Mental health sequelae in survivors of cardiogenic shock complicating myocardial infarction. A population-based cohort study.

PURPOSE: Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) is associated with substantial short- and long-term morbidity and mortality. However, there are limited data on mental health sequelae that survivors experience following discharge. METHODS: We conducted a retrospective, population-based cohort study in Ontario, Canada of critically ill adult (≥ 18 years) survivors of AMI-CS, admitted to hospital between April 1, 2009 and March 31, 2019. We compared these patients to AMI survivors without shock. We captured outcome data using linked health administrative databases. The primary outcome was a new mental health diagnosis (a composite of mood, anxiety, or related disorders; schizophrenia/psychotic disorders; and other mental health disorders) following hospital discharge. We secondarily evaluated incidence of deliberate self-harm and death by suicide. We compared patients using overlap propensity score-weighted, cause-specific proportional hazard models. RESULTS: We included 7812 consecutive survivors of AMI-CS, from 135 centers. Mean age was 68.4 (standard deviation (SD) 12.2) years, and 70.3% were male. Median follow-up time was 767 days (interquartile range (IQR) 225-1682). Incidence of new mental health diagnosis among AMI-CS survivors was 109.6 per 1,000 person-years (95% confidence interval (CI) 105.4-113.9), compared with 103.8 per 1000 person-years (95% CI 102.5-105.2) among AMI survivors without shock. After propensity score adjustment, there was no difference in the risk of new mental health diagnoses following discharge [hazard ratio (HR) 0.99 (95% CI 0.94-1.03)]. Factors associated with new mental health diagnoses following AMI-CS included female sex, pre-existing mental health diagnoses, and discharge to a long-term hospital or rehabilitation institute. CONCLUSION: Survivors of AMI-CS experience substantial mental health morbidity following discharge. Risk of new mental health diagnoses was comparable between survivors of AMI with and without shock. Future research on interventions to mitigate psychiatric sequelae after AMI-CS is warranted.

Preexisting Diabetes Mellitus and All-Cause Mortality in Adult Patients With Sepsis: A Population-Based Cohort Study.

OBJECTIVES: We assessed the association of preexisting diabetes mellitus with all-cause mortality and organ support receipt in adult patients with sepsis. DESIGN: Population-based cohort study. SETTING: Ontario, Canada (2008-2019). POPULATION: Adult patients (18 yr old or older) with a first sepsis-related hospitalization episode. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure of interest was preexisting diabetes (either type 1 or 2). The primary outcome was all-cause mortality by 90 days; secondary outcomes included receipt of invasive mechanical ventilation and new renal replacement therapy. We report adjusted (for baseline characteristics using standardization) risk ratios (RRs) alongside 95% CIs. A main secondary analysis evaluated the potential mediation by prior metformin use of the association between preexisting diabetes and all-cause mortality following sepsis. Overall, 503,455 adults with a first sepsis-related hospitalization episode were included; 36% had preexisting diabetes. Mean age was 73 years, and 54% of the cohort were females. Preexisting diabetes was associated with a lower adjusted risk of all-cause mortality at 90 days (RR, 0.81; 95% CI, 0.80-0.82). Preexisting diabetes was associated with an increased risk of new renal replacement therapy (RR, 1.53; 95% CI, 1.46-1.60) but not invasive mechanical ventilation (RR, 1.03; 95% CI, 1.00-1.05). Overall, 21% (95% CI, 19-28) of the association between preexisting diabetes and reduced risk of all-cause mortality was mediated by prior metformin use. CONCLUSIONS: Preexisting diabetes is associated with a lower risk of all-cause mortality and higher risk of new renal replacement therapy among adult patients with sepsis. Future studies should evaluate the underlying mechanisms of these associations.

Venous thromboembolism in critically ill adult patients with hematologic malignancy: a population-based cohort study.

