BACKGROUND:Whether sedative prescriptions after hospital admissions are associated with poor patient outcomes is unknown. We sought to determine the incidence and risk of adverse events associated with sedatives in older adults within 30 days after hospital discharge. METHODS:We conducted a population-based cohort study involving older adults (age ≥ 66 yr) discharged alive from hospital in Ontario (2003 to 2023). We assessed the association of sedative prescriptions (benzodiazepines, antidepressant sedatives, or antipsychotics) filled within 7 days after discharge with falls (with or without fracture), emergency department (ED) visits, and hospital readmission. We used cause-specific proportional hazard regression for outcomes other than death and Cox proportional hazard models for death to assess the association between a sedative prescription filled after discharge and the outcomes. Because of an interaction with prehospital sedative prescription, we stratified results for prehospital sedative-naive and sedative-exposed status. RESULTS:Among 1 868 484 older adults (mean age 77 yr, 52.1% female), 13.2% filled a sedative prescription after discharge; of these patients, 31.0% were sedative naive before hospital admission. Falls occurred in 1.6% (n = 30 626), ED visits in 21.3% (n = 397 402), hospital readmissions in 12.4% (n = 231 191), and death in 3.8% (n = 70 661). The adjusted hazard ratio (HR) for all outcomes was increased among those who filled a sedative prescription after discharge (v. no filled prescription) and were sedative naive before hospital admission (fall: 1.20, 95% confidence interval [CI] 1.13 to 1.26; ED visit 1.20, 95% CI 1.19 to 1.22; hospital readmission: 1.20, 95% CI 1.17 to 1.22; and death: 1.78, 95% CI 1.73 to 1.83). For those who were exposed to sedatives before their hospital admission, there was an increased hazard of death (adjusted HR 1.08, 95% CI 1.05 to 1.11), but not for the other outcomes. For sedative-naive older adults, benzodiazepines were associated with an increased hazard of all outcomes, antipsychotics were associated with an increased hazard of falls and death, and antidepressant sedatives were associated with a decreased hazard of falls. INTERPRETATION:New sedative prescriptions filled within 7 days after discharge were associated with increased hazards of a fall, ED visit, hospital admission, and death within 30 days after discharge, with differences based on the sedative class. These findings have important implications for in-hospital medication review and falls-risk assessment for older adults in Canada.

OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects (benefits and harms) of catheter retention (or delayed removal after an initial catheter retention strategy) compared to prompt catheter replacement or removal in people of all ages with a short- or long-term central venous catheter or any arterial catheter, and either (i) catheter-related or -associated infection, (ii) bloodstream infection from an uncertain source or (iii) sepsis from an uncertain source.

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.

Aims: To examine the relationship between surgical treatment type (acute total hip arthroplasty (THA) vs open reduction and internal fixation (ORIF)) and in-hospital medical complications in older adult trauma patients with operatively managed acetabulum fractures. Methods: We conducted a retrospective cohort study of patients aged ≥ 50 years who presented to institutions participating in the Trauma Quality Improvement Program between 1 January 2017 and 31 December 2022, and who underwent acetabulum fracture surgery within three weeks of admission. Our primary outcome was the development of in-hospital medical complications. Secondary outcomes included each medical complication alone, hospital length of stay, and discharge disposition. Acute THA patients were matched 1:1 without replacement to patients treated with ORIF on the logit of the propensity score using a greedy nearest-neighbour matching algorithm. Generalized estimating equations were used to calculate percent absolute risk differences with 95% CIs for categorical outcomes in the propensity score-matched sample. Wilcoxon signed-rank tests were used compare within pair differences in continuous outcomes. Results: A total of 10,213 patients were included in our study, of which 1,226 (12%) were treated with an acute THA and 8,987 (88%) were treated with ORIF. A total of 1,223 acute THA patients were matched to 1,223 ORIF patients. After matching, there were no meaningful differences in any baseline characteristics between the two treatment groups. There was no difference in the risk of in-hospital complications between patients treated with acute THA (216/1,223 (17.7%) vs patients who were treated with ORIF (201/1,223 (16.4%)) (absolute risk difference 1.23%, 95% CI -1.71 to 4.17, p = 0.414). There were no significant differences in the risk of each complication, length of stay, or discharge disposition. Conclusion: Our results suggest that acute THA and ORIF demonstrate similar risks of postoperative medical complications among older patients with acetabular fractures. Cite this article: Bone Jt Open 2026;7(5):643–650.

