Decreased serum L-arginine and L-citrulline levels in major depression.

RATIONALE: It has been suggested that endothelial dysfunction caused by a decreased endothelial production of nitric oxide (NO) may contribute to the consistently observed increased risk of developing cardiovascular disease (CVD) in physically healthy patients suffering from major depression (MD). NO is a gas synthesized from Larginine (a conditionally essential amino acid) and oxygen by endothelial nitric oxide synthase (eNOS). The end products of NO production include both NO and L-citrulline. NO is rapidly reduced to the anions nitrite and nitrate, classically referred to as NO metabolites. Their measurement has been used as a surrogate measurement for endothelial NO production. We and others have shown decreased levels of NO metabolites in the serum of MD patients. The mechanism of this decreased production of NO by the endothelium has not yet been elucidated. OBJECTIVES: The purpose of this study is to assess serum levels of L-arginine and L-citrulline in patients with MD. METHODS: Levels of L-arginine and L-citrulline were measured in 35 unmedicated physically healthy MD patients and 36 healthy controls (HCs). RESULTS: L-arginine and L-citrulline concentrations were significantly lower in MD patients than in healthy controls (L-arginine, 73.54 + 21.53 µmol/L and 84.89 + 25.16, p = 0.04 µmol/L and L-citrulline 31.58 + 6.05 µmol/L and 35.19 + 6.85 µmol/L, p = 0.03, respectively). CONCLUSIONS: The decrease in L-arginine levels in MD patients is a possible explanation for the decrease in NO metabolites in MD patients and therefore may contribute, through endothelial dysfunction, to the increased CV risk associated with MD.

Cost-effectiveness analysis of adding pharmacists to primary care teams to reduce cardiovascular risk in patients with Type 2 diabetes: results from a randomized controlled trial.

BACKGROUND: Adding pharmacists to primary care teams significantly improved blood pressure control and reduced predicted 10-year cardiovascular risk in patients with Type 2 diabetes. This pre-specified sub-study evaluated the economic implications of this cardiovascular risk reduction strategy. METHODS: One-year outcomes and healthcare utilization data from the trial were used to determine cost-effectiveness from the public payer perspective. Costs were expressed in 2014 Canadian dollars and effectiveness was based on annualized risk of cardiovascular events derived from the UKPDS Risk Engine. RESULTS: The 123 evaluable trial patients included in this analysis had a mean age of 62 ( ± 11) years, 38% were men, and mean diabetes duration was 6 ( ± 7) years. Pharmacists provided 3.0 ( ± 1.9) hours of additional service to each intervention patient, which cost $226 ( ± $1143) per patient. The overall one-year per-patient costs for healthcare utilization were $190 lower in the intervention group compared with usual care [95% confidence interval (CI): -$1040, $668). Intervention patients had a significant 0.3% greater reduction in the annualized risk of a cardiovascular event (95% CI: 0.08%, 0.6%) compared with usual care. In the cost-effectiveness analysis, the intervention dominated usual care in 66% of 10,000 bootstrap replications. At a societal willingness-to-pay of $4000 per 1% reduction in annual cardiovascular risk, the probability that the intervention was cost-effective compared with usual care reached 95%. A sensitivity analysis using multiple imputation to replace missing data produced similar results. CONCLUSIONS: Within a randomized trial, adding pharmacists to primary care teams was a cost-effective strategy for reducing cardiovascular risk in patients with Type 2 diabetes. In most circumstances, this intervention may also be cost saving.

Adding pharmacists to primary care teams reduces predicted long-term risk of cardiovascular events in type 2 diabetic patients without established cardiovascular disease: results from a randomized trial.