PURPOSE: The aim of this study was to describe the incidence of venous thromboembolism (VTE) and major bleeding among hospitalized patients with hematologic malignancy, assessing its association with critical illness and other baseline characteristics. METHODS: We conducted a population-based cohort study of hospitalized adults with a new diagnosis of hematologic malignancy in Ontario, Canada, between 2006 and 2017. The primary outcome was VTE (pulmonary embolism or deep venous thrombosis). Secondary outcomes were major bleeding and in-hospital mortality. We compared the incidence of VTE between intensive care unit (ICU) and non-ICU patients and described the association of other baseline characteristics and VTE. RESULTS: Among 76,803 eligible patients (mean age 67 years [standard deviation, SD, 15]), 20,524 had at least one ICU admission. The incidence of VTE was 3.7% in ICU patients compared to 1.2% in non-ICU patients (odds ratio [OR] 3.08; 95% confidence interval [CI] 2.77-3.42). The incidence of major bleeding was 7.6% and 2.4% (OR 3.33; 95% CI 3.09-3.58), respectively. The association of critical illness and VTE remained significant after adjusting for potential confounders (OR 2.92; 95% CI 2.62-3.25). We observed a higher incidence of VTE among specific subtypes of hematologic malignancy and patients with prior VTE (OR 6.64; 95% CI 5.42-8.14). Admission more than 1 year after diagnosis of hematologic malignancy (OR 0.64; 95% CI 0.56-0.74) and platelet count ≤ 50 × 109/L at the time of hospitalization (OR 0.63; 95% CI 0.48-0.84) were associated with a lower incidence of VTE. CONCLUSION: Among patients with hematologic malignancy, critical illness and certain baseline characteristics were associated with a higher incidence of VTE.

The impact of referring hospital resources on interfacility overtriage: A population-based analysis.

BACKGROUND: Nearly half of patients transferred from non-trauma to trauma centres have minor injuries. The transfer of patients with minor injuries to trauma centres is not associated with any known patient benefit and represents an opportunity to reduce healthcare costs and improve patient experience. In this study, we evaluated the relationship between hospital resources and overtriage, with the objective of identifying targets for system-level intervention. METHODS: We conducted a population-based cohort study of adults, age ≥ 16, presenting with minor injuries to non-trauma centres in Ontario, Canada (2009-2020). The primary outcome was overtriage, defined as transfer to a trauma centre. Hierarchical logistic regression was used to evaluate the association between hospital resources and a patient's likelihood of being overtriaged, adjusting for case-mix. RESULTS: amongst 165,302 patients with minor injuries, 15,641 (9.5 %) were transferred to a trauma centre (overtriage). Presence of a CT scanner, surgical support, or intensive care unit had no impact on a patient's likelihood of overtriage. Relative to community hospitals, presentation to a teaching hospital was independently associated with greater odds of overtriage (OR 2.97, 95 % CI: 1.26-7.00). Accounting for case-mix and resources, the median difference in a patient's odds of overtriage varied 3.7-fold across non-trauma centres (MOR 3.76). CONCLUSIONS: There is significant variability in overtriage across non-trauma centres, even after adjusting for case-mix and hospital resources. These finding suggests that some centres have developed processes to minimize overtriage independent of available resources. Broad implementation of these processes may represent an opportunity for system-wide quality improvement.

Internal and external validation of an updated ICD-10-CA to AIS-2005 update 2008 algorithm.

BACKGROUND: Administrative data are a powerful tool for population-level trauma research but lack the trauma-specific diagnostic and injury severity codes needed for risk-adjusted comparative analyses. The objective of this study was to validate an algorithm to derive Abbreviated Injury Scale (AIS-2005 update 2008) severity scores from Canadian International Classification of Diseases (ICD-10-CA) diagnostic codes in administrative data. METHODS: This was a retrospective cohort study using data from the 2009 to 2017 Ontario Trauma Registry for the internal validation of the algorithm. This registry includes all patients treated at a trauma center who sustained a moderate or severe injury or were assessed by a trauma team. It contains both ICD-10-CA codes and injury scores assigned by expert abstractors. We used Cohen's kappa (𝜅) coefficient to compare AIS-2005 Update 2008 scores assigned by expert abstractors to those derived using the algorithm and the intraclass correlation coefficient to compare assigned and derived Injury Severity Scores. Sensitivity and specificity for detection of a severe injury (AIS score, ≥ 3) were then calculated. For the external validation of the algorithm, we used administration data to identify adults who either died in an emergency department or were admitted to hospital in Ontario secondary to a traumatic injury (2009-2017). Logistic regression was used to evaluate the discriminative ability and calibration of the algorithm. RESULTS: Of 41,869 patients in the Ontario Trauma Registry, 41,793 (99.8%) had at least one diagnosis matched to the algorithm. Evaluation of AIS scores assigned by expert abstractors and those derived using the algorithm demonstrated a high degree of agreement in identification of patients with at least one severe injury (𝜅 = 0.75; 95% confidence interval [CI], 0.74-0.76). Likewise, algorithm-derived scores had a strong ability to rule in or out injury with AIS ≥ 3 (specificity, 78.5%; 95% CI, 77.7-79.4; sensitivity, 95.1; 95% CI, 94.8-95.3). There was strong correlation between expert abstractor-assigned and crosswalk-derived Injury Severity Score (intraclass correlation coefficient, 0.80; 95% CI, 0.80-0.81). Among the 130,542 patients identified using administrative data, the algorithm retained its discriminative properties. CONCLUSION: Our ICD-10-CA to AIS-2005 update 2008 algorithm produces reliable estimates of injury severity and retains its discriminative properties with administrative data. Our findings suggest that this algorithm can be used for risk adjustment of injury outcomes when using population-based administrative data. LEVEL OF EVIDENCE: Diagnostic Tests/Criteria; Level II.

