Qiang Li

Background and ObjectivesObesity is a key risk factor underlying both obstructive sleep apnea (OSA) and cardiovascular disease (CVD). The objective of this study was to determine differential stren...

Introduction: ICH is a severe form of stroke with increasing global burden. Although more common in older adults, ICH in younger individuals (≤50 years) is a clinically distinct but understudied subgroup. This secondary analysis of the INTERACT3 trial compared baseline characteristics, management and outcomes between younger and older ICH patients. Patients and methods: INTERACT3 was a stepped-wedge, cluster-randomised trial conducted in 122 hospitals across 10 countries (2017–2021), evaluating a bundled care intervention for acute ICH. This sub-study analysed 7031 patients and compared demographics, imaging features, in-hospital treatment and 6-month outcomes between age groups. Primary outcomes were functional status (mRS), mortality and quality of life (EQ-5D-3L). Outcomes were analysed using generalised linear-mixed models accounting for clustering by hospital (random effect) and fixed effects for time period and cluster treatment assignment, with additional adjustment for pre-specified patient-level covariates. Results: Of 7031 patients, 1351 (19.2%) were aged ≤ 50 years. Younger patients were more often male (70.8% vs 62.4%, P < .0001), had higher body mass index (BMI) (25.3 vs 23.8 kg/m2, P < .0001) and were more likely to smoke (36.1% vs 21.4%) and consume alcohol (33.2% vs 13.3%). Despite having slightly larger haematoma volumes (18.0 vs 15.0 mL, P < .0001), younger patients had significantly better outcomes, with lower 6-month mortality (9.1% vs 16.6%; adjusted OR 0.42; 95% CI, 0.33–0.54) and reduced rates of death or disability (46.5% vs 57.8%; OR 0.56; 95% CI, 0.48–0.65). A significant age-by-treatment interaction was observed (P = .0251). Conclusion: Younger ICH patients demonstrated a distinct risk profile and better recovery, and benefiting more from bundled care interventions. These findings highlight the importance of early, intensive management and tailored prevention strategies targeting modifiable lifestyle risks in younger populations.

BACKGROUND: Early intensive blood pressure (BP) lowering improves outcomes in acute intracerebral hemorrhage, but its perioperative benefit among patients undergoing surgical hematoma evacuation is uncertain. We evaluated whether earlier achievement of intensive BP targets is associated with improved outcomes in this population. METHODS: Post hoc secondary analysis of the INTERACT3 (the third Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial) pragmatic, international, multicenter, blinded-end point, and stepped-wedge cluster-randomized trial. Among 7036 enrolled intracerebral hemorrhage patients at 121 hospitals, those who underwent surgical hematoma evacuation were included. Patients were categorized by time from hospital arrival to achieving the target systolic BP 2 hours. The primary outcome was 6-month mortality. Key secondary outcomes included death or disability (modified Rankin Scale scores 4–6), modified Rankin Scale score shift, health-related quality-of-life (EuroQol 5-Dimension 3-Level [EQ-5D-3L] domains, visual analog scale, and health utility index), and serious adverse events. Adjusted associations were estimated using Cox, logistic, ordinal logistic, and linear regression models, controlling for age, sex, treatment type, and admission Glasgow Coma Scale. RESULTS: Of 7036 patients with acute intracerebral hemorrhage, 1506 underwent surgical hematoma evacuation (mean [SD] age, 59.7 [11.8] years; 33.9% women). Overall, there was no statistically significant difference in 6-month mortality between patients who achieved target BP within 2 hours of treatment initiation and those who achieved it after 2 hours (adjusted hazard ratio, 0.81 [95% CI, 0.63–1.04]; P =0.09). Early BP achievement was associated with a lower risk of death or disability (adjusted odds ratio [OR], 0.71 [95% CI, 0.56–0.90]; P =0.01), a favorable shift in the distribution of modified Rankin Scale scores (adjusted common OR, 0.73 [95% CI, 0.60–0.89]; P P =0.02). EuroQol 5-Dimension 3-Level outcomes also favored the early group, with significant improvements in mobility (adjusted OR, 0.76 [95% CI, 0.60–0.97]; P =0.03), pain/discomfort (adjusted OR, 0.72 [95% CI, 0.54–0.95]; P =0.02), and usual activities (adjusted OR, 0.79 [95% CI, 0.62–1.00]; P =0.05), as well as higher visual analog scale (mean difference, 0.08 [95% CI, 0.002–0.17]; P =0.04) and health utility scores (mean difference, 0.05 [95% CI, 0.02–0.09]; P <0.01). CONCLUSIONS: In patients with intracerebral hemorrhage undergoing surgical hematoma evacuation, perioperative intensive BP reduction appears safe. Achieving systolic BP <140 mm Hg within 2 hours was associated with better functional and quality-of-life outcomes, and fewer serious adverse events. These time-sensitive associations support prioritizing ultra-early perioperative BP control; confirmatory prospective analyses are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03209258.

