Which method is best for the induction of labour?: A systematic review, network meta-analysis and cost-effectiveness analysis

Background: More than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour. Objective: To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. Methods: We carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group’s Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012–13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves. Results: We identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 μg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 μg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed ‘best’. Few studies collected information on women’s views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective. Limitations: There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. Conclusions: Overall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention

United Kingdom Survey of Culture-Negative Peritonitis and Dialysate Sampling Practice.

Peritonitis is a major cause of technique failure in peritoneal dialysis (PD) and accurate diagnosis ensures successful management and avoids unnecessary antibiotic exposure. United Kingdom (UK) registry data on peritonitis rates are not routinely reported. We conducted an electronic survey amongst senior PD nurses and microbiologists to obtain information about PD effluent sampling and processing practices in the UK. The survey was completed by 53 of 79 centres (67% response rate). The median annual culture-negative rate was 15% (range 5 – 38%). The main findings were wide variation in reported sampling volumes and processing methods that may in part explain the variation in culture-negative rates. Adherence to guidelines might reduce culture-negative rates informed by reporting data into national registries

Follow-on rifaximin for the prevention of recurrence following standard treatment of infection with clostridium fifficile (RAPID): a randomised placebo controlled trial

©2018 The Authors. Published by BMJ. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.1136/gutjnl-2018-316794Background Clostridium difficile infection (CDI) recurs after initial treatment in approximately one in four patients. A single-centre pilot study suggested that this could be reduced using ’follow-on’ rifaximin treatment. We aimed to assess the efficacy of rifaximin treatment in preventing recurrence. Methods A multisite, parallel group, randomised, placebo controlled trial recruiting patients aged ≥18 years immediately after resolution of CDI through treatment with metronidazole or vancomycin. Participants received either rifaximin 400mg three times a day for 2weeks, reduced to 200mg three times a day for a further 2weeks or identical placebo. The primary endpoint was recurrence of CDI within 12 weeks of trial entry. Results Between December 2012 and March 2016, 151 participants were randomised to either rifaximin or placebo. Primary outcome data were available on 130. Mean age was 71.9 years (SD 15.3). Recurrence within 12 weeks was 29.5% (18/61) among participants allocated to placebo compared with 15.9% (11/69) among those allocated to rifaximin, a difference between groups of 13.7% (95% CI −28.1% to 0.7%, p=0.06). The risk ratio was 0.54 (95% CI 0.28 to 1.05, p=0.07). During 6-month safety follow-up, nine participants died in each group (12%). Adverse event rates were similar between groups. Conclusion While ’follow-on’ rifaximin after CDI appeared to halve recurrence rate, we failed to reach our recruitment target in this group of frail elderly patients, so the estimated effect of rifaximin lacks precision. A meta-analysis including a previous trial suggests that rifaximin may be effective; however, further, larger confirmatory studies are needed.The trial was sponsored by the University of Nottingham, was coordinated from the Nottingham Clinical Trials Unit and was supported by the National Institute for Health Research Clinical Research Network

Genetic Association Study Of Exfoliation Syndrome Identifies A Protective Rare Variant At Loxl1 And Five New Susceptibility Loci

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 x 10(-14)) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 x 10(-8)). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.Wo