Opioid prescribing and health outcomes in opioid-naive patients: Analysis of a statewide health information exchange.

BACKGROUND: Widespread use of prescription opioids is associated with adverse outcomes. OBJECTIVE: To identify factors associated with adverse health outcomes and health care use using a statewide health information exchange. METHODS: This is a retrospective cohort study using the Indiana Network for Patient Care. Adult opioid-naive patients who received an opioid prescription between January 2012 and December 2017 were included. The outcomes included (1) a composite outcome of any combination of opioid abuse, dependence, or overdose, (2) all-cause mortality, and (3) health care use. Independent variables included opioid dosage, dispensed amount, days supply, concurrent use of short-acting (SA) and long-acting (LA) opioids, and concurrent use with benzodiazepine or gabapentinoids. Additional variables included patients' age, sex, race, modified Charlson Comorbidity Index score, mental health conditions, and medications for opioid use disorders. Factors associated with composite outcome and mortality were identified using Cox proportional hazards and reported as adjusted hazard ratio (aHR) and 95% CI. Factors associated with health care use were identified using Poisson regression and reported as adjusted incidence rate ratio (aIRR) and 95% CI. RESULTS: 1,328,287 opioid prescriptions were identified for 341,722 patients. Opioid-related factors associated with the composite outcome, mortality, and hospitalizations, respectively, included opioid dosage (aHR 1.003 [95% CI 1.001-1.006]; aHR not applicable; aIRR 1.07 [1.06-1.08]), opioid days supply (aHR 1.03 [1.02-1.03]; aHR 1.009 [1.005-1.014]; aIRR 0.94 [0.92-0.96]), concurrent SA/LA opioids (aHR 2.12 [1.78-2.54]; aHR 1.40 [1.14-1.70]; aIRR 1.40 [1.37-1.42]), and use of benzodiazepines/gabapentinoids (aHR 1.68 [1.38-2.04]; aHR 1.23 [1.01-1.51]; aIRR 1.25 [1.23-1.27]). CONCLUSION: Many factors are associated with poor health outcomes, especially concurrent use of SA and LA opioids and overlapping prescriptions of opioids with benzodiazepines or gabapentinoids. Identification of factors associated with adverse outcomes may help identify patients at risk for poor outcomes and could inform possible interventions.

Ondansetron blocks wild-type and p.F503L variant small-conductance Ca2+-activated K+ channels.

Apamin-sensitive small-conductance Ca2+-activated K+ (SK) current ( IKAS) is encoded by Ca2+-activated K+ channel subfamily N ( KCNN) genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT syndrome (diLQTS), we screened for KCNN variants among patients with diLQTS, determined the properties of heterologously expressed wild-type (WT) and variant KCNN channels, and determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS. We searched 2,306,335 records in the Indiana Network for Patient Care and found 11 patients with diLQTS who had DNA available in the Indiana Biobank. DNA sequencing discovered a heterozygous KCNN2 variant (p.F503L) in a 52-yr-old woman presenting with corrected QT interval prolongation at baseline (473 ms) and further corrected QT interval lengthening (601 ms) after oral administration of ondansetron. That patient was also heterozygous for the p.S38G and p.P2835S variants of the QT-controlling genes KCNE1 and ankyrin 2, respectively. Patch-clamp experiments revealed that the p.F503L KCNN2 variant heterologously expressed in human embryonic kidney (HEK)-293 cells augmented Ca2+ sensitivity, increasing IKAS density. The fraction of total F503L-KCNN2 protein retained in the membrane was higher than that of WT KCNN2 protein. Ondansetron at nanomolar concentrations inhibited WT and p.F503L SK2 channels expressed in HEK-293 cells as well as native SK channels in ventricular cardiomyocytes. Ondansetron-induced IKAS inhibition was also demonstrated in Langendorff-perfused murine hearts. In conclusion, the heterozygous p.F503L KCNN2 variant increases Ca2+ sensitivity and IKAS density in transfected HEK-293 cells. Ondansetron at therapeutic (i.e., nanomolar) concentrations is a potent IKAS blocker. NEW & NOTEWORTHY We showed that ondansetron, a 5-HT3 receptor antagonist, blocks small-conductance Ca2+-activated K+ (SK) current. Ondansetron may be useful in controlling arrhythmias in which increased SK current is a likely contributor. However, its SK-blocking effects may also facilitate the development of drug-induced long QT syndrome.

