The Lancet Regional Health - Americas

BackgroundApproximately 300 million people worldwide live with a rare disease, and the majority of rare diseases manifest in childhood. For families, the period before diagnosis is often protracted and distressing, marked by repeated consultations, inconclusive investigations, conflicting medical opinions, and the absence of a recognisable name for their childs condition. While the clinical and epidemiological dimensions of the diagnostic odyssey have been documented, the narrative and experiential dimensions of how parents live through and make sense of prolonged diagnostic uncertainty remain underexplored, particularly in low- and middle-income country contexts. AimTo explore the narrative experiences of parents navigating diagnostic uncertainty for children with rare diseases in Brazil. MethodsA narrative inquiry informed by the three-dimensional narrative space framework of Clandinin and Connelly was conducted. Sixteen parents (twelve mothers and four fathers) of children who had experienced a diagnostic delay of at least two years were recruited from two rare disease referral centres in Sao Paulo and Belo Horizonte. Data were collected through two narrative interviews per participant, supplemented by participant-produced timelines and family photographs. Analysis followed a narrative analytical approach attending to temporality, sociality, and place. FindingsThree narrative threads were woven across the parents stories: (a) "Living in the space before the name," capturing the disorienting experience of caring for a child whose suffering could not be categorised, explained, or predicted; (b) "Fighting to be believed," describing the relentless advocacy required to sustain medical attention in a system that struggled to accommodate conditions falling outside familiar diagnostic categories; and (c) "Rewriting the story," illuminating how the eventual arrival (or non-arrival) of a diagnosis reshaped parents understanding of their child, their family, and themselves. ConclusionDiagnostic uncertainty for parents of children with rare diseases is not a passive waiting period but an active, effortful, and identity-transforming experience. The findings highlight the need for healthcare systems to provide structured psychosocial support during the pre-diagnostic period and for clinicians to develop communication practices that acknowledge, rather than dismiss, the legitimacy of undiagnosed suffering.

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.

BackgroundTimely cancer diagnosis in children and adolescents is critical to improving outcomes, yet substantial variation in diagnostic intervals persists across cancer types and care settings. We aimed to quantify time to diagnosis and assess variations by patient, demographic, and system-level factors. MethodsWe conducted a retrospective population-based study of children and adolescents aged 0-19 years diagnosed with one of 12 common cancers between 2010 and 2022 in Quebec, Canada. The diagnostic interval was defined as the time from first cancer-related healthcare encounter to diagnosis. We calculated medians and interquartile ranges (IQR) overall and by cancer type and used multivariable quantile regression to identify factors associated with time to diagnosis at the 25th, 50th, and 75th percentiles. ResultsAmong 2,927 individuals with cancer, diagnostic intervals varied by cancer type and age. Median intervals were longest for carcinomas (100 days; IQR 33-192) and shortest for leukemias (8 days; IQR 3-44). Compared with children living in Montreal, living in regional areas and other large urban centres was associated with longer 50th and 75th percentiles of time to diagnosis for hepatic and central nervous system (CNS) tumours. Diagnostic intervals were shorter in the post-pandemic period (2020-2022) across several cancer sites, with CNS tumours showing reductions across all quantiles. InterpretationDiagnostic timeliness differed by cancer type, age, and rurality, but not by sex, material, or social deprivation. The shorter diagnostic intervals observed in the post-pandemic period suggest that pandemic-related changes in care pathways may have expedited diagnosis for some cancers.

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.

