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Reproductive endocrine health in pubertal females with epilepsy on antiepileptic drugs: time to screen?

Although previous studies suggest that valproate (VPA) may induce reproductive endocrine disorders, the effects of newer antiepileptic drugs (AEDs) on reproductive endocrine health have not been widely investigated and compared with those of older AEDs. Therefore, this multicenter cross-sectional study aimed to evaluate the prevalence of reproductive endocrine dysfunctions in pubertal females with epilepsy receiving VPA, lamotrigine (LTG), or levetiracetam (LEV) monotherapy. Pubertal girls on VPA (n = 11), LTG (n = 8), or LEV (n = 13) monotherapy for at least 6 months were recruited. Healthy sex-matched and age-matched subjects were enrolled as controls (n = 32). Each participant underwent a comprehensive physical examination concerning signs of hyperandrogenism. The Ferriman-Gallwey score of hirsutism was assessed. In addition, all patients completed a standardized questionnaire regarding epilepsy, menstrual cycle, and hirsutism features. Adiposity indices were measured and weight gain was documented for each subject. Hirsutism score, occurrence of hyperandrogenism features, and adiposity indices were significantly higher in the VPA group when compared with LEV and control groups. VPA therapy was more frequently associated with weight gain when compared with LTG and controls, whereas no significant differences with regard to signs of hyperandrogenism were found between VPA and LTG groups. Furthermore, no differences in menstrual disorders were observed between groups.

Pubertal girls with epilepsy receiving VPA monotherapy were more likely to develop signs of hyperandrogenism, that is, hirsutism and acanthosis, than those on LEV or controls. However, no differences in occurrence of menstrual disorders and other reproductive dysfunctions were found between VPA, LTG, LEV, and control groups. These findings do not allow us to clearly determine whether or not VPA, LEV, and LTG monotherapies considerably affect reproductive endocrine health in pubertal girls with epilepsy. Therefore, further prospective studies of larger sample sizes are needed to establish if screening tests should be recommended.

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Prospective evaluation of 18F-fluorodeoxyglucose positron emission tomography-computed tomography for response evaluation in recurrent carcinoma cervix: does metabolic response predict survival?

This study aimed to assess the role of (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in response assessment of patients with recurrent carcinoma cervix and in evaluating the predictive value of metabolic response for progression-free survival (PFS) and overall survival (OS). Thirty-six patients with histopathologically or clinically evident recurrent cervical carcinoma underwent a pretherapy and a posttherapy (18)F-FDG PET-CT for treatment response evaluation. Positron emission tomography-CT images were analyzed by 2 experienced nuclear medicine physicians. Response was categorized using European Organization for Research and Treatment of Cancer (EORTC) criteria into complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). Clinical/imaging follow-up (minimum of 6 months) and/or histopathologic findings were taken as reference standard. Patients were categorized into 2 groups, those with PMD and those without PMD (ie, CMR, PMR, and SMD). Progression-free survival and OS based on PET-CT response were measured from the date of posttherapy PET-CT to the first documentation of progression of disease and death, respectively. On the basis of metabolic response on posttherapy PET-CT, 6 patients had CMR, 12 patients had PMR, 7 patients had SMD, and 11 patients had PMD. Progression-free survival for patients with cervical carcinoma ranged from 0.5 to 26.5 months (mean [SD], 6.7 [6.1]months). Median PFS for patients with PMD was 3.1 months, whereas median PFS for those without PMD was not reached. Patients who did not show PMD on posttherapy PET-CT had a significantly better PFS than those patients who showed PMD (P<0.0001; HR, 0.14). There was no statistically significant difference in OS between the 2 groups (P = 0.187; HR, 0.39).

(18)F-fluorodeoxyglucose PET-CT is an effective tool for treatment response evaluation in recurrent carcinoma cervix. Patients with metabolically progressive disease on posttherapy (18)F-FDG PET-CT have a significantly shorter PFS.

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Is the area under an ROC curve a valid measure of the performance of a screening or diagnostic test?

The area under a receiver operating characteristic (ROC) curve (the AUC) is used as a measure of the performance of a screening or diagnostic test. We here assess the validity of the AUC. Assuming the test results follow Gaussian distributions in affected and unaffected individuals, standard mathematical formulae were used to describe the relationship between the detection rate (DR) (or sensitivity) and the false-positive rate (FPR) of a test with the AUC. These formulae were used to calculate the screening performance (DR for a given FPR, or FPR for a given DR) for different AUC values according to different standard deviations of the test result in affected and unaffected individuals. The DR for a given FPR is strongly dependent on relative differences in the standard deviation of the test variable in affected and unaffected individuals. Consequently, two tests with the same AUC can have a different DR for the same FPR. For example, an AUC of 0.75 has a DR of 24% for a 5% FPR if the standard deviations are the same in affected and unaffected individuals, but 39% for the same 5% FPR if the standard deviation in affected individuals is 1.5 times that in unaffected individuals.

The AUC is an unreliable measure of screening performance because in practice the standard deviation of a screening or diagnostic test in affected and unaffected individuals can differ. The problem is avoided by not using AUC at all, and instead specifying DRs for given FPRs or FPRs for given DRs.

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Living alone and psychological well-being in mid-life: does partnership history matter?

Previous studies have found that the duration since a union dissolution and the number of union dissolutions are associated with psychological well-being. However, these two aspects of partnership history have rarely been considered jointly in models of mental health. This study aims to investigate how the time since the most recent union dissolution and the number of union dissolutions are related to two indicators of psychological well-being-life satisfaction and the General Health Questionnaire-among middle-aged solo-living British men and women. Data from the United Kingdom Household Longitudinal Study from 2009 to 2010 are analysed for 1201 50-64 year olds who were living alone and have ever been in a co-resident union (472 men and 729 women). Logistic regression analysis is used to investigate how life satisfaction and General Health Questionnaire 12 (GHQ-12) caseness are associated with partnership characteristics. GHQ-12 caseness is significantly and positively associated with the number of union dissolutions and negatively with the duration since the most recent union dissolution. This is the case among both genders, in models in which these partnership characteristics are entered separately and jointly, and in models controlling for parenthood status, socioeconomic status and physical health.

The results suggest that there is a short-term deterioration in mental health after a partnership break-up and that experiencing multiple union dissolutions is detrimental for psychological well-being. The association between partnership characteristics and the two measures of psychological well-being differs, which is in line with previous research showing that negative affect and life satisfaction are two separate constructs.

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Is the macromolecule signal tissue-specific in healthy human brain?

The macromolecule signal plays a key role in the precision and the accuracy of the metabolite quantification in short-TE (1) H MR spectroscopy. Macromolecules have been reported at 1.5 Tesla (T) to depend on the cerebral studied region and to be age specific. As metabolite concentrations vary locally, information about the profile of the macromolecule signal in different tissues may be of crucial importance. The aim of this study was to investigate, at 7T for healthy subjects, the neurochemical profile differences provided by macromolecule signal measured in two different tissues in the occipital lobe, predominantly composed of white matter tissue or of grey matter tissue. White matter-rich macromolecule signal was relatively lower than the gray matter-rich macromolecule signal from 1.5 to 1.8 ppm and from 2.3 to 2.5 ppm with mean difference over these regions of 7% and 12% (relative to the reference peak at 0.9 ppm), respectively. The neurochemical profiles, when using either of the two macromolecule signals, were similar for 11 reliably quantified metabolites (CRLB < 20%) with relatively small concentration differences (<0.3 μmol/g), except Glu (± 0.8 μmol/g).

Given the small quantification differences, we conclude that a general macromolecule baseline provides a sufficiently accurate neurochemical profile in occipital lobe at 7T in healthy human brain.

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Ferritin in dialysis-related arthropathy: could it be a possible biochemical indicator of articular chronic pain?

The aim of our study was to evaluate laboratory data behaviour in two dialysis populations, with and without dialysis-related arthropathy and pain. We produced an elaboration of more than 160,000 items of biochemical data of 25 dialysis-related arthropathy patients with chronic articular pain, and 25 patients asymptomatic for joint pain and arthropathy. The pain visual analogue scale (VAS) was employed for pain intensity determination. The serum level of β-2 microglobulin was similar in the two groups of patients, while ferritin values were significantly higher in symptomatic patients. We excluded the possibility that the ferritin difference between the two groups was due to different iron storage and to an inflammatory profile. Furthermore, the pain VAS mean value was higher in patients who had higher ferritin and pain than in asymptomatic patients.

It is important to underline that the higher value of ferritin in patients with chronic pain due to dialysis- -related arthropathy could represent a new stimulus for a deeper investigation of this indicator, setting a periodic revelation of pain intensity.

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Fluridone: a combination germination stimulant and herbicide for problem fields?

Problem weeds in agriculture, such as Lolium rigidum Gaud., owe some of their success to their large and dormant seed banks, which permit germination throughout a crop-growing season. Dormant weed seed banks could be greatly depleted by application of a chemical that stimulates early-season germination and then kills the young seedlings. Fluridone, a phytoene desaturase-inhibiting herbicide that can also break seed dormancy, was assessed for its efficacy in this regard. The germination of fluridone-treated Lolium rigidum seeds was stimulated on soils with low organic matter, and almost 100% seedling mortality was observed, while the treatment was only moderately effective on a high-organic-matter potting mix. Seedlings from wheat, canola, common bean and chickpea seeds sown on fluridone-treated sandy loam were bleached and did not survive, but lupins and field peas grew normally.

This proof-of-concept study with fluridone suggests that it may be possible to design safe and effective molecules that act as germination stimulants plus herbicides in a range of crop and soil types: a potentially novel way of utilising herbicides to stimulate seed bank germination and a valuable addition to an integrated weed management system.

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Pregnancy with oocytes characterized by narrow perivitelline space and heterogeneous zona pellucida: is intracytoplasmic sperm injection necessary?

This retrospective study analyzed fertilization protocols and pregnancy outcomes for oocytes with with narrow perivitelline space and heterogeneous zona pellucid (NPVS/HZP). In 63 in-vitro fertilization cycles filled with NPVS/HZP oocytes (abnormal oocytes group) and 521 cycles with normal oocytes (normal oocytes group), major clinical and laboratory parameters were recorded and compared in different fertilization cycles (conventional IVF cycles, rescue ICSI cycles, and traditional ICSI cycles). NPVS/HZP oocytes meant lower MIIoocytes rates in both IVF and ICSI cycles compared with normal oocytes (p<0.05). The 2PN rates for abnormal oocytes were significantly lower than those for normal oocytes in both conventional IVF cycles (58.8% VS 71.3%, P<0.05) and rescue ICSI cycles (58.0% VS 78.0%, P = 0.0000). The high-quality embryo rates in normal oocytes groups were significantly higher than those in abnormal oocytes groups in different fertilization cycles (52.2% VS 35.0%, P<0.01; 42.9% VS 23.9%, P<0.001; 50.6% VS 31.0%, P = 0.0000, respectively). No clinical pregnancy was obtained from abnormal oocytes in 11 conventional IVF cycles. The clinical pregnancy rates in rescue ICSI and traditional ICSI cycles were comparatively lower in abnormal oocytes groups, but there was no significant difference as compared with normal oocytes groups (35.0% VS 48.1% and 26.7% VS 50.7%, P>0.05, respectively).

Retrieval of oocytes characterized by NPVS/PZP from cycle to cycle was one of the reasons for obscure infertility. ICSI may be the right way to avoid fertilization failure and get pregnancy in women with NPVS/HZP oocytes.

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Do body mass index and fat volume influence vocal quality, phonatory range, and aerodynamics in females?

To analyze the impact of body weight and body fat volume on selected parameters of vocal quality, phonatory range, and aerodynamics in females. Based on measurements of body mass index in combination with body fat volume, 29 normophonic female subjects were classified as normal weight, underweight, and obese. Voice quality was investigated via auditory-perceptual ratings of breathiness, roughness, and overall dysphonia severity, via various acoustic measures and a multiparametric index. Phonatory range performance was examined using selected measures of the voice range profile and speech range profile. Measures of vocally relevant aerodynamics included vital capacity (i.e., VC), expected VC, phonation quotient, and maximum phonation time (i.e., MPT). Significant differences between the three weight groups were found across several measures of intensity, VC, MPT, and shimmer. As compared to the other groups, significantly higher values of maximum and minimum intensity levels, as well as sound pressure level during habitual running speech were observed for the obese group (all p-values<0.05); whereas, the underweight group had significantly lower values for VC and ratio of expected to measured VC (p-values<0.01). Furthermore, underweight subjects differed significantly as compared to normal weight subjects with lower MPT (p=0.025) and higher lowest-F0 (p=0.035). Finally the obese group showed significantly lower shimmer values than the normal weight subjects (p<0.05).

Body weight and body fat volume appear to influence select objective measures of voice quality, vocal aerodynamics, and phonatory range performance.

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Is urinary incontinence the hidden secret complications after total hip arthroplasty?

We hypothesized that posterior approach (PA) dissecting the short external rotators and anterior approach (AA) not dissecting these have different influences on the pelvic floor muscles and subsequently affect urinary incontinence. The objective of this study was to investigate whether AA advantageously influences symptoms of urinary incontinence. The subjects were 76 female patients who underwent their primary total hip arthroplasty. The presence or absence of urinary incontinence before and after surgery was surveyed by a direct interview at the time of outpatient examination within a period from 1.5 year after surgery using the international consultation on incontinence questionnaire-short form. Urinary incontinence improved after surgery in eight patients (22.2%), slightly improved in one (2.8%), remained unchanged in 26 (72.2%), slightly aggravated in one (2.8%) in the AA group. In the PA group, urinary incontinence improved after surgery in one (2.5%), remained unchanged in 30 (75%), slightly aggravated in four (10%), and aggravated in five (12.5%). Symptoms of urinary incontinence were significantly improved in the AA group and aggravated in the PA group (Mann-Whitney U test, P = 0.0057).

As the anatomical characteristic of the short external rotators, the root of the internal obturator muscle is connected to the levator ani muscle. Among the pelvic floor muscles, this levator ani muscle is closely involved in supporting the pelvic organs. Since the short external rotators may have been atrophied due to hip joint dysfunction before surgery, if the strength of this muscle group recovers, support of the pelvic organs and urinary incontinence may be improved. It was assumed that surgery through AA improved external rotation contracture of the hip joint and leg length, which increased tension of the internal obturator muscle, with which tension of the pelvic floor muscle also increased and improved urinary incontinence.

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Does retirement reduce the risk of myocardial infarction?

Recent studies have suggested that retirement may have beneficial effects on health outcomes. In this study we examined whether the risk of myocardial infarction (MI) was reduced following retirement in a Danish population sample. Participants were 617 511 Danish workers, born between 1932 and 1948, entering the study at the age of 60, without previous known incidents of ischaemic heart disease. Information on retirement and MI were obtained from Danish national registers. A Cox proportional hazard model was used to address the relation between retirement and onset of MI, while adjusting for age, sex, income, occupational position, education, cohabitation and immigrant status. The participants were followed for up to 7 years. Of the study population, 3% were diagnosed with MI during follow-up. Retirement was associated with a modestly higher risk of MI with a hazard ratio of 1.11 (95% confidence interval: 1.06, 1.16) when comparing retirees with active workers of the same age.

This study does not support the hypothesis that retirement reduces risk of MI. On the contrary, we find that retirement is associated with a modestly increased risk of MI.

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Do Malassezia species play a role in exacerbation of scalp psoriasis?

Clinical expression of psoriasis is in part dependent on external factors, such as drugs, microorganisms or stress. However convincing evidence of the role of Malassezia species in the pathogenesis of the psoriasis is still lacking. Samples taken from scalp skin of 40 psoriatic patients and the same number of healthy individuals were observed under direct microsocopic examination and cultured on modified Dixon agar. Direct microscopy examination of psoriatic scalp scales was positive in 30 (75%) patients; while it was positive in only 12 (30%) healthy subjects (P=0.003). Half of the cultures from healthy subjects showed no growth of colonies, but only 8 (15%) of psoriatic patients were negative. When an exacerbation has occurred in the previous weeks, pseudohyphaes were observed in 12 (40%) patients, Malassezia globosa was isolated in 18 (45%) patients and Malassezia restricta was isolated in 12 (30%) patients. In the group of patients having stable lesion, without any exacerbation in the previous weeks, no pseudohypahes were observed, M. globosa was not isolated, M. restricta was isolated in 4 (10%), and cultures were negative in 6 of them (15%).

Malassezia species form an integral part of normal cutaneous microflora in humans, however we found that during the episodes of exacerbation of the disease the presence of these yeasts, and particularly M. globosa, was increased.

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Are depressive symptomatology and self-focused attention associated with subjective memory impairment in older adults?

Subjective memory impairment (SMI) refers to conditions in which people complain of memory problems despite intact cognition. The primary purpose of the present study was to examine the roles of self-focused attention and depressive symptomatology in subjective memory complaints. One hundred and eight patients who visited a memory disorder clinic with complaints of memory decline, but who were found on subsequent neuropsychological assessment to have normal cognitive function, were recruited to participate in the study. The severity of subjective memory complaints was measured with the modified Multifactorial Memory Questionnaire. In addition, neuropsychological functions, self-focused attention, and depressive symptomatology were also assessed. The results showed that the severity of SMI was not significantly correlated with any of the neuropsychological test scores except for the complex figure copy. The severity of SMI, however, was significantly correlated with self-focused attention and depressive symptomatology. Hierarchical regression analysis revealed that self-focused attention and depressive symptomatology significantly contributed to the severity of subjective memory complaints over and above the neuropsychological test performance. The interaction effects between self-focused attention/depressive symptomatology and objective memory performance on the severity of SMI were not significant.

