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A range of first-line similarly effective medications ranging in price are recommended for treating uncomplicated hypertension. Considering drug costs alone, thiazides and thiazide-like diuretics are the most cost-efficient option. We determined incident prescribing of thiazides for newly diagnosed hypertension as first-line treatment in Alberta, factors that predicted receiving thiazides vs more costly medications, and how much could be saved if more patients were prescribed thiazides.Using a retrospective cohort design, factors predicting receiving thiazides vs other agents were determined using mixed effects logistic regression. Cost savings were simulated by shifting patients from other antihypertensive medications to thiazides and calculating the difference.Within our cohort of 89,548 adults, only 12% received thiazides as first-line treatment whereas 44% received angiotensin converting enzyme inhibitors, 17% received angiotensin receptor blockers, 16% received calcium channel blockers, and 10% received β-blockers. Antihypertensive medications were typically prescribed by office-based, general practitioners (88%). Being male and receiving a prescription from a physician with ≥ 20 years of practice and a high clinical workload were associated with increased odds of receiving nonthiazides. In the extreme case that all patients received thiazides as their first prescription, spending would have been reduced by a maximum of 95% (CAD$1.8 million).Only 12% of Albertan adults with incident, uncomplicated hypertension were prescribed thiazides as first-line treatment. With the opportunity for drug cost savings, future research should evaluate the risk of adverse events and side effects across the drug classes and whether the costs associated with managing those risks could offset the savings achieved through increased thiazide use.De nombreux médicaments tous aussi efficaces les uns que les autres, mais de prix variable, sont recommandés pour le traitement de première intention de l’hypertension non compliquée. Si l’on tient compte du coût du médicament seulement, les thiazides et les diurétiques apparentés aux thiazides sont les options les plus économiques. Nous avons évalué le taux de prescription d’un thiazide pour le traitement de première intention de l’hypertension nouvellement diagnostiquée en Alberta, les facteurs de prédiction de la prescription d’un thiazide plutôt que d’un autre médicament plus coûteux, ainsi que les économies qui pourraient être réalisées si on prescrivait un thiazide à un plus grand nombre de patients.Dans le cadre de notre étude de cohorte rétrospective, nous avons déterminé les facteurs de prédiction de la prescription d’un thiazide plutôt que d’un autre agent à l’aide d’une régression logistique à effets mixtes. Nous avons simulé les économies qui pourraient être réalisées en faisant passer à un thiazide les patients à qui un autre médicament antihypertenseur a été prescrit et en calculant la différence.Dans notre cohorte de 89 548 adultes, seulement 12 % des patients ont reçu un thiazide en première intention; 44 % ont reçu un inhibiteur de l’enzyme de conversion de l’angiotensine; 17 %, un antagoniste des récepteurs de l’angiotensine; 16 %, un inhibiteur calcique; et 10 %, des bêtabloquants. Les agents antihypertenseurs sont généralement prescrits par des omnipraticiens en cabinet (88 %). Le fait d’être un homme et le fait d’obtenir une prescription auprès d’un médecin exerçant depuis au moins 20 ans et ayant une lourde charge de travail clinique étaient associés à une probabilité supérieure de recevoir un agent autre qu’un thiazide. Dans le cas extrême où tous les patients se verraient prescrire un thiazide en première intention, la réduction des dépenses pourrait atteindre 95 % (soit 1,8 million de dollars canadiens).En Alberta, un thiazide a été prescrit en première intention à seulement 12 % des adultes venant de recevoir un diagnostic d’hypertension non compliquée. Compte tenu des économies qui pourraient être réalisées si un thiazide était prescrit dans ce contexte, il conviendrait d’effectuer des recherches plus poussées pour évaluer le risque de manifestations indésirables et d’effets secondaires associé aux différentes classes de médicaments, et pour déterminer si les coûts liés à la prise en charge de ce risque annuleraient les économies réalisées en augmentant le recours aux thiazides.

This protocol outlines the planned methodology for a systematic review and meta-analysis. The primary objective of the review is to identify all-cause readmission rates for individuals hospitalized for an upper GI bleed (UGIB). Secondary objectives will include GI bleed-specific readmission rates, mortality (all-cause and GI bleed-specific), readmission diagnosis, and length of stay on readmission visit. High-risk subgroups will also be explored including age, sex, type of GI bleed (e.g., variceal or not), anti-coagulation status, and comorbidity status. Through this review, the research team aims to describe an important quality indicator, which has implications for both patient safety post-discharge after an UGIB and healthcare resource utilization.

Background: Hospital-acquired Clostridioides difficile infection (HA-CDI) rates are highly variable over time, posing problems for research assessing interventions that might improve rates. By understanding seasonality in HA-CDI rates and the impacts that other factors such as influenza admissions might have on these rates, we can account for them when establishing the relationship between interventions and infection rates. We assessed whether there were seasonal trends in HA-CDI and whether they could be accounted for by influenza rates. Methods: We assessed HA-CDI rates per 10,000 patient days, and the rate of hospitalized patients with influenza per 1,000 admissions in 4 acute-care facilities (n = 2,490 beds) in Calgary, Alberta, from January 2016 to December 2018. We used 4 statistical approaches in R (version 3.5.1 software): (1) autoregressive integrated moving average (ARIMA) to assess dependencies and trends in each of the monthly HA-CDI and influenza series; (2) cross correlation to assess dependencies between the HA-CDI and influenza series lagged over time; (3) Poisson harmonic regression models (with sine and cosine components) to assess the seasonality of the rates; and (4) Poisson regression to determine whether influenza rates accounted for seasonality in the HA-CDI rates. Results: Conventional ARIMA approaches did not detect seasonality in the HA-CDI rates, but we found strong seasonality in the influenza rates. A cross-correlation analysis revealed evidence of correlation between the series at a lag of zero (R = 0.41; 95% CI, 0.10–0.65) and provided an indication of a seasonal relationship between the series (Fig. 1). Poisson regression suggested that influenza rates predicted CDI rates (P < .01). Using harmonic regression, there was evidence of seasonality in HA-CDI rates (2 [2 df] = 6.62; P < .05) and influenza rates (2 [2 df] = 1,796.6; P < .001). In a Poisson model of HA-CDI rates with both the harmonic components and influenza admission rates, the harmonic components were no longer predictive of HA-CDI rates. Conclusions: Harmonic regression provided a sensitive means of identifying seasonality in HA-CDI rates, but the seasonality effect was accounted for by influenza admission rates. The relationship between HA-CDI and influenza rates is likely mediated by antibiotic prescriptions, which needs to be assessed. To improve precision and reduce bias, research on interventions to reduce HA-CDI rates should assess historic seasonality in HA-CDI rates and should account for influenza admissions.Funding: NoneDisclosures: None

