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AIDS

Ovid Technologies (Wolters Kluwer Health)

Preprints posted in the last 7 days, ranked by how well they match AIDS's content profile, based on 32 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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Multidimensional Social Vulnerability and Hepatic and Extrahepatic Outcomes in Adults With HIV/HBV Coinfection in the United States

Yendewa, G.; Chengsupanimit, T.; Dehghani, A.; Ahmed, A.; Mohareb, A.; Cohen, C.; Freeman, M.; Kim, H. N.; Ofotokun, I.; Dube, K.

2026-09-02 hiv aids 10.64898/2026.08.31.26361853 medRxiv
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Background: HIV/HBV coinfection is associated with substantial liver-related morbidity and mortality, yet the impact of social vulnerability (SV) on clinical outcomes has not been systematically assessed. We evaluated associations of multidimensional SV with mortality, hepatic, virologic, and extrahepatic organ outcomes among adults with HIV/HBV. Methods: We conducted a retrospective cohort study using TriNetX data from 110 U.S. healthcare organizations (2010-2026). We propensity score matched adults with HIV/HBV with and without documented SV 1:1 (2,024 per group). SV was defined using a four-domain framework encompassing material, healthcare access and engagement, interpersonal, and psychosocial vulnerability. Results: Over 15,900 person-years, SV was associated with higher mortality (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.72-2.47), liver composite events (HR, 1.37; 95% CI, 1.07-1.76), hepatic decompensation (HR, 1.94; 95% CI, 1.39-2.70), hepatic failure (HR, 2.39; 95% CI, 1.53-3.73), HBV viremia (HR, 1.69; 95% CI, 1.32-2.16), and HIV viremia (HR, 2.05; 95% CI, 1.71-2.46). SV was also associated with major adverse cardiovascular events (HR, 1.47), chronic kidney disease (HR, 1.49), and diabetes (HR, 1.25). Multidomain SV generally showed stronger associations than single-domain SV for most hepatic and virologic outcomes, with HR ranges of 1.76-2.62 versus 1.35-1.76 for single-domain SV. Healthcare access and engagement vulnerability was most consistently associated with mortality and hepatic outcomes. Conclusions: SV was associated with mortality, hepatic disease, impaired HIV/HBV control, extrahepatic organ morbidity, and acute care utilization in adults with HIV/HBV. SV assessment may improve risk stratification and identify actionable intervention targets during HIV/HBV care.

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Diagnostic performance, implementation fidelity, and costs of the World Health Organization three-test HIV testing strategy in Malawi: a national retrospective evaluation

Chimpandule, T.; Tweya, H.; Goeke, L.; Masina, T.; Macheso, S.; Low, N.; Jahn, A.; Imai-Eaton, J. W. W.

2026-09-01 hiv aids 10.64898/2026.08.30.26361753 medRxiv
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Background: In 2019, WHO recommended three consecutive reactive serological test results for HIV diagnosis to reduce false-positive diagnoses. Malawi changed from a two-test to a three-test strategy in 2022 as HIV test positivity declined. We assessed diagnostic performance, implementation fidelity, and costs. Methods: We analysed national HIV testing data from Nov 1, 2022, to Oct 31, 2025. Using observed three-test classifications as the reference standard, we reconstructed classifications under the two-test strategy. We estimated positive predictive value (PPV), implementation fidelity, potential false-positive diagnoses prevented, incremental costs, and time to offset testing costs through avoided antiretroviral therapy expenditure. Results: Among 9,885,599 encounters eligible for implementation-fidelity analysis, 99.98% followed a valid three-test pathway. The diagnostic-performance analysis included 9,862,908 encounters, of which 171,351 (1.7%) were classified HIV-positive and 9,138 (0.09%) were inconclusive. Under the two-test strategy, 1,209 inconclusive encounters with a T1+/T2+/T3- sequence would have been classified as HIV-positive. Retesting and reference-laboratory data indicated that 82.5% of these would subsequently be classified as HIV-negative, corresponding to 997 false-positive diagnoses prevented (10.3 per 100 000 three-test non-positive encounters; 95% CI 9.7-10.9). Retesting within 1-2 weeks was associated with the highest odds of potential false-positive classification (adjusted OR 39.37, 95% CrI 30.63-50.61). The incremental cost was US$471 per false-positive diagnosis averted and was offset within 7.30 years. Conclusions: Malawi's transition to a three-test HIV testing strategy prevented false-positive diagnoses and unnecessary antiretroviral therapy at modest cost, supporting broader adoption of WHO guidance in similar settings. Funding: Gates Foundation.

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BCG vaccination recalibrates innate immunity in ART-treated people with HIV

Dolle, C.; Tutumlu, T. K.; Bartl, L.; Depouilly, B.; Russenberger, D.; Zeeb, M.; Kusejko, K.; West, E.; Braun, D. L.; Schwarzmüller, M.; Elie, B.; Trkola, A.; Günthard, H. F.; Nemeth, J.

2026-09-02 hiv aids 10.64898/2026.08.28.26361620 medRxiv
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Despite suppressive antiretroviral therapy, many people with HIV (PWH) retain chronic interferon-associated immune dysregulation. Observational data from the Swiss HIV Cohort Study linked asymptomatic mycobacterial exposure to lower viral set points, reduced interferon-associated activity, and attenuated HIV-specific antibody responses, a pattern sharing features with HIV elite controllers and natural hosts of primate lentiviruses. We therefore examined whether Bacillus Calmette-Guerin (BCG) vaccination could induce a related immune configuration in ART-treated PWH. Using longitudinal systems-level profiling within the BELIEVE trial, we found that BCG reduced constitutive NK cell IFN-{gamma} production and PBMC-mediated direct cytotoxicity without impairing inducible cytokine responses or antibody-dependent cellular cytotoxicity. Multiomic and proteomic analyses showed reduced interferon- and activation-associated programs, while adaptive immune parameters remained largely stable and follow-up revealed no obvious adverse clinical pattern. This configuration, reduced baseline interferon activity coexisting with preserved Fc-dependent effector function, shares selected features with immune states described in natural lentiviral control and provides a rationale for testing BCG in combination with antibody-based HIV interventions.

