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Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.

BACKGROUND: Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. METHODS: In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. RESULTS: Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P&#x2009;=&#x2009;0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. CONCLUSIONS: Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).

Adolescent

Smart crutch tipsTM real-time feedback improves adherence to partial weight-bearing protocols following lower extremity fracture surgery: a pilot study.

PURPOSE: To evaluate the effectiveness of Smart Crutch Tips&#x2122; in promoting adherence to prescribed early partial weight-bearing (PWB) protocols and to assess patient experience with real-time weight-bearing feedback during home rehabilitation. METHODS: Twenty patients with lower extremity fractures prescribed partial weight-bearing (PWB) were randomized into two groups utilizing real-time feedback crutch tips (RFC). The Intervention group (n&#x2009;=&#x2009;10) used Smart Crutch Tips&#x2122; (ComeBack Mobility Inc., Kiev, Ukraine), which provided real-time feedback on weight-bearing compliance. The Control group (n&#x2009;=&#x2009;10) also used crutches equipped with Smart Crutch Tips&#x2122;, but notifications were disabled, allowing passive data collection without patient feedback. Weight-bearing compliance was defined as the percentage of steps within &#xb1;&#x2009;10% of the prescribed target. Secondary outcomes included patient satisfaction and device usability assessed using the System Usability Scale (SUS) throughout the home rehabilitation period. RESULTS: The Intervention group demonstrated significantly greater PWB compliance compared with the Control group (73.6% vs. 21.1%, p&#x2009;<&#x2009;0.01). The Intervention group reported a mean SUS score of 84.25, indicating excellent usability. No device-related complications or adverse events were observed. Patient satisfaction, assessed through video interviews, was high, with participants in the Intervention group expressing a strong willingness to recommend the device to others with similar injuries and rating it 10 out of 10. CONCLUSION: Smart Crutch Tips&#x2122; significantly improved adherence to prescribed partial weight-bearing protocols following lower extremity fracture surgery. The RFC device demonstrated high usability, excellent patient satisfaction, and no device-related complications during home rehabilitation throughout the study period.

Humans

Efficacy of targeted neuromodulation treatments: a clinical report.

BACKGROUND: Peripheral neuropathy is a debilitating condition characterized by chronic pain, numbness, tingling, burning, and tightness/swelling. Conventional therapies often focus on symptom management, and some patients experience chronic and refractory symptoms. RESEARCH DESIGN AND METHODS: This retrospective clinical analysis evaluated the clinical outcomes of neuromodulation neuropathy treatment using the NeuroGen-Series device in patients with diabetic peripheral neuropathy (DPN) or idiopathic peripheral neuropathy (IPN). 9,805 unique patients who underwent 133,741 treatments between 18 August 2017, and 23 July 2024, were analyzed. Patients were divided into treatment completers (&#x2265;24 sessions) and noncompleters (<24 sessions). Paired t-tests confirmed statistically significant reductions in pre- and post-treatment symptom scores (p&#x2009;<&#x2009;0.001). RESULTS: Among completers, symptom severity decreased by an average of 46.2%. Tingling and pain showed the greatest improvement, while tightness/swelling and numbness showed the least reduction. 64% of patients reported improvement after one session, and 84% reported improvement after 24 sessions. Nonresponders accounted for 5.8% of patients overall. Younger patients and those with higher initial symptom severity were more likely to discontinue treatment. CONCLUSIONS: Overall, neuromodulation treatment resulted in statistically significant reductions in symptom severity, though nonresponders and high attrition rate highlight the need for individualized treatment strategies and further investigation.

Humans

Higher versus Routine Intraoperative Blood Pressure Targets in Noncardiac Surgery: A Systematic Review and Meta-analysis with Trial Sequential Analysis of Randomized Trials.

