PurposeTreatment guidelines recommend insulin progression (switching from basal to a premixed insulin regimen, adding bolus doses, and/or increasing dosing frequency) to achieve A1C targets as type 2 diabetes progresses, but fewer patients are being progressed than would be indicated based on their disease status. This systematic review proposes 2 questions regarding insulin progression among patients with type 2 diabetes: (1) What are the patient, provider, and health system barriers to insulin progression? (2) Do insulin progression barriers differ between insulin-naive and insulin-experienced patients?MethodsWe conducted a systematic review in the MEDLINE, EMBASE, Science Citation Index, PsycINFO, CINAHL, and Cochrane Library databases through July 2011.ResultsOf 745 potentially relevant articles, 10 met inclusion criteria: 7 evaluated patient and 2 evaluated provider barriers, and 1 was an intervention to reduce barriers among physicians. Patients with prior insulin experience had fewer barriers arising from injection-related concerns and worries about the burden of insulin progression than did insulin-naive patients. Physician barriers included concerns about patients' ability to follow more complicated regimens as well as physicians' own inexperience with insulin and progression algorithms. The cross- sectional nature, narrow scope, and failure of all studies to examine patient, provider, and health systems barriers concurrently limited both barrier identification and an assessment of their impact on progression.ConclusionsPatient and physician experience with insulin and diabetes/insulin education were associated with fewer perceived barriers to insulin progression. Future studies should use multilevel longitudinal designs to quantify the relative impact of potential patient, provider, and health system factors on progression and health outcomes.

BACKGROUND: Given the huge burden of coronary artery disease and the effectiveness of medication therapy, understanding and quantifying known impacts of poor medication adherence for primary and secondary prevention is crucial. We sought to systematically review the literature on this topic area with a focus on quantified cost and clinical outcomes related to adherence. METHODS: We conducted a systematic review of the literature between 1966 and November 2011 using a fixed search strategy, multiple reviewers, and a quality rating scale. We found 2636 articles using this strategy, eventually weaning them down to 25 studies that met our inclusion criteria. Three reviewers independently reviewed the studies and scored them for quality using the Newcastle Ottawa Scoring Scale. RESULTS: We found 5 studies (4 of which focused on statins) that measured the impact of medication adherence on primary prevention of coronary artery disease and 20 articles that focused on the relationship between medication adherence to costs and outcomes related to secondary prevention of coronary artery disease. Most of these latter studies focused on antihypertensive medications and aspirin. All controlled for confounding comorbidities and sociodemographic characteristics, but few controlled for likelihood of adherent patients to have healthier behaviors ("healthy adherer effect"). Three studies found that high adherence significantly improves health outcomes and reduces annual costs for secondary prevention of coronary artery disease (between $294 and $868 per patient, equating to 10.1%-17.8% cost reductions between high- and low-adherence groups). The studies were all of generally of high quality on the Newcastle Ottawa Scale (median score 8 of 9). CONCLUSIONS: Increased medication adherence is associated with improved outcomes and reduced costs, but most studies do not control for a "healthy adherer" effect.

Non-adherence to evidence-based medications is a major public health problem. Less than 50 % of patients with coronary artery disease adhere to their prescribed therapies and this has important implications for morbidity, mortality, and health care spending. Like most complex behaviors, medication non-adherence is not solely the result of poor patient choices. Rather, there are myriad potential contributors attributable to patients, health care providers, and, more broadly, the health care system. Interventions including patient education and behavioral modification, improving patient-physician communication, and eliminating copayments for preventive pharmacotherapy have all been studied. Clinicians play a critical role in helping improve adherence and assessment of adherence must become a standard component of each clinical encounter. Ultimately, given the various etiologies that contribute to non-adherence, achieving meaningful gains will undoubtedly require payors, providers, and policymakers to develop, rigorously evaluate, and systematically deploy strategies that address key patient, clinician, and health system factors.

Background  Generic prescription drugs are bioequivalent to brand-name versions but may not have consistent color or shape, which can cause confusion and lead to interruptions in medication use. We sought to determine whether switching among different-appearing antiepileptic drugs (AEDs) is associated with increased rates of medication nonpersistence, which can have serious medical, financial, and social consequences.Methods  We designed a nested case-control study of commercially insured patients in the United States who initiated an AED. Cases were patients who became nonpersistent, defined as failure to fill a prescription within 5 days of the elapsed days supplied. Controls had no delay in refilling and were matched by sex, age, number of refills, and the presence of a seizure disorder diagnosis. We evaluated the 2 refills preceding nonpersistence and determined whether pill color and/or shape matched (“concordant”) or did not match (“discordant”). We compared the odds of discordance among cases and controls using multivariate conditional logistic regression, adjusting for baseline characteristics, and drug type. We repeated our analysis among patients with a seizure diagnosis.Results  The AEDs dispensed had 37 colors and 4 shapes. A total of 11 472 patients with nonpersistence were linked to 50 050 controls. Color discordance preceded 136 cases (1.20%) but only 480 controls (0.97%) (adjusted odds ratio [OR], 1.27 [95% CI, 1.04-1.55]). Shape discordance preceded 18 cases (0.16%) and 54 controls (0.11%) (OR, 1.47 [95% CI, 0.85-2.54]). Within the seizure disorder diagnosis subgroup, the risk of nonpersistence after changes in pill color was also significantly elevated (OR, 1.53 [95%, CI 1.07-2.18]).Conclusions  Changes in pill color significantly increase the odds of nonpersistence; this may have important clinical implications. Our study supports a reconsideration of current regulatory policy that permits wide variation in the appearance of bioequivalent drugs.

OBJECTIVES: To evaluate the association between social support and medication adherence. STUDY DESIGN: A search of articles published before November 2010 in peer-reviewed, healthcarerelated journals was conducted using PubMed, EMBASE, and Web of Science, and search terms related to social support (social support OR friend OR family OR agency) and adherence (patient compliance OR medication adherence), yielding 5331 articles. METHODS: Articles were included if they directly measured the relationship between medication adherence and some form of social support. Excluded were case studies, studies with participants < 18 years of age, and non-English language studies. Four social support categories were reported: structural, practical, emotional, and combination. Medication adherence was reported in the manner in which it was described in each study. RESULTS: Fifty studies were included in the final analysis. A greater degree of practical support was most consistently associated with greater adherence to medication; evidence for structural or emotional support was less compelling. However, most studies were limited in size and design, and substantial variability in designs and outcome measurement prohibited pooling of results, necessitating qualitative evaluation of the studies. CONCLUSIONS: This qualitative analysis found that practical social support was most consistently associated with greater medication adherence. Interventions that use existing contacts (friends or family) to engage patients in the mundane and practical aspects of medication purchasing and administration may be an effective approach to promoting better medication adherence.

BACKGROUND: In the treatment of patients with refractory atrial fibrillation (AF), the safety and efficacy of atrioventricular nodal ablation (AVNA) versus pharmacotherapy alone remains unclear. Additionally, the impact of AVNA in patients with reduced systolic function is of growing interest. METHODS AND RESULTS: A total of 5 randomized or prospective trials were included for efficacy review (314 patients), 11 studies for effectiveness review (810 patients), and 47 studies for safety review (5632 patients). All-cause mortality was similar between AVNA and medical therapy (3.1% versus 3.3%; relative risk ratio, 1.05; 95% confidence interval [CI], 0.29-3.85). There was no significant difference in exercise duration or ejection fraction (EF) with AVNA relative to pharmacotherapy. In subgroup analysis, patients with baseline systolic dysfunction (116 patients; mean EF, 44%) showed significant relative improvement in EF after AVNA (+4% greater; 95% CI, 3.11-4.89). In pooled observational analysis, AVNA was also associated with significant improvement in EF only in patients with systolic dysfunction (+7.44%; 95% CI, 5.4-9.5). The incidence of procedure-related mortality (0.27%) and malignant arrhythmia (0.57%) was low. At mean follow-up of 26.5 months, the incidence of sudden cardiac death after AVNA was 2.1%. There was significant heterogeneity in quality-of-life scales used; compared with pharmacotherapy, AVNA was associated with significant improvement in several symptoms (palpitations, dyspnea). CONCLUSIONS: In the management of refractory AF, AVNA is associated with improvement in symptoms and quality of life, with a low incidence of procedure morbidity. In patients with reduced systolic function, AVNA demonstrates small but significantly improved echocardiographic outcomes relative to medical therapy alone.

To the Editor: Direct-to-consumer advertising (DTCA) can influence the use of prescription drugs.1 - 2 The US Food and Drug Administration (FDA) regulates prescription drug advertising, including requirements to provide consumers with a “fair balance” of risks and benefits. When prescription drugs switch to over-the-counter (OTC) status, regulatory oversight of their advertising shifts to the Federal Trade Commission (FTC). Unlike the FDA, the FTC holds drug advertisements to the same standards as any consumer product: it applies a “reasonable consumer” standard of truthfulness and nondeception that does not require any balancing of potential benefits and harms. Such a shift may be associated with changes in content.

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BACKGROUND: Controversy exists regarding the optimal preventative therapy for venous thromboembolism (VTE) after coronary artery bypass graft (CABG) surgery. We sought to compare the effectiveness and safety of the most commonly used regimens. METHODS AND RESULTS: We assembled a cohort of 92 699 patients who underwent CABG between 2004 and 2008, using the Premier database. Patients were categorized by method of VTE prevention initiated within 48 hours of surgery, including no preventative therapy (n=55 400), mechanical preventative therapy (n=21 162), subcutaneous unfractio--nated or low-molecular-weight heparin (n=10 718), subcutaneous fondaparinux (n=88), and concurrent mechanical-chemical therapy (n=5331). The incidence of VTE and major bleeding events within 6 weeks of CABG were compared, using multivariable and propensity score adjustment. The overall incidence of VTE for the entire cohort was 0.74%, and the incidence of major bleeding was 1.43%. VTE and bleeding events occurred with similar incidence in each of the patient categories (VTE: 0.70%, 0.79%, 0.81%, 1.14%, and 0.73%; major bleeding: 1.36%, 1.45%, 1.69%, 3.41%, 1.50%; no prevention, mechanical prevention, subcutaneous heparin, subcutaneous fondaparinux, concurrent mechanical-chemical prevention, respectively). Compared with receiving no prevention, the use of mechanical prevention or subcutaneous heparin did not significantly reduce the risk of VTE or change the risk of major bleeding (P=NS). CONCLUSION: Venous thromboembolism occurs infrequently after CABG. Compared with the use of no prevention, the administration of chemical or mechanical preventative therapies to CABG patients does not appreciably lower the risk of VTE. These data provide support for the common practice of administering no VTE preventative therapy after CABG, used for nearly 60% of patients within this cohort.

BACKGROUND: Dabigatran, an oral thrombin inhibitor, and rivaroxaban and apixaban, oral factor Xa inhibitors, have been found to be safe and effective in reducing stroke risk in patients with atrial fibrillation. We sought to compare the efficacy and safety of the 3 new agents based on data from their published warfarin-controlled randomized trials, using the method of adjusted indirect comparisons. METHODS AND RESULTS: We included findings from 44 535 patients enrolled in 3 trials of the efficacy of dabigatran (Randomized Evaluation of Long-Term Anticoagulation Therapy [RELY]), apixaban (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]), and rivaroxaban (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET-AF]), each compared with warfarin. The primary efficacy end point was stroke or systemic embolism; the safety end point we studied was major hemorrhage. To address a lack of comparability between trial populations caused by the restriction of ROCKET-AF to high-risk patients, we conducted a subgroup analysis in patients with a CHADS(2) score >/=3. We found no statistically significant efficacy differences among the 3 drugs, although apixaban and dabigatran were numerically superior to rivaroxaban. Apixaban produced significantly fewer major hemorrhages than dabigatran and rivaroxaban. CONCLUSIONS: An indirect comparison of new anticoagulants based on existing trial data indicates that in patients with a CHADS(2) score >/=3 dabigatran 150 mg, apixaban 5 mg, and rivaroxaban 20 mg resulted in statistically similar rates of stroke and systemic embolism, but apixaban had a lower risk of major hemorrhage compared with dabigatran and rivaroxaban. Until head-to-head trials or large-scale observational studies that reflect routine use of these agents are available, such adjusted indirect comparisons based on trial data are one tool to guide initial therapeutic choices.

BACKGROUND: Disclosure of conflicts of interest in biomedical research is receiving increased attention. The authors sought to define current disclosure policies and how they relate to disclosure statements provided by authors in major oncology journals. METHODS: The authors identified all oncology journals listed in the Thomson Institute for Scientific Information and sought their policies on conflict-of-interest disclosure. For a subset of journals with an Impact Factor >2.0, they catalogued the number and type of articles and the details of the published disclosures in all papers from the 2 most recent issues. RESULTS: Disclosure policies were provided by 112 of 131 journals (85%); 99 (88%) of these requested that authors disclose conflicts of interest (mean Impact Factor for these journals: 4.6), whereas the remaining 13 (12%) did not (mean Impact Factor: 2.9). Ninety-three journals (94%) required financial disclosure, and 42 (42%) also sought nonfinancial disclosures. For a subset of 52 higher-impact journals (Impact Factor >2.0), we reviewed 1734 articles and identified published disclosures in 51 journals (98%). Many of these journals (31 of 51, 61%) included some disclosure statement in >90% of their articles. Among 27 journals that published editorials/commentaries, only 14 (52%) included disclosures with such articles. There was no publication of any nonfinancial conflicts of interest in any article reviewed. CONCLUSIONS: Disclosure policies and the very definition of conflict of interest varied considerably among journals. Although most journals had some policy in this area, a substantial proportion did not publish disclosure statements consistently, with deficiencies particularly among editorials and commentaries.

BACKGROUND: The affordability of prescription medications continues to be a major public health issue in the United States. Estimates of cost-related medication underuse come largely from surveys of ambulatory patients. Hospitalized patients may be vulnerable to cost-related underuse and its consequences, but have been subject to little investigation. OBJECTIVE: To determine impact of medication costs in a cohort of hospitalized managed care beneficiaries. METHODS: We surveyed consecutive patients admitted to medical services at an academic medical center. Questions about cost-related underuse were based on validated measures; predictors were assessed with multivariable models. Participants were asked about strategies to improve medication affordability, and were contacted after discharge to determine if they had filled newly prescribed medications. RESULTS: One-hundred thirty (41%) of 316 potentially eligible patients participated; 93 (75%) of these completed postdischarge surveys. Thirty patients (23%) reported cost-related underuse in the year prior to admission. In adjusted analyses, patients of black race were 3.39 times (95% confidence interval [CI], 1.05 to 11.02) more likely to report cost-related underuse than non-Hispanic white patients. Virtually all respondents (n = 123; 95%) endorsed at least 1 strategy to make medications more affordable. Few (16%) patients, prescribed medications at discharge, knew how much they would pay at the pharmacy. Almost none had spoken to their inpatient (4%) or outpatient (2%) providers about the cost of newly prescribed drugs. CONCLUSIONS: Cost-related underuse is common among hospitalized patients. Individuals of black race appear to be particularly at risk. Strategies should be developed to address this issue around the time of hospital discharge. Journal of Hospital Medicine 2011. (c) 2011 Society of Hospital Medicine.

On January 31, 2012, Pfizer recalled nearly 1 million packs of birth control pills because of concerns that inert and active pills were miscounted and incorrectly ordered in their blister packs.1 This and other recent recalls highlight concerns about the potential clinical impact of defective and otherwise compromised drug products. However, little is known about the public health burden of drug recalls and whether health care providers are properly notified about clinically important recalls. We sought to quantify the frequency, cause, and extent of distribution of drug recalls in the United States and to evaluate the processes by which the US Food and Drug Administration (FDA) communicates clinically important recall information to health care providers.