Background:Clostridioides difficile infection (CDI) is the most common cause of infectious diarrhea in hospitalized patients. Probiotics have been studied as a measure to prevent CDI. Timely probiotic administration to at-risk patients receiving systemic antimicrobials presents significant challenges. We sought to determine optimal implementation methods to administer probiotics to all adult inpatients aged 55 years receiving a course of systemic antimicrobials across an entire health region. Methods: Using a randomized stepped-wedge design across 4 acute-care hospitals (n = 2,490 beds), the probiotic Bio-K+ was prescribed daily to patients receiving systemic antimicrobials and was continued for 5 days after antimicrobial discontinuation. Focus groups and interviews were conducted to identify barriers, and the implementation strategy was adapted to address the key identified barriers. The implementation strategy included clinical decision support involving a linked flag on antibiotic ordering and a 1-click order entry within the electronic medical record (EMR), provider and patient education (written/videos/in-person), and local site champions. Protocol adherence was measured by tracking the number of patients on therapeutic antimicrobials that received BioK+ based on the bedside nursing EMR medication administration records. Adherence rates were sorted by hospital and unit in 48- and 72-hour intervals with recording of percentile distribution of time (days) to receipt of the first antimicrobial. Results: In total, 340 education sessions with >1,800 key stakeholders occurred before and during implementation across the 4 involved hospitals. The overall adherence of probiotic ordering for wards with antimicrobial orders was 78% and 80% at 48 and 72 hours, respectively over 72 patient months. Individual hospital adherence rates varied between 77% and 80% at 48 hours and between 79% and 83% at 72 hours. Of 246,144 scheduled probiotic orders, 94% were administered at the bedside within a median of 0.61 days (75th percentile, 0.88), 0.47 days (75th percentile, 0.86), 0.71 days (75th percentile, 0.92) and 0.67 days (75th percentile, 0.93), respectively, at the 4 sites after receipt of first antimicrobial. The key themes from the focus groups emphasized the usefulness of the linked flag alert for probiotics on antibiotic ordering, the ease of the EMR 1-click order entry, and the importance of the education sessions. Conclusions: Electronic clinical decision support, education, and local champion support achieved a high implementation rate consistent across all sites. Use of a 1-click order entry in the EMR was considered a key component of the success of the implementation and should be considered for any implementation strategy for a stewardship initiative. Achieving high prescribing adherence allows more precision in evaluating the effectiveness of the probiotic strategy.Funding: Partnerships for Research and Innovation in the Health System, Alberta Innovates/Health Solutions Funding: AwardDisclosures: None

Background: Research has shown that inpatients may not accurately report interacting with a pharmacist. Objective: To determine accuracy of patients’ recollection of meeting with a pharmacist at 2 acute care teaching hospitals in Edmonton, Alberta, Canada. Methods: Retrospective review of 391 surveyed patients discharged from April 2013 to March 2014. Responses to meeting a pharmacist (yes/no) were compared with 2 reference standards: pharmacist documentation in patient charts and pharmacist clinical workload data. Sensitivity, specificity, positive predictive, and negative predictive values were calculated. Results: One hundred ninety-five (49.9%) respondents reported meeting with a pharmacist. Of these, 71 (36.4%) had corresponding pharmacist chart documentation. Of the 196 respondents who reported not speaking with a pharmacist, 73 (37.2%) had documentation present. Compared with patient charts, sensitivity and specificity were 49.3% and 49.8%, respectively. Positive and negative predictive values were 36.4% and 62.8%, respectively. Similar results were seen in comparison with the workload data. Conclusions: Patients often inaccurately reported meeting with a pharmacist in the acute care setting. The results are useful for pharmacist training, patient education, and for refinement of the current survey question.

Proper assessment of antimicrobial use in pediatric populations is challenging due to the common metric unit, the defined daily dose. In this study, the authors quantified pediatric antimicrobial use using days of therapy per 100 patient days, a value that is numerically comparable with adult antibiotic use. An overview of systemic antibacterial and antifungal use according to ward at the Alberta Children’s Hospital (Calgary, Alberta) is also provided. The authors suggest that their data act as a benchmark for future reference in other antimicrobial studies and pediatric institutions., BACKGROUND: Antimicrobial resistance is a concern that is challenging the ability to treat common infections. Surveillance of antimicrobial use in pediatric acute care institutions is complicated because the common metric unit, the defined daily dose, is problematic for this population. OBJECTIVE: During a four-year period in which no specific antimicrobial stewardship initiatives were conducted, pediatric antimicrobial use was quantified using days of therapy (DOT) per 100 patient days (PD) (DOT/100 PD) at the Alberta Children’s Hospital (Calgary, Alberta) for benchmarking purposes. METHODS: Drug use data for systemic antimicrobials administered on wards at the Alberta Children’s Hospital were collected from electronic medication administration records. DOT were calculated and rates were determined using 100 PD as the denominator. Changes over the surveillance period and subgroup proportions were represented graphically and assessed using linear regression. RESULTS: Total antimicrobial use decreased from 93.6 DOT/100 PD to 75.7 DOT/100 PD (19.1%) over the 2010/2011 through to the 2013/2014 fiscal years. During this period, a 20.0% increase in PD and an essentially stable absolute count of DOT (2.9% decrease) were observed. Overall, antimicrobial use was highest in the pediatric intensive care and oncology units. DISCUSSION: The exact changes in prescribing patterns that led to the observed reduction in DOT/100 PD with associated increased PD are unclear, but may be a topic for future investigations. CONCLUSION: Antimicrobial use data from a Canadian acute care pediatric hospital reported in DOT/100 PD were compiled for a four-year time period. These data may be useful for benchmarking purposes.

