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Effect of walking training on blood glucose control and metabolic health in patients with type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the improvement effect of walking training on blood glucose control and metabolic health indicators in type 2 diabetes patients, and to explore the effect of different intervention program characteristics on the efficacy through subgroup analysis. METHOD: The system searched PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO databases, with a search period from the establishment of the database to March 15, 2026. Include a randomized controlled trial with the main intervention measures of walking behavior, with an intervention period of &#x2265;8&#xa0;weeks. Two researchers independently conducted literature screening, data extraction, and bias risk assessment. Meta-analysis was conducted using RevMan 5.4 software, with mean difference (MD) and its 95% confidence interval (CI) as effect measures for continuous variables. Select fixed effects model or random effects model for combined analysis based on heterogeneity size, and conduct subgroup analysis according to intervention program characteristics. RESULTS: Totally 5 randomized controlled trials were included, including 483 patients with type 2 diabetes (241 cases in the intervention group and 242 cases in the control group). Participants had a mean age of 54.2&#xa0;&#xb1;&#xa0;6.5&#xa0;years, BMI of 29.1&#xa0;&#xb1;&#xa0;3.2&#xa0;kg/m2, and 48.5% were male. The meta-analysis results showed that walking training significantly reduced glycated hemoglobin levels, with a combined effect of -0.48% (95% CI: -0.60 to -0.36, P&#xa0;<&#xa0;0.00001), There is moderate heterogeneity among the studies (I2&#xa0;=&#xa0;67%). Subgroup analysis showed that the "walking&#xa0;+&#xa0;other interventions" subgroup (combined effect size -0.58%, 95% CI: -0.96 to -0.20) and the "clear step target" subgroup (combined effect size -0.52%, 95% CI: -0.65 to -0.39) had larger effect sizes and lower heterogeneity within the subgroups. The bias risk assessment shows that the overall quality of the included research methodology is good. CONCLUSION: Walking training can significantly improve the blood glucose control in patients with type 2 diabetes. Combined with diet or behavioral intervention, setting clear goals for the number of steps may achieve better results. Walking training can be used as an effective auxiliary treatment for the management of type 2 diabetes in clinical promotion. Due to limitations in the number and quality of studies included, the above conclusions still require more high-quality research to validate.

Humans

Deimplementation of inappropriate feeding practices in early care and education: a Hybrid Type 3 cluster-randomized trial.

BACKGROUND: The science of deimplementation-reducing harmful or ineffective practices-has focused almost exclusively on clinical prescribing, with no studies conducted in community or educational settings. Early care and education (ECE) settings offer a strategic venue for shaping eating behaviors, with children consuming up to 500 meals annually in these environments. However, ECE educators routinely use feeding practices that undermine self-regulation, including pressuring children to eat, rushing mealtimes, and offering food as reward. These practices contribute to food aversions, diminished self-regulation, and obesity risk. METHODS: We will conduct a Hybrid Type 3 cluster-randomized trial evaluating a co-designed deimplementation strategy package (WISE Words) across 88 ECE sites in Arkansas and Louisiana. Sites will be randomized 1:1 to WISE Words or usual practice, with usual practice sites receiving the intervention after two years (waitlist design). WISE Words includes six strategies: dynamic training using improvisation methods, peer learning collaboratives with goal setting, external facilitation, audit and feedback, environmental reminders, and tailored educational materials. The primary outcome is de-adoption of inappropriate feeding practices measured via direct mealtime observation (Table Talk). Secondary outcomes include adoption of evidence-based practices, acceptability, appropriateness, and sustainability at 12- and 24-months post-intervention. Child outcomes include Body Mass Index, skin carotenoid levels (Veggie Meter) willingness to try new foods (observed) and food neophobia (teacher and caregiver report). An explanatory sequential mixed methods design will test mechanisms of change derived from the Implementation Trust Building Theory of Change examining whether trust mediates strategy effects on outcomes. DISCUSSION: This trial extends deimplementation science into community settings by targeting culturally embedded behavioral practices rather than clinical prescribing behaviors. Results will inform approaches to shifting entrenched practices in ECE and similar settings while testing trust as a deimplementation mechanism. Sustainability assessments will address a notable gap, as few studies have examined whether deimplementation effects persist. TRIAL REGISTRATION: NCT07101321, July 20, 2025.

