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.     

Access to mechanical thrombectomy for cerebral ischaemia: A population-based study in the North-of-France

Background and purposeHospitals admitting acute strokes should offer access to mechanical thrombectomy (MT), but local organisations are still based on facilities available before MT was proven effective. MT rates and outcomes at population levels are needed to adapt organisations. We evaluated rates of MT and outcomes in inhabitants from the North-of-France (NoF) area.MethodWe prospectively evaluated rates of MT and outcomes of patients at 3 months, good outcomes being defined as a modified Rankin scale (mRS) 0 to 2 or like the pre-stroke mRS.ResultsDuring the study period (2016–2017), 666 patients underwent MT (454, 68.1% associated with intravenous thrombolysis [IVT]). Besides, 1595 other patients received IVT alone. The rate of MT was 81 (95% confidence interval [CI] 72–90) per million inhabitants-year, ranging from 36 to 108 between districts. The rate of IVT was 249 (95% CI 234–264) per million inhabitants-year, ranging from 155 to 268. After 3 months, 279 (41.9%) patients who underwent MT had good outcomes, and 167 (25.1%) had died. Patients living outside the district of Lille where the only MT centre is, were less likely to have good outcomes at 3 months, after adjustment on age, sex, baseline severity, and delay.ConclusionThe rate of MT is one of the highest reported up to now, even in low-rate districts, but outcomes were significantly worse in patients living outside the district of Lille, and this is not only explained by the delay.     

Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region

IntroductionInherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer.MethodsWe conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer.ResultsWe detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722–0.820; p value 5.31 × 10^-16), rs380286 (OR: 0.770, 95% CI: 0.723–0.820; p value 4.32 × 10^-16), and rs4975616 (OR: 0.778, 95% CI: 0.730–0.829; p value 1.04 × 10^-14). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate.ConclusionsWe found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease.     

Development of a trail running injury screening instrument: A multiple methods approach

ObjectiveTo develop a trail running injury screening instrument (TRISI) for utilisation as clinical decision aid in determining if a trail runner is at an increased risk for injury.DesignMultiple methods approach.MethodsThe study utilised five phases 1) identification of injury risk factors 2) determining the relevance of each identified risk factor in a trail running context, 3) creating the content of the Likert scale points from 0 to 4, 4) rescaling the Likert scale points to determine numerical values for the content of each Likert scale point, and 5) determining a weighted score for each injury risk factor that contributes to the overall combined composite score.ResultsOf the 77 identified injury risk factors, 26 were deemed relevant in trail running. The weighted score for each injury risk factor ranged from 2.21 to 5.53 with the highest calculated score being 5.53. The final TRISI includes risk categories of training, running equipment, demographics, previous injury, behavioural, psychological, nutrition, chronic disease, physiological, and biomechanical factors.ConclusionThe developed TRISI aims to assist the clinician during pre-race injury screening or during a training season to identify meaningful areas to target in designing injury risk management strategies and/or continuous health education.     

艾烟的作用与安全性评价＊

艾灸作为中医学最古老的疗法之一，作用多样，应用广泛，疗效显著。随着科技的发展，人们对灸法的认识逐渐深入，其中艾烟的相关研究也硕果累累，其安全性广受关注。通过对艾烟作用和安全性评价研究中取得的成果进行归纳分析，以期为艾灸临床安全应用提供指导。     

刘中勇从“气血瘀滞”论治不寐的临证经验

不寐,现代医学称睡眠障碍,是一种临床常见病和多发病,本病发病原因尚不明确,通常不伴明显器质性病变,病人自觉症状重,西医尚无明确的治愈方法。祖国医学很早就认识到本病,积累了丰富的经验。刘中勇教授在古人的基础上提出从"气血瘀滞"的角度论治不寐,临床取得较好疗效,本文将从病因病机、理论探析、辨证论治三个方面介绍其相关经验,供同行参考。