Race disparities in genetic alterations within Wilms tumor specimens

BackgroundWilms tumor (WT) affects Black children disproportionately. Genetic aberrations within WT specimens that contribute to this disparity have not been reported.MethodsThe Therapeutically Applied Research to Generate Effective Treatments (TARGET) database was queried for WT patient and genomic features. Clinical and genetic variables were compared by race.ResultsWithin the discovery set (enriched for adverse events; N = 94 White, 19 Black, 14 Other/unreported patients), Black children were more likely to present with advanced stage disease (p = 0.019). Within the validation set (primarily a random sampling of NWTS-5; N = 360 White, 92 Black, 72 Other/Unreported), Black children appeared older at diagnosis (p = 0.050), had decreased median follow-up time (p<0.0005) and were over-represented (17.4%) relative to the concurrent U.S. Census (12.8%). Among the 37 target genes sequenced, ACTB (p = 0.030) and DICER1 (p = 0.026) mutations were more common in Black patient specimens, whereas DGCR8 (p = 0.041) mutations were more common in White patient specimens. White patient specimens were more likely to contain one or multiple targeted mutations (p = 0.026).ConclusionWithin the TARGET database, Black children were over-represented and harbored WT specimens containing more frequent ACTB and DICER1 mutations. In contrast, WT from White children contained overall more mutations in targeted genes and specifically in DGCR8.Level of EvidenceIII.     

Obesity in early onset breast cancer in African American patients

Obesity is a modifiable risk factor in breast cancer patients and is predictive of disease outcomes in early-onset breast cancer survivors. The purpose of this review is to summarize the current evidence in the association between early-onset breast cancer and obesity, specifically in African-American women. Reviewing the molecular mechanisms and social determinants of disease in this population can provide a foundation for future interventions in prevention, detection, and treatment aiming at improving outcomes for young breast cancer patients.     

Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81–0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R² 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.     

Improving community health and social care practitioners’ confidence,perceived competence and intention to use behaviour change techniques in health behaviour change conversations

Community health and social care practitioners play an increasingly important role in the health promotion agenda, but lack confidence in having effective health behaviour change (HBC) conversations with members of the public. This study reports the development and evaluation of a training intervention based on health psychology to improve health and social care practitioner self-rated confidence, competence and intention to use five behaviour change techniques (BCTs) in their HBC conversations. A 2-day behavioural science interprofessional skills training course plus online learning module was designed for health and social care staff across North East Scotland, teaching five evidence-based BCTs (e.g. Action Planning), plus person-centred communication skills. Participants rated confidence, competence and future intention to use the BCTs on likert scales (1–10) pre-course and post-course, and provided acceptability data. 177 participants aged 20–64 took part, qualitative and quantitative data suggested that the course had high acceptability. Paired samples t tests (n = 120 with complete data) showed significant improvements in confidence, competence and intention following the course, which remained significant with a conservative analysis (n = 174) assuming no change for missing data. Perceived competence in Action Planning increased most during the course (mean change 3.09). In conclusion, health psychology-based skills training can improve practitioner confidence, competence and intention to use evidence-based BCTs; further evaluation is needed to assess practice change.     

A qualitative exploration of barriers to HIV prevention,treatment and support: Perspectives of transgender women and service providers

Transgender (trans) women experience barriers to access to HIV care, which result in their lower engagement in HIV prevention, treatment and support relative to cisgender people living with HIV. Studies of trans women's barriers to HIV care have predominantly focused on perspectives of trans women, while barriers are most often described at provider, organisation and/or systems levels. Comparing perspectives of trans women and service providers may promote a shared vision for achieving health equity. Thus, this qualitative study utilised focus groups and semi-structured interviews conducted 2018–2019 to understand barriers and facilitators to HIV care from the perspectives of trans women (n = 26) and service providers (n = 10). Barriers endorsed by both groups included: (a) anticipated and enacted stigma and discrimination in the provision of direct care, (b) lack of provider knowledge of HIV care needs for trans women, (c) absence of trans-specific services/organisations and (d) cisnormativity in sexual healthcare. Facilitators included: (a) provision of trans-positive trauma-informed care, (b) autonomy and choice for trans women in selecting sexual health services and (c) models for trans-affirming systems change. Each theme had significant overlap, yet nuanced perspective, between trans women and service providers. Specific recommendations to improve HIV care access for trans women are discussed. These recommendations can be used by administrators and service providers alike to work collaboratively with trans women to reduce barriers and facilitators to HIV care and ultimately to achieve health equity for trans women.     

Antigen-induced T-cell changes: Modulation by pharmacologic agents

To determine the effect of pharmacologic modulation of alterations of peripheral blood T-cell subsets caused by antigen-induced bronchoconstriction, we administered albuterol immediately after antigen-induced bronchoconstriction in a double-blind to protocol to 12 atopic asthmatic subjects. We also administered cromolyn sodium before antigen to 7 of the same subjects. Peripheral blood T-cell subset composition (CD4, CD8, la) of a highly purified T-cell preparation was determined before, 24, 48, 72, and 168 h after bronchoconstriction. We found that placebo inhalation immediately after antigen-induced bronchoconstriction did not affect subsequent peripheral blood T-cell subset changes (decrease in CD4+ and increase in Ia+ T lymphocytes). In contrast, inhaled albuterol abolished these T-cell subset changes. Although cromolyn sodium significantly decreased the severity of antigen-induced bronchoconstriction, it did not affect T-cell subset composition changes at the dosage used. We conclude that albuterol can ablate T-cell subset changes associated with antigen-induced bronchoconstriction. Cromolyn sodium ameliorates bronchoconstriction, but has no affect on T-cell subset composition changes. This implies that T-cell changes and bronchoconstriction caused by antigen inhalation are mediated through different pathways.     

Prediction of perinatal outcome in fetuses suspected to have intrauterine growth restriction: Doppler US study of fetal cerebral, renal, and umbilical arteries

PURPOSE: To determine and compare the diagnostic performance of fetal middle cerebral (MCA), renal (RA), and umbilical (UA) arterial Doppler ultrasonography (US) for prediction of adverse perinatal outcome in suspected intrauterine growth restriction (IUGR). MATERIALS AND METHODS: Two hundred ninety-three small-for-gestational age fetuses (24-39 weeks at recruitment and US-estimated weight or abdominal circumference below 10th percentile) were prospectively examined with Doppler US of the UA, MCA, and RA. Clinicians were blinded to MCA and RA Doppler measurements. RESULTS: Seventy-six fetuses (25.9%) had at least one major or minor adverse perinatal outcome. Major outcomes included stillbirth, neonatal death, neurologic complication, and necrotizing enterocolitis. The MCA pulsatility index (PI), compared with the UA PI and RA PI, was more sensitive (72.4% vs 44.7% and 8.3%) but less specific (58.1% vs 86.6% and 92.6%) in predicting adverse outcome. The UA PI had the highest positive likelihood ratio (ratio, 3.3); the MCA PI had the lowest negative likelihood ratio (ratio, 0.48). When gestational age at the first Doppler US examination was less than 32 weeks, the MCA PI had a sensitivity of 95.5% and negative predictive value of 97.7% for major adverse outcome (negative likelihood ratio, 0.10). CONCLUSION: In suspected IUGR, while an abnormal UA PI is a better predictor of adverse perinatal outcome than an abnormal MCA or RA PI, a normal MCA PI may help to identify fetuses without major adverse perinatal outcome, especially before 32 weeks gestational age.