OBJECTIVES: The aim of this study was to evaluate the impact of reductions in statin and clopidogrel copayments on cardiovascular resource utilization, major coronary events, and insurer spending. BACKGROUND: Copayments are widely used to contain health spending but cause patients to reduce their use of essential cardiovascular medications. Reducing copayments for post-myocardial infarction secondary prevention has beneficial effects, but the impact of this strategy for lower risk patients and other drugs remains unclear. METHODS: An evaluation was conducted of health care spending and resource use by a large self-insured employer that reduced statin copayments for patients with diabetes or vascular disease and reduced clopidogrel copayments for all patients prescribed this drug. Eligible individuals in the intervention company (n = 3,513) were compared with a control group from other companies without such a policy (n = 49,803). Analyses were performed using segmented regression models with generalized estimating equations. RESULTS: Lowering copayments was associated with significant reductions in rates of physician visits (relative change: statin users 0.80; 95% confidence interval [CI]: 0.57 to 0.98; clopidogrel users: 0.87; 95% CI: 0.59 to 0.96) and hospitalizations and emergency department admissions (relative change: statin users 0.90; 95% CI: 0.80 to 0.92; clopidogrel users: 0.89; 95% CI: 0.74 to 0.90) although not major coronary events. Patient out-of-pocket spending for drugs and other medical services decreased (relative change: statin users 0.79; 95% CI: 0.75 to 0.83; clopidogrel users 0.74; 95% CI: 0.66 to 0.82). Providing more generous coverage did not increase overall spending (relative change: statin users 1.03; 95% CI: 0.97 to 1.09; clopidogrel users 0.94; 95% CI: 0.87 to 1.03). CONCLUSIONS: Lowering copayments for statins and clopidogrel was associated with reductions in health care resource use and patient out-of-pocket spending. The policy appeared cost neutral with respect to overall health spending.

A substantial threat to the overall health of the American public is nonadherence to medications used to treat diabetes, as well as physicians' failure to initiate patients' use of those medications. To address this problem, we evaluated an integrated, pharmacy-based program to improve patients' adherence and physicians' initiation rates. The study included 5,123 patients with diabetes in the intervention group and 24,124 matched patients with diabetes in the control group. The intervention consisted of outreach from both mail-order and retail pharmacists who had specific information from the pharmacy benefit management company on patients' adherence to medications and use of concomitant therapies. The interventions improved patients' medication adherence rates by 2.1 percent and increased physicians' initiation rates by 38 percent, compared to the control group. The benefits were greater in patients who received counseling in the retail setting than in those who received phone calls from pharmacists based in mail-order pharmacies. This suggests that the in-person interaction between the retail pharmacist and patient contributed to improved behavior. The interventions were cost-effective, with a return on investment of approximately $3 for every $1 spent. These findings highlight the central role that pharmacists can play in promoting the appropriate initiation of and adherence to therapy for chronic diseases.

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BACKGROUND: Acute kidney injury is a frequent postoperative complication that confers increased mortality, morbidity, and costs. The purpose of this study was to evaluate whether preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. METHODS: We assembled a retrospective cohort of 98,939 patients who underwent a major open abdominal, cardiac, thoracic, or vascular procedure between 2000 and 2010. Statin users were pair-matched to nonusers on the basis of surgery type, baseline kidney function, days from admission until surgery, and propensity score based on demographics, comorbid conditions, and concomitant medications. Acute kidney injury was defined based on changes in serum creatinine measurements applying Acute Kidney Injury Network and Risk-Injury-Failure staging systems, and on the need for renal replacement therapy. Associations between statin use and acute kidney injury were estimated by conditional logistic regression. RESULTS: Across various acute kidney injury definitions, statin use was consistently associated with a decreased risk: adjusted odds ratios (95% confidence intervals) varied from 0.74 (0.58-0.95) to 0.80 (0.71-0.90). Associations were similar among diabetics and nondiabetics, and across strata of baseline kidney function. The protective association of statins was most pronounced among patients undergoing vascular surgery and least among patients undergoing cardiac surgery. CONCLUSIONS: Preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. Future randomized clinical trials are needed to determine causality.

BACKGROUND: Little is known about the use of warfarin in hemodialysis (HD) patients with atrial fibrillation (AF). We studied temporal trends of AF among older HD patients, and of warfarin use among those with AF. METHODS: We linked US Medicare and prescription claims from older patients undergoing HD in 2 Eastern US states. We established annual cohorts of prevalent HD patients; AF was ascertained from >2 claims (>7 days apart) in the same year, with a diagnosis code indicating AF. Among those with AF, we defined current and past warfarin use. Demographic and clinical characteristics were also ascertained for each cohort. We used repeated-measures logistic regression to define the odds of AF and of current or past versus absence of warfarin use. RESULTS: Of 6,563 unique patients, 2,185 were determined to have AF. The prevalence of AF increased from 26% in 1998 to 32% in 2005. In 2005, current warfarin use was present in 24% of AF patients and past use in 25%; 51% had no evidence of any warfarin use. No significant trends in utilization were observed from 1998 through 2005. Patients aged =85 years and nonwhites were less likely to have received warfarin; most comorbidities were not associated with warfarin use except for patients with past pulmonary embolism or deep venous thrombosis who were more likely than those without such history. CONCLUSION: While the prevalence of AF has been increasing among older HD patients, warfarin use was low and unchanged over time, perhaps reflecting the lack of evidence supporting its use.

ABSTRACT: BACKGROUND: Although consensus guidelines recommend insulin progression among patients with type 2 diabetes (T2DM) who fail to meet glycemic targets over time, many fewer patients are progressed than may benefit. We describe the rationale and design of the MOSAIc (Multinational Observational Study Assessing Insulin use) study, a multinational observational cohort study to identify patient-, physician, and health care environment-based factors associated with insulin progression for patients with T2DM in real-world practice. Methods/design We will enroll 4,500 patients with T2DM taking initial insulin therapy for [greater than or equal to]3 months across 175 physician practice sites in 18 countries. Extensive demographic, clinical, and psychosocial data at the patient and physician level and practice site characteristics will be collected at baseline and regular intervals during a 24-month follow-up period. We will use a multivariable logistic regression model to identify predictors of insulin progression and highlight potential opportunities for health behavior intervention to improve insulin progression rates. Secondary outcomes include evaluating factors associated with glycemic control, hypoglycemia, and treatment adherence among patients who do and do not progress beyond their initial insulin therapy and exploring geographic heterogeneity in treatment. DISCUSSION: Practice site and patient recruitment began in 2011 and baseline data will be available in late 2012. The MOSAIC study's longitudinal observational design as well as the breadth and depth of data will be used to explore and quantify predictors of insulin progression and to identify potential opportunities for health behavior intervention in order to improve T2DM treatment and clinical outcomes.

Aims Previous studies have suggested that upstream medical therapy to modulate the renin-angiotensin axis may facilitate left atrial remodelling and thereby prevent new-onset atrial fibrillation (AF). The purpose of this study was to evaluate the association between angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARB) on new-onset AF in a large cohort of patients with coronary artery disease (CAD).Methods and results This was a population-based study of 28 620 patients, from community-dwelling Medicare beneficiaries who had been hospitalized for acute myocardial infarction or coronary revascularization (1995–2004). All patients, 65 years and older, had a mean follow-up period of upto 3.8 ± 3.0 years. Patients with a history of AF before and during hospitalization were excluded.  We compared the incidence of new-onset AF between patients who were (N= 10 918) and were not (N= 17 702) prescribed ACEI and/or ARB within 1 month of hospital discharge following cardiac event. New-onset AF within 5 and 10 years was 39.1 and 61.1%, respectively, in patients who received ACEI/ARB, compared  34.9 and 53.6% in patients who did not receive them [unadjusted hazard ratio (HR): 1.16; 95% confidence interval (CI): 1.11, 1.21]. Multivariable analysis adjusting for patient- and hospital-related characteristics indicated that ACEI/ARB use independently had no impact on the risk of developing new-onset AF compared with non-users (adjusted HR: 0.99; 95% CI: 0.94, 1.04). Adjustment for propensity-score and health-seeking behaviours yielded nearly identical results.Conclusion Angiotensin converting enzyme inhibitor/ARB therapy initiated within 1 month after hospital discharge is not associated with a reduction in the risk of new-onset AF after myocardial infarction or coronary revascularization.

Given rising pharmaceutical expenditures and the widespread use of reference pricing as a costcontainment instrument abroad, we systematically reviewed the evidence evaluating reference pricing policies. We performed a structured electronic search of peer-reviewed journals for studies published before that reported on the effects of reference pricing policies on medication use, payer and patient spending, and resource consumption. Our search yielded 16 studies describing 9 reference-pricing policies from 6 countries. Reference-pricing policies led to decreases in drug prices and increases in utilization of targeted medications, while also reducing payer and patient expenditures. In addition, these policies did not lead to increased use of medical services, such as physician office visits and hospitalization. These results suggest that reference pricing may be an attractive policy strategy for the US healthcare system.

OBJECTIVES To determine whether adherence interventions should be administered to all medication takers or targeted to nonadherers. DATA SOURCES AND STUDY SELECTION Systematic search (Medline and Embase, 1966-2009) of randomized controlled trials of interventions to improve adherence to medications for preventing or treating cardiovascular disease or diabetes. DATA EXTRACTION Articles were classified as (1) broad interventions (targeted all medication takers), (2) focused interventions (targeted nonadherers), or (3) dynamic interventions (administered to all medication takers; real-time adherence information targets nonadherers as intervention proceeds). Cohen's d effect sizes were calculated. DATA SYNTHESIS We identified 7,190 articles; 59 met inclusion criteria. Broad interventions were less likely (18%) to show medium or large effects compared with focused (25%) or dynamic (32%) interventions. Of the 33 dynamic interventions, 6 used externally generated adherence data to target nonadherers. Those with externally generated data were less likely to have a medium or large effect (20% vs. 34.8% self-generated data). CONCLUSION Adherence interventions targeting nonadherers are heterogeneous but may have advantages over broad interventions. Dynamic interventions show promise and require further study.

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BACKGROUND: : In January 2008, the Food and Drug Administration (FDA) communicated concerns about the efficacy of ezetimibe, but did not provide clear clinical guidance, and substantial media attention ensued. We investigated the proportion of patients who discontinued therapy and switched to a clinically appropriate alternative after the FDA communication. METHODS: : Using claims data from a national pharmacy benefits manager, we created a rolling cohort of new users of ezetimibe between January 2006 and August 2008 and created a supply diary for each patient in the year after cohort entry. A patient was identified as nonpersistent if a gap of 90 days was seen in the diary. Using segmented linear regression, we compared rates of nonpersistence before and after the FDA communication and assessed patient-level characteristics associated with discontinuation. Among nonpersistent patients, we determined whether a patient made a clinically appropriate switch in the subsequent 90 days by adding a new cholesterol-lowering medication or by increasing the dose of an existing one. We used a weighted t test to compare the rates of appropriate switching before and after the communication. RESULTS: : Among 867,027 new ezetimibe users, 407,006 (46.9%) were nonpersistent in the first year. After the FDA communication, the monthly level of ezetimibe nonpersistence increased by 5.7 percentage points (P<0.0001). Younger patients, those who lived in low-income zip codes, and female patients were less likely to discontinue therapy (P<0.0001 for all). Among nonpersistent patients, rates of clinically appropriate switching increased from 10.8% before to 16.5% after the FDA warning (P=0.004). CONCLUSIONS: : A substantial increase in ezetimibe nonpersistence rates was seen after an FDA communication regarding its efficacy and following associated media attention, and a small proportion of patients made a clinically appropriate switch after discontinuation. Further consideration is needed to deliver messages that promote appropriate use of chronic therapy rather than simply reduce use.

Low levels of statin adherence have been documented in patients with coronary artery disease (CAD), but whether coronary revascularization is associated with improved adherence rates has yet to be evaluated. We identified all Medicare beneficiaries enrolled in 2 statewide pharmacy assistance programs who were >/=65 years old, who had been hospitalized for CAD from 1995 through 2004, and who had been prescribed statin therapy within 90 days of discharge (n = 13,130). Statin adherence was measured based on the proportion of days covered with statin therapy after hospital discharge, and full adherence was defined as proportion of days covered >/=80%. Statin adherence was compared in patients with CAD treated with medical therapy (n = 3,714), percutaneous coronary intervention (n = 6,309), or coronary artery bypass graft surgery (n = 3,107). Statin adherence significantly increased over the period of the study from 70.5% to 75.4% (p <0.0001). After hospitalization for CAD, patients treated with percutaneous coronary intervention and coronary artery bypass graft surgery had full adherence rates of 70.6% and 70.2%, respectively. Full adherence rates were significantly lower for patients treated with coronary revascularization compared to patients treated with medical therapy (79.4%, p <0.0001). Independent predictors of higher statin adherence included treatment with medical therapy, later year of hospital admission, white race, previous statin use, and use of other cardiac medications after CAD hospitalization (p <0.01 for all comparisons). In conclusion, in patients receiving invasive coronary treatment, statin adherence remains suboptimal, despite strong evidence supporting their use. Given the health and economic consequences of nonadherence, these findings highlight the need for developing cost-effective strategies to improve medication adherence after coronary revascularization.

Objective: To explore caregiver adherence to chronic medications and predictors of appropriate medication use.Design: Descriptive, nonexperimental, cross-sectional study.Setting: United States in May 2009.Participants: 2,000 adults randomly selected from a large national consumer panel.Intervention: Web-based survey of community pharmacy patients.Main outcome measure: Self-reported medication adherence.Results: 21% of those invited (3,775) responded to the survey invitation. Of the 2,000 individuals who were eligible to participate, 38% described themselves as caregivers. Among caregivers, 45% agreed that they were more likely to forget their own medications than medications for their caregivees. Caregivers were 10% more likely to forget to take their medications, 11% more likely to stop taking medications if they felt well, and 13% more likely to forget to refill their medications than noncaregivers (P < 0.001 for all). In fully adjusted models, caregivers had 36% greater odds (95% CI 0.52-0.79) of reporting that they were nonadherent compared with noncaregivers and increased medication use among caregivees was associated with worse adherence among caregivers (P < 0.05).Conclusion: Medication nonadherence was common in this population, and caregivers were more likely to report poor medication adherence than noncaregivers. Considering that caregivers often engage health professionals, physicians and pharmacists may choose to screen for caregiving status. Pharmacists are uniquely positioned to intervene to enhance appropriate medication adherence.

BACKGROUND: All US states have adopted generic substitution laws to reduce medication costs. However, physicians may override these regulations by prescribing branded drugs and requesting that they are dispensed as written. Patients also can make these requests. Little is known about the frequency and correlates of dispense as written requests or their association with medication filling. METHODS: We identified beneficiaries of a large pharmacy benefits manager who submitted a prescription claim from any pharmacy in January 2009. We categorized claims as a physician-assigned dispense as written, patient-assigned dispense as written, or no dispense as written. We described rates of these requests and used generalized estimating equations to evaluate physician, patient, treatment, and pharmacy characteristics associated with dispense as written requests. We also used generalized estimating equations to assess the relationship between dispense as written designation and rates prescriptions are not filled by patients. RESULTS: Our sample included 5.6 million prescriptions for more than 2 million patients. More than 2.7% were designated as dispense as written by physicians, and 2.0% were designated as dispense as written by patients. Substantial variation in dispense as written requests were seen by medication class, patient and physician age, and geographic region. The odds of requesting dispense as written was 78.5% greater for specialists than generalists (P<;.001). When chronic prescriptions were initiated, physician dispense as written (odds ratio 1.50, P<;.001) and patient dispense as written (odds ratio 1.60, P<;.001) were associated with greater odds that patients did not fill the prescription. CONCLUSION: Dispense as written requests were common and associated with decreased rates of prescription filling. Options to reduce rates of dispense as written requests may reduce costs and improve medication adherence.