New antipsychotic prescription and recurrent infections among adult sepsis survivors: A population-based cohort study.

PURPOSE: Antipsychotic agents, which may increase the risk of infection through dopaminergic dysregulation, are prescribed to a fraction of patients following critical illness. We compared the rate of recurrent sepsis among patients who filled a prescription for antipsychotics with high- or low-D2 affinity. METHODS: Population-based cohort with active comparator design. We included sepsis survivors older than 65 years with intensive care unit admission and new prescription of antipsychotics in Ontario 2008-2019. The primary outcome were recurrent sepsis episodes within 1 year of follow-up. Patients who filled a prescription within 30 days of hospital discharge for high-D2 affinity antipsychotics (e.g., haloperidol) were compared with patients who filled a prescription within 30 days of hospital discharge for low-D2 affinity antipsychotics (e.g., quetiapine). Multivariable zero-inflated Poisson regression models with robust standard errors adjusting for confounding at baseline were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI). RESULTS: Overall, 1879 patients filled a prescription for a high-D2, and 1446 patients filled a prescription for a low-D2 affinity antipsychotic. Patients who filled a prescription for a high-D2 affinity antipsychotic did not present a higher rate of recurrent sepsis during 1 year of follow-up, compared with patients who filled a prescription for a low-D2 affinity antipsychotic (IRR: 1.12; 95% CI: 0.94, 1.35). CONCLUSIONS: We did not find conclusive evidence of a higher rate of recurrent sepsis associated with the prescription of high-D2 affinity antipsychotics (compared with low-D2 affinity antipsychotics) by 1 year of follow-up in adult sepsis survivors with intensive care unit admission.

SARS-CoV-2 vaccination prevalence by mental health diagnosis: a population-based cross-sectional study in Ontario, Canada.

BACKGROUND: Since the onset of the COVID-19 pandemic, there has been concern about the impact of SARS-CoV-2 infection among individuals with mental illnesses. We analyzed the SARS-CoV-2 vaccination status of Ontarians with and without a history of mental illness. METHODS: We conducted a population-based cross-sectional study of all community-dwelling Ontario residents aged 19 years and older as of Sept. 17, 2021. We used health administrative data to categorize Ontario residents with a mental disorder (anxiety, mood, substance use, psychotic or other disorder) within the previous 5 years. Vaccine receipt as of Sept. 17, 2021, was compared between individuals with and without a history of mental illness. RESULTS: Our sample included 11 900 868 adult Ontario residents. The proportion of individuals not fully vaccinated (2 doses) was higher among those with substance use disorders (37.7%) or psychotic disorders (32.6%) than among those with no mental disorders (22.9%), whereas there were similar proportions among those with anxiety disorders (23.5%), mood disorders (21.5%) and other disorders (22.1%). After adjustment for age, sex, neighbourhood income and homelessness, individuals with psychotic disorders (adjusted prevalence ratio 1.19, 95% confidence interval [CI] 1.18-1.20) and substance use disorders (adjusted prevalence ratio 1.35, 95% CI 1.34-1.35) were more likely to be partially vaccinated or unvaccinated relative to individuals with no mental disorders. INTERPRETATION: Our study found that psychotic disorders and substance use disorders were associated with an increased prevalence of being less than fully vaccinated. Efforts to ensure such individuals have access to vaccinations, while challenging, are critical to ensuring the ongoing risks of death and other adverse consequences of SARS-CoV-2 infection are mitigated in this high-risk population.

