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Purpose To provide population-level estimates of the association of frailty with one-year outcomes after critical illness. Materials and methods Retrospective cohort study of patients who survived an ICU admission between April 2002 and March 2015. Pre-existing frailty was classified using the Johns Hopkins Adjusted Clinical Groups frailty indicator. Multivariable Cox regression and Fine and Gray models were used to examine the association between frailty and mortality and hospital readmission. Results Of 534,991 patients, 19.3% had pre-existing frailty. Compared to non-frail survivors, at one-year frail patients had higher mortality (18.3% vs 9.5%, adjusted HR 1.17 95% CI: 1.15–1.19) and hospital readmission (44.4% vs 36.6%, adjusted HR 1.10 95% CI: 1.08–1.11) and a CAN$19,628 (95% CI: $19,279–$19,997) greater increase in healthcare costs compared to the year prior to hospitalization. The association between frailty and mortality was stronger among older individuals, but the risk of readmission among frail patients decreased with age. Conclusion Patients with pre-existing frailty who develop critical illness have higher rates of hospital readmission and death than patients without frailty, and age modifies these associations. These data highlight the importance of considering both frailty and age when seeking to identify at-risk patients who might benefit from closer follow-up after discharge.

Background Many patients use opioids chronically before surgery; it is unclear if surgery alters the likelihood of ongoing opioid consumption in these patients. Methods We performed a population-based matched cohort study of adults in Ontario, Canada undergoing one of 16 non-orthopaedic surgical procedures and who were chronically using opioids, defined as (1) an opioid prescription that overlapped the index date and (2) either a total of 120 or more cumulative calendar days of filled opioid prescriptions, or 10 or more prescriptions filled in the prior year. Each surgical patient was matched based on age, sex, Charlson comorbidity index, and daily preoperative opioid dose to three non-surgical patients who were also chronic opioid users. The primary outcome was time to opioid discontinuation. Results The cohort included 4755 surgical and 14 265 matched non-surgical patients. After adjustment for sociodemographic characteristics and comorbidities, surgery was associated with an increased likelihood of opioid discontinuation (adjusted hazard ratio: 1.34, 95% confidence interval [CI]: 1.27, 1.42). Among surgical patients, factors associated with a reduced odds of discontinuation included a mean preoperative opioid dose above 90 morphine milligram equivalents (adjusted odds ratio [aOR]: 0.39; 95% CI: 0.32, 0.49) or filling a prescription for oxycodone (aOR: 0.73; 95% CI: 0.56, 0.98). Receipt of an in-patient Acute Pain Service consultation (aOR: 1.34; 95% CI: 1.06, 1.69) or residing in the highest neighbourhood income quintile (aOR: 1.35; 95% CI: 1.04, 1.79) were associated with a greater odds of opioid discontinuation. Conclusions For chronic opioid users, surgery was associated with an increased likelihood of discontinuation of opioids in the following year compared with non-surgical chronic opioid users.

OBJECTIVE: The aim of this study was to determine the relationship between surgeon opioid prescribing intensity and subsequent persistent opioid use among patients undergoing surgery. SUMMARY BACKGROUND DATA: The extent to which different postoperative prescribing practices lead to persistent opioid use among surgical patients is poorly understood. METHODS: Retrospective population-based cohort study assessing opioid-naive adults who underwent one of four common surgeries. For each surgical procedure, the surgeons’ opioid prescribing intensity was categorized into quartiles based on the median daily dose of morphine equivalents of opioids dispensed within 7 days of the surgical visit for all the surgeons’ patients. The primary outcome was persistent opioid use in the year following surgery, defined as 180 days or more of opioids supplied within the year after the index date excluding prescriptions filled within 30 days of the index date. Secondary outcomes included a refill for an opioid within 30 days and emergency department visits and hospitalizations within 1 year. RESULTS: Among 112,744 surgical patients, patients with surgeons in the highest intensity quartile (Q4) were more likely to fill an opioid prescription within 7 days after surgery compared with those in the lowest quartile (Q1) (83.3% Q4 vs 65.4% Q1). In the primary analysis, the incidence of persistent opioid use in the year after surgery was rare in both highest and lowest quartiles (0.3% Q4 vs 0.3% Q1), adjusted odds ratio (AOR) of 1.18, 95% CI 0.83–1.66). However, multiple analyses using stricter definitions of persistent use that included the requirement of a prescription filled within 7 days of discharge after surgery showed a significant association with surgeon quartile (up to an AOR 1.36, 95% CI 1.25, 1.47). Patients in Q4 were more likely to refill a prescription within 30 days (4.8% Q4 vs 4.0% Q1, AOR 1.14, 95% CI 1.04–1.24). CONCLUSIONS: Surgeons’ overall prescribing practices may contribute to persistent opioid use and represent a target for quality improvement. However, the association was highly sensitive to the definition of persistent use used.