In conclusion, self-focused attention and depressive symptomatology appear to play important roles in the severity of SMI, even though it is not clear how these factors interact with objective memory performance. Clinical implications as well as limitations of the present study were discussed.

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Is our residency program successful?

In an attempt to better define the success of our residency program with regard to resident development, we committed to develop an ongoing assessment of residency performance and devised an outcomes assessment system. We describe the process and structure that we used to construct an outcomes assessment system. We discuss the process we used to discern whether or not our program is successful as well as offer tips on what data to collect and track should other residency programs decide to devise a similar outcomes assessment database.

Taking time to "step back" to take inventory of a residency program and ensure year over year and at the end of training residents have developed and matured as planned is an educationally sound practice. Structuring an outcomes assessment system like the one that we discuss here can aid program directors with this important task.

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Should general surgery residents be taught laparoscopic pyloromyotomies?

The authors examine the ethical implications of teaching general surgery residents laparoscopic pyloromyotomy.DESIGN/ Using the authors' previously presented ethical framework, and examining survey data of pediatric surgeons in the United States and Canada, a rigorous ethical argument is constructed to examine the question: should general surgery residents be taught laparoscopic pyloromyotomies? A survey was constructed that contained 24 multiple-choice questions. The survey included questions pertaining to surgeon demographics, if pyloromyotomy was taught to general surgery and pediatric surgery residents, and management of complications encountered during pyloromyotomy. A total of 889 members of the American Pediatric Surgical Association and Canadian Association of Paediatric Surgeons were asked to participate. The response rate was 45% (401/889). The data were analyzed within the ethical model to address the question of whether general surgery residents should be taught laparoscopic pyloromyotomies.

From an ethical perspective, appealing to the ethical model of a physician as a fiduciary, the answer is no.

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Can leisure activities slow dementia progression in nursing home residents?

To examine the effects of complex cognitive (mahjong) and physical (Tai Chi) activities on dementia severity in nursing home residents with dementia. Cluster-randomized open-label controlled design. 110 residents were randomized by nursing home into three conditions: mahjong, Tai Chi, and simple handicrafts (control). Activities were conducted three times a week for 12 weeks. Clinical Dementia Rating (CDR) was taken at 0 (baseline), 3 (post-treatment), 6, and 9 months. The outcome measure was CDR sum-of-box, which is a composite measure of both cognitive and functional deterioration in dementia. Intent-to-treat analyses were performed using multilevel regression models. Apolipoprotein E ε4 allele and education were included as covariates. Neither treatments had effects on the cognitive and functional components of the CDR, but mahjong had a significant interaction with time on the CDR sum-of-box total, suggesting a slower rate of global deterioration in the mahjong group as compared with the control group.

Mahjong led to a gradual improvement in global functioning and a slightly slower rate of dementia progression over time. The effect was generalized and was not specific to cognition or daily functioning.

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Current practice in the treatment of AO type 31-A2 hip fractures: does sub-specialty and experience of surgeon determine type of fixation?

Debate surrounds the optimal treatment of AO type 31-A2 fractures of the hip. Two principal treatment modalities are the compression hip screw (CHS) and cephallomedullary device (CMD). The use of CMD's is steadily increasing, for fixation of this fracture type, despite a lack of supportive evidence. 100 trauma consultants were asked for their opinion towards treatment of an AO type 31-A2 fracture. Subspecialty and length of time in post were also recorded. A significant proportion of consultants opted to use a CMD. Consultants who had been in post for a shorter time, and those in specialties other than lower limb were more likely to use a CMD. NICE guidelines suggest CHS for AO type 31-A2 fractures.

CMD accounts for a large percentage of treatment in our study, despite NICE guidelines, and other studies suggest their use is rising. We suggest there is a trend of less experienced consultants, and consultants whose specialties are those other than lower limb, using CMD more often. This may be creating an increased cost burden to the NHS, with no evidence to support their use.

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Can cognitive deficits differentiate between schizophrenia with and without obsessive-compulsive symptoms?

The frequent occurrence of obsessive-compulsive symptoms (OCS) in the course of schizophrenia and their impact on the functional outcome of the illness underlie the suggestion that the presence of OCS represents a separate subtype of schizophrenia, with a distinct clinical presentation and prognosis and specific neurobiological characteristics. This study investigated whether the presence of OCS in schizophrenia is associated with worse cognitive functioning in the domains of processing speed, executive functions and visuospatial memory. We also explored whether the degree of impairment in any of these cognitive domains could predict group membership (i.e. Schizophrenia with OCS [Sch-OCS] and Schizophrenia without OCS) and if there was a relationship between cognitive functioning and severity of OCS within the Sch-OCS group. Forty patients with schizophrenia, 20 with and 20 without OCS, individually matched for age, gender, years of education and severity of psychotic symptoms and 20 healthy controls underwent a comprehensive neuropsychological assessment. Only lower performance in processing speed discriminated patients with OCS from patients without OCS. Processing speed impairment not only classified patients in OCS or non-OCS group but was also independent of the severity of OCS symptoms.

The notion of additive effects of both schizophrenia and OCD on the structural and functional integrity of the brain circuits that support cognitive functions warrants further investigation in longitudinal neuropsychological and neuroimaging studies with larger samples and sufficient variation in the severity of OCS.

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Is "pelvic radiation disease" always the cause of bowel symptoms following prostate cancer intensity-modulated radiotherapy?

Pelvic radiation disease (PRD) also widely known as "radiation proctopathy" is a well recognised late side-effect following conventional prostate radiotherapy. However, endoscopic evaluation and/or specialist referral for new or persistent post-prostate radiotherapy bowel symptoms is not routine and serious diagnoses may potentially be missed. Here we report a policy of endoscopic evaluation of bowel symptoms persisting>90 days post radiotherapy for prostate cancer. A consecutive series of 102 patients who had radical prostate intensity-modulated radiotherapy (IMRT)/image-guided radiotherapy (IGRT) and who had new or ongoing bowel symptoms or positive faecal occult blood tests (FOBT) on follow up visits more than three months after treatment, were referred for endoscopic examination. All but one (99%) had full colonoscopic investigation. Endoscopic findings included gastric/colonic/rectal polyps (56%), diverticular disease (49%), haemorrhoids (38%), radiation proctopathy (29%), gastritis/oesophagitis (8%) and rarer diagnoses, including bowel cancer which was found in 3%. Only four patients (4%) had radiation proctopathy without associated pathology and 65 patients (63%) had more than one diagnosis. If flexible sigmoidoscopy alone were used, 36.6% of patients and 46.6% patients with polyp(s) would have had their diagnoses missed.

Our study has shown that bowel symptoms following prostate IMRT/IGRT are due to numerous diagnoses other than PRD, including malignancy. Routine referral pathways should be developed for endoscopic evaluation/specialist review for patients with new or persistent bowel symptoms (or positive FOBT) following prostate radiotherapy. This recommendation should be considered for incorporation into national guidelines.

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Widely used track and trigger scores: are they ready for automation in practice?

Early Warning Scores (EWS) are widely used for early recognition of patient deterioration. Automated alarm/alerts have been recommended as a desirable characteristic for detection systems of patient deterioration. We undertook a comparative analysis of performance characteristics of common EWS methods to assess how they would function if automated. We evaluated the most widely used EWS systems (MEWS, SEWS, GMEWS, Worthing, ViEWS and NEWS) and the Rapid Response Team (RRT) activation criteria in use in our institution. We compared their ability to predict the composite outcome of Resuscitation call, RRS activation or unplanned transfer to the ICU, in a time-dependent manner (3, 8, 12, 24 and 36 h after the observation) by determining the sensitivity, specificity and positive predictive values (PPV). We used a large vital signs database (6,948,689 unique time points) from 34,898 unique consecutive hospitalized patients. PPVs ranged from less than 0.01 (Worthing, 3 h) to 0.21 (GMEWS, 36 h). Sensitivity ranged from 0.07 (GMEWS, 3 h) to 0.75 (ViEWS, 36 h). Used in an automated fashion, these would correspond to 1040-215,020 false positive alerts per year.

When the evaluation is performed in a time-sensitive manner, the most widely used weighted track-and-trigger scores do not offer good predictive capabilities for use as criteria for an automated alarm system. For the implementation of an automated alarm system, better criteria need to be developed and validated before implementation.

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Oncologic colorectal resection after endoscopic treatment of malignant polyps: does endoscopy have an adverse effect on oncologic and surgical outcomes?

Early colorectal cancer is increasingly treated by endoscopic removal. In cases of incomplete resection or high-risk carcinoma, additional surgery is necessary. To evaluate the frequency of subsequent oncologic surgery after endoscopic resection of colorectal cancer, the rate of lymph node metastasis, residual cancer, and morbidity and mortality rates of the operation. Any eventual adverse effect of the prior endoscopic therapy on the surgical and oncologic outcome was assessed. Retrospective review of prospectively collected data. University hospital. Sixty-six consecutive patients with incomplete endoscopic treatment and need for additional surgery between 2004 and 2011. The data of these patients were compared with those of a group of patients with surgery for early colorectal cancer during the same period without prior endoscopic resection as the control group. Rate of lymph node metastasis and residual cancer, perioperative morbidity and mortality. The lymph node metastasis rate after oncologic resection was 8.6%, and the residual cancer rate was 41%. Risk factors for residual cancer were macroscopic incomplete resection (P<.0001), positive resection margins (P = .03), and piecemeal resection (P = .004). No mortality was observed. Perioperative morbidity, mortality, and oncologic outcome were not significantly different in the group with prior endoscopic resection compared with the primarily operated group. Retrospective study.

Endoscopic treatment of malignant polyps does not worsen surgical and oncologic outcomes in cases of subsequent surgery. Because mortality and morbidity are low, oncologic resection generally should be done in the presence of risk factors for residual cancer.

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Is it possible to discriminate between neoplastic and nonneoplastic lesions in ulcerative colitis by magnifying colonoscopy?

Colitis-associated cancer/dysplasia is an intestinal tract condition that can affect the life expectancy of patients with ulcerative colitis. It is often difficult to detect neoplastic lesions. This study evaluated whether any endoscopic features are effective for distinguishing colitis-associated cancer/dysplasia from nonneoplastic lesions in patients with ulcerative colitis. The study involved 52 patients with 61 lesions treated at Hiroshima University Hospital between September 1999 and May 2012: 10 patients with 11 dysplastic lesions, 5 patients with 5 intramucosal carcinomas, 3 patients with 3 submucosal carcinomas, and 34 patients with 42 nonneoplastic lesions. All patients had undergone targeted biopsy. Endoscopic findings were compared between patients with biopsy-determined neoplasia and those with biopsy-determined nonneoplasia. Multivariate regression analysis was performed to identify magnifying chromocolonoscopy features predictive of neoplasia. No significant difference was found in conventional endoscopy features between the neoplastic and nonneoplastic lesions. Under magnifying chromocolonoscopy, the pit density of the neoplastic lesions was found to be significantly greater than that of the nonneoplastic lesions (89% [17/19] versus 60% [25/42], respectively). Pit margins were more frequently irregular in the neoplastic lesions than in the nonneoplastic lesions (63% [12/19] versus 33% [14/42], respectively).

In differentiating between colitis-associated neoplastic and nonneoplastic lesions, focus should be on the high residual density of pits and irregular pit margins observed under magnifying chromocolonoscopy.

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Can the relationship between ethnicity and obesity-related behaviours among school-aged children be explained by deprivation?

It is unclear whether cultural differences or material disadvantage explain the ethnic patterning of obesogenic behaviours. The aim of this study was to examine ethnicity as a predictor of obesity-related behaviours among children in England, and to assess whether the effects of ethnicity could be explained by deprivation. Five primary care trusts in England, 2010-2011. Parents of white, black and South Asian children aged 4-5 and 10-11 years participating in the National Child Measurement Programme (n=2773). Parent-reported measures of child behaviour: low level of physical activity, excessive screen time, unhealthy dietary behaviours and obesogenic lifestyle (combination of all three obesity-related behaviours). Associations between these behaviours and ethnicity were assessed using logistic regression analyses. South Asian ethnic groups made up 22% of the sample, black ethnic groups made up 8%. Compared with white children, higher proportions of Asian and black children were overweight or obese (21-27% vs16% of white children), lived in the most deprived areas (24-47% vs 14%) and reported obesity-related behaviours (38% with obesogenic lifestyle vs 16%). After adjusting for deprivation and other sociodemographic characteristics, black and Asian children were three times more likely to have an obesogenic lifestyle than white children (OR 3.0, 95% CI 2.1 to 4.2 for Asian children; OR 3.4, 95% CI 2.7 to 4.3 for black children).

Children from Asian and black ethnic groups are more likely to have obesogenic lifestyles than their white peers. These differences are not explained by deprivation. Culturally specific lifestyle interventions may be required to reduce obesity-related health inequalities.

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Prognostic factors for primary gastrointestinal stromal tumours: are they the same in the multidisciplinary treatment era?

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumour of the gastrointestinal tract. The introduction of tyrosine kinase inhibitors (TKIs) has lead to increasing use of combination of medical and surgical therapy. The aim of this study was to look at outcomes from a series of surgically treated GISTs and determine prognostic factors in the context of multimodal therapy. We analysed 104 single surgeon's patients with GIST. End points of the study were disease-specific survival (DSS), disease-free survival (DFS) and post-operative complications. Three- and 5-year DSS rates were 96.7 and 94.6 %. On univariate analysis, clear resection margins were predictive of DSS. Patients with R2 resection had a worse prognosis (3-year DSS rate of 83.3 %; 5-year DSS rate of 62.5 %) compared to patients with R0 (3-year DSS rate of 98 %; 5-year DSS rate of 98 %) or R1 resection (3-year DSS rate of 100 %; 5-year DSS rate of 100 %) (R0 vs R1 vs. R2 p = 0.001). Pre-operative factors associated with R2 resection were clinical metastatic disease (p<0.001), non-gastric tumour site (p = 0.002) and large tumour diameter (p = 0.031). Three- and 5-year DFS rates were 65.5 and 59.8 %. Serosal perforation (p = 0.013) and mitotic rate (p = 0.05) were found to be independently predictive of increased DFS. The presence of serosal perforation was associated with tumour site (p = 0.018), mitotic rate (p = 0.035), tumour diameter (p<0.001), growth pattern (p = 0.007) and age (p = 0.040).

In the multidisciplinary management of GIST, serosal perforation may represent an additional predictor of recurrence along with mitotic rate. Complete macroscopic surgical resection is the most reliable prognostic factor, and an aggressive surgical approach should be advocated.

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Increasing lateral tibial slope: is there an association with articular cartilage changes in the knee?

The geometry of the lateral tibial slope (LTS) plays an important role in the overall biomechanics of the knee. Through this study, we aim to assess the impact of LTS on cartilage degeneration in the knee. A retrospective analysis of 93 knee MRI scans (1.5 T or 3 T) for patients aged 20-45 years with no history of trauma or knee surgery, and absence of internal derangement. The LTS was calculated using the circle method. Chondropathy was graded from 0 (normal) to 3 (severe). Linear regression analysis was used for statistical analysis (p < 0.05). In our cohort of patients, a statistically significant association was seen between increasing LTS and worsening cartilage degenerative changes in the medial patellar articular surface and the lateral tibial articular surface (p < 0.05). There was no statistically significant association between increasing LTS and worsening chondropathy of the lateral patellar, medial trochlea, lateral trochlea, medial femoral, lateral femoral, and medial tibial articular surfaces.

Our results show a statistically significant association between increasing LTS and worsening cartilage degenerative changes in the medial patella and the lateral tibial plateau. We speculate that increased LTS may result in increased femoral glide over the lateral tibial plateau with subsequent increased external rotation of the femur predisposing to patellofemoral articular changes. Future arthroscopic studies are needed to further confirm our findings.

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Does a 3-min all-out test provide suitable measures of exercise intensity at the maximal lactate steady state or peak oxygen uptake for well-trained runners?

To examine whether a 3-min all-out test can be used to obtain accurate values for the maximal lactate steady state (vMLSS) and/or peak oxygen uptake (VO2peak) of well-trained runners. The 15 male volunteers (25 ± 5 y, 181 ± 6 cm, 76 ± 7 kg, VO2peak 69.3 ± 9.5 mL · kg-1 · min-1) performed a ramp test, a 3-min all-out test, and several submaximal 30-min runs at constant paces of vEND (mean velocity during the last 30 s of the 3-min all-out test) itself and vEND +0.2, +0.1, -0.1, -0.2, -0.3, or -0.4 m/s. vMLSS and vEND were correlated (r = .69, P = .004), although vMLSS was lower (mean difference: 0.26 ± 0.32 m/s, 95% CI -.44 to -.08 m/s, P = .007, effect size = 0.65). The VO2peak values derived from the ramp and 3-min all-out tests were not correlated (r = .41, P = .12), with a mean difference of 523 ± 1002 mL (95% CI 31 to 1077 mL).

A 3-min all-out test does not provide a suitable measure of vMLSS or VO2peak for well-trained runners.

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Is laparoscopy a safe approach for diffuse appendicular peritonitis?

