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Corticosteroids as adjunctive therapy to standard treatment in Kawasaki disease: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

UNLABELLED: Kawasaki disease (KD) is an acute systemic vasculitis and the leading cause of acquired heart disease in children in developed countries. While IVIG plus aspirin remains standard treatment, 10-20% of patients are IVIG-resistant and face an elevated risk of coronary artery abnormalities. Corticosteroids have been explored as adjunctive therapy, though evidence on their benefit remains inconsistent. To assess the efficacy and safety of adjunctive corticosteroids in Kawasaki disease across key clinical outcomes. This PRISMA 2020-compliant systematic review and meta-analysis included RCTs identified through database searches up to April 2026. Risk of bias was assessed using Cochrane RoB 2.0. Data were pooled using random-effects models to estimate risk ratios (RRs) and mean differences (MDs) with 95% CIs. Subgroup analyses, leave-one-out sensitivity analyses, and GRADE certainty appraisal were also performed. Eight studies (n = 4106) were included. No significant differences were found in coronary artery abnormalities (CAA) within 1 month (RR 0.49, 95% CI 0.17-1.42), after 1 month (RR 0.81, 95% CI 0.43-1.55), fever duration (MD - 1.75, 95% CI - 3.71 to 0.21), or adverse events (RR 1.08, 95% CI 0.57-2.07). Hospital stay was modestly shorter with corticosteroids (MD - 0.99, 95% CI - 1.86 to - 0.11). Exploratory subgroup analyses suggested potential benefits with prednisolone-based and prolonged corticosteroid regimens for selected outcomes; however, these findings should be interpreted cautiously given multiple subgroup comparisons. Overall certainty of evidence was very low. CONCLUSION:  Adjunctive corticosteroids did not significantly improve major outcomes in KD. Prednisolone-based regimens showed some promise, but high-quality trials are still needed before any firm conclusions can be drawn. WHAT IS KNOWN: • Corticosteroids have been studied as adjunctive therapy for Kawasaki disease, but their effects on coronary outcomes and other clinical outcomes remain inconsistent. WHAT IS NEW: • This meta-analysis found no significant improvement in major outcomes with adjunctive corticosteroids, although prednisolone-based and prolonged regimens may provide benefits for selected outcomes.

Humans

Hyper-oncotic albumin administration reduces mortality in acute Respiratory Distress Syndrome compared to crystalloid: a systematic review and meta-analysis.

BACKGROUND: To evaluate the association between albumin administration as volume replacement and mortality in adult ARDS patients, we performed this meta-analysis and trial sequential analysis (TSA). METHODS: We searched databases including PubMed, Science Direct, Scopus, Web of Science databases and Cochrane Central Register of Controlled Trials up to 12 December 2024. We screened trials that included adult ARDS patients and compared albumin with crystalloid. The 28-day mortality served as the primary endpoint, while the oxygenation change, the length of ICU stay and the length of hospital stay were designated as secondary outcomes. To clarify the differing concentrations of albumin, we formed two distinct subgroups: the hyper-oncotic albumin subgroup (&#x2265;20%) and the iso-oncotic albumin subgroup (4%&#x223c;5%). Statistical synthesis was performed with Cochrane Review Manager 5.4.1, employing random-effects models. To mitigate random errors, TSA was implemented with &#x3b1;&#x2009;=&#x2009;0.05 and &#x3b2;&#x2009;=&#x2009;0.20 parameters. RESULTS: The analysis incorporated 5 publications: 3 randomized controlled trials (RCTs) and 2 non-randomized studies (NRSs). Overall mortality was lower in the albumin group (33.2%, 97/292) than in the crystalloid group (44.9%, 133/296) (OR = 0.61, 95%CI 0.43-0.85, p&#x2009;=&#x2009;0.004). RCTs (n&#x2009;=&#x2009;204) showed no benefit (OR = 0.83, p&#x2009;=&#x2009;0.54), but NRSs (n&#x2009;=&#x2009;384) demonstrated reduced mortality (OR = 0.52, p&#x2009;=&#x2009;0.002). Hyper-oncotic albumin was associated with lower mortality in NRSs (OR = 0.40, p&#x2009;=&#x2009;0.02) but not in RCTs (OR = 0.74, p&#x2009;=&#x2009;0.57). Iso-oncotic albumin showed no benefit (OR = 0.88, p&#x2009;=&#x2009;0.72). Regarding the impact of albumin on oxygenation, significant improvements in oxygenation were observed only on the first (p&#x2009;=&#x2009;0.05) and second days (p&#x2009;<&#x2009;0.0001). The TSA indicated a continued need for high-quality RCTs. CONCLUSIONS: Our analysis suggests that hyper-oncotic albumin may reduce mortality and improve early oxygenation in ARDS patients compared to crystalloids. Larger RCTs are urgently needed to validate these findings and define their potential role in clinical management.

