Yvonne Shevchuk

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 A1c); 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.

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.

Vancomycin-induced neutropenia resolves after substitution with teicoplanin

Neutropenia is an uncommon adverse effect associated with prolonged vancomycin therapy. Neutrophil counts normally recover after discontinuation of vancomycin in this situation, but treatment options are needed for those patients who require ongoing antibiotic therapy. We describe a case of vancomycin-induced neutropenia in which the neutropenia resolved after vancomycin was replaced by the structurally related compound teicoplanin.

Recurrent Clostridium difficile diarrhea associated with mitoxantrone and etoposide : A case report and review

Clostridium difficile colitis most commonly occurs in association with antibiotic administration and infrequently with antineoplastic agents. Our patient experienced recurrent C. difficile diarrhea associated with mitoxantrone and etoposide. He received antibiotics during the 6 months, but each episode of diarrhea was preceded by at least a 6‐week antibiotic‐free period. In addition, antineoplastic therapy preceded each episode by 8 or 9 days. Clinicians should be aware that antineoplastic drugs may precipitate overgrowth of C. difficile in the bowel.

Contamination Study of Multiple-Dose Vials

OBJECTIVE: To document the number of opened, dated, and expired multiple-dose vials (MDVs) in patient-care areas and to determine what proportion of MDVs were contaminated with bacteria or cellular debris. DESIGN: Every tenth opened MDV (69/656) identified on the wards was collected, ensuring representation from each nursing unit. Contents were examined for contamination. SETTING: Medical-school-affiliated, tertiary care center. MAIN OUTCOME MEASURES: (1) Visual inspection for debris, medication type, location, lot number, manufacturers expiration date, and date of opening; (2) culture in solid and broth media for bacterial growth; and (3) staining and microscopic examination for cellular constituents. RESULTS: No vials had been dated after opening and 4.6 percent were expired according to the manufacturers expiration date. No bacterial contamination was evident; however, one vial was contaminated with red blood cells. CONCLUSIONS: Transmission of infection via contaminated MDVs has been well documented and contamination with red blood cells raises concerns about potential for transmission of bloodborne pathogens. Recommendations include dating MDVs after opening, emphasizing the need for proper aseptic technique, and discarding MDVs on the manufacturers date of expiration.

Antibiotic-associated hypoprothrombinemia

Abstract An individual patients vitamin K status and concomitant risk factors related to underlying disease determine the likelihood of hypoprothrombinemia and bleeding in patients requiring antibiotics. Patients at highest risk should be identified and monitored more aggressively or given prophylactic vitamin K. The propensity of various antibiotics to cause hypoprothrombinemia and bleeding differ substantially. Cefamandole, cefoperazone, and moxalactam appear to be most frequently implicated. Although the contribution of the NMTT moiety of specific antibiotics and the propensity to produce hypoprothrombinemia and bleeding remains controversial, in the setting of already compromised vitamin K status (or dietary intake and elimination or alteration of bowel flora) the NMTT moiety may be a contributing factor. When antimicrobial regimens are compared in clinical trials, hypoprothrombinemia and bleeding should be considered potential adverse effects and appropriate prospective monitoring should be performed. Costs of monitoring for and management of this adverse effect should be considered in cost-benefit analysis.

Comparison of anti-infective drug use in elderly persons in Manitoba, Nova Scotia, and Saskatchewan, Canada: Relationship to drug insurance reimbursement policies

BACKGROUND Antimicrobial drug resistance continues to be a concern. Inappropriate use of antimicrobial agents is a well-documented contributory factor in the development of resistance. Canadian publicly funded drug insurance (pharmacare) programs have various approaches to reimbursement for antimicrobial drugs and promoting the appropriate prescribing of these agents. OBJECTIVE The objective of this study was to examine changes in antimicrobial use over a 3-year period in relation to the reimbursement policies of the public drug insurance programs for elderly persons in Manitoba, Nova Scotia, and Saskatchewan. METHODS The pharmacare databases of the 3 provincial drug insurance programs were accessed for fiscal years 1995/96, 1996/97, and 1997/98. Antimicrobial drug use was reported as mean age- and sex-standardized defined daily doses (DDDs) dispensed per 1000 beneficiaries per year. Provincial antimicrobial drug use was compared and related to provincial reimbursement policies. RESULTS The rates and types of antimicrobial drugs dispensed to elderly beneficiaries of the Manitoba, Nova Scotia, and Saskatchewan pharmacare programs varied. Between fiscal years 1995/96 and 1997/98, DDDs of antimicrobials per 1000 beneficiaries per year decreased by 11.5% in Saskatchewan and increased by 1.2% in Manitoba and 6.2% in Nova Scotia. Rates of use of broadspectrum agents such as amoxicillin/clavulanate, azithromycin, clarithromycin, and fluoroquinolones were lower in the provinces that had reimbursement guidelines. Even when reimbursement policies were similar, as for fluoroquinolones in Manitoba and Saskatchewan, rates of use varied markedly, possibly as a result of the method of implementing the reimbursement guidelines. Use of fluoroquinolones, macrolides, penicillins, beta-lactamase-resistant penicillins, and tetracyclines was lower and use of sulfonamides and trimethoprim was greater in Saskatchewan than in Nova Scotia and Manitoba. CONCLUSIONS The reimbursement guidelines of provincial drug insurance programs are among the factors affecting the use of antimicrobial agents. Both the type of reimbursement policy and the policy implementation mechanism affected the rate of utilization. Further research is needed to link drug-use information with data such as antimicrobial resistance patterns, diagnoses, physician visits, and hospitalizations.

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

BackgroundTraditional 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/DesignCommunity 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 ≥80%, and persistence with statin use.DiscussionThis 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 RegistrationClinicalTrials.gov no. NCT00971412.

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.

Aminoglycoside Volume of Distribution in Pediatric Patients

Pharmacokinetic parameters of three aminoglycoside antibiotics were studied retrospectively in 218 pediatric patients to determine an apparent volume of distribution (Vd) for this age group and to determine if Vd is significantly different in pediatric patients compared with adults. Data on patients considered for inclusion in the study were obtained from the files of the aminoglycoside monitoring services at Saskatoon University Hospital and Regina General Hospital. Both services use a computer program that calculates pharmacokinetic parameters using the Sawchuk-Zaske method. Children between the ages of 1 and 16 years with normal renal function from whom serum concentrations had been obtained were included in the study. Exclusion criteria included abnormal or unstable renal function, cystic fibrosis, and pregnancy. The mean age of the pediatric group was 8.65 ± 5.37 years. Average values for Vd and half-life were 0.34 L/kg and 2.3 h, respectively. No strong correlation was found between the Vd (L/kg) and age. The patients were subdivided into three age groups: 1–4.9 years, 5–9.9 years, and 10–16 years. Group 1 (1–4.9 years) had a larger Vd than the other groups and the Vd of all three groups were significantly different from the estimated Vd of 0.20 L/kg for adult patients. A “normal” pediatric value for the Vd of aminoglycosides could not be determined; however, the Vd in children is significantly larger than the Vd in adults and dosage regimens should be adjusted accordingly.