Association of Regular Opioid Use With Incident Dementia and Neuroimaging Markers of Brain Health in Chronic Pain Patients: Analysis of UK Biobank.

OBJECTIVES: We aimed to investigate the association of regular opioid use, compared with non-opioid analgesics, with incident dementia and neuroimaging outcomes among chronic pain patients. DESIGN: The primary design is a prospective cohort study. To triangulate evidence, we also conducted a nested case-control study analyzing opioid prescriptions and a cross-sectional study analyzing neuroimaging outcomes. SETTING AND PARTICIPANTS: Dementia-free UK Biobank participants with chronic pain and regular analgesic use. MEASUREMENTS: Chronic pain status and regular analgesic use were captured using self-reported questionnaires and verbal interviews. Opioid prescription data were obtained from primary care records. Dementia cases were ascertained using primary care, hospital, and death registry records. Propensity score-matched Cox proportional hazards analysis, conditional logistic regression, and linear regression were applied to the data in the prospective cohort, nested case-control, and cross-sectional studies, respectively. RESULTS: Prospective analyses revealed that regular opioid use, compared with non-opioid analgesics, was associated with an increased dementia risk over the 15-year follow-up (Hazard ratio [HR], 1.18 [95% confidence interval (CI): 1.08-1.30]; Absolute rate difference [ARD], 0.44 [95% CI: 0.19-0.71] per 1000 person-years; Wald χ2 = 3.65; df = 1; p <0.001). The nested case-control study suggested that a higher number of opioid prescriptions was associated with an increased risk of dementia (1 to 5 prescriptions: OR = 1.21, 95% CI: 1.07-1.37, Wald χ2 = 3.02, df = 1, p = 0.003; 6 to 20: OR = 1.27, 95% CI: 1.08-1.50, Wald χ2 = 2.93, df = 1, p = 0.003; more than 20: OR = 1.43, 95% CI: 1.23-1.67, Wald χ2 = 4.57, df = 1, p < 0.001). Finally, neuroimaging analyses revealed that regular opioid use was associated with lower total grey matter and hippocampal volumes, and higher white matter hyperintensities volumes. CONCLUSION: Regular opioid use in chronic pain patients was associated with an increased risk of dementia and poorer brain health when compared to non-opioid analgesic use. These findings imply a need for re-evaluation of opioid prescription practices for chronic pain patients and, if further evidence supports causality, provide insights into strategies to mitigate the burden of dementia.

Association between metabolic syndrome and risk of incident dementia in UK Biobank.

INTRODUCTION: The association between metabolic syndrome (MetS) and incident dementia remains inconclusive. METHODS: In 176,249 dementia-free UK Biobank participants aged ≥60 years at baseline, Cox proportional-hazards models were used to investigate the association between MetS and incident dementia. MetS was defined as the presence of ≥3 of the following: elevated waist circumference, triglycerides, blood pressure, blood glucose, and reduced high-density lipoprotein cholesterol. RESULTS: Over 15 years of follow-up (median = 12.3), 5255 participants developed dementia. MetS was associated with an increased risk of incident dementia (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.06, 1.18). The association remained consistent when restricting to longer follow-up intervals: >5 to 10 years (HR: 1.17, 95% CI: 1.07, 1.27) and >10 years (HR: 1.22, 95% CI: 1.12, 1.32). Stronger associations were observed in those with ≥4 MetS components and in apolipoprotein-E (APOE)-ε4 non-carriers. DISCUSSION: In this large population-based prospective cohort, MetS was associated with an increased risk of dementia. HIGHLIGHTS: MetS was associated with a 12% increased risk of incident all-cause dementia. Associations remained similar after restricting the analysis to those with longer follow-up. The presence of four or five MetS components was significantly associated with dementia. Stronger associations were observed in those with a low genetic risk for dementia.

Intracerebral Hemorrhage Incidence, Mortality, and Association With Oral Anticoagulation Use: A Population Study.

