Non-Adherence to COPD Medications and its Association with Adverse Events: A Longitudinal Population Based Cohort Study of Older Adults.

OBJECTIVE: To determine the association between non-adherence to long term chronic obstructive pulmonary disease (COPD) medications and COPD related emergency department (ED) visits and hospitalizations in patients with incident COPD, utilizing time varying measures of adherence as well as accounting for time-varying confounding impacted by prior adherence. STUDY DESIGN AND SETTING: We conducted a population-based retrospective cohort study between 2007-2017 among individuals aged 66 years and older with incident COPD using multiple linked administrative health databases from the province of Ontario, Canada. Adherence to COPD medications was measured using time varying proportion of days covered based on insurance claims for medications dispensed at community pharmacies. The parametric g-formula was used to assess the association between time-varying adherence (in the last 90-days) to COPD medications and risk of COPD related hospitalizations and ED visits while accounting for time varying confounding by COPD severity. RESULTS: Overall, 60,251 individuals with incident COPD were included; mean age was 76 (SD 7) and 59% were male. Mean adherence over the entire follow-up was 23% (SD 0.3). There were 7,248 (12%) COPD related ED visits (2.8 events per 100 person years [PY]) and 9,188 (15%) COPD related hospitalizations (3.5 events per 100 PY). Compared to those with 0% 90-day adherence, those with adherence between 1-33% had a 19% decreased risk of COPD related ED visits (adjusted risk ratio[aRR]:0.81, 95% confidence interval [CI]:0.78-0.83), those with adherence between 34%-67% had a 18% decreased risk (aRR: 0.82, 95% CI: 0.77-0.85) while those with 68%-100% 90-day adherence had a 63% increased risk of COPD related ED visits (aRR: 1.63, 95% CI: 1.47-1.78). Nearly identical results were obtained for COPD specific hospitalizations. CONCLUSION: After accounting for time varying confounding by COPD severity, the highest time varying 90-days adherence was associated with an increased risk of both COPD related ED visits and hospitalizations compared to the lowest adherence categories. Differences in COPD severity between adherence categories, perception of need for medication management in the higher adherence categories, and potential residual confounding makes it difficult to disentangle the independent effects of adherence from the severity of the condition itself.

Medication clusters at hospital discharge and risk of adverse drug events at 30 days postdischarge: A population-based cohort study of older adults.

AIMS: Certain combinations of medications can be harmful and may lead to serious adverse drug events (ADEs). Identifying potentially problematic medication clusters could help guide prescribing and/or deprescribing decisions in hospital. The aim of this study is to characterize medication prescribing patterns at hospital discharge and determine which medication clusters were associated with an increased risk of ADEs in the 30-day posthospital discharge. METHODS: All residents of the province of Ontario in Canada aged 66 years or older admitted to hospital between March 2016 and February 2017 were included. Identification of medication clusters prescribed at hospital discharge was conducted using latent class analysis. Cluster identification and categorization were based on medications dispensed up to 30-day posthospitalization. Multivariable logistic regression was used to assess the potential association between membership to a particular medication cluster and ADEs postdischarge, while also evaluating other patient characteristics. RESULTS: In total, 188 354 patients were included in the study cohort. Median age (interquartile range) was 77 (71-84) years, and patients had a median (IQR) (interquartile range [IQR]) of 9 (6-13) medications dispensed prior to admission. Within the study population, 6 separate clusters of dispensing patterns were identified: cardiovascular (14%), respiratory (26%), complex care needs (12%), cardiovascular and metabolic (15%), infection (10%), and surgical (24%). Overall, 12 680 (7%) patients had an ADE in the 30 days following discharge. After considering other patient characteristics, those belonging to the respiratory cluster had the highest risk of ADEs (adjusted odds ratio: 1.12, 95% confidence interval: 1.08-1.17) compared with all the other clusters, while those in the complex care needs cluster had the lowest risk (adjusted odds ratio: 0.82, 95% confidence interval: 0.77-0.87). CONCLUSION: This study suggests that ADEs post hospital discharge can be linked with identifiable medication clusters. This information may help clinicians and researchers better understand patient populations that are more or less likely to benefit from peri-hospital discharge interventions aimed at reducing ADEs.

Smart About Meds (SAM): a pilot randomized controlled trial of a mobile application to improve medication adherence following hospital discharge.