Prognostic factors associated with favourable functional outcome among adult patients requiring extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established. METHODS: We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach. FINDINGS: We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes). INTERPRETATION: The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.

Accounting for Competing Events When Evaluating Long-Term Outcomes in Survivors of Critical Illness.

The clinical trajectory of survivors of critical illness after hospital discharge can be complex and highly unpredictable. Assessing long-term outcomes after critical illness can be challenging because of possible competing events, such as all-cause death during follow-up (which precludes the occurrence of an event of particular interest). In this perspective, we explore challenges and methodological implications of competing events during the assessment of long-term outcomes in survivors of critical illness. In the absence of competing events, researchers evaluating long-term outcomes commonly use the Kaplan-Meier method and the Cox proportional hazards model to analyze time-to-event (survival) data. However, traditional analytical and modeling techniques can yield biased estimates in the presence of competing events. We present different estimands of interest and the use of different analytical approaches, including changes to the outcome of interest, Fine and Gray regression models, cause-specific Cox proportional hazards models, and generalized methods (such as inverse probability weighting). Finally, we provide code and a simulated dataset to exemplify the application of the different analytical strategies in addition to overall reporting recommendations.

Long-Term Outcomes of Cardiogenic Shock Complicating Myocardial Infarction.

BACKGROUND: Cardiogenic shock secondary to acute myocardial infarction (AMI-CS) is associated with substantial short-term mortality; however, there are limited data on long-term outcomes and trends. OBJECTIVES: This study sought to examine long-term outcomes of AMI-CS patients. METHODS: This was a population-based, retrospective cohort study in Ontario, Canada of critically ill adult patients with AMI-CS who were admitted to hospitals between April 1, 2009 and March 31, 2019. Outcome data were captured using linked health administrative databases. RESULTS: A total of 9,789 consecutive patients with AMI-CS from 135 centers were included. The mean age was 70.5 ± 12.3 years, and 67.7% were male. The incidence of AMI-CS was 8.2 per 100,000 person-years, and it increased over the study period. Critical care interventions were common, with 5,422 (55.4%) undergoing invasive mechanical ventilation, 1,425 (14.6%) undergoing renal replacement therapy, and 1,484 (15.2%) receiving mechanical circulatory support. A total of 2,961 patients (30.2%) died in the hospital, and 4,004 (40.9%) died by 1 year. Mortality at 5 years was 58.9%. Small improvements in short- and long-term mortality were seen over the study period. Among survivors to discharge, 2,870 (42.0%) required increased support in care from their preadmission baseline, 3,244 (47.5%) were readmitted to the hospital within 1 year, and 1,047 (15.3%) died within 1 year. The mean number of days at home in the year following discharge was 307.9 ± 109.6. CONCLUSIONS: Short- and long-term mortality among patients with AMI-CS is high, with minimal improvement over time. AMI-CS survivors experience significant morbidity, with high risks of readmission and death. Future studies should evaluate interventions to minimize postdischarge morbidity and mortality among AMI-CS survivors.

Prevalent diabetes and long-term cardiovascular outcomes in adult sepsis survivors: a population-based cohort study.

