 2020 Jul; 21(7):2117-2121 | 2021-06-19 06:23:11 | CC BY | no |
['PMC7573404'] | ['32711440'] | ['T1', 'T1', 'T2', 'T3', 'T4', 'T5'] | Characteristics of the sample in the homogeneous study and control group in the age group, sex, nutritional status and diagnosis (p> 0.05) as shown inTable 1. The ratio of male and female sex ratio in the glutamine group was 31/17. There were more ALLs in boys than girls (Rubenstein et al., 2004). ALL subjects who participated in the glutamine group had the nutritional status, including 37.5% underweight, 4.2% overweight and 8.3% obesity. Whereas in the placebo group there were children with 29.2% underweight, 12.5% overweight and 16.7% obesity (Table 1). In the treatment group, 23 subjects suffered from oral mucositis, whereas in the placebo group found 15 subjects suffered from oral mucositis. Comparative analysis of the incidence of oral mucositis showed a statistically significant difference (p <0.05). Odds ratio of glutamine administration to the incidence of mucositis in children with ALL with high-dose methotrexate therapy was 0.026. This study showed the results of statistical tests using the Mann-Whitney Test for the incidence of oral mucositis were significantly lower in the glutamine group than in the control group (4.2% vs 62.5%; p value <0.05) (Table 2). In the treatment group, the stage of oral mucositis was lower than in the placebo group (Table 3). There were no subjects in the glutamine group suffered from oral mucositis (stages 3 and 4). In one incident oral mucositis obtained in the glutamine group occurred on the 3rd day which was the first day of initial observation with a severity of stage 2 where the patient was experiencing pain, mild ulcers and subjects were still able to swallow solid food, then on the fourth and fifth day observations there was improvement in oral mucositis to stage 1 and oral mucositis was not obtained on the 6thday of observation until the 14thday until continued 2 weeks after supplementation. No recurrence of oral mucositis was reported from the patient’s parents. The highest peak in this study was on the 4th day. This study suggested that glutamine can reduce the incidence and severity of oral mucositis in ALL children receiving high-dose methotrexate chemotherapy (Table 4). Glutamine administration affected the duration of treatment, in which the glutamine group had shorter treatments (7.67 days + 0.59 SD) than the placebo group (12 days + 2.57 SD). This also affected the amount of costs incurred, where the glutamine group had a total cost that was almost 2 times lower (Rp. 4,709,828 + SD 9,049) than the placebo group (Rp. 9,336,405 + SD 2,517), as inTable 5. | PMC7573404 | Research Article | null | 32,711,440 | Efficacy Oral Glutamine to Prevent Oral Mucositis and Reduce Hospital Costs During Chemotherapy in Children with Acute Lymphoblastic Leukemia | Widjaja NA, Pratama A, Prihaningtyas R, Irawan R, Ugrasena I. | Asian Pac J Cancer Prev. 2020 Jul 1;21(7):2117-2121. doi: 10.31557/APJCP.2020.21.7.2117. | Widjaja NA | Asian Pac J Cancer Prev | 2,020 | 2020/07/27 | PMC7573404 | null | 10.31557/APJCP.2020.21.7.2117 | oa_comm/txt/all/PMC7573404.txt | 957df72e53dee96ed7af60faeb7e8949 | Asian Pac J Cancer Prev. 2020 Jul; 21(7):2117-2121 | 2021-06-19 06:23:11 | CC BY | no |
['PMC7573404'] | ['32711440'] | [] | Nutritional status is important in terms of its effect on long-term prognosis and also as a predisposition to the incidence of infection. Leukemic children with poor and poor nutrition are more prone to experience toxicity that affects the occurrence of mucositis (Niscola et al., 2007). Oral mucositis can be very painful and significantly affect nutrition intake, oral health and quality of life (Duncan et al., 2005; Lalla et al., 2008) and experience a weight loss of> 5% (Lalla and Peterson 2005). Mucositis also affects energy requirements, speech difficulties, and decreased or increased saliva, ulcerations that cause systemic infections and delayed chemotherapy. This condition will affect the nutritional condition of the patient (Sonis 2004; Silverman 2007; Vadhan-Raj 2010). In this study 62.5% of subjects in the placebo group experienced mucositis after the administration of high-dose methotrexate, while the treatment group receiving glutamine experienced 4.2% mucositis. Oral mucositis is the most common complaint arising from administration of high doses of methotrexate, but until now there has been no effective therapy in the prevention and treatment of oral mucositis (Petersen 2005). Previous studies showed glutamine supplementation can reduce the incidence and severity of mucositis during chemotherapy by repairing cell damage and cell recovery (Chang et al., 2017). Biological formation of mucositis is found in five phases: (a) the initiation phase in which chemotherapy acts as a free radical that can damage DNA; (b) The message generation phase in which the activation of transcription factors (NF-kβ) regulates the amount of pro-inflammatory cytokine / interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Cytokines IL-1β play a role for inflammation and dilation of blood vessels so that it is likely to increase the concentration of chemotherapy in the area, and TNF-α causes tissue damage; (c) The signaling and amplification phase in which TNF-α activates NF-kβ, mitogen activated protein kinase (MAPK), and sphingomyelinase pathways that magnify cell and tissue damage resulting in erythema and epithelial atrophy 4-5 days after the initial stage of chemotherapy. Minor trauma from daily activities such as swallowing and chewing can cause ulceration; (d) Ulceration / bacteriological phase if neutropenia is suspected to occur bacterial colonization of the ulcer so that in the mucosal tissue there are many endotoxins and the subsequent release of IL-1 and TNF-alpha; (e) The healing phase in which re-epithelialization occurs in the ulcer (Sonis, 2004). In these conditions glutamine will accelerate the division of leukocytes and macrophages in the body’s immune system, stimulating the synthesis of hexosamine as a mucin-forming material that lines the mucosa as well as a barrier in preventing bacterial translocation. Glutamine is an immune system fuel that stimulates IgA which produces plasma cells through IL-4 and IL-10 which produce IgA. SIgA is IgA which is related to the secretory component. Mucosal immune system will increase preventing bacterial translocation and sepsis (Neu, 2001). Methotrexate in experimental animals histologically showed significant damage to the shape of the crypt and improvement signs of the crypt, severe damage to the epithelial villi with atrophy, degeneration and shortening of the size of the villus, and infiltration of polymorphonuclear leukocytes in the lamina propria (Sukhotnik et al., 2014). Giving glutamine can prevent mucositis in children with ALL who receive high-dose methotrexate therapy. The exact mechanism of glutamine’s role in preventing mucositis remains unclear. Glutamine is thought to be the main oxidative fuel of the gastrointestinal epithelium and helps maintain the integrity of the intestinal structure under normal conditions and stress conditions, so glutamine is very useful in preventing mucositis in patients who are at risk of developing mucositis (Klimberg et al., 1990). Significantly glutamine is provided by skeletal muscle during hyper-catabolic conditions such as cancer. This causes glutamine to be depleted excessively (Luo et al., 2014). Under depleted conditions, glutamine synthesis cannot replace the amount of glutamine lost (Sayles et al., 2016). Until now there has been no research that found dangerous side effects from the use of glutamine supplementation even in large doses, because glutamine is an amino acid that is naturally present in the human body and is well regulated by the body (Sonis, 2004). The duration of mucositis can increase the severity of mucositis, duration of pain, opioid use, dysphagia, total use of parenteral nutrition, incidence and/or duration of fever and infection, and duration of antibiotic use (McCann et al., 2009). The degree of mucositis is significantly related to the duration of parenteral drug administration and TPN, the incidence of infection, the length of stay and the total cost of hospitalization (Vera-Llonch et al., 2007). Giving Glutamine can reduce the length of patient care in the hospital, because glutamine is able to prevent oral mucositis and reduce the duration and severity of mucositis. the incidence of mucositis prolongs the length of treatment, and oral glutamine administration provides benefits for overcoming and shortening treatment days (Chang et al., 2017). In medical intervention in reducing the incidence and severity of mucositis, the duration of treatment is significantly shorter (Suzuki et al., 2014). The duration of treatment is influenced by the severity of the disease. Mucositis extended the length of treatment by 2.3 days (McCann et al., 2009). In this study, the cost of treating patients who received glutamine decreased significantly, because patients who received chemotherapy and had mucositis needed supportive care such as total parenteral nutrition, fluid replacement, and prophylaxis against infection. Oral mucositis is a significant toxicity and limits the dose of cancer therapy, with clinical and economic implications (Lalla et al., 2008). This is in line with previous research which showed that mucositis affects the cost of hospitalization for patients, including the cost of a doctor’s visit, the cost of a nutritionist and the cost of pain reduction therapy (Murphy et al., 2009). A one-point increase in mucositis scores is associated with an increase in days of fever, a 2.1-fold increase in risk of