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The Lancet Regional Health - Americas

Elsevier BV

Preprints posted in the last 90 days, ranked by how well they match The Lancet Regional Health - Americas's content profile, based on 22 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Impact of Connecticut's 2021 Repeal of Religious Vaccine Exemptions on Kindergarten Vaccine Coverage

Benzaken, C. L.; Ganem, J. M.; Araujo, B. L.; Aparicio-Llorente, C.; Oliva, I.; Wats, A. L.; Hijano, D. R.; Oliveira, C. R.

2026-06-22 public and global health 10.64898/2026.06.19.26356105 medRxiv
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Importance: Religious vaccine exemptions remain central to debates over school-entry immunization mandates, but evidence on exemption repeal outside outbreak-driven policy responses and across communities with different religious contexts remains limited. Objective: To estimate changes in kindergarten vaccination coverage associated with Connecticut's 2021 repeal of religious vaccine exemptions, examine variation by school type and local religious congregation density, and compare trends with states that retained exemptions. Design/Setting/Participants: Interrupted time series analysis using kindergarten vaccination data from 2012-2025. Vaccine coverage trends in Connecticut were compared to Arizona, Louisiana, and Oregon, which retained religious exemptions during the study period. Intervention: The intervention studied was Public Act 21-6, which eliminated religious vaccine exemptions from school-entry immunization requirements. Main Outcomes and Measures: Outcomes included annual coverage for measles-mumps-rubella (MMR), varicella, diphtheria-tetanus-acellular pertussis (DTaP), polio, and hepatitis B vaccines. Models estimated pre-policy trends, immediate level changes, and post-policy slope changes. Analyses were stratified by public and private schools and by county-level religious congregation density. Results: Before policy implementation, kindergarten vaccination coverage in Connecticut declined across all vaccines by 0.16-0.20% per year (p < 0.001). Repeal of the religious exemptions occurred during a period of increasing religious congregation density and was associated with improved school-entry vaccination coverage, with annual coverage increasing 0.88-1.02% per year (p < 0.001). Coverage increased in both public and private schools, with larger post-policy gains in private schools. Coverage increases did not differ significantly between high- and low-religiosity counties. In segmented regression analyses, Connecticut's post-policy MMR slope was significantly higher than those of Arizona, Oregon, and Louisiana by 1.36, 1.71, and 1.15 percentage points per year, respectively (p < 0.001). By 2024/25, Connecticut MMR coverage reached 98.2%, exceeding coverage in comparison states by 5.6-9.6%. Cumulatively, the model-estimated policy impact represented an estimated 2,579 additional kindergarteners immunized against MMR compared with the no-policy counterfactual. Conclusions and Relevance: Connecticut's repeal of religious vaccine exemptions was associated with increases in kindergarten vaccination coverage across public and private schools, independent of local religious congregation density. These findings suggest that removal of religious vaccine exemptions may be an effective policy approach to improve childhood immunization coverage.

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Using fragmented data to characterize community healthcare utilization

McCready, T.; Thorpe, L.; Roy, B.; Renson, A.

2026-07-15 health systems and quality improvement 10.64898/2026.07.13.26357976 medRxiv
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Community-level estimates of healthcare utilization are essential for identifying inequities, allocating resources, and evaluating place-based interventions. However, in the United States, no single data source adequately captures healthcare utilization within geographically defined populations. Population-based surveys often lack sufficient geographic resolution, insurance claims represent only covered populations, and electronic health records are limited to care delivered within participating health systems. Increasingly, researchers combine these fragmented data sources, yet limited guidance exists for conducting valid population-based descriptive analyses using incomplete and overlapping data. We review the strengths and limitations of major data sources used to characterize community healthcare utilization and propose an approach for conducting population-based descriptive analyses using fragmented data. Rather than focusing on the limitations of individual data sources, our approach begins by explicitly defining the target population and the ideal observational study that would answer the research question. Available data sources are then conceptualized as incomplete or imperfect realizations of that ideal, providing a structured approach to (a) identifying sources of selection bias, missingness, and measurement error, (b) articulating required assumptions, and (c) selecting appropriate analytic strategies. We illustrate our approach using colorectal cancer screening utilization among adults residing in Brooklyn, New York during 2022. By shifting attention from individual data sources to the target community and the assumptions required for valid inference, this approach provides a practical approach for strengthening descriptive analyses of community healthcare utilization and informing place-based public health research, policy, and practice.

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Cancer care disruption during the COVID-19 pandemic in Ontario, Canada: A sequential mixed-methods study

Timilshina, N.; Jacobson, D.; Birze, A.; Wodchis, W. P.; Kuluski, K.; Strumpf, E.; Ammi, M.