Several studies have assessed feasibility and early outcomes of the laparoscopic approach for complicated appendicitis (CA). However, these studies suffer from limitations due to the heterogeneous definitions used for CA. No studies have assessed feasibility and early post-operative outcomes of the laparoscopic approach in the specific management of diffuse appendicular peritonitis (DAP). Consequently, outcomes of the laparoscopic approach for the management of DAP are poorly documented. The laparoscopic approach is the first-line standardised procedure used by our team for the management of DAP. All patients (aged>16 years) who underwent laparoscopy for DAP (CA with the presence of purulent fluid with or without fibrin membranes in at least a hemi abdomen) between 2004 and 2012 were prospectively included. Post-operative outcomes were analysed according to the Clavien-Dindo classification. Laparoscopy for DAP was performed for 141 patients. Mean age was 39.6 ± 20 (16-92) years. A total of 45 patients (31.9%) had pre-operative contracture. The mean pre-operative leukocyte count was 14,900 ± 4,380 mm(-3). The mean pre-operative C-reactive protein (CRP) serum concentration was 135 ± 112 (2-418) mg/dl. The conversion rate was 3.5%. The mean operative time was 80 ± 27 (20-180) min. There were no deaths. The rate of grade III morbidity was 6.5%. Ten patients (7.1%) experienced intra-abdominal abscess (IAA); seven of these cases were treated conservatively. The mean length of hospital stay was 6.9 ± 5 (2-36) days. A pre-operative leukocyte count>17,000 mm(-3), and CRP serum concentration>200 mg/dl were significant predictive factors for IAA in multivariate analyses [odds ratio (OR) 25.0, 95% confidence interval (CI) 2.4-250, p = 0.007 and OR 16.4, 95% CI 1.6-166, p = 0.02, respectively].

The laparoscopic approach for DAP is a safe and feasible procedure with a low conversion rate and an acceptable rate of IAA in view of the severity of the disease. Pre-operative leukocyte counts>17,000 mm(-3) and pre-operative CRP serum concentrations>200 mg/dl indicate a high risk of IAA.

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Amphetamine-induced appetitive 50-kHz calls in rats: a marker of affect in mania?

Animal models aimed to mimic mania have in common the lack of genuine affective parameters. Although rodent amphetamine-induced hyperlocomotion is a frequently used behavioral model of mania, locomotor activity is a rather unspecific target for developing new pharmacological therapies, and does not necessarily constitute a cardinal symptom in bipolar disorder (BD). Hence, alternative behavioral markers sensitive to stimulants are required. Since D-amphetamine induces appetitive 50-kHz ultrasonic vocalizations (USV) in rats, we asked whether established or potential antimanic drugs would inhibit this effect, thereby possibly complementing traditional analysis of locomotor activity. Amphetamine-treated rats (2.5 mg/kg) were systemically administered with the antimanic drugs lithium (100 mg/kg) and tamoxifen (1 mg/kg). Since protein kinase C (PKC) activity has been implicated in the pathophysiology of bipolar disorder and the biochemical effects of mood stabilizers, the new PKC inhibitor myricitrin (10, 30 mg/kg) was also evaluated. We demonstrate for the first time that drugs with known or potential antimanic activity were effective in reversing amphetamine-induced appetitive 50-kHz calls. Treatments particularly normalized amphetamine-induced increases of frequency-modulated calls, a subtype presumably indicative of positive affect in the rat.

Our findings suggest that amphetamine-induced 50-kHz calls might constitute a marker for communicating affect that provides a useful model of exaggerated euphoric mood and pressured speech. The antimanic-like effects of the PKC inhibitors tamoxifen and myricitrin support the predictive and etiological validity of both drugs in this model and highlight the role of PKC signaling as a promising target to treat mania and psychosis-related disorders.

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Does the association between broken partnership and first time myocardial infarction vary with time after break-up?

Marriage is associated with lower risk of coronary heart disease, but it is unknown if the association depends on time since break-up with a partner. In this study we included both married and unmarried couples to study if the association between broken partnership (BP) and first time incident myocardial infarction (MI) changes with time since BP. Register study of the entire Danish population: the population was restricted to those aged 30 to 65 years with follow-up for incident MI between 1985 and 2006 with an annual record on each individual; in total 43 million records. The register data were used to identify MI events. Poisson regression was used to study associations between time since BP and MI adjusted for socio-demographic confounders and hospital admissions. Analyses were stratified by sex. Compared with unexposed (no BP), the incidence rate ratio (IRR) of MI in men with BP in the same year was 0.97 [95% confidence interval (CI) 0.90-1.05], year before BP was 1.25 (95% CI 1.17-1.34), 2-3 years after BP was 1.12 (95% CI 1.06-1.18), 4-8 years after BP was 1.09 (95% CI 1.05-1.14) and 9+ years since BP was 1.09 (95% CI 1.05-1.12). In women, the IRR same year as BP was 1.45 (95% CI 1.26-1.66), the year after BP was 1.30 (95% CI 1.14-1.50), 2-3 years after BP was 1.26 (95% CI 1.13-1.39), 4-8 years after BP was 1.17 (95% CI 1.08-1.26) and 9+ years since BP was 1.24 (95% CI 1.17-1.32).

We found both a short-term elevated risk of first time MI following BP and a weaker long-term elevated risk, in both men and women.

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Effectiveness of ritonavir-boosted protease inhibitor monotherapy in the clinical setting: same results as in clinical trials?

Ritonavir-boosted protease inhibitor monotherapy (PIMT) is a maintenance strategy that prevents nucleoside reverse transcriptase inhibitor toxicity and reduces costs. Some trials compare PIMT with combined antiretroviral therapy, but restricted selection criteria and low sample size hamper data extrapolation to routine practice. Here, we analyse the effectiveness and safety of PIMT in clinical practice. This was a retrospective, observational, multicentre study. Adult HIV-1 patients receiving PIMT with darunavir or lopinavir were included. A Cox regression model identified independent predictors for virological failure (VF). A total of 664 patients (435 on darunavir/ritonavir and 229 on lopinavir/ritonavir) [74% male, median age of 54 years, one-third with previous protease inhibitor VF, CD4 nadir 189 cells/mm(3) and 42% coinfected with hepatitis C virus (HCV)] were analysed. After a median follow-up of 16 months, 78% of patients (95% CI 74%-81%) remained free from therapeutic failure (TF) (change between ritonavir-boosted PIs not considered failure). At 12 months, by intention-to-treat analysis (change between ritonavir-boosted PIs equals failure), 83% of patients were free from TF (87% darunavir/ritonavir versus 77% lopinavir/ritonavir, P = 0.001). Regarding VF, 88% of patients maintained viral suppression at 12 months (93% darunavir/ritonavir versus 88% lopinavir/ritonavir, P = not significant). CD4 nadir<200 cells/mm(3) [hazard ratio (HR) 1.58, 95% CI 1.01-2.49] and undetectable viral load prior to PIMT<24 months (HR 1.86, 95% CI 1.20-2.91) were independent predictors for VF. Prior protease inhibitor failure, HCV coinfection and the protease inhibitor/ritonavir used were not associated with PIMT outcome. A total of 158 patients stopped PIMT, 6% due to adverse events. Two patients developed encephalitis.

PIMT effectiveness was consistent with data from clinical trials. Viral suppression duration prior to PIMT and CD4 cell count nadir were independent predictors for PIMT outcome.

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Do smokers support smoke-free laws to help themselves quit smoking?

A growing number of smokers support smoke-free laws. The theory of self-control provides one possible explanation for why smokers support laws that would restrict their own behaviour: the laws could serve as a self-control device for smokers who are trying to quit. To test the hypothesis that support for smoke-free laws predicts smoking cessation. We used longitudinal data (1999-2000) from a US national sample of adult smokers (n=6415) from the Current Population Survey, Tobacco Use Supplements. At baseline, smokers were asked whether they made a quit attempt in the past year. They were also asked whether they thought smoking should not be allowed in hospitals, indoor sporting events, indoor shopping malls, indoor work areas, restaurants, or bars and cocktail lounges. At 1-year follow-up, smokers were asked whether they had quit smoking. Smokers who supported smoke-free laws were more likely to have made a recent quit attempt. At 1-year follow-up, those who supported smoke-free laws in 4-6 venues were more likely to have quit smoking (14.8%) than smokers who supported smoke-free laws in 1-3 venues (10.6%) or smokers who supported smoke-free laws in none of the venues (8.0%). These differences were statistically significant in multivariate analyses controlling for demographics.

Support for smoke-free laws among smokers correlates with past quit attempts and predicts future quitting. These findings are consistent with the hypothesis that some smokers support smoke-free laws because the laws could help them quit smoking.

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Is serum zinc associated with pancreatic beta cell function and insulin sensitivity in pre-diabetic and normal individuals?

Cross sectional study of a random sample of older community-dwelling men and women in Newcastle, New South Wales, Australia. Beta cell function, insulin sensitivity and insulin resistance were calculated for normoglycaemic and prediabetes participants using the Homeostasis Model Assessment (HOMA-2) calculator. A total of 452 participants were recruited for this study. Approximately 33% (N = 149) had diabetes, 33% (N = 151) had prediabetes and 34% (N = 152) were normoglycaemic. Homeostasis Model Assessment (HOMA) parameters were found to be significantly different between normoglycaemic and prediabetes groups (p<0.001). In adjusted linear regression, higher serum zinc concentration was associated with increased insulin sensitivity (p = 0.01) in the prediabetic group. There was also a significant association between smoking and worse insulin sensitivity.

Higher serum zinc concentration is associated with increased insulin sensitivity. Longitudinal studies are required to determine if low serum zinc concentration plays a role in progression from pre-diabetes to diabetes.

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Generalized linear mixed models for binary data: are matching results from penalized quasi-likelihood and numerical integration less biased?

Over time, adaptive Gaussian Hermite quadrature (QUAD) has become the preferred method for estimating generalized linear mixed models with binary outcomes. However, penalized quasi-likelihood (PQL) is still used frequently. In this work, we systematically evaluated whether matching results from PQL and QUAD indicate less bias in estimated regression coefficients and variance parameters via simulation. We performed a simulation study in which we varied the size of the data set, probability of the outcome, variance of the random effect, number of clusters and number of subjects per cluster, etc. We estimated bias in the regression coefficients, odds ratios and variance parameters as estimated via PQL and QUAD. We ascertained if similarity of estimated regression coefficients, odds ratios and variance parameters predicted less bias. Overall, we found that the absolute percent bias of the odds ratio estimated via PQL or QUAD increased as the PQL- and QUAD-estimated odds ratios became more discrepant, though results varied markedly depending on the characteristics of the dataset.

Given how markedly results varied depending on data set characteristics, specifying a rule above which indicated biased results proved impossible. This work suggests that comparing results from generalized linear mixed models estimated via PQL and QUAD is a worthwhile exercise for regression coefficients and variance components obtained via QUAD, in situations where PQL is known to give reasonable results.

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Is there an alternative to continuous opioid infusion for neonatal pain control?

Continuous opioid infusion (COI) remains the mainstay of analgesic therapy in the neonatal intensive care unit (NICU). Parent/nurse-controlled analgesia (PNCA) has been accepted as safe and effective for pediatric patients, but few reports include use in neonates. This study sought to compare outcomes of PNCA and COI in postsurgical neonates and young infants. Twenty infants treated with morphine PNCA were retrospectively compared with 13 infants treated with fentanyl COI in a Midwestern pediatric hospital in the United States. Outcome measures included opioid consumption, pain scores, frequency of adverse events, and subsequent methadone use. The PNCA group (median 6.4 μg · kg(-1) · h(-1) morphine equivalents, range 0.0-31.4) received significantly less opioid (P<0.001) than the COI group (median 40.0 μg · kg(-1) · h(-1) morphine equivalents; range 20.0-153.3), across postoperative days 0-3. Average daily pain scores (based on 0-10 scale) were low for both groups, but median scores differed nonetheless (0.8 PNCA vs 0.3 COI, P<0.05). There was no significant difference in the frequency of adverse events or methadone use.

Results suggest PNCA may be a feasible and effective alternative to COI for pain management in postsurgical infants in the NICU. Results also suggest PNCA may provide more individualized care for this vulnerable population and in doing so, may potentially reduce opioid consumption; however, more studies are needed.

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Does the DVR(®) plate restore bony anatomy following distal radius fractures?

Fractures of the distal radius are common. Malreduced fractures are associated with residual functional deficiency. There has been a trend over the last few years for using fixed angle volar locking plates to surgically stabilise this injury. Our unit uses the DVR(®) plate (DePuy, Warsaw, IN, US). Nevertheless, it is unknown whether the normal bony anatomy is recreated or merely restored to acceptable limits with its usage. The aim of this study was to evaluate the reduction achieved compared with an uninjured population and pre-existing quoted 'normal' values. Furthermore, we wanted to identify the percentage of cases that were reduced to acceptable limits, and determine whether the grade of the surgeon and fracture type was a confounding influence on this reduction. A retrospective review of the 3-month postoperative radiography of 48 eligible patients who underwent open reduction and internal fixation of a distal radius fracture with a DVR(®) plate was undertaken. Volar tilt, radial length and inclination were different to quoted normal values (p<0.01). Despite this, these parameters fell within acceptable limits in 46 cases; this was not influenced by fracture type or grade of operating surgeon.

The DVR(®) plate restores the bony anatomy to within acceptable limits in the majority of patients who have sustained a fracture of the distal radius although of all parameters investigated, the widest variability is seen in volar tilt.

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Active or passive pulmonary vein in atrial fibrillation: is pulmonary vein isolation always essential?

The role of pulmonary veins (PVs) in persistent atrial fibrillation (AF) perpetuation appears less important than in paroxysmal AF. Electrogram-based substrate ablation is not widely performed as a stand-alone strategy. To evaluate PV activity in AF perpetuation and efficacy of our patient-tailored ablation strategy (electrogram-based substrate ablation with or without pulmonary vein isolation [PVI]). One hundred twenty-one patients with paroxysmal (n = 19; 15.7%), persistent (n = 77; 63.6%), or long-standing persistent (n = 25; 20.7%) AF underwent electrogram-based substrate ablation with AF termination end point: sinus rhythm or atrial tachycardia conversion. Before ablation, we classified PVs as "passive" if silent PV or if PV cycle length is greater than left atrial appendage cycle length. No PVI was performed in such cases. Passive PVs were observed in 52 of 121 patients (paroxysmal AF = 0%, persistent AF = 40%, and long-standing persistent AF = 76%; P<.0001]). Substrate ablation terminated AF in 95.6% (sinus rhythm conversion in 80.2%). Compared with patients with active PVs, patients with passive PVs had longer AF sustained duration (19.1 ± 29.7 months vs 4.9 ± 11.1 months; P<.0001), larger left atrial diameter (46.9 ± 7.3 mm vs 41.9 ± 6.0 mm; P = .0014), lower left ventricular ejection fraction (45.4% ± 13.5% vs 55.1% ± 9.4%; P<.0001), and more often structural heart disease (57% vs 33%; P = .02). After a follow-up of 20.39 ± 11.23 months (1.6 procedures per patient), 82% were arrhythmia free with this strategy.

PV activity during AF decreases with AF chronicity, left atrial dilatation, and left ventricular ejection fraction. Our patient-tailored ablation strategy without systematic PVI provides good results.

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An analysis of reported independent prognostic factors for survival in squamous cell carcinoma of the vulva: is tumor size significance being underrated?

To assess independent prognostic factors described in the literature. Thus, to identify different risk groups. Review of the records with a diagnosis of primary vulvar squamous cell carcinoma (January/1992-January/2012). depth of stromal invasion (DSI)>1mm, pathological tumor size>2 cm, and pathological tumor-free margin ≥ 8 mm. Patients who underwent neoadjuvant therapy due to locoregionally advanced vulvar cancer were excluded. All the patients underwent radical, both local and regional, surgery. Adjuvant radiation therapy was administered to all patients with positive nodes. Features of lymph nodes, tumor size, age, grade, lymphovascular space invasion (LVSI), DSI, type of radical surgery, pathological margin distance and stage were evaluated by univariate and multivariate analysis. 194 patients were included. Median age: 67 years. Median follow-up: 62 months. 5-year OS and DFS: 65.5% and 58.2%. Positive lymph nodes were found in 91 (46.9%) patients. After a multivariate analysis, the number of positive lymph nodes, extra-nodal growth, pathologic tumor size and DSI proved to be independent prognostic factors. A high risk group for failure to survive (5y-OS 24%) was identified: tumor size ≥ 6-7.9 cm and DSI>4mm or ≥ 8 cm irrespective of DSI; and extra-nodal growth or ≥2 positive lymph nodes irrespective of tumor size and DSI.

A new high-risk group was identified based on different cutoff values for tumor size, extra-nodal growth and number of positive lymph nodes. This could be very important in the tailored treatment of a specific group of patients with bulky primary tumors and a poorer prognosis.

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Can low-dose CT with iterative reconstruction reduce both the radiation dose and the amount of iodine contrast medium in a dynamic CT study of the liver?

To investigate whether low-dose dynamic CT of the liver with iterative reconstruction can reduce both the radiation dose and the amount of contrast medium. This study was approved by our institutional review board. 113 patients were randomly assigned to one of two groups. Group A/group B (fifty-eight/fifty-five patients) underwent liver dynamic CT at 120/100 kV, with 0/40% adaptive statistical iterative reconstruction (ASIR), with a contrast dose of 600/480 mg I/kg, respectively. Radiation exposure was estimated based on the manufacturer's phantom data. The enhancement value of the hepatic parenchyma, vessels and the tumor-to-liver contrast of hepatocellular carcinomas (HCCs) were compared between two groups. Two readers independently assessed the CT images of the hepatic parenchyma and HCCs. The mean CT dose indices: 6.38/4.04 mGy, the dose-length products: 194.54/124.57 mGy cm, for group A/group B. The mean enhancement value of the hepatic parenchyma and the tumor-to-liver contrast of HCCs with diameters greater than 1cm in the post-contrast all phases did not differ significantly between two groups (P>0.05). The enhancement values of vessels in group B were significantly higher than that in group A in the delayed phases (P<0.05). Two reader's confidence levels for the hepatic parenchyma in the delayed phases and HCCs did not differ significantly between the groups (P>0.05).

Low-dose dynamic CT with ASIR can reduce both the radiation dose and the amount of contrast medium without image quality degradation, compared to conventional dynamic CT without ASIR.