BACKGROUND AND PURPOSE: Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke associated with significant morbidity and mortality. Recent epidemiological data on incidence, mortality, and association with oral anticoagulation are needed. METHODS: Retrospective cohort study of adult patients (≥18 years) with ICH in the entire population of Ontario, Canada (April 1, 2009-March 30, 2019). We captured outcome data using linked health administrative databases. The primary outcome was mortality during hospitalization, as well as at 1 year following ICH. RESULTS: We included 20 738 patients with ICH. Mean (SD) age was 71.3 (15.1) years, and 52.6% of patients were male. Overall incidence of ICH throughout the study period was 19.1/100 000 person-years and did not markedly change over the study period. In-hospital and 1-year mortality were high (32.4% and 45.4%, respectively). Mortality at 2 years was 49.5%. Only 14.5% of patients were discharged home independently. Over the study period, both in-hospital and 1-year mortality reduced by 10.4% (37.5% to 27.1%, P<0.001) and 7.6% (50.0% to 42.4%, P<0.001), respectively. Use of oral anticoagulation was associated with both in-hospital mortality (adjusted odds ratio 1.37 [95% CI, 1.26-1.49]) and 1-year mortality (hazard ratio, 1.18 [95% CI, 1.12-1.25]) following ICH. CONCLUSIONS: Both short- and long-term mortality have decreased in the past decade. Most survivors from ICH are likely to be discharged to long-term care. Oral anticoagulation is associated with both short- and long-term mortality following ICH. These findings highlight the devastating nature of ICH, but also identify significant improvement in outcomes over time.

Non-pharmacological therapies for pain management in Parkinson's disease: A systematic review.

Among the various non-motor symptoms of Parkinson's disease (PD), pain is often cited as the most common and debilitating feature. Currently, the literature contains gaps in knowledge with respect to the various forms of treatment available, particularly non-pharmacological therapies. Thus, the purpose of this systematic review is to provide an examination of the literature on non-pharmacological therapies for pain in PD. We compared the findings of research articles indexed within various literature databases related to non-pharmacological treatments of pain in PD patients. Our review identified five major non-pharmacological methods of pain therapy in PD: acupuncture, hydrotherapy, massage therapy, neuromodulation, and exercise. Treatments such as exercise therapy found a reduction in pain perception due to various factors, including the analgesic effects of neurotransmitter release during exercise and increased activity leading to a decrease in musculoskeletal rigidity and stiffness. By the same token, hydrotherapy has been shown to reduce pain perception within PD patients, with authors often citing a combined treatment of exercise and hydrotherapy as an effective treatment for pain management. Multiple methods of neurostimulation were also observed, including deep brain stimulation and spinal cord stimulation. Deep brain stimulation showed efficacy in alleviating certain pain types (dystonic and central), while not others (musculoskeletal). Hence, patients may consider deep brain stimulation as an additive procedure for their current treatment protocol. On the other hand, spinal cord stimulation showed significant improvement in reducing VAS scores for pain. Finally, although the literature on massage therapy and acupuncture effectiveness on pain management is limited, both have demonstrated a reduction in pain perception, with common reasons such as tactile stimulation and release of anti-nociceptive molecules in the body. Although literature pertaining to non-pharmacological treatments of pain in PD is sparse, there is copious support for these treatments as beneficial to pain management. Further exploration in the form of clinical trials is warranted to assess the efficacy of such therapies.

Association between high cost user status and end-of-life care in hospitalized patients: A national cohort study of patients who die in hospital.

BACKGROUND: Studies comparing end-of-life care between patients who are high cost users of the healthcare system compared to those who are not are lacking. AIM: The objective of this study was to describe and measure the association between high cost user status and several health services outcomes for all adults in Canada who died in acute care, compared to non-high cost users and those without prior healthcare use. SETTINGS AND PARTICIPANTS: We used administrative data for all adults who died in hospital in Canada between 2011 and 2015 to measure the odds of admission to the intensive care unit (ICU), receipt of invasive interventions, major surgery, and receipt of palliative care during the hospitalization in which the patient died. High cost users were defined as those in the top 10% of acute healthcare costs in the year prior to a person's hospitalization in which they died. RESULTS: Among 252,648 people who died in hospital, 25,264 were high cost users (10%), 112,506 were non-high cost users (44.5%) and 114,878 had no prior acute care use (45.5%). After adjustment for age and sex, high cost user status was associated with a 14% increased odds of receiving an invasive intervention, a 15% increased odds of having major surgery, and an 8% lower odds of receiving palliative care compared to non-high cost users, but opposite when compared to patients without prior healthcare use. CONCLUSIONS: Many patients receive aggressive elements of end-of-life care during the hospitalization in which they die and a substantial number do not receive palliative care. Understanding how this care differs between those who were previously high- and non-high cost users may provide an opportunity to improve end of life care for whom better care planning and provision ought to be an equal priority.