Background Pregnancy-related critical illness results in approximately 300,000 deaths globally each year. The objective was to describe the variation in ICU admission and the contribution of patient- and hospital-based factors in ICU admission among acute care hospitals for pregnant and postpartum women in Canada. Methods A nationwide cohort study between 2004 and 2015, comprising all pregnant or postpartum women admitted to Canadian hospitals. The primary outcome was ICU admission. Secondary outcomes were severe maternal morbidity (a potentially life-threatening condition) and maternal death (during and within 6 weeks after pregnancy). The proportion of total variability in ICU admission rates due to the differences among hospitals was described using the median odds ratio from multi-level logistic regression models, adjusting for individual hospital clusters. Results There were 3,157,248 identifiable pregnancies among women admitted to 342 Canadian hospitals. The overall ICU admission rate was 3.2 per 1000 pregnancies. The rate of severe maternal morbidity was 15.8 per 1000 pregnancies, of which 10% of women were admitted to an ICU. The most common severe maternal morbidity events included postpartum hemorrhage (n = 16,364, 0.52%) and sepsis (n = 11,557, 0.37%). Of the 195 maternal deaths (6.2 per 100,000 pregnancies), only 130 (67%) were admitted to ICUs. Patients dying in hospital, without admission to ICU, included those with cardiovascular compromise, hemorrhage, and sepsis. For 2 pregnant women with similar characteristics at different hospitals, the average (median) odds of being admitted to ICU was 1.92 in 1 hospital compared to another. Hospitals admitting the fewest number of pregnant patients had the highest incidence of severe maternal morbidity and mortality. Patient-level factors associated with ICU admission were maternal comorbidity index (OR 1.88 per 1 unit increase, 95%CI 1.86–1.99), urban residence (OR 1.09, 95%CI 1.02–1.16), and residing at the lowest income quintile (OR 1.44, 95%CI 1.34–1.55). Conclusions Most women who experience severe maternal morbidity are not admitted to an ICU. There exists a wide hospital-level variability in ICU admission, with patients living in urban locations and patients of lowest income levels most likely to be admitted to ICU. Cardiovascular compromise, hemorrhage, and sepsis represent an opportunity for improved patient care and outcomes.

Objective Pregnancy-associated morbidity results in hundreds of thousands of deaths annually worldwide. Reducing maternal mortality is a key United Nations Millennium Development Goal. Although maternal mortality has declined in high-income countries, contemporary estimates of maternal morbidity and mortality trends in Canada are lacking. Methods This population-based study investigated all antepartum, peripartum, and postpartum women presenting to an acute care hospital in Canada from April 1, 2004 to March 31, 2015. The primary outcome was the change in rates of severe maternal morbidity over time. Secondary outcomes included severe maternal mortality and intensive care unit admission, including by province and territory (level of evidence: II2). Results The cohort comprised 2 035 453 mothers with 3 162 303 pregnancies. There were 17.7 per 1000 episodes of severe maternal morbidity, with annual increases of 1.3% (95% confidence interval [CI] 0.60–2.0) for severe maternal morbidity. The maternal mortality rate was 6.2 per 100 000 deliveries and stable over time (estimated percentage of annual change of −0.46%; 95% CI −5.0 to 4.3). The most common causes of severe maternal morbidity were postpartum hemorrhage (5.5 per 1000 deliveries), sepsis (3.8 per 1,000 deliveries), and cardiac failure (1.5 per 1000 deliveries). Severe maternal morbidity varied across Canadian regions but was highest in the Territories at 22.8 per 1000 deliveries. Conclusion Although maternal mortality has been stable in Canada over time, rates of severe maternal morbidity are increasing and are associated with substantial regional variation, with the highest rates experienced by women in the northern Territories.

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 P P P P 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.

Rationale: Patients who receive invasive mechanical ventilation (IMV) are usually exposed to opioids as part of their sedation regimen. The rates of posthospital prescribing of opioids are unknown. Objectives: To determine the frequency of persistent posthospital opioid use among patients who received IMV. Methods: We assessed opioid-naive adults who were admitted to an ICU, received IMV, and survived at least 7 days after hospital discharge in Ontario, Canada over a 26-month period (February, 2013 through March, 2015). The primary outcome was new, persistent opioid use during the year after discharge. We assessed factors associated with persistent use by multivariable logistic regression. Patients receiving IMV were also compared with matched hospitalized patients who did not receive intensive care (non-ICU). Measurements and Main Results: Among 25,085 opioid-naive patients on IMV, 5,007 (20.0%; 95% confidence interval [CI], 19.5–20.5) filled a prescription for opioids in the 7 days after hospital discharge. During the next year, 648 (2.6%; 95% CI, 2.4–2.8) of the IMV cohort met criteria for new, persistent opioid use. The patient characteristic most strongly associated with persistent use in the IMV cohort was being a surgical (vs. medical) patient (adjusted odds ratio, 3.29; 95% CI, 2.72–3.97). The rate of persistent use was slightly higher than for matched non-ICU patients (2.6% vs. 1.5%; adjusted odds ratio, 1.37 [95% CI, 1.19–1.58]). Conclusions: A total of 20% of IMV patients received a prescription for opioids after hospital discharge, and 2.6% met criteria for persistent use, an average of 300 new persistent users per year in a population of 14 million. Receipt of surgery was the factor most strongly associated with persistent use.

