Socioeconomic Status, Palliative Care, and Death at Home Among Patients With Cancer Before and During COVID-19.

Importance: The COVID-19 pandemic had a profound impact on the delivery of cancer care, but less is known about its association with place of death and delivery of specialized palliative care (SPC) and potential disparities in these outcomes. Objective: To evaluate the association of the COVID-19 pandemic with death at home and SPC delivery at the end of life and to examine whether disparities in socioeconomic status exist for these outcomes. Design, Setting, and Participants: In this cohort study, an interrupted time series analysis was conducted using Ontario Cancer Registry data comprising adult patients aged 18 years or older who died with cancer between the pre-COVID-19 (March 16, 2015, to March 15, 2020) and COVID-19 (March 16, 2020, to March 15, 2021) periods. The data analysis was performed between March and November 2023. Exposure: COVID-19-related hospital restrictions starting March 16, 2020. Main Outcomes and Measures: Outcomes were death at home and SPC delivery at the end of life (last 30 days before death). Socioeconomic status was measured using Ontario Marginalization Index area-based material deprivation quintiles, with quintile 1 (Q1) indicating the least deprivation; Q3, intermediate deprivation; and Q5, the most deprivation. Segmented linear regression was used to estimate monthly trends in outcomes before, at the start of, and in the first year of the COVID-19 pandemic. Results: Of 173 915 patients in the study cohort (mean [SD] age, 72.1 [12.5] years; males, 54.1% [95% CI, 53.8%-54.3%]), 83.7% (95% CI, 83.6%-83.9%) died in the pre-COVID-19 period and 16.3% (95% CI, 16.1%-16.4%) died in the COVID-19 period, 54.5% (95% CI, 54.2%-54.7%) died at home during the entire study period, and 57.8% (95% CI, 57.5%-58.0%) received SPC at the end of life. In March 2020, home deaths increased by 8.3% (95% CI, 7.4%-9.1%); however, this increase was less marked in Q5 (6.1%; 95% CI, 4.4%-7.8%) than in Q1 (11.4%; 95% CI, 9.6%-13.2%) and Q3 (10.0%; 95% CI, 9.0%-11.1%). There was a simultaneous decrease of 5.3% (95% CI, -6.3% to -4.4%) in the rate of SPC at the end of life, with no significant difference among quintiles. Patients who received SPC at the end of life (vs no SPC) were more likely to die at home before and during the pandemic. However, there was a larger immediate increase in home deaths among those who received no SPC at the end of life vs those who received SPC (Q1, 17.5% [95% CI, 15.2%-19.8%] vs 7.6% [95% CI, 5.4%-9.7%]; Q3, 12.7% [95% CI, 10.8%-14.5%] vs 9.0% [95% CI, 7.2%-10.7%]). For Q5, the increase in home deaths was significant only for patients who did not receive SPC (13.9% [95% CI, 11.9%-15.8%] vs 1.2% [95% CI, -1.0% to 3.5%]). Conclusions and Relevance: These findings suggest that the COVID-19 pandemic was associated with amplified socioeconomic disparities in death at home and SPC delivery at the end of life. Future research should focus on the mechanisms of these disparities and on developing interventions to ensure equitable and consistent SPC access.

Prognostic Factors Associated With Development of Venous Thromboembolism in Critically Ill Patients-A Systematic Review and Meta-Analysis.

OBJECTIVE: To identify prognostic factors for the development of venous thromboembolism in the ICU. DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception to March 1, 2021. STUDY SELECTION: We included English-language studies describing prognostic factors associated with the development of venous thromboembolism among critically ill patients. DATA EXTRACTION: Two authors performed data extraction and risk-of-bias assessment. We pooled adjusted odds ratios and adjusted hazard ratios for prognostic factors using random-effects model. We assessed risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. DATA SYNTHESIS: We included 39 observational cohort studies involving 729,477 patients. Patient factors with high or moderate certainty of association with increased odds of venous thromboembolism include older age (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29 per 10 yr), obesity (adjusted odds ratio, 1.25; 95% CI, 1.18-1.32), active malignancy (adjusted odds ratio, 1.70; 95% CI, 1.18-2.44), history of venous thromboembolism (adjusted odds ratio, 4.77; 95% CI, 3.42-6.65), and history of recent surgery (adjusted odds ratio, 1.77; 95% CI, 1.26-2.47). ICU-specific factors with high or moderate certainty of association with increased risk of venous thromboembolism include sepsis (adjusted odds ratio, 1.41; 95% CI, 1.12-1.78), lack of pharmacologic venous thromboembolism prophylaxis (adjusted odds ratio, 1.80; 95% CI, 1.14-2.84), central venous catheter (adjusted odds ratio, 2.93; 95% CI, 1.98-4.34), invasive mechanical ventilation (adjusted odds ratio, 1.74; 95% CI, 1.36-2.24), and use of vasoactive medication (adjusted odds ratio, 1.86; 95% CI, 1.23-2.81). CONCLUSIONS: This meta-analysis provides quantitative summaries of the association between patient-specific and ICU-related prognostic factors and the risk of venous thromboembolism in the ICU. These findings provide the foundation for the development of a venous thromboembolism risk stratification tool for critically ill patients.

