Plens GM, Morais CCA, Gregol T
… +12 more, Colpani PB, Alcala GC, Pacheco É, Xia YHW, Dos Santos AC, Malbouisson LM, Brochard L, Kassis EB, Goligher EC, Carvalho CRR, Amato MBP, Costa ELV
Crit Care Med
· 2026 Jul · PMID 42165647
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OBJECTIVE: Current methods for estimating inspiratory muscle pressure ( Pmus ) during mechanical ventilation are either invasive or dependent on occlusion maneuvers. A noninvasive artificial intelligence (AI) algorithm e...OBJECTIVE: Current methods for estimating inspiratory muscle pressure ( Pmus ) during mechanical ventilation are either invasive or dependent on occlusion maneuvers. A noninvasive artificial intelligence (AI) algorithm estimating in real-time the amplitude and timing of Pmus , enabling continuous monitoring of patient effort, driving pressure, and synchrony with the ventilator was designed, and its performance was evaluated against the gold standard obtained with esophageal manometry ( Pmus,es ). DESIGN: A prospective diagnostic accuracy study. SETTING: Two ICUs from the University of São Paulo, Brazil. PATIENTS: Adult patients under pressure support ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pmus estimated using AI ( Pmus,AI ) was compared with Pmus,es and to values derived from occlusion maneuvers, the pressure muscle index and the occlusion pressure ( Pocc ). Automatic detection of dyssynchronies based on Pmus,AI was compared with experts' classification. A total of 48 participants with 4918 cycles were analyzed. Pmus,es varied from 1.0 to 28.4 cm H 2 O. Pmus,AI showed a bias of 0.9 cm H 2 O, 95% limits of agreement -5.1, 6.9 cm H 2 O and detected extreme values of both Pmus,es and dynamic driving pressure with area under the receiver operating characteristic curve greater than 0.8. Pmus,AI accuracy was comparable to occlusion-based techniques. Sensitivity and specificity to detect ineffective effort, autotriggering or reverse triggering were 86.5% and 77.4%, respectively. CONCLUSIONS: AI presented good performance in detecting high and low Pmus , and allowed the automatic detection of specific types of dyssynchronies. This novel noninvasive method was comparable to intermittent techniques requiring occlusion maneuvers.
Harrison DS, Dhruva N, Ford JL
… +5 more, Greer DM, Wahlster S, Chhabra N, Morris NA, Simulation-based mastery learning to assess and Ensure COmpetency in death by Neurologic criteria Determination (SECOND) Study Group
Crit Care Med
· 2026 Jun · PMID 42161897
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OBJECTIVES: To develop a comprehensive checklist, define critical actions, and establish a minimal passing standard for adult and pediatric critical care clinicians as well as other clinicians to facilitate formative and...OBJECTIVES: To develop a comprehensive checklist, define critical actions, and establish a minimal passing standard for adult and pediatric critical care clinicians as well as other clinicians to facilitate formative and summative assessment of brain death/death by neurologic criteria (BD/DNC) determination. DESIGN: A prespecified three-round modified Delphi consensus process to define checklist items followed by a modified Angoff standard setting process to determine critical actions and item average ratings. SETTING: Electronic surveys. SUBJECTS: Selected authors of the 2023 Pediatric and Adult BD/DNC Consensus Practice Guideline, World Brain Death Project, and experts recommended by these authors ( n = 16) participated in the Delphi panel. Neurocritical Care United Council for Neurologic Subspecialties and Accreditation Council for Graduate Medical Education examination committee members ( n = 13) participated in Angoff standard setting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 98 unique checklist items related to assessment of prerequisites (23 items), performance of the clinical examination (28 items), apnea testing (36 items), and ancillary testing (11 items) were retained by the Delphi panel. Seven items were designated as critical actions based upon Angoff panelist consensus. The remaining 91 items were assigned item average ratings. The minimum passing score for an assessment including all noncritical items was set at 89%. CONCLUSIONS: These guideline-concordant consensus checklist items, including critical actions and noncritical actions with their assigned item average ratings, may be applied selectively to simulated cases of BD/DNC determination for adults and children to determine a minimum passing score and readiness for independent practice, mitigating the risk of inaccurate BD/DNC determination among critical care clinicians. Our process for systematically defining critical actions on a behavior checklist may be replicated for simulation-based summative assessment of learners in other critical care scenarios.