BackgroundThe Toto Bora trial tested whether a course of azithromycin reduced rates of re-hospitalization or death in the 6 months following hospitalization among Kenyan children. We hypothesized that azithromycin would reduce enteric bacteria and increase carriage of macrolide resistance in the subsequent 3 months. MethodsKenyan children (1-59 months) hospitalized and subsequently discharged for non-traumatic conditions provided fecal samples before and 3 months after randomization to a 5-day course of azithromycin or placebo. Quantitative PCR identified enteropathogens and AMR-conferring genes in fecal samples. Generalized estimating equations assessed the impact of the randomization arm on pathogen and resistance gene detection, accounting for baseline presence and site. ResultsAmong 1,393 baseline stools, 12.4% had at least one bacterial enteropathogen, 94.7% had at least one macrolide-resistance gene, and 92.6% had at least one beta-lactamase-resistance gene identified. At month 3, children randomized to azithromycin had a 6.1% higher likelihood of carrying a macrolide resistance gene compared to placebo (adjusted prevalence ratio [aPR], 1.06; 95% CI, 1.04-1.08; P<0.001). Specifically, azithromycin randomization was associated with a higher relative prevalence of erm(B) (aPR, 1.09 [95% CI, 1.04-1.15]; P=0.001), erm(C) (aPR, 1.23 [95% CI, 1.14-1.31]; P<0.001), msr(A) (aPR, 1.14 [95% CI, 1.04-1.25]; P=0.007), and msr(D) (aPR, 1.07 [95% CI, 1.03-1.11]; P=0.001). There was no difference in overall bacterial pathogen prevalence (18.9% vs 17.3%) between randomization arms, but a slightly lower proportion of children had Shigella after randomization in the azithromycin arm (3% vs. 5%, aPR, 0.79 [95% CI, 0.62, 1.01]; P=0.063). InterpretationAzithromycin at hospital discharge was associated with higher carriage of macrolide-resistance-conferring genes in the post-discharge period compared with placebo, without significant declines in enteric pathogen carriage other than modest changes to Shigella. The potential benefits and risks of empiric azithromycin need to be considered, as children are increasingly exposed to this broad-spectrum antibiotic.

BackgroundEvidence from real-world implementation of follow-up and pharmacovigilance for Plasmodium vivax treatment in population scale interventions targeting asymptomatic individuals remains limited, especially among highly mobile, hard-to-reach groups. This study describes the follow-up strategy used in the CUREMA project and assesses its implementation, as well as safety, tolerability, and adherence outcomes. MethodsThe CUREMA project implemented a PvTDA (P. vivax targeted drug administration) intervention in cross-border Amazonian settings, consisting in a full course treatment with chloroquine and primaquine (7 days) or tafenoquine (single dose), after screening its main contraindications (including semiquantitative G6PD testing); its target population was represented by artisanal and small scale migrant miners evaluated as at risk for asymptomatic P. vivax carriage. Treatment follow-up was mandatory for PvTDA participants and combined in-person visits or telephone interviews, and/or a tailored smartphone application, to be compatible with target population high mobility. Planned follow-up visits were scheduled 2, 5, and 14 days after treatment initiation. Univariate analyses described app uptake, follow-up completion, adverse events and treatment declared adherence; multivariable regression models explored factors associated with these outcomes. ResultsAmong 294 participants who received PvTDA, 269 (91.5%) configured the smartphone application, 100 (34.0%) selected telephone follow-up and/or 44 (15.0%) selected in-person follow-up. Overall, 210/294 participants (71.4%) completed at least one follow-up questionnaire, and 81/294 (27.6%) completed the three follow-up visits At least one adverse event was recorded in 49/294 participants (16.7%); events were generally mild to moderate, and no serious adverse event was identified. The declared adherence to the 7-days chloroquine and primaquine treatment was 79.2% [95% CI 72.5-86.4]. ConclusionsActive follow-up of P. vivax radical treatment was feasible in a highly mobile, remote population when multiple complementary tools were combined. This supports pharmacovigilance and safe implementation of radical cure strategies in similarly challenging settings.

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.

New tuberculosis (TB) vaccines for adults and adolescents could transform TB prevention programs, but their impact depends on successful implementation. We investigated willingness to be vaccinated with a new TB vaccine in a high HIV and TB burden setting in southern Mozambique in 2024 using a mixed methods approach involving a cross-sectional survey and concurrent in-depth interviews. In 151 surveys and 23 interviews, we found that willingness to receive a new TB vaccine among adults and adolescents was 77% (148/192) overall. In multivariable analysis, adolescents were more willing to receive a new TB vaccine than adults even when adjusting for other factors which may influence vaccination decisions (adjusted OR: 5.6, 95% CI: 1.7-17.7). Personal experience with TB and greater knowledge of the disease was also linked with willingness to be vaccinated. Qualitative findings reinforced quantitative findings, further clarifying that even among those who expressed hesitancy, a safe and effective TB vaccine endorsed by healthcare workers, government agencies, and community leaders would likely have high uptake. Our findings are specific to southern Mozambique and can shape vaccine introduction efforts after a TB vaccine is licensed and approved for use in this age group.

