An overview of translational prostate cancer cohorts for prognostic and predictive studies

The aim of this review is to describe the characteristics of patient cohorts commonly used for translational biomarker research in prostate cancer and to outline the most prominent contemporary cohorts which serve as a source of prognostic and predictive biomarkers. A non‐systematic review of the literature was performed to identify and summarise well‐characterized translational prostate cancer cohorts that provide state‐of‐the‐art characterization of (i) primary and (ii) metastatic and castration‐resistant prostate cancer. The main advantages and features of these cohorts are a substantial number of patients, unique patient groups, comprehensive genetic characterisation of tumours using multi‐omics/next‐generation sequencing approaches, high‐quality control standards and fully or partially open data for the research community. This overview includes the contemporary cohorts which serve as a rich source of new targets for prognostic and predictive biomarkers as well as a reference database for validation of known biomarkers, therefore representing the cohorts whose impact extends over the current state of biomarker research into the near future (5–10 years).     

Predictive factors analysis of the efficacy of cyclophosphamide combined with glucocorticoids in the treatment of idiopathic membranous nephropathy

Objective To investigate the predictive factors affecting the efficacy of cyclophosphamide (CTX) combined with glucocorticoids in the treatment of idiopathic membranous nephropathy (IMN), and to evaluate the efficacy of calcineurin inhibitor (CNI) adjustment due to poor treatment. Methods A retrospective cohort study was conducted. Two hundreds and twenty-eight patients with IMN diagnosed by renal biopsy in the People's Hospital of Guangxi Zhuang Autonomous Region from January 1, 2007 to December 1, 2016 were enrolled. All subjects were treated with CTX in combination with glucocorticoids. The patients were divided into two groups: remission group and no remission group. Multivariable logistic regression analysis was used to determine the baseline clinical-pathological influencing factors for the remission of IMN in the enrolled patients. Results The number of total remission (including complete and partial remission) of the first CTX combined with glucocorticoid treatment in 228 patients with IMN was 188(82.5%). Among them, 141 patients (61.8%) had complete remission (CR), the median time for CR was 8(6, 12) months, and the median time for partial remission (PR) was 3(1, 4) months. The median follow-up time for this study was 25(13, 43) months. Compared with the remission group, the serum albumin level was lower in the non-remission group, the 24-hour urine protein content, the blood complement C3 and C4 levels were higher, and the pathological stage was milder (all P﹤0.05). Multivariate logistic regression analysis suggested that the levels of baseline serum albumin, complement C4, and pathological stage were independent predictors of clinical remission in IMN patients. Twenty-four non-remission patients were treated with CNI. The overall response rate was 66.7%(16/24) at 6 months and 77.3%(17/22) at 12 months. Conclusions The levels of baseline albumin, blood complement C4, and pathological stage were independent predictors of clinical remission in IMN patients treated with CTX plus glucocorticoids. The non-remission patients with CTX combined with glucocorticoid therapy can still achieve a higher response rate after adjusting for CNI.     

The Chinese National Twin Registry: a ‘gold mine’ for scientific research

The Chinese National Twin Registry (CNTR) currently includes data from 61 566 twin pair from 11 provinces or cities in China. Of these, 31 705, 15 060 and 13 531 pairs are monozygotic, same‐sex dizygotic and opposite‐sex dizygotic pairs, respectively, determined by opposite sex or intrapair similarity. Since its establishment in 2001, the CNTR has provided an important resource for analysing genetic and environmental influences on chronic diseases especially cardiovascular diseases. Recently, the CNTR has focused on collecting biologic specimens from disease‐concordant or disease‐discordant twin pairs or from twin pairs reared apart. More than 8000 pairs of these twins have been registered, and blood samples have been collected from more than 1500 pairs. In this review, we summarize the main findings from univariate and multivariate genetic effects analyses, gene–environment interaction studies, omics studies exploring DNA methylation and metabolomic markers associated with phenotypes. There remains further scope for CNTR research and data mining. The plan for future development of the CNTR is described. The CNTR welcomes worldwide collaboration.     

Treatment sequence network meta-analysis in Crohn’s disease: a methodological case study

Objective: Several biologic therapies are available for the treatment of mild-to-moderate Crohn’s disease (CD). This network meta-analysis (NMA) aimed to assess the comparative efficacy of ustekinumab, adalimumab, vedolizumab and infliximab in the maintenance of clinical response and remission after 1?year of treatment.

Methods: A systematic literature search was performed to identify relevant randomized controlled trials (RCTs). Key outcomes of interest were clinical response (CD activity index [CDAI] reduction of 100 points; CDAI-100) and remission (CDAI score under 150 points; CDAI < 150). A treatment sequence Bayesian NMA was conducted to account for the re-randomization of patients based on different clinical definitions, the lack of similarity of the common comparator for each trial and the full treatment pathway from the induction phase onwards.

Results: Thirteen RCTs were identified. Ustekinumab 90?mg q8w was associated with statistically significant improvement in clinical response relative to placebo and vedolizumab 300?mg. For clinical remission, ustekinumab 90?mg q8w was associated with statistically significant improvement relative to placebo and vedolizumab 300?mg q8w. Findings from sub-population analyses had similar results but were not statistically significant.

