The Lancet Regional Health - Americas

Background and Objectives: SARS-CoV-2 (COVID-19) continues to mutate, circulate, and adversely impact health and quality of life. While COVID-19 vaccines remain safe and effective, uptake remains low, especially among children, the youngest of whom were not vaccine-eligible until after Omicron and are underrepresented in published research. This study estimated vaccine effectiveness (VE) among under-5-year-olds. Methods: We used Virginia Department of Health surveillance data from June 2022 through October 2022 to conduct a test negative case-control study. We estimated VE derived from odds ratios (ORs) of reported infections using logistic regression among children aged 6-months to 5-years. Results: Using the earliest positive (cases) or negative (controls) post-vaccine-eligible test results, the VE associated with two doses of a COVID-19 vaccine was 78% (95% CI=45%, 93%; p=0.004) in unadjusted analyses and 70% (95% CI=25%, 91%, p=0.023) when adjusting for age, sex, prior testing behavior, and prior reported infections. The adjusted VE was 74% (95% CI=28%, 94%; p=0.025) among those with no prior positives reported and 45% (95% CI=-302%, 97%; p=0.569) among those with a prior positive reported. Conclusions: These results show that even though the vaccine was not closely matched to the dominant variants circulating during the time period analyzed, it was effective at reducing the risk of reported infections. This study adds to the body of knowledge on pediatric COVID-19 VE in an underrepresented age-group and in a rural region, illustrates the utility of surveillance data for evaluation, and can inform vaccine decisions to improve vaccine uptake for young children.

Background Appendicitis is a readily treatable surgical emergency, yet it remains a cause of preventable death among children in resource-limited settings. While recent studies have documented the global burden of pediatric appendicitis, none have systematically examined its geographic clustering or spatial spillover effects. Understanding whether high-mortality countries cluster geographically, and whether neighboring countries influence each other's outcomes, is essential for designing regional surgical capacity strategies. Methods We conducted a spatial analysis of pediatric appendicitis case fatality rates in children aged 0-14 years across 169 countries from 2000 to 2019. Data were obtained from the Global Burden of Disease Study 2023 and World Bank databases. We calculated global Moran's I to assess spatial autocorrelation, used Getis-Ord Gi* to identify local hotspots, and fitted spatial lag and spatial error regression models to quantify spatial spillovers while adjusting for GDP per capita, physician density, and basic sanitation access. Results Global Moran's I was 0.621 in 2000 (p < 0.001), 0.621 in 2010 (p < 0.001), and 0.592 in 2019 (p < 0.001), indicating strong and persistent spatial clustering. Hotspots at 99% confidence were consistently concentrated in sub-Saharan Africa and parts of South Asia, with little change in geographic distribution over two decades. The spatial error model provided the best fit (AIC = 212.6), with a spatial error coefficient ({lambda}) of 0.663 (p < 0.001), suggesting that approximately 66% of residual variation was explained by unobserved regional factors. In the final model, higher GDP per capita ({beta} = -0.497, p < 0.001) and higher physician density ({beta} = -0.568, p < 0.001) were independently associated with lower case fatality, while basic sanitation access showed no significant association (p = 0.284). Conclusions Pediatric appendicitis case fatality exhibits strong and persistent geographic clustering. The substantial spatial spillover effect suggests that regional coordination of surgical capacity building may be more effective than country-by-country investments. Priority should be given to hotspot countries in sub-Saharan Africa and South Asia, with emphasis on surgical workforce expansion rather than broad economic development alone.

Background: Diarrheal illness in children leads to 3.5 million care visits and 200,000 hospitalizations annually in the US. Viruses are responsible for most pediatric diarrheal cases, yet limited guidance on distinguishing viral from bacterial etiologies complicates clinical decision-making, especially regarding empiric antibiotic use. Methods: We used clinical and qualitative molecular etiologic data from the Implementation of Molecular Diagnostics for Pediatric Acute Gastroenteritis (IMPACT) study to develop prediction models for viral etiology of diarrhea. We used conditional random forests to identify informative clinical and environmental predictors and evaluated model performance using logistic regression and random forests within a 5-fold cross-validation framework. We conducted external validation using the Alberta Provincial Pediatric Enteric Infection Team (APPETITE) dataset. Results: Variables predictive of viral etiology included younger age, non-bloody diarrhea, winter season, and presence of vomiting. External validation showed that an AUC of 0.82 can be achieved with a parsimonious 5-variable model, yielding a sensitivity of 0.92 and specificity of 0.55 Conclusion: Our results suggest that in North American healthcare settings, clinical prediction models can inform decision-making by identifying children with a high probability of viral diarrhea, improving diagnostic clarity, and reducing unnecessary testing and treatment.