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

Antimicrobial resistance (AMR) is classified by the World Health Organization (WHO) as one of humanity's ten global public health threats. This review aimed to estimate the prevalence, temporal trends and regional distribution of AMR in WHO priority bacteria across human, animal and environmental sources in Cameroon. This review was conducted following PRISMA 2020 guidelines, with the protocol registered in PROSPERO. A systematic literature search was conducted in Google Scholar, PubMed, African Journals Online, Hinari, and Africa indexus Medicus. Random effects models were used to estimate pooled prevalence and 95% confidence intervals (CIs), with subgroup analyses by bacterial source, region, and sampling period. Of 1566 articles screened, 115 met the inclusion criteria. The reported data encompassed 16 bacteria-antibiotic combinations in 16,948 isolates. Globally, third-generation cephalosporin (3GC) resistance in E. coli was the most prevalent (49.0%, 95% CI: 39.0-60.0%, I2=97.7%), reaching 77.0% (95% CI: 46.0-98.0%, I2=95.6%) in environmental isolates. The pooled prevalence of ESBL production in all included Enterobacterales was 37.0% (95% CI: 30.0-45.0%). Most of the highest resistance rates were observed in the Littoral region. The resistance rates between 2016 and 2025 were significantly higher than those from 2000 to 2015. These increases were more marked in fluoroquinolone-resistant Salmonella spp (1.0% to 48.0%, I2=97.3%, p<0.001), carbapenem-resistant E. coli (0% to 15%, I2=93.5%, p<0.001), and 3GC-resistant E. coli (34.0% to 64.0%, I2=97.6%, p=0.003). Antimicrobial resistance in WHO priority bacteria in Cameroon is high, unevenly distributed across regions and significantly increasing over time. These results underscore the crucial need for strengthened AMR surveillance to curb the growing threat of AMR in Cameroon.

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.

Globally, respiratory tract infections (RTI) are the main cause of morbidity, and in Low-middle-income countries (LMICs) RTI including pneumonia are a leading cause of morbidity and mortality in children <5 years. Diarrheal illness increases RTI risk in young children through micronutrient depletion, and immune stress, yet data on post-diarrhea RTI burden in LMICs are limited. We determined the prevalence and risk factors of RTI within three months following medically-attended diarrhea (MAD) in children aged 6-35 months enrolled in seven EFGH country sites in Asia, Africa and South America. The EFGH study prospectively enrolled children aged 6-35 months with MAD in selected health facilities during a 24-month period from 2022 to 2024 and followed them for three months. RTI was defined as cough or difficulty breathing and the presence of one of the following symptoms at any scheduled or unscheduled visit during follow-up: stridor; fast-breathing; oxygen saturation <90%; or chest indrawing. The period prevalence and 95% confidence intervals of RTI were calculated, and correlates of RTI were assessed using modified-Poisson regression. From June 2022 to August 2024, 9,476 children aged 6-35 months presenting with MAD in the EFGH study sites were screened: 9,116 (96.2%) included in the current study. Nearly half were female (46.7%), and median age was 15 months. Overall, 48.5% received all age-appropriate vaccines, and 87.6% received the pneumococcal vaccine, with significant variation across countries. Nearly one-quarter of children were stunted, 17.2% wasted, and 21.9% underweight. RTI occurred in 3.8% of children during the three-month follow-up, mostly within the first month. Higher prevalence of RTI occurred among children aged 12-23 months (8.7%), those undernourished (16.1%), unvaccinated (4.0%) or living in poor sanitation settings (4.1%). While children who received all age-appropriate or pneumococcal vaccinations had a lower crude prevalence of RTI, these associations were not statistically significant after adjusting for age, sex and study site. RTI was infrequently observed in the three months following MAD presentation, with significant variability by site and with the highest prevalence in Malawi. RTI risk was highest in 12-23-month-olds and among children with undernutrition, and those living in poor sanitation conditions.