BACKGROUND: Observational studies consistently link intraoperative hypotension to adverse postoperative outcomes, leading guidelines to recommend maintaining mean arterial pressure 60 to 65 mmHg or greater during noncardiac surgery. Whether targeting higher intraoperative blood pressure values improves clinical outcomes remains uncertain. METHODS: The authors conducted a Preferred Reporting Items for Systematic Reviews and Meta-analyses-guided search on PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Embase from inception to April 2026. Randomized trials comparing higher intraoperative blood pressure targets, either as fixed absolute thresholds or personalized to preoperative baseline, versus routine blood pressure management in adults undergoing elective noncardiac surgery with general anesthesia were included. Outcomes included in-hospital or 30-day mortality, postoperative delirium, acute kidney injury (AKI), 30-day major cardiovascular events, acute myocardial injury, stroke, length of stay, and intraoperative hypotension. RESULTS: Fifteen trials (15,603 patients) were included. Higher targets did not reduce AKI (risk ratio [RR], 0.95; 95% CI, 0.85 to 1.06; P = 0.36; I 2 = 16%) or acute myocardial injury (RR, 1.02; 95% CI, 0.94 to 1.12; P = 0.59; I 2 = 0%) compared with routine targets, with firm evidence from trial sequential analysis. Higher targets were associated with a significant reduction in postoperative delirium (RR, 0.73; 95% CI, 0.54 to 0.98; P = 0.04; I 2 = 26%), although trial sequential analysis indicated the cumulative evidence remained insufficient to draw firm conclusions. No significant effect was observed on in-hospital or 30-day mortality (RR, 1.00; 95% CI, 0.75 to 1.34; P = 1.00; I 2 = 0%); evidence on 30-day major cardiovascular events, stroke, and length of stay was similarly insufficient to draw firm conclusions. CONCLUSION: In adults undergoing elective noncardiac surgery, targeting higher intraoperative blood pressure values does not improve major postoperative outcomes compared with routine management. A potential reduction in postoperative delirium warrants confirmation in adequately powered trials.

Humans

Corneal Epithelial Alterations Associated With Cyclin-Dependent Kinase 4/6 Inhibitor Therapy in Hormone Receptor-Positive Breast Cancer.

IMPORTANCE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. By blocking the G1/S cell-cycle transition, these agents may impair renewal of the corneal epithelium. No controlled study has systematically evaluated corneal epithelial changes in patients receiving CDK4/6 inhibitors. OBJECTIVE: To determine whether CDK4/6 inhibitor-based therapy is associated with cornealepithelial alterations independent of aromatase inhibitor exposure and tear film dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective comparative cross-sectional study at a tertiary ophthalmology center. A total of 132 women were enrolled: 45 receiving a CDK4/6 inhibitor plus an aromatase inhibitor (CDKAI group), 44 receiving aromatase inhibitor monotherapy (AI group), and 43 age-matched postmenopausal controls without systemic oncologic therapy. EXPOSURES: CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) combined with an aromatase inhibitor; aromatase inhibitor alone; or no systemic oncologic therapy. MAIN OUTCOMES AND MEASURES: Prevalence and severity of punctate epitheliopathy and vortex keratopathy, assessed by a masked ophthalmologist. Secondary outcomes included Schirmer I test, tear film break-up time, and Ocular Surface Disease Index (OSDI). RESULTS: PE was present in 44.4% of eyes in the CDKAI group vs 4.7% in the AI group and 2.3% in controls (&#x3c7;&#xb2; = 34.31; P < .001). All moderate (13.3%) and severe/complicated (8.9%) PE cases occurred exclusively in the CDKAI group. Vortex keratopathy was observed in 13.3% of CDKAI patients and in none of the other groups (P = .025). Schirmer values, tear film break-up time, and OSDI scores did not differ among groups (all P > .05). Within the CDKAI group, PE was not associated with treatment duration (P = .963) or tear film parameters. CONCLUSIONS AND RELEVANCE: In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of PE and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Symptom scores were low, although OSDI interpretation was limited by incomplete responses. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.

Humans

Predictors of transition readiness in adolescents with neurogenic lower urinary tract dysfunction.