OBJECTIVE: The objectives of this pilot study were (1) to assess the feasibility of a larger evaluation of Smart About Meds (SAM), a patient-centered medication management mobile application, and (2) to evaluate SAM's potential to improve outcomes of interest, including adherence to medication changes made at hospital discharge and the occurrence of adverse events. MATERIALS AND METHODS: We conducted a pilot randomized controlled trial among patients discharged from internal medicine units of an academic health center between June 2019 and March 2020. Block randomization was used to randomize patients to intervention (received access to SAM at discharge) or control (received usual care). Patients were followed for 30 days post-discharge, during which app use was recorded. Pharmacy claims data were used to measure adherence to medication changes made at discharge, and physician billing data were used to identify emergency department visits and hospital readmissions during follow-up. RESULTS: Forty-nine patients were eligible for inclusion in the study at hospital discharge (23 intervention, 26 control). In the 30 days of post-discharge, 15 (65.2%) intervention patients used the SAM app. During this period, intervention patients adhered to a larger proportion of medication changes (83.7%) than control patients (77.8%), including newly prescribed medications (72.7% vs 61.7%) and dose changes (90.9% vs 81.8%). A smaller proportion of intervention patients (8.7%) were readmitted to hospital during follow-up than control patients (15.4%). CONCLUSION: The high uptake of SAM among intervention patients supports the feasibility of a larger trial. Results also suggest that SAM has the potential to enhance adherence to medication changes and reduce the risk of downstream adverse events. This hypothesis needs to be tested in a larger trial. TRIAL REGISTRATION: Clinicaltrials.gov, registration number NCT04676165.

Smart about medications (SAM): a digital solution to enhance medication management following hospital discharge.

OBJECTIVE: To outline the development of a software solution to improve medication management after hospital discharge, including its design, data sources, intrinsic features, and to evaluate the usability and the perception of use by end-users. MATERIALS AND METHODS: Patients were directly involved in the development using a User Center Design (UCD) approach. We conducted usability interviews prior to hospital discharge, before a user started using the application. A technology acceptance questionnaire was administered to evaluate user self-perception after 2 weeks of use. RESULTS: The following features were developed; pill identification, patient-friendly drug information leaflet, side effect checker, and interaction checker, adherence monitoring and alerts, weekly medication schedule, daily pill reminders, messaging service, and patient medication reviews. The usability interviews show a 98.3% total success rate for all features, severity (on a scale of 1-4) 1.4 (SD 0.79). Regarding the self-perception of use (1-7 agreement scale) the 3 highest-rated domains were: (1) perceived ease of use 5.65 (SD 2.02), (2) output quality 5.44 (SD 1.65), and (3) perceived usefulness 5.29 (SD 2.11). DISCUSSION: Many medication management apps solutions have been created and most of them have not been properly evaluated. SAM (Smart About Medications) includes the user perspective, integration between a province drug database and the pharmacist workflow in real time. Its features are not limited to maintaining a medication list through manual entry. CONCLUSION: We can conclude after evaluation that the application is usable and has been self-perceived as easy to use by end-users. Future studies are required to assess the health benefits associated with its use.

Patient-initiated consultations in community pharmacies.

BACKGROUND: Mobilizing pharmacists practicing in community pharmacies as a new player in primary care has recently emerged as a cost-effective strategy for clinical consultations related to minor ailments. However, little is known about these consultations initiated by patients. The objectives of this study were to describe patient initiated consultations in community pharmacies, and to estimate the impact of these consultations on care-seeking behaviors of patients. METHODS: A cross sectional study was conducted in 11 retail pharmacies in Quebec, Canada, from October until December 2017, using two data sources: 1) an application and 2) structured interviews. Pharmacists had to compile all consultations in the app during a 4 week-period. Consenting patients were interviewed on the day of the consultation and one week after. Descriptive statistics on the number of consultations were calculated, as well as on the recommendation and the experience of the patient. RESULTS: A total number of 4994 consultations were entered in the app by 55 pharmacists, with an average of 18 consultations (SD = 7) per pharmacy per day. Of the 900 patients consented to participate to the study, 600 (67%) completed the two interviews. Pharmacists reported that they recommended another healthcare resource to patients (e.g. emergency department (ED), walk-in clinic) in only 15% of cases. In the week following the consultation, 105 (18%) patients reported that they avoided going to the ED as a result of the consultation. Patients in rural regions or consulting in a pharmacy far from a medical clinic were more likely to report avoiding an ED visit as a result of the consultation with the pharmacist. CONCLUSIONS: This study suggests that patients are seeking advice from pharmacists for a variety of health care concerns and that pharmacists are able to manage most of these consultations, with a high level of patient satisfaction.