PURPOSE: Cancer outcomes in sub-Saharan Africa are driven by delayed diagnosis and treatment initiation. We evaluated the magnitude and determinants of diagnostic and treatment delays among cancer patients in Kinshasa, Democratic Republic of the Congo (DRC). METHODS: We conducted a hospital-based cross-sectional study of 460 adults with confirmed cancer at Nganda Hospital Center in Kinshasa, DRC. Two outcomes were assessed: delay from symptom onset to diagnosis and delay from diagnosis to treatment initiation. Log-normal regression models were fitted for each outcome to estimate adjusted geometric mean ratios (aGMRs) and 95% confidence intervals (CIs). Covariates included demographic, socioeconomic, clinical, behavioral, and stigma-related factors. RESULTS: The median age was 55 years, and 76.2% of participants were women. Overall, 55.0% of participants experienced symptom-to-diagnosis delays >6 months, and 49.4% experienced diagnosis-to-treatment delays >3 months. Older age was associated with longer diagnostic delay (aGMR 1.55, 95% CI 1.03-2.31) and treatment delay (1.51, 1.07-2.14). Unemployment was strongly associated with both diagnostic delay (1.68, 1.15-2.47) and treatment delay (2.27, 1.54-3.33), as was hepatitis B co-infection (1.88, 1.06-3.34 and 2.42, 1.15-5.11, respectively). Longer diagnostic delay was additionally associated with informal trading (1.99, 1.21-3.28), taxi or motorbike transport (1.92, 1.25-2.94), and smoking history (2.25, 1.03-4.91), while high cancer-stereotype stigma was associated with longer treatment delay (1.56, 1.04-2.34). CONCLUSION: Substantial delays exist across the DRC cancer care continuum, driven by socioeconomic vulnerability, transport barriers, hepatitis B co-infection, and cancer-related stigma. These findings highlight the need for integrated interventions to improve timely diagnosis and treatment initiation, including strengthening financial protection, decentralizing cancer services, and reducing stigma in cancer care.

Abstract Background Cancer is an increasing public health challenge in Kenya, particularly in rural and underserved regions where surveillance systems and diagnostic capacity remain limited. Kilifi County, located along the Kenyan coast, lacks a population-based cancer registry, and data on the local cancer burden is not available. This study aimed to characterize the demographic distribution of patients, cancer burden in the county, and management of cancer cases diagnosed at Kilifi County Referral Hospital (KCRH) over ten years. Methods This retrospective study analyzed the patterns of cancer in Kilifi County using patient records from KCRH during the study period (January 1, 2014, to January 1, 2024). Results A total of 101 patients with cancer were identified, 58% female, with a mean age of 54 years. Most patients were from Kilifi North (47%), with a high proportion reporting no formal occupation (41%) or farming (26%). Esophageal and cervical cancers were the most common (18% each), followed by breast and prostate cancers (5% each), with other malignancies occurring infrequently. Histopathology was the primary diagnostic modality (88%). Staging data were incomplete in 70% of cases; among documented cases, the majority presented with advanced disease (21% stage IV). Due to limited local treatment capacity, approximately half of the patients were referred to tertiary centers for chemotherapy, radiotherapy, or surgery. At data cut-off, 43% had died, 25% were on treatment, and 29% were lost to follow-up, with only 2% completing treatment or under follow-up. Conclusions This study demonstrates a substantial cancer burden in Kilifi County and highlights critical gaps in diagnostic capacity, staging, and continuity of care. Strengthening cancer surveillance systems, expanding diagnostic and treatment infrastructure, and establishing a population-based cancer registry are essential to improving cancer outcomes and advancing equitable care in rural Kenya

Background Complex gastrointestinal (GI) oncologic surgeries carry substantial perioperative risk, and nationwide outcomes in low- and middle-income countries (LMICs) are underreported. This study aimed to evaluate national trends in surgical volume, in-hospital mortality, and intensive care unit (ICU) utilization for major GI cancer surgery in Brazils Unified Health System (SUS) over a 14-year period. Methods A population-based analysis was performed using national administrative databases to identify all adult patients undergoing colectomy, gastrectomy, pancreatic resection or esophagectomy for cancer in the SUS from 2010-2023. Annual rates were age-standardized according to the WHO standard population. Temporal trends were assessed using Poisson regression to estimate average annual percent change (AAPC) with 95% confidence intervals (CIs). Results A total of 179,337 hospital admissions were analyzed (median age 63 years; 48% female). Colectomies accounted for 72% of cases, followed by gastrectomies (19%), pancreatic resections (5%), and esophagectomies (3%). Although crude surgical volume increased, population-adjusted rates declined overall (AAPC -2.09%; 95% CI -2.58 to -1.59), mainly due to reductions in gastrectomies and esophagectomies. Median hospital stay decreased from 9 to 7 days (AAPC -1.93%; 95% CI -2.79 to -1.06). Overall in-hospital mortality declined from 8.1% to 5.7% (AAPC -2.88%; 95% CI -4.15 to -1.59). ICU utilization rose from 37% to 43% of admissions (AAPC +1.31%; 95% CI 0.91 to 1.71). Conclusion Over 14 years, in-hospital mortality and length of stay for major gastrointestinal cancer surgery declined within Brazils universal public health system. These temporal trends occurred alongside expansion of accredited oncology services and increased ICU utilization, although causal relationships cannot be established from administrative data. These findings should be interpreted as hypothesis-generating and highlight the need for more granular hospital-level data in LMIC settings.