AIM: To determine the impact of adding pharmacists to primary care teams on predicted 10-year risk of cardiovascular events in patients with Type 2 diabetes without established cardiovascular disease. METHODS: This was a pre-specified secondary analysis of randomized trial data. The main study found that, compared with usual care, addition of a pharmacist resulted in improvements in blood pressure, dyslipidaemia, and hyperglycaemia for primary care patients with Type 2 diabetes. In this sub-study, predicted 10-year risk of cardiovascular events at baseline and 1 year were calculated for patients free of cardiovascular disease at enrolment. The primary outcome was change in UK Prospective Diabetes Study (UKPDS) risk score; change in Framingham risk score was a secondary outcome. RESULTS: Baseline characteristics were similar between the 102 intervention patients and 93 control subjects: 59% women, median (interquartile range) age 57 (50-64) years, diabetes duration 3 (1-6.5) years, systolic blood pressure 128 (120-140) mmHg, total cholesterol 4.34 (3.75-5.04) mmol/l and HbA(1c) 54 mmol/mol (48-64 mmol/mol) [7.1% (6.5-8.0%)]. Median baseline UKPDS risk score was 10.2% (6.0-16.7%) for intervention patients and 9.5% (5.8-15.1%) for control subjects (P = 0.80). One-year post-randomization, the median absolute reduction in UKPDS risk score was 1.0% greater for intervention patients compared with control subjects (P = 0.032). Similar changes were seen with the Framingham risk score (median reduction 1.2% greater for intervention patients compared with control subjects, P = 0.048). The two risk scores were highly correlated (rho = 0.83; P < 0.001). CONCLUSION: Adding pharmacists to primary care teams for 1 year significantly reduced the predicted 10-year risk of cardiovascular events for patients with Type 2 diabetes without established cardiovascular disease.

Weight management experiences of overweight and obese Canadian adults: findings from a national survey.

INTRODUCTION: We know little about how the 2006 Canadian Clinical Practice Guidelines for the management and prevention of obesity relate to Canadians' weight management experiences or whether these experiences reflect the recommendations in the Guidelines. METHODS: We used data from a general population omnibus survey to understand these two issues, particularly in relation to chronic disease. The survey included 23 questions related to weight management practices as well as those related to demographic characteristics. RESULTS: Of 2004 respondents, 33% were classified as overweight and 20% as obese. In the 12 months before the survey, 48% of overweight and obese respondents reported asking their physician about weight loss, while 30% reported that their physician advised them to lose weight without them specifically asking. With regard to the recommendations within the Guidelines, 14% of overweight and 18% of obese respondents reported having their waist circumference measured, 82% of overweight and 87% of obese respondents reported having their blood pressure measured, and 36% of overweight and 50% of obese respondents reported having a test for diabetes. CONCLUSION: These findings have implications for chronic disease identification and management.

OS104. Are preeclampsia and adverse obstetrical outcomes predictors for longterm cardiovascular disease?

INTRODUCTION: Epidemiologic studies suggest that pregnancy complications such as preeclampsia, gestational diabetes, preterm delivery and low birth weight independently increase maternal risk for future development of cardiovascular disease. OBJECTIVES: To further investigate whether preeclampsia, gestational diabetes, and adverse obstetrical outcomes such as placental abruption, intrauterine growth restriction and preterm delivery, are independent risk factors for longterm cardiovascular disease. METHODS: This was a case-control study where 252 parous women (cases) with coronary artery disease were matched with a parous woman within 5 years of age with no known coronary artery disease (controls). Participants were recruited from the Royal Alexandra Hospital in cardiac catheterization lab recovery room in Edmonton, Canada. Women with significant angiographic coronary artery stenosis were eligible as cases and those without were eligible as controls. Participants were interviewed on their pregnancy histories and traditional cardiovascular risk factors, such as hypertension, diabetes etc. Descriptive statistics, chi-square tests and conditional regression analysis were performed. RESULTS: We recruited 244 cases and 246 controls. The average age was 66.3 and 65.8 respectively. Cases were more likely obese, had more pregnancies as well as traditional cardiovascular risk factors than controls. Adverse pregnancy outcomes were similar between the two groups except gestational hypertension. However, it was not statistically significant in the conditional logistic regression model. Independent risk factors for future cardiovascular diseases were: dyslipidemia (OR 12.8), hypertension (3.0), and being a current (OR 7.4) or former smoker (1.8). Adverse pregnancy outcomes CONCLUSION: In this study, adverse pregnancy outcomes were not independently associated with cardiovascular disorders. Our study was limited by recall bias, and ascertainment of diagnosis.Our study supports that dyslipidemia, hypertensiion and smoking increase future cardiovascular disease. Further studies are needed to examine a postpartum intervention model to proactively manage cardiovascular risk factors, such as lipids, in these at-risk women.