OBJECTIVES: We sought to evaluate the cost-effectiveness of applying the JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial results into clinical practice. BACKGROUND: The JUPITER trial found that rosuvastatin reduces vascular events in apparently healthy subjects with elevated high-sensitivity C-reactive protein (hs-CRP) but normal low-density lipoprotein (LDL) cholesterol levels. The implications of expanding treatment recommendations based on these results have not been evaluated. METHODS: We constructed a cost-effectiveness model of men >/=50 years and women >/=60 years with LDL cholesterol levels of <130 mg/dl and no known cardiovascular disease. We compared: 1) hs-CRP testing followed by rosuvastatin treatment for patients with hs-CRP levels >/=2.0 mg/l; and 2) usual care (i.e., no testing and no treatment). Estimates of treatment effectiveness were based on the JUPITER trial and were varied in sensitivity analyses. RESULTS: Among patients with LDL <130 mg/dl and hs-CRP levels >/=2.0 mg/l, rosuvastatin had an incremental cost-effectiveness of $25,198 per quality-adjusted life year (QALY) gained compared to usual care. If the effectiveness of rosuvastatin were 50% of that observed in JUPITER, the incremental cost-effectiveness ratio would increase to $50,871 per QALY. Implementing this strategy only in patients with a Framingham risk score >/=10% yielded an incremental cost-effectiveness of $14,205 per QALY. Among such intermediate-risk patients, a JUPITER-based strategy becomes cost-saving at a rosuvastatin price of <$0.86 per day. CONCLUSIONS: Rosuvastatin treatment for JUPITER-eligible patients appears to be cost-effective, particularly among those with a Framingham risk score >/=10%.

SummaryBackground and objectives Although generally recommended in atrial fibrillation (AF) patients, the effectiveness and safety of oral anticoagulation in dialysis patients with AF is unknown.Design, setting, participants, & measurements We assembled a cohort of older hemodialysis patients who initiated dialysis without prior record of AF and who had prescription drug benefits through three state-administered programs. The index event was a first hospitalization with diagnosed AF; patients with any recorded prior warfarin use were excluded. Eligible patients survived >/=30 days from discharge, and new warfarin use was recorded from prescription records during that 30-day window. Propensity-matched warfarin users and nonusers were compared using Cox regression. Outcomes included ischemic stroke, hemorrhagic stroke, and mortality.Results Among 2313 patients with new AF who survived 30 days from discharge, 249 (10.8%) filled a prescription for warfarin. Comparing 237 warfarin users and 948 propensity-matched nonusers over 2287 person-years of follow-up, the occurrence of ischemic stroke was similar (HR = 0.92; 95% CI, 0.61 to 1.37), whereas warfarin users experienced twice the risk of hemorrhagic stroke (HR = 2.38; 95% CI, 1.15 to 4.96). The risks of stroke, gastrointestinal hemorrhage, and mortality did not differ between groups. As-treated analyses yielded similar findings, as did analyses restricted to patients with CHADS(2) scores >/=2.Conclusions Although we confirmed association between warfarin use and hemorrhagic stroke in dialysis patients with AF, we found no association between warfarin use and ischemic stroke. Adequately powered randomized trials are required to conclusively determine the risks and benefits of the studied warfarin indication in hemodialysis patients.

Background Adherence to medications that are prescribed after myocardial infarction is poor. Eliminating out-of-pocket costs may increase adherence and improve outcomes. Methods We enrolled patients discharged after myocardial infarction and randomly assigned their insurance-plan sponsors to full prescription coverage (1494 plan sponsors with 2845 patients) or usual prescription coverage (1486 plan sponsors with 3010 patients) for all statins, beta-blockers, angiotensin-converting-enzyme inhibitors, or angiotensin-receptor blockers. The primary outcome was the first major vascular event or revascularization. Secondary outcomes were rates of medication adherence, total major vascular events or revascularization, the first major vascular event, and health expenditures. Results Rates of adherence ranged from 35.9 to 49.0% in the usual-coverage group and were 4 to 6 percentage points higher in the full-coverage group (P<0.001 for all comparisons). There was no significant between-group difference in the primary outcome (17.6 per 100 person-years in the full-coverage group vs. 18.8 in the usual-coverage group; hazard ratio, 0.93; 95% confidence interval [CI], 0.82 to 1.04; P=0.21). The rates of total major vascular events or revascularization were significantly reduced in the full-coverage group (21.5 vs. 23.3; hazard ratio, 0.89; 95% CI, 0.90 to 0.99; P=0.03), as was the rate of the first major vascular event (11.0 vs. 12.8; hazard ratio, 0.86; 95% CI, 0.74 to 0.99; P=0.03). The elimination of copayments did not increase total spending ($66,008 for the full-coverage group and $71,778 for the usual-coverage group; relative spending, 0.89; 95% CI, 0.50 to 1.56; P=0.68). Patient costs were reduced for drugs and other services (relative spending, 0.74; 95% CI, 0.68 to 0.80; P<0.001). Conclusions The elimination of copayments for drugs prescribed after myocardial infarction did not significantly reduce rates of the trial's primary outcome. Enhanced prescription coverage improved medication adherence and rates of first major vascular events and decreased patient spending without increasing overall health costs. (Funded by Aetna and the Commonwealth Fund; MI FREEE ClinicalTrials.gov number, NCT00566774 .).

BACKGROUND: Patients with chronic disease often take many medications multiple times per day. Such regimen complexity is associated with medication nonadherence. Other factors, including the number of pharmacy visits patients make to pick up their prescriptions, may also undermine adherence. Our objective was to estimate the extent of prescribing and filling complexity in patients prescribed a cardiovascular medication and to evaluate its association with adherence. METHODS: The study population comprised individuals prescribed a statin (n = 1 827 395) or an angiotensin- converting enzyme inhibitor or renin angiotensin receptor blocker (ACEI/ARB) (n = 1 480 304) between June 1, 2006, and May 30, 2007. We estimated complexity by measuring the number of medications, prescribers, pharmacies, pharmacy visits, and refill consolidation (a measure of the number of visits per fill) during the 3 months from the first prescription. The number of daily doses was also measured in ACEI/ARB users. After this period, adherence was evaluated over the subsequent year. The relationship between complexity and adherence was assessed with multivariable linear regression. RESULTS: The statin cohort had a mean age of 63 years and were 49% male. On average, during the 3-month complexity assessment period, statin users filled 11.4 prescriptions for 6.3 different medications, had prescriptions written by 2 prescribers, and made 5.0 visits to the pharmacy. Results for ACEI/ARB users were similar. Greater prescribing and filling complexity was associated with lower levels of adherence. In adjusted models, patients with the least refill consolidation had adherence rates that were 8% lower over the subsequent year than patients with the greatest refill consolidation. CONCLUSION: Medication use and prescription filling for patients with cardiovascular disease is complex, and strategies to reduce this complexity may help improve medication adherence.

BACKGROUND: Several disease-specific information exchanges now exist on Facebook and other online social networking sites. These new sources of knowledge, support, and engagement have become important for patients living with chronic disease, yet the quality and content of the information provided in these digital arenas are poorly understood. OBJECTIVE: To qualitatively evaluate the content of communication in Facebook communities dedicated to diabetes. DESIGN: We identified the 15 largest Facebook groups focused on diabetes management. For each group, we downloaded the 15 most recent "wall posts" and the 15 most recent discussion topics from the 10 largest groups. PATIENTS: Four hundred eighty unique users were identified in a series of 690 comments from wall posts and discussion topics. MAIN MEASURES: Posts were abstracted and aggregated into a database. Two investigators evaluated the posts, developed a thematic coding scheme, and applied codes to the data. KEY RESULTS: Patients with diabetes, family members, and their friends use Facebook to share personal clinical information, to request disease-specific guidance and feedback, and to receive emotional support. Approximately two-thirds of posts included unsolicited sharing of diabetes management strategies, over 13% of posts provided specific feedback to information requested by other users, and almost 29% of posts featured an effort by the poster to provide emotional support to others as members of a community. Approximately 27% of posts featured some type of promotional activity, generally presented as testimonials advertising non-FDA approved, "natural" products. Clinically inaccurate recommendations were infrequent, but were usually associated with promotion of a specific product or service. Thirteen percent of posts contained requests for personal information from Facebook participants. CONCLUSIONS: Facebook provides a forum for reporting personal experiences, asking questions, and receiving direct feedback for people living with diabetes. However, promotional activity and personal data collection are also common, with no accountability or checks for authenticity.

BACKGROUND: With constrained health-care resources, there is a need to understand barriers to cost-effective medication use. OBJECTIVE: To study physician perceptions about generic medications. METHODS: Physicians used 5-point Likert scales to report perceptions about cost-related medication nonadherence, the efficacy and quality of generic medications, preferences for generic use, and the implications of dispensing medication samples. Descriptive statistics were used to assess physician perceptions and logistic regression models were used to evaluate predictors of physician perceptions. RESULTS: Among the invited sample, 839 (30.4%) responded and 506 (18.3%) were eligible and included in the final study population. Over 23% of physicians surveyed expressed negative perceptions about efficacy of generic drugs, almost 50% reported negative perceptions about quality of generic medications, and more than one quarter do not prefer to use generics as first-line medications for themselves or for their family. Physicians over the age of 55 years were 3.3 times more likely to report negative perceptions about generic quality, 5.8 times more likely to report that they would not use generics themselves, and 7.5 times more likely to state that they would not recommend generics for family members (p < 0.05 for all). Physicians reported that pharmaceutical company representatives are the most common (75%) source of information about market entry of a generic medication. Almost half of the respondents expressed concern that free samples may adversely affect subsequent affordability, yet two thirds of respondents provide free samples. CONCLUSIONS: A meaningful proportion of physicians expressed negative perceptions about generic medications, representing a potential barrier to generic use. Payors and policymakers trying to encourage generic use may consider educational campaigns targeting older physicians.

BACKGROUND:: Pulmonary vein isolation (PVI) is recognized as a potentially curative treatment for atrial fibrillation (AF). Ablation of complex fractionated atrial electrograms (CFAEs) in addition to PVI has been advocated as a means to improve procedural outcomes, but the benefit remains unclear. OBJECTIVE:: To synthesize the available data testing the incremental benefit of adding CFAE ablation to PVI. METHODS:: We performed a meta-analysis of controlled studies comparing the effect of PVI with CFAE ablation versus PVI alone in patients with paroxysmal and nonparoxysmal AF. RESULTS:: Of the 481 reports identified, 8 studies met our inclusion criteria. There was a statistically significant increase in freedom from atrial tachyarrhythmia (AT) with the addition of CFAE ablation (RR 1.15, p=0.03). In the 5 reports of nonparoxsymal AF (3 randomized controlled trials, one controlled clinical trial, and one trial using matched historical controls), addition of CFAE ablation resulted in a statistically significant increase in freedom from AT (n=112/181 [62%] for PVI+CFAE versus n=84/179 [47%] for PVI alone; RR 1.32, p=0.02). In trials of paroxysmal AF (3 randomized controlled trials and one trial using matched historical controls), addition of CFAE ablation did not result in a statistically significant increase in freedom from AT (n=131/166 [79%] for PVI+CFAE versus n=122/164 [74%] for PVI alone; RR 1.04, p=0.52). CONCLUSIONS:: In these studies of patients with nonparoxysmal AF, addition of CFAE ablation to PVI results in greater improvement in freedom from AF. No additional benefit of this combined approach was observed in patients with paroxysmal AF.

BACKGROUND: Medications are a cornerstone of the prevention and management of cardiovascular disease. Long-term medication adherence has been the subject of increasing attention in the developed world but has received little attention in resource-limited settings, where the burden of disease is particularly high and growing rapidly. To evaluate prevalence and predictors of non-adherence to cardiovascular medications in this context, we systematically reviewed the peer-reviewed literature. METHODS: We performed an electronic search of Ovid Medline, Embase and International Pharmaceutical Abstracts from 1966 to August 2010 for studies that measured adherence to cardiovascular medications in the developing world. A DerSimonian-Laird random effects method was used to pool the adherence estimates across studies. Between-study heterogeneity was estimated with an I(2) statistic and studies were stratified by disease group and the method by which adherence was assessed. Predictors of non-adherence were also examined. FINDINGS: Our search identified 2,353 abstracts, of which 76 studies met our inclusion criteria. Overall adherence was 57.5% (95% confidence interval [CI] 52.3% to 62.7%; I(2) 0.98) and was consistent across study subgroups. Studies that assessed adherence with pill counts reported higher levels of adherence (62.1%, 95% CI 49.7% to 73.8%; I(2) 0.83) than those using self-report (54.6%, 95% CI 47.7% to 61.5%; I(2) 0.93). Adherence did not vary by geographic region, urban vs. rural settings, or the complexity of a patient's medication regimen. The most common predictors of poor adherence included poor knowledge, negative perceptions about medication, side effects and high medication costs. INTERPRETATION: Our study indicates that adherence to cardiovascular medication in resource-limited countries is sub-optimal and appears very similar to that observed in resource-rich countries. Efforts to improve adherence in resource-limited settings should be a priority given the burden of heart disease in this context, the central role of medications in their management, and the clinical and economic consequences of non-adherence.

BACKGROUND: Patient nonadherence to prescribed medication is common and limits the effectiveness of treatment for many conditions. Most adherence studies evaluate behavior only among patients who have filled a first prescription. The advent of electronic prescribing (e-prescribing) systems provides the opportunity to track initial prescriptions and identify nonadherence that may have previously been undetected. METHODS: We analyzed e-prescribing data and filled claims for all patients with CVS Caremark (Woonsocket, RI) drug coverage who received e-prescriptions from the iScribe e-prescribing system in calendar 2008. We matched e-prescriptions with filled claims by using data on the drug name, date of e-prescription, and date of filled claims, allowing up to 180 days for patients to fill e-prescriptions. We evaluated the rate of primary nonadherence to newly prescribed medications across multiple characteristics of patients, prescribers, and prescriptions and developed multivariable models to identify predictors of nonadherence. RESULTS: We identified 423,616 e-prescriptions for new medications, with 3634 prescribers and 280,081 patients. The primary nonadherence rate was 24.0%. Several factors were associated with nonadherence to e-prescriptions, including nonformulary status of medications (odds ratio [OR] 1.31 compared with preferred medications; 95% confidence interval [CI], 1.26-1.36; P<.001) and residence in a low-income ZIP code (OR 1.23 compared with high-income ZIP code; 95% CI, 1.17-1.30; P<.001) Nonadherence occurred less often when e-prescriptions were transmitted directly to the pharmacy rather than printed to give to patients (OR 0.54; 95% CI, 0.52-0.57; P<.001). CONCLUSION: 24% of e-prescriptions for new medications were not filled. Our results suggest that interventions to address economic barriers and increase electronic integration in the healthcare system may be promising approaches to improve medication adherence.

In this article we highlight the important role that medication therapy can play in preventing disease and controlling costs. Focusing on coronary artery disease, we demonstrate that prevention, with the appropriate use of generic medications, appears far more cost-effective than previously documented, and it may even save on costs. For example, an earlier study estimated that reducing blood pressure to widely established clinical guidelines in nondiabetic patients cost an estimated $52,983 per quality-adjusted life-year if a brand-name drug was used. However, we estimate that the cost is just $7,753 per quality-adjusted life-year at generic medication prices. As the nation attempts to find strategies to improve population health without adding to the unsustainably high cost of care, policy makers should focus on ensuring that patients have access to essential generic medications.

PURPOSE: Myocardial infarction (MI) survivors benefit from receiving secondary prevention, including beta-blockers, angiotensin-blocking agents, and statins, as recommended by guidelines. Compliance with these guidelines is suboptimal. We sought to describe the initiation of secondary prevention in MI survivors, and to describe the variation in initiation by discharging the hospital, the physician, and the physician "responsible" for secondary prevention prescribing decisions in British Columbia in 1997-2004. METHODS: We assembled a cohort of 28 613 patients discharged alive from the hospital after their first MI and were not readmitted within 30 days. Physicians responsible for prescribing post-MI secondary prevention medications were identified as the physicians prescribing the greatest number of cardiac medications (post-discharge cardiac prescribers). We used multilevel logistic regression to assess the variation in drug initiation at discharging hospital, discharging physician, and post-discharge cardiac prescriber levels, which were adjusted for patient and provider characteristics during the study period. RESULTS: Beta-blockers initiation increased from 56 to 71% over the 8-year study period; angiotensin-converting enzyme/angiotensin II receptor blocker initiation increased from 37 to 70%, and statin initiation increased from 22 to 66% (0-28% for high-potency statins). The probability for initiating an average patient with the study drugs varied widely in age-sex-adjusted models at the hospital and physician levels. Further adjustment did not meaningfully change findings. The variation was largest for statins. The maximum between-provider variance was found for high-potency statins in 2003-2004 at the post-discharge cardiac prescriber level. CONCLUSIONS: Study-drug initiation is increasing among MI survivors, but the variation in initiation is wide between discharging hospitals and physicians. Copyright (c) 2011 John Wiley & Sons, Ltd.