Antihypertensive Medication and Dementia Risk in Older Adult African Americans with Hypertension: A Prospective Cohort Study.

BACKGROUND: African Americans are especially at risk of hypertension and dementia. Antihypertensive medications reduce the risk of cardiovascular events, but may also reduce the risk of dementia. OBJECTIVE: To assess the longitudinal effects of antihypertensive medications and blood pressure on the onset of incident dementia in a cohort of African Americans. DESIGN: Prospective cohort. PARTICIPANTS: 1236 community-dwelling patients from an inner-city public health care system, aged 65 years and older, with a history of hypertension but no history of dementia, and who had at least three primary care visits and a prescription filled for any medication. MAIN MEASURES: Blood pressure was the average of three seated measurements. Dementia was diagnosed using a two-stage design, with a screening evaluation every 2 to 3 years followed by a comprehensive in-home clinical evaluation for those with a positive screen. Laboratory, inpatient and outpatient encounter data, coded diagnoses and procedures, and medication records were derived from a health information exchange. KEY RESULTS: Of the 1236 hypertensive participants without dementia at baseline, 114 (9%) developed incident dementia during follow-up. Individuals prescribed any antihypertensive medication (n = 816) were found to have a significantly reduced risk of dementia (HR = 0.57, 95% CI 0.37-0.88, p = 0.0114) compared to untreated hypertensive participants (n = 420). When this analysis was repeated including a variable indicating suboptimally treated blood pressure (> 140 mmHg systolic or >90 mmHg diastolic), the effect of antihypertensive medication was no longer statistically significant (HR = 0.65, 95% CI 0.32-1.30, p = 0.2217). CONCLUSIONS: Control of blood pressure in older adult African American patients with hypertension is a key intervention for preventing dementia, with similar benefits from most of the commonly available antihypertensive medications.

Changes of glucose levels precede dementia in African-Americans with diabetes but not in Caucasians.

INTRODUCTION: Changes in glucose levels may represent a powerful metabolic indicator of dementia in African-Americans with diabetes. It is unclear whether these changes also occur in Caucasians. METHODS: A secondary data analysis using electronic medical records from 5228 African-Americans and Caucasians aged ≥65 years was carried out. Mixed effects models with repeated serum glucose measurements were used to compare changes in glucose levels between African-Americans and Caucasian patients with and without incident dementia. RESULTS: African-Americans and Caucasians with diabetes had significantly different changes in glucose levels by dementia status (P < .0001). African-Americans experienced a significant decline in glucose levels before the dementia diagnosis (estimated glucose decline 1.3421 mg/dL per year, P < .0001) than those who did not develop dementia. Caucasians with and without dementia showed stable glucose levels over time (P = .3071). DISCUSSION: Significant changes in glucose levels precede dementia in African-American patients with diabetes but not in Caucasians.

Triamterene Enhances the Blood Pressure Lowering Effect of Hydrochlorothiazide in Patients with Hypertension.

BACKGROUND: Triamterene, because of its potassium-sparing properties, is frequently used in combination with hydrochlorothiazide (HCTZ) to treat patients with hypertension. By inhibiting the epithelial sodium channel (ENaC) in the cortical collecting duct, triamterene reduces potassium secretion, thus reducing the risk of hypokalemia. Whether triamterene has an independent effect on blood pressure (BP) has not been well studied. OBJECTIVE: To determine if triamterene provides an effect to further lower BP in patients treated with HCTZ. DESIGN: We conducted an observational study using electronic medical record data from the Indiana Network for Patient Care. Participants were 17,291 patients with the diagnosis of hypertension between 2004 and 2012. MAIN MEASURES: BP was the primary outcome. We compared the BP between patients who were taking HCTZ, with and without triamterene, either alone or in combination with other antihypertensive medications, by using a propensity score analysis. For each medication combination, we estimated the propensity score (i.e., probability) of a patient receiving triamterene using a logistic regression model. Patients with similar propensity scores were stratified into subclasses and BP was compared between those taking triamterene or not within each subclass; the effect of triamterene was then assessed by combining BP differences estimated from all subclasses. KEY RESULTS: The mean systolic BP in the triamterene + HCTZ group was 3.8 mmHg lower than in the HCTZ only group (p < 0.0001); systolic BP was similarly lower for patients taking triamterene with other medication combinations. Systolic BP reduction was consistently observed for different medication combinations. The range of systolic BP reduction was between 1 and 4 mm Hg, depending on the concurrently used medications. CONCLUSIONS: In the present study, triamterene was found to enhance the effect of HCTZ to lower BP. In addition to its potassium-sparing action, triamterene's ability to lower BP should also be considered.