Sosnowski KJ, Ranse KL, Mitchell ML
… +5 more, Ware RS, White HT, Morrison LA, Schweitzer VC, Chaboyer WP
Crit Care Med
· 2026 Jul · PMID 42159452
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OBJECTIVES: To test whether the ABCDEF bundle, compared with usual care, decreases delirium incidence and duration, improves functional status in the ICU, and enhances 90-day post-ICU discharge quality of life in critica...OBJECTIVES: To test whether the ABCDEF bundle, compared with usual care, decreases delirium incidence and duration, improves functional status in the ICU, and enhances 90-day post-ICU discharge quality of life in critically ill Australian adults. DESIGN: Single-center, pragmatic, randomized controlled trial. SETTING: Eight-bed medical/surgical ICU in a metropolitan Australian hospital. PATIENTS: Adult patients expected to remain in ICU for at least 48 hours. INTERVENTIONS: ABCDEF bundle or usual care. MEASUREMENTS AND MAIN RESULTS: Complete ABCDEF bundle adherence was achieved in 50% of patients each study day. The primary outcome, cumulative incidence of delirium (measured with the Confusion Assessment Method for ICU), was similar between groups (ABCDEF, 37.9%; usual care, 36.4%; odds ratio, 1.1; 95% CI, 0.5-2.2; p = 0.86), as was median delirium duration (ABCDEF, 2.0 d; interquartile range [IQR], 1.3-3.5 d; usual care, 2.5 d; IQR, 1.0-4.4 d; mean difference, -0.4 d; 95% CI, -1.6 to 0.8 d; p = 0.53). Median functional scores at ICU discharge (measured with the Functional Independence Measure) were 55.0 (IQR, 37.0-67.3) in the ABCDEF group and 53.0 (IQR, 43.8-62.5) in the usual care group (mean difference, 0.0; 95% CI, -7.7 to 7.6; p = 0.83). At 90 days post-ICU discharge, the ABCDEF bundle group reported higher scores in the "usual activities" domain ( p < 0.001) (measured with the EuroQol 5D five-level questionnaire), with no differences in other domains. CONCLUSIONS: In adult ICU patients, the ABCDEF bundle, compared with usual care, did not reduce the cumulative incidence or duration of delirium. While no effect was observed on the primary outcomes, higher scores in the "usual activities" quality of life domain suggest potential long-term benefits that warrant further investigation.
Crit Care Med
· 2026 Jul · PMID 42159375
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OBJECTIVE: Sepsis-associated acute kidney injury (SAKI) is a heterogeneous condition that lacks disease-modifying treatments, and precision medicine approaches are needed. We previously derived two reproducible pediatric...OBJECTIVE: Sepsis-associated acute kidney injury (SAKI) is a heterogeneous condition that lacks disease-modifying treatments, and precision medicine approaches are needed. We previously derived two reproducible pediatric SAKI subphenotypes (pSAKI-1 and pSAKI-2) from readily available clinical data. We aimed to externally validate the prognostic relevance of these subphenotypes, evaluate their molecular signatures, and assess for heterogeneity of treatment effect (HTE) across subphenotypes with sepsis therapies. DESIGN: Secondary analysis of an ongoing multicenter, prospective, observational study of children. SETTING: Ten PICUs in the United States from January 2002 to February 2025. PATIENTS: Patients 1 week to 18 years old with early (day 1-2) SAKI. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 871 patients, 665 (76%) were assigned pSAKI-1 and 206 (24%) to pSAKI-2. On day 1-2, the pSAKI-2 cohort had greater severity of illness, including higher acute kidney injury stage and vasoactive burden, lower platelet counts, and higher lactate values and International Normalized Ratios. These pSAKI-2 patients also had uniformly worse outcomes, including independently higher odds of day 7 severe acute kidney injury (adjusted odds ratio [aOR] 3.2; 95% CI, 2.1-4.7; p < 0.001), death (aOR 2.7; 95% CI, 1.6-4.4; p < 0.001), and fewer PICU-free and vasoactive-free days ( p < 0.001). The biomarker signature of pSAKI-2 was characterized by greater inflammation, endothelial dysfunction, and hyperreninemia. On propensity score matched (PSM) analysis, pSAKI-1 patients who received corticosteroids had more day 7 severe acute kidney injury (28% vs. 19%, p = 0.023), 2 fewer PICU-free days ( p = 0.04) and greater mortality (10% vs. 3.7%, p = 0.008); no differences were seen in pSAKI-2 patients. Although no HTE was identified on PSM analysis for vasopressin, inverse probability treatment weighting analysis demonstrated a significant interaction between subphenotype-, vasopressin- and vasoactive-free days ( p = 0.003). CONCLUSIONS: We externally validated the prognostic relevance of two pSAKI subphenotypes derived from readily available data. These subphenotypes have unique biomarker signatures and differential responses to treatment, representing a potential mechanism for bedside enrichment.
