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Clinical Trial: Phase 3 Trial of Resmetirom Versus Placebo in Metabolic Dysfunction-Associated Steatohepatitis-Reanalysis of Fibrosis Stage 2-3 Subset.

BACKGROUND: Resmetirom is an oral thyroid hormone receptor beta agonist clinically used to treat metabolic dysfunction-associated steatohepatitis (MASH) among adults with stage F2 or F3 fibrosis. AIMS: Because the pivotal, 52-week, randomized, controlled, phase 3 MAESTRO-NASH trial (once-daily oral resmetirom 80 or 100&#x2009;mg or placebo) included patients with F1, F2, or F3 fibrosis, we conducted a post hoc analysis aimed at assessing treatment response in the subset of patients with stages F2 and F3 fibrosis, consistent with the approved label population. METHODS: Co-primary end points were MASH resolution (hepatocellular ballooning score 0, lobular inflammation score &#x2264;&#x2009;1, and &#x2265;&#x2009;2-point nonalcoholic fatty liver disease activity score [NAS] reduction from baseline) with no fibrosis worsening, and &#x2265;&#x2009;1-stage fibrosis improvement with no NAS worsening at Week 52. RESULTS: Among 917 patients with F2 or F3 fibrosis, metabolic risk factor prevalence was high (hypertension, 78.0%; dyslipidemia, 71.1%; type 2 diabetes, 67.0%). MASH resolution was achieved by 25.7% in the 80-mg group, 29.9% in the 100-mg group, and 9.5% in the placebo group (p&#x2009;<&#x2009;0.0001 for both comparisons with placebo). Respective percentages with fibrosis improvement were 26.5%, 28.9%, and 17.3% (p&#x2009;<&#x2009;0.01 for both comparisons). From baseline to Week 24, low-density lipoprotein cholesterol decreased by 11.7% and 13.7% in the 80- and 100-mg resmetirom groups, respectively, and increased by 2.3% with placebo (p&#x2009;<&#x2009;0.0001 for both comparisons). No new safety signals emerged. CONCLUSION: Results among patients with F2 and F3 fibrosis were consistent with the primary MAESTRO-NASH analysis population, demonstrating efficacy and safety of resmetirom after 52&#x2009;weeks.

Humans

Tissue origins of the plasma proteomic response to glucose ingestion in humans.

AIMS/HYPOTHESIS: Circulating proteins act as important hormonal signals of nutrient intake. We aimed to systematically characterise the time-resolved proteomic response to glucose ingestion in humans, and to assess its robustness following prolonged complete caloric restriction. METHODS: We conducted oral glucose tolerance tests (OGTTs) in 11 healthy volunteers before and after 7 days of complete caloric restriction and measured the response of >2900 targets through high-resolution plasma protein profiling. RESULTS: We identified a signature of 44 proteins that changed significantly following glucose ingestion, which was reproducible after 7 days without food, and was strongly (20-fold) enriched for 'stomach-specific' proteins. We report that annexin A10 (ANXA10) shows the most significant post-glucose change observed, similar to the trajectories of secreted hormones. We present observational human evidence from multiple sources suggesting that ANXA10 is secreted upon sensing an increase in gastric pH, with the stomach as the major contributing tissue. Despite a profound metabolic shift after 7 days of complete caloric restriction, characterised by delayed insulin secretion and postprandial hyperglycaemia, only four proteins showed robust evidence for a differential trajectory during both OGTTs. This included plasma levels of tryptophanyl-tRNA synthetase&#xa0;1 (WARS), for which we found a genetic association with glucose homeostasis and coronary artery disease. CONCLUSIONS/INTERPRETATION: Our exploratory study identifies the proteomic response to glucose ingestion and demonstrates its reproducibility despite major shifts in glucose homeostasis. We characterise the gastrointestinal origin of these changes, and hypothesise a hitherto under-recognised role for sensing of changes in gastric pH on the plasma proteome.

Humans

Immersive virtual reality-assisted anatomy training improves endotracheal intubation performance in simulation: a randomized controlled trial among Chinese non-anesthesiology residents.

