Increased frequency and mortality in persons with neurological disorders during COVID-19.

Determining the frequency and outcomes of neurological disorders associated with coronavirus disease 2019 (COVID-19) is imperative for understanding risks and for recognition of emerging neurological disorders. We investigated the susceptibility and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among persons with premorbid neurological disorders, in addition to the post-infection incidence of neurological sequelae, in a case-control population-based cohort. Using health service data collected between 1 March 2020 and 30 June 2021, we constructed a cohort of SARS-CoV-2 RNA-positive (n = 177 892) and -negative (n = 177 800) adults who were age, sex and comorbidity matched and underwent RT-PCR testing at similar times. COVID-19-associated mortality rates were examined within the cohort. Neurological sequelae were analysed during the acute (<3 months) and the post-acute (3-9 months) phases post-infection. The risk of death was significantly greater in the SARS-CoV-2 RNA-positive (2140 per 100 000 person years) compared with RNA-negative (922 per 100 000 person years) over a follow-up of 9 months, particularly amongst those with premorbid neurological disorders: adjusted odds ratios (95% confidence interval) in persons with a prior history of parkinsonism, 1.65 (1.15-2.37); dementia, 1.30 (1.11-1.52); seizures, 1.91 (1.26-2.87); encephalopathy, 1.82 (1.02-3.23); and stroke, 1.74 (1.05-2.86). There was also a significantly increased risk for diagnosis of new neurological sequelae during the acute time phase after COVID-19, including encephalopathy, 2.0 (1.10-3.64); dementia, 1.36 (1.07-1.73); seizure, 1.77 (1.22-2.56); and brain fog, 1.96 (1.20-3.20). These risks persisted into the post-acute phase after COVID-19, during which inflammatory myopathy (2.57, 1.07-6.15) and coma (1.87, 1.22-2.87) also became significantly increased. Thus, persons with SARS-CoV-2 infection and premorbid neurological disorders are at greater risk of death, and SARS-CoV-2 infection was complicated by increased risk of new-onset neurological disorders in both the acute and post-acute phases of COVID-19.

Variation in Testing for and Incidence of Celiac Autoimmunity in Canada: A Population-Based Study.

BACKGROUND & AIMS: The incidence of biopsy-confirmed celiac disease has increased. However, few studies have explored the incidence of celiac autoimmunity based on positive serology results. METHODS: A population-based cohort study assessed testing of tissue transglutaminase antibodies (tTG-IgA) in Alberta from 2012 to 2020. After excluding prevalent cases, incident celiac autoimmunity was defined as the first positive tTG-IgA result between 2015 and 2020. Testing and incidence rates for celiac autoimmunity were calculated per 1000 and 100,000 person-years, respectively. Incidence rate ratios (IRRs) were calculated to identify differences by demographic and regional factors. Average annual percent changes (AAPCs) assessed trends over time. RESULTS: The testing rate of tTG-IgA was 20.2 per 1000 person-years and remained stable from 2012 to 2020 (AAPC, 1.2%; 95% confidence interval [CI], -0.5 to 2.9). Testing was higher in female patients (IRR, 1.66; 95% CI, 1.65-1.66), those living in metropolitan areas (IRR, 1.39; 95% CI, 1.38-1.40), and in areas of lower socioeconomic deprivation (lowest compared to highest IRR, 1.24; 95% CI, 1.23-1.25). Incidence of celiac autoimmunity was 33.8 per 100,000 person-years and increased from 2015 to 2020 (AAPC, 6.2%; 95% CI, 3.1-9.5). Among those with tTG-IgA results ≥10 times the upper limit of normal, the incidence was 12.9 per 100,000 person-years. The incidence of celiac autoimmunity was higher in metropolitan settings (IRR, 1.28; 95% CI, 1.21-1.35) and in the least socioeconomically deprived areas compared to the highest (IRR, 1.22; 95% CI, 1.14-1.32). CONCLUSIONS: Incidence of celiac autoimmunity is high and increasing, despite stable testing rates. Variation in testing patterns may lead to underreporting the incidence of celiac autoimmunity in nonmetropolitan areas and more socioeconomically deprived neighborhoods.

Comparing Analytical Methods for Composite End Points in Clinical Trials: Insights from the Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction Trial.