PURPOSE: Adolescents with Neurogenic Lower Urinary Tract Dysfunction (NLUTD) face significant challenges in their quality of life and readiness to transition to adult healthcare services. This study examines the impact of various demographic and clinical factors on transition readiness. METHODS: We performed a retrospective review of prospectively collected data from 75 adolescents with NLUTD managed at a specialized tertiary referral pediatric facility. We employed multivariate linear regression analysis to explore the relationship between transition readiness scores collected from the Good2Go questionnaire, including the total transition readiness score and its sub-domains (self-advocacy, knowledge, self-care, and social support), and predictors such as age, sex, reconstructive surgery status, and clean intermittent catheter (CIC) usage. RESULTS: The mean age of participants was 16.74 years (SD 2.44). Reconstructive surgery had been performed in 32 % of patients, and 77.3 % were on CIC. Multivariate regression analysis indicated that age significantly predicted transition readiness across several domains. Each additional year of age was associated with a 4.40-point increase in the total transition readiness score, a 3.66-point increase in knowledge, a 4.26-point increase in self-advocacy and a 5.41-point increase in self-care. Conversely, CIC significantly negatively impacted the social support domain, with scores decreasing by 9.69 points. Reconstructive surgery was significantly associated with lower self-care scores, with an average decrease of 12.12 points among those who had undergone surgery. CONCLUSION: Age significantly improves transition readiness in adolescents with NLUTD, reflecting cognitive and developmental growth. However, the negative effects of CIC on social support and reconstructive surgery on self-care underscore the need for personalized interventions to optimize health outcomes during the transition to adult care.

Humans

Ameliorating Effects and Autonomic Mechanisms of Transcutaneous Auricular Vagus Nerve Stimulation on Abdominal Pain in Patients With Functional Dyspepsia and Irritable Bowel Syndrome.

BACKGROUND: Patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS) often experience abdominal pain and reduced quality of life and need effective treatments. This exploratory study aimed to evaluate whether transcutaneous auricular vagus nerve stimulation (taVNS) could improve abdominal pain and quality of life in patients with FD and IBS, and whether the effects were mediated via the autonomic mechanisms. METHODS: A total of 64 patients with abdominal pain (43 FD and 21 IBS) with a pain score of 3 out of 10 or higher were randomized to receive 2&#x2009;weeks of taVNS or sham-taVNS treatment. The primary outcome was numeric rating scale (NRS) for abdominal pain. The dyspeptic symptom scales (DSS), IBS symptom severity scale score (IBS-SSS), anxiety and depression scores, and the SF36 quality of life scale were assessed before and after the treatment. The electrocardiogram was also recorded for the assessment of autonomic function at baseline and after the treatment. KEY RESULTS: (1) taVNS reduced the abdominal pain score (p&#x2009;<&#x2009;0.001 for both FD and IBS), the frequency of abdominal pain (p&#x2009;<&#x2009;0.001 for both FD and IBS), and overall symptom scores in both FD patients and IBS patients (p&#x2009;<&#x2009;0.001 for FD and IBS). There was no significant difference in the effect of taVNS on abdominal pain between FD and IBS patients. (2) taVNS improved quality of life compared with baseline in both FD and IBS patients. (3) taVNS decreased anxiety (p&#x2009;<&#x2009;0.001) and depression (p&#x2009;<&#x2009;0.001). (4) taVNS increased vagal activity. At the end of the taVNS treatment, the vagal activity was negatively correlated with the pain score (r&#x2009;=&#x2009;-0.491, p&#x2009;=&#x2009;0.004). CONCLUSIONS: Non-invasive taVNS improves abdominal pain, quality of life, and anxiety and depression in patients with FD and patients with IBS, possibly attributed to the enhancement of vagal activity. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2400085697.

Humans

Impact of education protocols and physiotherapeutic management in improving pain, symptoms, activities of daily living, and quality of life in patients with knee osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis is a debilitating condition of the knee joint and the major cause of disability globally, with an increased economic burden on healthcare. Patient education (PE) has emerged as a primary care treatment approach in chronic conditions. This review aims to evaluate the effectiveness of PE along with exercise in reducing pain, alleviating symptoms, improving activities of daily living, and promoting quality of life among individuals with knee osteoarthritis. METHOD: A systematic search was conducted across three electronic databases, PubMed, Cochrane Library, and PEDro. The search was limited to between 2020 and 2025, and included only randomized controlled trials. The Cochrane Risk of Bias Tool and the PEDro Scale were used to evaluate the methodological evidence. Statistical synthesis was analysed using mean differences (MDs) with 95% confidence intervals (CIs) under a random-effects model. RESULTS: Eight trials were included, of which four studies evaluated the four Knee Injury and Osteoarthritis Outcome Score (KOOS) domains, and three studies evaluated the Visual Analogue Scale (VAS) and KOOS activities of daily living domain in patients with knee osteoarthritis. For the meta-analysis, we assessed all five domains of the KOOS scale and VAS. Statistical analysis of the studies showed a significant reduction in pain (VAS) for the PE along with exercise group (MD&#xa0;=&#xa0;-3.28, 95% CI (-4.85; -1.70), and I2&#xa0;=&#xa0;69.6%), but there was no significant improvement in the domains of the KOOS scale. CONCLUSION: The study highlights the importance of PE along with exercise in reducing pain. It might not be more effective when compared with exercise therapy as a standalone intervention in improving ADLs, QoL, and symptoms, but it has demonstrated some degree of effectiveness. It additionally promotes self-management and self-efficacy as a physiotherapeutic rehabilitation treatment intervention.