INTRODUCTION: This study aimed to compare immersive virtual reality (IVR)-assisted versus conventional anatomy training for teaching endotracheal intubation (ETI) to novice non-anesthesiology residents enrolled in China's Standardized Residency Training program. METHODS: A total of 90 non-anesthesiology residents without prior ETI experience were randomly assigned to either an IVR group receiving IVR-assisted anatomy training (n&#x2009;=&#x2009;45) or a control group receiving conventional anatomy training (n&#x2009;=&#x2009;45). All participants underwent a standardized teaching protocol. The primary endpoint was residents' ETI performance on a simulator, assessed using both the Global Rating Scale (GRS) and a task-specific checklist. The secondary endpoints included changes in written multiple-choice question (MCQ) scores and residents' evaluations of the course. RESULTS: In practical ETI assessments on a manikin, the IVR group achieved significantly higher scores on the task-specific checklist than the control group (90.34&#x2009;&#xb1;&#x2009;2.89 vs. 87.20&#x2009;&#xb1;&#x2009;3.29; p&#x2009;<&#x2009;0.001), whereas GRS scores were comparable between groups. Both groups showed significant post-training improvement in knowledge scores (p&#x2009;<&#x2009;0.001), with the IVR group showing a greater gain in theoretical knowledge (54.0% vs. 36.3%; p&#x2009;<&#x2009;0.001). Participants in the IVR group also expressed a stronger preference for their training method (80.8%) and reported higher levels of motivation, confidence, and enjoyment (all p&#x2009;<&#x2009;0.05). CONCLUSION: IVR-assisted anatomy training enhances the effectiveness of ETI training for novice non-anesthesiology residents, offering an interactive, engaging, and reproducible approach within China's Standardized Residency Training framework.

Humans

Cerebellar iTBS enhances gait adaptation by modulating cortical sensorimotor network dynamics: a randomized controlled trial.

Gait adaptation enables individuals to maintain locomotor stability under persistent perturbations. Although the cerebellum is critical for sensory prediction error-based (SPE) adaptation, how cerebellar neuromodulation reshapes cortical sensorimotor networks to enhance gait adaptation remains unclear. This study investigated the behavioral effects and underlying cortical neurodynamic mechanisms of cerebellar intermittent theta-burst stimulation (iTBS) on gait adaptation. Thirty-two healthy adults received either active or sham cerebellar iTBS. Participants performed a split-belt treadmill adaptation task before and after intervention. Cortical responsiveness was evaluated using TMS-evoked EEG over primary motor cortex (M1), while resting-state EEG was analyzed to assess spectral power and directional functional connectivity. Compared to sham, cerebellar iTBS significantly enhanced gait adaptation, evidenced by a faster adaptation rate (p&#x202f;=&#x202f;0.035) and enhanced Early Adaptation SLS (p&#x202f;=&#x202f;0.011), without altering initial perturbation responses or post-adaptation outcomes. The iTBS increased TMS-evoked &#x3b1; (p&#x202f;=&#x202f;0.031) and &#x3b3; (p&#x202f;=&#x202f;0.022) power in M1, while the &#x3b1; power was correlated with faster adaptation (r&#x202f;=&#x202f;0.526, p&#x202f;=&#x202f;0.002). Furthermore, iTBS strengthened PPC-to-M1 directed connectivity in the &#x3b2; (p&#x202f;=&#x202f;0.025) and &#x3b3; (p&#x202f;=&#x202f;0.013) bands. Enhanced parieto-motor directionality were positively associated with adaptation rate (&#x3b2;: r&#x202f;=&#x202f;0.515, p&#x202f;=&#x202f;0.003; &#x3b3;: r&#x202f;=&#x202f;0.463, p&#x202f;=&#x202f;0.009). These findings suggest that cerebellar iTBS facilitates gait adaptation by modulating cortical responsiveness and directional sensorimotor network connectivity, providing multi-level neurodynamic evidence for the cerebello-cortical modulation during gait adaptation and offering a strong physiological rationale for targeted neuromodulation in gait rehabilitation strategies.