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Does excessive dynamic airway collapse have any impact on dynamic pulmonary function tests?

Excessive dynamic airway collapse (EDAC) represents pathologic obstruction, but the flow resistance it creates and the possible impact on pulmonary function tests is unclear. Our aims were to explore the flow resistance in a model, and in patients to relate observed EDAC to pulmonary function tests. Model study: A garden hose was compressed from 1 side to simulate the posterior tracheal wall bulging into the lumen for 2 lengths, 3 and 12 cm, in 8 steps. Resistance was measured at each step for airflows 1 L/s through 9 L/s. Digital photos of the luminal area at each obstruction step were analyzed by a computer to estimate the cross-sectional area reduction and the corresponding shortest distance between the bulging (posterior) and the opposite (anterior) wall (AP-distance). Patient study: A total of 104 stable chronic obstructive pulmonary disease patients studied by pulmonary function tests and bronchoscopy. The tracheal obstruction was observed during forced expiration and cough, and the cross-sectional area reduction was estimated from the observed AP-distance using the results from the model study. Model study: The flow resistance increases significantly when the cross-sectional area is reduced to>70% for an obstruction length of 3 cm. Patient study: EDAC was found in 18 patients during cough, none during forced expiration. There was no correlation between the obstructions found and the results from pulmonary function tests.

EDAC during peak pressure has negligible impact on pulmonary function tests and breathing symptoms. The importance of the severity, length, and duration of the EDAC is discussed.

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Is transcranial magnetic stimulation effective in treatment-resistant combat related posttraumatic stress disorder?

To examine the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in patients with treatment-resistant posttraumatic stress disorder (PTSD) with co-occurring major depression. We examined data on 20 male combat related PTSD patients admitted to the Post Traumatic Stress Disorder Clinic of Gülhane Military Medical Academy, Ankara, Turkey between January 2011 and December 2012 that received rTMS in addition to medical therapy. We obtained the data by examining the case files and hospital computer records. Decreases in the Impact of Event Scale (IES) hyperarousal scores were statistically significant. However, there were no statistically significant differences between the total IES scores, IES intrusion scores, IES avoidance scores, Beck Depression Inventory, and Beck Anxiety Inventory scores before and after rTMS treatment.

The efficacy of rTMS on the hyperarousal symptoms indicated that rTMS could be used in the treatment of patients with treatment-resistant PTSD. The role of rTMS in the clinical management of PTSD should be identified in further comprehensive studies.

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Incidental thyroid cancer detected by (18)F-FDG PET: does it have different clinicopathological features?

The prevalence and risk of malignancy in thyroid incidentalomas has been investigated in previous studies; however, these studies have not looked at the characteristics of incidental thyroid cancer (ITC) detected by fluorine-18 fluorodeoxyglucose PET. Therefore, we aimed to assess the clinicopathologic features of ITC. From March 2008 to December 2011, a total of 2892 patients underwent total thyroidectomy for papillary thyroid cancer. Among them, patients belonging to the ITC group were defined as those in whom focal thyroid uptake was reported as an incidental finding on PET imaging and further evaluation revealed the presence of malignancy. In addition, two control groups with non-PET incidental thyroid cancer (NITC) were selected: NITC-A patients (n=48) who underwent a total thyroidectomy in March 2008 and NITC-B patients (n=48) who underwent a total thyroidectomy for papillary thyroid cancer and were matched for the confounding effects of age and sex. There were no significant differences in clinicopathologic features, except for age and tumour node metastasis (TNM) staging, between ITC and NITC-A patients. More ITC than NITC-A patients were aged 45 years or older. Although T, N, or M staging was not different between ITC and NITC-A, there were more ITC patients with stage III/IV tumours. After matching for age and sex, none of the clinicopathologic features showed significant differences between ITC and NITC-B patients.

No significant differences were observed between ITC and NITC patients except for age and TNM staging. More ITC patients had advanced TNM stage most likely due to patient age.

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Localization of metastasis within the sentinel lymph node biopsies: a predictor of additional axillary spread of breast cancer?

To explore the relationship between morphological characteristics and histologic localization of metastasis within sentinel lymph nodes (SLN) and axillary spread in women with breast cancer. We selected 119 patients with positive SLN submitted to complete axillary lymph node dissection from July 2002 to March 2007. We retrieved the age of patients and the primary tumor size. In the primary tumor, we evaluated histologic and nuclear grade, and peritumoral vascular invasion (PVI). In SLNs we evaluated the size of metastasis, their localization in the lymph node, number of foci, number of involved lymph nodes, and extranodal extension. Fifty-one (42.8%) patients had confirmed additional metastasis in non-sentinel lymph nodes (NLSN). High histologic grade, PVI, intraparenchymatous metastasis, extranodal neoplastic extension and size of metastasis were associated with positive NLSN. SLN metastasis affecting the capsule were associated to low risk incidence of additional metastasis. After multivariate analysis, PVI and metastasis size in the SLN remained as the most important risk factors for additional metastasis.

The risk of additional involvement of NSLN is higher in patients with PVI and it increases progressively according the histologic localization in the lymph node, from capsule, where the afferent lymphatic channel arrives, to the opposite side of capsule promoting the extranodal extension. Size of metastasis greater than 6.0 mm presents higher risk of additional lymph node metastasis.

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Is preoperative chemotherapy followed by surgery the appropriate treatment for signet ring cell containing adenocarcinomas of the esophagogastric junction and stomach?

Recent data suggest primary resection as the preferable approach in patients with signet ring cell gastric cancer (SRC). The aim of our retrospective exploratory study was to evaluate the influence of SRC on prognosis and response in esophagogastric adenocarcinoma treated with neoadjuvant chemotherapy. A total of 723 locally advanced esophagogastric adenocarcinomas (cT3/4 N any) documented in a prospective database from two academic centers were classified according to the WHO definition for SRC (more than 50 % SRC) and analyzed for their association with response and prognosis after neoadjuvant treatment. A total of 235 tumors (32.5 %) contained SRC. Median survival of SRC was 26.3 compared with 46.6 months (p<0.001) for non-SRC. SRC were significantly associated with female gender, gastric localization, advanced ypT and R1/2 categories, and lower risk of surgical complications and anastomotic leakage (each p<0.001). Clinical (21.1 vs. 33.7 %, p = 0.001) and histopathological response (less than 10 % residual tumor: 16.3 vs. 28.9 %, p<0.001) were significantly less frequent in SRC. Clinical response (p = 0.003) and complete histopathological response (pCR) (3.4 %) (p = 0.003) were associated with improved prognosis in SRC. Clinical response, surgical complications, ypTN categories, but not SRC were independent prognostic factors in forward Cox regression analysis in R0 resected patients. Risk of peritoneal carcinomatosis was increased (p<0.001), while local (p = 0.015) and distant metastases (p = 0.02) were less frequent than in non-SRC.

Prognosis of SRC is unfavorable. Although response to neoadjuvant chemotherapy is rare in SRC, it is associated with improved outcome. Thus, chemotherapy might not generally be abandoned in SRC. A stratification based on SRC should be included in clinical trials.

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Is there a role for community health workers in tobacco cessation programs?

Studies have shown that with appropriate training, Community Health Workers (CHWs) can be actively involved in health promotion and disease prevention (including tobacco cessation). This study examined the perceptions of administrators and health care professionals regarding the actual and potential role(s) of CHWs in a tobacco cessation program (TCP) within a universal health care system. This study was part of a larger exploratory, cross-sectional comprehensive assessment of the implementation of the TCP through the primary care public health system in 7 towns in the state of Paraná, Brazil. Questionnaires were administered to 84 administrators at different levels (regional, municipal, and health units) and 80 health care professionals who were directly involved in the TCP. For this study, we assessed the perceptions of administrators and health care professionals on the actual and potential role(s) of CHWs in the TCP. The overall response rate was 56.2%. Although 48.4% of respondents indicated that CHWs already participated in the TCP, there was a wide range in the participants' responses regarding their involvement (33.3% among regional administrators and 65% among health care professionals). Identification/referral of patients and promotion of the TCP in the community were the most frequent CHWs' activities reported. Overall, respondents were very receptive about trained CHWs having multiple roles in the TCP, except for delivery of a brief intervention.

With appropriate training, health care administrators and health care professionals are very receptive regarding the involvement of CHWs in a TCP delivered through a public health system.

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Should males ever undergo wedge resection for stage 1 non-small-cell lung cancer?

Wedge resections are frequently performed for small peripheral lesions in patients unfit for a more extensive resection. We aimed to investigate whether patient sex and histology type are important factors determining survival in patients undergoing a wedge resection for stage I lung cancer. We retrospectively analysed a prospective thoracic database of patients (n = 2859) who had undergone potentially curative wedge resection for stage I non-small-cell lung cancer. Only patients with adenocarcinoma or squamous carcinoma were included (n = 540). We benchmarked our 5-year survival against the sixth International Association for the Study of Lung Cancer results. Kaplan-Meier, Cox multivariate regression analysis and propensity analysis were utilized to assess the effect of sex and histology on survival post-wedge resection with regard to long-term survival. Cox regression of patients who had undergone wedge resection demonstrated that adenocarcinoma (odds ratio [OR]: 2.16, 95% confidence interval [CI]: 1.11-4.19), P = 0.02 was the only significant term determining long-term survival. Cox regression of male patients identified adenocarcinoma (OR: 3.29, 95% CI: 1.22-8.86), P = 0.02 as the only significant term determining long-term survival. Cox regression of female patients failed to identify any significant factors that determine long-term survival. Propensity matching based on gender identified that gender had no effect on survival, P = 0.46; however, histology was associated with a difference in survival, P = 0.02. This effect occurred in males, P = 0.02, but not females, P = 0.26. Propensity matching based on histology identified that gender had no effect on survival, P = 0.29; however, histology was associated with a difference in survival, P = 0.01. This effect occurred in males, P = 0.01, but not females, P = 0.26. Differing life expectancy between males and females was adjusted for by the use of the Framingham-predicted life expectancy.

Long-term survival of patients with stage I non-small-cell lung cancer who undergo a wedge resection is affected by gender and histological type. Male patients undergoing wedge resections for adenocarcinoma have outcomes inferior to those of patients with squamous carcinoma. Histology type does not affect survival in female patients undergoing wedge resections.

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Is single dose povidone iodine sclerotherapy effective in chyluria?

To evaluate the effectiveness and safety of single dose 0.2 % povidone iodine renal pelvic instillation sclerotherapy for the treatment for chyluria. In a prospective study from August 2010 till July 2013, 41 patients presenting with milky urine were included. Apart from ether test, the presence of lymphocytes in urine and urine triglycerides levels were also done to confirm chyluria. On a day care basis under local anesthesia, 5F open-ended ureteric catheter was introduced in the ureteric orifice of affected side. Freshly prepared 7-10 ml of 0.2 % povidone iodine solution was instilled with the patient in Trendelenburg position. Total of 41 patients were enrolled (27 males and 14 females; mean age 40 years, SD 8.9, range 19-61) with a mean follow-up of 20 months. Immediate clearance was seen in all patients and recurrence in 7 (17 %). Mean disease-free duration was 18 months. Two patients had moderate to severe flank pain.

Single dose 0.2 % povidone iodine sclerotherapy is safe and effective treatment for chyluria. As it offers treatment on a day care basis, continuous ureteral and urethral catheterizations can be avoided.

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Does moderate unconjugated hyperbilirubinemia in healthy term neonates play a role on their neurodevelopmental status at the age of 18 months?

In a case-control study, the developmental status of 18-month-old children referred to Azadshar primary health care center in Yazd, Iran, between December 2007 and June 2009 was evaluated via the Persian version of Ages and Stages Questionnaires (ASQ). Children in the case group were healthy term neonates with total serum bilirubin level of 20-25 mg/dl, birth weight of 2500-4000 g and no birth asphyxia who were admitted to hospital and had undergone phototherapy. The control group consisted of children who were healthy term neonates without history of neonatal hyperbilirubinemia. 112 children (56 in each group) were evaluated. Four children in the case group and one in the control group had delay in communication skills. Three in the case group and three in the control group had fine motor delay. Only one child in the case group showed delay in problem solving. Statistically significant differences were not seen in the frequency of developmental delay as well as in the mean scores of all developmental domains in both groups.

Based on the results of the present study by ASQ, the developmental status at the age of 18 months of healthy term neonates with moderate unconjugated hyperbilirubinemia was not different from the control group.

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Is [F-18]-fluorodeoxy-D-glucose positron emission tomography of value in the management of patients with craniofacial bone sarcomas undergoing neo-adjuvant treatment?

We evaluated the role of 18FDG PET/CT used to assess response to preoperative chemotherapy in patients with primary craniofacial bone sarcomas. Fourteen patients with craniofacial bone sarcomas (13 osteosarcoma, 1 spindle cell sarcoma) were retrospectively evaluated. All patients received up to 6 cycles of preoperative chemotherapy followed by resection of the primary tumour. Response to treatment was assessed using MRI (RECIST criteria) and 18FDG PET/CT (EORTC guidelines), performed at least at baseline, after 2-4 cycles and pre-operatively. The median baseline 18FDG PET/CT SUV was 10.2 (range 0-41); in 2 patients no uptake was detected. The preoperative 18FDG PET/CT, compared with the baseline, demonstrated a partial metabolic response in 7 patients (59%), complete metabolic response in 2 (16%) and stable metabolic disease in 3 (25%). In contrast, only two patients achieved a RECIST response on MRI: 10 (83%) had stable disease. One patient underwent early resection due to clinical progression after an initial response to treatment. This was confirmed by PET (SUV from 21 to 42) but not on MRI. Twelve of 14 patients (86%) had<90% histological necrosis in the resected tumour. At a median follow-up 23 months, 11 patients (79%) remain disease free, two had metastatic progression (14%) and 1 a local relapse (7%). The median DFS was 17 months. For those patients who achieved a response to preoperative 18FDG PET/CT the median DFS was 19 months (range: 1-66) compared with 3 months (range: 3-13) in those who did not (p = 0.01). In contrast, the median disease free survival (DFS) did not differ according to histological response (19 versus 17 months,>90% versus<90% necrosis, p = 0.45) or resection margins (19 months for R0 versus 18 months for R1, p = 0.2).

18FDG PET/CT is more reliable than standard imaging in evaluating response to neo-adjuvant chemotherapy in craniofacial bone sarcomas, changed management in one patient, and in this small series, correlated better with patient outcome than histological response and resection margins. These results warrant prospective validation in a larger cohort of patients.

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Does systemic low-grade inflammation associate with fat accumulation and distribution?

Knowledge about the interrelationship between adiposity and systemic low-grade inflammation during pubertal growth is important in detecting early signs of obesity-related metabolic disorders. The objective of the study was to evaluate the developmental trajectories of fat mass (FM) and high sensitive C-reactive protein (hsCRP) levels and factors that could explain the relationship between FM and hsCRP in girls from prepuberty to early adulthood. This was a 7.5-year longitudinal study. The study was conducted at the University of Jyväskylä Sports and Health Science laboratory. Three hundred ninety-six healthy Finnish girls aged 11.2 ± 0.8 years participated in the study. Body composition was assessed by a dual-energy X-ray absorptiometry and serum concentrations of hsCRP, adipokines, and sex hormones by ELISA. Both FM and hsCRP increased with age and had similar trajectories but different inter- and intravariance patterns. A joint analysis of fat distribution and hsCRP indicated that the linkage probabilities across different trajectory subgroups between regional FM and the corresponding hsCRP levels varied from 16% to 53%. In a longitudinal regression model, the common predictor for both FM and hsCRP was T (β = .065, P<0.01, and β = -.213, P<0.05, respectively) before menarche. Other factors predicting FM before menarche were SHBG (β = -.196, P<0.01) and leptin (β = .381, P<.01); and after menarche hsCRP (β = .048, P<0.01), T (β = .089, P<.01), leptin (β = .340, P<.01), and adiponectin (β = -.086, P<.05). Of the factors assessed, only FM was associated with hsCRP both before and after menarche (β =1.058, P<.01 and β =1.121, P<.01, respectively).

The differences in regional body fat depots and hsCRP levels in adulthood are largely established early in childhood. However, the intra- and interindividual variances differed between FM and hsCRP. FM explained the variance of hsCRP during pubertal growth, but the reverse was not true, which suggests that FM contributes to low-grade inflammation and not vice versa.

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Heavy smoking and lung cancer: are women at higher risk?

Whether women are more or equally susceptible to the carcinogenic effects of cigarette smoke on the lungs compared with men is a matter of controversy. Using a large French population-based case-control study, we compared the lung cancer risk associated with cigarette smoking by gender. The study included 2276 male and 650 female cases and 2780 male and 775 female controls. Lifetime smoking exposure was represented by the comprehensive smoking index (CSI), which combines the duration, intensity and time since cessation of smoking habits. The analysis was conducted among the ever smokers. All of the models were adjusted for age, department (a regional administrative unit), education and occupational exposures. Overall, we found that the lung cancer risk was similar among men and women. However, we found that women had a two-fold greater risk associated with a one-unit increase in CSI than men of developing either small cell carcinoma (OR=15.9, 95% confidence interval (95% CI) 7.6, 33.3 and 6.6, 95% CI 5.1, 8.5, respectively; P<0.05) or squamous cell carcinoma (OR=13.1, 95% CI 6.3, 27.3 and 6.1, 95% CI 5.0, 7.3, respectively; P<0.05). The association was similar between men and women for adenocarcinoma.

Our findings suggest that heavy smoking might confer to women a higher risk of lung cancer as compared with men.

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Can single pulse electrical stimulation provoke responses similar to spontaneous interictal epileptiform discharges?

