Background Patients in the intensive care unit (ICU) receive frequent routine blood tests, such as repeat testing in electrolyte replacement protocols, which may not be associated with patient-important outcomes. Research Question Does reducing ICU electrolyte replacement protocol repeat blood testing for magnesium, potassium, and phosphorous impact resource utilization or patient outcomes in a quality improvement (QI) program. Study Design and Methods This three-hospital prospective intervention occurred October 31, 2024. Five follow-up electrolyte blood tests were removed from an existing ICU electrolyte replacement protocol. These five orders were identified by the QI workgroup as low-value testing unlikely to change patient management. The primary outcome was the number of green-top chemistry blood tubes per ICU patient-day. Secondary outcomes included the number of electrolyte-related blood draws, target electrolyte tests, and cost and carbon footprint of testing. Balancing measures included incidence of critically low electrolyte levels, mean and distribution of electrolyte levels, and unit-level incidence of atrial fibrillation/flutter or other tachyarrhythmia. Outcomes were evaluated using interrupted time series and statistical process control charts. Results There were 23,230 patient-days in the 12-month pre- and 22,530 patient-days in the 12-month post-intervention period. The number of green-top blood tubes decreased from 1.70 to 1.36 per patient day; step change decrease attributed to the electrolyte protocol change was -0.21 tubes per patient-day (95%CI -0.12 to -0.29, p<0.01). Annually, the intervention saved 4,805 tubes, 3,432 target electrolyte tests, $11,440 CAD, and reduced the blood testing carbon footprint by an estimated 915 kgCO2e per year. There was no change in electrolyte distribution, the incidence of critically low electrolyte results, or the incidence of atrial fibrillation/flutter or other tachyarrhythmia in the ICU. Interpretation Removal of low value repeat blood test orders from ICU electrolyte replacement protocols was associated with reduced resource use, cost, and carbon footprint, without evidence of associated harm.

OBJECTIVES:To evaluate the association between socioeconomic position (SEP) and mortality in patients with sepsis or septic shock. DATA SOURCES:We searched MEDLINE, Embase, and Cochrane CENTRAL from inception to August 11, 2025. STUDY SELECTION:We included English-language observational studies that evaluated the association between SEP indicators and mortality in adults with sepsis and/or septic shock. DATA EXTRACTION:Two reviewers independently and in duplicate performed data extraction and risk-of-bias assessment using the Quality in Prognosis Studies tool. We pooled adjusted odds ratios (aORs) or adjusted hazard ratios (aHRs) using random-effects models and assessed certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS:We included 13 observational studies involving 3,951,677 patients. Lack of private insurance (aOR, 1.34; 95% CI, 1.19-1.51; high certainty) was associated with increased mortality while lower neighborhood socioeconomic status (aOR, 1.35; 95% CI, 1.29-1.41; moderate certainty) and lower income (aOR, 1.06; 95% CI, 1.01-1.11; aHR, 1.51; 95% CI, 1.01-2.25; moderate certainty) were probably associated with increased mortality. Less education (aOR, 1.33; 95% CI, 1.14-1.55; low certainty) and unemployment (aOR, 1.91; 95% CI, 1.00-3.63; low certainty) may be associated with increased mortality. CONCLUSIONS:We found that several indicators of SEP were associated with increased short-term mortality in patients with sepsis and septic shock. These findings underscore the need for routine collection of equity-relevant variables in sepsis research to inform health policy and support equitable care delivery. Given that some of these variables are potentially modifiable, targeted interventions may help improve outcomes and reduce disparities in disadvantaged populations.