Humans

Viscoelastic-Assisted Patient Interface Docking: A Technical Optimization in LenSx Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To evaluate the efficacy of viscoelastic-assisted patient interface docking in LenSx (Alcon Laboratories, Inc) femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a randomized controlled trial. Patients undergoing FLACS from January to August 2025 at Aier Eye Hospital of Wuhan University were randomized via a random number table to receive balanced salt solution (BSS) or visoeleastic as the patient interface docking medium. The primary outcome was docking efficiency, measured by one-time docking success rate, the number of docking attempts, and mean docking time. Secondary outcomes included surgical safety (subconjunctival hemorrhage, capsulotomy completeness/tear rate), laser treatment duration (anterior capsulotomy time, nucleus pretreatment time, total laser emission time), and patient comfort (post-laser pain sensation). RESULTS: A total of 100 patients were enrolled, 50 in each group. Suction loss occurred in 7 patients (14%) in the BSS group and 1 patient (2%) in the viscoelastic group; the one-time docking success rate was significantly higher in the viscoelastic group (98%) than in the BSS group (86%) (chi-square = 3.93, P < .05). The viscoelastic group also had fewer mean docking attempts (1.02 &#xb1; 0.14) than the BSS group (1.16 &#xb1; 0.42), showing a significant difference (t = 2.23, P < .05). The viscoelastic group exhibited significantly shorter mean docking time (44.66 &#xb1; 4.47 seconds) compared to the BSS group (48.62 &#xb1; 3.11 seconds) (t = 2.17, P < .05). No significant differences were observed between the groups in subconjunctival hemorrhage, capsulotomy completeness/tear rate, anterior capsulotomy time, nucleus pretreatment time, total femtosecond laser emission time, or patient-reported pain sensation (all P > .05). CONCLUSIONS: Viscoelastic-assisted patient interface docking in FLACS effectively elevates one-time docking success rate, reduces docking attempts, and shortens docking time.

Humans

The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: Preoperative rehabilitation training can optimize functional reserve before radical prostatectomy (RP), thereby improving postoperative outcomes. However, its effects on urinary incontinence, erectile function, and quality of life (QoL) remain controversial. This study systematically evaluated these outcome measures. METHODS: Data from randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, Embase, and CINAHL databases. The risk of bias was assessed using the RoB-2 tool, and meta-analysis was performed using Stata 18.0 software. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity. Outcomes included urinary incontinence incidence, urinary incontinence severity, erectile function, and QoL at different postoperative follow-up time points. RESULTS: 16 randomized controlled trials involving 1,542 participants were included. Prehabilitation significantly reduced the incidence of urinary incontinence at 1&#xa0;month (OR&#x2009;=&#x2009;0.58, 95% CI 0.39-0.84) and 6&#xa0;months (OR&#x2009;=&#x2009;0.52, 95% CI 0.28-0.96) after RP, with a non-significant borderline reduction at 3&#xa0;months, and no significant benefit at 12&#xa0;months. No significant improvement was observed in urinary incontinence severity or erectile function at any follow-up time point. Prehabilitation significantly improved QoL within 3&#xa0;months (SMD&#x2009;=&#x2009;-0.70, 95% CI -1.08 to -0.32) and 6&#xa0;months (SMD&#x2009;=&#x2009;-0.45, 95% CI -0.74 to -0.16) postoperatively. However, within 12&#xa0;months, the effect size attenuated, showing only a marginal trend that did not reach statistical significance (SMD&#x2009;=&#x2009;-0.33, 95% CI -0.66 to 0.00). Risk of bias was generally moderate. CONCLUSION: Prehabilitation reduces early incontinence and improves QoL post-RP, but its effects on severity and erectile function remain unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [CRD420251183407].

Humans

Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis.