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Social Determinants of Health in HIV/HBV Coinfection Compared with HIV and HBV Monoinfection: A Framework for Dynamic Social Vulnerability

Yendewa, G.; Chengsupanimit, T.; Dehghani, A.; Ahmed, A.; Mohareb, A.; Freeman, M.; Cohen, C.; Ofotokun, I.; Dube, K.

2026-09-02 hiv aids 10.64898/2026.08.31.26361856 medRxiv
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Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection is associated with accelerated liver disease, but whether coinfection is associated with newly documented social determinants of health (SDoH) is unclear. We conducted a retrospective cohort study using TriNetX across 110 U.S. healthcare organizations (2010-2026). We propensity score matched adults with HIV/HBV to adults with HIV or HBV monoinfection. We organized newly documented SDoH indicators using a dynamic individual-level framework with four clinically recognized domains of social disadvantage: material vulnerability, healthcare access and engagement, interpersonal adversity, and psychosocial vulnerability. Matched cohorts included 10,071 HIV/HBV-HIV pairs and 9,659 HIV/HBV-HBV pairs (mean age, 47 years; 79% male; 66% non-White; median follow-up, 3.3 years). Over 178,900 person-years, HIV/HBV was associated with higher risk of the primary SDoH composite compared with HIV (11.5% vs 9.7%; incidence rate, 2.50 vs 1.97 per 100 person-years; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.15-1.37) and HBV (11.0% vs 6.4%; incidence rate, 2.39 vs 1.67; HR, 1.50; 95% CI, 1.35-1.67). HIV/HBV was also associated with higher material vulnerability and healthcare access and engagement composites in both comparisons, including housing instability, food insecurity, financial insecurity, insurance instability, and care disengagement/nonadherence (HR range, 1.22-3.33 vs HIV; 1.31-1.94 vs HBV). In the HBV comparison, HIV/HBV was additionally associated with interpersonal adversity, primary support stressors, and violence or victimization (HR range, 1.36-2.16). Findings were robust across sensitivity analyses. HIV/HBV was associated with more newly documented SDoH than monoinfection, supporting dynamic SDoH assessment.

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The use of computerised testing to assess cognitive performance in people with HIV in South Africa

Edmond, E. C.; Dreyer, A. J.; Winston, A.; Khoo, S. H.; Joska, J.; Nightingale, S.

2026-08-31 hiv aids 10.64898/2026.08.27.26361083 medRxiv
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Background Computerised cognitive testing may address the global challenge in identifying cognitive changes in people living with HIV scalably and affordably. We assessed a computerised battery (CB) of cognitive tests, in a prospective cohort (CONNECT) of people with HIV in a low-income peri-urban area of Cape Town, South Africa during a national programmatic switch from efavirenz- to dolutegravir-based antiretroviral therapy (ART). Methods We recruited 170 people with HIV and 91 people without HIV (controls) (140[82%] and 41[45%] followed up). The CB and gold-standard pen&paper cognitive testing (P&P) were performed at both timepoints. Technology familiarity/use questionnaire data were also collected. We compared performance in detecting lower group-level cognitive performance associated with efavirenz treatment. Furthermore, the CB was compared to P&P in classifying individuals with low cognitive performance, correlation of global test scores and domain-level scores between batteries, and practice effects between timepoints. Exploratory principal component analysis was also performed. Results People with HIV on efavirenz at baseline had lower performance on the computerised battery than controls, {Delta}T=2.6, p=0.0047. This difference was lost after switching to dolutegravir-based ART at follow-up. CB and P&P global T were moderately correlated (R2=0.203, p<0.001), and the CB performed moderately in classification of low cognitive performance against the gold standard (AUC 0.70, sensitivity 0.52, specificity 0.76, PPV 0.40, and NPV 0.84). Selecting the first three principal components improved both classification of low cognitive performance (AUC 0.77) and correlation strength with P&P global T (R2=0.3, p<0.001). The CB did not show practice effects. Most participants owned a mobile phone (95%, 85.9% of these smartphones). Performance was better in smartphone owners ({Delta}T=1.8) and computer owners (23%, {Delta}T=1.8). Conclusions Delivering computerised cognitive testing was feasible in this low-income southern African setting. The CB showed reasonable construct validity (detecting known lower cognitive performance associated with efavirenz-ART) and may detect broad cognitive characteristics such as processing speed and accuracy. However, correlation of CB results with gold standard P&P testing was low-moderate and may limit its applicability as a diagnostic tool. This might be improved by including a wider range of cognitive domains tested in the CB, or data driven analysis. Brief CBs may fulfil an initial screening role, followed by more detailed clinical assessment.

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Projected Population-Level Impact of Digital Return of Results for Cardiovascular-Kidney-Metabolic Screening at US Blood Donation Centers: A Monte Carlo Simulation Study

Qian, Z.; Khera, A.; Makhnoon, S.; Chapman, B. E.; Bryant, B.; Sayers, M.; Compton, F.; Eason, S.; Xing, C.; Ahmad, Z.