Background & Aims Although there have been meta-analyses of the effects of exercise-only prehabilitation on patients undergoing colorectal surgery, little is known about the effects of nutrition-only (oral nutritional supplements with and without counseling) and multimodal (oral nutritional supplements with and without counseling and with exercise) prehabilitation on clinical outcomes and patient function after surgery. We performed a systemic review and meta-analysis to determine the individual and combined effects of nutrition-only and multimodal prehabilitation compared with no prehabilitation (control) on outcomes of patients undergoing colorectal resection. Methods We searched Medline, EMBASE, CINAHL, CENTRAL, and ProQuest for cohort and randomized controlled studies of adults awaiting colorectal surgery who received at least 7 days of nutrition prehabilitation with or without exercise. We performed a random-effects meta-analysis to estimate the pooled risk ratio for categorical data and the weighted mean difference for continuous variables. The primary outcome was length of hospital stay; the secondary outcome was recovery of functional capacity based on results of a 6-minute walk test. Results We identified 9 studies (5 randomized controlled studies and 4 cohort studies) composed of 914 patients undergoing colorectal surgery (438 received prehabilitation and 476 served as controls). Receipt of any prehabilitation significantly decreased days spent in the hospital compared with controls (weighted mean difference of length of hospital stay = −2.2 days; 95% confidence interval = −3.5 to −0.9). Only 3 studies reported on functional outcomes but could not be pooled owing to methodologic heterogeneity. In the individual studies, multimodal prehabilitation significantly improved results of the 6-minute walk test at 4 and 8 weeks after surgery compared with standard Enhanced Recovery Pathway care and at 8 weeks compared with standard Enhanced Recovery Pathway care with added rehabilitation. The 4 observational studies had a high risk of bias. Conclusions In a systematic review and meta-analysis, we found that nutritional prehabilitation alone or combined with an exercise program significantly decreased length of hospital stay by 2 days in patients undergoing colorectal surgery. There is some evidence that multimodal prehabilitation accelerated the return to presurgical functional capacity.

Nasal-swab screening for methicillin-resistantTo describe the diagnostic characteristics of nasal-swab screening in predicting MRSA infections in hospitalized patients receiving empiric treatment with IV vancomycin.A retrospective observational chart review was conducted for newly admitted adult patients of the Peter Lougheed Centre in Calgary, Alberta, who were treated empirically with IV vancomycin from January to October 2015 and who underwent nasal-swab screening for MRSA. The diagnostic characteristics of nasal-swab screening were calculated in relation to corresponding culture results for samples collected on admission.For the 273 patients included in this study, nasal-swab screening for MRSA showed the following diagnostic characteristics in relation to bacterial culture results: sensitivity 58.3% (95% confidence interval [CI] 28.6%-83.5%), specificity 93.9% (95% CI 90.0%-96.3%), positive predictive value 30.4% (95% CI 14.1%-53.0%), negative predictive value 98.0% (95% CI 95.1%-99.3%), positive likelihood ratio 9.5 (95% CI 4.9-18.7), and negative likelihood ratio 0.4 (95% CI 0.2-0.9).Given the high specificity of this rapid method, clinicians should ensure that patients who are receiving empiric treatment for MRSA infection and who have a positive result on nasal-swab screening continue to receive MRSA coverage until culture results are available. In addition, the high negative predictive value and positive likelihood ratio for nasal-swab screening in a low-prevalence setting suggest that a negative result significantly reduces the probability of MRSA infection. Although nasal-swab screening for MRSA is currently used for determining isolation precautions, this method also had utility in helping clinicians to predict the probability of MRSA infection and in guiding decisions about antimicrobial therapy.Le dépistage duPrésenter les caractéristiques diagnostiques du dépistage par écouvillonnage nasal comme outil servant à prédire les infections à SARM chez les patients hospitalisés qui reçoivent un traitement empirique de vancomycine par voie intraveineuse.On a mené une analyse d’observation rétrospective au moyen des dossiers médicaux de patients adultes nouvellement admis au Peter Lougheed Centre à Calgary, en Alberta, ayant reçu un traitement empirique de vancomycine par voie intraveineuse entre janvier 2015 et octobre 2015 et ayant subi un dépistage du SARM par écouvillonnage nasal. Les caractéristiques diagnostiques du dépistage par écouvillonnage nasal ont été obtenues par comparaison avec les résultats de culture correspondants qui provenaient des échantillons recueillis à l’admission.Pour ce qui est des 273 patients retenus pour la présente étude, le dépistage du SARM par écouvillonnage nasal a affiché les caractéristiques diagnostiques suivantes comparativement aux résultats des cultures bactériennes : sensibilité de 58,3 % (intervalle de confiance [IC] à 95 % de 28,6 % à 83,5 %), spécificité de 93,9 % (IC à 95 % de 90,0 % à 96,3 %), valeur prédictive positive de 30,4 % (IC à 95 % de 14,1 % à 53,0 %), valeur prédictive négative de 98,0 % (IC à 95 % de 95,1 % à 99,3 %), rapport de vraisemblance positif de 9,5 (IC à 95 % de 4,9 à 18,7) et rapport de vraisemblance négatif de 0,4 (IC à 95 % de 0,2 à 0,9).Compte tenu de la spécificité élevée de cette technique rapide, les cliniciens devraient s’assurer que les patients qui reçoivent un traitement empirique pour une infection à SARM et dont le résultat du dépistage du SARM par écouvillonnage nasal se révèle positif continuent à être traités contre le SARM jusqu’à l’obtention des résultats de culture. De plus, la valeur prédictive négative élevée et le rapport de vraisemblance positif élevé associés au dépistage par écouvillonnage nasal dans un contexte de faible prévalence suggèrent qu’un résultat négatif réduit de façon significative les probabilités d’infection à SARM. Enfin, bien que le dépistage du SARM par écouvillonnage nasal soit présentement utilisé pour déterminer les précautions à prendre concernant l’isolation, ce type d’analyse avait aussi le potentiel d’aider les cliniciens à prévoir les probabilités d’infection à SARM et de guider leur choix quant à l’antibiothérapie.