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High copayments for medical services can cause patients to underuse essential therapies. Value-based health insurance design attempts to address this problem by explicitly linking cost sharing and value. Copayments are set at low levels for high-value services. The Mercer National Survey of Employer-Sponsored Health Plans demonstrates that value-based insurance design use is increasing and that 81 percent of large employers plan to offer it in the near future. Despite this increase, few studies have adequately evaluated its ability to improve quality and reduce health spending. Maximizing the benefits of value-based insurance design will require mechanisms to target appropriate copayment reductions, offset short-run cost outlays, and expand its use to other health services.

Mounting evidence suggests that statins possess antiarrhythmic properties and inhibit atrial fibrillation (AF). The goal of this study was to evaluate the relation between statin use and new-onset AF in a large cohort of patients with coronary artery disease. We identified all Medicare beneficiaries > or =65 years old who had been hospitalized for acute myocardial infarction or coronary revascularization from 1995 to 2004 and participated in 1 of 2 government-sponsored medication benefit programs. Patients with a history of AF before and during hospitalization were excluded. This yielded a cohort of 29,088. The incidence of new AF was compared between patients who were (n = 8,450) and were not (n = 20,638) prescribed statins within 1 month of hospital discharge after their cardiac event. New-onset AFs within 5 and 10 years were 32.6% and 51.2%, respectively, in patients who received statins compared to 38.3% and 58.0% in patients who did not receive statins (unadjusted hazard ratio 0.82, 95% confidence interval 0.78 to 0.86). Multivariable analysis controlling for demographic and clinical confounders indicated that statin use independently decreased the risk of developing new-onset AF compared to nonusers (adjusted hazard ratio 0.90, 95% confidence interval 0.85 to 0.94). Adjustment for propensity-score and health-seeking behaviors yielded nearly identical results. In conclusion, statin therapy initiated within 1 month after hospital discharge is independently associated with a decrease in the risk of new-onset AF after myocardial infarction or coronary revascularization. These findings lend support to the antiarrhythmic effects of statins and suggest another benefit for their use in patients with coronary artery disease.

To date, there has been little empirical evidence to support the broader use of value-based insurance design, which lowers copayments for services with high value relative to their costs. To address this lack of data, we evaluated the impact of the value-based insurance program of a US corporation, Pitney Bowes. The program eliminated copayments for cholesterol-lowering statins and reduced them for clopidogrel, a blood clot inhibitor. We found that the policy was associated with an immediate 2.8 percent increase in adherence to statins relative to controls, which was maintained for the subsequent year. For clopidogrel, the policy was associated with an immediate stabilizing of the adherence rate and a four-percentage-point difference between intervention and control subjects a year later. Our study thus provides an empirical basis for the use of this approach to improve the quality of health care.

BACKGROUND: Picking up prescriptions is an essential but previously unstudied component of adherence for patients who use retail pharmacies. Understanding the epidemiology and correlates of prescription abandonment may have an important effect on health care quality. OBJECTIVE: To evaluate the rates and correlates of prescription abandonment. DESIGN: Cross-sectional cohort study. SETTING: One large retail pharmacy chain and one large pharmacy benefits manager (PBM) in the United States. MEASUREMENTS: Prescriptions bottled at the retail pharmacy chain between 1 July 2008 and 30 September 2008 by patients insured by the PBM were identified. Pharmacy data were used to identify medications that were bottled and either dispensed or returned to stock (RTS) or abandoned. Data from the PBM were used to identify previous or subsequent dispensing at any pharmacy. The first (index) prescription in a class for each patient was assigned to 1 of 3 mutually exclusive outcomes: filled, RTS, or RTS with fill (in the 30 days after abandonment, the patient purchased a prescription for a medication in the same medication class at any pharmacy). Outcome rates were assessed by drug class, and generalized estimating equations were used to assess patient, neighborhood, insurance, and prescription characteristics associated with abandonment. RESULTS: 10 349 139 index prescriptions were filled by 5 249 380 patients. Overall, 3.27% of index prescriptions were abandoned; 1.77% were RTS and 1.50% were RTS with fill. Patients were least likely to abandon opiate prescriptions. Prescriptions with copayments of $40 to $50 and prescriptions costing more than $50 were 3.40 times and 4.68 times more likely, respectively, to be abandoned than prescriptions with no copayment (P < 0.001 for both comparisons). New users of medications had a 2.74 times greater probability of abandonment than prevalent users (P < 0.001), and prescriptions delivered electronically were 1.64 times more likely to be abandoned than those that were not electronic (P < 0.001). LIMITATION: The study included mainly insured patients and analyzed data collected during the summer months only. CONCLUSION: Although prescription abandonment represents a small component of medication nonadherence, the correlates to abandonment highlight important opportunities to intervene and thereby improve medication taking. PRIMARY FUNDING SOURCE: CVS Caremark.

OBJECTIVE: To determine the efficacy of healthcare information technology (HIT) interventions in improving adherence. STUDY DESIGN: Systematic search of randomized controlled trials of HIT interventions to improve medication adherence in cardiovascular disease or diabetes. METHODS: Interventions were classified as 1-way patient reminder systems, 2-way interactive systems, and systems to enhance patient-provider interaction. Studies were subclassified into those with and without real-time provider feedback. Cohen's d effect sizes were calculated to assess each intervention's magnitude of effectiveness. RESULTS: We identified 7190 articles, only 13 of which met inclusion criteria. The majority of included studies (54%, 7 studies) showed a very small ES. The effect size was small in 15%, large in 8%, and was not amenable to calculation in the remainder. Reminder systems were consistently effective, showing the largest effect sizes in this review. Education/counseling HIT systems were less successful, as was the addition of realtime adherence feedback to healthcare providers. Interactive systems were rudimentary and not integrated into electronic health records; they exhibited very small effect sizes. Studies aiming to improve patient-provider communication also had very small effect sizes. CONCLUSIONS: There is a paucity of data about HIT's efficacy in improving adherence to medications for cardiovascular disease and diabetes, although simple patient reminder systems appear effective. Future studies should focus on more sophisticated interactive interventions that expand the functionality and capabilities of HIT and better engage patients in care.

OBJECTIVE: To determine the optimal modes of delivery for interventions to improve adherence to cardiovascular medications. STUDY DESIGN: Systematic review. METHODS: We conducted systematic searches of English-language, peer-reviewed publications in MEDLINE and EMBASE, 1966 through December 31, 2008. We selected randomized controlled trials of interventions to improve adherence to medications for preventing or treating cardiovascular disease or diabetes. Articles were classified based on mode of delivery of the main intervention as (1) person-independent interventions (mailed, faxed, or hand distributed; or delivered via electronic interface) or (2) person-dependent interventions (nonautomated phone calls, in-person interventions). RESULTS: We identified 6550 articles. Of these, 168 were reviewed in full and 51 met inclusion criteria. Among person-independent interventions (56% successful), electronic interventions were most successful (67%). Among person-dependent interventions (52% successful), phone calls showed low success rates (38%). In-person interventions at hospital discharge were more effective (67%) than clinic interventions (47%). In-person pharmacist interventions were effective when held in a pharmacy (83% successful), but were less effective in clinics (38%). CONCLUSIONS: Future medication adherence studies should explore new electronic approaches and in-person interventions at the site of medication distribution. Identifying times of increased patient receptivity to the adherence message such as hospital discharge also will be important.

BACKGROUND:: Although many patient, physician, and payment predictors of adherence have been described, knowledge of their relative strength and overall ability to explain adherence is limited. OBJECTIVES:: To measure the contributions of patient, physician, and payment predictors in explaining adherence to statins. RESEARCH DESIGN:: Retrospective cohort study using administrative data. SUBJECTS:: A total of 14,257 patients insured by Horizon Blue Cross Blue Shield of New Jersey who were newly prescribed a statin cholesterol-lowering medication. MEASURES:: Adherence to statin medication was measured during the year after the initial prescription, based on proportion of days covered. The impact of patient, physician, and payment predictors of adherence were evaluated using multivariate logistic regression. The explanatory power of these models was evaluated with C statistics, a measure of the goodness of fit. RESULTS:: Overall, 36.4% of patients were fully adherent. Older patient age, male gender, lower neighborhood percent black composition, higher median income, and fewer number of emergency department visits were significant patient predictors of adherence. Having a statin prescribed by a cardiologist, a patient's primary care physician, or a US medical graduate were significant physician predictors of adherence. Lower copayments also predicted adherence. All of our models had low explanatory power. Multivariate models including patient covariates only had greater explanatory power (C = 0.613) than models with physician variables only (C = 0.566) or copayments only (C = 0.543). A fully specified model had only slightly more explanatory power (C = 0.633) than the model with patient characteristics alone. CONCLUSIONS:: Despite relatively comprehensive claims data on patients, physicians, and out-of-pocket costs, our overall ability to explain adherence remains poor. Administrative data likely do not capture many complex mechanisms underlying adherence.

BACKGROUND: Medications for the prevention and treatment of cardiovascular disease save lives but adherence is often inadequate. The optimal role for physicians in improving adherence remains unclear. OBJECTIVE: Using existing evidence, we set the goal of evaluating the physician's role in improving medication adherence. DESIGN: We conducted systematic searches of English-language peer-reviewed publications in MEDLINE and EMBASE from 1966 through 12/31/2008. SUBJECTS AND INTERVENTIONS: We selected randomized controlled trials of interventions to improve adherence to medications used for preventing or treating cardiovascular disease or diabetes. MAIN MEASURES: Articles were classified as either (1) physician "active"-a physician participated in designing or implementing the intervention; (2) physician "passive"-physicians treating intervention group patients received patient adherence information while physicians treating controls did not; or (3) physicians noninvolved. We also identified studies in which healthcare professionals helped deliver the intervention. We did a meta-analysis of the studies involving healthcare professionals to determine aggregate Cohen's D effect sizes (ES). KEY RESULTS: We identified 6,550 articles; 168 were reviewed in full, 82 met inclusion criteria. The majority of all studies (88.9%) showed improved adherence. Physician noninvolved studies were more likely (35.0% of studies) to show a medium or large effect on adherence compared to physician-involved studies (31.3%). Among interventions requiring a healthcare professional, physician-noninvolved interventions were more effective (ES 0.47; 95% CI 0.38-0.56) than physician-involved interventions (ES 0.25; 95% CI 0.21-0.29; p < 0.001). Among physician-involved interventions, physician-passive interventions were marginally more effective (ES 0.29; 95% CI 0.22-0.36) than physician-active interventions (ES 0.23; 95% CI 0.17-0.28; p = 0.2). CONCLUSIONS: Adherence interventions utilizing non-physician healthcare professionals are effective in improving cardiovascular medication adherence, but further study is needed to identify the optimal role for physicians.

To stem the rising costs of medications provided to patients enrolled in Medicaid, states have implemented varying policies about generic substitution. These policies differ in the extent to which pharmacists or patients can influence which medications they choose. Using national Medicaid data, we evaluated the relationship between different generic substitution policies and the use of generic simvastatin, a cholesterol-lowering drug, after the patent for the brand-name equivalent, Zocor, expired. States that implemented policies requiring patients' consent prior to generic substitution experienced rates of substitution that were 25 percent lower than those of states that did not require patient consent. By eliminating patient consent requirements, state Medicaid programs could expect to save more than $100 million in coverage for three top-selling medications that are nearing patent expiration. Although these consent requirements are probably intended to increase patient autonomy, policy makers should consider the sizable opportunity costs.

BACKGROUND: Coronary artery disease (CAD) is highly prevalent in nursing home residents and is associated with a substantial clinical and economic burden. Statins reduce mortality and hospitalization rates in older patients with CAD. OBJECTIVES: To assess rates and predictors of statin use among high-risk patients with symptomatic coronary artery disease (CAD) admitted to nursing homes after acute cardiac hospitalization. DESIGN: Cohort study. PARTICIPANTS: Medicare beneficiaries enrolled in either a state-run drug assistance program or Medicaid in nursing homes in New Jersey from 1994 through 2005. MEASUREMENTS: Statin utilization within 60 days of nursing home admission was determined for patients recently hospitalized with symptomatic CAD in whom statins are indicated consisting of those with: acute coronary syndrome (ACS) without revascularization, ACS with revascularization and congestive heart failure (CHF) with revascularization. Predictors of statin use were evaluated with multivariate logistic regression models. RESULTS: While statin use over the 11-year period increased from 1.2% to 31.8%, overall utilization was very low. Predictors of greater statin use included prior cardiac hospitalization [odds ratio (OR) 1.32, 95% confidence interval (95% CI) 1.13 to 1.57], prior statin use (OR 6.92, 95% CI 5.86 to 8.82) and receipt of a concurrent cardiac medication (range of odds ratios, 2.36-3.40). Older patients admitted for ACS with or without revascularization were less likely to receive a statin. Patients who had received anti-platelets or angiotensin-modifying agents prior to their hospitalization were less likely to receive statins after discharge. Renal disease, prior stroke, diabetes, hypertension and hyperlipidemia did not influence statin utilization. Predictors of treatment did not change when the cohort was dichotomized according to length of stay. CONCLUSIONS: Patients are infrequently treated with statins when discharged to nursing homes following hospitalization for a symptomatic cardiovascular event. Barriers to statin treatment in this setting require closer examination.

Although the complexity of treatment regimens for patients with heart failure (HF) has increased over time because of the increased availability of efficacious medications, little is known about temporal trends in adherence to treatment regimens in these patients. We assessed trends in adherence to angiotensin-system blockers (ABs), beta-blockers (BBs), and spironolactone (SL) for HF in Medicare beneficiaries enrolled in two statewide pharmacy benefit programs from 1995 to 2004. The proportion of days covered (PDC) (%) was assessed after the first dispensing among users of an AB, BB, or SL. Proportions of full adherence (PDC >80%) did not change over time for ABs (54% in both 1996 and 2003) but increased slightly for BBs (from 47% in 1996 to 57% in 2003) and SL (from 31% in 1996 to 42% in 2003). Black race and dialysis treatment predicted poor adherence to any medications. Adherence to BBs and SL increased modestly over time, but overall nonadherence remained high.

Pharmacy benefit managers (PBMs) have a unique opportunity to promote health and generate value in the healthcare system. Today, PBMs are largely evaluated on their ability to control costs rather than improve health. Pharmacy benefit managers should be evaluated along 3 dimensions in which they can increase value: (1) use of cost-effective medications, (2) timely initiation of appropriate medication therapy, and (3) adherence to that therapy. Value creation requires the development of integrated data systems, stronger partnerships with patients and physicians, and improved measurement and reporting of results. Incentives for PBMs to promote value should drive innovation and improve health outcomes.

BACKGROUND: Prescription medication labels contain valuable health information, and better labels may enhance patient adherence to chronic medications. A new prescription medication labeling system was implemented by Target pharmacies in May 2005 and aimed to improve readability and understanding. OBJECTIVE: We evaluated whether the new Target label influenced patient medication adherence. DESIGN AND PATIENTS: Using claims from two large health plans, we identified patients with one of nine chronic diseases who filled prescriptions at Target pharmacies and a matched sample who filled prescriptions at other community pharmacies. MEASUREMENTS: We stratified our cohort into new and prevalent medication users and evaluated the impact of the Target label on medication adherence. We used linear regression and segmented linear regression to evaluate the new-user and prevalent-user analyses, respectively. RESULTS: Our sample included 23,745 Target users and 162,368 matched non-Target pharmacy users. We found no significant change in adherence between new users of medications at Target or other community pharmacies (p = 0.644) after implementing the new label. In prevalent users, we found a 0.0069 percent reduction in level of adherence (95% CI -0.0138-0.0; p < 0.001) and a 0.0007 percent increase in the slope in Target users (the monthly rate of change of adherence) after implementation of the new label (95% CI 0.0001-0.0013; p = 0.001). CONCLUSIONS: We found no changes in adherence of chronic medication in new users, and small and likely clinically unimportant changes in prevalent users after implementation of the new label. While adherence may not be improved with better labeling, evaluation of the effect of labeling on safety and adverse effects is needed.