Humans

Effectiveness of the DASH diet versus alternative dietary interventions for hypertension management: A systematic review and meta-analysis.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet is widely recommended for blood pressure control; however, its comparative effectiveness relative to other structured dietary interventions remains uncertain. OBJECTIVE: To evaluate the comparative effectiveness of the DASH diet versus alternative dietary interventions on blood pressure and cardiometabolic outcomes in adults. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA guidelines. Multiple databases were searched from inception to February 2026. Eligible studies included adults with elevated blood pressure or hypertension comparing the DASH diet with other dietary interventions or usual care. Continuous outcomes were pooled using random-effects models and expressed as mean differences (MD) or standardized mean differences (SMD). Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 22 randomized controlled trials were included in the qualitative synthesis, of which 10 were included in the meta-analysis. The DASH diet did not demonstrate a statistically significant advantage over comparator diets in reducing systolic blood pressure (MD = 1.30; 95% CI: -1.54 to 4.14) or diastolic blood pressure (MD = 0.21; 95% CI: -3.72 to 4.14), with substantial heterogeneity observed across studies. Significant effects were identified for selected cardiometabolic outcomes, including reductions in urinary sodium excretion (MD = -32.89; 95% CI: -62.76 to -3.01), LDL cholesterol (MD = -8.59; 95% CI: -14.64 to -2.54), and glycated hemoglobin (HbA1c) (MD = -0.49; 95% CI: -0.52 to -0.46), as well as an increase in urinary potassium excretion (MD = 11.76; 95% CI: 4.08 to 19.44). The certainty of evidence ranged from moderate to very low across outcomes. CONCLUSIONS: The DASH diet was not superior to other dietary interventions in reducing blood pressure; however, it demonstrated consistent benefits in selected cardiometabolic parameters. Given the overall low certainty of evidence and substantial heterogeneity, these findings should be interpreted cautiously. Future research should focus on well-designed trials with standardized outcomes and longer follow-up to clarify comparative effectiveness.

Humans

The effect of dexmedetomidine in mechanically ventilated patients with sepsis and septic shock: a meta-analysis of randomized controlled trials.

PURPOSE: Dexmedetomidine (DEX) is a central sympatholytic with sedative properties widely used in critically ill patients. However, its effects in patients with sepsis and septic shock remain controversial. This meta-analysis evaluated the efficacy and safety of DEX compared to other sedatives in mechanically ventilated patients with sepsis and septic shock. METHODS: A systematic search was conducted across PubMed, Embase, Scopus, and Cochrane Library from inception through May 1, 2025 for randomized controlled trials comparing DEX with other sedatives or placebo in mechanically ventilated patients with sepsis and septic shock. Primary outcomes included overall mortality and Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes encompassed duration of mechanical ventilation (MV), length of stay in Intensive Care Unit (ICU), incidence of hypotension and bradycardia. RESULTS: Fifteen studies involving 3,882 patients (1,945 in the DEX group, 1,937 in the control group) were included. DEX was demonstrated no significant differences compared to other sedatives or placebo in overall mortality (Risk Ratio [RR] 0.98, 95% Confidence Interval [CI] 0.90 to 1.07, p&#x2009;=&#x2009;0.71, I2&#x2009;=&#x2009;0%), SOFA scores (Mean Difference [MD]&#x2009;-&#x2009;0.14, 95% CI -0.81 to 0.52, p&#x2009;=&#x2009;0.67, I2&#x2009;=&#x2009;0%), length of stay in ICU (MD -0.32, 95% CI -1.69 to 1.06, p&#x2009;=&#x2009;0.65, I2&#x2009;=&#x2009;77%), or incidence of hypotension (RR 1.15, 95% CI 0.81 to 1.62, p&#x2009;=&#x2009;0.44, I2&#x2009;=&#x2009;14%). However, DEX significantly reduced the duration of MV (MD -0.54, 95% CI -0.98 to -0.10, p&#x2009;=&#x2009;0.02, I2&#x2009;=&#x2009;25%) but was associated with an increased incidence of bradycardia (RR 1.67, 95% CI 1.22 to 2.28, p&#x2009;=&#x2009;0.001, I2&#x2009;=&#x2009;0%). CONCLUSIONS: In mechanically ventilated patients with sepsis and septic shock, DEX shortened duration of MV but was associated increased bradycardia risk. No mortality or organ dysfunction benefits were observed. These findings suggest DEX is a reasonable therapeutic option to facilitate earlier ventilator weaning in selected patients (particularly those without shock), but careful monitoring for cardiovascular adverse effects is warranted.

Humans

Efficacy, tolerability, and threshold effect of atropine eye drops for myopia control: A systematic review and dose-response meta-analysis.

