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Medicine

Ovid Technologies (Wolters Kluwer Health)

Preprints posted in the last 90 days, ranked by how well they match Medicine's content profile, based on 30 papers previously published here. The average preprint has a 0.08% match score for this journal, so anything above that is already an above-average fit.

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Integrated Clinical and Network Pharmacology Study Reveals the Efficacy and Multi-Target Mechanism of Shenfu Injection in Septic Shock

Shi, Y.; Zhang, B.; Tian, Y.; Liu, Q.; Zhou, X.

2026-03-25 emergency medicine 10.64898/2026.03.20.26348945 medRxiv
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Background The high mortality of septic shock demands novel adjunctive therapies. Shenfu Injection (SFI), a traditional Chinese medicine, shows potential but its mechanism remains unclear. Method s We conducted an open-label, randomized trial in 80 patients with septic shock. Patients received standard care with or without adjunctive SFI for 7 days. The primary outcome was 28-day mortality. Key secondary outcomes included inflammatory markers, lactate clearance, and vasopressor duration. Concurrently, network pharmacology analyzed SFIs bioactive components, predicted targets, and enriched pathways, with validation by molecular docking. Results The 28-day mortality was significantly lower in the SFI group (20.0% vs. 42.5%, P=0.030). SFI accelerated clinical improvement, evidenced by greater reductions in IL-6 and procalcitonin, higher 6-hour lactate clearance (35.2% vs. 18.5%, P<0.001), shorter vasopressor duration (48 vs. 72 hours, P<0.001), and more rapid SOFA score decline. Network pharmacology identified 145 SFI-septic shock common targets, with IL-6, SRC, and MAPK3 as central hubs. Pathway analysis revealed significant enrichment in TNF, PI3K-Akt, and IL-17 signaling pathways. Molecular docking confirmed strong binding of key SFI components (e.g., Ginsenoside Rh2) to core targets like IL-6. Conclusion s Adjunctive Shenfu Injection reduces mortality and improves clinical recovery in septic shock, potentially through a multi-target mechanism involving modulation of inflammatory and cellular signaling pathways. This integrative study provides both clinical evidence and a mechanistic framework supporting SFI's use. Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020435.

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A novel parameter for predicting postoperative shoulder balance in Lenke Type 1 and 2 adolescent idiopathic scoliosis patients

Chi, P.; Tian, Z.; Zhang, B.; Wang, Z.; Song, K.

2026-02-01 orthopedics 10.64898/2026.01.26.26344281 medRxiv
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PurposeTo evaluate the predictive value of the thoracic spine-clavicle angle (TSCA) and the thoracic cage-clavicle angle (TCCA) for immediate postoperative shoulder balance. MethodsA total of 154 Lenke type 1 and 2 AIS patients who underwent corrective surgery in our hospital were included. The degree of clavicle angle (CA), thoracic spine tilt angle (TSTA), thoracic cage tilt angle (TCTA), proximal thoracic curve (PTC) Cobb angle, and main thoracic curve (MTC) Cobb angle were measured on standing full-length posteroanterior spine radiographs before and after surgery. Five parameters, TSCA, TCCA, correction rate of PTC, correction rate of MTC, relative PT/MT residual Cobb angle (RRCA), were calculated. Multinomial Logistic Regression was used to determine the risk factors of PSB. A p-value of less than 0.05 was considered statistically significant. ResultsFor TCCA, in group R (vs group B), pre-op right high (vs pre-op left high) (OR=8.102, 95%CI [1.650, 39.786], p=0.01) and RRCA (OR=1.015, 95%CI [1.004, 1.026], p=0.009) are risk factors. Pre-op left high (vs pre-op right high) (OR=0.123, 95%CI [0.025, 0.606], p=0.01) and correction rate of MTC (OR=0.886, 95%CI [0.809, 0.971], p=0.009) are protective factors. Correction rate of PTC shows no significant effect. In group L (vs group B), pre-op left high (vs pre-op right high) (OR=2.648, 95%CI [1.084, 6.469], p=0.033) is a risk factor. Pre-op right high (vs pre-op left high) (OR=0. 378, 95%CI [0. 155, 0.922], p=0. 033) is a protective factor. Correction rate of PTC, correction rate of MTC, and RRCA show no significant effect. ConclusionPreoperative shoulder balance, as defined by the TCCA, serves as an independent risk factor for PSB. Using postoperative balanced shoulders as the reference group, preoperative left shoulder high (vs right high) significantly increased the risk of postoperative left shoulder high, while significantly reducing the risk of postoperative right shoulder high. Preoperative right shoulder high (vs left high) significantly increased the risk of postoperative right shoulder high, while significantly reducing the risk of postoperative left shoulder high. The correction rate of MTC was an independent protective factor against postoperative right shoulder high, whereas RRCA was an independent risk factor for postoperative right shoulder high.

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Determining Decision Thresholds For Physicians And Parents For Instituting A Do Not Attempt Resuscitation Order For Pediatric Inhospital Cardiac Arrest Patients. A Cross-Sectional Study Of Parents And Physicians In The United States

Mawani, M.; Shen, Y.; Knight, J. H.; McNally, B.; Ebell, M.