Humans

Effects of Time-Based and Distance-Based Repeated Sprint Training on Physical and Physiological Adaptations in Collegiate Basketball Players.

PURPOSE: This study aimed to compare the effects of time-based (TB) and distance-based (DB) repeated-sprint training (RST) on athletic performance adaptations in collegiate basketball players during preseason and to examine whether the 2 training prescriptions produce different levels of homogeneity in the magnitude of individual adaptations. METHODS: Thirty young male basketball players (age = 21.3 [1.4]&#xa0;y) were randomly and equally assigned to 3 groups (n = 10): DB-RST, TB-RST, and an active control group. Participants completed a 7-week RST program performed 3 times per week, consisting of 4 sets of 4 to 9 repetitions per session. The DB-RST group completed each sprint by covering a fixed 35-m distance, whereas the TB-RST group performed each sprint maximally for a fixed 5-second duration. Performance assessments including countermovement vertical jump, 20-m sprint, Illinois change-of-direction speed, reactive strength index, Wingate anaerobic power, and cardiorespiratory fitness were conducted before and after the 7-week training period. RESULTS: Both training groups demonstrated significant performance improvements over the 7-week intervention and relative to the control group (P < .05). Similar gains were observed in the magnitude of adaptations in the countermovement vertical jump, 20-m sprint, Illinois change-of-direction speed, and reactive strength index for the DB-RST and TB-RST groups. Interestingly, the TB-RST group showed more gains than the DB-RST in the magnitude of adaptations in the peak and mean power outputs, as well as cardiorespiratory fitness. Moreover, the TB-RST group showed lower intersubject variability in adaptive responses across the measured performance outcomes following the training intervention. CONCLUSION: Our findings indicate that RST effectively enhances the performance of basketball players, and that implementing a TB-RST protocol is more effective than a DB-RST approach for producing greater adaptations in physiological variables-specifically anaerobic power output and cardiorespiratory fitness-over the 7-week preseason period.

Humans

Effectiveness of Wearable Digital Therapeutics in Improving Sleep Outcomes Among Individuals With Insomnia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. OBJECTIVE: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta&#x2011;Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta&#x2011;Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the I&#xb2; statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] -4.52, 95% CI -8.38 to -0.67, PI -9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%-2.11%, PI 1.85%-2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98-35.24, PI -16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (R&#xb2;=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (P=.07). Certainty of evidence ranged from moderate to high. CONCLUSIONS: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base.

Humans

Two-Year Outcomes of a 211 Care Coordination Trial.

BACKGROUND AND OBJECTIVES: Early screening for developmental concerns enables timely diagnosis and referral, yet many families face barriers accessing services. Prior work showed that early childhood care coordination could improve timely service connection. This study assessed developmental outcomes among children participating in a randomized controlled trial of Information and Referral Federation of Los Angeles County (211LA). METHODS: Participants, aged 21-42&#xa0;months, were randomized to usual care or the 211LA intervention. Developmental and behavioral measures, including the Parental Evaluation of Developmental Status Developmental Milestones Assessment Level (PEDS-DM-AL) and the Child Behavior Checklist (CBCL), were collected at baseline and 24&#xa0;months later. The sample included 499 participants, 250 in the 211LA intervention and 249 in usual care. Primary analyses examined changes in PEDS-DM-AL and CBCL scores over the 24-month period by study arm. Post hoc analyses compared family characteristics between intervention and control families who enrolled in services. RESULTS: Developmental and behavioral measures showed some clinically insignificant change over time, but these changes did not differ by condition (expressive/receptive language skills mastered: P&#x2009;>&#x2009;.9; autism, attention, aggression, and externalizing behavior T scores: P&#x2009;>&#x2009;.4). Post hoc analyses identified potentially relevant imbalances between the treatment arms at baseline as well as in the subgroup that enrolled in services, with families assigned to the 211LA intervention being more likely to have a non-US born parent and a parent with limited English proficiency compared with families assigned to usual care. Intervention families enrolled in services also used telehealth more frequently and received a lower duration of services than those receiving usual care. CONCLUSIONS: This study measured the indirect influence of service enrollment through 211LA care coordination on developmental outcomes. Although increased service enrollment through 211LA did not affect developmental outcomes, we hypothesize this may be because of several factors, including overrepresentation of a subset of historically underrepresented families in the 211LA intervention, suboptimal performance of our developmental assessment tool, and complexity of conducting a trial of this magnitude during the COVID-19 pandemic, which may have diminished the ability of this trial to demonstrate developmental benefits despite demonstrated service enrollment gains.

