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Disability and Rehabilitation

Informa UK Limited

Preprints posted in the last 7 days, ranked by how well they match Disability and Rehabilitation'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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"Most inactive in my life": patient-reported barriers to cardiac rehabilitation in heart failure.

Khodneva, Y.; Nordberg, M.; Brown, T.; Cherrington, A. L.; Hearld, L.

2026-07-09 rehabilitation medicine and physical therapy 10.64898/2026.06.26.26356375 medRxiv
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Background & Objective. Cardiac rehabilitation is an existing guideline-concordant intervention for heart failure that provides benefits but is grossly underutilized by both physicians and patients. We aimed to identify patient-reported barriers and facilitators of participation in cardiac rehabilitation. Design, participants, approach: Qualitative theory-guided in-depth interviews were conducted with adults with heart failure, recruited from ambulatory settings with oversampling of those with heart failure with preserved ejection fraction. Thematic analysis was applied to interview data. Depressive symptoms and perceived stress were assessed by Patient Health Questionnaire (PHQ-8) and Perceived Stress Scale (PSS), respectively. Key results: Twenty-two adults with heart failure, aged 27-85, completed the study; of them 59.1% were women, 68.2% - African American, 4.5% - Hispanic; 77.3% had public insurance or were self-pay; 68.2% had heart failure with preserved ejection fraction. Mean PHQ-8 score was 11.4 (SD= 2.9) and mean PSS score - 20.4 (SD=4.5). Patient-reported barriers to cardiac rehabilitation included unawareness of cardiac rehabilitation and its benefits, perceived inability to exercise, depression, and weight gain, specifically for heart failure with preserved ejection fraction. Perceived inability to exercise stemmed from uncontrolled heart failure symptom burden and exercise intolerance, medication side effects, non-cardiac pain, fear of exercise, and low motivation for exercise. Facilitators of participation included intrinsic and extrinsic motivating factors and specific features of programs, such as individualized and supervised interventions with moderate level of exercise. Conclusion: Participants reported multiple barriers to cardiac rehabilitation; some of them can be modified by providing counselling and referral to cardiac rehabilitation from primary care physicians and simultaneously addressing heart failure symptom burden, pain, stress and depression. Combining cardiac rehabilitation and weight management can benefit adults with heart failure with preserved ejection fraction specifically. Increasing insurance coverage for cardiac rehabilitation for heart failure is warranted.

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Distinct Patterns of Mobility Recovery After Stroke Using Routine Clinical Data

French, M. A.; Marsh, E. B.; Roemmich, R. T.; Raghavan, P.

2026-07-13 rehabilitation medicine and physical therapy 10.64898/2026.07.08.26357600 medRxiv
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Background: Mobility recovery after stroke is highly variable, yet is typically described using average patterns that obscure meaningful differences between individuals. Identifying distinct recovery trajectories may improve prognostication and guide rehabilitation strategies. Methods: We conducted a retrospective cohort study of adults admitted for stroke to a large health system between 2016 and 2024. Mobility was assessed using Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility, which was collected during routine clinical care. Growth mixture modeling was used to identify subgroups with distinct mobility recovery trajectories during the first 180 days after stroke. Subgroups were then characterized with baseline personal and clinical characteristics. Results: Seven hundred and fifty individuals contributed 3,389 mobility observations (median 4 per person). A five-class solution was selected based on model fit and classification quality. Distinct trajectories were identified: low stable (n=127), low rapidly improving (n=29), mid declining (n=169), mid improving (n=365), and high stable (n=60). Subgroups differed in both baseline mobility and patterns of change over time, with some demonstrating improvement, others remaining stable, and one declining. Individuals in improving subgroups were generally younger, more likely to be independent before stroke, received physical therapy on a greater proportion of hospital days, and were more frequently discharged to inpatient rehabilitation. In contrast, those in low or declining trajectories had lower baseline function, longer hospital stays, and were more likely to be discharged to skilled nursing facilities. Conclusions: The distinct mobility recovery trajectories identified in this work reflect the heterogeneity present in routine clinical practice. Subgroups differed in both recovery patterns and characteristics. Early identification of trajectory membership may improve prognostication and inform more targeted rehabilitation strategies.

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An mHealth intervention based on behavior change techniques to promote physical activity and nutrition in older patients with cancer: protocol for an N-of-1 trial

Brusseau, M.; Deffrennes, J.; Gallet-Suchet, B.; Cristol, L.; Dray, G.; Gendrault, S.; Harguem, L.; Dadier, R.; Boiche, J.

2026-07-09 rehabilitation medicine and physical therapy 10.64898/2026.07.06.26356658 medRxiv
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BACKGROUND: Older adults with cancer often struggle to achieve recommended levels of physical activity and dietary intake. Ecological momentary assessment combined with accelerometry can provide insights into the temporal dynamics of psychological and behavioral processes at the individual level, such as motivation towards health behaviors. OBJECTIVE: This N-of-1 study aims to improve physical activity and nutritional behaviors among older patients with cancer using an mHealth behavioral intervention. METHODS: A single-subject ABA' design will be employed among older patients with cancer ([≥] 70 years). A 2-week baseline phase (A) will be followed by an 8-week intervention phase (B) and a two-week withdrawal phase (A'). Throughout all these phases, participants will complete a daily data collection protocol combining ecological momentary assessment questionnaires and an ActiGraph wGT3X-BT accelerometer worn on the waist to measure physical activity. Ecological momentary assessment questionnaires will be delivered via a digital application to collect information on nutritional behavior, fatigue, and motivational constructs based on the Theory of Planned Behavior. The intervention (B) will consist of an mHealth intervention based on behavior change techniques, delivered via weekly calls, personalized messages, and a digital application. Data will be analyzed using piecewise and segmented regression models. In addition, a semi-structured interview will be conducted to assess patient experience. These qualitative data will help identify contextual factors, such as treatment-related side effects or variations in health status, that may have influenced behavior change and participation in data collection. CONCLUSION: This N-of-1 study explores intra-individual behavioral dynamics using intensive longitudinal data rather than testing a strictly reversible intervention effect. The mHealth intervention is based on behavior change techniques and tailored to each patient, with adjustments made based on repeated daily assessments in a real-world setting using a wGT3X-BT accelerometer and ecological momentary assessment questionnaires. The results will contribute to the evidence base for mHealth interventions designed to promote sustained physical activity and dietary intake among older adults with cancer.