Atropine is an emerging therapy for myopia, yet the optimal concentration for prescription remains uncertain. We searched PubMed, Embase, Web of Science, Cochrane Library, World Health Organization International Clinical Trials, and ClinicalTrials.gov registry platforms. We included the randomized clinical trials (RCTs) that compared any dose of atropine against a placebo in myopic children. Among 3566 studies assessed, we identified 33 eligible RCTs involving 6301 children aged 4-18 years, with 10 different concentrations and a mean follow-up time of 19.5&#x202f;&#xb1;&#x202f;12.3 months. A nonlinear relationship was observed between atropine dosage and treatment efficacy (P&#x202f;<&#x202f;0.001). Compared to placebo groups, the mean differences in reducing annual spherical equivalent refraction progression for atropine concentrations of 0.01%, 0.02%, 0.03%, 0.04%, and 0.05% were 0.21 diopters (D) (95% CI, 0.13-0.28), 0.35 D (95% CI, 0.23-0.46), 0.42 D (95% CI, 0.28-0.56), 0.45 D (95% CI, 0.30-0.60), and 0.46 D (95% CI, 0.32-0.61) respectively For higher concentrations, the estimates were 0.49 D (95% CI, 0.34-0.63) for 0.1% and 0.99 D (95% CI, 0.66-1.31) for 1%, although these were based on fewer and smaller trials. Higher doses of atropine were associated with decreased amplitude of accommodation (P&#x202f;=&#x202f;0.02), increased pupil diameters (P&#x202f;=&#x202f;0.01) and a higher frequency of photophobia (P&#x202f;=&#x202f;0.02). Our findings suggest that the increase in treatment efficacy with higher concentrations may plateau beyond a certain range, and that the current practice of increasing atropine concentrations for children who show inadequate responses to lower doses should be confined to a specific concentration range. This analysis is limited by the number, design heterogeneity, and sample sizes of available trials for higher concentrations, and by the frequent lack of pre-intervention refractive history in included studies. Therefore, estimates-particularly for doses exceeding 0.1%-should be interpreted with caution.

Humans

Artificial intelligence enabled social robotic interventions (PARO) in Australian dementia care: A systematic review and meta-analysis.

BACKGROUND: Although there is a growing body of research indicating that Personal Robot/Social Robot could be used in various aspects of care for individuals with dementia, little is known about how well these types of interventions work in an actual hospital setting in Australia. AIMS & OBJECTIVES: The objective of the present systematic review and meta-analysis is to assess the effectiveness of PARO-based socially assistive robotic intervention in terms of its effectiveness outcomes towards the reduction of dementia-related behavioural and psychological symptoms in Australian based healthcare settings. METHODS: A systematic search was conducted across five electronic databases, including MEDLINE (PubMed), EMBASE, CINAHL, PsycINFO, and the Cochrane Library, to identify randomised controlled trials (RCTs) investigating PARO-based socially assistive robotic interventions for dementia in Australian healthcare settings. This review was registered with PROSPERO (CRD420251251916) and followed the PRISMA 2020 guidelines. In addition, the Cochrane Risk of Bias tool (RoB 2) was used to evaluate the risk of bias across all studies. Pooled standardised mean differences (SMD) with 95&#xa0;% confidence intervals (CI) were calculated for agitation, anxiety, and depression. Heterogeneity across studies was evaluated using the I2 statistic. RESULTS: Six RCTs involving 1444 participants were identified for inclusion in this review. AI-enabled socially assistive robotic interventions, specifically the PARO therapeutic robot, significantly reduced agitation and anxiety when compared to standard treatment or control conditions. The pooled analysis showed that agitation [SMD&#xa0;=&#xa0;-0.44 (95&#xa0;% CI: -0.70, -0.18) p&#xa0;=&#xa0;0.0008] and anxiety [SMD&#xa0;=&#xa0;-0.59 (95&#xa0;% CI: -0.91, -0.27) p&#xa0;=&#xa0;0.0003] were reduced significantly, while the decrease in depression [SMD&#xa0;=&#xa0;-0.44 (95&#xa0;% CI: -0.95, -0.07) p&#xa0;=&#xa0;0.09] scores was non-significant among dementia patients receiving PARO-based socially assistive robotic interventions as compared to the control. The overall risk of bias across all six studies was considered low to moderate. CONCLUSION: PARO-based socially assistive robotic interventions may provide preliminary evidence of effectiveness in reducing agitation and anxiety in individuals with dementia in Australian healthcare, but the evidence regarding the reduction of depression remains unclear. Therefore, additional high-quality trials with consistent methodology and extended follow-up will be necessary to determine both the short-term and long-term clinical efficacy and practicality of implementing these interventions into practice.

Humans

Exploring the dose-response relationship between prenatal exercise and postpartum depression: A systematic review and meta-analysis of randomized controlled trials.

IMPORTANCE: Postpartum depression (PPD) is a hidden and widespread global public health crisis affecting millions of mothers and infants annually. Prenatal exercise is a potentially accessible nonpharmacological strategy for PPD prevention, but its optimal dose remains uncertain. OBJECTIVE: To explore the dose-response relationship between prenatal exercise and the incidence of PPD through meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library using MeSH terms and keywords related to "pregnant women," "prenatal exercise," and "postpartum depression," up to June 23, 2025. STUDY SELECTION: RCTs included examined prenatal exercise interventions in pregnant women without a history of depression, with PPD incidence reported using validated depression scales (such as EPDS, CES-D). Non-RCT studies, duplicate publications, and studies with insufficient data were excluded. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted data according to the PRISMA guidelines. A random-effects model was used to pool odds ratios (OR) and their 95% confidence intervals (CI). Linear and nonlinear dose-response models were employed to analyze and evaluate the relationship between exercise dose (measured in METs-min/week) and the incidence of PPD. MAIN OUTCOME(S) AND MEASURE(S): The primary outcome is the incidence of PPD, analyzing its relationship with prenatal exercise dose. RESULTS: Eight RCTs involving 2231 pregnant women were included. The pooled analysis showed that prenatal exercise was associated with a potential reduction in PPD incidence, although the overall effect did not reach statistical significance (OR=0.58, 95% CI [0.33, 1.02]). In dose-stratified analysis, exercise doses &#x2265;500 METs-min/week were associated with significantly lower PPD incidence (OR=0.44, 95% CI [0.24, 0.78]). Subgroup analyses suggested trends toward greater benefits among women aged &#x2265;30 years and those initiating exercise between 14 and 28 weeks of gestation; however, subgroup differences did not reach statistical significance. The linear dose-response trend did not reach statistical significance (p = 0.0533), and neither the overall spline association (p = 0.1704) nor the test for nonlinearity (p = 0.6361) was statistically significant. CONCLUSIONS AND RELEVANCE: Prenatal exercise may be associated with a lower risk of PPD, but the overall pooled effect did not reach statistical significance. Findings concerning &#x2265;500 METs-min/week and the apparent flattening of the dose-response curve should be considered exploratory and require confirmation in larger trials.