Characteristics and resource utilization of high-cost users in the intensive care unit: a population-based cohort study.

BACKGROUND: Healthcare expenditure within the intensive care unit (ICU) is costly. A cost reduction strategy may be to target patients accounting for a disproportionate amount of healthcare spending, or high-cost users. This study aims to describe high-cost users in the ICU, including health outcomes and cost patterns. METHODS: We conducted a population-based retrospective cohort study of patients with ICU admissions in Ontario from 2011 to 2018. Patients with total healthcare costs in the year following ICU admission (including the admission itself) in the upper 10th percentile were defined as high-cost users. We compared characteristics and outcomes including length of stay, mortality, disposition, and costs between groups. RESULTS: Among 370,061 patients included, 37,006 were high-cost users. High-cost users were 64.2 years old, 58.3% male, and had more comorbidities (41.2% had ≥3) when likened to non-high cost users (66.1 years old, 57.2% male, 27.9% had ≥3 comorbidities). ICU length of stay was four times greater for high-cost users compared to non-high cost users (22.4 days, 95% confidence interval [CI] 22.0-22.7 days vs. 5.56 days, 95% CI 5.54-5.57 days). High-cost users had lower in-hospital mortality (10.0% vs.14.2%), but increased dispositioning outside of home (77.4% vs. 42.2%) compared to non-high-cost users. Total healthcare costs were five-fold higher for high-cost users ($238,231, 95% CI $237,020-$239,442) compared to non-high-cost users ($45,155, 95% CI $45,046-$45,264). High-cost users accounted for 37.0% of total healthcare costs. CONCLUSION: High-cost users have increased length of stay, lower in-hospital mortality, and higher total healthcare costs when compared to non-high-cost users. Further studies into cost patterns and predictors of high-cost users are necessary to identify methods of decreasing healthcare expenditure.

The association between varying levels of palliative care involvement on costs during terminal hospitalizations in Canada from 2012 to 2015.

BACKGROUND: Inpatient palliative care is associated with lower inpatient costs; however, this has yet to be studied using a more nuanced, multi-tiered measure of inpatient palliative care and a national population-representative dataset. Using a population-based cohort of Canadians who died in hospital, our objectives were to: describe patients' receipt of palliative care and active interventions in their terminal hospitalization; and examine the relationship between inpatient palliative care and hospitalization costs. METHODS: Retrospective cohort study using data from the Discharge Abstract Database in Canada between fiscal years 2012 and 2015. The cohort were Canadian adults (age ≥ 18 years) who died in hospital between April 1st, 2012 and March 31st, 2015 (N = 250,640). The exposure was level of palliative care involvement defined as: medium-high, low, or no palliative care. The main measure was acute care costs calculated using resource intensity weights multiplied by the cost of standard hospital stay, represented in 2014 Canadian dollars (CAD). Descriptive statistics were represented as median (IQR), and n(%). We modelled cost as a function of palliative care using a gamma generalized estimating equation (GEE) model, accounting for clustering by hospital. RESULTS: There were 250,640 adults who died in hospital. Mean age was 76 (SD 14), 47% were female. The most common comorbidities were: metastatic cancer (21%), heart failure (21%), and chronic obstructive pulmonary disease (16%). Of the decedents, 95,450 (38%) had no palliative care involvement, 98,849 (38%) received low involvement, and 60,341 (24%) received medium to high involvement. Controlling for age, sex, province and predicted hospital mortality risk at admission, the cost per day of a terminal hospitalization was: $1359 (95% CI 1323: 1397) (no involvement), $1175 (95% CI 1146: 1206) (low involvement), and $744 (95% CI 728: 760) (medium-high involvement). CONCLUSIONS: Increased involvement of palliative care was associated with lower costs. Future research should explore whether this relationship holds for non-terminal hospitalizations, and whether palliative care in other settings impacts inpatient costs.

Five-year risk of admission to long-term care home and death for older adults given a new diagnosis of dementia: a population-based retrospective cohort study.