Background and ObjectivesWhile moderate and rapid systolic blood pressure (SBP) lowering was associated with better functional outcomes after intracerebral hemorrhage (ICH), large reductions in SBP...

Background/Objectives: (P)rehabilitation, comprising structured exercise, nutritional optimisation, and/or psychological support delivered pre- or postoperatively, has demonstrated efficacy in improving outcomes across the cancer care continuum. However, access remains limited. Technology-enabled (p)rehabilitation offers a novel solution with the potential to enhance equity and continuity of care. This systematic review aimed to evaluate the efficacy of technology-enabled (p)rehabilitation on perioperative and patient-reported outcomes among individuals undergoing thoracic and/or abdominopelvic cancer surgery. Methods: Six databases were search from inception to October 2024. Eligible studies were randomised controlled trials (RCTs) comparing technology-enabled (p)rehabilitation with usual care, placebo, or non-technology-based interventions in adults undergoing thoracic and/or abdominopelvic cancer surgery. Outcomes included postoperative complications, hospital readmissions, hospital length of stay (LOS), quality of life (QoL), pain, anxiety, depression, fatigue, distress, and satisfaction. Higher scores indicated improved QoL or worse symptom severity. Risk of bias was assessed using the revised Cochrane tool, and evidence strength was determined using GRADE methodology. Relative risks (RR) and mean differences (MD) were calculated using random-effects meta-analysis. Results: Seventeen RCTs (18 publications, n = 1690) were included. Trials most commonly evaluated application-based platforms (n = 8) and the majority exhibited some risk of bias. Technology-enabled (p)rehabilitation was associated with a significant reduction in LOS (MD = 1.33 days; 95% CI: 0.59–2.07; seven trials), and improvements in pain (MD = 6.12; 95% CI: 3.40–8.84; four trials), depression (MD = 2.82; 95% CI: 0.65–4.99; five trials), fatigue (MD = 10.10; 95% CI: 6.97–13.23; three trials) and distress (MD = 1.23; 95% CI: 0.30–2.16; single trial) compared with controls. Conclusions: Technology-enabled (p)rehabilitation shows promise in reducing LOS and improving selected patient-reported outcomes following thoracic and abdominopelvic cancer surgery. Although evidence is limited due to the small number of studies, modest sample sizes, methodological heterogeneity, and intervention variability, the overall findings justify further investigation. Large-scale, adequately powered clinical trials are required to confirm efficacy and guide clinical effectiveness and implementation studies.

