Are Guideline-concordant Processes of Care Consistent Across the Rural-Urban Continuum? A Retrospective Cohort Study of Adults Newly Treated for Type 2 Diabetes.

OBJECTIVES: Our aim in this study was to identify the association between place of residence (metropolitan, urban, rural) and guideline-concordant processes of care in the first year of type 2 diabetes management. METHODS: We conducted a retrospective cohort study of new metformin users between April 2015 and March 2020 in Alberta, Canada. Outcomes were identified as guideline-concordant processes of care through the review of clinical practice guidelines and published literature. Using multivariable logistic regression, the following outcomes were examined by place of residence: dispensation of a statin, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), eye examination, glycated hemoglobin (A1C), cholesterol, and kidney function testing. RESULTS: Of 60,222 new metformin users, 67% resided in a metropolitan area, 10% in an urban area, and 23% in a rural area. After confounder adjustment, rural residents were less likely to have a statin dispensed (adjusted odds ratio [aOR] 0.83, 95% confidence interval [CI] 0.79 to 0.87) or undergo cholesterol testing (aOR 0.86, 95% CI 0.83 to 0.90) when compared with metropolitan residents. In contrast, rural residents were more likely to receive A1C and kidney function testing (aOR 1.14, 95% CI 1.08 to 1.21 and aOR 1.17, 95% CI 1.11 to 1.24, respectively). ACEi/ARB use and eye examinations were similar across place of residence. CONCLUSIONS: Processes of care varied by place of residence. Limited cholesterol management in rural areas is concerning because this may lead to increased cardiovascular outcomes.

Rurality is associated with lower likelihood of dipeptidyl peptidase 4 inhibitor use for treatment intensification.

Background: Antihyperglycemic drug utilization studies are conducted frequently and describe the uptake of new drug therapies across may jurisdictions. An increasingly important, yet often absent, aspect of these studies is the impact of rurality on drug utilization. Objectives: The objective of this study was to explore the association between place of residence (rural, urban, metropolitan) and the use of dipeptidyl peptidase 4 inhibitors (DPP-4i) for first treatment intensification of type 2 diabetes. Methods: A retrospective cohort study was conducted from April 1, 2008 to March 31, 2019 of new metformin users. A multivariable logistic regression analysis was performed to determine the association between place of residence (using postal codes) and likelihood of DPP-4i dispensing. Results: After adjusting for confounders, analysis revealed that rural-dwellers are less likely to have a DPP-4i dispensed, compared with metropolitan-dwellers (aOR:0.64; 95%CI:0.61-0.67) and over-time, the uptake in rural areas was slower. Conclusions: This study demonstrates that rurality can have an impact on drug therapy decisions at first treatment intensification, with respect to the utilization of new therapies.

Effectiveness of Bio-K+ for the prevention of Clostridioides difficile infection: Stepped-wedge cluster-randomized controlled trial.

OBJECTIVE: To evaluate the impact of administering probiotics to prevent Clostridioides difficile infection (CDI) among patients receiving therapeutic antibiotics. DESIGN: Stepped-wedge cluster-randomized trial between September 1, 2016, and August 31, 2019. SETTING: This study was conducted in 4 acute-care hospitals across an integrated health region. PATIENTS: Hospitalized patients, aged ≥55 years. METHODS: Patients were given 2 probiotic capsules daily (Bio-K+, Laval, Quebec, Canada), containing 50 billion colony-forming units of Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2. We measured hospital-acquired CDI (HA-CDI) and the number of positive C. difficile tests per 10,000 patient days as well as adherence to administration of Bio-K+ within 48 and 72 hours of antibiotic administration. Mixed-effects generalized linear models, adjusted for influenza admissions and facility characteristics, were used to evaluate the impact of the intervention on outcomes. RESULTS: Overall adherence of Bio-K+ administration ranged from 76.9% to 84.6% when stratified by facility and periods. Rates of adherence to administration within 48 and 72 hours of antibiotic treatment were 60.2% -71.4% and 66.7%-75.8%, respectively. In the adjusted analysis, there was no change in HA-CDI (incidence rate ratio [IRR], 0.92; 95% confidence interval [CI], 0.68-1.23) or C. difficile positivity rate (IRR, 1.05; 95% CI, 0.89-1.24). Discharged patients may not have received a complete course of Bio-K+. Our hospitals had a low baseline incidence of HA-CDI. Patients who did not receive Bio-K+ may have differential risks of acquiring CDI, introducing selection bias. CONCLUSIONS: Hospitals considering probiotics as a primary prevention strategy should consider the baseline incidence of HA-CDI in their population and timing of probiotics relative to the start of antimicrobial administration.

