Predictors of hospitalization in a Canadian MS population: A matched cohort study.

OBJECTIVE: Hospitalizations are the most costly component of healthcare in Canada, and hospitalization rates are higher in the multiple sclerosis (MS) population compared to the general population. This study aimed to examine predictors of hospitalizations in the MS population in Saskatchewan, Canada. METHODS: This retrospective cohort study used population-based health administrative data from Saskatchewan, Canada from 1996 to 2016. Subjects with MS were identified using a validated definition (≥3 hospital, physician, or drug claims for MS). Up to five general population controls were identified for each MS case and matched on sex, age, and geographical location. The rate of hospitalizations and reason for admission were determined for each case and control. Negative binomial (hospitalization rate) and binary logistic (reason for admission) regression models fitted with generalized estimating equations were used to test the following potential predictors: sex, age, median household income, calendar year, prior hospitalizations, and comorbidity status. RESULTS: We identified 4,878 MS cases (11,744 hospitalizations), and 23,662 matched controls (32,541 hospitalizations). Higher comorbidity burden, older age, and prior hospital admissions were associated with an increased rate of all-cause hospitalizations for both cohorts. Males were more likely to be hospitalized than females for all-cause (adjusted rate ratio: 1.20; 95% CI: 1.07 - 1.34) and MS-specific (adjusted odds ratio: 1.34; 95% CI 1.15 - 1.55) hospitalizations. The rate of MS-specific hospitalizations decreased with age, and there was no association with comorbidity or prior hospitalizations. A diagnosis of MS was associated with decreased odds of hospitalization due to neoplasms, diseases of the circulatory system, and mental health and behavioural disorders. CONCLUSION: Increased age, comorbidity, and prior hospital admissions are predictors of all-cause hospitalizations. Conversely, MS-related hospitalizations decreased as subjects aged, and there was no association with comorbidity. Our results highlight that reasons for hospitalizations can differ by age, and clinicians should consider this when managing patients, as they make efforts to reduce hospitalizations in the MS population.

Individualised behaviour change strategies for physical activity in multiple sclerosis (IPAC-MS): protocol for a randomised controlled trial.

BACKGROUND: Multiple sclerosis (MS) is a chronic, degenerative disease of the central nervous system. Because of the long-term and unpredictable nature of the disease, the burden of MS is significant from both a patient and societal perspective. Despite a recent influx of disease-modifying therapies to treat MS, many individuals continue to experience disability that negatively affects productivity and quality of life. Previous research indicates that physical activity has a positive impact on walking function in individuals with MS, in addition to the usual beneficial effects on overall health. However, most people with MS are not active enough to gain these benefits, and a lack of support to initiate and maintain physical activity has been identified as a major barrier. This study will evaluate the impact of a novel intervention involving individualised behaviour change strategies delivered by neurophysiotherapists on increasing physical activity levels in individuals with MS who are currently inactive. METHODS/DESIGN: This single-blind, parallel-group, randomised controlled trial will be conducted in Saskatchewan, Canada. Eligible participants include individuals with MS who are ambulatory but identified as currently inactive by the self-reported Godin Leisure-Time Exercise Questionnaire (GLTEQ). The intervention will be delivered by neurophysiotherapists and includes individualised behaviour change strategies aimed at increasing physical activity over a 12-month period. The control group will receive usual care during the 12-month study period. The primary outcome is the change in physical activity level, as measured by the change in the GLTEQ score from baseline to 12 months. Secondary outcomes include the change in patient-reported outcome measures assessing MS-specific symptoms, confidence and quality of life. DISCUSSION: Physical activity has been identified as a top research priority by the MS community. Findings from this novel study may result in new knowledge that could significantly impact the management and overall health of individuals with MS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04027114. Registered on 10 July 2019.

Impact of Pilates Exercise in Multiple Sclerosis: A Randomized Controlled Trial.

