Evidence for remote multicomponent rehabilitation among critical care survivors is sparse. To investigate the effects of a 6-week, remote, multicomponent rehabilitation intervention in survivors of critical illness following discharge from the hospital after an intensive care unit (ICU) admission compared with standard care on health-related quality of life at 8 weeks. Pragmatic, multicenter, assessor-blinded, randomized clinical trial conducted from December 2022 to November 2025 at 52 National Health Service hospitals in the UK. Participants were adults who had been discharged from the hospital within the last 12 weeks with an ICU admission (required mechanical ventilation for ≥48 hours during ICU stay). Individuals were randomized to a 6-week, remote, multicomponent, individualized, rehabilitation intervention incorporating weekly symptom management; targeted exercise; psychological support; and peer support and information commenced within 12 weeks of hospital discharge (n = 231) or standard care (n = 198). The primary outcome was health-related quality of life at 8 weeks measured by the EuroQoL 5-dimension 5-level questionnaire (EQ-5D-5L) utility score (from -0.285 [worst/worse than dead] to 1 [best health]; minimum clinically important difference: 0.08) and analyzed using linear regression (adjusted for baseline covariates). The secondary outcomes included leg strength and exercise capacity; self-reported perception of fatigue, anxiety, or depression; illness perception; and acceptability of the intervention and any adverse events. Of the 3705 screened patients, 429 (12%) were randomized (mean age, 55.4 [SD, 13.9] years; 184 female [42.9%]; 245 male [57.1%]; and had median Acute Physiology and Chronic Health Evaluation II score of 18 [IQR, 14 to 22]). The mean EQ-5D-5L utility score at 8 weeks was 0.69 (SD, 0.26) in the intervention group compared with 0.67 (SD, 0.27) in the standard care group (adjusted mean difference, 0.04 [95% CI, -0.001 to 0.09]; P = .05). The intervention improved 4 of the 6 secondary outcomes, including leg strength and exercise capacity, fatigue, anxiety, and acceptability of the intervention and any adverse events; there was no change in perception of depression or illness. A 6-week, multicomponent, rehabilitation program did not improve health-related quality of life at 8 weeks after discharge in ICU survivors who required mechanical ventilation. isrctn.org Identifier: ISRCTN11266403.

Digitalis glycosides may be used as additional therapy in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HF with reduced EF (HFrEF). To assess the effect of digitalis glycosides on clinical outcomes in patients with HFmrEF or HFrEF. PubMed was searched from inception to March 1, 2026, using medical subject headings and keywords related to digitalis glycosides and HF. The review was restricted to placebo-controlled randomized clinical trials including more than 1000 patients and articles published in the English language. Data were extracted by 2 reviewers who followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Risk of bias was assessed with the Cochrane Risk of Bias tool (version 2). A fixed-effects model was used to estimate the hazard ratios (HRs) with 95% CIs. The primary end point was the composite of time to cardiovascular death or first worsening HF event. Secondary outcomes included individual components of the composite outcome and time to all-cause death. A total of 3 studies met the inclusion criteria and included 9013 patients with HFmrEF or HFrEF (weighted mean age, 64.5 [weighted SD, 11.2] years; 22% female and 78% male). The composite outcome of cardiovascular death or first worsening HF event occurred in 1852 of 4510 patients (41%) in the digitalis glycoside group vs 2037 of 4503 patients (45%) in the placebo group (HR, 0.85 [95% CI, 0.80-0.90]; P < .001). First worsening HF event occurred in 1183 (26%) patients in the digitalis glycoside group vs 1474 (33%) patients in the placebo group (HR, 0.75 [95% CI, 0.69-0.81]; P < .001). There were 1224 cardiovascular events in the digitalis glycoside group vs 1224 in the placebo group (27% of participants in each group; HR, 0.99 [95% CI, 0.92-1.07]; P = .81) and there were 1466 vs 1497, respectively, all-cause deaths (32% of participants vs 33%; HR, 0.97 [95% CI, 0.90-1.04]; P = .41). There was no statistically significant heterogeneity by trial, type of digitalis glycoside treatment, or extent of background HF therapy. Treatment with digitalis glycosides was associated with a lower risk of the composite of cardiovascular death or first worsening HF event in patients with HFmrEF or HFrEF, mainly through a lower risk of worsening HF events. There was no statistically significant interaction with important study characteristics, including the extent of HF background therapy or type of digitalis glycosides treatment. These results suggest digitalis glycosides may be used as additional medical therapy to reduce worsening HF events in patients with HFmrEF or HFrEF.

Whether intravenous tenecteplase prior to endovascular treatment (EVT) for ischemic stroke reduces disability in the late time window is unclear. To investigate the adverse events and efficacy of tenecteplase prior to EVT in patients 4.5 to 24 hours after ischemic stroke onset due to proximal middle cerebral artery (MCA) occlusion. Multicenter, phase 3, randomized, open-label, blinded end point, superiority trial conducted at 40 centers in China. Adult (≥18 years) patients with acute ischemic stroke 4.5 to 24 hours after last known to be well due to MCA-M1 or proximal M2 occlusion with salvageable brain tissue (ischemic core volume <70 mL, mismatch ratio ≥1.8, and mismatch volume ≥15 mL) identified on computed tomography-perfusion or magnetic resonance-perfusion-diffusion imaging were enrolled from January 25, 2024, through July 21, 2025, and followed up for 90 days. Final follow-up occurred on October 14, 2025. Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg) before EVT (n = 199) or EVT alone (n = 192). The primary outcome was functional independence, defined as a score of 0 to 2 on the modified Rankin Scale (range, 0-6, with higher scores indicating greater disability) at 90 days. Adverse events outcomes included symptomatic intracranial hemorrhage and death. All of the 391 patients enrolled (median age, 68 years [IQR, 59-75]; 155 [39.6%] females) completed the trial. Functional independence at 90 days occurred in 88 patients (44.2%) in the tenecteplase before EVT group and 83 patients (43.2%) in the EVT alone group (adjusted relative rate, 1.01 [95% CI, 0.83-1.24]; P = .89; risk difference, 0.99% [95% CI, -8.84% to 10.83%]). Mortality within 90 days was 12.7% (25/197) in the tenecteplase before EVT group and 14.2% (27/190) in the EVT alone group. Symptomatic intracranial hemorrhage within 36 hours was 5.1% (10/197) and 2.6% (5/190), respectively. In patients presenting to EVT-capable centers 4.5 to 24 hours after stroke onset with proximal MCA occlusion, intravenous tenecteplase before EVT did not improve clinical outcomes vs EVT alone. ClinicalTrials.gov Identifier: NCT06221371.