Characterizing the burden of biliary tract cancers across 28 hospitals in Ontario, Canada.

BACKGROUND AND AIMS: The incidence of biliary tract cancers (BTC) appears to be increasing worldwide. We analyzed the characteristics of BTC-related hospitalizations under medical services across 28 hospitals in Ontario, Canada. METHODS: This study uses data collected by GEMINI, a hospital research data network. BTC-related hospitalizations from 2015 to 2021 under the Department of Medicine or intensive care unit were captured using the International Classification of Diseases, 10th revision, codes for intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma, and gallbladder cancers. RESULTS: A total of 4596 BTC-related hospitalizations (2720 iCCA, 1269 extrahepatic cholangiocarcinoma, 607 gallbladder cancers) were analyzed. The number of unique patients with BTC-related hospitalizations increased over time. For iCCA-related hospitalizations, the total number of hospitalizations increased (from 385 in 2016 to 420 in 2021, p = .005), the hospital length of stay decreased over the study period (mean 10 days [SD, 12] in 2016 to 9 days [SD, 8] in 2021, p = .04), and the number of in-hospital deaths was stable (from 68 [18%] in 2016 to 55 [13%] in 2021, p = .62). Other outcomes such as 30-day readmissions, medical imaging tests, intensive care unit-specific hospitalizations, and length of stay were stable over time for all cohorts. The cost of hospitalization for the BTC cohort increased from median $8203 CAD (interquartile range, 5063-15,543) in 2017 to $8507 CAD (interquartile range, 5345-14,755) in 2021. CONCLUSIONS: This real-world data analysis showed a rising number of patients with BTC-related hospitalizations and rising number of iCCA-related hospitalizations across 28 hospitals in Ontario between 2015 and 2021.

Young adults with a 22q11.2 microdeletion and the cost of aging with complexity in a population-based context.

PURPOSE: Information about the impact on the adult health care system is limited for complex rare pediatric diseases, despite their increasing collective prevalence that has paralleled advances in clinical care of children. Within a population-based health care context, we examined costs and multimorbidity in adults with an exemplar of contemporary genetic diagnostics. METHODS: We estimated direct health care costs over an 18-year period for adults with molecularly confirmed 22q11.2 microdeletion (cases) and matched controls (total 60,459 person-years of data) by linking the case cohort to health administrative data for the Ontario population (∼15 million people). We used linear regression to compare the relative ratio (RR) of costs and to identify baseline predictors of higher costs. RESULTS: Total adult (age ≥ 18) health care costs were significantly higher for cases compared with population-based (RR 8.5, 95% CI 6.5-11.1) controls, and involved all health care sectors. At study end, when median age was <30 years, case costs were comparable to population-based individuals aged 72 years, likelihood of being within the top 1st percentile of health care costs for the entire (any age) population was significantly greater for cases than controls (odds ratio [OR], for adults 17.90, 95% CI 7.43-43.14), and just 8 (2.19%) cases had a multimorbidity score of zero (vs 1483 (40.63%) controls). The 22q11.2 microdeletion was a significant predictor of higher overall health care costs after adjustment for baseline variables (RR 6.9, 95% CI 4.6-10.5). CONCLUSION: The findings support the possible extension of integrative models of complex care used in pediatrics to adult medicine and the potential value of genetic diagnostics in adult clinical medicine.

An Update to the Kaiser Permanente Inpatient Risk Adjustment Methodology Accurately Predicts In-Hospital Mortality: a Retrospective Cohort Study.

BACKGROUND: Methods to accurately predict the risk of in-hospital mortality are important for applications including quality assessment of healthcare institutions and research. OBJECTIVE: To update and validate the Kaiser Permanente inpatient risk adjustment methodology (KP method) to predict in-hospital mortality, using open-source tools to measure comorbidity and diagnosis groups, and removing troponin which is difficult to standardize across modern clinical assays. DESIGN: Retrospective cohort study using electronic health record data from GEMINI. GEMINI is a research collaborative that collects administrative and clinical data from hospital information systems. PARTICIPANTS: Adult general medicine inpatients at 28 hospitals in Ontario, Canada, between April 2010 and December 2022. MAIN MEASURES: The outcome was in-hospital mortality, modeled by diagnosis group using 56 logistic regressions. We compared models with and without troponin as an input to the laboratory-based acute physiology score. We fit and validated the updated method using internal-external cross-validation at 28 hospitals from April 2015 to December 2022. KEY RESULTS: In 938,103 hospitalizations with 7.2% in-hospital mortality, the updated KP method accurately predicted the risk of mortality. The c-statistic at the median hospital was 0.866 (see Fig. 3) (25th-75th 0.848-0.876, range 0.816-0.927) and calibration was strong for nearly all patients at all hospitals. The 95th percentile absolute difference between predicted and observed probabilities was 0.038 at the median hospital (25th-75th 0.024-0.057, range 0.006-0.118). Model performance was very similar with and without troponin in a subset of 7 hospitals, and performance was similar with and without troponin for patients hospitalized for heart failure and acute myocardial infarction. CONCLUSIONS: An update to the KP method accurately predicted in-hospital mortality for general medicine inpatients in 28 hospitals in Ontario, Canada. This updated method can be implemented in a wider range of settings using common open-source tools.