Testing for non-inferior mortality: a systematic review of non-inferiority margin sizes and trial characteristics.

OBJECTIVE: To describe the size and variability of non-inferiority margins used in non-inferiority trials of medications with primary outcomes involving mortality, and to examine the association between trial characteristics and non-inferiority margin size. DESIGN: Systematic review. DATA SOURCES: Medline, Medline In Process, Medline Epub Ahead of Print and Embase Classic+Embase databases from January 1989 to December 2019. ELIGIBILITY CRITERIA: Prospective non-inferiority randomised controlled trials comparing pharmacological therapies, with primary analyses for non-inferiority and primary outcomes involving mortality alone or as part of a composite outcome. Trials had to prespecify non-inferiority margins as absolute risk differences or relative to risks of outcome and provide a baseline risk of primary outcome in the control intervention. RESULTS: 3992 records were screened, 195 articles were selected for full text review and 111 articles were included for analyses. 82% of trials were conducted in thrombosis, infectious diseases or oncology. Mortality was the sole primary outcome in 23 (21%) trials, and part of a composite primary outcome in 88 (79%) trials. The overall median non-inferiority margin was an absolute risk difference of 9% (IQR 4.2%-10%). When non-inferiority margins were expressed relative to the baseline risk of primary outcome in control groups, the median relative non-inferiority margin was 1.5 (IQR 1.3-1.7). In multivariable regression analyses examining the association between trial characteristics (medical specialty, inclusion of paediatric patients, mortality as a sole or part of a composite primary outcome, presence of industry funding) and non-inferiority margin size, only medical specialty was significantly associated with non-inferiority margin size. CONCLUSION: Absolute and relative non-inferiority margins used in published trials comparing medications are large, allowing conclusions of non-inferiority in the context of large differences in mortality. Accepting the potential for large increases in outcomes involving mortality while declaring non-inferiority is a challenging methodological issue in the conduct of non-inferiority trials.

Temporal Trends and Sex Differences in Intensity of Healthcare at the End of Life in Adults With Heart Failure.

Background Patients with chronic disease prefer an adequately supported death at home, but often die in the hospital. We assessed temporal trends and sex differences in healthcare intensity and location of death among decedents with heart failure. Methods and Results This was a retrospective cohort study of adults with heart failure who died between April 1, 2004 and March 31, 2017 in Ontario, Canada. We used population-based administrative databases to assess healthcare utilization during the last 6 months of life and applied multilevel multivariable logistic regression to assess whether sex was independently associated with location of death. Among 396 024 decedents with heart failure, mean (SD) age was 81.8 (10.7) years, 51.5% were women, and 53.4% had in-hospital deaths. From 2004 to 2016, there was an increase in patients receiving mechanical ventilation (15.1%-19.6%), hemodialysis (5.2%-6.8%), and cardiac revascularization (1.7%-2.3%). Relative to men, women spent fewer days in a hospital (mean, 16.4 versus 18.3; mean difference, 1.9; 95% CI, 1.7-2.0; P<0.001) and in an intensive care unit (mean, 2.1 versus 3.0; mean difference, 0.9; 95% CI, 0.8-0.9; P<0.001); and less commonly received mechanical ventilation (15.5% versus 20.8%; P<0.001); hemodialysis (4.8% versus 7.7%; P<0.001); or cardiac catheterization (2.8% versus 4.6%; P<0.001). Female sex was independently associated with lower odds of in-hospital death (odds ratio, 0.88; 95% CI, 0.87-0.89). Mean (SD) 6-month direct healthcare cost was greater for in-hospital ($52 349 [$55 649]) than out-of-hospital ($35 998 [$31 900]) death. Conclusions Among decedents with heart failure, invasive care in the last 6 months increased in prevalence over time but was less common in women, who had lower odds of dying in a hospital.

Comparison of 2 Triage Scoring Guidelines for Allocation of Mechanical Ventilators.