BACKGROUND: Pilates is a series of exercises based on whole-body movement and may improve mobility in people with multiple sclerosis (MS). The purpose of this study was to determine the effect of Pilates on walking performance in people with MS. METHODS: 30 individuals with MS who were not restricted to a wheelchair or scooter (Patient-Determined Disease Steps scale score <7) were randomized to receive Pilates (twice weekly) and massage therapy (once weekly) or once-weekly massage therapy only (control group). The Pilates was delivered in a group setting (five to ten participants per session). The primary outcome was change in walking performance (6-Minute Walk Test) after 12 weeks. Secondary outcomes included functional ability (Timed Up and Go test), balance (Fullerton Advanced Balance Scale), flexibility (sit and reach test), body composition (dual-energy X-ray absorptiometry), core endurance (plank-hold test), and muscle strength and voluntary activation (quadriceps). Intention-to-treat analysis was performed using a two-factor repeated-measures analysis of variance. RESULTS: Walking distance increased by a mean (SD) of 52.4 (40.2) m in the Pilates group versus 15.0 (34.1) m in the control group (group × time, P = .01). Mean (SD) time to complete the Timed Up and Go test decreased by 1.5 (2.8) seconds in the Pilates group versus an increase of 0.3 (0.9) seconds in the control group (group × time, P = .03). There were no other significant differences between groups over time. CONCLUSIONS: Pilates improved walking performance and functional ability in persons with MS and is a viable exercise option to help manage the disease.

Establishing the Incidence and Prevalence of Multiple Sclerosis in Saskatchewan.

OBJECTIVE: To validate a case definition of multiple sclerosis (MS) using health administrative data and to provide the first province-wide estimates of MS incidence and prevalence for Saskatchewan, Canada. METHODS: We used population-based health administrative data between January 1, 1996 and December 31, 2015 to identify individuals with MS using two potential case definitions: (1) ≥3 hospital, physician, or prescription claims (Marrie definition); (2) ≥1 hospitalization or ≥5 physician claims within 2 years (Canadian Chronic Disease Surveillance System [CCDSS] definition). We validated the case definitions using diagnoses from medical records (n=400) as the gold standard. RESULTS: The Marrie definition had a sensitivity of 99.5% (95% confidence interval [CI] 92.3-99.2), specificity of 98.5% (95% CI 97.3-100.0), positive predictive value (PPV) of 99.5% (95% CI 97.2-100.0), and negative predictive value (NPV) of 97.5% (95% CI 94.4-99.2). The CCDSS definition had a sensitivity of 91.0% (95% CI 81.2-94.6), specificity of 99.0% (95% CI 96.4-99.9), PPV of 98.9% (95% CI 96.1-99.9), and NPV of 91.7% (95% CI 87.2-95.0). Using the more sensitive Marrie definition, the average annual adjusted incidence per 100,000 between 2001 and 2013 was 16.5 (95% CI 15.8-17.2), and the age- and sex-standardized prevalence of MS in Saskatchewan in 2013 was 313.6 per 100,000 (95% CI 303.0-324.3). Over the study period, incidence remained stable while prevalence increased slightly. CONCLUSION: We confirm Saskatchewan has one of the highest rates of MS in the world. Similar to other regions in Canada, incidence has remained stable while prevalence has gradually increased.

Community Pharmacists Assisting in Total Cardiovascular Health (CPATCH): A Cluster-Randomized, Controlled Trial Testing a Focused Adherence Strategy Involving Community Pharmacies.