INTRODUCTION:Optimal management for patients with acute pulmonary embolism (PE) at elevated risk of decompensation remains unclear given the lack of predictors and the limitations of existing risk stratification tools. Thus, we aimed to evaluate the prognostic association between clinical variables and short-term mortality in patients with acute PE. METHODS:Medline and EMBASE were searched from inception through 19 May 2025. We included English-language studies that described adult inpatients with a confirmed acute PE and evaluated prognostic factors associated with short-term mortality. Two authors performed citation screening and data extraction. Only adjusted OR were included in the data synthesis. We performed pooling using a random-effects model and inverse variance weighting. Risk of bias was evaluated using the Quality in Prognosis Studies tool. We assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. RESULTS:We included 70 studies involving 1 446 190 participants in our review. Variables with a moderate or high certainty association with short-term mortality in acute PE include increasing age, an elevated Pulmonary Embolism Severity Index (PESI) Score, an abnormal simplified PESI Score, an elevated heart rate, a reduced systolic blood pressure, a lower oxygen saturation, a higher respiratory rate, active malignancy, heart failure, chronic lung disease, an elevated troponin, a larger right ventricle (RV) to left ventricle ratio and evidence of RV dysfunction. DISCUSSION:We identified multiple variables associated with early mortality in acute PE. Notably, we demonstrate that RV function, a marker omitted from commonly used risk stratification tools, represents an important prognostic variable that is supported by multiple society guidelines. REGISTRATION:We registered the protocol with the Open Science Framework (https://osf.io/9w2jg).

RATIONALE:Venous thromboembolism (VTE) remains an important complication of critical illness, but contemporary population-level estimates of clinically recognized VTE and ICU-associated risk are limited. OBJECTIVES:To quantify 90-day VTE incidence in ICU vs non-ICU hospitalizations, estimate the adjusted association between ICU exposure and VTE, and identify factors associated with VTE within the ICU cohort. METHODS:We conducted a population-based cohort study using linked health administrative data in Ontario, Canada (ICES). We included patients aged ≥16 years and randomly selected one hospitalization per patient. ICU exposure was identified using discharge abstract special care unit codes. Clinically recognized VTE within 90 days was identified using ICD-10-CA diagnosis codes with confirmatory imaging/procedure codes in the same encounter or within ±7 days. We estimated cumulative incidence with death as a competing risk and fit cause-specific Cox models to estimate adjusted hazard ratios (aHRs), including an ICU-restricted model with ICU therapies and ICU length-of-stay. RESULTS:Among 4,821,130 index hospitalizations, 575,155 (11.9%) had ICU exposure. Ninety-day VTE occurred in 43,913 (0.9%) overall and was higher in ICU vs non-ICU hospitalizations (1.6% vs 0.8%; Gray's test P < 0.001). Hospitalizations involving ICU exposure were associated with higher VTE hazard after adjustment (aHR 1.38, 95% CI 1.34-1.43). In the ICU cohort, higher VTE risk was associated with prior VTE, cancer, recent surgery, prolonged ICU stay, extracorporeal membrane oxygenation, and traumatic brain injury. CONCLUSIONS:Hospitalizations involving ICU exposure were associated with higher 90-day clinically recognized VTE risk, and risk was concentrated in identifiable high-risk ICU subgroups, supporting risk stratification and risk-enriched future studies.

OBJECTIVES:To determine the relationships between subprophylactic anti-Xa levels and low-molecular-weight heparin (LMWH) thromboprophylaxis regimens with venous thromboembolism (VTE) risk, and to identify predictors of subprophylactic anti-Xa levels in critically ill adults. DATA SOURCES:Medline and Embase were searched from inception to May 7, 2025. STUDY SELECTION:We included studies enrolling critically ill adults receiving LMWH thromboprophylaxis and assessing the relationship between anti-Xa levels and risk of subprophylactic measurements associated with: 1) standard dosing strategies; 2) VTE risk; or 3) predisposing factors. DATA EXTRACTION:We extracted or calculated mean, sd , median, interquartile range, mean difference (MD), unadjusted odds ratios (uORs), and adjusted odds ratios (aORs), when available. Risk of bias was evaluated using Cochrane tools. We assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. DATA SYNTHESIS:We included 39 studies (7124 patients). The proportion of patients receiving LMWH prophylaxis achieving target anti-Xa levels was 47% (95% CI, 36-57%). Subprophylactic anti-Xa levels were associated with an increased risk of VTE (uOR, 2.87; 95% CI, 1.42-5.81; low certainty). Variables with a moderate certainty association with subprophylactic anti-Xa levels include male sex (aOR, 2.65; 95% CI, 1.07-6.56), increased weight (MD, 4.90 kg higher weight compared with those with target levels; 95% CI, 2.78-7.02), and elevated body mass index (MD, 1.36 per kg/m 2 higher compared with those with target levels; 95% CI, 0.64-2.09). CONCLUSIONS:Less than half of critically ill patients achieved their prophylactic anti-Xa targets despite LMWH thromboprophylaxis. Subprophylactic anti-Xa levels may be associated with an increased risk of VTE. Male sex, increased weight, and elevated body mass index have a moderate certainty association with developing subprophylactic anti-Xa levels. This study highlights the clinical importance of anti-Xa level monitoring in critically ill adults and the need for a future randomized controlled trial to further evaluate this topic.