Community pharmacist-initiated screening program for osteoporosis: randomized controlled trial.

SUMMARY: This study evaluated the effect of a multifaceted intervention (screening and patient education) by community pharmacists on testing or treatment of osteoporosis. One hundred and twenty-nine patients randomized to receive the intervention were compared to 133 patients who did not receive the intervention. Twice as many patients who got the intervention received further testing or treatment for osteoporosis. INTRODUCTION: The objective of this study was to determine the effect of a community pharmacist screening program on testing and treatment of osteoporosis. METHODS: In this randomized, controlled trial, 262 patients meeting bone mineral density (BMD) testing guidelines [men or women aged > or = 65 years or 50-64 years with one major risk factor including previous fracture, family history of osteoporosis, glucocorticoids for > 3 months, or early menopause] were allocated to intervention (129) or control (133). Intervention consisted of printed materials, education, and quantitative ultrasound. Primary outcome was a composite endpoint of BMD or prescription for osteoporosis medication within 4 months. RESULTS: Primary endpoint of BMD or osteoporosis treatment was achieved by 28 intervention patients (22%) compared with 14 controls (11%) (RR 2.1, 95% CI 1.1-3.7). This was driven by BMD testing (28 (22%) vs. 13 (10%) for controls, p = 0.011). Calcium intake increased more among intervention patients than controls (30% vs. 19%, RR 1.6, 95% CI 1.0-2.5). There was no effect on knowledge or quality of life. CONCLUSION: A pharmacist screening program doubled the number of patients tested for osteoporosis. Nevertheless, many patients eligible for BMD did not receive appropriate care suggesting more intensive interventions are needed.

Evaluation of attitudes and perceptions of key clinical stakeholders regarding out-of-hospital diagnosis and treatment of ST elevation myocardial infarction patients using a region-wide survey.

INTRODUCTION: In ST elevation myocardial infarction (STEMI), prehospital management (PHM) may improve clinical outcomes through a reduction in reperfusion delay. The purpose of this study was to evaluate perceptions among healthcare stakeholder groups relating to the barriers and facilitators of implementing a PHM programme. METHODS: A 25-question cross-sectional survey, using a four-point Likert scale assessing barriers and facilitators of PHM, was distributed to paramedics, cardiologists, emergency physicians and emergency nurses within the Edmonton region, where prehospital STEMI treatment is established. The proportion of responses on each question was compared and differences between groups were determined using chi(2) and Fisher's exact tests. RESULTS: 57% (355/619) of subjects responded: 69% paramedics, 50% cardiologists, 54% emergency physicians and 45% emergency nurses. A majority believed PHM reduced treatment delays in both rural (96-100%) and urban (86-96%) areas, while decreasing patient mortality (paramedics 97%, cardiologists 74%, emergency physicians 85%, emergency nurses 88%). Regarding the capability of paramedics to deliver PHM, paramedics 25%, cardiologists 33%, emergency physicians 67%, and emergency nurses 47% stated that urban paramedics are better equipped and trained than rural paramedics. Although 81% of paramedics supported the possibility of PHM delivery without physician overview, 0% of cardiologists, 98% of emergency physicians and 95% emergency nurses agreed. A majority (71-88%) favoured mandatory signed informed consent. CONCLUSIONS: While stakeholders agreed on the benefits of PHM, perceptual differences existed on paramedics' ability to deliver PHM without physician overview. Addressing real and perceived barriers through communication and educational programmes may enhance PHM within this healthcare region and facilitate the implementation of PHM programmes.

The effects of angiotensin-receptor blockers on mortality and morbidity in heart failure: a systematic review.