2026-02-18 pediatrics 10.64898/2026.02.17.26346477 medRxiv
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Background and ObjectivesDecision-making about resuscitating a critically ill child is complex yet common. We aimed to study the survival thresholds at which physicians, compared to parents, decide to treat or withhold resuscitating a child. Moreover, we aimed to compare physicians survival estimates with those from a nationwide registry. MethodsWe conducted a cross-sectional survey-based study in the United States. Clinical vignettes based on hypothetical survival probabilities were used to study and compare the decision thresholds for parents and physicians. Vignettes developed using the Get-With-The-Guidelines-Resuscitation registry were used to explore physicians decision thresholds and compare their survival estimates with those from the data. Thresholds were determined using mixed-effect logistic regression models. ResultsWe had decisions for 501 and 257 vignettes from 167 parents and 43 physicians, respectively. The decision threshold for survival to discharge was 5.3% (95% CI: 3.7 to 7.0) for physicians and 1.2% (95% CI: -0.8 to 3.0) for parents. Whereas the decision threshold for survival to discharge with PCPC 1 or 2 was 3.5% (95% CI: 1.1 to 7.1) for physicians and 0.6% (95% CI: -1.2 to 1.8) for parents. About 58% of the physicians overestimated the likelihood of survival. ConclusionsThe study found that the decision threshold for the physicians was higher than that for the parents (5.3% vs. 1.2%). This illustrates that parents still want to attempt resuscitation at a survival probability where physicians would recommend withholding resuscitation. These findings have implications for clinical practice and counseling the parents of critically ill hospitalized children.

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The efficacy and safety of argatroban with clopidogrel versus aspirin with clopidogrel for acute minor ischemic stroke (ACAP): study protocol for a multicenter, randomized controlled trial

Zhang, H.; Ma, X.; Xiao, Y.; Liao, G.; Kong, N.; Qin, T.; Huang, M.; Yin, Z.; Chen, W.; Wu, J.; Xian, J.; Fu, J.; Xie, F.; Jin, C.; Liao, Z.; Liang, W.; Lin, L.; Xian, W.; Nguyen, T. N.; Wang, D.; Zhong, W.

2026-03-31 neurology 10.64898/2026.03.30.26349790 medRxiv
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Background: Previous studies have shown the benefit of dual antiplatelet therapy (DAPT) for acute minor ischemic stroke. Argatroban, is a thrombin inhibitor and is primarily used in patients with acute ischemic stroke experiencing early neurological deterioration. There is no study about the benefit of antiplatelet plus anticoagulant in this population. We aim to study the difference between the combination of argatroban and clopidogrel and DAPT in the outcomes of patients with acute minor ischemic stroke (AMIS, NIHSS <5) presenting within 72 hours after onset. Methods: Argatroban combined with clopidogrel versus aspirin combined with clopidogrel in Stroke (ACAP study) is an investigator-initiated, multicenter, prospective, randomized, open-label trial with blinded endpoint evaluation conducted at four centers in China. This trial will randomize 464 eligible patients with minor ischemic stroke of NIHSS 5 (232 in each arm) within 72 hours of the last known well to receive intravenous argatroban with clopidogrel (treatment group) or aspirin plus clopidogrel (control group). The primary outcome is the proportion of patients achieving excellent outcome, defined as a score of 0-1 on the modified Rankin scale, at 90 days. Conclusions: The ACAP trial will provide important data on the role of intravenous argatroban in patients with acute minor ischemic stroke presenting within 72 hours of last known well.

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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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Adjunct tirofiban treatment after successful endovascular thrombectomy recanalisation in acute anterior circulation ischemic stroke (ATTRACTION): protocol of a multicenter, prospective, double-blind, randomised trial

Luo, X.; Huang, H.; Xu, S.; Li, G.; Zhang, Y.; Luo, Y.; Kong, Q.; Liu, C.; Xie, Y.; Deng, G.; Wang, Y.; Ao, D.; Lan, L.; Yu, Y.; Tang, Z.; Wang, W.

2026-02-26 neurology 10.64898/2026.02.25.26346143 medRxiv
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BackgroundSuccessful recanalisation without functional independence is a frequent phenomenon following endovascular thrombectomy for large vessel occlusion stroke. AimTo demonstrate safety and efficacy of adjunct tirofiban therapy after endovascular thrombectomy in patients with anterior circulation large vessel occlusion stroke achieving successful recanalization defined as modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3. DesignThe study of adjunct tirofiban treatment after successful endovascular thrombectomy recanalisation (ATTRACTION) is a multicenter, prospective, double-blind, randomized trial enrolling 1360 patients in China. Eligible patients will be randomised 1:1 to either the tirofiban or placebo group. OutcomeThe primary efficacy outcomes is assessed as the proportion of participants with a modified Rankin Scale (mRS) score of 0-2 at 90 days, and the primary safety outcome is symptomatic intracranial haemorrhage within 48 hours from randomisation. ConclusionThis study will provide evidence on the efficacy and safety of sequential tirofiban therapy after successful recanalisation in patients with anterior circulation large vessel occlusion stroke. Trial registration numberNCT06265051 WHAT IS ALREADY KNOWN ON THIS TOPICSuccessful recanalization without functional independence is a frequent phenomenon following endovascular thrombectomy and previous small-sample, retrospective studies supported the administration of adjunct tirofiban therapy in patients after endovascular thrombectomy achieving successful recanalization. WHAT THIS STUDY ADDSThe ATTRACTION trial aims to access the efficacy and safety of adjunct tirofiban therapy and the protocol describes the rationale and design of the trial. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYATTRACTION trial will inform whether tirofiban therapy after successful recanalisation by endovascular thrombectomy can improve patient outcomes.