Sepsis is a recognized risk factor for upper gastrointestinal bleeding, yet sepsis-specific randomized evidence informing stress ulcer prophylaxis remains limited. This protocol describes the rationale, methods, and statistical analysis plan for a post hoc subgroup analysis evaluating pantoprazole versus placebo in invasively ventilated critically ill adults with septic shock enrolled in the REVISE trial (NCT03374800). This study will be a post hoc extended subgroup analysis of the international, blinded, randomized REVISE trial, which enrolled 4821 mechanically ventilated adults in 68 ICUs across 8 countries. Patients were randomized to intravenous pantoprazole 40 mg once daily or placebo during invasive mechanical ventilation. Septic shock will be defined as receipt of vasopressors or inotropes at baseline together with an admitting diagnosis of infection according to APACHE III diagnostic categories. The primary efficacy outcome will be clinically important upper gastrointestinal bleeding in the ICU within 90 days after randomization, and the primary safety outcome will be all-cause mortality within 90 days. Additional trial outcomes will include patient-important upper gastrointestinal bleeding, ventilator-associated pneumonia, Clostridioides difficile infection during hospitalization, new renal replacement therapy, mortality in the ICU and hospital, and duration of ICU and hospital stay. Analyses will be adjusted for prehospital acid suppression; the mortality analyses will be additionally adjusted for APACHE II score. This protocol and statistical analysis plan describes an evaluation of the efficacy and safety of pantoprazole in patients with septic shock within a large randomized trial dataset. Trial Registration: ClinicalTrials.gov identifier: NCT03374800.

BACKGROUND AND AIMS:Patients with cancer and venous thromboembolism (VTE) have a high risk of recurrent VTE and anticoagulant-related bleeding. This study aimed to identify prognostic factors for these complications. METHODS:A systematic review was performed for randomized trials and cohort studies evaluating prognostic factors for recurrent VTE or anticoagulant-related bleeding in adult patients with cancer and VTE. Adjusted hazard ratios (aHRs) for factors were pooled using random-effects meta-analysis. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS:Thirty-three studies (n = 96 753) were included in the meta-analyses. Factors with high certainty of association with increased risk of recurrent VTE included a previous history of VTE [aHR 1.50 (95% CI 1.08-2.09)], Eastern Cooperative Oncology Group (ECOG) performance status >0 [1.81 (1.34-2.46)] or >1 [2.44 (1.55-3.84)], advanced cancer [1.38 (1.15-1.65)], and specific cancer sites including lung [1.78 (1.29-2.46)], hepatobiliary [2.37 (1.70-3.30)], pancreas [3.20 (2.06-4.96)], and genitourinary [1.38 (1.14-1.67)]. Conversely, recent surgery [aHR 0.56 (95% CI 0.40-0.76)] and breast cancer [0.43 (0.23-0.81)] had a high certainty of association with a decreased risk. Factors with a high certainty of association with an increased risk of anticoagulant-related bleeding included a history of bleeding [aHR 2.41 (95% CI 1.50-3.88)], ECOG performance status ≥2 [2.10 (1.48-2.99)], advanced cancer [1.60 (1.29-1.97)], and cancers of the brain [2.25 (1.64-3.09)], gastrointestinal system [1.74 (1.44-2.11)], genitourinary system [1.90 (1.48-2.45)], and prostate [1.72 (1.26-2.34)]. CONCLUSIONS:The prognostic factors identified in this meta-analysis should be considered as part of risk stratification frameworks for anticoagulation management in patients with cancer and VTE.