Humans

Weight regain following discontinuation of glucagon-like peptide-1 receptor agonists in adults who are overweight or obese: a systematic review and meta-analysis.

OBJECTIVE: This study aims to explore the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on weight changes and the occurrence of adverse reactions in overweight or obese adults after drug withdrawal. METHODS: Computerized searches were conducted in evidence-based databases such as PubMed, Embase, Cochrane Library and Scopus. The search period was from the establishment of the database to December 2025. Collect randomised controlled trials (RCTs) and controlled trials on GLP-1RAs, including tirzepatide, semaglutide, liraglutide, and dulaglutide, for the treatment of overweight or obese adult patients. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias V2.0 tool provided by the Cochrane Collaboration, and meta-analysis was performed using the R programming language. RESULTS: A total of 699 studies were initially retrieved. Eventually, six studies involving 8,993 patients were included in the quantitative analysis, comprising 5,553 patients in the discontinuation group and 3,440 in the continued treatment group. The results of the meta-analysis showed that, compared with the continued treatment group, the weight difference in the discontinuation group was mean difference (MD) = 17.90%, 95% confidence interval (CI) [14.11-21.69], P&#xa0;<&#xa0;0.0001. It can be seen that there was a significant rebound in weight after drug withdrawal, and there was statistical heterogeneity among the studies (P&#xa0;=&#xa0;0.0082). Subgroup analysis further revealed that the weight rebound amplitude after discontinuation of tirzepatide was significantly higher than that of semaglutide. This result suggests that the differences in the mechanism of action of different GLP-1RAs may be the reason for the differences in weight changes after discontinuation. In addition, the percentage difference in body weight between after and before drug withdrawal was MD = 9.11%, 95% CI [7.91-10.30], P&#xa0;<&#xa0;0.0001, further verifying the trend of weight rebound after drug withdrawal. The summary of adverse reaction reports analyzed and studied indicates that after drug withdrawal, the overall adverse reactions of patients decreased, gastrointestinal adverse reactions decreased, and the incidence of cardiovascular events was not affected by drug withdrawal. CONCLUSION: There is a significant weight rebound phenomenon after discontinuation of GLP-1RAs, and the rebound magnitudes vary among different types of drugs. At the same time, there is a risk of adverse reactions during the use of such drugs.

Humans

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

Effects of GLP-1 Receptor Agonists and Dual GIP/GLP-1 Receptor Agonists on Inflammatory and Metabolic Biomarkers in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GIP/GLP-1 receptor agonists improve cardiovascular outcomes in type 2 diabetes mellitus (T2DM), but their effects on inflammatory and oxidative biomarkers are not fully defined. MATERIALS AND METHODS: We searched PubMed, Ovid MEDLINE, Scopus, Web of Science and the Cochrane Library from inception to 19 February 2026 for randomised controlled trials (RCTs) in adults with T2DM comparing a GLP-1RA or dual GIP/GLP-1 agonist with placebo or active therapy, and reporting C-reactive protein (CRP or high-sensitivity CRP [hs-CRP]), interleukin-6 (IL-6), tumour necrosis factor-&#x3b1; (TNF-&#x3b1;), monocyte chemoattractant protein-1 (MCP-1), malondialdehyde (MDA) or adiponectin. Random-effects meta-analyses were conducted using standardised mean differences (SMDs). RESULTS: Forty-one RCTs were included. GLP-1RAs significantly reduced CRP/hs-CRP (27 studies, 1991 participants; SMD -0.37, 95% CI -0.59 to -0.14) and MDA (3 studies, 272 participants; SMD -0.98, 95% CI -1.65 to -0.30), and increased adiponectin (16 studies, 1327 participants; SMD 0.30, 95% CI 0.13 to 0.46). Pooled effects on IL-6 (17 studies, 1068 participants; SMD -0.14, 95% CI -0.37 to 0.10), TNF-&#x3b1; (16 studies, 1164 participants; SMD -0.25, 95% CI -0.61 to 0.12) and MCP-1 (7 studies, 450 participants; SMD -0.27, 95% CI -0.58 to 0.03) were not statistically significant, although MCP-1 decreased in sensitivity analyses. Across biomarkers, heterogeneity was moderate to high. Two tirzepatide RCTs (562 participants) showed a significant reduction in IL-6 (SMD -0.28, 95% CI -0.47 to -0.09) and a non-significant trend towards lower CRP/hs-CRP. CONCLUSIONS: In adults with T2DM, incretin-based therapies consistently lower CRP/hs-CRP, reduce oxidative stress (MDA) and increase adiponectin, while effects on IL-6 and TNF-&#x3b1; are more variable. These data support a selective anti-inflammatory and metabolic regulatory profile of GLP-1-based therapy, but heterogeneity and limited data for some biomarkers warrant cautious interpretation and further mechanistic studies. TRIAL REGISTRATION: PROSPERO number: CRD420261321430.