Importance: In the current setting of the coronavirus disease 2019 pandemic, there is concern for the possible need for triage criteria for ventilator allocation; to our knowledge, the implications of using specific criteria have never been assessed. Objective: To determine which and how many admissions to intensive care units are identified as having the lowest priority for ventilator allocation using 2 distinct sets of proposed triage criteria. Design, Setting, and Participants: This retrospective cohort study conducted in spring 2020 used data collected from US hospitals and reported in the Philips eICU Collaborative Research Database. Adult admissions (N = 40 439) to 291 intensive care units from 2014 to 2015 who received mechanical ventilation and were not elective surgery patients were included. Exposures: New York State triage criteria and original triage criteria proposed by White and Lo. Main Outcomes and Measures: Sequential Organ Failure Assessment (SOFA) scores were calculated for admissions. The proportion of patients who met initial criteria for the lowest level of priority for mechanical ventilation using each set of criteria and their characteristics and outcomes were assessed. Agreement was compared between the 2 sets of triage criteria, recognizing differences in stated criteria aims. Results: Among 40 439 intensive care unit admissions of patients who received mechanical ventilation, the mean (SD) age was 62.6 (16.6) years, 54.9% were male, and the mean (SD) SOFA score was 4.5 (3.7). Using the New York State triage criteria, 8.9% (95% CI, 8.7%-9.2%) were in the lowest priority category; these lowest priority admissions had a mean (SD) age of 62.9 (16.6) years, used a median (interquartile range) of 57.3 (20.1-133.5) ventilator hours each, and had a hospital survival rate of 38.6% (95% CI, 37.0%-40.2%). Using the White and Lo triage criteria, 4.3% (95% CI, 4.1%-4.5%) were in the lowest priority category; these admissions had a mean (SD) age of 68.6 (13.2) years, used a median (interquartile range) of 61.7 (24.3-142.8) ventilator hours each, and had a hospital survival rate of 56.2% (95% CI, 53.8%-58.7%). Only 655 admissions (1.6%) were in the lowest priority category for both guidelines, with the κ statistic for agreement equal to 0.20 (95% CI, 0.18-0.21). Conclusions and Relevance: Use of 2 initially proposed ventilator triage guidelines identified approximately 1 in every 10 to 25 admissions as having the lowest priority for ventilator allocation, with little agreement. Clinical assessment of different potential criteria for triage decisions in critically ill populations is important to ensure valid and equitable allocation of resources.

Adverse Events After Transition From ICU to Hospital Ward: A Multicenter Cohort Study.

OBJECTIVES: To examine adverse events and associated factors and outcomes during transition from ICU to hospital ward (after ICU discharge). DESIGN: Multicenter cohort study. SETTING: Ten adult medical-surgical Canadian ICUs. PATIENTS: Patients were those admitted to one of the 10 ICUs from July 2014 to January 2016. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two ICU physicians independently reviewed progress and consultation notes documented in the medical record within 7 days of patient's ICU discharge date to identify and classify adverse events. The adverse event data were linked to patient characteristics and ICU and ward physician surveys collected during the larger prospective cohort study. Analyses were conducted using multivariable logistic regression. Of the 451 patients included in the study, 84 (19%) experienced an adverse event, the majority (62%) within 3 days of transfer from ICU to hospital ward. Most adverse events resulted only in symptoms (77%) and 36% were judged to be preventable. Patients with adverse events were more likely to be readmitted to the ICU (odds ratio, 5.5; 95% CI, 2.4-13.0), have a longer hospital stay (mean difference, 16.1 d; 95% CI, 8.4-23.7) or die in hospital (odds ratio, 4.6; 95% CI, 1.8-11.8) than those without an adverse event. ICU and ward physician predictions at the time of ICU discharge had low sensitivity and specificity for predicting adverse events, ICU readmissions, and hospital death. CONCLUSIONS: Adverse events are common after ICU discharge to hospital ward and are associated with ICU readmission, increased hospital length of stay and death and are not predicted by ICU or ward physicians.

Association between Chinese or South Asian ethnicity and end-of-life care in Ontario, Canada.