BACKGROUND:Little is known about end-of-life trajectories in survivors of cardiogenic shock complicating acute myocardial infarction (AMI-CS) who die beyond their index admission, or utilization of palliative care services in AMI-CS survivors. OBJECTIVES:This study aimed to examine long-term palliative and end-of-life care among AMI-CS survivors. METHODS:This was a population-based, retrospective cohort of AMI-CS survivors in Ontario, Canada, from 2009 to 2020 who died during longitudinal follow-up. RESULTS:We identified 3,881 AMI-CS survivors (2009-2020) who died after discharge and before March 2024. The median survival time was 1,096 days (IQR: 312-2,139 days). Overall, 2,100 patients (54.1%) died in acute care, with no difference between those who did and did not receive palliative care. Patients who did not receive palliative care were more likely to die in intensive care units (ICU) than those who did (23% vs 17%, absolute standard difference 0.15). Most patients received palliative care in the final year of life (n = 2,485, 64%); 1,057 patients (42.5%) had outpatient visits, 505 patients (20.3%) had inpatient palliative care consultations, and 327 patients (13.2%) had palliative care hospitalizations. Palliative care, however, was most commonly initiated in the last 14 days of life (1,185 patients, 47.7%). Earlier palliative care referrals were associated with reduced rates of dying in hospital (adjusted OR: 0.50; 95% CI: 0.42-0.65) and ICU (adjusted OR: 0.34; 95% CI: 0.26-0.45). CONCLUSIONS:Early and intermediate term palliative care involvement was associated with reduced risk of death in hospital and ICU. Such consultation may improve end-of-life outcomes in AMI-CS survivors.

Background Corticosteroid use in septic shock remains variable in clinical practice. Uncertainty persists regarding the role of fludrocortisone. Research Question What are current clinician self-reported practices and beliefs about optimal corticosteroid use in septic shock? Study Design and Methods We conducted a cross-sectional survey of critical care practitioners within the Society of Critical Care Medicine and the Canadian Critical Care Society from May through August 2025 to characterize current self-reported practices and beliefs regarding optimal corticosteroid regimens and the need for further randomized controlled trials for corticosteroid regimens in critical illness. Results We found 14,814 individuals to be eligible for the survey. The survey response rate was 5.8% (n = 861). Most respondents (87%) were from the United States; 33 countries were represented. A diversity of practice type, clinical role, base specialty, and years of experience was reported. Thirty-nine percent of respondents reported always or almost always prescribing corticosteroids for vasopressor-dependent septic shock, and 12% of respondents always or almost always coprescribed fludrocortisone. Seventy-six percent of respondents use a threshold such as ≥ 0.1 to 0.25 μg/kg/min norepinephrine equivalents as a trigger to initiate corticosteroids. A wide range of beliefs in the efficacy or nonefficacy of both glucocorticoids and mineralocorticoids was reported. Most respondents (91%) were receptive to future randomized trials examining the role of fludrocortisone in patients with acute hypoxemic respiratory failure with or without sepsis. Interpretation Our results show that substantial variability exists in self-reported practices and beliefs regarding optimal corticosteroid regimens. Future investigations should evaluate factors for decision-making in prescribing corticosteroids for patients with septic shock.