PURPOSE Opioids are commonly prescribed for acute pain after surgery. However, it is unclear whether these prescriptions are usually modified to account for patient age and, in particular, opioid-related risks among older adults. We therefore sought to describe postoperative opioid prescriptions filled by opioid-naive adults undergoing four common surgical procedures. METHODS This retrospective cohort study used individually linked surgery and prescription opioid dispensing data from Ontario, Canada to create a population-based sample of 135 659 opioid-naive adults who underwent one of four surgical procedures (laparoscopic cholecystectomy, laparoscopic appendectomy, knee meniscectomy, or breast excision) between 2013 and 2017. Patient age, in years, was categorized as 18 to 64, 65 to 69, 70 to 74, and 75 and over. Postoperative opioid prescriptions were identified as those filled on or within 6 days of surgical discharge date. For those who filled a prescription, we assessed the total morphine milligram equivalent (MME) dose, types of opioids, and any subsequent opioid prescriptions filled within 30 days of surgical discharge date. Results were presented stratified by surgical procedure. RESULTS For three of the four surgical procedures we assessed, the proportion of patients who filled a postoperative opioid prescription decreased with age (P

Objective To evaluate whether the male predominance of older people admitted to intensive care units (ICUs) is due to gender differences in the presence of spouses, partners, or children; rates of gender-specific disease; or triage decisions made by health system personnel. Data sources and collection Three population-based datasets, 2004-2012, of Canadians ≥65 years: provincial health care data from Manitoba (n = 250 190) and national data of nursing home residents (n = 133 982) and community-based homecare recipients (n = 210 090). Study design Retrospective observational study, using multivariable Cox proportional hazards and logistic regression. Principal findings Males predominated in ICU admissions: from Manitoba (hazard ratio [HR] = 1.87, 95% CI = 1.80-1.95), nursing homes (HR = 1.47, 1.35-1.60), and homecare (odds ratio = 1.14, 1.11-1.17). Adjustment for spouses, partners, and children did not attenuate this effect. The HR for gender was lower by 13.5 percent, relative, after excluding ICU care for cardiac causes. Male predominance was not present during a second ICU admission among survivors of a first ICU-containing hospitalization (HR = 1.07, 0.96-1.20). Conclusions In three older cohorts, the male predominance of ICU admission was not explained by gender differences in the presence of a spouse, partner, or children, or cardiac disease rates. The third finding suggests that triage bias is unlikely to be responsible for the male predominance.

Background Health care utilization increase towards the end of life. There is little known about the intensity of care, including use of in-hospital services, critical care units, and invasive procedures at the end of life in heart failure (HF). Aims To determine the type and intensity of health care services offered at the end of life to patients with HF, and to establish the determinants of and costs associated with death in the hospital versus at home. Methods We conducted a retrospective cohort study of adults (≥18 years) who died between April 1, 2004 and March 31, 2017 in Ontario, Canada. We included decedents with a diagnosis of HF in the 2 years preceding their death and a hospitalization for HF in their last year of life. We obtained demographic, clinical, healthcare utilization, and healthcare cost data from population-based administrative databases, using unique encrypted identifiers to link records. We calculated direct costs from the perspective of the Ministry of Health in our publicly-funded healthcare system. We used descriptive statistics and a 2-level multivariable logistic regression model) with patients (1st level) nested in regions (2nd level) to assess for predictors of death in the hospital versus at home. Results We identified 396,024 adults with HF who died between April 1, 2004 and March 31, 2017. Mean (standard deviation [SD]) age at death was 81.8 (10.7) years, and 48.5% were men. During the last 6 months of life, patients commonly experienced hospitalizations (78.1%), care from >10 different physicians (62.2%); intensive care unit (ICU) admissions (26.4%); mechanical ventilation (18.1%); hemodialysis (6.2%); and cardiac catheterization (3.7%). In the last 6 months of life, patients spent a mean (SD) of 17.4 (23.0) days in the hospital; 2.5 (8.3) days in an ICU; and 1.6 (7.9) days on a ventilator. While the proportion of deaths at home increased from 32.6% in 2004–2005 to 38% in 2016–2017, a majority of patients (53.4%) died in hospital during the study period. Factors independently associated with in-hospital death included age (OR 0.53 [95% CI 0.51–0.55] for age >85 years vs Conclusion In this large cohort study in Ontario, Canada, patients with HF commonly received in-hospital, intensive, and invasive care in the last 6 months of life, and a majority of patients died in hospital. Death in hospital was associated with higher costs of care in the terminal 6 months than death outside hospital. Acknowledgement/Funding Heart and Stroke Foundation of Ontario, Canadian Institutes of Health Research

Background There are sex-based disparities in care and outcomes among patients with heart failure (HF), but the association between sex and health care services received at the end-of-life health is unknown. Purpose To assess for sex-based differences in location of death and the type and intensity of health care services received at the end of life among patients with HF. Methods We conducted a retrospective cohort study of adults (≥18 years) who died between April 1, 2004 and March 31, 2017 in Ontario, Canada. We included decedents who had a diagnosis of HF and a hospitalization for HF in the year preceding their death. We obtained demographic, clinical, health care utilization, and healthcare system cost data from population-based administrative databases, using unique encrypted identifiers to link records. We used descriptive statistics and a 2-level multivariable logistic regression model with patients (1st level) nested in regions (2nd level) to assess whether sex was independently associated with death in hospital. Results We identified 396,024 adults (51.5% women) who died of HF between April 1, 2004 and March 31, 2017. Mean (SD) age at death was 81.8 (10.7) years and a majority of deaths (53.4%) occurred in the hospital. During the last 6 months of life, a significantly lower proportion of women than men experienced emergency department visits (81.7% vs 86.5%; p Conclusion In this large cohort study in Ontario, Canada, women with HF received disproportionately lower in-hospital and invasive care services than men in their last 6 months of life and were more likely than men to die at home. Acknowledgement/Funding Canadian Institutes of Health Research