Humans

Perioperative Depression and Anxiety Care in Older Patients: A Randomized Clinical Trial.

IMPORTANCE: Depression and anxiety are common among older adults undergoing surgery and are associated with adverse postoperative outcomes. However, effective tailored perioperative mental health interventions are lacking. OBJECTIVE: To evaluate a perioperative intervention to optimize mental health. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, hybrid, type 1, effectiveness-implementation randomized clinical trial was conducted (November 1, 2022, to March 31, 2025), with 3-month postoperative follow-up, at a US academic and community practice hospital network. Participants were 60 years or older; scheduled for cardiac, oncologic, or orthopedic surgery; and had clinically meaningful symptoms of depression and/or anxiety based on the Patient Health Questionnaire-Anxiety and Depressive Symptom (PHQ-ADS) scale. A total of 3159 patients were screened for eligibility, with 1518 ineligible, 1079 declining participation, and 236 excluded for other reasons. A total of 326 patients were enrolled and randomized (1:1), with 20 excluded after surgery cancelation. INTERVENTION: Participants were assigned to receive a perioperative intervention combining psychological management and pharmacologic optimization or enhanced usual care (materials for self-managing symptoms). MAIN OUTCOMES AND MEASURES: The primary outcome was change in PHQ-ADS score from baseline to 3 months after surgery. Other outcomes included persistent postsurgical pain, delirium, falls, quality of life, patient satisfaction, length of stay, and rehospitalizations. Implementability was evaluated through semistructured interviews and reach, acceptability, feasibility, appropriateness, and fidelity measures. RESULTS: A total of 306 older adults were included in analysis (mean [SD] age, 68.5 [6.1] years; 209 [68.3%] female; 153 randomized to intervention and 153 randomized to enhanced usual care): 102 cardiac, 100 oncologic, and 104 orthopedic patients. Participants' mean (SD) baseline PHQ-ADS score was 18.5 (7.4). At 3 months, there was a significant decrease in PHQ-ADS scores in the intervention group compared with the enhanced usual care group (mean difference, 2.20; 95% CI, 0.16-4.24; P&#x2009;=&#x2009;.03). Effects varied by surgical subgroups (oncologic patients: mean difference, 4.93; 95% CI, 1.51-8.36; P&#x2009;=&#x2009;.005; cardiac patients: mean difference, 2.68; 95% CI, -0.98 to 6.35; P&#x2009;=&#x2009;.15; and orthopedic patients: mean difference, -1.11; 95% CI, -4.62 to 2.40; P&#x2009;=&#x2009;.54). Patients and interventionists perceived the intervention as appropriate, with high-fidelity delivery and broad reach across the target population. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, psychological management and pharmacologic optimization reduced anxiety and depression in older adults undergoing surgery. Future studies should assess reproducibility and determine which patients benefit most. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT05575128, NCT05685511, and NCT05697835.

Humans

Comparison of a Modified Regimen of Prophylactic Phenylephrine Boluses Versus Variable Rate Infusion During Elective Cesarean Delivery Under Spinal Anesthesia: A Noninferiority Randomized Double-Blind Study.

BACKGROUND: Prophylactic phenylephrine boluses have been found to be as effective as variable rate infusions during elective cesarean delivery but require a higher number of physician interventions to maintain blood pressure near baseline values. Therefore, there is a need to find a feasible regimen of bolus administration that is equally efficacious to the infusion regimen while at the same time requires a comparable number of physician interventions and is thus non-inferior to the infusion regimen. METHODS: Healthy pregnant women with term, uncomplicated, singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomly divided into two groups. The Bolus group received a phenylephrine bolus 100 &#x3bc;g immediately after spinal anesthesia and then at every systolic blood pressure value <90% of the baseline. The infusion group received a prophylactic variable-rate infusion of phenylephrine beginning at 50 &#x3bc;g/min and titrated to maintain systolic blood pressure at 90-99% of baseline. The primary outcome was the number of physician interventions needed to maintain the target systolic blood pressure; the secondary outcomes included phenylephrine requirements, incidence of hypotension/hypertension/bradycardia, umbilical arterial and venous blood gas analysis, Apgar scores, and maternal complications. The primary outcome was analyzed in terms of non-inferiority using a non-inferiority margin of two interventions. RESULTS: Eighty patients were included in the study. The median (interquartile range [IQR]) number of physician interventions was 6 (5-8) in the infusion group and 3 (2-4) in the bolus group (P < .001). The difference of medians (95% confidence interval [CI]) between the two groups was -3 (-4 to -2). Phenylephrine requirements were higher in the infusion group (630 [426-765] &#x3bc;g) compared to the bolus group (300 [200-400] &#x3bc;g; P < .001). Blood pressure was higher at certain time points in the infusion group, but overall accuracy of blood pressure control was not different between the groups. Incidence of hypotension, hypertension, and bradycardia, neonatal outcomes, and maternal complications did not differ between the groups. CONCLUSIONS: The modified regimen of prophylactic boluses is non-inferior to variable rate prophylactic phenylephrine infusion in terms of physician interventions needed to maintain systolic blood pressure within the target range and maternal and neonatal outcomes.

