Diagnostic Value of MAML2 Rearrangements in Mucoepidermoid Carcinoma.

Mucoepidermoid carcinoma (MEC) is often seen in salivary glands and can harbor MAML2 translocations (MAML2+). The translocation status has diagnostic utility as an objective confirmation of the MEC diagnosis, for example, when distinction from the more aggressive adenosquamous carcinoma (ASC) is not straightforward. To assess the diagnostic relevance of MAML2, we examined our 5-year experience in prospective testing of 8106 solid tumors using RNA-seq panel testing in combinations with a two-round Delphi-based scenario survey. The prevalence of MAML2+ across all tumors was 0.28% (n = 23/8106) and the majority of MAML2+ cases were found in head and neck tumors (78.3%), where the overall prevalence was 5.9% (n = 18/307). The sensitivity of MAML2 for MEC was 60% and most cases (80%) were submitted for diagnostic confirmation; in 24% of cases, the MAML2 results changed the working diagnosis. An independent survey of 15 experts showed relative importance indexes of 0.8 and 0.65 for "confirmatory MAML2 testing" in suspected MEC and ASC, respectively. Real-world evidence confirmed that the added value of MAML2 is a composite of an imperfect confirmation test for MEC and a highly specific exclusion tool for the diagnosis of ASC. Real-world evidence can help move a rare molecular-genetic biomarker from an emerging tool to the clinic.

Commentary: Cancer research quality and tumour classification.

Cancer researchers require accurate diagnoses for the samples, cell lines, patients or populations that they study. These diagnoses are underpinned by an internationally accepted taxonomy - the World Health Organization Classification of Tumours. This is still largely based on the histopathological examination of biopsy specimens, but increasingly also molecular methods and radiological examination of patients. Classifications evolve as new evidence arises, and for tumours that evidence is available in a quantity that is both remarkable and daunting. Evaluating this deluge of new information and incorporating it into the World Health Organization Classification of Tumours is now the responsibility of an editorial board, and up to 200 editors and authors work on each system to update it within the new 5th edition. Just as cancer researchers depend on the classification for diagnoses, so too the classification depends on the generation of high-quality, trustworthy data by cancer researchers. It is not just a case of quantity but quality too. Scientific fraud is thankfully rare, but high-profile cases are damaging and standards need to improve, not least to ensure that accurate information enters the classification.

Revising the WHO classification: female genital tract tumours.

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.

Differences between men and women in substance use: the role of educational level and employment status.

OBJECTIVE: To determine differences between men and women in hazardous drinking, heavy cannabis use and hypnosedative use according to educational level and employment status in the economically active population in Spain. METHOD: Cross-sectional study with data from 2013 Spanish Household Survey on Alcohol and Drugs on individuals aged 25-64 [n=14,113 (women=6,171; men=7,942)]. Dependent variables were hazardous drinking, heavy cannabis use and hypnosedative consumption; the main independent variables were educational level and employment situation. Associations between dependent and independent variables were calculated with Poisson regression models with robust variance. All analyses were stratified by sex. RESULTS: Hazardous drinking and heavy cannabis use were higher in men, while women consumed more hypnosedatives. The lower the educational level, the greater the gender differences in the prevalence of this substances owing to different consumption patterns in men and women. While men with a lower educational level were higher hazardous drinkers [RII=2.57 (95%CI: 1.75-3.78)] and heavy cannabis users [RII=3.03 (95%CI: 1.88-4.89)] compared to higher educational level, in women the prevalence was the same. Women with a lower education level and men with a higher education level had higher hypnosedative consumption. Unemployment was associated with increased heavy cannabis use and hypnosedative use in both women and men and with lower hazardous drinking only in women. CONCLUSIONS: 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.

Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies.

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.

Potential bias due to outcome-related loss to follow-up in cohort studies on incidence of drug injection: systematic review and meta-analysis.