To assess temporal trends in pre-existing opioid exposure prior to hospitalization among elderly intensive care unit (ICU) patients and its association with adverse outcomes.We performed a population-based retrospective cohort study using health administrative data from the province of Ontario, Canada. We included all older adult (65 years) admissions to an ICU between April 2002 and March 2015. The exposure was opioid use before admission categorized as chronic use, intermittent use, and non-use.The cohort included 711,312 elderly patient admissions to an ICU. Of these, 6.8% (n = 48,363) were chronic opioid users, 28.1% (n = 200,149) intermittent users, and 65.0% (n = 462,800) non-users. Compared with non-users, chronic opioid users and intermittent users had higher in-hospital mortality (adjusted odds ratio: 1.12, 95% CI, 1.09-1.15, p 0.0001 for chronic users; adjusted odds ratio: 1.09, 95% CI, 1.07-1.11, p 0.0001 for intermittent users), and a lower subdistribution hazard of time to hospital discharge, translating to a longer hospital length of stay (adjusted hazard ratio: 0.87, 95% CI, 0.85-0.88, p 0.0001 for chronic users; adjusted hazard ratio: 0.93, 95% CI, 0.92-0.94, p 0.0001 for intermittent users).Among elderly ICU patients, opioid exposure prior to admission is prevalent and use is associated with higher in-hospital mortality.

BACKGROUND: High rates of health care utilization at the end of life may be a marker of care that does not align with patient-stated preferences. We sought to describe trends in end-of-life care and factors associated with dying in hospital. METHODS: We conducted a population-level retrospective cohort study of adult decedents in Ontario between Apr. 1, 2004, and Mar. 31, 2015, using linked administrative data sets, including the Office of the Registrar General for Deaths database, the hospital Discharge Abstract Database, the National Ambulatory Care Reporting System and physicians’ billing claims (Ontario Health Insurance Plan). The primary outcome was place of death. To determine health care utilization and health care costs during the 6 months before death, we also identified admissions to hospital and to the intensive care unit, emergency department visits, and receipt of mechanical ventilation and palliative care. RESULTS: In the last 6 months of life, 77.3% of 962 462 decedents presented to an emergency department, 68.4% were admitted to hospital, 19.4% were admitted to an intensive care unit, and 13.9% received mechanical ventilation. Forty-five percent of all deaths occurred in hospital, a proportion that declined marginally over time, whereas receipt of palliative care increased during terminal hospital admissions (from 14.0% in fiscal year 2004/05 to 29.3% in 2014/15, p < 0.001) and in the last 6 months of life (from 28.1% in 2004/05 to 57.7% in 2014/15, p < 0.001). The proportion of decedents who presented to the emergency department, were admitted to hospital or were admitted to the intensive care unit in the last 6 months of life did not change over 11 years. The mean total health care costs in the last 6 months of life were highest among those dying in hospital, with most costs attributable to inpatient medical care. INTERPRETATION: Health care utilization in the last 6 months of life was substantial and did not decrease over time. It is possible that increased capacity for palliative, hospice and home care at the end of life may help to better align health system resources with the preferences of most patients, a topic that should be explored in future studies.

Key Points Question What are the characteristics of intensive care unit admissions identified by 2 proposed pandemic ventilator allocation triage guidelines using Sequential Organ Failure Assessment scores when applied retrospectively to critically ill US patients who received mechanical ventilation? Findings In this cohort study of 40 439 admissions to intensive care units that received mechanical ventilation, the New York State guideline identified 9% who would likely meet criteria for the lowest priority for ventilator allocation compared with 4% from the original White and Lo guideline. Only 655 admissions (1.6%) were in the lowest priority category for both guidelines, with 39% survival to hospital discharge for admissions identified as lowest priority using the New York State guideline compared with 56% for admissions identified using White and Lo. Meaning Two distinct approaches to triage for mechanical ventilation showed little agreement, suggesting that further clinical assessment of different potential criteria for triage decisions is important to ensure equitable allocation of resources., 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., This cohort study compares the New York State Ventilator Allocation Guideline with the original triage criteria proposed by White and Lo to determine which and how many admissions to US intensive care units are identified as having the lowest priority for ventilator allocation.

The number of elderly patients with dementia receiving invasive mechanical ventilation is increasing over time in the United States, while the balance of potential benefits and harms of intensive care interventions in this population is unclear. In this report, we describe trends in use of invasive mechanical ventilation in elderly individuals with and without dementia in Ontario, Canada, and provide projections of the use of invasive mechanical ventilation through 2025. We show that rates of invasive mechanical ventilation for elderly patients with dementia are increasing faster than for the rest of the elderly (nondementia) population.

Objective Macrophage accumulation in adipose tissue (AT) during obesity contributes to inflammation and insulin resistance. Recruitment of monocytes to obese AT has been the most studied mechanism explaining this accumulation. However, recent evidence suggests that recruitment-independent mechanisms may also regulate pro-inflammatory AT macrophage (ATM) numbers. The role of increased ATM survival during obesity has yet to be explored. Results We demonstrate that activation of apoptotic pathways is significantly reduced in ATMs from diet-induced and genetically obese mice. Concurrently, pro-survival Bcl-2 family member protein levels and localization to the mitochondria is elevated in ATMs from obese mice. This increased pro-survival signaling was associated with elevated activation of the transcription factor, NF-κB, and increased expression of its pro-survival target genes. Finally, an obesogenic milieu increased ATM viability only when NF-κB signaling pathways were functional. Conclusions Our data demonstrate that obesity promotes survival of inflammatory ATMs, possibly through an NF-κB-regulated mechanism., Graphical abstract, Highlights • Macrophage apoptosis is decreased in obese adipose tissue. • ATMs from obese mice display increased mitochondrial localization of Bcl-2. • The pro-survival targets of NF-κB are increased in ATMs from obese mice. • NF-κB activation in ATMs during metabolic stimulation increases their survival. • Decreased ATM apoptosis contributes to macrophage accumulation in obesity.