STUDY OBJECTIVE: To test a brief intervention for preventing statin nonadherence among community pharmacy patrons. DESIGN: Prospective, cluster-randomized, controlled trial (the Community Pharmacists Assisting in Total Cardiovascular Health [CPATCH] trial). SETTING: Thirty community pharmacies in Saskatchewan, Canada. PATIENTS: Participating pharmacies were randomized to 15 intervention pharmacies where a brief statin adherence intervention was delivered by pharmacists (intervention group [907 patients]) or 15 usual care pharmacies where no statin adherence intervention was delivered (usual care group [999 patients]) to new users of statins (defined as less than 1 yr of statin therapy). INTERVENTION: Staff (pharmacy managers, staff pharmacists, and technicians) from intervention pharmacies attended a 2.5-hour workshop on the CPATCH program that prepared pharmacists to deal with the adherence barriers most likely associated with statin use (e.g., safety, cost, patient-provider relationship, and tolerability). Intervention pharmacists screened for new statin users and assessed these adherence barriers. Pharmacists were then instructed to tailor their follow-up plan based on the individual patient's situation. Investigators contacted the intervention pharmacies monthly to assess their compliance with the protocol and to offer additional support to motivate ongoing participation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mean difference in statin adherence between the intervention and usual care groups. Adherence was measured by the proportion of days covered (PDC) between 6 and 12 months following the original prescription fill date. General estimating equations were used to evaluate the difference in mean adherence between groups. Secondary outcomes included the percentage of new statin users exhibiting optimal adherence (defined as PDC of 80% or higher) and the percentage exhibiting nonpersistence (defined as the cessation of all statin dispensations within 3 mo of the first dispensation). Among 1906 eligible patients, no significant differences in mean adherence were observed between those receiving the intervention and those receiving usual care (71.6% vs 70.9%, p=0.64), the percentage of patients achieving optimal adherence (57.3% vs 55.9%, p=0.51), or the percentage exhibiting nonpersistence (9.4% vs 8.3%, p=0.41). However, compliance to the study protocol was extremely low in several intervention pharmacies. In a post hoc analysis, a higher level of protocol compliance among intervention pharmacies was significantly associated with higher adherence (p<0.01 for trend). Pharmacies falling in the highest tertile of compliance to the study protocol exhibited higher mean adherence among their patients compared with those in the usual care group (ß = 0.056, 95% confidence interval [CI] 0.010-0.101, p=0.01), and a significantly higher percentage of patients achieving optimal adherence (odds ratio 1.32, 95% CI 1.08-1.61; p<0.01); however, nonpersistence did not significantly differ between the two groups (5.5% vs 8.3%, p=0.27). CONCLUSION: The CPATCH intervention was ineffective for improving patient adherence to statin therapy in community pharmacies. However, poor effectiveness may have resulted from a failure to deliver the protocol consistently in several intervention pharmacies.

The association between market availability and adherence to antihypertensive medications: an observational study.

BACKGROUND: High adherence to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reported in observational studies has frequently been attributed to improved tolerability. However, these agents are also relatively new to the market compared to other antihypertensive medications. We aimed to determine if an association exists between adherence and market availability of a specific antihypertensive agent. METHODS: This retrospective cohort study used administrative data from Saskatchewan, Canada. Subjects were ≥40 years of age and received a new antihypertensive medication between 1994 and 2002. The primary outcome was the proportion of subjects achieving optimal adherence (≥80%) at 1 year, stratified by antihypertensive medication class and the year of availability. Adherence was measured using the cumulative mean gap ratio. RESULTS: A total of 36,214 subjects met the inclusion criteria. Optimal adherence was observed in 4987 of 8623 (57.8%) subjects receiving ACEIs and 1013 of 1600 (63.3%) subjects receiving ARBs, but adherence appeared inconsistent when examined within each antihypertensive class. A pattern of increasing mean adherence was observed according to availability in the ACEI subgroup (Spearman r = 0.82; P = 0.007) but not the ARB subgroup (Spearman r = 0.41; P = 0.49). However, the association between availability and optimal adherence converged when ARB and ACEI users were combined (Spearman r = 0.85, P < 0.001). CONCLUSIONS: Optimal adherence with ACEIs and ARBs compared to other antihypertensive agents may be associated with their relative availability. To what extent optimal adherence is also associated with improved tolerability, as currently believed, remains to be determined.

First-fill medication discontinuations and nonadherence to antihypertensive therapy: an observational study.