Humans

Does future-oriented imagery rescripting increase willingness to carry out a social anxiety-related behavioral experiment? An extended replication.

BACKGROUND AND OBJECTIVES: Mental images of threat are common in social anxiety disorder and could impede exposure to fear-relevant situations. Landkroon et al. (2022) found that imagery rescripting of anticipated future threat, compared to no-task, increases willingness of non-clinical individuals to conduct a social anxiety-related behavioral experiment. The aim of this two-day preregistered extended replication study was to examine whether the effects persist beyond the intervention session by scheduling the behavioral experiment 1-7 days after the intervention. METHODS: On Day 1, 60 pre-screened participants were asked to design a behavioral experiment to test an idiosyncratic negative belief about a feared social situation. They were then randomly assigned to imagery rescripting (focused on their worst feared outcome of the behavioral experiment) or no-task. Participants' willingness to do the behavioral experiment and their threat beliefs was measured. On Day 2, they were asked to carry out the behavioral experiment. RESULTS: The imagery rescripting group, compared to the control group, did not show increased willingness or compliance to do the behavioral experiment on Day 1 or 2. Furthermore, the imagery rescripting did not lead to greater reductions in threat beliefs on either day. LIMITATIONS: The quality of the imagery rescripting intervention was not assessed, and given the brief nature of the intervention, any effects may have dissipated before participants decided whether to carry out the behavioral experiment. CONCLUSIONS: There was no evidence that imagery rescripting leads to changes in willingness or compliance to do a fear-relevant behavioral experiment. More research is needed to examine interventions that can enhance exposure in socially anxious people.

Humans

Clopidogrel Versus Dual-Antiplatelet Therapy for Long-Term Maintenance After Coronary Stenting in Ischemic and Bleeding Birisk Patients With Acute Coronary Syndromes and Diabetes: A Prespecified Subgroup Analysis of the OPT-BIRISK Trial.

BACKGROUND: Among patients with acute coronary syndromes at both high bleeding and ischemic risk (birisk), extended clopidogrel monotherapy after 9 to 12&#x2009;months of dual-antiplatelet therapy reduces bleeding without increasing ischemia. Whether this benefit extends to birisk patients with diabetes is unknown. METHODS: This prespecified subgroup analysis of the OPT-BIRISK (Optimal Antiplatelet Therapy for High Bleeding and Ischemic Risk Patients) trial included birisk patients with acute coronary syndrome who had completed 9 to 12&#x2009;months of dual-antiplatelet therapy after percutaneous coronary intervention. Patients were then randomized 1:1 to 9&#x2009;months of clopidogrel&#x2009;plus&#x2009;placebo versus clopidogrel&#x2009;plus&#x2009;aspirin. Outcomes were compared by diabetes status. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding at 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events, defined as a composite outcome of all-cause death, myocardial infarction, stroke, or clinically driven revascularization. RESULTS: Of 7758 patients, 4072 (52.5%) had diabetes. Clopidogrel monotherapy decreased Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (2.1% versus 3.2%; hazard ratio [HR], 0.66 [95% CI, 0.45-0.97]) with no increase in major adverse cardiac and cerebral events (2.9% versus 3.6%; HR, 0.79 [95% CI, 0.56-1.12]) compared with clopidogrel plus aspirin in patients with diabetes. Outcomes were consistent in patients without diabetes, with no significant interactions by diabetes status. CONCLUSIONS: In birisk patients with acute coronary syndrome who were stable on dual-antiplatelet therapy with clopidogrel plus aspirin for 9 to 12 months after percutaneous coronary intervention, clopidogrel monotherapy for an additional 9 months reduced clinically relevant bleeding without increasing ischemic events compared with continued dual-antiplatelet therapy, irrespective of diabetes status. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03431142.