BACKGROUND:Septic shock is associated with high mortality rates ranging from 30% to 50%. In this systematic review and meta-analysis, we aimed to identify prognostic factors of early mortality in septic shock. METHODS:A systematic review and meta-analysis of prognostic factors associated with early mortality in septic shock was performed. MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from database inception to Aug 13, 2025, were searched. All observational and randomised controlled trial studies that evaluated prognostic factors and early mortality (in-hospital or up to 31-days) in septic shock were included. Studies were excluded if they evaluated children or were post-mortem studies. Title and abstracts were reviewed by two independent reviewers. Summary data were extracted from published reports. The primary objective was to evaluate prognostic factors associated with mortality, reported as adjusted odds ratios (OR) using generic inverse variance method and random effects model and variables were significant if the p value was less than 0·05. This study was registered with Open Science Framework (OSF: 10.17605/OSF.IO/75H4G). FINDINGS:Of 6814 records identified by our search, 1420 articles were assessed for full-text review, of these, 95 studies of 4 831 379 patients were included. Of 95 included studies, 90 (95%) were observational studies and five (5%) were randomised controlled trials. In 4 831 379 patients, the mean age was 64 years, 58% of participants were male, 42% were female, and early hospital mortality occurred in 1 606 384 patients (33·2% [IQR 29·5-37·3]). Patient factors significantly associated with increased mortality included increasing age (adjusted OR 1·02 per 1 year [95% CI 1·01-1·02; I2 =64%; moderate certainty), Black race (1·23 [1·21-1·25]; I2 =0%; moderate certainty), hepatic cirrhosis (1·85 [1·64-2·08]; I2 =0%; high certainty), malignancy (1·43 [1·09-1·88]; I2 =91%; high certainty), and increased Charlson comorbidity index (1·22 per point [1·19-1·25]; I2 =0%; high certainty). Presentation factors associated with increased mortality included acute kidney injury (1·88 [1·32-2·68]; I2 =86%; high certainty) and higher severity-of-illness scores, including Acute Physiology and Chronic Health Evaluation II score (1·10 per point increase [1·08-1·12]; I2 =60%; high certainty), Simplified Acute Physiology Score II (1·08 per point increase [1·06-1·09]; I2 =0%; high certainty), and Sequential Organ Failure Assessment (1·21 per point increase [1·15-1·28]; I2 =66%; high certainty). Treatment and biochemical factors associated with increased mortality included invasive mechanical ventilation (2·12 [1·00-4·51]; I2 =86%; moderate certainty), norepinephrine use (3·60 [2·73-4·74]; I2 =0%; high certainty), and elevated serum lactate (1·13 per 1 mmol/L [1·01-1·26]; I2 =72%; high certainty). INTERPRETATION:This systematic review and meta-analysis identified prognostic factors associated with early mortality in septic shock. The identification of these prognostic factors could aid in clinical risk application, goals of care discussions, and identifying the subset of patients at highest and lowest risk of early mortality for patients with septic shock. FUNDING:None.

Critical illness is characterized by a catabolic, proinflammatory state. Anabolic agents, such as testosterone, have therefore been proposed as therapeutic targets. Our objectives were to assess the effects of testosterone in critically ill populations on patient-important outcomes and identify design limitations to inform future studies. We searched for randomized control trials (RCTs) through Medline, Embase, and EBM Reviews databases from inception through February 24, 2026, including English language articles enrolling adults (≥18 years) admitted to ICU where anabolic androgen therapies (AAT) were compared with placebo or standard of care. Studies had to report at least one of: mortality, ICU and hospital lengths of stay, or duration of mechanical ventilation. We extracted data independently using a standardized data extraction tool, and feedback was received from all co-authors to ensure agreement. For each outcome, we performed meta-analyses using a random-effects model with inverse variance weighting in RevMan. We used the GRADE approach to assess certainty in pooled estimates of effect. Of 1325 screened articles, we found 4 that fit our inclusion criteria. Together, we judged risk of bias as 'some concerns' in 3 trials and 'high' in the final trial, and ultimately found that the effects of anabolic-androgen therapy on patient-important outcomes uncertain. With the uncertainty of current evidence for the effects of anabolic-androgen therapy in critically ill adults, there is insufficient support for its routine use. Future randomized evidence is needed to determine whether anabolic-androgen therapy improves clinically-important outcomes and better define its safety profile in critically ill adults.

Aims:Prediction of future deterioration in emergency department patients with infection is difficult, and existing prognostic tools are inaccurate. We evaluated the feasibility of deployment of a clinical decision support tool, Sepsis Advisor, which utilizes heart rate variability and laboratory values to predict future deterioration in emergency department patients with treated infection. Methods:This study was an observational, prospective, Pilot Phase 1 feasibility implementation study involving two sites within a single academic health sciences centre. Then, 71 patients were enrolled, all with suspected/treated infection and systemic inflammatory response. Patients underwent 30 min of electrocardiograph recording. The generated predictive model and Sepsis Advisor report were shown to physicians observationally, > 48 h after clinical encounter, while assessing perceived usability, value, barriers and drivers with using the tool through interviews with nurses and physicians. Results:Of the 71 patients enrolled, 65 (92%) had adequate duration of heart rate variability measurements to generate a predictive model (average recording: 25 ± 7 min); 100% had clinical data entry. Creatinine, lactate, and INR were drawn 97%, 56%, and 28% of the time and were incorporated into predictive models. Physician and nurse reported drivers for use included potential to facilitate communication, improve care, and ease of integration. Barriers included the need to understand and interpret results from the tool, time constraints, changing routines, and gaining buy-in. User-centered feedback informed four improved versions of the tool. Conclusions:Observational deployment of a heart rate variability-based clinical decision support tool within the emergency department is feasible and perceived to have the potential to improve care.