2026-09-03 public and global health 10.64898/2026.09.01.26360806 medRxiv
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Background. Cardiovascular-kidney-metabolic (CKM) syndrome affects nearly 90% of US adults, yet most individuals at early, modifiable stages remain unidentified outside clinical care. Blood donation centers offer a scalable, non-clinical venue for CKM screening, but the potential benefit of screening in this context remains unclear. We projected the population-level impact of effective digital return of results (ROR) to inform the design of a pragmatic trial. Methods. We developed a Monte Carlo simulation (100,000 iterations) of the incident major adverse cardiovascular events (MACE), end-stage renal disease (ESRD), and type 2 diabetes (T2DM) preventable by ROR-prompted, guideline-concordant follow-up among donors in CKM Stages 1-2. The estimand counts only events averted by donors who act because of ROR; the intervention effect was modeled directly on strictly positive support, and action was translated into prevented events through a hazard-based cumulative-incidence difference that counts each donor at most once. We evaluated 18 design cells (donor volumes 300,000, 1 million, and 8 million/year; 5- and 10-year horizons; action-rate gains of +10, +20, and +30 percentage points [pp]) and, in a complementary two-arm simulation, the assurance (expected power) of detecting the effect in a single deployment. Results. Under the primary +20 pp scenario, ROR at a single large blood center (300,000 donors/year) is projected to prevent a median of 2,201 events (95% uncertainty interval [UI], 1,099-4,364) over 10 years, scaling to 58,526 (29,154-116,769) at the national donor pool. All 18 design cells had strictly positive 95% lower bounds. The number needed to screen was 136 and the screening cost $2,045 per event prevented (at $15/donor), both invariant to donor volume. Impact scaled linearly with volume and effect size but sub-linearly with the horizon. Detection of the effect was effectively certain at gains of +20 pp or larger (assurance [&ge;]99.6% in every cell and >99.9% in all but the smallest 5-year cell). Conclusions. Even under the conservative scenario, digital CKM ROR at blood donation centers is projected to prevent hundreds to tens of thousands of incident cardiometabolic events at a screening cost per event well within accepted prevention benchmarks, providing prospective, quantitative justification for a pragmatic, randomized evaluation of digital ROR in non-clinical screening settings.

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Sex Differences in the Impact of Allosensitization on Waitlist Access and Post-Transplant Outcomes in Adults with Congenital Heart Disease

Joseph, A.; Kearney, K.; Henricks, C.; Morgan, J. L.; Tan, W.; Shafer, K.; Wrobel, C.; Lacelle, C.; Burns, K.; Jawaid, A.; Tapaskar, N.; Solmonson, A.; Nelson, D. B.; Truby, L. K.

2026-09-02 transplantation 10.64898/2026.08.31.26361832 medRxiv
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Background: Adult congenital heart disease (ACHD) patients are prone to HLA-antibody formation from multiple surgeries, transfusions, and prosthetic surgical material. Females with ACHD may accrue additional, non-surgical alloantigen exposure. Whether sex modifies the impact of allosensitization on heart transplant (HT) access and outcomes in ACHD remains unknown. Methods: We retrospectively analyzed the OPTN/UNOS registry of adults with ACHD listed for first-time HT (2018-2025). Sensitization was defined by calculated panel reactive antibodies (cPRA) at listing. We tested the sex x sensitization (highly sensitized, cPRA >50%) interaction on transplant access using Fine-Gray competing-risks regression, treating transplantation as the event of interest and death or removal from the waitlist as competing events, and on post-transplant survival using multivariable Cox proportional-hazards regression, both adjusted for age at listing, mechanical support at listing, and the number of distinct prior cardiac surgery categories. Results: Among 856 candidates (38% female), females were more often highly sensitized than males (23% vs 14%; age-adjusted OR 1.81, 95% CI 1.26-2.61), even after adjusting for surgical burden. Sensitization reduced transplant access in females (84% to 71%; median wait 60 to 110 days, p < 0.001) but not males (79% vs 79%, median wait 88 vs 98 days). In adjusted Fine-Gray models, the subdistribution hazard for transplant was reduced in sensitized females (sHR 0.54, 95% CI 0.41-0.72) with no effect in males (sHR 0.96, 95% CI 0.73-1.26), and the sex x sensitization interaction was significant (interaction sHR 0.64, 95% CI 0.44-0.94, p = 0.02). Post-transplant mortality was numerically higher in sensitized than non-sensitized candidates in both sexes and the sex x sensitization interaction on 1-year mortality was not significant. The sex-asymmetric effect persisted and was more pronounced in the multiorgan candidates. Conclusions: Allosensitization is not a sex-neutral barrier to transplant in HT candidates with ACHD. Females are more sensitized and have reduced transplant access without differences in 1-year mortality. The female excess in sensitization is not accounted for by surgical burden, and the exposures responsible remain to be defined. These findings warrant a sex-aware listing strategy and further studies.

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Investigation of mediating effects of sexual behaviours on the effect of a novel digital intervention on sexually transmitted reinfections: secondary analysis of a randomised controlled trial

Landray, I.; Carpenter, J.; Free, C.