BACKGROUND: In VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), participants with heart failure (HF) and reduced ejection fraction, vericiguat decreased the primary composite outcome (time to first HF hospitalization [HFH] or cardiovascular death [CVD]) (897 events) compared with placebo (972 events) (hazard ratio, 0.90; 95% confidence interval [CI], 0.82-0.98; P = .02). In this prespecified secondary analysis, we applied the weighted composite end point (WCE) and the win ratio (WR) methods to provide complementary assessments of treatment effect. METHODS AND RESULTS: The WCE method estimated the mean HFH-adjusted survival based on prespecified weights from a Delphi panel of the VICTORIA executive committee and national leaders: mild (weight per event, 0.39), moderate (0.5), or severe (0.67) HFH, and CVD (1.0). The unmatched WR was estimated for the descending hierarchy of CVD, then recurrent HFH. The WCE used all 3412 primary clinical events: 875 severe HFH (vericiguat, 416/ placebo, 459), 1614 moderate HFH (767/847), 68 mild HFH (38/30), and 855 CVD (414/441). Improved HFH-adjusted survival occurred with vericiguat (mean 78.2% vs 75.6%, difference 2.4%, 95% CI, 1.7%-3.2%, P < .0001). Based on a comparison of 6,375,624 pairs, the WR of 1.13 (95% CI 1.03-1.24, P = .01) also indicated improved clinical outcomes with vericiguat. CONCLUSIONS: The results of the WCE and WR methods were consistent with the primary analysis of the time to first HFH or CVD. Although both WCE and WR assessed recurrent events, the WCE allowed inclusion of all recurrent events, insights on the severity of HFH events, and an absolute measure of the participant-treatment experience. This approach complements conventional assessment, better informing consumers of new therapeutics and future trial designs.

The empirical estimate of the survival and variance using a weighted composite endpoint.

BACKGROUND: Composite endpoints for estimating treatment efficacy are routinely used in several therapeutic areas and have become complex in the number and types of component outcomes included. It is assumed that its components are of similar asperity and chronology between both treatment arms as well as uniform in magnitude of the treatment effect. However, these assumptions are rarely satisfied. Understanding this heterogeneity is important in developing a meaningful assessment of the treatment effect. METHODS: We developed the Weighted Composite Endpoint (WCE) method which uses weights derived from stakeholder values for each event type in the composite endpoint. The derivation for the product limit estimator and the variance of the estimate are presented. The method was then tested using data simulated from parameters based on a large cardiovascular trial. Variances from the estimated and traditional approach are compared through increasing sample size. RESULTS: The WCE method used all of the events through follow-up and generated a multiple recurrent event survival. The treatment effect was measured as the difference in mean survivals between two treatment arms and corresponding 95% confidence interval, providing a less conservative estimate of survival and variance, giving a higher survival with a narrower confidence interval compared to the traditional time-to-first-event analysis. CONCLUSIONS: The WCE method embraces the clinical texture of events types by incorporating stakeholder values as well as all events during follow-up. While the effective number of events is lower in the WCE analysis, the reduction in variance enhances the ability to detect a treatment effect in clinical trials.

Symptoms associated with a positive result for a swab for SARS-CoV-2 infection among children in Alberta.

BACKGROUND: Research involving children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has primarily focused on those presenting to emergency departments. We aimed to determine the symptoms most commonly associated with a positive result for a SARS-CoV-2 swab among community-based children. METHODS: We conducted an observational study among children tested and followed for SARS-CoV-2 infection using nasal, nasopharyngeal, throat or other (e.g., nasopharyngeal aspirate or tracheal secretions, or unknown) swabs between Apr. 13 and Sept. 30, 2020, in Alberta. We calculated positive likelihood ratios (LRs) for self-reported symptoms and a positive SARS-CoV-2 swab result in the entire cohort and in 3 sensitivity analyses: all children with at least 1 symptom, all children tested because of contact tracing whether they were symptomatic or not and all children 5 years of age or older. RESULTS: We analyzed results for 2463 children who underwent testing for SARS-CoV-2 infection; 1987 children had a positive result and 476 had a negative result. Of children with a positive test result for SARS-CoV-2, 714 (35.9%) reported being asymptomatic. Although cough (24.5%) and rhinorrhea (19.3%) were 2 of the most common symptoms among children with SARS-CoV-2 infection, they were also common among those with negative test results and were not predictive of a positive test (positive LR 0.96, 95% confidence interval [CI] 0.81-1.14, and 0.87, 95% CI 0.72-1.06, respectively). Anosmia/ageusia (positive LR 7.33, 95% CI 3.03-17.76), nausea/vomiting (positive LR 5.51, 95% CI 1.74-17.43), headache (positive LR 2.49, 95% CI 1.74- 3.57) and fever (positive LR 1.68, 95% CI 1.34-2.11) were the symptoms most predictive of a positive result for a SARS-CoV-2 swab. The positive LR for the combination of anosmia/ageusia, nausea/vomiting and headache was 65.92 (95% CI 49.48-91.92). INTERPRETATION: About two-thirds of the children who tested positive for SARS-CoV-2 infection reported symptoms. The symptoms most strongly associated with a positive SARS-CoV-2 swab result were anosmia/ageusia, nausea/vomiting, headache and fever.