Aged

The Impact of Upper Extremity Rehabilitation on Fatigue in Individuals With Multiple Sclerosis: A Systematic Review.

BACKGROUND: Although numerous interventions have been investigated to alleviate fatigue in people with multiple sclerosis (PwMS), evidence regarding the effects of upper extremity rehabilitation on fatigue remains limited. OBJECTIVE: The objective of this review was to evaluate and synthesize the available evidence on the effects of upper extremity rehabilitation interventions on fatigue in PwMS. METHODS: This review was conducted in accordance with the PRISMA guidelines and was prospectively registered in the PROSPERO database. A systematic search of PubMed, Web of Science, and Scopus was performed up to August 2026. Studies were eligible if they investigated the effects of upper extremity rehabilitation interventions on fatigue in PwMS. The risk of bias of randomized controlled trials was assessed using the Risk of Bias 2 (RoB 2), and the certainty of the evidence was appraised using the GRADE methodology. RESULTS: Nine studies including 250 participants (136 intervention, 114 control) met the inclusion criteria. The included studies evaluated a range of technology-assisted, exercise-based, home-based, and task-oriented upper extremity rehabilitation approaches, with some interventions incorporating more than one therapeutic or technological component. Fatigue outcomes were measured using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Risk of bias was low in three randomized controlled trials, with some concerns in two and high in two; among the two crossover studies, one was rated as low risk and one as high risk. GRADE assessment showed low certainty of evidence for studies using the FSS and very low certainty for those using the MFIS, indicating an overall low certainty of the available evidence. CONCLUSIONS: The available evidence is insufficient to draw definitive conclusions regarding the effects of upper extremity rehabilitation on fatigue in PwMS. Further high-quality randomized controlled trials are required.

Humans

Integrated Telehealth Rehabilitation and Quality of Life in Mechanically Ventilated Adults: A Randomized Clinical Trial.

IMPORTANCE: Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. OBJECTIVE: To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. INTERVENTIONS: A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. MAIN OUTCOMES AND MEASURES: Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). RESULTS: Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P&#x2009;=&#x2009;.04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P&#x2009;=&#x2009;.34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P&#x2009;=&#x2009;.03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P&#x2009;<&#x2009;.001). CONCLUSIONS AND RELEVANCE: In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06343545.

Humans

Review: The African turquoise killifish as a model for the integrative physiology of vertebrate aging.

With increasing emphasis on extending healthy lifespan, aging research requires vertebrate models that permit efficient mechanistic investigation and intervention testing within practical time and cost constraints. The African turquoise killifish (Nothobranchius furzeri) has attracted growing attention because it combines an exceptionally short life cycle with an intact vertebrate physiological context and an expanding genetic toolkit, enabling relatively rapid evaluation of candidate aging interventions and mechanistic analysis across molecular, tissue, and organismal levels. This review assesses N. furzeri from an integrative-physiology perspective, focusing on germline-soma interactions, gut microbiota-host crosstalk, nutrient sensing and metabolic remodeling, temperature responsiveness, and AMPK-mTOR-linked programs. It also examines expanding genome-engineering and reporter approaches that support mechanistic and tissue-resolved investigation of these physiological processes. Building on recent reviews of killifish biology, disease modeling, regeneration, and the hallmarks of aging, we synthesize evidence across major intervention domains, distinguish established phenotypic effects from incompletely resolved mechanisms, and highlight functional endpoints, methodological standardization, and the appropriate interpretation of the model's translational relevance. Together, these features position N. furzeri as a strategically useful vertebrate platform for rapid mechanistic testing, intervention evaluation, and prioritization of aging-related pathways. Future progress will require improved methodological standardization, tissue-resolved causal studies, and question-driven cross-species validation where appropriate.

Animals

Acceptability of alcohol-based hand rub during neonatal care in rural Ugandan households: a qualitative study nested within the BabyGel trial.