Rationale: Mechanically ventilated patients require complex care and are at high risk for rehospitalization, but different systems of care may result in different hospital discharge practices and rates of rehospitalization. Objectives: To compare lengths of hospitalization, discharge patterns, and rehospitalization rates in New York in the United States and Ontario in Canada. Methods: We conducted a retrospective cohort study of mechanically ventilated patients who survived an acute care hospitalization in New York or Ontario from 2010 to 2012, using linkable administrative healthcare data. Results: The primary outcome was the cumulative incidence of first rehospitalization within 30 days of discharge, accounting for the competing risk of death. Of 71,063 mechanically ventilated patients in New York, and 41,875 in Ontario who survived to hospital discharge, median length of initial hospital stay was similar in New York and Ontario (15 d, interquartile range = 8–28 vs. 16 d [9–30]), but was systematically shorter in New York when stratified by patient subgroups of different illness severity. Fewer patients in New York were discharged directly home (53.6% vs. 71.4%). Of patients in New York, 15,527 (cumulative incidence 21.9%) had a first rehospitalization within 30 days versus 5,580 (cumulative incidence 13.3%) in Ontario (P

Purpose Pregnancy-related critical illness leads to death for 3–14% of affected women. Although identifying patients at risk could facilitate preventive strategies, guide therapy, and help in clinical research, no prior systematic review of this literature exploring the validity of risk prediction models for maternal mortality exists. Therefore, we have systematically reviewed and meta-analyzed risk prediction models for maternal mortality. Methods Search strategy: MEDLINE, EMBASE and Scopus, from inception to May 2017. Selection criteria: Trials or observational studies evaluating risk prediction models for maternal mortality. Data collection and analysis: Two reviewers independently assessed studies for eligibility and methodological quality, and extracted data on prediction performance. Results Thirty-eight studies that evaluated 12 different mortality prediction models were included. Mortality varied across the studies, with an average rate 10.4%, ranging from 0 to 41.7%. The Collaborative Integrated Pregnancy High-dependency Estimate of Risk (CIPHER) model and the Maternal Severity Index had the best performance, were developed and validated from studies of obstetric population with a low risk of bias. The CIPHER applies to critically ill obstetric patients (discrimination: area under the receiver operating characteristic curve (AUC) 0.823 (0.811–0.835), calibration: graphic plot [intercept—0.09, slope 0.92]). The Maternal Severity Index applies to hospitalized obstetric patients (discrimination: AUC 0.826 [0.802–0.851], calibration: standardized mortality ratio 1.02 [0.86–1.20]). Conclusions Despite the high heterogeneity of the study populations and the limited number of studies validating the finally eligible prediction models, the CIPHER and the Maternal Severity Index are recommended for use among critically ill and hospitalized pregnant and postpartum women for risk adjustment in clinical research and quality improvement studies. Neither index has sufficient discrimination to be applicable for clinical decision making at the individual patient level.

Key Points Question What are the patterns of care at the end of life for physicians compared with nonphysicians? Findings In this cohort study of 2507 physicians and 7513 nonphysicians who died in Ontario, Canada, physicians were no more likely to die at home than nonphysicians. Overall, they did not consistently opt for less-aggressive care but instead used both intensive and palliative care more than nonphysicians. Meaning These findings highlight a more nuanced perspective of what physicians may perceive to be optimal care at the end of life., This cohort study compares the location of death and measures of health care use in the last 6 months of life for physicians vs nonphysicians in Canada., 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.

Macrophage and T cell infiltration into metabolic tissues contributes to obesity-associated inflammation and insulin resistance (IR). C-C chemokine receptor 5 (CCR5), expressed on macrophages and T cells, plays a critical role in the recruitment and activation of proinflammatory M1 and TH1 immune cells to tissues and is elevated in adipose tissue (AT) and liver of obese humans and mice. Thus, we hypothesized that deficiency of CCR5 would protect against diet-induced inflammation and IR. CCR5-deficient (CCR5−/−) mice and C57BL/6 (WT) controls were fed 10% low-fat (LF) or 60% high-fat (HF) diets for 16 wk. HF feeding increased adiposity, blood glucose, and plasma insulin levels equally in both genotypes. Opposing our hypothesis, HF-fed CCR5−/− mice were significantly more glucose intolerant than WT mice. In AT, there was a significant reduction in the M1-associated gene CD11c, whereas M2 associated genes were not different between genotypes. In addition, HF feeding caused a twofold increase in CD4+ T cells in the AT of CCR5−/− compared with WT mice. In liver and muscle, no differences in immune cell infiltration or inflammatory cytokine expression were detected. However, in AT and muscle, there was a mild reduction in insulin-induced phosphorylation of AKT and IRβ in CCR5−/− compared with WT mice. These findings suggest that whereas CCR5 plays a minor role in regulating immune cell infiltration and inflammation in metabolic tissues, deficiency of CCR5 impairs systemic glucose tolerance as well as AT and muscle insulin signaling.