Objectives In Quebec, Canada, vaccination against human papillomavirus (HPV) has been publicly-funded since January 2016 for gay, bisexual, and other men who have sex with men (GBM) aged [&le;]26 years. The study aimed to analyze data collected in Greater Montreal (Engage study) to evaluate the HPV vaccination program for GBM in Quebec. Study Design Engage is a cohort of sexually active GBM aged [&ge;]16 recruited via respondent-driven-sampling (RDS) in Canada. Participants completed a questionnaire and tested for sexually transmitted infections. Methods RDS-II weights were applied to adjust for recruitment. Subgroups were compared using standardized mean differences. Odds ratios of HPV vaccination and prevalence ratios of anal HPV infection adjusted for potential confounders were estimated using robust regression models. Results Of 1179 participants, 309 were eligible for free HPV vaccination. Vaccine coverage among eligible GBM was 42%. Among those who disclosed same-sex sexual activity and discussed HPV vaccination with their healthcare provider, coverage reached 82%. Anal HPV prevalence among eligible GBM was 26.5% for [&ge;]1 HPV-6/11/16/18 genotypes without significant difference between vaccinated and unvaccinated individuals. Among unvaccinated GBM aged [&le;]26 who were aware of the vaccine, 60% intended to get vaccinated within the next year. Conclusions One to two years after GBM aged [&le;]26 were included in the Quebec HPV vaccination program, 42% of eligible GBM in Greater Montreal had been vaccinated. Anal HPV prevalence was high among GBM. Vaccinees were more likely to self-report a prior STI diagnosis. Offering vaccination to all preadolescents in schools appears essential to maximize vaccination benefits.

Background: The rising prices of cancer medicines have intensified concerns about treatment access and health system sustainability particularly in low- and middle-income settings. Systematic facility level evidence on what medicines is actually available, at what prices, and at what cost to patients remains scarce, constraining evidence-based policy reform. Methods: Using adapted WHO/Health action international methodology, we conducted a cross-sectional survey of 52 cancer medicines across five therapeutic classes at five health facilities in Kisumu County, Kenya. Availability was measured as the proportion of facilities stocking each medicine. Affordability was assessed using days' wages required for the lowest-paid government worker to purchase standard treatment regimens, calculated per one chemotherapy cycle and maximum possible cycles. Results: Overall medicine availability was 48.1%, with marked inter-facility variation. Affordability analysis revealed severe financial barriers. The breast cancer AC regimen required 19.6-47.4 days' wages per full course; cervical cancer cisplatin, 19.8-49.2 days' wages; colorectal FOLFOX, 80.0-303.6 days' wages; and prostate docetaxel reached 437 days' wages at the highest-cost facility. The Social Health Authority's (SHA) KES 550,000 annual ceiling adequately covered cytotoxic regimens for common cancers at competitive prices but was exceeded by 24-116% for HER2-positive breast cancer requiring trastuzumab, with further strain for recurrent cervical and metastatic prostate cancers. Conclusions: Cancer medicines in Kisumu County are inconsistently available and highly variable in price resulting in inequitable access. We call for urgent retail price markup regulation, expanded pooled procurement through KEMSA, inclusion of priority targeted therapies on the Kenya Essential Medicines List, and SHA benefit packages redesigned around full-course regimen costs.

Background Pancreatic Ductal Adenocarcinoma will be the 2nd-most common cause of cancer mortality by 2030. It is associated with rapid deterioration, severe symptoms, and significant quality-of-life concerns. Using input from patients, family caregivers (FCGs), and provider stakeholders, we designed an intervention, PAL-CHW-PDAC, delivered by a community health worker that involves proactive symptom monitoring and management, care navigation, and disease education. Methods We conducted a pilot randomized controlled trial of 60 patients with newly diagnosed PDAC (within 2 weeks of diagnosis) and their caregivers at Loma Linda University Health from 09/2025 to 05/2026. Patients were randomized 1:1 to receive the PAL-CHW-PDAC intervention (6 CHW visits over 3 months) or an attention control. The control comparator involved receiving standard handouts and videos on pancreatic cancer, along with check-in visits with research staff. The primary outcome was symptom burden, defined using the NCCN/FACT Hepatobiliary Symptom Index. Secondary outcomes included quality of life (QoL) measured by the FACT-Hep and psychological distress (measured by the NCCN-Distress Thermometer). Caregiver outcomes included burden, preparedness, quality of life, and psychological distress. Results: 60 out of 74 eligible (81%) were enrolled. The median age was 71, 60% of patients were Hispanic. 68% of patients presented with metastatic PDAC, 23% with borderline resectable disease and 9% with resectable PDAC. There was a trend towards improved symptom burden at 12 weeks (mean increase of 5.3 points vs. decrease of 3.2 points; p=0.093) with the intervention compared to the attention control. The intervention group also had improved psychological distress at 12 weeks (3.31 vs. 5.95, p=0.01), caregiver psychological distress (3.26 vs. 6.86, p<0.001) and caregiver preparedness (2.92 vs. 2.11) at 12 weeks. Telehealth utilization for symptom-focused visits improved with the intervention (82%) compared to the control. (14%, p=0.01) Hospice utilization also improved with the intervention (41% vs 7%, p-0.12). Conclusions: A pilot RCT of the PAL-CHW-PDAC intervention demonstrated preliminary efficacy with a trend towards improved symptom burden, psychological distress, and caregiver psychological distress and preparedness. A larger definitive clinical trial is needed to understand the impact of this promising intervention. ClinicalTrials.gov number, NCT07591571