BACKGROUND: Medication nonadherence is a barrier to successfully managing hypertension, but little is known about the contribution that immediate discontinuations have on antihypertensive (AHT) nonadherence. The purpose of this study was to determine the proportion of new AHT users who discontinue after a single dispensation, and to examine potential predictors of these discontinuations. METHODS: This retrospective cohort study utilizing linked administrative data from Saskatchewan, Canada. Subjects were ≥40 years of age and received a new AHT between 1994-2002. The primary end point was the proportion of subjects who discontinued their AHT after the first dispensation (first-fill discontinuation). The proportion of nonadherence attributed to first-fill discontinuations was then calculated. Multivariate regression identified factors associated with first-fill discontinuations. RESULTS: 52,039 subjects were included in the analyses. Mean age was 59.4 (s.d. 12.5) years, and 42% were male. Overall, 25,812/52,039 (50%) subjects were nonadherent at 1 year; first-fill discontinuations accounted for 39.1% (10,081/25,812) of this nonadherence. Approximately 20% (10,081/52,039) of all subjects discontinued all AHT therapy after the first fill. A higher chronic disease score (adjusted odds ratio (OR) 1.09, 95% confidence interval (CI) 1.08-1.11) and antidepressant medication usage during the observation year (adjusted OR 1.17, 95% CI 1.09-1.26) was associated with increased risk for first-fill discontinuations. Older age, starting AHT therapy after 1994, frequent physician visits, or use of a statin, acetylsalicylic acid, warfarin or antihyperglycemic during the observation year was associated with a lower risk for first-fill discontinuations. CONCLUSION: A substantial proportion of nonadherence to AHT medications is due to discontinuations after only a single dispensation.

Diabetes and cardiovascular disease interventions by community pharmacists: a systematic review.

OBJECTIVE: To systematically review and assess the quality of studies evaluating community pharmacist interventions for preventing or managing diabetes or cardiovascular disease (CVD) and/or their major risk factors. DATA SOURCES: A comprehensive literature search was performed using MEDLINE (1950-February 2011), EMBASE (1980-February 2011), International Pharmaceutical Abstracts (1970-February 2011), Cumulative Index to Nursing and Allied Health Literature (1982-June 2007), and Cochrane Central Register of Controlled Trials (1898-February 2011). Search terms included: community pharmacy(ies), community pharmacist(s), cardiovascular, diabetes, and intervention. The grey literature was searched using the ProQuest Dissertations and Theses, Theses Canada, and OAlster databases. STUDY SELECTION AND DATA EXTRACTION: Articles published in English or French with all study designs were considered for the review. Studies were included if they contained interventions designed to reduce the incidence, risk, or mortality of CVD or diabetes; affect clinical indicators of CVD or diabetes mellitus (including hypertension, dyslipidemia, or hemoglobin A(1c)); and/or improve adherence to treatment strategies. Only studies involving interventions carried out primarily by pharmacists in community pharmacy settings were included. Study quality was assessed using a checklist validated for both randomized and nonrandomized studies. DATA SYNTHESIS: A total of 4142 studies were initially identified, with 40 meeting our inclusion criteria. Eleven studies were randomized controlled trials, 4 were cluster randomized trials, and 2 studies had randomized before-after designs. The remaining studies were controlled before-after (n = 2), cohort (n = 4), and uncontrolled before-after (n = 17) designs. Interventions focused on diabetes (n = 12), hypertension (n = 9), medication adherence (n = 9), lipids (n = 5), evidence-based medication initiation or optimization (n = 3), risk factor prediction scores (n = 1), and body mass index (n = 1). All studies contained interventions focused at the patient level and the majority of studies (34/40) involved interventions directed at both the physician and patient. No specific intervention emerged as superior, and study quality was generally poor, making it difficult to determine the true effect of the interventions. CONCLUSIONS: Poor study quality, time-intensive interventions, and unproven clinical significance warrant the need for further high-quality studies of community pharmacist interventions for preventing or managing diabetes or CVD and/or their major risk factors.

The Collaborative Cardiovascular Risk Reduction in Primary Care (CCARP) study.