Utilizing an integrated infrastructure for outcomes research: a systematic review.

OBJECTIVE: To explore the ability of an integrated health information infrastructure to support outcomes research. METHODS: A systematic review of articles published from 1983 to 2012 by Regenstrief Institute investigators using data from an integrated electronic health record infrastructure involving multiple provider organisations was performed. Articles were independently assessed and classified by study design, disease and other metadata including bibliometrics. RESULTS: A total of 190 articles were identified. Diseases included cognitive, (16) cardiovascular, (16) infectious, (15) chronic illness (14) and cancer (12). Publications grew steadily (26 in the first decade vs. 100 in the last) as did the number of investigators (from 15 in 1983 to 62 in 2012). The proportion of articles involving non-Regenstrief authors also expanded from 54% in the first decade to 72% in the last decade. During this period, the infrastructure grew from a single health system into a health information exchange network covering more than 6 million patients. Analysis of journal and article metrics reveals high impact for clinical trials and comparative effectiveness research studies that utilised data available in the integrated infrastructure. DISCUSSION: Integrated information infrastructures support growth in high quality observational studies and diverse collaboration consistent with the goals for the learning health system. More recent publications demonstrate growing external collaborations facilitated by greater access to the infrastructure and improved opportunities to study broader disease and health outcomes. CONCLUSIONS: Integrated information infrastructures can stimulate learning from electronic data captured during routine clinical care but require time and collaboration to reach full potential.

Corrigendum to "Medication safety practices in hospitals: A national survey in Saudi Arabia" [Saudi Pharm. J. 21(2) (2013) 159-164].

[This corrects the article DOI: 10.1016/j.jsps.2012.07.005.].

Memory and comprehension for health information among older adults: distinguishing the effects of domain-general and domain-specific knowledge.

While there is evidence that knowledge influences understanding of health information, less is known about the processing mechanisms underlying this effect and its impact on memory. We used the moving window paradigm to examine how older adults varying in domain-general crystallised ability (verbal ability) and health knowledge allocate attention to understand health and domain-general texts. Participants (n = 107, age: 60-88 years) read and recalled single sentences about hypertension and about non-health topics. Mixed-effects modelling of word-by-word reading times suggested that domain-general crystallised ability increased conceptual integration regardless of text domain, while health knowledge selectively increased resource allocation to conceptual integration at clause boundaries in health texts. These patterns of attentional allocation were related to subsequent recall performance. Although older adults with lower levels of crystallised ability were less likely to engage in integrative processing, when they did, this strategy had a compensatory effect in improving recall. These findings suggest that semantic integration during reading is an important comprehension process that supports the construction of the memory representation and is engendered by knowledge. Implications of the findings for theories of text processing and memory as well as for designing patient education materials are discussed.

Incidence of adverse drug events in an academic hospital: a prospective cohort study.