BACKGROUND: Ethnicity may be associated with important aspects of end-of-life care, such as what treatments are received, access to palliative care and where people die. However, most studies have focused on end-of-life care of white, Hispanic and black patients. We sought to compare end-of-life care delivered to people of Chinese and South Asian ethnicity with that delivered to others from the general population, in Ontario, Canada. METHODS: In this population-based cohort study, we included all people who died in Ontario, Canada, between Apr. 1, 2004, and Mar. 31, 2015. People were identified as having Chinese or South Asian ethnicity on the basis of a validated surname algorithm. We used modified Poisson regression analyses to assess location of death and care received in the last 6 months of life. RESULTS: We analyzed 967 339 decedents, including 18 959 (2.0%) of Chinese and 11 406 (1.2%) of South Asian ethnicity. Chinese (13.6%) and South Asian (18.5%) decedents were more likely than decedents from the general population (10.1%) to die in the intensive care unit (ICU). The adjusted relative risk of dying in intensive care was 1.21 (95% confidence interval [CI] 1.15 to 1.27) for Chinese and 1.25 (95% CI 1.20 to 1.30) for South Asian decedents. In their last 6 months of life, decedents of Chinese and South Asian ethnicity experienced significantly more ICU admission, hospital admission, mechanical ventilation, dialysis, percutaneous feeding tube placement, tracheostomy and cardiopulmonary resuscitation than the general population. INTERPRETATION: Decedents of Chinese and South Asian ethnicity in Ontario were more likely than decedents from the general population to receive aggressive care and to die in an ICU. These findings may be due to communication difficulties between patients and clinicians, differences in preferences about end-of-life care or differences in access to palliative care services.

Early experience with medical assistance in dying in Ontario, Canada: a cohort study.

BACKGROUND: Medical assistance in dying (MAiD) was legalized across Canada in June 2016. Some have expressed concern that patient requests for MAiD might be driven by poor access to palliative care and that social and economic vulnerability of patients may influence access to or receipt of MAiD. To examine these concerns, we describe Ontario's early experience with MAiD and compare MAiD decedents with the general population of decedents in Ontario. METHODS: We conducted a retrospective cohort study comparing all MAiD-related deaths with all deaths in Ontario, Canada, between June 7, 2016, and Oct. 31, 2018. Clinical and demographic characteristics were collected for all MAiD decedents and compared with those of all Ontario decedents when possible. We used logistic regression analyses to describe the association of demographic and clinical factors with receipt of MAiD. RESULTS: A total of 2241 patients (50.2% women) were included in the MAiD cohort, and 186 814 in the general Ontario decedent cohort. Recipients of MAiD reported both physical (99.5%) and psychologic suffering (96.4%) before the procedure. In 74.4% of cases, palliative care providers were involved in the patient's care at the time of the MAiD request. The statutory 10-day reflection period was shortened for 26.6% of people. Compared with all Ontario decedents, MAiD recipients were younger (mean 74.4 v. 77.0 yr, standardized difference 0.18);, more likely to be from a higher income quintile (24.9% v. 15.6%, standardized difference across quintiles 0.31); less likely to reside in an institution (6.3% v. 28.0%, standardized difference 0.6); more likely to be married (48.5% v. 40.6%) and less likely to be widowed (25.7% v. 35.8%, standardized difference 0.34); and more likely to have a cancer diagnosis (64.4% v. 27.6%, standardized difference 0.88 for diagnoses comparisons). INTERPRETATION: Recipients of MAiD were younger, had higher income, were substantially less likely to reside in an institution and were more likely to be married than decedents from the general population, suggesting that MAiD is unlikely to be driven by social or economic vulnerability. Given the high prevalence of physical and psychologic suffering, despite involvement of palliative care providers in caring for patients who request MAiD, future studies should aim to improve our understanding and treatment of the specific types of suffering that lead to a MAiD request.

End-of-Life Care Received by Physicians Compared With Nonphysicians.

Importance: The idea that physicians as patients choose less-aggressive care at the end of life for themselves is an often-cited rationale to advocate for less technology-laden end-of-life care. Objective: To assess end-of-life care received by physicians compared with nonphysicians in a system with universal health care. Design, Setting, and Participants: In this population-level decedent cohort study of data from April 1, 2004, through March 31, 2015 (fiscal years 2004-2014), in Ontario, Canada, 2507 physicians were matched approximately 1:3 to 7513 nonphysicians (ie, individuals who never were registered as a physician with the College of Physicians and Surgeons of Ontario) according to age, sex, income quintile, and location of residence. Main Outcomes and Measures: The primary outcome was location of death. Other outcomes included measures of health care use in the last 6 months of life. Differences were assessed using Poisson regression with robust error variances, adjusting for the Charlson Comorbidity Index. Results: In total, 2516 physicians and 954 836 nonphysicians died between April 1, 2004, and March 31, 2015, in Ontario; 2247 physicians (89.3%) and 474 182 nonphysicians (49.7%) were men. The median (interquartile range) age at death was 82 (74-87) years for the physicians and 80 (68-87) years for the nonphysicians. After matching, data for 2507 physicians and 7513 nonphysicians were analyzed. For physicians, the risk of death at home was no different from that for nonphysicians (42.8% vs 39.0%; adjusted relative risk [aRR], 1.04; 95% CI, 0.99-1.09), but the risk of death in an intensive care unit was increased (11.9% vs 10.0%; aRR, 1.22; 95% CI, 1.08-1.39). In the prior 6 months, physicians had a decreased risk of an emergency department visit (73.0% vs 78.4%; aRR, 0.96; 95% CI, 0.94-0.98) but increased risks of an intensive care unit admission (20.8% vs 19.1%; aRR, 1.14; 95% CI, 1.05-1.24) and of receipt of palliative care services (52.9% vs 47.4%; aRR, 1.18; 95% CI, 1.13-1.23). Among a subgroup of 457 physicians and 1347 nonphysicians with cancer, the risk of death at home or intensive care unit was increased (37.6% vs 28.6%; aRR, 1.30; 95% CI, 1.13-1.50), as was the risk of receiving chemotherapy in the last 6 months of life. Conclusions and Relevance: There was no difference overall for physicians compared with nonphysicians in terms of the likelihood of dying at home; physicians were more likely to die in an intensive care unit and to receive chemotherapy, but also to receive palliative care services. These findings suggest that physicians do not consistently opt for less-aggressive care but instead receive end-of-life care that includes both intensive and palliative care. These findings inform a more nuanced perspective of what physicians may perceive to be optimal care at the end of life.