OBJECTIVES:To identify factors associated with short-term mortality among patients receiving microaxial flow pump (mAFP) therapy for acute myocardial infarction-related cardiogenic shock (AMI-CS). DATA SOURCES:We searched four databases (MEDLINE, Embase, CENTRAL, and Scopus) from January 1, 2004, to January 1, 2025. STUDY SELECTION:We selected English-language studies that included adults with AMI-CS receiving mAFP and evaluated factors associated with short-term mortality. We excluded patients receiving concurrent venoarterial extracorporeal membrane oxygenation, as well as studies that solely included patients presenting with out-of-hospital cardiac arrest. DATA EXTRACTION:Two authors performed citation screening and data extraction. For each factor evaluated in at least two studies, we performed meta-analyses of adjusted odds ratios (aORs) using a random-effects model. Risk of bias was evaluated using the Quality in Prognosis Studies tool, and the certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. DATA SYNTHESIS:Our primary analysis included 18 studies, encompassing 20,617 patients. Median short-term mortality across studies was 50.7% (interquartile range 38.4-55.3%). Factors associated with short-term mortality based on high-certainty evidence included: increased age (aOR, 1.04 per year [95% CI, 1.03-1.05 per year] or ≥ 65 yr (aOR, 2.42 yr [95% CI, 0.77-7.64 yr]), female sex (aOR, 1.26 [95% CI, 1.09-1.45]), higher body mass index (aOR, 1.05 per point [95% CI, 1.04-1.07 per point]), higher heart rate (aOR, 1.02 per beats/min [95% CI, 1.01-1.02 per beats/min]), higher serum creatinine (aOR, 1.35 per mg/dL [95% CI, 1.08-1.70 per mg/dL]), mechanical ventilation (aOR, 2.53 [95% CI, 1.82-3.53]), vasopressors (aOR, 1.52 [95% CI, 1.11-2.08] for any vasopressors and aOR, 1.37 [95% CI, 1.18-1.58] per each vasopressor), presentation with ST-elevation myocardial infarction (aOR, 1.59 [95% CI, 1.11-2.26]), cardiac arrest (aOR, 2.85 [95% CI, 2.22-3.64]), and hypoxic-ischemic brain injury (aOR, 5.36 [95% CI, 3.03-9.47]). CONCLUSIONS:We identified several prognostic factors associated with short-term mortality in AMI-CS patients receiving mAFP support. This work may help inform clinicians, patients, and families regarding utilization of mAFP in AMI-CS.