BACKGROUND: Trials evaluating angiotensin-receptor blockers in heart failure (HF) have shown inconsistent results. OBJECTIVE: To evaluate the effect of angiotensin II (AII) receptor blockers in HF patients on total mortality and HF hospitalisations. METHODS: Systematic search of the literature through MEDLINE (1980-2007) and abstracts of major cardiovascular congresses from 2002 to 2007. ELIGIBILITY CRITERIA: (i) randomised controlled trials with more than 500 patients and follow up > 6 months, (ii) availability of total mortality and/or (iii) availability of hospital admission because of worsening HF. Data retrieved by two independent reviewers. DerSimonian random effects model was used. RESULTS: Mortality data were available from 27,495 patients. When AII receptor blockers plus angiotensin-converting enzyme inhibitors (ACE-I) were compared with ACE-I in chronic HF trials, the relative risk (RR) for death was 0.98 (95% CI: 0.84-1.15). When AII receptor blockers were compared with ACE-I the RR for death was 1.06 (95% CI: 0.56-1.62). Similar results were found for postmyocardial infarction trials. The effects on hospital admission revealed a RR of 0.83 (95% CI: 0.71-0.97) and 1.09 (95% CI: 0.74-1.60) respectively. CONCLUSION: Angiotensin II receptor blockers did not show any beneficial effect on mortality when used in combination with ACE-I or when compared with ACE-I alone. A 17% reduction in hospital admissions was observed.

Women's Recovery from Sternotomy-Extension (WREST-E) study: examining long-term pain and discomfort following sternotomy and their predictors.

OBJECTIVE: To examine incision and breast pain and discomfort, and their predictors in women 12 months following sternotomy. DESIGN: Extension survey following participation in a clinical trial. SETTING: 10 Canadian centres. PATIENTS: Women (n = 326) who completed the Women's Recovery from Sternotomy Trial. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Pain and discomfort data (numeric rating scales) collected by standardised interview at 5 days, 12 weeks and 12 months following sternotomy. RESULTS: More patients reported having incision or breast discomfort (46.6%) than pain (18.1%) at 12 months postoperatively. No symptoms at 5 days postoperatively were significantly associated with symptom presence at 12 postoperative months. However, having incision pain and discomfort as well as breast pain and discomfort at 12 postoperative weeks was associated with incision pain (odds ratio (OR) = 3.26, 95% confidence interval (CI) 1.51 to 7.07), incision discomfort (OR = 4.87, 95% CI 3.01 to 7.88), breast pain (OR = 9.36, 95% CI 3.91 to 22.38) and breast discomfort (OR = 6.42, 95% CI 3.62 to 11.37), respectively, at 12 postoperative months. Increasing chest circumference was associated with having ongoing incision pain (OR = 1.12, 95% CI 1.03 to 1.21) and breast pain (OR = 1.10, 95% CI 1.00 to 1.22). Harvesting of bilateral internal mammary arteries (IMAs) was associated with having ongoing incision pain (OR = 4.71, 95% CI 1.54 to 14.3), while harvesting only the left IMA was associated with having ongoing breast pain (OR = 2.78, 95% CI 1.06 to 7.32) and breast discomfort (OR 1.80, 95% CI 1.02 to 3.19). CONCLUSIONS: Patients reported incision and breast pain and discomfort as long as 12 months post-sternotomy. Improved management of postoperative pain and discomfort up to at least 12 weeks following surgery may render reduced long-term pain and discomfort symptoms.

Systematic review: renal and other clinically relevant outcomes in hepatorenal syndrome trials.

