Family-based interventions to increase physical activity in children: a meta-analysis and realist synthesis protocol.

INTRODUCTION: Despite the established relationship between physical activity and health, data suggest that many children are insufficiently active, and that levels decline into adolescence. Engaging the family in interventions may increase and maintain children's physical activity levels at the critical juncture before secondary school. Synthesis of existing evidence will inform future studies, but the heterogeneity in target populations recruited, behaviour change techniques and intervention strategies employed, and measurement conducted, may require a multifaceted review method. The primary objective of this work will therefore be to synthesis evidence from intervention studies that explicitly engage the family unit to increase children's physical activity using an innovative dual meta-analysis and realist approach. METHODS AND ANALYSIS: Peer-reviewed studies will be independently screened by two authors for inclusion based on (1) including 'healthy' participants aged 5-12 years; (2) having a substantive intervention aim of increasing physical activity, by engaging the family and (3) reporting on physical activity. Duplicate data extraction and quality assessment will be conducted using a specially designed proforma and the Effective Public Health Practice Project Quality Assessment Tool respectively. STATA software will be used to compute effect sizes for meta-analyses, with subgroup analyses conducted to identify moderating characteristics. Realist syntheses will be conducted according to RAMESES quality and publication guidelines, including development of a programme theory and evidence mapping. DISSEMINATION: This review will be the first to use the framework of a traditional review to conduct a dual meta-analysis and realist synthesis, examining interventions that engage the family to increase physical activity in children. The results will be disseminated through peer-reviewed publications, conferences, formal presentations to policy makers and practitioners and informal meetings. Evidence generated from this synthesis will also be used to inform the development of theory-driven, evidence-based interventions aimed at engaging the family to increase physical activity levels in children. PROTOCOL REGISTRATION: International Prospective Register for Systematic Reviews (PROSPERO): number CRD42013005780.This is the published version of the manuscript that is available online at: http://bmjopen.bmj.com/content/4/8/e005439.abstract. It is published by the BMJ Group in BMJ Open

Podoconiosis in Rwanda: knowledge, attitudes and practices among health professionals and environmental officers

Background Podoconiosis is a neglected tropical disease commonly found in volcanic regions, where soil is rich in silica. It usually manifests as bilateral lower limb edema. The majority of people affected by podoconiosis are farmers who do not wear shoes. The condition was recently documented in all 30 districts in Rwanda but knowledge, attitudes and practices (KAP) of Rwandan health professionals and environmental officers towards podoconiosis are unknown. Methodology/Findings The objective of this study was to assess the knowledge, attitudes and practices (KAP) of Rwandan health providers and environmental officers towards podoconiosis in order to improve patient healthcare experiences and health outcomes, and to reduce stigma against affected individuals. To achieve this goal, we administered a KAP assessment to physicians (N = 13), nurses/midwives (N = 59), community health workers (N = 226), and environmental officers (N = 38) in the third highest podoconiosis prevalence district in Rwanda (Musanze). All 336 respondents had heard of podoconiosis, but 147 (44%) respondents correctly identified soil as the only direct cause of podoconiosis. The awareness of signs and symptoms and risk groups was lower than any other category (31.5% and 47.5%, respectively). The overall attitude toward podoconiosis was positive (86.1%), with CHWs least likely to harbor negative beliefs against podoconiosis patients. One particular area where most respondents (76%) expressed negative attitude was that they saw people with podoconiosis as a threat to their own health and their family’s health. Prescription of antibiotics and use of ointments/soap to manage wounds was low (5% and 32.2%, respectively), in part due to supply shortages at health facilities. Conclusions This study identified clear gaps in health provider knowledge and practices that affect patient care for those with podoconiosis. Improved access to essential medicines at health facilities and podoconiosis-focused training sessions for practicing health providers are necessary to minimize the burden and stigma of affected individuals

Does adding risk-trends to survival models improve in-hospital mortality predictions? A cohort study