Background Pediatric immunizations for Respiratory Syncytial Virus (RSV), including monoclonal antibodies for infants and vaccines for pregnant people, have become broadly available and can prevent severe RSV outcomes in infants. However, quantifying the impact of RSV immunization in prevention of severe pediatric illness at the population-level is limited by lack of RSV case surveillance data. The Massachusetts Department of Public Health (DPH) conducted a modeling analysis using routine public health surveillance data to estimate the state-level impact of new RSV immunization products on Emergency Department (ED) visits and hospitalizations in Massachusetts for highest risk pediatric groups. Methods A scenario projection tool, called R.Scenario.Vax, was utilized to simulate RSV-associated ED hospital encounters by age group in the context of newly available immunizations. ED visit and hospitalization data from the National Syndromic Surveillance Program (NSSP) during the time period 10/08/2017--10/19/2024 were analyzed, scaled to account for changes in RSV testing practices over time and missing encounter volume in historic data, and utilized to inform model fit of a "typical" RSV season. RSV immunization data from the Massachusetts Immunization Information System (MIIS) for the 2023--2024 and 2024--2025 RSV seasons informed high and moderate pediatric RSV immunization coverage scenarios and their impact was compared to a counterfactual reference scenario of no new immunizations. Median projections were quantitatively and qualitatively compared to observed 2024--2025 season data. Percent reduction in hospital encounters and encounters averted per 10,000 population were calculated for each scenario as compared to the reference. Results Projections for the youngest at-risk age groups showed significantly lower RSV-associated ED visits and hospitalizations during the 2024--2025 season for both high and moderate immunization coverage scenarios. Median projections for infants under 6 months old in the highest coverage scenario, wherein nearly all infants were immunized, showed 72.6% lower ED visits and 73.4% lower hospitalizations when compared to the reference scenario, equating to 262 ED visits and 85 hospitalizations averted per 10,000 population. Conclusions Our results support the use of modeling methods for public health insights and suggest that RSV immunizations for infant populations result in significantly lower RSV-related ED encounters in Massachusetts.

Objective: Lyme disease diagnosis in children is challenging due to atypical presentations and testing limitations. We sought to evaluate the association between Lyme disease and socio-geographic risk factors in children. Materials and methods: We enrolled children undergoing evaluation for acute Lyme disease at one of eight Pedi Lyme Net pediatric emergency departments located in high Lyme disease incidence states over a ten-year period (2015-2024). We defined a case of Lyme disease with an erythema migrans (EM) lesion or a positive two-tier serology result in a child with signs and/or symptoms of acute disease. We linked each childs primary residential county to the following factors: urban-rural residence, socioeconomic status, population-level disease incidence, wildland-urban interface, and "Lyme disease" Google searches. We performed a multi-level logistic regression analysis to evaluate associations between Lyme disease and county factors after adjusting for individual demographics. Results: Among 5,529 children enrolled, 1,396 (25.2%) had Lyme disease: 101 (7.2%) with early-localized disease, 584 (41.8%) with early-disseminated disease, and 711 (50.9%) with late-disseminated disease. Rural residence (aOR 1.9, 95% CI 1.3-2.9), higher socioeconomic advantage (aOR 1.3, 95% CI 1.1-1.4), more "Lyme disease" Google searches (aOR 1.1, 95% CI 1.0-1.2), and higher wildland urban interface (aOR 1.2, 95% CI: 1.0-1.4) were independently associated with Lyme disease. Conclusion: Incorporating socio-geographic factors alongside clinical data may augment diagnostic risk assessment in children with suspected Lyme disease. However, these factors should be incorporated carefully to ensure clinical assessments are not based on a childs geographic location alone.