BACKGROUND: Despite the burden of tobacco use, access to cessation support in South Asia remains scarce. OBJECTIVE: This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia. METHODS: Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (n&#x2009;=&#x2009;6; 16.2%), nicotine replacement therapy (n&#x2009;=&#x2009;7; 18.9%), behavioral counseling (n&#x2009;=&#x2009;12; 32.4%), or combined/multicomponent interventions (n&#x2009;=&#x2009;12; 32.4%). Most studies were conducted in India (n&#x2009;=&#x2009;26; 70.3%), followed by Pakistan (n&#x2009;=&#x2009;6; 16.2%), Nepal (n&#x2009;=&#x2009;3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3&#x2009;months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3&#x2009;months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3&#x2009;months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (p&#x2009;=&#x2009;0.06). CONCLUSION: Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.

Humans

Impact of Baseline Polyneuropathy Severity on Eplontersen Efficacy in the NEURO-TTRansform Clinical Trial.

BACKGROUND AND AIMS: In the NEURO-TTRansform clinical trial (NCT04136184), eplontersen improved neuropathy impairment and quality of life (QoL) through Week 66 versus the NEURO-TTR historical placebo in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This analysis assessed the impact of baseline ATTRv-PN severity on eplontersen response in patients from NEURO-TTRansform. METHODS: This post hoc analysis grouped patients into tertiles by baseline Neuropathy Impairment Score (NIS): T1 (least baseline impairment: 3.5 to <&#x2009;27.5; n&#x2009;=&#x2009;67), T2 (27.5 to <&#x2009;55.0; n&#x2009;=&#x2009;67), and T3 (55.0 to <&#x2009;127.8; n&#x2009;=&#x2009;66). Outcomes assessed were neuropathy impairment (modified NIS+7 [mNIS+7] and NIS, Neuropathy Symptom and Change, Polyneuropathy Disability), QoL (Norfolk QoL-Diabetic Neuropathy), physical functioning (36-Item Short-Form Health Survey Physical Component Summary), nutritional status (modified body mass index), and serum transthyretin levels; these were compared with NEURO-TTR historical placebo. Autonomic dysfunction (Composite Autonomic Symptom Score-31), disability (Rasch-built Overall Disability Scale), and walking speed (10-Meter Walk Test) were also assessed. Final assessments were carried out following 65/66 or 81/85&#x2009;weeks of treatment. RESULTS: Mean mNIS+7 composite scores were maintained over 85&#x2009;weeks with eplontersen (changes from baseline of -4.5 [T1], -1.3 [T2], and -2.6 [T3] points). Other disease parameter scores were similarly maintained or improved with eplontersen. Patients receiving placebo experienced disease worsening across outcomes. T1 mean disease scores were typically better than in T2 and T3. INTERPRETATION: Consistent, sustained benefits of eplontersen were observed regardless of baseline ATTRv-PN severity. These findings strengthen the importance of early treatment initiation for patients with ATTRv-PN across the disease spectrum.

Humans

Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a &#x2265;15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). RESULTS: Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). CONCLUSIONS: Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00094302.

Humans

Incidence of silent cerebral lesions during pulsed field ablation for paroxysmal atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is a first-line treatment for paroxysmal atrial fibrillation (PAF). Complications such as silent cerebral lesion (SCL) may occur during ablation. Pulsed field ablation (PFA) is a non-thermal method thatablates cardiac tissue via irreversible electroporation. Limited studies have reported the incidence of SCL during PFA, with highly variable results. However, randomized controlled trials (RCTs) remain scarce. The objective of this study was to compare perioperative SCL incidence between PFA and RFCA, and to identify risk factors for SCL during PFA. METHODS: In this prospective pilot RCT (ChiCTR2400088774), 62 patients with PAF were randomized 1:1 to undergo PFA or RFCA. Cerebral MRI (3.0 T) was performed preoperatively and 24-48h postoperatively. SCL was defined as a new acute brain lesion on MRI without neurological deficits. Baseline and surgical data of the patients were collected. RESULTS: SCL was detected post-procedure in 6.45% (2/31) in the RFCA group, 12.90% (4/31) in the PFA group. No statistically significant difference in the incidence of postoperative SCL was detected between the two groups (p&#x2009;=&#x2009;0.67). Left atrium dimension (LAD), left atrial operation time (LAOT), left ventricular end-diastolic dimension (LVEDD), and total operation time (TOT) were significantly higher in SCL group than those in no-SCL group (p&#x2009;<&#x2009;0.05) through univariate analyses. CONCLUSIONS: SCL incidence was 12.90% in the PFA group versus 6.45% in the RFCA group. While no statistically significant difference was detected between two groups, the numerically higher rate in the PFA group warrants larger studies to evaluate cerebral safety associated with PFA.