EMERGE: Evaluating the value of Measuring Random Plasma Glucose Values for Managing Hyperglycemia in the Inpatient Setting.

IMPORTANCE: A diagnosis of diabetes is considered when a patient has hyperglycemia with a random plasma glucose ≥200 mg/dL. However, in the inpatient setting, hyperglycemia is frequently non-specific, especially among patients who are acutely unwell. As a result, patients with transient hyperglycemia may be incorrectly labeled as having diabetes, leading to unnecessary treatment, and potential harm. DESIGN, SETTING, AND PARTICIPANTS: We conducted a multicenter cohort study of patients hospitalized at six hospitals in Ontario, Canada, and identified those with a glucose value ≥200 mg/dL (including standing measurements and randomly drawn). We validated a definition for diabetes using manual chart review that included physician notes, pharmacy notes, home medications, and hemoglobin A1C. Among patients with a glucose value ≥200 mg/dL (11.1 mmol/L), we identified patients without diabetes who received a diabetes medication, and the number who experienced hypoglycemia during the same admission. MAIN OUTCOMES AND MEASURES: To determine the diagnostic value of using random blood glucose to diagnose diabetes in the inpatient setting, and its impact on patient outcomes. RESULTS: We identified 328,786 hospitalizations from hospital between 2010 and 2020. A blood glucose value of ≥200 mg/dL (11.1 mmol/L) had a positive predictive value of 68% and a negative predictive value of 90% for a diagnosis of diabetes. Of the 76,967 patients with an elevated glucose value reported, 16,787 (21.8%) did not have diabetes, and of these, 5375 (32%) received a diabetes medication. Hypoglycemia was frequently reported among the 5375 patients that received a diabetes medication, with 1406 (26.2%) experiencing hypoglycemia and 405 (7.5%) experiencing severe hypoglycemia. CONCLUSIONS AND RELEVANCE: Hyperglycemia in hospital is common but does not necessarily indicate a patient has diabetes. Furthermore, it can lead to treatment with diabetes medications with potential harm. Our findings highlight that clinicians should be cautious when responding to elevated random plasma glucose tests in the inpatient setting.

Physician antimicrobial prescribing and patient outcomes on general medical wards: a multicentre retrospective cohort study.

BACKGROUND: Variability in antimicrobial prescribing may indicate an opportunity for improvement in antimicrobial use. We sought to measure physician-level antimicrobial prescribing in adult general medical wards, assess the contribution of patient-level factors to antimicrobial prescribing and evaluate the association between antimicrobial prescribing and clinical outcomes. METHODS: Using the General Medicine Inpatient Initiative (GEMINI) database, we conducted a retrospective cohort study of physician-level volume and spectrum of antimicrobial prescribing in adult general medical wards in 4 academic teaching hospitals in Toronto, Ontario, between April 2010 and December 2019. We stratified physicians into quartiles by hospital site based on volume of antimicrobial prescribing (days of therapy per 100 patient-days and antimicrobial-free days) and antibacterial spectrum (modified spectrum score). The modified spectrum score assigns a value to each antibacterial agent based on the breadth of coverage. We assessed patient-level differences among physician quartiles using age, sex, Laboratory-based Acute Physiology Score, discharge diagnosis and Charlson Comorbidity Index. We evaluated the association of clinical outcomes (in-hospital 30-day mortality, length of stay, intensive care unit [ICU] transfer and hospital readmission) with antimicrobial volume and spectrum using multilevel modelling. RESULTS: The cohort consisted of 124 physicians responsible for 124 158 hospital admissions. The median physician-level volume of antimicrobial prescribing was 56.1 (interquartile range 51.7-67.5) days of therapy per 100 patient-days. We did not find any differences in baseline patient characteristics by physician prescribing quartile. The difference in mean prescribing between quartile 4 and quartile 1 was 15.8 days of therapy per 100 patient-days (95% confidence interval [CI] 9.6-22.0), representing 30% higher antimicrobial prescribing in the fourth quartile than the first quartile. Patient in-hospital deaths, length of stay, ICU transfer and hospital readmission did not differ by physician quartile. In-hospital mortality was higher among patients cared for by prescribers with higher modified spectrum scores (odds ratio 1.13, 95% CI 1.04-1.24). INTERPRETATION: We found that physician-level variability in antimicrobial prescribing was not associated with differences in patient characteristics or outcomes in academic general medicine wards. These findings provide support for considering the lowest quartile of physician antimicrobial prescribing within each hospital as a target for antimicrobial stewardship.