BACKGROUND: After diagnosis of a health condition, information about survival and potential transition from community into institutional care can be helpful for patients and care providers. We sought to describe the association between a new diagnosis of dementia and risk of admission to a long-term care home and death at 5 years. METHODS: We conducted a population-based retrospective cohort study using linked health administrative databases. We identified individuals aged 65 years or older, living in the community, with a first documented diagnosis of dementia between Jan. 1, 2010, and Dec. 31, 2012, in Ontario, Canada. Dementia diagnosis was captured using diagnostic codes from hospital discharges, physician billings, assessments conducted for home care and long-term care, and dispensed prescriptions for cholinesterase inhibitors. Our primary outcome measures were 5-year risk of death and placement in a long-term care home, adjusted for sociodemographic and clinical factors. RESULTS: We identified 108 757 individuals in our study cohort. By the end of 5 years, 24.4% remained alive in the community and 20.5% were living in a long-term care home. Of the 55.1% who died, about half (27.9%) were admitted to a long-term care home before death. Three risk factors were associated with increased odds of death: older age (age ≥ 90 yr; odds ratio [OR] 9.5, 95% confidence interval [CI] 8.8-10.2 [reference: age 65-69 yr]), male sex (OR 1.7, 95% CI 1.6-1.7), and the presence of organ failure, including chronic obstructive pulmonary disease (OR 1.7, 95% CI 1.7-1.8), congestive heart failure (OR 2.0, 95% CI 1.9-2.0) and renal failure (OR 1.7, 95% CI 1.6-1.8). Groups formed by combinations of these 3 factors had an observed 5-year risk of death varying between 22% and 91%. INTERPRETATION: Among community-dwelling older adults with newly identified dementia in Ontario, the majority died or were admitted to a long-term care home within 5 years. This information may be helpful for discussions on prognosis and need for admission to long-term care.

Long-term survival and costs following extracorporeal membrane oxygenation in critically ill children-a population-based cohort study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used to provide temporary cardiorespiratory support to critically ill children. While short-term outcomes and costs have been evaluated in this population, less is known regarding long-term survival and costs. METHODS: Population-based cohort study from Ontario, Canada (October 1, 2009 to March 31, 2017), of pediatric patients (< 18 years of age) receiving ECMO, identified through the use of an ECMO procedural code. Outcomes were identified through linkage to provincial health databases. Primary outcome was survival, measured to hospital discharge, as well as at 1 year, 2 years, and 5 years following ECMO initiation. We evaluated total patient costs in the first year following ECMO. RESULTS: We analyzed 342 pediatric patients. Mean age at ECMO initiation was 2.9 years (standard deviation [SD] = 5.0). Median time from hospital admission to ECMO initiation was 5 days (interquartile range [IQR] = 1-13 days). Overall survival to hospital discharge was 56.4%. Survival at 1 year, 2 years, and 5 years was 51.5%, 50.0%, and 42.1%, respectively. Among survivors, 99.5% were discharged home. Median total costs among all patients in the year following hospital admission were $147,957 (IQR $70,571-$300,295). Of these costs, the large proportion were attributable to the inpatient cost from the index admission (median $119,197, IQR $57,839-$250,675). CONCLUSIONS: Children requiring ECMO continue to have a significant in-hospital mortality, but reassuringly, there is little decrease in long-term survival at 1 year. Median costs among all patients were substantial, but largely reflect inpatient hospital costs, rather than post-discharge outpatient costs. This information provides value to providers and health systems, allowing for prognostication of short- and long-term outcomes, as well as long-term healthcare-related expenses for pediatric ECMO survivors.

Long-term mortality and costs following use of Impella® for mechanical circulatory support: a population-based cohort study.

PURPOSE: The Impella® device is a form of mechanical circulatory support (MCS) used in critically ill adults with cardiogenic shock. We sought to evaluate short- and long-term outcomes following the use of Impella, including mortality, healthcare utilization, and costs. METHODS: Population-based, retrospective cohort study of adult patients (≥ 16 yr) receiving Impella in Ontario, Canada (1 April 2012-31March 2019). We captured outcomes through linkage to health administrative databases. The primary outcome was mortality during hospitalization. Secondary outcomes included mortality at 30 days, 90 days, and one year following Impella insertion. We analyzed health system costs in Canadian dollars in the year following the date of the index admission, including the costs of inpatient admission. RESULTS: We included 162 patients. Mean (standard deviation) age was 59.2 (14.5) yr, and 73.5% of patients were male. Median [interquartile range (IQR)] time to Impella insertion from date of hospital admission was 2 [1-9] days. In-hospital mortality was 56.8%, and a significant proportion of patients were bridged to a ventricular assist device (67.9%). Mortality at one year was 61.7%. Among hospital survivors, only 38.6% were discharged home independently. Median [IQR] total cost in the year following admission among all patients was $88,397 [32,718-225,628], of which $66,529 [22,789-183,165] was attributed to inpatient care. CONCLUSIONS: In-hospital mortality among patients with cardiogenic shock receiving Impella is high, but with minimal increase at one year. While Impella patients accrued substantial costs, these largely reflected inpatient costs, and not costs incurred following hospital discharge.