STUDY OBJECTIVE: To evaluate whether a simple pharmacist protocol, consisting of patient screening and cardiovascular risk stratification, identification and reminders about uncontrolled risk factors, and drug adherence support, can significantly reduce cardiovascular risk. DESIGN: Prospective, randomized, controlled pilot study. SETTING: Large primary care medical clinic in Saskatoon, Saskatchewan, Canada. PATIENTS: One hundred seventy-six adult patients (mean age 60 yrs) who exhibited a 10-year Framingham risk score of 15% or greater, or a coronary artery disease risk equivalent (coronary artery disease, peripheral artery disease, cerebrovascular disease, or diabetes mellitus). INTERVENTION: Eligible patients initially met with the pharmacist to receive general counselling about cardiovascular disease and were then randomly assigned to receive ongoing follow-up by the pharmacist (follow-up group [88 patients]) or to return to usual care (single-contact group [88 patients]) for a minimum of 6 months. MEASUREMENTS AND MAIN RESULTS: The primary end point was mean reduction in the 10-year Framingham risk score. Secondary end points included individual modifiable risk factors (systolic and diastolic blood pressures; total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL], and triglyceride levels; total cholesterol:HDL ratio; and hemoglobin A(1c) value), as well as statin utilization, initiation, and adherence rates. Baseline characteristics were similar across both groups. Neither the mean reduction in 10-year risk (-2.68 for the follow-up group and -1.25 for the single-contact group, one-tailed p=0.098) nor individual risk factors were significantly different between groups. The proportion of patients exhibiting statin adherence of 80% or greater did not significantly differ between groups at study end (73.1% [57/78] and 80.0% [52/65], respectively, p=0.333). However, 85.2% (75/88) in the follow-up group continued with statin therapy at the end of the study compared with 67.0% (59/88) in the single-contact group (p=0.005). Statin initiations were more frequent in the follow-up group than in the single-contact group (75.0% [30/40) vs 48.9% [22/45], p=0.013). CONCLUSION: This simple cardiovascular care protocol for nonspecialist pharmacists did not result in a clear improvement to cardiovascular risk reduction success among patients in a primary care medical clinic. The intervention did, however, appear to improve statin utilization.

A pragmatic cluster randomized trial evaluating the impact of a community pharmacy intervention on statin adherence: rationale and design of the Community Pharmacy Assisting in Total Cardiovascular Health (CPATCH) study.

BACKGROUND: Traditional randomized controlled trials are considered the gold standard for evaluating the efficacy of a treatment. However, in adherence research, limitations to this study design exist, especially when evaluating real-world applicability of an intervention. Although adherence interventions by community pharmacists have been tested, problems with internal and external validity have limited the usefulness of these studies, and further well-designed and well-conducted research is needed. We aimed to determine the real-world effectiveness of a community pharmacy adherence intervention using a robust study design. This novel design integrates cluster randomization and an outcome evaluation of medication adherence using a population-based administrative data source in the province of Saskatchewan, Canada. METHODS/DESIGN: Community pharmacies from across the province of Saskatchewan, Canada were randomized to deliver an adherence intervention to their patients or usual care. Intervention pharmacies were trained to employ a practical adherence strategy targeted at new users of statin medications. While randomization and implementation of the intervention occurred at the community pharmacy level, the outcome analysis will occur at the level of the individual subjects. The primary outcome is the mean statin adherence among all eligible new users of statin medications. Secondary outcomes include the proportion of new statin users who exhibit adherence>or=80%, and persistence with statin use. DISCUSSION: This novel study design was developed to combine the rigor of a randomized trial with a pragmatic approach to implementing and capturing the results in a real-world fashion. We believe this approach can serve as an example for future study designs evaluating practice-based adherence interventions. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT00971412.

Retrospective observational assessment of statin adherence among subjects patronizing different types of community pharmacies in Canada.