Humans

Impact of early nurse-led implementation of an intensive care unit diary following major trauma on quality of life: The QUALITRAU randomized controlled trial.

BACKGROUND: Survivors of major trauma often experience long-term impairments in health-related quality of life (HRQoL) and post-traumatic stress disorder (PTSD). Intensive care unit (ICU) diaries have been proposed to reduce psychological sequelae, but evidence remains conflicting and not specific to trauma patients. OBJECTIVE: To assess whether, in patients with major trauma, a nurse-led ICU diary implemented within the first 48&#xa0;h after trauma improves HRQoL at 1&#xa0;year vs. usual care. METHODS: The QUALITRAU randomized controlled trial was conducted in three ICUs of a French tertiary hospital. Adult patients with major trauma (Injury Severity Score&#xa0;>&#xa0;15) were randomized within 48&#xa0;h of admission to receive either an ICU diary combined with usual care or usual care alone. The primary outcome was HRQoL at 12&#xa0;months, assessed with the 4 domains of the WHOQOL-BREF questionnaire. Secondary outcomes included PTSD severity measured with the Impact of Event Scale (IES). Analyses were performed on an intention-to-treat basis. RESULTS: Between November 2014 and November 2016, 208 patients were randomized (101 intervention, 107 control), with primary outcome available for 121 (53 intervention, 68 control). Median age was 35&#xa0;years [IQR 25-51], 81% were men, and 63% had severe traumatic brain injury. At 12&#xa0;months, there were no differences between intervention and control groups in the WHOQOL-BREF domains (physical: 5.7 [IQR 4.6-11.4] vs 9.1 [IQR 4.6-13.1],P&#xa0;=&#xa0;0.16; psychological: 8.0 [IQR 6.7-13.3] vs 11.3 [IQR 6.7-13.3],P&#xa0;=&#xa0;0.08; social: 5.3 [IQR 4.0-14.7] vs 12.0 [IQR 4.0-14.7],P&#xa0;=&#xa0;0.10; environment: 8.0 [IQR 5.5-14.5] vs 12.0 [IQR 5.5-15.5], P&#xa0;=&#xa0;0.05). IES scores were also not different. CONCLUSIONS: Early implementation of nurse-led ICU diaries was not associated with improved long-term HRQoL or reduced PTSD symptoms in patients with major trauma. IMPLICATION FOR CLINICAL PRACTICE: These findings suggest that ICU diaries may need to be integrated into broader, multimodal rehabilitation strategies and may depend on factors such as timing, content, or patient characteristics.

Humans

Ultrashort vs Standard-Duration Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing PCI: A Meta-Analysis.

BACKGROUND: The efficacy and safety of ultrashort (&#x2264;1-month) dual antiplatelet therapy (DAPT) followed by antiplatelet monotherapy remain uncertain in acute coronary syndrome (ACS) patients. OBJECTIVES: This study sought to compare ultrashort vs standard-duration DAPT in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials until February 15, 2026. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), major bleeding, and net adverse clinical event (NACE). Prespecified subgroup analyses examined by ethnicity (East Asian vs non-East Asian) and abbreviation strategy (intensive: &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy vs moderate: &#x2265;2-week DAPT, followed by ticagrelor/prasugrel monotherapy). RESULTS: Across 10 trials (n = 29,232), ultrashort DAPT did not increase MACCE risk (HR: 1.06; 95% CI: 0.93-1.20; P = 0.38; I2 = 24%), with higher MACCE risk observed in ST-segment elevation myocardial infarction (STEMI) but not non-ST-segment elevation ACS (NSTE-ACS), and significantly reduced major bleeding (HR: 0.47; 95% CI: 0.35-0.64; P < 0.00001; I2 = 44%), resulting in a net clinical benefit (HR: 0.83; 95% CI: 0.72-0.97; P = 0.02; I2 = 61%). Bleeding reduction was more pronounced in East Asians (HR: 0.35; 95% CI: 0.25-0.49; P < 0.00001; I2 = 0%) than non-East Asians (HR: 0.63; 95% CI: 0.43-0.93; P = 0.02; I2 = 44%), with a significant interaction (P = 0.02). The abbreviation strategy significantly modified outcomes (P for interaction = 0.003): intensive abbreviation raised MACCE risk (HR: 1.37; 95% CI: 1.11-1.69; P = 0.003; I2 = 0%), while moderate abbreviation had no statistically significant difference (HR: 0.96; 95% CI: 0.85-1.08; P = 0.47; I2 = 0%). CONCLUSIONS: In patients with ACS undergoing PCI, ultrashort DAPT reduced bleeding without increasing ischemic events overall, although a signal of increased MACCE was observed in STEMI but not in NSTE-ACS. Bleeding reduction was greater in East Asians, while &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy may increase ischemic risk.

Humans

Efficacy and Safety of Psychedelic Microdosing on Psychological Outcomes in Healthy Adults: A Systematic Review and Meta-analysis.