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From Cause to Recovery: The Influence of Traumatic Brain Injury Mechanisms on Long-Term Functional Independence

Beth, M. J.; Marwitz, J.; Valadi, N.; Baweja, N.; Baweja, H. S.

2026-07-13 neurology 10.64898/2026.07.10.26357252 medRxiv
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Background/Objectives: This systematic review examines how different mechanisms of Traumatic Brain Injury (TBI) influence post-injury functional independence and aims to clarify whether recovery patterns vary by injury type. A total of 105 studies (n = 59,621) involving adults with TBI were synthesized. These findings can guide clinicians and researchers in predicting outcomes and effectively customizing rehabilitation plans. Methods: A review following PRISMA standards analyzed English-language studies published from 1975 to 2025, assessed functional outcomes using the Functional Independence Measure (FIM) or the Glasgow Outcome Scale-Extended (GOSE), converted them to z-scores, and aggregated them via a random-effects model with inverse-variance weighting to demonstrate their relevance. Results: Recreational TBIs show the highest functional independence (z = +1.77), followed by MVAs (z = +1.56), with falls (z = +0.70) and assault-related TBIs (z = -0.12) showing moderate outcomes, and TBIs with penetrating trauma (z = -1.15) indicating the most adverse results. Conclusions: TBI mechanisms appear to meaningfully influence long-term post-injury functional independence. Highlighting this can inspire clinicians and researchers to trust these insights to improve prognosis and rehabilitation strategies, underscoring their crucial role in advancing patient care.

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Association of Insurance Payor with Time to Discharge to Inpatient Rehabilitation After Ischemic Stroke

Shah, R. J.; King, B.; Strobel, S.; Feyisetan, R.

2026-07-13 health policy 10.64898/2026.07.08.26357596 medRxiv
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Background: Transition timing to post-acute rehabilitation after ischemic stroke is heavily influenced by non-clinical factors, introducing potential systemic disparities in care access. We evaluated the association between insurance payor status and acute hospital length of stay (LOS) prior to inpatient rehabilitation discharge among critically ill stroke patients. Methods: Using the MIMIC-IV database, we identified ICU-admitted adults with ischemic stroke discharged to inpatient rehabilitation (n=1,285). The primary outcome was hospital LOS prior to rehab transfer. Multivariable log-transformed linear regression evaluated the association with insurance payor (Medicare, private, other/unknown; reference: Medicaid), adjusting for demographics, diagnostic-code counts (medical complexity), and ICU LOS (acute illness severity). Results: Median hospital LOS before rehab discharge was longest for Medicaid patients (13.2 days) compared with private insurance (11.0 days) and Medicare (9.5 days). In the adjusted model, Medicare insurance was associated with a significantly shorter transition time to inpatient rehabilitation, corresponding to a 13.5% shorter acute hospital stay (adjusted LOS ratio 0.87; 95% CI: 0.79-0.96; p=0.005) relative to Medicaid. Private insurance demonstrated a descriptive trend toward shorter LOS that did not achieve statistical significance (adjusted LOS ratio 0.93; 95% CI: 0.84-1.02; p=0.122). Other and unknown payor categories showed no significant differences. Conclusions: Insurance payor status serves as an independent predictor of acute care transition timing for stroke patients requiring inpatient rehabilitation. The prolonged acute stays observed among Medicaid beneficiaries suggest significant non-clinical, administrative bottlenecks in post-acute placement, underscoring the critical need for standardized, streamlined insurance approval pathways to ensure equitable neurological recovery.

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Divergent Recovery Trajectories: The Influence of Injury Mechanism on Stair-Climbing Outcomes After Traumatic Brain Injury - a TBI Model Systems Study

Beth, M. J.; Marwitz, J.; Valadi, N.; Baweja, N.; Baweja, H. S.

2026-07-10 neurology 10.64898/2026.07.04.26357287 medRxiv
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Background/Objectives: Traumatic Brain Injuries (TBIs) often cause profound functional impairments, yet the influence of TBI mechanisms on stair-climbing functional independence over extended timelines remains poorly understood. This study assesses whether Rasch-transformed FIM Stairs scores varied by TBI mechanism over follow-ups spanning 10 years or more. Methods: Data from the TBI Model Systems database were analyzed. The original 30,768 data entries were reduced to 6,226, corresponding to individuals with at least 10 years of data. Functional Independence Measure Stairs data were transformed to logit units via Rasch analysis before being evaluated with a linear mixed-effects regression, incorporating TBI mechanisms, age, follow-up time, and their interactions, with random effects accounting for the participant ID and pre-injury residence location. Results: TBI mechanisms meaningfully shape very long-term stair-climbing. Gunshot wounds and pedestrian-related accidents are associated with poorer performances, whereas motorcycles, bicycles, unclassified vehicular accidents, winter sports, other sports, and fall-related TBIs demonstrated relatively better function. Age, follow-up time, and their interaction also reached significance. Conclusions: Stair-climbing recovery trajectories over extended time significantly vary by TBI mechanism, with individuals with TBIs from gunshots and pedestrian-related accidents showing the most unfavorable recoveries. These findings support the development of mechanism-specific prognostic guidance and individualized rehabilitation strategies, thereby encouraging tailored approaches to improve outcomes.