Introduction: A prominent symptom of post-acute sequelae of SARS-CoV-2 infection (i.e., Long COVID) is exercise intolerance with or without post-exertional malaise (PEM). PEM is characterized by the worsening of both symptoms and function following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. Individualized, supervised cardiopulmonary rehabilitation is considered a safe and effective intervention for many cardiac and pulmonary conditions, and has been effective in gradually improving function in previously hospitalized and nonhospitalized patients with severe COVID-19. While traditional cardiopulmonary rehabilitation approaches appear helpful in some situations, the exercise intolerance symptoms experienced by many individuals with Long COVID may require a different approach, especially when attempts to increase physical activity result in PEM. No clear consensus exists on the optimal treatment of PEM, and no major studies have evaluated the efficacy in individuals with Long COVID of either carefully supervised, individualized cardiopulmonary rehabilitation programs for exercise intolerance without significant PEM or activity pacing interventions designed to treat or prevent PEM. Methods and Analysis: The Researching COVID to Enhance Recovery Clinical Trials (RECOVER-CT) initiative funded by the National Institutes of Health (NIH) included a prospective, multicenter, randomized controlled platform trial (RECOVER-ENERGIZE) designed to assess two interventions in patients with Long COVID and exercise intolerance: (1) cardiopulmonary rehabilitation for patients without significant PEM and (2) structured activity pacing to prevent or reduce PEM in participants who experience the symptom. The intervention duration will be 12 weeks. The primary endpoints for the trial include the Endurance Shuttle Walk Test as a measure of endurance capacity for the cardiopulmonary rehabilitation intervention and a modified version of the DePaul Symptom Questionnaire - Post-Exertional Malaise for the pacing intervention. Assessments will be completed at baseline, middle of intervention, end of intervention, and 12 weeks after completion of the intervention, and include physical performance measures and patient-reported surveys. Ethics and Dissemination: The RECOVER-ENERGIZE trial protocol has been approved by an institutional review board (Advarra), and written informed consent will be obtained from all participants prior to enrollment. The trial is registered on ClinicalTrials.gov (NCT06404047). Formally assessing PEM and developing a structured activity pacing intervention delivered by local pacing coaches are novel features of this trial. Results will be disseminated through peer-reviewed publications, presentations at scientific conferences, and communication with participants, patient advocacy organizations, and the broader Long COVID community. De-identified participant data will be made available through the NIH RECOVER data repository in accordance with NIH data-sharing policies. If successful, this protocol will provide accessible tools that clinicians can use to address exercise intolerance and PEM in patients with Long COVID.

Background: Adults with severe mental health conditions (often referred to as severe mental illness, SMI) experience 15 to 20 year mortality gap relative to the general population, with lung cancer a significant contributor. National cancer policy targets earlier diagnosis but does not explicitly address how pathways function for this group. Aims: This study aimed to describe lung cancer risk, prevalence, screening eligibility, referral activity and diagnostic pathway performance for adults with SMI in South East London (SEL), and to examine where along the pathway inequalities arise. Methods: Co-designed with experts with lived experience and voluntary sector, this exploratory mixed-methods service evaluation combined quantitative analysis of routinely collected data from the Quality Outcomes Framework (QOF), SMI Register and Cancer Waiting Times Record (April 2023-March 2024) with semi-structured qualitative interviews (n=11 clinical staff) and focus groups (n=6 adults with lived experience of SMI). Quantitative and qualitative data were analysed using descriptive statistics and framework-based thematic analysis respectively, and findings were integrated using a joint display approach, organised by the Consolidated Framework for Implementation Research (CFIR). Results: Lung cancer prevalence was approximately double among adults with SMI (0.17% vs 0.09% in the general population). Despite Urgent Suspected Cancer (USC) referral rates being more than twice as high in the SMI population (63 vs 28 per 100,000), fewer cancers were detected via planned general practice (GP) routes (11% vs 20%), the 28-day Faster Diagnosis Standard was not met for any SMI patient diagnosed with lung cancer during the study period; overall FDS performance was 76% in the SMI population compared with 84% in the general population; and appointment non-attendance was more than double that in the general population (6% vs 3%). Qualitative findings identified individual, service and system-level mechanisms, including stigma, diagnostic overshadowing, fragmented coordination, and rigid pathway protocols, that compound disadvantage across lung cancer pathway stages. Conclusions: Inequality in lung cancer outcomes for adults with SMI accumulates across the pathway rather than arising at a single point of failure. Addressing this requires proportionate adaptations within existing cancer pathways, alongside routine reporting of cancer outcomes stratified by SMI population. Keywords: severe mental health conditions, lung cancer, health inequalities, cancer screening, diagnostic pathway, mixed methods