BACKGROUND: Sepsis survivors are at elevated risk for cardiovascular disease during long-term follow-up. Whether diabetes influences cardiovascular risk after sepsis survival remains unknown. We sought to describe the association of diabetes with long-term cardiovascular outcomes in adult sepsis survivors. METHODS: Population-based cohort study in the province of Ontario, Canada (2008-2017). Adult survivors of a first sepsis-associated hospitalization, without pre-existing cardiovascular disease, were included. Main exposure was pre-existing diabetes (any type). The primary outcome was the composite of myocardial infarction, stroke, and cardiovascular death. Patients were followed up to 5 years from discharge date until outcome occurrence or end of study period (March 2018). We used propensity score matching (i.e., 1:1 to patients with sepsis but no pre-existing diabetes) to adjust for measured confounding at baseline. Cause-specific Cox proportional hazards models with robust standard errors were used to estimate hazard ratios (HR) alongside 95% confidence intervals (CI). A main secondary analysis evaluated the modification of the association between sepsis and cardiovascular disease by pre-existing diabetes. RESULTS: 78,638 patients with pre-existing diabetes who had a sepsis-associated hospitalization were matched to patients hospitalized for sepsis but without diabetes. Mean age of patients was 71 years, and 55% were female. Median duration from diabetes diagnosis was 9.8 years; mean HbA1c was 7.1%. Adult sepsis survivors with pre-existing diabetes experienced a higher hazard of major cardiovascular disease (HR 1.25; 95% CI 1.22-1.29)-including myocardial infarction (HR 1.40; 95% CI 1.34-1.47) and stroke (HR 1.24; 95% CI 1.18-1.29)-during long-term follow-up compared to sepsis survivors without diabetes. Pre-existing diabetes modified the association between sepsis and cardiovascular disease (risk difference: 2.3%; 95% CI 2.0-2.6 and risk difference: 1.8%; 95% CI 1.6-2.0 for the effect of sepsis-compared to no sepsis-among patients with and without diabetes, respectively). CONCLUSIONS: Sepsis survivors with pre-existing diabetes experience a higher long-term hazard of major cardiovascular events when compared to sepsis survivors without diabetes. Compared to patients without sepsis, the absolute risk increase of cardiovascular events after sepsis is higher in patients with diabetes (i.e., diabetes intensified the higher cardiovascular risk induced by sepsis).

Neuroprognostication in the Post Cardiac Arrest Patient: A Canadian Cardiovascular Society Position Statement.

Cardiac arrest (CA) is associated with a low rate of survival with favourable neurologic recovery. The most common mechanism of death after successful resuscitation from CA is withdrawal of life-sustaining measures on the basis of perceived poor neurologic prognosis due to underlying hypoxic-ischemic brain injury. Neuroprognostication is an important component of the care pathway for CA patients admitted to hospital but is complex, challenging, and often guided by limited evidence. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to evaluate the evidence underlying factors or diagnostic modalities available to determine prognosis, recommendations were generated in the following domains: (1) circumstances immediately after CA; (2) focused neurologic exam; (3) myoclonus and seizures; (4) serum biomarkers; (5) neuroimaging; (6) neurophysiologic testing; and (7) multimodal neuroprognostication. This position statement aims to serve as a practical guide to enhance in-hospital care of CA patients and emphasizes the adoption of a systematic, multimodal approach to neuroprognostication. It also highlights evidence gaps.

A qualitative study of older adult trauma survivors' experiences in acute care and early recovery.

BACKGROUND: Older adults (aged ≥ 65 yr) account for a substantial proportion of hospital admissions for severe injury, yet little is known about their care experiences and views regarding outcomes. We sought to characterize the acute care and early recovery experiences of older adults who had been discharged after traumatic injury, with a long-term goal to inform the selection of patient-centred process and outcome measures in geriatric trauma. METHODS: From June 2018 to September 2019, we conducted telephone interviews with adults aged 65 years or older who had been discharged after traumatic injury within 6 months from Sunnybrook or London Health Sciences Centres in Ontario, Canada. Using interpretive description and thematic analysis, we drew on social science theories of illness and aging for data interpretation. We analyzed data to the point of theoretical saturation. RESULTS: We interviewed 25 trauma survivors aged 65-88 years. Most were injured in a fall. Four themes characterized participants' experiences, as follows: "I don't feel like a senior" (i.e., participants disliked being viewed as a senior or as needing senior-specific care); "don't bother telling him anything" (i.e., participants perceived ageist assumptions and treatment in acute care processes); getting back to normal (i.e., participants emphasized their active lifestyles and functional recovery as goals of care); "I have lost control of my life" (i.e., substantial social and personal losses linked to participants' experiences and adaptations to aging generally). INTERPRETATION: Findings suggest that older adults experience social and personal loss after injury, and underscore how implicit age bias may influence care experiences and outcomes. This can inform improvements in injury care and guide providers in the selection of patient-centred outcome measures.