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From Injury to Independence: Longitudinal Locomotor Recovery Patterns Following Traumatic Brain Injury - a TBI Model Systems Study

Beth, M. J.; Marwitz, J.; Murrah, W.; Valadi, N.; Baweja, N.; Baweja, H. S.

2026-07-09 neurology 10.64898/2026.07.07.26357255 medRxiv
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Background/Objectives: Traumatic Brain Injuries (TBIs) affect more than 50 million individuals worldwide each year. Approximately 90% of individuals survive and experience persistent motor, cognitive, and emotional deficits, substantially contributing to a reduced quality of life and a global economic burden. TBI mechanisms are a foundational determinant of long-term recovery. The objective of this study was to examine long-term trends in functional locomotion ability over extended follow-up durations (>10 years) across distinct TBI mechanisms. The researchers hypothesized that TBIs caused by falls or violent mechanisms would be associated with poorer functional locomotor abilities and, subsequently, lower item scores than those sustained through automotive or recreational activities. Methods: Data were obtained from the Traumatic Brain Injury Model Systems (TBIMS) database at Craig Hospital in Englewood, Colorado, the largest longitudinal TBI data repository in the world. Functional locomotion was assessed using the Functional Independence Measure (FIM) Locomotion item as the primary outcome measure. To enhance measurement precision and ensure interval-level scaling, raw FIM scores were converted into logit-based estimates of latent functional ability using Rasch modeling. Longitudinal changes of these Rasch-transformed scores were analyzed using linear mixed-effects regression, accounting for individual-level variability and unbalanced follow-up data. Results: The findings demonstrated a clinically meaningful decline in functional ability among individuals with TBIs from violent mechanisms, particularly assault-related injuries and gunshot wounds, which were associated with chronic medical complications and limited functional independence. Conversely, TBIs from bicycling, unclassified vehicular incidents, and winter sports showed significant positive estimates, possibly reflecting higher premorbid physical fitness. Motor vehicle, motorcycle, pedestrian, and fall-related TBIs demonstrated steep early gains, followed by a period of recovery stabilization and plateau. In contrast, violence-related mechanisms were characterized by consistently low median scores, with minimal long-term improvement. Falls, gymnastics, track & field, and water sports did not exhibit meaningful changes in the context of the primary hypothesis. Conclusions: TBI mechanisms play a vital role in shaping long-term functional locomotion outcomes, with violence-related TBIs associated with poorer long-term functional independence. The results have clinically important implications, supporting earlier identification of high-risk populations and the development of targeted rehabilitation strategies during periods of heightened neuroplasticity. Rasch analysis integrated with linear mixed-effects modeling yields a robust analytic framework that uncovers subtle but meaningful differences in recovery trajectories across TBI mechanisms.

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Remote Ischemic Perconditioning and 90-Day Cognitive Outcomes After Acute Ischemic Stroke: A REMOTE-CAT Substudy

Pereira, C.; REMOTE-CAT Trial Investigators, ; Arque, G.; Regue, A.; Mauri-Capdevila, G.; Jimenez-Fabrega, X.; Subirats, T.; Ropero, J. R.; Vicente-Pascual, M.; Rovira, A.; Salvany, S.; Garcia-Vazquez, C.; Cirer-Sastre, R.; Purroy, F.

2026-07-13 neurology 10.64898/2026.07.08.26357601 medRxiv
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Background: Remote ischemic perconditioning (RIperC) is a simple, noninvasive neuroprotective strategy based on brief cycles of limb ischemia-reperfusion during cerebral ischemia. REMOTE-CAT suggested a potential functional benefit of prehospital RIperC in acute ischemic stroke. However, its effect on poststroke cognitive outcomes, which may not be fully captured by global disability scales, remains uncertain. Methods: We performed an exploratory cognitive substudy of the multicenter, randomized, double-blind, sham-controlled REMOTE-CAT trial. Patients with suspected acute ischemic stroke within 8 hours, prestroke modified Rankin Scale score <3, and RACE motor score >0 were randomized prehospital to RIperC or sham. RIperC consisted of five 5-minute cuff inflation-deflation cycles during ambulance transfer. At 90 days, patients from one center underwent a standardized neuropsychological battery assessing five cognitive domains. Results: Among 122 patients in the primary analysis, 58 (47.5%) completed neuropsychological assessment: 26 allocated to RIperC and 32 to sham. No statistically significant between-group differences were observed in domain-specific Z scores. Cognitive impairment in at least one domain was numerically less frequent with RIperC than sham (26.9% versus 34.4%). Impairment in more than one domain was also less frequent with RIperC (7.7% versus 21.9%), although the overall distribution of impaired domains did not differ significantly between groups (P=0.244). The largest domain-specific difference was observed for visual memory impairment (3.8% versus 21.9%). Conclusions: In this exploratory substudy, prehospital RIperC did not significantly improve 90-day cognitive outcomes after acute ischemic stroke. Nevertheless, RIperC-treated patients showed numerically favorable trends, particularly in global cognitive burden and visual memory. These hypothesis-generating findings support incorporating standardized cognitive outcomes in future ischemic conditioning trials.

