BackgroundMajor depression is a disabling psychiatric illness with complex origins. Life stress (childhood adversity and recent stressful events) is a robust risk factor for depression. The relationship between life stress and Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has received much attention. The aim of the present work was to review and conduct a meta-analysis on the results from published studies examining this interaction.MethodsA literature search was conducted using PsychINFO and PubMed databases until 22 November 2013. A total of 22 studies with a pooled total of 14,233 participants met the inclusion criteria, the results of which were combined and a meta-analysis performed using the Liptak-Stouffer z-score method.ResultsThe results suggest that the Met allele of BDNF Val66Met significantly moderates the relationship between life stress and depression (P = 0.03). When the studies were stratified by type of environmental stressor, the evidence was stronger for an interaction with stressful life events (P = 0.01) and weaker for interaction of BDNF Val66Met with childhood adversity (P = 0.051).ConclusionsThe interaction between BDNF and life stress in depression is stronger for stressful life events rather than childhood adversity. Methodological limitations of existing studies include poor measurement of life stress.

Background: Major depression is a disabling psychiatric illness with complex origins. Life stress (childhood adversity and recent stressful events) is a robust risk factor for depression. The relationship between life stress and Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has received much attention. The aim of the present work was to review and conduct a meta-analysis on the results from published studies examining this interaction. Methods: A literature search was conducted using PsychINFO and PubMed databases until 22 November 2013. A total of 22 studies with a pooled total of 14,233 participants met the inclusion criteria, the results of which were combined and a meta-analysis performed using the Liptak-Stouffer z-score method. Results: The results suggest that the Met allele of BDNF Val66Met significantly moderates the relationship between life stress and depression (P = 0.03). When the studies were stratified by type of environmental stressor, the evidence was stronger for an interaction with stressful life events (P = 0.01) and weaker for interaction of BDNF Val66Met with childhood adversity (P = 0.051). Conclusions:The interaction between BDNF and life stress in depression is stronger for stressful life events rather than childhood adversity. Methodological limitations of existing studies include poor measurement of life stress.

Alcohol use disorders (AUD) cause significant morbidity and mortality worldwide, but pharmacological treatments for them are underused, despite evidence of efficacy.Acamprosate, naltrexone, nalmefene and disulfiram are all approved in one or more region for the treatment of alcohol use disorders. Baclofen currently has a temporary indication in France. Safety considerations for using psychopharmacological treatments in this patient group include the impact of concurrent alcohol consumption at high levels, multiple physical comorbidities which may interfere with pharmacological effects, distribution and metabolism, and concomitant medication for the treatment of comorbid physical and psychiatric conditions. The five drugs, including an extended-release injectable suspension of naltrexone, have different safety profiles which need to be balanced with the objective of treatment (initiation or continuation of abstinence, or reduction of drinking), individual patient preferences and comorbid conditions. Appropriate treatment will be based on the unique riskbenefit profile in each case. KEY POINTS Acamprosate has an excellent safety profile and is recommended as first line treatment for patients wishing abstinence. Naltrexone and nalmefene are contraindicated with opioid-containing medication, but have reasonable tolerability  The disulfiram-alcohol reaction is integral to its use, but careful patient selection and monitoring can mitigate safety risks  Baclofen is a CNS depressant so there are potential concerns regarding overdose: it may have a role in patients with severe liver disease Pharmacological treatments for alcohol dependence 3

BackgroundThe evidence suggests that brief alcohol-focused interventions, directed at hazardous and harmful drinkers in non-specialist settings such as primary care are effective in reducing alcohol consumption. However, there is a need for further research in the hospital setting. This is a randomised controlled trial to investigate the effectiveness of a 10-minute brief intervention amongst 'at risk’ drinkers admitted to general hospital wards. Unlike some previous trials, this trial is randomised, used blinded assessors, includes an intention-to-treat analysis, included female subjects and excluded people with alcohol dependence.MethodsA total of 250 'at risk’ drinkers admitted to King’s College Hospital were identified using the Alcohol Use Disorders Identification Test (AUDIT). Some 154 subjects entered the study and were randomly allocated to the control and intervention groups. Subjects in the control group received no advice about their drinking whilst subjects in the intervention group received 10 minutes of simple advice on reducing alcohol consumption. Recruitment took place between 1995 and 1997. The primary outcome was the AUDIT questionnaire at 12 months. Secondary outcomes were a previous week’s Drinks Diary, questionnaires (General Health Questionnaire, Alcohol Problems Questionnaire and the Severity of Alcohol Dependence Questionnaire) and laboratory blood tests (gamma glutamyl transferase, mean cell volume and haemoglobin).ResultsAt 3-month and 12-month follow-up, all participants were included in the intention-to-treat analysis. At both time points there was no evidence of an intervention effect that could be attributed to the brief intervention. Both the intervention and control groups had an improved AUDIT score and reduced levels of alcohol consumption as measured by a subjective Drinks Diary at 3 months which was maintained at 12 months.ConclusionsThis study has added further evidence on brief interventions in the hospital setting. In contrast to the recent Cochrane review by McQueen et al., the results of this study do not support the effectiveness of a brief alcohol intervention in general hospital wards. However our study was underpowered and there were flaws in the statistical analyses, and these limitations temper the strength of our conclusions.

Brief cognitive tests designed for severe dementia such as the SIB-8 and sMMSE have been evaluated in this project to be shorter in administration duration and highly correlated with gold standard instruments: the SIB and MMSE.

It is estimated that half of all trials have never been published which can lead to patients being denied the most effective treatment and being exposed to unnecessary side effects.  Furthermore the trial participants have been misinformed since the trial results have not contributed to the care of future patients.However the non-publication of trials is often not due to a deliberate decision to cover up results.  Commonly in academia it is due to more understandable reasons such as researchers having busy clinical posts, moving onto other more demanding projects, changing research areas or starting a family.  This is called the “file drawer” problem.The examples in this editorial demonstrate that it is possible to go back, even decades later, and make the results available to inform future evidence based medicine.  We call on others to look into their “file drawer” for unpublished trials.

No abstract