OBJECTIVES:To study the prevalence and characteristics of outcome switching, the completeness of outcome prespecification, and factors associated with outcome switching in observational cohort studies of interventions. DESIGN:Longitudinal meta-epidemiological study. SETTING:Registry records and journal publications. PARTICIPANTS:Controlled cohort studies investigating the effects of interventions. Eligible studies were registered on ClinicalTrials.gov within one month of their start date (2014-16) and had published results in peer reviewed journals by 2024. MAIN OUTCOMES MEASURES:Firstly, proportion of studies with outcome switching identified by comparing the prespecified outcomes in the registry and those reported in the journal publication of results. Discrepancies were categorised as omission (prespecified primary outcomes not reported), downgrading (prespecified primary outcomes reported as non-primary), upgrading (prespecified non-primary outcomes reported as primary), and introduction of new primary outcomes (not registered as an outcome). Secondly, proportion of studies with completely prespecified primary outcomes, defined as registry entries that include the measurement variable, analysis metric, method of aggregation (the statistic summarising the outcome within each study group), and time point. RESULTS:Of 9965 registration records screened, 124 eligible studies with results published between 2015 and 2024 were included. Only 30 studies (24%) completely prespecified their primary outcomes. Outcome switching occurred in 60 (48%) studies, but only two provided an explanation. The most common types of switching were omission (n=32, 26%) and downgrading (n=32, 26%), followed by the introduction of new primary outcomes (n=25, 20%), and upgrading (n=2, 2%). Among 57 studies with outcome switching other than omission (ie, outcome results were reported), statistically significant results were favoured in 77% (44/57) by introducing or upgrading a new significant primary outcome or downgrading a non-significant one. No study characteristics were significantly associated with outcome switching in multivariable logistic regression. CONCLUSIONS:Outcome switching and inadequate outcome prespecification were common in cohort studies of interventions. Most changes were unexplained and favoured statistically significant results, raising concerns about potential selective reporting and highlighting the need for improved transparency in outcome reporting. STUDY REGISTRATION:Open Science Framework (https://osf.io/xn5zt/).

OBJECTIVE:To provide national data on intensivist coverage and interprofessional team staffing in Canadian ICUs. DESIGN:Cross-sectional survey. SETTING:All Canadian hospitals identified as potentially having an adult ICU. SUBJECTS:ICU nurse/physician leaders. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We contacted ICU nurse/physician leadership by email. The questionnaire included questions about interprofessional ICU staffing, availability and roles. Questionnaires were administered from September 2024 to February 2025; data were cleaned and analyzed February to May 2025. We included responses from 137 unique adult ICUs in 123 hospitals (40.9% of 301 hospitals queried), representing all Canadian provinces and territories with ICUs. ICU size varied (median [interquartile range]: 14 beds [8, 20]); most were for mixed patient populations (123 [89.8%]) and had intensivist coverage (119 [86.9%]). Among units with intensivists, they were onsite 24 hr/d in 28/119 (23.5%), and intensivists had simultaneous responsibilities outside the ICU in 47/119 (39.5%). Physicians-in-training were present on weekdays in 112/137 units (81.8%) and advanced practice providers (APPs) in 32/136 (23.5%). For mechanically ventilated patients, the nurse:patient ratio was most commonly 1:1 (66.7%). Respiratory therapists were available on weekdays in 133/137 (97.1%), clinical pharmacists in 123/136 (90.4%) and physical therapists in 126/134 (94.0%). CONCLUSIONS:Most Canadian adult ICUs were staffed by intensivists with less than 25% having onsite intensivist coverage 24 hr/d. Physicians-in-training were present in the majority of ICUs, whereas APPs were uncommon. Nurses most commonly provided care for one mechanically ventilated patient each shift. These data establish contemporary staffing benchmarks to inform assessment of baseline ICU workforce needs and guide surge planning at local, provincial, and national levels. They also enable international comparisons and provide essential context for interpreting Canadian critical care research.