BACKGROUND: Poor access to water, sanitation and hygiene exacerbates the spread of infections among newborns. The BabyGel cluster randomised trial assessed the effectiveness of a community-level alcohol-based hand rub with a training component in reducing infection or death rates among newborns in Uganda. OBJECTIVE: Nested in the BabyGel trial, this study investigated the acceptability of the BabyGel intervention among mothers and household members in Eastern Uganda, using the Theoretical Framework of Acceptability. METHODS: In 2022, we conducted individual semistructured interviews with mothers, and group interviews with mothers and other household members, all recruited from intervention-arm clusters. Thematic analysis combined inductive and deductive coding, structured by the framework's seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy. RESULTS: Twenty mothers and 14&#xa0;household members participated in 10 individual and 10 small group interviews. Participants found the intervention generally acceptable, appreciating its convenience and perceived protection against infection. Many described hand hygiene changes that persisted beyond the intervention period. However, concerns related to its harmful effects, spiritual beliefs and social tensions with visitors occasionally influenced its use. CONCLUSION: Alcohol-based hand rub combined with a training component was generally well accepted, driven by perceived health and practical benefits, although concerns related to safety, belief systems and social dynamics remained. Because data collection coincided with the COVID-19 pandemic, a period of heightened hygiene awareness, the acceptability observed could differ in nonpandemic periods. Culturally adapted education, community engagement and reinforcement of correct use may enhance acceptability and sustainability in similar settings.

Humans

Mobile health apps improve Health-Related Quality of Life in Type 2 Diabetes Mellitus by enhancing medication adherence: A multicentre randomised controlled trial with mediation analysis.

AIMS: This study evaluated whether a gamified mHealth application (CareAide&#xae;) improves Health-Related Quality of Life (HRQoL) in Type 2 Diabetes Mellitus (T2DM) and whether this effect is mediated by medication adherence. METHODS: Prespecified secondary analysis of the T2DM cohort from a 6-month multicentre RCT (NCT06068309; N&#x202f;=&#x202f;663; three Malaysian hospitals). Participants were randomised 1:1 to standard care or CareAide&#xae;. Adherence (MMAS-8), EQ-5D-5L utility (Malaysian value set), and AQoL-6D were assessed at baseline and 6 months. Simple mediation analysis (PROCESS Model 4; 5000 bootstraps) adjusted for baseline HRQoL. RESULTS: CareAide&#xae; significantly predicted higher MMAS-8 scores (mean difference +1.756; d = 1.638; p&#x202f;<&#x202f;0.001). Higher MMAS-8 scores significantly predicted improved AQoL-6D utility (b = 0.024; p&#x202f;<&#x202f;0.001). The direct effect on AQoL-6D was non-significant (p&#x202f;=&#x202f;0.248). Bootstrapped indirect effect confirmed full mediation via AQoL-6D (0.042; 95% CI [0.024, 0.060]). A sensitivity analysis adjusting for baseline HbA1c confirmed full mediation (indirect = 0.034; 95% CI [0.015, 0.052]; n&#x202f;=&#x202f;563). EQ-5D-5L utility showed a significant direct between-group difference at 6 months (p&#x202f;=&#x202f;0.012) but did not operate as a mediation outcome. CONCLUSIONS: Medication adherence fully mediates the AQoL-6D HRQoL benefit of a gamified mHealth intervention in T2DM, as confirmed by both the primary and HbA1c-adjusted sensitivity analyses. These findings support integration of behaviourally informed digital adjuncts into routine primary diabetes care.

Humans

Excimer laser angioplasty for acute coronary occlusion: a stratified meta-analysis of efficacy against aspiration thrombectomy and conventional PCI.