2026-09-03 sexual and reproductive health 10.64898/2026.08.29.26361435 medRxiv
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Background Preventing sexually transmitted re-infections brings health benefits and can be significantly less costly than treating their sequelae. Safetxt is a potential novel digital intervention developed to promote safer sexual behaviours. However, a recent randomised controlled trial of safetxt found no effect on reinfection at 1 year (OR 1.13, 95%CI: 0.98-1.31). We investigated if safetxt's effect was mediated through sexually risky behaviours. Methods We used data from 6248 young people with STIs from 92 UK sexual health clinics. The direct and indirect effects of safetxt on reinfection were estimated using the counterfactual approach. Condom use at last sexual encounter, number of sexual partners and STI testing were assessed as mediators. These were analysed singly and together, using regression models and a formal weighting approach. The assumptions of each approach were considered and tested. Analyses were repeated in the subgroup showing the most promising effect of safetxt: men who have sex with men or with men and women (MSM/MSMW). Results No evidence was found for the total, indirect or direct effects differing from the null. Despite not being significant, for MSM/MSMW, some of safetxt's effect on reducing reinfection was identified as being offset through its effect on number of sexual partners. Conclusions There was no evidence that safetxt's effect on reinfection was mediated through changes in sexually risky behaviours. Adaptations to specifically target these behaviours are unlikely to improve safetxt's overall effect. However, improving safetxt's effect on the number of sexual partners a participant has may improve its effect for MSM/MSMW.

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Vaginal Steaming Practices Among Women At Mulago Sti Clinic, Uganda: Prevalence, Lactobacilli Proportion Differences, And Associated Factors.

Kakai, D.; Twinamasiko, N.; Kigozi, E.; Namutale, R.; Mutesi, B. A.; Bagaya, J.; Akinyi, L.; Kajumbula, H.; Nakubulwa, S.

2026-09-01 obstetrics and gynecology 10.64898/2026.08.28.26361407 medRxiv
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Abstract Background: Vaginal steaming has gained popularity among women for reasons known best to them. However, the effects of vaginal steaming on vaginal lactobacilli levels remain poorly understood and understudied. This study investigated the prevalence, assessed differences in the presence of bacterial vaginosis (BV) among women who practiced vaginal steaming and those who do not and determined the factors associated with vaginal steaming among women attending Mulago Sexually Transmitted Infections (STI) clinic in Uganda. Methods: This study utilized a cross-sectional design to enroll 181 women aged 18 to 49 years who were systematically sampled at Mulago STI clinic. Interviews were conducted to obtain the demographic characteristics of the participants. Vaginal swabbing and Gram staining were done to attain lactobacilli counts by microscopy which were categorized using the Nugent score. Data were analyzed using Stata. The potential confounding effects of other variables on the relation between vaginal steaming and the presence of bacterial vaginosis as well as factors associated with vaginal steaming were assessed using modified Poisson regression. Results: Prevalence of vaginal steaming was 40.3%, (95% confidence interval (CI) 33.0% - 48.0%). There were 41.1% women who practiced vaginal steaming occasionally, 53.4% who used hot water having herbs and 78.1% who practiced vaginal steaming for medical reasons. There was no difference in the presence of bacterial vaginosis when women who practiced vaginal steaming were compared to those who did not (p-value = 0.286). Factors that were significantly associated with vaginal steaming included having experienced vaginal issues (aPR = 0.07, 95% CI 0.01 - 0.12, p value = < 0.001) and contraceptive use (aPR= 0.52, 95% CI 0.37 - 0.72, p value = 0.001). Conclusions: About 2 in every 5 women at Mulago STI clinic reported to have indulged in vaginal steaming. There was no difference in the presence of bacterial vaginosis when women who practiced vaginal steaming were compared to those who did not. Having experienced vaginal issues and contraceptive use were significantly associated with vaginal steaming among women at Mulago STI clinic, Uganda. The Ministry of Health of Uganda should establish targeted screening and treatment for bacterial vaginosis alongside other sexually transmitted infections.

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Socioeconomic position, adverse childhood experiences, and menstrual symptoms in two generations of a prospective UK cohort.

Sawyer, G.; Farooq, B.; Birnie, K.; Fraser, A.; Lawlor, D. A.; Sharp, G. C.; Howe, L. D.

2026-08-31 epidemiology 10.64898/2026.08.27.26361513 medRxiv
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Background: Inequalities exist for many health outcomes, but there is limited evidence regarding menstrual symptoms despite their importance for health and wellbeing. We aimed to investigate inequalities in menstrual symptoms according to socioeconomic position and childhood adversity. Methods: In two generations (G0 mothers and G1 offspring) from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK prospective cohort study, we examined associations of multiple indicators of socioeconomic position (SEP) and adverse childhood experiences (ACEs) with menstrual symptoms (pain, abnormal uterine bleeding, and premenstrual syndrome (PMS) measured 3-8-years post-birth in G0 and 17-21-years-old in G1), using multivariable logistic regression. Samples ranged from 4,828 to 9,335 G0 participants and 1,288 to 2,757 G1 participants depending on the exposure-outcome association. Missing data were addressed using multiple imputation and inverse probability weighting. Results: Financial difficulties were associated with greater odds of menstrual pain (G1 OR 1.41; 95% CI 1.07, 1.86: G0 OR 1.55; 95% CI 1.36, 1.76) and irregular cycles (G1 OR 1.60; 95% CI 1.12, 2.29: G0 OR 1.48; 95% CI 1.27, 1.72) in both generations, as well as with short/long cycle lengths in G0 only. Lower education and manual social class were also associated with these three menstrual symptoms in at least one generation. Conversely, higher SEP was associated with PMS in both generations. Higher cumulative ACEs were consistently associated with menstrual pain (4+ compared to none: G1 OR 2.15; 95% CI 1.48, 3.11: G0 OR 1.52; 95% CI 1.29, 1.80) and irregular cycles (G1 OR 1.92; 95% CI 1.20, 3.09: G0 OR 1.54; 95% CI 1.26, 1.87) but not cycle length. Lower parental education, financial difficulties, and cumulative ACEs were associated with heavy bleeding in G1 offspring only, whereas financial difficulties, own manual social class, and cumulative ACEs were associated with prolonged bleeding in G0 mothers only. Higher cumulative ACEs were also associated with PMS in G1 offspring only. Conclusions: We found evidence of inequalities according to socioeconomic disadvantage and childhood adversity for multiple menstrual symptoms, although some associations were only observed in one generation. Findings suggest that menstrual symptoms are disproportionately experienced by socially and socioeconomically disadvantaged women.

