A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease

Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. Results: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. Conclusions: These data do not justify use of CoQ as a treatment to slow functional decline in HD

Ageing and dementia in low and middle income countries - Using research to engage with public and policy makers

Abstract While two thirds of the 24 million people with dementia worldwide live in low and middle income countries, very little research has been conducted to support policy making in these regions. Among the non-communicable diseases, dementia (in common with other chronic NCDs linked more to long-term disability than to mortality) has been relatively under-prioritized. International agreements, plans and policy guidelines have called for an end to ageist discrimination and a focus upon reducing disadvantage arising from poverty and the consequences of ill health. Social protection, access to good quality age-appropriate healthcare and addressing the problem of disability are all key issues. However, as yet, little progress has been made in addressing these concerns. In this review we outline the current international policy agenda for older individuals, and its specific relevance to those with dementia and other disabling non-communicable diseases. We consider the potential for epidemiological research to raise awareness, refine the policy agenda, and promote action, using the example of the dissemination strategy developed by the 10/66 Dementia Research Group

A Phase 1 Trial of MSP2-C1, a Blood-Stage Malaria Vaccine Containing 2 Isoforms of MSP2 Formulated with Montanide® ISA 720

Background: In a previous Phase 1/2b malaria vaccine trial testing the 3D7 isoform of the malaria vaccine candidate Merozoite surface protein 2 (MSP2), parasite densities in children were reduced by 62%. However, breakthrough parasitemias were disproportionately of the alternate dimorphic form of MSP2, the FC27 genotype. We therefore undertook a dose-escalating, double-blinded, placebo-controlled Phase 1 trial in healthy, malaria-naïve adults of MSP2-C1, a vaccine containing recombinant forms of the two families of msp2 alleles, 3D7 and FC27 (EcMSP2-3D7 and EcMSP2-FC27), formulated in equal amounts with Montanide® ISA 720 as a water-in-oil emulsion. Methodology/Principal Findings: The trial was designed to include three dose cohorts (10, 40, and 80 μg), each with twelve subjects receiving the vaccine and three control subjects receiving Montanide® ISA 720 adjuvant emulsion alone, in a schedule of three doses at 12-week intervals. Due to unexpected local reactogenicity and concern regarding vaccine stability, the trial was terminated after the second immunisation of the cohort receiving the 40 μg dose; no subjects received the 80 μg dose. Immunization induced significant IgG responses to both isoforms of MSP2 in the 10 μg and 40 μg dose cohorts, with antibody levels by ELISA higher in the 40 μg cohort. Vaccine-induced antibodies recognised native protein by Western blots of parasite protein extracts and by immunofluorescence microscopy. Although the induced anti-MSP2 antibodies did not directly inhibit parasite growth in vitro, IgG from the majority of individuals tested caused significant antibody-dependent cellular inhibition (ADCI) of parasite growth. Conclusions/Significance: As the majority of subjects vaccinated with MSP2-C1 developed an antibody responses to both forms of MSP2, and that these antibodies mediated ADCI provide further support for MSP2 as a malaria vaccine candidate. However, in view of the reactogenicity of this formulation, further clinical development of MSP2-C1 will require formulation of MSP2 in an alternative adjuvant. Trial Registration: Australian New Zealand Clinical Trials Registry 12607000552482

Self-care support for children and adolescents with long-term conditions : the REfOCUS evidence synthesis

Background: Self-care support (e.g. education, training, peer/professional support) is intended to enhance the self-care capacities of children and young people, while simultaneously reducing the financial burden facing health-care systems. Objectives: To determine which models of self-care support for long-term conditions (LTCs) are associated with significant reductions in health utilisation and costs without compromising outcomes for children and young people. Design: Systematic review with meta-analysis. Population: Children and young people aged 0–18 years with a long-term physical or mental health condition (e.g. asthma, depression). Intervention: Self-care support in health, social care, educational or community settings. Comparator: Usual care. Outcomes: Generic/health-related quality of life (QoL)/subjective health symptoms and health service utilisation/costs. Design: Randomised/non-randomised trials, controlled before-and-after studies, and interrupted time series designs. Data sources: MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, ISI Web of Science, NHS Economic Evaluation Database, The Cochrane Library, Health Technology Assessment database, Paediatric Economic Database Evaluation, IDEAS, reference scanning, targeted author searches and forward citation searching. All databases were searched from inception to March 2015. Methods: We conducted meta-analyses, simultaneously plotting QoL and health utilisation effects. We conducted subgroup analyses for evidence quality, age, LTC and intervention (setting, target, delivery format, intensity). Results: Ninety-seven studies reporting 114 interventions were included. Thirty-seven studies reported adequate allocation concealment. Fourteen were UK studies. The vast majority of included studies recruited children and young people with asthma (n = 66, 68%). Four per cent of studies evaluated ‘pure’ self-care support (delivered through health technology without additional contact), 23% evaluated facilitated self-care support (≤ 2 hours’/four sessions’ contact), 65% were intensively facilitated (≥ 2 hours’/four sessions’ contact) and 8% were case management (≥ 2 hours’ support with multidisciplinary input). Self-care support was associated with statistically significant, minimal benefits for QoL [effect size (ES) –0.17, 95% confidence interval (CI) –0.23 to –0.11], but lacked clear benefit for hospital admissions (ES –0.05, 95% CI –0.12 to 0.03). This finding endured across intervention intensities and LTCs. Statistically significant, minimal reductions in emergency use were observed (ES –0.11, 95% CI –0.17 to –0.04). The total cost analysis was limited by the small number of data. Subgroup analyses revealed statistically significant, minimal reductions in emergency use for children aged ≤ 13 years (ES –0.10, 95% CI –0.17 to –0.04), children and young people with asthma (ES –0.12, 95% CI –0.18 to –0.06) and children and young people receiving ≥ 2 hours per four sessions of support (ES –0.10, 95% CI –0.17 to –0.03). Preliminary evidence suggested that interventions that include the child or young person, and deliver some content individually, may optimise QoL effects. Face-to-face delivery may help to maximise emergency department effects. Caution is required in interpreting these findings. Limitations: Identification of optimal models of self-care support is challenged by the size and nature of evidence available. The emphasis on meta-analysis meant that a minority of studies with incomplete but potentially relevant data were excluded. Conclusions: Self-care support is associated with positive but minimal effects on children and young people’s QoL, and minimal, but potentially important, reductions in emergency use. On current evidence, we cannot reliably conclude that self-care support significantly reduces health-care costs. Future work: Research is needed to explore the short- and longer-term effects of self-care support across a wider range of LTCs. Study registration: This study is registered as PROSPERO CRD42014015452. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Astronomisches aus Babylon; oder, Das wissen der Chaldäer über den gestirnten himmel.

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