2026-06-12 health systems and quality improvement 10.64898/2026.06.10.26355360 medRxiv
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Introduction The COVID-19 pandemic profoundly disrupted healthcare delivery worldwide, with cancer care among the most affected services. Prior studies documented delays in referrals, reduced specialist access, and increased provider burden. However, the extent to which these experiences were reflected at the system level remains unclear. Objective To document cancer care experiences and examine whether these experiences were reflected in population-level health system indicators across Ontario, Canada. Methods We used an exploratory sequential mixed-methods design. Qualitative data were collected through focus groups and semi-structured interviews with 32 participants, including patients with cancer (n=8), caregivers (n=5), healthcare providers (n=14), and decision-makers (n=5) across two hospital settings in Ontario, Canada. Emergent themes informed the development of quantitative indicators. We then conducted a retrospective population-based analysis of linked administrative health databases for cancer patients in Ontario (n=87,786) to assess the prevalence of identified themes. Results Four themes emerged: (I) delays in diagnosis and screening; (II) disrupted access to primary care; (III) barriers to specialist and mental health services; and (IV) fragmented care for patients with multimorbidity. Quantitative findings corroborated major themes. Screening rates declined for cervical (64.8% to 57.5%) and breast cancer (64.5% to 57.2%). While in-person primary care shifted almost entirely to virtual modalities (8.5% to 95.4%), overall visit volumes remained stable. Specialist care showed uneven patterns, with increased oncology visits but declines in cardiology and mental health services. Patients with multiple comorbidities experienced the largest reductions in non-oncology specialist care. Conclusion The pandemic disrupted key components of cancer care, particularly screening, access to certain specialist services, and care for patients with complex needs. Integrating qualitative and quantitative evidence highlights areas of system vulnerability and underscores the need for coordinated, resilient cancer care capable of maintaining essential services during future crises.

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The 2026 public charge rule and long-term health impacts among NYC immigrants: a simulation study

Nadhamuni, K.; Curcio, E.; Solomon, S.; Lim, S.; Van Wye, G.; Parakh, M.

2026-07-27 health policy 10.64898/2026.07.23.26358686 medRxiv
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Importance: The 2026 public charge rule could discourage immigrants from accessing health coverage programs, creating a chilling effect that potentially leads to negative health outcomes; However, its long-term health impact is poorly understood. Objective: To model potential impacts of the 2026 public charge rule on primary care and premature mortality among immigrants in New York City (NYC). Design, Setting, and Participants: The simulation used a deterministic compartmental model with Ordinary Differential Equations (ODEs) using 2023 NYC Vital statistics data and American Community Survey, and estimates obtained from 2 previous studies about effects of healthcare access on primary care and Medicaid expansion on premature mortality. Main Outcomes and Measures: Rates of primary care outcomes (access, doctor's visits) in 5 years, and premature mortality in 5 and 20 years, projected by the model under conservative, moderate, and aggressive scenarios of avoidance/disenrollment due to the public charge rule, known as the 'chilling effect'. Effects of the avoidance/disenrollment on primary care outcomes and premature mortality were obtained from 2 previous studies. Projected rates of the outcomes under each scenario were compared with counterfactuals to estimate the health impacts of the chilling effect. Results: Implementation of the public charge rule was projected to decrease the primary care access rate by 4.1% (conservative) to 9.9% (aggressive) over 5 years, relative to the counterfactual scenario without the rule. The rate of doctors' visits was projected to decrease over 5 years by 5.1% (conservative) to 12.2% (aggressive). Premature mortality was projected to increase by 4.4% (conservative) to 10.6% (aggressive) in 5 years and 7.4% (conservative) to 17.4% (aggressive) in 20 years. Legal noncitizens and Black immigrant New Yorkers were predicted to experience higher burdens of premature mortality attributed to the chilling effect, compared with other immigrant groups and racial/ethnic groups, respectively. Conclusions and Relevance: This study demonstrates adverse health consequences of federal public charge rule changes among immigrants in NYC. The model projected a decrease in primary care visits and increase in premature mortality across various scenarios. These findings suggest urgent reconsideration of a regulatory change that disproportionately increases risk of premature mortality among immigrants in NYC.

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Cold spots of postacute rehabilitation therapy delivery among Original Medicare beneficiaries across the United States: Statistical spatial clustering analysis

Jesus, T. S.; Frazier, M.; Monteiro, P. C.; Pinho, C. S.; Delaney, G. K.; Heinemann, A. W.; Deutsch, A.

2026-07-31 health systems and quality improvement 10.64898/2026.07.29.26359230 medRxiv
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This study aims to map significant cold spots of postacute rehabilitation therapy delivery rates for Original Medicare beneficiaries in the U.S. and determine the prevalence of those cold spots in rural areas. Statistical spatial clustering of postacute therapy delivery rates was conducted in ArcGIS Pro using hot and cold spot analyses (Getis-Ord Gi*). County-level therapy delivery volume was defined as the total minutes of physical, occupational, and speech therapy provided by skilled nursing facilities (SNFs), home health agencies (HHAs), and inpatient rehabilitation facilities (IRFs). Therapy delivery rates were then computed as minutes per Original Medicare beneficiary at the county level and adjusted using a county-level Hierarchical Condition Category risk score. Spatial clustering identified cold spots (statistically significant clusters of low rates) and hot spots (clusters of high rates). We also computed the proportion of cold spots in rural counties and the relative percentage difference compared to the national rural county baseline, using two rural classification systems. Identified coldspots varied by provider type. For SNFs, they were notably identified in the Mountain and West North Central US divisions. For HHAs, cold spots appeared across more U.S. Census Divisions, including areas (e.g., Kentucky, Indiana, southern Illinois) where SNFs showed hot spots. Cold spots were more prevalent in rural--and especially in small rural--counties across all provider types. In rural counties, cold spot rates were 42.8% to 71.5% higher than the rural county baseline. In small rural counties, differences were larger, at 69.1% to 95.5% higher. Concluding, cold spots of postacute therapy delivery varied across the continental U.S. by provider type but were more prevalent in rural and especially in rural counties with smaller population size -- across provider types. Identifying these cold-spot locations may support geographically targeted policy responses and the development of alternative service?delivery models in underserved areas.