Increased Rate of Long-term Mortality Among Burn Survivors: A Population-based Matched Cohort Study.

OBJECTIVE: To estimate long-term mortality following major burn injury compared with matched controls. SUMMARY BACKGROUND DATA: The effect of sustaining a major burn injury on long-term life expectancy is poorly understood. METHODS: Using health administrative data, all adults who survived to discharge after major burn injury between 2003 and 2013 were matched to between 1 and 5 uninjured controls on age, sex, and the extent of both physical and psychological comorbidity. To account for socioeconomic factors such as residential instability and material deprivation, we also matched on marginalization index. The primary outcome was 5-year all-cause mortality, and all patients were followed until death or March 31, 2014. Cumulative mortality estimates were estimated using the Kaplan-Meier method. Cox proportional hazards modeling was used to estimate the association of burn injury with mortality. RESULTS: In total, 1965 burn survivors of mean age 44 (standard deviation 17) years with median total body surface area burn of 15% [interquartile range (IQR) 5-15] were matched to 8671 controls and followed for a median 5 (IQR 2.5-8) years. Five-year mortality was significantly greater among burn survivors (11 vs 4%, P < 0.001). The hazard ratio was greatest during the first year (4.15, 95% CI 3.17-5.42), and declined each year thereafter, reaching 1.65 (95% CI 1.02-2.67) in the fifth year after discharge. Burn survivors had increased mortality related to trauma (mortality rate ratio, MRR 9.8, 95% CI 5-19) and mental illness (MRR 9.1, 95% CI 4-23). CONCLUSIONS: Burn survivors have a significantly higher rate of long-term mortality than matched controls, particularly related to trauma and mental illness. Burn follow-up should be focused on injury prevention, mental healthcare, and detection and treatment of new disease.

Burn center care reduces acute health care utilization after discharge: A population-based analysis of 1,895 survivors of major burn injury.

BACKGROUND: Improvements in survival after burns have resulted in more patients being discharged home after severe injury. However, the postdischarge health care needs of burn survivors are not well understood. We aimed to determine the rate and causes of unplanned presentation to acute care facilities in the 5 years after major burn injury. METHODS: Data derived from several population-based administrative databases were used to conduct a retrospective cohort study. All patients aged ≥16 years who survived to discharge after a major burn injury in 2003-2013 were followed for 1-5 years. All emergency department visits and unplanned readmissions were identified and classified by cause. Factors associated with emergency department visits were modeled using negative binomial generalized estimating equations. Factors associated with readmission were modeled using multivariable competing risk regression. RESULTS: We identified 1,895 patients who survived to discharge; 68% of patients had at least one emergency department visit and 30% had at least one readmission. Five-year mortality was 10%. The most common reason for both emergency department visits and readmissions was traumatic injury. After risk adjustment, patients who received their index care in a burn center experienced significantly less need for subsequent unplanned acute care, fewer emergency department visits (relative risk 0.61, 95% confidence interval, 0.52-0.72), and fewer hospital readmissions (hazard ratio 0.77, 95% confidence interval, 0.65-0.92). CONCLUSION: Acute health care utilization is frequent after burn injury and is most commonly related to traumatic injuries. Burn-related events are uncommon beyond 30 days after discharge, suggesting low rates of burn recidivism. Patients treated at burn centers have significantly reduced unplanned health care utilization after their injury.