Humans

The impact of routine traffic encounters that include procedural justice on police perceptions.

OBJECTIVES: Despite procedural justice in police-citizen interactions being widely studied, there is limited research regarding police perceptions of these interactions. This study addresses this by exploring police perceptions of two different types of random breath test (RBT) - standard and procedurally just - in an experimental trial. Officers were asked to report on whether they believe that their RBT interaction with drivers and riders changed behaviour, developed more positive perceptions of police and resulted in slower travel. Additionally, they were asked if they thought that the RBT interaction took too long. METHODS: This study was a six month randomised control trial with two operational conditions: a control condition with a standard (n&#xa0;=&#xa0;18&#xa0;days) and an experimental condition with a procedurally just (n&#xa0;=&#xa0;17&#xa0;days) RBT. Police officers completed post-operation surveys (n&#xa0;=&#xa0;80). RESULTS: Police officers incorporating the principles of procedural justice into RBT had limited impact on officer perceptions. However, those officers who were more open to innovation believed that the interaction would result in more positive perceptions of police. Police officers who believed that their RBTs with motorcycle riders would make a difference perceived that the riders would both change their behaviour and travel more slowly after the interaction. There were no differences in perceived interaction length by police officers across both conditions. CONCLUSIONS: This study has shown that police officer openness to innovation has an important role to play in police officers having more positive perceptions regarding the outcomes of RBT interactions. As such police organisations should undertake activities, such as training, to improve innovation. The lack of perceived differences in RBT length between standard and procedurally just interactions suggests that these enhanced interactions can be implemented without concerns that police officers believe that they 'take too long'.

Humans

Systematic Review on the Effectiveness of Photobiomodulation Therapy on Enhancing Musculoskeletal Rehabilitation Outcomes after Total Knee and Hip Arthroplasty.

BACKGROUND: Total knee and hip arthroplasty (TKA/THA) effectively alleviate chronic pain and improve joint function and quality of life. However, postoperative recovery is often hindered by pain, edema, restricted range of motion (ROM), and muscle weakness, necessitating structured physical rehabilitation. Photobiomodulation Therapy (PBMT) has been proposed as an adjunct modality to enhance rehabilitation outcomes. This systematic review evaluates the efficacy of PBMT in reducing postoperative pain and edema as well as improving ROM and functional performance compared with placebo or standard physical therapy in post-arthroplasty patients. METHODS: A systematic search of PubMed, ProQuest, ScienceDirect, and Google Scholar was conducted from inception to May 31, 2025. Only prospective controlled trials assessing PBMT effects on postoperative pain, swelling, ROM, or functional performance following TKA or THA were included. Case reports, uncontrolled studies, and trials focusing on unrelated outcomes were excluded. Article selection involved title, abstract, and full-text screening, with additional studies identified through reference lists. The review is registered in PROSPERO (CRD420251123169). RESULTS: Four randomized controlled trials (RCTs; n = 133 participants) met the inclusion criteria, three studies focused on TKA, and one study examined THA. PBMT significantly improved postoperative pain and edema reduction in three trials, while two studies demonstrated enhanced ROM and functional outcomes compared with control or placebo interventions. PEDro scores ranged from 8 to 10, indicating moderate-to-high methodological quality. CONCLUSIONS: PBMT shows promising short-term benefits in reducing postoperative pain and swelling and improving functional performance after knee or hip arthroplasty. However, due to heterogeneity in treatment parameters and limited high-quality trials, conclusive evidence remains insufficient. Future large-scale RCTs with standardized PBMT parameters and extended follow-up are warranted to confirm its clinical efficacy.

Humans

Effect of intraoperative 40-hz gamma-frequency auditory stimulation on postoperative delirium in older adults undergoing major surgery: a randomized clinical trial protocol.

