Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol)

BackgroundA venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines.AimThe aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration.MethodsThrough a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports.     

Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

Background Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank.Methods A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure.Results After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death.Conclusion We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.Subject terms: Predictive markers, Prostate cancer, Risk factors     

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

A Decade of Change in Obesity Surgery

Background: The International (formerly National) Bariatric Surgery Registry began collecting data in January 1986. The aim of this study was to examine changes in the practice of surgical treatment of severe obesity that occurred during the decade of 1986 through 1995, as observed in the IBSR data. Methods: All data submitted to the IBSR during the decade were transferred to the IBM mainframe computer for analysis. Characteristics of operative type populations were compared over time using analysis of variance (ANOVA) for age, body mass index (BMI), operative weight and Chi-square (χ²) test for gender. Results: There has been a steady increase over the decade in mean patient weight. The operations used have changed from predominantly ‘simple’ operations to more frequent use of ‘complex’ operations. Within the categories of ‘simple’ and ‘complex’, an increase in the variety of operations occurred. As a group, patients with ‘simple’ operations have been heavier, more often male and public pay patients than those who have undergone ‘complex’ operations. One year weight loss was greater for Roux-en-Y gastric bypass (RGB) than vertical banded gastroplasty (VBG), but follow-up rates were too low to study the relative merits of the operations used. The reported incidence of operative mortality and serious complications (leak with peritonitis, abscess and pulmonary embolism) remained low. Conclusions: These observations and their implications can be summarized in three statements which relate to action for improved patient care in the beginning of the new century: (1) increasing weight of candidates for surgical treatment during this decade indicates the need for earlier use of operative treatment before irreversible complications of obesity can develop; (2) low risk of obesity surgery, decreasing postoperative hospital stay, and early weight control support the continued and increased use of surgical treatment; (3) continued widespread use of both ‘simple’ and ‘complex’ operations with increased modifications of standard RGB and VBG procedures emphasizes the need for standardized long-term data and analyses regarding both weight control and postoperative side-effects.     

Missed opportunities for participation in prevention of mother to child transmission programmes: Simplicity of nevirapine does not necessarily lead to optimal uptake, a qualitative study

Background  

The objective of this study was to examine missed opportunities for participation in a prevention of mother-to-child transmission (PMTCT) programme in three sites in South Africa. A rapid anthropological assessment was used to collect in-depth data from 58 HIV-positive women who were enrolled in a larger cohort study to assess mother-to-child HIV transmission. Semi-structured interviews were conducted with the women in order to gain an understanding of their experiences of antenatal care and to identify missed opportunities for participation in PMTCT.     

Evaluating the responsiveness of the endometriosis health profile questionnaire: The EHP-30

OBJECTIVES: To evaluate the sensitivity to change of the Endometriosis Health Profile-30 (EHP-30) questionnaire. SETTING: The Women's Center, John Radcliffe Hospital, Oxford. DESIGN: Postal survey to 66 women undergoing conservative surgery for the treatment of endometriosis-associated pain. The EHP-30 and the Short Form-36 (SF-36) were administered 2 weeks before the operation, and 4 months post-operatively. At T2 a transition question was included to evaluate changes in patients health status. To evaluate responsiveness effect sizes, standardised response means, the index of responsiveness and the minimally and clinically important differences were calculated. RESULTS: Forty (66.6%) patients returned the questionnaires at time 1 and 2. Overall less responsive effect size scores were found for the SF-36 (0.1-0.5) compared to the EHP-30 (-0.1-1.1) for all patients who had undergone treatment. Minimally important differences and the index of responsiveness were overall higher for the EHP-30 (0.4-2.0) compared to the SF-36 (0.1-1.0). Change scores for four of the five scales were significantly correlated with women's responses to the transition question. CONCLUSIONS: Results suggest that the EHP-30 is sensitive to change. Its application in clinical trials should prove beneficial in assessing the impact of medical and surgical interventions upon quality of life for women with endometriosis.     

Effects of amyotrophic lateral sclerosis serum on cultured chick spinal neurons

We used a quantitative immunoassay to examine the effects of human serum and immunoglobulins on neurofilament protein expression in cultures of chick spinal neurons. Compared with cultures grown in the presence of serum from healthy controls or patients with other neurologic disorders, ALS serum lowered the level of neurofilament proteins. Effects were similar with or without muscle-derived neurotrophic factors; there was no specificity for motor neurons. No neurotoxic activity was found in immunoglobulin fractions, and there was no evidence of circulating antibodies that might neutralize muscle-derived neurotrophic factors or induce cytolysis of spinal neurons.