Stephen Shalansky

Self-Reported Morisky Score for Identifying Nonadherence with Cardiovascular Medications

BACKGROUND: The Morisky medication adherence scale is a commonly used adherence screening tool. It is composed of 4 yes/no questions about past medication use patterns and is thus quick and simple to use during drug history interviews. OBJECTIVE: To evaluate the use of the self-reported Morisky score as a screening tool for identifying patients who have been nonadherent with chronic cardiovascular medications. METHODS: Patients who had taken an angiotensin-converting enzyme inhibitor or lipid-lowering agent for at least 3 consecutive months were interviewed using a structured questionnaire including the Morisky scale. Nonadherence was defined as taking <80% of chronic cardiovascular medications based on prescription refill data over the previous 14 months. RESULTS: Forty-nine of 377 (13%) patients were categorized as nonadherent; however, only 12 (3%) patients had Morisky scores suggesting a high likelihood of nonadherence (3 or 4). While the Morisky score was a significant independent predictor of nonadherence by multivariate analysis, there was no threshold score or individual question that yielded concurrent high sensitivity and positive predictive values (PPVs) for identifying nonadherent patients. The internal consistency of the questions was low (α 0.32), as were item-to-total score correlations, suggesting that the individual questions were not measuring the same attribute. CONCLUSIONS: Using the Morisky scale to identify patients who have been nonadherent with chronic cardiovascular medications may be reasonable in some settings; however, the threshold score would have to be chosen based on a trade-off between sensitivity and PPV. These results were likely influenced by the low rate of nonadherence in this cohort. Rewording the questions, increasing the number of questions, and the use of graded response options may improve consistency.

Frequency of Heparin‐Induced Thrombocytopenia in Critical Care Patients

The diagnosis of heparin‐induced thrombocytopenia (HIT) in critically ill patients is complicated by lack of information on the frequency of HIT relative to thrombocytopenia from other causes. In addition, results from HIT diagnostic tests have not been clearly evaluated for clinical utility. In this prospective study, we estimated the frequency of HIT and the predictive performance of the heparin‐platelet factor 4 enzyme‐linked immunosorbent assay (heparin‐PF4 ELISA) in 748 consecutive, heparin‐treated patients in a combined intensive and coronary care unit. The criteria for diagnosis were as follows: two or more consecutive platelet counts below 150 times 103/mm3 or a 33% or greater decrease in platelet count 5 or more days after beginning heparin, or any time after starting heparin for patients exposed to the agent within the previous 8 weeks; and a positive 14C‐serotonin release assay (SRA), the reference standard. Specificity and predictive values for the heparin‐PF4 ELISA were estimated in patients who met the clinical criteria for HIT. Of 748 patients, 267 were exposed to heparin for a sufficient length of time to be considered to be at risk for HIT. Forty of these patients (15.0%, 95% confidence interval [CI] 10.7%‐19.3%) met the clinical criteria for HIT. Serum samples were available for 32 of these patients, one of whom tested positive by the SRA, yielding a HIT frequency of 0.39% (95% CI 0.01–2.1%). The specificity of the heparin‐PF4 ELISA among thrombocytopenic patients with negative SRA results was 71%, and the positive (PPV) and negative (NPV) predictive values of this test were estimated to be 10% and 100%, respectively. The point estimate of the frequency of HIT in critically ill patients was less than 1% in this cohort. The low PPV and high NPV of the heparin‐PF4 ELISA suggest that it can be used to exclude HIT as a cause of thrombocytopenia in this patient population.

Effect of Number of Medications on Cardiovascular Therapy Adherence

OBJECTIVE: Increasing regimen complexity is generally assumed to result in lower medication adherence, but there is conflicting evidence. This study determined the relationship between the number of medications dispensed and adherence with chronic cardiovascular regimens. METHODS: A survey was administered to 367 patients who had taken an angiotensin-converting enzyme inhibitor or lipid-lowering medication for at least 3 consecutive months. Information was collected on nonprescription drug use, demographics, adverse effects, and use of adherence aids. Prescription drug use data over the previous 12 months were obtained for each subject from the British Columbia prescription claims database. Adherence for each prescription medication was calculated based on prescription fill dates and number of days supplied. Univariate and multivariate analyses were used to identify predictors of nonadherence (>80%) with cardiovascular medications. RESULTS: Forty-five subjects (12%) were categorized as nonadherent. Nonadherent subjects took fewer regularly scheduled prescription medications per day (4.1 ± 2.7 vs. 5.9 ± 3.4; p = 0.001), fewer pills per day (5.3 ± 3.6 vs. 9.2 ± 7.1; p < 0.001), and had fewer administration × per day (1.8 ± 0.7 vs. 2.4 ± 0.9; p = 0.001). A multivariate logistic regression model adjusting for age, gender, reported adverse effects, reported nonprescription drug use, and use of adherence aids identified fewer regularly scheduled prescription drugs as an independent predictor of nonadherence with chronic cardiovascular medications (OR = 0.85 per medication, 95% CI 0.74 to 0.94; p = 0.01). CONCLUSIONS: Contrary to popular belief, taking fewer medications was associated with lower adherence with chronic cardiovascular regimens.

Risk of Warfarin-Related Bleeding Events and Supratherapeutic International Normalized Ratios Associated with Complementary and Alternative Medicine: A Longitudinal Analysis

Study Objective. To determine the risk of bleeding and supratherapeutic international normalized ratios (INRs) associated with use of complementary and alternative medicine (CAM) in patients receiving warfarin.