Implementation strategies for hospital-based probiotic administration in a stepped-wedge cluster randomized trial design for preventing hospital-acquired Clostridioides difficile infection.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +). METHODS: We used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research. RESULTS: A total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals. CONCLUSIONS: Use of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

Hydrochlorothiazide use and risk of keratinocyte carcinoma and melanoma: A multisite population-based cohort study.

BACKGROUND: The association between hydrochlorothiazide (HCTZ) and skin cancer remains controversial. OBJECTIVE: To determine whether HCTZ is associated with an increased risk of skin cancer compared with angiotensin-converting enzyme inhibitors and calcium channel blockers. METHODS: Two new-user, active comparator cohorts were assembled using 6 Canadian databases. Site-specific hazard ratios (HRs) with 95% CIs were estimated using standardized morbidity ratio weighted Cox proportional hazard models and pooled using random-effects meta-analysis. RESULTS: HCTZ was not associated with an overall increased risk of keratinocyte carcinoma compared with angiotensin-converting enzyme inhibitors or calcium channel blockers, although increased risks were observed with longer durations (≥10 years; HR: 1.12; 95% CI: 1.03-1.21) and higher cumulative doses (≥100,000 mg; HR: 1.49; 95% CI: 1.27-1.76). For melanoma, there was no association with angiotensin-converting enzyme inhibitors, but a 32% increased risk with calcium channel blockers (crude incidence rates: 64.2 vs 58.4 per 100,000 person-years; HR: 1.32; 95% CI: 1.19-1.46; estimated number needed to harm at 5 years of follow-up: 1627 patients), with increased risks with longer durations and cumulative doses. LIMITATIONS: Residual confounding due to the observational design. CONCLUSIONS: Increased risks of keratinocyte carcinoma and melanoma were observed with longer durations of use and higher cumulative doses of HCTZ.

30-day readmission rates among upper gastrointestinal bleeds: A systematic review and meta-analysis.

BACKGROUND AND AIM: Upper gastrointestinal bleeding (UGIB) is a common emergency, with high rates of hospitalization and in-patient mortality compared to other gastrointestinal diseases. Despite readmission rates being a common quality metric, little data are available for UGIBs. This study aimed to determine readmission rates for patients discharged following an UGIB. METHODS: Adhering to PRISMA guidelines, MEDLINE, Embase, CENTRAL, and Web of Science were searched to October 16, 2021. Randomized and non-randomized studies that reported hospital readmission for patients following an UGIB were included. Abstract screening, data extraction, and quality assessment were conducted in duplicate. A random-effects meta-analysis was performed, with statistical heterogeneity measured using I2 . The GRADE framework, with a modified Downs and Black tool, was used to determine certainty of evidence. RESULTS: Seventy studies were included of 1847 screened abstracted, with moderate interrater reliability. Within these studies, 4 292 714 patients were analyzed with a mean age of 66.6 years, and 54.7% male. UGIB had a 30-day all-cause readmission rate of 17.4% (95% confidence interval [CI] 16.7-18.2%), stratification revealed a higher rate for variceal UGIB [19.6% (95% CI 17.6-21.5%)] than non-variceal [16.8% (95% CI 16.0-17.5%)]. Only one third were readmitted due to recurrent UGIB (4.8% [95% CI 3.1-6.4%]). UGIB due to peptic ulcer bleeding had the lowest 30-day readmission rate [6.9% (95% CI 3.8-10.0%)]. Certainty of evidence was low or very low for all outcomes. CONCLUSIONS: Almost one in five patients discharged after an UGIB are readmitted within 30 days. These data should prompt clinicians to reflect on their own practice to identify areas of strength or improvement.