Background: Nasal-swab screening for methicillin-resistant Staphylo coccus aureus (MRSA) has a quicker turnaround time than other bacterial culture methods, with results available within 24 h. Although MRSA nasal-swab screening is not intended to guide antimicrobial therapy, this method may give clinicians additional information for earlier tailoring of empiric antimicrobial agents.Objective: To describe the diagnostic characteristics of nasal-swab screening in predicting MRSA infections in hospitalized patients receiving empiric treatment with IV vancomycin.Methods: A retrospective observational chart review was conducted for newly admitted adult patients of the Peter Lougheed Centre in Calgary, Alberta, who were treated empirically with IV vancomycin from January to October 2015 and who underwent nasal-swab screening for MRSA. The diagnostic characteristics of nasal-swab screening were calculated in relation to corresponding culture results for samples collected on admission.Results: For the 273 patients included in this study, nasal-swab screening for MRSA showed the following diagnostic characteristics in relation to bacterial culture results: sensitivity 58.3% (95% confidence interval [CI] 28.6%–83.5%), specificity 93.9% (95% CI 90.0%–96.3%), positive predictive value 30.4% (95% CI 14.1%–53.0%), negative predictive value 98.0% (95% CI 95.1%–99.3%), positive likelihood ratio 9.5 (95% CI 4.9–18.7), and negative likelihood ratio 0.4 (95% CI 0.2–0.9).Conclusions: Given the high specificity of this rapid method, clinicians should ensure that patients who are receiving empiric treatment for MRSA infection and who have a positive result on nasal-swab screening continue to receive MRSA coverage until culture results are available. In addition, the high negative predictive value and positive likelihood ratio for nasal-swab screening in a low-prevalence setting suggest that a negative result significantly reduces the probability of MRSA infection. Although nasal-swab screening for MRSA is currently used for determining isolation precautions, this method also had utility in helping clinicians to predict the probability of MRSA infection and in guiding decisions about antimicrobial therapy.RÉSUMÉContexte : Le dépistage du Staphylococcus aureus résistant à la méthicilline (SARM) par écouvillonnage nasal procure des résultats d’examen plus promptement que les autres techniques de culture bactérienne, les résultats étant disponibles dans les 24 heures. Bien que les résultats du dépistage du SARM par écouvillonnage nasal ne soient pas destinés à guider le choix de traitement antimicrobien, cette technique peut fournir aux cliniciens des informations supplémentaires leur permettant de préciser plus rapidement les antibiothérapies empiriques adéquates. Objectif : Présenter les caractéristiques diagnostiques du dépistage par écouvillonnage nasal comme outil servant à prédire les infections à SARM chez les patients hospitalisés qui reçoivent un traitement empirique de vancomycine par voie intraveineuse.Méthodes : On a mené une analyse d’observation rétrospective au moyen des dossiers médicaux de patients adultes nouvellement admis au Peter Lougheed Centre à Calgary, en Alberta, ayant reçu un traitement empirique de vancomycine par voie intraveineuse entre janvier 2015 et octobre 2015 et ayant subi un dépistage du SARM par écouvillonnage nasal. Les caractéristiques diagnostiques du dépistage par écouvillonnage nasal ont été obtenues par comparaison avec les résultats de culture correspondants qui provenaient des échantillons recueillis à l’admission. Résultats : Pour ce qui est des 273 patients retenus pour la présente étude, le dépistage du SARM par écouvillonnage nasal a affiché les caractéristiques diagnostiques suivantes comparativement aux résultats des cultures bactériennes : sensibilité de 58,3 % (intervalle de confiance [IC] à 95 % de 28,6 % à 83,5 %), spécificité de 93,9 % (IC à 95 % de 90,0 % à 96,3 %), valeur prédictive positive de 30,4 % (IC à 95 % de 14,1 % à 53,0 %), valeur prédictive négative de 98,0 % (IC à 95 % de 95,1 % à 99,3 %), rapport de vraisemblance positif de 9,5 (IC à 95 % de 4,9 à 18,7) et rapport de vraisemblance négatif de 0,4 (IC à 95 % de 0,2 à 0,9).Conclusions : Compte tenu de la spécificité élevée de cette technique rapide, les cliniciens devraient s’assurer que les patients qui reçoivent un traitement empirique pour une infection à SARM et dont le résultat du dépistage du SARM par écouvillonnage nasal se révèle positif continuent à être traités contre le SARM jusqu’à l’obtention des résultats de culture. De plus, la valeur prédictive négative élevée et le rapport de vraisemblance positif élevé associés au dépistage par écouvillonnage nasal dans un contexte de faible prévalence suggèrent qu’un résultat négatif réduit de façon significative les probabilités d’infection à SARM. Enfin, bien que le dépistage du SARM par écouvillonnage nasal soit présentement utilisé pour déterminer les précautions à prendre concernant l’isolation, ce type d’analyse avait aussi le potentiel d’aider les cliniciens à prévoir les probabilités d’infection à SARM et de guider leur choix quant à l’antibiothérapie.

