atrophy plus syndrome, or costeff optic atrophy syndrome): identification of the OPA3 gene and its

deficiencies in a male with cardiomyopathy and 3-methylglutaconic aciduria, ” J Inherit Metab Dis

Integration of vitamin A supplementation with the expanded program on immunization does not affect seroconversion to oral poliovirus vaccine in infants.

Childhood immunization programs may provide infrastructure for delivering vitamin A supplements to infants in developing countries. The effect of giving vitamin A, an immune enhancer, on antibody responses to trivalent oral poliovirus vaccine (TOPV) is unknown. A randomized, double-blind, placebo-controlled clinical trial was conducted to determine the effect of giving

Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability.

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted next-generation sequencing. Likely pathogenic rare variants were found in ∼11% of the cases (113 variants in 107/986 individuals: ∼8% of the individuals had a likely pathogenic loss-of-function [LoF] variant, whereas ∼3% had a known pathogenic missense variant). Variants in SETD5, ATRX, CUL4B, MECP2, and ARID1B were the most common causes of ID. This study assessed the value of sequencing a cohort of probands to provide a molecular diagnosis of ID, without the availability of DNA from both parents for de novo sequence analysis. This modeling is clinically relevant as 28% of all UK families with dependent children are single parent households. In conclusion, to diagnose patients with ID in the absence of parental DNA, we recommend investigation of all LoF variants in known genes that cause ID and assessment of a limited list of proven pathogenic missense variants in these genes. This will provide 11% additional diagnostic yield beyond the 10%-15% yield from array CGH alone.Action Medical Research (SP4640); the Birth Defect Foundation (RG45448); the Cambridge National Institute for Health Research Biomedical Research Centre (RG64219); the NIHR Rare Diseases BioResource (RBAG163); Wellcome Trust award WT091310; The Cell lines and DNA bank of Rett Syndrome, X-linked mental retardation and other genetic diseases (member of the Telethon Network of Genetic Biobanks (project no. GTB12001); the Genetic Origins of Congenital Heart Disease Study (GO-CHD)- funded by British Heart Foundation (BHF)This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/humu.2290

The impact of different doses of vitamin A supplementation on male and female mortality. A randomised trial from Guinea-Bissau

<p>Abstract</p> <p>Background</p> <p>Vitamin A supplementation (VAS) given to children between 6 months and 5 years of age is known to reduce mortality in low-income countries. We have previously observed that girls benefit more from a lower dose of VAS than the one recommended by WHO, the effect being strongest if diphtheria-tetanus-pertussis vaccine (DTP) was the most recent vaccination. We aimed to test these observations.</p> <p>Methods</p> <p>During national immunisations days in Guinea-Bissau, West Africa, combining oral polio vaccination and VAS, we randomised 8626 children between 6 months and 5 years of age to receive the dose of VAS recommended by WHO or half this dose. Mortality rate ratios (MRRs) were assessed after 6 and 12 month.</p> <p>Results</p> <p>The overall mortality rate among participants was lower than expected. There was no significant difference in mortality at 6 months and 12 months of follow up between the low dose VAS group and the recommended dose VAS group. The MRRs were 1.23 (0.60-2.54) after 6 months and 1.17 (0.73-1.87) after 12 months. This tendency was similar in boys and girls. The low dose was not associated with lower mortality in girls if the most recent vaccine was DTP (MRR = 0.60 (0.14-2.50) after 6 months).</p> <p>Conclusion</p> <p>Our sample size does not permit firm conclusions since mortality was lower than expected. We could not confirm a beneficial effect of a lower dose of VAS on mortality in girls.</p> <p>Trial registration</p> <p>The study was registered under clinicaltrials.gov, number <a href="http://www.clinicaltrials.gov/ct2/show/NCT00168636">NCT00168636</a></p

Efficacy of early neonatal vitamin A supplementation in reducing mortality during infancy in Ghana, India and Tanzania: study protocol for a randomized controlled trial

Vitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo. The trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrollment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation. The three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies

Comparison of hospital variation in acute myocardial infarction care and outcome between Sweden and United Kingdom: population based cohort study using nationwide clinical registries

To assess the between hospital variation in use of guideline recommended treatments and clinical outcomes for acute myocardial infarction in Sweden and the United Kingdom