BACKGROUND: Although reversal of pretransplant renal dysfunction in hepatorenal syndrome reduces post-transplant complications, the overall impact on morbidity and mortality requires clarification. AIM: To review trials of pharmacologic interventions in hepatorenal syndrome, with specific assessment of trial quality and study endpoints, including patient survival and renal outcome measures. METHODS: Literature search and selection was carried out by a single reviewer. Data extraction and quality analysis were carried out by two independent reviewers. RESULTS: Of 848 identified articles, 36 were eligible for inclusion. Twenty-one were full-text. Only 19% were randomized-controlled trials. About 50% of studies included only Type 1 hepatorenal syndrome patients. Serum creatinine, urine output and urine sodium were the most common renal outcome measures. Only 42% defined a primary renal endpoint. About 88% of articles reported mortality rates. CONCLUSIONS: Existing literature of pharmacologic agents for use in hepatorenal syndrome is limited by poor study design, including non-randomization, heterogeneous study populations, lack of power, and limited use of clinically relevant outcomes. There is insufficient information in most trials to judge the impact of pharmacologic therapy on mortality or rates of transplantation. The validity of renal outcome measures as surrogate markers of more clinically relevant endpoints has not been established.

Statin use in Type 2 diabetes mellitus is associated with a delay in starting insulin.

AIMS: It has been suggested that HMG Co-A reductase inhibitors ('statins') may reduce the risk of developing Type 2 diabetes mellitus. This study was designed to evaluate whether use of statins would also delay progression to insulin therapy. METHODS: This was a retrospective cohort study using Saskatchewan Health databases to identify subjects newly started on oral antidiabetic agents from 1991 to 1996. SUBJECTS: < 30 years of age or with previous lipid-lowering drug use were excluded. Medications known to influence glycaemic control, co-morbidity, and demographic data were collected. Statin exposure was defined as at least 1 year of use. Primary outcome was starting insulin treatment. Multivariate Cox proportional hazards models were used to examine the association between statin use and starting insulin. RESULTS: The final cohort included 10,996 new users of oral antidiabetic agents, of which 484 (4.4%) used statins. Mean age was 64 years and 55% were male. Mean duration of follow-up was 5.1 years; 11.1% (n = 1221) eventually started insulin treatment. Statin users were no less likely than non-users to start insulin treatment eventually (11.6% vs. 11.1%, P = 0.74). After multivariate adjustment, however, statin use was associated with a 10-month delay before newly treated diabetic subjects needed to start insulin treatment (adjusted hazard ratio 0.74; 95% confidence interval 0.56, 0.97, P = 0.028). CONCLUSION: The use of statins is associated with a delay in starting insulin treatment in patients with Type 2 diabetes initially treated with oral antidiabetic agents. Whether this relationship exists for patients at high risk of developing diabetes should be examined in a randomized trial.

Underutilisation of ACE inhibitors in patients with congestive heart failure.

Congestive heart failure (CHF) is associated with substantial morbidity and mortality, and is the only major cardiovascular disease increasing in prevalence. Despite abundant evidence to support their efficacy and cost-effectiveness, angiotensin-converting enzyme (ACE) inhibitors are sub-optimally used in patients with CHF. This paper reviews the evidence for the sub-optimal use of ACE inhibitors in patients with CHF, the factors contributing to this, and its implications for health systems. A systematic review of all articles assessing practice patterns (specifically the use of ACE inhibitors in CHF) identified by MEDLINE, search of bibliographies, and contact with content experts was undertaken. 37 studies have documented the use of ACE inhibitors in patients with CHF. Studies assessing use among all patients with CHF document 33% to 67% (median 51%) of all patients discharged from hospital and 10% to 36% (median 26%) of community dwelling patients were prescribed ACE inhibitors. Rates of ACE inhibitor use range from 43% to 90% (median of 71%) amongst those discharged from hospital having known systolic dysfunction, and from 67% to 95% (median of 86%) for those monitored in specialty clinics. Moreover, the dosages used in the 'real world' are substantially lower than those proven efficacious in randomised, controlled trials, with evaluations reporting only a minority of patients achieving target doses and/or an overall mean dose achieved to be less than one-half of the target dose. Factors predicting the use and optimal dose administration of ACE inhibitors are identified, and include variables relating to the setting (previous hospitalisation, specialty clinic follow-up), the physician (cardiology specialty versus family practitioner or general internist, board certification), the patient (increased severity of symptoms, male, younger), and the drug (lower frequency of administration). In light of the substantial evidence for reductions in morbidity and mortality, clearly, the prescription of ACE inhibitors is sub-optimal. Wide variability in ACE inhibitor use is noted, with higher rates consistently reported among patients having systolic dysfunction confirmed by an objective assessment--an apparent minority of the those having CHF. Optimisation of the prescription of proven efficacious therapies has the potential to confer a substantial reduction in the total cost of care for patients with CHF by reducing hospitalisations and lengths of hospital stays. It is likely that only multifaceted programs targeted toward the population at large will yield benefits to the healthcare system, given the widespread nature of the sub-optimal prescription of therapies proven effective in the management of patients with CHF.