Sato R, Kondo S, Ali A
… +3 more, Abu Za'nouneh F, Hasegawa D, Daoud EG
Crit Care Med
· 2026 Jul · PMID 42153811
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OBJECTIVES: To investigate the association between mechanical power and mortality in adult critically ill patients receiving invasive mechanical ventilation. DATA SOURCES: We conducted a systematic search of MEDLINE, Emb...OBJECTIVES: To investigate the association between mechanical power and mortality in adult critically ill patients receiving invasive mechanical ventilation. DATA SOURCES: We conducted a systematic search of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials on August 12, 2025. STUDY SELECTION: We included studies comparing mechanical power between survivors and nonsurvivors or reporting adjusted mortality estimates in adult critically ill patients receiving invasive mechanical ventilation. DATA EXTRACTION: Two reviewers independently extracted study characteristics, ventilator variables, and mortality outcomes. DATA SYNTHESIS: Pooled mean differences (MDs) were calculated using inverse-variance random-effects models. Secondary analyses evaluated mechanical power normalized to predicted body weight and respiratory system compliance. Adjusted odds ratios (AORs) and adjusted hazard ratios (AHRs) for mortality per 1 J/min increase in mechanical power were synthesized separately using generic inverse-variance random-effects models. A total of 34 studies met inclusion criteria and were included in the meta-analyses. Mechanical power was higher in nonsurvivors than survivors (MD, 1.91 J/min; 95% CI, 1.30-2.51 J/min). Mechanical power normalized to predicted body weight (MD, 0.06 J/min/kg; 95% CI, 0.04-0.08 J/min/kg) and normalized to respiratory system compliance (MD, 0.28 J/min/mL/cm H 2 O; 95% CI, 0.10-0.45 J/min/mL/cm H 2 O) were also higher among nonsurvivors. Mechanical power was independently associated with mortality, with pooled AOR (1.04 per 1 J/min increase; 95% CI, 1.03-1.06 per 1 J/min increase) and pooled AHR (1.03; 95% CI, 1.00-1.07). A mechanical power threshold older than 17 J/min was associated with greater mortality (odds ratio, 1.60; 95% CI, 1.34-1.91). CONCLUSIONS: Higher mechanical power was consistently associated with increased mortality in invasively ventilated adults. Mechanical power may serve as a clinically relevant marker of ergotrauma; however, whether interventions that reduce mechanical power improve outcomes requires prospective investigation.
