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Journal of the American Medical Directors Association

Elsevier BV

Preprints posted in the last 7 days, ranked by how well they match Journal of the American Medical Directors Association's content profile, based on 13 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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Menopausal hormone therapy at age 45 to 60 years old, future dementia or cognitive decline: Systematic review and meta-analysis

Law, S. Y. R.; Mukadam, N.; Pourhadi, N.; Chaudry, A.; Shiakalli, A.; Rai, U.; Livingston, G.

2026-04-22 psychiatry and clinical psychology 10.64898/2026.04.20.26351058 medRxiv
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ObjectiveTo examine whether menopausal women who initiate systemic menopausal hormone therapy (MHT) around menopause (45-60 years old) have a different risk of developing dementia than those not taking MHT. DesignSystematic review and meta-analysis of randomised controlled trials and longitudinal observational studies. Risk of bias was assessed using ROB-2 and ROBINS I-V2. Data sourcesMEDLINE, Web of Science, EMBASE, and Cochrane Library to 27 March 2026. Eligibility criteria for selecting studiesStudies which measured dementia or cognitive decline in women who initiated systemic MHT between ages 45-60 or within 5 years of menopause, compared with placebo or no MHT. Authors contacted for additional details if needed. Main outcome measuresDementia, Alzheimers disease (AD), cognitive decline. Results10 studies totalling 213,678 participants (189,525 in studies with the primary population). There was no significant increased risk in women with a uterus for all cause dementia (pooled hazard ratio (HR): 1.12; 95% CI 0.91-1.31, N=78,613, I2 = 96.9%), but increased AD risk (HR: 1.14; 95% CI 1.02, 1.29, N=134,865, I2 = 35.6%). Results were similar in sensitivity analyses including women with or without a uterus. Results for cognitive decline were variable. ConclusionsMHT initiated around the age of menopause should not be prescribed for cognition or dementia prevention. It is not protective against dementia and may increase risk slightly. The magnitude of risk was similar in AD and dementia, but the latter with larger confidence intervals. Studies which followed up individuals rather than on health records lost people to follow up. This may account for difference in cognitive decline outcomes between studies, as people with cognitive impairment and dementia are more likely not to attend. MHT prescribing should balance benefits against risks, including evidence of a small increased dementia risk. There are few high-quality studies, so further research would inform recommendations. Systematic review registration Prospero CRD420251010663 What is already known on this topic?O_LIMenopausal hormone therapy (MHT) is effective for alleviating vasomotor symptoms. Contemporary guidelines recommend treatment should be initiated for such symptoms under age 60 and or within 10 years of menopause onset. C_LIO_LIA large randomised trial on the topic found increased risk of dementia in women initiating MHT after the age of 65. C_LIO_LIIt is unknown whether initiating MHT around the age of menopause impacts the risk of dementia or cognitive decline. C_LI What this study addsO_LIThere was no evidence that taking MHT around the time of menopause decreases the risk of dementia or cognitive impairment. C_LIO_LIThey should not be prescribed for these indications. C_LIO_LIWe were able to find more studies which examine this question by contacting authors for additional data. C_LIO_LIInitiating MHT in women with a uterus around the age of menopause increased the risk of Alzheimers disease slightly, by over 10%, and there is a similar but not significant effect in the fewer studies of all cause dementia. Women with or without a uterus show similar results. C_LIO_LIWe found no significant difference shown in cognitive decline, possibly due to loss to follow up. This may be because most studies of cognitive decline follow up C_LI

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Neighborhood Deprivation Is Associated with Accelerated Epigenetic Aging Via Greater Individual Adversity

Koirala, A. S.; Shields, J. R.; Vijan, A. S.; Wemm, S.; Xu, K.; Ku, B. S.; Sinha, R.; Harvanek, Z. M.

2026-04-27 psychiatry and clinical psychology 10.64898/2026.04.24.26351669 medRxiv
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Importance: Adverse neighborhood conditions can lead to poorer health outcomes, potentially through accelerated biological aging. However, whether these relationships are explained by individual- or neighborhood-level factors remains unclear. Objective: To examine the association between neighborhood deprivation, measured by the Area Deprivation Index (ADI), and epigenetic age acceleration and assess whether individual- and neighborhood-level characteristics mediate or modify these associations. Design: Cross-sectional study using data from a Yale Stress Center study between 2008 and 2012. Data analysis was conducted from July 2025 to January 2026. Setting: Community-based sample from the greater New Haven, CT area. Participants: A total of 370 healthy adults aged 18 to 50 years without major psychiatric, medical, or cognitive disorders who provided blood samples for DNA methylation analysis. Main Outcomes and Measures: Epigenetic age acceleration measured from DNA methylation using four second-generation epigenetic clocks, with associations assessed among aging, neighborhood deprivation, and individual- and neighborhood-level factors. Results: Data were analyzed from 370 participants (212 women [57.3%], 158 men [42.7%]; mean [SEM] age, 29.3 [0.46] years). Greater neighborhood deprivation was associated with greater lifetime adversity ({beta}=0.112, p<.001) and lower educational attainment ({beta}=-0.019, p=.012), and accelerated epigenetic aging as measured by GrimAge ({beta}=0.037, p<.001), PCGrimAge ({beta}=0.019, p<.001), and PCPhenoAge ({beta}=0.041, p<.001), but not PhenoAge (p=.23). In multivariable models accounting for individual factors, neighborhood deprivation remained associated with these three clocks. Lifetime adversity partially mediated the association between ADI and accelerated GrimAge (20.3% of total effect) and PCGrimAge (23.3%). Race moderated the direct association between ADI and epigenetic aging, with stronger associations between neighborhood deprivation and accelerated GrimAge ({beta}=0.061, p=.004) and PCPhenoAge ({beta}=0.057, p=.02) observed among Black participants compared to White. Conclusions: Greater neighborhood deprivation was associated with accelerated epigenetic aging across multiple second-generation clocks, with lifetime adversity partially mediating these associations. Stronger effects were observed among Black participants. These findings suggest that neighborhood environments and cumulative stress may contribute to biological aging and racial disparities in aging trajectories.

