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Systematic Reviews

Springer Science and Business Media LLC

Preprints posted in the last 30 days, ranked by how well they match Systematic Reviews's content profile, based on 11 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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Prespecified Internal Pilot and Feasibility Framework for a Pragmatic Randomized Controlled Trial Comparing Mechanical Diagnosis and Therapy Versus Generalized Exercise in Surgeons With Chronic Spinal Pain: A Protocol

Kjaergaard, C.; Madeleine, P.; Dalboege, A.; Steinhilber, B.; Olesen, A. V.; Nielsen, T. K.

2026-04-08 occupational and environmental health 10.64898/2026.04.08.26350288 medRxiv
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Background Trials in occupational populations, such as surgeons, face feasibility challenges due to high workload, restricted availability, and clinical heterogeneity, which may compromise recruitment, adherence, and retention. Objective To prespecify the feasibility framework and progression criteria for an internal pilot phase embedded within a pragmatic randomized controlled trial (RCT) comparing Mechanical Diagnosis and Therapy with generalized exercise in surgeons with chronic spinal pain. Design Protocol for a prespecified internal pilot phase embedded within a pragmatic, two-arm, parallel-group RCT. Methods The internal pilot will include the first four months of recruitment and aims to randomize at least 12 participants. Feasibility will be assessed across predefined domains, i.e., recruitment, eligibility, consent, intervention uptake, adherence, retention, data completeness, and treatment fidelity. Each domain is operationally defined and linked to prespecified progression criteria to ensure interpretability and decision-making utility. Criteria will be interpreted collectively to guide trial continuation. A minimal qualitative process evaluation will be embedded. Ethics and dissemination The host trial has received ethical approval (N-20240046) and is registered at ClinicalTrials.gov (NCT07293130). The findings from the internal pilot will be reported in a separate feasibility manuscript.

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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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Effects of Mindfulness-Based Interventions on Executive Function in Children and Adolescents: A Systematic Review and Meta-Analysis

Li, N.

2026-04-20 psychiatry and clinical psychology 10.64898/2026.04.18.26351184 medRxiv
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BackgroundMindfulness-based interventions (MBIs) have been increasingly adopted in educational settings to support cognitive development in youth. Executive function (EF)--encompassing inhibitory control, working memory, and cognitive flexibility--is a plausible target of MBI given its reliance on attention regulation. However, prior reviews have yielded mixed conclusions, partly due to inconsistent construct definitions and the pooling of heterogeneous outcome measures. ObjectivesTo (1) estimate the pooled effect of MBI on EF in youth aged 3-18 years using only construct-validated, direct EF measures, (2) examine potential moderators including age group, EF domain, and risk of bias, and (3) test dose-response relationships via meta-regression on intervention duration. MethodsWe searched PubMed, PsycINFO, CINAHL, Scopus, and Web of Science from inception to March 2026, supplemented by reference-list searches from two existing systematic reviews and a scoping review. Only English-language publications were eligible. Eligible studies were randomised controlled trials (RCTs) or quasi-RCTs of MBI (excluding yoga-only interventions) in typically developing youth, with at least one direct behavioural or computerised EF outcome. Risk of bias was assessed using Cochrane RoB 2. Hedges g was computed for each study, and pooled using a DerSimonian-Laird random-effects model. Subgroup analyses by age group, EF domain, and risk of bias were conducted, alongside leave-one-out sensitivity analyses, Eggers regression test, trim-and-fill, and Knapp-Hartung-adjusted meta-regression on intervention duration. Evidence certainty was rated using GRADE. ResultsThirteen RCTs (nine school-age, four preschool; total N = 1,560) met inclusion criteria. The pooled effect was g = 0.365 (95% CI 0.264 to 0.465; p < .00001), with negligible heterogeneity (I2 = 0.0%; Q = 6.76, p = .87). Effects were consistent across age groups (school-age g = 0.389; preschool g = 0.318) and EF domains (inhibitory control, working memory, cognitive flexibility; pbetween = .60). Meta-regression on intervention duration (4-20 weeks) was non-significant (p = .79). The effect was robust in leave-one-out analyses, in the low risk-of-bias subgroup (g = 0.361; k = 8), and after trim-and-fill adjustment (g = 0.354). The 95% prediction interval (0.252 to 0.477) was entirely positive. GRADE certainty was rated MODERATE, downgraded once for risk of bias. ConclusionsMBIs appear to produce a small, statistically significant improvement in EF in youth aged 3-18 years, with moderate certainty of evidence per the GRADE framework. The effect is consistent across preschool and school-age samples and across EF domains, with no significant dose-response relationship within the 4-20 week range studied. Emerging mediation evidence suggests that EF improvement may serve as an important pathway through which MBI supports emotion regulation, though this requires replication. Further large-scale, pre-registered RCTs with active control conditions and longitudinal follow-up are warranted.

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Effect of a theory-driven health education intervention on personal protective equipment use among commercial motorcycle riders in Cameroon: A quasi-experimental study

Ukah, C. E.; Tendongfor, N.; Hubbard, A.; Tanue, E. A.; Oke, R.; Bassah, N.; Yunika, L. K.; Ngu, C. N.; Christie, S. A.; Nsagha, D. S.; Chichom-Mefire, A.; Juillard, C.

2026-04-12 public and global health 10.64898/2026.04.08.26350441 medRxiv
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BackgroundCommercial motorcycle riders are among the most vulnerable road users in low- and middle-income countries and contribute substantially to the burden of road traffic injuries. The use of personal protective equipment (PPE), including helmets and protective clothing, reduces injury severity; however, uptake remains suboptimal. This study evaluated the effectiveness of a theory-driven health education intervention in improving knowledge, attitudes, and use of PPE among commercial motorcycle riders in Cameroon. MethodsA quasi-experimental, non-randomized controlled before-and-after study was conducted in Limbe (intervention) and Tiko (control) Health Districts between August 4, 2024, and April 6, 2025. Participants were recruited from a cohort of commercial motorcycle riders and followed over an eight-month intervention period. The intervention, guided by the Health Belief Model and developed using the Intervention Mapping framework, combined face-to-face sensitization sessions with mobile phone-based educational messaging adapted to participants literacy levels and communication preferences. Data were collected at baseline and endline using structured questionnaires and direct observation checklists. Intervention effects were estimated using difference-in-differences analysis with generalized estimating equations, adjusting for socio-demographic factors. ResultsA total of 313 riders were enrolled at baseline (183 intervention, 130 control), with 249 retained at endline (149 intervention, 100 control). The intervention was associated with significant improvements in PPE knowledge ({beta} = 2.91; 95% CI: 2.14-3.68; p < 0.001) and attitudes ({beta} = 5.76; 95% CI: 4.32-7.21; p < 0.001) compared with the control group. No statistically significant effect was observed for PPE practice scores ({beta} = 0.21; 95% CI: -0.09-0.52; p = 0.171). Among individual PPE items, helmet use increased significantly in the intervention group relative to the control group (AOR = 2.38; 95% CI: 1.19-9.45; p = 0.036), while no significant effects were observed for gloves, trousers, eyeglasses, or closed-toe shoes. ConclusionThe theory-driven health education intervention significantly improved knowledge and attitudes toward PPE and increased helmet use among commercial motorcycle riders but did not lead to broader improvements in the uptake of other protective equipment. These findings highlight the need for complementary structural and policy interventions to address persistent barriers to PPE use in similar low-resource settings. Trial registrationClinicalTrials.gov Identifier: NCT07087444 (registered July 28, 2025, retrospectively)

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The Effect of Vitamin-D Supplementation on HDAC2 Levels in Stable COPD Patients

Donastin, A.; Irawan, D.; Effendy, E.; Iryawan, R. D. A.; Nuari, N.; Oktaviana, B. M.; Yahya, D.; Muhammad, A. R.

2026-04-08 respiratory medicine 10.64898/2026.04.05.26348641 medRxiv
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Background: Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of global mortality, with persistent lung inflammation contributing to disease progression. This inflammation is partly associated with reduced levels of histone deacetylase 2 (HDAC2). Previous studies suggest that Vitamin D may modulate HDAC2 levels. This study aimed to evaluate the effect of Vitamin D supplementation on HDAC2 expression in stable COPD patients. This experimental study aimed to evaluate the effect of vitamin D supplementation on HDAC2 expression in stable COPD patients at Jemursari Islamic Hospital. Methods: Five COPD patients received a daily dose of 5000 IU of Vitamin D for three months. Serum levels of 25(OH)D3 and HDAC2 were measured before and after the intervention. Results: Vitamin D supplementation resulted in a significant increase in both 25(OH)D and HDAC2 levels. Pulmonary function parameters showed an increasing trend, however, no statistically significant differences were observed. Conclusion: Vitamin D supplementation was associated with increased HDAC2 levels, suggesting a potential anti-inflammatory effect. However, no significant improvement in pulmonary function was observed. Further studies are needed to determine its clinical impact.

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Risk of Post-acute Symptoms and Conditions After SARS-CoV-2 Compared to Other Respiratory Viral Infections: A Systematic Review and Meta-Analysis

Pinto, T. F.; Santoro, A.; Oliveira, A. L. G.; Tavares, T. S.; Almeida, A.; Incardona, F.; Marchetti, G.; Cozzi-Lepri, A.; Pinto, J.; Caporali, J. F. M.

2026-04-13 infectious diseases 10.64898/2026.04.11.26350682 medRxiv
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Background: How post-COVID-19 condition (PCC) differs from post-acute infection syndromes (PAIS) caused by other respiratory viruses remains uncertain. Comparing these conditions may clarify whether post-acute symptoms reflect specific consequences of SARS-CoV-2 infection or broader post-viral mechanisms. Methods: We conducted a systematic review and meta-analysis of cohort studies comparing persistent symptoms or conditions in adults after SARS-CoV-2 infection with those following other acute respiratory viral infections. PubMed, Embase, and Scopus were searched. Random-effects models were used to estimate pooled risks. Results: Among 9,371 records screened, 22 studies were included and 14 contributed to the meta-analysis. Increased risk after SARS-CoV-2 infection was observed for pulmonary embolism, abnormal breathing, fatigue, hemorrhagic stroke, memory loss/brain fog, and palpitations; heart rate abnormalities showed borderline significance. For most other outcomes pooled estimates were inconclusive. Conclusions: Only a subset of outcomes appears more frequent after SARS-CoV-2 infection, suggesting many symptoms attributed to PCC may reflect broader post-viral syndromes.

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Preventive care in orthopaedic clinical services - testing the acceptability of an online health risk self-assessment tool using a multi-method design

Davidson, S. R.; Browne, S.; Giles, L.; Gillham, K.; Haskins, R.; Campbell, E.

2026-04-10 public and global health 10.64898/2026.04.09.26350435 medRxiv
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Abstract Background Musculoskeletal conditions, such as back pain and osteoarthritis, are common and disabling disorders. Musculoskeletal conditions are closely related to chronic disease risk factors like smoking/vaping, poor nutrition, alcohol misuse and physical inactivity and impact a person's risk of falling (SNAPF). Preventive care for SNAPF risks is often overlooked. Online delivery of preventive care may increase the provision of this care. We aimed to assess if an online tool for SNAPF risks would be used by and acceptable to patients waiting for an orthopaedic consultation. Methods We completed a multi-method study to test an online health risk self-assessment tool. A random sample of 300 people on the orthopaedic outpatient waiting list aged 18-64 years were sent the tool in batches of 20-50. The tool assessed SNAPF risks and provided feedback against national guidelines. After each batch, we completed feedback interviews with participants to assess acceptability and updated the tool. We summarised quantitative data using descriptive statistics and qualitative data using thematic analysis. Results Of the 300 participants sent the tool, 51.3% were female, 8.6% identified as Aboriginal and/or Torres Strait Islander, with a mean (SD) age of 52.0 years (11.2). There were 170 participants (59.2%) who completed the tool, 117 who did not complete it, and 13 participants who were excluded from analysis because they did not receive the SMS. We conducted 184 feedback interviews, including 125 'completers' and 59 'non-completers'. The percentage of participants who felt that SMS was an appropriate way to receive the tool was 84.7% of 'completers' and 50% of 'non-completers'. The two most common reasons for not completing the tool were due to perceived risk (13/59, 22.0%), and the SMS was received at an inconvenient time (11/59, 18.6%). Qualitative data from the feedback interviews captured three enablers: i) design, ii) high importance, and iii) engagement with health service, along with four barriers: i) design, ii) risk, iii) relevance, and iv) engagement with health service. Conclusion Our study found that an online health risk self-assessment tool appears to be an acceptable way to assess chronic disease and falls risk factors for people on an orthopaedic waitlist.

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The Effects of Gender Affirming Hormone Treatment on Transgender Mens Musculoskeletal Health: A Systematic Review and Meta-Analysis

Hu, K.; Brown, A.; Montagner-Moraes, S.; Singh, J.; Charlton, L.; Barrett, J.; Hamilton, B. R.

2026-04-02 endocrinology 10.64898/2026.03.31.26349844 medRxiv
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Background: A previous meta-analysis by Singh-Ospina et al. (2017) suggested that Gender affirming hormone treatment (GAHT) does not change transgender mens bone mineral density (BMD) at any clinically relevant site; emerging studies and advances in synthesis methods necessitate an updated evaluation. The primary aim was to update the bone measures of Singh-Ospina et al. (2017), with the secondary aim to expand measures to how GAHT affects musculoskeletal health. Methods: A systematic review with meta-analysis was conducted using studies published in English up to 31 July 2024, identified through three electronic databases (PubMed, Embase, SportDiscus), and final cross-referencing in summer 2025. Primary outcomes were longitudinal changes in femoral neck (FN), lumbar spine (LS), and total hip (TH) bone mineral density (BMD). Secondary outcomes included body composition and muscle strength. Standardised effect sizes (Hedges g) were pooled using the inverse heterogeneity (IVhet) model. Results: GAHT (4 years) was not associated with significant longitudinal changes in FN, LS, or TH BMD. In contrast, substantial anabolic effects were observed, including increases in BMI (g = 0.13), body mass (g = 0.18), fat-free mass (g = 0.59), and muscle strength (g = 0.86). Heterogeneity was high for muscle strength, FN and TH BMD, limiting confidence in pooled estimates. Conversely, changes in LS BMD, BMI, body mass and fat-free mass demonstrated low heterogeneity and greater consistency across studies. Conclusion: Masculinising GAHT does not negatively affect clinically relevant BMD sites while reliably increasing lean mass and muscle strength; however, the evidence base remains methodologically weak and highly variable, particularly for FN and TH. The need for continued clinical monitoring of bone health and muscle function, alongside high-quality longitudinal research incorporating advanced imaging modalities such as HR pQCT is emphasised. Strengthening the evidence base will be essential for clarifying long-term skeletal trajectories as transgender men age. PROSPERO registration: CRD42024573102

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The Beat Goes On: A Mixed-Methods Analysis in Developing Effective Police Leaver Transitions

Vaportzis, E.; Edwards, W.

2026-03-31 occupational and environmental health 10.64898/2026.03.26.26348236 medRxiv
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The end-of-career stage of the police lifecycle represents a profound shift in identity and psychological stability, yet it remains historically neglected in research. This mixed-methods study investigated perspectives of UK police leavers and those approaching retirement (N = 325) regarding desired improvements to organisational support. Content analysis identified four themes: Holistic support and long-term welfare, Institutional culture and professional worth, Navigating the structural transition, and Individual and systemic perspectives. Findings suggest that the psychological contract between the officer and the organisation is often breached at the exit point, shifting from a relational bond to a transactional disposal. Middle-ranking officers and early leavers report the highest levels of institutional abandonment. To address these gaps, this paper makes recommendations for developing effective transitions. By implementing post-service welfare, and adopting structured resettlement models, police organisations can fulfil their duty of care and mend the psychological contract for those who have served.

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A living systematic review, meta-analysis, and open data resource of trials of MDMA-assisted therapy for PTSD

Sevchik, B. L.; Singleton, S. P.; Lahey, A.; Cuijpers, P.; Harrer, M.; Jones, M. T.; Nayak, S. M.; Strain, E. C.; Vandekar, S. N.; Yaden, D. B.; Dworkin, R. H.; Scott, J. C.; Satterthwaite, T. D.

2026-03-30 psychiatry and clinical psychology 10.64898/2026.03.27.26349536 medRxiv
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3,4-methylenedioxymethamphetamine (MDMA) has emerged as a potential treatment for post-traumatic stress disorder (PTSD), generating considerable enthusiasm in the field. However, rapidly changing evidence in a fast-moving field can be challenging to integrate. Here, we present a living systematic review and open-data meta-analytic resource on MDMA treatment for PTSD. In this initial release, six randomized controlled trials comprising 286 participants are included in the database. Our primary model uses inverse-variance random-effects meta-analysis of standardized mean differences on primary outcomes of PTSD. Compared to control conditions, MDMA showed a greater reduction in PTSD symptoms (Hedges' g = -0.71). Meta-regression on both the number of dosing sessions and cumulative dose showed that a higher number of dosing sessions and a higher cumulative dose was related to larger effects of MDMA. Treatment with MDMA as compared to placebo also resulted in higher response (risk ratio (RR) = 1.35) and remission (RR = 2.25) rates. Most studies included in the database had a low risk of bias according to Cochrane guidelines, though these fail to capture pertinent challenges in the field such as expectancy, functional unblinding, potential issues with study conduct, and safety. The current findings were assigned an overall low certainty rating using the GRADE approach. Together, this systematic review and meta-analysis suggests that MDMA-assisted therapy results in short-term decreases in PTSD symptoms across studies to date, though more trials are needed. This living systematic review, meta-analysis, database, and online dashboard (sypres.io) will continue to be updated as evidence emerges, providing a valuable, open, and transparent resource for researchers in a rapidly evolving field.

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Heat Exposure, Occupational Injury Risk, and Economic Costs in New York State

Laskaris, Z.; Baron, S.; Markowitz, S. B.

2026-04-22 occupational and environmental health 10.64898/2026.04.20.26351297 medRxiv
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ObjectivesRising temperatures are a major climate-related hazard for U.S. workers, increasing heat-related illness and a broad range of occupational injuries through indirect pathways often overlooked in economic evaluations. We examined the association between temperature and occupational injury and illness and quantified heat-attributable injuries (including illnesses) and costs in New York State. MethodsWe conducted a time-stratified case-crossover study of 591,257 workers compensation (WC) claims during the warm season (2016-2024). Daily maximum temperature was linked to injury date and county and modeled using natural cubic splines, with effect modification by industry and worker characteristics. ResultsInjury risk increased with temperature, becoming statistically significant at approximately 78{degrees}F. Relative to 65{degrees}F, injury odds increased to 1.06 (95% CI: 1.01-1.10) at 80{degrees}F, 1.12 (1.07-1.18) at 90{degrees}F, and 1.17 (1.11-1.23) at 95{degrees}F. Overall, 5.0% of claims (2,322 annually) were attributable to heat. At temperatures [&ge;]80{degrees}F, an estimated 1,729 excess injuries occurred annually, generating approximately $46 million in WC costs. An estimated $3.2 million to $36.1 million in medical expenditures were associated with incomplete claims, likely borne outside the WC system. ConclusionsThese findings demonstrate substantial economic costs not fully captured within WC and support workplace heat protections as a cost-containment strategy that can reduce health care spending and strengthen workforce resilience.

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DR. INFO at the Point of Care: A Prospective Pilot Study of an Agentic AI Clinical Assistant

Corga Da Silva, R.; Romano, M.; Mendes, T.; Isidoro, M.; Ravichandran, S.; Kumar, S.; van der Heijden, M.; Fail, O.; Gnanapragasam, V. E.

2026-04-01 health informatics 10.64898/2026.03.31.26349817 medRxiv
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Background: Clinical documentation and information retrieval consume over half of physicians working hours, contributing to cognitive overload and burnout. While artificial intelligence offers a potential solution, concerns over hallucinations and source reliability have limited adoption at the point of care. Objective: To evaluate clinician-reported time savings, decision-making support, and satisfaction with DR. INFO, an agentic AI clinical assistant, in routine clinical practice. Methods: In this prospective, single-arm pilot study, 29 clinicians across multiple specialties in Portuguese healthcare institutions used DR. INFO v1.0 over five working days within a two-week period. Outcomes were assessed via daily Likert-scale evaluations and a final Net Promoter Score. Non-parametric methods were used throughout. Results: Clinicians reported high perceived time saving (mean 4.27/5; 95% CI: 3.97-4.57) and decision support (4.16/5; 95% CI: 3.86-4.45), with ratings stable across all study days and no evidence of attrition bias. The NPS was 81.2, with no detractors. Conclusions: Clinicians across specialties and career stages reported sustained satisfaction with DR. INFO for both time efficiency and clinical decision support. Validation in larger, controlled studies with objective outcome measures is warranted. Keywords: Medical AI assistant, LLMs in healthcare, Agentic AI, Clinical decision support, Point of care AI

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Cochrane Evaluation of (Semi-) Automated Review (CESAR) Methods: Protocol for an adaptive platform study within reviews

Gartlehner, G.; Banda, S.; Callaghan, M.; Chase, J.-A.; Dobrescu, A.; Eisele-Metzger, A.; Flemyng, E.; Gardner, S.; Griebler, U.; Helfer, B.; Jemiolo, P.; Macura, B.; Minx, J. C.; Noel-Storr, A.; Rajabzadeh Tahmasebi, N.; Sharifan, A.; Meerpohl, J.; Thomas, J.

2026-04-15 health informatics 10.64898/2026.04.13.26350802 medRxiv
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Background: Artificial intelligence (AI) has the potential to improve the efficiency of evidence synthesis and reduce human error. However, robust methods for evaluating rapidly evolving AI tools within the practical workflows of evidence synthesis remain underdeveloped. This protocol describes a study design for assessing the effectiveness, efficiency, and usability of AI tools in comparison to traditional human-only workflows in the context of Cochrane systematic reviews. Methods: Members of the Cochrane Evaluation of (Semi-) Automated Review (CESAR) Methods Project developed an adaptive platform study-within-a-review (SWAR) design, modeled after clinical platform trials. This design employs a master protocol to concurrently evaluate multiple AI tools (interventions) against a standard human-only process (control) across three key review tasks: title and abstract screening, full-text screening, and data extraction. The adaptive framework allows for the addition or removal of AI tools based on interim performance analyses without necessitating a restart of the study. Performance will be assessed using metrics such as accuracy (sensitivity, specificity, precision), efficiency (time on task), response stability, impact of errors, and usability, in alignment with Responsible use of AI in evidence SynthEsis (RAISE) principles. Results: The study will generate comparative data about the performance and usability of specific AI tools employed in a semi- or fully automated manner relative to standard human effort. The protocol provides a flexible framework for the assessment of AI tools in evidence synthesis, addressing the limitations of static, one-time evaluations. Discussion: This study protocol presents a novel methodological approach to addressing the challenges of evaluating AI tools for evidence syntheses. By validating entire workflows rather than individual technologies, the findings will establish an evidence base for determining the viability of integrating AI into evidence-synthesis workflows. The adaptive design of this study is flexible and can be adopted by other investigators, ensuring that the evaluation framework remains relevant as new tools emerge.

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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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No One Left Behind: Adaptive Tablet Modalities for Digitally Excluded Emergency Department Patients Design, Implementation, and Social Evidence for an Impairment-First Interface

Chowdhury, A.; Irtiza, A.

2026-04-13 health systems and quality improvement 10.64898/2026.04.11.26350686 medRxiv
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Background: The urgent care departments in Europe face a structural paradox: accelerating digitalisation is accompanied by a patient population that is disproportionately unable to engage with standard digital tools. An internal analysis at the Emergency Department (Akutafdelingen) of Nordsjaellands Hospital in Hilleroed, Denmark found that 43% of emergency patients struggle with digital solutions - a figure that reflects the predictable composition of acute care populations rather than any individual failing. Objective: This paper presents the design, iterative development, and secondary validation of the ED Adaptive Interface (v5): a prototype adaptive patient terminal developed in response to this challenge. The system operationalises what the author terms impairment-first design - a methodology that treats the most constrained patient experience as the primary design problem and derives the standard experience as a subset. The interface configures itself in under ten seconds via nurse-led setup, adapting across four axes of impairment: visual, motor, speech, and cognitive. System: Version 4 supports five accessibility modes, a heatmap pain assessment grid, a Privacy and Dignity panel, a live workflow tracker with care notifications, structured dual-category help requests, and plain-language medical term definitions across four languages. Version 5, reported here for the first time, introduces a Condition Worsening Escalation button, a Referral Pathway Display, a "Why Am I Waiting?" triage explainer, a Symptom Progression Log, MinSP/Yellow Card Scan simulation, expanded language support (seven languages: English, Danish, Arabic with full RTL layout, Turkish, Romanian, Polish, and Somali), and an expanded ten-item Communication Board. The entire system runs as a single 79-kilobyte HTML file with zero infrastructure requirements. Methods: To base the design on patient-generated evidence, two independent social media threads were subjected to an inductive thematic analysis (Braun and Clarke, 2006): a primary corpus of 83 entries in the Facebook group Foreigners in Denmark (collected March 2026) and a corroborating corpus in an international community group in the Aarhus region (collected April 2026). All identifiers in both datasets were fully anonymised under GDPR Article 89 research provisions prior to analysis. No participants were contacted. Generative AI tools were used to assist with drafting, writing, and prototype code development; all scientific content, data collection, analysis, and conclusions are the sole responsibility of the authors. Results: The first discourse corpus produced five major themes corresponding to the five problem areas the prototype was designed to address: system navigation and triage literacy gaps (31 entries); language and cultural barriers (6 entries); communication failures during care (5 entries); staff overload and capacity constraints (8 entries); and pain and severity assessment failures (14 entries). The corroborating dataset supported all five themes and introduced two additional themes: differential treatment of international patients and medical gaslighting as a long-term pattern of patient advocacy failure. One structural finding - the five most-liked comments incorrectly criticised the original poster for self-referring when she had received explicit 1813 telephone triage approval - directly inspired the Referral Pathway Display and "Why Am I Waiting?" features in v5. Conclusions: The convergence of design rationale and independent social evidence across all five problem categories suggests that impairment-first design is not a niche accessibility concern but a structural approach to healthcare interface quality. The prototype is ready for a structured clinical pilot using the System Usability Scale (SUS) and semi-structured staff interviews. The long-term roadmap includes full MinSP integration, hospital PMS connectivity, and clinical validation.

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A rights-based intervention integrating social work and ophthalmic care for people experiencing or at risk of homelessness

Hassani, A.; Pecar, K.; Soliman, M.; Bunyon, P.; Ellinger, C.; Tulysewskid, G.; Croft, J.; Carillo, C.; Wewegama, G.; du Plessis-Schneider, S.; Estevez, J. J.

2026-04-24 public and global health 10.64898/2026.04.22.26351525 medRxiv
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Background Individuals experiencing or at risk of homelessness face substantial barriers to preventive eye care that are poorly addressed by standard service models. Interdisciplinary optometry-social work collaboration offers a rights-based approach to improving engagement and continuity of care. Methods A convergent mixed-methods study was conducted between February and August 2024 at a multidisciplinary community centre. Clients experiencing or at risk of homelessness received integrated optometry and social work assessment and were prioritised as high, medium, or low based on combined clinical and social risk. Social work follow-up was guided by the Triple Mandate and W-Questions framework. Quantitative data were summarised using mean (SD), median [IQR], or n (%). Qualitative case notes were analysed using content analysis with inductive coding and secondary review for consistency. Results A total of 165 clients had priority categories coded (high: 68; medium: 47; low: 154). Demographic data were available for 132 clients (60% male; mean age 49.5 years [SD 16]); 27% had not completed high school, 89% reported weekly income below AUD 1000, and 28% had vision impairment. Two hundred forty-five case-note entries were consolidated into 146 unique records. SMS (46%) and phone calls (38%) were the most documented contact methods, although only 21% of calls were answered; missed calls (13%) and disconnected numbers (7%) were common. Multi-modal contact was more frequently documented for higher-priority clients. Appointment assistance was the most recorded facilitator (71%), while rights-based supports, including interpreter and transport assistance, were infrequently documented (<=5%). Qualitative analysis identified unstable communication, reliance on informal supports, and service fragmentation as key influences on recall outcomes. Conclusion This study supports an interdisciplinary, rights-based optometry-social work model to address barriers to preventive eye care among people experiencing or at risk of homelessness. Embedding structured handovers and tiered recall processes within community-based services may strengthen continuity and accountability for high-priority clients. Future implementation should evaluate outcomes related to equity of reach, service integration, and sustained engagement in care.

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Public involvement and co-design of longitudinal studies of sleep health alongside young people with rare genetic conditions

Clayton, J. P.; Haddon, J. E.; Hall, J.; Attwood, M.; Jarrold, C.; Berndt, L. C. S.; Saka, A.; van den Bree, M. B. M.; Jones, M. W.; Collaboration: Sleep Detectives Lived Experience Advisory Panel,

2026-04-13 psychiatry and clinical psychology 10.64898/2026.04.07.26348880 medRxiv
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BackgroundThe mechanisms underpinning associations between sleep and psychiatric conditions are poorly understood, partly due to challenges with longitudinal sleep studies outside the laboratory. Children and young people with rare genetic conditions caused by micro-deletions or -duplications (Copy Number Variants or CNVs) have increased risk of disrupted sleep and poorer neurodevelopmental (ND) outcomes. The Sleep Detectives study aims to investigate this by tracking behavioural and neurophysiological signatures of sleep health in young people with ND risk or ND-CNVs. To optimally achieve this, we have worked with families with ND-CNVs and charity partners to co-design our tools, methods, study protocol, and materials. MethodWe established a Lived Experience Advisory Group (LEAP) with nine parents and 13 children and young people with ND-CNVs, alongside representatives of UK charities Max Appeal and Unique. Together, the research team and LEAP co-designed two in-person family workshops in which we collected feedback on the acceptability of sleep monitoring devices, the design of bespoke cognitive tasks, and overall study protocol. Informal interviews and surveys were conducted with LEAP members and researchers, to enable the team to reflect and learn from their Patient/Public Involvement (PPI) experiences. ResultsKey outputs included pre-workshop invitation and briefing materials and insights that iteratively refined the main study design, including the need for flexibility to increase accessibility, selection of sleep devices, customisation of cognitive tasks, and choice of language in documents. The PPI process was highly valued by LEAP members, workshop attendees, and the research team. One investigator described the PPI work as "reinvigorating my love of research by helping me focus on science that matters". Participating families also established peer support networks. ConclusionsInvolving families affected by ND-CNVs in co-designing the Sleep Detectives study maximised opportunities for acceptability, accessibility and scalability. The research team gained inspiration and deeper understanding of the impact of ND-CNVs on families. Families gained awareness about research, established connections with each other and peer support, and were enthusiastic about future research involvement. This experience empowered families to engage more deeply with the research process and helped the PPI work to be more impactful and inclusive. Plain English summaryChildren and young people with rare genetic conditions caused by small deletion or duplication of genetic material are more likely to experience sleep difficulties such as insomnia, restless sleep, and tiredness. They also show an increased likelihood of neurodevelopmental conditions such as learning disability and autism, and mental health issues such as anxiety. The Sleep Detectives team wanted to explore how these genetic conditions affect childrens sleep, cognition and psychiatric health. To make sure that the project design was well suited to the children and young people that would be invited to participate, the team worked closely with families to design the study. Parents and caregivers of affected children and young people were invited to join a Lived Experience Advisory Panel (LEAP), together with charity representatives and Sleep Detective researchers, to co-design two hands-on workshops, and advise on study design. Children and young people and parents/caregivers attending the workshops tried out and provided feedback on tools and devices that the research team were developing. They also advised on the arrangements and support families might need whilst taking part, and on the study protocol. This collaborative approach helped ensure the study design was optimally suited for the recruitment and participation of children and young people and their families. This report documents our public involvement work for the Sleep Detectives study, illustrating the difference the partnership between researchers and families has made to the project, and the wider benefits for all concerned.

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Researcher perspectives on the value and impact of population-based cohort studies

O'Connor, M.; O'Connor, E.; Hughes, E. K.; Bann, D.; Knight, K.; Tabor, E.; Bridger-Staatz, C.; Gray, S.; Burgner, D.; Olsson, C. A.

2026-04-07 epidemiology 10.64898/2026.04.06.26349895 medRxiv
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Background: Population-based cohort studies are increasingly expected to demonstrate benefits for public health and wider society. However, there is limited systematic evidence on what such impact entails or how it is generated and sustained. To address this gap, we examined researcher perspectives on the impact of cohort studies. Methods: We conducted, to our knowledge, the first quantitative study of researcher views on cohort impact, recruiting active cohort researchers through national and international networks between August and December 2025. The anonymous cross-sectional survey captured researcher characteristics, perceived contributions, impact processes, challenges, and open-ended reflections. Results: A total of 163 cohort researchers participated, primarily from Australia (42%) and the UK (23%). Participants perceived their work as informing a wide range of societal issues and reported investing an average of 24% of their work time in impact-related activities. While most respondents (73%) believed their research leads to tangible policy or practice change, two thirds indicated that impact is rarely or never demonstrable shortly after study completion (67%) and seldom attributable to a single study (67%). Key concerns included pressure to overstate contributions (80%), perceived disadvantages for cohort studies in impact assessments (78%), and inadequate skills or resources to achieve impact (65%). Conclusions: Cohort researchers perceive their work as generating broad societal contributions and invest substantial effort in supporting impact. However, they face systemic challenges in both achieving and demonstrating impact. These findings highlight the need for impact frameworks that better capture complexity, long-term influence, and cumulative contributions, while mitigating unintended consequences.

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Assessing the efficacy of behaviourally informed invitation messaging in increasing attendance at the NHS Targeted Lung Health Check: A randomised experimental study

Tan, X.; Danka, M. N.; Urbanski, S.; Kitsawat, P.; McElvaney, T. J.; Jundi, S.; Porter, L.; Gericke, C.

2026-04-24 public and global health 10.64898/2026.04.12.26350693 medRxiv
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Background: Lung cancer screening can reduce lung cancer mortality through early detection, but uptake of the NHS Targeted Lung Health Check (TLHC) programme remains low. Behaviourally informed invitation messages have been proposed as a low-cost approach to increase attendance, but evidence of their effectiveness in lung cancer screening is mixed. Few intervention studies used evidence-based behaviour change frameworks, and rarely tailored invitation strategies to empirically identified barriers and enablers. Methods: In an online experiment, 3,274 adults aged 55-74 years and with a history of smoking were randomised to see one of four behaviourally informed invitation messages or a control message. Participants then rated their intention to attend a TLHC appointment, and selected barriers and enablers to attending from a pre-defined list, which were classified according to the Theoretical Domains Framework. Invitation messages were mapped to Behaviour Change Techniques using the Theory and Techniques Tool. Message conditions were compared on intention to attend TLHC using bootstrapped ANOVA followed by pairwise comparisons. Exploratory counterfactual mediation analyses examined the role of fear in intention to attend. Results: Behaviourally informed invitation messages did not meaningfully increase intention to attend TLHC compared with the control message. While a GP-endorsed message showed a small potential benefit relative to the other conditions, this finding was not robust after adjustment for multiple comparisons. Participants most frequently reported barriers related to Emotion (particularly fear), Social Influence, and Knowledge, while Beliefs about Consequences emerged as the primary enabler of attendance. Only around half of reported barriers and enablers were addressed by the invitation messages. Exploratory analyses found that fear was associated with lower intention to attend a TLHC appointment, yet none of the behaviourally informed messages appeared to reduce fear compared to the control message. Conclusions: Improving lung cancer screening uptake will likely require invitation messages that directly address emotional concerns, particularly fear, alongside credible recommendations. These findings highlight the importance of systematically aligning invitation message content with empirically identified behavioural influences when designing scalable interventions to improve lung cancer screening uptake.

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Low-Cost 3D-Printed Molds for PMMA Cranioplasty: Case Series and Workflow Analysis

Gondra, T.; Gimbatti, R. A.; Santangelo, P.

2026-04-07 neurology 10.64898/2026.04.02.26349771 medRxiv
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BACKGROUND: Cranioplasty is an essential procedure to restore cranial integrity, protect neural structures, and improve cosmetic outcomes. However, commercially available implants are often costly, limiting their accessibility in public healthcare systems. Three dimensional (3D) printing offers a low cost alternative for producing patient-specific solutions. METHODS: A retrospective case series of eight patients undergoing cranioplasty using customized polymethylmethacrylate (PMMA) implants fabricated with 3D printed molds was conducted. Computed tomography (CT) scans were used for segmentation and digital modeling. Patient specific molds were designed and printed preoperatively. Variables analyzed included design time, printing time, intraoperative workflow, and clinical outcomes. RESULTS: Design time ranged from approximately 1 hour for small defects to 3 hours for larger defects. Printing time ranged from 2 3 hours for smaller defects and up to 8 10 hours for larger reconstructions. Satisfactory aesthetic outcomes were achieved in 7 of 8 patients (87.5%). No major implant related complications were observed. CONCLUSION: Low cost 3D printing for PMMA cranioplasty is a feasible, accessible, and effective technique for cranial reconstruction, particularly in resource limited settings. Keywords: Cranioplasty; 3D printing; Cranial defect reconstruction; Low cost surgery; Patient specific implants; Polymethylmethacrylate; Skull reconstruction