Failure to follow medication changes made at hospital discharge is associated with adverse events in 30 days.

OBJECTIVE: To evaluate the hypothesis that nonadherence to medication changes made at hospital discharge is associated with an increased risk of adverse events in the 30 days postdischarge. STUDY SETTING: Patients admitted to hospitals in Montreal, Quebec, between 2014 and 2016. STUDY DESIGN: Prospective cohort study. DATA COLLECTION: Nonadherence to medication changes was measured by comparing medications dispensed in the community with those prescribed at hospital discharge. Patient, health system, and drug regimen-level covariates were measured using medical services and pharmacy claims data as well as data abstracted from the patient's hospital chart. Multivariable Cox models were used to determine the association between nonadherence to medication changes and the risk of adverse events. PRINCIPAL FINDINGS: Among 2655 patients who met our inclusion criteria, mean age was 69.5 years (SD 14.7) and 1581 (60%) were males. Almost half of patients (n = 1161, 44%) were nonadherent to at least one medication change, and 860 (32%) were readmitted to hospital, visited the emergency department, or died in the 30 days postdischarge. Patients who were not adherent to any of their medication changes had a 35% higher risk of adverse events compared to those who were adherent to all medication changes (1.41 vs 1.27 events/100 person-days, adjusted hazard ratio: 1.35, 95% CI: 1.06-1.71). CONCLUSIONS: Almost half of all patients were not adherent to some or all changes made to their medications at hospital discharge. Nonadherence to all changes was associated with an increased risk of adverse events. Interventions addressing barriers to adherence should be considered moving forward.

Both New and Chronic Potentially Inappropriate Medications Continued at Hospital Discharge Are Associated With Increased Risk of Adverse Events.

BACKGROUND: Admission to hospital provides the opportunity to review patient medications; however, the extent to which the safety of drug regimens changes after hospitalization is unclear. OBJECTIVE: To estimate the number of potentially inappropriate medications (PIMs) prescribed to patients at hospital discharge and their association with the risk of adverse events 30 days after discharge. DESIGN: Prospective cohort study. SETTING: Tertiary care hospitals within the McGill University Health Centre Network in Montreal, Quebec, Canada. PARTICIPANTS: Patients from internal medicine, cardiac, and thoracic surgery, aged 65 years and older, admitted between October 2014 and November 2016. MEASURES: Abstracted chart data were linked to provincial health databases. PIMs were identified using AGS (American Geriatrics Society) Beers Criteria®, STOPP, and Choosing Wisely statements. Multivariable logistic regression and Cox models were used to assess the association between PIMs and adverse events. RESULTS: Of 2,402 included patients, 1,381 (57%) were male; median age was 76 years (interquartile range [IQR] = 70-82 years); and eight discharge medications were prescribed (IQR = 2-8). A total of 1,576 (66%) patients were prescribed at least one PIM at discharge; 1,176 (49%) continued a PIM from prior to admission, and 755 (31%) were prescribed at least one new PIM. In the 30 days after discharge, 218 (9%) experienced an adverse drug event (ADE) and 862 (36%) visited the emergency department (ED), were rehospitalized, or died. After adjustment, each additional new PIM and continued community PIM were respectively associated with a 21% (odds ratio [OR] = 1.21; 95% confidence interval [CI] = 1.01-1.45) and a 10% (OR = 1.10; 95% CI = 1.01-1.21) increased odds of ADEs. They were also respectively associated with a 13% (hazard ratio [HR] = 1.13; 95% CI = 1.03-1.26) and a 5% (HR = 1.05; 95% CI = 1.00-1.10) increased risk of ED visits, rehospitalization, and death. CONCLUSIONS: Two in three hospitalized patients were prescribed a PIM at discharge, and increasing numbers of PIMs were associated with an increased risk of ADEs and all-cause adverse events. Improving hospital prescribing practices may reduce the frequency of PIMs and associated adverse events. J Am Geriatr Soc 68:1184-1192, 2020.