Importance:The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) trial showed that 7 days of antibiotics was noninferior to 14 days among patients with bacteremia. However, it is unknown whether patients with high serum procalcitonin (PCT) level at day 7 of therapy would benefit from a prolonged treatment course. Objective:To investigate whether an elevated serum PCT level at day 7 of bacteremia was associated with increased mortality among patients treated with 7 vs 14 days of antibiotics. Design, Setting, and Participants:This cohort study was a planned secondary analysis of the BALANCE trial from 2014 to 2023, a multicenter randomized clinical trial where serum was collected on day 7 of bacteremia and patients were followed up for 90 days after study enrollment. Serum samples were collected from patients 7 days after initiation of antibiotics; PCT levels were later quantified by an antibody-based assay and therefore were not available to clinicians. Data were analyzed from January to June 2025. Intervention:Patients were randomized to receive either 7 or 14 days of antibiotics. Antibiotic selection, dosing, and route were at the discretion of the treating team. Main Outcomes and Measures:The primary outcome was defined as death from any cause within 90 days of the positive index blood culture result. Secondary outcomes included death by any cause while admitted to the ICU, death by any cause while admitted to the hospital, number of days alive and not admitted to the ICU within 28 days of the index positive blood culture, number of days alive and not admitted to hospital within 28 days of the index positive blood culture, and the duration of mechanical ventilation. Results:A total of 125 patients (median age 63, [IQR, 58-79] years; 80 [64.0%] male) were included in this study. Sixty-five participants (52%) had low PCT levels (<250 pg/mL) and 60 (48%) had high PCT levels (≥250 pg/mL) on day 7. The high PCT group was older, had more comorbidities, and had a higher prevalence of community-acquired bacteremia. Ninety-day mortality was higher in the high vs low PCT group: 21.6% (13 of 60) vs 6.2% (4 of 65) (absolute risk difference [ARD] 15.5%; 95% CI, 3.6%-27.5%). Among patients with high PCT level, 90-day mortality was not different among participants with 7 vs 14 days of antbiotics (ARD, -19.9%; 95% CI, -1.7 to 41.7). Conclusions and relevance:In this cohort study, elevated PCT level on day 7 was associated with increased 90-day mortality. However, prolonging antibiotics beyond 7 days was not associated with improved mortality in patients with a residually high PCT level. Seven days of antibiotics appears sufficient for most patients with bloodstream infections independent of day 7 serum PCT level.

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.

INTRODUCTION:Vasopressors are essential medications used in the intensive care unit (ICU) to maintain blood pressure in patients with life-threatening hypotension. While vasopressors can be lifesaving, they carry potential risks, such as reducing blood flow to certain organs and increasing the work that the heart must do to pump blood to the body. Despite their frequent use, little is known about how patients, families, and the public perceive the benefits and risks of vasopressor therapy. OBJECTIVES:The objective of this study was to explore perspectives of former ICU patients, their families, and the public on the use, and benefits, and risks of vasopressor therapy in the ICU. METHODS:We conducted a qualitative study using interviews and focus groups with 25 participants: nine former ICU patients (36%), eight family members (32%), and eight public members (32%). Participants received education on hypotension and vasopressor use before discussions. Topics included factors influencing willingness to receive vasopressors, perceived benefits and risks, and priority outcomes. Data were analysed using inductive content analysis. RESULTS:Perspectives were influenced by three contextual factors: (i) level of consciousness during vasopressor administration; (ii) pre-existing health conditions or medications; and (iii) life stage. Willingness to undergo therapy was shaped by a focus on stabilisation and survival, perceived low risk of side effects, belief that side effects could be managed, and trust in clinicians. Participants also expressed concerns about social, physical, and mental wellbeing challenges following vasopressor therapy. CONCLUSIONS:While vasopressors were broadly accepted as lifesaving, participants emphasised the importance of aligning treatment decisions with long-term outcomes. Many of the themes identified overlap with general ICU survivorship concerns, highlighting the need for improved communication about risks and benefits and patient-centred discussions regarding ICU therapies and post-ICU outcomes.