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Physical Therapy Utilization and 12-Month Pain and Functional Improvement in Patients Undergoing Arthroscopic Rotator Cuff Repair Surgery: A Case Series

Pierson, C. J.; Moore, B. P.; Elias, T.; Harris, J. C.; Somerson, J.

2026-02-24 orthopedics 10.64898/2026.02.19.26346640 medRxiv
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BackgroundArthroscopic rotator cuff repair (RCR) is a common surgical intervention used to address rotator cuff-related pain after other conservative interventions have been exhausted. With a continuing increase in procedures, evidence-based outcomes research is needed to identify key parameters of postoperative rehabilitation planning. ObjectiveWe aim to identify rehabilitation planning factors leading to better outcomes while also providing clinicians with reference data to describe the magnitude of pain and functional improvement following RCR. MethodsFor this observational study of patients undergoing RCR surgery and physical therapy, demographic variables and patient-reported outcome measures (PRO) were collected preoperatively and up to 12 months postoperatively Four multiple linear regression models were created, one for 12-month Visual Analog Scale (VAS) score, the second for VAS improvement, the third for 12-month American Shoulder and Elbow Surgeons (ASES) function score, and the fourth for ASES function improvement. ResultsThe 29 participants had a median age of 62 years, median baseline VAS of 4.9, ASES composite score of 45, and Veterans-Rand 12 Mental Component Score of 53.5. In univariate analysis, one variable was associated with 12-month VAS score and two were associated with 12-month VAS improvement. No associations were found with 12-month ASES function score, and one variable was associated with ASES function improvement. With our sample, multivariable analyses provided no significant association or predictor for VAS or ASES function scores. ConclusionsOur hypothesis was not supported, and we did not find an association between physical therapy wait time prior to evaluation or visit frequency and PRO measures or improvements. We observed that 12-month PRO measures and improvements can be predicted using baseline measures among this population.

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Assessing the recovery after cardiac surgery: Development and validation of the Fuwai-CRS (Fuwai-Cardiac Recovery Scale)

Sun, R.; Lin, S.; Jiao, Z.; Rao, C.; Su, X.; Hu, S.; Zhao, Y.; Zhang, H.; Shi, Q.; Liu, S.; Feng, W.; Cheng, Z.; Wang, X.; Zhou, C.; Wang, J.; Ling, Y.; Shen, Z.; Tian, H.; Zheng, Z.

2026-03-04 cardiovascular medicine 10.64898/2026.03.03.26347484 medRxiv
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BackgroundCardiac surgery significantly improves clinical endpoints but imposes challenges in postoperative recovery. Assessing patient-reported outcome is crucial for optimal care. However, no cardiac surgery-specific tools currently exist to adequately capture postoperative recovery experience. ObjectivesTo develop and validate a recovery scale after cardiac surgery (Fuwai-CRS). MethodsThis study was conducted from May 2023 to December 2024, comprising: (1) a qualitative study (Cohort 1) enrolling postoperative patients of cardiac surgery and medical staffs to develop the draft scale through literature review, semi-structured interview and Delphi consensus; and (2) a single-center prospective validation study (Cohort 2) to finalize the scale and evaluate psychometric properties. ResultsIn Cohort 1, a 17-item draft Fuwai-CRS was generated based on literature review, semi-structured interview (40 patients and medical staffs) and a Delphi study (15 experts). In Cohort 2 (n=500), a 9-item Fuwai-CRS was finalized by data distribution assessment, hierarchical cluster and factor analysis, and its understandability, reliability, validity and responsiveness were found acceptable. ConclusionsThe Fuwai-CRS is a concise and valid tool for recovery assessment after cardiac surgery.

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A Remote Comprehensive Neurocognitive Test Battery to Monitor Postoperative Neurocognitive Dysfunction in Older Adults: A Prospective Observational Study

Rockholt, M. M.; Wu, R. R.; Seidenberg, B.; Martinez, H.; Momesso, G.; Zhu, E.; Saba, B. v.; Perez, R.; Bi, C.; Park, W.; Bruno, G.; Waren, D.; O'Brien, C.; Denoon, R. B.; Commeh, E. B.; Aggarwal, V. K.; Rozell, J. C.; Furgiuele, D.; Park, H. G.; Schulze, E. T.; Macaulay, W.; Schwarzkopf, R.; Wisniewski, T.; Osorio, R. S.; Doan, L. v.; Wang, J.