RéSUMé: OBJECTIF: Le dispositif Impella® est un système d'assistance circulatoire mécanique utilisé chez les adultes en état critique souffrant d'un choc cardiogénique. Nous avons souhaité évaluer les issues à court et à long terme liées à l'utilisation de l'Impella, notamment la mortalité, l'utilisation des soins de santé et les coûts. MéTHODE: Nous avons réalisé une étude de cohorte rétrospective basée sur une population de patients adultes (≥ 16 ans) recevant un Impella en Ontario, au Canada (1er avril 2012­31 mars 2019). Nous avons saisi les données pertinentes à nos critères d'évaluation en créant des liens avec les bases de données administratives de santé. Le critère d'évaluation principal était la mortalité pendant l'hospitalisation. Les critères d'évaluation secondaires comportaient la mortalité à 30 jours, 90 jours et un an après l'insertion de l'Impella. Nous avons analysé les coûts pour le système de santé en dollars canadiens au cours de l'année suivant la date d'admission initiale, notamment les coûts hospitaliers. RéSULTATS: Nous avons inclus 162 patients. L'âge moyen (écart type) était de 59,2 (14,5) ans, et 73,5 % des patients étaient des hommes. Le temps médian [écart interquartile (ÉIQ)] jusqu'à insertion de l'Impella depuis l'admission à l'hôpital était de 2 [1­9] jours. La mortalité hospitalière était de 56,8 %, et un dispositif d'assistance ventriculaire a été implanté chez une importante proportion de patients (67,9 %). La mortalité à un an était de 61,7 %. Parmi les survivants hospitaliers, seuls 38,6 % ont reçu leur congé pour un retour indépendant à la maison. Le coût total médian [ÉIQ] pour l'année suivant l'admission parmi tous les patients était de 88 397 $ [32 718 ­ 225 628 $], dont 66 259 $ [22 789 ­ 183 165 $] étaient attribuables aux soins hospitaliers. CONCLUSION: La mortalité hospitalière parmi les patients en choc cardiogénique chez lesquels un Impella est installé est élevée, mais on n'observe qu'une augmentation minimale à un an. Alors que les patients ayant reçu un Impella ont engendré des coûts importants, ces coûts reflètent principalement les coûts hospitaliers et non les coûts encourus après le congé de l'hôpital.

Describing the characteristics and healthcare use of high-cost acute care users at the end of life: a pan-Canadian population-based study.

BACKGROUND: A minority of individuals use a large portion of health system resources, incurring considerable costs, especially in acute-care hospitals where a significant proportion of deaths occur. We sought to describe and contrast the characteristics, acute-care use and cost in the last year of life among high users and non-high users who died in hospitals across Canada. METHODS: We conducted a population-based retrospective-cohort study of Canadian adults aged ≥18 who died in hospitals across Canada between fiscal years 2011/12-2014/15. High users were defined as patients within the top 10% of highest cumulative acute-care costs in each fiscal year. Patients were categorized as: persistent high users (high-cost in death year and year prior), non-persistent high users (high-cost in death year only) and non-high users (never high-cost). Discharge abstracts were used to measure characteristics and acute-care use, including number of hospitalizations, admissions to intensive-care-unit (ICU), and alternate-level-of-care (ALC). RESULTS: We identified 191,310 decedents, among which 6% were persistent high users, 41% were non-persistent high users, and 46% were non-high users. A larger proportion of high users were male, younger, and had multimorbidity than non-high users. In the last year of life, persistent high users had multiple hospitalizations more often than other groups. Twenty-eight percent of persistent high users had ≥2 ICU admissions, compared to 8% of non-persistent high users and only 1% of non-high users. Eleven percent of persistent high users had ≥2 ALC admissions, compared to only 2% of non-persistent high users and < 1% of non-high users. High users received an in-hospital intervention more often than non-high users (36% vs. 19%). Despite representing only 47% of the cohort, persistent and non-persistent high users accounted for 83% of acute-care costs. CONCLUSIONS: High users - persistent and non-persistent - are medically complex and use a disproportionate amount of acute-care resources at the end of life. A greater understanding of the characteristics and circumstances that lead to persistently high use of inpatient services may help inform strategies to prevent hospitalizations and off-set current healthcare costs while improving patient outcomes.