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Cost-Utility Analysis of First-Line Olaparib plus Abiraterone for Metastatic Castration-Resistant Prostate Cancer in China after Volume-Based Procurement

SHI, J.; Gu, Q.; Pan, J.; Yang, A.; Fan, M.

2026-08-31 health economics 10.64898/2026.08.26.26361314 medRxiv
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To evaluate the cost-utility and 5-year budget impact of first-line olaparib plus abiraterone versus abiraterone alone for metastatic castration-resistant prostate cancer (mCRPC) in China after the eleventh round of volume-based procurement (VBP). The intention-to-treat (ITT) population was assigned primary decision-analytic weight; the prespecified BRCA1/2-mutated (BRCAm) subgroup was a supporting analysis.

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A Multi-Agent Large Language Model Reasoning Engine for Early Detection of Pediatric Growth Disorders

Rabbani, N.; Mettner, J.; Lee, K.; Soto-Rivera, C. L.; Windberger, A.; Santiago, K.; Hatoun, J.; Correa, E. T.; Vernacchio, L.; Kohane, I.

2026-08-31 health informatics 10.64898/2026.08.28.26361655 medRxiv
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Routine childhood growth surveillance is a cornerstone of pediatric care. Growth pattern abnormalities are often early manifestations of chronic disease. Yet subtle abnormalities are frequently underrecognized, leading to diagnostic delays and avoidable morbidity. We introduce SPROUT (System for Pediatric Recognition Of Undiagnosed Trajectories), a generalized, multi-agent large language model (LLM) reasoning system designed to identify a broad spectrum of pediatric growth-related conditions from longitudinal electronic health records (EHRs) earlier than standard clinical practice. Using a large pediatric primary care EHR dataset, we developed and validated SPROUT as a two-stage system. First, a highly specific LLM screener flags concerning longitudinal growth patterns. Second, an Orchestrator module coordinates a multidisciplinary panel of LLM agents to generate a ranked differential diagnosis. To correct systemic reasoning errors, a Trainer module injects meta-knowledge into the panel via a dedicated "Learner" agent. Diagnostic capability was evaluated using a walk-forward, visit-by-visit simulation leading up to the diagnosis date. The SPROUT screener model achieved 98% (83/85) specificity and 28% (9/32) sensitivity on a gold-standard dataset of pediatric primary care patients when evaluated one year before the index date, and 100% specificity and 47% sensitivity when evaluated using longitudinal data up to the day of diagnosis. When applied to 300 control patients (i.e., healthy or undiagnosed), the screener flagged 15. Subsequent expert panel review confirmed high suspicion for undiagnosed pathology in 33% (5/15) of these cases. In chronological walk-forward validation on disease cases, the diagnostic engine identified conditions well before standard-of-care documentation. One year prior to clinical diagnosis, the system achieved sensitivities of 81% for type 1 diabetes mellitus, 56% for pituitary disorders, and 44% for celiac disease. The SPROUT multi-agent system demonstrates the ability to detect a significant portion of latent growth-related pediatric conditions months to years before current clinical standards while minimizing false positives. These results support its potential as a decision support tool for reducing diagnostic delays in pediatric care.

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Clinically Generalisable End-to-End Graph Learning for CT Image-Based Multitask Stroke Diagnosis

Lu, Z.; Uddin, S.; Uribe, S.; White, S.; Martins, R. T.; Chau, S.; Mosaddek, A. S. M.; Islam, M. S.; Nahar, N.; Azad, A. K. M.; Hossain, K. M. N.; Choudhury, H. S.; Hasan, K. M. R.; Mosaddek, N.; Rahman, S.; Hossain, M. M.; Sizar, K. M. M. H.; Angione, C.; Lio, P.; Islam, M. T.; Moni, M. A.

2026-08-31 radiology and imaging 10.64898/2026.08.26.26360026 medRxiv
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Stroke remains a leading cause of mortality and long-term disability worldwide, yet rapid diagnosis is often limited by the shortage of trained radiologists, particularly in resource-constrained settings. Automated analysis of CT imaging offers a potential solution, but existing methods often struggle to achieve clinically generalisable performance while jointly addressing multiple diagnostic tasks. Here we present the Intelligent Integrated Stroke Diagnosis System IISDS, an end-to-end deep learning framework built upon StrokeGNN, a graph-based architecture that integrates 3D contextual feature extraction with U-Net-based 2D lesion segmentation to enable comprehensive stroke analysis from non-contrast CT scans. IISDS performs stroke subtype classification, lesion segmentation and lesion volume estimation within a unified pipeline. To develop and validate the system, we collected and curated BGD-ISD through a collaboration between AI researchers, neurologists, radiologists and clinicians, resulting in a large multi-centre dataset comprising 1,507 CT scans from 597 stroke cases acquired across six hospitals and medical centres in Bangladesh. Across BGD-ISD and multiple publicly available datasets, IISDS achieves state-of-the-art performance on all tasks, improving segmentation accuracy by [&ge;]0.011 Dice score, reducing lesion volume estimation error by [&ge;]0.3 average symmetric surface distance (ASSD), and increasing classification performance by [&ge;]0.018 area under the receiver operating characteristic curve (AUC) compared with existing approaches. These results demonstrate the potential of graph-based deep learning to enable clinically generalisable, automated and scalable stroke diagnosis from CT imaging, supporting rapid clinical decision-making, particularly in healthcare environments with limited access to expert radiological interpretation.