Walker HGM, Vo TK, Santamaria J
… +4 more, Serpa Neto A, Subramaniam A, Brown AJ, Australian and New Zealand Intensive Care Society Center for Outcome and Resource Evaluation (ANZICS CORE) Committee
Crit Care Med
· 2026 May · PMID 42153779
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OBJECTIVES: Frailty and readmission to the ICU are common, and both are associated with worse outcomes. However, there is limited literature that assesses how frailty impacts those patients who require readmission to the...OBJECTIVES: Frailty and readmission to the ICU are common, and both are associated with worse outcomes. However, there is limited literature that assesses how frailty impacts those patients who require readmission to the ICU during a hospitalization. Therefore, we sought to assess whether the association between ICU readmission and death differ by frailty state. DESIGN: A registry-based study used the Australian and New Zealand Intensive Care Society Adult Patient Database. SETTING AND PATIENTS: All adult patients (age ≥ 18 yr) admitted to 203 ICUs in Australia and New Zealand between January 2017 and December 2022 with a documented Clinical Frailty Scale (frailty defined as a score ≥ 5) were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 60-day mortality. A Cox proportional hazards model, treating time to readmission as a time-dependent covariate and including an interaction term between frailty state and readmission, was used. Regression standardization was used to estimate absolute risk and risk differences, with 95% CIs calculated using a nonparametric bootstrap. A competing risk analysis was conducted, treating in-hospital death without ICU readmission as a competing risk. Secondary outcomes included length of hospital stay and discharge location. Six hundred fifteen thousand seven hundred nineteen ICU admission episodes were analyzed. Of the entire cohort, 19% (115,453) were frail, and 4.1% (25,329) were readmitted to the ICU. By day 60, 2.7% patients had died (16,353) in the hospital. Patients with frailty were at increased risk of both ICU readmission (subdistribution hazard ratio [SHR], 1.10; 95% CI, 1.07-1.14) and death without readmission (SHR, 2.83; 95% CI, 2.72-2.94). Observed 60-day mortality was greatest in frail, readmitted patients (22.7%). The standardized risk increase in 60-day mortality associated with ICU readmission was similar between patients with and without frailty (14.6% [95% CI, 13.7-15.6%] vs. 14.9% [95% CI, 13.4-16.6%]), respectively. CONCLUSIONS: This large, multicenter, retrospective study found that ICU readmission was associated with increased 60-day mortality in patients with and without frailty. Readmitted patients with frailty had the greatest risk of 60-day mortality; however, frailty state did not modify the incremental absolute risk of death relative to nonreadmitted patients.
Fresilli S, Belletti A, Labanca R
… +8 more, Monti G, Schultz MJ, Corbo F, Luciano AP, Ferrara B, Turi S, Landoni G, Nebulized Heparin Study Group
Crit Care Med
· 2026 Jul · PMID 42148826
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OBJECTIVES: Dysregulated pulmonary coagulation and inflammation is a hallmark of respiratory failure in various etiologies. Excessive fibrin deposition contributes to alveolar collapse, impaired gas exchange, and progres...OBJECTIVES: Dysregulated pulmonary coagulation and inflammation is a hallmark of respiratory failure in various etiologies. Excessive fibrin deposition contributes to alveolar collapse, impaired gas exchange, and progression to pulmonary fibrosis. Nebulized heparin can mitigate these coagulation and inflammation disturbances. Although several randomized controlled trials have explored its effects, results remain inconsistent and limited by small patient populations. We conducted a random-effects meta-analysis to calculate the risk ratio (RR) and 95% CIs. DATA SOURCES: We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials comparing nebulized unfractionated heparin to standard care or placebo in adult patients with respiratory failure either invasively mechanical ventilated or not. The primary outcome was all-cause mortality at the longest follow-up. STUDY SELECTION: We included randomized clinical trials enrolling adult patients with respiratory failure, comparing nebulized heparin vs. standard care or placebo, and reporting at least one clinical outcome, including all-cause mortality. DATA EXTRACTION: Two independent investigators extracted data on trial design, setting, etiology of respiratory failure, heparin dosing regimens, follow-up duration, and outcomes. Discrepancies were resolved by consensus. DATA SYNTHESIS: We identified 16 studies (787 receiving nebulized heparin, 833 control). Six (38%) were multicenter, five focused on COVID-19, 12 enrolled ICU patients, and dosing clustered around 25,000 international units (IUs) three times a day (~75,000 IU/d for ~10 d). At the longest follow-up, nebulized heparin reduced all-cause mortality vs. control (110/645 [17.1%] vs. 157/711 [22.1%]; RR, 0.79; 95% CI, 0.66-0.95; with ten studies included). Nebulized heparin was also associated with more ventilation-free days by day 28 (mean difference, +4.85; 95% CI, 1.47-8.24). Major bleeding was rare (1.1 vs. 0.7%; RR, 1.48; 95% CI, 0.42-5.18), while no minor bleeding or heparin-induced thrombocytopenia was reported. CONCLUSIONS: Nebulized unfractionated heparin may improve survival in patients with respiratory failure without increasing adverse events.