2026-02-17 anesthesia 10.64898/2026.02.16.26346401 medRxiv
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INTRODUCTIONRisks for postoperative cognitive dysfunction remain poorly understood. Traditional cognitive screening tools such as the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) are used for perioperative cognitive evaluation but have limited scope, whereas comprehensive in-person testing poses problems for long-term follow up. METHODSThis prospective cohort study assesses the feasibility of using a remotely performed comprehensive neurocognitive test battery, the Uniform Data Set tele-adapted neuropsychological battery version 3 (UDS v3.0 T-cog), administered at baseline and 1 week, 1 month, and 3 months postoperatively, to comprehensively study neurocognitive outcomes in older adults undergoing orthopedic joint arthroplasty. Patient satisfaction with T-cog was assessed through four survey questions evaluating technical issues, duration, willingness to participate in in-person assessment, and satisfaction with remote assessment at 3 months after surgery. Further assessment of pain and mood also included PROMIS scales, McGill Pain Questionnaire, and Pain Catastrophizing Scale, before and 3 months after surgery. RESULTS127 participants were enrolled, and out of 120 participants who completed baseline cognitive assessment and underwent surgery, 98 completed cognitive assessments at 3 months. At 3 months, 17% of participants showed an objective decline in cognitive function based on this comprehensive assessment. The remote assessment format was well-received with high participant satisfaction. The UDS v3.0 T-cog identified deficits in specific domains that would have been missed by brief screening instruments, supporting its values for perioperative use. DISCUSSIONThis is the first study to utilize this comprehensive remote cognitive assessment tool to study long-term cognitive function. The assessment can be combined with other preoperative outcome assessments in older adults undergoing surgery. HighlightsO_LICurrent detection of perioperative cognitive outcomes in older adults rely on in-person cognitive assessments that are varied in methodology and often lack sensitivity and specificity C_LIO_LIThe UDS v3.0 T-cog identified objective cognitive decline in 17% of patients after orthopedic arthroplasty while also detecting early non-memory cognitive decline through the more comprehensive test battery with high participant satisfaction and retention, supporting remote assessment feasibility. C_LIO_LIThese findings suggest that remote comprehensive cognitive assessments are an effective tool to provide early detection and risk stratification for perioperative neurocognitive dysfunction in older patients. C_LI

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The effects of different course assessment methods on college studentstennis performance and basic psychological needs: A cluster randomized controlled trial

wang, y.; Luo, Y.

2026-04-19 sports medicine 10.64898/2026.04.16.26351011 medRxiv
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Purpose: This study aimed to examine the effects of formative and summative assessments on college students tennis performance and basic psychological needs. Methods: A total of 128 undergraduate students (64 males, 64 females; Mage = 19.22, SD = 0.91) participated in this study. Participants were cluster-randomized to either a formative assessment group (n = 64) or a summative assessment group (n = 64). The formative assessment intervention involved setting personalized learning goals and success criteria, administering periodic tests, and providing process-oriented and individualized feedback. The summative assessment intervention involved setting uniform goals for all students, offering instructor feedback only on common problems, and requiring students to practice independently after class without personalized guidance. Both interventions were implemented over 10 weeks, with one 90-minute session each week. Tennis skills and basic psychological needs (i.e., autonomy, competence, and relatedness) were assessed before and after the intervention. Tennis skills were reassessed 1 week after the intervention. Two-way mixed-effects analysis of variance (ANOVA) was used to examine the impact of group, time, and their interaction on tennis skills and basic psychological needs. Results: The results showed that the interaction between group and time was significant for all of the outcome variables. Simple effects analyses indicated that, at pre-test, the two groups did not differ significantly in tennis performance or in satisfaction of autonomy, competence, and relatedness (p > 0.05). At post-intervention, the formative assessment group demonstrated significantly better performance than the summative assessment group in tennis skills (MD = 3.50, 95% CI = [1.303, 5.697], p = 0.002), autonomy (MD = 2.44, 95% CI = [1.816, 3.059], p < 0.001), relatedness (MD = 1.33, 95% CI = [0.679, 1.977], p < 0.001), and competence (MD = 1.75, 95% CI = [1.046, 2.454], p < 0.001). At the 1-week follow-up session, the formative assessment group also showed significantly better tennis performance than the summative assessment group (MD = 6.81, 95% CI = [4.667, 8.958], p < 0.001). Conclusion: Formative assessment was more effective than summative assessment in improving college students tennis performance and satisfying their basic psychological needs. These findings suggest that incorporating personalized goals, process-oriented evaluation, and individualized feedback into tennis instruction could promote both skill development and psychological outcomes in college physical education.

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Parakinesia Brachialis Oscitans and Post-Stroke Motor Recovery: A Propensity Score-Matched Cohort Study

Wang, C.-c.; Wang, R.; Hu, H.; Su, Z.; Guo, S.; Tian, X.

2026-02-02 neurology 10.64898/2026.01.29.26345175 medRxiv
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ObjectiveA comparative analysis was conducted on the rehabilitation effects of limb functions in patients with post-stroke yawning-induced parakinesia brachialis oscitansysis (PBO), patients without PBO, and patients whose PBO naturally disappeared after the onset of the disease. MethodsThe study included ischemic stroke patients diagnosed and treated in our hospital from March 2024 to June 2024. Patients were divided into two groups: the PBO group and the non-PBO group, based on whether PBO was administered. Propensity score matching was employed to account for all covariates and perform a 1:2 matching to balance the baseline characteristics of the two groups. The matched data were used for subsequent analysis to observe the Lovett scores and FMA scores of the two groups 3 months after the onset. For 33 patients with PBO, they were divided into two groups: the persistent group and the disappearing group, based on whether the PBO lasted for more than 1 month. The Lovett scores and FMA scores of the two groups were observed 3 months after the onset. ResultsAfter propensity score matching, there were 26 patients in the PBO group and 52 patients in the non-PBO group. The baseline characteristics of the two groups were basically balanced, and the difference was not statistically significant (P>0.05). Compared with the non-PBO group, the Lovett scores and FMA scores of the PBO group 3 months after the onset were higher, and the difference was statistically significant (P < 0.05). Compared with the PBO persistent group, the FMA score of the PBO disappearing group 3 months after the onset was higher than that of the persistent group, and the difference was statistically significant (P < 0.05). There was no statistically significant difference in Lovett muscle strength between the two groups (P > 0.05). ConclusionThe functional recovery of patients with PBO was better than that of patients without PBO manifestation 3 months after the initial diagnosis. Moreover, patients whose PBO appeared first and then disappeared had better functional recovery than those whose PBO persisted.