OBJECTIVE: To determine the incidence of adverse drug events (ADEs) and assess their severity and preventability. DESIGN: A prospective cohort study. SETTING: A 900-bed tertiary academic hospital. PARTICIPANTS: A total of 977 patients admitted to two medical, one surgical and two intensive care units over four months. MAIN OUTCOME MEASURES: The primary outcomes were the incidence of ADEs, preventability of ADEs, potential ADEs and medication errors. A physician and a clinical pharmacist independently determined the likelihood that incidents were caused by medications and judged severity and preventability. RESULTS: Pharmacists reviewed the medical records of the 977 patients. Pharmacists identified 361 incidents, of which 281 (78%) were considered to be an ADE, potential ADE or medication error by reviewers. The incidence of ADEs was 8.5 per 100 admissions (95% confidence interval (CI) 6.8-10.4), with the highest rate found in the intensive care unit (21.1 per 100 admissions) (95% CI 15.1-28.8). Of all ADEs, 59% were rated as significant, 35% as serious and 6% as life threatening. Thirty percent of ADEs were preventable and 96% of these occurred in the ordering stage. The incidence of potential ADEs was 13.8 per 100 admissions (95% CI 11.5-16.2). Overall, 223 medication errors were identified, 66 (30%) were harmless, 132 (59%) had the potential to cause harm and 25 (11%) resulted in harm. CONCLUSIONS: The incidence of ADEs in a Saudi Hospital was 8.5 per 100 admissions. Preventable ADEs most commonly occurred in the ordering stage; therefore, interventions to reduce ADEs should target the ordering stage.

Medication safety practices in hospitals: A national survey in Saudi Arabia.

BACKGROUND: Medication errors in hospitals are a worldwide concern. The World Health Organization has recommended the implementation of basic applications in healthcare systems to improve medication safety, but it is largely unknown whether these recommendations are adhered to by hospitals. We assessed the presence of core medication safety practices in Saudi Arabian hospitals. METHODS: We developed and validated a survey to assess medication safety practices in hospitals. Major headings included Look-Alike Sound-Alike (LASA) medications, control of concentrated electrolyte solutions, transitions in care, information technology, drug information and other medication safety practices. Trained pharmacists visited samples of hospitals from all regions of Saudi Arabia. RESULTS: Seventy-eight hospitals were surveyed. Only 30% of the hospitals had a medication safety committee and 9% of hospitals had a medication safety officer. Only 33% of hospitals had a list of LASA medications and 50% had a list of error-prone abbreviations. Concentrated electrolytes were available in floor stock in 60% of the hospitals. No hospital involved pharmacists in obtaining medication histories and only 37% of the hospitals provided a medication list to the patients at discharge. While 61% of hospitals used a computer system in their pharmacy to enter prescriptions, only 29% of these hospitals required entry of patient's allergies before entering a drug order. CONCLUSIONS: Core practices to improve medication safety were not implemented in many hospitals in Saudi Arabia. In developing countries, an effort must be made at the national level to increase the adoption of such practices.

Pharmacogenetics and healthcare outcomes in patients with chronic heart failure.

PURPOSE: To test for associations between genetic polymorphisms of adrenergic receptors (AR) and other candidate genes and healthcare utilization in heart failure patients, taking into account other important factors, such as medication adherence. METHODS: One year-hospital utilization data were collected from 140 participants with heart failure, aged 50 years or older. Medication adherence was measured. Hospitalization and emergency department (ED) visits due to heart failure were used as healthcare outcomes. The genotypes of polymorphisms in six genes were determined: α(2C)-AR (ADRA2C), ß1-AR (ADRB1), ß2-AR (ADRB2), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and CYP4A11. Haplotypes for ADRB1 and ADRB2 were estimated. The genotype effects on healthcare outcomes were examined using log-linear regression models. RESULTS: Compared to ADRB1 Arg389 carriers, homozygous Gly389Gly carriers experienced fewer ED visits [incidence rate ratio (IRR) 0.07, 95 % confidence interval (CI) 0.01-0.54, P = 0.022]. Compared to ADRB2 homozygous Gly16Gly carriers, Arg16Gly carriers had fewer ED visits (IRR 0.23, 95 % CI 0.09-0.59, P = 0.006). Polymorphisms in ADRB1 as well as those in ADRB2 were in linkage disequilibrium, with three defining haplotypes, respectively. For ADRB2, the risk of hospitalizations and ED visits were relatively lower in Arg16/Gln27 carriers but relatively higher in homozygous Gly16/Gln27 carriers (P < 0.05). Compared to eNOS 894TT homozygous variants, 894GG and 894GT carriers had notably fewer ED visits (IRR 0.05, 95 % CI 0.01-0.25, P = 0.0013 and IRR 0.10, 95 % CI 0.02-0.42, P = 0.006, respectively). The other polymorphisms showed no association with healthcare outcomes. CONCLUSIONS: After controlling for demographics, functional status, and treatment adherence, polymorphisms in ADRB1, ADRB2 and eNOS are associated with healthcare outcomes in heart failure patients.