Risk markers for thrombocytopenia in critically ill patients: A prospective analysis

Study Objective. To identify independent risk markers for thrombocytopenia in critically ill patients.

Prevalence of Use and the Risk of Adverse Effects Associated with Complementary and Alternative Medicine in a Cohort of Patients Receiving Warfarin

Background The use of complementary and alternative medicine (CAM), including orally administered herbals, botanicals, vitamins, and supplements, may pose a risk to patients on warfarin therapy. Objective To estimate the prevalence of CAM use among patients taking warfarin and evaluate the impact of CAM exposure on the risk of warfarin-related adverse effects. Methods A survey was administered to hospital inpatients and clinic outpatients on drug exposure (including CAM) over the previous month, self-reported bleeding events, use of alcohol and vitamin K–rich foods, and medical conditions. Prescription medication use was verified, and laboratory records were checked for out-of-range international normalized ratios (INRs) (defined as INR >4 or <2). The use of CAM, including products with reported or theoretical interactions with warfarin, was compared between patients with and without self-reported bleeding or out-of-range INR. Results Among the 314 patients who completed the survey, 44.3% reported using CAM at least weekly. Potentially interacting CAM was used by 34.1% of all patients, or 18.2% if vitamin E was excluded as an interacting CAM. Vitamin E was used by 24.2% of all patients and 71.0% of those who used potentially interacting CAM. There was no significant difference in CAM use or consumption of vitamin K–rich foods between patients with and without INRs greater than 4 or for patients with and without INRs less than 2. Conclusions The use of potentially interacting CAM in this cohort was higher than the use previously reported among patients on warfarin therapy. However, exposure to CAM was not associated with an increase in the risk of self-reported bleeding or out-of-range INR.

N-acetylcysteine for prevention of radiographic contrast material-induced nephropathy: is the intravenous route best?

Use of oral N‐acetylcysteine for preventing radiographic contrast material–induced nephropathy (RCIN) has become widespread, despite conflicting results from clinical trials and meta‐analyses. The variability in study results may reflect differences in baseline risks in study patients, hydration regimens, choice of contrast agent, definition of RCIN, and the oral dosage formulation of N‐acetylcysteine used. Injectable N‐acetylcysteine recently has become available in the United States. Although oral N‐acetylcysteine regimens are typically administered during a 48‐hour period, more rapid intravenous administration could offer an important advantage for urgent procedures such as coronary angiography. However, the three published studies in which intravenous N‐acetylcysteine protocols were used have produced divergent results, likely because of substantially different dosage regimens. With few intravenous studies available, clinicians may look to more broadly studied oral regimens to estimate equivalent intravenous dosages. In the oral studies, however, a wide range of formulations were used, and the bioavailability of each product was uncertain. In addition, the intravenous route circumvents first‐pass metabolism, resulting in less glutathione production, perhaps compromising the antioxidant effects of N‐acetylcysteine administration. Overall, little evidence exists that any studied N‐acetylcysteine protocol improves clinical outcomes in terms of reducing length of hospital stay, need for dialysis, or mortality. Furthermore, N‐acetylcysteine may directly affect serum creatinine level, which all clinical trials to date have used as a primary outcome measure. If oral or intravenous N‐acetylcysteine is used with the intention of preventing RCIN, more‐established preventive measures should not be overlooked, including adequate hydration with isotonic saline, avoidance of potentially nephrotoxic drugs, and use of iso‐osmolar radiographic contrast media.

Estradiol in premenstrual asthma: a double-blind, randomized, placebo-controlled, crossover study.

Study Objectives. To characterize asthma symptoms and pulmonary function throughout two menstrual cycles, with and without exogenous estradiol administration, in women with premenstrual asthma, and to determine the effect of estradiol administration on asthma symptoms, pulmonary function, quality of life, and biomarkers of airway inflammation.

Accuracy of a Provincial Prescription Database for Assessing Medication Adherence in Heart Failure Patients

Background: British Columbias central prescription database, PharmaNet, is often used for both clinical and research applications. However, PharmaNet details prescription transactions, not actual medication consumption, resulting in many potential sources of inaccuracy when the information is assumed to reflect population or individual drug utilization. Objective: To assess the accuracy of PharmaNet for adherence assessment in patients with heart failure who are taking β-blockers. Methods: A 6-month prospective, longitudinal assessment of adherence to the prescribed β-blocker regimen was carried out using both PharmaNet data and the Medication Event Monitoring System (MEMS) for each patient enrolled. The limit of agreement between the 2 adherence assessment methods was assessed using the Bland-Altman approach. Results: Fifteen of 58 patients initially enrolled in the study were excluded, most due to misuse of MEMS or failure to return the MEMS vial despite thorough follow-up. For the 43 patients included in the final analysis, mean ± SD adherence was 97.8 ± 11.8% when assessed by PharmaNet and 97.1 ± 7.3% when MEMS was used. However, the limit of agreement, reported as the mean of the differences ± 2SD, was 6.8 ± 18.5%, indicating a moderate-to-high level of agreement between the 2 methods when the confidence interval is taken into consideration. Conclusions: These results suggest that PharmaNet data accurately reflect medication adherence for most patients. The MEMS system proved unreliable in several cases, illustrating the difficulty of identifying a gold standard for adherence assessment.