To estimate the proportion of patients where EEG responses to single pulse electrical stimulation (SPES) are similar to spontaneous interictal epileptiform discharges (IEDs) in the same patient, and whether such resemblance is related to seizure onset. We have visually compared the morphology, topography and distribution of IEDs and of SPES responses in 36 patients with intracranial EEG recordings during presurgical evaluation. Each patient showed between 3 and 17 different IED patterns, located at seizure onset zone and elsewhere. Only 13 patients showed the highest incidence and amplitude of IEDs at the site of focal seizure onset. Twenty-eight patients showed early responses which were similar to at least one IED pattern. Thirty patients showed delayed responses which were always similar to at least one IED pattern and were always located at seizure onset or in its vicinity.

Early SPES responses often, and delayed responses always, were similar to at least one IED pattern in the same patient. The IEDs resembling delayed responses were those associated with seizure onset.

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Managing serum phosphate in haemodialysis patients: time for an innovative approach?

Hyperphosphataemia, a common biochemical abnormality in chronic kidney disease, poses significant management challenges. This study aims to determine whether the reasons for this are multifactorial; including poor dietary knowledge, poor adherence to a low phosphate diet and phosphate-binding medications and the impact of age on these parameters.SUBJECTS/ In order to compare serum phosphate and other associated parameters to the UK Renal Association Clinical Practice Guidelines 2010 an audit and service evaluation questionnaire was carried out in May 2011 on 130 haemodialysis outpatients attending the Plymouth Dialysis Unit. Fifty-three percent of patients had serum phosphate within the target range of 1.1-1.7 mmol/l, 77% and 85% had serum calcium and parathyroid hormone within target ranges, respectively. Younger patients (18-45 years) were significantly less likely to have serum phosphate within range χ(2) (2, n=124)=18.77, P<0.001. Despite better knowledge of their own phosphate levels (P=0.005), phosphorus-rich foods (P<0.001), symptoms of hyperphosphataemia (P<0.001) and increased use of Renal Patient View (P=0.002),<65 years old had significantly higher phosphate levels than those>65 years (P<0.001). No significant associations were found between phosphate control and the following factors: gender, timing of dialysis shift, years on dialysis or dialysis adequacy.

In this population, despite better knowledge, younger patients have worse phosphate control than older patients. Using the same dietary education techniques may not be suitable for all ages, more innovative approaches supported by skilled health professionals are needed to motivate and engage with younger patients to promote self-management and adherence.

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Does cigarette smoking really have detrimental effects on outcomes of IVF?

Cigarette smoke contains many toxic chemicals associated with poor reproductive outcome and reduced fertility. It also has a negative effect on sperm motility and morphology. The aim of this study was to analyze the effects of male and female cigarette smoking on the outcomes of in vitro fertilization (IVF). In this comparative prospective analysis, the effects of smoking on outcomes of IVF including semen parameters, oocyte quality, fertilization rate, transfer day embryo scores and pregnancy rates were analyzed. For this purpose, patients were grouped based on their follicular or seminal fluid cotinine (a nicotine metabolite) levels as smokers and non-smokers (non-smokers: female (n=171), male (n=118), smokers: female (n=43), male (n=96)). The mean age and baseline hormonal levels of all groups were found to be comparable. While the numbers of total and mature oocytes collected were higher in the smoker group (p=0.005 and p=0.006, respectively), oocyte quality index, fertilization rate, embryo development rate and pregnancy rate were not significantly different between the groups (p>0.05). Analysis based on the type of ovarian hyperstimulation protocol (GnRH agonist, antagonist and others) showed that within the antagonist group the mean age of smokers was significantly lower and the total number of collected oocytes was significantly higher compared with non-smokers. Cigarette smoking among men did not have a significant negative effect on outcomes of IVF whether their partners were smokers or nonsmokers. Regression analysis did not give any significant difference when male and/or female smoking status was analyzed for fertilization rates, transferred embryo qualities and clinical pregnancy rates.

Cigarette smoking does not have detrimental effects on outcomes of IVF.

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Is pneumoconiosis a factor of severity in acute exacerbation of chronic obstructive pulmonary disease?

Although working in a coal mine is a wellknown risk factor for chronic obstructive pulmonary disease (COPD), there insufficient data explaining the association between acute exacerbation of COPD (AECOPD) and coal worker pneumoconiosis (CWP). This study aimed to evaluate the features of patients with complicated CWP admitted for AECOPD and whether complicated CWP has any effect on increasing the severity of this disease. This study was designed as a retrospective cohort study. A total of 106 hospitalized patients were identified to have CWP. Patients who did not perform spirometry and with simple CWP were excluded. A total of 51 patients with complicated CWP, was included in the study group. Comparison group was selected from the patients with AECOPD without pneumoconiosis. Patients with complicated CWP, when compared to patients without pneumoconiosis, had longer hospitalization times (12.96 ± 8.49 days, 9.67 ± 5.21 days respectively, p=0.021), a higher cost of hospitalization (€2029 ± 2724, €931 ± 820 respectively, p=0.003), and higher rates of infective microorganisms in respiratory secretions and/ or blood cultures (61.3%, 29.6% respectively, p=0.016). We found that significance of high cost was dependent on duration of hospitalization and culture positivity. The most frequently encountered infective microorganism in both groups with complicated CWP and without pneumoconiosis was pseudomonas aeruginosa.

Preventive measures for CWP in regions with high prevalence of coal mining have a very important role in the fight against COPD, which has significant morbidity and mortality rates.

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Abdominal aortic calcification and renal resistive index in patients with chronic kidney disease: is there a connection?

We aimed to evaluate the relationship between abdominal aortic calcification (AAC) and renal resistive index (RRI), parameters associated with cardiovascular outcome, in non-dialysis chronic kidney disease (CKD) patients. Seventy-seven stable patients mainly in CKD stages 3B and 4 (44 and 28%), median age 69 years, with a positive history of systemic atherosclerosis were prospectively enrolled. RRI, carotid intima-media thickness (IMT), Kauppila score for AAC (AACs), cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) were assessed. Traditional and non-traditional atherosclerosis risk factors were also evaluated. Vascular (50%), diabetic (26%) and primary glomerular nephropathies (8 %) were the main causes of CKD. AAC was highly prevalent (77%). In the whole cohort, RRI was directly related to AACs (rs = 0.35, p<0.001). AACs correctly identified patients with RRI>0.7 in 69% (56-81%) of cases, a cut-off of 5 resulting the best combination of sensitivity (65%) and specificity (68%). Compared to those with AACs<5, patients with AACs>5 were older, had higher serum cholesterol, C-reactive protein and IMT, lower ABI, but similar CAVI, estimated glomerular filtration rate, serum calcium and phosphate. In the whole cohort, AACs was negatively correlated with ABI (rs = -0.51, p<0.001) and positively with IMT (rs = 0.27, p = 0.01), supporting a role for Kauppila score in integrating information on both intra- and extrarenal atherosclerosis.

As Kauppila score correlates with RRI in non-dialysis CKD patients, it could be a fast, convenient and relatively inexpensive tool for estimating RRI, and consequently the intrarenal vascular status, but further research is warranted.

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Are arterial calcifications a marker of remodeling in vertebrobasilar territory?

Intracranial atherosclerosis is responsible for a substantial proportion of stroke, and vessel calcifications as seen on native computed tomographic scans could be an estimate of its burden. The presence of vertebrobasilar artery calcifications is associated with risk factors. This study is a retrospective clinical study on 449 consecutive patients with stroke. Native computed tomographic scans were assessed for the presence of calcification in the intracranial segment of vertebrobasilar artery, and the area of each vessel was calculated from 2 perpendicular diameters. A comprehensive assessment of standard risk factors was recorded. A total of 245 (54.6%) patients had visible calcifications in vertebrobasilar artery. Calcifications were positively associated with advanced age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P<0.001), larger total vessel area (odds ratio, 1.01; 95% confidence interval, 1.00-1.01; P<0.001), and history of previous transient ischemic attack/stroke (odds ratio, 1.82; 95% confidence interval, 1.08-3.07; P=0.024).

Higher prevalence of calcifications in vertebrobasilar artery territory of patients with stroke is associated with advanced age, larger arterial area, and history of previous transient ischemic attack/stroke.

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Does abnormal circadian blood pressure pattern really matter in patients with transient ischemic attack or minor stroke?

Patients with stroke are more likely to have impaired autonomic nervous function and abnormal circadian blood pressure (BP) patterns. It remains unclear whether circadian BP patterns in patients with transient ischemic attack or minor stroke (National Institutes of Health Stroke Scale ≤3) differ from those in the normal population. Participants were assessed using a 24-hour ambulatory BP monitor and a short-term measurement of heart rate variability. There were 76 patients (mean age, 67.2 years; 57.9% men; and 61.8% transient ischemic attack) and 82 controls (65.6 years; 54.9% men). A history of hypertension was more prevalent in patients (72.4%; controls 48.8%). Circadian BP patterns were distributed similarly among patients and controls, and heart rate variability was also consistent between patients and controls.

In contrast to previous findings among patients with acute stroke, patients with transient ischemic attack or minor stroke had similar BP patterns and autonomic nervous system function, when compared with controls.

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Do mechanical markers of myocardial ischaemia predict the transmural extent of myocardial infarction in man?

The present study aimed to explore the relationship between the transmural extent of myocardial necrosis and mechanical markers of myocardial ischaemia in man. A group of 40 patients with previous Q-wave myocardial infarction and a left ventricular ejection fraction (LVEF) of 27 +/- 11% was studied by cine and contrast-enhanced magnetic resonance imaging. Necrotic areas of delayed contrast enhancement were present in every patient and involved 20 +/- 8% of left ventricular myocardium. In involved segments, the transmural extent of contrast enhancement varied from 5% to 100%, being on average 38 +/- 25% of the wall thickness. End-diastolic left ventricular wall thickness and systolic wall thickening were lower in contrast-enhanced segments than in the other segments (P<0.001). Furthermore, although left ventricular wall thickness and systolic wall thickening decreased as the transmural extent of contrast enhancement increased, the correlations were weak (r = -0.382 and -0.45, respectively). Finally, a delayed contrast enhancement was present in 89% of akinetic and in 94% of dyskinetic segments; however, contrast enhancement was also present in 18% of the segments with normal wall motion and in 56% of hypokinetic segments.

Although mechanical markers of myocardial ischaemia substantially reflect the transmural extent of myocardial infarction, none of them can be considered as a substitute for the direct observation of necrotic tissue and its transmural extent, as provided by contrast-enhanced magnetic resonance imaging.

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Is hepatitis C more aggressive in renal transplant patients than in patients with end-stage renal disease?

The eventual impact of immunosuppression on the natural history of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is still unknown because of the lack of comparative data for HCV-infected patients with ESRD and renal transplant patients. The aim of this study was to compare the biochemical and histological characteristics of chronic HCV infection in renal transplants patients and ESRD patients undergoing hemodialysis. Thirty-eight renal transplant patients and 38 ESRD patients undergoing hemodialysis who were chronically infected with HCV and were matched for gender, age at infection, and estimated time of infection were included in the study. The groups were compared regarding laboratory and histological variables. Renal transplant patients showed similar alanine aminotransferase and higher gamma-glutamyltransferase levels (P = 0.05) when compared with ESRD patients. Comparative analysis of histological variables revealed a higher proportion of cases with septal fibrosis (P = 0.04) and confluent necrosis (P = 0.01) among transplant-recipient patients. No difference between groups was observed regarding the intensity of portal and periportal inflammatory infiltrates. Steatosis was more prevalent among transplant-recipient patients (P<0.001). There was no difference between groups regarding the prevalence of lymphoid aggregates or bile duct injury.

Renal transplant patients had a larger proportion of cases with septal fibrosis and confluent necrosis than did ESRD patients, suggesting that renal transplantation might modify the natural history of hepatitis C in ESRD patients, leading to a more aggressive liver disease.

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Do women give the same information on binge drinking during pregnancy when asked repeatedly?

To study if pregnant women give the same answers to questions on frequency and timing of binge drinking when asked more than once during and after pregnancy. Cohort study. The Danish National Birth Cohort. The study is based on 76 307 pregnant women with repeated information on binge drinking during the early part of pregnancy and 8933 pregnant women with information on binge drinking during pregnancy weeks 30-36, obtained while pregnant and 6 months after delivery. More women reported binge drinking, if the interview took place close to the period in question. As the report of binge drinking was highest in the first of two interviews referring to the same period, as well as women who participated in the first interview in pregnancy week 12 or earlier reported more binge drinking compared to women who participated in the interview later in pregnancy.

Self-reported information on binge drinking is more frequently under-reported when the recall period is long. To improve the validity of data on binge drinking, future birth cohorts should obtain information several times during pregnancy.

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Acute hepatitis due to kava-kava and St John's Wort: an immune-mediated mechanism?

In an otherwise healthy 48-year-old female patient, acute hepatitis with transaminase increase (GOT up to 613 U/l, GPT up to 752 U/l), inconspicuous hepatitis serology findings, negative autoantibody status and negative virus serology was observed after a 10-week long intake of kava-kava (1-3 x 200 mg/day) and St John's Wort (1 x 425 mg/day). Biopsy of the liver showed lobular and portal necroinflammatory activity without indication of cirrhosis. Due to these findings with proven T-cell activity (lymphocyte typing, neopterin determination) as well as the aetiopathology, this form of hepatitis with histological characteristics of a nutritive/medicinal toxic origin was classified as induced immunologic idiosyncratic hepatitis, possibly in terms of an antibody-negative autoimmune hepatitis. Discontinuation of the existing medication and simultaneous onset of immunosuppressive combination therapy of cortisone, azathioprine and ursodeoxycholic acid resulted in normalisation of the liver parameters within a period of two months.

On the one hand, it appears that simultaneous intake of St John's Wort possibly potentiates the toxicity of kavapyrones. On the other hand, an immune-mediated mechanism, induced by kava-kava, cannot be completely excluded in the present case. It must be stressed that in patients with autoimmune hepatitis, precise history of medication intake should also be available.

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Low rates of colorectal, cervical, and breast cancer screening in Asian Americans compared with non-Hispanic whites: Cultural influences or access to care?

Asian Americans have lower cancer screening rates compared with non-Hispanic whites (NHWs). Little is known about mechanisms that underlie disparities in cancer screening. The objectives of the current study were 1) to determine the relation between nativity, years in the United States, language, and cancer screening in NHWs and Asian Americans, independent of access to care and 2) to determine whether Asians reported different reasons than NHWs for not obtaining cancer screening. This population-based study included 36,660 NHWs, 1298 Chinese, 944 Filipinos, 803 Koreans, 857 Vietnamese, and 1036 Other Asians from the 2001 California Health Interview Survey. The main study outcomes were 1) self-reported colorectal, cervical, and breast cancer screening and 2) reasons for not obtaining cancer screening. After adjusting for access to care, several Asian subgroups still had significantly lower rates of all types of cancer screening compared with NHWs. Adjusting for nativity, years in the United States, and English language attenuated the relation between Asian ethnicity and lower rates of colorectal and breast cancer screening. When they were asked what the most important reason was for not having each screening test, foreign-born Asians were significantly more likely than United States-born NHWs to report that they "didn't have problems/symptoms" (P<.01).

Nativity, years in the United States, and English language may be markers of cultural differences that are mediating cancer screening disparities. Foreign-born Asians may believe that cancer screening is in response to symptoms rather than tests that are used prior to the development of symptoms. Health education messages must consider how to communicate effectively that "cancer screening is valuable, because it finds cancer before it is advanced enough to cause symptoms."

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Does the frequency of anxiety and depressive disorders differ between diagnostic subtypes of anorexia nervosa and bulimia?

The objective of the present work is to determine whether the prevalence of depressive and anxiety disorders varies in subgroups of eating disorders (ED) according to age, ED duration, mode of care provision, and body mass index (BMI). Using the Mini International Neuropsychiatric Interview (MINI), the frequency of anxiety and depressive disorders was evaluated in 271 ED participants. Their prevalence was compared in subgroups of anorexics (AN-R and AN-BN) and bulimics (BN), both before and after controlling for potential confounding variables. Current or lifetime comorbidity of anxiety and depressive disorders did not differ between AN-R and AN-BN groups. Social phobia, panic disorders, and obsessive-compulsive disorder (OCD) were significantly more frequent in AN-BN and AN-R groups. Panic disorder was more frequent in the BN group.

Several confounding factors, in particular those identified in the present study, may explain previous conflicting results on the frequency of anxiety and depressive disorders in ED. Nevertheless, the study confirmed that OCD is more frequent in AN, even after controlling for confounding factors.

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Are we underestimating the problem of ultrafiltration in peritoneal dialysis patients?

Accurate measurement of ultrafiltration (UF) is important to improve the morbidity and mortality of peritoneal dialysis (PD) patients. The introduction of "flush-before-fill" PD systems has led to improved peritonitis rates. Partly to compensate for dialysate lost during flush-before-fill, extra dialysate was added to each PD bag. A 2-L PD bag now contains a mean volume of 2.225 L. That overfill volume might be erroneously measured as UF. We previously studied how this confounding factor might be affecting the diagnosis of UF failure and found that almost all units were overestimating daily UF by 900 mL. We now repeat the study to determine if the accuracy of UF estimation has improved. We conducted a telephone survey of PD units in the UK to determine how drain bags are weighed and how UF is calculated during formal assessment of adequacy and the peritoneal equilibrium test (PET). We also retrospectively analyzed our last 100, 24-hour dialysate collections and PET results to determine the potential clinical impact of overestimating UF. There has been an improvement since our last study, but 70% of PD units in the UK are still overestimating daily UF in patients on continuous ambulatory PD (CAPD). Half the surveyed units also inaccurately calculate UF during the PET, and 85% were reporting results of PET and 24-hour dialysate collections through the software provided by Baxter Healthcare. By including the overfill volume, 73% of patients with daily UF<750 mL would not be diagnosed as having inadequate daily UF (assuming that all were fluid overloaded and anuric). Similarly, 73% with potential UF failure during the PET (4-hour UF<100 mL) would be missed if overfill volume was misrepresented as UF.

