The association between family and community social capital and health risk behaviours in young people: an integrative review

Background: Health risk behaviours known to result in poorer outcomes in adulthood are generally established in late childhood and adolescence. These ‘risky’ behaviours include smoking, alcohol and illicit drug use and sexual risk taking. While the role of social capital in the establishment of health risk behaviours in young people has been explored, to date, no attempt has been made to consolidate the evidence in the form of a review. Thus, this integrative review was undertaken to identify and synthesise research findings on the role and impact of family and community social capital on health risk behaviours in young people and provide a consolidated evidence base to inform multi-sectorial policy and practice.<p></p> Methods: Key electronic databases were searched (i.e. ASSIA, CINAHL, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Embase, Medline, PsycINFO, Sociological Abstracts) for relevant studies and this was complemented by hand searching. Inclusion/exclusion criteria were applied and data was extracted from the included studies. Heterogeneity in study design and the outcomes assessed precluded meta-analysis/meta-synthesis; the results are therefore presented in narrative form.<p></p> Results: Thirty-four papers satisfied the review inclusion criteria; most were cross-sectional surveys. The majority of the studies were conducted in North America (n=25), with three being conducted in the UK. Sample sizes ranged from 61 to 98,340. The synthesised evidence demonstrates that social capital is an important construct for understanding the establishment of health risk behaviours in young people. The different elements of family and community social capital varied in terms of their saliency within each behavioural domain, with positive parent–child relations, parental monitoring, religiosity and school quality being particularly important in reducing risk.<p></p> Conclusions: This review is the first to systematically synthesise research findings about the association between social capital and health risk behaviours in young people. While providing evidence that may inform the development of interventions framed around social capital, the review also highlights key areas where further research is required to provide a fuller account of the nature and role of social capital in influencing the uptake of health risk behaviours.<p></p&gt

Bioinformatics-Based Identification of Expanded Repeats: A Non-reference Intronic Pentamer Expansion in RFC1 Causes CANVAS

Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole-genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG)exp] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders

Patient-provider communication regarding drug costsin Medicare Part D beneficiaries with diabetes: a TRIAD Study

<p>Abstract</p> <p>Background</p> <p>Little is known about drug cost communications of Medicare Part D beneficiaries with chronic conditions such as diabetes. The purpose of this study is to assess Medicare Part D beneficiaries with diabetes' levels of communication with physicians regarding prescription drug costs; the perceived importance of these communications; levels of prescription drug switching due to cost; and self-reported cost-related medication non-adherence.</p> <p>Methods</p> <p>Data were obtained from a cross-sectional survey (58% response rate) of 1,458 Medicare beneficiaries with diabetes who entered the coverage gap in 2006; adjusted percentages of patients with communication issues were obtained from multivariate regression analyses adjusting for patient demographics and clinical characteristics.</p> <p>Results</p> <p>Fewer than half of patients reported discussing the cost of medications with their physicians, while over 75% reported that such communications were important. Forty-eight percent reported their physician had switched to a less expensive medication due to costs. Minorities, females, and older adults had significantly lower levels of communication with their physicians regarding drug costs than white, male, and younger patients respectively. Patients with < $25 K annual household income were more likely than higher income patients to have talked about prescription drug costs with doctors, and to report cost-related non-adherence (27% vs. 17%, p < .001).</p> <p>Conclusions</p> <p>Medicare Part D beneficiaries with diabetes who entered the coverage gap have low levels of communication with physicians about drug costs, despite the high perceived importance of such communication. Understanding patient and plan-level characteristics differences in communication and use of cost-cutting strategies can inform interventions to help patients manage prescription drug costs.</p

Symptomatic benefits of testosterone treatment in patient subgroups : a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

Acknowledgments This work was supported by the UK National Institute for Health and Care Research (NIHR)'s Health Technology Assessment Programme (project number 17/68/01). The views expressed herein are those of the authors and not necessarily those of the National Health Service, the NIHR Health Technology Assessment Programme, or the UK Department of Health and Social Care. The Health Services Research Unit at the University of Aberdeen is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The Section of Endocrinology and Investigative Medicine at Imperial College London is funded by grants from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award, and an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Biomedical Research Centre Funding Scheme. WSD is funded by an NIHR Research Professorship. CNJ is funded by an NIHR Post-Doctoral Fellowship. ShB receives NIH research grant funding. The authors are grateful to the clinical and methodological experts and patient partners who contributed to the advisory group for this study.Peer reviewedPublisher PD

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

Background Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. Methods We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. Findings 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60–72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95–7·10]; τ²=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40–2·89]; τ²=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males’ Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). Interpretation In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-mediumterm testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity

Development of environmental tools for anopheline larval control

<p>Abstract</p> <p>Background</p> <p>Malaria mosquitoes spend a considerable part of their life in the aquatic stage, rendering them vulnerable to interventions directed to aquatic habitats. Recent successes of mosquito larval control have been reported using environmental and biological tools. Here, we report the effects of shading by plants and biological control agents on the development and survival of anopheline and culicine mosquito larvae in man-made natural habitats in western Kenya. Trials consisted of environmental manipulation using locally available plants, the introduction of predatory fish and/or the use of <it>Bacillus thuringiensis </it>var. <it>israelensis </it>(<it>Bti</it>) in various combinations.</p> <p>Results</p> <p>Man-made habitats provided with shade from different crop species produced significantly fewer larvae than those without shade especially for the malaria vector <it>Anopheles gambiae</it>. Larval control of the African malaria mosquito <it>An. gambiae </it>and other mosquito species was effective in habitats where both predatory fish and <it>Bti </it>were applied, than where the two biological control agents were administered independently.</p> <p>Conclusion</p> <p>We conclude that integration of environmental management techniques using shade-providing plants and predatory fish and/or <it>Bti </it>are effective and sustainable tools for the control of malaria and other mosquito-borne disease vectors.</p

The phenotype of Floating-Harbor syndrome: Clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results. Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from

The phenotype of floating-harbor syndrome:clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background\ud Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.\ud \ud Methods and results\ud Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.\ud \ud Conclusions\ud This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.The authors would like to thank the families for their cooperation and permission to publish these findings. SdM would like to thank Barto Otten. Funding was provided by the Government of Canada through Genome Canada, the Canadian Institutes of Health Research (CIHR) and the Ontario Genomics Institute (OGI-049), by Genome Québec and Genome British Columbia, and the Manton Center for Orphan Disease Research at Children’s Hospital Boston. KMB is supported by a Clinical Investigatorship Award from the CIHR Institute of Genetics. AD is supported by NIH grant K23HD073351. BBAdV and HGB were financially supported by the AnEUploidy project (LSHG-CT-2006-37627). This work was selected for study by the FORGE Canada Steering Committee, which consists of K. Boycott (University of Ottawa), J. Friedman (University of British Columbia), J. Michaud (University of Montreal), F. Bernier (University of Calgary), M. Brudno (University of Toronto), B. Fernandez (Memorial University), B. Knoppers (McGill University), M. Samuels (Université de Montréal), and S. Scherer (University of Toronto). We thank the Galliera Genetic Bank - “Telethon Genetic Biobank Network” supported by Italian Telethon grants (project no. GTB07001) for providing us with specimens

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

Background The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. Methods We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. Results We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10(-14)). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. Conclusions We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.)