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Exploring stakeholder perspectives on the content, delivery, and contextual delivery of shared decision-making for people living with subacromial pain syndrome: a multimethod study with future workshops and interviews

Lyng, K. D.; Johansen, S. K.; Foster, N. E.; Olesen, J. L.; Thomsen, J. L.; Soendergaard, J.; Rathleff, M. S.

2026-07-10 pain medicine 10.64898/2026.07.02.26356879 medRxiv
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Background: Shared decision-making (SDM) is a key component in patient-centered care for people consulting health care due to chronic musculoskeletal pain, including subacromial pain syndrome (SAPS). Limited research has explored how patients, relatives, and healthcare professionals perceive the content and delivery of SDM for managing SAPS in primary care. Thus, this study aims to explore stakeholder perspectives on the content, delivery, and contextual requirements for a context-specific SDM intervention for SAPS, and to identify shared challenges and co-develop ideas to inform intervention development. Methods: We conducted three separate future workshops (patients/relatives, physiotherapists/chiropractors, and general practitioners), each consisting of structured critique, fantasy, and implementation phases. A rapid preliminary analysis of workshop data was followed by semi-structured stakeholder interviews to validate, challenge, or elaborate the findings. All data were analysed thematically using an iterative, reflexive approach. Results: Twenty-eight participants took part across three workshops: patients/relatives (n = 10), physiotherapists/chiropractors (n = 12), and general practitioners (n = 6). Six additional stakeholders provided inputs via subsequent interviews (three physiotherapists, one patient, one relative and one GP). Thematic analysis identified 20 themes and 59 sub-themes, which were refined into two overarching categories: (1) shared barriers to SDM in SAPS care, including diagnostic uncertainty, fragmented clinical care pathways, time constraints, and decision fatigue; and (2) stakeholder visions for future SDM interventions, emphasising continuity, tailored communication tools, and supportive digital ecosystems. Conclusion: Based on stakeholder input, SDM in SAPS care may consider integrating dynamic, integrated systems that account for diagnostic ambiguity, contextual constraints, and varying patient capacities. These findings provide an actionable foundation for co-developing and piloting a context specific SDM intervention for primary care.

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Wearable Electrical Impedance Myography for Continuous, Non-Invasive Detection of Acute Compartment Syndrome: A Preclinical Feasibility Study

Shariyate, M. J.; Khak, M.; Sonbas-Cobb, B.; Velasquez Hammerle, M. V.; Wei, B.; Robicheau, S.; Dunlap, K.; Hedayatzadeh Razavi, A.; Keko, M.; Rutkove, S.; Nazarian, A.

2026-07-10 orthopedics 10.64898/2026.07.06.26357418 medRxiv
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Introduction: Acute compartment syndrome (ACS) is a limb-threatening complication of extremity trauma that requires timely diagnosis to prevent irreversible muscle and nerve injury. Current diagnostic methods are invasive, intermittent, and operator-dependent. We evaluated the feasibility of a novel, Bluetooth-enabled electrical impedance myography (EIM) device (mAlert, Myolex, Inc., Brookline, MA, USA) for continuous, noninvasive detection of ACS-related tissue changes. Methods: Ten Yorkshire swine underwent anterior tibial compartment monitoring using three ACS models: albumin infusion (ALB, n=3), femoral artery and vein ligation (LIG, n=3), and combined albumin infusion plus ligation (ALB+LIG, n=4). Resistance (R), reactance (X), and phase (P) were measured every minute across 1 to 199 kHz alongside continuous intra-compartmental pressure (ICP) monitoring. Group differences in normalized impedance trends were evaluated using the Kruskal Wallis test with Dunn post hoc correction. As a proof-of-concept human study, nine healthy volunteers wore the device for up to five days to assess electrode durability and signal stability. Tissue ischemia was validated using pimonidazole immunohistochemistry. Results: ALB infusion produced progressive, frequency-dependent decreases in R, X, and P, whereas LIG produced consistent increases in R and X across frequencies. The ALB+LIG model generated mixed responses, reflecting the competing effects of edema and ischemia. Normalized phase slopes differed significantly among groups (H=6.14, p=0.046), with post hoc testing showing significant divergence between the ALB and LIG models (p=0.041). Control limbs remained stable throughout monitoring. Pimonidazole staining confirmed hypoxic injury in the intervention limb. In the human pilot study, three participants completed five days of monitoring, demonstrating sustained signal acquisition, while electrode degradation limited data collection in the remaining participants. Conclusions: This preliminary feasibility study demonstrates that wearable EIM can continuously detect model-specific physiological changes associated with ACS in a large-animal model. These findings support further development and clinical evaluation of wearable EIM as a non-invasive monitoring technology for early ACS detection in trauma patients.

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Association of anti-Ro-52 positivity with cardiovascular outcomes in patients with anti-synthetase syndrome

Potharazu, A. V.; Chung, J.-H.; Yanek, L.; Kelly, W.; Gilotra, N.; Adamo, L.; Paik, J.