Limited data are available to characterize the long-term outcomes and associated costs for patients who require prolonged mechanical ventilation (PMV; defined here as mechanical ventilation for longer than 21 d).To examine the association between PMV and mortality, health care utilization, and costs after critical illness.Population-based cohort study of adults who received mechanical ventilation in an intensive care unit (ICU) in Ontario, Canada between 2002 and 2013.We used linked administrative databases to determine discharge disposition, and ascertain 1-year mortality (primary outcome), readmissions to hospital and ICU, and health care costs for hospital survivors. Overall, 11,594 (5.4%) patients underwent PMV, with 42.4% of patients dying in the hospital (vs. 27.6% of patients who did not undergo prolonged ventilation; P 0.0001). Patients on prolonged ventilation were more frequently discharged to other facilities or home with health care support (84.8 vs. 43.5%, P 0.0001). Among hospital survivors, estimated mortality was higher for patients who underwent PMV: 16.6 versus 11% at 1 year and 42.0 versus 30.4% at 5 years. At 1 year after hospital discharge, patients on prolonged ventilation had higher rates of hospital readmission (47.2 vs. 37.7%; adjusted odds ratio = 1.20; 95% confidence interval = 1.14-1.26), ICU readmission (19.0 vs. 11.6%; adjusted odds ratio = 1.49; 95% confidence interval: 1.39, 1.60), and total health care costs: median (interquartile range) Can $32,526 ($20,821-$56,102) versus Can $13,657 ($5,946-$38,022). Increasing duration of mechanical ventilation was associated with higher mortality and health care utilization.Critically ill patients who undergo mechanical ventilation in an ICU for longer than 21 days have high in-hospital mortality and greater postdischarge mortality, health care utilization, and health care costs compared with patients who undergo mechanical ventilation for a shorter period of time.

Background The purpose of this study was to examine hospital mortality, long-term mortality, and health service utilization among critically ill patients. We also determined whether these outcomes differed according to demographic and clinical characteristics. Methods We conducted a retrospective cohort study of adults (age ≥18 years) who survived admission to an intensive care unit (ICU) in Ontario, Canada, between 1 April 2002 and 31 March 2012, excluding isolated admissions to step-down or intermediate ICUs, coronary care ICUs, or cardiac surgery ICUs. Adults (age ≥18 years) who survived an acute hospitalization that did not include an ICU stay formed the comparator group. The primary outcome was mortality following hospital discharge. Secondary outcomes were healthcare utilization, including emergency room admissions and hospital readmissions during follow-up. Results Over the study interval, 500,124 patients were admitted to ICUs and 420,187 (84 %) survived to hospital discharge. Median follow-up for survivors was 5.3 (interquartile range 2.5, 8.2) years. Patients admitted to an ICU were more likely to subsequently visit the emergency department, be readmitted to the hospital and ICU, receive home care support, require rehabilitation, and be admitted for long-term care. Those requiring more resources within the ICU required more resources after discharge. One-third of patients admitted to the ICU died during long-term follow-up, with overall probabilities of death of 11 % and 29 % at 1 year and 5 years, respectively. In the adjusted analysis, there was an increasing hazard of death with increasing age, reaching a hazard ratio of 18.08 (95 % confidence interval 16.60–19.68) for those ≥85 years of age compared with those aged 18–24 years. Conclusions Healthcare utilization after hospital discharge was higher among ICU patients, and also among those requiring more healthcare resources during their ICU admission, than among all hospitalized patients as a group. One-third of ICU patients died within the 5 years following discharge, and age was the most influential determinant of outcome. These findings should help target post–ICU discharge services for high-risk groups and better inform goals-of-care discussions for elderly critically ill patients. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1248-y) contains supplementary material, which is available to authorized users.

Evidence suggests that there may be an association between transfer status (direct admission or interhospital transfer) and outcomes in trauma patients. The purpose of this study was to systematically review the current evidence of the association between transfer status and outcomes for patients.Systematic search of Medline and EMBASE databases to identify eligible control trials or observational studies that examined the impact of transfer status on trauma patient outcomes. Data were extracted on study design, quality, participants, outcomes, and risk estimates reported. Pooled odds ratio based on data from retrieved studies was calculated using a random effect model.Thirty-six observational studies were identified. There were no significant differences in length of stay (LOS) between transfer and direct admissions although costs were marginally higher for transferred patients, (relative increase, 1.09; 95% confidence interval, 1.08-1.09). We found no significant association between transfer status (transfer vs. direct) and in-hospital mortality (pooled odds ratio, 1.06; 95% confidence interval, 0.90-1.25); however, heterogeneity of the studies was high (I2 = 82%).Available evidence suggests there is no difference in mortality between transfer and direct admissions. However, the significant heterogeneity across studies precludes deriving any definitive conclusions regarding the impact of interhospital transfer on mortality after major trauma. Moreover, most studies excluded patients dying at outlying hospitals, which may underestimate the association of transfer status with mortality. Prospective studies that address the limitations of the current evidence, including use of population-based trauma registries, are warranted to establish whether the process of interhospital transfer to higher level care when compared with direct admission to a trauma center negatively impacts clinical outcomes for trauma patients.