Diversity among health care leaders in Canada: a cross-sectional study of perceived gender and race.

BACKGROUND: Diverse health care leadership teams may improve health care experiences and outcomes for patients. We sought to explore the race and gender of hospital and health ministry executives in Canada and compare their diversity with that of the populations they serve. METHODS: This cross-sectional study included leaders of Canada's largest hospitals and all provincial and territorial health ministries. We included individuals listed on institutional websites as part of the leadership team if a name and photo were available. Six reviewers coded and analyzed the perceived race and gender of leaders, in duplicate. We compared the proportion of racialized health care leaders with the race demographics of the general population from the 2016 Canadian Census. RESULTS: We included 3056 leaders from 135 institutions, with reviewer concordance on gender for 3022 leaders and on race for 2946 leaders. Reviewers perceived 37 (47.4%) of 78 health ministry leaders as women, and fewer than 5 (< 7%) of 80 as racialized. In Alberta, Saskatchewan, Prince Edward Island and Nova Scotia, provinces with a centralized hospital executive team, reviewers coded 36 (50.0%) of 72 leaders as women and 5 (7.1%) of 70 as racialized. In British Columbia, New Brunswick and Newfoundland and Labrador, provinces with hospital leadership by region, reviewers perceived 120 (56.1%) of 214 leaders as women and 24 (11.5%) of 209 as racialized. In Manitoba, Ontario and Quebec, where leadership teams exist at each hospital, reviewers perceived 1326 (49.9%) of 2658 leaders as women and 243 (9.2%) of 2633 as racialized. We calculated the representation gap between racialized executives and the racialized population as 14.5% for British Columbia, 27.5% for Manitoba, 20.7% for Ontario, 12.4% for Quebec, 7.6% for New Brunswick, 7.3% for Prince Edward Island and 11.6% for Newfoundland and Labrador. INTERPRETATION: In a study of more than 3000 health care leaders in Canada, gender parity was present, but racialized executives were substantially under-represented. This work should prompt health care institutions to increase racial diversity in leadership.

The risk of death or unplanned readmission after discharge from a COVID-19 hospitalization in Alberta and Ontario.

BACKGROUND: The frequency of readmissions after COVID-19 hospitalizations is uncertain, as is whether current readmission prediction equations are useful for discharge risk stratification of COVID-19 survivors or for comparing among hospitals. We sought to determine the frequency and predictors of death or unplanned readmission after a COVID-19 hospital discharge. METHODS: We conducted a retrospective cohort study of all adults (≥ 18 yr) who were discharged alive from hospital after a nonpsychiatric, nonobstetric, acute care admission for COVID-19 between Jan. 1, 2020, and Sept. 30, 2021, in Alberta and Ontario. RESULTS: Of 843 737 individuals who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction during the study period, 46 412 (5.5%) were adults admitted to hospital within 14 days of their positive test. Of these, 8496 died in hospital and 34 846 were discharged alive (30 336 discharged after an index admission of ≤ 30 d and 4510 discharged after an admission > 30 d). One in 9 discharged patients died or were readmitted within 30 days after discharge (3173 [10.5%] of those with stay ≤ 30 d and 579 [12.8%] of those with stay > 30 d). The LACE score (length of stay, acuity, Charlson Comorbidity Index and number of emergency visits in previous 6 months) for predicting urgent readmission or death within 30 days had a c-statistic of 0.60 in Alberta and 0.61 in Ontario; inclusion of sex, discharge locale, deprivation index and teaching hospital status in the model improved the c-statistic to 0.73. INTERPRETATION: Death or readmission after discharge from a COVID-19 hospitalization is common and had a similar frequency in Alberta and Ontario. Risk stratification and interinstitutional comparisons of outcomes after hospital admission for COVID-19 should include sex, discharge locale and socioeconomic measures, in addition to the LACE variables.

