Faculty Bibliography

INTRODUCTION/BACKGROUND:Research has increasingly underscored the impact of factors such as socioeconomic status, education, healthcare access, housing and environmental conditions in shaping population health outcomes. These factors, collectively called social determinants of health (SDOH), provide crucial context for understanding drivers of health outcomes. In sub-Saharan Africa (SSA), the study of SDOH is critical due to the region's unique sociocultural and economic conditions. Understanding how SDOH interacts with health systems and capturing SDOH in data is crucial for informing modelling efforts and policies improving population health more effectively. This scoping review aims to map the types of data used to capture SDOH in research conducted in SSA, to identify research gaps and to summarise key findings. METHODS:, providing best practices for identifying, selecting and analysing eligible studies. Key steps include (1) identifying the research question, (2) identifying relevant studies, (3) selecting eligible studies via a locally curated search, (4) extracting information, (5) collating, summarising and reporting results and (6) consultation with stakeholders. ETHICS AND DISSEMINATION/BACKGROUND:Ethical approval is not required, as this review relies solely on published literature. Findings will be disseminated across academic channels (journals, conferences) and through targeted stakeholder engagement efforts, such as policy briefs and public health workshops, to reach policymakers, healthcare practitioners and community health organisations. This dissemination strategy aims to inform health policy and drive programme development in SSA.

The prevalence and incidence of Crohn's disease (CD) in pediatric populations have been steadily increasing. Growing evidence suggests that gut microbiomal community differences play a critical role in the pathogenesis of CD. Additionally, the clinical course of patients with CD is unpredictable, making treatment decisions challenging. We investigated the fecal microbiome of newly diagnosed, treatment-naïve pediatric CD patients (n = 43) compared to age- and sex-matched controls with other functional gastrointestinal disorders (n = 139). We also correlated microbial changes with CD disease activity, measured by the Pediatric Crohn's Disease Activity Index (PCDAI). Our results showed that microbial richness and diversity were significantly lower in CD patients. Furthermore, taxonomic analysis revealed an enrichment in pro-inflammatory bacteria (Fusobacteria and Proteobacteria) and depletion in favorable bacteria (Firmicutes and Verrucomicrobia). Higher PCDAI scores were linked to the enrichment of genera harboring pro-inflammatory taxa (Hungatella and Veillonella) and decreased abundance of genera harboring protective taxa (Lachnospiraceae). Our study underscores the potential of fecal microbiome profiling as an effective tool for understanding CD pathogenesis, identifying microbial biomarkers, and predicting disease activity for treatment response. This, in turn, can help to improve personalized treatment and management strategies in pediatric CD.

BACKGROUND/UNASSIGNED:Home blood pressure (BP) monitoring (HBPM) is increasingly used as an alternative to office BP. However, factors influencing agreement between office and home BP among very old adults remain unclear. METHODS/UNASSIGNED:During ARIC (Atherosclerosis Risk in Communities) visit 10, participants underwent 3 automated office BP (AOBP) measurements using an Omron HEM-907XL and performed HBPM twice daily for 8 days using an Omron BP7450. Discordance was defined as a systolic BP difference of ±10 mm Hg between mean AOBP and HBPM. Multivariable regression models evaluated demographic, anthropometric, and clinical factors associated with discordance. RESULTS/UNASSIGNED:Among 792 participants (58% female; mean age, 84±3.7 years), mean systolic BP was 130.6 mm Hg (AOBP) and 129.6 mm Hg (HBPM). Despite a minimal average difference (1.0±15.7 mm Hg), 49% had ≥10 mm Hg systolic BP discordance. Higher AOBP was associated with greater discordance. Compared with females, males had lower AOBP relative to HBPM (-4.69 mm Hg [95% CI, -6.86 to -2.51]). Smaller arm circumference was associated with higher discordance (β=14.4 mm Hg [95% CI, 4.78-24.04]). Frail adults had lower AOBP relative to HBPM (β, -5.1 mm Hg [95% CI, -11.0 to 0.9]). Baseline AOBP systolic BP ≥140 mm Hg strongly predicted discordance ≥+10 mm Hg (odds ratio, 8.27 [95% CI, 5.52-12.40]). Participants aged 91 to 100 years had lower AOBP than those aged 78 to 80 years (β, -5.0 mm Hg [95% CI, -10.06 to 0.001]). CONCLUSIONS/UNASSIGNED:Among very old adults, substantial BP discordance between AOBP and HBPM was common and influenced by higher BP, age, male sex, arm circumference, and frailty.