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Decision-making in patients with ALS: experiences and implications for decision support

Nagase, M.; Hino, K.; Sakamoto, A.; Seo, M.

2026-04-24 nursing 10.64898/2026.04.22.26351518 medRxiv
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Patients with amyotrophic lateral sclerosis (ALS) face critical decisions regarding life-sustaining treatments, such as invasive mechanical ventilation and percutaneous endoscopic gastrostomy. Advance care planning and shared decision-making are standard supportive frameworks but they often fail to account for structural pressures like progressive decline, shifting patient values, and fear of becoming a burden that may influence decision-making. This study explores how patients with ALS interpret ventilator and care options amid progressive physical decline, thereby reconsidering approaches to decision support. Using a qualitative descriptive design, the researcher (a nurse/sociologist) conducted 2-3 hour home interviews with five purposively sampled patients with ALS. Data, including eye-tracking-aided responses, were analysed via Sandelowskis framework. Rigour was ensured through team-based triangulation, independent coding by two researchers, and a reflexive audit trail. Subjective narratives were prioritised without medical record cross-referencing to capture patients experiences. Four categories emerged: (1) Rewriting clinical prognosis into a narrative of exploration via peer models, where meeting active ventilator users transformed future perceptions; (2) The conflict between securing care infrastructure and the burden on family, which greatly influenced the will to survive; (3) Existential fluctuation, where patients intentions shifted with daily fulfilment and family events; and (4) Governance of the body via pre-emptive technology use and training carers as physical extensions. Findings showed decision-making was a multi-layered process redefining lifes meaning within social resources. This necessitate shifting from independent to relational autonomy, where agency relies on care infrastructure, not physical ability. Treatment choice is a dynamic exploration requiring narrative companions to support existential fluctuations. Professionals must coordinate environments to reduce patient indebtedness. Limitations include the small, resource-advantaged sample (N = 5) and reliance on subjective narratives without medical record verification. Living with ALS means governing a new self through relational support and continuous dialogue.

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Prediabetes and glycemic transitions as determinants of frailty and functional decline in adults aged 50 years and older: A longitudinal analysis from five multinational aging cohorts

Malagon-Liceaga, A.; Basile-Alvarez, M. R.; Fermin-Martinez, C. A.; Ramirez-Rivera, D. L.; Perezalonso Espinosa, J.; Diaz-Sanchez, J. P.; Garcia-Gonzalez, S. B.; Carrillo-Herrera, K. B.; Cabrera-Quintana, L. A.; Antonio-Villa, N. E.; Gomes-Goncalves, N.; Garcia-Pena, C.; Bello-Chavolla, O. Y.

2026-04-24 geriatric medicine 10.64898/2026.04.22.26351540 medRxiv
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Background: Prediabetes is highly prevalent in older adults and is characterized by heterogeneous clinical trajectories, including regression to normoglycemia and progression to diabetes. While prediabetes has been associated with impaired physical function and frailty, the longitudinal impact of both a single diagnosis and dynamic glycemic transitions on functional outcomes remains unclear. We aimed to evaluate associations between baseline prediabetes and glycemic transitions over time with trajectories of functional capacity and frailty in older adults. Methods: We conducted a pooled analysis of harmonized data from five nationally representative longitudinal aging cohorts (MHAS, HRS, CHARLS, ELSA, CRELES) within the Gateway to Global Aging Data, including adults aged [&ge;]50 years with [&ge;]1 HbA1c measurements. Prediabetes was defined per ADA criteria (HbA1c 5.7-6.4%). Functional outcomes included activities of daily living (ADL), instrumental ADL (IADL), and frailty assessed using Fried phenotype, FRAIL scale, and a deficit-accumulation Frailty Index (FI). Mixed-effects Poisson models estimated incidence rate ratios (IRRs) for baseline prediabetes, while generalized estimating equations assessed time-varying glycemic status and transition trajectories. Models were adjusted for age, sex, cohort, and time-varying covariates, with sensitivity analyses including BMI, smoking, and alcohol intake. Findings: Among 18,571 participants (median follow-up 13.6 years), baseline prediabetes was associated with increased progression of functional deficits and frailty compared with normoglycemia, including higher FI values and accelerated FI progression. Prediabetes was associated with higher incidence of ADL, IADL, and multimorbidity deficits from early follow-up, although time-dependent changes in incidence rates were not significant. In time-varying analyses (n=7,840), both prediabetes and diabetes were associated with higher incidence of functional deficits compared with normoglycemia, with diabetes showing the strongest effects across all outcomes. Diabetes was associated with greater FI burden and accelerated progression, whereas prediabetes showed a smaller increase, with attenuation over time. Among individuals with baseline prediabetes, regression to normoglycemia occurred in 20.8% and was associated with increased incidence of ADL and frailty deficits. In contrast, progression to diabetes occurred in 24.3%, and was associated with lower risk of incident ADL and Fried frailty deficits compared to stable prediabetes. Interpretation: Prediabetes is associated with increased risk of functional decline, frailty, and deficit accumulation in older adults, independent of progression to diabetes. Regression to normoglycemia was associated with higher risk of functional deterioration. These findings suggest that prediabetes reflects a state of metabolic vulnerability linked to biological aging rather than solely a precursor to diabetes and highlights a need to reframe its clinical significance in older populations. Funding: This research was supported by Instituto Nacional de Geriatria in Mexico. Keywords: Prediabetes; Glycemic transitions; Frailty; Functional decline; Aging; Multimorbidity

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Generic versus personalized foot-ground contact models for predictive simulations of walking: Is personalization worth the effort?