Rural Residence Is Associated With a Delayed Trend Away From Sulfonylurea Use for Treatment Intensification of Type 2 Diabetes.

OBJECTIVE: To examine the intersection between location of residence along the rural-urban continuum (metropolitan, urban, and rural) and sulfonylurea dispensation records for the management of type 2 diabetes. RESEARCH DESIGN AND METHODS: This retrospective cohort study used administrative health records of adult new metformin users between April 2008 and March 2019 in Alberta, Canada. Multivariable logistic regression was performed to examine the association between sulfonylurea-based treatment intensification and location of residence. RESULTS: Treatment was intensified in 66,084 (38%) of 171,759 new metformin users after a mean of 1.5 years. At treatment intensification, mean age was 55 years, 62% of users were male, and 27% were rural residents. The most common antihyperglycemic drug, given to 30,297 people (46%) for treatment intensification, was a sulfonylurea. At the beginning of our observation period, the proportion of people dispensed a sulfonylurea at first treatment intensification was highest in rural (57%), compared with urban (54%) and metropolitan (52%) areas (P = 0.009). Although proportions decreased over time across the province, rural residents continued to constitute the highest proportion of sulfonylurea users (45%), compared with urban (35%) and metropolitan (37%) residents (P < 0.001), and the trend away from sulfonylurea use was delayed by ∼4 years for rural residents. Adjusting for potential sources of confounding, rural residence was associated with a significantly higher likelihood of using a sulfonylurea compared with metropolitan residence (adjusted odds ratio 1.34; 95% CI 1.29-1.39). CONCLUSIONS: Variation in sulfonylurea dispensation across the rural-urban continuum provides a basis for continued research in the differences in process of care by location.

Laboratory testing and antihypertensive medication adherence following initial treatment of incident, uncomplicated hypertension: A real-world data analysis.

In this study on medication adherence among newly diagnosed patients with uncomplicated, incident hypertension, we conducted a retrospective cohort study using available administrative and laboratory data from April 1, 2012 to March 31, 2017 in Alberta, Canada to understand the extent to which baseline laboratory assessment and/or subsequent follow-up was associated with persistence with antihypertensive therapy. We determined the frequency of baseline and follow-up testing and compared the rates of medication persistence by patient-, neighbourhood-, and treatment-related factors. Of 103 232 patients with newly diagnosed, uncomplicated hypertension who filled their first prescription within our study timeframe, 52.5% were non-persistent within 6 months. Persistent patients were more often female and residing in neighbourhoods with higher social status (with exception to rurality). Aside from older age, the strongest predictor of persistence was performance of laboratory testing related to hypertension with an apparent effect in which higher levels of medication persistence were seen with more frequent laboratory testing. We concluded that medication persistence was far from optimal, dropping off considerably after 6 months for more than half of patients. Medication persistence is a substantial barrier to realizing the full societal benefits of antihypertensive treatment. Ongoing follow up with patients, including laboratory testing, may be a critical component of better long term treatment persistence.

Health State Utility Values in People With Stroke: A Systematic Review and Meta-Analysis.

Background Health state utility values are commonly used to provide summary measures of health-related quality of life in studies of stroke. Contemporaneous summaries are needed as a benchmark to contextualize future observational studies and inform the effectiveness of interventions aimed at improving post-stroke quality of life. Methods and Results We conducted a systematic search of the literature using Medline, EMBASE, and Web of Science from January 1995 until October 2020 using search terms for stroke, health-related quality of life, and indirect health utility metrics. We calculated pooled estimates of health utility values for EQ-5D-3L, EQ-5D-5L, AQoL, HUI2, HUI3, 15D, and SF-6D using random effects models. For the EQ-5D-3L we conducted stratified meta-analyses and meta-regression by key subgroups. We screened 14 251 abstracts and 111 studies met our inclusion criteria (sample size range 11 to 12 447). EQ-5D-3L was reported in 78% of studies (study n=87; patient n=56 976). The pooled estimate for EQ-5D-3L at ≥3 months following stroke was 0.65 (95% CI, 0.63-0.67), which was ≈20% below population norms. There was high heterogeneity (I2>90%) between studies, and estimates differed by study size, case definition of stroke, and country of study. Women, older individuals, those with hemorrhagic stroke, and patients prior to discharge had lower pooled EQ-5D-3L estimates. Conclusions Pooled estimates of health utility for stroke survivors were substantially below population averages. We provide reference values for health utility in stroke to support future clinical and economic studies and identify subgroups with lower healthy utility. Registration URL: https://www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42020215942.