BackgroundLynch syndrome (LS) is a cancer susceptibility syndrome caused by germline pathogenic variants in DNA mismatch repair (MMR) genes. Due to increased risk of colorectal cancer (CRC), enhanced colonoscopic surveillance is recommended for heterozygote MMR-carriers. ObjectiveUsing a registry of English LS patients linked to digital National Health Service records, we aimed to assess adherence of MMR-carriers to national surveillance guidelines, and to determine the impact of surveillance on CRC incidence and mortality. DesignWe described the frequency of colonoscopies in 4,732 MMR-carriers and used logistic regression to determine predictors of surveillance adherence. For MMR-carriers with a record of surveillance and those without, we: estimated age-specific annual CRC incidence rates (AS-AIRs) and cumulative lifetime risks, assessed for stage-shift by comparing CRC stage distributions and stage-specific AS-AIRs, and estimated risks of death from CRC and any cause using Kaplan-Meier methods and Cox Proportional Hazards regression. ResultsSurveillance at a mean interval of [&le;] 3 years (n=3028) was associated with a decrease in CRC-specific and all-cause mortality, without an associated change in total CRC incidence, even after multivariate adjustment. No strong evidence of stage-shift was observed. Colonoscopic surveillance at a mean interval of [&le;] 2 years (n=1569) was associated with an increase in total CRC incidence. Incidence of early-stage cancers was also higher, with no corresponding decrease in late-stage cancers, which may reflect the short follow-up period or the impact of overdiagnosis. ConclusionThe observed reduction in all-cause mortality amongst regularly-surveilled MMR-carriers may indicate an impact of surveillance on CRC-specific mortality, though in the context of a non-randomised study likely reflects the influence of selection bias. KEY MESSAGES OF ARTICLEO_ST_ABSWhat is already known on this topicC_ST_ABSRegular surveillance colonoscopy is recommended in Lynch syndrome, though evidence to support this remains mixed. We searched PubMed for articles published from inception to 01/05/2024 using the terms "Lynch syndrome", "HNPCC", "colonoscopy", "sigmoidoscopy", "surveillance", and "screening". We found one controlled trial and several small analytical studies dating from the early 2000s which compared surveilled and non-surveilled populations and found surveillance to be associated with reduced colorectal cancer (CRC) incidence and improved survival. More recent longitudinal observational studies, most without comparator groups, found a high incidence of CRC in LS populations despite being resident in countries where surveillance was recommended. A small number of studies directly assessed time since last colonoscopy against CRC incidence and stage with mixed findings. Finally, cross-sectional comparisons between countries of CRC incidence rates and surveillance interval recommendations found no relationship between the two1,2. What this study addsHere, we conduct an observational cohort study on a large national cohort of MMR germline pathogenic variant (GPV) carriers (MMR-carriers) in England (n=4,732), comparing CRC incidence and mortality in individuals with a record of regular surveillance to those without. Through linkage of the English National Lynch Syndrome Registry to Hospital Episodes Statistics data, we are uniquely able to study a comprehensive national population of MMR-carriers and identify the dates on which colonoscopies were undertaken over time, allowing assessment of adherence to national surveillance guidelines and the impact this has on CRC outcomes. Notably, receipt of regular colonoscopy was strongly associated with deprivation as well as ethnicity. The results show that regular surveillance at an average interval of 3 years (or less) is not associated with a reduction in CRC incidence when compared to less frequent surveillance, but an apparent decrease in both CRC-specific and overall mortality is observed, even after adjustment for confounding variables. Conversely, regular surveillance at an average interval of 2 years (or less) is associated with an increase in CRC incidence when compared to less frequent surveillance, which may suggest increased diagnosis of early-stage cancers or, due to the absence of a reduction in late-stage cancers, overdiagnosis. The observed impact of surveillance on overall mortality may demonstrate the impact of surveillance on CRC-specific mortality, or, in the context of an observational (non-randomised) study, indicate that the results are subject to selection bias. How this study might affect research, practice, or policyEvidence for the benefit of surveillance colonoscopy remains mixed. Whilst polypectomy would be anticipated to prevent CRC development (thus reducing CRC incidence), several studies have observed increased frequency of CRCs in MMR-carriers undergoing frequent surveillance colonoscopy, which may reflect overdiagnosis. The selection bias inherent to observational studies of surveillance renders mortality outcomes challenging to interpret. Randomised controlled trials of colonoscopic surveillance in MMR-carriers are required for effectiveness of this intervention to be accurately assessed. Given ethical and feasibility challenges, randomised controlled trials might be complemented by quasi-experimental designs using advanced observational methods for assessing effectiveness.