Williams, S. T.; Li, G.; Fregly, B. J.

2026-04-21 bioengineering 10.64898/2026.04.16.719049 medRxiv
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PurposeQuantification of walking function, including joint motions, ground reactions, and joint loads, outside the lab is a growing research area. Because only joint motions can currently be measured outside the lab, researchers are utilizing tracking optimizations of walking to estimate associated ground reactions and inverse dynamic joint loads. However, foot-ground contact models used in such optimizations have been generic rather than personalized, which may limit the accuracy of estimated ground reactions and joint loads. This study compares the predictive capabilities of generic versus personalized foot-ground contact models. MethodsGeneric and personalized foot-ground contact models were evaluated in calibration and tracking optimizations performed using experimental walking data collected from three subjects in varying states of health. Foot-only calibration optimizations evaluated how well both models could reproduce experimental ground reaction and foot motion data while tracking both types of data simultaneously, while whole-body tracking optimizations evaluated how well both models could reproduce experimental ground reactions, joint motion, and joint load data while tracking only experimental joint motion data and achieving dynamic consistency. ResultsFor all three subjects and both types of optimizations, personalized foot-ground contact models reproduced experimental ground reaction, joint motion, and joint load data more accurately than generic foot-ground contact models. ConclusionPersonalized foot-ground contact models can improve the accuracy with which ground reactions and joint loads can be estimated via tracking optimizations of walking using only experimental motion data as inputs. Personalized models require little time and effort to calibrate using freely available software tools and should improve the accuracy of predictive simulations of walking as well.

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Development and Evaluation of iSupport-Malaysia: A Multimedia Web-Based Psychoeducational Intervention for Dementia Caregivers

Loh, K. J.; Lee, W. L.; Ng, A. L. O.; Chung, F. F. L.; Renganathan, E.

2026-04-21 geriatric medicine 10.64898/2026.04.14.26350743 medRxiv
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BackgroundCaring for people with dementia can impose a considerable psychological burden on caregivers, yet access to caregiver support in Malaysia remains limited. The World Health Organizations iSupport for Dementia program provides dementia education via textual, e-learning format. However, a culturally adapted Malaysian version has not been available. ObjectiveThis study aimed to develop and gather user feedback on a culturally adapted, multimedia version of iSupport tailored for Malaysia (iSupport-Malaysia). MethodsGuided by a four-phase cultural adaptation framework, the generic iSupport content was translated into Bahasa Malaysia, adapted to local customs, and transformed into multimedia lessons on an e-learning platform. A mixed-methods design was used to explore user perceptions and evaluate usability through four homogeneous focus group discussions and 15 individual usability test sessions with informal caregivers (FG: n=9; UT: n=9) and healthcare professionals (FG: n=11; UT: n=6). Focus groups examined aesthetics, ease of use, clarity, cultural relevance, comprehensiveness, and satisfaction. Usability testing involved Think Aloud tasks, post-test questionnaires, and brief interviews. Qualitative data was analysed thematically, and descriptive statistics summarised usability performance. ResultsiSupport-Malaysia demonstrated good usability (M=74.3{+/-}18.0), with most tasks completed without assistance. Strengths included interactive learning activities, peer discussion features, and flexible self-paced learning. Content was viewed as culturally appropriate, credible, and useful. Suggested improvements included enhancing visual aesthetics, shortening videos, refining quizzes, and increasing practical relevance. ConclusionUser insights indicate that iSupport-Malaysia is usable and culturally appropriate. These findings will inform refinement of the platform prior to the pilot feasibility study and provide recommendations for future multimedia-based caregiver interventions.

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Assessing medication-related burden and medication adherence among older patients from Central Nepal: A machine learning approach

Giri, R.; Agrawal, R.; Lamichhane, S. R.; Barma, S.; Mahatara, R.

2026-04-23 geriatric medicine 10.64898/2026.04.22.26351447 medRxiv
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We are pleased to submit our Original article entitled "Assessing medication-related burden and medication adherence among older patients from Central Nepal: A machine learning approach" for consideration in your esteemed journal. In this paper, we assessed medication burden using validated Living with medicines Questionnaire (LMQ-3) and medication adherence using Adherence to Medication refills (ARMS) Scale. In this paper we analysed our result through machine learning approach in spite of traditional statistical approach to identify the complex factors influencing both. Six ML architectures (Ordinary Least Square, LightGBM, Random Forest, XGBoost, SVM, and Penalized linear regression) were employed to predict ARMS and LMQ scores using various socio-demographic, clinical and medication-related predictive features. Model explainability was provided through SHAP (Shapley Additive exPlanations). Our study identified the moderate medication burden with moderate non-adherence among older adults. Requiring assistance for medication and polypharmacy were the strongest drivers for the medication burden and non-adherence. The high predictive accuracy by ML suggests the appropriate clinical intervention like deprescribing to cope with the high prevalent medication burden and non-adherence among older adults in Nepal.