BACKGROUND: Psychedelic microdosing has gained increasing popularity for enhancing mood and cognition, yet its effects on psychological outcomes in healthy adults remain unclear. We aim to evaluate the efficacy and safety of psychedelic microdosing on psychological outcomes in healthy/non-clinical adult&#xa0;population. METHODS: This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251035294). We searched Embase, MEDLINE, and PsycINFO from inception to February 2026 for original studies in healthy adults using sub-hallucinogenic psychedelic doses on separate days. We included randomized studies, nonrandomized prospective studies, cross-sectional studies, and observational longitudinal designs and stratified meta-analyses by design. Random-effects models were used; safety in randomized controlled trials (RCTs) was pooled as risk differences (RDs). Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. RESULTS: 24 studies (3,681 participants) met inclusion criteria, 6 contributed to meta-analyses. RCTs of psilocybin and LSD microdosing showed subjective and neurophysiological effects but minimal impact on cognition, creativity, or sustained mood. Psilocybin altered EEG and speech with little behavioral change, while LSD caused transient mood and minor physiological effects without lasting cognitive or personality benefits. Observational studies indicated mood and personality improvements, likely influenced by expectancy or lifestyle factors. Meta-analyses included two parallel RCTs (3 comparisons; n = 117) and three non-RCT studies (n = 1,013). Adverse event analyses included two RCTs (4 comparisons; n = 109). RCTs showed no clear evidence of immediate symptom reduction: depressive symptoms (SMD = -0.19; 95% CI -0.56, 0.19; I2 = 0%), anxiety (SMD = -0.20; 95% CI -1.11, 0.71; I2 = 82.3%),and stress (SMD = 0.02; 95% CI -0.39, 0.43; I2 = 0%). Non-RCT within-arm estimates were imprecise and heterogeneous for depressive symptoms (SMCC -0.33; 95% CI -0.75, 0.08) and anxiety (SMCC -0.29; 95% CI-0.84, 0.26). Exploratory pooling across all designs suggested decreases in depressive symptoms and stress, while anxiety remained uncertain. Adverse event risks were similar between treatment and control. CONCLUSIONS: Microdosing does not show consistent immediate benefits for depressive, anxiety, or stress symptoms in healthy adults, and evidence from RCTs remains inconclusive. Although improvements were observed in some studies, these effects were not significantly different from placebo. Larger, well-designed RCTs are needed to clarify the efficacy and safety of psychedelic microdosing beyond placebo.

Humans

High-Flow Nasal Oxygen and the Risk of Gastric Insufflation: A Systematic Review and Meta-Analysis Supplemented by Narrative Synthesis.

High-flow nasal oxygen (HFNO) generates positive airway pressure, raising concerns about gastric insufflation and aspiration risk. Although most studies report minimal or no gastric distension, some suggest significant changes. This systematic review and meta-analysis applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to evaluate the effect of HFNO on gastric insufflation and related markers across clinical settings. We searched Medline, Embase, Emcare, and CINAHL through August 2025 for studies reporting qualitative or quantitative markers of gastric insufflation during HFNO use, including comet-tail artifacts, antral cross-sectional area, and gastric volume. Eligible designs included randomized trials, observational and volunteer studies, and case reports. Methodological quality was evaluated using the Mixed Methods Appraisal Tool, and certainty of evidence was rated with GRADE. Meta-analysis was performed for outcomes reported in two or more studies. Six randomized trials, five observational studies, two volunteer studies, one case series, and two case reports were included. Observational studies primarily assessed outcomes before and after HFNO intervention. Pooled analysis of four randomized controlled trials (RCTs; n = 375) showed HFNO significantly reduced gastric insufflation compared with face-mask ventilation during elective peri-intubation (risk ratios [RR] = 0.32; 95% confidence interval [CI], 0.19-0.52; P < .00001; I 2 = 0%), rated moderate-certainty. For antral cross-sectional area, pooled analysis of three RCTs (n = 318) found no significant difference between HFNO and face-mask ventilation (MD -0.33 cm 2 ; 95% CI, -0.72 to 0.05; P = .09; I 2 = 74%), rated moderate-certainty. Observational studies assessing pre- and post-HFNO changes showed no significant increase in antral cross-sectional area (MD 0.08 cm 2 ; 95% CI, -0.29 to 0.45; P = .67; I 2 = 0%) and no significant change in gastric liquid volume (MD -0.01 ml/kg; 95% CI, -0.07 to 0.06; P = .80; I 2 = 0%), both rated low certainty. Nonpooled data suggested possible increases in critically ill patients, but the evidence was of very low certainty. A single study assessing microaspiration found HFNO reduced gastroesophageal reflux and prevented microaspiration compared with face-mask ventilation. No clinically significant aspiration events were reported across studies. Moderate-certainty evidence supports HFNO as safe regarding gastric insufflation and antral cross-sectional area in most elective and procedural contexts. Low-certainty evidence suggests no increase in gastric volume. Caution is warranted due to limited, low-to-very-low-certainty evidence at higher flow rates and among critically ill patients. Larger multicenter trials and robust observational studies are necessary to confirm safety in these settings.