Humans

Nociception-guided opioid administration within multimodal analgesia for laparoscopic endometriosis surgery: a randomized controlled trial.

Women with endometriosis are at increased risk of severe postoperative pain due to nociceptive sensitization. While multimodal analgesia reduces opioid use, the added value of objective nociception monitoring remains unclear. This study evaluated whether NOL&#xae;-guided opioid titration improves perioperative outcomes within a standardized multimodal regimen. In this prospective, randomized, single-blinded trial, premenopausal women undergoing laparoscopic surgery for suspected endometriosis or adenomyosis were assigned to NOL&#xae;-guided analgesia or standard care based on clinical assessment. All patients received a standardized multimodal protocol. The primary outcome was total perioperative opioid consumption. Secondary outcomes included postoperative pain scores (NRS) and PACU length of stay. Exploratory analyses assessed the association between preoperative pain (Mankoski Pain Scale, MPS) and postoperative outcomes. A total of 111 patients were analyzed (NOL&#xae;: n&#x2009;=&#x2009;54; control: n&#x2009;=&#x2009;57). Total perioperative opioid consumption did not differ significantly between groups (adjusted mean difference&#x2009;=&#x2009;14&#xa0;&#x3bc;g for Fentanyl and 52&#xa0;&#x3bc;g for Remifentanil; p&#x2009;=&#x2009;0.8). Surgery duration was an independent predictor of opioid use (p&#x2009;<&#x2009;0.001) and PACU length of stay (p&#x2009;=&#x2009;0.01), whereas treatment group had no significant effect. Postoperative pain scores were comparable between groups at all time points. NOL&#xae;-derived metrics were not associated with opioid consumption or pain. Higher preoperative MPS scores independently predicted higher pain scores in the late PACU phase. NOL&#xae;-guided opioid titration did not reduce perioperative opioid consumption or improve early postoperative outcomes compared with standard multimodal analgesia in women undergoing laparoscopic surgery for endometriosis.

Humans

MRI-Negative Posterior Reversible Encephalopathy Syndrome: Comparison of Hypertensive Encephalopathy With and Without Vasogenic Edema.

OBJECTIVE: To explore whether posterior reversible encephalopathy syndrome (PRES) can present with negative magnetic resonance imaging (MRI) by comparing clinical features between cases of PRES with vasogenic edema and cases of hypertensive encephalopathy without MRI changes. PATIENTS AND METHODS: Patients diagnosed with hypertensive encephalopathy from August 1, 2008, to December 31, 2017, were identified retrospectively and matched by age (&#xb1;5 years) and sex in a 1:2 ratio to patients retrospectively identified as having PRES from January 1, 2002, to November 30, 2017. A review of MRI images and clinical information was performed. RESULTS: We identified 16 cases of hypertensive encephalopathy and 32 age- and sex-matched controls with PRES showing vasogenic edema on MRI. There were no statistically significant differences in the odds of presentation with headache (odds ratio [OR], 1.372; 95% CI, 0.458 to 4.106), encephalopathy (OR, 2.303; 95% CI, 0.433 to 12.236), visual disturbance (OR, 0.826; 95% CI, 0.185 to 3.697), or focal neurologic deficit (OR, 4.000; 95% CI, 0.767 to 20.872). Seizures were more common in patients with vasogenic edema (OR, 0.082; 95% CI, 0.010 to 0.664). There were no significant differences in odds of acute kidney injury (OR, 2.90; 95% CI, 0.679 to 12.449) or odds of having a history of malignancy (OR, 0.295; 95% CI, 0.076 to 1.152), transplantation (OR, 3.347; 95% CI, 0.594 to 18.880), or autoimmune disease (OR, 0.400; 95% CI, 0.104 to 1.532). Systolic blood pressure at presentation was higher in patients with hypertensive encephalopathy and negative MRI as compared with patients with PRES and vasogenic edema (OR, 1.03; 95% CI, 1.01 to 1.05). CONCLUSION: Most presenting symptoms and risk factors were not significantly different between cases of hypertensive encephalopathy with and without vasogenic edema, arguing that the diagnosis of PRES in the setting of acute severe hypertension may not depend on MRI confirmation.