BACKGROUND:Patients with a transient ischemic attack (TIA) or minor stroke have an increased risk of subsequent stroke that persists for at least 10 years. We aimed to identify prognostic factors associated with long-term risk of stroke in this patient group, and estimate their population attribution fraction (PAF). METHODS:A systematic review was performed of MEDLINE, Embase, and Web of Science for cohort studies including patients with TIA or minor stroke that evaluated factors for subsequent stroke over a follow-up period of ≥1 year. We pooled hazard ratios adjusted for relevant confounders using random-effect meta-analysis and determined the PAF of factors based on their pooled prevalence and adjusted hazard ratio (aHR). We assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study is registered in PROSPERO (CRD42023476551). RESULTS:From 14 732 identified citations, we included 28 cohort studies comprising 86 810 patients with TIA or minor stroke (median age, 69 years [IQR, 65-71]; 52-60% male patients). Factors that had high certainty evidence of association with increased long-term risk of stroke included older age (aHR 1.04 per year increase, 95% CI 1.02-1.05), male sex (1.25, 1.15-1.36; PAF 13.0%, 95% CI 7.8-18.7), atrial fibrillation (1.34, 1.18-1.52; 3.8%, 95% CI 0.3-9.9), diabetes mellitus (1.52, 1.32-1.75; 7.7%, 3.1-14.1), hypertension (1.60, 1.31-1.94; 19.3%, 8.4-31.6), ischemic heart disease (1.67, 1.28-2.18; 10.7%, 2.8-22.9), history of stroke or TIA before the index event (1.70, 1.43-2.02; 12.0%, 5.2-21.4), smoking (1.29, 1.05-1.60; 11.2%, 1.0-30.7), ABCD2 score of ≥4 (1.59, 1.31-1.94; 18.0%, 2.9-39.9), presence of acute infarct on neuroimaging (1.97, 1.41-2.74; 19.0%, 5.2-38.9) including diffusion-weighted imaging positive lesions (1.86, 1.02-3.37; 14.0%, 7.0-25.0), minor stroke as index event (1.75, 1.35-2.27 vs TIA; 28.0%, 10.2-47.6), presentation with aphasia or dysarthria (1.45, 1.24-1.69; 19.2%, 0.2-53.1), presentation with paresis (1.45, 1.15-1.84; 22.0%, 3.8-43.4), and etiologic stroke subtypes including cardioembolism (2.16, 1.53-3.05; 14.6%, 3.1-33.5), large artery atherosclerosis (2.19, 1.68-2.86; 13.2%, 5.1-25.5), and small vessel disease (1.69, 1.14-2.49; 16.8%, 5.0-34.3). CONCLUSIONS:These findings can help identify patients with a particularly enduring risk of stroke who are most likely to benefit from ongoing monitoring and treatment, and facilitate the development and implementation of targeted stroke prevention strategies.

OBJECTIVES:Summarize the prognostic performance of existing clinical prediction models (CPMs) for neuroprognostication after out-of-hospital cardiac arrest (OHCA). DATA SOURCES:We searched Medline and Embase databases from inception to June 1, 2025. STUDY SELECTION:We selected English-language studies that included adults with OHCA and evaluated a CPM for the prediction of poor functional outcome. We excluded derivation cohorts for prognostic scores and excluded models without at least two external validation cohorts. DATA EXTRACTION:Two authors performed citation screening and data extraction. Where possible, we pooled the sensitivity and specificity of poor functional outcome, and the area under the receiver operating characteristic curve (AUROC) values for each CPM. We assessed risk of bias using the Prediction model study Risk of Bias Assessment Tool, and rated the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation. DATA SYNTHESIS:We included 39 observational cohorts (95,037 patients) evaluating 11 different CPMs, with the two most common scores being the OHCA and Cardiac Arrest Hospital Prognosis (CAHP) scores. An OHCA score greater than or equal to 17 had a pooled sensitivity of 81.8% (95% CI, 65.8-91.4%) and specificity of 74.2% (95% CI, 58.8-85.3%), while a score of greater than or equal to 32 had a pooled sensitivity of 64.9% (95% CI, 44.0-81.3%) and specificity of 89.5% (95% CI, 75.9-95.8%) for poor functional outcome (low certainty). A CAHP score greater than or equal to 150 had a pooled sensitivity of 81.3% (95% CI, 77.7-84.4%) and specificity of 77.0% (95% CI, 70.6-82.4%) for poor functional outcome (moderate certainty). Pooled AUROCs across the 11 CPMs varied from 0.75 to 0.88, with substantial heterogeneity. CONCLUSIONS:CPMs for neuroprognostication after OHCA demonstrate only moderate accuracy, with substantial heterogeneity across validation cohorts. These limitations restrict their clinical utility, particularly for irreversible decisions such as withdrawal of life-sustaining therapy.