Importance The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) trial showed that 7 days of antibiotics was noninferior to 14 days among patients with bacteremia. However, it is unknown whether patients with high serum procalcitonin (PCT) level at day 7 of therapy would benefit from a prolonged treatment course. Objective To investigate whether an elevated serum PCT level at day 7 of bacteremia was associated with increased mortality among patients treated with 7 vs 14 days of antibiotics. Design, Setting, and Participants This cohort study was a planned secondary analysis of the BALANCE trial from 2014 to 2023, a multicenter randomized clinical trial where serum was collected on day 7 of bacteremia and patients were followed up for 90 days after study enrollment. Serum samples were collected from patients 7 days after initiation of antibiotics; PCT levels were later quantified by an antibody-based assay and therefore were not available to clinicians. Data were analyzed from January to June 2025. Intervention Patients were randomized to receive either 7 or 14 days of antibiotics. Antibiotic selection, dosing, and route were at the discretion of the treating team. Main Outcomes and Measures The primary outcome was defined as death from any cause within 90 days of the positive index blood culture result. Secondary outcomes included death by any cause while admitted to the ICU, death by any cause while admitted to the hospital, number of days alive and not admitted to the ICU within 28 days of the index positive blood culture, number of days alive and not admitted to hospital within 28 days of the index positive blood culture, and the duration of mechanical ventilation. Results A total of 125 patients (median age 63, [IQR, 58-79] years; 80 [64.0%] male) were included in this study. Sixty-five participants (52%) had low PCT levels (<250 pg/mL) and 60 (48%) had high PCT levels (≥250 pg/mL) on day 7. The high PCT group was older, had more comorbidities, and had a higher prevalence of community-acquired bacteremia. Ninety-day mortality was higher in the high vs low PCT group: 21.6% (13 of 60) vs 6.2% (4 of 65) (absolute risk difference [ARD] 15.5%; 95% CI, 3.6%-27.5%). Among patients with high PCT level, 90-day mortality was not different among participants with 7 vs 14 days of antbiotics (ARD, −19.9%; 95% CI, −1.7 to 41.7). Conclusions and relevance In this cohort study, elevated PCT level on day 7 was associated with increased 90-day mortality. However, prolonging antibiotics beyond 7 days was not associated with improved mortality in patients with a residually high PCT level. Seven days of antibiotics appears sufficient for most patients with bloodstream infections independent of day 7 serum PCT level.

BACKGROUND AND OBJECTIVES:Immigration status is associated with stroke incidence and outcomes; however, its association with admission to and length of stay in the intensive care unit (ICU) in patients with stroke is unknown. We aimed to determine the association between immigration status and intensity of ICU care among patients with ischemic stroke. METHODS:We conducted a population-based retrospective cohort study of adults hospitalized for ischemic stroke in Ontario, Canada, between April 1, 2014, and March 30, 2023. People born outside Canada and who arrived after 1985 were defined as immigrants. We reported rates of thrombolysis, thrombectomy (reperfusion treatments), ventilatory support, and feeding tube insertion in immigrants and long-term residents. We calculated adjusted odds ratios (aOR) of ICU admission using logistic models and adjusted risk ratios (aRR) of longer ICU stays using negative binomial models, comparing immigrants with long-term residents, in the entire cohort and among those who did not receive reperfusion treatments. RESULTS:Of 85,507 patients included (45% female), 12.9% were immigrants. Immigrants were younger (median age 69 years vs 76 years, standardized difference = 0.38), had lower stroke severity and rates of reperfusion, and had higher rates of life-sustaining treatments compared with long-term residents. Immigrants had similar odds of ICU admission compared with long-term residents (18.2% vs 19.7%; aOR 0.97; 95% CI 0.91-1.04), but their ICU stays were longer (mean 5.6 ± 18.5 days vs 3.8 ± 7.7 days; aRR 1.30; 1.13-1.48) in the adjusted models, and this remained the case for those who did not receive reperfusion treatments (length of stay; aRR 1.27; 1.09-1.49). These associations did not vary by whether a hospital cared for a higher-than-median proportion of immigrants across all hospitals. Immigrants who came as refugees, and those who came from Africa, East Asia, and the Middle East, had longer ICU stays than long-term residents. DISCUSSION:Immigrant ischemic stroke patients have similar ICU admission rates, but longer ICU stays. The longer ICU stays among immigrant stroke patients may in part be driven by higher rates of life-saving treatments; however, the impact of these differences on the long-term functional outcomes remains to be studied.