<p>Abstract</p> <p>Background</p> <p>Clinicians informally assess changes in patients' status over time to prognosticate their outcomes. The incorporation of trends in patient status into regression models could improve their ability to predict outcomes. In this study, we used a unique approach to measure trends in patient hospital death risk and determined whether the incorporation of these trend measures into a survival model improved the accuracy of its risk predictions.</p> <p>Methods</p> <p>We included all adult inpatient hospitalizations between 1 April 2004 and 31 March 2009 at our institution. We used the daily mortality risk scores from an existing time-dependent survival model to create five trend indicators: absolute and relative percent change in the risk score from the previous day; absolute and relative percent change in the risk score from the start of the trend; and number of days with a trend in the risk score. In the derivation set, we determined which trend indicators were associated with time to death in hospital, independent of the existing covariates. In the validation set, we compared the predictive performance of the existing model with and without the trend indicators.</p> <p>Results</p> <p>Three trend indicators were independently associated with time to hospital mortality: the absolute change in the risk score from the previous day; the absolute change in the risk score from the start of the trend; and the number of consecutive days with a trend in the risk score. However, adding these trend indicators to the existing model resulted in only small improvements in model discrimination and calibration.</p> <p>Conclusions</p> <p>We produced several indicators of trend in patient risk that were significantly associated with time to hospital death independent of the model used to create them. In other survival models, our approach of incorporating risk trends could be explored to improve their performance without the collection of additional data.</p

Validation of the prognostic performance of Breast Cancer Index (BCI) in hormone receptor-positive (HR+) postmenopausal breast cancer patients in the TEAM trial

Purpose: Early-stage HR+ breast cancer patients face a prolonged risk of recurrence even after adjuvant endocrine therapy. The Breast Cancer Index (BCI) is significantly prognostic for overall (0-10 years) and late (5-10 years) distant recurrence risk (DR) in N0 and N1 patients. Here, BCI prognostic performance was evaluated in HR+ postmenopausal women from the TEAM trial.Experimental Design: 3544 patients were included in the analysis (N=1519 N0, N=2025 N+). BCI risk groups were calculated using pre-specified cut-points. Kaplan-Meier analyses and logranktests were used to assess the prognostic significance of BCI risk groups based on DR. Hazard ratios (HR) and confidence intervals (CI) were calculated using Cox models with and without clinical covariates.Results: For overall 10-year DR, BCI was significantly prognostic in N0 (N=1196) and N1 (N=1234) patients who did not receive prior chemotherapy (p&lt;0.001). In patients who were DRfree for 5 years, 10-year late DR rates for low- and high-risk groups were 5.4% and 9.3% (N0 cohort, N=1285) and 4.8% and 12.2% (N1 cohort, N=1625) with multivariate HRs of 2.25 (95% CI: 1.30-3.88; p=0.004) and 2.67 (95% CI: 1.53-4.63; p=&lt;0.001), respectively. Late DR performance was substantially improved using previously optimized cut-points, identifying BCIlow-risk groups with even lower 10-year late DR rates of 3.8% and 2.7% in N0 and N1 patients, respectively.Conclusions: The TEAM trial represents the largest prognostic validation study for BCI to date and provides a more representative assessment of late DR risk to guide individualized treatment decision-making for HR+ early-stage breast cancer patients

The GALEX Arecibo SDSS Survey. I. Gas Fraction Scaling Relations of Massive Galaxies and First Data Release

We introduce the GALEX Arecibo SDSS Survey (GASS), an on-going large program that is gathering high quality HI-line spectra using the Arecibo radio telescope for an unbiased sample of ~1000 galaxies with stellar masses greater than 10^10 Msun and redshifts 0.025<z<0.05, selected from the SDSS spectroscopic and GALEX imaging surveys. The galaxies are observed until detected or until a low gas mass fraction limit (1.5-5%) is reached. This paper presents the first Data Release, consisting of ~20% of the final GASS sample. We use this data set to explore the main scaling relations of HI gas fraction with galaxy structure and NUV-r colour. A large fraction (~60%) of the galaxies in our sample are detected in HI. We find that the atomic gas fraction decreases strongly with stellar mass, stellar surface mass density and NUV-r colour, but is only weakly correlated with galaxy bulge-to-disk ratio (as measured by the concentration index of the r-band light). We also find that the fraction of galaxies with significant (more than a few percent) HI decreases sharply above a characteristic stellar surface mass density of 10^8.5 Msun kpc^-2. The fraction of gas-rich galaxies decreases much more smoothly with stellar mass. One of the key goals of GASS is to identify and quantify the incidence of galaxies that are transitioning between the blue, star-forming cloud and the red sequence of passively-evolving galaxies. Likely transition candidates can be identified as outliers from the mean scaling relations between gas fraction and other galaxy properties. [abridged]Comment: 25 pages, 12 figures. Accepted for publication in MNRAS. Version with high resolution figures available at http://www.mpa-garching.mpg.de/GASS/pubs.ph