Clinical impact of vancomycin-resistant enterococci colonization in nonliver solid organ transplantation and its implications for infection control strategies: A single-center, 10-year retrospective study.

BACKGROUND: Vancomycin-resistant enterococci (VRE) colonization in nonliver solid organ transplantation (SOT) is poorly defined. Infection control management of these patients is influenced by the association of VRE with adverse outcomes in liver transplantation. This study examines the frequency and clinical impact of VRE colonization specifically on nonliver SOT patients and discusses implications for nosocomial VRE control. METHODS: We retrospectively reviewed all nonliver SOT patients at a single transplant center from 2005 to 2015. We determined colonization rates in the peritransplant period and the rate of VRE infections. The association between VRE colonization with 90-day mortality and other clinical outcomes was examined. RESULTS: There were 1786 nonliver SOTs from 2005 to 2015, with 81 (4.6%) colonized with VRE in the peritransplantation period. The colonization prevalence varied by organ type: 45 of 423 lung (10.6%), 12 of 352 heart (3.4%), one of 18 heart-lung (5.6%), 20 of 884 kidney (2.3%), three of 63 kidney-pancreas (4.8%), zero of 11 pancreas, zero of five small bowel, and zero of 11 multivisceral. Peritransplant VRE colonization was not associated with 90-day mortality odds ratio = 2.35 (95% CI = 0.53, 10.29) and adjusted odds ratio = 1.52 (95% CI = 0.34, 6.88). In the multivariable logistic regression, there was no association with mortality at 1 year or 5 years, hospital length of stay, rehospitalization, or days alive out of hospital. There were 14 inpatient VRE infections up to 1 year after transplantation. CONCLUSION: Nonliver SOT patients have lower rates of VRE colonization than liver SOT, and colonization was not associated with increased adverse clinical outcomes. Although infection control strategies for VRE in hospital remain controversial, nonliver SOT should be considered among typical hospitalized patients when designing strategies for prevention.

Prevalence of Mental Disorders and Suicidality in Canadian Provinces.

OBJECTIVE: There is limited information to guide health-care service providers and policy makers on the burden of mental disorders and addictions across the Canadian provinces. This study compares interprovincial prevalence of major depressive disorder (MDD), bipolar disorder, generalized anxiety disorder (GAD), alcohol use disorder, substance use disorders, and suicidality. METHOD: Data were extracted from the 2012 Canadian Community Health Survey-Mental Health (n = 25,113), a representative sample of Canadians over the age of 15 years across all provinces. Cross tabulations and logistic regression were used to determine the prevalence and odds of the above disorders for each province. Adjustments for provincial sociodemographic factors were performed. RESULTS: The past-year prevalence of all measured mental disorders and suicidality, excluding GAD, demonstrated significant interprovincial differences. Manitoba exhibited the highest prevalence of any mental disorder (13.6%), reflecting high prevalence of MDD and alcohol use disorder compared to the other provinces (7.0% and 3.8%, respectively). Nova Scotia exhibited the highest prevalence of substance use disorders (2.9%). Quebec and Prince Edward Island exhibited the lowest prevalence of any mental disorder (8.5% and 7.7%, respectively). Manitoba also exhibited the highest prevalence of suicidal ideation (5.1%); however, British Columbia and Ontario exhibited the highest prevalence of suicidal planning (1.4% and 1.3%, respectively), and Ontario alone exhibited the highest prevalence of suicide attempts (0.7%). CONCLUSIONS: Significant interprovincial differences were found in the past-year prevalence of mental disorders and suicidality in Canada. More research is necessary to explore these differences and how they impact the need for mental health services.

The effect of provider affiliation with a primary care network on emergency department visits and hospital admissions.