INTRODUCTION: Postoperative delirium (POD) is a common and clinically significant complication among older adults undergoing major surgery under general anesthesia. Gamma-frequency (40-Hz) auditory stimulation has demonstrated potential neuroprotective and cognition-enhancing effects, suggesting a plausible role in perioperative delirium prevention. However, direct clinical evidence supporting intraoperative 40-Hz auditory stimulation in reducing POD remains limited, warranting rigorous evaluation in a randomized trial. PATIENTS AND METHODS: This prospective, parallel-group, randomized controlled trial will enroll 550 older adults scheduled for major noncardiac, nonneurosurgical surgery under general anesthesia. Participants will be randomized in a 1:1 ratio to either the active stimulation group, receiving intraoperative 40-Hz gamma-frequency auditory stimulation delivered via headphones for 2&#x2009;h following successful anesthesia induction, or the sham stimulation group, wearing headphones without active auditory output. The primary outcome is the incidence of POD on postoperative day 1 though 3, assessed using the Confusion Assessment Method (CAM) or the CAM for the ICU (CAM-ICU). Secondary outcomes include POD severity, sleep quality, pain scores, analgesic consumption, the incidence of postoperative nausea and vomiting (PONV), rescue antiemetic use, duration of post-anesthesia care unit (PACU) stay, length of hospital stay, quality of postoperative recovery, incidence of perioperative adverse events; postoperative morbidity, health-related quality of life, and all-cause 30-day mortality. DISCUSSION: This trial will determine whether intraoperative 40-Hz gamma-frequency auditory stimulation reduces the incidence of POD among older adults undergoing major surgery under general anesthesia. If efficacious, this noninvasive intervention could constitute a feasible perioperative strategy to mitigate delirium risk and enhance postoperative recovery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500115156).

Humans

Pictographs: feasibility and acceptability of a novel method of newborn identification to reduce wrong-patient errors in the NICU.

Wrong-patient errors cause serious harm in newborns. These errors involve ordering and administering tests, procedures, medications, and breast milk to an unintended patient. Newborns receiving care in neonatal intensive care units (NICUs) are at particularly high risk. Although more distinct newborn naming conventions as recommended by the Joint Commission significantly reduce wrong-patient orders, name similarities among multiple-birth infants and truncation of differentiating information in some electronic health record (EHR) systems contribute to this persistent increased risk. Accordingly, novel newborn identifiers are urgently needed. We propose Pictographs&#xa0;-&#xa0;images that are appealing, recognizable, and appropriate&#xa0;-&#xa0;to serve as visual identifiers for newborns in NICUs. Pictographs are selected by caregivers, uploaded into the EHR, and displayed at bedside. As part of a multicenter randomized controlled trial assessing effectiveness of Pictographs to prevent wrong-patient order errors, we initially evaluated feasibility and acceptability of Pictographs at two study sites. Pictographs as novel visual identifiers for newborns in the NICU were generally well received by caregivers and clinicians, and the vast majority of caregivers selected a Pictograph for their infant(s), which was posted at the bedside and uploaded into the EHR. Ordering clinicians&#xa0;-&#xa0;the primary target of the intervention to prevent wrong-patient errors&#xa0;-&#xa0;recognized the potential for Pictographs to provide a visual cue when placing orders, particularly for multiple-birth infants. Here, we describe the rationale, implementation, framework, feasibility, usefulness, and acceptability of Pictographs among key stakeholders. If found effective for preventing wrong-patient errors, Pictographs could be adopted as a patient safety solution in hospitals worldwide.