Effect of an Electronic Medication Reconciliation Intervention on Adverse Drug Events: A Cluster Randomized Trial.

Importance: Adverse drug events (ADEs) account for up to 16% of emergency department (ED) visits and 7% of hospital admissions. Medication reconciliation is required for hospital accreditation because it can reduce medication discrepancies, but there is no evidence that reducing discrepancies reduces ADEs or other adverse outcomes. Objective: To evaluate whether electronic medication reconciliation reduces ADEs, medication discrepancies, and other adverse outcomes compared with usual care. Design, Setting, and Participants: This cluster randomized trial involved 3491 patients who were discharged from 2 medical units and 2 surgical units at the McGill University Health Centre, Montreal, Quebec, Canada, between October 2014 and November 2016. Data analysis took place from July 2017 to July 2019. Intervention: The RightRx intervention electronically retrieved community drugs from the provincial insurer and aligned them with in-hospital drugs to facilitate reconciliation and communication at care transitions. Main Outcomes and Measures: The primary outcome was ADEs in 30 days after discharge. Secondary outcomes included medication discrepancies, ED visits, hospital readmissions, and a composite outcome of ED visits, readmissions, and death up to 90 days after discharge. Results: Of 4656 eligible patients, 3567 (76.6%) consented to participate (2060 [57.8%] men; mean [SD] age, 69.8 [14.9] years). Overall, 76 patients died during the hospital stay, so 3491 patients were included in the analysis. There was no significant difference in the risk of ADEs between intervention and control groups (76 [4.6%] vs 73 [4.0%]; OR, 0.97; 95% CI, 0.33-1.48), ED visits (433 [26.2%] vs 488 [26.6%]; OR, 0.83; 95% CI, 0.36-1.42), hospital readmission (170 [10.3%] vs 261 [14.2%]; OR, 0.22; 95% CI, 0.06-1.14), or the composite outcome (447 [27.0%] vs 506 [27.6%]; OR, 0.75; 95% CI, 0.34-1.27) at 30 days. Medication discrepancies were significantly reduced in the intervention group compared with the control group (437 [26.4%] vs 1029 [56.0%]; OR, 0.24; 95% CI, 0.12-0.57). Changes made to community medications (OR, 1.05; 95% CI, 1.01-1.10) and new medications (OR, 1.09; 95% CI, 1.01-1.18) were significant risk factors for ADEs. Conclusions and Relevance: Electronic medication reconciliation reduced medication discrepancies but did not reduce ADEs or other adverse outcomes. Hospital accreditation should focus on interventions that reduce the risk of adverse events for patients with multiple changes to community medications. Trial Registration: ClinicalTrials.gov identifier: NCT01179867.

Evaluation of a Mobile Application to Enhance Medication Management Following Hospital Discharge: Study Protocol for a Pilot Randomized Controlled Trial.

Over 3 million hospitalizations and 17 million ER visits occur in Canada each year. A substantial proportion of these encounters are preventable and attributable to medication non- adherence. Non-adherence to medication changes during discharge increases the risk of adverse events post-discharge. A mobile application was developed to improve medication management of post-discharge patients. A pilot randomized controlled trial was conducted to assess the application's usability and efficacy in decreasing non-adherence to medication changes made at discharge.

Challenges at Care Transitions: Failure to Follow Medication Changes Made at Hospital Discharge.