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The Burden of Long COVID: Re-Infection, Symptoms, and Barriers to Care in the Arizona CoVHORT Study

Pogreba-Brown, K.; McFadden, C.; Heslin, K. M.; Carr, D. L.; Falk, L. P.; Catalfamo, C.; Ernst, K.; Farland, L. V.; Cordova-Marks, F.; Sun, X.; Barraza, L.; Austhof, E.

2026-08-21 epidemiology 10.64898/2026.08.18.26360693 medRxiv
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Long COVID (LC) impacts quality of life, daily functioning, and healthcare utilization. Understanding the onset and duration of symptoms, characteristics of those at higher risk, and the barriers and facilitators for healthcare access and therapeutics are key to addressing this growing disease burden. In 2024 the Arizona CoVHORT, an ongoing 6-year longitudinal study, distributed a cross-sectional LC survey to gain additional in-depth information. Of 1,543 participants, 700 reported LC symptoms lasting 2-49 months. Following their first infection, LC+ participants had a 21% higher risk for a second infection and were 3.2 times more likely to report LC symptoms after that second infection compared to LC- participants. Significant factors associated with LC included female sex (OR=2.3), Hispanic ethnicity (OR=1.5), BMI>34.5 (OR= 1.7) and >2 infections (OR=3.2), while vaccination prior to first infection decreased the odds of reporting LC by 51% (R=0.49). Qualitative analyses detailed significant barriers to care and encounters with providers who lacked knowledge to test for or treat LC symptoms. With an estimated 400 million people impacted globally by LC, it is critical to gain in-depth information from patients to improve both access and quality of care, improve messaging, and target mitigation strategies to decrease the burden over time.

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From Epidemic to Endemic: Longitudinal Surveillance of Congenital Zika Syndrome in Brazil

Oliveira Ferreira, R.; Ma, H. L.; Pestana Garcez, P.; Zatz, M.

2026-07-10 epidemiology 10.64898/2026.07.07.26357442 medRxiv
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Zika virus (ZIKV) emerged in Brazil in 2015, causing an unprecedented epidemic of Congenital Zika Syndrome (CZS). A decade later, longitudinal analyses evaluating temporal trends and subnational heterogeneity in CZS burden remain limited. Using publicly available data from SINAN/DATASUS and the RESP-Microcephaly registry (SVS/Ministry of Health, updated July 2024), we conducted a descriptive ecological analysis of ZIKV infection and CZS in Brazil from 2015 to 2023. Of 331,309 notified Zika cases (2015-2023), 213,350 occurred in 2016, followed by an 91.75% decline in 2017 and sustained low-level endemic circulation thereafter. Among 3,751 confirmed microcephaly cases, 1,828 were confirmed with ZIKV etiology. The Northeast region accounted for 75.4% of confirmed cases despite representing approximately 27% of the national population. State-level analyses revealed distinct epidemiological patterns, including persistent microcephaly notifications of non-Zika etiology in Minas Gerais and continued detection of ZIKV-attributed CZS in Amazonas and Goias through 2023. These findings highlight pronounced geographic disparities in congenital Zika burden, reflect significant heterogeneity in diagnostic capacity, and underscore the need for sustained surveillance and systematic etiological investigation of congenital abnormalities in the post-epidemic era.

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Spatial structure and demographic decoupling of chikungunya transmission and severity in Brazil, 2015 to 2025

Zhang, Q.; Souza Campos, F.; Vieira Santos de Abreu, F.; de Souza, W. M.; Chen, S.; Bento, A. I.

2026-06-29 epidemiology 10.64898/2026.06.26.26356655 medRxiv
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Brazil bears one of the largest chikungunya burdens in the Americas (more than 1.2 million confirmed cases since 2014), and the 2024-25 wave expanded further south than any prior outbreak. IXCHIQ entered Sistema Unico de Saude (SUS) deployment in February 2026 despite an August 2025 US FDA biologics license suspension over serious adverse events in adults aged 60 years and older; regulatory authorities in the EU (EMA), Brazil (ANVISA), and Canada maintained licensing with revised prescribing guidance requiring individual benefit-risk assessment. Evidence to guide rollout targeting is lacking. We analyzed 1,235,424 confirmed chikungunya cases reported to Sistema de Informacao de Agravos de Notificao SINAN (2015-2025) across 5,570 municipalities. A Bayesian hierarchical spatiotemporal model quantified spatial structure and persistence of transmission across municipalities, controlling for national arboviral co-circulation trends. Disease progression was assessed with Cox models stratified by age and sex. Municipal 2024-25 incidence rate ratios and proportions aged 65 years or older (tertiles) defined transmission-control, clinical-preparedness, and combined-priority municipalities. Transmission epicenters shifted from the Northeast (2016-17) to the Central-West (2024-25; peak municipality IRRs >2.7 times the national median); clustering and seasonality persisted. Cases concentrated among adults aged 25 to 55, while post-hospitalization mortality rose steeply with age (HR 10.57, 95% CI 7.64-14.62 for ages 80 years and older versus adults aged 20 to 29). Males had faster progression to hospitalization (HR 1.26) and death (HR 1.76, onset to death) despite fewer notifications. The Central-West led transmission yet had lower case fatality among hospitalized cases (3.54%, 81 deaths out of 2,285 hospitalized) than the Southeast (4.95%, 163 deaths out of 3,291 hospitalized), reflecting demographic rather than purely clinical differences between regions. A municipality-level allocation framework classified 832 municipalities as transmission-control priority (high recent transmission, younger population; predominantly Central-West), 832 as clinical-preparedness priority (lower transmission, older population; predominantly Southeast and South), and 461 as combined-priority (high on both dimensions; predominantly Northeast and Southeast). Chikungunya transmission and mortality are spatially decoupled in Brazil: regions driving epidemic expansion (Central-West) are not those bearing the highest case fatality (Southeast). An age-only vaccination allocation rule would leave 82% of 2024-25 reported cases in municipalities it would not prioritize. A rule that targets only older adults without accounting for geography is likely to miss the municipalities where transmission is actively expanding. A dual-axis framework addressing both dimensions is required for the SUS rollout.