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Impact of Detection-Isolation-Leakage on the 2026 DRC Bundibugyo Ebolavirus Outbreak

Oraby, T.; Falay, D.; Ndeffo-Mbah, M. L.

2026-08-31 public and global health 10.64898/2026.08.25.26361360 medRxiv
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The 17th Ebola outbreak in the Democratic Republic of the Congo, announced on 15 May 2026, was attributed to Bundibugyo ebolavirus (BDBV). Although case isolation is the main control strategy, its effectiveness is compromised when patients escape isolation facilities before recovery. Between 14 May and 17 June 2026, 175 individuals reportedly left isolation facilities without formal discharge across Ituri Province. We assessed how this "isolation leakage" affects community transmission. We refined the SEIHFR framework to distinguish undetected community infections, detected but not-yet-isolated cases, isolated individuals, leakage, funeral-associated transmission, and removals. Using Bayesian inference, we fitted the model to daily Ituri surveillance data, escapee counts, and isolation census records. We estimated the leakage rate, reporting and detection probabilities, and the transmission rate, while fixing other parameters based on the BDBV literature. The model reproduced confirmed cases, deaths, discharges, and escapees. We estimated R_0=3.67 (95% HDI: 2.0-5.7), a leakage rate of {rho} {approx} 0.034 day^-1 (0.022-0.051), and high contact-tracing-driven detection (p_d {approx} 0.91-0.99). Leakage increased the detection-dependent reproduction number [R](p_d) from approximately 3.2 to above 5. Eliminating leakage reduced cumulative infections by about one-third, from 1,120 to 764, while the minimum detection level required for control increased from p_d [&ge;] 0.73 without leakage to p_d [&ge;] 0.87 at the fitted leakage rate. Shortening time to isolation prevented the most infections (73.4%; 59-84), followed by reducing leakage (29.7%; 14-52) and re-isolating escapees (12.6%; 6-24). Delaying leakage reduction until week 4 reduced its benefit from about 27% to below 2%. Isolation leakage represents a major transmission pathway that has until now gone largely unmeasured. While rapid initiation of isolation is highly beneficial, it cannot compensate for permeable isolation; therefore, early, community-driven efforts to control leakage, embedded within a multilayered response, are critical.

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When Screening is a Death Sentence: A qualitative study of fear and delay of cervical pre-cancer screening in Kilombero District, Tanzania

Somba, M.; Dumbaugh, M.; Mhalu, G.; Merten, S.; Mtenga, S.

2026-08-31 public and global health 10.64898/2026.08.26.26361100 medRxiv
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Background: In Tanzania, over 10,000 women aged 15-44 are diagnosed with cervical cancer annually, and more than 6525 die. The majority are diagnosed at an advanced stage, which contributes to delays in treatment enrollment and illness complications. Multiple factors can affect womens willingness and ability to access cervical pre-cancer screening. Purpose: To explore the barriers and facilitators to attending cervical pre-cancer screening among women living in a resource-constrained area of Southern Tanzania Methods: A qualitative study of 17 focus group discussions and 12 in-depth interviews was conducted from December 2023 to July 2024. Data collection took place in the community and health centers of a town and the surrounding rural areas in Kilombero district. The study used purposive sampling to recruit 112 women and 23 men aged 18- 50+ years. Results: Fear of death emerged as a central theme in the data, acting as both a barrier to and a facilitator of womens screening behavior. Women linked death with the screening procedure, receiving results and undergoing treatment. Participants mistrusted the speculum itself and linked it to pain, vaginal infection, and infertility. Conversely, fear of physical and social death motivated other women to attend the screening to learn about their health and prevent the consequences of a positive diagnosis. Public trust in the healthcare system and the role of health information sources were also identified as influencing women's decisions to undergo or not undergo screening. Conclusion: Our findings showed that cervical cancer screening uptake is influenced by fear of death and other co-factors. To improve early cervical cancer screening, programs and policy interventions are needed to raise awareness of the disease while also addressing womens specific concerns. Also, strengthening structural dimensions such as the availability of the healthcare workforce, healthcare facilities, and ensuring equitable service availability are essential to reducing cervical cancer complications and avoidable mortality.

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Patient factors influencing participation in aerobic exercise during inpatient and outpatient rehabilitation post stroke: a prospective cohort study

Barzideh, A.; Devasahayam, A. J.; Marzolini, S.; Munce, S.; Sibley, K. M.; Inness, E. L.; Mansfield, A.

