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.     

Experimentelle Untersuchungen über die Entzündung der Hornhaut

Ohne ZusammenfassungHierzu Taf. XV–XVI.     

Interactions of angiotensin IV and oxytocin on behaviour in mice.

INTRODUCTION: Angiotensin (Ang) IV enhances learning and memory in rats but there are strain differences in its effects in mice. Oxytocin (OT) also influences learning and memory in rats and mice and, in the light of the proposed effects of Ang IV on oxytocinase, the hypothesis that the effects of Ang IV on cognition in mice involve OT was tested. MATERIALS AND METHODS: The effects of Ang IV and OT, alone and combined, were determined in rat isolated uterine smooth muscle and in object recognition and forced swim tests in BKW mice. RESULTS: Ang potentiated the contractile effects of OT in the uterus. Neither peptide had any effect on object recognition nor locomotor activity. Ang IV had no effect in the forced swim test but abolished the effects of OT. CONCLUSIONS: Ang IV influences the actions of OT in vitro and in vivo, possibly by inhibition of oxytocinase, but the lack of effect of Ang IV on object recognition in BKW mice is unlikely to be a consequence of a deficiency endogenous OT. Unlike OT, Ang IV alone has no effect on learned helplessness in the forced swim test, an effect often used to predict potential antidepressant efficacy in humans.     

Women's knowledge, practises, and intentions regarding correct pelvic floor exercises.

AIM: Although research has demonstrated the efficacy of pelvic floor exercises (PFXs) for the prevention and treatment of female urinary incontinence (FUI), adherence to PFX regimens is commonly poor. There is some evidence that this finding is in part due to a lack of knowledge about how to perform PFXs correctly and misconceptions about the required frequency and duration of PFX regimens. METHODS: By using a sample of 720 postpartum women, this study investigates women's PFX regimens both before and during pregnancy and postpartum. RESULTS: Findings demonstrated that most women were aware of the required frequency for PFXs (at least every second day): just over half had done them this often during pregnancy and 91% intended to do so postpartum. However, few had done them at this level before pregnancy and less than half knew that PFXs should be carried out indefinitely throughout the lifetime. Moreover, only two thirds were confident that they were doing PFXs correctly. CONCLUSION: The findings suggest that, despite good knowledge of the required frequency of PFXs, few women practise them regularly over their lifetime, many apparently perceiving PFXs as relevant only to the childbirth years. Implications for health professionals in addressing these gaps in women's knowledge and practises are discussed.     

骨钙素酶免疫检测方法的研究和应用

目的：建立骨钙素酶免疫测定方法，并应用于临床检测血清骨钙素。方法：应用了3种检测模式，根据检测灵敏度、剂量反应曲线的形态进行分析，选择出合适的模式进一步应用于临床血清标本的骨钙素检测。结果：所采用的骨钙素单克隆抗体是钙离子依赖型的。固相抗原竞争法适合于临床定量测定骨钙素。最低可测限为1．4μg/L;20μg/L骨钙素样品批内CV＝3．98％，批间CV＝12．67％。测定正常献血员140名（年龄17－45岁），第5－95百分位点的骨钙素含量，男性为7．5－15．0μg/L女性为7.0-17.5μg/L。70例疑有骨质疏松症患者血清骨钙素含量2．91－30．20μg/L，以第95百分位点的骨钙素含量为cut-off值，升高5例。与进口试剂盒（Novocalcin,USA）相比较，有较好的相关性，r=0.81。结论：固相抗原竞争法酶免疫测定可以灵敏地检测血清中骨钙素含量，有实用价值。