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Active treatments outperform minimal intervention for adults with rotator cuff tendinopathy: a systematic review with predictive and network meta-analyses of complex interventions

Rabello, R.; Fearon, A.; Sharif, F.; Neal, B. S.; Newman, P.; Lack, S.; Haleem, Z.; Tzortziou Brown, V.; Cooper, K.; Swinton, P.; Morrissey, D.

2026-03-25 sports medicine 10.64898/2026.03.23.26349060 medRxiv
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OBJECTIVE To guide treatment of adults with rotator cuff tendinopathy (RoCuTe) by evaluating the relative efficacy of treatments, benchmarked against minimal intervention, for the co-primary outcomes of pain, function and quality-of-life (QoL) across short, medium, and long-term follow-up. DESIGN Systematic review with Bayesian predictive and network meta-analyses for synthesising complex interventions, guided by stakeholder involvement. FUNDING Private Physiotherapy Education Foundation (UK) Silver Jubilee Award. DATA SOURCES PubMed, Embase, Web of Science, CINAHL, and SPORTDiscus, searched to 22/8/2025. ELIGIBILITY CRITERIA FOR SELECTING STUDIES High-quality (PEDro score equal or above 7) randomised controlled trials comparing any intervention with another active or minimal intervention for patients clinically diagnosed with RoCuTe of either traumatic or insidious presentation; and reporting outcomes for pain, function and/or QoL. METHODS Title and abstract screening, full-text screening, and quality assessments were completed by two reviewers. Data extraction used the Elicit AI tool and was manually checked. Interventions were classified by treatment focus. Guided by patient and public involvement, pooled results from active interventions at short (1 to 12 weeks included), mid (>12 weeks to <12 months) and long-term (12 months included or more) were calculated for the primary analysis using Bayesian predictive meta-analysis models of within group change scores. Outcomes were benchmarked against an empirically derived minimal-intervention comparator (wait-and-see or sham). As a secondary analysis, network meta-analyses were conducted to synthesise relative effects and provide comparative rankings of active interventions. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence evaluated using GRADE. RESULTS We retained and analysed 140 high-quality studies that included 10,260 patients, 55.9% female, with a mean age of 48 (SD 8) years. Minimal interventions were associated with small short-term improvements, modest medium-term improvements and some regression in the long-term; in pain (0 to 100 scale: short=2.6; mid=23.3; long=21.1), function (standardised mean change (SMC): short=0.13; mid=0.87; long=0.76), and QoL (SMC: short=0.05; mid=0.33). At all timepoints, all active interventions with sufficient data were superior to minimal intervention for pain (0 to 100 scale: short = 18.1 to 37.9 [14 categories]; mid = 25.8 to 34.8 [8 categories]; long = 30.8 to 45.0 [6 categories]), function (SMC: short = 1.1 to 2.4 [14 categories]; mid = 1.1 to 2.0 [11 categories]; long = 1.0 to 1.8 [10 categories]), and QoL (short = 0.8 to 1.7 [7 categories]; mid = 0.9 to 1.8 [6 categories]). Certainty varied widely. Accordingly, three recommendation groups were defined based on the availability of comparative evidence and presence of higher-certainty findings. The strongest recommendation group included strengthening, range-of-motion exercises, complex interventions and movement pattern retraining. CONCLUSIONS A range of active treatments were superior to minimal intervention at each time point, so a wait-and-see approach should not be used, even in in the short-term. The most credible evidence was for interventions with a focus on strengthening, range-of-motion exercises, movement pattern retraining, and complex interventions. Clinicians should prioritise active management and deploy personalised clinical reasoning to tailor treatment to patient preferences and the available resources. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42024584126

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Reach, implementation fidelity, and safety of bubble continuous positive airway pressure (bCPAP) therapy in children with severe pneumonia in Pakistan

Ijaz, N.; Shabbir, A.; Bachal, P.; Rizwan, H.; Uzair, M.; Ul Ain, N.; Qasmi, Z.; Shakoor, I.; Davis, J. L.; Jehan, F.; McCollum, E. D.; Abbas, Q.

2026-03-22 pediatrics 10.64898/2026.03.19.26348802 medRxiv
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Bubble continuous positive airway pressure (bCPAP) is a low-cost respiratory support device that has demonstrated different outcomes for children with severe pneumonia in different settings. Some differences in outcomes may be attributable to implementation factors (e.g., patient monitoring and feeding practices). We aimed to characterize bCPAP reach, implementation fidelity, and safety outcomes for children with severe pneumonia in Pakistan. We conducted a prospective cohort study at Aga Khan University Hospital and Abbasi Shaheed Hospital from February through May 2025. We enrolled children 1-59 months who met WHO criteria for severe pneumonia within 24 hours of presentation to the emergency department. Participants were followed daily via chart review, caregiver survey, and physical exam through discharge, transfer, or death. We reported the proportion of children receiving bCPAP ("reach") and constructed a mixed-effects, multinomial logistic regression model with robust standard errors to report: fidelity (child location in a highly monitored area, continuous monitoring, avoidance of unplanned disruptions to bCPAP, and avoidance of oral feeding); safety (aspiration events and pneumothorax); bCPAP failure (death, respiratory support escalation, or leaving against medical advice); and in-hospital mortality. Of 165 children with severe pneumonia, 88 (53%) received bCPAP over 141 bCPAP days. The average predicted probabilities (95% CI) of our fidelity measures were: 85% (78-92%) for location in a highly monitored area; 56% (51-60%) for continuous monitoring; 66% (57-75%) for continuous bCPAP without disruptions; 46% (36-55%) for avoidance of oral feeding while on bCPAP. Among children receiving bCPAP, 9 (10%) experienced an aspiration event, 1 (2.2%) experienced a pneumothorax; 19 (22%) experienced bCPAP treatment failure. One child (1.1%) died; 6 (6.8%) required respiratory support escalation; 14 (16%) left against medical advice. We identified several gaps in bCPAP reach and fidelity. These may be modifiable by individual-and team-targeted strategies to reduce bCPAP-related complications and pneumonia-related child deaths.

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Comparison Of Postoperative Pain Severity And Analgesic Consumption Within 24 Hours Between Primary And Repeat Cesarean Sections Under Spinal Anesthesia: A Prospective Cohort Study

Bitewlign, M. Z.; Gemeda, L. A.; Delile, S. T.; Seife, M. A.; Zeleke, M. E.; Gebrewahd, T. H.; Gebreslase, L. G.; Tesfagergse, Y. T.

2026-03-06 anesthesia 10.64898/2026.03.05.26347682 medRxiv
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BackgroundCesarean section is one of the most commonly performed surgical procedures worldwide and is frequently associated with moderate to severe postoperative pain. While overall pain after cesarean delivery is well described, evidence comparing pain intensity and analgesic use between primary and repeat cesarean sections remains limited. ObjectiveTo compare postoperative pain severity and total analgesic consumption within the first 24 hours among women undergoing primary versus repeat cesarean sections under spinal anesthesia at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia, from January 1 to March 30, 2025. MethodsA prospective cohort study was conducted among 203 women who underwent cesarean delivery under spinal anesthesia. Participants were selected using systematic random sampling and categorized into primary and repeat cesarean groups. Demographic and clinical characteristics were summarized using descriptive statistics. Group comparisons were performed using independent t-tests or Mann-Whitney U tests for continuous variables and Chi-square tests for categorical variables. A p-value < 0.05 was considered statistically significant. ResultsWomen undergoing repeat cesarean sections experienced significantly higher postoperative pain. During movement, 92.1% of women in the repeat group reported moderate to severe pain compared with 66.7% in the primary group (p < 0.001). At rest, moderate to severe pain occurred in 74.3% of the repeat group versus 52.9% of the primary group (p = 0.002). Pain scores within the first 6 hours were also higher in the repeat group (median NRS 7, IQR 7-8) than in the primary group (median NRS 5, IQR 4-7; p < 0.001). Total analgesic consumption was significantly greater among women in the repeat group (243.3 {+/-} 98.4 mg) compared with the primary group (146.3 {+/-} 82.5 mg; p < 0.001). ConclusionsRepeat cesarean sections are associated with higher early postoperative pain and increased analgesic requirements. These findings support the need for individualized and intensified pain management strategies for women undergoing repeat cesarean delivery. Clinical trial numberNot applicable

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Efficacy of Vitamin C in Acute Musculoskeletal Pain Management: A Double-Blind Randomized Controlled Pilot Study

Daoust, R.; Williamson, D.; Arbour, C.; Perry, J. J.; Berthelot, S.; Huard, V.; Archambault, P.; Emond, M.; Rouleau, D.; Morris, J.; Lessard, J.; Kochoedo, M.; Cournoyer, A.

2026-02-27 emergency medicine 10.64898/2026.02.25.26347033 medRxiv
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IntroductionRecent evidence has shown that vitamin C has analgesic properties in immediate postoperative context. However, while a clinical trial is currently underway to evaluate vitamin C for reducing opioid consumption in acute musculoskeletal (MSK) injuries emergency department (ED) patients, its direct analgesic effect in this population has not yet been established. This pilot study evaluated the feasibility of conducting a randomized placebo-controlled trial to determine the analgesic effect of vitamin C alone compared with placebo in acute MSK injured ED patients. MethodsWe conducted a double-blind, randomized controlled pilot trial stratified by fracture status in a tertiary care center. Adults ([&ge;]18 years) presenting to the ED with MSK injuries of [&le;] 48 hours duration and pain intensity >3/10 were randomized to receive vitamin C 900 mg twice daily for three days or placebo. Participants completed a six-day diary (electronic or paper) and were contacted on day six to document analgesic use, treatment adherence, and pain intensity. ResultsOverall, 147 patients were screened; 63 (42.9%) were excluded, 24 (16.4%) refused, leaving 60 (41.1%) participants, with a consent rate of 13.0/month. Mean age (SD) was 41.8 years (14.23) and 50% were female. Lost to follow-up rate differed between participants with electronic diary (n=7; 16.7%) and participants with paper diary (n=10; 55.6%). Patients compliance with treatment was 97.6%. The least-squares mean difference between group A and group B in the time-weighted sum of pain intensity differences over 72 hours (SPID72) was 348.7 (95% confidence interval [CI]:-698.9 to 1396.4) for the intention-to-treat analysis and 357.6 (95%CI:-709.67 to 1424.82) for the per-protocol analysis. ConclusionThis pilot study supports the feasibility of a larger randomized controlled trial on the analgesic properties of vitamin C for acute MSK injured ED patients. Strategies to reduce the missed patients and lost to follow-up rates are proposed. Trial registration numberNCT06306183, ClinicalTrials.gov

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Measuring the impact of lived experience and caregiver engagement in research on the research conducted: development and pilot testing of an assessment tool

Hawke, L. D.; Hou, J.; Upham, K.; van Kesteren, M. R.; Munro, C.; Hauer, S.; Sendanyoye, C.; Halsall, T.; Quilty, L.; Hamilton, C.; Barbic, S. P.; Wang, W.

