Eating disorders: the current status of molecular genetic research

Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders characterized by disordered eating behavior where the patient’s attitude towards weight and shape, as well as their perception of body shape, are disturbed. Formal genetic studies on twins and families suggested a substantial genetic influence for AN and BN. Candidate gene studies have initially focused on the serotonergic and other central neurotransmitter systems and on genes involved in body weight regulation. Hardly any of the positive findings achieved in these studies were unequivocally confirmed or substantiated in meta-analyses. This might be due to too small sample sizes and thus low power and/or the genes underlying eating disorders have not yet been analyzed. However, some studies that also used subphenotypes (e.g., restricting type of AN) led to more specific results; however, confirmation is as yet mostly lacking. Systematic genome-wide linkage scans based on families with at least two individuals with an eating disorder (AN or BN) revealed initial linkage regions on chromosomes 1, 3 and 4 (AN) and 10p (BN). Analyses on candidate genes in the chromosome 1 linkage region led to the (as yet unconfirmed) identification of certain variants associated with AN. Genome-wide association studies are under way and will presumably help to identify genes and pathways involved in these eating disorders. The elucidation of the molecular mechanisms underlying eating disorders might improve therapeutic approaches

The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke:a study protocol for three multicentre randomised controlled trials

BACKGROUND: Several small trials have suggested that fluoxetine improves neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials that aim to determine whether routine administration of fluoxetine (20 mg daily) for 6 months after acute stroke improves patients' functional outcome. METHODS/DESIGN: The three trial investigator teams have collaboratively developed a core protocol. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia and New Zealand (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will subsequently provide the most precise estimate of the overall effect of fluoxetine after stroke and establish whether any effects differ between trials and subgroups of patients. The trials include patients ≥18 years old with a clinical diagnosis of stroke, persisting focal neurological deficits at randomisation between 2 and 15 days after stroke onset. Patients are randomised centrally via web-based randomisation systems using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for 6 months. Our primary outcome measure is the modified Rankin scale (mRS) at 6 months. Secondary outcomes include the Stroke Impact Scale, EuroQol (EQ5D-5 L), the vitality subscale of the Short-Form 36, diagnosis of depression, adherence to medication, adverse events and resource use. Outcomes are collected at 6 and 12 months. The methods of collecting these data are tailored to the national setting. If FOCUS, AFFINITY and EFFECTS combined enrol 6000 participants as planned, they would have 90 % power (alpha 5 %) to detect a common odds ratio of 1.16, equivalent to a 3.7 % absolute difference in percentage with mRS 0-2 (44.0 % to 47.7 %). This is based on an ordinal analysis of mRS adjusted for baseline variables included in the minimisation algorithm. DISCUSSION: If fluoxetine is safe and effective in promoting functional recovery, it could be rapidly, widely and affordably implemented in routine clinical practice and reduce the burden of disability due to stroke. TRIAL REGISTRATION: FOCUS: ISRCTN83290762 (23/05/2012), AFFINITY: ACTRN12611000774921 (22/07/2011). EFFECTS: ISRCTN13020412 (19/12/2014)

Self-management behaviors to reduce exacerbation impact in COPD patients: a Delphi study

Yvonne JG Korpershoek,1,2,* Joyce C Bruins Slot,1,* Tanja W Effing,3,4 Marieke J Schuurmans,1,2 Jaap CA Trappenburg1 1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 2Research Group Chronic Illnesses, University of Applied Sciences Utrecht, Utrecht, the Netherlands; 3Department of Respiratory Medicine, Southern Adelaide Local Health Network, 4School of Medicine, Flinders University, Adelaide, SA, Australia *These authors contributed equally to this work Background: Little is known about which self-management behaviors have the highest potential to influence exacerbation impact in COPD patients. We aimed to reach expert consensus on the most relevant set of self-management behaviors that can be targeted and influenced to maximize reduction of exacerbation impact.Materials and methods: A 2-round Delphi study was performed using online surveys to rate the relevance and feasibility of predetermined self-management behaviors identified by literature and expert opinion. Descriptive statistics and qualitative analyses were used.Results: An international expert panel reached consensus on 17 self-management behaviors focusing on: stable phase (n=5): pharmacotherapy, vaccination, physical activity, avoiding stimuli and smoking cessation; periods of symptom deterioration (n=1): early detection; during an exacerbation (n=5): early detection, health care contact, self-treatment, managing stress/anxiety and physical activity; during recovery (n=4): completing treatment, managing stress/anxiety, physical activity and exercise training; and after recovery (n=2): awareness for recurrent exacerbations and restart of pulmonary rehabilitation.Conclusion: This study has provided insight into expert opinion on the most relevant and feasible self-management behaviors that can be targeted and influenced before, during and after an exacerbation to exert the highest magnitude of influence on the impact of exacerbations. Future research should focus at developing more comprehensive patient-tailored interventions supporting patients in these exacerbation-related self-management behaviors. Keywords: COPD, self-management, exacerbation, Delphi study, self-care, Delphi technique and behavio

An assessment of randomized controlled trials (RCTs) for non-communicable diseases (NCDs): more and higher quality research is required in less developed countries

Research is crucial to implement evidence-based health interventions for control of non-communicable diseases (NCDs). This study aims to assess main features of randomized controlled trials (RCTs) for the control of NCDs, and to identify gaps in clinical research on NCDs between high-income and less developed countries. The study included 1177 RCTs in 82 Cochrane Systematic reviews (CSRs) and evaluated interventions for adults with hypertension, diabetes, stroke, or heart diseases. Multivariate logistic regression analyses were conducted to explore factors associated with risk of bias in the included RCTs. We found that 78.2% of RCTs of interventions for major NCDs recruited patients in high-income countries. The number of RCTs included in the CSRs was increasing over time, and the increasing speed was more noticeable for RCTs from middle-income countries. RCTs in less developed countries tended to be more recently published, less likely to be published in English, with smaller sample sizes, and at a higher risk of bias. In conclusion, there is still a lack of research evidence for control of NCDs in less developed countries. To brace for rising NCDs and avoid waste of scarce research resources, not only more but also higher quality clinical trials are required in low-and-middle-income countries