BACKGROUND:The expansion of treatment options for prostate cancer (PC) has improved disease-specific and overall survival outcomes but has also raised questions about the optimal level of treatment needed for patients based on their individual prognosis and accounting for potential toxicity, incorporating quality of life considerations. METHODS:A panel of experts met to discuss current controversies in the care of patients with PC across the disease continuum. Multidisciplinary experts review advances and persistent uncertainties in biomarker-guided assessment, imaging, and systemic therapy for prostate cancer. The discussion outlines priority gaps in evidence that must be addressed to optimize individualized patient care. RESULTS:Workshop topics included use of genomic biomarkers and artificial intelligence-guided tools to identify and manage high-risk and very-high risk localized disease, management of biochemical recurrence, identification of patients with metastatic hormone-sensitive PC who warrant treatment escalation, radiopharmaceutical therapy for metastatic castration-resistant PC including optimal sequencing of approved therapies, role of imaging in identification and management of extraprostatic disease, and lifestyle interventions to optimize survivorship. CONCLUSIONS:Many questions remain about management of PC related to biomarker-based risk stratification to guide treatment selection, use of prostate-specific membrane antigen-positron emission tomography, and balancing the risk for PC-related death with risks for treatment-related toxicity. Ongoing research efforts are needed to optimize risk-based treatment, sequence of therapies throughout the disease continuum, and survivorship care.

Osteoarthritis, especially knee osteoarthritis, is a leading cause of disability and reduced quality of life. The etiology of pain in osteoarthritis is multifactorial, and one promising potential treatment approach involves targeting chemokine systems. The present study was a phase 2, multisite, multiperiod randomized crossover trial of CNTX-6970, a small molecule and selective oral cytokine chemokine receptor type 2 (CCR2) and CCR5 antagonist, in patients with painful knee osteoarthritis (OA). It represents the first trial performed within the National Institutes of Health's Early Phase Pain Investigation Clinical Network. The primary objectives were to evaluate the safety and efficacy of CNTX-6970, relative to placebo, for the treatment of moderate to severe pain related to knee OA. A total of 55 participants were randomized in this multiperiod crossover trial. Linear mixed effects models revealed no significant pain-related benefits of active medication; indeed, trial participants reported slightly higher knee pain intensity when taking the novel chemokine antagonist CNTX-6970 than when taking placebo. In addition, biomarker analysis revealed notably higher level of serum monocyte chemoattractant protein 1 levels when patients were on CNTX-6970 compared to placebo. Overall, although CNTX-6970 was safe and relatively well-tolerated, pharmacologic blockade of specific chemokine receptors with this compound was not effective in reducing moderate-to-severe knee osteoarthritis pain.

BACKGROUND:Obstructive sleep apnea (OSA) is associated with Alzheimer's disease (AD) risk. Racial-, ethnic-, and sex-specific mechanisms of OSA and AD risk were examined. METHODS:We analyzed data from 3978 polysomnography patients without cognitive decline aged ≥ 60 including 663 OSA+ patients (284 non-Hispanic White, 207 Black, 172 Hispanic) matched to OSA- cohorts (1:1, n = 663; 1:4, n = 2652) and followed for AD through 2013. RESULTS:During the 8.5 (standard deviation 1.4) year period, 358 patients developed AD. AD risk was higher for Black (adjusted hazard ratio [aHR] 2.24 [1.24-2.71]), Hispanic (aHR 1.73, [1.38-3.51]), White (aHR 1.83, [1.21-3.37]), male (aHR 2.38, [1.31-3.47]), and female (aHR 1.37, [1.14-2.41]) patients. Hypoxia, sleep fragmentation, and sleep duration (p < 0.01) were associated with increased risk. Black and Hispanic, and female patients showed stronger effects for hypoxia and duration, and fragmentation, respectively. DISCUSSION/CONCLUSIONS:Hypoxia, fragmentation, and duration may underlie racial-, ethnic-, and sex-specific effects of AD risk.

OBJECTIVE:Health systems have finite capacity. During crises, policymakers may explicitly reallocate health system resources, or capacity limitations may necessitate implicit resource reallocation. This study modelled timing and intensity of pre-vaccination health system resource reallocation policies to predict excess mortality during the COVID-19 pandemic. METHODS:This longitudinal panel analysis included 85 countries (752 country-months, January 2020-January 2021). The predictor was resource reallocation scope, scale (summarized as intensity, 0-100), and timing. The outcome was all-cause excess mortality (percentage deaths greater than historical average/month). Covariates included COVID-19 incidence and health system parameters. RESULTS:= -0.58, 95%CI -0.93-0.23: e.g., 42,010 fewer deaths per unit increased resource reallocation, March 2020, all study countries). Effects were magnified in older populations. Health system capacity and preparedness were associated with lower mortality. CONCLUSIONS:In the pre-vaccination COVID-19 pandemic, preemptive health system resource reallocation was associated with lower mortality, whereas simultaneous resource reallocation was associated with greater mortality. This longitudinal multinational study indicates that readiness, capacity building, and proactive resource reallocation improve crisis response.