BACKGROUND: Primary care networks are designed to facilitate access to inter-professional, team-based care. We compared health outcomes associated with primary care networks versus conventional primary care. METHODS: We obtained data on all adult residents of Alberta who visited a primary care physician during fiscal years 2008 and 2009 and classified them as affiliated with a primary care network or not, based on the physician most involved in their care. The primary outcome was an emergency department visit or nonelective hospital admission for a Patient Medical Home indicator condition (asthma, chronic obstructive pulmonary disease, heart failure, coronary disease, hypertension and diabetes) within 12 months. RESULTS: Adults receiving care within a primary care network (n = 1 502 916) were older and had higher comorbidity burdens than those receiving conventional primary care (n = 1 109 941). Patients in a primary care network were less likely to visit the emergency department for an indicator condition (1.4% v. 1.7%, mean 0.031 v. 0.035 per patient, adjusted risk ratio [RR] 0.98, 95% confidence interval [CI] 0.96-0.99) or for any cause (25.5% v. 30.5%, mean 0.55 v. 0.72 per patient, adjusted RR 0.93, 95% CI 0.93-0.94), but were more likely to be admitted to hospital for an indicator condition (0.6% v. 0.6%, mean 0.018 v. 0.017 per patient, adjusted RR 1.07, 95% CI 1.03-1.11) or all-cause (9.3% v. 9.1%, mean 0.25 v. 0.23 per patient, adjusted RR 1.08, 95% CI 1.07-1.09). Patients in a primary care network had 169 fewer all-cause emergency department visits and 86 fewer days in hospital (owing to shorter lengths of stay) per 1000 patient-years. INTERPRETATION: Care within a primary care network was associated with fewer emergency department visits and fewer hospital days.

Do stable non-ST-segment elevation acute coronary syndromes require admission to coronary care units?

BACKGROUND: Clinical practice guidelines recommend admitting patients with stable non-ST-segment elevation acute coronary syndrome (NSTE ACS) to telemetry units, yet up to two-thirds of patients are admitted to higher-acuity critical care units (CCUs). The outcomes of patients with stable NSTE ACS initially admitted to a CCU vs a cardiology ward with telemetry have not been described. METHODS: We used population-based data of 7,869 patients hospitalized with NSTE ACS admitted to hospitals in Alberta, Canada, between April 1, 2007, and March 31, 2013. We compared outcomes among patients initially admitted to a CCU (n=5,141) with those admitted to cardiology telemetry wards (n=2,728). RESULTS: Patients admitted to cardiology telemetry wards were older (median 69 vs 65years, P<.001) and more likely to be female (37.2% vs 32.1%, P<.001) and have a prior myocardial infarction (14.3% vs 11.5%, P<.001) compared with patients admitted to a CCU. Patients admitted directly to cardiology telemetry wards had similar hospital stays (6.2 vs 5.7days, P=.29) and fewer cardiac procedures (40.3% vs 48.5%, P<.001) compared with patients initially admitted to CCUs. There were no differences in the frequency of in-hospital mortality (1.3% vs 1.2%, adjusted odds ratio [aOR] 1.57, 95% CI 0.98-2.52), cardiac arrest (0.7% vs 0.9%, aOR 1.37, 95% CI 0.94-2.00), 30-day all-cause mortality (1.6% vs 1.5%, aOR 1.50, 95% CI 0.82-2.75), or 30-day all-cause postdischarge readmission (10.6% vs 10.8%, aOR 1.07, 95% CI 0.90-1.28) between cardiology telemetry ward and CCU patients. Results were similar across low-, intermediate-, and high-risk Duke Jeopardy Scores, and in patients with non-ST-segment myocardial infarction or unstable angina. CONCLUSIONS: There were no differences in clinical outcomes observed between patients with NSTE ACS initially admitted to a ward or a CCU. These findings suggest that stable NSTE ACS may be managed appropriately on telemetry wards and presents an opportunity to reduce hospital costs and critical care capacity strain.

Symptômes associés au frottis SRAS-CoV-2-positif chez des enfants de l'Alberta.