OBJECTIVES:Most ICUs use protocolized magnesium supplementation, yet the clinical effect of this practice is unknown. DESIGN:Pseudo-randomized retrospective study comparing patients who were and were not assigned to receive magnesium supplementation, using a protocol where supplementation occurs when serum levels are less than or equal to 0.95 mmol/L (2.31 mg/dL). Primary outcome was atrial fibrillation or flutter within 24 hours. Secondary outcomes were tachyarrhythmia (supraventricular tachycardia or ventricular arrhythmia) and death within 24 hours. SETTING:ICUs with a shared magnesium supplementation protocol, in five hospitals in Ontario, Canada, from January 1, 2022, to December 31, 2024. PATIENTS:Adults (18 yr old or older) admitted to ICU with a magnesium protocol order, at their first magnesium level of 0.92-0.99 mmol/L (2.24-2.41 mg/dL). To minimize confounding, we included only patients with a level near the supplementation threshold. INTERVENTIONS:None. EXPOSURE:Magnesium level 0.92-0.95 mmol/L (2.24-2.31 mg/dL, supplementation group) vs. 0.96-0.99 mmol/L (2.32-2.41 mg/dL, no supplementation group). MEASUREMENTS AND MAIN RESULTS:We identified 4198 patients; median age 70 years, 41% female, 39% invasively ventilated; 2144 (51%) in the supplementation group, of whom 77% received magnesium, and 2054 (49%) in the no supplementation group, of whom 9% received magnesium. Atrial fibrillation or flutter occurred within 24 hours in 355 (16.6%) in the supplementation group and 375 (18.3%) in the no supplementation group. Bayesian logistic regression, adjusted for hospital, showed a 1.6% absolute risk reduction associated with supplementation (95% credible interval, 3.8% reduction to 0.8% increase; probability of reduction, 0.91). For the composite outcome of atrial fibrillation and flutter, tachyarrhythmia, and death, the absolute risk reduction associated with supplementation was 2.2% (CrI, 4.3% reduction to 0.1% increase; probability of risk reduction, 0.97). CONCLUSIONS:Protocolized magnesium supplementation at a threshold of 0.95 mmol/L (2.31 mg/dL) may be associated with reduced 24-hour incidence of atrial fibrillation and flutter in critically ill patients.

The presence and severity of acute kidney injury (AKI) upon ICU admission provides important short- and long-term prognostic information. Existing reports have been limited by inadequate baseline kidney function assessment, incomplete outcome capture, limited adjustment for illness severity, and small sample sizes. We conducted a population-level study of all adult (≥ 18 years) Ontario, Canada residents with available outpatient baseline creatinine measurements admitted to the ICU from 2009–2021. AKI at the time of ICU admission was determined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Outcomes included death and kidney replacement therapy (KRT). Multivariable logistic regression modeling was used to estimate adjusted odds ratios (aOR). The study cohort included 484,956 adults (43

Introduction High quality randomized controlled trials (RCTs) are essential for evaluating the efficacy and safety of interventions in trauma care, but their external validity is often limited by restrictive eligibility criteria and challenges with obtaining timely informed consent. To assess the eligibility criteria and consent practices of RCTs involving trauma patients, with a focus on the justification of exclusion criteria and the consideration of sociodemographic characteristics. Methods We conducted a systematic review of RCTs involving adult trauma patients, searching Medline and Embase from January 1, 2000 through April 11, 2025. We assessed eligibility criteria independently and in duplicate as strongly, potentially, or poorly justified based on prespecified criteria. We also evaluated the inclusion of PROGRESS-Plus sociodemographic characteristics and various consent approaches that were used. Results Of 1839 citations, we included 55 eligible RCTs. Among these studies, we identified 302 unique exclusion criteria, of which 247 (82%) were strongly or potentially justified. Age restrictions and pregnancy or lactation exclusions were common; poorly justified criteria most often involved unexplained age thresholds or pregnancy/lactation exclusions without a trial-specific safety rationale. Approximately two thirds of patients screened were ineligible for inclusion. Among PROGRESS-Plus factors, only age and sex were consistently reported as part of baseline characteristics. Consent approaches differed across studies, with the majority (62%) of trials obtaining consent from patients or their substitute decision-makers. Besides studies using waivers of consent (16%), consent was most frequently obtained a priori (67%), with a further 11% not reporting their method of consent and 6% using deferred consent. Conclusions Trauma RCTs can exclude patients based on poorly justified criteria, thereby limiting external generalizability. Greater transparency and inclusivity with regards to eligibility criteria, as well as systematic approaches to consent are necessary to improve the applicability of trauma research.