2026-04-03 health systems and quality improvement 10.64898/2026.04.01.26349956 medRxiv
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Background. People with lived/living experience of health conditions, as well as caregivers, are increasingly engaged in research. This study aimed to develop and pilot test a new tool measuring the impact of lived/living experience engagement on the research. The measure is called the Measure of Engagement Tool for Research and lived Experience (METRE). Method. We conducted a qualitative descriptive study among 28 people with lived/living experience and caregivers and 12 academic researchers to understand the impacts of engagement. Using the findings, we drafted the METRE. We pilot tested the METRE among 13 people with lived/living experience and caregivers and 10 academic researchers. Insights were used to refine the scale. Results. Qualitatively, participants identified multiple domains of impact of engagement on research, which guided scale development. Pilot testing of the draft METRE revealed it being straightforward to complete, providing a thorough evaluation of the impact of engagement. However, some areas of improvement were recommended. The draft items showed acceptable preliminary performance. Conclusions. An assessment tool is now available to assess the impact of lived/living experience engagement on the research. Additional research is required to evaluate its psychometric properties. Tools to evaluate the impact of engagement on research will help advance the science of engagement and support engaged research teams in their work.

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Theory-based self-management interventions for stroke survivors: a systematic review and meta-analysis

Meng, G.; Chen, Y.; Dai, M.; Tang, S.; Chen, Q.

2026-03-02 neurology 10.64898/2026.03.02.26346812 medRxiv
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AbstractsO_ST_ABSBackgroundC_ST_ABSSelf-management is essential for stroke survivors to maintain a healthy lifestyle and reduce recurrence risk. Although theory-based self-management interventions are widely recommended, the theoretical frameworks underpinning them and their comparative effectiveness remain unclear. AimsTo systematically identify the theories, models, and frameworks (TMFs) used in self-management interventions for stroke survivors, to explore how they guide interventions, and evaluate their effectiveness on self-management behaviors and self-efficacy. MethodsPubMed, Embase, Web of Science, ProQuest Health & Medical Collection and the Cochrane Library were searched from inception to July 15, 2025. Randomized controlled trials or quasi-experimental studies evaluating theory-based self-management interventions for stroke survivors were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias (Cochrane RoB 2.0). Meta-analyses were performed using random-effects models. ResultsFrom 11,495 records, 32 studies with 3,212 participants were included. Sixteen distinct TMFs were identified; self-efficacy theory was most frequent (13/32), followed by social cognitive theory (6/32). All TMFs were middle-range theories. Meta-analysis showed TMFs-based interventions significantly improved self-management behaviors (SMD = 4.26, 95%CI: 0.20-8.31, I{superscript 2} = 98.2%) and self-efficacy (SMD = 0.60, 95%CI: 0.32-0.88, I{superscript 2} = 72.8%). However, the effect for behaviors is likely inflated due to extreme heterogeneity and theoretical diversity. Theory-specific analysis of self-efficacy theory (k = 8) confirmed significant effects on self-efficacy (SMD = 0.64, 95%CI: 0.21-1.08). ConclusionsThis review identified 16 distinct theoretical models; self-efficacy theory was most frequently applied, followed by social cognitive theory. Theory-based interventions significantly improved self-management behaviours and self-efficacy.

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Translation, Adaptation, and Validation of Medical Office Survey on Patient Safety Culture for Ambulatory Care in Japanese Clinics

Myint, K. Z. Y.; Genka, I.; Taguchi, J.; Kusano, T.

2026-02-06 health systems and quality improvement 10.64898/2026.02.05.26345699 medRxiv
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ObjectiveThere is no validated questionnaire in Japan to measure the culture of safety in ambulatory care clinics. Therefore, we developed the Japanese version of the Medical Office Survey on Patient Safety Culture (MOSPSC) of the Agency of Healthcare Research and Quality (AHRQ) in the United States with the aim to establish a tool for evaluating and benchmarking the safety culture of outpatient clinics in Japan. Materials and methodsThis research uses both qualitative and quantitative approaches to translate, adapt and validate the MOSPSC questionnaire which consists of 62 questions. The process involved seven steps such as translation by two independent bilingual physicians, drafting and reviewing, backtranslation by two separate translation companies, semantic equivalence assessment by AHRQ and revision, pretest, focused discussion, and finalizing the questionnaire after expert review and proofreading. An actual safety culture survey was conducted with mainly online and paper versions at four clinics in Tokyo. The survey results were then evaluated for patient safety dimensions, reliability and construct validity. ResultsEfforts are made to select appropriate terminology during tool adaptation processes due to different language and medical system between Japan and the United States. The response rate in the actual survey was 66.4% (242/364). Confirmatory factor analysis showed that factor loading and goodness of fit indices were better when 3 items were removed from the original 10-composite model with 38 items. The Cronbachs alpha coefficients of composite measures ranged from 0.62 to 0.78 in the original model and 0.62 to 0.85 in the new model, indicating good internal consistencies. ConclusionsConsidering the differences in medical systems, culture, and language between the United States and Japan, the instrumented was adapted with a satisfactory content validity and reliability.