CONTEXTE: La recherche sur les enfants atteints d'une infection à coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) a principalement porté sur les enfants amenés aux services des urgences. Nous avons voulu identifier les symptômes plus souvent associés à un frottis SRAS-CoV-2-positif chez les enfants non hospitalisés. MÉTHODES: Nous avons procédé à une étude observationnelle chez des enfants soumis au dépistage et suivis pour une infection à SRAS-CoV-2 confirmée sur des prélèvements de sécrétions nasales, nasopharyngées, de la gorge et autres (p. ex., aspiration nasopharyngée, sécrétions trachéales ou non spécifiées) entre le 13 avril et le 30 septembre 2020 en Alberta. Nous avons calculé les rapports de vraisemblance (RV) positifs entre les symptômes autodéclarés et les frottis SRAS-CoV-2-positifs dans la cohorte entière et dans 3 analyses de sensibilité : tous les enfants présentant au moins 1 symptôme, tous les enfants, symptomatiques ou non, soumis au dépistage par suite d'une recherche de contacts, et tous les enfants de 5 ans et plus. RÉSULTATS: Nous avons analysé les résultats chez 2463 enfants soumis au dépistage de l'infection à SRAS-CoV-2; 1987 enfants se sont révélés positifs et 476 négatifs. Parmi les enfants SRAS-CoV-2-positifs, 714 (35,9 %) n'ont déclaré aucun symptôme. Même si la toux (24,5 %) et la rhinorrhée (19,3 %) étaient les 2 symptômes les plus fréquents chez les enfants ayant contracté le SRAS-CoV-2, elles étaient fréquentes également chez ceux dont les résultats étaient négatifs et ne permettaient pas de prédire un résultat positif (RV positif 0,96, intervalle de confiance [IC] à 95 % 0,81­1,14 et 0,87, IC à 95 % 0,72­1,06, respectivement). L'anosmie/agueusie (RV positif 7,33, IC à 95 % 3,03­17,76), les nausées et vomissements (RV positif 5,51, IC à 95 % 1,74­17,43), les céphalées (RV positif 2,49, IC à 95 % 1,74­3,57) et la fièvre (RV positif 1,68, IC à 95 % 1,34­2,11) ont été les symptômes les plus prédictifs d'un résultat SRAS-CoV-2-positif. Le RV positif pour la combinaison anosmie et agueusie, nausées et vomissements, et céphalées était de 65,92 (IC à 95 % 49,48­91,92). INTERPRÉTATION: Environ les deux tiers des enfants déclarés SRAS-CoV-2-positifs ont manifesté des symptômes, et les symptômes les plus étroitement associés à un frottis SRAS-CoV-2-positif étaient l'anosmie/agueusie, les nausées et les vomissements, les céphalées et la fièvre.

Applying novel methods to assess clinical outcomes: insights from the TRILOGY ACS trial.

AIMS: Several methods provide new insights into understanding clinical trial composite endpoints, using both conventional and novel methods. The TRILOGY ACS trial is used as a contemporary example to prospectively compare these methods side by side. METHODS AND RESULTS: The traditional time-to-first-event, Andersen-Gill recurrent events method, win ratio, and a weighted composite endpoint (WCE) are compared using the randomized, active-control TRILOGY ACS trial. This trial had a neutral result and randomized 9326 patients managed without coronary revascularization within 10 days of their acute coronary syndrome to receive either prasugrel or clopidogrel and followed them for up to 30 months. The traditional composite, win ratio, and WCE demonstrated no significant survival advantage for prasugrel, whereas the Andersen-Gill method demonstrated a statistical advantage for prasugrel [hazard ratio (HR), 0.86 (95% CI, 0.72-0.97)]. The traditional composite used 73% of total patient events; 40% of these were derived from the death events. The win ratio used 66% of total events; deaths comprised 57% of these. Both Andersen-Gill and WCE methods used all events in all participants; however, with the Andersen-Gill method, death comprised 41% of the proportion of events, whereas with the WCE method, death comprised 64% of events. CONCLUSION: This study addresses the relative efficiency of various methods for assessing clinical trial events comprising the composite endpoint. The methods accounting for all events, in particular those incorporating their clinical relevance, appear most advantageous, and may be useful in interpreting future trials. This clinical and statistical advantage is especially evident with long-term follow-up where multiple non-fatal events are more common. CLINICAL TRIAL REGISTRATION: NCT00699998.

External validation of the Hospital-patient One-year Mortality Risk (HOMR) model for predicting death within 1 year after hospital admission.

BACKGROUND: Predicting long-term survival after admission to hospital is helpful for clinical, administrative and research purposes. The Hospital-patient One-year Mortality Risk (HOMR) model was derived and internally validated to predict the risk of death within 1 year after admission. We conducted an external validation of the model in a large multicentre study. METHODS: We used administrative data for all nonpsychiatric admissions of adult patients to hospitals in the provinces of Ontario (2003-2010) and Alberta (2011-2012), and to the Brigham and Women's Hospital in Boston (2010-2012) to calculate each patient's HOMR score at admission. The HOMR score is based on a set of parameters that captures patient demographics, health burden and severity of acute illness. We determined patient status (alive or dead) 1 year after admission using population-based registries. RESULTS: The 3 validation cohorts (n = 2,862,996 in Ontario, 210 595 in Alberta and 66,683 in Boston) were distinct from each other and from the derivation cohort. The overall risk of death within 1 year after admission was 8.7% (95% confidence interval [CI] 8.7% to 8.8%). The HOMR score was strongly and significantly associated with risk of death in all populations and was highly discriminative, with a C statistic ranging from 0.89 (95% CI 0.87 to 0.91) to 0.92 (95% CI 0.91 to 0.92). Observed and expected outcome risks were similar (median absolute difference in percent dying in 1 yr 0.3%, interquartile range 0.05%-2.5%). INTERPRETATION: The HOMR score, calculated using routinely collected administrative data, accurately predicted the risk of death among adult patients within 1 year after admission to hospital for nonpsychiatric indications. Similar performance was seen when the score was used in geographically and temporally diverse populations. The HOMR model can be used for risk adjustment in analyses of health administrative data to predict long-term survival among hospital patients.