AIMS: A systematic review and meta-analysis were conducted to synthesize results from cohort studies on initiation into drug injection among vulnerable populations, to quantify heterogeneity in the estimated incidence rates of drug injection and to identify potential sources of heterogeneity and bias. METHODS: MEDLINE, EMBASE, PsycINFO and LILACS were searched for relevant studies published between 1980 and 2012. Investigators independently reviewed studies for inclusion, retrieved information on baseline population characteristics and follow-up features and assessed study quality. Study-specific incidence rates of drug injection were calculated as the number of new injectors divided by the person-years at risk. The I(2) statistic was used to quantify heterogeneity in incidence rates across studies, and random-effects meta-regression models were used to identify determinants of heterogeneity and bias. RESULTS: Nine cohorts totalling 1843 participants met the inclusion criteria, with individual sample sizes of 70-415 participants and follow-up lengths of 6 months-3.4 years. The incidence of drug injection varied widely, from 2.1 to 24.2 cases per 100 person-years. The strong between-study heterogeneity (I(2) = 90%, P<0.001) was reduced significantly after accounting for the different follow-up lengths (I(2) = 17%, P = 0.30), with a 57% (95% confidence interval 46-66%) decrease in the pooled incidence of drug injection per 1-year increase in average follow-up. CONCLUSIONS: The incidence of drug injection decreases sharply with increasing follow-up length in cohort studies on drug injection initiation. Low retention rates and potential for downward selection bias in cohort studies on drug injection initiation are caused primarily by greater loss to follow-up among individuals at higher risk of starting injection, compared with other participants.

[Research methods on alcohol-related harm in the population]. / Métodos de investigación sobre daños en la población relacionados con el alcohol.

The aim of this paper is to describe the available methods to quantify the main health and social harms related to alcohol consumption in the population and to provide recommendations to improve research on these issues. Methods using individual and aggregate level data for the study of the relationship between alcohol consumption and related harms are taken into account, highlighting their strengths and weaknesses. Methodological aspects to quantify the magnitude and trends of alcohol-related and alcohol-attributable mortality, including alcohol dependence, acute intoxication, injury, violent behavior, disease burden and social costs are widely considered. There are often discrepancies between the study results mainly due to the difficulty of adequately measuring alcohol consumption and its relationship to health conditions. In the future we must strengthen research on the effect of drinking patterns and context in chronic diseases using appropriate controls, clarify the relationship of alcohol use disorders and other mental disorders , improve the measurement of alcohol intoxication when acute problems occurs, periodically quantify the disease burden and social costs attributable to alcohol (using country- specific attributable fractions) and develop valid and comparable methods and indicators for monitoring alcohol-related harm.

Métodos de investigación sobre daños en la población relacionados con el alcohol / Research methods on alcohol related harm in the population

El objetivo de este trabajo es describir los principales métodos disponibles para cuantificar los danos sociales y sanitarios relacionados con el alcohol en la población y hacer recomendaciones para mejorar la investigación sobre estos aspectos. Se consideran los métodos para estudiar la naturaleza de la relación entre el consumo de alcohol y los danos a partir de datos individuales y agregados, señalando sus ventajas y limitaciones. Se describen los métodos para cuantificar la magnitud y las tendencias de los danos relacionados con alcohol en la población, incluyendo dependencia, intoxicación aguda, lesiones o conductas violentas, mortalidad, carga de enfermedad y costes sociales atribuibles. A menudo hay discrepancias entre los resultados de los estudios por la dificultad para medir adecuadamente el consumo y su relación con las condiciones de salud. Hay que potenciar la investigación sobre el efecto de patrones y contexto de consumo en las enfermedades crónicas utilizando grupos control adecuados, aclarar la relación de la dependencia alcohólica con otros trastornos mentales, mejorar la medida del grado de intoxicación alcohólica cuando se producen otros problemas agudos, cuantificar periodicamente la carga de enfermedad y los costes atribuibles a alcohol (usando fracciones atribuibles específicas de país) y desarrollar métodos e indicadores validos y comparables para monitorizar los danos relacionados con alcohol (AU)

The aim of this paper is to describe the available methods to quantify the main health and social harms related to alcohol consumption in the population and to provide recommendations to improve research on these issues. Methods using individual and aggregate level data for the study of the relationship between alcohol consumption and related harms are taken into account, highlighting their strengths and weaknesses. Methodological aspects to quantify the magnitude and trends of alcohol-related and alcohol- attributable mortality, including alcohol dependence, acute intoxication, injury, violent behavior, disease burden and social costs are widely considered. There are often discrepancies between the study results mainly due to the difficulty of adequately measuring alcohol consumption and its relationship to health conditions. In the future we must strengthen research on the effect of drinking patterns and context in chronic diseases using appropriate controls, clarify the relationship of alcohol use disorders and other mental disorders , improve the measurement of alcohol intoxication when acute problems occurs, periodically quantify the disease burden and social costs attributable to alcohol (using country- specific attributable fractions) and develop valid and comparable methods and indicators for monitoring alcohol-related harm (AU)