infection, an additional 2.7 days of TPN, an additional 2.6 days of injection of narcotic therapy, an additional 2.6 days of hospitalization and a 3.9-fold increase in the risk of death by 100 days, collectively contributing more than $ 25,000 in additional hospital costs (Lalla et al., 2008). In conclusion, this study is the first RCT in Indonesia that evaluates the administration of oral glutamine at a dose of 400mg/kg BW/day against the prevention of oral mucositis in children with acute lymphoblastic leukemia receiving high-dose methotrexate chemotherapy in the consolidation phase. Oral glutamine dose of 400 mg/kg/day can prevent oral mucositis, shorten the length of treatment and reduce the cost of care for ALL child patients due to the administration of high-dose methotrexate chemotherapy in the consolidation phase | PMC7573404 | Research Article | null | 32,711,440 | Efficacy Oral Glutamine to Prevent Oral Mucositis and Reduce Hospital Costs During Chemotherapy in Children with Acute Lymphoblastic Leukemia | Widjaja NA, Pratama A, Prihaningtyas R, Irawan R, Ugrasena I. | Asian Pac J Cancer Prev. 2020 Jul 1;21(7):2117-2121. doi: 10.31557/APJCP.2020.21.7.2117. | Widjaja NA | Asian Pac J Cancer Prev | 2,020 | 2020/07/27 | PMC7573404 | null | 10.31557/APJCP.2020.21.7.2117 | oa_comm/txt/all/PMC7573404.txt | 957df72e53dee96ed7af60faeb7e8949 | Asian Pac J Cancer Prev. 2020 Jul; 21(7):2117-2121 | 2021-06-19 06:23:11 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | Rheumatoid arthritis (RA) is a common immune disease characterized by the symmetrical destruction of multiple joints.[1]The prevalence of RA in China is 0.32% to 0.36%,[2]and RA incidence is on the rise.[3]If not thoroughly treated, RA gradually leads to cartilage erosion and, ultimately, joint deformity, causing great pain to patients and seriously affecting their quality of life. Thus, RA has gradually become one of the serious diseases affecting people health. RA is still the number one joint disease causing disability in China[4]; hence, RA prevention and treatment have been an important research topic.[5]Nevertheless, the specific pathogenesis of RA is not fully clarified.[6]At this stage, there is still a lack of ideal drugs and methods for RA treatment. The first-line antirheumatic agents, such as methotrexate (MTX), iguratimod, and leflunomide, can delay RA progression but still lack ideal effects on the progression of bone destruction. Moreover, biologics and targeted drugs are more expensive and cause certain serious adverse effects; therefore, most patients cannot adhere to them. Chinese traditional medicine has a curative effect in the treatment of RA. These medicines—such as Glucosidorum Tripterygll Totorum and total glucosides ofPaeonia, which are modern drugs developed based on the traditional theory of Chinese medicine—have definite efficacy for patients who cannot tolerate immunosuppressants or the poor effect of biologics and are very important and effective complementary alternative medical treatments. Jishe Qushi capsules (JSQS) (Qian Medicine System Z20160028) were developed by the Miao medicine Jin Wu Jian Gu founded by Professor WuKai Ma of the Department of Rheumatology and Immunology of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine. The results of a randomized controlled trial[7]have shown that JSQS effectively relieved and improved the symptoms of RA and slowed down disease progression, with definite clinical efficacy. Additionally, the annual clinical reception of related patients was more than 50,000, with the annual sales of the in-hospital preparation of JSQS exceeding 5 million yuan.[8,9]However, the drug is an empirical formula, and laboratory studies are lacking. This study used a combination of network pharmacology and clinical control trials to elucidate the material basis and molecular mechanism of JSQS in RA treatment. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database was used to retrieve all chemical components of the Chinese herbal medicine composition ofPaeonia lactiflora, Panax notoginseng, Homalomena occulta, Curcuma longa, andCaulis Sinomeniifor the collection of active ingredients and protein targets using oral bioavailability of ≥30% and drug similarity (DL) of ≥0.18 as screening conditions. Because the TCMSP database did not provide the chemical components ofZaocys dhumnades, Cibotium barometz, andGardneria angustifolia, we searched for them in the literature, and the protein targets of the compounds were collected using the ChemMapper database. After the targets retrieved from both data platforms were merged and de-duplicated, the protein target names were normalized using the Uniprot protein database, setting human as the species parameter. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | Using “rheumatoid arthritis” as the keyword, we searched the GeneCards and Online Mendelian Inheritance in Man human gene platforms for confirmed genes related to RA, downloaded the database into Excel, and de-duplicated the genes. The cross-targets of diseases and drugs were obtained by using Weishengxin. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | The targets of RA intersection with JSQS were imported into the String database, and the species was set as “homo sapiens.” Additionally, the minimum interaction score correlation was set as “highest confidence” (≥0.400). The drug–disease protein–protein interaction (PPI) network map was initially obtained by downloading the TSV file and processing it with Cytoscape 3.90 software. The core targets were selected by analyzing the network degree and other parameters with the help of the plug-in Network Analyzer. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | The compounds and related targets obtained from JSQS were categorized, as well as the targets that intersected with the diseases. The active ingredient-target network of the capsules for RA treatment was constructed by Cytoscape 3.90 software. The network topology parameters, such as degree and betweenness, were used to screen the key active ingredients of the drug using the built-in tools of the software. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | The drug-disease intersection targets were imported into the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the species was set as human species. The kyoto encyclopedia of genes and genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were submitted to establish a “core target-biological pathway” network to screen out the major pathways. The KEGG enrichment bubble chart and GO term enrichment were created online using the results of bioinformatics analysis to reflect the interactions between drug targets and RA target-related pathways. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | We obtained the 3D crystal structure of the target protein from the RCSB PDB (http://www.rcsb.org/) protein crystal structure database or the Uniprot database. Then, we obtained the 3D structure of the compound corresponding to the protein we wanted to analyze from the TCMSP database, followed by importing the protein and compound into Discovery Studio 2016 Client software for molecular docking. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | Ninety-nine patients with RA treated at the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from January 2021 to 2022 were selected for the study. Among them, 18 cases were men, and 81 cases were women. Their age ranged from 24 to 75 years, with an average age of 56.34 ± 12.80 years. Disease duration ranged from 7 months to 11 years, with an average disease duration of 5.21 ± 2.74 years. Inclusion criteria comprised: patients aged 18 to 60 years; patients that met the diagnostic criteria of active RA according to Chinese Guidelines for Rheumatoid Arthritis Treatment (2018 edition); patients diagnosed for the first time, patients who did not receive formal drug treatment after diagnosis, or patients who received formal treatment but stopped taking drugs for more than 3 months; and patients with 2.6 ≤ Disease Activity Score using 28 joint counts <5.1, joint function classification of I to III, and X-ray stage I to III of both hands. Exclusion criteria were: patients aged <18 years or >60 years; patients with grade IV joint function and/or X-ray stage IV of both hands; patients with a history of hormone and/or biological treatment within 1 month; patients with severe cardiac, hepatic, renal, or another important organ insufficiency; patients with other serious diseases, such as malignancy, active gastrointestinal ulcer, and infectious diseases; patients with severe extra-articular manifestations, such as peripheral neuropathy, proteinuria, and interstitial pulmonary fibrosis; and patients with allergy to the drug of our study. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | The control group received MTX (16 tablets/bottle, Shanghai Xinyi Pharmaceutical Co., Ltd., Lot no. 036180503) 10 mg once a week and Glucosidorum Tripterygll Totorum (100 tablets/bottle, Guizhou Hanfang Pharmaceutical Co., Ltd., lot no. 1459001) 20 mg thrice daily for 4 consecutive weeks. The treatment group received MTX, 10 mg once a week, combined with JSQS (0.45 g, 36 capsules/bottle, from Department of Pharmacy, Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, lot no. 20180101) 4 capsules each time, thrice daily for 4 consecutive weeks. Both groups took folic acid tablets 10 mg (100 tablets/bottle, Changzhou Pharmaceutical Factory Co., Ltd., lot no. 18082511) on the next day during the MTX administration. Patients of both groups were allowed to take celecoxib capsules (6 capsules/box, Pfizer Pharmaceutical Co., Ltd., lot no. W64713) orally at a maximum dose of 2 capsules per day during the study period due to joint pain, and the number of taken capsules and the withdrawal time were recorded separately for both groups. The criteria for determining efficacy were formulated with reference to the Guiding Principles for Clinical Research on New Chinese Medicines (Trial) 2020. Efficacy was defined as the overall improvement rate of patients’ main symptoms and signs of ≥75%, while erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were normal or significantly improved. Progress was defined as the overall improvement rate of patients’ main symptoms and signs of ≥50%, while ESR and CRP improved. Effectiveness was defined as the overall improvement rate of patients’ major symptoms and signs of ≥30%, while ESR and CRP were improved or not improved. Ineffectiveness was defined as the overall improvement rate of patients’ main symptoms and signs of <30%, while ESR and CRP did not improve. The total effective rate was calculated as follows: Total effective rate = (significant + improvement + effective)/ total number of cases. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | The joint pressure pain, swollen joint count, time of morning stiffness, and visual analog scale (VAS) of the 2 groups were compared before and after treatment. As VAS, a 10-cm scale was selected, with 0 representing a completely pain-free state and 10 representing intolerably severe pain. Patients chose the corresponding scale according to their pain level, and the physician in charge chose the corresponding score. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | First, 5 mL of fasting venous blood was collected from patients in both groups before and after treatment. After centrifugation at 3000 r/min for 10 minutes, the supernatant was pretreated and stored at low temperature and used to detect the relevant indexes of patients. Blood ESR was measured by the Westergren methods. CRP was measured by immunodiffusion. Rheumatoid factor (RF) was measured by latex agglutination test. Anti-cyclic citrullinated peptide (anti-CCP) was measured by enzyme-linked immunosorbent assay. The reagents were purchased from Shanghai Chemical Biotechnology Co., and the operation procedure was performed strictly according to the manufacturer instructions. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | Five mL of fasting venous blood was collected from patients in both groups before and after treatment. After centrifugation at 3000 r/min for 10 minutes, the supernatant was pretreated and stored at 4°C and used to detect the relevant indexes of patients. The levels of serum interleukin-6 (IL-6), serum interleukin-17 (IL-17), and tumor necrosis factor (TNF-α) in the 2 groups were measured by enzyme-linked immunosorbent assay. The respective kits were purchased from Shanghai Enzyme Link Biotechnology Co., and the operation procedure was performed strictly according to the manufacturer instructions. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | First, 5 mL of fasting venous blood was collected from patients in both groups before and after treatment. After centrifugation at 3000 r/min for 10 minutes, the supernatant was taken for pre-treatment. The changes in the expression levels of helper T cells 17 (Th17) and regulatory T cells (Treg) were detected using a flow cytometer (Serena [China] Medical Technology Co., Ltd, model Sparrow), and the operation procedure was performed strictly according to the manufacturer instructions. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | We observed the adverse reactions during treatment in both groups. No obvious clinical signs and symptoms of discomfort were found. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | Statistical differences were considered as significant if thePvalue was below .05. All analyses were performed using IBM SPSS Statistics, version 23.0 (IBM SPSS Inc., Chicago). Thettest was used for measurement data, expressed as ‾x ±s. The χ2test was used for count data. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['T1', 'T2'] | A total of 33 active compounds were collected fromPaeonia lactiflora, Panax notoginseng, Homalomena occulta, Curcuma longa, andCaulis Sinomeniithrough the TCMSPS platform with settings of oral bioavailability of ≥30% and DL of ≥0.18, as shown in Table1. Sixty-six potentially active compounds were retrieved from 3 Chinese herbal medicines—namelyZaocys dhumnades, Cibotium barometzandGardneria angustifolia—in ChemMapper (71 potential compounds, of which 5 compounds were excluded), as shown in Table2. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['F1', 'T3'] | A total of 4881 and 28 RA-related targets were obtained from the GeneCards and Online Mendelian Inheritance in Man databases, respectively. The RA targets collected from the 2 databases were integrated and de-duplicated, providing a total of 4791 targets. The disease and drug targets were imported into Weishengxin to obtain the Venn diagram, as shown in Figure1. There were 118 cross-targets of RA with JSQS, which are shown in Table3. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['F2'] | A total of 118 targets based on the intersection of JSQS and RA were imported into the String platform. The PPI network map was initially obtained after setting the corresponding parameters, and the downloaded TSV file was opened in Cytoscape 3.90 software to draw the PPI network map. The larger the value of Degree and Betweenness Centrality, the larger the shape of the node, and the larger the value of Betweenness Centrality, the closer the color of the node was to dark green, as shown in Figure2. The core targets were TP53, INS, IL6, VEGFA, MYC, CASP3, ESR1, EGF, CCND1, PPARG, ERBB2, NFKBIA, TLR4, RELA, and CASP8. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['F3', 'F4'] | One hundred eighteen common targets were used to construct a “Chinese herbal medicine-active ingredient-target” network containing 166 nodes and 423 edges, using Cytoscape software, as shown in Figure3. The degree of each node was calculated by the built-in data analysis, and the higher the degree value, the higher the possibility of the compound playing a therapeutic role. Seven key potent molecules were screened by degree values in the network, namely quercetin, vanillic acid, 4-hydroxybenzaldehyde, kaempferol, protocatechuic aldehyde, scopoletin, and physcion, as demonstrated in Table4. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['F4', 'F5', 'T5'] | The targets were imported into the DAVID data platform for GO annotation analysis using “homo sapiens” as the study context. A total of 210 entries were obtained for GO enrichment analysis, including 159 entries for biological process (BP), 12 entries for cell composition (CC), and 39 entries for molecular function (MF). The top 10 entries were visualized (Q < 0.05) and ranked by gene size. BP was mainly involved in the positive regulation of gene expression, positive regulation of transcription from RNA polymerase II promoter, positive regulation of cell proliferation, positive regulation of transcription, DNA-templated, negative regulation of transcription from RNA polymerase II promoter, response to drug, negative regulation of apoptotic process, regulation of transcription from RNA polymerase II promoter, positive regulation of mitogen-activated protein kinase (MAPK) cascade, and response to estradiol. CC was mainly involved in cytoplasm, nucleoplasm, cytosol, nucleus, chromatin, macromolecular complex, receptor complex, transcription factor complex, perinuclear region of cytoplasm, and death-inducing signaling complex. MF was mainly involved in protein binding, identical protein binding, transcription factor binding, enzyme binding, macromolecular complex binding, transcription factor activity, sequence-specific DNA binding, RNA polymerase II core promoter proximal region sequence-specific DNA binding, RNA polymerase II transcription factor activity, sequence-specific DNA binding, DNA binding, and ubiquitin protein ligase binding. All 3 processes with respective involvement are shown in Figure4. 98 pathways were obtained by KEGG enrichment analysis through the DAVID data platform, and the top 20 pathways were screened for visualization, which showed that the key targets were mainly involved in Pathways in cancer, phosphatidylinositol-3-kinaseRAC–serine/threonine-protein kinase signaling pathway, Kaposi sarcoma-associated herpesvirus infection, Human cytomegalovirus infection, Measles, Hepatitis C, Hepatitis B, Epstein-Barr virus infection, Proteoglycans in cancer, Lipid and atherosclerosis, MAPK signaling pathway, Prostate cancer, aryl hydrocarbon receptor nuclear translocator signaling pathway, Alcoholic liver disease, Salmonella infection, Human papillomavirus infection, Bladder cancer, Legionellosis, Pancreatic cancer, Small cell lung cancer as shown in Figure5and Table5. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['F6', 'T6'] | TP53, INS, IL6, VEGFA, MYC, CASP3, ESR1, EGF, CCND1, PPARG, ERBB2, NFKBIA, TLR4, RELA, and CASP8 were selected to find the corresponding effective chemical components for molecular docking, and the docking scores were used to determine the affinity. The docking results are shown in Figure6and Table6. It can be seen that the binding scores between PPARG and VEGFA and 3,5-dimethyl-4-hydroxybenzaldehyde, protocatechuic-aldehyde, and vanillic acid were high and had a good affinity. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['T7'] | After treatment, the total effective rate of the control and treatment groups was 87.69% and 96.92%, respectively, and the difference between the 2 groups was statistically significant (P< .05) in Table7. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['F7', 'T8'] | After treatment, the time of morning stiffness, swollen joint count, joint pain count, and VAS score were significantly reduced in both groups compared with those before treatment. The improvement in these indexes was significantly bigger in the treatment group than in the control group (P< .05), as shown in Figure7and Table8. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['F8', 'T9'] | After treatment, the levels of ESR, CRP, RF, and anti-CCP in both groups were significantly lower than those before treatment (P< .05). The levels these indexes in the treatment group were significantly lower than those in the control group (P< .05), as shown in Figure8and Table9. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['F9', 'F11', 'T10'] | After treatment, the levels of TNF-α, IL-6, and IL-17 in both groups were significantly lower than those before treatment (P< .05). The levels of these indicators in the treatment group were significantly lower than those in the control group (P< .05), as demonstrated in Figures9–11and Table10. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | ['F12', 'T11'] | After treatment, the Th17 ratio and Th17/Treg value decreased in both groups, while the Treg cell ratio increased in both groups (P< .05). The improvement in these indexes was significantly bigger in the treatment group (P< .05), as shown in Figure12and Table11. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | There were no adverse events that seriously affected the treatment of patients in both groups. Two patients had a mild elevation of glutamate transaminase, 1 patient had nausea, and 1 patient had thrombocytopenia during the treatment in the treatment group, and the incidence of adverse reactions was 8.2%. In the control group, 2 patients had a mild elevation of glutamate transaminase, and 1 patient had vomiting during the treatment period, with an adverse reaction incidence of 6.0%. All of them received symptomatic treatment, which did not affect RA treatment, and there was no significant difference in the incidence of adverse reactions between the 2 groups. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | The clinical drugs used for the treatment of RA can be broadly classified into 2 categories according to their mode of action: those for the improvement of symptoms and those for the improvement of cartilage metabolism. However, symptom improvement drugs cannot fundamentally reverse the development of RA pathology. With the development of Chinese medicine extraction technology, the application of Chinese medicine preparation extracts for the treatment of RA has been increasingly reported and supported by relevant basic experimental studies. JSQS can effectively protect chondrocytes and maintain the integrity of cartilage, reduce the level of inflammatory cytokines, and play a certain therapeutic role in RA.[10]In this study, we elaborated the material basis and molecular mechanism of RA treatment with JSQS through network pharmacology and verified the effect through clinical control trials. It was confirmed that JSQS has multicomponent, multipathway, and multitarget synergistic intervention characteristics in RA and can effectively reverse the pathological development of RA and improve the function of the knee joint and quality of life. In this study, 141 chiropteran capsule targets were mapped to 4791 RA target genes, 118 anti-RA key targets of JSQS were obtained, and a JSQS-key target-RA composite target network map was constructed. The quercetin inPanax notoginseng, vanillic acid, scopoletin, physcion inZaocys dhumnades, 3,5-dimethyl-4-hydroxybenzaldehyde inCibotium barometz, kaempferol inPaeonia lactiflora, and protocatechuic inGardneria angustifoliaBioinformatics were the main active chemical components in the composite target network. The network showed that 1 active chemical component could correspond to 1 or even multiple targets, and multiple targets corresponded to the same active chemical component, indicating that the JSQS has the characteristics of multicomponent and multitarget synergistic intervention in RA treatment. Quercetin has an anti-inflammatory effect on RA by reducing the ratio of MMP-13/TIMP-1, promoting the inhibition of cartilage extracellular matrix degradation, and protecting articular cartilage.[10]Scopoletin is a coumarin-like compound with anti-swelling, anti-inflammatory, analgesic, antibacterial, and acaricidal biological activities.[11]Physcion, as its mechanism of action on TNF-α-induced RA was identified by immunofluorescence, western blot, and reverse-transcription PCR, dose-dependently inhibits the expression of ERK1/2 and p38MAPK in fibroblast-like synovial cells to attenuate the inflammatory response.[12]In terms of apoptosis induction,[13]physcion at concentrations of 6 to 10 mol/L significantly inhibits the activity of synovial cells in a mixture of type II collagen and incomplete Freund adjuvant to induce RA model rats. Pan Shuhan et al[14]confirmed that physcion (40 mg/kg) significantly reduces the expression of Cat-G, Cat-S, and autophagy marker LC3 in synovial tissues using immunohistochemistry and enzyme-linked immunosorbent assay in an equal volume emulsion of collagen-induced arthritis rat model. Physcion has been found to present a quantitative and temporal relationship in inhibiting the metastasis and proliferation of RA–fibroblast-like synoviocytes cultured in vitro.[15]At the cellular level, kaempferol exerts anti-inflammatory effects, reducing the production and mRNA expression of pro-inflammatory cytokines, such as thymic stromal lymphopoietin, TNF-α, and interleukin-18.[16] The results of KEGG enrichment analysis showed that JSQS were mainly used to treat RA through the pathways in cancer, phosphatidylinositol-3-kinaseRAC–serine/threonine-protein kinase signaling pathway, MAPK signaling pathway, and aryl hydrocarbon receptor nuclear translocator signaling pathway, among others. The topological analysis of this study showed that TP53, INS, IL6, VEGFA, MYC, CASP3, ESR1, EGF, CCND1, PPARG, ERBB2, NFKBIA, TLR4, RELA, and CASP8 are the core key targets. Molecular docking was performed according to the corresponding active chemical components, suggesting binding fractions of >70 between PPARG and VEGFA and 3,5-dimethyl-4-hydroxybenzaldehyde, protocatechuic-aldehyde, vanillic acid, which had good binding energy. It indicated that these active chemical components might play an important role in RA treatment. However, further in vivo and in vitro studies are needed to confirm the possible existence of a therapeutic axis. PPAR, a member of the nuclear receptor superfamily that regulates lipid, glucose, and amino acid metabolism,[17]belongs to the nuclear hormone receptors and consists of 3 different isoforms, namely PPARα, PPARγ (PPARG), and PPARβ/δ. PPARγ activators or compounds that positively regulate PPAR gene expression may represent a new class of nonsteroidal anti-inflammatory drugs for local or systemic treatment of many inflammatory conditions. PPAR activation has been reported to reduce the level of Th2 immune response,[18]and high expression of PPARG inhibits IL-6 and TNF-α by suppressing nuclear factor kappa B activity, which, in turn, suppresses the overexcited inflammatory response. Additionally, PPARG activates osteoclasts, which cause bone destruction in RA patients, preserving the patient joint structure. The active osteoclasts cause bone destruction in RA patients, resulting in abnormalities in joint structure, resulting in morning stiffness, reduced motion, and long-term joint deformation. Synovitis and vasculitis of joints are the basic pathological factors of RA. Neovascularization is considered to be one of the main factors in the formation and maintenance of pannus in RA, and some studies have shown that VEGF can increase vascular permeability and play a very critical role in the formation and development of pannus in RA synovitis.[19,20]Furthermore, it is important in promoting the formation and development of inflammation, especially for the formation of chronic inflammation. This study identified the possible material basis and molecular mechanism of JSQS in RA treatment. Thus, our team conducted a controlled clinical trial to verify the therapeutic effect of JSQS in RA treatment. The results showed that the capsules could effectively improve morning stiffness, joint pain, VAS score, other indicators of RA, clinical symptoms, and patient quality of life. The results of laboratory tests, such as ESR, CRP, RF, and anti-CCP, also indicated effective disease control, reduced levels of inflammation-related factors, such as TNF-α, IL-6, and IL-17, and significantly improved Th17/Treg balance. In conclusion, the multicomponent, multipathway, and multitarget synergistic interventions of JSQS can significantly improve clinical symptoms and quality of life of RA patients and delay the progression of the disease. Insufficient sample size is a regret of this study due to time and financial constraints. After obtaining the preliminary results, we will carry out a multicenter study, and at the same time, we will optimize the design of the study protocol on the line, in order to provide a theoretical basis and guidance for the clinical application of Chinese medicine. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC10470707'] | ['37653836'] | [] | Data curation:Nannan Zhang. Formal analysis:Xin Peng. Funding acquisition:Xueming Yao. Project administration:Cong Huang. Software:Nannan Zhang. Supervision:Wukai Ma, Xueming Yao. Writing – original draft:Yujie Li, Xin Peng. Writing – review & editing:Yuanxing Qin, Xudong Zhang. | PMC10470707 | 3800; Research Article; Observational Study | null | 37,653,836 | Network pharmacology analysis and clinical verification of Jishe Qushi capsules in rheumatoid arthritis treatment | Li Y, Zhang N, Peng X, Ma W, Qin Y, Yao X, Huang C, Zhang X. | Medicine (Baltimore). 2023 Aug 25;102(34):e34883. doi: 10.1097/MD.0000000000034883. | Li Y | Medicine (Baltimore) | 2,023 | 2023/09/01 | PMC10470707 | null | 10.1097/MD.0000000000034883 | oa_comm/txt/all/PMC10470707.txt | 73f3f889770e1980a0e744c883bb0b44 | Medicine (Baltimore). 2023 Aug 25; 102(34):e34883 | 2023-09-15 23:33:31 | CC BY | no |