Female

Effects of adjunctive memantine on executive function and global cognition in bipolar disorder (BD): A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Cognitive impairment contributes substantially to disability in bipolar disorder (BD), but effective pharmacologic options remain limited. This trial evaluated whether adjunctive memantine improves global cognition and executive function in BD. METHODS: In this double-blind, placebo-controlled randomized trial, patients with bipolar I disorder (B1D) receiving lithium and olanzapine were assigned to memantine or placebo. Memantine was titrated to 20&#xa0;mg/day over 6&#xa0;weeks. Cognitive outcomes were assessed at baseline, week 6, and week 18. Global cognition was measured with the Neurocognitive Assessment Battery (NuCog), and executive function with the Frontal Assessment Battery (FAB). Data were analyzed using generalized estimating equations and Bonferroni-adjusted post-hoc tests. RESULTS: Sixty-three participants were randomized (memantine, n&#xa0;=&#xa0;31; placebo, n&#xa0;=&#xa0;32), and all completed follow-up. Groups were comparable at baseline for demographic and clinical variables and for most cognitive measures. Both groups improved over time (P&#xa0;<&#xa0;0.001), but improvement was greater with memantine for global cognition at week 6 (MD&#xa0;=&#xa0;9.32; 95% CI, 4.84-13.81; P&#xa0;<&#xa0;0.001) and week 18 (MD&#xa0;=&#xa0;12.69; 95% CI, 8.67-16.71; P&#xa0;<&#xa0;0.001). FAB total scores favored memantine at week 18 (MD&#xa0;=&#xa0;2.68; 95% CI, 1.76-3.61; P&#xa0;<&#xa0;0.001), but not at week 6. Domain analyses showed significant benefits for NuCog attention, visuoconstructional ability, memory, and executive function, and for several FAB subscales by week 18. CONCLUSIONS: Adjunctive memantine improved global cognition and, over longer follow-up, executive function in BD. These findings support NMDA receptor modulation as a potential strategy for cognitive dysfunction in BD.

Humans

Multimodal Therapy With Metformin, Inositol and Dietary Restriction Improves Insulin Resistance and Endocrine Outcomes in Women With Polyendocrine Metabolic Ovarian Syndrome: A Randomized Controlled Trial.

INTRODUCTION: Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is a common endocrine-metabolic disorder characterized by insulin resistance, hyperandrogenism and ovulatory dysfunction. Metformin, inositol supplementation and lifestyle modification are widely used treatments, but direct comparative evidence remains limited. Multimodal therapy combining metformin, inositol and dietary restriction produces greater metabolic and reproductive improvement than single-modality interventions. METHODS: We conducted a 12-week randomized controlled trial in 192 women aged 18-35 years diagnosed with PMOS according to Rotterdam criteria. Participants were allocated to metformin (1500-2000 mg/day), inositol (myo-inositol 2&#x2009;g plus d-chiro-inositol 50&#x2009;mg twice daily), calorie-restricted diet (1200-1500&#x2009;kcal/day), or combination therapy. Primary outcomes included changes in body mass index (BMI) and insulin resistance assessed by HOMA-IR. Secondary outcomes included testosterone, LH/FSH ratio and menstrual regularity. Analysis was performed using analysis of covariance (ANCOVA), with post-intervention values as dependent variables and corresponding baseline values as covariates. Categorical outcomes were compared using the Chi-square test. RESULTS: All interventions improved metabolic and endocrine parameters. Combination therapy resulted in the greatest reduction in HOMA-IR (-&#x2009;2.64, 95% CI&#x2009;-&#x2009;2.82 to -2.46, p&#x2009;<&#x2009;0.001) and BMI (-&#x2009;2.8&#x2009;kg/m2, 95% CI&#x2009;-&#x2009;3.05 to -2.55, p&#x2009;<&#x2009;0.001). Menstrual cyclicity improved across all groups, with the highest proportion of participants reporting cycle regularisation in the combination therapy group (85.4%), compared with dietary restriction (72.9%), inositol (64.6%), and metformin (39.6%) (p&#x2009;<&#x2009;0.001). Given the short follow-up duration, these findings reflect early improvements rather than sustained normalisation. CONCLUSION: Multimodal therapy was associated with superior metabolic and reproductive outcomes compared with single-modality interventions in women with PMOS. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov (NCT07380841).

Humans

SBUF-SMUF: On the path to the optimum hemofiltration technique in pediatric cardiopulmonary bypass: A randomized clinical trial.