Physician experience and outcomes among patients admitted to general internal medicine teaching wards.

BACKGROUND: Physician scores on examinations decline with time after graduation. However, whether this translates into declining quality of care is unknown. Our objective was to determine how physician experience is associated with negative outcomes for patients admitted to hospital. METHODS: We conducted a retrospective cohort study involving all patients admitted to general internal medicine wards over a 2-year period at all 7 teaching hospitals in Alberta, Canada. We used files from the Alberta College of Physicians and Surgeons to determine the number of years since medical school graduation for each patient's most responsible physician. Our primary outcome was the composite of in-hospital death, or readmission or death within 30 days postdischarge. RESULTS: We identified 10 046 patients who were cared for by 149 physicians. Patient characteristics were similar across physician experience strata, as were primary outcome rates (17.4% for patients whose care was managed by physicians in the highest quartile of experience, compared with 18.8% in those receiving care from the least experienced physicians; adjusted odds ratio [OR] 0.88, 95% confidence interval [CI] 0.72-1.06). Outcomes were similar between experience quartiles when further stratified by physician volume, most responsible diagnosis or complexity of the patient's condition. Although we found substantial variability in length of stay between individual physicians, there were no significant differences between physician experience quartiles (mean adjusted for patient covariates and accounting for intraphysician clustering: 7.90 [95% CI 7.39-8.42] d for most experienced quartile; 7.63 [95% CI 7.13-8.14] d for least experienced quartile). INTERPRETATION: For patients admitted to general internal medicine teaching wards, we saw no negative association between physician experience and outcomes commonly used as proxies for quality of inpatient care.

Association between frailty and 30-day outcomes after discharge from hospital.

BACKGROUND: Readmissions after hospital discharge are common and costly, but prediction models are poor at identifying patients at high risk of readmission. We evaluated the impact of frailty on readmission or death within 30 days after discharge from general internal medicine wards. METHODS: We prospectively enrolled patients discharged from 7 medical wards at 2 teaching hospitals in Edmonton. Frailty was defined by means of the previously validated Clinical Frailty Scale. The primary outcome was the composite of readmission or death within 30 days after discharge. RESULTS: Of the 495 patients included in the study, 162 (33%) met the definition of frailty: 91 (18%) had mild, 60 (12%) had moderate, and 11 (2%) had severe frailty. Frail patients were older, had more comorbidities, lower quality of life, and higher LACE scores at discharge than those who were not frail. The composite of 30-day readmission or death was higher among frail than among nonfrail patients (39 [24.1%] v. 46 [13.8%]). Although frailty added additional prognostic information to predictive models that included age, sex and LACE score, only moderate to severe frailty (31.0% event rate) was an independent risk factor for readmission or death (adjusted odds ratio 2.19, 95% confidence interval 1.12-4.24). INTERPRETATION: Frailty was common and associated with a substantially increased risk of early readmission or death after discharge from medical wards. The Clinical Frailty Scale could be useful in identifying high-risk patients being discharged from general internal medicine wards.

Case management for blood pressure and lipid level control after minor stroke: PREVENTION randomized controlled trial.

BACKGROUND: Optimization of systolic blood pressure and lipid levels are essential for secondary prevention after ischemic stroke, but there are substantial gaps in care, which could be addressed by nurse- or pharmacist-led care. We compared 2 types of case management (active prescribing by pharmacists or nurse-led screening and feedback to primary care physicians) in addition to usual care. METHODS: We performed a prospective randomized controlled trial involving adults with recent minor ischemic stroke or transient ischemic attack whose systolic blood pressure or lipid levels were above guideline targets. Participants in both groups had a monthly visit for 6 months with either a nurse or pharmacist. Nurses measured cardiovascular risk factors, counselled patients and faxed results to primary care physicians (active control). Pharmacists did all of the above as well as prescribed according to treatment algorithms (intervention). RESULTS: Most of the 279 study participants (mean age 67.6 yr, mean systolic blood pressure 134 mm Hg, mean low-density lipoprotein [LDL] cholesterol 3.23 mmol/L) were already receiving treatment at baseline (antihypertensives: 78.1%; statins: 84.6%), but none met guideline targets (systolic blood pressure ≤ 140 mm Hg, fasting LDL cholesterol ≤ 2.0 mmol/L). Substantial improvements were observed in both groups after 6 months: 43.4% of participants in the pharmacist case manager group met both systolic blood pressure and LDL guideline targets compared with 30.9% in the nurse-led group (12.5% absolute difference; number needed to treat = 8, p = 0.03). INTERPRETATION: Compared with nurse-led case management (risk factor evaluation, counselling and feedback to primary care providers), active case management by pharmacists substantially improved risk factor control at 6 months among patients who had experienced a stroke. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT00931788.