Outcomes in patients with and without disability admitted to hospital with COVID-19: a retrospective cohort study.

BACKGROUND: Disability-related considerations have largely been absent from the COVID-19 response, despite evidence that people with disabilities are at elevated risk for acquiring COVID-19. We evaluated clinical outcomes in patients who were admitted to hospital with COVID-19 with a disability compared with patients without a disability. METHODS: We conducted a retrospective cohort study that included adults with COVID-19 who were admitted to hospital and discharged between Jan. 1, 2020, and Nov. 30, 2020, at 7 hospitals in Ontario, Canada. We compared in-hospital death, admission to the intensive care unit (ICU), hospital length of stay and unplanned 30-day readmission among patients with and without a physical disability, hearing or vision impairment, traumatic brain injury, or intellectual or developmental disability, overall and stratified by age (≤ 64 and ≥ 65 yr) using multivariable regression, controlling for sex, residence in a long-term care facility and comorbidity. RESULTS: Among 1279 admissions to hospital for COVID-19, 22.3% had a disability. We found that patients with a disability were more likely to die than those without a disability (28.1% v. 17.6%), had longer hospital stays (median 13.9 v. 7.8 d) and more readmissions (17.6% v. 7.9%), but had lower ICU admission rates (22.5% v. 28.3%). After adjustment, there were no statistically significant differences between those with and without disabilities for in-hospital death or admission to ICU. After adjustment, patients with a disability had longer hospital stays (rate ratio 1.36, 95% confidence interval [CI] 1.19-1.56) and greater risk of readmission (relative risk 1.77, 95% CI 1.14-2.75). In age-stratified analyses, we observed longer hospital stays among patients with a disability than in those without, in both younger and older subgroups; readmission risk was driven by younger patients with a disability. INTERPRETATION: Patients with a disability who were admitted to hospital with COVID-19 had longer stays and elevated readmission risk than those without disabilities. Disability-related needs should be addressed to support these patients in hospital and after discharge.

Predictors of ICU admission associated with gastrointestinal endoscopy in medical inpatients: A retrospective cohort study.

BACKGROUND AND AIM: Gastrointestinal (GI) endoscopic procedures are commonly performed in medical inpatients. Limited prior research has examined factors associated with intensive care unit (ICU) admission after GI endoscopy in medical inpatients. METHODS: This retrospective cohort study was conducted using routinely-collected clinical and administrative data from all general medicine hospitalizations at five academic hospitals in Toronto, Canada between 2010 and 2020. We describe ICU admission and death within 48 h of GI endoscopy in medical inpatients. We examined adjusted associations of patient and procedural factors with ICU admission or death using multivariable logistic regression. RESULTS: Among 18 290 medical inpatients who underwent endoscopy, 900 (4.9%) required ICU admission or died within 48 h of endoscopy. Following risk adjustment, ICU admission or death were associated with the following procedural factors: endoscopy on the day of hospital admission (aOR 3.16 [2.38-4.21]) or 1 day after admission (aOR 1.92 [1.51-2.44]) and esophagogastroduodenoscopy (EGD) procedures; and the following patient factors: Charlson comorbidity index of two (aOR 1.38 [1.05-1.81]) or three or greater (aOR 1.84 [1.47-2.29]), older age, male sex, lower hemoglobin prior to endoscopy, increased creatinine prior to endoscopy, an admitting diagnosis of liver disease and certain medications (antiplatelet agents and corticosteroids). CONCLUSIONS: ICU admission or death after endoscopy was associated with procedural factors such as EGD and timing of endoscopy, and patient factors indicative of acute illness and greater comorbidity. These findings can contribute to improved triage and monitoring for patients requiring inpatient endoscopy.

Outcomes for upper gastrointestinal bleeding during the first wave of the COVID-19 pandemic in the Toronto area.