BACKGROUND: Recent studies have raised concerns about the reduced efficacy of clopidogrel when used concurrently with proton pump inhibitors (PPIs), but those studies may have overestimated the risk. METHODS AND RESULTS: We studied the potential for increased risk of adverse cardiovascular events among users of clopidogrel with versus without concurrent use of PPIs in 3 large cohorts of patients > or =65 years of age, treated between 2001 and 2005. All patients had undergone percutaneous coronary intervention or had been hospitalized for acute coronary syndrome in Pennsylvania, New Jersey, or British Columbia, and subsequently had initiated treatment with clopidogrel. We recorded myocardial infarction hospitalization, death, and revascularization among PPI users and nonusers. We assessed our primary end point of myocardial infarction hospitalization or death using cohort-specific and pooled regression analyses. We entered 18 565 clopidogrel users into our analysis. On a pooled basis, 2.6% of those who also initiated a PPI versus 2.1% of PPI nonusers had a myocardial infarction hospitalization; 1.5% versus 0.9% died; and 3.4% versus 3.1% underwent revascularization. The propensity score-adjusted rate ratio for the primary end point of myocardial infarction or death was 1.22 (95% confidence interval, 0.99 to 1.51); for death, 1.20 (95% confidence interval, 0.84 to 1.70); and for revascularization, 0.97 (95% confidence interval, 0.79 to 1.21). Matched analyses generally yielded similar results. CONCLUSIONS: Although point estimates indicated a slightly increased risk of myocardial infarction hospitalization or death in older patients initiating both clopidogrel and a PPI, we did not observe conclusive evidence of a clopidogrel-PPI interaction of major clinical relevance. Our data suggest that if this effect exists, it is unlikely to exceed a 20% risk increase.

CONTEXT: Thiazolidenediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor-gamma and have been shown to reduce bone mineral density. Recent results from several randomized controlled trials find an increased risk of fracture with TZDs compared with other oral antidiabetic agents. OBJECTIVE: The aim of the study was to determine the association between TZD use and fracture risk among older adults with diabetes. DESIGN: We conducted a cohort study. PARTICIPANTS: Medicare beneficiaries with at least one diagnosis of diabetes initiating monotherapy for an oral hypoglycemic agent participated in the study. MAIN OUTCOME: We measured the incidence of fracture within the cohort. RESULTS: Among the 20,964 patients with diabetes eligible for this study, 686 (3.3%) experienced a fracture during the median follow-up of approximately 10 months. Although not statistically significant, patients using only a TZD were more likely to experience a fracture than those using metformin (adjusted relative risk, 1.31; 95% confidence interval, 0.98-1.77; P = 0.071) or a sulfonylurea (adjusted relative risk, 1.21; 95% confidence interval, 0.94-1.55; P = 0.12). Each individual TZD was associated with an increased risk, with confidence intervals overlapping unity, compared with both metformin and sulfonylureas. The adjusted risk of any fracture associated with TZD use compared with metformin was elevated for non-insulin-using patients, women and men. If TZD use is associated with fractures, the number needed for one excess fracture when comparing TZD users to sulfonylurea users was 200, and the number was 111 when comparing TZDs with metformin. CONCLUSIONS: As has been found with other analyses, our data suggest that TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin.

BACKGROUND: CYP2C9 and VKORC1 genotyping has been advocated as a means of improving the accuracy of warfarin dosing. However, the effectiveness of genotyping in improving anticoagulation control and reducing major bleeding has not yet been compellingly demonstrated. Genotyping currently costs $400 to $550. METHODS AND RESULTS: We constructed a Markov model to evaluate whether and under what circumstances genetically-guided warfarin dosing could be cost-effective for newly diagnosed atrial fibrillation patients. Estimates of clinical event rates, treatment and adverse event costs, and utilities for health states were derived from the published literature. The cost-effectiveness of genetically-guided dosing was highly dependent on the assumed effectiveness of genotyping in increasing the amount of time patients spend appropriately anticoagulated. If genotyping increases the time spent in the target international normalized ratio range by <5 percentage points, its incremental cost-effectiveness ratio would be greater than $100,000 per quality-adjusted life year. The incremental cost-effectiveness ratio falls below $50,000 per quality-adjusted life year if genotyping increases the time spent in range by 9 percentage points. The results were also sensitive to assumptions about the rate of major bleeding events during treatment initiation and the cost of the test. CONCLUSIONS: Our results suggest that genotyping before warfarin initiation will be cost-effective for patients with atrial fibrillation only if it reduces out-of-range international normalized ratio values by more than 5 to 9 percentage points compared with usual care. Given the current uncertainty surrounding genotyping efficacy, caution should be taken in advocating the widespread adoption of this strategy.

BACKGROUND: Although combination pharmacotherapy after myocardial infarction dramatically reduces morbidity and mortality, the full benefits of secondary prevention medications remain unrealized owing to medication non-adherence. Because financial barriers are a major determinant of non-adherence, we examined the costs and benefits of providing free medications to myocardial infarction patients who do not have private insurance and are ineligible for substantial public coverage. METHODS: An economic evaluation combining decision analysis and Markov modelling was conducted to compare full public coverage of secondary prevention medications with the status quo. Costs and benefits were estimated using Canadian data wherever possible. The main outcome was the incremental cost-effectiveness ratio measured in cost per quality-adjusted life-year (QALY) gained. RESULTS: From the perspective of the publicly funded healthcare system, full coverage resulted in greater quality-adjusted survival than the status quo (7.02 vs. 6.13 QALYs) but at increased cost ($20,423 vs. $17,173). The incremental cost-effectiveness ratio (ICER) for full coverage compared to the status quo was $3,663/QALY. This result was robust to a wide range of sensitivity analyses. In a secondary analysis from the perspective of government, the ICER for full coverage compared to the status quo was $12,350/QALY. In this analysis, the ICER was sensitive to changes in price elasticity, but remained below $50,000/QALY as long as the elasticity remained below -0.035. INTERPRETATION: Public payers in Canada should consider providing secondary prevention medications to myocardial infarction patients without private insurance free of charge. Full public coverage is cost-effective compared to the status quo.

CONTEXT: Many patients have palpitations and seek advice from general practitioners. Differentiating benign causes from those resulting from clinically significant cardiac arrhythmia can be challenging and the clinical examination may aid in this process. OBJECTIVE: To systematically review the accuracy of historical features, physical examination, and cardiac testing for the diagnosis of cardiac arrhythmia in patients with palpitations. Data Source, Study Selection, and DATA EXTRACTION: MEDLINE (1950 to August 25, 2009) and EMBASE (1947 to August 2009) searches of English-language articles that compared clinical features and diagnostic tests in patients with palpitations with a reference standard for cardiac arrhythmia. Of the 277 studies identified by the search strategy, 7 studies were used for accuracy analysis and 16 studies for diagnostic yield analysis. Two authors independently reviewed articles for study data and quality and a third author resolved disagreements. DATA SYNTHESIS: Most data were obtained from single studies with small sample sizes. A known history of cardiac disease (likelihood ratio [LR], 2.03; 95% confidence interval [CI], 1.33-3.11), having palpitations affected by sleeping (LR, 2.29; 95% CI, 1.33-3.94), or while the patient is at work (LR, 2.17; 95% CI, 1.19-3.96) slightly increase the likelihood of a cardiac arrhythmia. A known history of panic disorder (LR, 0.26; 95% CI, 0.07-1.01) or having palpitations lasting less than 5 minutes (LR, 0.38; 95% CI, 0.22-0.63) makes the diagnosis of cardiac arrhythmia slightly less likely. The presence of a regular rapid-pounding sensation in the neck (LR, 177; 95% CI, 25-1251) or visible neck pulsations (LR, 2.68; 95% CI, 1.25-5.78) in association with palpitations increases the likelihood of a specific type of arrhythmia (atrioventricular nodal reentry tachycardia). The absence of a regular rapid-pounding sensation in the neck makes detecting the same arrhythmia less likely (LR, 0.07; 95% CI, 0.03-0.19). No other features significantly alter the probability of clinically significant arrhythmia. Diagnostic tests for prolonged periods of electrocardiographic monitoring vary in their yield depending on the modality used, duration of monitoring, and occurrence of typical symptoms during monitoring. Loop monitors have the highest diagnostic yield (34%-84%) for identifying an arrhythmia. CONCLUSIONS: While the presence of a regular rapid-pounding sensation in the neck or visible neck pulsations associated with palpitations makes the diagnosis of atrioventricular nodal reentry tachycardia likely, the reviewed studies suggest that the clinical examination is not sufficiently accurate to exclude clinically significant arrhythmias in most patients. Thus, prolonged electrocardiographic monitoring with demonstration of symptom-rhythm correlation is required to make the diagnosis of a cardiac arrhythmia for most patients with recurrent palpitations.

Drug company-sponsored patient assistance programs (PAPs) provide access to brand-name medications at little or no cost and have been advocated as a safety net for inadequately insured patients. Yet little is known about these programs. We surveyed drug company-sponsored PAPs and found much variability in their structures and application processes. Most cover one or two drugs. Only 4 percent disclosed how many patients they had directly helped, and half would not disclose their income eligibility criteria. A better understanding of PAPs might clarify their role in improving access to medications, the adequacy of existing public programs, and their impact on cost-effective medication use.

BACKGROUND AND OBJECTIVES: In the general population, an early invasive strategy of routine coronary angiography is superior to a conservative strategy of selective angiography in patients who are admitted with unstable angina or non-ST segment elevation myocardial infarction (MI), but the effectiveness of this strategy in individuals with chronic kidney disease (CKD) is uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a collaborative meta-analysis with data provided by the main authors of identified trials to estimate the effectiveness of early angiography in patients with CKD. The Cochrane, Medline, and EMBASE databases were searched to identify randomized trials that compared invasive and conservative strategies in patients with unstable angina or non-ST MI. Pooled risks ratios were estimated using data from enrolled patients with estimated GFR <60 ml/min per 1.73 m(2). RESULTS: Five randomized trials that enrolled 1453 patients with CKD were included. An early invasive strategy was associated with nonsignificant reductions in all-cause mortality, nonfatal MI, and a composite of death or nonfatal MI. The invasive strategy significantly reduced rehospitalization. CONCLUSIONS: This collaborative study suggests that the benefits of an early invasive strategy are preserved in patients with CKD and that an early invasive approach reduces the risk for rehospitalization and is associated with trends of reduction in the risk for death and nonfatal re-infarction in patients with CKD. Coronary angiography should be considered for patients who have CKD and are admitted with non-ST elevation acute coronary syndromes.

BACKGROUND: Medication errors represent a major public health concern, and inadequate prescription drug labels have been identified as a root cause of errors. A new prescription medication labeling system was implemented by Target pharmacies in May 2005 and aimed to improve health outcomes. OBJECTIVES: To evaluate whether the new Target label influenced patient health services utilization. SUBJECTS: Derived from 2 large health plans. RESEARCH DESIGN AND MEASURES: Using administrative claims, we identified patients with 1 of 9 chronic diseases who filled prescriptions at Target pharmacies and a matched sample who filled prescriptions at other community pharmacies. We stratified our cohort into new and prevalent medication users and evaluated the impact of the Target label on outpatient, emergency department and inpatient health services use. We used linear regression and segmented linear regression to evaluate the new-user and prevalent-user analyses, respectively. RESULTS: Our sample included 23,745 Target pharmacy users and 162,369 matched non-Target pharmacy users. In the new-user analysis, we found no significant change in rates of both outpatient (event rate ratio: 0.53; 95% CI: 0.15-1.86) and inpatient and emergency department (Event rate ratio: 0.88; 95% CI: 0.62-1.24) health services utilization in Target users after implementation when compared with non-Target users. Similarly, in the prevalent user analysis, we found no change in the level or slope of outpatient or emergency/inpatient services in Target users after implementation of the new label when compared with non-Target users. CONCLUSIONS: We found no statistically significant change in health services use attributable to the implementation of the new prescription drug label at Target pharmacies. These findings highlight the challenge of influencing health outcomes with interventions to improve health literacy.

OBJECTIVES: To propose standardized methods for measuring concurrent adherence to multiple related medications and to apply these definitions to a cohort of patients with diabetes mellitus. STUDY DESIGN: Retrospective cohort study of 7567 subjects with diabetes prescribed 2 or more classes of oral hypoglycemic agents in 2005. METHODS: For each medication class, adherence for each patient was estimated using prescription-based and interval-based measures of proportion of days covered (PDC) from cohort entry until December 31, 2006. Concurrent adherence was calculated by applying these 2 measures in the following 3 ways: (1) the mean of each patient's average PDC, (2) the proportion of days during which patients had at least 1 of their medications available to them, and (3) the proportion of patients with a PDC of at least 80% for all medication classes. Because patients taking multiple related medications have distinct patterns of use, the analysis was repeated after classifying patients into mutually exclusive groups. RESULTS: Concurrent medication adherence ranged from 35% to 95% depending on the definition applied. Interval-based measures provide lower estimates than prescription-based techniques. Definitions that require the use of at least 1 drug class categorize virtually all patients as adherent. Requiring patients to have a PDC of at least 80% for each of their drugs results in only 30% to 40% of patients being defined as adherent. The variability in adherence is greatest for patients whose treatment regimen changed the most during follow-up. CONCLUSIONS: The variability in adherence estimates derived from different definitions may substantially impact qualitative conclusions about concurrent adherence to related medications. Because the measures we propose have different underlying assumptions, the choice of technique should depend on why adherence is being evaluated.

Insurers and policymakers encourage the use of generic drugs to reduce costs, but generics remain underused. We conducted a national survey of commercially insured adults to evaluate their perceptions about generic drugs. Patients agreed that generics are less expensive and a better value than brand-name drugs, and are just as safe. However, although 56 percent reported that Americans should use more generics, only 37.6 percent prefer to take generics. We discuss perceptions about communicating with practitioners about generics, generic substitution, and policymakers' role in influencing generic use. These findings underscore the challenge that providers, insurers, and policymakers face in stimulating the cost-effective use of medications.

BACKGROUND: Highly effective generic cardiovascular medications are frequently underused, leading to greater overall drug costs and cost-related nonadherence. OBJECTIVE: We sought to assess an intervention to stimulate appropriate generic cardiovascular drug use without creating administrative or financial barriers that may impede essential medication use. TRIAL DESIGN: The SAMPLES (Study Assessing the Effect of Cardiovascular Medications Provided as Low-cost, Evidence-based Generic Samples) trial is a clustered, randomized controlled trial of the effect of providing physicians with free generic samples of hydrochlorothiazide for hypertensive patients and simvastatin for patients with hyperlipidemia. We will randomize 660 primary care physicians in Pennsylvania, clustered by physician practice, to receive free samples for both conditions or to receive no samples. We will use data on filled prescriptions obtained from a state-sponsored prescription drug assistance program to perform an intention-to-treat evaluation of the impact of the intervention on physician prescribing behavior (proportion of prescriptions that are generic) and patient adherence. Secondary outcomes will include physician adherence to established guidelines and overall prescription drug costs. CONCLUSION: This trial will define the potential role of an innovative approach to stimulate clinically appropriate cost-effective prescribing. We will determine whether free generic samples can reduce overall drug costs as well as out-of-pocket costs to the patient without sacrificing efficacy and whether this approach results in improved adherence to essential cardiovascular medications. This intervention may also improve adherence to practice guidelines and improve the quality of care received. If effective, this strategy could be used broadly by private insurers or government payers aiming to stimulate more cost-effective and higher-quality care.