Humans

Deucravacitinib 5-Year Safety and Efficacy Results in Plaque Psoriasis: A Phase 3 Open-Label Extension of Randomized Clinical Trials.

BACKGROUND: Deucravacitinib, an oral, selective, tyrosine kinase 2 inhibitor, is approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and for adults with active psoriatic arthritis. OBJECTIVE: We evaluated deucravacitinib safety and efficacy over 5 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials in patients with moderate to severe plaque psoriasis. METHODS: PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib. Safety was reported as exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY). Clinician- and patient-reported outcomes were analyzed using modified nonresponder imputation in patients receiving continuous deucravacitinib from day 1 (PSO-1/PSO-2) through 5 years. RESULTS: Overall, 1519 patients received one or more deucravacitinib dose; total exposure was 5046.7 PY through data cutoff (September 2, 2024). EAIRs/100 PY were comparable or decreased from the 1-year to 5-year cumulative period for adverse events (AEs) (229.23, 127.40, respectively), serious AEs (5.68, 5.06), discontinuation due to AEs (4.38, 2.09), deaths (0.20, 0.22), serious infections excluding coronavirus disease 2019 (COVID-19) (1.53, 0.94), malignancies (1.02, 0.92), major adverse cardiovascular events (0.30, 0.34), and venous thromboembolism (0.20, 0.06). Clinical outcomes were well-maintained in patients receiving continuous deucravacitinib (n = 513) from 1 through 5 years, including achievement of a &#x2265;&#xa0;75% reduction from baseline in the Psoriasis Area and Severity Index (1 year, 72.1% [95% CI 68.2-76.1]; 5 years, 67.3% [62.0-72.6]) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (1 year, 57.5% [53.1-61.9]; 5 years, 52.6% [47.0-58.1]). Dermatology Life Quality Index 0 or 1 was well-maintained from 1 year (52.5% [48.0-57.1]) through 5 years (45.4% [40.0-50.8]). CONCLUSIONS: These findings demonstrate a consistent safety profile with no new safety signals and durable clinical response through 5 years of treatment with deucravacitinib. CLINICAL TRIAL REGISTRATION: NCT03624127, NCT03611751, NCT04036435.

Humans

Robotic assistance in total hip arthroplasty: a systematic review and meta-analysis of leg length, cup orientation, and early outcomes.

This review examined whether robotic assistance alters postoperative leg-length discrepancy (LLD), acetabular cup orientation, or early hip-specific outcomes relative to conventional total hip arthroplasty (THA). We searched PubMed and Web of Science through May 2026 for comparative English-language reports. Study eligibility, data extraction, and methodological appraisal were undertaken independently by two reviewers. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated in Review Manager 5.4. Model selection was based on the target estimand and anticipated clinical and methodological diversity; leave-one-out and alternative-model sensitivity analyses were undertaken for heterogeneous outcomes. The protocol is registered with PROSPERO (CRD420261454043). The review included seven studies and 968 participants. Compared with conventional THA, robot-assisted THA yielded a smaller postoperative LLD (MD = -2.02, 95% CI -3.46 to -0.58; P = 0.006) and a higher Harris Hip Score (MD = 2.96, 95% CI 1.12 to 4.80; P = 0.002). Mean cup anteversion was lower in the robotic group (MD = -1.52, 95% CI -2.29 to -0.76; P < 0.0001), whereas cup inclination did not differ (MD = -0.71, 95% CI -3.26 to 1.83; P = 0.58). The robotic group also had higher Forgotten Joint Score (MD = 14.68, 95% CI 5.02 to 24.33; P = 0.003) and Oxford Hip Score values (MD = 2.61, 95% CI 0.71 to 4.51; P = 0.007). Robotic assistance was linked to a modest improvement in leg-length restoration and to higher scores on several early functional measures. The limited number of studies, predominance of nonrandomized designs, and marked heterogeneity in some analyses temper the certainty of these findings.