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Psychomotor retardation and risk of Parkinson's disease in unipolar depression: a retrospective cohort study

Morrin, H.; Badenoch, J. B.; Burchill, E.; Fayosse, A.; Singh-Manoux, A.; Shotbolt, P.; Zandi, M. S.; David, A. S.; Lewis, G.; Rogers, J. P.

2026-04-27 psychiatry and clinical psychology 10.64898/2026.04.26.26351763 medRxiv
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Background: Depression is associated with an increased risk of subsequent Parkinson's disease. Neuroimaging studies suggest a neurobiological overlap in mechanisms underlying Parkinson's disease and psychomotor retardation in depression. Our aim was to investigate whether, among individuals with depression, the presence of psychomotor retardation was associated with the development of subsequent Parkinson's disease. Methods: In a retrospective cohort study, electronic healthcare records from individuals diagnosed with depression at age 40 or over in a large mental health service in London, UK were examined for the presence of psychomotor retardation. Linkage to general hospital records was used to ascertain diagnoses of Parkinson's disease between 2007 and 2023. Cox regression was used to compare the hazard of Parkinson's disease in individuals with depression with and without psychomotor retardation. Results: Among 6327 patients with depression, 2402 (38.0%) had psychomotor retardation. The adjusted hazard ratio for development of Parkinson's in those with psychomotor retardation was 1.43 (95% CI 1.02 - 2.01, p = 0.04). Secondary analyses demonstrated a significant difference in psychomotor retardation incidence at least 10 years before Parkinson's diagnosis. Conclusions: Psychomotor retardation in later-life depression is associated with increased risk of subsequent Parkinson's diagnosis over an extended period of time, suggesting that the relationship cannot solely be explained by misdiagnosis. Psychomotor retardation may therefore serve as a marker of prodromal Parkinson's disease.

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Running Style and Stability During Uphill Running Are Largely Preserved with Increasing Shoe Sole Thickness

Kettner, C.; Stetter, B. J.; Stein, T.

2026-04-21 bioengineering 10.64898/2026.04.16.719110 medRxiv
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Advanced footwear technology (AFT) shoes incorporate increased sole thickness and compliant midsole materials that may alter running biomechanics. While these effects have been widely studied during level running, little is known about how sole thickness influences running style and stability during uphill running. This study examined the effects of two AFT shoes differing in sole thickness (35 mm-AFT35; 50 mm-AFT50) and a traditional control shoe (27 mm-CON27) on running style and stability during uphill running. Seventeen experienced male runners performed treadmill running at a 10% incline at 6.5 and 10 km/h in three shoe conditions. Running style was assessed using duty factor, normalized step frequency, center-of-mass oscillation, vertical and leg stiffness, and lower-limb joint kinematics. Running stability was evaluated using local dynamic stability via the maximum Lyapunov exponent and detrended fluctuation analysis of stride time. Duty factor and normalized step frequency did not differ between shoes. However, AFT shoes showed greater center-of-mass oscillation (p = 0.004), lower vertical stiffness (p = 0.022) compared to CON27. Joint kinematics revealed significant shoe effects at the ankle (p = 0.001), particularly increased dorsiflexion and eversion in AFT conditions. Running stability showed only minor changes. Local dynamic stability differed at the trunk (p = 0.027), with reduced stability in AFT50 compared with CON27 (p = 0.006), while global stability remained unchanged. No shoe x speed interactions were observed for any variable. Overall, uphill running style and stability remained largely preserved across shoe conditions, suggesting that sole thickness alone had limited influence.

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Risk Factors for Antimicrobial Resistance in Cancer Patients and Cancer Survivors: An Electronic Health Record Study

Hu, F.; Wei, J.; Muller-Pebody, B.; Hope, R.; Brown, C.; Carreira, H.; Demirjian, A.; Walker, A. S.; Eyre, D. W.

2026-04-25 infectious diseases 10.64898/2026.04.17.26351097 medRxiv
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Objectives: To identifiy risk factors for antimicrobial resistance (AMR) in seven pathogen-antimicrobial combinations in patients with cancer and cancer survivors. Methods: Using data from patients with recent or past cancer diagnostic codes in Oxfordshire, UK, we examined associations between 22 potential risk-factors and AMR in blood culture isolates, collected between 1-April-2015 and 31-March-2025. Results: Among 5,975 bacteraemias in 4,365 adults, we analysed 3,141 (52.6%) due to Enterobacterales and 620 (10.4%) due to Enterococcus faecalis/faecium in 2,752 patients. Fourteen risk-factors for antimicrobial-resistant bacteraemia were identified, varying across pathogen-antimicrobial combinations. Compared with no previous antimicrobial susceptibility test result, prior resistance to the same antibiotic in any culture in the last year was strongly associated with AMR across all pathogen-antimicrobial combinations (all p<=0.001). Prior antibiotic exposure and younger age were also positively associated with AMR in four and five combinations, respectively. Cancer type showed modest effects; lymphoid/haematopoietic malignancies were associated with higher odds (vs colorectal cancer) of trimethoprim-sulfamethoxazole-resistant Enterobacterales (aOR=2.07 95%CI 1.40-3.06) and vancomycin-resistant Enterococcus bacteraemia (aOR=6.68, 1.21-36.91). Conclusions: Previous resistance was the greatest risk factor for bacteraemia with AMR in cancer patients and survivors, with prior antibiotic exposure and age also contributing. Lymphoid/haematopoietic malignancies increased risk of resistance to specific antimicrobials. Keywords: antimicrobial resistance, bacteraemia, cancer, risk factors

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Retrospective analysis of clinical and environmental genotyping reveals persistence of Pseudomonas aeruginosa in the water system of a large tertiary children's hospital in England

Sheth, E.; Case, L.; Shaw, F.; Dwyer, N.; Poland, J.; Wan, Y.; Larru, B.

