Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent.

BACKGROUND: Selenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation. OBJECTIVES: A GWAS was performed to identify the single nucleotide polymorphisms (SNPs) associated with changes in Se concentrations after 1 year of supplementation. A GWAS of basal plasma Se concentrations at study entry was conducted to evaluate whether SNPs for Se responses overlap with SNPs for basal Se levels. METHODS: A total of 428 participants aged 40-80 years of European descent from the Selenium and Celecoxib Trial (Sel/Cel Trial) who received daily supplementation with 200 µg of selenized yeast were included for the GWAS of responses to supplementation. Plasma Se concentrations were measured from blood samples collected at the time of recruitment and after 1 year of supplementation. Linear regression analyses were performed to assess the relationship between each SNP and changes in Se concentrations. We further examined whether the identified SNPs overlapped with those related to basal Se concentrations. RESULTS: No SNP was significantly associated with changes in Se concentration at a genome-wide significance level. However, rs56856693, located upstream of the NEK6, was nominally associated with changes in Se concentrations after supplementation (P = 4.41 × 10-7), as were 2 additional SNPs, rs11960388 and rs6887869, located in the dimethylglycine dehydrogenase (DMGDH)/betaine-homocysteine S-methyltransferase (BHMT) region (P = 0.01). Alleles of 2 SNPs in the DMGDH/BHMT region associated with greater increases in Se concentrations after supplementation were also strongly associated with higher basal Se concentrations (P = 8.67 × 10-8). CONCLUSIONS: This first GWAS of responses to Se supplementation in participants of European descent from the Sel/Cel Trial suggests that SNPs in the NEK6 and DMGDH/BHMT regions influence responses to supplementation.

Enteric Pathogens and Reactive Arthritis: Systematic Review and Meta-Analyses of Pathogen-Associated Reactive Arthritis.

The objective of this systematic review and meta-analysis was to estimate the proportion of postinfectious reactive arthritis (ReA) after bacterial enteric infection from one of four selected pathogens. We collected studies from PubMed, Web of Science, and Embase, which assessed the proportion of postinfectious ReA published from January 1, 2000 to April 1, 2018. Papers were screened independently by title, abstract, and full text; papers in English, Spanish, and Portuguese utilizing a case-control (CC) or cohort study design, with a laboratory confirmed or probable acute bacterial enteric infection and subsequent ReA, were included. The proportion of ReA cases was pooled between and across pathogens. Factors that can induce study heterogeneity were explored using univariate meta-regression, including region, sample size, study design, and ReA case ascertainment. Twenty-four articles were included in the final review. The estimated percentage of cases across studies describing Campylobacter-associated ReA (n = 11) was 1.71 (95% confidence interval [CI] 0.49-5.84%); Salmonella (n = 17) was 3.9 (95% CI 1.6-9.1%); Shigella (n = 6) was 1.0 (95% CI 0.2-4.9%); and Yersinia (n = 7) was 3.4 (95% CI 0.8-13.7%). Combining all four pathogens, the estimated percentage of cases that developed ReA was 2.6 (95% CI 1.5-4.7%). Due to high heterogeneity reflected by high I2 values, results should be interpreted with caution. However, the pooled proportion developing ReA from studies with sample sizes (N) <1000 were higher compared with N > 1000 (6% vs. 0.3%), retrospective cohort studies were lower (1.1%) compared with CC or prospective cohorts (6.8% and 5.9%, respectively), and those where ReA cases are identified through medical record review were lower (0.3%) than those identified by a specialist (3.9%) or self-report (12%). The estimated percentage of people who developed ReA after infection with Campylobacter, Salmonella, Shigella, or Yersinia is relatively low (2.6). In the United States, this estimate would result in 84,480 new cases of ReA annually.

Interventions to increase uptake of cervical screening in sub-Saharan Africa: a scoping review using the integrated behavioral model.

BACKGROUND: Sub-Saharan Africa (SSA) experiences disproportionate burden of cervical cancer incidence and mortality due in part to low uptake of cervical screening, a strategy for prevention and down-staging of cervical cancer. This scoping review identifies studies of interventions to increase uptake of cervical screening among women in the region and uses the Integrated Behavioral Model (IBM) to describe how interventions might work. METHODS: A systematic search of literature was conducted in PubMed, Web of Science, Embase, and CINAHL databases through May 2019. Screening and data charting were performed by two independent reviewers. Intervention studies measuring changes to uptake in screening among women in SSA were included, with no restriction to intervention type, study setting or date, or participant characteristics. Intervention type and implementation strategies were described using behavioral constructs from the IBM. RESULTS: Of the 3704 citations the search produced, 19 studies were selected for inclusion. Most studies were published between 2014 and 2019 (78.9%) and were set in Nigeria (47.4%) and South Africa (26.3%). Studies most often assessed screening with Pap smears (31.6%) and measured uptake as ever screened (42.1%) or screened during the study period (36.8%). Education-based interventions were most common (57.9%) and the IBM construct of knowledge/skills to perform screening was targeted most frequently (68.4%). Willingness to screen was high, before and after intervention. Screening coverage ranged from 1.7 to 99.2% post-intervention, with six studies (31.6%) reporting a significant improvement in screening that achieved ≥60% coverage. CONCLUSIONS: Educational interventions were largely ineffective, except those that utilized peer or community health educators and mHealth implementation strategies. Two economic incentivization interventions were moderately effective, by acting on participants' instrumental attitudes, but resulted in screening coverage less than 20%. Innovative service delivery, including community-based self-sampling, acted on environmental constraints, striving to make services more available, accessible, and appropriate to women, and were the most effective. This review demonstrates that intent to perform screening may not be the major determinant of screening behavior, suggesting other theoretical frameworks may be needed to more fully understand uptake of cervical screening in sub-Saharan Africa, particularly for health systems change interventions.

Baseline quality of life is associated with survival among people with advanced lung cancer.

INTRODUCTION: Lung cancer patients presenting with advanced cancer face low survival rates and a high symptom burden. There have been mixed findings for the association between survival and various patient reported outcomes (PROs). METHODS: We used prospective data from 111 lung cancer patients with advanced stage III/IV disease to investigate the association of survival with PROs (European Organization for Research and Treatment of Cancer Core-30 and Lung Module). Cox proportional hazard models were used to examine the individual association between several PRO measures and survival. RESULTS: Pain in chest and global quality of life (QoL) were found to have the strongest association with survival with a 20% increased hazard of death per 10% increase in pain in chest and 14% decrease in hazard of death per 10% increase in global QoL. CONCLUSION: Our results provide more evidence for the value of PRO data to inform clinical and patient decision-making.