Humans

Healthcare transition readiness in an adolescent and young adult urologic population: The ADHERENT study.

INTRODUCTION: There is a paucity of research regarding transition to adult services within pediatric and adolescent urology. Several recent articles have discussed the barriers in transitioning urologic patients from pediatric to adult health care, but empiric data that may drive intervention are lacking. This study proposes to begin to address this gap in literature and to provide information that may lead to improved understanding of how best to support transition in urologic care. OBJECTIVES: 1) to identify modifiable and non-modifiable factors related to transition readiness as measured by Transition Readiness Assessment Questionnaire (TRAQ) scores in a congenital urologic population and 2) to evaluate the relationships between TRAQ scores (a validated questionnaire measuring transition readiness) and scores measuring anxiety levels related to transition (using an adapted, non-validated questionnaire). STUDY DESIGN: This is a cross-sectional study of adolescent and young adult patients with complex congenital urologic diagnoses. Subjects were electronically administered the validated TRAQ and a study-developed ADHERENT survey, which assesses anxiety and worry surrounding transition. Regression models for the outcomes of the TRAQ and ADHERENT scales were developed to assess multivariable associations with variables of clinical importance. RESULTS: The youngest subgroup (14-17 years of age) compared to the oldest subgroup (21-25 years of age) had significantly lower TRAQ scores [regression estimate = 12.3 (95 % CI: 2.9, 21.7), p = 0.010]. Additionally, single participants versus those in a stable relationship had significantly lower TRAQ scores [estimate = 8.7 (95 % CI: 1.9, 15.4), p = 0.012]. The Spearman correlation coefficient between TRAQ and ADHERENT scores was 0.52 (p = <0.001), indicating a positive, moderate relationship between the two measures, suggesting more readiness correlated with less anxiety. DISCUSSION: This study found that age, higher education, and stable relationship status were associated with higher measures of transition readiness. There was a correlation found between more transition readiness and less anxiety surrounding transition. This finding can be used to inform future research and emphasizes the need for multidisciplinary support throughout the transition process. CONCLUSION: Early discussion of transition of care and education around transition readiness are not the only solution to improving transition success. The second phase of ADHERENT seeks to understand the patient experience and to include adolescents and young adults in shaping effective healthcare transition strategies.

Humans

Assessment and CommuniCation ExcelLEnce foR sAfe paTient outcomEs (ACCELERATE): A stepped-wedge cluster randomised trial evaluating the effectiveness of a nurse-led assessment and handover communication intervention on patient adverse events.