BACKGROUND AND AIM: Changes to endoscopy service availability during the COVID-19 pandemic may have affected management of upper gastrointestinal bleeding (UGIB). The aim of this study was to describe the impact of the pandemic on UGIB outcomes in the Toronto area in Canada. METHODS: We described all adults admitted to general medicine wards or intensive care units at six hospitals in Toronto and Mississauga, Canada, with UGIB during the first wave of the COVID-19 pandemic (March 1 to June 30, 2020) and compared them with a historical cohort (March 1 to June 30, 2018 and 2019). We compared clinical outcomes (in-hospital mortality, length of stay, 30-day readmission, intensive care utilization, receipt of endoscopy, persistent bleeding, receipt of second endoscopy, and need for angiographic or surgical intervention) using multivariable regression models, controlling for demographics, comorbidities, and severity of clinical presentation. RESULTS: There were 82.5 and 215.5 admissions per month for UGIB during the COVID-19 and control periods, respectively. There were no baseline differences between groups for demographic characteristics, comorbidities, or severity of bleeding. Patients in the COVID-19 group did not have significantly different unadjusted (3.9% vs 4.2%, P = 0.983) or adjusted mortality (adjusted odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.25-1.48, P = 0.322). Patients in COVID-19 group were less likely to receive endoscopy for UGIB in the unadjusted (61.8% vs 71.0%, P = 0.003) and adjusted (adjusted OR = 0.64, 95% CI = 0.49-0.84, P < 0.01) models. There were no differences between groups for other secondary outcomes. CONCLUSIONS: While patients admitted for UGIB during the first wave of the pandemic were less likely to receive endoscopy, this had no impact on mortality or any secondary outcomes.

Using machine learning to predict severe hypoglycaemia in hospital.

AIM: To predict the risk of hypoglycaemia using machine-learning techniques in hospitalized patients. METHODS: We conducted a retrospective cohort study of patients hospitalized under general internal medicine (GIM) and cardiovascular surgery (CV) at a tertiary care teaching hospital in Toronto, Ontario. Three models were generated using supervised machine learning: least absolute shrinkage and selection operator (LASSO) logistic regression; gradient-boosted trees; and a recurrent neural network. Each model included baseline patient data and time-varying data. Natural-language processing was used to incorporate text data from physician and nursing notes. RESULTS: We included 8492 GIM admissions and 8044 CV admissions. Hypoglycaemia occurred in 16% of GIM admissions and 13% of CV admissions. The area under the curve for the models in the held-out validation set was approximately 0.80 on the GIM ward and 0.82 on the CV ward. When the threshold for hypoglycaemia was lowered to 2.9 mmol/L (52 mg/dL), similar results were observed. Among the patients at the highest decile of risk, the positive predictive value was approximately 50% and the sensitivity was 99%. CONCLUSION: Machine-learning approaches can accurately identify patients at high risk of hypoglycaemia in hospital. Future work will involve evaluating whether implementing this model with targeted clinical interventions can improve clinical outcomes.

Characteristics and outcomes of hospital admissions for COVID-19 and influenza in the Toronto area.

BACKGROUND: Patient characteristics, clinical care, resource use and outcomes associated with admission to hospital for coronavirus disease 2019 (COVID-19) in Canada are not well described. METHODS: We described all adults with COVID-19 or influenza discharged from inpatient medical services and medical-surgical intensive care units (ICUs) between Nov. 1, 2019, and June 30, 2020, at 7 hospitals in Toronto and Mississauga, Ontario. We compared patient outcomes using multivariable regression models, controlling for patient sociodemographic factors and comorbidity level. We validated the accuracy of 7 externally developed risk scores to predict mortality among patients with COVID-19. RESULTS: There were 1027 hospital admissions with COVID-19 (median age 65 yr, 59.1% male) and 783 with influenza (median age 68 yr, 50.8% male). Patients younger than 50 years accounted for 21.2% of all admissions for COVID-19 and 24.0% of ICU admissions. Compared with influenza, patients with COVID-19 had significantly greater in-hospital mortality (unadjusted 19.9% v. 6.1%, adjusted relative risk [RR] 3.46, 95% confidence interval [CI] 2.56-4.68), ICU use (unadjusted 26.4% v. 18.0%, adjusted RR 1.50, 95% CI 1.25-1.80) and hospital length of stay (unadjusted median 8.7 d v. 4.8 d, adjusted rate ratio 1.45, 95% CI 1.25-1.69). Thirty-day readmission was not significantly different (unadjusted 9.3% v. 9.6%, adjusted RR 0.98, 95% CI 0.70-1.39). Three points-based risk scores for predicting in-hospital mortality showed good discrimination (area under the receiver operating characteristic curve [AUC] ranging from 0.72 to 0.81) and calibration. INTERPRETATION: During the first wave of the pandemic, admission to hospital for COVID-19 was associated with significantly greater mortality, ICU use and hospital length of stay than influenza. Simple risk scores can predict in-hospital mortality in patients with COVID-19 with good accuracy.