Despite significant reductions in malaria cases across Brazil, residual transmission persists in the Legal Amazon, threatening the national goal of elimination by 2035. The Amazonian socio-ecological landscape creates a complex environment where environmental degradation and socioeconomic vulnerabilities intersect. However, the independent and combined effects of these drivers remain poorly quantified at a regional scale. We conducted a retrospective, longitudinal ecological study analyzing a comprehensive panel dataset from 2021 to 2025 across all 773 municipalities in the Brazilian Legal Amazon. We evaluated the independent effects of prior-year deforestation, extreme poverty, population density, fire activity, macroclimatic variables, and primate reservoir abundance on malaria incidence. Deforestation emerged as the dominant predictor of malaria intensity. A one-standard-deviation increase in lagged deforestation area was associated with a 48.3% increase in expected malaria cases. Socioeconomic deprivation also significantly sustained transmission, with extreme poverty increasing cases by 18.8%. Conversely, population density exhibited a strong protective effect, reducing incidence by 72.2%, reflecting the phenomenon of urban protection. While an overall temporal decline of 17.4% annually was observed, profound spatial heterogeneity persisted, with the state of Amazonas maintaining consistently high transmission without a discernible downward trend. Macroclimatic factors and primate abundance did not show statistically significant independent effects at the annual municipal scale. The persistence of malaria in the Brazilian Amazon is not merely a biomedical issue but a profound sustainable development challenge driven by the synergistic effects of land-use change and socioeconomic inequality. Deforestation and extreme poverty create a resilient reservoir of transmission risk that undermines conventional control efforts. Achieving the 2035 elimination goal demands a paradigm shift toward a One Health approach, integrating rigorous environmental protection, targeted social development, and spatially stratified public health interventions. Ultimately, the health of the Amazonian population is inextricably linked to the health of the forest itself.