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Comparative Effectiveness of Recommended and Delayed Dosing Schedules for Rotavirus Vaccine: Target Trial Emulation

Gantt, S.; Komura, T.; McQuade, E. R.; Shioda, K.

2026-07-16 infectious diseases 10.64898/2026.07.13.26357904 medRxiv
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Background: Live oral rotavirus vaccines were found to be less effective in low-income countries compared to high-income countries when using the same product and dosing schedule. We investigated whether altering dose timing may improve immune protection using a target trial emulation approach. Methods: We emulated a target trial with clone-censor weighting to compare the effectiveness of the recommended 2-dose rotavirus vaccine schedule with a delayed schedule among children under two years of age in Peru and Brazil. Secondary data from the Malnutrition and Enteric Disease Study (MAL-ED) birth cohort (2009-2014) were analyzed. Children were followed from the date of birth until the earliest occurrence of a rotavirus outcome (infection confirmed by PCR or enzyme immunoassay (EIA) or diarrhea confirmed by EIA), protocol nonadherence, loss to follow-up, or their second birthday. Results: We included 154 children in Brazil and 192 in Peru. At two years of follow-up, the risk ratio (RR) for PCR-confirmed infection, using the recommended schedule as the reference, was 1.00 (95% confidence interval [CI]: 0.73-1.37) in Peru and 0.85 (95% CI: 0.31-1.66) in Brazil. In Peru, the delayed schedule was associated with a higher cumulative risk of EIA-confirmed rotavirus diarrhea (RR at two years: 1.73; 95% CI: 1.02-2.77). Conclusions: Delaying the two-dose rotavirus vaccine schedule did not change the cumulative risk of rotavirus infection, but the delayed schedule was associated with a higher risk of rotavirus diarrhea in Peru, where rotavirus incidence was higher.

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Multilevel Factors Associated with Nonresponse to Patient-Reported Outcome Measures in Routine Radiation Oncology Care

Liu, J. B.; Chen, Y.-J.; Edelen, M. O.; Pusic, A. L.; Martin, N. E.; Zeng, C.

2026-07-17 health systems and quality improvement 10.64898/2026.07.15.26358162 medRxiv
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Purpose: Nonresponse to routinely collected patient-reported outcome measures (PROMs) threatens the representativeness of aggregated data. We characterized patient-, provider-, and clinic-level factors associated with PROMIS Global-10 nonresponse in routine radiation oncology care. Methods: In this retrospective cohort study, all adults seen at five Mass General Brigham radiation oncology clinics over one year were included. The primary outcome was patient-level nonresponse, defined as never completing the portal-administered Global-10 versus completing it at least once. Using iterative mixed-effects logistic regression, we modeled patient-, provider-, and clinic-level factors. Results: Among 12,214 patients, 71 providers, and five clinics, patient- and appointment-level response rates were 35.4% and 10.9%, with patient-level response ranging nearly fivefold across clinics (12.8% to 66.2%). In Model 1, male sex, lower education, not working, and recent surgery had higher odds of nonresponse, and longer time since diagnosis lower odds. After provider- and clinic-level factors were added, patient sex, education, and employment became nonsignificant, whereas recent surgery (adjusted odds ratio [aOR] 1.97) and longer time since diagnosis (aOR 0.46 for >12 months) persisted. A provider's historical collection rate was protective but attenuated at the clinic level. There, a later program launch (aOR 0.29) and higher historical collection rate (aOR 0.79) correlated with lower nonresponse, whereas academic versus community setting did not. Conclusions: Nonresponse to routinely collected PROMs is a multilevel phenomenon driven substantially by clinic-level implementation factors, not patient characteristics alone. Because response rate is only a proxy for representativeness, PROMs programs and PRO-based performance measures should prioritize representative collection over volume.

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Variability in US COVID Mortality, Viral Evolution, and the Emergence of Acquired Social Immune Dysfunction

Morris, R. D.