Barriers to Goals of Care Discussions With Patients Who Have Advanced Heart Failure: Results of a Multicenter Survey of Hospital-Based Cardiology Clinicians.

BACKGROUND: Conversations about goals of care in hospital are important to patients who have advanced heart failure (HF). METHODS: We conducted a multicenter survey of cardiology nurses, fellows, and cardiologists at 8 Canadian teaching hospitals. The primary outcome was the importance of barriers to goals-of-care discussions in hospital (1 = extremely unimportant; 7 = extremely important). We also elicited perspectives on roles of different practitioners in having these conversations. RESULTS: Questionnaires were returned by 770/1024 (75.2%) eligible clinicians. The most important perceived barriers were: family members' and patients' difficulty in accepting a poor prognosis (mean [SD] score 5.9 [1.1] and 5.7 [1.2], respectively), family members' and patients' lack of understanding about the limitations and harms of life-sustaining treatments (5.8 [1.1] and 5.7 [1.2], respectively), and lack of agreement among family members about goals of care (5.8 [1.2]). Interprofessional team members were viewed as having different but important roles in goals-of-care discussions. CONCLUSIONS: Cardiology clinicians perceive family and patient-related factors as the most important barriers to goals-of-care discussions in hospital. Many members of the interprofessional team were viewed as having important roles in addressing goals of care. These findings can inform the design of future interventions to improve communication about goals of care in advanced HF.

Expanding the scope of Critical Care Rapid Response Teams: a feasible approach to identify adverse events. A prospective observational cohort.

INTRODUCTION: Adverse events (AEs) affect 3-12% of hospitalised patients. These are estimates from a labour-intensive chart review process,which is not feasible outside research. Clinical deterioration on the wards triggers a rapid response teams (RRTs) consult and can be used to identify an AE prospectively. OBJECTIVES: To demonstrate the feasibility of using RRT to detect AEs and compare this methodology to the rates reported using an electronic safety reporting system. METHODS: Prospective observational cohort of RRT consults. Three independent physicians reviewed all cases for the occurrence of an AE and its preventability. We summarise AEs as rates per 1000 patient-days, and compared the rates between RRT and the safety reporting system using a Poisson model. RESULTS: There were 8713 hospital admissions, with 531 RRT consults and 247 (2.8%) cases included. Forty-four (17.8%) and 35 cases (14.2%) were judged as AEs and preventable AEs, respectively. RRT identified 0.52 AE/1000 patient-days, compared with 0.21 AE/1000 patient-days detected through the electronic safety reporting system (rate ratio 2.4, 95% CI 1.4 to 4.2, p=0.0014). Patients in surgical wards had more AEs (0.83/1000 vs 0.36/1000, p<0.01) and preventable AEs (0.70 vs 0.21, p<0.01) than patients in medical wards. Agreement for AE (κ 0.46, 95% CI 0.39 to 0.53) and preventable AE (κ 0.47, 95% CI 0.40 to 0.53) was moderate among reviewers. CONCLUSIONS: Reviewing RRT consults identified a high proportion of AEs and preventable AEs. This methodology detected twice as many AEs as the hospital's safety reporting system. RRT clinicians provide a complementary and more sensitive mechanism than traditional safety reporting systems to identify possible AEs in hospitals.

Barriers to goals of care discussions with seriously ill hospitalized patients and their families: a multicenter survey of clinicians.

IMPORTANCE: Seriously ill hospitalized patients have identified communication and decision making about goals of care as high priorities for quality improvement in end-of-life care. Interventions to improve care are more likely to succeed if tailored to existing barriers. OBJECTIVE: To determine, from the perspective of hospital-based clinicians, (1) barriers impeding communication and decision making about goals of care with seriously ill hospitalized patients and their families and (2) their own willingness and the acceptability for other clinicians to engage in this process. DESIGN, SETTING, AND PARTICIPANTS: Multicenter survey of medical teaching units of nurses, internal medicine residents, and staff physicians from participating units at 13 university-based hospitals from 5 Canadian provinces. MAIN OUTCOMES AND MEASURES: Importance of 21 barriers to goals of care discussions rated on a 7-point scale (1 = extremely unimportant; 7 = extremely important). RESULTS: Between September 2012 and March 2013, questionnaires were returned by 1256 of 1617 eligible clinicians, for an overall response rate of 77.7% (512 of 646 nurses [79.3%], 484 of 634 residents [76.3%], 260 of 337 staff physicians [77.2%]). The following family member-related and patient-related factors were consistently identified by all 3 clinician groups as the most important barriers to goals of care discussions: family members' or patients' difficulty accepting a poor prognosis (mean [SD] score, 5.8 [1.2] and 5.6 [1.3], respectively), family members' or patients' difficulty understanding the limitations and complications of life-sustaining treatments (5.8 [1.2] for both groups), disagreement among family members about goals of care (5.8 [1.2]), and patients' incapacity to make goals of care decisions (5.6 [1.2]). Clinicians perceived their own skills and system factors as less important barriers. Participants viewed it as acceptable for all clinician groups to engage in goals of care discussions-including a role for advance practice nurses, nurses, and social workers to initiate goals of care discussions and be a decision coach. CONCLUSIONS AND RELEVANCE: Hospital-based clinicians perceive family member-related and patient-related factors as the most important barriers to goals of care discussions. All health care professionals were viewed as playing important roles in addressing goals of care. These findings can inform the design of future interventions to improve communication and decision making about goals of care.