BACKGROUND: Patients continue to experience harm from undetected deterioration, falls and pressure injuries. We aimed to implement and evaluate an organisational, ward-level nurse-led assessment and communication intervention to proactively reduce patient adverse events. METHODS: A stepped-wedge cluster randomised Trial over 12-months was conducted at three metropolitan hospitals. Our intervention comprised a comprehensive, systematic patient assessment at shift commencement; a structured patient-centred bedside nurse-to-nurse clinical handover; and multidisciplinary communication consisting of nurse participation in medical ward rounds. Evidence-based implementation strategies informed intervention delivery to nine clusters (20-35 bed-wards with &#x2265;70% permanent nurses) over three sequential 14-week steps. Routinely collected patient-level data were used to measure intervention effect. The primary outcome was a composite measure of medical emergency team calls, unplanned intensive care unit admissions, in-hospital falls; and stage 2-4 pressure injuries. Secondary outcomes were: individual measures of the primary outcome; nurse-reported perceptions of safety culture; organisational readiness to change; barriers to physical assessment; staff engagement; and patient-reported experience measures of safety and overall hospital experience. Analyses were adjusted for age, sex, hospital, pre/post intervention, and Trial step (fortnight), with random effects for ward and patient. RESULTS: There were 13,753 eligible admissions. No change was observed in the primary composite outcome measure (odds ratio (OR) [95% confidence interval (CI)]: 0.99 [0.77, 1.28]; p&#xa0;=&#xa0;0.95). There was no significant difference in medical emergency team calls (OR [95% CI]: 1.02 [0.75, 1.39]; p&#xa0;=&#xa0;0.91); unplanned intensive care unit admissions (OR [95% CI]: 1.35 [0.57, 3.20]; p&#xa0;=&#xa0;0.50) and falls (OR [95% CI]: 1.53 [0.96, 2.45]; p&#xa0;=&#xa0;0.07). However, stage 2-4 pressure injuries significantly decreased by 41% (OR [95% CI]: 0.59 [0.38, 0.93]; p&#xa0;=&#xa0;0.02); a significant absolute effect improvement of 0.8% ([95% CI: 0.3%-1.3%], p&#xa0;<&#xa0;0.01). There were statistically significant improvements in nurses' overall perceptions of Safety Attitudes (Pre: 74.6, Post: 79.7; p&#xa0;=&#xa0;0.02), and the Organisational Readiness to Change subscales of, leader culture (Pre: 3.73, Post 3.91; p&#xa0;=&#xa0;0.02), leadership behaviour (Pre: 3.85, Post: 4.11; p&#xa0;=&#xa0;0.03), and general resources (Pre: 3.06, Post: 3.30; p&#xa0;=&#xa0;0.03). A statistically significant decrease in Barriers to Physical Assessment (Pre: 2.48, Post: 2.24; p&#xa0;<0.001) and in six of seven sub-scales was observed. Patients' overall Measure of Safety remained high, but unchanged (Pre: 3.94 Post: 3.92; p&#xa0;=&#xa0;0.07). CONCLUSION: The ACCELERATE Trial demonstrated that nurse-driven initiatives, emphasising structured physical assessments by nurses, patient-centred clinical handovers, and multidisciplinary communication, significantly: reduced pressure injuries; decreased nurses' perceived barriers to performing physical assessments; and improved leadership behaviour, communication, and ward safety culture perceptions. Results highlight the transformative potential of this approach, which now warrants testing at scale for broader implementation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ID: ACTRN12621000265875.

Humans

Early-stage trajectories of social-occupational functioning and long-term functional outcome prediction in early psychosis: A 12-year follow-up of the randomized controlled trial on extended early intervention.

BACKGROUND: Functional impairment in psychosis often persists despite symptomatic remission. There is a paucity of research examining early-course psychosocial functioning trajectories, and none has been conducted to examine relationship between the trajectories and prospective long-term functional outcomes in early psychosis sample. METHODS: We conducted 12-year follow-up of a randomized controlled trial on extended early intervention for first-episode psychosis to identify early-course social-occupational functioning trajectories and their baseline predictors and associations with 12-year outcomes. Participants who completed Social and Occupational Functioning Scale (SOFAS) scores at three or more timepoints between baseline and 3-year follow-up were included in the study. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Latent growth mixture modeling was employed to derive early-course social-occupational functioning trajectories based on SOFAS scores over 3-year follow-up. RESULTS: A total of 148 participants were included in this study, with 106 patients having completed the 12-year follow-up. Our results identified four distinct trajectories, including persistently-good class, gradually-improved class, suboptimal-stable class, and persistently-poor class. Patients in persistently-poor class had more severe negative symptoms at baseline compared to patients in persistently-good class. Patients with persistently-poor trajectory had worse long-term outcomes than those with other classes in the majority of functional measures at 12-year follow-up. CONCLUSIONS: The majority of patients were classified in early-stage suboptimal or poor functional trajectories. Above one-fourth of the participants exhibited persistently-poor social-occupational functioning trajectory, which predicted worse functional outcomes at 12-year follow-up. These findings highlighted the importance of tracking functional changes during the initial years of illness.

Humans

Effects of intradialytic nutrition on dialysis adequacy and fatigue in hemodialysis patients: a randomized crossover study.

OBJECTIVE: To assess intradialytic nutrition's effects on dialysis adequacy and fatigue in maintenance hemodialysis patients. METHODS: A randomized, two-period, two-sequence, self-controlled crossover trial was conducted in two outpatient hemodialysis centers in T&#xfc;rkiye. Thirty-six patients were randomized; 32 completed both periods. The participants received standardized intradialytic nutrition in one period and no food intake during the control period. Dialysis adequacy was evaluated using the urea reduction ratio and single-pool Kt/V. Intradialytic blood pressure was recorded during dialysis sessions, and fatigue severity was measured using the Piper Fatigue Scale at the end of each period. RESULTS: No significant differences were observed in dialysis adequacy or fatigue scores between the two periods. Intradialytic nutrition was associated with greater reductions in systolic and diastolic blood pressure, particularly during the second hour of dialysis. No clinically relevant adverse events occurred. CONCLUSION: Intradialytic nutrition did not compromise dialysis adequacy or worsen fatigue severity but was associated with increased intradialytic blood pressure reductions. Individualized clinical decisions and careful hemodynamic monitoring are warranted when implementing intradialytic nutritional interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07687498.