Rationale: One in three Americans under 65 years of age does not have health insurance during some portion of each year. Patients who are critically ill and lack health insurance may be at particularly high risk of morbidity and mortality due to the high cost of intensive care. Objectives: To systematically review the medical and nonmedical literature to determine whether differences in critical care access, delivery, and outcomes are associated with health insurance status. Methods: Nine electronic databases (inception to 11 April 2008) were independently screened and abstracted in duplicate. Measurements and Main Results: From 5,508 citations, 29 observational studies met eligibility criteria. Among the general U.S. population, patients who were uninsured were less likely to receive critical care services than those with insurance (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.55–0.56). Once admitted to the intensive care unit, patients who were uninsured had 8.5% (95% CI, 6.0–11.1) fewer procedures, were more likely to experience hospital discharge delays (OR 4.51; 95% CI, 1.46–13.93), and were more likely to have life support withdrawn (OR 2.80; 95% CI, 1.12–7.02). Lack of insurance may confer an independent risk of death for patients who are critically ill (OR 1.16; 95% CI, 1.01–1.33). Patients in managed care systems had 14.3% (95% CI, 11.5–17.2) fewer procedures in intensive care, but were also less likely to receive “potentially ineffective” care. Differences in unmeasured confounding factors may contribute to these findings. Conclusions: Patients in the United States who are critically ill and do not have health insurance receive fewer critical care services and may experience worse clinical outcomes. Improving preexisting health care coverage, as opposed to solely delivering more critical care services, may be one mechanism to reduce such disparities.

Prolonged stay in the intensive care unit (ICU) is associated with high mortality, morbidity, and costs. Identifying those patients who are most likely to benefit from an extended ICU stay would be helpful in guiding clinical decisions. We sought to describe the characteristics and outcomes for a heterogeneous group of patients who required a prolonged ICU stay.Observational study.Adult ICUs of three teaching and five community hospitals.The study group comprised 5,881 patients consecutively admitted to the ICUs during a 10-month period.A prolonged stay was defined as one21 days at teaching hospitals and10 days at community hospitals. For patients meeting the criteria of prolonged stay, Therapeutic Intervention Scoring System (TISS) score and Multiple Organ Dysfunction Score (MODS) were measured prospectively from days 10 and 21 in community and teaching hospitals, respectively, and retrospectively before this. Prolonged-stay patients represented 5.6% of ICU admissions and 39.7% of ICU bed-days. Compared with short-stay patients, they were significantly older and had higher admission Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p.01). ICU and hospital mortality for prolonged-stay patients were 24.4% and 35.2%, respectively, compared with 11% and 15.9% for short-stay patients (p.001). Mean admission TISS and MODS scores for prolonged-stay patients were 30.8 (sd, 11.1) and 4.8 (sd, 3.3) respectively. For prolonged-stay patients the dominant reason for ICU care was multiple organ failure (37.8%), ventilator support (30.7%), or nonventilated single organ failure (31.5%). Hospital mortality was highest in the group with multiple organ failure (53%).We developed a method to broadly classify a heterogeneous population of prolonged-stay ICU patients on the basis of MODS and the ICU interventions received. Mortality among prolonged-stay patients was highest for those with multiple organ failure. Future research should evaluate whether the proposed classification system can be used to influence the delivery of ICU care.

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. Language: en

BACKGROUND. The results of chemotherapy for patients with esophagogastric carcinoma have generally been modest but regimens developed more recently have produced higher response rates, and rekindled interest in neoadjuvant chemotherapy. One such regimen is epirubicin, cisplatin, and 5-fluorouracd (ECF). This study evaluates its efficacy, toxicity, impact on quality of life (QL), and impact on survival in a large consecutive series of patients with metastatic and locally advanced disease (LAD). METHODS. Patients with histologically confirmed esophagogastric carcinoma were treated with ECF (epirubicin 50 mglm' and cisplatin 60 mglm' every 3 weeks with continuous infusion of 5-fluorouracil (5-FU) 200 mg/m'/d). Responses were evaluated with computed tomography (CTJ scan and endoscopy. QL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. RESULTS. A total of 235 patients were treated, 173 with metastatic disease and 62 with LAD. The mean number of cycles delivered was 6 (range: 1-11) and patients were followed-up for a median of 8 months. Response was observed in 135 of 220 (61%) evaluable patients, with a complete response (CR), 11% of the patients and a partial response in 50% of the patients. Patients with moderately differentiated adenocarcinomas and LAD responded most favorably. Symptomatic improvement was achieved in the majority of cases (63-78% depending on the symptom). Toxicity was generally only mild to moderate, with severe non hematologic toxicity in less than 12% of the patients and only 6 (2.5%) treatment related deaths. QL assessment showed no significant negative impact on emotional functioning and good symptomatic control. Surgery following response to ECF was performed in 29 of the LAD patients, and in 19 cases (66%) a potentially curative resection was possible, with histologic CR in 32% of the patients. CONCLUSIONS. ECF is a highly active regimen with acceptable toxicity in patients with esophagogastric adenocarcinoma. In a proportion of patients with LAD, chemotherapy enabled potentially curative surgery to be performed. The results justify further investigation of this regimen in a neoadjuvant setting. Cancer 1996; 721978-85. 0 1996 Americari Cancer Society.

