Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Predictors of mortality within prison and after release among persons living with HIV in Indonesia

Gabriel J Culbert,1,2 Forrest W Crawford,3–5 Astia Murni,6 Agung Waluyo,2 Alexander R Bazazi,7,8 Junaiti Sahar,2 Frederick L Altice7–9 1Department of Health Systems Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, USA; 2Center for HIV/AIDS Nursing Research, Faculty of Nursing, Universitas Indonesia, Depok, Indonesia; 3Department of Biostatistics, Yale School of Public Health, 4Operations, Yale School of Management, 5Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA; 6Directorate General of Corrections, Indonesian Ministry of Law and Human Rights, Jakarta, Indonesia; 7Department of Epidemiology of Microbial Diseases, School of Public Health, 8Department of Medicine, Section of Infectious Diseases, AIDS Program, School of Medicine, Yale University, New Haven, CT, USA; 9Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia Objectives: HIV-related mortality is increasing in Indonesia, where prisons house many people living with HIV and addiction. We examined all-cause mortality in HIV-infected Indonesian prisoners within prison and up to 24 months postrelease. Materials and methods: Randomly selected HIV-infected male prisoners (n=102) from two prisons in Jakarta, Indonesia, completed surveys in prison and were followed up for 2 years (until study completion) or until they died or were lost to follow-up. Death dates were determined from medical records and interviews with immediate family members. Kaplan–Meier and Cox proportional hazards regression models were analyzed to identify mortality predictors. Results: During 103 person-years (PYs) of follow-up, 15 deaths occurred, including ten in prison. The crude mortality rate within prison (125.2 deaths per 1,000 PYs) was surpassed by the crude mortality rate (215.7 deaths per 1,000 PYs) in released prisoners. HIV-associated opportunistic infections were the most common probable cause of death. Predictors of within-prison and overall mortality were similar. Shorter survival overall was associated with being incarcerated within a specialized “narcotic” prison for drug offenders (hazard ratio [HR] 9.2, 95% confidence interval [CI] 1.1–76.5; P=0.03), longer incarceration (HR 1.06, 95% CI 1.01–1.1; P=0.01), and advanced HIV infection (CD4+ T-cell count <200/µL, HR 4.8, 95% CI 1.2–18.2; P=0.02). Addiction treatment was associated with longer survival (HR 0.1, 95% CI 0.01–0.9; P=0.03), although treatment with antiretroviral therapy (ART) or methadone was not. Conclusion: Mortality in HIV-infected prisoners is extremely high in Indonesia, despite limited provision of ART in prisons. Interventions to restore immune function with ART and provide prophylaxis for opportunistic infections during incarceration and after release would likely reduce mortality. Narcotic prisons may be especially high-risk environments for mortality, emphasizing the need for universal access to evidence-based HIV treatments. Keywords: antiretroviral therapy, HIV/AIDS, Indonesia, mortality, prisoners, substance us

Psychological adjustment and quality of life in children and adolescents following open-heart surgery for congenital heart disease: a systematic review

BACKGROUND: Children with congenital heart defects (CHD) requiring open-heart surgery are a group at high risk for health-related sequelae. Little consensus exists regarding their long-term psychological adjustment (PA) and health-related quality of life (QoL). Thus, we conducted a systematic review to determine the current knowledge on long-term outcome in this population. METHODS: We included randomized controlled trials, case control, or cohort studies published between 1990-2008 evaluating self- and proxy-reported PA and QoL in patients aged between two and 17 years with a follow-up of at least two years after open heart surgery for CHD. RESULTS: Twenty-three studies assessing psychological parameters and 12 studies assessing QoL were included. Methodological quality of the studies varied greatly with most studies showing a moderate quality. Results were as follows: (a) A considerable proportion of children experienced psychological maladjustment according to their parents; (b) studies on self-reported PA indicate a good outcome; (c) the studies on QoL suggest an impaired QoL for some children in particular for those with more severe cardiac disease; (d) parental reports of psychological maladjustment were related to severity of CHD and developmental delay. CONCLUSION: A significant proportion of survivors of open-heart surgery for CHD are at risk for psychological maladjustment and impaired QoL. Future research needs to focus on self-reports, QoL data and adolescents

Placental miR-340 mediates vulnerability to activity based anorexia in mice

Anorexia nervosa is characterised by self-starvation but its etiology is not completely understood. Here the authors describe how prenatal stress can induce activity-based anorexia in the offspring during early adulthood by upregulating miR-340 expression in the placenta that affects expression of nutrient transporters

The Mortality After Release from Incarceration Consortium (MARIC): Protocol for a multi-national, individual participant data meta-analysis

Introduction : More than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance. Objectives: To comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison. Methods: We created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology. Results: The combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up. Conclusions: The consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population

The Mortality After Release from Incarceration Consortium (MARIC): Protocol for a multi-national, individual participant data meta-analysis.

IntroductionMore than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance.ObjectivesTo comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison.MethodsWe created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology.ResultsThe combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up.ConclusionsThe consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population.Key wordsMortality; incarceration; prison; release; individual participant data meta-analysis; consortium; cohort

The Mortality After Release from Incarceration Consortium (MARIC): Protocol for a multi-national, individual participant data meta-analysis

Introduction: More than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance. Objectives: To comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison. Methods: We created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology. Results: The combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up. Conclusions: The consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population.</p