Benchmarking time to initiation of end-of-life homecare nursing: a population-based cancer cohort study in regions across Canada.

BACKGROUND: Several studies have demonstrated the benefits of early initiation of end-of-life care, particularly homecare nursing services. However, there is little research on variations in the timing of when end-of-life homecare nursing is initiated and no established benchmarks. METHODS: This is a retrospective cohort study of patients with a cancer-confirmed cause of death between 2004 and 2009, from three Canadian provinces (British Columbia, Nova Scotia, and Ontario). We linked multiple administrative health databases within each province to examine homecare use in the last 6 months of life. Our primary outcome was mean time (in days) to first end-of-life homecare nursing visit, starting from 6 months before death, by region. We developed an empiric benchmark for this outcome using a funnel plot, controlling for region size. RESULTS: Of the 28 regions, large variations in the outcome were observed, with the longest mean time (97 days) being two-fold longer than the shortest (55 days). On average, British Columbia and Nova Scotia had the first and second shortest mean times, respectively. The province of Ontario consistently had longer mean times. The empiric benchmark mean based on best-performing regions was 57 mean days. CONCLUSIONS: Significant variation exists for the time to initiation of end-of-life homecare nursing across regions. Understanding regional variation and developing an empiric benchmark for homecare nursing can support health system planners to set achievable targets for earlier initiation of end-of-life care.

Place of Death and Place of Care at the End of Life: Are They Correlated? A Retrospective Cohort Study of Ontario Decedents.

Background: Dying in nonpalliative acute care is generally considered inappropriate and avoidable. Place of death, a commonly reported big-dot indicator of end-of-life care quality, is often used as a proxy for place of care despite no empirical evidence for their correlations. Thus, we examined the correlations between place of death and place of care in the last month of life. We also investigated anecdotal claims that individuals cared in acute care often get discharged to die at home, and vice versa. Methods: We conducted a retrospective cohort study of Ontario decedents (18+) who died between January 1, 2015 and December 31, 2017. We identified individuals who died in nonpalliative acute care, palliative care unit, subacute care, long-term care (LTC), and the community. We calculated the number of days decedents spent in each setting in their last month of life, and used descriptive analyses to investigate their correlations. Results: Decedent's place of death generally correlated with their place of care in the last month of life-individuals who died in a particular setting spent more time in that setting than individuals who died elsewhere. Furthermore, 75.0% of individuals who spent more than two weeks of their last month in acute care died in acute care. Among individuals who died in the community and in LTC, 65.4% and 75.0%, respectively, spent zero days in acute care. Interpretation: We showed that place of death can be a useful high-level performance indicator, by itself and as a proxy for place of care, to gauge end-of-life quality and service provision/implementation.

Association of Metabolic Syndrome With Neuroimaging and Cognitive Outcomes in the UK Biobank.

OBJECTIVE: Metabolic syndrome (MetS) has been linked to dementia. In this study, we examined the association of MetS with neuroimaging and cognition in dementia-free adults, offering insight into the impact of MetS on brain health prior to dementia onset. RESEARCH DESIGN AND METHODS: We included 37,395 dementia-free adults from the UK Biobank database. MetS was defined as having at least three of the following components: larger waist circumference; elevated levels of triglycerides, blood pressure, HbA1c; or reduced HDL cholesterol levels. Multivariable-adjusted linear regression was used to assess associations of MetS with structural neuroimaging and cognitive domains. RESULTS: MetS was associated with lower total brain (standardized ß: -0.06; 95% CI -0.08, -0.04), gray matter (ß: -0.10; 95% CI -0.12, -0.08) and hippocampal (for left side, ß: -0.03, 95% CI -0.05, -0.01; for right side, ß: -0.04, 95% CI -0.07, -0.02) volumes, and greater white matter hyperintensity (WMH) volume (ß: 0.08; 95% CI 0.06, 0.11). Study participants with MetS performed poorer on cognitive tests of working memory (ß: -0.10; 95% CI -0.13, -0.07), verbal declarative memory (ß: -0.08; 95% CI -0.11, -0.05), processing speed (ß: -0.06; 95% CI -0.09, -0.04), verbal and numerical reasoning (ß: -0.07; 95% CI -0.09, -0.04), nonverbal reasoning (ß: -0.03; 95% CI -0.05, -0.01), and on tests of executive function, where higher scores indicated poorer performance (ß: 0.05; 95% CI 0.03, 0.08). More MetS components were also associated with less brain volume, greater WMH, and poorer cognition across all domains. CONCLUSIONS: MetS was associated poorer brain health in dementia-free adults, characterized by less brain volume, greater vascular pathology, and poorer cognition. Further research is necessary to understand whether reversal or improvement of MetS can improve brain health.