BackgroundPeople with schizophrenia are at significantly greater risk of cardiovascular disease-related mortality. We set out to determine if people with and without schizophrenia who undergo coronary artery catheterization differ with respect to coronary anatomy, coronary artery disease management, or outcome.Methods and resultsThis study used provincial administrative data and a clinical registry that included all individuals who undergo coronary catheterization in Alberta, Canada. Individuals with schizophrenia were identified in hospital discharge data using ICD-9 codes. We identified 271 Albertans with a hospital discharge diagnosis of schizophrenia and a subsequent coronary catheterization and were matched with 1083 controls without schizophrenia that had undergone a coronary catheterization. Extent of coronary disease was assessed using 1) left ventricular ejection fraction; 2) the Duke Jeopardy Score (a valid measure of myocardium at risk for ischemic injury); and 3) a categorical assessment of coronary anatomy risk. People with schizophrenia were less likely to be categorized as high risk on the Duke coronary index (p < .005) and more likely to be categorized as having a normal coronary anatomy (p < .05). Significant differences in mortality were found among those with and without schizophrenia both before and after adjustment for clinical differences.ConclusionsOur results suggest that people with schizophrenia have less severe coronary atherosclerosis, and are less likely to receive revascularization. Despite less severe coronary atherosclerosis, individuals with schizophrenia had a significantly higher mortality following catheterization. Interventions to increase therapeutic adherence and clinical follow up of patients with mental illness may improve health outcomes.

Objective To evaluate the relationship between initiation of atypical antipsychotic agents and the risk of hyperglycemic emergencies. Method We conducted a multicentre retrospective cohort study using administrative health data from 7 Canadian provinces and the UK Clinical Practice Research Datalink. Hospitalizations for hyperglycemic emergencies (hyperglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic state) were compared between new users of risperidone (reference), and new users of olanzapine, other atypical antipsychotics, and typical antipsychotics. We used propensity scores with inverse probability of treatment weighting and proportional hazard models to estimate the site-specific hazard ratios of hyperglycemic emergencies in the year following drug initiation separately for adults under and over age 66 years. Site-level results were pooled using meta-analytic methods. Results Among 725,489 patients, 55% were aged 66 + years; 5% of younger and 19% of older patients had pre-existing diabetes. Hyperglycemic emergencies were rare (1–2 per 1000 person years), but more frequent in patients with pre-existing diabetes (6–12 per 1000 person years). We did not find a significant difference in risk of hyperglycemic emergencies with initiation of olanzapine versus risperidone; however heterogeneity existed between sites. The risk of an event was significantly lower with other atypical (99% quetiapine) compared to risperidone use in older patients [adjusted hazard ratio, 95% confidence interval (CI): 0.69, 0.53–0.90]. Conclusions Risk for hyperglycemic emergencies is low after initiation of antipsychotics, but patients with pre-existing diabetes may be at greater risk. The risk appeared lower with the use of quetiapine in older patients, but the clinical significance of the findings requires further study.

BACKGROUND: Published information evaluating frequency of and risk factors for vancomycin-induced acute kidney injury (AKI) in the pediatric intensive care unit (PICU) population is conflicting. OBJECTIVES: The primary objective was to describe the proportion of our PICU patients who developed AKI with intravenous (IV) vancomycin. The secondary objective was to describe the associated potential risk factors. METHODS: Pediatric patients (0–18 years) who received their first IV vancomycin dose in the PICU were evaluated in this retrospective chart review. AKI was defined based on Pediatric-Modified RIFLE (pRIFLE) criteria. Patient demographics, vancomycin trough concentrations, concomitant nephrotoxins, and estimated creatinine clearance changes were analyzed. RESULTS: Of 265 patients included, the primary outcome of AKI (defined by meeting any pRIFLE criteria) occurred in 62 (23.4%) patients (48 category R, 11 category I, 3 category F). Patients who received vancomycin treatment for = 5 days were more likely to develop AKI (unadjusted odds ratio [uOR]: 2.52; 95% confidence interval [CI]: 1.11–5.73), as were patients with a maximum vancomycin trough level = 20 mg/L (OR: 2.99; 95% CI: 1.54–5.78) and patients on 1 (uOR: 2.29; 95% CI: 1.12–4.66) or more concurrent nephrotoxin (uOR: 3.11; 95% CI: 1.43–6.77). Among nephrotoxins, patients receiving furosemide concomitantly with vancomycin were more likely to develop AKI (uOR: 3.47; 95% CI: 1.92–6.27). After adjustment, only furosemide was a significant predictor of risk of AKI/AKI (adjusted OR: 3.52; 95% CI: 1.88–6.62). The study was limited by its retrospective and observational design, and confounding variables. CONCLUSIONS: Patients who were receiving vancomycin with concurrent furosemide were at highest risk of developing AKI.

Background and objectives A safety signal regarding cases of AKI after exposure to serotonin-norepinephrine reuptake inhibitors (SNRIs) was identified by Health Canada. Therefore, this study assessed whether the use of SNRIs increases the risk of AKI compared with selective serotonin reuptake inhibitors (SSRIs) and examined the risk associated with each individual SNRI. Design, setting, participants, & measurements Multiple retrospective population-based cohort studies were conducted within eight administrative databases from Canada, the United States, and the United Kingdom between January 1997 and March 2010. Within each cohort, a nested case-control analysis was performed to estimate incidence rate ratios (RRs) of AKI associated with SNRIs compared with SSRIs using conditional logistic regression, with adjustment for high-dimensional propensity scores. The overall effect across sites was estimated using meta-analytic methods. Results There were 38,974 cases of AKI matched to 384,034 controls. Current use of SNRIs was not associated with a higher risk of AKI compared with SSRIs (fixed-effect RR, 0.97; 95% confidence interval [95% CI], 0.94 to 1.01). Current use of venlafaxine and desvenlafaxine considered together was not associated with a higher risk of AKI (RR, 0.96; 95% CI, 0.92 to 1.00). For current use of duloxetine, there was significant heterogeneity among site-specific estimates such that a random-effects meta-analysis was performed showing a 16% higher risk, although this risk was not statistically significant (RR, 1.16; 95% CI, 0.96 to 1.40). This result is compatible with residual confounding, because there was a substantial imbalance in the prevalence of diabetes between users of duloxetine and users of others SNRIs or SSRIs. After further adjustment by including diabetes as a covariate in the model along with propensity scores, the fixed-effect RR was 1.02 (95% CI, 0.95 to 1.10). Conclusions There is no evidence that use of SNRIs is associated with a higher risk of hospitalization for AKI compared with SSRIs.