The mechanism by which macrophages and other immune cells accumulate in adipose tissue (AT) has been an area of intense investigation over the past decade. Several different chemokines and their cognate receptors have been studied for their role as chemoattractants in promoting recruitment of immune cells to AT. However, it is also possible that chemoattractants known to promote clearance of immune cells from tissues to regional lymph nodes might be a critical component to overall AT immune homeostasis. In this study, we evaluated whether CCR7 influences AT macrophage (ATM) or T‐cell (ATT) accumulation. CCR7 −/− and littermate wild‐type (WT) mice were placed on low‐fat diet (LFD) or high‐fat diet (HFD) for 16 weeks. CCR7 deficiency did not impact HFD‐induced weight gain, hepatic steatosis, or glucose intolerance. Although lean CCR7 −/− mice had an increased proportion of alternatively activated ATMs, there were no differences in ATM accumulation or polarization between HFD‐fed CCR7 −/− mice and their WT counterparts. However, CCR7 deficiency did lead to the preferential accumulation of CD8 + ATT cells, which was further exacerbated by HFD feeding. Finally, expression of inflammatory cytokines/chemokines, such as Tnf , Il6 , Il1β , Ccl2 , and Ccl3 , was equally elevated in AT by HFD feeding in CCR7 −/− and WT mice, while Ifng and Il18 were elevated by HFD feeding in CCR7 −/− but not in WT mice. Together, these data suggest that CCR7 plays a role in CD8 + ATT cell egress, but does not influence ATM accumulation or the metabolic impact of diet‐induced obesity.

Patients with hereditary spherocytosis (HS) are often thought to have an increased risk of blunt splenic injury (BSI) from trauma due to splenomegaly. We aim to quantify this risk. Using a population-based database consisting of all injury-related admissions in Canada from 2001 to 2010, we identified patients with BSI and HS based on the discharge diagnoses. Intercensal population estimates were used to derive rates of BSI. The HS population at risk for BSI was estimated based on population rates of HS obtained from the literature. Rates of BSI in the HS population were estimated and the relative rates of BSI were calculated to compare the populations with and without HS. There were 10,106 patients with BSI over 202,405,788 person-years of observation, yielding an overall rate of BSI in the general population of 5.0 BSI per 100,000 person-years. Of these BSI patients, only two had a history of HS. Population rates of HS in the literature range from 1 in 2,000 to 5,000, corresponding to a low estimate of 2.0 and a high estimate of 4.9 BSI per 100,000 person-years in the HS population. The relative rate of BSI in the population with HS compared to the population without HS ranged from a low of 0.4 (95 % CI 0.1–1.4) to a high of 1.0 (0.1–3.6). The rate of BSI in the HS patient population appears not to differ significantly from those in the general population.

In the last decade, CT angiography has become the dominant diagnostic modality for blunt aortic injury and endovascular repair has become the leading aortic repair strategy. The impact of these shifts on incidence, aortic repair rate, and mortality remains poorly characterized. Our objective was to perform a population-based analysis of secular trends in the incidence, management, and in-hospital mortality of blunt thoracic aortic injury.From the population-based Canadian National Trauma Registry, we identified a cohort of all adults hospitalized between April 2002 and March 2010 with a diagnosis of thoracic aortic injury after blunt trauma. Trends over time in the incidence of hospitalization, frequency and type of aortic repair, as well as risk-adjusted in-hospital mortality, were evaluated.A total of 487 incident cases of blunt thoracic aortic injury were identified. During the study period, the incidence of hospitalization for blunt thoracic aortic injury remained stable (trend p = 0.16). Although the proportion of repairs undertaken via an endovascular approach increased (11% to 78% of repairs; trend p0.001), the frequency of any repair (endovascular or open) declined (55% to 36%; trend p = 0.003). Across all patients, when controlling for age, sex, mechanism of injury, and presence of severe extrathoracic injuries, mortality remained unchanged during the study period (odds ratio = 0.92 per 1 year; 95% CI, 0.82-1.03). However, in patients managed nonoperatively, risk-adjusted mortality decreased over time (odds ratio = 0.85 per 1 year; 95% CI, 0.80-0.98).The increasing frequency of patients managed nonoperatively and decreasing risk-adjusted mortality in these patients suggests that defining the evolving role of nonoperative management should be a major focus of research in the endovascular era.

The provision of geriatric training for undergraduate medical students should be a condition of accreditation of medical schools, as well as a competency tested on licensing exams. That stance lies at the core of a campaign by the Canadian Geriatrics Society (CGS) and the National Initiative for the

It is a truism that Canadian physicians and other health workers are legally compelled to report cases of specified communicable diseases and infections. In some provinces, the list tops 110 diseases, while in others, it’s as low as 60. It also appears to be a fact that most physicians are about

Purpose We examined the association between access to intensive care services and mortality in a cohort of critically ill patients. Materials and Methods We conducted an observational study involving 6298 consecutive admissions to the intensive care units (ICUs) of a tertiary care hospital. Data including demographics, admission source, and outcomes were collected on all patients. Admission source was classified as “transfer” for patients admitted to the ICU from other hospitals, “ER” for patients admitted from the emergency room, and “ward” for patients admitted from non-ICU inpatient wards. Results Transfer patients had higher crude ICU and hospital mortality rates compared with emergency room admissions (crude odds ratio [OR], 1.51; 95% confidence interval [CI], 1.32-1.75). After adjusting for age, sex, diagnosis, comorbidities, and acute physiology scores, the difference in ICU mortality remained significant (OR, 1.30; 95% CI, 1.09-1.56); however, hospital mortality did not (OR, 1.19; 95% CI, 1.00-1.41). Compared with ward patients, transfer from other hospitals was associated with lower hospital mortality after adjusting for severity of illness and other case-mix variables (OR, 0.81; 95% CI, 0.68-0.95). Conclusions We found some evidence to suggest that differential access to intensive care services impacts mortality within this case mix of patients. These findings may have implications for current efforts to centralize and regionalize critical care services.

Even the notion that there might come a day when a Canadian medical school might issue a press release hailing an improved rating on a scorecard designed to measure conflicts of interest between faculty and industry, as several American institutions have over the past month, seems unfathomable.