Objective To compare the risk for all cause and overdose mortality in people with opioid dependence during and after substitution treatment with methadone or buprenorphine and to characterise trends in risk of mortality after initiation and cessation of treatment. Design Systematic review and meta-analysis. Data sources Medline, Embase, PsycINFO, and LILACS to September 2016. Study selection Prospective or retrospective cohort studies in people with opioid dependence that reported deaths from all causes or overdose during follow-up periods in and out of opioid substitution treatment with methadone or buprenorphine. Data extraction and synthesis Two independent reviewers performed data extraction and assessed study quality. Mortality rates in and out of treatment were jointly combined across methadone or buprenorphine cohorts by using multivariate random effects meta-analysis. Results There were 19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years. Pooled all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61). In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment. All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment. Conclusions Retention in methadone and buprenorphine treatment is associated with substantial reductions in the risk for all cause and overdose mortality in people dependent on opioids. The induction phase onto methadone treatment and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies to mitigate such risk. These findings are potentially important, but further research must be conducted to properly account for potential confounding and selection bias in comparisons of mortality risk between opioid substitution treatments, as well as throughout periods in and out of each treatment.

The upcoming revision of the World Health Organisation (WHO) classification of tumours of the female genital tract is scheduled for release in the second quarter of 2020. It will feature significant changes compared to earlier editions. In this review, we outline the process of revising this important reference source for those diagnosing tumours or engaged in cancer research and describe the significant changes. The WHO classification of tumours is increasingly evidence‐based, with a clear update cycle, improved quality of illustrations and content, led by an editorial board comprised mainly of pathologists, but increasingly incorporating input from other disciplines. The advent of the new website allows the use of whole‐slide images and hyperlinks to evidence or external bodies that produce guidance on staging or reporting.

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At present, there is no evidence supporting the clinical use of antipsychotic medications in the treatment of cocaine dependence, although results come from only 14 trials, with small sample sizes and moderate to low quality of evidence.

There are differences between men and women in the use of psychoactive substances that can be explained by the unequal distribution of substance use in them according to educational level. Unemployment was associated with substance use in both men and women.

Dear Sir, The World Health Organization (WHO) Classification of Tumors series, published as the WHO Blue Books (Fig. 1) and the accompanying website, are essential resources for pathologists across the globe, providing the standards against which tumors are classified to aid cancer diagnosis, research, treatment and prognosis. Each book tackles the classifications of up to 300 tumor types, defining for each of these the etiology, pathogenesis, epidemiology, clinical features, macroscopic appearances, histology, cytology, molecular pathology, essential and desirable diagnostic features, staging, prognostic factors and predictive biomarkers. If each tumor were to require one formal review, this would mean finding or conducting up to 3,600 such reviews for each book which would not be practicable or time-efficient. The current approach therefore relies largely on subject experts drawing on published literature searches according to their individually perceived need to inform the content of these books. However, these decisions affect the classification, and hence the diagnosis and management of cancer patients worldwide. Consequently, to minimize the risk of including biased information, the evidence is weighed and decisions made by an editorial board. This editorial board is composed of standing members and content experts (mainly practicing pathologists) who meet, propose, revise and agree on definitions and core criteria for each tumor systematically for every new edition.Over-reliance on expert consensus at editorial board meetings for this purpose may lead to problems (Table 1). First, evidence needs to be reviewed to assess all relevant issues in a WHO Blue Book. But, even if all participating experts are required to perform literature reviews, their different expertise and inevitable time constraints produce variable results with potential for studies that are relevant to decisions to be missed. In the first book of the new 5th edition, up to 130 tumors or subjects were described as "unknown" and 200 labeled as clinically not relevant, this often being the only description of a whole section. 1 Sections such as etiology or pathogenesis are frequently summarized as "unknown," without providing more details, leaving unclear whether an exhaustive search of the literature has been performed. This does not necessarily indicate that systematic reviews should be routinely performed when such questions arise and indeed, it would not be possible for standing members and content experts to do so given the number that would be required. Often the statements requiring evidence are more related to background information than issues relevant to classification, and introducing systematic approaches to the literature searches would not improve the evidence base of the review results.

Summary To summarize the microbiome's role in metabolic disorders (insulin resistance, hyperglycemia, type 2 diabetes, obesity, hyperlipidemia, hypertension, nonalcoholic fatty liver disease [NAFLD], and metabolic syndrome), systematic reviews on observational or interventional studies (prebiotics/probiotics/synbiotics/transplant) were searched in MEDLINE and Embase until September 2020. The 87 selected systematic reviews included 57 meta‐analyses. Methodological quality (AMSTAR2) was moderate in 62%, 12% low, and 26% critically low. Observational studies on obesity (10 reviews) reported less gut bacterial diversity with higher Fusobacterium, Lactobacillus reuteri, Bacteroides fragilis, and Staphylococcus aureus, whereas lower Methanobrevibacter, Lactobacillus plantarum, Akkermansia muciniphila, and Bifidobacterium animalis compared with nonobese. For diabetes (n = 1), the same was found for Fusobacterium and A. muciniphila, whereas higher Ruminococcus and lower Faecalibacterium, Roseburia, Bacteroides vulgatus, and several Bifidobacterium spp. For NAFLD (n = 2), lower Firmicutes, Rikenellaceae, Ruminococcaceae, whereas higher Escherichia and Lactobacillus were detected. Discriminating bacteria overlapped between metabolic disorders, those with high abundance being often involved in inflammation, whereas those with low abundance being used as probiotics. Meta‐analyses (n = 54) on interventional studies reported 522 associations: 54% was statistically significant with intermediate effect size and moderate between‐study heterogeneity. Meta‐evidence was highest for probiotics and lowest for fecal transplant. Future avenues include better methodological quality/comparability, testing functional differences, new intervention strategies, and considerating other body habitats and kingdoms.