BACKGROUND: In-hospital medication reconciliation has not demonstrated reductions in adverse health outcomes, possibly because patients do not follow the changes made to their preadmission medications. Our objective was to determine the incidence of and variables associated with failure to follow newly prescribed therapies, discontinued medications, and dose changes. METHODS: A prospective cohort study of patients admitted to hospitals in Montreal, Quebec between 2014 and 2016 was conducted. Failure to follow medication changes 30 days post discharge was measured by comparing prescribed and dispensed medications. Multivariable logistic regression was used to determine characteristics associated with failure to follow changes. RESULTS: Among 2655 patients, mean age was 69.5 years (SD 14.7), and 1581 (60%) were males. There were 10,068 medication changes made at hospital discharge and 24% were not followed in the 30 days post discharge. Thirty percent of dose modifications were filled at the incorrect dose, 27% of new medications were not filled, and 12% of discontinued medications were filled. A number of factors increased the risk of failure to follow medication changes, including increasing out-of-pocket medication costs (adjusted odds ratio [aOR] 1.12; 95% confidence interval [CI], 1.07-1.18), discharge to long-term care facility (aOR 2.29; 95% CI, 1.63-3.08), and not having medications dispensed prior to admission (aOR 4.67; 95% CI, 3.75-5.90). CONCLUSION: One in 4 hospital medication changes was not followed post discharge. Health policy aimed at eliminating out-of-pocket medication costs and investigation of factors influencing failure to follow changes for those not dispensed medications prior to admission and for long-term care residents are important next steps to address this issue.

Benzodiazepine receptor agonist dispensations in Alberta: a population-based descriptive study.

BACKGROUND: There is increasing concern over the use of benzodiazepine receptor agonists (BZRAs). The objective of this study was to describe BZRA dispensations in the province of Alberta in 2015 according to age, sex and appropriateness. METHODS: A population-based descriptive study of people 10 years of age or older with at least 1 BZRA dispensation in Alberta, Canada, between Jan. 1 and Dec. 31, 2015, was conducted. Prevalence of BZRA use, characteristics of BZRAs dispensations, use at the individual level and appropriateness were determined. RESULTS: A total of 372 870 people received 2 463 585 BZRA dispensations in Alberta in 2015. Prevalence of use at the population level was 10% overall, increased with age (p value for trend < 0.001) and was consistently highest among females. Twenty percent of patients used both Z-drugs and benzodiazepines. BZRA users had an average of 7 dispensations (standard deviation [SD] 20), 137 days of use overall (SD 123) and a maximum period of consecutive use of 90 days (SD 95). Days of consecutive use were highest among those aged 65 years or older (126 d). A total of 62 795 (17%) people used more than 1 distinct BZRA ingredient concurrently and 10% had 3 or more distinct prescribers. INTERPRETATION: The prevalence of BZRA use was high and a substantial proportion of use appeared to be potentially inappropriate. This study supports the need for continued monitoring for the prescribing and use of these medications at the population level.

Ability to Predict New-Onset Psychological Distress Using Routinely Collected Health Data: A Population-Based Cohort Study of Women Diagnosed With Breast Cancer.

Objectives: The primary objective of this study was to identify the predictors of new-onset psychological distress available in routinely collected administrative health databases for women diagnosed with breast cancer. The secondary objective was to explore whether the predictors vary based on the period of cancer care. Methods: A population-based cohort study followed 16,495 female patients with newly diagnosed breast cancer who did not experience psychological distress during the 14 months before breast cancer surgery. The incidence of psychological distress was reported overall and by type of mental health problem. Time-varying Cox proportional hazards models were developed to identify predictors of new-onset psychological distress during 2 key periods of cancer care: (1) hospital-based treatment during which women undergo treatment with breast surgery, chemotherapy, and/or radiation, and (2) 1-year transitional survivorship when women begin follow-up care. Results: The incidence of psychological distress was 16% within each period. Anxiety was present in 85.1% and 65.5% of new cases during hospital-based treatment and transitional survivorship, respectively. Predictors during both periods were younger age, receipt of axillary lymph node dissection, rheumatologic disease, and baseline menopausal symptoms, as well as new opioid dispensations, emergency department visits, and hospital contacts that occurred during follow-up. Other predictors varied based on the period of cancer care. More advanced breast cancer and type of treatment were associated with onset of psychological distress during hospital-based treatment. Psychological distress during transitional survivorship was predicted by diagnosis of localized breast disease, shorter duration of hospital-based treatment, receipt of additional hospital-based treatment in survivorship, and newly diagnosed comorbidities or symptoms. Conclusions: This study identified the predictors of new-onset psychological distress available in routinely collected administrative health databases, and showed how predictors change between hospital-based treatment and transitional survivorship periods. The results highlight the importance of developing predictive models tailored to the period of cancer care.

Acute vs cumulative benefits of metformin use in patients with type 2 diabetes and heart failure.