Palliative End-of-Life Medication Prescribing Rates in Long-Term Care: A Retrospective Cohort Study.

BACKGROUND: Medications are often needed to manage distressing end-of-life symptoms (eg, pain, agitation). OBJECTIVES: In this study, we describe the variation in prescribing rates of symptom relief medications at the end of life among long-term care (LTC) decedents. We evaluate the extent these medications are prescribed in LTC homes and whether prescribing rates of end-of-life symptom management can be used as an indicator of quality end-of-life care. DESIGN: Retrospective cohort study using administrative health data. SETTING AND PARTICIPANTS: LTC decedents in all 626 publicly funded LTC homes in Ontario, Canada, between January 1, 2017, and March 17, 2020. METHODS: For each LTC home, we measured the percent of decedents who received 1+ prescription(s) for a subcutaneous end-of-life symptom management medication ("end-of-life medication") in their last 14 days of life. We then ranked LTC homes into quintiles based on prescribing rates. RESULTS: We identified 55,916 LTC residents who died in LTC. On average, two-thirds of decedents (64.7%) in LTC homes were prescribed at least 1 subcutaneous end-of-life medication in the last 2 weeks of life. Opioids were the most common prescribed medication (overall average prescribing rate of 62.7%). LTC homes in the lowest prescribing quintile had a mean of 37.3% of decedents prescribed an end-of-life medication, and the highest quintile mean was 82.5%. In addition, across these quintiles, the lowest prescribing quintile had a high average (30.3%) of LTC residents transferred out of LTC in the 14 days compared with the highest prescribing quintile (12.7%). CONCLUSIONS AND IMPLICATIONS: Across Ontario's LTC homes, there are large differences in prescribing rates for subcutaneous end-of-life symptom relief medications. Although future work may elucidate why the variability exists, this study provides evidence that administrative data can provide valuable insight into the systemic delivery of end-of-life care.

Changes in End-of-Life Symptom Management Prescribing among Long-Term Care Residents during COVID-19.

OBJECTIVE: To examine changes in the prescribing of end-of-life symptom management medications in long-term care (LTC) homes during the COVID-19 pandemic. DESIGN: Retrospective cohort study using routinely collected health administrative data in Ontario, Canada. SETTING AND PARTICIPANTS: We included all individuals who died in LTC homes between January 1, 2017, and March 31, 2021. We separated the study into 2 periods: before COVID-19 (January 1, 2017, to March 17, 2020) and during COVID-19 (March 18, 2020, to March 31, 2021). METHODS: For each LTC home, we measured the percentage of residents who died before and during COVID-19 who had a subcutaneous symptom management medication prescription in their last 14 days of life. We grouped LTC homes into quintiles based on their mean prescribing rates before COVID-19, and examined changes in prescribing during COVID-19 and COVID-19 outcomes across quintiles. RESULTS: We captured 75,438 LTC residents who died in Ontario's 626 LTC homes during the entire study period, with 19,522 (25.9%) dying during COVID-19. The mean prescribing rate during COVID-19 ranged from 46.9% to 79.4% between the lowest and highest prescribing quintiles. During COVID-19, the mean prescribing rate in the lowest prescribing quintile increased by 9.6% compared to before COVID-19. Compared to LTC homes in the highest prescribing quintile, homes in the lowest prescribing quintile experienced the highest proportion of COVID-19 outbreaks (73.4% vs 50.0%), the largest mean outbreak intensity (0.27 vs 0.09 cases/bed), the highest mean total days with a COVID-19 outbreak (72.7 vs 24.2 days), and the greatest proportion of decedents who were transferred and died outside of LTC (22.1% vs 8.6%). CONCLUSIONS AND IMPLICATIONS: LTC homes in Ontario had wide variations in the prescribing rates of end-of-life symptom management medications before and during COVID-19. Homes in the lower prescribing quintiles had more COVID-19 cases per bed and days spent in an outbreak.