Evaluation of early percutaneous coronary intervention vs. standard therapy after fibrinolysis for ST-segment elevation myocardial infarction: contribution of weighting the composite endpoint.

AIMS: The selection of optimal endpoints for cardiovascular clinical trials continues to be challenging. We examined an alternative interpretation of a series of trials when the individual event severity is considered. METHODS AND RESULTS: We analysed three contemporary myocardial infarction (MI) trials of early percutaneous coronary intervention after fibrinolysis, using a weighted composite method. This method allows the examination of the heterogeneity in the direction and magnitude of component endpoints, and multiple events (vs. first event). We incorporated a physician-assessed severity of each component endpoint in all patients for the five-item composite in the largest study, Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), which enrolled 1059 ST-elevation MI patients. The traditional approach yielded event-free survival probabilities of 0.89 [95% confidence interval (CI) 0.86-0.91] for the early invasive arm and 0.83 (95% CI 0.79-0.86) for the standard care arm (P = 0.004). After accounting for the clinician-investigator-determined weights, the effective survival probabilities were 0.93 (95% CI 0.91-0.95) for the early invasive arm and 0.93 (95% CI 0.90-0.95) with no significant difference (P = 0.54). The same pattern was observed in the three-trial cohort using a four-item composite with an observed improvement in event-free survival outcomes (P = 0.01), which was no longer apparent after the severity weights were considered (P = 0.44). CONCLUSION: This analysis highlights the importance of considering the relative severity and multiple events in the evaluation of a clinical trial.

Validation of a Novel Clinical Dyspnea Scale - A Retrospective Pilot Study.

Objective: to examine the validity of a novel dyspnea scale, Edmonton Dyspnea Inventory in idiopathic pulmonary fibrosis (IPF). Methods: Edmonton Dyspnea Inventory (EDI), is a clinical instrument to measure dyspnea severity with activities of daily living, exercise and rest using a numeric rating scale (0 -10). Consecutive IPF patients (2012-2018) with baseline MRC and EDI were included. To validate EDI, psychometric analysis was conducted. Correlations between EDI, MRC and lung function were examined. Group-based trajectory modeling was used to group patients based on dyspnea severity. Net Reclassification Improvement (NRI) was calculated to assess the improvement in 1-year mortality prediction by adding trajectory groups to MRC grade. Results: 100 consecutive IPF patients were identified; mean age 73 years (SD = 9) and 65% males; 73% were in MRC grades ≥3. Item analysis showed all 8 EDI components have excellent discrimination power with ability to differentiate patients with varying dyspnea severity. EDI has good internal consistency (Cronbach α = .92). Exploratory factor analysis showed a one-factor solution with loadings from .66 to .89 suggesting 8 EDI components measured essentially one dimension of dyspnea. All EDI components were correlated with MRC and some with lung function. Modeling data identified three EDI dyspnea severity groups with differing mortality (P = .009). The addition of EDI dyspnea severity groups to the MRC score improved 1-year mortality prediction (NRI = .66; 95% CI, .18-1.14). Conclusions: EDI is a valid dyspnea instrument, correlated with MRC and lung function. It can categorize IPF patients into 3 dyspnea severity groups associated with increased mortality. Key Message: We describe the development of a novel scale, Edmonton Dyspnea Inventory, that facilitates measurement of dyspnea severity in the context of daily activities in patients with IPF. The results indicate that the new instrument is valid and correlated to MRC. It identifies 3 categories of severity not recognized by MRC with impact on mortality. Knowledge of dyspnea severity can help triage patients and assign appropriate therapies.

The Impact of Integrated Palliative Care on Survival in Idiopathic Pulmonary Fibrosis: A Retrospective Multicenter Comparison.