2026-04-24 infectious diseases 10.64898/2026.04.23.26351604 medRxiv
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Background Pseudomonas aeruginosa is a major cause of healthcare-associated infections in paediatric settings, where its persistence in moist environments such as hospital water and wastewater systems poses a particular risk to neonates and immunocompromised children. Aim The aim of this study was to showcase the long-term survival and transmission of P. aeruginosa in a large tertiary children's hospital in England which is crucial to develop strategies for water-safe care. Methods Environmental P. aeruginosa isolates were collected from taps, sinks, showers, and baths in augmented care areas of a 330-bed tertiary children's hospital built to NHS water-safety standards. Clinical isolates were classified as invasive (blood, cerebrospinal fluid, and bronchoalveolar lavage) or non-invasive (respiratory, urine, ear, abdominal, and rectal surveillance). Variable number tandem repeat (VNTR) profiles and metadata were extracted from PDF reports, de-identified, deduplicated, and curated using Python and R. Findings This retrospective study analysed nine-locus VNTR profiles of 457 P. aeruginosa isolates submitted to the UK Health Security Agency from a large tertiary children's hospital, identifying 56 isolate clusters (each with [&ge;]2 isolates), of which 19 (34%) contained at least one invasive isolate. The most persistent cluster (Cluster 1, n=20) spanned from July 2016 to September 2024, containing environmental and clinical (invasive and non-invasive) isolates. Conclusion These findings demonstrate long-term persistence of certain genotypes and temporal overlap between environmental and clinical isolates, highlighting the difficulty in detecting and eradicating P. aeruginosa in hospital water and wastewater systems and reinforcing the need for continuous rigorous water system controls.

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Ethnic inequalities in respiratory virus epidemics in England: a mathematical modelling study

Robert, A.; Goodfellow, L.; Pellis, L.; van Leeuwen, E.; Edmunds, W. J.; Quilty, B. J.; van Zandvoort, K.; Eggo, R. M.

2026-04-21 infectious diseases 10.64898/2026.04.18.26350858 medRxiv
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BackgroundIn England, the burden of respiratory infections varies by ethnicity, contributing to health inequalities, but the role of additional demographic factors remains underexplored. We quantified how differences in social mixing and demographic characteristics between ethnic groups cause inequalities in transmission dynamics. MethodsWe analysed the association between the ethnicity and the number of contacts of 12,484 participants in the 2024-2025 Reconnect social contact survey, using a negative binomial regression model. We simulated respiratory pathogen epidemics using a compartmental model stratified by age, ethnicity, and contact levels, at a national level and in major cities in England. FindingsAfter adjusting for demographic variables, participants of Black and Mixed ethnicities had more contacts than those of White ethnicity (rate ratios (RR): 1.18 [95% Credible Interval (CI): 1.11-1.26], and 1.31 [95% CI: 1.14-1.52]). Participants of Asian ethnicity had fewer contacts (RR: 0.85 [95% CI: 0.79-0.91]). In national-level simulations, individuals of White ethnicity had the lowest attack rates due to demographic differences and mixing patterns. Local demographic structures changed simulated dynamics: attack rates in individuals of Black and Mixed ethnicities were approximately double those of White ethnicity in Birmingham, but less than 60% higher in Liverpool. InterpretationDemographic characteristics and mixing patterns create inequalities in transmission dynamics between ethnicities, while local demographic characteristics and pathogen infectiousness change the expected relative burden. To ensure mitigation strategies are effective and equitable, their evaluation must explicitly account for inequalities arising from local context. FundingMedical Research Council, National Institute for Health and Care Research, Wellcome Trust Research in context Evidence before this studyWe searched PubMed for population-based studies quantifying differences in respiratory infections between ethnic groups, up to 1 April 2026, with no language restrictions. Keywords included: (respiratory pathogens OR influenza OR COVID-19) AND (ethnic* OR race) AND (inequ*) AND (compartmental model OR incidence rate ratio OR hazard ratio). We excluded studies that focused on non-respiratory pathogens (e.g. looking at consequences of COVID-19 on incidence of other pathogens). A population-based cohort study showed that influenza infection risk was higher in South Asian, Black, and Mixed ethnic groups compared to White ethnicity in England. Another population-based cohort study highlighted that during the first wave of COVID-19 in England, the South Asian, Black, and Mixed ethnic groups were more likely to test positive and to be hospitalised than the White ethnic group. Census data in England showed that the distributions of age, household size, household income and employment status differed between ethnic groups, and the recent Reconnect social contact surveys highlighted the impact of each demographic factor on the participants number of contacts. Added value of this studyOur study shows that social contact patterns, mixing, and demographic structure all lead to unequal infection risk between ethnic groups in respiratory pathogen epidemics. Using the largest available social contact survey in England, we show that both the average number of contacts and the proportion of high-contact individuals varied by ethnic group, even after adjusting for participants demographics. These differences, together with mixing patterns and age structure, led to lower expected incidence among individuals of White ethnicity than in all other ethnic groups in simulated outbreaks. The level of inequality between ethnic groups changed when we used different values of pathogen transmissibility. Finally, as ethnic composition and population structure differ between cities in England, our results show differences in expected inequalities at a local level. Implications of all the available evidenceInequalities in infection risk between ethnic groups are context- and pathogen-dependent. They arise from both local population structure and contact patterns. Detailed information on mixing between groups and population structure is needed to accurately measure group-specific infection risk. These findings indicate that public health interventions based only on national-level estimates conceal regional variation in risk and may ultimately increase inequalities. Public health interventions need to be tailored to local contexts to be equitable and effective. Finally, our findings provide a foundation for understanding the progression from infection-risk inequalities to disparities in disease presentation and clinical outcomes.