Humans

The analgesic efficacy of intrathecal morphine compared to peripheral regional analgesia in total hip arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Following elective total hip arthroplasty, pain continues to be a significant problem. Intrathecal morphine or peripheral regional analgesia, that is local infiltration analgesia or peripheral nerve block, are common analgesic modalities, but it is still not known which is superior. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: The following electronic databases were searched from inception to 24 March 2026: CENTRAL; Ovid Embase; Ovid MEDLINE; Scopus; and Web of Science. ELIGIBILITY CRITERIA: Randomised controlled trials that compared intrathecal morphine to peripheral regional analgesia in patients scheduled for elective total hip arthroplasty under general or spinal anaesthesia. RESULTS: Eight trials and 471 patients were included. The peripheral regional analgesia was peripheral nerve block in six trials and local infiltration analgesia in two trials. No difference was demonstrated between intrathecal morphine and peripheral regional analgesia in regard to the first coprimary outcome, the pain score at rest at 24&#x200a;h. The quality of evidence was moderate. Intrathecal morphine was found to be superior to peripheral regional analgesia with respect to the second coprimary outcome, the cumulative intravenous morphine equivalent consumption at 24&#x200a;h. Mean difference (95% CI) was 11.38&#x200a;mg (4.31-18.45; P &#x200a;=&#x200a;0.002, I2 &#x200a;=&#x200a;81%). The quality of evidence was low. Intrathecal morphine was revealed to be superior to peripheral regional analgesia at 8-12&#x200a;h for the pain score at rest, 1.24 (0.60-1.88); P &#x200a;=&#x200a;0.0001, I2 &#x200a;=&#x200a;68%; pain score on movement, 1.15 (0.12-2.17), P &#x200a;=&#x200a;0.03, I2 &#x200a;=&#x200a;65%; but the rate of in hospital pruritus was reduced with peripheral regional analgesia, 0.31 (0.17-0.58), P &#x200a;=&#x200a;0.0002, I2 &#x200a;=&#x200a;0%. No differences in functional status were shown. CONCLUSIONS: We found no difference between intrathecal morphine and peripheral regional analgesia in regard to pain score at rest at 24 h. Intrathecal morphine may lead to a favourable effect on some but not all analgesic indices compared to peripheral regional analgesia in elective total hip arthroplasty. The quality of evidence for these positive effects was low. Intrathecal morphine reduced the systemic opioid consumption, but is not in itself an opioid free strategy. This notion is supported by the increased incidence of in hospital pruritus with intrathecal morphine. The quality of evidence for this was high. In view of the quality of evidence, high quality randomised controlled trials are required to substantiate these results.

Humans

Isometric Exercises for Tendinopathies: A Systematic Literature Review.

PURPOSE: Musculoskeletal disorders are among the most common reasons for medical consultation, with tendinopathies accounting for up to 30% of such presentations. Although exercise remains the cornerstone of management, the most effective modality continues to be debated. Eccentric exercise has long been the mainstay, but the role of isometric exercise in pain modulation and functional recovery remains unclear. This systematic review aims to evaluate the current evidence on the efficacy of isometric exercises in the management of tendinopathies across various anatomic sites. METHODS: A systematic search was conducted in PubMed, MEDLINE, Embase, and the Cochrane Library from inception to August 1, 2025. Eligible studies included randomized controlled trials and prospective or retrospective cohort studies assessing isometric exercise interventions for tendinopathy, with or without comparator groups. Case series and case reports were excluded. Data extracted included participant demographic characteristics, site of tendinopathy, symptom duration, treatment duration, adherence, and outcome measures such as Victorian Institute of Sports Assessment (A, P, or G), visual analog scale, Patient-Specific Functional Scale, 36 item short form health survey (SF-36), and EuroQol 5-Dimension questionnaires. Imaging outcomes (ultrasound or magnetic resonance imaging) were recorded where available. Methodological quality and risk of bias were assessed using the Cochrane Risk of Bias tool in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. FINDINGS: The search identified 304 articles, of which 13 randomized controlled trials met the inclusion criteria, encompassing 336 participants (40% female). Tendinopathy sites included the patellar (n = 4), Achilles (n = 3), lateral elbow (n = 2), rotator cuff (n = 2), wrist extensor (n = 1), and gluteal (n = 1) tendons. Median symptom duration was 23 months (interquartile range, 3-51 months). Intervention periods ranged from a single 45-minute session to 4-month exercise programs. Treatment adherence was high initially (nearly 100%) but declined over time, with 70% of participants in the isometric and 58% in the control (isotonic) groups completing &#x2265;80% of sessions. Pain reduction and functional improvement were statistically significant in only 3 studies. Imaging-based outcomes were inconsistently reported, and study heterogeneity precluded meta-analysis. Overall methodological quality was rated as good in 3 studies and poor in 10. IMPLICATIONS: Current evidence provides limited support for the superiority of isometric exercise in tendinopathy management. Although isometric regimens appear tolerable and may confer short-term analgesic benefits, their long-term efficacy relative to eccentric or isotonic protocols remains uncertain. Future research should prioritize standardized outcome measures, longer follow-up, and uniform diagnostic criteria to strengthen the evidence base for exercise prescription in tendinopathies.

Humans

Artificial Intelligence Cannot Replace Peer Reviewers but May Help Editors Triage: A Comparative Analysis of a Large Language Model and Human Reviewer Recommendations at the American Journal of Sports Medicine.