2026-08-31 rehabilitation medicine and physical therapy 10.64898/2026.08.26.26361451 medRxiv
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Background: Aerobic exercise is recommended during stroke rehabilitation to improve cardiorespiratory fitness and support recovery; however, participation rates remain low. While institutional and system-level barriers have been widely examined, less is known about how individual patient factors influence engagement in aerobic exercise during rehabilitation. Objectives: We aimed to determine whether depressive symptoms, apathy, self-efficacy and outcome expectations for exercise, perceived barriers, or past exercise history were associated with aerobic exercise participation in stroke rehabilitation. Methods: In this prospective cohort sub-study, adults admitted to in- or out-patient stroke rehabilitation at three urban hospitals completed validated questionnaires assessing depressive symptoms, apathy, exercise self-efficacy, outcome expectations for exercise, perceived barriers to being active, and premorbid exercise history. Participants were separated into two groups for analysis: those who completed aerobic exercise during rehabilitation and those who did not. Equivalence testing and between-group comparisons were performed. Results: Sixty-two participants were enrolled; 16 participated in aerobic exercise and 46 did not. Groups were not equivalent on any individual-level factors. Compared to non-participants, those who performed aerobic exercise had significantly higher depressive symptom scores (p=0.0025) and lower self-efficacy for exercise (p=0.0087). Non-participants demonstrated significantly higher apathy (p=0.0007). No significant differences were found for outcome expectations, perceived barriers, or exercise history. Conclusion: Depressive symptoms and lower self-efficacy did not impede aerobic exercise participation during rehabilitation. Increased apathy, however, was associated with non-participation. Findings highlight the need for individually tailored aerobic exercise prescriptions that consider motivational and affective factors to optimize engagement during stroke rehabilitation.

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Acceptability, feasibility, quality of life and diabetes distress score outcomes: A pragmatic randomised clinical trial on continuous glucose monitoring for people with type 1 diabetes

Marban-Castro, E.; Muhwava, L.; Girdwood, S.; Kemp, T.; Freitas, J.; Kamau, Y.; Otieno, M.; Akach, D.; Morato, A.; Sanz, S.; Fiechter, V.; Erkosar, B.; Watson, M.; Vetter, B.; Haldane, C.; Shilton, S.; Rheeder, P.; Dave, J. A.; Carrihill, M.; Karsas, M.

2026-08-31 endocrinology 10.64898/2026.08.26.26361479 medRxiv
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Introduction: Continuous glucose monitoring (CGM) offers an advancement over traditional self-monitoring of blood glucose (SMBG) for people living with type 1 diabetes (T1D). However, evidence on the acceptability and feasibility of different CGM use cases in African populations remains limited. Methods: This was a pragmatic three-arm, randomised controlled trial on CGM conducted among people living with T1D in three public healthcare clinics in South Africa. Participants were assigned to Arm 1 (continuous CGM), Arm 2 (periodic CGM), or Arm 3 (SMBG). Diabetes education was provided at all study visits. Feasibility was assessed by adherence to CGM use and through the Glucose Monitoring Satisfaction Survey (GMSS). Diabetes distress was measured by the Diabetes Distress Scale (DDS), health-related quality of life (HRQoL) by the EQ-5D scales, and acceptability using the Theoretical Framework of Acceptability (TFA). Surveys were collected on paper and transferred to OpenClinica. Analyses were performed in R. The trial was registered in the Clinical Trials Registry (NCT05944718) on July 13, 2023. Results: A total of 83 participants were included in Arm 1, 85 in Arm 2, and 80 in Arm 3. CGM mean active time was 55% in Arm 1 versus 69% in Arm 2. The proportion of participants meeting the [&ge;]70% active time threshold was higher in Arm 2 (52%) than in Arm 1 (34%). Diabetes' distress declined across arms during the intervention period, with no significant difference between arms; distress increased slightly six months post-intervention but remained below baseline. At 6 months, glucose monitoring satisfaction was significantly higher in both CGM arms than in the SMBG arm, and satisfaction increased over time in CGM arms. Health-related quality of life remained stable across arms during the intervention period with no significant difference between arms. High acceptability was observed in both CGM arms, with higher ratings in the periodic arm. Conclusions: CGM was acceptable to people living with type 1 diabetes and feasible to use in public-sector clinics in South Africa, with high acceptability under continuous and periodic use. Health-related quality of life remained stable across arms, and diabetes-related distress declined, during the intervention period, across arms. Glucose monitoring satisfaction rose significantly in both CGM arms compared to SMBG. Periodic CGM might be a promising and potentially more scalable option than continuous use for public-sector care.

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Policy implementation gap: a qualitative evaluation of the implementation of Ghana's national cancer control strategy

Jawhara, B.; Baatiema, L.

2026-08-31 health policy 10.64898/2026.08.28.26361597 medRxiv
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Background: Cancer is a growing public health challenge in Ghana, with 27,385 new cases and 17,944 deaths recorded in 2022. Ghana developed a National Cancer Control Strategy (NCCS) in 2011 to guide prevention, early detection, treatment, and palliative care. The strategy expired in 2016 and has not been formally evaluated or renewed, leaving cancer control efforts without a guiding policy framework for nearly a decade. This study examined how the strategy was implemented, what barriers were encountered and what stakeholders recommend for a strengthened national cancer response. Methods: We conducted a qualitative descriptive study using semi-structured key informant interviews. Fifteen participants were recruited through purposive sampling, supplemented by snowball referrals, representing three groups: Ministry of Health policymakers, frontline healthcare providers and representatives of cancer-focused non-governmental organisations. Data were collected between June and September 2025 and analysed using Braun and Clarke's six-phase thematic analysis framework, guided deductively by the WHO Health Systems Building Blocks framework Results: Three themes emerged: NCCS interventions and systems implemented, capturing progress in cancer awareness, HPV vaccination and pilot screening programmes alongside persistent geographic and financial inequities in access; barriers to implementation, including inadequate financing, infrastructure and workforce shortages, the absence of a national cancer registry and governance failures, among them the finding that no frontline healthcare provider interviewed had any awareness of the NCCS; and recommended implementation strategies, including co-production of a renewed strategy, establishment of a dedicated National Cancer Control Programme, expanded health insurance coverage and decentralisation of oncology services. Conclusion: The NCCS was not operationally embedded in the health system. The evidence points to failures in policy dissemination as a constraint that precedes resource constraints. Addressing Ghana's rising cancer burden requires renewed political commitment, co-produced governance structures and accountability mechanisms. These findings have relevance for other low- and middle-income country settings facing similar challenges.