2026-07-07 rheumatology 10.64898/2026.07.04.26357290 medRxiv
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Background: Anti-synthetase syndrome (ASyS) is a subgroup of idiopathic inflammatory myopathies that is increasingly recognized as a distinct entity with features of myositis, interstitial lung disease, inflammatory arthritis, and Raynaud phenomenon. Co-reactivity with anti-Ro-52, an antibody directed against the Ro-52 E3 ubiquitin ligase, has been shown to be associated with progressive interstitial lung disease within this patient population. However, less is known regarding the association of anti-Ro-52 positivity with cardiovascular outcomes. Methods: A sub-cohort of patients with anti-synthetase antibodies at a large single institution center was retrospectively analyzed to define presence of anti-Ro-52 positivity (defined as anti-Ro-52 titer greater than or equal to 11 utilizing the line immunoblot platform, Euroline Autoimmune Inflammatory Myopathies, EuroImmun Diagnostics, Lubeck, Germany). Patients who did not meet 2017 ACR/EULAR classification criteria for idiopathic inflammatory myopathies were excluded from the final analysis. Cardiovascular outcomes ascertained via retrospective chart review included atrial fibrillation, left bundle branch block, right bundle branch block, pulmonary hypertension (confirmed via right heart catheterization), heart failure with reduced ejection fraction (HFrEF, defined as ejection fraction less than or equal to 40 percent), acute coronary syndrome (based on clinical diagnosis and angiography if available), and myocarditis (based on clinician diagnosis and either cardiac MRI or troponin elevation). When a pre-specified cardiac outcome was identified, the date of onset was recorded. Differences in proportions were analyzed via Chi-squared and Fishers exact tests, and time-to-event analyses were performed via Cox Proportional Hazards Models, incorporating a false discovery rate correction for multiple outcomes. All analyses were performed using SAS v9.4. Results: 88 patients were included in the final analysis, of whom 69 (78.4 percent) were categorized as anti-Ro-52 positive. Patients with anti-Ro-52 positivity had a higher maximum recorded serum creatine kinase (median 1297 vs 395 units per liter, p = 0.042). No significant associations between anti-Ro-52 positivity and the pre-defined cardiovascular outcomes were found over median follow up time of 12.5 years. Conclusions: In a large, single-center cohort of patients with ASyS, anti-Ro-52 positivity was not associated with an increased burden of negative cardiovascular outcomes, including the onset of pulmonary hypertension. Future studies may seek to further elucidate the mechanisms underlying the pleiotropic effects of anti-Ro-52 antibodies on the cardiopulmonary system.

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Oral levosulpiride adjuvant to intravitreal ranibizumab for diabetic macular oedema: A 24-week randomized placebo-controlled trial

Adan-Castro, E.; Nunez-Amaro, C. D.; Villareal, J.; H. Islas, I.; Hernandez-Quijano, A.; Rodriguez-Chagoya,, B. E.; Garcia-Roa, M.; Lopez-Star, E.; Garcia-Franco,, R.; Robles-Osorio,, M. L.; Martinez de la Escalera, G.; Clapp, C.

2026-07-07 ophthalmology 10.64898/2026.07.04.26357144 medRxiv
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Background/Objective: Diabetic macular oedema (DMO) is a leading cause for visual impairment primarily managed with intravitreal anti-VEGF agents such as ranibizumab (RBZ). Levosulpiride (LSP), a prokinetic medication, was recently repositioned as a safe oral treatment for naive DMO. Here, we investigated the adjuvant effect of oral LSP in combination with intravitreal RBZ injections for treating persistent DMO. Subjects/Methods: Double-blinded, dual-centre, phase 2 trial in patients with centre-involving DMO randomly assigned to be orally treated with placebo (15 patients, 18 eyes) or LSP (18 patients, 19 eyes) along with 3 successive (4 weeks apart) RBZ intravitreal injections and a 24-week follow-up. Results: Baseline best-corrected visual acuity (BCVA) improved (p[&le;]0.04) at week 12 in both RBZ+placebo and RBZ+LSP, but improvement was maintained (p=0.009) at week 24 only in RBZ+LSP. In agreement, longitudinal changes from baseline in BCVA from weeks 12 to 24 defined superior (p=0.02) visual gains measured by the Area Under the Curve (AUC) in RBZ+LSP vs. RBZ+placebo. The baseline value of mean central foveal thickness (CFT) decreased (p[&le;]0.002) in both groups at week 12 and CFT reduction was significant (p=0.006) at week 24 only in RBZ+LSP. Also, longitudinal changes from baseline in CFT resulted in a higher AUC reduction (p[&le;]0.04) at weeks 4 to12 in RBZ+LSP vs. RBZ+placebo. No significant adverse side effects were detected. Conclusions: Adjunctive LSP showed functional and anatomical benefits over the first-line therapy with RBZ. Adjuvant properties may involve the LSP-induced intraocular upregulation and downregulation of vasoinhibin and VEGF, respectively. Larger clinical trials are warranted.

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Muscle stability deficits are strongly associated with musculoskeletal complaints in football (soccer) players: the AF-Ratio outperforms conventional strength parameters--a cross-sectional study with preliminary follow-up

Schaefer, L. V.; Bittmann, F. N.; Ulrich, J.; Prill, R.; Becker, R.