Noninvasive Oxygenation Strategies in Adult Patients With Acute Hypoxemic Respiratory Failure: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Several recently published randomized controlled trials have evaluated various noninvasive oxygenation strategies for the treatment of acute hypoxemic respiratory failure. RESEARCH QUESTION: Which available noninvasive oxygen strategies are effective for acute hypoxic respiratory failure? STUDY DESIGN AND METHODS: A systematic review of Medline, Embase, Cochrane CENTRAL, CINAHL, Web of Science, MedRxiv, and Research Square was conducted from inception to October 1, 2022. A random effects frequentist network meta-analysis was performed, and the results are presented using absolute risk difference per 1,000 patients. The Grading of Recommendations, Assessment, Development and Evaluation framework was used to rate the certainty of the evidence. Mortality, invasive mechanical ventilation, duration of hospitalization and ICU stay, ventilator-free days, and level of comfort are reported. RESULTS: Thirty-six trials (7,046 patients) were included. It was found that helmet CPAP probably reduces mortality compared with standard oxygen therapy (SOT) (231 fewer deaths per 1,000; 95% CI, 126-273 fewer) (moderate certainty). A high-flow nasal cannula (HFNC) probably reduces the need for invasive mechanical ventilation (103.5 fewer events per 1,000; 95% CI, 40.5-157.5 fewer) (moderate certainty). All noninvasive oxygenation strategies may reduce the duration of hospitalization as compared with SOT (low certainty). Helmet bilevel ventilation (4.84 days fewer; 95% CI, 2.33-7.36 days fewer) and helmet CPAP (1.74 days fewer; 95% CI, 4.49 fewer-1.01 more) may reduce the duration of ICU stay as compared with SOT (both low certainty). SOT may be more comfortable than face mask noninvasive ventilation and no different in comfort compared with an HFNC (both low certainty). INTERPRETATION: A helmet interface for noninvasive ventilation probably reduces mortality and the risk of mechanical ventilation, as well as the duration of hospital and ICU stay. An HFNC probably reduces the risk of invasive mechanical ventilation and may be as comfortable as SOT. Further research is necessary to understand the role of these interfaces in acute hypoxemic respiratory failure.

Risk Factors for Major Cardiovascular Events in Adult Sepsis Survivors: A Population-Based Cohort Study.

OBJECTIVES: To describe risk factors for major cardiovascular events in adults following hospital discharge after sepsis. DESIGN: Population-based cohort study. SETTING: Ontario, Canada (2008-2017). PATIENTS: Adult patients (age 18 yr or older) who survived a first sepsis hospitalization without preexisting cardiovascular disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary composite outcome was myocardial infarction, stroke, or cardiovascular death up to 5 years following hospital discharge. We used cause-specific Cox proportional hazards models that accounted for the competing risk of noncardiovascular death to describe factors associated with major cardiovascular events. We identified 268,259 adult patients without cardiovascular disease (median age, 72 yr), of whom 10.4% experienced a major cardiovascular event during a median follow-up of 3 years. After multivariable adjustment, age (hazard ratio [HR], 1.53 for every 10 yr; 95% CI, 1.51-1.54), male sex (HR, 1.23; 95% CI, 1.20-1.26), diabetes mellitus (HR, 1.24; 95% CI, 1.21-1.27), hypertension (HR, 1.34; 95% CI, 1.30-1.38), prevalent atrial fibrillation (HR, 1.46; 95% CI, 1.40-1.52), and chronic kidney disease (HR, 1.11; 95% CI, 1.06-1.16) were associated with major cardiovascular events during long-term follow-up. Sepsis characteristics such as site of infection (pneumonia vs other: HR, 1.09; 95% CI, 1.05-1.12), septic shock (HR, 1.08; 95% CI, 1.05-1.11), and renal replacement therapy (HR, 1.51; 95% CI, 1.38-1.64) were also associated with subsequent cardiovascular events. In an analysis restricting to patients with troponin values measured during the hospitalization (26,400 patients), an elevated troponin was also associated with subsequent cardiovascular events (HR, 1.23; 95% CI, 1.13-1.33). CONCLUSIONS: Classic cardiovascular risk factors, comorbid conditions, and characteristics of the sepsis episode were associated with a higher hazard of major cardiovascular events in adult sepsis survivors. These findings may inform enrichment strategies for future studies.

Epinephrine in Out-of-Hospital Cardiac Arrest: A Network Meta-analysis and Subgroup Analyses of Shockable and Nonshockable Rhythms.

BACKGROUND: Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed. RESEARCH QUESTION: What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA? STUDY DESIGN AND METHODS: In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome. RESULTS: We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95% CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95% CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85). INTERPRETATION: Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm. TRIAL REGISTRY: Center for Open Science: https://osf.io/arxwq.