For patients undergoing CAPD, there requires standardization on when drain bags are weighed. Awareness that calculation of UF must exclude overfill volumes has improved but remains poor. The PD Adequest software (Baxter Healthcare, Compton, UK) is widely adopted in the UK and perhaps it could draw attention of users to the potential of UF overestimation in CAPD patients.

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Can the inflammation markers of patients with high peritoneal permeability on continuous ambulatory peritoneal dialysis be reduced on nocturnal intermittent peritoneal dialysis?

Patients with high peritoneal permeability have the greatest degree of inflammation on continuous ambulatory peritoneal dialysis (CAPD), which may be associated with their higher mortality. Nocturnal intermittent peritoneal dialysis (NIPD; "dry day") may decrease inflammation by reducing the contact between dialysate and peritoneum and/or providing better fluid overload control. Therefore, the aims of this study were to determine and compare serum and dialysate concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) of patients with high or high-average peritoneal transport on CAPD, changed to NIPD, and ultimately to continuous cyclic peritoneal dialysis (CCPD). Crossover clinical trial in 11 randomly selected patients. All subjects had been on CAPD and were changed to NIPD, and ultimately to CCPD (6.4 +/- 3.1 months after initiation of study). All patients used glucose-based dialysate. Evaluations of clinical and biochemical parameters, dialysis adequacy, and serum and dialysis inflammation markers were performed at baseline on CAPD, 7 - 14 days after changing to NIPD, 7 - 14 days after switching to CCPD, and after 1 year of follow-up. All patients used only 1.5% glucose dialysate during evaluation days. CRP was determined by nephelometry, and IL-6 and TNF-alpha by ELISA. Seven patients were high transporters and 4 high average. Ultrafiltration increased (p<0.05) when patients changed from CAPD [0.38 L (-0.3 - 1.1 L)] to NIPD [2.64 L (0.7 - 4.7 L)]; it then decreased on CCPD [0.88 L (0.4 - 1.3 L) and at the end of study [0.65 L (0.3 - 1.0 L)]. This better fluid overload control was accompanied by decreased weight and systolic and diastolic blood pressure when patients changed from CAPD (89 +/- 13 kg, 160 +/- 23 and 97 +/-9 mmHg, respectively) to NIPD (86 +/- 17 kg, 145 +/- 14 and 86 +/- 9 mmHg, respectively), and increased weight and systolic and diastolic blood pressure on CCPD (85 +/- 15 kg, 143 +/-23 and 88 +/- 14 mmHg, respectively) and at the end of follow-up (87 +/- 16 kg, 155 +/- 24 and 89 +/- 12 mmHg, respectively). Median serum CRP decreased (p = 0.03), from 3.8 (1.6 - 8.5) mg/L on CAPD to 1.0 (0.4 - 4.4) mg/L on NIPD, but increased on CCPD [1.8 (1.3 - 21) mg/L]and at the end of the study [3.2 (0.3 - 8.2) mg/L]. Dialysate CRP decreased nonsignificantly, from 0.10 (0 - 0.5) mg/L on CAPD to 0 (0 - 0.03) mg/L on NIPD, to 0.01 (0 - 0.08) mg/L on CCPD, and to 0 (0 - 0) mg/L at final evaluation. Serum TNF-alpha concentration decreased, from 0.14 (0.04 - 0.6) pg/mL on CAPD to 0.01 (0 - 0.08) pg/mL on NIPD, and then increased to 0.06 (0 - 0.4) pg/mL on CCPD and to 0.11 (0 - 0.2) pg/mL at the end of the study; whereas dialysate TNF-alpha decreased, from 0.08 (0.03 - 0.2) pg/mL on CAPD to 0.04 (0 - 0.2) pg/mL on NIPD, and to 0 (0 - 0) pg/mL and 0 (0 - 0.05) pg/mL on CCPD and final evaluation respectively. Serum IL-6 decreased (p = 0.07), from 2.5 (2.0 - 4.2) pg/mL on CAPD to 1.0 (0.7 - 2.0) pg/mL on NIPD, and to 1.0 (0.8 - 2.9) pg/mL on CCPD and 1.0 (0.5 - 9.8) pg/mL at the end of the study; whereas dialysate levels remained similar on CAPD [8.0 (3.7 - 13) pg/mL]and NIPD [7.8 (5.1 - 23) pg/mL], and increased on CCPD [11.2 (9.5 - 19) pg/mL]and at final evaluation [11.2 (8.3 - 15) pg/mL].

NIPD significantly decreased serum CRP and displayed a trend to decrease TNF-alpha and IL-6 serum concentrations compared with CAPD; whereas CCPD tended to reverse these effects. These results did not appear to be due to decreased local peritoneal inflammation, but they could be associated with better control of fluid overload on NIPD. Thus, NIPD, as Long as the residual renal function allows it, may be useful in reducing the systemic inflammation of patients with high peritoneal membrane permeability.

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Does potentized HgCl2 (Mercurius corrosivus) affect the activity of diastase and alpha-amylase?

Homeopathic drugs even with dilutions beyond 10(23) (high potencies) are frequently used, although their working mechanism is still unknown. Curative information preserved in solvent structure is postulated to exert biologic effects. The objective was to test for a stimulating or inhibiting effect of high potencies of the homeopathic remedy HgCl2 (Mercurius corrosivus) on two sugar hydrolases. High potencies were produced using stepwise dilution plus shaking. Controls included potentized solvent (aqua bidestillata), equimolar dilutions without shaking, and enzyme-free references. Tested were potencies with dilution factors 1:200 (CC) on diastase extract from winter barley, and 1:100 (C) on alpha-amylase from hog pancreas. Enzyme activity was colorimetrically determined by Lugol's iodine-starch reaction. An inhibiting effect of HgCl2 on enzyme activities was observed only in low potencies and dilutions. Statistically significant differences between potencies and controls were not found in randomized and blinded experiments.

This experimental design provided independent reproducible results of cell-free in vitro assays. However, it did not indicate an effect of potentized HgCl2 on hydrolases. Demonstrating potency effects may require additional experimental features.

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Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects?

To evaluate the effects of gender, food and grapefruit juice on the pharmacokinetics of primaquine in healthy subjects. In a randomized, two-phase cross-over study, 10 male and 10 female healthy Vietnamese subjects were administered 30 mg primaquine in the fasting state or with food, followed by administration of primaquine with grapefruit juice. The pharmacokinetics of primaquine were comparable between male and female subjects, with geometric mean ratios of Cmax = 0.89 [95% confidence interval (CI) 0.65, 1.22] and AUC = 0.80 (95% CI 0.56, 1.15). The mean CL/F of primaquine was slightly higher in males than in females [0.52 l h(-1) kg(-1)vs. 0.43 l h(-1) kg(-1), mean difference of 0.09 (95% CI -0.10, 0.28), P = 0.32]. When compared with fasting state values, food increased the geometric mean Cmax of primaquine by 26% (95% CI 12, 40) and the AUC by 14% (95% CI 3, 27). Similarly, grapefruit juice increased the geometric mean Cmax by 23% (95% CI 4, 45) and the AUC by 19% (95% CI 4, 37).

The disposition of primaquine was comparable between genders, suggesting no need to modify the dose of primaquine for malaria treatment or prophylaxis. Food increased the oral bioavailability of primaquine, which may lead to higher antimalarial efficacy. Grapefruit juice increased the bioavailability of primaquine, with marked interindividual differences suggesting that people should not take primaquine with grapefruit juice.

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Does physiotherapy management of low back pain change as a result of an evidence-based educational programme?

The concept of evidence-based medicine is important in providing efficient health care. The process uses research findings as the basis for clinical decision making. Evidence-based practice helps optimize current health care and enables the practitioners to be suitably accountable for the interventions they provide. Little work has been undertaken to examine how allied health professionals change their clinical practice in light of the latest evidence. The use of opinion leaders to disseminate new evidence around the management of low back pain into practice has been proposed. The aim of this study was to investigate if physiotherapists' clinical management of patients with low back pain would change following an evidence-based education package, which utilized local opinion leaders and delivered the best evidence. Thirty musculoskeletal physiotherapists from a Community Trust in North Staffordshire were cluster randomized by location of work, to two groups. The intervention group received an evidence-based programme on the management of low back pain, including advice regarding increasing activity levels and return to normal activity and challenging patients' fears and beliefs about their pain. The control group received a standard in-service training package on the management of common knee pathologies. The physiotherapists' clinical management of patients with low back pain was measured prior to training and 6 months post training. Outcome measures were based on physiotherapists completing 'discharge summary' questionnaires, which included information relating to the use and importance of therapies for treating their low back pain patients. There were few significant differences in treatment options between the intervention and control groups post training. Whilst there was some indication that physiotherapists were already utilizing aspects of psychosocial management for patients with low back pain, there was little change in what physiotherapists perceived to be important to patient recovery and actual clinical practice following the intervention.

Psychosocial factors have been identified as an important factor in the recovery of patients with low back pain. This project incorporated the latest evidence on the management of low back pain and utilized the theory of opinion leaders to disseminate this evidence into clinical practice. Whilst there were some limitations in the overall size of the study, the results help to give an insight into the challenges faced by the health care system and researchers alike to ensure quality evidence is actually utilized by practitioners for the benefits of patient care.

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Periodontal disease: Is it a risk factor for premature labor, low birth weight or preeclampsia?

To determine if periodontal disease (PD) is a risk factor for premature labor, low birth weight, or preeclampsia, and to look for a potential association between the different clinical forms of PD and the obstetric results indicated. This is an analytical, cross-sectional and prospective study of all women who gave birth in Dr. José Penna Hospital, in the city of Bahía Blanca, Argentina, between 1 February and 18 July 2003 and between 1 March and 31 May 2004. Women who met the inclusion criteria (being over 18 years old, having at least 18 teeth, not being diabetic, and having had children who survived labor) underwent a dental exam to look for hemorrhage when teeth were probed, loose teeth, or inflammation of the gums, and any loss of insertion was measured clinically. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated, and the results were adjusted according to smoking status and the presence or absence of anemia. A total of 2,003 births and 1,982 labor episodes were registered. In all, 420 women (21.2%) were excluded from the study because they did not meet the inclusion criteria or because no diagnostic exam could be carried out. Of the 1,562 women who were examined, 809 (51.8%) had at least one of the problems being sought; of these women, 274 (17.5%) had severe periodontal disease, and 535 (34.3%) had gingivitis. In all, there were 149 (9.5%) cases of premature labor; 161 (10.3%) cases of low birth weight, and 157 (10.0%) cases of preeclampsia. No association was noted between PD and premature labor (OR = 1.06; 95% CI: 0.74 to 1.50), low birth weight (OR = 1.05; 95% CI: 0.74 to 1.47), or preeclampsia (OR = 0.99; 95% CI: 0.70 to 1.40). The risk of giving birth to an infant with low birth weight in the subgroup of women who smoked more than 10 cigarettes a day was greater among women who had severe PD than among those who had good oral health (OR = 3.81; 95% CI: 1.46 to 10.05; P = 0.001). Anemia was found to be a risk factor for low birth weight (OR = 1.74; IC 95%: 1.03 to 2.94; P = 0.02).

No significant association was found between PD and premature labor, low birth weight, or preeclampsia.

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Bronchoplastic lobectomy: do early results depend on the underlying pathology?

This study evaluates the impact of the underlying disease upon the surgical outcome of bronchoplastic lobectomy, comparing typical carcinoid tumours with primary lung carcinoma. This retrospective study includes 98 consecutive patients (78 males, 20 females). Eighteen patients had a typical carcinoid tumour (group 1), and 80 had a primary bronchial carcinoma (group2). Fifty-six patients underwent bronchoplasty with full sleeve resection (10 patients from group 1, 46 from group 2) and 42 patients had a bronchoplasty with bronchial wedge resection (8 from group 1 and 34 from group 2). Right upper lobectomy was the most common procedure. We compared demographic data, surgical indications, the type of bronchoplasty and postoperative complications. The average age in group 1 (38.5+/-16.3 years; range 15-77) was significantly lower than in group 2 (61.4+/-9.5 years; range 14-75) (p<0.001). There were no postoperative deaths. Procedure-specific complications (anastomotic dehiscence and atelectasis) were found in 7 patients (8.75%) in group 2 (of which, three had a combination of two of the above-mentioned complications) but none (0%) in group 1 (p=0.23). Seven patients from group 2 (8.75%) required treatment for a residual pneumothorax for none (0%) in group 1 (p=0.23). The mean duration for air leak was comparable in both groups (p=0.366). Three patients (16.67%) from group 1 had non-surgical complications compared to 17 (21.25%) in group 2 (of which, one had a combination of two non-surgical complications) (p=0.35).

Bronchoplastic resection is a safe operation in patients with carcinoid tumours and should be the reference for treatment.

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Does gravidity influence the success of in vitro fertilization-embryo transfer cycles?

To evaluate the influence of gravidity on the results of in vitro fertilization (IVF)-embryo transfer (ET) cycles. All consecutive women aged<35 years admitted to our IVF unit from January 2002 to December 2004 were enrolled in the study. Only patients undergoing one of their first three IVF cycle attempts were included. Gravidity, ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and clinical pregnancy rate were assessed. Three hundred and forty-two consecutive IVF cycles were evaluated. One hundred and sixty-one cycles were from nulligravidas and 181 from women with a history of at least one previous clinical pregnancy. Forty-eight (29.8%) clinical pregnancies were observed in the nulligravida group and 56 (30.9%) in the gravida group. There were no differences between nulligravidas and gravidas in causes of infertility, length of ovarian stimulation, peak estradiol and progesterone levels, number of oocytes retrieved, fertilization rate and number of embryos transferred. Gravidas were significantly older (30.4 vs. 27.6 years, p<0.001) and used more gonadotropin ampoules (36.1 vs. 31.8, p<0.004) compared with the nulligravidas.

Patient gravidity has no influence on the likelihood of achieving pregnancy in IVF-ET cycles.

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Does use of isotretinoin rule out a career in flying?

A retrospective, non-interventional, consecutive case series of 47 individuals with a confirmed history of oral isotretinoin use were compared to 20 age and sex matched controls. 47 individuals (44 males and three females), age range 17-33, underwent Goldmann-Weekers dark adaptation (DA) and standard electroretinogram (ERG) according to ISCEV protocols. 34 patients showed no abnormality in any parameters. Two patients had abnormal DA and ERGs. The mean scotopic ERG b wave amplitude of the isotretinoin group was 496.5 microV (SD 51.3 microV) compared with 501.7 microV (62.3.1 microV) among the controls. The group mean a:b ratio was 0.55 (0.04) compared to 0.69 (0.08) in the controls.

Previous use of isotretinoin may have caused retinal toxicity in two subjects and laboratory evidence of night blindness in 11 further subjects. One subject had subclinical changes remaining in the ERG 96 months after cessation of isotretinoin. This may justify the directed use of electrophysiological screening in professions that are night vision critical.

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Tuberculosis of the craniovertebral junction: is surgery necessary?

Tuberculosis of the craniovertebral junction is an uncommon entity and its optimal management remains controversial. In this study, we present the evolution of management protocol of this disease in our institute in the past 3 decades. A total of 51 patients with craniovertebral junction tuberculosis presenting as atlantoaxial dislocation from 1978 through 2004 were reviewed. The disease was rated from Stage I to Stage III, depending on the radiological findings. All patients received antitubercular treatment for 18 months. In the initial period of this study (1978-1986), all patients (n = 10) underwent surgery, usually a posterior fusion. In the second period (1987-1998), patients with less severe disease (Stages I and II, n = 14) were managed with external rigid immobilization, whereas patients with severe disease (Stage III, n = 11) underwent either a transoral decompression with or without posterior fusion or posterior fusion alone. More recently (1999-2004), all patients (n = 16) in all stages (Stages I-III) have been managed without surgery by a rigid external immobilization. Except for two patients who died (one because of miliary tuberculosis, the other because of acute hydrocephalus), clinical recovery occurred in all. Follow-up imaging demonstrated radiological healing as well, with regrowth of the destroyed bone.

The mainstay of management of tuberculosis of the craniovertebral junction is prolonged antitubercular treatment with a rigid external immobilization. Surgery is not necessary, even in patients with advanced stages of disease. Complete clinical and radiological healing occurs in all patients with conservative treatment.

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Ultrasound in adhesive capsulitis of the shoulder: is assessment of the coracohumeral ligament a valuable diagnostic tool?

To determine the accessibility of the coracohumeral ligament (CHL) by ultrasound (US) and to determine CHL thickness in adhesive capsulitis of the shoulder. US examinations were carried out in 498 consecutive shoulders of 306 individuals (194 women and 112 men), mean age 47.4 years (range 15-92 years), in order to identify and measure the maximum thickness of the CHL. The patients were divided into three study groups: asymptomatic shoulders (n=121), painful shoulders (n=360) and shoulders with arthrographic evidence of adhesive capsulitis (n=17). The mean maximal thickness of CHL was compared among the 3 study groups (non-parametric test of Kruskal-Wallis, p<0.05). The CHL was visualized in 92 out of 121 shoulders in the asymptomatic group (76.0%), in 227 out of 360 shoulders in the painful shoulder group (63.0%), and in 15 out of 17 shoulders in the adhesive capsulitis group (88.2%). The average thickness of the CHL was significantly greater in adhesive capsulitis (3 mm) than in the asymptomatic (1.34 mm) and painful (1.39 mm) shoulders. No significant difference was found between asymptomatic and painful shoulders.