Prediction of personal protective equipment use in hospitals during COVID-19.

Demand for Personal Protective Equipment (PPE) such as surgical masks, gloves, and gowns has increased significantly since the onset of the COVID-19 pandemic. In hospital settings, both medical staff and patients are required to wear PPE. As these facilities resume regular operations, staff will be required to wear PPE at all times while additional PPE will be mandated during medical procedures. This will put increased pressure on hospitals which have had problems predicting PPE usage and sourcing its supply. To meet this challenge, we propose an approach to predict demand for PPE. Specifically, we model the admission of patients to a medical department using multiple independent [Formula: see text] queues. Each queue represents a class of patients with similar treatment plans and hospital length-of-stay. By estimating the total workload of each class, we derive closed-form estimates for the expected amount of PPE required over a specified time horizon using current PPE guidelines. We apply our approach to a data set of 22,039 patients admitted to the general internal medicine department at St. Michael's hospital in Toronto, Canada from April 2010 to November 2019. We find that gloves and surgical masks represent approximately 90% of predicted PPE usage. We also find that while demand for gloves is driven entirely by patient-practitioner interactions, 86% of the predicted demand for surgical masks can be attributed to the requirement that medical practitioners will need to wear them when not interacting with patients.

Insecurity, polio vaccination rates, and polio incidence in northwest Pakistan.

Pakistan is one of three countries in which endemic transmission of poliovirus has never been stopped. Insecurity is often cited but poorly studied as a barrier to eradicating polio. We analyzed routinely collected health data from 32 districts of northwest Pakistan and constructed an index of insecurity based on journalistic reports of the monthly number of deaths and injuries resulting from conflict-related security incidents. The primary outcomes were the monthly incidence of paralytic polio cases within each district between 2007 and 2014 and the polio vaccination percentage from 666 district-level vaccination campaigns between 2007 and 2009, targeting ∼5.7 million children. Multilevel Poisson regression controlling for time and district fixed effects was used to model the association between insecurity, vaccinator access, vaccination rates, and polio incidence. The number of children inaccessible to vaccinators was 19.7% greater (95% CI: 19.2-20.2%), and vaccination rates were 5.3% lower (95% CI: 5.2-5.3%) in "high-insecurity" campaigns compared with "secure" campaigns. The unadjusted mean vaccination rate was 96.3% (SD = 8.6) in secure campaigns and 88.3% (SD = 19.2) in high-insecurity campaigns. Polio incidence was 73.0% greater (95% CI: 30-131%) during high-insecurity months (unadjusted mean = 0.13 cases per million people, SD = 0.71) compared with secure months (unadjusted mean = 1.23 cases per million people, SD = 4.28). Thus, insecurity was associated with reduced vaccinator access, reduced polio vaccination, and increased polio incidence in northwest Pakistan. These findings demonstrate that insecurity is an important obstacle to global polio eradication.

A genetic model for multimorbidity in young adults.

PURPOSE: Multimorbidity is increasing in younger adults but is understudied in this population. We used 22q11.2 deletion syndrome (22q11.2DS) as a genetic model to investigate multimorbidity in young to middle-aged adults. METHODS: Using the Anatomical Therapeutic Chemical (ATC) Classification System and setting five or more concurrent prescription medications as a proxy for multimorbidity, we compared data on 264 adults with 22q11.2DS (median age 27.8, range 17.3-68.3 years) with that for a community-based Canadian general population sample (n = 25,287). We used logistic regression to examine possible predictors of multimorbidity in 22q11.2DS. RESULTS: Multimorbidity in 22q11.2DS in the 25-44 year age group (34.7%) was significantly more prevalent than in the general population, both for the same age group (2.9%, prevalence ratio [PR] = 11.9, 95% CI 8.4-17.1) and compared with those aged 45-64 years (16.4%, PR = 2.1, 95% CI 1.6-2.7). Neuropsychiatric and endocrinological medication classes predominated. Within 22q11.2DS, older age and psychotic illness, but not sex, major congenital heart disease, or intellectual disability, were significant predictors of multimorbidity. CONCLUSION: The results indicate that adults with 22q11.2DS have a significant burden of illness with levels of multimorbidity comparable with those of the general population several decades older. In younger adults with multimorbidity, certain disease patterns may help identify genetic disorders in "big data."