New and Persistent Sedative Prescriptions Among Older Adults Following a Critical Illness: A Population-Based Cohort Study.

BACKGROUND: ICU survivors often have complex care needs and can experience insufficient medication reconciliation and polypharmacy. It is unknown which ICU survivors are at risk of new sedative use posthospitalization. RESEARCH QUESTION: For sedative-naive, older adult ICU survivors, how common is receipt of new and persistent sedative prescriptions, and what factors are associated with receipt? STUDY DESIGN AND METHODS: This population-based cohort study included ICU survivors aged ≥ 66 years who had not filled sedative prescriptions within ≤ 6 months before hospitalization (sedative-naive) in Ontario, Canada (2003-2019). Using multilevel logistic regression, demographic, clinical, and hospital characteristics and their association with new sedative prescription within ≤ 7 days of discharge are described. Variation between hospitals was quantified by using the adjusted median OR. Factors associated with persistent prescriptions (≤ 6 months) were examined with a multivariable proportional hazards model. RESULTS: A total of 250,428 patients were included (mean age, 76 years; 61% male). A total of 15,277 (6.1%) filled a new sedative prescription, with variation noted across hospitals (2% [95% CI, 1-3] to 44% [95% CI, 3-57]); 8,458 (3.4%) filled persistent sedative prescriptions. Adjusted factors associated with a new sedative included: discharge to long-term care facility (adjusted OR [aOR], 4.00; 95% CI, 3.72-4.31), receipt of inpatient geriatric (aOR, 1.95; 95% CI, 1.80-2.10) or psychiatry (aOR, 2.76; 95% CI, 2.62-2.91) consultation, invasive ventilation (aOR, 1.59; 95% CI, 1.53-1.66), and ICU length of stay ≥ 7 days (aOR, 1.50; 95% CI, 1.42-1.58). The residual heterogeneity between hospitals (adjusted median OR, 1.43; 95% CI, 1.35-1.49) had a stronger association with new sedative prescriptions than the Charlson Comorbidity Index score or sepsis. Factors associated with persistent sedative use were similar with the addition of female subjects (subdistribution hazard ratio, 1.07; 95% CI, 1.02-1.13) and pre-existing polypharmacy (subdistribution hazard ratio, 0.88; 95% CI, 0.80-0.93). INTERPRETATION: One in 15 sedative-naive, older adult ICU survivors filled a new sedative within ≤ 7 days of discharge; more than one-half of these survivors filled persistent prescriptions. New prescriptions at discharge varied widely across hospitals and represent the potential value of modifying prescription practices, including medication review and reconciliation.

Safety Outcomes of Direct Discharge Home From ICUs: An Updated Systematic Review and Meta-Analysis (Direct From ICU Sent Home Study).

OBJECTIVE: To evaluate the impact of direct discharge home (DDH) from ICUs compared with ward transfer on safety outcomes of readmissions, emergency department (ED) visits, and mortality. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature from inception until March 28, 2022. STUDY SELECTION: Randomized and nonrandomized studies of DDH patients compared with ward transfer were eligible. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the Newcastle-Ottawa Scale for observational studies. A random-effects meta-analysis model and heterogeneity assessment was performed using pooled data (inverse variance) for propensity-matched and unadjusted cohorts. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS: Of 10,228 citations identified, we included six studies. Of these, three high-quality studies, which enrolled 49,376 patients in propensity-matched cohorts, could be pooled using meta-analysis. For DDH from ICU, compared with ward transfers, there was no difference in the risk of ED visits at 30-day (22.4% vs 22.7%; relative risk [RR], 0.99; 95% CI, 0.95-1.02; p = 0.39; low certainty); hospital readmissions at 30-day (9.8% vs 9.6%; RR, 1.02; 95% CI, 0.91-1.15; p = 0.71; very low-to-low certainty); or 90-day mortality (2.8% vs 2.6%; RR, 1.06; 95% CI, 0.95-1.18; p = 0.29; very low-to-low certainty). There were no important differences in the unmatched cohorts or across subgroup analyses. CONCLUSIONS: Very low-to-low certainty evidence from observational studies suggests that DDH from ICU may have no difference in safety outcomes compared with ward transfer of selected ICU patients. In the future, this research question could be further examined by randomized control trials to provide higher certainty data.