BACKGROUND: Insurers and policymakers strive to stimulate more cost-effective prescribing and, increasingly, are educating beneficiaries about generics. OBJECTIVES: To evaluate the relationship between patient beliefs and communication about generic drugs and actual drug use. RESEARCH DESIGN AND SUBJECTS: We performed a national mailed survey of a random sample of 2500 commercially-insured adults. Patient responses were linked to pharmacy claims data to assess actual generic medication use. MEASURES: We used factor analysis to develop 5 multi-item scales from patient survey responses that measured: (1) general preferences for generics, (2) generic safety/effectiveness, (3) generic cost/value, (4) comfort with generic substitution, and (5) communication with providers about generics. The relationship between each scale and the proportion of prescriptions filled for generics was assessed using linear regression, controlling for demographic, health, and insurance characteristics. Separate models were created for each scale and then all 5 scales were included simultaneously in a fully-adjusted model. RESULTS: The usable response rate was 48%. When evaluated independently, a 1 SD increase in each of the 5 scales was associated with a 3.1% to 6.3% increase in generic drug use (P < 0.05 for each). In the fully adjusted model, only 2 scales were significantly associated with generic drug use: comfort with generic substitution (P = 0.021) and communication with providers about generic drugs (P = 0.012). CONCLUSIONS: Generic drug use is most closely associated with the 2 actionable items we evaluated: communication with providers about generics and comfort with generic substitution. Educational campaigns that focus on these 2 domains may be most effective at influencing generic drug use.

BACKGROUND: The clarity of prescription drug instructions is a health literacy and medication safety concern. OBJECTIVE: To assess the variability of pharmacy interpretations of physician prescriptions. DESIGN: Identically written prescriptions for 4 common medications (atorvastatin, alendronate, trimethoprim/sulfamethoxazole, ibuprofen) were filled in 6 pharmacies (2 largest chains, 2 grocery stores, 2 independents) in 4 cities (Boston, Chicago, Los Angeles, Austin). MEASUREMENT: Components of the instruction were coded as dose, frequency, administration route, timing, indication, and auxiliary instructions. RESULTS: In all, 85 labels were evaluated. Dose frequency was omitted on 6% of instructions ("take 1 tablet for cholesterol"). Timing was explicitly stated on 2% of instructions ("in the morning"). All prescriptions included indications; pharmacies transcribed these onto 38% of labels. The prescription for alendronate stated not to lie down for at least 30 minutes after taking; this was transcribed with 50% of instructions. Reading difficulty was above recommended levels for 46% of instructions; with 14% greater than a high school level. CONCLUSIONS: Efforts are needed to ensure patients receive clear, consistent information supporting safe medication use.

OBJECTIVE: To determine whether retail prices for prescription drugs are higher in poorer areas. DATA SOURCES: The MyFloridarx.com website, which provides retail prescription prices at Florida pharmacies, and median ZIP code income from the 2000 Census. STUDY DESIGN: We compared mean pharmacy prices for each of the four study drugs across ZIP code income groups. Pharmacies were classified as either chain pharmacies or independent pharmacies. DATA COLLECTION: Prices were downloaded in November 2006. PRINCIPAL FINDINGS: Across the four study drugs, mean prices were highest in the poorest ZIP codes: 9 percent above the statewide average. Independent pharmacies in the poorest ZIP codes charged the highest mean prices. CONCLUSIONS: Retail prescription prices appear to be higher in poorer ZIP codes of Florida.

OBJECTIVES: This study is a meta-analysis of prospective cohort studies comparing the impact of cardiac resynchronization therapy (CRT) for patients in atrial fibrillation (AF) and sinus rhythm (SR). BACKGROUND: Although close to one-third of advanced heart failure patients exhibit AF, the impact of CRT in this group remains unclear. METHODS: Prospective cohort studies comparing patients in normal SR and chronic AF treated with CRT were included. All studies reported death, New York Heart Association functional class, ejection fraction, 6-min walk test, and the Minnesota score or its equivalent as outcomes. Data sources included Ovid MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Central Register of Controlled Trials, the Database of Abstracts of Reviews of Effects, and the American College of Physicians Journal Club. RESULTS: Of 2,487 reports identified, 5 studies following a total of 1,164 patients were included. Both AF and SR patients benefited significantly from CRT. Mortality was not significantly different at 1 year (relative risk ratio: 1.57, 95% confidence interval [CI]: 0.87 to 2.81). The New York Heart Association functional class improved similarly for both groups (-0.90 for SR patients, -0.84 for AF patients). SR patients showed greater relative improvement in the 6-min walk test (11.6 m greater, 95% CI: 10.4 to 12.8 m) and the Minnesota score (3.9 points less, 95% CI: 3.4 to 4.5 points) than AF patients. AF patients, however, achieved a small but statistically significant greater change in ejection fraction (0.39% greater change in ejection fraction, 95% CI: 0.22% to 0.55%). CONCLUSIONS: Patients in AF show significant improvement after CRT, with similar or improved ejection fraction as SR patients, but smaller benefits in regard to functional outcomes.

CONTEXT: Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs. OBJECTIVES: To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue. DATA SOURCES: Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008. STUDY SELECTION: Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution. DATA EXTRACTION: We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors' positions on generic substitution as negative, positive, or neutral. RESULTS: We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of beta-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of alpha-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was -0.03 (95% confidence interval, -0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution. CONCLUSIONS: Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs.

BACKGROUND: The AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) trial demonstrated that rate control and rhythm control strategies result in similar survival and quality of life for patients with atrial fibrillation (AF). Because of superior safety and lower cost, rate control is now the recommended strategy for the management of most elderly, high-risk AF patients. OBJECTIVE: To determine the extent to which the AFFIRM trial results have been adopted into actual practice. METHODS: We conducted a time-series analysis of 3 population-based cohorts of patients with AF who were 66 years of age or older in Pennsylvania and Ontario. We stratified patients in Ontario by socioeconomic status (SES) and examined changes in quarterly prescription rates for rate control and rhythm controlling medications as well as cardioversion procedures before and after publication of the AFFIRM trial. RESULTS: The publication of the AFFIRM trial resulted in statistically significant reductions in the use of rhythm controlling medications in all 3 cohorts (p < 0.01). The magnitude of these changes in the non-low SES Canadian cohort was approximately 1% per quarter and was greater than the magnitude observed in the other cohorts (p < 0.001). The use of cardioversion procedures also decreased in all study regions (p < 0.01). In contrast, AFFIRM publication was also associated with a small increase in the use of rate controlling medications in Canada (p < 0.01) but not in the US (p = 0.23). CONCLUSIONS: Publication of the AFFIRM trial resulted in small but statistically significant changes in the care of patients with AF.

BACKGROUND: Effective therapies for the secondary prevention of coronary heart disease-related events are significantly underused, and attempts to improve adherence have often yielded disappointing results. Elimination of patient out-of-pocket costs may be an effective strategy to enhance medication use. We sought to estimate the incremental cost-effectiveness of providing full coverage for aspirin, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins (combination pharmacotherapy) to individuals enrolled in the Medicare drug benefit program after acute myocardial infarction. METHODS AND RESULTS: We created a Markov cost-effectiveness model to estimate the incremental cost-effectiveness of providing Medicare beneficiaries with full coverage for combination pharmacotherapy compared with current coverage under the Medicare Part D program. Our analysis was conducted from the societal perspective and considered a lifetime time horizon. In a sensitivity analysis, we repeated our analysis from the perspective of Medicare. In the model, post-myocardial infarction Medicare beneficiaries who received usual prescription drug coverage under the Part D program lived an average of 8.21 quality-adjusted life-years after their initial event, incurring coronary heart disease-related medical costs of $114,000. Those who received prescription drug coverage without deductibles or copayments lived an average of 8.56 quality-adjusted life-years and incurred $111,600 in coronary heart disease-related costs. Compared with current prescription drug coverage, full coverage for post-myocardial infarction secondary prevention therapies would result in greater functional life expectancy (0.35 quality-adjusted life-year) and less resource use ($2500). From the perspective of Medicare, full drug coverage was highly cost-effective ($7182/quality-adjusted life-year) but not cost saving. CONCLUSIONS: Our analysis suggests that providing full coverage for combination therapy to post-myocardial infarction Medicare beneficiaries would save both lives and money from the societal perspective.

BACKGROUND: Clinical trials have helped clarify the efficacy of clopidogrel for the treatment and prevention of vascular disease. Costs for its use exceeded $5.9 billion in 2005, making it the second greatest source of drug expenditure in the world. However, little is known about the appropriateness of that use. Overuse of clopidogrel could have important implications for health care quality and drug expenditures. METHODS: We conducted a retrospective cohort study linking all filled prescriptions to all clinical encounter data for Medicare beneficiaries enrolled in a large state-wide pharmacy assistance program. We identified all patients newly prescribed clopidogrel during a recent 2-year period and determined the proportion who had indications for clopidogrel, the mean number of tablets filled by patients with and without apparent indications in the year after starting therapy, and the costs associated with the observed patterns of clopidogrel use. RESULTS: We identified 4977 patients who were newly prescribed clopidogrel. Of these patients, only 47% had > or = 1 documented indications for clopidogrel according to clinical trial findings. Using looser criteria, the number of patients with appropriate indications was 56%. During the first year of therapy, 43% ($2.05 million) of total clopidogrel expenditures for the patients studied was spent on patients without an indication that this agent was required, using the extended criteria for evidence-based use. CONCLUSIONS: More than 40% of the clopidogrel used in this population appears to have been prescribed to patients for whom the drug had no documented advantage over aspirin or no antiplatelet therapy. If the same proportion applies nationally, in 2005, it would represent almost $1.5 billion of potentially unnecessary health care expenditure.

BACKGROUND: -The benefits of statins have been demonstrated for patients with a remote history of coronary artery bypass grafting (CABG); however, no investigation to date has evaluated whether initiation of statin therapy in the early months after surgery improves clinical outcomes. Methods and Results-A retrospective cohort of 7503 Medicare patients >/=65 years of age who underwent CABG (1995-2003) was assembled by use of linked hospital and pharmacy claims data. Rates of all-cause mortality and major adverse cardiovascular events were compared between patients who were (n=1745) and were not (n=5788) prescribed statins within 1 month of CABG discharge. Additional analyses evaluated the impact of statin initiation between 1 and 6 months after surgery. Multivariable and propensity score analysis demonstrated that statin use within 1 month of CABG discharge independently reduced the risk of all-cause mortality (adjusted hazard ratio 0.82, 95% confidence interval 0.72 to 0.94) compared with no statin use. Similarly, statin use within 1 month of CABG discharge independently reduced the risk of major adverse cardiovascular events (adjusted hazard ratio 0.89, 95% confidence interval 0.81 to 0.98). Initiation of statin therapy between 1 and 6 months after CABG discharge was also associated with reductions in major adverse cardiovascular events and mortality; however, outcome rates between early (

In response to increasing prescription drug costs, more U.S. patients and policymakers are importing less-expensive pharmaceutical products from other countries. Large-scale prescription drug importation is currently illegal, but the U.S. Food and Drug Administration permits individuals to bring in 90-day supplies of drugs for personal use. As patient use of foreign-bought drugs has increased, federal legislators have continued to debate the full legalization of importation. Three factors help guide whether U.S. patients and policymakers can rely on other countries as sources of imported prescription drugs: whether the safety of the product can be ensured, how the import price compares with domestic prices, and how importation might affect the exporting country's pharmaceutical market. In wealthier countries with active regulatory systems, drug safety can be adequately ensured, and brand-name products are usually less expensive than in the United States (although generic drugs may be more expensive). However, implementing large-scale importation can negatively impact the originating country's market and can diminish the long-term cost savings for U.S. consumers. In low- and middle-income countries, prices may be reduced for both brand-name and generic drugs, but the prevalence of unauthorized products on the market makes ensuring drug safety more difficult. It may be reasonable for individual U.S. consumers to purchase essential medicines from certain international markets, but the most effective way to decrease drug costs overall is the appropriate use of domestic generic drugs, which are available for almost every major therapeutic class.

Antiplatelet agents are central to the treatment and prevention of cardiovascular disease. Although aspirin is the most widely used agent, randomized trials have assessed whether adding clopidogrel to aspirin ("dual-antiplatelet therapy") offers additional benefit with acceptable safety. Unfortunately, these trials have reached conflicting results, in part because of the heterogenous populations they studied. To clarify the role of dual-antiplatelet therapy for patients with vascular disease, a systematic review and meta-analysis of randomized controlled trials was performed. Medline and the Cochrane Collaboration and American College of Physicians Journal Club databases were searched for trials published from 1966 to August 2006 that compared aspirin and clopidogrel with antiplatelet monotherapy. Only trials that presented clinically relevant efficacy and safety outcomes were included. From each trial, demographic data and outcomes were recorded. Summary odds ratios and 95% confidence intervals (CIs) were calculated using a random-effects model. Eight trials comprising 91,744 patients were included. Mean follow-up ranged from 28 days to 18 months. Compared with aspirin alone, dual therapy with aspirin and clopidogrel reduced the odds ratio of the composite outcome of death, reinfarction, and stroke by 15% (95% CI 23% to 6%) in patients with acute coronary syndromes and by 34% (95% CI 44% to 22%) in patients who underwent percutaneous coronary intervention. Dual therapy also significantly reduced the odds of fatal and nonfatal reinfarction in these patient groups but did not significantly reduce the odds of all-cause mortality. Dual therapy was associated with significantly increased risk for major bleeding in studies >1 month in duration (odds ratio 1.80, 95% CI 1.40 to 2.30). In conclusion, combining aspirin and clopidogrel significantly reduces the odds of major cardiovascular events in patients with acute coronary syndromes or those who undergo percutaneous coronary intervention but at the expense of significant increases in the risk for bleeding.

BACKGROUND: Undertreatment of osteoporosis after hip or wrist fracture has been well documented, but the reasons for current patterns of care are poorly understood. OBJECTIVE: We tested the role of physician and patient characteristics in predicting undertreatment when osteoporosis management was clearly indicated after a hip or wrist fracture in women over age 65. METHODS: We assembled a cohort of 9,698 female Medicare beneficiaries aged > or = 65 years who experienced hip or wrist fracture between 2000 and 2004 and their prescribing physicians. MEASUREMENTS: The dominant prescriber was identified as the physician prescribing at least 50% of patient prescriptions in the year after the fracture. Multivariate logistic regression estimated the role of physician and patient characteristics on osteoporosis management after hip or wrist fracture. RESULTS: Patients older than 90 and black patients were less likely to be treated for osteoporosis relative to patients aged 65-69 and white patients. Female providers were more likely to manage osteoporosis. Models including patient characteristics discriminated well between managed and unmanaged patients (C statistic 0.81), while adding physician predictors to the model provided no additional discriminatory ability (C statistic 0.81). CONCLUSIONS: Our findings highlight that osteoporosis management rates are similar across providers, but vary considerably by patient types.

BACKGROUND: Medication nonadherence is a major public health problem, especially for patients with coronary artery disease. The cost of prescription drugs is a central reason for nonadherence, even for patients with drug insurance. Removing patient out-of-pocket drug costs may increase adherence, improve clinical outcomes, and even reduce overall health costs for high-risk patients. The existing data are inadequate to assess whether this strategy is effective. TRIAL DESIGN: The Post-Myocardial Infarction Free Rx and Economic Evaluation (Post-MI FREEE) trial aims to evaluate the effect of providing full prescription drug coverage (ie, no copays, coinsurance, or deductibles) for statins, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers to patients after being recently discharged from the hospital. Potentially eligible patients will be those individuals who receive their health and pharmacy benefits through Aetna, Inc. Patients enrolled in a Health Savings Account plan, who are > or =65 years of age, whose plan sponsor (ie, the employer, union, government, or association that sponsors the particular benefits package) has opted out of participating in the study, and who do not receive both medical services and pharmacy coverage through Aetna will be excluded. The plan sponsor of each eligible patient will be block randomized to either full drug coverage or current levels of pharmacy benefit, and all subsequently eligible patients of that same plan sponsor will be assigned to the same benefits group. The primary outcome of the trial is a composite clinical outcome of readmission for acute MI, unstable angina, stroke, congestive heart failure, revascularization, or inhospital cardiovascular death. Secondary outcomes include medication adherence and health care costs. All patients will be followed up for a minimum of 1 year. CONCLUSION: The Post-MI FREEE trial will be the first randomized study to evaluate the impact of reducing cost-sharing for essential cardiac medications in high-risk patients on clinical and economic outcomes.