2026-07-10 sports medicine 10.64898/2026.07.07.26357205 medRxiv
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Objectives: Given the high injury burden in football and the documented limitations of strength-based screening, novel approaches are warranted. Adaptive Force (AF)being closer to injury-prone movements than pushing/pulling strength--offers an alternative. This study examined the association between AF-based muscle stability and musculoskeletal complaints in football players and compared AF-derived and conventional strength parameters in their discriminative capacity, complemented by a preliminary prospective follow-up. Methods: AF and maximal voluntary isometric contraction (MVIC) were measured in 23 male football players across five bilateral muscle groups (knee extensors/flexors; hip flexors/adductors/abductors). AF parameters (maximal isometric AF, maximal AF, AF-Ratio), MVIC and hamstrings-to-quadriceps (H:Q) ratio were compared between players with and without complaints assessed via questionnaire at baseline and six-month follow-up (n=13). Results: Stability deficits were strongly associated with complaints (OR=54.0, 82% side concordance). AF-Ratio discriminated clearly between players with and without complaints (d=-1.47), with hip abductors showing the strongest effect (d=-1.64). Players with subsequent complaints showed lower baseline AF-Ratio (d=-1.45) and more stability deficits (d=1.67). MVIC and H:Q ratio did not discriminate (p>0.430). Conclusion: The findings suggest that muscle stability assessment outperforms conventional strength parameters in discriminating players with and without complaints, with preliminary follow-up data providing tentative support for predictive value. The concept of functional instability syndrome (FIS) provides a mechanistic framework for non-contact injuries and musculoskeletal complaints. AF assessment offers potential for screening, including return-to-sport decisions. Further studies are needed to verify the results, investigate predictive value, and evaluate whether personalised stability-based interventions can reduce injury incidence.

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Sociodemographic Predictors of Consent: A Protocol and Statistical Analysis Plan for a Nested Observational Study of Canadian Sites in the REVISE Trial

Bauer, N.; Binnie, A.; Lad, V.; Marticorena, M.; Tsang, J.; Poirier Zytaruk, N.; Heels-Ansdell, D.; Cook, D. J.

2026-07-09 intensive care and critical care medicine 10.64898/2026.07.06.26357216 medRxiv
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Background: In Canada, there is a lack of data relating sociodemographic characteristics to the likelihood of consent and clinical trial participation. Objective: The overall objective of this study is to examine the association of hospital-level sociodemographic variables with a priori informed consent rates for participation in the REVISE trial. Design: This study is a retrospective observational analysis of Canadian sites participating in the international REVISE trial. Methods: Sociodemographic characteristics for 42 hospitals participating in the REVISE trial will be supplemented by national data from the 2021 Canadian Census of Population Profile at the census tract level corresponding to the hospital's location. Hospital level information for Ontario sites will be derived from the Institute for Clinical Evaluate Sciences (ICES) database. Site clustering will be performed using latent class analysis, a flexible clustering technique that identifies meaningful subgroups based on sociodemographic variables purposively selected from data available through the Statistics Canada 2021 census profile, ICES, and hospital-reported data. Clustering analysis will be performed for all Ontario hospitals with available ICES data, followed by a separate analysis for all Canadian REVISE sites using Statistics Canada data. Concordance in the clustering of REVISE sites will be examined by comparing the assignment of hospitals to the latent classes separately identified using ICES and Statistics Canada data. If there is a high degree of agreement between the two datasets, sociodemographic predictors will be analyzed using the clusters identified through ICES for Ontario sites with the concordant classes based on Statistics Canada data for Canadian sites outsite Ontario. If there is disagreement in cluster assignment between the two datasets, separate analyses of sociodemographic factors will be conducted for Ontario sites using ICES data and for all Canadian sites using the 2021 Census Profile. Multivariate linear regression models will be used to analyze the association between hospital-level characteristics and the likelihood of a priori and deferred consent. Results: Results of this study will generate information about the relationship between informed consent to participate in a low-risk critical care clinical trial using different consent models, and socioeconomic patient characteristics at the hospital site level (e.g., educational attainment, knowledge of official languages, citizenship rates, family income, poverty, rurality and immigration patterns). Conclusions: This study will fill an evidence gap by generating information on the relationship between sociodemographic variables and the likelihood of informed consent to participate in a critical care clinical trial in Canada.

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Bench-stepping training improves stair-walking dynamics in older women: evidence from an exploratory nonlinear kinematic analysis

Baggen, R. J.; van Schooten, K. S.; Van Roie, E.; Verschueren, S. M.; Delecluse, C.; Delbaere, K.; Lord, S. R.; van Dieen, J. H.

2026-07-07 sports medicine 10.64898/2026.07.02.26357116 medRxiv
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Introduction: Stair walking challenges balance and coordination in older people. Bench-stepping training improves stair climbing speed in healthy older women. This study assessed whether bench-stepping also improves dynamic balance and movement complexity during stair walking. Methods: Stair walking data were obtained from a previous study involving 45 healthy older women (69y+/-4) that assessed the effects of a 12-week bench-stepping intervention with non-training controls. Centre-of-mass acceleration was measured during stair ascent and descent. Linear dynamics included time, acceleration magnitude, and harmonic ratios (HR; indicating symmetry). Movement complexity was quantified using nonlinear dynamics including sample entropy (SE), recurrence quantification analysis (RQA), and fractal dimension (FD). Results: For stair ascent, increased speed (p =0.018, R2partial =0.093,) was accompanied by proportional increases in acceleration magnitudes (p=<0.039, R2partial =0.078-0.101). SE decreased more in the intervention group (p=<0.012, R2partial =0.049-0.101), indicating more predictable dynamics. In contrast, for stair descent, no changes in speed or acceleration magnitudes were observed. However, SE (p =0.001, R2partial =0.082) and maximum RQA line length (p= 0.008, R2partial =0.057) of vertical acceleration increased significantly compared to controls, indicating lower predictability and more persistent recurring patterns. No significant changes were found for other outcomes. Exploratory factor analysis revealed distinct differences in motor behaviour between stair ascent and descent. Conclusion: Bench-stepping training induced measurable changes in stair walking dynamics. Specifically, sample entropy shows potential as a sensitive marker of altered motor complexity, particularly of vertical accelerations. Interestingly, the direction of changes in unpredictability differed between stair ascent and descent, suggesting different underlying control strategies.

