Prediction of significant OHSS by ovarian reserve and ovarian response - implications for elective freeze-all strategy.

Ovarian Hyperstimulation Syndrome (OHSS) remains a risk to women undergoing assisted conception despite available preventative measures, which are usually applied on the basis of ovarian response. We performed a retrospective cohort study with robust ascertainment of OHSS cases in women undergoing treatment using GnRH antagonist. FSH dose was based on Anti-Mullerian Hormone concentration. A total of 1492 cycles were carried out over 18 months. Moderate/severe OHSS occurred in 24 cycles (1.6%). AMH of 35 pmol/L and/or AFC of 20 or more identified 18/24 (76%) OHSS cases. The optimal thresholds for predicting OHSS were 22.5 pmol/L for AMH (sensitivity 87.5%, specificity 60.6%), 19.5 for AFC (sensitivity 70.8%, specificity 67%), and 9.5 for egg numbers (sensitivity 83.5%, specificity 62.7%). Peak oestradiol levels had no predictive value. The utility of egg number is limited as it is only known after the ovulatory trigger has been administered. Thus, ovarian reserve parameters are better than ovarian response at predicting the risk of significant OHSS in GnRH antagonist cycles in modern clinical practice. Patients with a high ovarian reserve are at risk of OHSS even if their ovarian response is not excessive. Decisions about preventative measures should be based on ovarian reserve rather than ovarian response.

The association between cardiac risk factors and the probability of acute myocardial infarction in the emergency department: analysis from a multicentre prospective observational study in the high sensitivity troponin era.

BACKGROUND AND OBJECTIVE: Hypertension, hyperlipidaemia, diabetes mellitus, smoking and family history are established risk factors for coronary artery disease. This study sought to determine the diagnostic value these factors have in patients presenting to an emergency department (ED) with suspected acute myocardial infarction (AMI). DESIGN, SETTINGS AND ANALYSIS: This secondary analysis of a prospective diagnostic test accuracy study took place across 14 hospitals in England. A total of 1273 patients, presenting with suspected cardiac chest pain, were included for analysis - 179 (14.1%) had an adjudicated diagnosis of AMI. OUTCOME MEASURE AND ANALYSIS: AMI diagnosis was adjudicated with serial troponin testing conducted on arrival and 3-12 hours later. The presence of any risk factors was documented at the time of initial presentation. RESULTS: The post-test probability of AMI in the absence of risk factors (9.7%) shifts to only 23.5% when 4-5 factors are present. Associations of risk factors with AMI diagnosis were found as follows; hypertension [odds ratio (OR) 1.47, confidence interval (CI) 1.07-2.02], hyperlipidaemia (OR 1.57, CI 1.14-2.16), diabetes mellitus (OR 1.51, CI 1.04-2.20), smoking (OR 1.51, CI 1.05-2.17) and family history (OR 0.98, CI 0.71-1.37). The area under the receiver operating characteristic curve was 0.58. CONCLUSION: Traditional cardiac risk factors have limited association with AMI in the ED, but an increasing risk factor burden is associated with increasing prevalence of AMI. These findings suggest that future work to refine existing decision aids used in this patient group may be of value.

Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis.

BACKGROUND: Naltrexone is an opioid antagonist used in many different conditions, both licensed and unlicensed. It is used at widely varying doses from 3 to 250 mg. The aim of this review was to extensively evaluate the safety of oral naltrexone by examining the risk of serious adverse events and adverse events in randomised controlled trials of naltrexone compared to placebo. METHODS: A systematic search of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, other databases and clinical trials registries was undertaken up to May 2018. Parallel placebo-controlled randomised controlled trials longer than 4 weeks published after 1 January 2001 of oral naltrexone at any dose were selected. Any condition or age group was included, excluding only studies in opioid or ex-opioid users owing to possible opioid/opioid antagonist interactions. The systematic review used the guidance of the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-analyses harms checklist throughout. Numerical data were independently extracted by two people and cross-checked. Risk of bias was assessed with the Cochrane risk-of-bias tool. Meta-analyses were performed in R using random effects models throughout. RESULTS: Eighty-nine randomised controlled trials with 11,194 participants were found, studying alcohol use disorders (n = 38), various psychiatric disorders (n = 13), impulse control disorders (n = 9), other addictions including smoking (n = 18), obesity or eating disorders (n = 6), Crohn's disease (n = 2), fibromyalgia (n = 1) and cancers (n = 2). Twenty-six studies (4,960 participants) recorded serious adverse events occurring by arm of study. There was no evidence of increased risk of serious adverse events for naltrexone compared to placebo (risk ratio 0.84, 95% confidence interval 0.66-1.06). Sensitivity analyses pooling risk differences supported this conclusion (risk difference -0.01, 95% confidence interval -0.02-0.00) and subgroup analyses showed that results were consistent across different doses and disease groups. Secondary analysis revealed only six marginally significant adverse events for naltrexone compared to placebo, which were of mild severity. CONCLUSIONS: Naltrexone does not appear to increase the risk of serious adverse events over placebo. These findings confirm the safety of oral naltrexone when used in licensed indications and encourage investments to undertake efficacy studies in unlicensed indications. TRIAL REGISTRATION: PROSPERO 2017 CRD42017054421 .