2026-07-01 epidemiology 10.64898/2026.06.29.26356883 medRxiv
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Background. The course of a pandemic depends on viral traits, available public health interventions, implementation, and individual behavior, all of which interact and vary over time and space. Understanding COVID-19 therefore requires considering these factors together. Methods. National mortality, state-level mortality per 100,000 population for four representative states, policy stringency, and vaccination coverage were assembled from publicly available sources for February 2020 through September 2022. Viral traits, mutation rates, and vaccine effectiveness were drawn from published systematic reviews and standardized relative to wild-type values. Results. Each state experienced a different worst wave, separated by as much as 18 months, with up to a 24-fold difference in state mortality during major waves. NPI stringency was initially high and responsive to COVID waves, but declined during 2021 in both magnitude and responsiveness as vaccination levels rose, then flattened. Viral evolution first increased transmissibility; as population immunity rose, immune escape increased sharply, particularly with Omicron, which produced similar mortality peaks in all four states and the second largest national peak. Conclusions. COVID-19 did not unfold as a single national pandemic but as regionally divergent epidemics that fragmented public perception and weakened cohesion. At the same time, SARS-CoV-2 evolved traits that reduced the apparent and actual effectiveness of interventions. Omicron brought these processes together: despite producing one of the largest national mortality waves, it elicited little renewed policy activation or booster uptake. I describe this progressive uncoupling of epidemic threat, intervention effectiveness, policy activation, and public compliance as Acquired Social Immune Dysfunction.

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Comparison of Influenza Vaccine Effectiveness Estimates Using Test-Negative Prospective Enrollment and Electronic Health Record Data, United States, 2024--2025

Price, A. M.; McLean, C.; Cleary, S.; Leis, A. M.; Vaughn, I. A.; House, S.; Ellsworth, S.; Moehling Geffel, K.; Taylor, L. H.; Gaglani, M.; Murthy, K.; Saade, E. A.; Ladikos, C.; Murugan, V.; Kramer, J. L.; Williamson, B. D.; Kiniry, E.; Walter, E. B.; Bontrager, N. A.; Ellington, S.; Flannery, B. M.; Chung, J.; US Flu VE Network Investigators,

2026-07-27 epidemiology 10.64898/2026.07.23.26358258 medRxiv
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Background: Influenza vaccine effectiveness (VE) is assessed annually through prospective enrollment of patients presenting with acute respiratory symptoms in a test-negative study design. Influenza VE has also been estimated from electronic health record (EHR) databases by linking medical diagnoses, laboratory test results, and patient influenza vaccination. There are limited data on agreement between influenza VE estimates from prospective enrollment versus EHR databases. Methods: The US Influenza Vaccine Effectiveness Network prospectively enrolled outpatients meeting clinical screening criteria and collected respiratory specimens to determine influenza virus infection. Seven study sites also identified EHR databases that included diagnostic codes for outpatient encounters associated with medically attended acute respiratory illness (MAARI), clinical respiratory virus testing, and influenza vaccination status. Effectiveness of influenza vaccination against laboratory-confirmed influenza was estimated from both data sources using logistic regression models including patient age, study site, and month of illness as 100(%) x (1 - adjusted odds ratio), comparing influenza vaccination among laboratory-confirmed influenza-positive patients versus laboratory-confirmed influenza-negative patients. Results: From October 2024--April 2025, 2,016 (30%) of 6,793 prospectively enrolled patients and 75,885 (24%) of 282,444 EHR MAARI encounters had laboratory-confirmed influenza virus infection. Effectiveness of vaccination against laboratory-confirmed influenza was 36% (95% confidence interval [CI]: 26-44) among prospectively enrolled patients and 38% (95% CI: 36-39) among EHR MAARI encounters. Comparing influenza VE estimates from the two data sources, confidence intervals overlapped for all age groups except for adults aged [&ge;]65 years: -3% (95% CI: -53-30) among prospective enrollment versus 35% (95% CI: 32-39) VE from EHR MAARI encounters. Conclusion: Overall, influenza VE estimates from retrospective EHR data were similar to VE estimates using the test-negative design with prospective enrollment. The age group-specific differences in estimated VE observed in US adults aged [&ge;]65 years compared with younger age groups merit further investigation.

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A policy for delivery of essential medicines to vulnerable population in Argentina: a case study of the REMEDIAR program

Havela, M.; Bartolomeu, L.; Rubinstein, A.

2026-06-08 health systems and quality improvement 10.64898/2026.06.05.26354987 medRxiv
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Essential medicines are one of the cornerstones of financial protection and health equity. The REMEDIAR Program is an initiative of the Argentine Ministry of Health aimed at ensuring free access to essential medicines for the uninsured at the point of care in primary healthcare centers (PHC). This study analyzes the financing, procurement, and distribution of this program over two decades (2002 to 2024). It evaluates how the program's capacity to navigate economic and political challenges ensured an uninterrupted supply of essential drugs at the primary healthcare level in a federal country where health services are devolved to provinces. We adopted a mixed-methods approach to examine the duality between international concessional loans and domestic treasury funding. Findings reveal that while international financing enhanced predictability and efficiency, reducing procurement timelines from 458 to 235 days, it also constrained domestic planning through external conditionalities. Conversely, while national centralized procurement achieved superior price efficiency and lower dispersion, it faced rigidities in adapting to local needs. Territorial distribution analysis confirms that REMEDIAR reduced access barriers for vulnerable households without formal insurance. However, the program entered a stabilization phase, failing to consolidate robust coordination with subnational policies, becoming entrenched in its own operational logic. The study concludes that program effectiveness depends not only on resource volume but on management quality. To guarantee long-term sustainability, transition to national financing requires profound institutional redesign. This must integrate operational capacities with federal coordination and domestic regulations, ensuring that the primary healthcare supply chain remains resilient to macroeconomic volatility and political shifts, aligned with sub-national strategies.