BACKGROUND CONTEXT:Optimal timing of pharmacologic thromboprophylaxis in patients with acute traumatic spinal cord injury (SCI) is unclear. Most guideline recommendations are consensus-based and lacking in primary large-scale data. This study evaluated an ideal timeframe for delivery of thromboprophylaxis in acute SCI. PURPOSE:Determine the ideal timeframe for initiation of chemical thromboprophylaxis in the setting of acute SCI. STUDY DESIGN/SETTING:Retrospective cohort study. North American trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program (2017-2022). PATIENT SAMPLE:Adults (≥16 years) with acute SCI secondary to blunt trauma who underwent surgical decompression within 24 hours. OUTCOME MEASURES:Primary: in-hospital venous thromboembolism. Secondary: in-hospital return to the operating room, death during admission and length of stay. METHODS:Restricted cubic splines identified an inflection point defining early versus late thromboprophylaxis initiation, which was used for propensity score-matched comparisons. Covariates for propensity matching included patient, injury, treatment, and hospital characteristics. Effect size was calculated using risk difference (RDs) and odds ratio (OR) for dichotomous outcomes and mean difference (MD) for linear outcomes with associated 95% confidence interval (CI). RESULTS:Total of 15,960 patients across 511 trauma centers were included. Spline analysis indicated increasing risk after 24-48 hours from surgery. In propensity-matched cohorts for postoperative day 1 (ie, early <48 hours; late ≥48 hours) (N=6,867 per group), early thromboprophylaxis was associated with lower VTE rates (4.7% vs 5.9%; p=.002; OR 1.26 [95% CI: 1.09, 1.46]), fewer returns to operating room overall (2.2% vs 2.9%; p=.004; OR 1.38 [95% CI 1.11, 1.71]), no difference in return to operating room for same-level spine procedure (0.7% vs 1.0%; p=.07; OR 1.4 [95% CI 0.98, 2.02]), lower mortality (4.0% vs 4.9%; p=.003; OR 1.28 [95% CI: 1.09, 1.51]), and shorter length of stay (15.8 vs 16.9 days; p<.001; MD 1.06 days [95% CI: 0.47, 1.65]). CONCLUSIONS:Thromboprophylaxis by postoperative day 1 after was associated with a decreased risk of venous thromboembolism, decreased returns to the operating room, no increased return to the operating room for related spine procedure, decreased risk of death, and decreased length of stay. Administration of thromboprophylaxis by postoperative day 1 for acute SCI patients may represent a new clinical standard for optimal patient outcomes.

Importance:Pantoprazole reduces clinically important upper gastrointestinal bleeding in critically ill patients. However, the cost-effectiveness of this strategy is unclear. Objective:To assess the cost-effectiveness of daily intravenous pantoprazole vs no pantoprazole for preventing upper gastrointestinal bleeding in mechanically ventilated patients. Design, Setting, and Participants:This prospective health economic evaluation was conducted alongside the Reevaluating the Inhibition of Stress Erosions (REVISE) trial over a time horizon of intensive care unit (ICU) admission to hospital discharge or death from a public health care payer's perspective. The REVISE trial included critically ill adults from Canada, Australia, the US, England, Saudi Arabia, Brazil, Kuwait, and Pakistan receiving invasive ventilation. Interventions:Daily intravenous pantoprazole (40 mg) or placebo (0.9% sodium chloride). Main Outcomes and Measures:The primary outcome was the incremental cost per clinically important upper gastrointestinal bleed prevented. The base-case analysis included all study site-specific resource utilization. Canadian costs were applied to measured resource uses across sites. Sensitivity analyses were conducted across cost ranges and using US-based cost estimates. Uncertainty was assessed using nonparametric bootstrapping simulations. All costs are presented in 2025 US dollars. Results:4821 invasively ventilated critically ill patients (mean [SD] age, 58.2 [16.4] years; 1752 female [36.3%]) were enrolled from 68 ICUs. For pantoprazole, the mean (SD) stay was 12.4 (11.7) days in the ICU and an additional 14.8 (28.0) days in the hospital, as compared with 13.3 (13.3) days in the ICU and 16.5 (42.9) days in the hospital for no pantoprazole. Mean (SD) total per-patient costs were $60 466 ($58 546) for pantoprazole vs $65 423 ($75 661) for no pantoprazole. The incremental cost per patient was -$4957 (95% CI, -$8777 to -$1136). In a sensitivity analysis, US costs were applied for pantoprazole, bleeding, and ICU and hospital stay to all patients; mean (SD) total per-patient costs were $130 179 ($123 456) for pantoprazole vs $140 770 ($153 195) for no pantoprazole (incremental cost: -$10 591; 95% CI, -$18 448 to $-2735). When excluding top 10% of patients in terms of ICU days, ward days, and total costs, the incremental costs were -$1151, -$3388, and -$1356, respectively. In 99% of simulations, the strategy of using pantoprazole was more effective and less costly than no pantoprazole. Conclusions and Relevance:In this economic evaluation, daily pantoprazole for invasively mechanically ventilated patients was less costly and more effective than care without pantoprazole, indicating both clinical benefits and economic value for the health care system.