Age-related trends in severe injury hospitalization in Canada.

BACKGROUND: We performed a population-based evaluation of age-related trends in severe injury hospitalization across Canada. METHODS: We identified hospitalizations following severe injury (Injury Severity Score [ISS] > 15) between 2002 and 2009 using the Canadian National Trauma Registry. Age-standardized severe injury hospitalization rates were calculated using the direct method referencing the 2006 Canadian population. The annual percent change in hospitalization rates were estimated using negative binomial regression. RESULTS: During the 8-year period, hospitalization rates for severe injury rose by 22% among individuals 65 years or older, compared with 10% among individuals younger than 65 years. Fall-related injuries accounted for 46% of all severe injury hospitalizations and increased by an average of 3% annually, with a twofold higher annual rate of increase among the elderly. Case-fatality rates declined by 10%, with the decline more than threefold higher among younger patients. CONCLUSION: Elderly patients accounted for an increasing proportion of hospitalizations, highlighting important opportunities for injury prevention among this age group. Case-fatality rates, while declining among younger patients, remained stable in the elderly population, suggesting the need for better strategies to manage the complex care needs of these patients. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Caring for critically ill patients with ebola virus disease. Perspectives from West Africa.

The largest ever Ebola virus disease outbreak is ravaging West Africa. The constellation of little public health infrastructure, low levels of health literacy, limited acute care and infection prevention and control resources, densely populated areas, and a highly transmissible and lethal viral infection have led to thousands of confirmed, probable, or suspected cases thus far. Ebola virus disease is characterized by a febrile severe illness with profound gastrointestinal manifestations and is complicated by intravascular volume depletion, shock, profound electrolyte abnormalities, and organ dysfunction. Despite no proven Ebola virus-specific medical therapies, the potential effect of supportive care is great for a condition with high baseline mortality and one usually occurring in resource-constrained settings. With more personnel, basic monitoring, and supportive treatment, many of the sickest patients with Ebola virus disease do not need to die. Ebola virus disease represents an illness ready for a paradigm shift in care delivery and outcomes, and the profession of critical care medicine can and should be instrumental in helping this happen.

Tracheostomy timing in traumatic brain injury: a propensity-matched cohort study.

BACKGROUND: The optimal timing of tracheostomy in patients with severe traumatic brain injury (TBI) is controversial; observational studies have been challenged through confounding by indication, and interventional studies have rarely enrolled patients with isolated TBI. METHODS: We included a cohort of adults with isolated TBI who underwent tracheostomy within 1 of 135 participating centers in the American College of Surgeons' Trauma Quality Improvement Program, during 2009 to 2011. Patients were classified as having undergone early tracheostomy (ET, ≤8 days) versus late tracheostomy (>8 days). Outcomes were compared between propensity score-matched groups to reduce confounding by indication. In sensitivity analyses, we used time-dependent proportional hazard regression to address immortal time bias and assessed the association between hospital ET rate and patients' outcome at the hospital level. RESULTS: From 1,811 patients, a well-balanced propensity-matched cohort of 1,154 patients was defined. After matching, ET was associated with fewer mechanical ventilation days (median, 10 days vs. 16 days; rate ratio [RR], 0.70; 95% confidence interval [CI], 0.66-0.75), shorter intensive care unit stay (median, 13 days vs. 19 days; RR, 0.70; 95% CI, 0.66-0.75), shorter hospital length of stay (median, 20 days vs. 27 days; RR, 0.80; 95% CI, 0.74-0.86), and lower odds of pneumonia (41.7% vs. 52.7%; odds ratio [OR], 0.64; 95% CI, 0.51-0.80), deep venous thrombosis (8.2% vs. 14.4%; OR, 0.53; 95% CI, 0.37-0.78), and decubitus ulcer (4.0% vs. 8.9%; OR, 0.43; 95% CI, 0.26-0.71) but no significant difference in pulmonary embolism (1.8% vs. 3.3%; OR, 0.52; 95% CI, 0.24-1.10). Hospital mortality was similar between both groups (8.4% vs. 6.8%; OR, 1.25; 95% CI, 0.80-1.96). Results were consistent using several alternate analytic methods. CONCLUSION: In this observational study, ET was associated with a shorter duration of mechanical ventilation, intensive care unit stay, and hospital stay but not hospital mortality. ET may represent a mechanism to reduce in-hospital morbidity for patients with TBI. LEVEL OF EVIDENCE: Therapeutic study, level II.