BACKGROUND: Hemofiltration during pediatric cardiopulmonary bypass (CPB) is essential to mitigate hemodilution, inflammatory responses, and postoperative complications. Conventional ultrafiltration (CUF) is widely practiced, but novel methods such as subzero balanced ultrafiltration combined with simple modified ultrafiltration (SBUF-SMUF) may offer superior outcomes. OBJECTIVE: To compare the clinical efficacy and safety of CUF versus SBUF-SMUF in pediatric patients undergoing open-heart surgery. METHODS: In this prospective randomized, outcome-assessor-blinded clinical trial, 80 pediatric patients with congenital heart disease were allocated to either CUF (n = 40) or SBUF-SMUF (n = 40) during CPB. Baseline demographics, intraoperative characteristics, fluid balance, blood product utilization, and postoperative outcomes were assessed. Statistical analysis was conducted using independent t-tests, Chi-square tests, and Fisher's exact tests. Statistical significance was defined as a two-tailed p-Value of less than 0.05. RESULTS: Demographic and preoperative variables were comparable between groups. Mean fluid balance was significantly positive in the CUF group (+192.1 &#xb1; 178.8 mL) but negative in the SBUF-SMUF group (-105.0 &#xb1; 78.9 mL, p < 0.001). The SBUF-SMUF group required significantly less intraoperative PRBC (141.7 &#xb1; 70.2 vs. 261.0 &#xb1; 68.8 mL, p < 0.001) and postoperative FFP transfusion (2% vs. 10%, p = 0.020). Post-bypass hematocrit levels were higher (31.2% vs. 27.3%, p = 0.001) and extubation occurred earlier in the SBUF-SMUF group (1.05 &#xb1; 1.03 vs. 2.27 &#xb1; 2.37 days, p = 0.006). No significant differences were observed in potassium levels or incidence of acute kidney injury. CONCLUSION: The SBUF-SMUF technique is safe, effective, and superior to CUF in optimizing fluid balance, reducing blood product utilization, and facilitating earlier extubation in pediatric cardiac surgery. No additional risk of oliguria or electrolyte imbalance was observed compared to CUF. Its simplicity and reproducibility support its consideration as a standard approach in pediatric CPB.

Humans

Protocol for project FIERCE: A randomized controlled trial to evaluate a positive emotion-focused meditation intervention for physicians with elevated stress.

INTRODUCTION: Nearly 80% of healthcare providers experience adverse psychological symptoms (e.g., depression, burnout, sleep disturbance) stemming from workplace stressors. Elevated levels of stress have been associated with unfavorable occupational, patient, and provider-related outcomes, imposing a heavy burden on a strained system. Given the impact of stress on both employee and patient health, effective interventions are urgently needed to reduce distress and promote well-being among healthcare professionals. Mindfulness-based interventions show promise for addressing these challenges. We developed a six-week, remotely delivered mindfulness intervention, the Building Emotional Strength Training (BEST) program, based on the Buddhist Four Immeasurables practice to cultivate the distinct emotional qualities of loving-kindness, compassion, joy, and equanimity. The present study aims to evaluate the feasibility and efficacy of a Four Immeasurables-based mindfulness intervention on perceived stress (primary outcome), burnout, depressive symptoms, and inflammatory biomarkers, while enhancing psychological well-being and sleep quality (secondary outcomes) in physicians. We will also investigate potential mediators of intervention effects, including compassion, positive affect, equanimity, and mindfulness. METHOD: We will enroll 90 full-time physicians in a remote, two-arm randomized controlled trial with 1:1 allocation to either the meditation intervention or waitlist control. Participants will complete self-report questionnaires and provide blood samples at baseline, mid-course, and post-intervention to assess outcomes and mediators. DISCUSSION: The project aims to advance the study of mindfulness-based interventions that reduce distress and promote well-being through practices that cultivate prosocial and altruistic feelings toward oneself and others. While mindfulness interventions have gained considerable interest, none have specifically drawn from the Four Immeasurables practice to target loving-kindness, compassion, joy, and equanimity. This novel investigation could expand our understanding of practices that foster kindness and compassion to reduce distress in an at-risk population. TRIAL REGISTRATION: ClinicalTrials.gov NCT07283744, registered on 2025/10/14. The Open Science Framework, registered on 2026/06/26.

Humans