BackgroundMultifaceted interventions that address barriers and facilitators have been shown to be most effective for increasing the adoption of high-value care, but there is a knowledge gap on this type of intervention for the de-implementation of low-value care. Trauma is a high-risk setting for low-value care, such as unnecessary diagnostic imaging and the use of specialized resources. The aim of our study was to develop and assess the usability of a multifaceted intervention to reduce low-value injury care.MethodsWe used the Consolidated Framework for Implementation Research and the Expert Recommendations for Implementing Change tool as theoretical foundations to identify barriers and facilitators, and strategies for the reduction of low-value practices. We designed an initial prototype of the intervention using the items of the Template for Intervention Description and Replication. The prototype's usability was iteratively tested through four focus groups and four think-aloud sessions with trauma decision-makers (n = 18) from seven Level I to Level III trauma centers. We conducted an inductive analysis of the audio-recorded sessions to identify usability issues and other barriers and facilitators to refine the intervention.ResultsWe identified barriers and facilitators related to individual characteristics, including knowledge and beliefs about low-value practices and the de-implementation process, such as the complexity of changing practices and difficulty accessing performance feedback. Accordingly, the following intervention strategies were selected: involving governing structures and leaders, distributing audit & feedback reports on performance, and providing educational materials, de-implementation support tools and educational/facilitation visits. A total of 61 issues were identified during the usability testing, of which eight were critical, 33 were moderately important, and 18 were minor. These issues led to numerous improvements, including the addition of information on the drivers and benefits of reducing low-value practices, changes in the definition of these practices, the addition of proposed strategies to facilitate de-implementation, and the tailoring of educational/facilitation visits.ConclusionsWe designed and refined a multifaceted intervention to reduce low-value injury care using a process that increases the likelihood of its acceptability and sustainability. The next step will be to evaluate the effectiveness of implementing this intervention using a pragmatic cluster randomized controlled trial.Trial registrationThis protocol has been registered on ClinicalTrials.gov (February 24th 2023, #NCT05744154, https://clinicaltrials.gov/ct2/show/NCT05744154).

Introduction SARS-CoV-2 is now endemic and expected to remain a health threat, with new variants continuing to emerge and the potential for vaccines to become less effective. While effective vaccines and natural immunity have significantly reduced hospitalisations and the need for critical care, outpatient treatment options remain limited, and real-world evidence on their clinical and cost-effectiveness is lacking. In this paper, we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). By evaluating multiple treatment options in a pragmatic adaptive platform trial, this study will generate high-quality, generalisable evidence to inform clinical guidelines and healthcare decision-making.Methods and analysis CanTreatCOVID is an open-label, individually randomised, multicentre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalised SARS-CoV-2 patients across Canada. Eligible participants must present with symptomatic SARS-CoV-2 infection, confirmed by PCR or rapid antigen testing (RAT), within 5 days of symptom onset. The trial targets two groups that are expected to be at higher risk of more severe disease: (1) individuals aged 50 years and older and (2) those aged 18–49 years with one or more comorbidities. CanTreatCOVID uses numerous approaches to recruit participants to the study, including a multifaceted public communication strategy and outreach through primary care, outpatient clinics and emergency departments. Participants are randomised to receive either usual care, including supportive and symptom-based management, or an investigational therapeutic selected by the Canadian COVID-19 Outpatient Therapeutics Committee. The first therapeutic arm evaluates nirmatrelvir/ritonavir (Paxlovid), administered two times per day for 5 days. The second therapeutic arm investigates a combination antioxidant therapy (selenium 300 µg, zinc 40 mg, lycopene 45 mg and vitamin C 1.5 g), administered for 10 days. The primary outcome is all-cause hospitalisation or death within 28 days of randomisation.Ethics and dissemination The CanTreatCOVID master protocol and subprotocols have been approved by Health Canada and local research ethics boards in the participating provinces across Canada. The results of the study will be disseminated to policy-makers, presented at conferences and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities. This study was approved by the Unity Health Toronto Research Ethics Board (#22-179) and Clinical Trials Ontario (Project ID 4133).Trial registration number NCT05614349