AIMS: To evaluate the association between metformin use and heart failure (HF) exacerbation in people with type 2 diabetes (T2D) and pre-existing HF using alternative exposure models. MATERIALS AND METHODS: We analysed data for patients with T2D and incident HF from a national US insurance claims database. We compared the results of several multivariable Cox models where time-varying use of metformin was modelled as: (1) current use; (2) total duration of past use; and (3) use within the past 30 days or 10 days. The outcome was defined as time to HF-related hospitalization. We then re-analysed the data using flexible weighted cumulative exposure (WCE) models. RESULTS: A total of 7620 patients with diabetes and incident HF were analysed. The mean (SD) patient age was 54 (8) years, and 58% (n = 4440) were men. In all, 3799 individuals (50%) were exposed to metformin, and 837 HF hospitalizations (11%) occurred (mean follow-up 1.7 years). Results of conventional models suggested potential acute benefits in reducing HF exacerbation with metformin use in the past 10 days (adjusted hazard ratio [aHR] 0.76, 95% confidence interval [CI] 0.60-0.97), while WCE models, which provided a better fit for the data, suggested lack of a systematic effect (aHR 0.91, 95% CI 0.69-1.20). CONCLUSIONS: Our results suggest that cumulative metformin exposure does not decrease the risk of HF-related exacerbation. Use of other anti-hyperglycaemic agents with proven efficacy in patients with HF should also be considered as treatment options in this population.

Usage and accuracy of medication data from nationwide health information exchange in Quebec, Canada.

Objective: (1) To describe the usage of medication data from the Health Information Exchange (HIE) at the health care system level in the province of Quebec; (2) To assess the accuracy of the medication list obtained from the HIE. Methods: A descriptive study was conducted utilizing usage data obtained from the Ministry of Health at the individual provider level from January 1 to December 31, 2015. Usage patterns by role, type of site, and tool used to access the HIE were investigated. The list of medications of 111 high risk patients arriving at the emergency department of an academic healthcare center was obtained from the HIE and compared with the list obtained through the medication reconciliation process. Results: There were 31 022 distinct users accessing the HIE 11 085 653 times in 2015. The vast majority of pharmacists and general practitioners accessed it, compared to a minority of specialists and nurses. The top 1% of users was responsible of 19% of access. Also, 63% of the access was made using the Viewer application, while using a certified electronic medical record application seemed to facilitate usage. Among 111 patients, 71 (64%) had at least one discrepancy between the medication list obtained from the HIE and the reference list. Conclusions: Early adopters were mostly in primary care settings, and were accessing it more frequently when using a certified electronic medical record. Further work is needed to investigate how to resolve accuracy issues with the medication list and how certain tools provide different features.

The Interplay Between Continuity of Care, Multimorbidity, and Adverse Events in Patients With Diabetes.

OBJECTIVES: To evaluate the impact of continuity of care and multimorbidity on health outcomes in patients with diabetes. RESEARCH DESIGN: Using a US claims database of insured patients, we identified those with incident diabetes between 2004 and 2008 and followed them until death, disenrollment, or December 31, 2010. Continuity of care was defined using Breslau's Usual Provider of Continuity (UPC; proportion of visits to the usual or predominant provider within 2 y of diabetes diagnosis). Multivariable logistic regression was used to determine the association between UPC in the first 2 years after diabetes diagnosis and subsequent 1-year composite primary outcome of all-cause hospitalization or death in year 3 in patients with/without multimorbidity. RESULTS: Of the 285,231 patients with incident diabetes, 74% had multimorbidity; their average age was 53 years (SD=10.5) and 49% were female. A total of 77,270 (27%) individuals had a mean UPC≥75% in the first 2 years. During year 3 of follow-up, 33,632 (12%) patients died or were hospitalized for any cause. Greater continuity of care (UPC≥75%) was associated with reduced risk of subsequent death or hospitalization [7.2% vs. 13.5%; adjusted odds ratio (aOR)=0.72; 95% CI, 0.70-0.75]. Although multimorbidity was independently associated with an increased risk of our primary composite endpoint (13.4% vs. 7.2%; aOR=1.26; 95% CI, 1.21-1.30), the association between greater continuity and better outcomes was similar in those with multimorbidity (aOR=0.71; 95% CI, 0.69-0.71) as in those without (aOR=0.75; 95% CI, 0.71-0.80). CONCLUSIONS: In patients with incident diabetes, greater continuity of care is associated with improved outcomes, irrespective of whether or not they have multimorbidity.