Humans

Effects of a programmed reflexology therapy on sleep quality, insomnia, and fatigue among individuals with poor sleep quality: evidence for autonomic nervous system modulation.

Poor sleep quality is closely associated with autonomic dysregulation and increased risks of cardiovascular, metabolic, and mental disorders. Foot reflexology is a widely used complementary therapy; however, its physiological mechanisms and comparative efficacy remain insufficiently explored. This study aimed to compare the effects of manual reflexology treatment (MRT) and foot massage equipment (FEM) on autonomic nervous system function, sleep quality, insomnia severity, and fatigue in adults with poor sleep quality. Using a randomized crossover design, 32 participants with poor sleep quality received MRT and FEM interventions for 6 weeks each (once weekly, 30-40&#x202f;min/session). Heart rate (HR), blood pressure, and heart rate variability (HRV; time- and frequency-domain indices) were assessed at weeks 1 and 6 before and after each intervention. Subjective outcomes included the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Fatigue Assessment Scale (FAS). Following MRT, participants demonstrated significantly greater reductions in global PSQI scores and all PSQI components compared with FEM. MRT also resulted in larger improvements in insomnia severity and both mental and physical fatigue. In contrast, FEM primarily improved physical fatigue. Physiologically, MRT induced an immediate decrease in HR and significant increases in HRV time-domain indices (SDNN, RMSSD, pNN50), which were sustained after 6 weeks. Frequency-domain analysis further revealed reduced LF, increased HF, and a lower LF/HF ratio, indicating enhanced parasympathetic activity and cumulative autonomic modulation. In conclusion, programmed manual reflexology, delivered according to the TIDieR framework, is more effective than mechanical foot massage in improving autonomic balance, sleep quality, insomnia severity, and fatigue in individuals with poor sleep quality. These findings support MRT as a feasible and evidence-based non-pharmacological complementary intervention for sleep health promotion. TRIAL REGISTRATION: clinicaltrials.gov; NCT Number: NCT07402460; Registered 3 February 2026.

Adult

Glycerophospholipid remodeling under osmotic stress in grass carp gills.

Salinity fluctuations represent a pervasive environmental challenge for freshwater fishes, yet the cellular and metabolic programs governing early osmoregulatory responses remain understudied. Here, we investigated the time-dependent gill responses of juvenile grass carp (Ctenopharyngodon idella) subjected to an acute, sublethal salinity increase 9 parts per thousand (ppt). Histological and biochemical analyses revealed progressive gill lesions accompanied by elevated lactate dehydrogenase (LDH) activity and lipid peroxidation, indicating rapid tissue injury under osmotic stress. Integrative metabolomic and transcriptomic profiling uncovered pronounced temporal reprogramming, consistently highlighting glycerophospholipid metabolism as a central axis of response. In particular, phosphatidylcholine (PC) species exhibited dynamic remodeling, coupled with transcriptional enrichment of lipid turnover, membrane transport, and innate immune pathways. Network-based integration identified a PC-centered remodeling module characterized by accelerated PC headgroup turnover, disruption of the PLA2-LPCAT2 lyso-PC reacylation cycle, and enhanced ABC transporter-associated lipid and sterol export, reflected by cholesteryl sulfate accumulation and a shifted n-6 polyunsaturated fatty acid-derived oxylipin signature. Functional assays further demonstrated that PC and linoleic acid (LA) supplementation improved cell viability and alleviated oxidative stress and pro-inflammatory signaling in grass carp cells under salinity challenge. Collectively, these findings reveal phospholipid-centered membrane remodeling as an early, integrative mechanism linking osmotic stress to gill injury and immune activation in freshwater fish, providing insights into potential strategies of environmental stress adaptation.

Animals