Acute precipitants of congestive heart failure exacerbations.

BACKGROUND: Few studies have prospectively and systematically explored the factors that acutely precipitate exacerbation of congestive heart failure (CHF) in patients with left ventricular dysfunction. Knowledge of such factors is important in designing measures to prevent deterioration of clinical status. The objective of this study was to prospectively describe the precipitants associated with exacerbation of CHF status in patients enrolled in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction Pilot Study. METHODS: We conducted a 2-stage, multicenter, randomized trial in 768 patients with CHF who had an ejection fraction of less than 40%. Patients were randomly assigned to receive enalapril maleate, candesartan cilexetil, or both for 17 weeks, followed by randomization to receive metoprolol succinate or placebo for 26 weeks. Investigators systematically documented information on clinical presentation, management, and factors associated with the exacerbation for any episode of acute CHF during follow-up. RESULTS: A total of 323 episodes of worsening of CHF occurred in 180 patients during 43 weeks of follow-up; 143 patients required hospitalization, and 5 died. Factors implicated in worsening of CHF status included noncompliance with salt restriction (22%); other noncardiac causes (20%), notably pulmonary infectious processes; study medications (15%); use of antiarrhythmic agents in the past 48 hours (15%); arrhythmias (13%); calcium channel blockers (13%); and inappropriate reductions in CHF therapy (10%). CONCLUSIONS: A variety of factors, many of which are avoidable, are associated with exacerbation of CHF. Attention to these factors and patient education are important in the prevention of CHF deterioration.

Use of statins and the subsequent development of deep vein thrombosis.

BACKGROUND: Some of the benefit of statins for the prevention of cardiovascular disease may be due to their antithrombotic properties. Little is known about the effect of these drugs on the development of deep vein thrombosis. MATERIALS AND METHODS: We conducted a retrospective cohort study over an 8-year period by linking Ontario provincial health care administrative databases covering more than 1.4 million Ontario residents aged 65 years or older. We excluded those with a documented history of atherosclerosis, venous thromboembolism, or cancer within 36 months prior to study enrollment, as well as those prescribed warfarin sodium within 12 months before enrollment. In the primary cohort, we evaluated the subsequent risk of deep vein thrombosis (DVT) among men and women prescribed thyroid replacement therapy, nonstatin lipid-lowering agents, or statins. A second cohort of women only was evaluated in a similar fashion, but estrogen use was added as a third comparison drug group. RESULTS: There were 125 862 men and women in the primary cohort. After adjusting for age; sex; prior hospitalization; newly diagnosed cancer; or prescribed aspirin, warfarin, or estrogen, statin users (n = 77 993) had an associated decreased risk of DVT relative to those prescribed thyroid replacement therapy (n = 35 978) (adjusted hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.69-0.87). Compared with thyroid replacement therapy, users of nonstatin lipid-lowering agents (n = 11 891) did not seem to be at lower risk for deep vein thrombosis (HR, 0.97; 95% CI, 0.79-1.18). In the secondary cohort of 89 508 women, after adjusting for age, prior hospitalization, newly diagnosed cancer, or prescribed aspirin or warfarin, estrogen users (n = 29 165) had an associated increased risk for DVT compared with those receiving thyroid replacement therapy (n = 22 118) (HR, 1.16; 95% CI, 1.01-1.33), while statin users had an associated decreased risk (HR, 0.68; 95% CI, 0.59-0.79). Nonstatin lipid-lowering agents (n = 5155) were not associated with a reduced risk of DVT compared with thyroid replacement therapy (HR, 0.84; 95% CI, 0.63-1.12). CONCLUSION: Among selected individuals aged 65 years or older, statins were associated with a 22% relative risk reduction in the risk of DVT. A randomized clinical trial is needed to evaluate the efficacy of statins for the primary and secondary prevention of DVT.