Sitagliptin use in patients with diabetes and heart failure: a population-based retrospective cohort study.

OBJECTIVES: The study objective was to evaluate the effects of sitagliptin in patients with type 2 diabetes (T2D) and heart failure (HF). BACKGROUND: There is uncertainty in the literature about whether dipeptidyl peptidase (DPP)-4 inhibitors cause harm in patients with HF and T2D. METHODS: We analyzed data from a national commercially insured U.S. claims database. Patients with incident HF were identified from individuals with T2D initially treated with metformin or sulfonylurea and followed over time. Subjects subsequently using sitagliptin were compared with those not using sitagliptin in the 90 days before our primary outcome of all-cause hospital admission or death using a nested case-control analysis after adjustment for demographics and clinical and laboratory data. HF-specific hospital admission or death also was assessed. RESULTS: A total of 7,620 patients with diabetes and incident HF met our inclusion criteria. Mean (SD) age was 54 years (9), and 58% (3,180) were male. Overall, 887 patients (12%) were exposed to sitagliptin therapy (521 patient years of exposure) after incident HF. Our primary composite endpoint occurred in 4,137 patients (54%). After adjustment, sitagliptin users were not at an increased risk for the primary endpoint (7.1% vs. 9.2%, adjusted odds ratio [aOR]: 0.84, 95% confidence interval [CI]: 0.69 to 1.03) or each component (hospital admission 7.5% vs. 9.2%, aOR: 0.93, 95% CI: 0.76 to 1.14; death 6.9% vs. 9.3%, aOR: 1.16, 95% CI: 0.68 to 1.97). However, sitagliptin use was associated with an increased risk of HF hospitalizations (12.5% vs. 9.0%, aOR: 1.84, 95% CI: 1.16 to 2.92). CONCLUSIONS: Sitagliptin use was not associated with an increased risk of all-cause hospitalizations or death, but was associated with an increased risk of HF-related hospitalizations among patients with T2D with pre-existing HF.

Cardiovascular medication utilization and adherence among adults living in rural and urban areas: a systematic review and meta-analysis.

BACKGROUND: Rural residents face numerous barriers to healthcare access and studies suggest poorer health outcomes for rural patients. Therefore we undertook a systematic review to determine if cardiovascular medication utilization and adherence patterns differ for rural versus urban patients. METHODS: A comprehensive search of major electronic datasets was undertaken for controlled clinical trials and observational studies comparing utilization or adherence to cardiovascular medications in rural versus urban adults with cardiovascular disease or diabetes. Two reviewers independently identified citations, extracted data, and evaluated quality using the STROBE checklist. Risk estimates were abstracted and pooled where appropriate using random effects models. Methods and reporting were in accordance with MOOSE guidelines. RESULTS: Fifty-one studies were included of fair to good quality (median STROBE score 17.5). Although pooled unadjusted analyses suggested that patients in rural areas were less likely to receive evidence-based cardiovascular medications (23 studies, OR 0.88, 95% CI 0.79, 0.98), pooled data from 21 studies adjusted for potential confounders indicated no rural-urban differences (adjusted OR 1.02, 95% CI 0.91, 1.13). The high heterogeneity observed (I(2) = 97%) was partially explained by treatment setting (hospital, ambulatory care, or community-based sample), age, and disease. Adherence did not differ between urban versus rural patients (3 studies, OR 0.94, 95% CI 0.39, 2.27, I(2) = 91%). CONCLUSIONS: We found no consistent differences in rates of cardiovascular medication utilization or adherence among adults with cardiovascular disease or diabetes living in rural versus urban settings. Higher quality evidence is needed to determine if differences truly exist between urban and rural patients in the use of, and adherence to, evidence-based medications.

A primary care based healthy-eating and active living education session for weight reduction in the pre-diabetic population.