Importance BRCA genetic testing is critical for cancer risk assessment, treatment and personalization, yet substantial underutilization persists. Socioeconomic and clinical factors may strongly influence testing uptake; therefore, identifying the potential drivers to BRCA testing and treatment is essential for addressing gaps in access, increasing retention into care, and improving cancer outcomes. Objective To quantify the putatively causal effects of SDoH on BRCA genetic testing among individuals with breast, ovarian, pancreatic, and prostate cancers and to develop a predictive model to identify patients at risk for underuse of testing. Design, Setting, and Participants This observational case-control study used data from a large multistate clinical research data network covering southern US (2012-2023). The network contained records of more than 26 million individuals and was linked with ZIP code-level SDoH variables derived from national socioeconomic datasets. Adults diagnosed with breast, ovarian, pancreatic, or prostate cancer were eligible for cases (received BRCA testing) or controls (did not receive BRCA testing, matched by cancer diagnosis). Exposure SDoH categories, including economic conditions, education, healthcare access, neighborhood conditions, and social connectedness. Main Outcomes and Measures The primary outcome was receipt of BRCA genetic testing after cancer diagnosis. Results Among 3,279 people diagnosed with cancer, 748 received BRCA testing and 2,531 served as controls. Study population mean [SD] age was 66.8 [15.7] years; 1,758 were women [53.6%], 2,238 [69.6%] were White and 616 [18.8%] were Black or African American. Breast (1,420 [42.8%]) and prostate (1,342 [40.9%]) cancers were the most common diagnoses, followed by pancreatic (242 [7.4%]), ovarian (238 [7.2%]), and multiple cancers (55 [1.7%]). Upon adjusting for potential confounding, higher educational attainment (odds ratio [OR], 1.19), public-sector employment (OR, 1.42), neighborhood safety (OR, 1.28), and social participation (OR, 1.72) showed an increased likelihood of undergoing BRCA testing, whereas economic instability, including housing cost burden and reliance on public insurance, had an effect of reduced testing. A random forest classifier demonstrated good discriminative performance (AUROC, 0.776) to predict cancer patients who were likely to take BRCA testing, where nativity, language, and residential stability ranked among the most influential social determinants according to SHapley Additive exPlanations (SHAP) analysis. Conclusions and Relevance In this observational case-control study, SDoHs were strongly associated with receipt of BRCA genetic testing among people with cancer. These findings suggest that disparities in genetic testing may reflect structural and social barriers rather than differences in clinical eligibility alone. Efforts to improve equitable access to genetic testing may benefit from integrating social-context information into clinical workflows and targeting outreach or navigation strategies toward socially disadvantaged populations.

Importance: Hereditary breast and ovarian cancer (HBOC) variant carriers benefit from risk-reducing interventions, but only if identified. The extent to which carriers are clinically recognized, and whether recognition is equitable across diverse populations, is poorly characterized in a single large U.S. cohort. Objective: To estimate P/LP HBOC carrier prevalence across genetic ancestry groups, quantify documented clinical genetic testing among carriers, and evaluate ancestry and socioeconomic disparities in testing. Design, Setting, and Participants: Cross-sectional analysis of the All of Us Research Program Controlled Tier (Curated Data Repository v8/C2024Q3R9), comprising participants with short-read whole genome sequencing and linked electronic health record (EHR) and survey data. Carriers were ascertained from research genomic data independent of clinical testing. Exposures: Genetically inferred ancestry (African [AFR], Admixed American [AMR], East Asian [EAS], European [EUR], Middle Eastern [MID], South Asian [SAS]); self-reported household income and educational attainment. Main Outcomes and Measures: (1) Carrier prevalence with Wilson 95% CIs; (2) documented clinical genetic testing (procedure codes) among carriers; (3) adjusted odds of documented testing among women, by ancestry, before and after socioeconomic adjustment, using multivariable logistic regression. Results: Among 414,830 participants, P/LP HBOC carrier prevalence was 1.42% (95% CI, 1.38-1.45) overall and similar across ancestry groups (AFR 1.24%, AMR 1.32%, EAS 1.19%, EUR 1.52%, MID 1.68%, SAS 1.33%; overlapping CIs). Among 250,071 women in the testing analysis, documented clinical genetic testing was rare: only 74 of 5,878 carriers overall (1.3%) and 59 of 3,572 European-ancestry carriers (1.7%) had a documented test, with counts below reportable thresholds in all other ancestry groups. African-ancestry women had lower adjusted odds of documented testing than European-ancestry women (Model 1 adjusted odds ratio [aOR], 0.32; 95% CI, 0.27-0.39), an association that attenuated but persisted after adjustment for income and education (Model 2 aOR, 0.48; 95% CI, 0.40-0.58; P < 0.001); Admixed American women also had reduced adjusted odds (aOR, 0.71; 95% CI, 0.61-0.84). Lower income and lower education were independently and dose-dependently associated with lower testing odds (income <$25,000 aOR, 0.46; high-school education aOR, 0.54). Conclusions and Relevance: High-risk HBOC variant carriers are present across all ancestry groups at similar frequencies, yet documented clinical genetic testing was disparate in the different ancestry groups. African-ancestry women experience a testing gap that is not fully explained by socioeconomic position, implicating structural barriers in access and referral. Population-level strategies that decouple carrier identification from current referral pathways may be required to close this gap.