Kruger N, Durr K, Fernando SM
… +8 more, Rochwerg B, Inaba K, Kim D, Yadav K, Kubelik D, Engels PT, Glen P, Tran A
Crit Care Med
· 2026 Jul · PMID 42138515
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OBJECTIVE: Necrotizing soft-tissue infections (NSTIs) are rapidly progressive infections often characterized by widespread necrosis, sepsis, and multiple organ failure. As such, it is important to individualize treatment...OBJECTIVE: Necrotizing soft-tissue infections (NSTIs) are rapidly progressive infections often characterized by widespread necrosis, sepsis, and multiple organ failure. As such, it is important to individualize treatment decisions using evidence-based prognostication. We aimed to summarize the prognostic association between patient and disease factors and mortality among adult patients with NSTI. DATA SOURCES: We searched three databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials) from inception to September 29, 2025. STUDY SELECTION: We included studies that enrolled adult patients with NSTI and evaluated prognostic factors associated with short-term mortality using adjusted models that account for at least age and comorbidity. DATA EXTRACTION: We pooled effect estimates using a random-effects model. We assessed risk-of-bias using the Quality in Prognosis Studies tool and assessed certainty of evidence using Grading of Recommendations, Assessment, Development, and Evaluations methodology. DATA SYNTHESIS: We included 41 observational cohort studies involving 168,261 patients. Studies were predominantly retrospective cohorts. Patient factors with a moderate or high certainty of association with increased mortality include older age, chronic liver disease, chronic kidney disease, high Charlson Comorbidity Index, and immunosuppression. Disease factors with a moderate or high certainty of association with increased mortality include hypotension, bacteremia, acute kidney injury, coagulopathy, thrombocytopenia, and shock. CONCLUSIONS: Several patient and illness factors demonstrate important association with mortality among patients with NSTI. Clinicians should consider these factors in decisions related to escalation of therapy, and counseling patients and family members on potential outcomes.
Hardt MM, Lichtenthal WG, Saviano S
… +7 more, Rosen A, Lief L, Berlin DA, Kolla S, Rogers M, Maciejewski PK, Prigerson HG
Crit Care Med
· 2026 Jul · PMID 42133624
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OBJECTIVES: Examine ICU caregivers' experience of patient-related financial strain and its association with caregiver psychological distress (i.e., posttraumatic stress, anxiety, and depressive symptoms) and healthcare p...OBJECTIVES: Examine ICU caregivers' experience of patient-related financial strain and its association with caregiver psychological distress (i.e., posttraumatic stress, anxiety, and depressive symptoms) and healthcare perceptions (i.e., medical mistrust, decisional regret). DESIGN: Cross-sectional secondary analysis using baseline data from an ongoing, multicenter randomized controlled trial intervention study ( ClinicalTrials.gov identifier NCT05587517). SETTING: Three medical ICU sites in the United States. SUBJECTS: Family caregivers ( n = 97) of patients in medical ICUs admitted from October 2022 to December 2025, with a mean age of 52.32 years, of whom 67 (69.1%) were female, and 42 (43.3%) were the spouse/partner of the patient. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Caregivers completed measures assessing degree of difficulty paying for patient medical care, posttraumatic stress symptoms, anxiety symptoms, depressive symptoms, medical mistrust, and decisional regret. Analyses found 63.9% participants reported difficulty paying for patient medical care and that financial strain was positively associated with severity of posttraumatic stress symptoms ( r = 0.35; p < 0.001; 95% CI, 0.15-0.52), anxiety symptoms ( r = 0.22; p < 0.05; 95% CI, 0.02-0.41), depressive symptoms ( r = 0.27; p < 0.01; 95% CI, 0.07-0.45), decisional regret ( r = 0.30; p < 0.05; 95% CI, 0.03-0.52), and medical mistrust ( r = 0.30; p < 0.01; 95% CI, 0.10-0.48). CONCLUSIONS: Over half of ICU caregivers endorsed difficulty paying for patient medical care. Caregivers with greater difficulty paying for patient medical care had more severe posttraumatic stress symptoms, anxiety symptoms, and depressive symptoms; greater decisional regret; and higher levels of medical mistrust.