['PMC7318217'] | ['32275086'] | ['jde15343-bib-0001', 'jde15343-bib-0002', 'jde15343-bib-0003', 'jde15343-bib-0004', 'jde15343-bib-0005', 'jde15343-bib-0006', 'jde15343-bib-0007', 'jde15343-bib-0008', 'jde15343-bib-0007', 'jde15343-bib-0008', 'jde15343-bib-0007', 'jde15343-bib-0009', 'jde15343-bib-0010', 'jde15343-bib-0011'] | Psoriasis is a systemic chronic inflammatory disease with an estimated global prevalence ranging 0.09–11.4%; the prevalence for all ages was 1.43–5.1% (1971–2009) in the USA1,2and 0.44% (2010–2011) in Japan.3,4Psoriatic patients experience a substantial burden of the disease, with physical and psychological comorbidities that further deteriorate the health‐related quality of life (HRQoL).5 As the interleukin (IL)‐17/IL‐23 axis is implicated in the pathogenesis of psoriasis, inhibition of IL‐17 has emerged as an important therapeutic strategy for the management of psoriasis.6 Brodalumab, a fully human immunoglobulin (Ig)G2 monoclonal antibody produced in Chinese hamster ovary (CHO) cells, binds selectively to the human IL‐17 receptor A (IL‐17RA) and inhibits the biological activities of IL‐17A, IL‐17C, IL‐17E, IL‐17F and IL‐17A/F heterodimers.7,8 Brodalumab is currently approved for the treatment of moderate to severe plaque psoriasis in adult patients7,8and is administrated s.c. at a dose of 210 mg at weeks 0, 1 and 2 of treatment, followed by 210 mg once every 2 weeks (Q2W).7In a 12‐week, phase II, randomized controlled study conducted in Japanese patients with moderate to severe psoriasis, brodalumab demonstrated rapid and robust efficacy with a favorable safety profile (NCT01748539).9It also showed a sustained clinical response with an acceptable safety profile over 52 weeks in Japanese patients with moderate to severe plaque psoriasis in an open‐label phase III study (NCT01782924).10Another phase III study was conducted in Japan to evaluate the efficacy and safety of brodalumab in patients with plaque psoriasis and in patients with pustular psoriasis or psoriatic erythroderma (NCT01782937).11This study was an extension of the above two phase III studies. The objectives of the present analysis were to evaluate the long‐term safety and efficacy of brodalumab in patients with plaque psoriasis except in those with pustular psoriasis and psoriatic erythroderma. | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | ['jde15343-bib-0012', 'jde15343-bib-0010', 'jde15343-bib-0013', 'jde15343-sup-0001', 'jde15343-bib-0009', 'jde15343-bib-0010'] | This long‐term, multicenter (54 study sites), open‐label extension (OLE) study (NCT0205260912) was tandemly conducted in patients with plaque psoriasis after the phase III study.10This OLE study converted into the post‐approval phase study (NCT0418388113; 4 July 2016 to 31 December 2016) after brodalumab was approved for use in Japan (Fig.S1). Here, we present the data of patients with plaque psoriasis who were enrolled in this extension phase after they completed the 12/52 weeks of treatment in the phase II and phase III studies9,10of brodalumab in Japan. Eligible patients with plaque psoriasis were treated with s.c. brodalumab at a dose of 140 mg on day 1 and 140 mg once every 4 weeks (Q4W) thereafter. The dose and dosing interval were modified at the physician’s discretion, if needed, based on specific criteria (mentioned below) until the study was converted to a PMS study, after which all patients were switched to receive brodalumab 210 mg Q2W. Overall, patients were followed up on day 1 (week 0) and Q2W thereafter until the end of the study (EOS). EOS was defined as either treatment discontinuation or the date of study completion. After enrollment (week 0), patient data were evaluated at week 28, week 108 and EOS. Although follow up was planned Q2W, a visit was not required if drug administration or assessment at the study site was not scheduled. The study protocol was approved by the institutional review board at each study site. The study was performed in compliance with the Declaration of Helsinki, and written informed consent was obtained from all patients. | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | ['jde15343-bib-0009', 'jde15343-bib-0010'] | Patients aged 18 years or more with plaque psoriasis (psoriasis vulgaris with/without psoriatic arthritis) who completed 64 weeks of treatment with brodalumab were enrolled in the study. Patients were required to be hepatitis B negative at and after 48 weeks of brodalumab treatment, with no radiographic or computed tomography findings indicative of tuberculosis at week 52 of the previous study. Women of child‐bearing potential were required to have a negative urine pregnancy test result on day 1. Patients were switched to the post‐approval phase study at the physician’s discretion after obtaining their written informed consent. Exclusion criteria were as follows: serious infections requiring systemic antibiotic or antiviral therapy (excluding oral administration); non‐compliance with the study protocol; suicidal ideation severity 4 or 5, or suicidal behavior of any type while on treatment with brodalumab in the previous studies,9,10as determined by the Columbia – Suicide Severity Rating Scale (C‐SSRS) score on day 1; mental disorder or a history of mental disorder; severe depression (Patient Health Questionnaire 8 [PHQ‐8] depression scale score, ≥15) on day 1; and unfit for enrollment according to the physician. Women (of child‐bearing potential) and fertile men who were unwilling to use a single, highly effective contraception method or a combination of two contraceptive methods from the date of consent (if women) or the start of administration (if men) until 12 weeks after the end of administration were also excluded. | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | ['jde15343-sup-0001'] | Subcutaneous treatment with brodalumab was initiated at a dose of 140 mg Q4W on day 1. Thereafter, two treatment strategies were implemented. Between weeks 2 and 28, the dose was either maintained or the dosing interval was shortened (140 mg Q4W → 140 mg Q2W), the dose directly escalated (140 mg Q4W → 210 mg Q2W) or both in a stepwise manner (140 mg Q4W → 140 mg Q2W → 210 mg Q2W) by using the static Physician’s Global Assessment (sPGA) score (either ≥3 [moderate or higher severity] or remains/is maintained at 2 [mild] for ≥4 weeks) at the physician’s discretion (rule 1). Eligible patients were switched to the Q2W dosing interval on an even week and further dose modification was allowed at the physician’s discretion; however, reverting to the Q4W dosing interval was not allowed. After week 28, in addition to an increase in the dose and dosing interval, a reduction in the dose and dosing interval only at the physician’s discretion even without an sPGA score was also allowed until drug approval (≥28 weeks; rule 2). However, when reducing the dose or extending the dosing interval, the following order was applied: 210 mg Q2W → 140 mg Q2W → 140 mg Q4W → 140 mg once every 8 weeks (Q8W). Finally, all patients were switched to brodalumab 210 mg Q2W after drug approval (Fig.S1). Use of the following treatments was prohibited: phototherapy; topical therapy with calcineurin inhibitors, active vitamin D or A analogs and steroids; systemic therapy with salazosulfapyridine, azathioprine, thioguanine, hydroxyurea, fumaric acid esters, corticosteroids, calcineurin inhibitors (cyclosporin and tacrolimus), methotrexate and vitamin D or A analogs; coal tar therapy; biologics (adalimumab, infliximab, ustekinumab and etanercept) and live vaccines; and investigational drugs or devices. After week 28, topical therapy for psoriasis and systemic therapy as long‐term corticosteroid therapy (14 consecutive days) for comorbid diseases other than psoriasis were permitted. | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | ['jde15343-bib-0009'] | The Psoriasis Area and Severity Index (PASI) scores were evaluated at baseline (week 64) in the phase II study,9on day 1 (week 52 of the previous study was considered as week 0), Q4W until week 28, and Q8W thereafter until week 108 or the week of discontinuation in the current extension study. Patients with psoriatic arthritis were evaluated using the American College of Rheumatology (ACR) response criteria for 20% (ACR 20), 50% (ACR 50) and 70% (ACR 70) improvement in the tender joint count on day 1, week 12, week 28, and every 16 weeks thereafter until week 108 or the week of discontinuation. The percentage of body surface area (BSA) involvement was evaluated at baseline in the phase II study, day 1, Q4W until week 28, and Q8W thereafter until week 108 or the week of discontinuation. Other efficacy parameters, such as the Nail Psoriasis Severity Index (NAPSI), Psoriasis Scalp Severity Index (PSSI) and Dermatology Life Quality Index (DLQI; patient‐reported outcome), were evaluated at baseline in the phase II study, day 1, week 12, week 28, and every 16 weeks thereafter until week 108 or the week of discontinuation. | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | ['jde15343-bib-0014'] | All adverse events (AE), including treatment‐related AE (TRAE), were recorded throughout the study period. Other serious TRAE were defined as serious TRAE with an outcome other than death, and other significant TRAE were defined as