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Burr-Hole Intersection of Middle Meningeal Artery Branches and Recurrence in Chronic Subdural Haematoma: a Multicentre Retrospective Cohort Study

Saba, T. M.; Moudgil-Joshi, J.; Pandit, A. S.; Penn, J.; Mallon, D.; Marcus, H. J.; Grover, P.

2026-08-31 surgery 10.64898/2026.08.26.26361348 medRxiv
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Background and Objectives: Recurrence following burr-hole drainage of chronic subdural haematoma (cSDH) occurs in 10-25% of cases, sustained by neovascularisation of the subdural neomembrane supplied by the middle meningeal artery (MMA). MMA embolisation reduces recurrence; whether incidental burr-hole intersection of MMA branches during drainage confers similar benefit is unknown. Methods: We performed a multicentre retrospective cohort study of consecutive adults undergoing burr-hole drainage for cSDH at two UK tertiary neurosurgical centres. Postoperative thin-slice CT was used to classify burr-hole intersection of the underlying MMA groove (no hit, distal-branch hit or main-branch hit) and measure perpendicular burr-hole-to-MMA-groove distance. Co-primary outcomes were radiological recurrence and recurrence requiring intervention. Patient-clustered multivariable logistic regression adjusted for prespecified clinical covariates and treating site. Results: 227 patients (284 operated hemispheres) were included. Radiological recurrence decreased from 34.4% with no branch hit to 22.9% with main-branch intersection, with the gradient confined predominantly to unilateral cSDH. Main-branch intersection was associated with lower adjusted odds of radiological recurrence in unilateral cSDH (adjusted OR 0.30, 95% CI 0.11- 0.81; P = .018), with a similar but non-significant association in the overall cohort (adjusted OR 0.53, 95% CI 0.26-1.07; P = .075). Burr-hole-to-MMA-groove distance demonstrated a more consistent association: in the overall cohort, each 5-mm increase independently increased the odds of radiological recurrence (adjusted OR 1.38, 95% CI 1.04-1.82; P = .025). In unilateral cSDH, each 5-mm increase was independently associated with both radiological recurrence (adjusted OR 1.45, 95% CI 1.03-2.04; P = .034) and recurrence requiring intervention (adjusted OR 1.52, 95% CI 1.05-2.20; P = .027). Conclusion: Main-branch intersection of the middle meningeal artery during routine burr-hole surgery is associated with lower recurrence of unilateral cSDH, while the accompanying burr-hole-to-MMA-groove distance gradient provides biologically plausible support for a dose-response relationship. Together, these findings provide mechanistic rationale for prospective evaluation of intentional neuronavigation-guided MMA targeting (BURR-MMA; NCT07549893).

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Investigating adiposity in childhood and adulthood on later life sleep health: a lifecourse Mendelian randomization study

pathak, s.; Richardson, T.; Sanderson, E.; Arora, N.; Strand, L.; Asvold, B. O.; Bhatta, L.; Brumpton, B.

2026-08-31 genetic and genomic medicine 10.64898/2026.08.27.26361310 medRxiv
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Background: Higher Body Mass Index (BMI) is an established risk factor of sleep disturbance. It is not known if the effect is homogeneous across the lifecourse or if there is a particular time point in life that might be best to target. Methods: Two-sample Mendelian randomization (MR) was used to investigated the effect of childhood adiposity (adjusting on adulthood adiposity and obstructive sleep apnea (OSA)) on insomnia, morning chronotype, sleep duration, daytime sleepiness and daytime napping. Similarly, total, and direct effect of adulthood adiposity on these outcomes was explored. We used summary statistics from a genome-wide association study (GWAS) of UK Biobank for childhood and adulthood adiposity (n=453,169) and large-scale consortia of OSA (Million Veteran Program) (n=410,268), insomnia, and chronotype (23andMe) (n=1,978,022 and n=248,1000, respectively). Results: Two-sample univariable MR analysis provided no evidence of an effect of genetically predicted childhood adiposity on later life insomnia (Odds ratio (OR)= 0.94, 95% Confidence interval (CI)= 0.87, 1.03). Whereas, multivariable MR (adjusted for adulthood adiposity) analysis provide strong evidence of direct protective effect of genetically predicted childhood adiposity on later life insomnia (OR= 0.70, CI= 0.64, 0.77). Further, both in univariable and multivariable MR, a strong positive effect of increased childhood body size on morning chronotype was observed (OR= 1.16, CI= 1.01, 1.33 and OR= 1.36, CI= 1.15, 1.62, respectively) after accounting for adulthood body size. In both analysis the estimate did not change considerably after aditionally adjusting for OSA. However, childhood and adulthood adiposity found to be associated with OSA and OSA with insomnia. In both univariable and multivariable analysis, increased body size in adulthood increased the risk of having insomnia and a morning chronotype. Conclusions: The findings suggest that higher body size in childhood is not a risk factor for later life insomnia, whereas higher body size in adulthood was. Further, if healthy body size is maintained in adulthood, high childhood adiposity may decrease the risk of insomnia and increase the risk of being a morning person in later life. Keywords: childhood, adulthood, obesity, insomnia, morning chronotype, medelian randomization