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International Adaptation of a brief Problem-Solving Skills (the IAPPS trial) training for people in custody with severe mental illness in Poland: an open multicentred, parallel group, feasibility randomised controlled trial.

Perry, A. E.; Zawadzka, M.; Rychlik, J.; Hewitt, C.

2026-04-25 forensic medicine 10.64898/2026.04.24.26351654 medRxiv
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Objectives: The primary aim of this study was to assess the feasibility of delivering an adapted problem-solving skills (PSS) intervention by quantifying the recruitment, follow-up and completion rates using a brief problem-solving intervention for people with a mental health diagnosis in two Polish prisons. Design: IAPPS is an open, multi-centred, parallel group feasibility randomised controlled trial (RCT). Setting: Two prisons in Poland. Participants: Men in custody aged 18 years and older, having a mental illness and living within the prison therapeutic unit. Interventions: The intervention consisted of an adapted PSS skills intervention plus care as usual (CAU) or care as usual only. Delivered in groups of up to five people in 1.5-hour sessions over the course of two weeks. Main outcome measures: Primary outcomes - rate of recruitment, follow-up, and feasibility to deliver the intervention. Secondary outcomes included measures of depression, general mental health, and coping strategies. Results: 129 male prisoners were screened, 64 were randomly allocated, with a mean age of 53.5 years (SD 14, range 23-84). 59 (95%) prisoners were of Polish origin. Our recruitment rate was 48%. There was differential follow up with those in the intervention group less likely to complete the post-test battery versus those who received care as usual. Outcome measures were successfully collected at both time points. Conclusions We were able to recruit, retain and deliver the intervention within the prison setting; some logistical challenges limited our assessment of intervention engagement. Our data helps to demonstrate how use of the RCT study design can be implemented and delivered within the complex prison environment. Trial registration number ISRCTN 70138247, protocol registration date May 2021

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Effect of NHS surgical hubs on elective primary hip-and-knee replacement volume, length of stay and waiting times: national longitudinal difference-in-differences study

Wen, J.; Anteneh, Z.; Castelli, A.; Street, A.; Gutacker, N.; Scantlebury, A.; Glerum-Brooks, K.; Davies, S.; Bloor, K.; Rangan, A.; Castro Avila, A.; Lampard, P.; Adamson, J.; Sivey, P.

2026-04-22 health policy 10.64898/2026.04.21.26351383 medRxiv
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ObjectivesTo evaluate the effect of surgical hubs on the volume of surgeries, patient waiting times, and length of hospital stay for elective hip and knee replacements in the English NHS. DesignA retrospective longitudinal study using a difference-in-differences approach to compare changes in outcomes at NHS trusts that opened surgical hubs with those that did not. SettingThe study was set in the English NHS, using administrative data from NHS acute trusts providing elective hip and knee replacements between April 2014 and September 2024. ParticipantsThe study included 76 NHS trusts. The treatment group consisted of 29 trusts that opened a surgical hub for trauma and orthopaedic surgery during the study period. The control group consisted of 47 trusts that did not. 48 trusts that performed fewer than 1,000 relevant procedures over the ten-year period or that reported data for fewer than 41 of the 42 quarters in the sample period were excluded. InterventionThe phased introduction of surgical hubs dedicated to elective procedures at 29 NHS trusts between Q1 2020 and Q3 2024. Main outcome measuresThe three main outcomes were, measured at the trust-quarter level: the total number of elective primary hip and knee replacements (surgical volume), the average length of stay in hospital, and the average waiting time from being added to the waiting list to hospital admission. ResultsThe opening of a surgical hub was associated with an increase of 43.75 hip and knee replacement surgeries per quarter (95% CI: 22.22 to 65.28), which represents a 19.1% increase compared to the pre-hub mean. Length of stay was reduced by 0.32 days (95% CI: - 0.48 to -0.16), a 7.8% reduction. There was no statistically significant effect on average waiting times (-14.96 days, 95% CI: -33.11 to 3.19). ConclusionsSurgical hubs appear to be effective at increasing the number of hip and knee replacements and reducing the time patients spend in hospital. However, in this study, they did not lead to a statistically significant reduction in waiting times overall.

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Therapist effects in real-world rehabilitation outcomes: a cohort study of the nationwide GLA:D osteoarthritis management program in Denmark

Obasohan, P. E.; Palmer, J.; Alderson, D.; Yu, D.; Gronne, D. T.; Roos, E. M.; Skou, S. T.; Peat, G. M.