all non‐serious TRAE that led to withdrawal or an interruption or reduction in the dose of administration. Other safety assessments, such as the C‐SSRS and PHQ‐8 scores,14were evaluated on day 1 and Q2W thereafter until week 108 or the week of discontinuation. These assessments were also performed Q4W throughout the study period at the physician’s discretion. | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | [] | The incidence of anti‐brodalumab‐binding antibodies was evaluated at weeks 12 and 28, every 16 weeks after 28 weeks, and at the week of discontinuation. Anti‐brodalumab antibodies were measured using an electrochemiluminescent immunoassay (PPD, Wilmington, NC, USA). Samples positive for anti‐brodalumab‐binding antibodies were subsequently evaluated for anti‐brodalumab‐neutralizing antibodies by using a cell‐based bioassay (PPD; and Amgen, Thousand Oaks, CA, USA). | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | [] | Efficacy and safety analyses were performed for all patients except those with missing data. All end‐points were evaluated using the full analysis set. All efficacy assessments, including the patient‐reported outcomes, are summarized descriptively. Categorical data are summarized as frequencies and percentages, and continuous variables are provided as summary statistics (number of patients, median [quartile 1, quartile 3], minimum and maximum). For patients who transitioned to the phase III study, “baseline” was defined as the time point before brodalumab initiation in the phase II study. The primary analysis was conducted using an intent‐to‐treat approach based on the actual brodalumab dose administered. Demographics and clinical characteristics are summarized for baseline and day 1. Quartiles of PASI and DLQI scores were calculated for each pre‐dose at week 28, week 108 and EOS after week 108. Quartiles for PASI, BSA, PSSI, NAPSI and DLQI were calculated, and frequencies for ACR 20, ACR 50 and ACR 70 were also determined. The quartiles for the PASI, DLQI, NAPSI and PSSI scores, and the numbers of patients for ACR 20, 50 and 70, were calculated and illustrated using a transition chart at baseline (except for ACR evaluation), on day 1, and at weeks 28 and 108. The number of relevant cases was also calculated for each time point and each pre‐dose. TRAE are presented according to the system organ class (SOC) and preferred term (PT) in the Medical Dictionary for Regulatory Activities – Japanese translation (MedDRA/J) version 17.1. Serious and other important TRAE were also tabulated similarly. PHQ‐8 assessments were extracted at the time of the initial survey (depending on the case, from day 1 to week 16). Numerical variables were calculated as quartiles, and categorical variables were calculated as frequencies and ratios. Changes in PHQ‐8 at all measurement time points were distributed according to the severity. The frequency and ratio of the C‐SSRS scores at all measurement time points were tabulated. All analyses were performed for patients without any missing data (i.e. list‐wise deletion or complete case analysis) using SAS software version 9.2 or 9.3 (SAS Institute, Cary, NC, USA). | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | ['jde15343-fig-0001', 'jde15343-tbl-0001'] | A total of 129 patients were enrolled, and all were switched to brodalumab 140 mg Q4W on day 1 (week 0). Of these, 107 (82.9%) patients completed the 108‐week or more follow up (EOS) (Fig.1). Seven patients discontinued or withdrew from treatment before week 108 because of AE (n= 3: at week 15 [140 mg Q4W], week 72 [210 mg Q2W] and week 78 [140 mg Q2W]), lack of efficacy (n= 1: at week 20 [210 mg Q2W]), withdrawal of consent (n= 2: at week 42 [140 mg Q4W] and week 104 [210 mg Q2W]) and other (n= 1: at week 100 [140 mg Q4W]; resection for colorectal cancer during the treatment period). Fifteen patients discontinued/withdrew from treatment between 108 or more and 140 weeks or less because of AE (n= 2: at week 117 [210 mg Q2W] and week 130 [210 mg Q2W]), lack of efficacy (n= 1: at week 123 [210 mg Q2W]) and withdrawal of consent or lost to follow up (n= 11: 210 mg Q2W; andn= 1: 140 mg Q4W). The median (interquartile range [IQR]) age of the patients was 43.0 years (37.0–55.0) and 80.6% were men. All patients enrolled in the study had well‐controlled psoriasis (median [IQR] PASI score, 0 [0.0–1.2]), with none to a small effect on HRQoL (median [IQR] DLQI score, 1 [0.0–2]) on day 1 (week 0) (Table1). | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | ['jde15343-tbl-0002', 'jde15343-fig-0002', 'jde15343-fig-0003', 'jde15343-fig-0004', 'jde15343-fig-0005'] | At week 28, 54 of 127 (42.5%) patients were escalated to brodalumab 210 mg Q2W and 48 of 127 (37.8%) patients continued to receive brodalumab 140 mg Q4W; the dosing interval was shortened to 140 mg Q2W in 25 of 127 (19.7%) patients. Thereafter, at week 108, 67 of 122 (54.9%) patients were escalated to brodalumab 210 mg Q2W, and 14 of 122 (11.5%) patients remained on the initial dose of brodalumab 140 mg Q4W. Overall, 107 of 129 (82.95%) patients continued brodalumab treatment beyond 108 weeks, with the dose modified to 210 mg Q2W. Median (IQR) PASI scores and DLQI scores were low throughout the follow‐up period (week 28, week 108 and EOS) (Table2, Fig.2). At EOS (range, 12–148 weeks), the severity of psoriasis was controlled in most patients, as indicated by the median (IQR) PASI score (0.00 [0–0.80]), BSA (0.00% [0–1.10]), PSSI score (0.0 [0–1.0]), NAPSI score (0.0 [0–2.0]), DLQI score (0.00 [0–1.0]) and PHQ‐8 score (0.0 [0–2]). At EOS (range, 12–148 weeks), of the 17 patients with psoriatic arthritis, eight (47.1%), five (29.4%) and four (23.5%) achieved ACR 20, 50, and 70, respectively. At week 28, 53 of 119 (44.5%) and 34 of 81 (42.0%) patients, respectively, with scalp and nail symptoms were also escalated to brodalumab 210 mg Q2W, whereas 41 of 119 (34.5%) and 30 of 81 (37.0%) patients, respectively, continued on brodalumab 140 mg Q4W. The dosing interval was shortened to 140 mg Q2W in 25 of 119 (21.0%) patients with scalp symptoms and in 17 of 81 (21.0%) patients with nail symptoms. Thereafter, at week 108, 64 of 114 (56.1%) and 42 of 76 (55.3%) patients, respectively, with scalp and nail symptoms were escalated to brodalumab 210 mg Q2W, and nine of 114 (7.9%) and five of 76 (6.6%) patients, respectively, remained on the initial dose of brodalumab 140 mg Q4W. The dosing interval was shortened to 140 mg Q2W in 41 of 114 (36.0%) patients with scalp symptoms and 29 of 76 (38.2%) patients with nail symptoms. Median (IQR) PSSI scores remained low throughout the 108‐week follow‐up period (Fig.3). The median (IQR) NAPSI score tended to increase at week 28 but remained low at week 108 (Fig.4). At week 28, nine of 17 (52.9%) patients with joint symptoms (ACR criteria) were escalated to brodalumab 210 mg Q2W and six of 17 (35.3%) patients continued to receive brodalumab 140 mg Q4W; the dosing interval was shortened to 140 mg Q2W in two of 17 (11.8%) patients. At week 108, 11 of 16 (68.8%) patients were escalated to brodalumab 210 mg Q2W and none of the patients remained on the initial dose of brodalumab 140 mg Q4W; the dosing interval was shortened to 140 mg Q2W in five of 16 (31.3%) patients. Compared with day 1, the proportion of patients who achieved ACR 20 and 70 tended to decrease at week 28; in contrast, the proportion of patients who achieved ACR 50 showed a consistent increase. Thereafter, the proportion of patients who achieved ACR 20, ACR 50 and ACR 70 showed an increase at week 108 (Fig.5). | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | ['jde15343-tbl-0003', 'jde15343-tbl-0004', 'jde15343-fig-0001', 'jde15343-fig-0006'] | Any TRAE were observed in 83 of 129 (64.3%) patients between day 1 and the EOS evaluation. The most commonly reported TRAE was nasopharyngitis (29/129 [22.5%]), followed by influenza and oral candidiasis (9/129 [7.0%] each), and folliculitis, cellulitis, pharyngitis, arthralgia, skin papilloma, periodontitis, diarrhea, upper respiratory tract inflammation and pyrexia (all reported in ≥3% of patients) (Table3). No deaths were reported. Serious TRAE were observed in four (3.1%) patients and other significant TRAE in 15 (11.6%) patients. Serious TRAE, such as appendicitis, brain abscess, bacterial meningitis, colon cancer, IgA nephropathy and tubulointerstitial nephritis, were reported in one patient each. No cases of serious candida infection or Crohn’s disease were observed (Table4). Treatment discontinuation due to AE was reported in five patients: one case before week 28, two cases between weeks 28 and 108, and two cases between week 108 and EOS (Fig.1). The maximum suicidal ideation score (C‐SSRS) of the patients was 0 throughout the study period, except for two patients (data not shown). The proportion of patients with mild to moderate depression rated using PHQ‐8 did not increase throughout the study period (from treatment initiation to EOS); the PHQ‐8 score distribution was also similar among the patients (Fig.6). No patient had a PHQ‐8 score of 15 points or more throughout the study period to the EOS evaluation. No anti‐brodalumab‐binding antibodies or brodalumab‐neutralizing antibodies were detected in any patient throughout the study period. | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | ['jde15343-bib-0010', 'jde15343-bib-0009', 'jde15343-bib-0010', 'jde15343-bib-0015', 'jde15343-bib-0016', 'jde15343-bib-0017', 'jde15343-bib-0018', 'jde15343-bib-0019', 'jde15343-bib-0020', 'jde15343-bib-0021', 'jde15343-bib-0022', 'jde15343-bib-0023'] | This OLE study demonstrated the safety and efficacy of long‐term brodalumab treatment in Japanese patients with plaque psoriasis who had completed the prior 64‐week