CHL depiction can be achieved in a reasonable proportion of shoulders. A thickened CHL is suggestive of adhesive capsulitis. More studies are needed for clinical validation of these data.

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Merkel cell carcinoma: Is there a role for 2-deoxy-2-[f-18]fluoro-D-glucose-positron emission tomography/computed tomography?

2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is becoming widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single study. The role of FDG-PET/CT is proven in lymphoma, melanoma, colorectal carcinoma, and other cancers. However, there are rare malignancies such as Merkel cell carcinoma that can potentially be evaluated with PET/CT. We were therefore prompted to review our experience with FDG-PET/CT in the management of patients with Merkel cell carcinoma. This is a retrospective case series of six patients with Merkel cell carcinoma, 58-81 years old (average 69 +/- 8.3), who had whole-body PET/CT at our institution from January 1st, 2003 to August 31st, 2005. Two patients were women and four were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed. Twelve examinations were acquired for the six patients (one patient had six PET/CT, one patient had two PET/CT, and four patients had one PET/CT). The injected FDG doses ranged 381.1-669.7 MBq (average 573.5 +/- 70.3). Four patients had the PET/CT as part of initial staging, and two patients had the exam for restaging (after surgery and XRT). A total of six Merkel lesions (pancreas, adrenal, lip, submandibular lymph nodes, cervical lymph nodes, and parapharyngeal soft tissue) were identified in three patients and confirmed on histopathological examination. The FDG uptake in these areas was intense, with maximum standardized uptake value (SUVmax) values of 5-14 (average 10.4 +/- 3.8). In one patient, the PET/CT scan identified abnormal focal distal sigmoid uptake that was biopsied and diagnosed as adenocarcinoma. Two patients had negative scans and had no clinical evidence of disease on follow-up office visits (up to one year after PET/CT).

This case series suggests that FDG-PET/CT may have a promising role in the management of patients with Merkel cell carcinoma.

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Best practices for smoking cessation in pregnancy: do obstetrician/gynecologists use them in practice?

To assess Ohio obstetrician/gynecologists' perceptions and use of the 5As method of smoking cessation (ask, advise, assess, assist, and arrange) with pregnant patients who smoke. A three-wave mailing procedure was used with a statewide random sample of obstetrician/ gynecologists who responded to a valid and reliable 31-item questionnaire. Regarding the 5As method of smoking cessation, almost all (98%) asked their pregnant patients about smoking, but fewer respondents engaged in advising (66%), assessing (42%), assisting (29%), and arranging for follow-up visits or referrals (6%). Higher efficacy expectations were associated with greater use of the 5As method (r = 0.52, p<0.001). A majority believed that two cessation activities would result in smoking cessation in pregnant smokers: explaining the dangers of smoking (65%) and referring pregnant smokers to smoking cessation programs (57%). However, 26% of physicians reported that they were "slightly confident" or "not confident at all" in their ability to refer pregnant smokers to such programs, and 6% of physicians reported always providing smoking cessation referrals. A significant proportion of respondents believed that prenatal smoking would not cause severe effects for the unborn child but would likely lead to moderate (46%) or minor (3%) health effects.

Obstetrician/gynecologists face many competing demands for their time and energy, yet 62% believed smoking cessation advice would be of significant value. Physicians with higher levels of efficacy expectations reported significantly greater use of the 5 As. Future research should explore ways to facilitate obstetrician/gynecologists' use of the 5As method.

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Success in treating renal calculi with single-access, single-event percutaneous nephrolithotomy: is a routine "second look" necessary?

Percutaneous nephrolithotomy (PCNL) is an effective procedure for the treatment of large renal calculi. An important consideration for patients undergoing PCNL is the management of any residual stone burden, which may include "second-look" nephroscopy. The utility of this practice is unproven, and we present our data on a series of patients in which second-look procedures were not performed. We retrospectively reviewed the records of 43 consecutive patients undergoing a total of 45 procedures by a single surgeon at a tertiary-care center. Patients were considered stone free if no calculi were evident by either plain film or noncontrast CT scan. Statistical analysis was used to look for correlations between radiographic stone clearance and various patient and stone characteristics. Of these procedures, 15% had immediate postoperative evidence of residual fragments. At a mean follow-up of 8 months, 32.5% had residual or recurrent stone. There were statistically significant correlations between both patient age and stone size and the risk of recurrent or residual stone.

In our study, PCNL was effective for the single-stage treatment of large renal calculi. Aggressive stone clearance obviated the need for routine second-look nephroscopy. Factors leading to an increased risk of residual or recurrent calculi included the presence of a staghorn calculus and younger patient age. The excellent stone-free rates achieved suggest that routine second-look nephroscopy may not be necessary for the majority of patients undergoing PCNL.

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Laparoscopic right donor nephrectomy: is there a right way?

There is a continuing reluctance among transplant surgeons to procure a right-kidney allograft laparoscopically. We describe our experience with right laparoscopic donor nephrectomy (RLDN) by three techniques. We retrospectively analyzed all seven RLDNs performed at our center from January 2002 to June 2005. The technique used in a particular case depended on the anatomy of the renal vasculature and included transperitoneal (N = 1), retroperitoneoscopic (N = 4), and retroperitoneoscopy-assisted approaches without the use of hand port or other assist devices (N = 2). No stapling or manual-assist devices were used in the last four cases for division of the renal vessels. The mean blood loss, operating time, hospital stay, and serum creatinine concentration on day 7 were 94.3 +/- 46.9 mL (SD), 212.8 +/- 66 minutes, 4.9 +/- 1.9 days, and 1.1 +/- 0.2 mg/dL, respectively. The overall warm ischemia time was 217 +/- 116 seconds. Our preferred technique currently is to go for a total retroperitoneoscopic approach to the right kidney initially. If the renal vein appears short, we make a small subcostal incision to retrieve the kidney openly at this stage (retroperitoneoscopy-assisted approach) with minimal risks to the donor and recipient.

Retroperitoneoscopic RLDN performed without hand-assist or stapling devices is safe and cost-effective and yields kidneys with excellent function. Rather than have a fixed approach to RLDN, we suggest a choice depending on the length of the renal vessels observed during surgery.

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Is there a minimum caseload that achieves acceptable operative mortality in abdominal aortic aneurysm operations?

Studies have shown correlation between operative workload and mortality for major operations. Is there a threshold for case volume that predicts an acceptable mortality for abdominal aortic aneurysm surgery? Hospital Episode Statistics (HES) Data for England between 1997-2002 was analysed using ICD-10 codes I71.x and OPCS-4 codes L16.x-L26.x. Mortality was identified by the method of discharge. 31,078 operations on abdominal aortic aneurysms were studied in 223 NHS Trusts. 6,007 in-hospital deaths were identified in both elective and emergency cases (overall mortality rates 7.7% and 40%, respectively). Trusts with large elective workloads had reduced mortality for both elective and emergency operations. Using parabolic regression and logarithmic transformation, 14 elective operations per Trust per year was identified as a cut-off point above which the decrease in mortality rate with increasing case volume was relatively small. A similar effect was not seen with increasing emergency workload alone.

HES data analysis suggests increasing elective workload correlates with lower in-hospital mortality for elective and emergency operations on abdominal aortic aneurysm. Data suggests a range of hospital caseload that correlate with an acceptable elective and emergency mortality rate.

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Long hours in paid and domestic work and subsequent sickness absence: does control over daily working hours matter?

To explore the associations of working hours (paid, domestic, commuting, and total) with sickness absence, and to examine whether these associations vary according to the level of employee control over daily working hours. Prospective cohort study among 25 703 full-time public sector employees in 10 towns in Finland. A survey of working hours and control over working hours was carried out in 2000-01. The survey responses were linked with register data on the number of self-certified (<or =3 days) and medically certified (>3 days) sickness absences until the end of 2003. Poisson regression analyses with generalised estimating equations were used to take into account the fact that the employees were nested within work units. Adjustments were made for work and family characteristics and health behaviour. The mean follow-up period was 28.1 (SD 8.1) months. Long domestic and total working hours were associated with higher rates of medically certified sickness absences among both genders. In contrast, long paid working hours were associated with lower rates of subsequent self-certified sickness absences. Long commuting hours were related to increased rates of sickness absence of both types. Low control over daily working hours predicted medically certified sickness absences for both the women and men and self-certified absences for the men. In combinations, high control over working hours reduced the adverse associations of long domestic and total working hours with medically certified absences.

Employee control over daily working hours may protect health and help workers successfully combine a full-time job with the demands of domestic work.

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Does a birthday predispose to vascular events?

To examine the influence of birthdays on the onset and course of vascular events such as stroke, TIA, and acute myocardial infarction (AMI). This population-based study included all emergency department (ED) admissions due to ischemic stroke, TIA, or AMI from April 2002 to March 2004 in Ontario, Canada. All cases were identified through the National Ambulatory Care Reporting System. Calculations of daily and weekly numbers of events were centered on the patient's birthday and the week of the birthday. Statistical analyses include binomial tests and logistic regression. During the study period, there were 24,315 ED admissions with acute stroke, 16,088 with TIAs, and 29,090 with AMI. The observed number of vascular events during the birthday was higher than the expected daily number of visits for stroke (87 vs 67; p = 0.009), TIA (58 vs 44; p = 0.02), and AMI (97 vs 80; p = 0.027) but not for selected control conditions (asthma, appendicitis, head trauma). Vascular events were more likely to occur on birthday (242 vs 191; odds ratio [OR] = 1.27). No significant differences were observed during the birthday week for any of the conditions. Multivariate logistic regression showed that birthday vascular events were more likely to occur in patients with a history of hypertension (OR = 1.88; 95% CI 1.09 to 3.24). Sensitivity analyses with alternative definitions of birthday week did not alter the results.

Stress associated with birthdays may trigger vascular events in patients with predisposing conditions.

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Routine urine culture at the time of percutaneous urinary drainage: does every patient need one?

To determine the clinical variables associated with bacteriuria in patients undergoing primary percutaneous antegrade urinary drainage procedures in order to predict the utility of routinely obtaining urine cultures at the time of the procedure. Between October 1995 and March 1998 urine cultures were prospectively obtained in all patients undergoing a primary percutaneous antegrade urinary drainage procedure. One hundred and eighty-seven patients underwent 264 procedures. Results were available in 252 cases. Culture results were correlated with clinical, laboratory, and demographic variables. Anaerobic cultures were not uniformly performed. Urine cultures were positive in 24 of 252 (9.5%) cases. An indwelling or recently removed ipsilateral device (catheter or stent) and a history of previous cystectomy with urinary diversion were significant predictors of a positive culture. Patients without either of these predictors, and without clinical or laboratory evidence of infection, were rarely found to have positive cultures.

The likelihood of a positive urine culture can be predicted on the basis of the aforementioned clinical variables. In the absence of these clinical indicators routine urine cultures are neither useful nor cost-effective.

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Is it time to reevaluate the entrance requirements for medical studies?

Since 1960, the number of female medical students has risen and now amounts to about 60% of the total. During this period, the entrance requirements for medical studies have been changed, meaning that it is average A-level marks that qualify students for studying medicine (Quota 1 students). Some students whose A-level marks are unsatisfactory can be admitted anyhow, if they have had occupational experience (Quota 2 students). The aim of this article is to present some of the conditions that are of importance to the students' rate of finishing their medical studies. From 1992 to 2002, four questionnaires were given to a cohort of medical students admitted to the university in summer 1992. The first questionnaire, the data from which are used in this article, was answered by 252 students (79%). Information about the graduation status of this group was extracted from the university database. The results showed that 49% of the 252 students were Quota 2 students and that these were on average somewhat older at time of admittance (22.3 years) than were Quota 1 students (20.3 years). More women (53%) than men were Quota 1 students. There was no difference between Quota 1 and 2 students as regarded the time spent on their studies and the percentage who graduated. Male students were significantly more successful in finishing their studies (75%) than were female students (61%). Furthermore, there was a majority of upper-class students, and these students, like the students with a background in natural science and those whose father had a university degree, had a high completion rate.

The study does not show that there is a basis for abolishing the Quota 2 arrangement. Even if the differences are minor, it might lead to a reduction in the number of male students. Seen from the point of view of gender equality, that would not be desirable. The fact that so many students, particularly the female students, do not finish their studies should be further examined.

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The newly graduated doctor.Is he or she sufficiently prepared to fulfill a doctor's responsibilities?

The goal of this study was to illuminate how a group of newly graduated medical doctors experienced their knowledge and resources in their work shortly after they had graduated. We performed a prospective study of the students who started medical school in 1992. 252 students (79%) answered questionnaire 1, which was sent to them at the beginning of medical school in 1992. Questionnaire 4 was sent to the students at their graduation in 2002, and 57% answered. 80% (n = 143) of those who had graduated answered questionnaire 4. 111 of those who had graduated had been practising medicine for more than 1 year and were included in the study. 72% of the medical doctors stated that the theoretical part of medical school had given them a solid foundation for clinical work but too little direction toward clinical work. They did not feel that they had developed a good foundation for collaborating with other professionals, did not have good role models or had not received good enough support for personal development. Only 55% felt that it was easy to talk about professional issues. At the start of medical school, many of the students reported having had psychological problems; this percentage fell during the course of medical school but was again high at graduation. 60% of the medical doctors stated that the clinical work had strengthened their self-esteem, but 41% felt that the clinical work had caused them personal problems. The study showed that conditions in the students' private life as well as at the university were important to the results. Women doctors had the most serious problems.

The medical doctors did not feel that they were well enough equipped for their clinical work. The study points out that it is important to make clinical education better and to give more personal support to the students during their time in medical school. Furthermore, focus is directed at the pattern of the gender roles, where women in particular are having problems.

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Is device closure for direct access valved stent implantation safe?

Despite the progress made in the development of valved stents for trans-apical valve replacement, a reliable closure of the access orifice remains a major issue. The present study was designed to evaluate if device closure of the ventricular wall is safe. Transventricular access for pulmonary valve replacement was simulated with a 26F sheath and the resulting orifice was closed with an Amplatzer Muscular VSD Occluder (AMuscVSDO) in chronic sheep experiments (body weight 45-48 kg). Mean procedure time, blood loss, and standard hemo-dynamics were recorded. The animals were sacrificed electively and the histopathological changes in and around AMuscVSDO in the right ventricular wall were systematically studied by semi-quantitative analysis of collagenisation, inflammatory response and 'resorptive' process. Mean procedure time was 31+/-10.7 min, blood loss was 22.5+/-8.7 ml, heart rate was 123+/-22.6 bits/min before and 128+/-28.7 bits/min after, mean arterial blood pressure was 88+/-16.7 mm Hg before and 82.6+/-18.3 mm Hg after the procedure. Mean survival was 5.3 weeks. The collagen and scar formation studies revealed three different periods: (1) initial fibrosis (0-3 weeks); (2) so-called 'capsulation' (3-9 weeks after the implantation of the Occluder); and (3) final remodelling and differentiation (9 weeks). The fabric inside the Occluder played the role of a collagenisation promoter, active from the 3rd week till it vanishes. Inflammation plays a role as a temporary reaction (0-3 weeks) during the healing process, with no signs of any active, focal or circumscribed, myocardial damage.

(1) The closure of the free ventricular wall perforation with AMuscVSDO is safe due to the scar tissue resulting from the healing process around and in the device. (2) The myocardial healing around and inside an implanted AMuscVSDO represents two processes: extensive fibrosis ensues around metallic wires with the progression towards the inside of the myocardium, whereas inside AMuscVSDO the loose connective tissue fills the myocardial lesion. During cicatrisation, the fabric elements of AMuscVSDO act as the ground for collagen formation and fibroblast proliferation. (3) The cicatrisation processes after ventricular AMuscVSDO implantation show remodelling, with rearrangement of collagen fibres architecture and distribution.

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Does off-pump surgery offer benefit in high respiratory risk patients?

The role of off-pump surgery in high respiratory risk patients remains unclear. In this study, we aim to evaluate the effect of off-pump surgery on high respiratory risk patients. To achieve comparative groups, a five digit propensity score matching with 18 pre-operative variables was performed on 4406 consecutive CABG patients operated between January 2000 and September 2003. Respiratory risk stratification was performed with the following variables: (1) FEV(1)<65% of predicted, (2) patients>75 years old, (3) history of current smoking, (4) body mass index more than 40 kg/m(2) and (5) NYHA class IV dyspnoea in combination with current respiratory medication. The presence of two or more variables defined high risk. The primary end point was post-operative ventilation time. We also compared alveolar arterial gradients (A-a gradient) on admission to ITU, 2 and 4h using Friedman rank time analysis. We matched 1353 off-pump patients with 1353 unique on-pump patients. Respiratory risk stratified selection resulted in 73 off-pump and 55 on-pump high-risk patients. In the off-pump group, four (5.5%) patients had more than two selection criteria, compared to one (1.8%) for on-pump patients (p=0.29). The off-pump group had more patients with FEV1<65% compared to on-pump: 65 (89.0%) versus 40 (72.7%); p=0.017. The median ventilation time was significantly shorter for off-pump patients (7h [IQR: 5-14] vs 12h [IQR: 7-18], p=0.003). In the off-pump group, three (4.1%) patients had a ventilation time>48 h compared to eight (14.6%) in the on-pump group, p=0.037. A-a gradient measurements on admission to ITU were lower in off-pump patients (median: 182.3 [IQR: 126.6-216.2]) compared to on-pump patients (median: 194.7 [IQR 139.7-245.4], p=0.064).

Off-pump surgery offers benefit to high respiratory risk patients by reducing post-operative ventilation time. Off-pump patients also have lower A-a gradients in the early post-operative period but this failed to reach significance.

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Does topical application of 5-fluorouracil ointment influence inner ear function?