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

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

A population-based study of factors associated with systemic treatment in advanced prostate cancer decedents.

INTRODUCTION: Life-prolonging therapies (LPTs) are rapidly evolving for the treatment of advanced prostate cancer, although factors associated with real-world uptake are not well characterized. METHODS: In this cohort of prostate-cancer decedents, we analyzed factors associated with LPT access. Population-level databases from Ontario, Canada identified patients 65 years or older with prostate cancer receiving androgen deprivation therapy and who died of prostate cancer between 2013 and 2017. Univariate and multivariable analyses assessed the association between baseline characteristics and receipt of LPT in the 2 years prior to death. RESULTS: Of 3575 patients who died of prostate cancer, 40.4% (n = 1443) received LPT, which comprised abiraterone (66.3%), docetaxel (50.3%), enzalutamide (17.2%), radium-223 (10.0%), and/or cabazitaxel (3.5%). Use of LPT increased by year of death (2013: 22.7%, 2014: 31.8%, 2015: 41.8%, 2016: 49.1%, and 2017: 57.9%, p < 0.0001), driven by uptake of all agents except docetaxel. Adjusted odds of use were higher for patients seen at Regional Cancer Centers (OR: 1.8, 95% CI: 1.5-2.1) and who received prior prostate-directed therapy (OR: 1.3, 95% CI: 1.0-1.5), but lower with advanced age (≥85: OR: 0.54, 95% CI:0.39-0.75), increased chronic conditions (≥6: OR: 0.62, 95% CI: 0.43-0.92), and long-term care residency (OR: 0.38, 95% CI: 0.17-0.89). Income, stage at presentation, and distance to the cancer center were not associated with LPT uptake. CONCLUSION: In this cohort of prostate cancer-decedents, real-world uptake of novel prostate cancer therapies occurred at substantially higher rates for patients receiving care at Regional Cancer Centers, reinforcing the potential benefits for treatment access for patients referred to specialist centers.

Characteristics and Outcomes of ICU Patients Without COVID-19 Infection-Pandemic Versus Nonpandemic Times: A Population-Based Cohort Study.

Outcomes for critically ill COVID-19 are well described; however, the impact of the pandemic on critically ill patients without COVID-19 infection is less clear. OBJECTIVES: To demonstrate the characteristics and outcomes of non-COVID patients admitted to an ICU during the pandemic, compared with the previous year. DESIGN: A population-based study conducted using linked health administrative data comparing a cohort from March 1, 2020, to June 30, 2020 (pandemic) to a cohort from March 1, 2019, to June 30, 2019 (nonpandemic). SETTING AND PARTICIPANTS: Adult patients (18 yr old) admitted to an ICU in Ontario, Canada, without a diagnosis of COVID-19 during the pandemic and nonpandemic periods. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause in-hospital mortality. Secondary outcomes included hospital and ICU length of stay, discharge disposition, and receipt of resource intensive procedures (e.g., extracorporeal membrane oxygenation, mechanical ventilation, renal replacement therapy, bronchoscopy, feeding tube insertion, and cardiac device insertion). We identified 32,486 patients in the pandemic cohort and 41,128 in the nonpandemic cohort. Age, sex, and markers of disease severity were similar. Fewer patients in the pandemic cohort were from long-term care facilities and had fewer cardiovascular comorbidities. There was an increase in all-cause in-hospital mortality among the pandemic cohort (13.5% vs 12.5%; p < 0.001) representing a relative increase of 7.9% (adjusted odds ratio, 1.10; 95% CI, 1.05-1.56). Patients in the pandemic cohort admitted with chronic obstructive pulmonary disease exacerbation had an increase in all-cause mortality (17.0% vs 13.2%; p = 0.013), a relative increase of 29%. Mortality among recent immigrants was higher in the pandemic cohort compared with the nonpandemic cohort (13.0% vs 11.4%; p = 0.038), a relative increase of 14%. Length of stay and receipt of intensive procedures were similar. CONCLUSIONS AND RELEVANCE: We found a modest increase in mortality among non-COVID ICU patients during the pandemic compared with a nonpandemic cohort. Future pandemic responses should consider the impact of the pandemic on all patients to preserve quality of care.