BACKGROUND: Community pharmacies vary widely in terms of ownership structures, location, and dispensing policies. It is unknown if an association exists between the type of community pharmacy and the degree of medication adherence exhibited by patrons-patients. OBJECTIVE: To describe adherence to statin therapy among subjects patronizing different types of community pharmacy categories (department- mass merchandise, chain-franchise, and independent-banner) in Saskatchewan, Canada, between 2000 and 2005. METHODS: Study data were obtained from the Saskatchewan Drug Plan and Extended Benefits database, which is maintained by the government of Saskatchewan, Canada. The study included all subjects who (a) filled a statin prescription within selected community pharmacies between January 1, 2000, and December 31, 2005; (b) had no record of statin prescriptions during the year prior to the first statin prescription, according to the records of the Saskatchewan Drug Plan and Extended Benefits; and (c) demonstrated active utilization in the drug plan database for at least 1 year after the first statin prescription. The proxy criterion for activity was any dispensing record for statin or nonstatin medications at least 1 year following the index claim. Statin adherence level was estimated as tablets per day, defined as the total number of tablets dispensed divided by the total number of days of observation. Each subject's observation period began on the index date and ended on the earlier of (a) 30 days after the last recorded fill for any type of prescription medication (statin or nonstatin), or (b) December 31, 2005. The primary end point was the proportion of subjects within each pharmacy category who maintained an adherence level of 80% or greater during their individual observation period. Additional adherence calculations were performed for each of 3 time periods, beginning on the index date and ending on days 365, 729, and 1094 (i.e., 1, 2, and 3 years). Patients were included in the analysis for each time period if they met a proxy criterion for availability for observation, defined as the dispensing of any drug at least 1 day after the end date of each period. Pearson chi square tests were used to assess the significance of differences in baseline characteristics and adherence proportions, comparing pharmacy categories. Logistic regression analysis estimated the odds of an adherence level of at least 80% during the individual observation period, adjusting for pharmacy category, sex, age 65 years or older, known low-income drug coverage, number of distinct drug classes filled concurrently during the first year of observation, loyalty to index pharmacy, and length of observation. Using similar methods, we also estimated "pharmacy loyalty" by calculating the proportion of subjects who refilled 75% or more of their statin prescriptions at the pharmacy that dispensed their first statin prescription. RESULTS: From an initial sample of 12,818 subjects who had at least 1 pharmacy claim for a statin in the period from January 1, 2000, through December 31, 2005, 8699 subjects met the inclusion criteria. Subjects were observed for a mean (SD, range) of 3.7 (1.7, 1.0-7.0) years after the index statin prescription. During the first year following the index claim, statin adherence rates were at least 80% for 1799 of 3761 (47.8%) patrons of department-mass merchandise, 1778 of 3235 (55.0%) patrons of chain-franchise, and 921 of 1703 (54.1%) patrons of independent-banner stores (P < 0.001). Measured from the index date through day 1094, 869 of 2292 (37.9%), 874 of 1887 (46.3%), and 457 of 975 (46.9%) subjects in the department-mass merchandise, chain-franchise, and independent banner categories, respectively, had a statin adherence level of at least 80% (P < 0.001). In logistic regression analysis, pharmacy category type was significantly associated with statin adherence; subjects in the chain franchise and independent-banner categories were more likely to be adherent to their statin medications during their observation periods than were those in the department-mass merchandise category (adjusted odds ratio [OR] = 1.36, 95% CI = 1.23-1.50, P < 0.001 and OR = 1.39, 95% CI = 1.24-1.57, P < 0.001, respectively). From the index date through day 1094, 1752 of 2292 (76.4%), 1475 of 1887 (78.2%), and 795 of 975 (81.5%) subjects remained pharmacy-loyal in the department-mass merchandise, chain franchise, and independent-banner categories, respectively (P = 0.006). Controlling for several potential confounders using logistic regression, independent-banner pharmacy patrons were more likely to remain pharmacy- loyal during their observation periods than were those patronizing department-mass merchandise (adjusted OR = 1.34, 95% CI = 1.16-1.54, P < 0.001) or chain-franchise stores (adjusted OR = 1.22, 95% CI = 1.06-1.42, P = 0.009). CONCLUSION: One year after their first statin fill, subjects demonstrated low rates of adherence, ranging from 48% to 55%, regardless of the type of pharmacy they patronized. Although the differences by type of pharmacy reached statistical significance, their clinical importance is not evident, reinforcing the fact that the problem of nonadherence appears to exist among all types of community pharmacies, regardless of their categorization.