Introduction Medication administration omissions (MAO) are usually considered medication errors but not all MAO are clinically relevant. We determined the frequency of clinically relevant MAO of antimicrobial drugs in adult hospitals in Calgary, Alberta, Canada based on electronic medication administration record (eMAR). Methods We examined 2011 data from eMAR records on medical wards and developed a reproducible assessment scheme to categorize and determine clinical relevance of MAO. We applied this scheme to records from 2012 in a retrospective cohort study to quantify clinically relevant MAO. Significant predictors of clinically relevant MAO were identified. Results A total of 294,718 dose records were assessed of which 10,282 (3.49%) were for doses not administered. Among these 4903 (1.66% of total); 47.68% of MAO were considered clinically relevant. Significant positive predictors of clinically relevant MAO included inhaled (OR 4.90, 95% CI 3.54-6.94) and liquid oral (OR 1.32, 95% CI 1.18-1.47) route of medication compared to solid oral and irregular dose schedules. Evening nursing shift compared to night shift (OR 0.77 95% CI 0.70-0.85) and parenteral (OR 0.50, 95% CI 0.46-0.54) were negative predictors, The commonest reasons for relevant MAO were patient preference, unspecified reason, administration access issues, drug not available or patient condition. Conclusion Assessment of MAO by review of computer records provides a greater scope and sample size than directly observed medication administration assessments without “observer” effect. We found that MAO of antimicrobials in inpatients were uncommon but were seen more frequently with orally administered antimicrobials which may have significance to antimicrobial stewardship initiatives.

Background: Vancomycin is widely used to treat infections caused by methicillin-resistant Staphylococcus aureus. Data for dosing and monitoring of this drug in pediatric patients are lacking, and clinicians who are treating children often follow guidelines established for adults. Objectives: To examine the total daily doses of vancomycin required to reach therapeutic trough levels (i.e., 10–20 mg/L) in infants, children, and adolescents, and to assess the number of pediatric patients in whom therapeutic trough levels are achieved with current empiric doses (40–60 mg/kg daily). Methods: This chart review evaluated patients 1 month to 18 years of age for whom vancomycin was prescribed at a single institution between November 2011 and October 2012. Patients’ demographic characteristics, vancomycin dosing parameters, and subsequent steady-state trough concentrations were analyzed. Results: Overall, the proportion of patients who reached therapeutic trough levels with current empiric doses was 39% (74 of 188). The mean total daily dose (± standard deviation) required to achieve therapeutic trough levels was 57.8 ± 11.5 mg/kg for patients 1 to 5 months of age, 68.9 ± 15.4 mg/kg for those 6 to 23 months of age, 65.8 ± 13.0 mg/kg for those 2 to 12 years of age, and 55.7 ± 11.8 mg/kg for those 13 to 18 years of age. Conclusions: Common empiric vancomycin dosing regimens (40–60 mg/kg daily) are not high enough to achieve trough levels of 10–20 mg/L in the majority of pediatric patients. Given these data, the authors suggest a starting dose of 60 mg/kg daily for patients 1 to 5 months of age and those 13 to 18 years of age and a starting dose of 70 mg/kg daily for patients 6 months to 12 years of age. RESUME Contexte : La vancomycine est couramment utilisee pour traiter les infections a Staphylococcus aureus resistant a la methicilline. Or, il n’y a pas assez de donnees sur l’adaptation posologique pour ce medicament et sur son suivi pharmacologique chez l’enfant. Les cliniciens qui traitent des enfants suivent donc souvent des lignes directrices concues pour les adultes. Objectifs : Analyser la posologie quotidienne de vancomycine necessaire a l’atteinte de concentrations minimales therapeutiques (c.-a-d. 10–20 mg/L) chez le nourrisson, l’enfant et l’adolescent, et evaluer le nombre d’enfants chez qui les concentrations minimales therapeutiques ont ete atteintes a l’aide des posologies empiriques utilisees presentement (40–60 mg/kg par jour). Methodes : L’etude consistait en l’analyse des dossiers medicaux de patients âges entre 1 mois et 18 ans qui se sont vu prescrire la vancomycine, et ce, dans un seul etablissement entre novembre 2011 et octobre 2012. Les donnees demographiques des patients, les parametres posologiques de la vancomycine et les subsequentes concentrations minimales a l’etat d’equilibre ont ete analyses. Resultats : Dans l’ensemble, la proportion de patients chez qui les concentrations minimales therapeutiques ont ete atteintes a l’aide des posologies empiriques presentement utilisees etait de 39 % (74 sur 188). La posologie quotidienne moyenne (± l’ecart-type) necessaire pour atteindre les concentrations minimales therapeutiques etait de 57,8 ± 11,5 mg/kg pour les patients âges de 1 a 5 mois, de 68,9 ± 15,4 mg/kg pour ceux âges de 6 a 23 mois, de 65,8 ± 13,0 mg/kg pour ceux âges de 2 a 12 ans et de 55,7 ± 11,8 mg/kg pour ceux âges de 13 a 18 ans. Conclusions : Les posologies empiriques courantes de 40–60 mg/kg par jour de vancomycine ne sont pas assez elevees et ne permettent pas d’atteindre des concentrations minimales de 10–20 mg/L chez la majorite des patients en pediatrie. Compte tenu de ces donnees, les auteurs suggerent une dose de depart quotidienne de 60 mg/kg pour les patients âges de 1 a 5 mois et ceux âges de 13 a 18 ans, et une dose de depart quotidienne de 70 mg/kg pour les patients âges de 6 mois a 12 ans.