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Tooth Loss, Oral Health-Related Quality of Life, and Sexual Function in Women

Novaes, V. M.; Pimenta, R. M. C.; Silva, C. S.; Netto, B. V. S.; de Bessa, J.; Oliveira, M. C.

2026-07-13 dentistry and oral medicine 10.64898/2026.07.09.26357487 medRxiv
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This cross-sectional study evaluated the association of tooth loss and oral health-related quality of life (OHRQoL) with sexual function in adult women attending a primary dental care service. Methodology: Ninety-nine sexually active women aged 19-66 years were consecutively recruited from a primary dental care service between January and October 2023. Tooth loss was quantified by standardized oral examination. OHRQoL was assessed using the Oral Health Impact Profile-14 (OHIP-14), and sexual function was assessed using the Female Sexual Function Index (FSFI). Sexual dysfunction was defined as FSFI <=26.5. Spearman rank correlation was used for bivariate analyses. Multivariable logistic regression was used to evaluate factors associated with sexual dysfunction, including number of missing teeth, OHIP-14 score, age, and relationship status. Results: Tooth loss was present in 83.8% of participants, with a median of 4 missing teeth (interquartile range [IQR], 1-10). Sexual dysfunction was identified in 62.6% of women. FSFI scores were negatively correlated with number of missing teeth (rho = -0.407; p < 0.001), OHIP-14 score (rho = -0.279; p = 0.005), and age (rho = -0.334; p < 0.001). In multivariable logistic regression, OHIP-14 score was independently associated with sexual dysfunction (OR = 1.05; 95% CI, 1.01-1.10; p = 0.015), whereas number of missing teeth was not independently associated after adjustment. Conclusion: Worse OHRQoL was independently associated with sexual dysfunction, whereas tooth loss was associated with lower FSFI scores only in bivariate analysis. These findings are compatible with the hypothesis that the impact of tooth loss on sexual function may be partly explained by oral health-related quality of life, but longitudinal studies are required to test causal and mediational pathways. Keywords: tooth loss; oral health; quality of life; sexual dysfunction, physiological; women; cross-sectional studies

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Study protocol: Empowering Singaporeans to better manage chronic heart failure

Bairavee, B.; Wang, Y.; Kanna Ravi, D.; Lee Shan Yin, A.; Ching Chiew Wong, R.; Loh, S. Y.; Graves, N.; Sung, S.; Yoon, S.; Hausenloy, D. J.; Low, L. L.; Yeo, K.-K.; Sim, K. L. D.; Zhang, Y.; Kularatna, S.; Senanayake, S.

2026-07-13 health systems and quality improvement 10.64898/2026.07.09.26357623 medRxiv
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Background The prevalence of chronic heart failure is increasing in Singapore and is associated with frequent hospitalisations, high costs, and impaired quality of life. Patient empowerment interventions for chronic diseases, which are structured approaches that enable patients to actively engage in and influence their care, have demonstrated promising effects on health-related outcomes. In chronic heart failure, however, many interventions focus on selected aspects of empowerment, and there remains limited synthesis of which approaches are most acceptable, preferred, and effective as comprehensive intervention packages. This protocol describes the methods for a study to identify an empowerment-based intervention for adults with chronic heart failure that is both contextually suitable and cost-effective in Singapore. Methods We will use a staged, sequential design comprising three objectives. Objective one is to conduct a systematic review (PROSPERO registration number CRD420251249957) and meta-analysis to synthesise international evidence of the effectiveness of empowerment-based interventions for adults with chronic heart failure. Objective two is to complete a mixed-methods study, including semi-structured interviews with chronic heart failure patients, as well as their caregivers, to identify empowerment-related needs, barriers and facilitators in local chronic heart failure care. This will be followed by a discrete choice experiment to elicit patients preferences for features of an empowerment-based intervention. Objective three is to conduct a cost-effectiveness analysis of the proposed intervention from the perspective of the Singapore health system. Discussion This series of studies integrates international evidence with local stakeholder perspectives and patient preferences to inform a feasible, patient-centred empowerment intervention for chronic heart failure in Singapore. The findings will inform intervention design and provide policy-relevant evidence on costs, health outcomes, and implementation decisions for empowerment-based chronic heart failure care in Singapore.

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Involvement of Mitophagy in Endothelin-1 Mediated Neurodegeneration in Rodent Models of Glaucoma

Brooks, C. D.; Kodati, B.; Prasad, S.; Cunningham, J.; Patel, P.; Mangan, M.; Curry, S.; FoxRun, D. K.; Ehsan, A.; Arya, O.; Flume, H.; Kunwar, K.; Woerner, A. E.; Inman, D. M.; Stankowska, D. L.; Krishnamoorthy, R. R.