A Protocol for a Systematic Review and Meta-Analysis of Hospital Readmissions Following Acute Upper Gastrointestinal Bleeding.

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.

Impact of using concomitant conventional DMARDs on adherence to biologic DMARD treatment in rheumatoid arthritis: Multi-centre, population-based cohort study.

PURPOSE: To evaluate the impact of concomitant use of conventional synthetic DMARDs (csCMARD) on adherence, switching and dose of biologic disease modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis (RA) patients treated with bDMARDs. PATIENTS AND METHODS: This was a population-based cohort study conducted in five provinces of Canada (Alberta, Manitoba, Ontario, Quebec, and Saskatchewan), and one American database (IBM® MarketScan® Databases). Adult RA patients entered the study after a 3-month initiation period of bDMARDs between 1 January 2007, and 30 March 2014. Concomitant csDMARD exposure was compared to non-csDMARD exposure on the following outcomes: discontinuation of bDMARD therapy, switching of bDMARDs, and percent change in dose of bDMARD compared to initial dose. The effect of the time-varying changes in csDMARD exposure was analyzed using marginal structural models. Dose change was analyzed using linear regression. Results from each participating site were combined using likelihood ratio meta-analysis. RESULTS: The study population comprised 20,221 new users of bDMARDs: adalimumab (7609), etanercept (9809), abatacept (1024), infliximab (1779). Concomitant use of csDMARD therapy was not significantly associated with reduced discontinuation of bDMARD treatment (hazard ratio 0.90, 95% intrinsic confidence interval 0.79 to 1.02) or reduced switching of bDMARDs (hazard ratio 0.95, 95% intrinsic confidence interval 0.80 to 1.11), but was associated with a small increase in bDMARD dose compared to the mean dose over the first three months of treatment (mean percentage change in dose +0.56% mg/day, 95% intrinsic confidence interval +0.14% to +0.97%). CONCLUSION: In this large study of RA patients using bDMARDs in Canada and the United States, we found no clear evidence that patients who received concomitant csDMARD therapy were less likely to discontinue, switch or increase their dose of bDMARD.

Antihypertensive Prescribing for Uncomplicated, Incident Hypertension: Opportunities for Cost Savings.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 ß-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). CONCLUSIONS: 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.

CONTEXTE: 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. MÉTHODOLOGIE: 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. RÉSULTATS: 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). CONCLUSIONS: 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.

Accuracy of Inpatient Recall of Interaction With a Pharmacist: A Validation Study From 2 Acute Care Teaching Hospitals.

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.

Clinical practice guidelines for creating an acute care hospital-based antimicrobial stewardship program: A systematic review.

BACKGROUND: Antimicrobial stewardship programs (ASPs) are dedicated to improving antimicrobial use. Although clinical practice guidelines (CPGs) are available for the development of ASPs, it is unclear what the quality of these guidelines are. We therefore systematically reviewed published CPGs for the development of acute care hospital-based ASPs. METHODS: Primary literature, CPG and health technology assessment databases, and infectious diseases society websites were searched. Abstract and full-text review of the search results for inclusion were performed independently by 2 assessors. Overall quality of included CPGs was assessed using the Appraisal of Guidelines for Research and Evaluation II instrument. RESULTS: We identified 1,064 unique publications; 18 warranted full-text review. Five publications were included in the final review. The National Institute for Care and Excellence from the United Kingdom, the Dutch Working Party on Antibiotic Policy, and the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America from the United States all had high quality guidelines on the Appraisal of Guidelines for Research and Evaluation II scale. DISCUSSION: We identified 5 CPGs for creating a hospital-based ASP. Prior authorization and/or restriction policies that appeared in all 5 guidelines should be considered essential for the development of an effective hospital-based ASP. CONCLUSIONS: High quality CPGs are available for implementation of ASPs in acute care hospitals.