BACKGROUND: The peer review system faces increasing strain from rising manuscript volumes, reviewer fatigue, and well-documented interreviewer disagreement. Large language models (LLMs) have shown potential to support the peer review process, but their ability to replicate editorial decisions at high-impact medical journals and their utility as manuscript screening tools remain unknown. PURPOSE: To compare the agreement between an LLM and the final editorial decision on manuscripts submitted to the American Journal of Sports Medicine and to evaluate the potential of LLMs as a manuscript screening tool. STUDY DESIGN: Cross-sectional agreement study. METHODS: Fifty-four manuscripts randomly selected from submissions to the American Journal of Sports Medicine (September 2024-October 2024) were reviewed by a locally deployed LLM (Ministral 3 14B; Mistral AI) using a standardized prompt. The artificial intelligence (AI) produced a categorical recommendation (reject, cascade, revision, or accept) and a numerical score (0-100) for each manuscript. Agreement with the final editorial decision was assessed by Cohen kappa (4-category model) for pooled human reviewers (n = 139 reviews) and the AI (n = 54). Screening performance was evaluated by positive predictive value (PPV), sensitivity, and specificity. RESULTS: Pooled human reviewers demonstrated fair agreement with the final decision (&#x3ba; = 0.181 [P < .001]; 42.4% agreement), while the AI demonstrated slight, nonsignificant agreement (&#x3ba; = 0.126 [P = .099]; 37.0% agreement). The AI recommended revision for 61.1% of manuscripts, of which 72.7% were ultimately rejected or cascaded, demonstrating systematic "revision bias." When the AI recommended rejection, 54.5% of those manuscripts were ultimately rejected and 27.3% were cascaded; when the AI recommended cascade, 50% were rejected and 50% were cascaded. However, when the AI recommended rejection or cascade (n = 21), 90.5% received a final decision of rejection or cascade (PPV, 90.5%; specificity, 81.8%). Manuscripts with an AI score <70 were rejected or cascaded 88.0% of the time (PPV, 88.0%). CONCLUSION: AI cannot replicate the nuanced judgment of human peer reviewers at a high-impact sports medicine journal. When AI recommended rejection or cascade, 90.5% of manuscripts received that final decision (descriptive PPV, 90.5%; 95% CI, 71.1%-97.3%), suggesting potential utility as an exploratory first-pass screening tool warranting further validation in larger cohorts. However, AI could not reliably distinguish manuscripts destined for outright rejection from those that would be cascaded to a sister journal-an important limitation for editorial triage applications.

Sports Medicine

Evaluating the utility of melatonin in spine surgery: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Spine surgery is increasingly performed worldwide, and acute postoperative stressors such as pain and anxiety remain highly prevalent despite historical management with opioids and other pharmacological agents. Recently, interest has emerged in melatonin administration given its endogenous physiological roles, low cost, favorable adverse event profile, and documented benefits throughout surgical literature. PURPOSE: This study aims to consolidate the existing evidence on melatonin's utility specifically in spine surgery, an area not yet comprehensively evaluated, to inform clinical practice and enhance spine surgeon comprehension. STUDY DESIGN/SETTING: Preregistered on PROSPERO, this systematic review queried PubMed/MEDLINE, CINAHL, SPORTDiscus, and Web of Science on November 21st, 2025, for studies reporting outcomes following melatonin administration in patients undergoing spine surgery. METHODS: Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Extracted variables included demographics, comparator medications, dosages, and other relevant details. Statistical analyses included frequency-weighted means (FWMs), associated standard deviations, narrative syntheses, and limited meta-analyses, where appropriate. RESULTS: A total of 6 moderate-quality randomized trials were included from 749 screened. Melatonin (3-10 mg) was administered to 227 patients (FWM age=43.3&#xb1;8.6 years; 46.2% male; BMI=26.6&#xb1;3.2 kg/m2), placebo to 125 patients (age=43.2&#xb1;10.1 years; 60% male; BMI=28.5&#xb1;4.3 kg/m2), and active pharmacologic comparators (fentanyl, gabapentin, dexmedetomidine, zolpidem) to 151 patients (age=46.6&#xb1;8.9 years; 40.5% male; BMI=26.3&#xb1;3.5 kg/m2). Procedures primarily involved uncomplicated lumbar laminectomies (1-4 levels), with outcomes assessed up to 24 hours postoperatively. Melatonin was associated with significant improvements in early postoperative VAS-pain scores, blood-pressure-related, analgesic-related, and anxiety-related outcomes versus placebo across most reporting studies. Compared with active pharmacologic agents, significant benefits were observed only in select nausea- and anxiety-related instances. Limited meta-analysis (n=2) demonstrated higher 24-hour VAS-pain for melatonin versus gabapentin, though mean difference was near-negligible and harbored extensive statistical constraints. CONCLUSION: Melatonin demonstrates variable utility following spine surgery, with generally consistent anxiolysis and frequent benefit versus placebo but less consistent and comparatively weaker efficacy relative to active pharmacologic comparators. Future outcome-homogenous studies incorporating more granular, expansive comparator arms and more robust quantitative analyses are needed to further elucidate melatonin's role in advancing spine care. LEVEL OF EVIDENCE: Level II.

Humans