Genotype-phenotype characterisation of long survivors with motor neuron disease in Scotland

Background: We investigated the phenotypes and genotypes of a cohort of ‘long-surviving’ individuals with motor neuron disease (MND) to identify potential targets for prognostication. Methods: Patients were recruited via the Clinical Audit Research and Evaluation for MND (CARE-MND) platform, which hosts the Scottish MND Register. Long survival was defined as &gt; 8 years from diagnosis. 11 phenotypic variables were analysed. Whole genome sequencing (WGS) was performed and variants within 49 MND-associated genes examined. Each individual was screened for C9orf72 repeat expansions. Data from ancestry-matched Scottish populations (the Lothian Birth Cohorts) were used as controls. Results: 58 long survivors were identified. Median survival from diagnosis was 15.5 years. Long survivors were significantly younger at onset and diagnosis than incident patients and had a significantly longer diagnostic delay. 42% had the MND subtype of primary lateral sclerosis (PLS). WGS was performed in 46 individuals: 14 (30.4%) had a potentially pathogenic variant. 4 carried the known SOD1 p.(Ile114Thr) variant. Significant variants in FIG4, hnRNPA2B1, SETX, SQSTM1, TAF15, and VAPB were detected. 2 individuals had a variant in the SPAST gene suggesting phenotypic overlap with hereditary spastic paraplegia (HSP). No long survivors had pathogenic C9orf72 repeat expansions. Conclusions: Long survivors are characterised by younger age at onset, increased prevalence of PLS and longer diagnostic delay. Genetic analysis in this cohort has improved our understanding of the phenotypes associated with the SOD1 variant p.(Ile114Thr). Our findings confirm that pathogenic expansion of C9orf72 is likely a poor prognostic marker. Genetic screening using targeted MND and/or HSP panels should be considered in those with long survival, or early-onset slowly progressive disease, to improve diagnostic accuracy and aid prognostication

The Procedural Index for Mortality Risk (PIMR): an index calculated using administrative data to quantify the independent influence of procedures on risk of hospital death

<p>Abstract</p> <p>Background</p> <p>Surgeries and other procedures can influence the risk of death in hospital. All published scales that predict post-operative death risk require clinical data and cannot be measured using administrative data alone. This study derived and internally validated an index that can be calculated using administrative data to quantify the independent risk of hospital death after a procedure.</p> <p>Methods</p> <p>For all patients admitted to a single academic centre between 2004 and 2009, we estimated the risk of all-cause death using the Kaiser Permanente Inpatient Risk Adjustment Methodology (KP-IRAM). We determined whether each patient underwent one of 503 commonly performed therapeutic procedures using Canadian Classification of Interventions codes and whether each procedure was emergent or elective. Multivariate logistic regression modeling was used to measure the association of each procedure-urgency combination with death in hospital independent of the KP-IRAM risk of death. The final model was modified into a scoring system to quantify the independent influence each procedure had on the risk of death in hospital.</p> <p>Results</p> <p>275 460 hospitalizations were included (137,730 derivation, 137,730 validation). In the derivation group, the median expected risk of death was 0.1% (IQR 0.01%-1.4%) with 4013 (2.9%) dying during the hospitalization. 56 distinct procedure-urgency combinations entered our final model resulting in a Procedural Index for Mortality Rating (PIMR) score values ranging from -7 to +11. In the validation group, the PIMR score significantly predicted the risk of death by itself (c-statistic 67.3%, 95% CI 66.6-68.0%) and when added to the KP-IRAM model (c-index improved significantly from 0.929 to 0.938).</p> <p>Conclusions</p> <p>We derived and internally validated an index that uses administrative data to quantify the independent association of a broad range of therapeutic procedures with risk of death in hospital. This scale will improve risk adjustment when administrative data are used for analyses.</p

Clinical trials in amyotrophic lateral sclerosis:a systematic review and perspective

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of phase II, phase II/III and phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15000 people with amyotrophic lateral sclerosis. 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis