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Systematic Reviews

Springer Science and Business Media LLC

Preprints posted in the last 7 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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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and grey literature (ICTRP and ProQuest database) without language or date restrictions to identify published and unpublished randomised controlled trials of FCT.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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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 [≥]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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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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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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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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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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Global burden of stigma and discrimination against transgender and gender-diverse adults: a systematic review and meta-analysis

Barre-Quick, M.; Yeh, P. T.; Kennedy, C. E.; Azuma, H.; McLellan, C.; Cooney, E. E.

2026-04-23 public and global health 10.64898/2026.04.22.26351490 medRxiv
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Abstract Importance Stigma and discrimination against transgender and gender-diverse people are prevalent across many settings and may contribute to substantial health disparities. Objective To synthesize global evidence on the prevalence of stigma, discrimination, and resilience among transgender (trans) and gender-diverse adults. Data Sources A systematic search was conducted in PubMed, Embase, CINAHL, Cochrane Central, LILACS, and PsycInfo for articles published between January 1, 2010 and January 2, 2023. This database search was supplemented by grey literature and secondary reference searches. Article Selection Studies were eligible if they presented primary quantitative data on prevalence of stigma, discrimination, and/or resilience among trans and gender-diverse adults (aged 18 and over), with no restrictions on study design, language, or geographic region. Data Extraction and Synthesis Two independent reviewers extracted data using standardized forms, with discrepancies resolved by consensus. The JBI Critical Appraisal Checklist for Prevalence Articles was used to assess risk of bias. Random effects meta-analysis was conducted for dichotomous prevalence measures using inverse variance weighting and logit transformation; non-dichotomous prevalence data were summarized descriptively. Main Outcomes and Measures Outcomes included prevalence estimates for various forms of stigma (anticipated, perceived, internalized, and experienced), discrimination in legal/institutional settings (housing, healthcare, employment, police/prison), and resilience. Results A total of 97 articles, with data from 72,158 unique trans and gender-diverse participants across 26 countries, met inclusion criteria. Studies showed moderate levels of anticipated stigma, perceived stigma, and internalized stigma. Meta-analyses of 36 studies provided pooled estimates of discrimination prevalence across multiple domains: 21.4% in housing (e.g., eviction, rental denial), 24.6% in healthcare (e.g., denial of care, mistreatment), 32.8% in employment (e.g., hiring bias, workplace harassment), and 39.1% in police/prison settings (e.g., profiling, mistreatment). High heterogeneity was observed across studies, reflecting regional and methodological differences. Resilience scores ranged from moderate to high, indicating variation within trans and gender-diverse communities. Conclusions and Relevance This systematic review and meta-analysis found that stigma and discrimination against trans and gender-diverse adults are pervasive globally. Variation in stigma and discrimination across settings and regions underscores the need for targeted interventions and policy reforms. Funding World Health Organization through a grant from the Elton John AIDS Foundation and the Bill and Melinda Gates Foundation.

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Effects of transcranial direct current stimulation (tDCS) combined with cognitive therapy in individuals with cognitive impairment: a systematic review and meta-analysis.

Soto-Ferndandez, P.; Toledo-Rodriguez, L.; Figueroa-Vargas, A.; Figueroa-Taiba, P.; Billeke, P.

2026-04-27 neurology 10.64898/2026.04.26.26351755 medRxiv
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Background: Cognitive impairment poses a significant challenge to healthcare systems worldwide, impacting patient autonomy, social participation, and quality of life, while placing a considerable burden on caregivers. Non pharmacological interventions, particularly cognitive training and non invasive brain stimulation, have emerged as promising therapeutic strategies. Objective: This study aims to quantify the synergistic effects of transcranial direct current stimulation (tDCS) with cognitive training on cognitive function across a spectrum of pathologies that induce cognitive impairment. Methods: We conducted a systematic review and metaanalysis following PRISMA guidelines. We searched PubMed for randomized controlled trials that investigated the effect of combined tDCS and cognitive training compared with cognitive training alone. The analysis was based on the GRADE framework for systematic reviews and metaanalyses. Results: Across 27 studies including 1,012 participants, tDCS combined with cognitive training showed a small effect compared with cognitive training alone (SMD = 0.36, 95% CI: 0.15 0.56). The effect was found only immediately after the intervention and declined during follow-up. Conclusion: tDCS combined with cognitive training may provide a small, short term benefit for cognitive function, but high heterogeneity across studies and loss of effect at follow up underscore the need for larger, better standardized trials to clarify its clinical value.

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Analyzing Access to Surgical Services in Central Equatoria State, South Sudan: A Baseline Cross-Sectional Assessment to Inform National Surgical Policy and Planning

Deng, M. D. A.; Alayande, B. T.; Sheferaw, E. D.; Ngutete Mukundwa, P.; Fofanah, T.; Peter, M. B.; Kuron, D.; Bekele, A.; Dau, A. D.

2026-04-22 public and global health 10.64898/2026.04.20.26351353 medRxiv
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BackgroundAccess to safe, equitable, and affordable surgical and anesthesia care is critical to reducing the burden of surgical diseases in Africa. To understand the state of access in South Sudan, we conducted a baseline assessment of surgical services in Central Equatoria State (CES) in May 2024. ObjectivesThis study aimed to survey public healthcare facilities in CES capable of providing essential surgical services. We used the capacity to perform cesarean section, laparotomy, and open fracture management--Bellwether procedures--as a proxy for assessing workforce, infrastructure, financing, information management, and service delivery. MethodsWe used a validated and contextualized Surgical Assessment Tool developed by the Harvard Program on Global Surgery and Social Change and the World Health Organization. Data were collected at the facility level and summarized descriptively using percentages, means (standard deviations), medians (minimum, maximum), and visualized in graphs, charts, and tables. ResultsAll three public health facilities assessed could perform Bellwether procedures for their catchment populations. However, workforce availability, financing, and surgical infrastructure were major constraints. The surgical workforce density was 2.27 surgical, anesthesia, and obstetric specialists per 100,000 population. Specialized procedures--such as repair of cleft lip and palate, clubfoot, and hydrocephalus shunt--were unavailable at all sites. None had magnetic resonance imaging (MRI) machines. The total average annual facility budget was $918,850, ranging from $3,960 to $800,000 at the teaching hospital--insufficient for proper operations. ConclusionWhile Bellwether procedures are routinely performed, access to quality and affordable care is compromised by deficits in workforce, financing, and infrastructure. We recommend that the Ministry of Health scale this survey nationally and develop a surgical policy and strategic plan focused on improving infrastructure, workforce, and financing for surgical and anesthesia care in South Sudan.

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Pilot Feasibility Clinical Trial of Virtual Reality for Pain Management During Repeated Pediatric Laser Procedures: Study Protocol for a Randomized Clinical Trial

Armstrong, M.; Williams, H.; Fernandez Faith, E.; Ni, A.; Xiang, H.

2026-04-22 dermatology 10.64898/2026.04.21.26351381 medRxiv
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BackgroundLasers have wide applications in medicine and dermatology, but are associated with pain and anxiety, particularly in younger patients. Pain mitigation is often limited to topical anesthetics in the outpatient setting. Distraction techniques are limited by the need for ocular protection, which can include adhesive eye patches that can completely occlude vision. Virtual reality is effective at managing procedural pain and anxiety under other short medical procedures and is a promising tool for this population. ObjectiveThis trial aims to assess the safety, feasibility, and efficacy of Virtual Reality Pain Alleviation Therapeutic (VR-PAT) for pain management during outpatient laser procedures. Methods40 patients requiring outpatient laser therapy for at least two sessions will be recruited from a pediatric hospital in the midwestern United States for this crossover randomized, two-arm clinical trial with a 1:1 allocation ratio. During the first laser visit, the participant will be randomly assigned to either play the VR-PAT game during their procedure or wear the headset with a dark screen. Participants will answer questions about their pain (Numeric Rating Scale (NRS) 0-10), anxiety (State Trait Anxiety Inventory for Children, NRS 0-10, Modified Yale Preoperative Anxiety Scale (mYPAS)), and pain medication usage. Those playing the VR-PAT will additionally report simulator sickness symptoms and their experience playing the game. At their second laser visit, participants will crossover to the opposite intervention from their first visit. The primary outcomes are the difference in self-reported pain and anxiety between the two interventions. Feasibility outcomes include the proportion of screened patients who are eligible, consent, and complete both visits and adverse events reported. To evaluate the efficacy of pain reduction, composite scores of pain score, pain medication will be calculated for each laser visit. To evaluate the efficacy of anxiety reduction, the change of mYPAS scores will be compared between control and VR groups at each visit using Wilcoxon rank sum tests. All statistical analyses will follow the intention-to-treat principle in regard to intervention assignment at each visit. ResultsThe study was funded in January 2023 and began enrollment at that time. A total of n=44 participants were recruited and data collection was completed in November 2025, with n=40 subjects completing both visits. The sample was balanced with n=40 subjects using the intervention and participating in the control condition. The age range of the complete sample was 6 to 21 years at recruitment and was 55% female sex. Data analysis is in progress with final results planned for June 2026. ConclusionsFindings from this innovative randomized clinical trial will provide early evidence on the efficacy of the VR-PAT for reducing self-reported pain and anxiety during outpatient laser procedures. The results from this trial will inform a large-scale, multisite study. Trial RegistrationClinicalTrials.gov: NCT05645224 [https://clinicaltrials.gov/study/NCT05645224]

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Assessment of Sleep Hygiene Practices and Its Effects on Sleep Quality Among Medical Students at UMST, Sudan

Abdelmajeed, M. A. A.; Rahmatalla, B. M. A.

2026-04-27 public and global health 10.64898/2026.04.26.26351757 medRxiv
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ABSTRACT Background Medical students face demanding academic schedules and elevated stress levels, predisposing them to poor sleep quality. Sleep hygiene, a set of behavioural and environmental practices aimed at optimising sleep, has been identified as a modifiable determinant of sleep quality, yet its role among medical students in Sudan remains unstudied. Objectives To assess current sleep hygiene practices among medical students at UMST and determine their association with sleep quality outcomes. Methods A facility based cross-sectional study was conducted at UMST among 240 medical students from three academic batches (3rd, 4th, and 5th year), selected via stratified random sampling. Data were collected using two validated self administered instruments: the Pittsburgh Sleep Quality Index (PSQI) and the Sleep Hygiene Index (SHI). Descriptive statistics, independent sample t tests, one way ANOVA, chi-square tests, Pearson correlation, and binary logistic regression were performed using SPSS version 23. Results Poor sleep quality (PSQI >5) was prevalent in 72.1% of participants (mean PSQI 7.25 +/- 2.66), and poor sleep hygiene (SHI >16) in 92.5% (mean SHI 27.1 +/- 7.9). SHI score (continuous) was the only significant independent predictor of sleep quality on logistic regression (OR = 1.13 per unit increase; 95% CI: 1.08-1.19; p < 0.001), equivalent to a 3.4-fold increase in odds per 10-unit rise in SHI score. Female sex was additionally identified as a significant predictor (OR = 1.88; 95% CI: 1.00-3.53; p = 0.049). A significant positive correlation was observed between PSQI and SHI scores (r = 0.359, p < 0.001). Conclusion Poor sleep hygiene is highly prevalent among UMST medical students and is the most significant modifiable predictor of poor sleep quality, with each unit increase in SHI score increasing the odds of poor sleep quality by 13%. These findings highlight a gap in sleep health education within Sudanese medical institutions and support the integration of targeted sleep hygiene interventions into the medical curriculum. Keywords: sleep hygiene; sleep quality; medical students; Sudan; PSQI; SHI; cross-sectional study

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Digital Therapeutic for Hwa-byung Based on Acceptance and Commitment Therapy: A Pilot Feasibility Trial

Kwon, C.-Y.; Lee, B.; Kim, M.; Mun, J.-h.; Seo, M.-G.; Yoon, D.

2026-04-22 psychiatry and clinical psychology 10.64898/2026.04.19.26351203 medRxiv
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BackgroundHwa-byung (HB) is a Korean culture-bound syndrome characterised by prolonged suppression of anger and somatic complaints. No evidence-based digital therapeutic (DTx) has been developed for HB. We evaluated the feasibility, user experience (UX), and preliminary clinical effect of an acceptance and commitment therapy (ACT)-based DTx application, Hwa-free, for HB. MethodsAdults aged 19-80 years diagnosed with HB were enrolled in a four-week app-based intervention with assessment at baseline (Week 0), Week 2, Week 4, and Week 8 follow-up. The primary outcome was UX assessed via a 22-item survey at Week 4. Secondary outcomes included HB-related symptom and personality scales, depression, anxiety, anger expression, psychological flexibility, health-related quality of life, and heart rate variability. ResultsOf 45 screened, 30 were enrolled and 28 constituted the modified intention-to-treat population. Mean app use was 19.9 {+/-} 7.9 days (71.2% adherence over 28 days). Adverse events were infrequent and unrelated to the intervention. Positive response rates exceeded 80% for video content (items 2-4: 82.8-89.7%), HB self-assessment (86.2%), meditation therapy (86.2%), and in-app guidance (85.7%). Pre-post improvements from baseline to Week 4 were observed in 11 of 18 clinical scales, including HB Symptom Scale ({Delta} = -9.8, Cohens d = -0.92), Beck Depression Inventory-II ({Delta} = -13.3, d = -1.11), and state anger ({Delta} = -7.8, d = -0.96). The HB screening-positive rate declined from 100% at baseline to 55.6% at Week 8. ConclusionsHwa-free demonstrated adequate feasibility, acceptable UX, and preliminary evidence of clinically meaningful improvement in HB-related symptoms. Future randomised controlled trial is warranted. Trial registrationCRIS, KCT0011105

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A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study of Chuanzhi Tongluo Capsule in Acute Ischemic Stroke (CONCERN): Study Rationale and Design

Yang, D.; Li, G.; Song, J.; Shi, X.; Xu, X.; Ma, J.; Guo, C.; Liu, C.; Yang, J.; Li, F.; Zhu, Y.; Zi, W.; Ding, Q.; Chen, Y.

2026-04-23 neurology 10.64898/2026.04.20.26351260 medRxiv
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Abstract Background: Acute ischemic stroke (AIS) remains a significant cause of disability worldwide. Current treatments, primarily intravenous thrombolysis (IVT), are limited by narrow time windows and reperfusion injury, leading to suboptimal outcomes for many patients. Chuanzhi Tongluo (CZTL), a traditional Chinese medicine, has been preliminarily recognized as a novel cerebral protection agent in animal models. Objectives: This trial investigates the efficacy and safety of CZTL capsule in patients with AIS who are not eligible for IVT or who experience early neurological deterioration after IVT. Methods and design: The CONCERN trial is an investigator-initiated, prospective, multicenter, double-blind, parallel-control, randomized clinical study in China. An estimated 1,208 eligible participants will be consecutively randomized to receive CZTL capsule therapy or placebo in 1:1 ratio across approximately 70 stroke centers in China. All enrolled patients are orally administered 2 capsules of CZTL or placebo 3 times a day together with antiplatelet agents for 3 months. Outcomes: The primary endpoint is an excellent functional outcome, defined as a score of 0 or 1 on the mRS at 90 days. Lead safety endpoints included 90-day mortality and symptomatic intracranial hemorrhage within 48 hours. Conclusions: Results of CONCERN trial will determine the clinical efficacy and safety of the traditional Chinese medicine CZTL capsule in the treatment of AIS patients. Trial registry number: ChiCTR2300074147 (www.chictr.org.cn).

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Linguistic Validation of the Rett Syndrome Behavior Questionnaire Spanish Translation: a Two-Stage Caregiver Study Across Latin America

Polo Sanchez, M.; Lesmes, A. C.; Muni, N.; Vigneault, F.; Novak, R.

2026-04-23 neurology 10.64898/2026.04.16.26349544 medRxiv
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Background: Rett Syndrome (RTT) is a severe neurodevelopmental disorder affecting approximately 1 in 10,000 live female births worldwide. The Rett Syndrome Behaviour Questionnaire (RSBQ), remains one of the most widely used standardized behavioral assessment tools for RTT. However, the RSBQ was originally validated only in British English, limiting its applicability for Spanish-speaking caregivers and clinical centers across Latin America and Spain. Objective: The primary aim of this study was to develop and validate the comprehension of the Spanish translation of the RSBQ to ensure cultural and linguistic equivalence, enhance data reliability, and facilitate earlier, more accurate clinical assessments among Spanish-speaking RTT populations. Methods: Surveys were administered in two phases to Spanish-speaking caregivers between November 2023 and September 2025. Phase I consisted of 12 guided survey administrations with participants being able to ask clarifying questions and offer linguistic modifications of RSBQ questions. Phase II consisted of independent online administration of the refined Spanish RSBQ and a retest at least 7 days later. Participants were recruited through direct outreach and supported virtually during questionnaire completion. Results: Following data cleaning and quality control, a total of 51 caregivers successfully completed both surveys. The Spanish RSBQ demonstrated high caregiver comprehension and strong engagement across multiple Latin American countries, including Argentina, Mexico, and Peru. Responses were highly correlated between test and retest timepoints, and no question showed biased response distributions. A slight effect of response interval on test-retest correlation was observed, potentially indicating the impact of natural disease progression confounding retest evaluation for long (>80 day) intervals; however this effect did not impact the overall linguistic validation results as analysis of only <21 day test-retest responders confirmed the findings. Conclusions: This linguistic validation study represents the first formal step toward the clinical validation of the Spanish RSBQ, enabling broader inclusion of Spanish-speaking populations in RTT research. The collaborative, bilingual data collection strategy proved both feasible and effective, paving the way for multinational trials and expanding therapeutic accessibility through localized, patient-centered innovation.

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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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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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Feasibility and acceptability of contextually adapted AVATAR therapy for distressing voices in Ethiopia and India: a study protocol for the AVATAR3 study

Ward, T.; Alem, A.; Craig, T. K. J.; Sinha Deb, K.; Devi, S.; Fekadu, A.; Gumley, A.; Hanlon, C.; Kelly, R.; Manyazewal, T.; Misganaw, E.; Murcutt, I.; Oshodi, E.; Patil, V.; Sharan, P.; Tesfaye, Y.; Verma, R.; Ul-Haq, S.; Rus-Calafell, M.; Choudhary, R.; Getachew, M.; Hardy, A.; Wondiye, M.; Mihretu, A.; Sood, M.

2026-04-21 public and global health 10.64898/2026.04.21.26348779 medRxiv
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IntroductionIn many Low- and Middle-Income countries (LMIC), access to psychological therapies for psychosis remains extremely limited, contributing to significant treatment gaps and persistent inequalities in care. Novel interventions that are effective, scalable, and culturally acceptable across diverse settings are urgently needed. AVATAR therapy is an innovative digital intervention for distressing voices in psychosis, developed in the UK. The therapy enables voice-hearers to engage in a series of facilitated dialogues with a customized computer-based representation of their main distressing voice. AVATAR3 represents the first initiative to contextually adapt AVATAR therapy and evaluate its acceptability in two LMIC settings (Ethiopia and India). Methods and analysisWe will establish Innovation and Implementation Hubs in Addis Ababa, Ethiopia (Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa) at Addis Ababa University (AAU) and Mental Health Service Users Association (MHSUA), Ethiopia) and New Delhi, India (All India Institute of Medical Sciences). Phase 1 employs formative work and diverse stakeholder engagement to inform context-specific adaptations. Reflexive thematic analysis will be used, with data synthesis informed by the Cultural Adaptation of Scalable Psychological Interventions (CASPI) framework and Ecological Validity Model (EVM). Phase 2 tests adapted AVATAR therapy through a parallel case series (n=15 per site, targeting 70% completion rate) measuring feasibility, acceptability, and safety indicators at baseline, 12-weeks, and 24-weeks. Qualitative research will explore the experiences of participants (n=10) and therapists (n=8) at each site. Ethics and disseminationEthical approval has been obtained from Addis Ababa University College of Health Science Institutional Review Board, All India Institute of Medical Sciences (AIIMS) Institutional Review Board and the Kings College London (study sponsor) Research Ethics Committee. Findings will be disseminated to inform the implementation of AVATAR therapy across diverse international settings. Strengths and limitations of this studyO_LIInterdisciplinary and participatory approach C_LIO_LIContextual adaptation of a digital innovation C_LIO_LIExpert by experience leadership and involvement from the conception of the study C_LIO_LIThe study will develop tools and share learning to support future digital mental health innovation across diverse international settings C_LIO_LIThe case-series at each site will not have a control group C_LI

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Pharmacist Led Nutritional Counselling as a Community Intervention for Obesity, Undernutrition, and Anaemia: Evidence from a 1135 Participant Prospective Interventional Study in India

Duddu, R.

2026-04-27 public and global health 10.64898/2026.04.25.26351725 medRxiv
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Objectives: To examine the pattern, magnitude, and demographic distribution of measurable improvements across five outcome parameters following three monthly pharmacist-led nutritional counselling sessions delivered to community-dwelling participants in semi-urban India. Design: Secondary analysis of interventional follow-up data from a prospective community-based study. Setting: Schools and colleges in Narasaraopeta, Andhra Pradesh, India, from September 2021 to March 2022. Participants: Of 1,200 participants assessed at baseline, 1,135 (94.6%) completed at least one counselling session and formed the analysis cohort. The age range was 10 to 60 years. The majority of participants, 92.4%, were aged between 11 and 20 years. All 1,135 were anaemic at baseline. Interventions: Three structured monthly counselling sessions were delivered by pharmacy students under qualified faculty pharmacist supervision. Each session included individualised dietary guidance, lifestyle modification advice, and culturally adapted written health education materials. Primary and secondary outcome measures: Cumulative proportion of participants achieving measurable improvement in body mass index (BMI), waist circumference (WC), hip circumference (HC), waist to hip ratio (WHR), and haemoglobin (Hb) concentration at each session, stratified by age group and sex. Results: All five parameters showed progressive cumulative improvement across sessions. By session three, 44 participants (3.6%) showed improved BMI, 39 (3.25%) achieved reduced WC, 34 (2.8%) reduced HC, 33 (2.75%) improved WHR, and 115 (9.5%) demonstrated improved Hb. Adolescents aged 11 to 20 years were consistently the most responsive subgroup. Haemoglobin showed the steepest improvement trajectory, rising from 1.75% at session one to 9.5% at session three, representing a 5.4 fold increase achieved through dietary counselling alone without pharmacological supplementation. Conclusions: Three monthly pharmacist led nutritional counselling sessions produce measurable and progressive improvements in both anthropometric and haematological outcomes in community settings. Adolescents are the most responsive population. These findings support the integration of pharmacists into community non communicable disease prevention programmes in India and provide a replicable low resource model applicable to comparable global settings.

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On the robustness of ethnic and socio-cultural determinants of healthcare decision-making autonomy among Hausa, Fulani, and Kanuri women in Northern Nigeria.

OGUNETIMOJU, A. M.; AJEBORIOGBON, S. A.

2026-04-22 public and global health 10.64898/2026.04.21.26351355 medRxiv
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BackgroundWomens autonomy in healthcare decision-making has become one of the most critical yet inequitably distributed determinants of health outcomes, gender equity, and sustainable development worldwide. In Northern Nigeria, the presence of ethnic and socio-cultural inequality is frequently concealed by the aggregated statistics of a region. MethodsThis cross-sectional secondary analysis utilized the 2024 Nigeria Demographic and Health Survey. The sample included 9,998 married women (15-49 years) identifying as Hausa, Fulani, or Kanuri in Northern Nigeria. Healthcare autonomy was categorized as husband/partner alone, respondent alone, or joint decision-making. Analysis included weighted descriptive statistics, Rao-Scott adjusted chi-square tests for residential associations, and complex sample multinomial logistic regression to identify multivariable correlates while adjusting for sampling weights, strata, and clusters. ResultsMean age was 30.38 years. Most participants lacked formal education (69.6%) and resided in rural areas (72.0%). Husband-only decision-making predominated (72.6%), while 22.5% reported joint and 4.9% independent autonomy. Joint decision-making was significantly higher in urban (33.3%) than rural areas (18.3%; Adjusted F=50.892, p<0.001). In adjusted models (Reference: Kanuri), Hausa and Fulani women had substantially lower odds of joint decision-making relative to husband-only outcomes. Rural residence correlated with lower odds of both independent and joint agency. Notably, wealth status was not a significant predictor after adjustment (p > 0.05). ConclusionsEthnicity and residence are robust determinants of healthcare autonomy among women in Northern Nigeria, persisting regardless of education or wealth. This "socio-cultural paradox" suggests that economic interventions alone are insufficient. Policies must complement socioeconomic approaches with culturally responsive strategies addressing household power dynamics and entrenched social norms.

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Proposed Classification System for the 445 nm Blue Light Laser for Treatment of Laryngeal Lesions

Khan, M.; Islam, A. M.; Abdel-Aty, Y.; Rosow, D.; Mallur, P.; Johns, M.; Rosen, C. A.; Bensoussan, Y. E.

2026-04-22 otolaryngology 10.64898/2026.04.20.26351290 medRxiv
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ObjectiveOnly preliminary investigations on the use of the 445 nanometer wavelength blue light laser (BLL) for various laryngeal pathologies have been described. Currently, no standard exists for reporting treatment technique and tissue effect with this modality. Here, we aim to establish and validate a classification system to describe laser-induced tissue effects. Study DesignRetrospective video-based study for classification development and reliability validation. MethodsVideo recordings from procedures performed with the BLL by multiple academic laryngologists were retrospectively reviewed. A preliminary 6-point classification (BLL 1-6) was developed based on expert consensus. Thirteen additional procedural clips were independently rated utilizing the classification schema to assess perceived tissue effect, and measure inter- and intra-rate reliability. ResultsThe final 5-point classification system (BLL 1-5) included angiolysis, blanching, tissue vaporization, ablation with mechanical tissue removal, and cutting. The consensus of the combined reviewers in rating all cases was 89% (58 of 65). Complete consensus was not achieved in 11% (7/65) of cases. Of those incorrect, 57% (4/7) were of clips illustrating the BLL-2 classification. Intra-rater reliability amongst the reviewers was 100%. ConclusionTissue effect of the 445 nm blue light laser can reliably be standardized with this proposed classification system. This rating system can be used to facilitate future systematic study of outcomes and effective communication between laryngologists and trainees.