Cholesterol risk management: a systematic examination of the gap from evidence to practice.

Hypercholesterolemia is a major risk factor for coronary heart disease, and data indicate that aggressive cholesterol reduction decreases mortality and morbidity associated with this disease. Many patients with hypercholesterolemia, however, are not screened, prescribed appropriate lipid-lowering therapy, or treated to target cholesterol levels. Practice patterns are particularly inadequate for those patients at highest risk for having a cardiac event. We performed a literature search to identify studies of practice patterns in the management of patients with hypercholesterolemia with regard to screening, implementing lipid-lowering therapy, and treating to lipid goals. The findings highlight the potential for substantial opportunities to improve patient outcomes. Future studies should evaluate reasons for suboptimal cholesterol management as well as provide steps to improve management.

Practice-based research: lessons from community pharmacist participants.

We designed this project to determine community pharmacists' opinions regarding the challenges and motivations of their recent participation in a pharmacy practice-based research study At the conclusion of a randomized, multicenter study, 87 community pharmacist-investigators were sent a questionnaire that explored four areas: motivating factors to participate, barriers to participation, communication tools used by study coordinators, and design issues for future studies. Fifty-eight (67%) completed questionnaires were returned. Key factors motivating participation in the study were desire to improve the profession and opportunity to learn. Time was the greatest barrier to participation. Pharmacy practice-based research has two distinct advantages. First, it translates clinical knowledge into direct application in the community. Second, it provides needed data to demonstrate the value of enhanced pharmacy practice. Thorough understanding of pharmacists' opinions is necessary to optimize the design of future studies.

Poor adherence with hypolipidemic drugs: a lost opportunity.

All articles assessing adherence to hypolipidemic drugs were reviewed and categorized by patient population (clinical trial, unselected) and reported as rates of nonadherence and discontinuation. Overall, levels of discontinuation reported in clinical trials (6-31%) and lipid clinics (2-38%) are similar, with unselected populations consistently reporting higher rates (15-78%). Rates of nonadherence in clinical trials and lipid clinics also are comparable, with unselected populations having the highest rates. Across all settings, rates of discontinuation and nonadherence are consistently reported to be poorer with resins and niacin than with hydroxy-6-methylglutamate coenzyme A reductase inhibitors. Adherence to hypolipidemic agents appears to decrease in parallel with level of follow-up. Data evaluating mechanisms of poor adherence are limited. While the search for new, efficacious therapies must continue, efforts focused on improving adherence to proven therapy may have a greater overall impact on health than any single new agent.

Economic impact of community pharmacist intervention in cholesterol risk management: an evaluation of the study of cardiovascular risk intervention by pharmacists.

The Study of Cardiovascular Risk Intervention by Pharmacists, a randomized, controlled trial in over 50 community pharmacies in Alberta and Saskatchewan, Canada, demonstrated that a pharmacist intervention program improved cholesterol risk management in patients at high risk for cardiovascular disease. In a substudy, costs and consequences were analyzed to describe the economic impact of the program. Two perspectives were taken: a government-funded health care system and a pharmacy manager. Costs were reported in 1999 Canadian dollars. Incremental costs to a government payor and community pharmacy manager were $6.40/patient and $21.76/patient, respectively, during the 4-month follow-up period. The community pharmacy manager had an initial investment of $683.50. The change in Framingham risk function for the intervention group from baseline also was reported. The 10-year risk of cardiovascular disease decreased from 17.3% to 16.4% (p<0.0001) during the 4 months. The intervention program in this study led to a significant reduction in cardiovascular risk in the intervention group during the 4-month follow-up period. The incremental cost to provide the program appeared minimal from both government and pharmacy manager perspectives. It is hoped that these results could support negotiations for reimbursement of clinical pharmacy services with payors.