BACKGROUND: Poor levels of medication adherence for patients with coronary heart disease (CHD) have been documented but it is unclear whether adherence has improved over time. METHODS: We assembled a retrospective cohort of lower-income Medicare beneficiaries who were discharged from the hospital after their first acute myocardial infarction (MI) between 1 January 1995 and 31 December 2003. For patients prescribed a statin, ACEI/ARB, beta-blocker, and all 3 of these medications after the hospital discharge, we evaluated medication adherence by determining the proportion of days covered (PDC) for each medication in the subsequent year. RESULTS: Our cohort consisted of a total of 33 646 patients. Adherence rates for statins and beta-blockers, but not ACEI/ARB, increased significantly over time but remained suboptimal. For example, among those patients that received a statin after discharge, 38.6% were fully adherent with therapy in 1995 in contrast to 56.2% in 2003 (p value for trend<0.001). Of patients prescribed all 3 of statin, beta-blocker, and ACEI/ARB, 29.1% and 46.4% were fully adherent in 1995 and 2003, respectively (p value for trend<0.001). CONCLUSIONS: Our analysis demonstrates statistically significant but modest improvements in medication adherence for statins and beta-blockers, but not ACEI/ARBs, among patients discharged from hospital after acute MI. Despite these improvements, rates of non-adherence to these highly effective therapies remain extremely high. Given the health and economic consequences of non-adherence, the development of cost-effective strategies to improve medication adherence should be a clear priority.

OBJECTIVE: To examine trends in osteoporosis drug prescribing after hip fracture from 1995 to 2004. METHODS: We conducted a population-based study of enrollees in the Pennsylvania Pharmaceutical Assistance Contract for the Elderly. Hip fractures were identified using Medicare hospital claims between January 1, 1995, and June 30, 2004. Osteoporosis treatment comprised oral bisphosphonates, calcitonin, hormone therapy, raloxifene, and/or teriparatide. Kaplan-Meier methods were used to estimate the probability of treatment within 6 months of fracture, censoring patients on their date of death or 6 months postfracture. RESULTS: Treatment within 6 months after hip fracture improved from 7% in 1995 to 31% in 2002, and then remained stable through 2004. Similar patterns were observed among new users, with treatment increasing from 4% in 1995 to 17% in 2002, with no subsequent increase through 2004. Bisphosphonates led other treatments in the frequency of prescribing, except during 1997-99, when calcitonin was the most common. Among women, hormone therapy prescribing decreased from 22% of those treated in 1995 to 4% in 2004, and raloxifene prescribing remained relatively constant (4%-10%) since its introduction (p for trend = 0.15). Of patients treated before and after hip fracture, 18% changed therapy postfracture. Significantly more patients changed therapy following fracture if a different physician prescribed treatment (26%) compared to those treated by the same physician pre- and postfracture (13%; p < 0.0001). CONCLUSION: Prescribing practices changed substantially over the 10 years of study. The proportion of hip fracture patients treated with osteoporosis drugs has increased, but remains low, with fewer than one-third receiving pharmacotherapy.

CONTEXT: Cardiac tamponade is a state of hemodynamic compromise resulting from cardiac compression by fluid trapped in the pericardial space. The clinical examination may assist in the decision to perform pericardiocentesis in patients with cardiac tamponade diagnosed by echocardiography. OBJECTIVE: To systematically review the accuracy of the history, physical examination, and basic diagnostic tests for the diagnosis of cardiac tamponade. DATA SOURCES: MEDLINE search of English-language articles published between 1966 and 2006, reference lists of these articles, and reference lists of relevant textbooks. STUDY SELECTION: We included articles that compared aspects of the clinical examination to a reference standard for the diagnosis of cardiac tamponade. We excluded studies with fewer than 15 patients. Of 787 studies identified by our search strategy, 8 were included in our final analysis. DATA EXTRACTION: Two authors independently reviewed articles for study results and quality. A third reviewer resolved disagreements. DATA SYNTHESIS: All studies evaluated patients with known tamponade or those referred for pericardiocentesis with known effusion. Five features occur in the majority of patients with tamponade: dyspnea (sensitivity range, 87%-89%), tachycardia (pooled sensitivity, 77%; 95% confidence interval [CI], 69%-85%), pulsus paradoxus (pooled sensitivity, 82%; 95% CI, 72%-92%), elevated jugular venous pressure (pooled sensitivity, 76%; 95% CI, 62%-90%), and cardiomegaly on chest radiograph (pooled sensitivity, 89%; 95% CI, 73%-100%). Based on 1 study, the presence of pulsus paradoxus greater than 10 mm Hg in a patient with a pericardial effusion increases the likelihood of tamponade (likelihood ratio, 3.3; 95% CI, 1.8-6.3), while a pulsus paradoxus of 10 mm Hg or less greatly lowers the likelihood (likelihood ratio, 0.03; 95% CI, 0.01-0.24). CONCLUSIONS: Among patients with cardiac tamponade, a minority will not have dyspnea, tachycardia, elevated jugular venous pressure, or cardiomegaly on chest radiograph. A pulsus paradoxus greater than 10 mm Hg among patients with a pericardial effusion helps distinguish those with cardiac tamponade from those without. Diagnostic certainty of the presence of tamponade requires additional testing.

Prescription drug cost containment is a key health policy priority. State Medicaid programs have implemented policies requiring prior authorization before paying for angiotensin-receptor blockers (ARBs), a costly class of blood pressure medications. We examined the impact of these policies on drug use. We found that policies using a stepped-therapy approach reduced ARB use by 1.6 percent when first implemented and decreased the subsequent trend in ARB use by 1.3 percent per quarter; alternative approaches were unsuccessful. These findings have important implications for the development of rational drug reimbursement policy under Medicare Part D and other health insurance plans.

OBJECTIVES: The benefits of statin therapy for patients with coronary artery disease have been well documented, including those occurring after coronary artery bypass graft surgery. The purposes of this study were to assess statin prescription rates in patients who have undergone coronary artery bypass graft surgery and to identify the determinants of postoperative statin administration. METHODS: A retrospective cohort of 9284 Medicare patients aged 65 years or older who underwent coronary artery bypass graft surgery (1995-2004) was assembled by using linked hospital and pharmacy claims data. Rates of statin use after hospital discharge were calculated, and predictors of postoperative statin use were identified by using generalized estimating equations. RESULTS: Overall, 35.9% of patients received statins within 90 days of coronary artery bypass graft surgery discharge. Use of statins within 90 days after coronary artery bypass graft surgery steadily improved during the study period, from 13.1% in 1995 to 60.9% in 2004. Patient factors independently associated with an increase in postoperative statin therapy included preoperative statin use (odds ratio, 7.69), later year of operation (odds ratio, 1.22 per additional year), and additional postoperative medications (odds ratio, 1.16 per additional medication). Factors independently associated with a decrease in postoperative statin therapy included peripheral vascular disease (odds ratio, 0.60), diabetes mellitus (odds ratio, 0.67), stroke (odds ratio, 0.77), and older age (odds ratio, 0.96 per additional year). Surgeon and hospital characteristics were not independently associated with postoperative statin use. CONCLUSIONS: Statins are considerably underused after coronary artery bypass graft surgery, although recent prescription rates are increasing. Patterns of use do not appear to correlate with coronary artery disease risk. These findings highlight the need for targeted quality improvement initiatives to increase the rate of statin administration to this at-risk population.

Taken in combination, aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins (combination pharmacotherapy) greatly reduce cardiac events. These therapies are underused, even among patients with drug insurance. Out-of-pocket spending is a key barrier to adherence. We estimated the impact of providing combination pharmacotherapy without cost sharing ("full coverage") to insured patients after a myocardial infarction (MI). Under base-case assumptions, compared to standard coverage, three years of full coverage will reduce mortality and reinfarction rates and will save 5,974 per patient. Our analysis suggests that covering combination therapy for such patients will save both lives and money.

OBJECTIVE: To compare the effectiveness of statins of different treatment intensity used to treat elderly patients with acute coronary syndrome (ACS) in typical care settings. DESIGN: Retrospective cohort study using linked hospital and pharmacy claims data. SETTING: Statewide pharmacy benefits programmes in Pennsylvania and New Jersey. PARTICIPANTS: 18,311 Medicare patients discharged alive after ACS who received a prescription for a statin within 90 days of hospital discharge. MAIN OUTCOME MEASURES: Using multivariable and propensity-matched Cox proportional hazards regression models, patients who were prescribed high-intensity and moderate-intensity statins were compared based on the drug-dose combination that they initially received. Individual drug-dose combinations were also compared. Our primary outcome was the composite of all-cause death or recurrent ACS. RESULTS: Patients who received moderate-intensity statins were as likely to experience a primary outcome as patients treated with high-intensity statins (adjusted HR 1.02, 95% CI 0.96 to 1.08). Propensity matching did not change the results. Individually, all moderate-intensity statins were as effective as high-intensity atorvastatin with the exception of lovastatin (adjusted HR 1.22, 95% CI 1.09 to 1.36). Similarly, all high-intensity statins seem as effective as high-intensity atorvastatin but the CIs surrounding these estimates were wide. CONCLUSIONS: This analysis of elderly patients with ACS treated in typical care settings does not demonstrate the superiority of high-intensity over moderate-intensity statin treatment or significant differences among individual statins.

BACKGROUND: Medication errors occur frequently, and poor medication labeling is cited as a potential cause. We assessed the format, content, and variability of prescription drug container labels dispensed in the community. METHODS: Identically written prescriptions for 4 commonly used medications (atorvastatin calcium [Lipitor], alendronate sodium [Fosamax], trimethoprim-sulfamethoxazole [Bactrim], and ibuprofen) were filled in 6 pharmacies (the 2 largest chains, 2 grocery stores, and 2 independent pharmacies) in 4 cities (Boston, Chicago, Los Angeles, and Austin [Texas]). Characteristics of the format and content of the main container label and auxiliary stickers were evaluated. Labels were coded independently by 2 abstractors, and differences were reconciled by consensus. RESULTS: We evaluated 85 labels after excluding 11 ibuprofen prescriptions that were filled with over-the-counter containers that lacked labels printed at the pharmacy. The pharmacy name or logo was the most prominent item on 71 (84%) of the labels, with a mean font size of 13.6 point. Font sizes were smaller for medication instructions (9.3 point), medication name (8.9 point), and warning and instruction stickers (6.5 point). Color, boldfacing, and highlighting were most often used to identify the pharmacy and items most useful to pharmacists. While the content of the main label was generally consistent, there was substantial variability in the content of instruction and warning stickers from different pharmacies, and independent pharmacies were less likely to use such stickers (P < .001). None of the ibuprofen containers were delivered with Food and Drug Administration-approved medication guides, as required by law. CONCLUSIONS: The format of most container labels emphasizes pharmacy characteristics and items frequently used by pharmacists rather than use instructions or medication warnings. The content of warning and instruction stickers is highly variable depending on the pharmacy selected.

Decreasing HRT use among postmenopausal women may have a reciprocal impact on other osteoporosis therapy. Time series analysis of prescribing trends for millions of Medicaid beneficiaries revealed a 57% decline in HRT without augmenting the pace of bisphosphonate use. Prescribing changes dramatically increased Medicaid spending on osteoporosis therapy over the last decade and requires further evaluation of cost effectiveness. Introduction: Hormone replacement therapy (HRT) has been commonly prescribed to postmenopausal women, but its use is decreasing because adverse cardiac outcomes were reported by the Wome|$$|Aans Health Initiative (WHI) in July 2002. The reciprocal impact of the WHI on other osteoporosis medications use and expenditure is unknown. Materials and Methods: We conducted a time series analysis on prescription data from 50 state Medicaid programs between 1995 and 2004. Five medication categories were used: HRT, bisphosphonates, calcium, calcitonin, and raloxifene. Results: HRT was increasing before publication of the WHI, reaching 5 million prescriptions per year by mid-2002 (136 prescriptions per 1000 beneficiaries). Bisphosphonate prescribing rose in parallel until mid-2002. WHI publication was associated with a rapid reduction in HRT use, declining 57% by mid-2004 to an average of 59 prescriptions per 1000 beneficiaries (p = 0.01). WHI publication did not augment bisphosphonates' nearly linear rate of rise (p = 0.43) as their prescribing pace continued, whereas HRT declined. Medicaid spending on osteoporosis therapy also changed dramatically during the last decade, as yearly expenditure increased 664% from $1465 to $9742 per 1000 beneficiaries. Over this period, a significant shift from daily to weekly bisphosphonates also occurred. Conclusions: A dramatic decline in HRT and continued rise in bisphosphonate prescribing has occurred since the publication of the WHI. During this time, there have also been substantial increases in osteoporosis medication spending within Medicaid. Determining whether these trends are clinically appropriate and cost effective for osteoporosis therapy will have important implications for the development of future drug reimbursement programs, especially for elderly patients.

OBJECTIVES: To quantify the influence of physicians' experiences of adverse events in patients with atrial fibrillation who were taking warfarin. DESIGN: Population based, matched pair before and after analysis. SETTING: Database study in Ontario, Canada. PARTICIPANTS: The physicians of patients with atrial fibrillation admitted to hospital for adverse events (major haemorrhage while taking warfarin and thromboembolic strokes while not taking warfarin). Pairs of other patients with atrial fibrillation treated by the same physicians were selected. MAIN OUTCOME MEASURES: Odds of receiving warfarin by matched pairs of a given physician's patients (one treated after and one treated before the event) were compared, with adjustment for stroke and bleeding risk factors that might also influence warfarin use. The odds of prescriptions for angiotensin converting enzyme (ACE) inhibitor before and after the event was assessed as a neutral control. RESULTS: For the 530 physicians who had a patient with an adverse bleeding event (exposure) and who treated other patients with atrial fibrillation during the 90 days before and the 90 days after the exposure, the odds of prescribing warfarin was 21% lower for patients after the exposure (adjusted odds ratio 0.79, 95% confidence interval 0.62 to 1.00). Greater reductions in warfarin prescribing were found in analyses with patients for whom more time had elapsed between the physician's exposure and the patient's treatment. There were no significant changes in warfarin prescribing after a physician had a patient who had a stroke while not on warfarin or in the prescribing of ACE inhibitors by physicians who had patients with either bleeding events or strokes. CONCLUSIONS: A physician's experience with bleeding events associated with warfarin can influence prescribing warfarin. Adverse events that are possibly associated with underuse of warfarin may not affect subsequent prescribing.

OBJECTIVES: Physicians may be aware of at least 2 types of costs when prescribing: patient's out-of-pocket costs and the actual costs of the medication. We evaluated physicians' perceptions about relevant costs for prescription drugs and the importance of communication about these costs. STUDY DESIGN: Mailed survey to a random sample of 1200 physician members of the California Medical Association, and a phone survey of a sample of nonresponders. METHODS: Descriptive statistics of survey items, McNemar's test to compare survey item responses, and logistic regression to evaluate the relationship between physician, practice, and system variables and physicians' perceptions of relevant medication costs. RESULTS: Of respondents with correct addresses, 49.6% responded to the survey; 13% of nonresponders were contacted by phone. Approximately 91% and 80% of physicians reported that it is important to manage patients' out-of-pocket costs and total medication costs, respectively. When comparing the relative importance of managing the 2 types of costs, 59% of physicians agreed that managing patients' out-of-pocket costs was more important than managing the total medication costs and only 16% disagreed. Physicians believed it was more important to discuss out-of-pocket costs than total costs with patients (P < .0001), but only 15% of physicians reported discussing out-of-pocket costs frequently and 5% reported talking about total medication costs frequently. Physicians who managed more Medicare patients had a greater likelihood than physicians managing fewer Medicare patients of prioritizing out-of-pocket cost rather than total cost management (P = .038), and generalists had a greater likelihood than medical subspecialists (P = .046). CONCLUSIONS: Physicians prioritize managing out-of-pocket costs over total medication costs. Pharmacy benefit designs that use patient out-of-pocket cost incentives to influence utilization are addressing the costs to which physicians may be most responsive. When physicians face conflicts between managing patients' out-of-pocket costs and total costs, they will likely try to protect the patients' resources at the expense of the insurer or society. Efforts to align patients', insurers', and societies' incentives will simplify prescribing decisions and result in better value in prescribing.