Background Post-acute sequelae are well described following COVID-19 but may also occur after other respiratory infections and Aedes-borne infections. Evidence remains fragmented due to heterogeneity in study design, populations, and exposure, outcome, and follow-up definitions. Methods We synthesized and compared post-acute sequelae across influenza, RSV-ARI, dengue fever, chikungunya, Zika, and yellow fever. We searched five databases from inception to 25-08-2025 for articles quantifying risk, incidence, or rates of post-acute sequelae following these diseases. Eligible non-randomized observational studies assessed post-acute neurological, psychiatric, gastrointestinal, cardiovascular, respiratory, renal, musculoskeletal, autoimmune, or endocrine outcomes after confirmed infection. Risk of bias was assessed using ROBINS-E. Random-effects meta-analyses with restricted maximum likelihood estimation were conducted when comparable effect estimates were available (PROSPERO #CRD420251124994). Findings 51 studies were included, predominantly from high-income regions. Most were retrospective cohorts using ICD-coded diagnoses; prospective studies used laboratory-confirmed infections. Data sources, comparator groups, exposure definitions, outcome ascertainment, and follow-up periods varied substantially. Meta-analyses were feasible for RSV, influenza, and dengue fever. All RSV-ARI studies were pediatric and assessed infections during infancy, which were associated with higher pooled odds of physician-diagnosed asthma (OR:2.93 [95%CI: 2.12-4.06]). Influenza studies used COVID-19-positive comparators; pooled estimates showed lower risk for neurological (HR:0.82 [0.76-0.89]) and composite outcomes (RR:0.88 [0.82-0.95]), with other organ systems non-significant. Dengue fever studies spanned all ages and showed increased risks of anxiety (HR:1.34 [1.01-1.78]), dementia (HR:1.61 [1.10-2.35]), autoimmune (RR:1.39 [1.17-1.67]), cardiovascular (HR:1.51 [1.27-1.80]), psychiatric (HR:1.17 [1.07-1.28]), and any sequelae (HR:1.19 [1.13-1.25]) versus those without prior infection. Interpretations Post-acute sequelae contribute to overall disease burden following RSV-ARI and dengue fever. The evidence remains limited by heterogeneity in study design, exposure and outcome definitions, comparator selection, and follow-up duration. Greater standardization in study design and reporting is needed to improve comparability and strengthen causal inference.

We assembled a multimodal clinical dataset describing demographics, placement history, prenatal substance exposure (PSE), birth characteristics, adverse childhood experiences (ACEs), International Classification of Diseases (ICD) diagnoses, and laboratory results for 3,685+ pediatric patients evaluated between 2014 and 2024 at the University of Minnesotas Adoption Medicine Clinic (AMC). Data were curated from electronic medical records through a combined manual and automated extraction protocol using a standardized operating procedure. The resulting dataset integrates structured EMR fields including neuropsychological, laboratory, and diagnostic information with manually pulled fields of ACE scores, PSE history, and placement history. We provide an overview of the population represented and describe the datasets structure, variable definitions, and validation procedures. This resource enables investigations into how early adversity impacts medical and developmental outcomes, and provides one of the largest standardized clinical placement history, PSE, and ACE datasets in an adoption and foster care pediatric population.

Background: Shigella is a leading cause of childhood diarrhea in low- and middle-income countries and is increasingly resistant to first-line antibiotics. We conducted a surveillance study to determine the incidence, genomic characteristics, and AMR profiles of Shigella infections in children under five with moderate to severe diarrhea (MSD) in Lusaka, Zambia. Methods: Between 15 September 2020 and 30 November 2021, a prospective cohort study of 1,400 children under five was enrolled during a community census in a peri-urban setting and passively followed for 9.5 months for MSD. During enrollment, socio-demographic data were collected using electronic questionnaires, while clinical data were collected through the DHIS platform. The main outcome, Shigella in diarrheal stool in under 5 children, was detected using culture and Loop-mediated Isothermal Amplification (LAMP) targeting the ipaH gene. Cox proportional hazards models were used to assess the incidence and risk factors of Shigella (ipaH) infections. Whole-genome sequencing (WGS) was used to characterize the genomic diversity and antimicrobial resistance genes, complemented by phenotypic antibiotic susceptibility testing. Results: There were 230 first episodes of Shigella over a follow-up time of 9,581.7 child-months, yielding an incidence of 24.0 (95% CI 21.1-27.3) cases per 1,000 child-months, with the highest incidence among 2 to 3-year-olds. The key risk factors identified were the water source (p=0.025) and age group (p=0.014). Genotypic characterization revealed 10 S. flexneri, 9 S. sonnei, and 3 S. boydii. The S. sonnei isolates formed two clusters, differing in virulence factors and plasmid profiles, indicating two possible circulating strains. Shigella isolates exhibited phenotypic and genotypic multidrug resistance, including against trimethoprim, aminoglycosides, and beta-lactams. Plasmid-mediated quinolone resistance (qnrS1) was identified in four S. flexneri isolates, with these genes located on the IncFIB(K) plasmid, highlighting the potential for horizontal transmission and spread of quinolone resistance in this region. No phenotypic and genotypic resistance to macrolides, the first-line treatment for Shigella in Zambia, was observed. Interpretation: We report a high burden of Shigella with multidrug resistance, including resistance to fluoroquinolones. These findings highlight the increasing resistance of Shigella to first-line antibiotics and underscore the importance of developing safe and effective vaccines, improving WASH conditions, and ongoing AMR surveillance. Funding: The EDCTP2 program, supported by the European Union, the Faculty for the Future Foundation (FFTF), the Netherlands Organization for Health Research and Development (ZonMw), and Health-Holland AMR-Global, Gloria, and Track-AMR.