Tirupakuzhi Vijayaraghavan BK, Patodia S, Gamage Dona D
… +8 more, Venkataraman R, Beane A, Haniffa R, de Keizer N, Adhikari NKJ, Ramakrishnan N, Fowler R, Indian Registry of IntenSive care (IRIS) collaboration
Crit Care Med
· 2026 Jul · PMID 42132466
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OBJECTIVES: To evaluate the association between sex assigned at birth and outcomes for critically ill patients in India. DESIGN: Retrospective registry-embedded cohort study. SETTING: Forty-five ICUs that are part of the...OBJECTIVES: To evaluate the association between sex assigned at birth and outcomes for critically ill patients in India. DESIGN: Retrospective registry-embedded cohort study. SETTING: Forty-five ICUs that are part of the Indian Registry of IntenSive care (IRIS). PATIENTS: We included adult (≥ 16 yr) patients admitted to ICUs in the IRIS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was sex at birth, and the primary outcome was ICU mortality. Secondary outcomes included in-hospital mortality, receipt of mechanical ventilation, kidney replacement therapy, and vasopressors. Logistic regression models for the primary and secondary outcomes were adjusted for prespecified baseline covariates. We included 82,151 patients from 45 ICUs. Median (interquartile range) age was 60.0 years (45.0-70.0 yr) and 38.2% ( n = 31,409) of the cohort was female. Baseline characteristics were similar. Comparing sexes, ICU mortality (9.5% females vs. 10.3% males; adjusted odds ratio [adjOR], 0.95; 95% CI, 0.90-1.00; p = 0.07) and hospital mortality (19.4% vs. 20.8%; adjOR, 1.00; 95% CI, 0.97-1.03; p = 0.66) were similar. Females less commonly received invasive ventilation (22.2% vs. 26.3%; adjOR, 0.78; 95% CI, 0.75-0.82; p < 0.001), kidney replacement therapy (4.9% vs. 6.3%; adjOR, 0.73; 95% CI, 0.68-0.78; p < 0.001), and vasopressors (19.1% vs. 20.2%; adjOR, 0.95; 95% CI, 0.92-0.99; p = 0.03). In contrast, females more commonly received noninvasive ventilation (11.7% vs. 9.7%; odds ratio, 1.23; 95% CI, 1.18-1.30; p < 0.001). Results of the sensitivity analyses were consistent with the primary findings. CONCLUSIONS: In this registry-embedded cohort study, critically ill females less commonly received most types of organ supports, yet had similar adjusted ICU mortality compared with males.
Hashmi M, Haniffa R, Jayakumar D
… +80 more, Beane A, Lorenzi E, Berry LR, Nasir Khoso M, Ain Khan Q, Kumar A, Altaf Kidwai A, Hills TE, Annane D, Aryal D, Au C, Baillie K, Beasley R, Best-Lane J, Bonten M, Bradbury CA, Brunkhorst FM, Burrell A, Buxton M, Cecconi M, Cheng AC, Cove ME, de Jong M, Detry MA, Duffy E, Estcourt LJ, Fitzgerald M, Fowler R, Goossens H, Green C, Hays LMC, Higgins AM, Huang DT, Ichihara N, Koirala S, Lamontagne F, Lawler PR, Lewis RJ, Litton E, Mahon N, Marshall JC, McAuley DF, McGlothlin A, McGuinness S, McQuilten ZK, McVerry BJ, Mouncey PR, Morpeth S, Netea M, Orr K, Parke RL, Parker JC, Patanwala A, Peters S, Reyes LF, Rowan KM, Saito H, Saunders CT, Santos M, Seymour CW, Shankar-Hari M, Singh V, Slater M, Tambyah PA, Tong SYC, Turgeon AF, Turner AM, van de Veerdonk F, Weis S, Zarychanski R, McArthur CJ, Angus DC, Berry SM, Gordon AC, Derde LPG, Webb SA, Murthy S, Arabi Y, Nichol AD, and the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) Investigators
Crit Care Med
· 2026 Jul · PMID 42101205