2026-04-21 rehabilitation medicine and physical therapy 10.64898/2026.04.20.26351120 medRxiv
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ObjectiveUnlike several other fields of healthcare, little is known about the size of therapist effects on patient outcomes following rehabilitation for musculoskeletal conditions. We aimed to estimate the proportion of variance in patient outcomes from a structured rehabilitation program explained by therapist effects. MethodsFor our observational cohort study we accessed data from the national multicentre Good Life with osteoArthritis in Denmark (GLA:D) osteoarthritis management program. Analyses included 23,021 consecutive eligible adults with hip or knee osteoarthritis (mean (SD) age 65.0 (9.8) years, 71% female) treated by 657 therapists between October 2014 and February 2019. The primary outcome was [&ge;]30% reduction in pain intensity on 0-100 VAS at 3 months. Therapist effects were estimated as the variance partition coefficient (intra-class correlation coefficient (ICC)) from two-level random intercept logistic regression models before and after adjusting for patient-level case-mix factors and therapist-level characteristics (number of patients treated, days since therapist certification). Analyses were repeated for a range of secondary outcomes using multiply imputed data and complete-case analysis. Results52% of patients reported a [&ge;]30% reduction in pain intensity on 0-100 VAS at 3 months. In the null model the ICC was 0.007 (95%CI: 0.005, 0.009), which changed little after adjusting for patient- and therapist-level covariates. Upper confidence limits for ICC estimates across all secondary outcomes in multiply imputed and complete case analyses were less than 0.03. ConclusionsIn a nationally implemented osteoarthritis management program delivered by trained healthcare professionals, therapist effects made a minimal contribution to variation in patient outcomes. KEY MESSAGESO_ST_ABSWhat is already known on this topicC_ST_ABS Therapist effects - defined as the effect of a given therapist on patient outcomes as compared to another therapist - have been observed in several fields of healthcare and have important consequences for selection, training, and service improvement. In musculoskeletal rehabilitation five previous studies suggest that 1-12% of variation in patient-reported outcomes may be attributable to therapist effects, but these estimates were based on relatively small datasets resulting in substantial uncertainty. What this study addsOur cohort study analysed registry data from 2014-2019 on 23,021 patients and 647 trained therapists from the nationally implemented GLA:D structured osteoarthritis management program in Denmark. We found that therapist effects accounted for less than 3% of total variation in patient-reported pain and quality of life outcomes 3 months after beginning the program How this study might affect research, practice, or policyOur findings suggest that contextual factors that relate to therapist effects - therapist characteristics or therapist-patient interaction and alliance - make a minimal contribution to variation in patient outcomes from this structured, group-based rehabilitation intervention. Any contextual effects must be attributable to alternative sources, e.g. patient expectations, intervention setting.

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Family Constellations for All Clinical Conditions: A Systematic Review and Meta-analysis Showing a Lack of Supporting Evidence

Souza, F. L.; Cabral Souza, N.; Mendes, J. A. d. A.

2026-04-21 psychiatry and clinical psychology 10.64898/2026.04.19.26351231 medRxiv
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IntroductionFamily Constellation Therapy (FCT) has been widely disseminated in clinical, public health, and judicial settings despite persistent concerns regarding its theoretical basis, safety, and the limited availability of rigorous randomised evidence supporting its clinical use. ObjectiveThe aim of this systematic review is to assess the effects of FCT across all clinical conditions, explicitly considering both benefits and harms; and summarise the characteristics of studies and intervention settings used in randomised controlled trials of FCT. MethodsFollowing a prospectively registered protocol (CRD420251136190), we conducted a systematic search of seven databases (PubMed, EMBASE, APA PsycInfo, CENTRAL, BVS, Web of Science, and CINAHL) and grey literature (ICTRP and ProQuest database) without language or date restrictions to identify published and unpublished randomised controlled trials of FCT. Study selection, data extraction, risk of bias (RoB 2), and certainty of evidence (GRADE) were performed in duplicate. Statistical analyses followed a prospectively registered analysis plan with prespecified criteria for data pooling and for handling analytical limitations. ResultsNo reliable evidence was found to support the use of FCT for any condition across both clinical and non-clinical samples. All trials included were judged to be at high risk of bias and all comparisons were rated as very low-certainty evidence. Concerns regarding potential adverse effects were identified, and the available data was insufficient to establish the effectiveness of the intervention, precluding any clinical recommendation. ConclusionClinicians, policymakers, and consumers should reconsider adopting FCT while reliable evidence is not available.

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Group A Streptococcus Molecular Point of Care testing in a Paediatric Emergency Department

Mills, E. A.; Bingham, R.; Nijman, R. G.; Sriskandan, S.

2026-04-22 infectious diseases 10.64898/2026.04.20.26351279 medRxiv
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BackgroundAn upsurge in Streptococcus pyogenes infections 2022-2023 highlighted potential benefits of point-of-care tests (POCT) to support clinical pathways, prevent outbreaks, and optimise antibiotic use. ObjectivesWe conducted a pilot research study in a west London paediatric emergency department (ED) to determine whether a molecular POCT had potential to alter management in children who were also having a conventional throat swab taken for culture. MethodsChildren <16 years presenting to ED who had a throat swab requested by a clinician were invited to have a second swab taken for research purposes only. Clinical management was unaffected by the research swab result, which was processed using a molecular POCT that was not approved for use in the host NHS Trust. ResultsPrevalence of streptococcal infection was low during the study (May 2023-June 2025); swab positivity in symptomatic children was 12.8% (6/47). Overall, 38/49 (77.6%) participants who had throat swabs received antibiotics. Of those children recommended to receive antibiotics, 29/38 (76.3%) had a negative POCT. Mean time to reporting of positive throat swab culture results was 3.67 days (range 3-5 days) leading to occasional delay in treatment, although POCT identified positive results within minutes. ConclusionAntibiotic use was frequent and could be avoided or stopped by use of a rule out POCT in over three-quarters of children in the ED, if suspicion of S. pyogenes is the main driver for prescribing. POCT were easy to process and produced immediate results compared with culture, in theory enabling timely decision-making and avoiding treatment delay.