Gamification as transformative assessment in Higher Education

Gamification in education is still a very new concept in South Africa. Being a 21st-century invention, it has already established itself in the world within the environs of the corporate market, marketing, training and the social world. This article will first discuss gamification (and all its other designations) and its applications in general; thereafter, the focus will be on the application of gamification within the environment of education, and more specifically with an emphasis on assessment. The burning question for South Africa is whether gamification can enhance a module or course on the level of higher education so much that an educational institution cannot do without it anymore, knowing that we are working with students belonging to the ‘Digital Wisdom generation’. This article would like to open the way for the implementation of gamification as a transformative online assessment tool in higher educationChristian Spirituality, Church History and Missiolog

CHOICE: Choosing Health Options In Chronic Care Emergencies

Background Over 70% of the health-care budget in England is spent on the care of people with long-term conditions (LTCs), and a major cost component is unscheduled health care. Psychological morbidity is high in people with LTCs and is associated with a range of adverse outcomes, including increased mortality, poorer physical health outcomes, increased health costs and service utilisation. Objectives The aim of this programme of research was to examine the relationship between psychological morbidity and use of unscheduled care in people with LTCs, and to develop a psychosocial intervention that would have the potential to reduce unscheduled care use. We focused largely on emergency hospital admissions (EHAs) and attendances at emergency departments (EDs). Design A three-phase mixed-methods study. Research methods included systematic reviews; a longitudinal prospective cohort study in primary care to identify people with LTCs at risk of EHA or ED admission; a replication study in primary care using routinely collected data; an exploratory and feasibility cluster randomised controlled trial in primary care; and qualitative studies to identify personal reasons for the use of unscheduled care and factors in routine consultations in primary care that may influence health-care use. People with lived experience of LTCs worked closely with the research team. Setting Primary care. Manchester and London. Participants People aged ≥ 18 years with at least one of four common LTCs: asthma, coronary heart disease, chronic obstructive pulmonary disease (COPD) and diabetes. Participants also included health-care staff. Results Evidence synthesis suggested that depression, but not anxiety, is a predictor of use of unscheduled care in patients with LTCs, and low-intensity complex interventions reduce unscheduled care use in people with asthma and COPD. The results of the prospective study were that depression, not having a partner and life stressors, in addition to prior use of unscheduled care, severity of illness and multimorbidity, were independent predictors of EHA and ED admission. Approximately half of the cost of health care for people with LTCs was accounted for by use of unscheduled care. The results of the replication study, carried out in London, broadly supported our findings for risk of ED attendances, but not EHAs. This was most likely due to low rates of detection of depression in general practitioner (GP) data sets. Qualitative work showed that patients were reluctant to use unscheduled care, deciding to do so when they perceived a serious and urgent need for care, and following previous experience that unscheduled care had successfully and unquestioningly met similar needs in the past. In general, emergency and primary care doctors did not regard unscheduled care as problematic. We found there are missed opportunities to identify and discuss psychosocial issues during routine consultations in primary care due to the ‘overmechanisation’ of routine health-care reviews. The feasibility trial examined two levels of an intervention for people with COPD: we tried to improve the way in which practices manage patients with COPD and developed a targeted psychosocial treatment for patients at risk of using unscheduled care. The former had low acceptability, whereas the latter had high acceptability. Exploratory health economic analyses suggested that the practice-level intervention would be unlikely to be cost-effective, limiting the value of detailed health economic modelling. Limitations The findings of this programme may not apply to all people with LTCs. It was conducted in an area of high social deprivation, which may limit the generalisability to more affluent areas. The response rate to the prospective longitudinal study was low. The feasibility trial focused solely on people with COPD. Conclusions Prior use of unscheduled care is the most powerful predictor of unscheduled care use in people with LTCs. However, psychosocial factors, particularly depression, are important additional predictors of use of unscheduled care in patients with LTCs, independent of severity and multimorbidity. Patients and health-care practitioners are unaware that psychosocial factors influence health-care use, and such factors are rarely acknowledged or addressed in consultations or discussions about use of unscheduled care. A targeted patient intervention for people with LTCs and comorbid depression has shown high levels of acceptability when delivered in a primary care context. An intervention at the level of the GP practice showed little evidence of acceptability or cost-effectiveness. Future work The potential benefits of case-finding for depression in patients with LTCs in primary care need to be evaluated, in addition to further evaluation of the targeted patient intervention