2026-07-08 neuroscience 10.64898/2026.07.02.735939 medRxiv
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The ultimate cause of blindness in glaucoma is the death of retinal ganglion cells, and understanding the mechanism behind retinal ganglion cell loss during glaucoma could lead to the development of novel treatments for glaucoma. Endothelin-1 has been shown to mediate retinal ganglion cell death during glaucoma through impairment of mitochondrial function. Retinal ganglion cells are highly metabolically active, and susceptible to oxidative damage and decreased respiratory capacity. Mitophagy is the process whereby damaged mitochondria are degraded to prevent further propagation of oxidative damage. The current study evaluates the effect of endothelin-1 on mitophagy in retinal ganglion cells. Electron microscopy revealed endothelin-1 administration lead to a decrease in healthy mitochondria in the optic nerve. The MitoQC mouse was used to evalute mitophagy in response to endothelin-1, along with immunohistochemical analysis of mitophagy proteins. Mitophagy follows different trends in the optic nerve and retinal ganglion cell bodies following endothelin-1 administration, mitophagy was increased in the optic nerve but decreased in the retina following endothelin administration. With elevation of intraocular pressure, mitophagy was increased in the retina but decreased in the optic nerve. In retinal ganglion cells, parkin expression and activation was unchanged 24 hours after endothelin-1 administration, but was decreased 72 hours following endothelin-1 administration. Taken together, these results suggest that endothelin-1 impacts mitophagy through parkin-independent mechanisms in retinal ganglion cell bodies, and the ganglion cell bodies and optic nerve appear to have different responses to endothelin-1.

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Double burden of malnutrition and cardiometabolic risk among older residents of a state social-care institution in Kazakhstan: a cross-sectional study

Abduldayeva, A. A.; Iskakova, S. A.; Doszhanova, G. N.; Kozhamkulov, O. M.; Tardjibayeva, S. K.; Bukeyeva, Z. K.; Shuakbayeva, A. B.; Suindik, K. B.; Tolegenova, Y. E.; Lenzatova, Z.; Aktanova, A. S.

2026-07-13 geriatric medicine 10.64898/2026.07.09.26357706 medRxiv
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Older adults in residential care are usually described as a group at high risk of undernutrition, yet data on the nutritional and cardiometabolic status of institutionalised older adults in Central Asia are scarce. We aimed to characterise the anthropometric, dietary and biochemical profile of older residents of a state social-care institution in Kazakhstan and to examine whether overnutrition, micronutrient inadequacy and cardiometabolic risk coexist. In this cross-sectional study, 62 adults aged 60 years and over from the "Sharapat" centre in Astana underwent anthropometry, bioelectrical impedance body-composition analysis, blood-pressure measurement, dietary assessment (specialized nutrition questionnaires, a 24-hour dietary recall and food diaries) with calculation of nutrient intakes, and venous blood and urine testing; serum 25-hydroxyvitamin D and trace elements were measured in 29 participants. Laboratory analyses and data processing were performed at the Research Institute of Preventive Medicine named after E.D. Dalenov, Astana Medical University. The sample (61.3% men; mean age 74.0 years) showed a high cardiometabolic burden, with arterial hypertension in 63%, total cholesterol of at least 5.0 mmol/L in 60%, LDL-cholesterol of at least 3.0 mmol/L in 71%, and overweight or obesity in 58%, whereas only 5% were underweight. Habitual diets were high in sodium (71% above 2000 mg/day) and low in potassium (92% below 3500 mg/day), calcium (85% below 1000 mg/day) and fibre (90% below 25 g/day). Among those tested, 79% had vitamin D deficiency, and overweight or obesity coexisted with vitamin D deficiency in 16 of 29 participants. None of 56 exploratory diet-risk correlations survived correction for multiple testing. Rather than the undernutrition typical of residential care, these residents displayed a double burden of malnutrition-excess adiposity and cardiometabolic risk alongside micronutrient-poor diets and widespread vitamin D deficiency-identifying concrete targets for institutional catering, supplementation and cardiometabolic screening.

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Perspectives in conducting task-based research in pediatric surgical epilepsy patients

Leisawitz, J. P.; Georges, S. F.; Field, A. M.; Asghar, S.; Foox, G.; Watrous, A. J.; Weiner, H. L.; Anderson, A. E.; Hamilton, L. S.

2026-07-08 neuroscience 10.64898/2026.07.02.734030 medRxiv
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Objective: Pediatric epilepsy patients undergoing stereo-electroencephalography (sEEG) for ictal onset evaluation provide a rare window to study the developing brain. While methodological frameworks for task-based sEEG research are well-established in adults, pediatric-specific guidance remains underdeveloped. Furthermore, many pediatric epilepsy patients have comorbidities that might typically exclude them from participating in research. We examine factors that influence research participation and discuss considerations for conducting sEEG research in children. Methods: Here, we present a retrospective analysis of task-based research participation patterns from an NIH-funded study of speech and language representations (1R01DC018579) in 66 patients (ages 4-24) undergoing sEEG monitoring at Texas Children's Hospital to determine whether specific comorbidities influenced research participation. Results: Eighty-nine percent (n=66) of patients approached for consent agreed to participate in the study. Despite high rates of comorbidities including neurocognitive disorder (66.67%), language delay (31.75%), global developmental delay (23.81%), mood disorders (33.33%), ADHD (46.03%), autism spectrum disorder (14.29%) or other cognitive/intellectual disabilities (36.51%), all participants engaged in at least one task. While the majority of these diagnoses did not appear to influence subject participation, global developmental delay was associated with a significant reduction in time spent on active tasks. Discussion: Despite high prevalence of neuropsychological comorbidities among participants, our evidence suggests that these participants contribute meaningfully to studies investigating important developmental questions. We suggest strategies for tailoring task-based research to accommodate the unique needs of individuals in this population. Such practices are important for ensuring that research studies reflect the true diversity of the population.