Conclusions: The NMA suggest that ustekinumab is associated with the highest likelihood of reaching response or remission at 1?year compared with placebo, adalimumab and vedolizumab. Results should be interpreted with caution because this is a novel methodology; however, the treatment sequence analysis may be the most methodologically sound analysis to derive estimates of comparative efficacy in CD in the absence of head-to-head evidence.     

绵阳市2017年男男性行为者性行为特征及无保护措施肛交影响因素

目的 了解男男性行为者(men who have sex with men ,MSM)性行为特征,分析无保护措施肛交影响因素。 方法 2017年1—10月,在四川省绵阳市采用滚雪球抽样法,进行MSM行为学及血清学的横断面抽样调查,用χ²检验、Logistic回归模型进行无保护措施肛交影响因素的单因素及多因素分析。 结果 回收有效问卷1 242份,近6个月肛交91.6%,其中71.4%有保护措施。近6个月商业性行为1.7%,其中31.6%有保护措施。近6个月异性性行为9.7%,其中30.8%有保护措施。近6个月高频率肛交24.5%,多性伴50.3%。近6个月肛交无保护措施的艾滋病病毒阳性率10.5%,高于有保护措施的1.8%(χ²=41.837,P＜0.001)。多因素分析结果,年龄＞30岁(OR=1.627,95%CI: 1.192～2.221)、使用Rush(OR=2.122, 95%CI:1.293～3.482)者近6个月无保护措施肛交可能性更大,高中及以上文化(OR=0.401,95%CI:0.269～0.600)、艾滋病防治知识全对(OR=0.639, 95%CI:0.428～0.954)、近1年接受预防服务(OR=0.537,95%CI:0.312～0.923)、近6个月多性伴(OR=0.635, 95%CI:0.480～0.841)者近6个月无保护措施肛交可能性更小。 结论 MSM性行为复杂,无保护、多性伴普遍,大年龄、低文化、艾滋病防治知识不全对、未接受预防服务者发生无保护措施肛交的风险较大,应针对性开展行为干预。     

La pleine conscience incarnée : un concept unificateur entre les traditions orientales et occidentales de la pleine conscience

ObjectiveThe interest in mindfulness as a concept continues to grow as shown in the increase in the number of publications pertaining to mindfulness in the last four decades. This increase is also a reflection of the fact that the term “mindfulness” is currently used as an umbrella for a variety of approaches that assign different meanings to the same word. Although differences among varying conceptualizations and definitions of “mindfulness” have been previously highlighted, few efforts have attempted to compare these varying conceptual approaches as a means to address commonalties between them. Therefore, the objective of this paper is to review different conceptualizations of mindfulness in order to understand their common and distinctive components.MethodIn order to investigate commonalities and distinctions among different mindfulness conceptualizations, we conducted a thorough qualitative review of theoretical and empirical papers belonging to three approaches in mindfulness: Eastern Buddhist traditions, Western modern mindfulness meditation programs, and Langerian mindfulness. Each of these approaches is presented first at a conceptual level (i.e., how it defines mindfulness) and then at a practical level (i.e., how to operationalize mindfulness). Empirical research pertaining to the effectiveness of each approach is presented and discussed. As Buddhism incorporates different schools of thoughts, this paper focuses primarily on the conceptualization of mindfulness outlined within Theravada Buddhism. It operationalizes mindfulness through an engagement in intensive and daily meditative practice, which includes both concentrative and open-monitoring meditation. In addition, Buddhism includes a set of ethical principles. Western modern mindfulness meditation programs are conceptualized according to Kabat-Zinn and other western scholars. Definitions varied to some extent according to different scholars, each including a different set of components (e.g., attention, awareness, acceptance, nonjudgement, observation). Western modern mindfulness meditation programs are operationalized though the development and implementation of structured psychosomatic interventions, such as Mindfulness-Based Stress Reduction and Mindfulness-Based Cognitive Therapy. Langerian mindfulness is conceptualized as a general style or mode of functioning through which individuals actively reconstruct their environment by creating new categories or distinctions, and seeking multiple perspectives. Langer operationalized mindfulness through a set of sociocognitive tasks. The role of the body in these three approaches and more specifically the mind-body connection is highlighted through the analysis of clinical, behavioral, and neuroscientific research findings.Results and DiscussionDefinitions from both eastern and western approaches share self-regulation of attention and awareness as central common elements. Both attention and awareness processes increase interoceptive and exteroceptive body awareness and mind-body connection, therefore suggesting a role of embodiment in conceptualizing and operationalizing mindfulness across different approaches. We therefore introduce the new concept of Embodied Mindfulness as an integration of top-down and bottom-up processes and argue for its utility in the empirical study of mindfulness across the three conceptual approaches.ConclusionsThe new notion of embodied mindfulness integrates different conceptualizations of mindfulness by allowing a common understanding of the mechanisms of change across these conceptualizations. This new notion has also both research and clinical implications. This new notion suggests further emphasizing the body and mind-body connection in both studying/measuring mindfulness and in developing/validating clinical interventions.