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"Isn't social prescribing what social workers have been doing forever"?: UK social worker perspectives on social prescribing and professional boundaries

White, C.; Price, E.; Walker, L.; Bell, J.; Revell, L.

2026-04-27 primary care research 10.64898/2026.04.24.26351583 medRxiv
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Social prescribing has assumed increasing dominance in policy and practice internationally, including in the UK, where it has an increasing role in addressing social needs such as isolation, and social determinants of ill health. Although General Practitioners are perceived as key referral sources, social workers in one locality were found to play a significant role in referral. This suggests that the social work role in this context has been under recognised and under explored. This study sought to explore social workers' perceptions and experiences of social prescribing through an online survey conducted from January to June 2022. All UK social workers were eligible to participate, regardless of whether they had made referrals. A total of 105 responses were collected from all UK nations. Data was analysed using inductive thematic analysis. Four key themes were generated: contended and contested boundaries; complementary spaces; delineated spaces of simplicity and complexity; social work under threat. Participants recognised that social prescribing could provide valuable client support and could be a useful resource for social workers. However, they also expressed concerns about overlapping professional boundaries and the potential for social prescribing to encroach on social work, perceiving it as most appropriate for the delivery of support to those with 'low level' needs.

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A Return-on-Investment Analysis of a Community-Based Diabetes Self-Management Program In New York City

Goldwater, J. C.; Harris, Y.; Das, S. K.; Fernandez Galvis, M. A.; Maru, D.; Jordan, W. B.; Sacaridiz, C.; Norwood, C.; Kim, S. S.; Neustrom, K.

2026-04-23 health economics 10.64898/2026.04.22.26351481 medRxiv
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OBJECTIVE: To evaluate the return on investment (ROI) of a community based Diabetes Self Management Program (DSMP) enhanced with health related social needs (HRSN) screening and referrals, implemented by the New York City (NYC) Department of Health and Mental Hygiene with three community based organizations in highly impacted, under resourced neighborhoods. RESEARCH DESIGN AND METHODS: A retrospective cost benefit analysis from a public sector payer perspective was conducted among 171 adults with type 2 diabetes who completed a six week, peer led DSMP delivered by community health workers (CHWs) in English, Spanish, and Korean during 2018 2019. A time driven, activity based costing model captured direct implementation costs, CHW workforce turnover, and administrative overhead. Monetized benefits included avoided diabetes related complications, reductions in self reported emergency department (ED) visits and hospitalizations, and quality adjusted life year (QALY) gains from improved medication adherence. Univariate sensitivity analyses tested robustness under conservative assumptions. RESULTS: Total program costs were $179,224; monetized benefits totaled $1,824,213, yielding a net benefit of $1,644,989 and an ROI of 918%, approximately $10 returned per $1 invested. Excluding QALY gains, ROI remained 551%. Self reported ED visits declined from 149 to 82 and hospitalizations from 93 to 24 in the six months following intervention. Over 80% of participants reported housing instability; 72% were Medicaid covered and 16% uninsured. Sensitivity analyses confirmed a positive ROI under all conservative scenarios. CONCLUSIONS: A CHW led, community based DSMP integrated with HRSN screening and referrals delivered substantial economic and public health value among adults facing housing instability and structural barriers to care. Findings support inclusion of DSMP as a covered benefit in Medicaid managed care, value based payment arrangements, and housing access initiatives to advance equitable diabetes outcomes.

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Stable isotopes (δ13C, δ15N, δ34S) suggest eelgrass (Zostera sp.) foddering of Late Iron Age sheep (Ovis aries) in Denmark

Jaeger, J. H.; Tarrant, D.; Richards, M. P.; Ulriksen, J.; Sarauw, T.; Kastholm, O. T.; Nielsen, J.

2026-04-22 zoology 10.64898/2026.04.19.719466 medRxiv
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Stable isotope analysis provides an important tool for reconstructing past livestock management practices and landscape use. However, isotopic data for sheep from Late Iron Age (AD 375/400-1050) Denmark remain limited. Here, we present bulk bone collagen {delta}{superscript 1}3C, {delta}{superscript 1}N, and {delta}3S isotope analyses of 27 sheep (Ovis aries) from six archaeological sites in Denmark, dated to the Germanic Iron Age (AD 375/400-750) and Viking Age (AD 750-1050). The analysed sheep exhibit a consistent pattern of enriched {delta}13C values relative to previously published isotopic datasets for Scandinavian livestock, while {delta}15N values display substantial inter-individual variability. Sulfur isotope values fall within moderate ranges consistent with mixed terrestrial and coastal environmental influences. The decoupling of {delta}13C enrichment from elevated {delta}15N values suggests that the observed carbon isotope signal does not reflect marine protein consumption but rather the incorporation of a 13C-enriched plant resource into sheep diets. We propose that eelgrass (Zostera sp.), either through direct grazing in coastal environments or supplementary foddering with harvested eelgrass, represents a plausible dietary source to explain this isotopic pattern. The results indicate that Late Iron Age sheep management strategies in Denmark incorporated coastal plant resources within flexible pastoral systems, potentially supporting intensified wool production associated with expanding textile economies. HighlightsO_LIStable isotope values of Late Iron Age sheep show some dietary marine input. C_LIO_LIEnriched {delta}13C values suggest eelgrass as supplementary fodder. C_LIO_LI{delta}34S values indicate adaptive grazing across coastal and inland landscapes. C_LI