Clinical and temporal patterns of severe pneumonia causing critical illness during Hajj.

BACKGROUND: Pneumonia is a leading cause of hospitalization during Hajj and susceptibility and transmission may be exacerbated by extreme spatial and temporal crowding. We describe the number and temporal onset, co-morbidities, and outcomes of severe pneumonia causing critical illness among pilgrims. METHOD: A cohort study of all critically ill Hajj patients, of over 40 nationalities, admitted to 15 hospitals in 2 cities in 2009 and 2010. Demographic, clinical, and laboratory data, and variables necessary for calculation of the Acute Physiology and Chronic Health Evaluation IV scores were collected. RESULTS: There were 452 patients (64.6% male) who developed critical illness. Pneumonia was the primary cause of critical illness in 123 (27.2%) of all intensive care unit (ICU) admissions during Hajj. Pneumonia was community (Hajj)-acquired in 66.7%, aspiration-related in 25.2%, nosocomial in 3.3%, and tuberculous in 4.9%. Pneumonia occurred most commonly in the second week of Hajj, 95 (77.2%) occurred between days 5-15 of Hajj, corresponding to the period of most extreme pilgrim density. Mechanical ventilation was performed in 69.1%. Median duration of ICU stay was 4 (interquartile range [IQR] 1-8) days and duration of ventilation 4 (IQR 3-6) days. Commonest preexisting co-morbidities included smoking (22.8%), diabetes (32.5%), and COPD (17.1%). Short-term mortality (during the 3-week period of Hajj) was 19.5%. CONCLUSION: Pneumonia is a major cause of critical illness during Hajj and occurs amidst substantial crowding and pilgrim density. Increased efforts at prevention for at risk pilgrim prior to Hajj and further attention to spatial and physical crowding during Hajj may attenuate this risk.

Critical care resources in the Solomon Islands: a cross-sectional survey.

BACKGROUND: There are minimal data available on critical care case-mix, care processes and outcomes in lower and middle income countries (LMICs). The objectives of this paper were to gather data in the Solomon Islands in order to gain a better understanding of common presentations of critical illness, available hospital resources, and what resources would be helpful in improving the care of these patients in the future. METHODS: This study used a mixed methods approach, including a cross sectional survey of respondents' opinions regarding critical care needs, ethnographic information and qualitative data. RESULTS: The four most common conditions leading to critical illness in the Solomon Islands are malaria, diseases of the respiratory system including pneumonia and influenza, diabetes mellitus and tuberculosis. Complications of surgery and trauma less frequently result in critical illness. Respondents emphasised the need for basic critical care resources in LMICs, including equipment such as oximeters and oxygen concentrators; greater access to medications and blood products; laboratory services; staff education; and the need for at least one national critical care facility. CONCLUSIONS: A large degree of critical illness in LMICs is likely due to inadequate resources for primary prevention and healthcare; however, for patients who fall through the net of prevention, there may be simple therapies and context-appropriate resources to mitigate the high burden of morbidity and mortality. Emphasis should be on the development and acquisition of simple and inexpensive tools rather than complicated equipment, to prevent critical care from unduly diverting resources away from other important parts of the health system.

Lipid membrane composition influences drug release from dioleoylphosphatidylethanolamine-based liposomes on exposure to ultrasound.

The effect of membrane composition on calcein release from dioleoylphosphatidylethanolamine (DOPE)-based liposomes on exposure to low doses of 1.13 MHz focused ultrasound (US) was investigated by multivariate analysis, with the goal of designing liposomes for US-mediated drug delivery. Regression analysis revealed a strong correlation between sonosensitivity and the non-bilayer forming lipids DOPE and pegylated distearoylphosphatidylethanolamine (DSPE-PEG 2000), with DOPE having the strongest impact. Unlike most of the previously studied distearoylphosphatidylethanolamine (DSPE)-based liposomes, all the current DOPE-based liposome formulations were found stable in 20% serum in terms of drug retention.