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Bivalent RSVpreF effectiveness against RSV-related lower respiratory tract disease hospitalization and ED visits across three RSV Seasons

Tartof, S. Y.; Zasowski, E. J.; Aliabadi, N.; Goodwin, G.; Slezak, J.; Hong, V.; Frankland, T. B.; Ackerson, B.; Liu, Q.; Shaw, S.; Welsh, S.; Kapadia, B.; Spence, B. C.; Davis, G. S.; Lewnard, J. A.; Chowdhry, H.; Dutro, M.; Chilson, E.; Cane, A.; Hayford, K.; Begier, E.

2026-07-13 infectious diseases 10.64898/2026.07.08.26357564 medRxiv
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Introduction: RSV vaccines reduce the risk of severe outcomes such as hospitalization and emergency department (ED) visits for at least 2 RSV seasons following vaccination. No data have been published on real-world RSV vaccine effectiveness (VE) beyond the second season after vaccination. This study evaluates bivalent RSVpreF VE against RSV-related lower respiratory tract disease (LRTD) hospitalizations/ED visits throughout 3 seasons after vaccination. Methods: This retrospective test-negative case-control evaluates bivalent RSVpreF VE among adults aged >/= 60 years at Kaiser Permanente Southern California with LRTD over 3 RSV seasons (11/24/20230-4/18/2026). Cases were RSV-positive without coinfection. Controls were negative for RSV, hMPV, influenza, SARS-CoV-2, and positive for a non-vaccine preventable disease pathogen. Exposure was bivalent RSVpreF (Abrysvo) receipt >/= 21 days before LRTD. Adjusted VE was estimated using odds ratios from multivariable logistic regression or generalized estimating equations. Results: Overall, adjusted VE against RSV-related LRTD hospitalization/ED visits was 80% (95% CI:68-87), 70% (95% CI:53-81), and 51% (95% CI:-12-78) in the first, second, and third season after vaccination, respectively. Among non-immunocompromised individuals, adjusted VE against RSV-related LRTD was 87% (95% CI:75-94), 76% (95% CI:55-87), and 58% (95% CI:-21-86) in the first, second, and third season after vaccination, respectively. Adjusted VE across the 3 combined seasons was 73% (95% CI: 64-80) overall and 80% (95% CI: 69-87) among non-immunocompromised individuals. Conclusion: These results suggest Bivalent RSVpreF provides protection against RSV-related LRTD outcomes for at least three seasons after vaccination in this population of older adults with a prevalence of comorbidities. This suggests RSV vaccination results in substantial individual and public health benefit.

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Socioeconomic Determinants of Guideline-Concordant Therapy for Early-Stage Non-Small Cell Lung Cancer: A Population-Based Analysis from Appalachian and Non-Appalachian Ohio, 2004-2015

Martin, J.; Waugh, W.

2026-06-23 oncology 10.64898/2026.06.20.26356121 medRxiv
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Purpose: To examine the relative contributions of insurance, county-level poverty, and other socioeconomic factors, as compared with Appalachian geography, to receipt of guideline-concordant therapy for early-stage non-small cell lung cancer (NSCLC) in Appalachian and non-Appalachian Ohio. Methods: Retrospective population-based cohort study using the Ohio Cancer Incidence Surveillance System. We identified adults diagnosed with early-stage NSCLC between 2004 and 2015 (N=26,756). The primary outcome was receipt of guideline-concordant local therapy (surgery or definitive radiation). Rural-urban classification used USDA Rural-Urban Continuum Codes. Multivariable logistic regression and Cox proportional hazards models assessed predictors of treatment and survival, with E-values, race-stratified models, and propensity score weighting as sensitivity analyses. Findings: Median age was 71 years; 50.3% were male, 83.8% non-Hispanic White, and 20.4% Appalachian. Overall, 83.6% received guideline-concordant local therapy (59.6% surgery, 24.0% radiation). In adjusted analysis, Medicaid (adjusted odds ratio [OR] 0.53, 95% confidence interval [CI] 0.44-0.63; adjusted risk ratio [RR] 0.94, 0.91-0.96), county-level poverty >20% (OR 0.77, 95% CI 0.68-0.87; RR 0.96, 0.95-0.98), and unmarried status were independently associated with lower therapy receipt, whereas Appalachian residence was associated with modestly higher receipt (OR 1.17, 95% CI 1.06-1.29; RR 1.02, 1.01-1.04). Therapy rates converged across regions over the study period (year x Appalachian interaction p<0.001). Mortality was independently associated with lack of local therapy (adjusted hazard ratio [HR] 4.33, 95% CI 4.10-4.56), Medicaid (HR 1.25, 95% CI 1.14-1.37), and poverty >20% (HR 1.13, 95% CI 1.07-1.20). Conclusions: Socioeconomic factors, particularly Medicaid insurance and county-level poverty, were the patient characteristics most strongly associated with lower receipt of guideline-concordant therapy, whereas Appalachian residence was not a barrier. Findings support targeted interventions addressing insurance-related and poverty-related barriers to lung cancer care in high-poverty communities regardless of geographic designation.

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The impact of neighborhood socioeconomic deprivation on metastatic pancreatic cancer treatment and survival: An incidence-based, causally-structured observational study

Raghu, A.; Shah, S.; Pattnaik, A.; Permuth, J. B.; Park, M. A.; Dhahri, H.; Huang, H. C.; Fleming, J. B.; Anaya, D. A.; Powers, B. D.