Adenoviruses (Ads) are widely used as vaccine vectors. However, pre-existing immunity to commonly used serotypes, like Ad5, can reduce vaccine immunogenicity, with neutralizing antibody titers >200 previously shown to impact vaccine efficacy. Gorilla adenovirus (GRAd) vectors have been developed to evade pre-existing anti-vector responses, but their seroprevalence in southern Africa is poorly defined. Here, we assessed seroprevalence to GRAd32, Ad26 and Ad5 before (baseline) and after COVID-19 vaccination, in cohorts from South Africa and Zimbabwe. Sera from South African participants enrolled in the Sisonke sub-study (n=100, prior to Ad26.COV2.S vaccination) and the follow-up "Booster after Sisonke" (BaSiS) study (n=226) were tested for neutralizing antibodies to Ad5, Ad26, and GRAd32. These samples included paired pre/post boost samples for 27 donors. We also tested sera from the Zimbabwean Mutala cohort (n=131, of which 44 were unvaccinated, and 87 vaccinated with inactivated vaccines). Participants living with HIV (PLWH) comprised 30-50% of each cohort. In the pre-vaccination samples from the Sisonke cohort, geometric mean titers (GMT) for anti-GRAd32, Ad26, and Ad5 antibodies were 78, 142, and 459, with neutralization titers >200 observed in 14%, 32%, and 68% of participants, respectively. Similarly, in the unvaccinated participants in the Mutala cohort, GMTs for GRAd32, Ad26, and Ad5 were 117, 245, and 536, with neutralizing titers >200 in 22%, 42%, and 69% of participants. We observed no significant difference in Ad antibody titers between PLWH and those living without HIV. We next assessed the impact of COVID-19 vaccination on titers. Vaccination with inactivated COVID-19 vaccines (Sinopharm/Sinovac) did not significantly affect Ad5, Ad26 or GRAd32 titers in an unpaired analysis. In contrast, [~]9 months after Ad26.COV2.S vaccination, anti-Ad26 titers for longitudinally sampled participants (n=27) increased 10-fold from a GMT of 141 to 1,426. By comparison, GRAd32 responses were not significantly altered by Ad26.COV2.S vaccination, while anti-Ad5 responses showed a modest <2-fold increase. Our data support previous findings that, whereas anti-Ad5 neutralizing antibody responses are commonly detected globally, GRAd32 responses are less frequent. Importantly, GRAd32 neutralizing responses remained unchanged after Ad26.COV2.S vaccination. HIV status had no significant effect on antibody titers. These results support the use of the GRAd32 vector in upcoming HIV vaccine trials, including in regions where Ad26-based COVID-19 vaccines were widely deployed.

Tuberculosis (TB) remains a major global health challenge, particularly in low- and middle-income countries such as Mozambique. To address this burden, promising new preventive TB vaccines targeting adolescents and adults are currently in phase III efficacy trials. This study aimed to assess stakeholders perspectives on priority high-risk groups, the challenges in reaching them, and potential strategies for delivering a TB vaccine. We conducted a qualitative study using semi-structured interviews with members of the National TB Program, the National Immunization Program, and the National Immunization Technical Advisory Group. Data were collected between March and July 2024. Our findings suggest that a TB vaccine program in Mozambique should prioritize individuals with comorbidities, especially those living with HIV or diabetes, and close contacts of TB patients, followed by healthcare workers, miners, and incarcerated populations. Although uptake is expected to vary across groups, relatively high coverage was anticipated among people living with HIV, TB contacts, and older adults, as well as healthcare workers, incarcerated individuals, formal miners, and in-school adolescents. To improve uptake, campaign-based strategies using mobile brigades were considered promising approaches to expand coverage. Stakeholder perspectives highlight the importance of prioritizing high-risk groups and adopting context-specific delivery strategies to support the effective introduction of a TB vaccine in Mozambique. Clinical trial numbernot applicable.