Comparative effects of non-steroidal anti-inflammatory drugs (NSAIDs) on blood pressure in patients with hypertension.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may disrupt control of blood pressure in hypertensive patients and increase their risk of morbidity, mortality, and the costs of care. The objective of this study was to examine the association between incident use of NSAIDs and blood pressure in patients with hypertension. METHODS: We conducted a retrospective cohort study of adult hypertensive patients to determine the effects of their first prescription for NSAID on systolic blood pressure and antihypertensive drug intensification. Data were collected from an electronic medical record serving an academic general medicine practice in Indianapolis, Indiana, USA. Using propensity scores to minimize bias, we matched a cohort of 1,340 users of NSAIDs with 1,340 users of acetaminophen. Propensity score models included covariates likely to affect blood pressure or the use of NSAIDs. The study outcomes were the mean systolic blood pressure measurement after starting NSAIDs and changes in antihypertensive therapy. RESULTS: Compared to patients using acetaminophen, NSAID users had a 2 mmHg increase in systolic blood pressure (95% CI, 0.7 to 3.3). Ibuprofen was associated with a 3 mmHg increase in systolic blood pressure compared to naproxen (95% CI, 0.5 to 4.6), and a 5 mmHg increase compared to celecoxib (95% CI, 0.4 to 10). The systolic blood pressure increase was 3 mmHg in a subgroup of patients concomitantly prescribed angiotensin converting enzyme inhibitors or calcium channel blockers and 6 mmHg among those prescribed a beta-adrenergic blocker. Blood pressure changes in patients prescribed diuretics or multiple antihypertensives were not statistically significant. CONCLUSION: Compared to acetaminophen, incident use of NSAIDs, particularly ibuprofen, is associated with a small increase in systolic blood pressure in hypertensive patients. Effects in patients prescribed diuretics or multiple antihypertensives are negligible.

Evaluation of the Health Utilities Index Mark-3 in heart failure.

BACKGROUND: The purpose of this study was to evaluate the reliability, validity, and responsiveness to change of the Health Utilities Index Mark-3 (HUI-3) in heart failure (HF) for use in cost-effectiveness studies. METHODS AND RESULTS: Two hundred eleven patients with HF recruited from outpatient clinics were enrolled; 165 completed the 26-week study. Patients completed 4 health-related quality of life questionnaires (baseline and 4, 8, and 26 weeks), including the HUI-3, the Medical Outcomes Study Short-form 12 (SF-12), the Minnesota Living with Heart Failure Questionnaire (LHFQ), and the Chronic Heart Failure Questionnaire (CHQ). The HUI-3 indicated moderate or fair health-related quality of life overall; the attributes most impaired were pain, ambulation, cognition, and emotion. Internal consistency reliability (Cronbach's alpha = 0.51) was low and test-retest reliability (intraclass correlation coefficient = 0.68) was adequate. The HUI-3 total score was significantly associated with the SF-12, LHFQ, and CHQ total scores. It discriminated among patients with varying New York Heart Association class (P < .001) and varying perceived health (P < .001). The HUI-3 was less responsive to perceived change in health condition than the LHFQ or the CHQ. CONCLUSIONS: The HUI-3 demonstrated satisfactory reliability and validity in this sample supporting its use in cost-effectiveness studies.

Curricular considerations for pharmaceutical comparative effectiveness research.