2026-08-10 oncology 10.64898/2026.08.06.26359821 medRxiv
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Purpose: Metastatic pancreatic ductal adenocarcinoma (PDAC) portends a poor prognosis. Prior studies have assessed the association of socioeconomic deprivation (SED) in PDAC often with large geographic areas. This study employed a causal framework to characterize neighborhood SED on treatment receipt and survival in metastatic PDAC. Methods: Using the incidence-based Florida Cancer Data System, metastatic PDAC patients diagnosed from 2007-2015 were identified. The Area Deprivation Index, a composite measure of SED that ranks neighborhoods from 1-100 (higher scores = higher deprivation), was used to assess receipt of systemic therapy and overall survival (OS). Exposures and covariates were assessed using descriptive statistics and a causal inference framework. Results: Overall, 9,574 patients met inclusion criteria. 46.6% of patients received systemic therapy, ranging 39.4% to 54% in the highest and lowest SED quartiles, respectively. After adjustment, the lowest quartile had increased odds of systemic therapy relative to the highest (OR 1.93; 95% CI 1.70-2.18). Median OS was 3.8 months for the lowest quartile and 2.4 months for the highest (p = 0.01). Patients in the highest quartile had an estimated 32% higher hazard of death than the lowest (HR 1.32, 95% bootstrap CI 1.20-1.40). Conclusion: In an incidence-based statewide cohort, most patients did not receive treatment for metastatic PDAC and median OS was poor-2.9 months. Using a causal inference framework, higher SED led to lower rates of systemic therapy receipt and worse overall survival in metastatic PDAC. Future research should focus on the mechanisms that shape these findings.

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Entrepreneurial Methods for Healthcare Redesign: A Pre-Post Cohort Study in Glioblastoma Care

Howran, J.; Sharma, A.; Andrews, K.; Pople McCord, D.; Salim, S. K.; Janka, D.; Ynoe Moraes, F.; Goldie, K.; Babiolakis, C.; Alkins, R.; Taslimi, S.; Pasarikovski, C.; Ebinu, J.; Cook, D. J.; Levy, R.; Purzner, J.; Purzner, T.

2026-07-29 surgery 10.64898/2026.07.28.26358976 medRxiv
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Objective: To evaluate whether entrepreneurial methodologies applied to system-wide healthcare redesign were associated with improved survival, care timeliness, and rural-urban equity among patients with glioblastoma. Design: Non-randomized pre-post cohort study Setting: Tertiary neuro-oncology centre in Ontario, Canada Participants: Adults aged >18 years with histologically confirmed glioblastoma who underwent surgical resection between January 1, 2018, and February 28, 2025 Interventions: Implementation of the Integrative Brain Tumor Program (IBTP), a system-wide care intervention grounded in user-defined priorities and developed using a design thinking approach (empathize, define, ideate, prototype, test) integrated with operational frameworks adapted from early-stage innovation. System change was treated as a deliberate, deployable intervention that could be designed, launched, iteratively refined, and evaluated. Coordinated changes were embedded across healthcare services within existing infrastructure and resource constraints through a single centralized nurse navigator who standardized referrals, patient education, and real-time care coordination. Main Outcomes and Measures: Primary outcomes were one-year overall survival and time to postoperative MRI completion and radiotherapy initiation. Secondary outcomes assessed rural-urban equity in these measures. Associations were evaluated using Cox proportional hazards and Fine-Gray competing-risk models adjusted for age, sex, rurality, MGMT promoter methylation status, and calendar time. Results: Among 297 patients (244 pre-implementation, 53 post-implementation), baseline demographic and tumor characteristics were similar across cohorts. One-year overall survival was higher in the post-implementation cohort (60.4% vs 42.2%), corresponding to an adjusted hazard ratio of 0.61 (95% CI, 0.38-0.99). Postoperative MRI completion within 48 hours increased from 45.9% to 66.0% (adjusted cause-specific hazard ratio, 1.50; 95% CI, 1.05-2.14) with similar improvements observed at 7 days. Time to radiotherapy initiation did not differ between cohorts. Survival and MRI timeliness did not differ by rural or urban residence in either period, though rural radiotherapy delays were attenuated postimplementation. Conclusions: Systematic application of entrepreneurial methods to health system redesign was associated with clinically meaningful improvements in glioblastoma survival and care timeliness using minimal resources (single nurse navigator). These findings suggest that treating system change as an intervention grounded in user-defined priorities and oriented toward integrated systems rather than sequential process optimization can support sustainable transformation of complex, coordination-dependent care pathways and warrants evaluation in other disease settings.

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Implementing ESAMyN: Ecuador's National Standard for Mother- and Baby-Friendly Health Facilities

Tello, B.; Ruilova-Maldonado, M.; Olmedo-Valarezo, A. J.

