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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 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.

Unplanned rehospitalization at a hospital other than the initial hospital may contribute to poor outcomes. We examined the location of rehospitalizations and assessed outcomes following critical illness in a single-payer healthcare system.Population-based retrospective cohort study using linked datasets (2012-2017) from Ontario, Canada including adults (≥18 years) with an unplanned rehospitalization within 30-days after an index hospitalization that included an ICU stay with mechanical ventilation. Outcomes were the percentage of 30-day rehospitalizations at non-index hospitals, mortality and costs. We employed logistic regression and generalized linear models to assess associations.There were 14,997 (16.4%) 30-day rehospitalizations. Of these 2765 (18.4%) occurred in a non-index hospital. Distance of home residence from the index hospital was the strongest predictor of a non-index rehospitalization (adjusted odds ratio (aOR) 8.40, 95%CI 7.05-10.01, highest vs. lowest distance quintile). Within 30-days of rehospitalization, deaths (aOR 0.91, 95%CI (0.80-1.04)) and total healthcare costs (adjusted relative risk 1.03 (1.00-1.06)), were similar for patients readmitted to the index or a non-index hospital.Non-index rehospitalization within 30-days of initial discharge is common following critical illness. These rehospitalizations were not significantly associated with an increased risk of harm or higher costs in a single-payer healthcare system.

Signaling by Toll-like receptors (TLRs) on intestinal epithelial cells (IECs) is critical for intestinal homeostasis. To visualize epithelial expression of individual TLRs in vivo, we generated five strains of reporter mice. These mice revealed that TLR expression varied dramatically along the length of the intestine. Indeed, small intestine (SI) IECs expressed low levels of multiple TLRs that were highly expressed by colonic IECs. TLR5 expression was restricted to Paneth cells in the SI epithelium. Intestinal organoid experiments revealed that TLR signaling in Paneth cells or colonic IECs induced a core set of host defense genes, but this set did not include antimicrobial peptides, which instead were induced indirectly by inflammatory cytokines. This comprehensive blueprint of TLR expression and function in IECs reveals unexpected diversity in the responsiveness of IECs to microbial stimuli, and together with the associated reporter strains, provides a resource for further study of innate immunity.

The intestinal barrier is vulnerable to damage by microbiota-induced inflammation that is normally restrained through mechanisms promoting homeostasis. Such disruptions contribute to autoimmune and inflammatory diseases including inflammatory bowel disease. We identified a regulatory loop whereby, in the presence of the normal microbiota, intestinal antigen-presenting cells (APCs) expressing the chemokine receptor CX3CR1 reduced expansion of intestinal microbe-specific T helper 1 (Th1) cells and promoted generation of regulatory T cells responsive to food antigens and the microbiota itself. We identified that disruption of the microbiota resulted in CX3CR1+ APC-dependent inflammatory Th1 cell responses with increased pathology after pathogen infection. Colonization with microbes that can adhere to the epithelium was able to compensate for intestinal microbiota loss, indicating that although microbial interactions with the epithelium can be pathogenic, they can also activate homeostatic regulatory mechanisms. Our results identify a cellular mechanism by which the microbiota limits intestinal inflammation and promotes tissue homeostasis.