BACKGROUND:How advanced practice providers (APPs) are deployed in adult US intensive care units (ICUs) is understudied. Further, whether state-level restrictions on practice affect the availability of these providers is unknown. OBJECTIVES:To describe staffing patterns of ICU APPs (nurse practitioners, physician assistants) in the context of physicians-in-training (interns, residents, fellows) and to explore the association between state-level APP practice restrictions and employment. METHODS:Data from a national survey of pre-COVID-19 (steady-state) ICU staffing linked to the 2020 American Hospital Association survey were used to examine staffing patterns (via descriptive statistics) and to explore the association of state-level practice restrictions with the presence of APPs in ICUs (via multivariable regression). RESULTS:The cohort included 588 adult ICUs, of which 336 (57.1%) reported both APPs and physicians-in-training, 124 (21.1%) APPs only, 73 (12.4%) physicians-in-training only, and 55 (9.4%) neither. Units with both provider types were more commonly surgical ICUs (17.6% vs ≤9.6%; P < .001), whereas those with neither were 98.2% mixed units. Those units with neither were smaller and more often in smaller, nonteaching, for-profit hospitals in nonmetropolitan areas. Two hundred twenty-five ICUs (38.3%) were in states allowing full APP practice scope. After adjustment, the odds of employing APPs were nonsignificantly higher in ICUs in full-practice states. CONCLUSIONS:Both APPs and physicians-in-training are commonly deployed in US adult ICUs, often together. Laws limiting practice scope may impede deployment of these providers in ICUs.

BACKGROUND:On September 27, 2024, Rwanda reported an outbreak of Marburg virus disease (MVD), after a cluster of cases of viral hemorrhagic fever was detected at two urban hospitals. METHODS:We report key aspects of the epidemiology, clinical manifestations, and treatment of MVD during this outbreak, as well as the overall response to the outbreak. We performed a retrospective epidemiologic and clinical analysis of data compiled across all pillars of the outbreak response and a case-series analysis to characterize clinical features, disease progression, and outcomes among patients who received supportive care and investigational therapeutic agents. RESULTS:Among the 6340 patients with suspected MVD who underwent testing, 66 had laboratory-confirmed MVD, 51 (77%) of whom were health care workers. The median estimated incubation period was 10 days (interquartile range, 8 to 13), and symptom onset occurred a median of 2 days (interquartile range, 1 to 3) before hospital admission. The results of epidemiologic investigations were highly suggestive of a zoonotic origin of the outbreak: an index patient was identified who had been exposed to Egyptian fruit bats at a mining site. The case fatality rate in the outbreak was 23% (15 deaths among 66 patients). Remdesivir and the monoclonal antibody MBP091 were used under expanded access and clinical trial protocols. In addition, 1710 frontline workers and high-risk contacts received the chimpanzee adenovirus 3-vectored vaccine ChAd3-MARV under emergency use authorization in a phase 2 clinical trial. CONCLUSIONS:Implementation of containment measures, advanced supportive care, and access to investigational countermeasures may have contributed to reduced mortality from MVD in this outbreak. Enhancing surveillance, improving infection prevention and control in health care settings, and ensuring timely deployment of medical countermeasures will be critical for mitigating the effects of future filovirus disease outbreaks.

ImportanceEligibility criteria for randomized clinical trials (RCTs) are designed to select clinically relevant patient populations. However, not all eligibility criteria are strongly justified, potentially excluding marginalized groups, and limiting the generalizability of trial findings.ObjectiveTo summarize and evaluate the justification of exclusion criteria in published RCTs in critical care medicine.Evidence ReviewA systematic sampling review of parallel-group RCTs published in the top 5 general internal medicine journals by impact factor (The Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine) between January 1, 2018, and February 23, 2023, was conducted. RCTs enrolling adults in intensive care units (ICUs) and RCTs enrolling critically ill patients who required life-sustaining interventions typically initiated in the ICU were included. All study exclusion criteria were categorized as either poorly justified, potentially justified, or strongly justified, adapting previously established criteria, independently and in duplicate.FindingsIn total, 225 studies were identified, 75 of which were included. The median (IQR) number of exclusion criteria per trial was 19 (14-24), with 1455 total exclusion criteria. Common exclusion criteria were related to the risk of adverse reaction to interventions (302 criteria [20.8%]), followed by inability to obtain consent (120 criteria [8.2%]), and treatment limitation decisions (97 criteria [6.7%]). Most exclusion criteria were either strongly justified (1080 criteria [74.2%]) or potentially justified (297 criteria [20.4%]), whereas 5.4% (78 criteria) were poorly justified. Of the 78 poorly justified exclusion criteria, the most common were pregnancy (19 criteria [24.4%]), communication barriers (11 criteria [14.1%]), lactation (10 criteria [12.8%]), and lack of health insurance (10 criteria [12.8%]). Overall, 45 of 75 studies (60.0%) had at least 1 poorly justified exclusion criteria.Conclusions and RelevanceMost exclusion criteria in critical care medicine RCTs were strongly justifiable. Across poorly justified criteria, the most common exclusions were pregnant or lactating persons, those with communication barriers, and individuals without health insurance. This highlights the need to carefully consider exclusion criteria when designing trials to minimize the inappropriate exclusion of participants and enhance generalizability.