Primary percutaneous coronary intervention (PCI) achieves epicardial reperfusion in most STEMI patients, yet microvascular obstruction persists in up to 60% of patients. Excimer laser coronary angioplasty (ELCA) vaporizes thrombus in situ and may reduce distal embolization, but the evidence base has not been systematically synthesized. This systematic review and meta-analysis (PROSPERO CRD420261422463) included comparative studies of adjunctive ELCA versus aspiration thrombectomy (Stratum A) or PCI alone (Stratum B) in acute coronary occlusion. Primary outcomes were final TIMI-3 flow and myocardial blush grade (MBG) 3; secondary outcomes were short-term mortality, MACCE, and slow-flow/no-reflow. A random-effects model with Hartung-Knapp-Sidik-Jonkman confidence intervals was applied to all outcomes. Certainty was assessed with GRADE. Ten studies (1 RCT, 9 observational) were included, from a total enrolled population exceeding 3,500. In Stratum A, no outcome reached significance: MBG-3 (OR 3.57, 95% CI 0.07-185.10), mortality (OR 0.31, 0.02-4.04), MACCE (OR 0.22, 0.04-1.26), TIMI-3 flow (OR 1.58, 0.67-3.75) and slow-flow/no-reflow (OR 0.78, 0.22-2.78). In Stratum B, using each study's propensity-matched data, no outcome differed significantly (TIMI-3 OR 0.88, 0.38-2.03; MBG-3 OR 1.06, 0.13-8.43; slow-flow/no-reflow OR 0.93, 0.29-3.02; mortality OR 0.44, 0.05-3.80). Composite endpoints were not pooled across incompatible follow-up horizons, and all outcomes were of very low certainty. Adjunctive ELCA-containing strategies during primary PCI were not associated with improved angiographic or short-term clinical outcomes against either comparator. Multicenter randomized trials are required before recommending clinical adoption.

Humans

Effect of a pharmacist-led mHealth app on adherence, quality of life, and glycaemic control in diabetes: A multicentre RCT.

AIMS: To evaluate whether CareAide&#xae;, a pharmacist-driven mHealth application, improves medication adherence, health-related quality of life (HRQoL), and glycaemic control in diabetes mellitus using structural equation modelling. METHODS: Pre-specified secondary analysis of the type 2 diabetes mellitus cohort from a 6-month multicentre open-label randomised controlled trial (N&#xa0;=&#xa0;663) across three Malaysian hospitals. Adherence was assessed by MMAS-8 (subjective) and Proportion of Days Covered (PDC; pharmacy-verified). HRQoL was measured by AQoL-6D and EQ-5D-5&#xa0;L. Structural equation modelling (SEM), Necessary Condition Analysis, and Importance-Performance Map Analysis (cIPMA) were applied. RESULTS: CareAide&#xae; produced large adherence gains (MMAS-8: 7.31 vs 5.55, d&#xa0;=&#xa0;1.64; PDC&#xa0;&#x2265;&#xa0;80%: 81.6% vs 33.0%; both p&#xa0;<&#xa0;0.001). Early 3-month adherence was the strongest predictor of sustained 6-month adherence in both models (&#x3b2; std&#xa0;=&#xa0;0.567 and 0.688; p&#xa0;<&#xa0;0.001). AQoL-6D utility improved significantly (0.669 vs 0.618; d&#xa0;=&#xa0;0.353, p&#xa0;<&#xa0;0.001), driven by coping (d&#xa0;=&#xa0;0.447) and relationships (d&#xa0;=&#xa0;0.254) domains. HRQoL did not mediate adherence; gains were a direct independent benefit. The intervention effect on HbA1c was not statistically significant in the PDC-based SEM model (&#x3b2;&#xa0;=&#xa0;&#xa0;-&#xa0;0.333, p&#xa0;=&#xa0;0.065); a group difference was, however, supported by baseline-adjusted ANCOVA (&#x3b2;&#xa0;=&#xa0;&#xa0;-&#xa0;0.41%, p&#xa0;=&#xa0;0.002), and the complete-case comparison was non-significant (p&#xa0;=&#xa0;0.153), so glycaemic findings warrant cautious interpretation. cIPMA identified the intervention as the primary optimisation target. CONCLUSIONS: CareAide&#xae; significantly improves medication adherence and psychosocial quality of life. Evidence for glycaemic benefit came from baseline-adjusted analysis (ANCOVA), though findings should be interpreted with caution given incomplete HbA1c data at one site. The first three months are the most critical period for pharmacist support. In this dataset, PDC appeared more sensitive than MMAS-8 to the HbA1c signal within 6&#xa0;months, but this finding requires confirmation in longer studies with more complete HbA1c data. TRIAL REGISTRATION: ClinicalTrials.gov NCT06068309.

Aged

Therapeutic Exercise Protocol During Hospitalization in Pediatric Oncohematological Patients: Randomized Clinical Trial.