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OBJECTIVE: To determine whether ivermectin improves outcomes for critically and noncritically ill hospitalized patients with COVID-19. DESIGN: An ongoing international, multifactorial, adaptive platform, randomized, cont...OBJECTIVE: To determine whether ivermectin improves outcomes for critically and noncritically ill hospitalized patients with COVID-19. DESIGN: An ongoing international, multifactorial, adaptive platform, randomized, controlled trial. SETTING: Hospitals in Pakistan, India, and Ireland between June 11, 2021, and September 9, 2022. PATIENTS: Critically and noncritically ill patients. INTERVENTIONS: Randomized to ivermectin or no ivermectin (control). MEASUREMENTS AND MAIN RESULTS: The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors. Analyses used a Bayesian cumulative logistic model. Enrollment was closed for operational futility, following external evidence suggesting no benefit with ivermectin in nonhospitalized patients with COVID-19. Among 61 critically ill patients, the median number of organ support-free days was -1, indicating death was the most common vital outcome (interquartile range [IQR], -1 to 17), for the ivermectin group and -1 (IQR, -1 to 17.25) for the control group (adjusted proportional odds ratio [OR], 0.94; 95% credible interval [CrI], 0.40-2.07) and the posterior probability of superiority to control was 44.2%. Among 89 noncritically ill patients, the median number of organ support-free days was 22 (IQR, 18.5-22) for ivermectin and 22 (IQR, 16-22) for control (adjusted proportional OR, 1.04; 95% CrI, 0.48-2.34) and the posterior probability of superiority was 53.7%. Among critically ill patients, hospital survival was 35.1% (13/37) for ivermectin and 37.5% (9/24) for control (adjusted OR, 1.00; 95% CrI, 0.39-2.32), posterior probability of superiority was 50.0%. Among noncritically ill patients, hospital survival was 84.1% (37/44) for ivermectin and 77.8% (35/45) for control (adjusted OR, 1.16; 95% CrI, 0.5-3.07), posterior probability of superiority was 63.3%. CONCLUSIONS: For critically and noncritically ill hospitalized patients with COVID-19, ivermectin was unlikely to improve the primary composite outcome of organ support-free days and hospital survival.
Crit Care Med
· 2026 Jul · PMID 42089734
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OBJECTIVES: To assess the socioeconomic consequences of critical illness by quantifying changes in household income level and unemployment among ICU survivors in a universal health coverage setting. DESIGN, SETTING, AND...OBJECTIVES: To assess the socioeconomic consequences of critical illness by quantifying changes in household income level and unemployment among ICU survivors in a universal health coverage setting. DESIGN, SETTING, AND PATIENTS: This nationwide retrospective cohort study used the Korean National Health Insurance Service database. Adult ICU survivors between January 1, 2020, and December 31, 2022, were included. Patients who died within 1 year or had missing data were excluded. The final cohort consisted of 582,341 survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the change in household income level (scale 0-20) between pre-ICU and post-ICU years, analyzed using generalized estimating equation models. The most salient finding was a profound financial polarization among survivors. While the overall cohort experienced a significant and progressive decline in income rank (1-yr ratio of means [RoM], 0.994; 2-yr RoM, 0.976; both p < 0.001), this average masked a severe impact on the highest income quartile (Q4), which exhibited a substantial 6.5% relative drop in mean rank (RoM, 0.935). In contrast, the lowest quartile (Q1) showed relative stability (RoM, 2.198) due to a "floor effect" and transitions into the social safety net. Descriptively, 160,682 survivors (27.6%) experienced income decline, 60,432 (10.4%) suffered catastrophic decline, and 12.3% of 326,125 previously employed survivors were no longer employed within 1 year. CONCLUSIONS: Critical illness is associated with progressive socioeconomic deterioration characterized primarily by financial polarization. Even with universal health coverage, the economic burden hits previously high-earning households most severely, while lower income groups face potential asset depletion before transitioning to social safety nets. Policies integrating sustained financial protection and vocational rehabilitation into post-ICU survivorship care are essential.