Objectives: To evaluate 1-year outcomes (mortality, and recurrent hospital and ICU readmission) in adult survivors of COVID-19 critical illness compared with survivors of critical illness from non-COVID-19 pneumonia. Design: Population-based retrospective observational cohort study. Setting: Province of Ontario, Canada. Patients: Six thousand ninety-eight consecutive adult patients (≥ 18 yr old) from 102 centers, admitted to ICU with COVID-19 (from January 1, 2020, to March 31, 2022), and surviving to hospital discharge. Interventions: None. Measurements and Main Results: The primary outcome was 1-year mortality. We also evaluated the number of emergency department (ED) visits, hospital readmissions, and ICU readmissions over this same time period. We compared patients using overlap propensity score-weighted, cause-specific proportional hazard models. Mean age was 59.6 years and 38.5% were female. Of these patients, 1610 (26.4%) and 375 (6.1%) were readmitted to hospital and ICU, respectively, and 917 (15.0%) died within 1 year. Compared with survivors of critical illness from non-COVID-19 pneumonia ( n = 2568), those who survived COVID-19 critical illness had a lower risk of ED visit (hazard ratio [HR], 0.65 [95% CI, 0.60–0.71]), hospital readmission (HR, 0.56 [95% CI, 0.51–0.62]), ICU readmission (HR, 0.44 [95% CI, 0.37–0.53]), and mortality (HR, 0.67 [95% CI, 0.58–0.78]) within 1 year. Conclusions: Risk of ED visit, hospital readmission, ICU readmission, and mortality within 1 year of discharge among survivors of COVID-19 critical illness was lower than survivors of critical illness from non-COVID-19 pneumonia.

BACKGROUND:Traumatic cerebral venous sinus thrombosis (CVST) is abnormal clotting in one or more cerebral veins or sinuses following trauma. Its clinical significance is uncertain. Management is challenging because patients are at increased risk for bleeding. Limited studies exist on traumatic CVST. METHODS:Retrospective cohort study of trauma patients admitted to a Level 1 trauma center between January 2014 and October 2023. Main objectives were to assess the following: (1) CVST prevalence, overall and according to head injury severity; (2) characteristics of trauma patients with CVST; and (3) management and outcomes of CVST patients. RESULTS:On admission, all CVST patients (n = 170) had a traumatic brain injury (TBI) and an intracranial hemorrhage, and all except one had a skull fracture. Prevalence of CVST was 0.9% (95% confidence interval [CI], 0.8-1.0) in the overall trauma patient population (n = 18,569), 2.1% (95% CI, 1.9-2.5) in patients with TBI (n = 7,920), and 4.8% (95% CI, 4.0-5.8) in patients with severe TBI (modified head Abbreviated Injury Scale score, ≥4; n = 2,035). Twenty-eight patients with CVST died (16.5%), usually shortly after admission. The majority of patients (n = 100) with CVST were treated with standard venous thromboembolism (VTE) prophylactic dose of anticoagulant while in hospital. During median follow-up of 3 months, none of the patients treated with standard VTE prophylactic dose of anticoagulant developed a symptomatic CVST-related adverse event (death, stroke, intracranial hemorrhage). One patient (1.0%) had asymptomatic CVST-related stroke, three patients (3.0%) developed asymptomatic CVST extension, and 3 patients (3.0%) developed a gastrointestinal bleed on anticoagulant. CONCLUSION:Traumatic CVST prevalence increases with head trauma severity and is unlikely to develop in the absence of skull fracture. Patients treated with standard VTE prophylactic doses of anticoagulants had favorable outcomes with minimal CVST-related complications during hospitalization. Longer-term data are needed to better evaluate traumatic CVST prognosis. LEVEL OF EVIDENCE:Prognostic and Epidemiological; Level IV.