Background: Early and integrated palliative care is recommended for patients with idiopathic pulmonary fibrosis. Unfortunately, palliative care delivery remains poor due to various barriers in practice. This study describes various palliative care delivery models in a real-world cohort of patients with idiopathic pulmonary fibrosis, examines the predictors of survival in this cohort of patients, and explores the impact of palliative care on survival. Design: Charts were reviewed retrospectively and analyzed. The primary outcome was survival during a 4-year follow-up period. Two multivariable models were created to examine the impact of therapeutic strategies including palliative intervention on survival. Results: 298 patients with idiopathic pulmonary fibrosis were enrolled from 3 interstitial lung disease clinics with different palliative care models in Edmonton, Canada; Bristol, UK; and Kingston, Canada. 200 (67%) patients received palliative care and 119 (40%) died during follow up. Primary palliative care models (Edmonton and Bristol) delivered palliative care to 96% and 100% respectively compared 21% in the referral model (Queens). Palliative care [adjusted hazard ratio (aHR) .28 (.12-.65)] along with the use of antifibrotics [aHR .56 (.37-.84)], and body mass index >30 [aHR .47 (.37-.85)] reduced the risk of death in our idiopathic pulmonary fibrosis cohort. Opioid use was associated with worse survival [aHR 2.11 (1.30-23.43)]. Conclusions: Both palliative care and antifibrotic use were associated with survival benefit in this cohort of patients with idiopathic pulmonary fibrosis after adjusting for covariates. The benefit was seen despite differences in disease severity and different palliative care delivery models.

Predicting inpatient rehabilitation length of stay for adults with traumatic spinal cord injury.

INTRODUCTION: Most post-injury traumatic spinal cord injury (TSCI) care occurs in the inpatient rehabilitation setting. The inpatient rehabilitation length of stay (R-LOS) has been shown to be a significant predictor of motor function restoration in persons with TSCI. Due to the complexity, and heterogeneity of individuals with TSCI, the R-LOS is challenging to predict at admission. PURPOSE: To identify the main predictors of R-LOS and derive an equation to estimate R-LOS in persons with TSCI. METHODS: This is a retrospective analysis of data from adults with TSCI from The Rick Hansen Spinal Cord Injury Registry in Alberta, Canada, who received rehabilitation care between May 10, 2005, and January 28, 2020. Multiple linear regression analysis was used to determine significant relationships between R-LOS and measures of participant demographics, length of stay, impairment and injury classification, and comorbidities. RESULTS: The analysis included 736 adults with TSCI from an eligible cohort of 1365. The median R-LOS was 65 days (IQR 39-99 days), ranging from 1 to 469 days. Multivariate linear regression analysis identified two significant predictors of R-LOS, total FIM score and the injury classification. This model was used to derive a R-LOS prediction equation, which explained 34% of the variance in R-LOS. CONCLUSION: We developed a simple equation to predict R-LOS based on the level of impairment and total FIM scores in persons with TSCI. These data have implications for health system planning, improvement, and innovation, and provide insights to support further research into the predictors of R-LOS, identification of higher-risk individuals.

Impact of COVID-19 Pandemic on Chronic Obstructive Pulmonary Disease Healthcare Use, Exacerbations, and Mortality: A Population Study.

Rationale: Existing work suggests that patients with chronic obstructive pulmonary disease (pwCOPD) presented less frequently to the emergency department and were less likely to be hospitalized during the coronavirus disease (COVID-19) pandemic, but it is unclear if this was due to improved health and disease management or to increased barriers and/or avoidance of health care. Objectives: The objective of this study was to determine the impact of the pandemic on inpatient and outpatient healthcare use, disease incidence, and mortality rates in pwCOPD. Methods: A retrospective population-based analysis using linked administrative datasets from Alberta, Canada 18 months before and after March 12, 2020 was conducted to measure hospitalization, emergency department and outpatient visits, and COPD outpatient exacerbations during these time periods. Mortality data were also analyzed before versus after the pandemic, taking confirmed COVID-19 infection within 30 days into account. Subgroup analysis based on COPD exacerbation risk stratification was undertaken to determine if healthcare use differed based on exacerbation risk. Finally, sex-based analysis of healthcare use during the pandemic was also completed. Results: Hospitalization or emergency department visits and outpatient treatment for acute exacerbations of COPD dropped, whereas total outpatient COPD visits, including both virtual and in person, increased during the pandemic for pwCOPD. The mortality rate increased even after adjusting for COVID-19-associated deaths. Sex-based subgroup analysis showed a greater drop in acute care use for females, but the rise in mortality was seen for both sexes, with men experiencing a greater rate of mortality than women. Conclusions: Overall, pwCOPD accessed acute care resources less during the pandemic, which may have contributed to a rise in non-COVID-19 all-cause mortality.