Preprints: a Timely Counterbalance for Big Data-Driven Research.

Big data promises to spark new discoveries but may also distort clinical research. Large datasets that permit numerous analyses could increase the number of spurious findings and threaten the reproducibility and validity of clinical research. The publication of unreproducible research is incentivized by a scientific culture that rewards novelty over rigor. Introducing preprint publication to clinical research could change the culture. The first clinical preprint platform, medRxiv, allows researchers to publish working papers in advance of peer-review to more easily share preliminary findings. Preprint publishing aims to be fast and frictionless, which fundamentally changes the incentive structure of academic publishing. Preprints offer a relatively weak reward (a preprint publication) for substantially less effort than peer-review publication. By reducing barriers to publication, preprints may help encourage scientists to publish null findings, which could mitigate publication bias. By enabling scientists to share preliminary work and publish evolving versions of manuscripts, preprints may also facilitate "workshopping" of ideas and detailed methodological review. This would better reflect the iterative nature of observational research than peer-reviewed publications, which immutably document the "final" results of a study. Preprint platforms are a timely innovation that may buffer the undesired effects of big data on clinical research.

The economic burden of inpatient diabetic foot ulcers in Toronto, Canada.

OBJECTIVE: Diabetic foot ulcer, which often leads to lower limb amputation, is a devastating complication of diabetes that is a major burden on patients and the healthcare system. The main objective of this study is to determine the economic burden of diabetic foot ulcer-related care. METHODS: We conducted a multicenter study of all diabetic foot ulcer patients admitted to general internal medicine wards at seven hospitals in the Greater Toronto Area, Canada from 2010 to 2015, using the GEMINI database. We compared the mean costs of care per patient for diabetic foot ulcer-related admissions, admissions for other diabetes-related complications, and admissions for the top five most costly general internal medicine conditions, using the Ontario Case Costing Initiative. Regression models were used to determine adjusted estimates of cost per patient. Propensity-score matched analyses were performed as sensitivity analyses. RESULTS: Our study cohort comprised of 557 diabetic foot ulcer patients; 2939 non-diabetic foot ulcer diabetes patients; and 23,656 patients with the top 5 most costly general internal medicine conditions. Diabetic foot ulcer admissions incurred the highest mean cost per patient ($22,754) when compared to admissions with non-diabetic foot ulcer diabetes ($8,350) and the top five most costly conditions ($10,169). Using adjusted linear regression, diabetic foot ulcer admissions demonstrated a 49.6% greater mean cost of care than non-diabetic foot ulcer-related diabetes admissions (95% CI 1.14-1.58), and a 25.6% greater mean cost than the top five most costly conditions (95% CI 1.17-1.34). Propensity-scored matched analyses confirmed these results. CONCLUSION: Diabetic foot ulcer patients incur significantly higher costs of care when compared to admissions with non-diabetic foot ulcer-related diabetes patients, and the top five most costly general internal medicine conditions.

Empiric Antibiotic Treatment Thresholds for Serious Bacterial Infections: A Scenario-based Survey Study.

BACKGROUND: Physicians face competing demands of maximizing pathogen coverage while minimizing unnecessary use of broad-spectrum antibiotics when managing sepsis. We sought to identify physicians' perceived likelihood of coverage achieved by their usual empiric antibiotic regimen, along with minimum thresholds of coverage they would be willing to accept when managing these patients. METHODS: We conducted a scenario-based survey of internal medicine physicians from across Canada using a 2 × 2 factorial design, varied by infection source (undifferentiated vs genitourinary) and severity (mild vs severe) denoted by the Quick Sequential Organ Failure Assessment (qSOFA) score. For each scenario, participants selected their preferred empiric antibiotic regimen, estimated the likelihood of coverage achieved by that regimen, and considered their minimum threshold of coverage. RESULTS: We had 238 respondents: 87 (36.6%) residents and 151 attending physicians (63.4%). The perceived likelihood of antibiotic coverage and minimum thresholds of coverage (with interquartile range) for each scenario were as follows: (1) severe undifferentiated, 90% (89.5%-95.0%) and 90% (80%-95%), respectively; (2) mild undifferentiated, 89% (80%-95%) and 80% (70%-89.5%); (3) severe genitourinary, 91% (87.3%-95.0%) and 90% (80.0%-90.0%); and (4) mild genitourinary, 90% (81.8%-91.3%) and 80% (71.8%-90%). Illness severity and infectious disease specialty predicted higher thresholds of coverage whereas less clinical experience and lower self-reported prescribing intensity predicted lower thresholds of coverage. CONCLUSIONS: Pathogen coverage of 80% and 90% are physician-acceptable thresholds for managing patients with mild and severe sepsis from bacterial infections. These data may inform clinical guidelines and decision-support tools to improve empiric antibiotic prescribing.