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

BackgroundFirst Nations children are over-represented in child protection systems in Australia and other colonised countries. Here, we apply a prevention and equity lens to the use of child protection data, to inform early opportunities to support Aboriginal children and families at risk of escalating child protection contact, from pregnancy to adolescence. MethodsWe followed 15 whole-population cohorts (born 2006-2020) of Aboriginal (n=119,716) and non-Aboriginal (n=1,456,698) children in New South Wales (NSW), Australia, to December 2021, using birth and child protection datasets linked for the NSW Child E-Cohort. In each Aboriginal and non-Aboriginal cohort (2006-2020), we calculated the cumulative incidence (risk) of first-time child protection contacts from the prenatal period up to age 15 years: child concern reports, screened in reports, investigations, child protection-defined substantiations, and OOHC placements. Risk differences and relative risks were also calculated. FindingsBy birth, 10-15% of Aboriginal children born 2006-2020 had a first report to child protection, with 48-54% by age 5y (2006-2016 births), and 74% by age 15y (2006 births), with similar risks of screened-in reports (e.g. 68% by age 15y). The risk of first-time substantiation was 1-5% of Aboriginal children by birth, 17-20% by 5y, and 32% by 15y, with higher risks in more contemporary cohorts. By age 1y, 3-4% of Aboriginal children born 2006-2020 had a first OOHC placement, with 7-9% by 5y, and 14% by 15y. The risk differences between Aboriginal and non-Aboriginal children were 23 and 3 percentage points for reports and OOHC by age 1y (2020 births), respectively, increasing as children age. InterpretationDespite extensive inquiries, calls for prevention and Closing the Gap targets, our study shows the lifetime risk of child protection involvement for Aboriginal families has not improved and inequities persist. These findings support the call for Aboriginal-led approaches and greater investment in early supports for First Nations children and families. Research in ContextEvidence before this study We searched PubMed and Medline for studies on the lifetime risk of child protection contacts among First Nations child populations, published January 2005 to May 2025. Thirteen studies reported various child protection contacts, from the perinatal period through childhood, among birth or synthetic cohorts of First Nations children, born between 1990 and 2018, created from population data sources in jurisdictions in Australia (n=5), the United States(US) (n=6), and Aotearoa/New Zealand (NZ) (n=2) (Table E1). O_TBL View this table: org.highwire.dtl.DTLVardef@1a0d510org.highwire.dtl.DTLVardef@4198eorg.highwire.dtl.DTLVardef@129da77org.highwire.dtl.DTLVardef@c5e234org.highwire.dtl.DTLVardef@18600d7_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable E1.C_FLOATNO O_TABLECAPTIONSystematic Review Results: Details of 13 studies on the lifetime risk of child protection contacts among First Nations child populations, published January 2005 to May 2025. C_TABLECAPTION C_TBL The most recently published study included First Nations children born 2000 to 2013 in Western Australia, which quantified the risk of reports, investigations, substantiations and removals into OOHC, from age 1 to 16 years. By age 1, 12% were reported and 3% were removed into OOHC. By age 16, 52% were reported, and 14% were removed into OOHC. Prior studies of birth or synthetic cohorts of First Nations children born 1990-2018, in the USA, NZ, and South Australia showed similar results. By age 5 years, 16% to 54% for reports, 20% for investigations, 7% to 11% for substantiations and 8% for removals into OOHC. Among the five studies with cohorts followed to 18 years, 42% were reported, 28% to 50% were investigated, 9% to 27% were substantiated, 7% to 16% were removed into OOHC and 0.8% to 3.8% had termination of parental rights. Added value of this study This is the largest and most contemporary study to quantify the lifetime risk of child protection contact among whole-populations of First Nations children internationally. Among 15 consecutive whole-population cohorts of First Nations children in New South Wales (NSW), Australia, born 2006 to 2020, we reported--for the first time--the full spectrum of child protection contacts, from the prenatal period. By birth, 16% were reported to child protection, 14% were investigated and 5% were substantiated in the most contemporary cohort born 2020. By age 1 year, 2.8% were removed into OOHC. In the oldest cohort born 2006, 74% were reported and 14.4% removed into OOHC by age 15 years. We also reveal the magnitude of the inequity in child protection contacts between First Nations and non-Indigenous children across the lifecourse. For example, among 2006 births, the risk of first-time reports to child protection for Aboriginal and non-Aboriginal children, respectively, was 10.5% versus 1.5% by birth (risk difference (RD), 9 percentage points; risk ratio (RR), 7.0), 53% vs 16% by age five (RD, 38pp; RR, 3.4) and 74% vs 33% by age 15 (RD, 41pp; RR 2.2). Implications of all the available evidence This study unequivocally shows that the lifetime risk of child protection involvement in the lives of First Nations families has not reduced in more contemporary whole-population cohorts and that inequities persist. This is consistent with evidence from prior studies internationally. It is critical that First Nations-led responses and investment in early family supports must be at the centre of system reform to realise the long-called-for shift toward prevention and to re-dress the pervasive inequities experienced by First Nations children and families in colonised countries such as Australia.

BackgroundEver since the COVID-19 vaccine became available, vaccinations in adolescents lagged behind adults. Whether adolescent vaccination rates were higher in states with "Minor Consent" policies remains unknown. MethodsWe accessed adolescent (aged 12-17) county-level vaccine administration data from the CDC (12/2020-05/2023) Our outcomes were COVID-19 vaccination counts for 1) initial dose, 2) completed series doses, 3) booster doses. Panel Poisson regression models with state and time random effects, seasonal fixed-effects, log-population offsets, and adult vaccination rates were estimated to calculate incidence rate ratios (IRR), testing the association between residing in a state with a Minor Consent policy and COVID-19 vaccine uptake. ResultsOverall, for the initial dose and complete series, there was no difference in adolescent COVID-19 vaccination between states with or without Minor Consent policies. However, we found that Minor Consent policies were associated with lower COVID-19 booster doses (IRR = 0.582; 95% CI: 0.409, 0.828; p=0.0026). This association was not found in urban (IRR = 0.867; CI = 0.722, 1.043; p = 0.1295), but only in rural counties (IRR 0.541; CI 0.401, 0.730; p<0.0001). ConclusionsMinor Consent policies were not associated with higher adolescent COVID-19 vaccination. Rather, we found that Minor Consent policies were associated with lower adolescent vaccination for booster doses in rural counties. Despite minimal evidence of impact, states continue to implement Minor Consent vaccination policies. Future research on the topic should investigate, not just other vaccines, but how Minor Consent policies impact parental trust in public health more broadly.