In the U.S. pharmacoepidemiology and related health professions can potentially flourish with the congressional appropriation of $1.1 billion of federal funding for comparative effectiveness research (CER). A direct result of this legislation will be the need for sufficient numbers of trained scientists and decision-makers to address the research and implementation associated with CER. An interdisciplinary expert panel comprised mostly of professionals with pharmaceutical interests was convened to examine the knowledge, skills, and abilities to be considered in the development of a CER curriculum for the health professions focusing predominantly on pharmaceuticals. A limitation of the panel's composition was that it did not represent the breadth of comparative effectiveness research, which additionally includes devices, services, diagnostics, behavioral treatments, and delivery system changes. This bias affects the generalizability of these findings. Notwithstanding, important components of the curriculum identified by the panel included study design considerations and understanding the strengths and limitations of data sources. Important skills and abilities included methods for adjustment of differences in comparator group characteristics to control confounding and bias, data management skills, and clinical skills and insights into the relevance of comparisons. Most of the knowledge, skills, and abilities identified by the panel were consistent with the training of pharmacoepidemiologists. While comparative effectiveness is broader than the pharmaceutical sciences, pharmacoepidemiologists have much to offer academic and professional CER training programs. As such, pharmacoepidemiologists should have a central role in curricular design and provision of the necessary training for needed comparative effectiveness researchers within the realm of pharmaceutical sciences.

The process-knowledge model of health literacy: evidence from a componential analysis of two commonly used measures.

We investigated the effects of domain-general processing capacity (fluid ability such as working memory), domain-general knowledge (crystallized ability such as vocabulary), and domain-specific health knowledge for two of the most commonly used measures of health literacy (S-TOFHLA and REALM). One hundred forty six community-dwelling older adults participated; 103 had been diagnosed with hypertension. The results showed that older adults who had higher levels of processing capacity or knowledge (domain-general or health) performed better on both of the health literacy measures. Processing capacity interacted with knowledge: Processing capacity had a lower level of association with health literacy for participants with more knowledge than for those with lower levels of knowledge, suggesting that knowledge may offset the effects of processing capacity limitations on health literacy. Furthermore, performance on the two health literacy measures appeared to reflect a different weighting for the three types of abilities. S-TOFHLA performance reflected processing capacity as well as general knowledge, whereas performance on the REALM depended more on general and health knowledge than on processing capacity. The findings support a process-knowledge model of health literacy among older adults, and have implications for selecting health literacy measures in various health care contexts.

Risk of hyperkalemia associated with selective COX-2 inhibitors.

BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors have been linked to cardiac death. The mechanism for this adverse effect appears to be by ischemic insult; however another mechanism could involve hyperkalemia. The objective of this study was to determine the effects of selective COX-2 inhibitors and non-selective nonsteroidal anti-inflammatory drugs (NSAIDs) on serum potassium concentration and the electrocardiogram. METHODS: A retrospective cohort study was conducted using propensity score matching of patients from an inner-city academic medical center at Indianapolis, Indiana. Two hundred and two patients prescribed selective COX-2 inhibitors were matched to 202 patients prescribed non-selective NSAIDs using propensity scores methods. Outcomes included change in serum potassium concentration from baseline and the risk of an abnormal electrocardiogram. RESULTS: Compared to patients prescribed non-selective NSAIDs, those prescribed a selective COX-2 inhibitor had a higher risk of serum potassium increase greater than 5 mEq/L (OR, 2.56; 95%CI, 1.03-6.36). However, patients prescribed selective COX-2 inhibitors had no greater risk of electrocardiogram abnormality (OR, 1.16; 95%CI, 0.74-1.82). CONCLUSIONS: Selective COX-2 inhibitors may have a greater risk of hyperkalemia than non-selective NSAIDs. This study was exploratory with small numbers of patients. Further studies are needed to confirm these results and any association with cardiovascular events.

Implementing pharmacy practice research programs for the management of heart failure.

It stands to reason that pharmacists would have a beneficial role in the treatment of patients with chronic illnesses wherein complicated pharmacotherapies are required to reduce the risk of acute exacerbation. For chronic heart failure, recent evidence bears this out. When pharmacists take time to provide self-care instructions for patients with heart failure or take part in collaborative healthcare teams, the need for costly urgent healthcare decreases with corresponding decreases in healthcare costs. Further research is needed to address the key supportive roles of pharmacists in the treatment of patients with heart failure.

Effect of ropinirole on sleep outcomes in patients with restless legs syndrome: meta-analysis of pooled individual patient data from randomized controlled trials.