To investigate the effect of 5-fluorouracil (5-FU) ointment on the inner ear of guinea pigs. In group A (n = 7), 5-FU ointment was applied into the left external auditory canal. In group B (n = 10), 5-FU ointment was applied to the left middle ear through myringotomy. In both groups, the right ear served as a control. One week later the endocochlear DC potential (EP) was measured and morphology of the cochleae was examined using scanning electron microscopy (SEM) and light microscopy. In group A, there was no significant difference between the EP values of the experimental side and the control side. In group B, there was a statistically significant difference between them (P<0.05). Morphologic findings showed no damage.

5-FU ointment application to the external ear seems to be safe but its application to the middle ear may pose some risk of ototoxicity.

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Magnetic resonance-based serial pelvimetry: do maternal pelvic dimensions change during pregnancy?

The purpose of the study was to evaluate the stability of the maternal pelvis over the course of the third trimester and the puerperium. Pregnant patients were recruited to undergo comparative magnetic resonance-based pelvimetry and fetal ultrasonography at 37 to 38 weeks of gestation. Most of the patients were recruited from a study of women who planned a trial of labor after a previous cesarean delivery for cephalopelvic disproportion. These results have been reported previously. Patients then underwent magnetic resonance-based pelvimetry within 3 days and at 3 months after delivery. Postdelivery analysis was used to answer the question: Do pelvic dimensions change after delivery? Eighteen patients completed the study. Eleven of the patients underwent cesarean deliveries, of which 4 deliveries were before labor. Seven patients had successful vaginal births after their previous cesarean delivery. Statistical analysis of the 18 patients determined that pelvic measurements did not demonstrate change over the course the study.

Serial magnetic resonance-based pelvimetry showed relative stability of pelvic measurements through the course of pregnancy and delivery. If comparative pelvimetry is to be useful as an antepartum predictor of labor success, then it may be possible to obtain reliable pelvimetry in those patients anytime after delivery.

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Stage IB nonsmall cell lung cancers: are they all the same?

There is renewed interest in adjuvant chemotherapy after complete resection of nonsmall cell lung cancer, including stage IB (T2N0) cancers. Given the heterogeneity of the T2 classification, we hypothesize that there are survival differences in patients with stage IB NSCLC based on specific histopathologic tumor characteristics. A retrospective evaluation of 119 consecutive patients from 1999 to 2004 with a pathologic diagnosis of T2N0 nonsmall cell lung cancer was performed. Patient follow-up was 97%. Overall survival and disease-free survival rates were calculated by the Kaplan-Meier method. Univariate analysis was performed using the log rank test and multivariate analysis by Cox's proportional hazard model. Data were significant if p<0.05. The 4-year overall survival and disease-free survival rates were 62% and 60%, respectively. The local and distant recurrence rates were 5% and 18%, respectively. Tumor size (p = 0.001), histologic grade (p = 0.002), the Eastern Cooperative Oncology Group performance status (p = 0.002), angioinvasion (p = 0.03), and visceral pleural involvement (p = 0.02) were predictors of overall survival by univariate analysis. Multivariate analysis demonstrated increasing tumor size (1.26 [95% confidence intervals 1.12, 1.64]) and histologic grade (4.05 [95% confidence intervals 1.38, 11.90]) to be significant independent predictors of a worse overall survival. The 4-year survival of patients without any of these variables was 89% compared with 56% if one or more of these factors were present (p = 0.03).

There is significant heterogeneity in the T2N0 class of nonsmall cell lung cancer. Risk stratification using specific histopathologic variables may help determine which patients will benefit most from adjuvant therapy.

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Limitations of EuroSCORE for measurement of risk-stratified mortality in aortic arch surgery using selective cerebral perfusion: is advanced age no longer a risk?

The European system for cardiac operative risk evaluation (EuroSCORE) is a risk stratification tool for perioperative mortality of cardiothoracic surgery that was developed in Europe and validated in North America in more than 500,000 patients. The operative mortality of aortic arch surgery has been improved by various novel operative techniques and adjuncts, whereas the number of such procedures for elderly patients has recently been increasing. The aim of this study was to examine the usefulness of the EuroSCORE, and our modification of it regarding age, in predicting mortality after aortic arch repair performed with selective cerebral perfusion. We reviewed 358 consecutive patients with a mean age of 69 +/- 10 years undergoing aortic arch repair with selective cerebral perfusion between January 1993 and February 2004. Observed in-hospital mortality was compared with predicted mortality as determined by both additive and logistic EuroSCOREs. We also evaluated a version of the EuroSCORE modified for age, which was obtained by subtracting the contribution of age from the original EuroSCORE. Score validities were assessed by calculating the areas under receiver operating characteristic curves. Overall hospital mortality was 6.2% compared with 7.7% (additive EuroSCORE) and 11.8% (logistic EuroSCORE). Area under the receiver operating characteristic curve was 0.58 for the additive EuroSCORE and 0.58 for the logistic EuroSCORE as well. The overall age-unrelated EuroSCOREs were 5.1% (additive) and 5.2% (logistic), respectively, and areas under the receiver operating characteristic curve were 0.70 for additive and 0.69 for logistic.

The original additive and logistic EuroSCOREs overpredicted mortality in this patient group, whereas the age-unrelated EuroSCORE was better in predicting mortality.

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Impaired natural immunity, cognitive dysfunction, and physical symptoms in patients with chronic fatigue syndrome: preliminary evidence for a subgroup?

The diagnostic criteria of chronic fatigue syndrome (CFS) define a heterogeneous population composed of several subgroups. Past efforts to identify subgroup markers have met with mixed success. This study was designed to examine natural killer cell activity (NKCA) as a potential subgroup marker by comparing the clinical presentations of CFS patients with and without clinically reduced NKCA. Forty-one female CFS patients were classified into having either low or normal NKCA levels. These subgroups were then compared on objective measures of cognitive functioning and subjective assessments of fatigue, vigor, cognitive impairment, and daytime dysfunction. Relative to CFS patients in the normal-NKCA subgroup, low-NKCA patients reported less vigor, more daytime dysfunction, and more cognitive impairment. In addition, low-NKCA patients performed less on objective measures of cognitive functioning relative to normal-NKCA patients.

The results are offered as preliminary evidence in support of using NKCA as an immunological subgroup marker in CFS. Findings are also discussed in terms of known associations between dysregulated immune functions, somatic symptoms, and psychological stress.

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In search of a new balance. Can high "action-proneness" in patients with chronic fatigue syndrome be changed by a multidisciplinary group treatment?

The purpose of this study is to investigate changes in action-proneness (a cognitive and behavioral tendency toward direct action) after a multidisciplinary group intervention, including cognitive behaviour therapy (CBT) and graded exercise therapy (GET). Patients with chronic fatigue syndrome (n=62) completed three versions of a Dutch self-report questionnaire evaluating action-proneness retrospectively that is (1) before illness onset, (2) before treatment and (3) after treatment. Significant others (n=62) also gave their opinion about the patients' action-proneness at time points 1 and 2. Premorbid action-proneness levels considerably dropped after illness onset. After treatment, action-proneness levels significantly increased again, although levels remained below premorbid levels.

High action-proneness retrospectively reported by CFS patients can be adaptively modified by a multidisciplinary group treatment including CBT and GET.

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Ultrasound-guided central venous cannulation: is there a difference between Doppler and B-mode ultrasound?

To compare the success of Doppler and B-mode ultrasound-guided internal jugular vein (IJV) catheterization with respect to body mass index (BMI). Prospective, randomized study. Section for cardiovascular anesthesia of a university hospital. 338 consenting patients were analyzed. Subjects receiving central venous catheters for scheduled cardiac surgery were divided into two groups. After induction of general anesthesia, the right or left IJV was assessed for midcervical cannulation approach. In the Doppler group (n = 189), a SonoGuide2 with a 5.0-MHz probe was used. In the B-mode group (n = 149), the SiteRite II ultrasound system with a 7.5-MHz transducer was used. There was a significant difference in the success rate of first needle pass between the two groups: Doppler group, 91% (172/189); B-mode group, 96.6% (144/149) (P = 0.045). A BMI of 30 and greater was associated with a significantly lower first needle pass success rate in the Doppler group (Doppler group, 77.1% [27/35]; B-mode group, 97.4% [38/39]; P = 0.011). The success rates in patients with a BMI below 30 for both methods were not different (Doppler group, 94.2% [145/154]; B-mode group, 96.4% [106/110]; P = 0.567). Arterial punctures occurred three times under Doppler guidance and twice under B-mode guidance.

Cannulation of the IJV can be ensured and first needle pass success rate maximized by both ultrasound techniques. In patients with a BMI greater than 30, B-mode technique is superior to Doppler ultrasound.

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Can the presence of carotid artery calcification on panoramic radiographs predict the risk of vascular diseases among 80-year-olds?

The purpose of this study was to evaluate whether subsequent vascular diseases and related death could be predicted by the presence of carotid artery calcification detected on panoramic radiographs among elderly persons. We evaluated 659 panoramic radiographs from 262 male and 397 female 80-year-old subjects and their general medical examination data to assess the relationship between the presence of carotid artery calcification and vascular disease risk at baseline examination. Of these subjects, the occurrence of vascular diseases within 5 years after baseline examination was examined in 191 subjects. Further, the causes of death were examined in 108 subjects who died within 5 years after baseline examination. There was a significant difference in the history of past vascular diseases among subjects with and without carotid artery calcifications; however, no significant difference in the occurrence of subsequent vascular diseases was found among them. Further, there was no significant difference in the occurrence of vascular disease-related death within 5 years after baseline examination among subjects with and without carotid artery calcifications (P = 0.719).

Our results suggest that the presence of carotid artery calcifications on panoramic radiographs may be related to the history of past vascular diseases; however, this is not a useful marker for subsequent vascular diseases and related death among 80-year-olds.

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Plastic specula: can we ease the passage?

For many years, genitourinary physicians have taught that specula should be used without lubrication other than water, as it was assumed that gel would interfere with the processing of samples, but there seems little evidence to support this. Many clinics are now using plastic specula to avoid reusable instruments, and one of the commonest problems with such specula is increased friction. We looked at the effect of Aquagel on the culture of different dilutions of Neisseria gonorrhoeae on three standard laboratory media. The effect of Aquagel on the chlamydial strand displacement assay (SDA) test was also assessed by mixing different amounts of Aquagel with the positive and negative control and processing in the usual way. There was found to be no inhibition of culture following emulsification of N gonorrhoeae in Aquagel at any concentration. All the results for the chlamydial SDA test were satisfactory following mixing with Aquagel.

We think that the clinician should now be more confident that if a difficult examination requires the use of a lubricant, the test results will not be compromised.

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Does unwantedness of pregnancy predict schizophrenia in the offspring?

We sought to replicate (or refute) a previous report of an association between unwantedness of a pregnancy and the risk of schizophrenia in the offspring. The study was conducted using a large, prospectively collected birth cohort as part of the Prenatal Determinants of Schizophrenia study (PDS). Attitude toward the pregnancy was assessed at the time of the mother's first visit to the prenatal clinic. Cases of schizophrenia and other schizophrenia spectrum disorders in the offspring of these mothers were subsequently ascertained and diagnosed. In univariate and multivariate analyses, we examined the relationship between attitude toward the pregnancy and risk of adult schizophrenia and other schizophrenia spectrum disorders. The unadjusted hazard ratio for the association between ambivalent or negative maternal attitude toward the pregnancy and the risk of schizophrenia spectrum disorders was 1.75, (95% CI=0.97, 3.17, P=0.06). This result was unchanged after adjustment for social class, paternal age, race/ethnicity and other potential confounders. Similar results were observed when only cases with schizophrenia were included in the analysis.

We did not find a statistically significant association in favor of the hypothesis that unwantedness of pregnancy is a risk factor for adult schizophrenia. On the other hand, the magnitude of the observed association was similar to the findings of the only previous study of this question and the confidence limits overlap those findings. Whether unwantedness of pregnancy is a risk factor for adult schizophrenia remains an open question that may be resolved by future research.

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Does continuity of care by well-trained breastfeeding counselors improve a mother's perception of support?

Social support has been shown to be greatly important for breastfeeding success. The objective of this study was to investigate if mothers who were attended by midwives and nurses specially trained in breastfeeding counseling perceived better continuity of care and emotional and informative breastfeeding support than mothers who received only routine care. Ten municipalities, each with an antenatal center and child health center, in southwest Sweden were randomized either to intervention or control municipalities. The intervention included a process-oriented training in breastfeeding counseling and continuity of care at the antenatal and child health centers. Primiparas were asked to evaluate the care given, and those living in the control municipalities were divided into control groups A and B. Data collection took place at different points in time for the two control groups. The 540 mothers responded to 3 questionnaires at 3 days and at 3 and 9 months postpartum. The perception of support provided by the health professionals and from the family classes was rated on Likert scales. Intervention group mothers rated the breastfeeding information given during the family class as significantly better during pregnancy than both control groups, and better than control group B mothers at 3 months postpartum; compared with both control groups, intervention group mothers perceived that they received significantly better overall support and that postnatal nurses provided better information about breastfeeding and the baby's needs. At 9 months, intervention group mothers were more satisfied with knowledge about social rights, information about the baby's needs, and their social network than control group B mothers. Both intervention group and control group B mothers perceived better overall support than control group A during pregnancy. At 3 and 9 months, intervention group mothers perceived that postnatal nurses were more sensitive and understanding compared with both control groups.

After implementation of a process-oriented breastfeeding training program for antenatal midwives and postnatal nurses that included an intervention guaranteeing continuity of care, the mothers were more satisfied with emotional and informative support during the first 9 months postpartum. The results lend support to family classes incorporating continuity of care.

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Do we primary care doctors improve our prescription of generic medicines after the intervention of the area pharmacist?

To evaluate the prescription of generic medicines by the primary care doctors in a health district after an intervention programme conducted by the area pharmacist. Intervention study. Two indicators were selected as indicators of pharmaceutical prescription of generics. Primary care. District 8 of Area 3, Valencian Community, Spain. Eleven family doctors and 2 paediatricians. a) Information session in the health centre given by the area pharmacist; b) delivery of the catalogue of generic medicines; c) delivery of the control panel to every physician; and d) possibility of connection to the GAIA system. A before-and-after evaluation was made (at 6 months and 12 months from the intervention) of every doctor. Values were compared with the 2 indicators of pharmaceutical prescription. Before the intervention, no doctor was fulfilling the Indicators of pharmaceutical prescription 1 and 2. At 6 months, all the doctors had increased their prescription of generics. Seven doctors met the objective of Indicator 1; and 8, that of indicator 2. At 12 months the increase remained and even grew.

The prescription of generics measured with indicators of pharmaceutical prescription 1 and 2 improved.

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Is surgery for multiple lung metastases reasonable?

Our objective was to define the role of a new 1318-nm Nd:YAG laser for lobe- and parenchyma-saving resection of multiple lung metastases. From January 1996 to December 2003, a total of 3267 nodules (10/patient) were removed from 328 patients (164 men/164 women, mean age 61 years). Criteria for eligibility were expanded to any primary tumors with no upper limit of metastases given. All parenchymal resections were performed with a new 1318-nm Nd:YAG laser whose effect on lung tissue differs significantly from that of the 1064-nm wavelength owing to a 10-fold higher absorption in water and one-third extinction in blood. In 93%, precision laser resection was achieved. The lobectomy rate was only 7%. Pathologic examination revealed 2546 metastases (8/patient) and lymph node disease in 19%. Complete resections (R0) were achieved in 93% of 177 patients undergoing unilateral procedures with a mean of 3 metastases (range 1%-29%) and 75% of 151 patients having bilateral operations with a mean of 13 metastases (range 2-124). The 5-year survival after R0 was 55% for solitary nodules, 41% for all patients, 28% for 10 metastases, and 26% for 20 or more metastases resected. Outcome was significantly poorer after incomplete resection (7%). No 30-day mortality was observed. Major postoperative complications included prolonged air leaks (n = 2), intrapleural bleeding (n = 2), and late pneumothorax (n = 2); all were treated successfully with a chest tube.

This new 1318-nm Nd:YAG laser facilitates complete resection of multiple bilateral centrally located metastases and thus is lobe sparing. Resection of 20 or more metastases is reasonable because long-term survival was significantly better than that observed with incomplete resection.

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Carotid intima-media thickness in HIV-infected individuals: relationship of premature atherosclerosis to neuropsychological deficits?

Intima-media thickness (IMT) measured by extracranial duplex sonography is a surrogate marker for atherosclerosis. It is well known that IMT is greater in HIV patients than in age-matched healthy controls due to HIV- induced endothelial damage and metabolic side-effects of antiretroviral therapy. However, it remains unclear whether atherosclerosis has an additional impact on cognitive function in HIV patients. Therefore, the objective of this study was to investigate the correlation between IMT and neuropsychological deficits in HIV patients. 47 HIV patients and 40 age-matched healthy controls were examined by extracranial ultrasound 2 and 3 cm before the flow divider to evaluate differences in IMT. Possible neuropsychological deficits in HIV patients were assessed using a battery of 10 neuropsychological tests. Results of neuropsychological tests and markers of disease severity were correlated with IMT in HIV patients. IMT was significantly greater in patients than in healthy controls (p<0.001). However, none of the neuropsychological tests correlated significantly with IMT measurements in HIV patients. There was only a weak correlation between deficits in attention and IMT in HIV patients (r = 0.44; p = 0.005), which was non-significant after correction for multiple comparisons. Markers of disease severity (CD4 cell count, HIV load in plasma, duration of HIV disease) did not correlate with IMT either.

IMT was greater in HIV patients compared to age-matched controls but it appears that premature atherosclerosis has no additional impact on the evolution of neuropsychological deficits in HIV patients. IMT did not correlate with the severity of immunodeficiency.

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