AIMS: Many studies have demonstrated the effectiveness of primary prevention strategies in type 2 diabetes, however, questions remain around the feasibility of high resource, intensive interventions within a healthcare setting. We report the results of a dietitian-led pre-diabetes education session targeting healthy eating and active living as strategies for weight reduction. METHODS: Participants were asked to complete a baseline questionnaire prior to completing the pre-diabetes education session and were sent follow-up questionnaires at 3 and 6 months. Differences between participants at baseline, 3 and 6 months were determined using χ(2), t-tests and ANOVA. RESULTS: Of the 211 participants asked to fill out baseline questionnaires, 45 participants completed questionnaires at baseline, 3 months and 6 months. Although we observed general trends towards improvements in diet, physical activity and weight related behaviours among the 45 completers, no significant changes were observed among participants between questionnaire periods. CONCLUSION: A "one-off", theory-guided group education session may be insufficient to support lifestyle modifications in the context of weight management in a pre-diabetic population. Further evaluation of the efficacy and feasibility of the PCN as a setting for lifestyle intervention is required.

Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients.

BACKGROUND: There is an ongoing controversy regarding the safety and effectiveness of metformin in the setting of heart failure (HF). Therefore, we undertook a systematic review of the trial and nontrial evidence for metformin in patients with diabetes mellitus and HF. METHODS AND RESULTS: We conducted a comprehensive search for controlled studies, evaluating the association between metformin and morbidity and mortality in people with diabetes mellitus and HF. Two reviewers independently identified citations, extracted data, and evaluated quality. Risk estimates were abstracted and pooled where appropriate. As measures of overall safety, we examined all-cause mortality and all-cause hospitalizations. Nine cohort studies were included; no randomized controlled trials were identified. Most (5 of 9) studies were published in 2010 and were of good quality. Metformin was associated with reduced mortality compared with controls (mostly sulfonylurea therapy): 23% versus 37% (pooled adjusted risk estimates: 0.80; 0.74-0.87; I(2)=15%; P<0.001). No increased risk was observed for metformin in those with reduced left ventricular ejection fraction (mortality pooled adjusted risk estimate: 0.91; 0.72-1.14; I(2)=0%; P=0.34), nor in those with HF and chronic kidney disease (pooled adjusted risk estimate: 0.81; 0.64-1.02; P=0.08). Metformin was associated with a small reduction in all-cause hospitalizations (pooled adjusted risk estimate: 0.93; 0.89-0.98; I(2)=0%; P=0.01). Metformin was not associated with increased risk of lactic acidosis. CONCLUSIONS: The totality of evidence indicates that metformin is at least as safe as other glucose-lowering treatments in patients with diabetes mellitus and HF and even in those with reduced left ventricular ejection fraction or concomitant chronic kidney disease. Until trial data become available, metformin should be considered the treatment of choice for patients with diabetes mellitus and HF.

Analysis of drug coverage before and after the implementation of Canada's Common Drug Review.

BACKGROUND: Canada's Common Drug Review was implemented to provide publicly funded drug plans (provincial and federal) with a transparent, rigorous and consistent approach for assessing the clinical effectiveness and cost-effectiveness of new drugs. We compared uptake of drug coverage across jurisdictions before and after the implementation of the Common Drug Review. METHODS: Using the IMS Brogan formulary acceptance: monitoring and evaluation database, we identified new drug products in Canada five years before and five years after the first recommendation was made by the Common Drug Review. For each jurisdiction, we compared the proportion of drugs listed, the median time-to-listing and the agreement between the listing decisions of the drug plans and the recommendations of the Common Drug Review. RESULTS: We identified 198 new drugs approved for use in Canada between May 26, 1999, and May 27, 2009, of which 53 had a recommendation from the Common Drug Review. The proportion of drugs listed decreased after the introduction of the Common Drug Review for all participating drug plans (81.1% to 71.3% overall [p ≤ 0.01 for all plans, with the exceptions of Ontario and Quebec [p = 0.07]). The change in median time-to-listing between the periods before and after the Common Drug Review varied by jurisdiction, ranging from a decrease of 691 days to an increase of 250 days. The change in median time-to-listing was not statistically significant for most jurisdictions, with the exceptions of Saskatchewan (increased, Mann-Whitney U test p = 0.01) and New Brunswick, Prince Edward Island, and Newfoundland and Labrador (all decreased, Mann-Whitney U test p < 0.01). INTERPRETATION: There was a decline in the proportion of new drugs listed after the introduction of the Common Drug Review for both participating and nonparticipating jurisdictions. The introduction of the review was associated with a decreased time-to-listing for certain smaller provinces.