BACKGROUND: Leukemias, lymphomas, and central nervous system tumors are among the most common pediatric cancers and may lead to motor deficits, impaired balance, reduced muscle strength, fatigue, and decreased functional capacity. Early physiotherapy during hospitalization may help prevent inactivity and support functional preservation in this population. OBJECTIVE: To evaluate the effects of a therapeutic exercise program on quality of life, muscle strength, fatigue, and functional capacity in hospitalized pediatric oncohematological patients. METHODS: Thirty participants aged 8-17&#xa0;years with oncohematological diseases were randomized to an intervention group (IG) or a minimal active physiotherapy comparator group (CG). Assessments included the 6-min walk test, handgrip dynamometry, the PedsQL Multidimensional Fatigue Scale, and the PedsQL Cancer Module at admission and discharge. The IG performed daily 25-min supervised sessions including aerobic, resistance, and breathing exercises with ambulation guidance, whereas the CG received breathing exercises and ambulation guidance. RESULTS: No significant group&#xa0;&#xd7;&#xa0;time interactions were observed for total fatigue or its domains, overall quality of life or its assessed domains, handgrip strength, or six-minute walk test distance. Time-related changes were observed for some outcomes, but these occurred without evidence of differential change between groups and were not interpreted as effects of the structured exercise protocol. No intervention-related adverse events requiring permanent protocol discontinuation were recorded. CONCLUSION: The structured in-hospital therapeutic exercise protocol could be delivered under close clinical supervision without recorded intervention-related adverse events requiring permanent discontinuation. However, the structured protocol did not demonstrate superiority over the minimal active physiotherapy comparator for fatigue, quality of life, muscle strength, or functional capacity. These findings should be interpreted cautiously because of the small sample size, clinical heterogeneity, variable intervention exposure, and limited intervention-fidelity data. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC), RBR-8sxnfyd.

Humans

A Novel Multiple Sensory Nerve Block Combination Using Ultrasound Guidance in Knee Arthroplasty: A Randomized Clinical Trial.

INTRODUCTION: Combining adductor canal block (ACB), infiltration between the popliteal artery and posterior capsule of the knee (IPACK), and genicular nerve blocks provides motor-sparing analgesia in total knee arthroplasty (TKA). Adding nerve blocks targeting the nerve to vastus medialis, vastus intermedius, and anterior femoral cutaneous nerve may improve postoperative pain management without affecting mobility. This study evaluated the effect of an eight-nerve block combination for pain relief after TKA versus local infiltration analgesia (LIA). METHODS: Participants were randomized into intervention or standard treatment groups. The intervention group received an eight-nerve block combination using 40 mL ropivacaine, 5&#x2009;mg/mL, with 75 &#xb5;g of clonidine. The control group received LIA comprising 150 mL ropivacaine, 2&#x2009;mg/mL, supplemented with 0.5&#x2009;mg adrenaline. The primary outcome was postoperative pain intensity, measured by the numeric rating scale (NRS) at postanesthesia care unit (PACU) arrival, 1 hour, 2 hours after PACU arrival, at ward arrival, evening of surgery, morning of postoperative day 1 (POD1), and at 14:00 POD1. Statistical analysis was performed using the Mann-Whitney U test. Secondary outcomes included 48-hour oral morphine equivalent (OME) consumption and length of hospital stay (LOS). RESULTS: A total of 217 patients scheduled for TKA were randomized. No significant differences were observed in the primary outcome. NRS at rest, presented as median (IQR), did not differ between groups at any time point. At PACU arrival 0 (0-3) vs 0 (0-4), at 1 hour 2 (0-4) vs 2 (0-5), at 2 hours 2 (0-6) vs 2.5 (0-4), at ward arrival 3 (2-5) vs 3 (2-5), on the evening of POD0 4 (3-5) vs 3.5 (2-6), on the morning of POD1 4 (3-6) vs 4 (2-5), and at 14:00 POD1 3 (2-5) vs 3 (2-5) for nerve block and LIA groups, respectively (all P > .05). Exploratory secondary outcomes indicated reduced 48-hour OME consumption presented as median (IQR), 70&#x2009;mg (52.5-96.3), vs 96&#x2009;mg (61.3-148.8); P = .008) and shortened hospital stay, median (IQR), 1 day (1-2), vs 2 days, (1-3); P < .001) in the nerve block group compared to the LIA group. CONCLUSIONS: No differences were observed in pain scores between the eight-nerve block combination and LIA. Secondary outcomes revealed a reduction in 48-hour opioid consumption and a modestly shorter hospital stay with nerve block compared to LIA.

Humans