Background: Morbidity due to cardiovascular disease is high among First Nations people. The extent to which this may be related to the likelihood of coronary angiography is unclear. We examined the likelihood of coronary angiography after acute myocardial infarction (MI) among First Nations and non–First Nations patients. Methods: Our study included adults with incident acute MI between 1997 and 2008 in Alberta. We determined the likelihood of angiography among First Nations and non–First Nations patients, adjusted for important confounders, using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. Results: Of the 46 764 people with acute MI, 1043 (2.2%) were First Nations. First Nations patients were less likely to receive angiography within 1 day after acute MI (adjusted odds ratio [OR] 0.73, 95% confidence interval [CI] 0.62–0.87). Among First Nations and non–First Nations patients who underwent angiography (64.9%), there was no difference in the likelihood of percutaneous coronary intervention (PCI) (adjusted hazard ratio [HR] 0.92, 95% CI 0.83–1.02) or coronary artery bypass grafting (CABG) (adjusted HR 1.03, 95% CI 0.85–1.25). First Nations people had worse survival if they received medical management alone (adjusted HR 1.38, 95% CI 1.07–1.77) or if they underwent PCI (adjusted HR 1.38, 95% CI 1.06–1.80), whereas survival was similar among First Nations and non–First Nations patients who received CABG. Interpretation: First Nations people were less likely to undergo angiography after acute MI and experienced worse long-term survival compared with non–First Nations people. Efforts to improve access to angiography for First Nations people may improve outcomes.

Objective: Current epidemiologic knowledge about bipolar disorder (BD) in Canada is inadequate. To date, only 3 prevalence studies have been conducted: only 1 was based on a national sample, and none distinguished between BD I and II. The objective of this study was to estimate the prevalence of BD I and II in Canada in 2012. Method: Data were obtained from the 2012 Canadian Community Health Survey: Mental Health and Well-being, a cross-sectional survey of a nationally representative sample of household residents ages 15 years and older ( n = 25 113). The survey response rate was 68.9%. Interviews were based on the World Health Organization Composite International Diagnostic Interview (CIDI). Prevalence was estimated using generalized linear modelling. Prevalence of self-reported diagnosis of BD and use of lithium were also estimated. Results: The estimated lifetime prevalence of BD I and II (based on the CIDI) in Canada in 2012 was 0.87% (95% CI 0.67% to 1.07%) and 0.57% (95% CI 0.44% to 0.71%), respectively. Prevalence did not differ by sex. The estimated prevalence of self-reported BD was 0.87% (95% CI 0.65% to 1.07%). There was a lack of congruence between CIDI-defined and self-reported BD, and few people taking lithium were positive for BD on the CIDI, which raises some concerns about the validity of the CIDI's assessment of BD. Conclusions: These prevalence estimates align with those reported in prior literature. However, caution should be exercised when interpreting general population studies that use CIDI-defined BD owing to the possibility of misclassification.

Objective: In Canada, treatment of children and adolescents with antipsychotics is almost always off label. A single atypical agent, aripiprazole, only recently received regulatory authorization for use in the group aged 15 to 17 years. This regulatory approval was restricted to treatment of schizophrenia. The objective of this review was to summarize pharmacoepidemiologic reports examining the frequency of use of these medications. Methods: A literature search was used to identify English-language studies examining the pharmacoepidemiology of antipsychotics in children and adolescents. The results of identified studies were summarized using narrative review methods. Results: In countries where longitudinal data are available, increased antipsychotic use has been consistently observed. Generally, most or all of this increase can be attributed to second-generation antipsychotics (SGAs). Major international differences are evident in the literature. European studies describe lower overall frequencies of use than North American studies (most of which were conducted in the United States). SGAs in children and adolescents are used more often in boys than in girls, and are increasingly used for treatment of attention-deficit hyperactivity disorder (ADHD) and conduct disorder (CD). Conclusions: Determining the most appropriate frequency of SGA use in children and adolescents will ultimately depend on decisive clarification of risks and benefits. The currently available literature highlights large international differences in the frequency of use. These differences may reflect fundamental dissimilarities in the therapeutic stance adopted toward ADHD and CD by physicians practicing in different countries.

Objectives: We examined trends in prescription recommendations for treatment of bipolar disorder (BD) in Canada during 2002-2010. Methods: Data collected by IMS Brogan in a database known as the Canadian Disease and Therapeutic Index were used for this analysis. These data are collected from a representative physician panel who record each drug recommendation and reason for recommendation in their practices for 2 consecutive days each calendar quarter of the year. Prescription patterns of medications for BD, including lithium, anticonvulsants, antipsychotic agents, anxiolytics, and antidepressants, were evaluated both for general practitioners and for specialists. Results: The number of prescription recommendations for BD increased by 72.1% from 2002 to 2009, and then dropped by 24.8% from 2009 to 2010. This increase from 2002 to 2009, and subsequent decrease from 2009 to 2010, was observed for all classes of medications. The overall increase from 2002 to 2010 was statistically significant for the atypical antipsychotics (P = 0.04). The largest change for an individual drug during this period was a 438% increase in recommendations for quetiapine (P = 0.01). Conclusions: The number of prescription recommendations for BD increased substantially from 2002 to 2009 and sharply dropped in the following year. These results suggest that the influence of the concept of the bipolar spectrum and its promotion may have resulted in a substantial increase in treatment that has recently begun to wane. Objectifs : Nous avons examine les tendances des recommandations de prescription pour le traitement du trouble bipolaire (TB) au Canada, de 2002 a 2010. Methodes : Les donnees recueillies par IMS Brogan dans une base de donnees nommee l'Index canathen des maladies et traitements ont ete utilisees pour cette analyse. Ces donnees sont recueillies aupres d'un groupe de medecins representatif qui enregistrent chaque recommandation d'un medicament et la raison de cette recommandation dans leurs pratiques, pendant 2 jours consecutifs de chaque trimestre de l'annee. Les modeles de prescription des medicaments pour le TB, notamment le lithium, les anticonvulsivants, les agents antipsychotiques, les anxiolytiques, et les antidepresseurs, ont ete evalues pour les omnipraticiens et les specialistes. Resultats : Le nombre de recommandations de prescription pour le TB s'est accru de 72,1 % de 2002 a 2009, puis a chute de 24,8 % de 2009 a 2010. Cette hausse de 2002 a 2009, et la diminution subsequente de 2009 a 2010, ont ete observees pour toutes les classes de medicaments. La hausse globale de 2002 a 2010 etait statistiquement significative pour les antipsychotiques atypiques (P = 0,04). Le changement le plus important pour un medicament individuel dans cette periode a ete une augmentation de 438 % des recommandations de quetiapine (P = 0,01). Conclusions : Le nombre de recommandations de prescription pour le TB a augmente substantiellement de 2002 a 2009 et chute radicalement l'annee suivante. Ces resultats suggerent que l'influence et la promotion du concept du spectre bipolaire peuvent avoir entraine une augmentation substantielle des traitements qui a recemment commence â flechir. Key Words: bipolar disorder, pharmacoepidemiology, prescriptions Manuscript received July 2012, revised, and accepted October 2011. Abbreviations AD antidepressant BD bipolar disorder CANMAT Canadian Network for Mood and Anxiety Treatment GP general practitioner ISBD International Society for BDs SRI serotonin reuptake inhibitor A controversial matter in the BD field is calls, for example in 2002, to expand this category into a bipolar spectrum1 3 such that its prevalence would reach 4% to 5% of the general population. We asked whether this has impacted prescribing practices by undertaking a 9-year analysis (2002-2010) of physicians' prescriptions for BD in Canada. …