Introduction: Fluid therapy is a cornerstone of acute management of diabetic ketoacidosis (DKA), yet the optimal fluid type is unknown. The Balanced Electrolyte Solution versus Saline Trial for Diabetic Ketoacidosis (BEST-DKA) trial has been designed to test the hypothesis that for patients with moderate to severe DKA, fluid therapy with Plasma-Lyte 148, compared with 0.9% saline, will lead to increased days alive and out of hospital to day-28 after enrolment. Purpose: To describe the statistical analysis plan for the BEST-DKA trial. Design, settings and participants: BEST-DKA is a currently recruiting cluster-randomised, crossover randomised controlled trial which will recruit a minimum of 400 patients with moderate or severe DKA at 22 hospitals in Australia, which will provide >91.4% power to detect a change of 2 days in the primary outcome, days alive and out of hospital to day-28 after enrolment. Hospitals will be randomised to either blinded saline or Plasma-Lyte 148 for a 12-month period, and then crossover to the alternate fluid for the next 12-month period. Conclusion: BEST-DKA started enrolment in March 2024 and recruitment is on target with scheduled completion in July 2026. 1 Administrative information: 1.1 Study identifiers: ClinicalTrials.gov register Identifier: NCT05752279 . 1.2 Revision history: 1.3 Contributors to the statistical analysis plan: 1.3.1 Roles and responsibilities: 1.3.2 Approvals: The undersigned have reviewed this plan and approve it as final. They find it to be consistent with the requirements of the protocol as it applies to their respective areas. They also find it to be compliant with ICH-E9 principles and in particular confirm that this analysis plan was developed in a completely blinded manner, i.e. without knowledge of the effect of the intervention(s) being assessed.

Introduction: Elevated blood pressure (BP) is a key modifiable risk factor for cardiovascular (CV) complications in patients with atrial fibrillation (AF). While current guidelines recommend modest BP targets, the optimal target in AF patients remains uncertain. The Cardiovascular Risk Reduction in Atrial Fibrillation Trial (CRAFT) is a multicenter, prospective, randomized, open-label, blinded endpoint trial that evaluates whether intensive home systolic BP control (<120 mm Hg) is superior to standard BP control (<135 mm Hg) in reducing major CV events. The primary outcome is a hierarchical composite of time to CV death, stroke, myocardial infarction, and heart failure hospitalization. A total sample of 1,675 participants provides 80% power to detect a win ratio of 1.50 between groups after a mean of 3 years of follow-up. Methods: This statistical analysis plan (SAP) was developed by the trial statistician and principal investigators, in collaboration with the Steering Committee and international experts. The SAP specifies the planned analyses of baseline characteristics, patients’ intervention, primary and secondary outcomes, subgroup effects, and safety outcomes. Analyses will be conducted on an intention-to-treat analysis using the win ratio method for the primary endpoint and Cox proportional hazards and Poisson regression for secondary analyses. Sensitivity analyses and strategies for handling missing data are also described. Conclusion: A predefined SAP was established for the CRAFT trial to ensure a transparent and verifiable analysis. The SAP was finalized prospectively, independent of treatment assignment, with the goal of preserving internal validity and minimizing analytical bias.

Purpose To determine whether there is an interaction between baseline serum chloride concentration and pH and treatment effects in Intensive Care Unit (ICU) patients receiving intravenous fluid therapy with balanced solution versus 0.9% sodium chloride (saline). Methods A secondary analysis of a randomized controlled trial in which patients were divided into cohorts according to quartiles of baseline serum chloride concentration and pH. The primary outcome was day-90 mortality. Results From 4846 patients with outcome data available, 4823 with relevant baseline data were included in this analysis, with 1347, 1333, 993 and 1150 patients in the chloride quartiles of < 102, 102–106, 107–109 and > 109 mmol/L, respectively. Data were also analysed in pH quartiles of ≤ 7.27, 7.27–7.34, 7.34–7.39 and > 7.39. The risk-adjusted odds ratio (95% confidence interval [CI]) for day-90 mortality for patients assigned balanced solution compared to saline was 1.23 (0.95–1.58), 0.95 (0.73–1.25), 0.88 (0.64–1.21), and 0.76 (0.57–1.01) for lowest to highest chloride subgroups, respectively (P value for interaction = 0.10), and 0.89 (95% CI 0.69–1.15), 0.94 (0.70–1.27), 0.96 (0.67–1.38) and 1.15 (0.82–1.60) for pH quartiles from lowest to highest, respectively (P value for interaction = 0.63). Conclusions There were no significant differences in the treatment effect of balanced solutions compared to saline according to baseline serum chloride concentration or pH.