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Association Between Changes In Psychological Readiness And Subjective Knee Function After Acl Reconstruction

Johnson, O. S.; Bond, C. W.; Noonan, B. C.

2026-03-06 sports medicine 10.64898/2026.03.06.26347201 medRxiv
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BackgroundPsychological readiness to return to sport and subjective knee function are critical outcomes following ACL reconstruction (ACLR), yet they do not always progress in parallel. An athlete may demonstrate high subjective knee function but low psychological readiness, suggesting a mental barrier to return, or conversely, report high readiness despite persistent functional limitations, raising concerns of overconfidence and reinjury risk. Understanding how these domains change together during recovery is essential for identifying mismatches that may require targeted intervention. PurposeThe purpose of this study is to examine the relationship between changes in psychological readiness (ACL-RSI) and subjective knee function (IKDC) from early to late recovery following ACLR. Study DesignSecondary analysis of prospectively collected data. MethodsAthletes (N = 48, Age at ACLR = 17.7 {+/-} 1.8 y) aged 15-25 years who underwent ACLR with an ipsilateral autograft, had a pre-injury MARX score > 8, and completed the ACL-RSI and IKDC questionnaires at 3.5 {+/-} 1 and 7 {+/-} 1 months post-ACLR were included. Percent changes in ACL-RSI and IKDC scores between early and late recovery were calculated. Spearmans rank correlation was used to examine the association between changes in psychological readiness and subjective knee function. Significance was set to p < .05. ResultsThe mean percent change in ACL-RSI was 40.7 {+/-} 57.1% and the mean percent change in IKDC was 24.8 {+/-} 18.1% from 3.5 {+/-} 1 months to 7 {+/-} 1 months post-ACLR. The percent changes in ACL-RSI and IKDC scores from 3.5 {+/-} 1 months to 7 {+/-} 1 months post-ACLR were moderately correlated ({rho} = 0.350 (95% CI [0.089, 0.584]), p = 0.012). DiscussionThe main finding of this study was that subjective knee function and psychological readiness to return to sport changed in parallel from 3.5 to 7 months following ACLR. Clinicians can use this information regarding the concordant progression of psychological readiness to return to sport and subjective knee function to personalize ACL rehabilitation for future patients. Overall, clinicians can understand that if psychological readiness improves, subjective knee function will likely improve over the 3.5- to 7-month post-ACLR time frame, and vice versa. Therefore, focusing on both of these components at multiple time points during the recovery process may be influential to ensure the greatest likelihood of returning to sport in athletes following ACLR.

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Validation of the Hindi Version of the Bronchiectasis Health Questionnaire in a Hindi-speaking Indian population

Palani, P. T.; Raut, S.; Sethi, P.; Gopalakrishnan, R. K.; Meena, V. P.; Sinha, S.; Wig, N.; Ray, A.

2026-02-09 respiratory medicine 10.64898/2026.02.04.26345330 medRxiv
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BackgroundBronchiectasis is a debilitating respiratory condition characterized by chronic cough with expectoration of thick sputum. It accounts for significant morbidity and mortality, especially when associated with exacerbations. Assessing the health-related quality of life (HR-QoL) of patients with bronchiectasis is important to ascertain the impact of the disease on day-to-day life, as well as to gauge the effect of targeted interventions. Conventionally used methods for assessing HR-QoL such as the St. Georges Respiratory Questionnaire (SGRQ) are time-consuming and have limitations in day-to-day application. The Bronchiectasis Health Questionnaire (BHQ) is a novel, compact tool used for assessing the HR-QoL, and has been validated for use in Korean and Turkish populations. MethodsWe attempted to develop and validate the Hindi version of the Bronchiectasis Health Questionnaire (BHQ) in Indian adults with bronchiectasis. We assessed the correlation between the Hindi BHQ (H-BHQ) scores and other measures of lung health including the Hindi version of the COPD Assessment Tool (H-CAT), pulmonary function tests and the bronchiectasis severity index (BSI). In addition, we assessed the correlation between the H-BHQ scores and the number of exacerbations and hospital admissions in the previous year. ResultsA total of 145 subjects with bronchiectasis were included. The mean ({+/-} SD) H-BHQ total score was 49.10 {+/-} 10.3. The H-BHQ score correlated well with the H-CAT score (Correlation coefficient -0.6534, p value < 0.0001) and the mMRC scale (Correlation coefficient of -0.4459,p value < 0.0001). The H-BHQ score also had a moderate correlation with the number of exacerbations and low correlation with hospital admissions in the previous year, with correlation coefficients of -0.4193 (p < 0.0001) and -0.3030 (p < 0.0001), respectively. The correlation between the H-BHQ and the Bronchiectasis Severity Index (BSI) score was weak (Correlation coefficient of -0.3012, p value < 0.01). ConclusionThe H-BHQ offers a simple and convenient method to assess the HR-QoL in patients with bronchiectasis, and correlates well with other measures of respiratory health, including the H-CAT, the mMRC score and the number of exacerbations and hospital admissions in the previous year.