study. Most patients completed the 108‐week extension study, and few patients discontinued because of AE or lack of efficacy during treatment, where the dose and dosing interval could be modified based on the severity of the disease at the physician’s discretion. Overall, 122 (94.6%) patients completed the 108‐week extension study, similar to 92% of patients who completed the previous 52‐week phase III study.10Overall, no deaths were reported, and 3.1% of other serious TRAE and 11.6% of other significant TRAE were observed in this patient population. Of note, one patient who had a history of alcoholic liver dysfunction reported brain abscess and meningitis bacterial during the treatment of brodalumab at week 115. He was treated with antiprotozoal and antibiotics after the study discontinuation and recovered without further problems. No cases of newly diagnosed tuberculosis, severe candidiasis or Crohn’s disease (developed or reactivated) were observed throughout the study period. The proportion of patients who continued brodalumab 140 mg Q4W in this study decreased to 37.8% at week 28 and 11.5% at week 108, despite the severity of psoriasis and HRQoL being well controlled throughout the study. It might have been necessary to escalate the dose or shorten the dosing interval considering the extent of worsening of the skin and scalp symptoms before evaluation, even if the PASI and PSSI scores were sufficiently low at each evaluation. Although the efficacy in patients with nail and joint symptoms tended to decrease temporarily at week 28, the severity of psoriasis and HRQoL were well controlled throughout the long‐term extension study. On the other hand, this study showed that almost all patients with plaque psoriasis who completed 64 weeks of treatment had a median PASI score of 0 and a median DLQI score of 0 at EOS, and indicated that the effects of brodalumab may be sustained over the long term with the appropriate dose and dosing interval. Brodalumab treatment was well tolerated throughout the long‐term extension study, and no new safety signals were identified. Although direct comparisons cannot be made because of differences in patients, follow‐up periods and brodalumab doses, the incidence and severity of AE were similar to those reported in previous clinical trials with brodalumab in psoriatic patients.9,10,15,16,17,18AE of interest that occur with IL‐17 inhibitors, such as serious candida infections or Crohn’s disease, were not observed in this study. Although this study did not enroll patients suspected to have or who were at risk of tuberculosis, we did not observe any new cases of tuberculosis in this study. By blocking critical mediators of adaptive and innate immunity, biotherapeutics may carry a risk of increased opportunistic infections. IL‐17A has a role in immune defense in mucocutaneous barrier tissues and may play a role duringMycobacterium tuberculosisinfection.19 Furthermore, depressive symptoms based on PHQ‐8 distribution appeared not to change through the study period from the first administration of brodalumab to EOS. The association between brodalumab exposure and suicidal ideation and behavior has been controversial,20,21but in this OLE study, two patients had a C‐SSRS maximum suicidal ideation severity with no causal association: one patient reported severity 2 at the evaluation after the start of the study and the other patient reported severity 1 at week 16. Only one patient had suicidal ideation and behavior; however, both events were due to economic troubles and were deemed by the physicians as unrelated to brodalumab. Another patient had suicidal ideation at week 16. Specifically, the patient stated, “thought about it a little because of exacerbation of psoriasis” and responded by saying “no” to a question about the specificity of active suicidal ideation. The degree of the suicidal ideation was also of the least severity. Thus, it may be also considered inadequate to reduce the dose or extend the dosing intervals easily even in the case of shared decision‐making with patients. Immunogenicity with brodalumab may be low. Although treatment discontinuation due to lack of efficacy was reported in two patients, we did not observe any anti‐brodalumab‐binding antibodies and anti‐brodalumab‐neutralizing antibodies in this patient population on long‐term brodalumab treatment at any assessment point. This observed low immunogenicity profile of brodalumab was consistent with that reported in previous clinical trials.22,23 In this study, no new safety signals were identified, and no anti‐brodalumab‐binding antibodies were observed with prolonged treatment. The severity of psoriasis and HRQoL were well controlled throughout the study period with brodalumab. Overall, the long‐term efficacy and safety of brodalumab were demonstrated, and the severity of psoriasis and HRQoL were well controlled over 108 weeks of treatment with brodalumab. | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | [] | This was a single‐arm study without a placebo arm for comparison of efficacy. The AE might have been underestimated because all patients did not receive the approved dose regimen of brodalumab. The baseline PHQ‐8 assessments were not evaluated; therefore, whether the PHQ‐8 scores changed because of the treatment with brodalumab remains unelucidated. The ACR has been evaluated in a limited number of patients with plaque psoriasis with arthritis, and their joint sites were not fully analyzed. | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC7318217'] | ['32275086'] | [] | This study was funded by Kyowa Kirin. Y. Y. reports grants and/or speaker honoraria from Kyowa Kirin, Celgene, Janssen Pharmaceutical, AbbVie, Maruho, Mitsubishi. Tanabe Pharma and Eli Lilly Japan outside the submitted work. H. N. received consulting fees and/or speaker honoraria from AbbVie, Eisai, Eli Lilly Japan, Janssen, Japan Tobacco, Kyowa, Kirin, LEO Pharma, Maruho, Novartis, Torii Pharmaceutical and UCB Japan. N. T. and K. O. are employees of Kyowa Kirin. | PMC7318217 | Original Article; Original Articles | null | 32,275,086 | Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study | Yamaguchi Y, Takatsu N, Ootaki K, Nakagawa H. | J Dermatol. 2020 Jun;47(6):569-577. doi: 10.1111/1346-8138.15343. Epub 2020 Apr 10. | Yamaguchi Y | J Dermatol | 2,020 | 2020/04/11 | PMC7318217 | null | 10.1111/1346-8138.15343 | oa_comm/txt/all/PMC7318217.txt | 300bcc8979441f9e9e7f874b1c1c639e | J Dermatol. 2020 Jun 10; 47(6):569-577 | 2021-06-19 05:43:45 | CC BY | no |
['PMC5894974'] | ['29641522'] | ['pone.0193441.ref001', 'pone.0193441.ref002', 'pone.0193441.ref003', 'pone.0193441.ref004', 'pone.0193441.ref005', 'pone.0193441.ref006', 'pone.0193441.ref007', 'pone.0193441.ref011', 'pone.0193441.ref012', 'pone.0193441.ref013', 'pone.0193441.ref014', 'pone.0193441.ref015', 'pone.0193441.ref015', 'pone.0193441.ref016', 'pone.0193441.ref017', 'pone.0193441.ref018', 'pone.0193441.ref019'] | Surgical procedures are increasingly carried out in a day-case setting [1,2]. The patients’ perception of perioperative health in day-case surgery is currently not dominated by medical factors but by psychological factors [3,4], including anxiety, depressive moods, aggression, and feelings of fatigue [5]. This situation calls for new research to identify predictive factors for these clinical psychological outcomes to aid early clinical decision making, a task that particularly falls to anesthesiologists in preoperative assessment [6]. Predicting psychological outcomes after day-case surgery is important because poor outcomes could lead to negative socioeconomic effects due to prolonged convalescence that delays a return to normal activities and work [7–11]. Furthermore, an estimated 80% of elective surgical procedures will be carried out as day-case surgery [12], a number that is likely to increase because more and more complex surgery (e.g., craniotomies for brain tumor resection) are carried out in this setting [13,14]. Accordingly, the probability that patients will experience poor psychological outcomes will increase, underlining the need for adequate prognostic models tailored to predict multiple psychological outcomes after surgery to facilitate prevention. Prognostic models are statistical models that combine data from patients to predict clinical outcome [15]. Such models based on data collected soon after presentation could in theory be used to aid early clinical decision making and allow for more accurate counseling of patients [15]. Conventionally, prognostic studies aim to find prognostic factors that accurately predict a single outcome variable [16]. However, joint prediction of interrelated outcome variables, such as psychological outcome variables, has not yet been studied extensively. To that end, advanced statistical methodology like Structural Equation Modeling (SEM) is needed. SEM enables joint analyses of several candidate prognostic factors on several outcome variables [17]. SEM has been used in many research fields and is currently coming into use in clinical medicine [18]. In the field of anesthesiology, however, it has been rarely used, although there have been calls to further establish use of this statistical methodology [19]. We aimed to develop a prognostic model based on sociodemographic, medical, and psychological variables assessed just before day-case surgery on psychological outcomes after surgery using SEM. This model could help to preserve the medical and socioeconomic success of surgery in a day-case setting. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | ['pone.0193441.ref005', 'pone.0193441.g001'] | This study is part of a larger double-blinded randomized controlled clinical trial conducted at the Erasmus University Medical Center, comparing the effects of lorazepam and placebo in day-case surgery patients [5]. However, the methods in this study have been adapted to address different objectives. We recruited patients from our day-case surgery department between October 2010 and September 2011. We included all patients who were referred for day-case surgery and aged at least 18 years. Patients were excluded if they met one or more of the following criteria: insufficient command of the Dutch language; severe learning difficulties; or undergoing ophthalmology surgery, extracorporeal shock wave lithotripsy, endoscopy, Botox treatment, abortion, or chronic pain treatment. The latter procedures are generally considered to be minimally invasive. Most practitioners are of the opinion that these procedures do not require premedication. Finally, prior use of psychopharmaceuticals and contraindication to lorazepam use–according to our national pharmacotherapeutic compass (available athttp://www.farmacotherapeutischkompas.nl; accessed 2010)–were also exclusion criteria. The study protocol was approved by the Medical Ethical Committee of Erasmus MC (Chairperson Prof. dr. H.W. Tilanus) and by the Netherlands Central Committee on Research involving Human Subjects (CCMO) and registered with EudraCT under number 2010-020332-19. The trial has also been registered under identification number NCT01441843 in the ClinicalTrials.gov protocol registration system. Written informed consent was obtained from all participants. The time schedule for the current study is shown inFig 1. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | [] | T0 = baseline assessment on the day of surgery (self-reported questionnaire); T1 = seventh postoperative day (self-reported questionnaire); STAI, State-Trait Anxiety Inventory; MFI, Multidimensional Fatigue Inventory; HADS, Hospital Anxiety and Depression Scale, STAS: State-Trait Anger Scale. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | ['pone.0193441.ref020', 'pone.0193441.ref020'] | Anxiety was measured using the Dutch version of the STAI [20]. The STAI consists of two 20-item scales. One scale measures how one feels in general (Trait anxiety) while the other measures how one feels at the present moment (State anxiety). Sum scores for both scales were calculated by adding the scores of all the items, ranging from 20 to 80. A higher score indicates a higher level of anxiety. STAI has good validity, and the STAI-State and STAI-Trait scales have similar reliability scores [20]. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | ['pone.0193441.ref021', 'pone.0193441.ref021'] | Fatigue was measured using the Dutch version of the MFI [21], a 20-item questionnaire covering five scales: General fatigue, Physical fatigue, Mental fatigue, Reduced motivation, and Reduced activity. A sum score was calculated by adding the scores of all the items, ranging from 20 to 100. A higher score indicates a higher degree of fatigue. In the majority of cases, MFI has good validity and reliability [21]. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | ['pone.0193441.ref022', 'pone.0193441.ref023'] | Depressive moods were measured using a Dutch version of the HADS [22], which consists of two 7-item scales: one for anxiety (HADS-A) and one for depression (HADS-D). Each item comprises four answer alternatives, and for each of the scales the total score ranges from 0 to 21. A higher score indicates a higher degree of either anxiety or depression. The HADS has adequate validity and internal consistency in the Dutch population [23]. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | ['pone.0193441.ref024', 'pone.0193441.ref024'] | Aggression regulation was assessed using the Dutch version of the STAS [24], which consists of two 10-item scales, one covering the State-aggression (how angry one feels at the moment) and one covering the Trait-aggression (how angry one feels in general). The sum scores range from 10 to 40. A higher score indicates a higher degree of aggression. Both subscales have adequate validity and reliability [24]. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | [] | The sociodemographic variables we considered were sex, age, educational level, marital status, employment, religion, having children, and type of nationality (i.e. Dutch versus non-Dutch). The medical variables we considered were Body Mass Index (BMI) and preoperative heart rate (HR). | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | [] | Baseline assessments of all psychological outcome variables were used as candidate prognostic variables. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | ['pone.0193441.ref025', 'pone.0193441.ref025'] | Self-esteem was measured using the 10-item Dutch version of the RSES [25]. The sum score ranges from 10 to 40. A higher score indicates a higher degree of self-esteem. RSES has good validity and reliability [25]. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | ['pone.0193441.ref026', 'pone.0193441.ref027'] | Self-efficacy was measured using the Dutch version of the GSES [26]. The sum score ranges from 10 to 40. A higher score indicates a higher degree of self-efficacy. In addition to an adequate validity, GSES also has an adequate reliability in the Dutch population [27]. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
['PMC5894974'] | ['29641522'] | ['pone.0193441.ref028', 'pone.0193441.ref029', 'pone.0193441.ref030', 'pone.0193441.ref031', 'pone.0193441.ref032', 'pone.0193441.ref033'] | We explored the relations between baseline assessments (T0, just before surgery) and outcome variables (T1, seventh day after surgery). We included sociodemographic, medical, and psychological variables assessed at baseline in the model simultaneously. Predictor variables were entered for all outcomes in the model to allow for insight into the relative importance of each predictor. The analyses were guided by statistical and clinical–theoretical criteria. The first step was to analyze all predictor variables together with the seven outcome variables that were assessed on the seventh day after surgery. In the second step, we eliminated less-relevant predictor variables according to the backward elimination procedure (P-to-remove > 0.20 on at least four outcome variables) provided that there was no substantial loss of information (i.e., a decrease in P value for model fit ≥ 0.10). Type of intervention as randomized was adjusted for. Modeling was performed using the Maximum Likelihood (ML) an estimation method. The distributions of the variables were considered non-normal, so the final modeling was performed using the Maximum Likelihood for Robustness (MLR) as an estimation method. The following measures were used to test for adequacy of the model fit: 1. Chi-square for model fit (low and non-significant values of the chi-square are desired; P value > 0.05); 2. Chi-square/degrees of freedom ratio (a value < 2.0 was considered to be acceptable); 3. Comparative Fit Index (CFI) and Tucker-Lewis Index (TLI) (high values are desired (> 0.95) [28,29]; 4. Root Mean Square Error of Approximation (RMSEA: a value < 0.05 indicates a close fit) [30]; and 5. Standardized Root Mean Squares of Residuals (SRMR: a value of < 0.08 indicates a reliable fit) [31]. After testing for goodness-of-fit, it was of particular clinical interest to calculate the percentages of explained variance for each outcome variable. There was little missing data (< 5% for all variables), which were not included in the prognostic analysis. Bootstrapping was used for internal validation [32,33]. Each subsample was a random sample with replacement from the full sample, and we checked the internal validity of the prognostic model using 1000 bootstrap samples. Bias-corrected standard errors were estimated. For each predictor, we estimated the unstandardized regression coefficients, including the 95% bootstrapped confidence intervals, and standardized regression coefficients as effect estimates. We used SPSS version 20.0 (IBM Corp. Armonk, NY) and Mplus version 7 (Muthén and Muthén, Los Angeles, CA) for statistical analyses. Estimates were regarded as statistically significant if the two-sided P value was < 0.05. | PMC5894974 | Research Article; Biology and Life Sciences; Psychology; Emotions; Anxiety; Social Sciences; Psychology; Emotions; Anxiety; Medicine and Health Sciences; Surgical and Invasive Medical Procedures; Medicine and Health Sciences; Mental Health and Psychiatry; Mood Disorders; Depression; Biology and Life Sciences; Behavior; Aggression; Medicine and Health Sciences; Diagnostic Medicine; Signs and Symptoms; Fatigue; Medicine and Health Sciences; Pathology and Laboratory Medicine; Signs and Symptoms; Fatigue; People and Places; Population Groupings; Age Groups; Children; People and Places; Population Groupings; Families; Children; Physical Sciences; Physics; Classical Mechanics; Damage Mechanics; Material Fatigue; Physical Sciences; Materials Science; Materials Physics; Material Fatigue; Physical Sciences; Physics; Materials Physics; Material Fatigue; Medicine and Health Sciences; Mental Health and Psychiatry | null | 29,641,522 | Prognostic model for psychological outcomes in ambulatory surgery patients: A prospective study using a structural equation modeling framework | Mijderwijk H, Stolker RJ, Duivenvoorden HJ, Klimek M, Steyerberg EW. | PLoS One. 2018 Apr 11;13(4):e0193441. doi: 10.1371/journal.pone.0193441. eCollection 2018. | Mijderwijk H | PLoS One | 2,018 | 2018/04/12 | PMC5894974 | null | 10.1371/journal.pone.0193441 | oa_comm/txt/all/PMC5894974.txt | 2ab04bb2a251199ccc7bdda01c13474f | PLoS One. 2018 Apr 11; 13(4):e0193441 | 2021-06-18 17:06:35 | CC BY | no |
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