STUDY OBJECTIVE: To compare the effects of ropinirole with those of placebo on sleep, as evaluated by specific domains of the Medical Outcomes Study (MOS) sleep scale, as well as the Clinical Global Impression-Improvement (CGI-I) scale, in patients with restless legs syndrome (RLS). DESIGN: Meta-analysis of six randomized, double-blind, placebo-controlled, parallel-group trials conducted in the United States and Europe. PATIENTS: A total of 1679 patients aged 18-79 years with primary moderate-to-severe RLS who received ropinirole (835 patients) or placebo (844 patients). MEASUREMENTS AND MAIN RESULTS: A systematic review of MEDLINE (January 1980-January 2007) and clinical trial registers was performed to identify placebo-controlled trials of ropinirole that used the 12-item MOS sleep scale to assess sleep in patients with RLS. Individual patient data from both published and nonpublished trials were pooled for meta-analysis. In the eligible studies, immediate-release ropinirole 0.25-6 mg or placebo had been given for at least 12 weeks. In addition, sleep scale summary scores for the domains of sleep quantity, adequacy, disturbance, and daytime somnolence had to have been assessed at baseline and at 12 weeks. Our meta-analysis found that at baseline study patients slept an average of 5.8 hours/night. At the end of 12 weeks, ropinirole-treated patients slept a mean of 2.5 hours/week more and had a 21% greater improvement from baseline in sleep adequacy scores compared with patients receiving placebo. Ropinirole-treated patients also had 14% less sleep disturbance and 8% less daytime somnolence than patients receiving placebo. Clinicians rated 63% of ropinirole-treated patients and 47% of patients receiving placebo as responders based on the CGI-I scale. Mixed effects analysis of covariance was used to estimate treatment effect adjusting for study center as a random effect, as well as the following fixed effects known to affect sleep: baseline sleep characteristics, age, sex, and chronic medical conditions. All differences were statistically significant (p<0.05), even after adjusting for multiple comparisons. CONCLUSION: Pooled data from six similarly designed clinical trials provide evidence that ropinirole improves sleep quantity and adequacy, and lessens sleep disturbance and daytime somnolence in patients with primary RLS.

Continuity of health care and the pharmacist: let's keep it simple.

Pharmacists are a cornerstone of quality medication management. High-quality continuity of care involves patient-centered medication therapy management, which could be bolstered for 26 million Part D Medicare beneficiaries. Yet, many patients do not receive sufficient instruction about their prescription medications. Patient-centered aspects are important because of the heterogeneity in patient types and severity of disease, varying treatment requirements, lifestyle factors, and differences in health literacy. Although time constraints for all health professionals are apparent, a simple but crucial contribution by pharmacists to the continuity of care is to increase the emphasis on patient-centered medication instruction.

Comparison of methods to assess medication adherence and classify nonadherence.

BACKGROUND: Medication adherence is suboptimal, and clinicians and researchers struggle with identifying nonadherent patients. Various measures of medication adherence exist, but there is controversy regarding which measures provide acceptable data and how nonadherence should be defined. OBJECTIVE: To assess agreement among patient self-report, pharmacy refill, and electronic adherence measures and compare the sensitivity and specificity of different cut-points for defining nonadherence. METHODS: Data were analyzed from 2 similarly designed randomized controlled trials that assessed a pharmacist's intervention to improve medication adherence among patients with hypertension or heart failure. For each participant, adherence was measured by patient self-report, prescription refill records, and electronic lids on medication containers. Agreement among measures was assessed using Spearman's correlation coefficient rho. Correlation coefficients were compared by patient characteristics using Fisher's Z transformation. The sensitivity and specificity of different cut-points for defining nonadherence were calculated. RESULTS: Median adherence was 84% for self-report, 86% for electronic, and 91% for prescription refill adherence measurement. Refill and electronic adherence demonstrated the best agreement among measures (rho = 0.48). Age, depression, and other comorbid conditions influenced agreement among measures. Measures were generally in agreement, regardless of how nonadherence was defined. A cut-point of 80% illustrated a fair balance between sensitivity and specificity for all measures. CONCLUSIONS: All measures provided similar estimates of overall adherence, although refill and electronic measures were in highest agreement. In selection of a measure, practitioners should consider population and disease characteristics, since measurement agreement could be influenced by these and other factors. The commonly used, clinically based cut-point of 80% had a reasonable balance between sensitivity and specificity in studies of adherence in patients with heart failure or hypertension.