2026-07-31 health systems and quality improvement 10.64898/2026.07.28.26359056 medRxiv
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Background Ecuador's Mother- and Baby-Friendly Health Facilities Standard (ESAMyN, Establecimientos de Salud Amigos de la Madre y el Nino) is an integrated national quality improvement strategy that combines evidence-based recommendations for antenatal, childbirth, postpartum, newborn and breastfeeding care within a single implementation and certification framework. However, little is known about the factors influencing its implementation in routine health services. This study explored the organizational, contextual and behavioural factors that facilitated or hindered ESAMyN implementation across public health facilities. Methods We conducted a secondary qualitative analysis of 36 semi-structured interviews originally collected during a programme systematization in 11 public health facilities across five Ecuadorian provinces. Participants included health authorities, managers, ESAMyN focal points, quality coordinators, healthcare professionals and women receiving maternity services. Interview transcripts were analysed inductively using thematic analysis. Results Implementation was perceived as an organizational transformation rather than the adoption of a new clinical guideline. Strong leadership, multidisciplinary teamwork, continuous training and institutional commitment facilitated implementation and promoted the adoption of respectful, family-centred and evidence-based maternity care practices. However, staff turnover, workload, infrastructure limitations, shortages of equipment and funding, and reliance on local adaptation challenged implementation and contributed to variability across facilities. Participants emphasized that sustaining ESAMyN required institutionalization beyond certification through continuous monitoring, refresher training, supportive supervision and stable organizational support. Conclusions Integrated national quality standards can strengthen maternal and newborn care through sustained leadership, adequate resources and continuous quality improvement, providing practical lessons for implementing WHO recommendations in routine health services.

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Reducing friction, enabling response: a realist evaluation of a mobile outreach model for marginalized populations

Cristancho, S.; Eby, D.; Dobbyn, F.; McNab, K.

2026-08-02 health systems and quality improvement 10.64898/2026.07.30.26358580 medRxiv
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Background: Mobile outreach initiatives have emerged to address persistent barriers to care for people experiencing homelessness, substance use, and mental illness. Although these models show promise, less is known about how and under what conditions they enable engagement and coordinated care. This study explains how, why, and under what circumstances a mobile, cross sector outreach model enables access to care for marginalized populations. Methods: We conducted a realist evaluation of Supportive Outreach Services (S.O.S.), a mobile, cross sector outreach program in Grey County, Ontario. Data included 31 semi structured interviews with outreach providers, partner organizations, system leaders, and clients, supplemented by document review and stakeholder feedback. Using retroductive reasoning and constant comparison, we developed and refined context mechanism outcome configurations to construct an explanatory program theory. Results: Five interconnected realist explanations account for how the model enables access to care. Trust built through repeated, non judgmental encounters supports engagement; proximity reduces barriers to participation; accessible support enables timely help seeking; cross sector relationships enable adaptive coordination; and visible results build legitimacy that sustains participation and resources. Together, these explanations provide a linked explanatory account of how mobile outreach reduces friction between marginalized populations and fragmented services while identifying the structural conditions that constrain its effectiveness. Conclusions: The effectiveness of mobile outreach depends less on the services delivered than on its capacity to reduce friction, sustain relationships, and adapt care across organizational boundaries. The resulting program theory offers transferable explanations for designing coordinated community based services while highlighting the structural conditions required for durable change.

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Development and Internal Validation of a County-Level Screening Index for Postpartum Medicaid Access Barriers

Howard, C.; Shekhar, P.

2026-07-07 health policy 10.64898/2026.07.05.26357332 medRxiv
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Background: Postpartum Medicaid coverage and support are central maternal health policy issues, but county-level tools for identifying where postpartum Medicaid populations may face overlapping administrative, clinical, and contextual access barriers remain limited. Methods: We developed and internally validated a county-level Postpartum Medicaid Access Barrier Index for all 3,144 counties and county equivalents in the 50 states and District of Columbia. Public data sources included geocoded Medicaid office locations from Shafer et al. (2024), U.S. Census county boundaries, American Community Survey 2024 5-year county indicators, the National Center for Health Statistics 2023 Urban-Rural Classification Scheme for Counties, and county-level hospital-based obstetric care status from the University of Minnesota Rural Health Research Center. Medicaid office locations were spatially assigned to counties, then merged with ACS indicators, rurality, and obstetric care status by county FIPS. The theoretical score range was 0-11; the index assigned higher weights to two core infrastructure measures and lower weights to contextual indicators. Internal validation assessed component structure, known-groups validity, geographic clustering, weighting sensitivity, added value over simpler infrastructure screens, and separation across concern levels. Results: Across 3,144 counties, observed scores ranged from 0 to 10 on the theoretical 0-11 score, with a mean of 3.65 and median of 3. High or highest concern counties accounted for 665 counties (21.2%), including 56 counties (1.8%) in the highest concern group. Component correlations were low-to-moderate, with an average absolute phi of 0.176 and no pairwise component correlation at or above 0.50. Known-groups validity was strong: dual administrative and clinical gap counties scored 4.43 points higher than counties with neither gap (Cohen's d = 3.28, p < 0.001). Scores were geographically clustered (Moran's I = 0.375, permutation p = 0.005). A dual-gap-only screen captured 386 of 665 high/highest concern counties (58.0%) but missed 279 high/highest counties; a parsimonious rule requiring one infrastructure gap plus at least four contextual flags recovered 265 of these 279 missed counties (95.0%) with 100.0% precision. Discussion: The Postpartum Medicaid Access Barrier Index provides a transparent county-level screening tool for identifying places where administrative, clinical, and contextual barriers may overlap for postpartum Medicaid populations and should be externally validated against Medicaid enrollment, renewal, churn, coverage continuity, and postpartum care outcomes.