Value of routine echocardiography in the management of stroke.

BACKGROUND: Transthoracic echocardiography is routinely performed in patients with stroke or transient ischemic attack (TIA) to help plan secondary stroke management, but recent data evaluating its usefulness in this context are lacking. We sought to evaluate the value of echocardiography for identifying clinically actionable findings for secondary stroke prevention. METHODS: We conducted a multicentre cohort study of patients admitted to hospital with stroke or TIA between 2010 and 2015 at 2 academic hospitals in Toronto, Ontario, Canada. Clinically actionable echocardiographic findings for secondary stroke prevention included cardiac thrombus, patent foramen ovale, atrial myxoma or valvular vegetation. We identified patient characteristics associated with clinically actionable findings using logistic regression. RESULTS: Of the 1862 patients with stroke or TIA we identified, 1272 (68%) had at least 1 echocardiogram. Nearly all echocardiograms were transthoracic; 1097 (86%) were normal, 1 (0.08%) had an atrial myxoma, 2 (0.2%) had a valvular vegetation, 11 (0.9%) had a cardiac thrombus and 66 (5.2%) had a PFO. Patent foramen ovale was less likely among patients older than 60 years (adjusted odds ratio [OR] 0.34, 95% confidence interval [CI] 0.20-0.57), with prior stroke or TIA (adjusted OR 0.31, 95% CI 0.09-0.76) or with dyslipidemia (adjusted OR 0.39, 95% CI 0.15-0.84). Among the 130 patients with cryptogenic stroke who had an echocardiogram (n = 110), a PFO was detected in 19 (17%) on transthoracic echocardiogram. INTERPRETATION: Most patients with stroke or TIA had a normal echocardiogram, with few having clinically actionable findings for secondary stroke prevention. Clinically actionable findings, specifically PFO, were more common in patients with cryptogenic stroke.

Fixed-dose combination antihypertensive medications, adherence, and clinical outcomes: A population-based retrospective cohort study.

BACKGROUND: The majority of people with hypertension require more than one medication to achieve blood pressure control. Many patients are prescribed multipill antihypertensive regimens rather than single-pill fixed-dose combination (FDC) treatment. Although FDC use may improve medication adherence, the impact on patient outcomes is unclear. We compared clinical outcomes and medication adherence with FDC therapy versus multipill combination therapy in a real-world setting using linked clinical and administrative databases. METHODS AND FINDINGS: We conducted a population-based retrospective cohort study of 13,350 individuals 66 years and older in Ontario, Canada with up to 5 years of follow-up. We included individuals who were newly initiated on one angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II-receptor blocker (ARB) plus one thiazide diuretic. High-dimensional propensity score matching was used to compare individuals receiving FDC versus multipill therapy. The primary outcome was a composite of death or hospitalization for acute myocardial infarction (AMI), heart failure, or stroke. We conducted 2 analyses to examine the association between adherence and patient outcomes. First, we performed an on-treatment analysis to determine whether outcomes differed between groups while patients were on treatment, censoring patients when they first discontinued treatment, defined as not receiving medications within 150% of the previous days' supply. Second, we conducted an intention-to-treat analysis that followed individuals allowing for breaks in treatment to quantify the difference in drug adherence between groups and assess its impact on clinical outcomes. As expected, there was no significant difference in the primary outcome between groups in the on-treatment analysis (HR 1.06, 95% CI 0.86-1.31, P = 0.60). In the intention-to-treat analysis, the proportion of total follow-up days covered with medications was significantly greater in the FDC group (70%; IQR 19-98) than in the multipill group (42%, IQR 11-91, P < 0.01), and the primary outcome was less frequent in FDC recipients (3.4 versus 3.9 events per 100 person-years; HR 0.89, 95% CI 0.81-0.97, P < 0.01). The main limitations of this study were the lack of data regarding cause of death and blood pressure measurements and the possibility of residual confounding. CONCLUSIONS: Among older adults initiating combination antihypertensive treatment, FDC therapy was associated with a significantly lower risk of composite clinical outcomes, which may be related to better medication adherence.