Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature

The SH3–SAM Adaptor HACS1 is Up-regulated in B Cell Activation Signaling Cascades

HACS1 is a Src homology 3 and sterile alpha motif domain–containing adaptor that is preferentially expressed in normal hematopoietic tissues and malignancies including myeloid leukemia, lymphoma, and myeloma. Microarray data showed HACS1 expression is up-regulated in activated human B cells treated with interleukin (IL)-4, CD40L, and anti–immunoglobulin (Ig)M and clustered with genes involved in signaling, including TNF receptor–associated protein 1, signaling lymphocytic activation molecule, IL-6, and DEC205. Immunoblot analysis demonstrated that HACS1 is up-regulated by IL-4, IL-13, anti-IgM, and anti-CD40 in human peripheral blood B cells. In murine spleen B cells, Hacs1 can also be up-regulated by lipopolysaccharide but not IL-13. Induction of Hacs1 by IL-4 is dependent on Stat6 signaling and can also be impaired by inhibitors of phosphatidylinositol 3-kinase, protein kinase C, and nuclear factor κB. HACS1 associates with tyrosine-phosphorylated proteins after B cell activation and binds in vitro to the inhibitory molecule paired Ig-like receptor B. Overexpression of HACS1 in murine spleen B cells resulted in a down-regulation of the activation marker CD23 and enhancement of CD138 expression, IgM secretion, and Xbp-1 expression. Knock down of HACS1 in a human B lymphoma cell line by small interfering ribonucleic acid did not significantly change IL-4–stimulated B cell proliferation. Our study demonstrates that HACS1 is up-regulated by B cell activation signals and is a participant in B cell activation and differentiation

Can a conditional financial incentive (CFI) reduce socio-demographic inequalities in home-based HIV testing uptake? A secondary analysis of the HITS clinical trial intervention in rural South Africa.

In sub-Saharan Africa, home-based HIV testing interventions are designed to reach sub-populations with low access to HIV testing such as men, younger or less educated people. Combining these interventions with conditional financial incentives (CFI) has been shown to be effective to increase testing uptake. CFI are effective for one-off health behaviour change but whether they operate differentially on different socio-demographic groups is less clear. Using data from the HITS trial in South Africa, we investigated whether a CFI was able to reduce existing home-based HIV testing uptake inequalities observed by socio-demographic groups. Residents aged ≥15 years in the study area were assigned to an intervention arm (16 clusters) or a control arm (29 clusters). In the intervention arm, individuals received a food voucher (∼3.5 US dollars) if they accepted to take a home-based HIV test. Testing uptake differences were considered for socio-demographic (sex, age, education, employment status, marital status, household asset index) and geographical (urban/rural living area, distance from clinic) characteristics. Among the 37,028 residents, 24,793 (9290 men, 15,503 women) were included in the analysis. CFI increased significantly testing uptake among men (39.2% vs 25.2%, p < 0.001) and women (45.9% vs 32.0%, p < 0.001) with similar absolute increase between men and women. Uptake was higher amongst the youngest or least educated individuals, and amongst single (vs in union) or unemployed men. Absolute uptake increase was also significantly higher amongst these groups resulting in increasing socio-demographic differentials for home-based HIV testing uptake. However, because these groups are known to have less access to other public HIV testing services, CFI could reduce inequalities for HIV testing access in our specific context. Although CFI significantly home-based HIV testing uptake, it did not do so differentially by socio-demographic group. Future interventions using CFI should make sure that the intervention alone does not increase existing health inequities

Home-Based Intervention to Test and Start (HITS): a community-randomized controlled trial to increase HIV testing uptake among men in rural South Africa.

INTRODUCTION: The uptake of HIV testing and linkage to care remains low among men, contributing to high HIV incidence in women in South Africa. We conducted the "Home-Based Intervention to Test and Start" (HITS) in a 2x2 factorial cluster randomized controlled trial in one of the World's largest ongoing HIV cohorts in rural South Africa aimed at enhancing both intrinsic and extrinsic motivations for HIV testing. METHODS: Between February and December 2018, in the uMkhanyakude district of KwaZulu-Natal, we randomly assigned 45 communities (clusters) (n = 13,838 residents) to one of the four arms: (i) financial incentives for home-based HIV testing and linkage to care (R50 [$3] food voucher each); (ii) male-targeted HIV-specific decision support application, called EPIC-HIV; (iii) both financial incentives and male-targeted HIV-specific decision support application and (iv) standard of care (SoC). EPIC-HIV was developed to encourage and serve as an intrinsic motivator for HIV testing and linkage to care, and individually offered to men via a tablet device. Financial incentives were offered to both men and women. Here we report the effect of the interventions on uptake of home-based HIV testing among men. Intention-to-treat (ITT) analysis was performed using modified Poisson regression with adjustment for clustering of standard errors at the cluster levels. RESULTS: Among all 13,838 men ≥ 15 years living in the 45 communities, the overall population coverage during a single round of home-based HIV testing was 20.7%. The uptake of HIV testing was 27.5% (683/2481) in the financial incentives arm, 17.1% (433/2534) in the EPIC-HIV arm, 26.8% (568/2120) in the arm receiving both interventions and 17.8% in the SoC arm. The probability of HIV testing increased substantially by 55% in the financial incentives arm (risk ratio (RR)=1.55, 95% CI: 1.31 to 1.82, p < 0.001) and 51% in the arm receiving both interventions (RR = 1.51, 95% CI: 1.21 to 1.87 p < 0.001), compared to men in the SoC arm. The probability of HIV testing did not significantly differ in the EPIC-HIV arm (RR = 0.96, 95% CI: 0.76 to 1.20, p = 0.70). CONCLUSIONS: The provision of a small financial incentive acted as a powerful extrinsic motivator substantially increasing the uptake of home-based HIV testing among men in rural South Africa. In contrast, the counselling and testing application which was designed to encourage and serve as an intrinsic motivator to test for HIV did not increase the uptake of home-based testing

Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel

Imputing genotypes from reference panels created by whole-genome sequencing (WGS) provides a cost-effective strategy for augmenting the single-nucleotide polymorphism (SNP) content of genome-wide arrays. The UK10K Cohorts project has generated a data set of 3,781 whole genomes sequenced at low depth (average 7x), aiming to exhaustively characterize genetic variation down to 0.1% minor allele frequency in the British population. Here we demonstrate the value of this resource for improving imputation accuracy at rare and low-frequency variants in both a UK and an Italian population. We show that large increases in imputation accuracy can be achieved by re-phasing WGS reference panels after initial genotype calling. We also present a method for combining WGS panels to improve variant coverage and downstream imputation accuracy, which we illustrate by integrating 7,562 WGS haplotypes from the UK10K project with 2,184 haplotypes from the 1000 Genomes Project. Finally, we introduce a novel approximation that maintains speed without sacrificing imputation accuracy for rare variants

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Forouzanfar MH, Afshin A, Alexander LT, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. LANCET. 2016;388(10053):1659-1724.Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57.8% (95% CI 56.6-58.8) of global deaths and 41.2% (39.8-42.8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211.8 million [192.7 million to 231.1 million] global DALYs), smoking (148.6 million [134.2 million to 163.1 million]), high fasting plasma glucose (143.1 million [125.1 million to 163.5 million]), high BMI (120.1 million [83.8 million to 158.4 million]), childhood undernutrition (113.3 million [103.9 million to 123.4 million]), ambient particulate matter (103.1 million [90.8 million to 115.1 million]), high total cholesterol (88.7 million [74.6 million to 105.7 million]), household air pollution (85.6 million [66.7 million to 106.1 million]), alcohol use (85.0 million [77.2 million to 93.0 million]), and diets high in sodium (83.0 million [49.3 million to 127.5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Copyright (C) The Author(s). Published by Elsevier Ltd

Nutrition Labelling on Food Products and Menus

Nutrition label information on food and drink products is intended to educate and enable consumers to make appropriate food choices. Legislation and policies surrounding the provision of nutrition information are outlined here, specifically those “back” and “front” of pack label versions which appear on pre-packed products, and calorie information on menus. This chapter will describe the practicalities of how consumers can use nutrition labelling to make healthier food choices and the skills and knowledge they need to be able to do so. Evidence on the impact of product and menu labelling on consumers’ purchases and dietary intakes will be reviewed. Efforts to increase the equity of nutrition labels on diets and health across consumer groups are also discussed here in terms of front-of-pack labelling, product reformulation and nutrition label education. Finally, this chapter will introduce the provision of online product nutrition information, including in supermarket websites, alongside the emerging evidence on consumers’ use of these “virtual” labels

Risk of Severe Postpartum Hemorrhage in Low-Risk Childbearing Women in New Zealand: Exploring the Effect of Place of Birth and Comparing Third Stage Management of Labor

Background: Primary postpartum hemorrhage is a leading cause of maternal mortality and morbidity internationally. Research comparing physiological (expectant) and active management of the third stage of labor favors active management, although studies to date have focused on childbirth within hospital settings, and the skill levels of birth attendants in facilitating physiological third stage of labor have been questioned. The aim of this study was to investigate the effect of place of birth on the risk of postpartum hemorrhage and the effect of mode of management of the third stage of labor on severe postpartum hemorrhage. Methods: Data for 16,210 low-risk women giving birth in 2006 and 2007 were extracted from the New Zealand College of Midwives research database. Modes of third stage management and volume of blood lost were compared with results adjusted for age, parity, ethnicity, smoking, length of labor, mode of birth, episiotomy, perineal trauma, and newborn birthweight greater than 4,000 g. Results: In total, 1.32 percent of this low-risk cohort experienced an estimated blood loss greater than 1,000 mL. Place of birth was not found to be associated with risk of blood loss greater than 1,000 mL. More women experienced blood loss greater than 1,000 mL in the active management of labor group for all planned birth places. In this low-risk cohort, those women receiving active management of third stage of labor had a twofold risk (RR: 2.12, 95% CI: 1.39-3.22) of losing more than 1,000 mL blood compared with those expelling their placenta physiologically. Conclusions: Planned place of birth does not influence the risk of blood loss greater than 1,000 mL. In this low-risk group active management of labor was associated with a twofold increase in blood loss greater than 1,000 mL compared with physiological management. © 2012, the Authors Journal compilation © 2012, Wiley Periodicals, Inc