Objective: The objective of this study was to evaluate the temporal trends in the incidence of acute myocardial infarction (AMI) and receipt of revascularization procedures in people with and without mental illness. Hypothesis: Individuals with mental illness will have higher rates of AMI, and lower rates of revascularization compared to people without mental illness. Methods: We did a population-based study using provincial administrative data from April 1, 1998 until March 31, 2009. We identified individuals 20 years of age and older as having mental illness (psychotic disorder [PD] or mood disorder [MD]) based on physician billing claims and hospitalization data, and compared them to those without mental illness by this definition. We identified incident AMI using a validated algorithm applied to hospitalization data. We used procedure codes to identify receipt of cardiac catheterization, coronary artery bypass grafting (CABG), or percutaneous transluminal coronary angioplasty (PTCA) in those with incident AMI. Rates were age-adjusted using the 2001 Canadian census population to perform direct standardization. Relative change over time was calculated by comparing rates in 2009 to rates in 1998. Results: A total of 3,639,480 subjects were included, of whom 576,411 (15.8%) had a mood disorder only, 38,116 (1.0%) had a psychotic disorder only, and 72,430 (2.0%) had both a MD and PD. People with MD were more likely to be female, whereas those with PD were older, than the other mentally ill and non-mentally ill populations. Incidence of AMI was highest in people with PD (210 per 100,000 in 2009) and lowest in people without mental illness (160 per 100,000 in 2009), however, incidence of AMI decreased over time in all groups. Use of catheterization decreased over time in people with MD (19% relative decrease) and PD (25% relative decrease), while increasing in people without mental illness (10.8% relative increase). Use of PTCA increased in all groups except people with PD (21.1% relative decrease). Conclusions: Incidence of AMI decreased over time in people with and without mental illness, however, people with mental illness consistently had a higher incidence of AMI compared to individuals without mental illness. Use of catheterization and PTCA increased in people without mental illness while decreasing in people with PD over the study period.

Whether access to primary and specialist care has an impact on treatment for people with schizophrenia and comorbid cardiac disease is unclear. The objective of this study was to compare use of general health care and specialized cardiac care by people with schizophrenia and by the rest of the population.A population-based period-prevalence study was conducted and included adults (N=2,310,391) in Alberta, Canada, by using administrative databases. People with schizophrenia were identified based on billing codes; all others served as the comparator cohort. Multivariable logistic regression analyses were conducted to compare claims for general (general practitioner visits) health care, urgent and emergent (emergency department visits and hospitalizations) health services, and specialized cardiac (cardiologist visits, revascularization) care.Individuals with schizophrenia (N=28,755) had a higher prevalence of coronary artery disease than those without schizophrenia (N=2,281,636) (20% versus 14%) and were more likely than those without schizophrenia to visit a general practitioner more than four times per year (76% versus 47%; adjusted odds ratio [AOR]=3.60, 95% confidence interval [CI]=3.49-3.71). In contrast, individuals with schizophrenia and coronary artery disease were less likely to visit a cardiologist (50% versus 59%; AOR=. 76, 95% CI=.72-.80) or undergo coronary revascularization (6% versus 12%; AOR=. 55, 95% CI=.49-.61).In this large population-based study, individuals with schizophrenia were less likely to visit cardiologists or undergo revascularization than were people without schizophrenia. Opportunities exist for better assessment and management of cardiovascular disease and risk factors among people with schizophrenia.

PurposeTo compare the prevalence of cardiovascular risk factors (CV-RF) and disease (CV-D) and health care use in people with and without schizophrenia.Subjects/materials and methodsData from the Canadian Community Health Survey (CCHS), cycle 3.1, were used. Prevalence of CV-RF, CV-D, and health care use were compared in those with and without schizophrenia using logistic regression analysis. Sampling weights and bootstrap variance estimates were used to account for survey design.ResultsA total of 399 (0.3%) people with schizophrenia were identified and compared to 120,044 (97.7%) people without. Individuals with schizophrenia were significantly more likely to be obese (34.8% vs. 15.6%) and report diabetes (11.9% vs. 5.3%). After accounting for sociodemographic variables, schizophrenia was not independently associated with diabetes (adjusted odds ratio [aOR]: 0.86; 0.49–1.51). Individuals with schizophrenia were more likely to be hospitalized (21.9% vs. 8.0%; aOR: 2.37; 95% CI: 1.51–3.74) but no more likely to visit their physician (86.7% vs. 85.7%; aOR: 1.23; 95% CI: 0.65–2.35).Discussion/conclusionOur findings suggest that people with schizophrenia access the primary health care system at least as frequently as someone without schizophrenia, and the opportunity for management of modifiable CV-RF exists in this vulnerable population.

Metformin is first-line therapy for people with type 2 diabetes. Due to potential lactic acidosis it is contraindicated in patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2, although little is known about its use among patients with chronic kidney disease (CKD). The objective of this study was to determine the association between kidney function and mortality among incident metformin users.