Background While the role of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) in secondary prevention of cardiovascular (CV) events and mortality is established, their value for primary prevention is less clear. To clarify the role of statins for patients without CV disease, we performed a meta-analysis of randomized controlled trials (RCTs). Methods MEDLINE, EMBASE, Cochrane Collaboration, and American College of Physicians Journal Club databases were searched for RCTs published between 1966 and June 2005. We included RCTs with follow-up of 1 year or longer, more than 100 major CV events, and 80% or more of the population without CV disease. From each trial, demographic data, lipid profile, CV outcomes, mortality, and adverse outcomes were recorded. Summary relative risk (RR) ratios with 95% confidence intervals (CIs) were calculated using a random effects model. Results Seven trials with 42 848 patients were included. Ninety percent had no history of CV disease. Mean follow-up was 4.3 years. Statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = .02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively. Statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = .13). No significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed. Conclusion In patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality.

PURPOSE: The study investigated the determinants of warfarin use in patients with atrial fibrillation (AF). METHODS: We assembled a retrospective cohort of community-dwelling elderly patients (aged > or = 66 years) with AF using linked administrative databases. We identified the physicians responsible for the ambulatory care of these patients using physician service claims and compared patients who did and did not have an identifiable provider. For those patients with an identifiable provider, we assessed the association between patient, physician, and hospital factors and warfarin use. RESULTS: Our cohort consisted of 140,185 patients, of whom 116,200 (83%) had an identifiable cardiac provider. Patients without a provider were significantly more likely to have comorbid conditions that increase their risk of warfarin-associated bleeding. After adjustment for clinical factors, patients without a provider were significantly less likely to receive warfarin (odds ratio 0.37, 95% confidence interval: 0.36-0.38). Of patients with providers, 50,551 patients (43.5%) received warfarin within 180 days after hospital discharge. Warfarin use was positively associated with AF-associated stroke risk factors (eg, prior stroke, congestive heart failure) and negatively associated with warfarin-associated bleeding risk factors (eg, history of intracerebral hemorrhage). After controlling for patient and hospital factors, patients cared for by noncardiologist physicians with cardiology consultation were more likely to receive warfarin then patients treated in noncollaborative environments. CONCLUSIONS: Warfarin continues to be substantially underprescribed to patients who are at high risk for AF-associated cardioembolic stroke. Our findings highlight the need for targeted quality improvement interventions and suggest preferred models of AF care involving routine collaboration between cardiologists and other physicians.

OBJECTIVE: To determine whether phlebotomy contributes to changes in hemoglobin and hematocrit levels in hospitalized general internal medicine patients. DESIGN: Retrospective cohort study. SETTING: General internal medicine inpatient service at a tertiary care hospital. PARTICIPANTS: All adult patients discharged from the Toronto General Hospital's internal medicine service between January 1 and June 30, 2001. A total of 989 hospitalizations were reviewed and 404 hospitalizations were included in our analysis. MEASUREMENTS AND MAIN RESULTS: Mean (SD) hemoglobin and hematocrit changes during hospitalization were 7.9 (12.6) g/L (P<.0001) and 2.1% (3.8%) (P<.0001), respectively. The mean (SD) volume of phlebotomy during hospital stay was 74.6 (52.1) mL. On univariate analysis, changes in hemoglobin and hematocrit were predicted by the volume of phlebotomy, length of hospital stay, admission hemoglobin/hematocrit value, age, Charlson comorbidity index, and admission intravascular volume status. The volume of phlebotomy remained a strong predictor of drop in hemoglobin and hematocrit after adjusting for other predictors using multivariate analysis (P<.0001). On average, every 100 mL of phlebotomy was associated with a decrease in hemoglobin and hematocrit of 7.0 g/L and 1.9%, respectively. CONCLUSIONS: Phlebotomy is highly associated with changes in hemoglobin and hematocrit levels for patients admitted to an internal medicine service and can contribute to anemia. This anemia, in turn, may have significant consequences, especially for patients with cardiorespiratory diseases. Knowing the expected changes in hemoglobin and hematocrit due to diagnostic phlebotomy will help guide when to investigate anemia in hospitalized patients.

PURPOSE: Patients with unstable angina or non-ST-segment elevation myocardial infarction (MI) may be managed with either an "invasive" or "conservative" strategy. It is unclear which of these strategies is superior. METHODS: We identified studies with MEDLINE and EMBASE searches (1966-September 2003) and by reviewing reference lists. Studies were included if they were randomized controlled trials comparing management strategies for patients in the early post-unstable angina/non-ST-segment elevation MI period and had follow-up data for at least 3 months. RESULTS: Seven trials that randomized a total of 9212 patients were included. The pooled odds ratio (OR) for all-cause mortality was 0.96 (95% confidence interval [CI]: 0.72 to 1.27). The occurrence of fatal or nonfatal re-infarction was reduced with an invasive strategy (OR 0.73; 95% CI: 0.61 to 0.88) as was readmission to hospital (OR 0.67; 95% CI: 0.48 to 0.94). The endpoints of nonfatal MI and the composite of death or nonfatal MI showed nonsignificant trends favoring an invasive strategy. Trials that included a higher proportion of patients with ST-segment depression on admission and trials in which a larger proportion of patients underwent revascularization showed a greater magnitude of benefit for an invasive strategy. CONCLUSION: For patients with unstable angina/non-ST-segment elevation MI, an invasive strategy reduces rates of fatal or nonfatal re-infarction and hospital readmission, but not all-cause mortality, when compared with a noninvasive strategy. These results suggest that an invasive management strategy should be considered for all patients with unstable angina/non-ST-segment elevation MI and perhaps in particular those with ST-segment depression.

In late 2004, the British government decided to allow a lipid-lowering agent to be sold as an over-the-counter medication. In contrast, the U.S. Food and Drug Administration recently decided not to do so. The United States and other countries will soon face similar decisions for other statins. Although statins have infrequent side effects and have been shown to be effective in moderate-risk primary prevention populations, many questions remain unanswered about their effectiveness at lower doses in over-the-counter use, the ability of patients to self-select themselves for appropriate therapy, and the social and economic implications associated with this method of distribution for preventive medications. A rational policy decision concerning over-the-counter statin use will require an effectiveness trial to provide data on how such drugs would be used in this context, as well as on the clinical outcomes that could be expected from this novel "route of administration."

U.S. health care has long featured a struggle between regulation and markets as vehicles of reform, and the community hospital is at the center of this struggle. The key to its financial viability is cross-subsidization, whereby revenues from insured patients subsidize the care of the uninsured and underinsured, and profits from well-compensated services support those operating at a loss. Cross-subsidization has been challenged by efforts to move highly compensated services and well-insured patients to ambulatory surgical centers and specialty hospitals. We review the ongoing battle between through a legal lens and offer conjectures about the outcome. Refined certificate-of-need regulation may be the preferable policy choice.

BACKGROUND: Physicians with more experience are generally believed to have accumulated knowledge and skills during years in practice and therefore to deliver high-quality care. However, evidence suggests that there is an inverse relationship between the number of years that a physician has been in practice and the quality of care that the physician provides. PURPOSE: To systematically review studies relating medical knowledge and health care quality to years in practice and physician age. DATA SOURCES: English-language articles in MEDLINE from 1966 to June 2004 and reference lists of retrieved articles. STUDY SELECTION: Studies that provided empirical results about knowledge or a quality-of-care outcome and included years since graduation or physician age as explanatory variables. DATA EXTRACTION: We categorized studies on the basis of the nature of the association between years in practice or age and performance. DATA SYNTHESIS: Overall, 32 of the 62 (52%) evaluations reported decreasing performance with increasing years in practice for all outcomes assessed; 13 (21%) reported decreasing performance with increasing experience for some outcomes but no association for others; 2 (3%) reported that performance initially increased with increasing experience, peaked, and then decreased (concave relationship); 13 (21%) reported no association; 1 (2%) reported increasing performance with increasing years in practice for some outcomes but no association for others; and 1 (2%) reported increasing performance with increasing years in practice for all outcomes. Results did not change substantially when the analysis was restricted to studies that used the most objective outcome measures. LIMITATIONS: Because of the lack of reliable search terms for physician experience, reports that provided relevant data may have been missed. CONCLUSIONS: Physicians who have been in practice longer may be at risk for providing lower-quality care. Therefore, this subgroup of physicians may need quality improvement interventions.

OBJECTIVE: Meta-analytic techniques are used to combine the results of different studies that have evaluated the accuracy of a given diagnostic test. The techniques commonly generate values that either describe the performance of a particular test or compare the discriminative ability of two tests. The later has received very little attention in the literature, and is the focus of this article. STUDY DESIGN AND SETTING: We summarize existing methods based on an odds ratio (OR) and propose a novel technique for conducting such analysis, the conditional relative odds ratio (CROR). We demonstrate how to extract the required data and calculate several different comparative indexes using a hypothetic example. RESULTS: A paired analysis is preferred to decrease selection bias and increase statistical power. There is no standard method of obtaining the standard error (SE) of each relative OR; thus, the SE of the summary index might be underestimated under the assumption of no within-study variability. CONCLUSION: The CROR method estimates less biased indexes with SEs, and conditioned on discordant results, it is much less problematic ethically and economically. However, small cell counts may lead to larger SEs, and it might be impossible to construct McNemar's 2 x 2 tables for some studies.

Patients who sustain a cardiac arrest have a less than 20% chance of surviving to hospital discharge. Patients may request do-not-resuscitate (DNR) orders if they believe that their chances for a meaningful recovery after cardiopulmonary arrest are low. However, in some identifiable circumstances, cardiopulmonary resuscitation (CPR) has a higher chance of success and lower likelihood of neurologic impairment. The probability of survival from a cardiac arrest influences patients' wishes regarding resuscitation; thus, when CPR has a higher likelihood of success, patients' expressed preferences for treatment as contained within a DNR order may not accurately reflect their intended goals. Patients should be offered the option of consenting to CPR for "higher-success" situations, including a witnessed cardiopulmonary arrest in which the initial cardiac rhythm is ventricular tachycardia or fibrillation, cardiac arrest in the operating room, and cardiac arrest resulting from a readily identifiable iatrogenic cause. This new level of resuscitation could be called a "limited aggressive therapy" order.

CONTEXT: Increasing contact has been reported between physicians and the pharmaceutical industry, although no data exist in the literature regarding potential financial conflicts of interest for authors of clinical practice guidelines (CPGs). These interactions may be particularly relevant since CPGs are designed to influence the practice of a large number of physicians. OBJECTIVE: To quantify the extent and nature of interactions between authors of CPGs and the pharmaceutical industry. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey of 192 authors of 44 CPGs endorsed by North American and European societies on common adult diseases published between 1991 and July 1999. One hundred authors (52%) provided usable responses representing 37 of 44 different CPGs that we identified. MAIN OUTCOME MEASURES: Nature and extent of interactions of authors with drug manufacturers; disclosure of relationships in published guidelines; prior discussion among authors regarding relationships; beliefs regarding whether authors' own relationships or those of their colleagues influenced treatment recommendations in guidelines. RESULTS: Eighty-seven percent of authors had some form of interaction with the pharmaceutical industry. Fifty-eight percent had received financial support to perform research and 38% had served as employees or consultants for a pharmaceutical company. On average, CPG authors interacted with 10.5 different companies. Overall, an average of 81% (95% confidence interval, 70%-92%) of authors per CPG had interactions. Similarly, all of the CPGs for 7 of the 10 diseases included in our study had at least 1 author who had some interaction. Fifty-nine percent had relationships with companies whose drugs were considered in the guideline they authored, and of these authors, 96% had relationships that predated the guideline creation process. Fifty-five percent of respondents indicated that the guideline process with which they were involved had no formal process for declaring these relationships. In published versions of the CPGs, specific declarations regarding the personal financial interactions of individual authors with the pharmaceutical industry were made in only 2 cases. Seven percent thought that their own relationships with the pharmaceutical industry influenced the recommendations and 19% thought that their coauthors' recommendations were influenced by their relationships. CONCLUSIONS: Although the response rate for this survey was low, there appears to be considerable interaction between CPG authors and the pharmaceutical industry. Our study highlights the need for appropriate disclosure of financial conflicts of interest for authors of CPGs and a formal process for discussing these conflicts prior to CPG development.

OBJECTIVE: To review evidence as to the precision and accuracy of clinical examination for aortic regurgitation (AR). METHODS: We conducted a structured MEDLINE search of English-language articles (January 1966-July 1997), manually reviewed all reference lists of potentially relevant articles, and contacted authors of relevant studies for additional information. Each study (n = 16) was independently reviewed by both authors and graded for methodological quality. RESULTS: Most studies assessed cardiologists as examiners. Cardiologists' precision for detecting diastolic murmurs was moderate using audiotapes (kappa = 0.51) and was good in the clinical setting (simple agreement, 94%). The most useful finding for ruling in AR is the presence of an early diastolic murmur (positive likelihood ratio [LR], 8.8-32.0 [95% confidence interval [CI], 2.8-32 to 16-63] for detecting mild or greater AR and 4.0-8.3 [95% CI, 2.5-6.9 to 6.2-11] for detecting moderate or greater AR) (2 grade A studies). The most useful finding for ruling out AR is the absence of early diastolic murmur (negative LR, 0.2-0.3 [95% CI, 0.1-0.3 to 0.2-0.4) for mild or greater AR and 0.1 [95% CI, 0.0-0.3] for moderate or greater AR) (2 grade A studies). Except for a test evaluating the response to transient arterial occlusion (positive LR, 8.4 [95% CI, 1.3-81.0]; negative LR, 0.3 [95% CI, 0.1-0.8]), most signs display poor sensitivity and specificity for AR. CONCLUSION: Clinical examination by cardiologists is accurate for detecting AR, but not enough is known about the examinations of less-expert clinicians.

The authors evaluated the accuracy of clinical impressions and Mini-Mental State Exam scores for assessing patient capacity to consent to major medical treatment, relative to expert psychiatric assessment. Consecutive medical inpatients (N = 63) facing a decision about major medical treatment received a clinical impression of capacity from their treating physician and the Standardized Mini-Mental State Exam (SMMSE); 48 received independent psychiatric assessment of capacity. Analyses revealed that both clinical impressions and SMMSE scores were generally inaccurate in determining capacity, although all 23 participants with a clinical impression of "definitely capable" were found capable by the psychiatrist. Given the importance of assessing capacity to consent to major medical treatment, better approaches to the clinical assessment of capacity are required. Several strategies are discussed.

OBJECTIVES: To examine funding priorities assigned by health ministry officials when choosing between clinical programs that offer similar overall benefits distributed in different ways (e.g. large gains for a few versus small gains for many), and to compare the relative magnitude of any distributional bias to age biases. METHODS: A survey consisting of paired hypothetical health care programs was mailed to the 135 most senior officials of the Health Ministry in Ontario, Canada (population 11.5 million). Respondents were asked to assume they were members of a panel allocating a fixed sum of money to one of two programs in each pair. All program descriptions included the number of persons affected each year by a given disease and the average survival gains from the hypothetical programs. Some scenarios also mentioned the side-effects associated with programs and/or the average age of the beneficiaries. RESULTS: Four respondents had retired/died. Of 131 eligible respondents, 80/131 (61%) provided usable responses. Asked to choose between providing large benefits to a few citizens and small benefits to a great many, 23% (95% CI: 14%, 33%) of respondents were unable to decide, but 55.8% (95% CI: 47%, 70%) favored providing large benefits to fewer patients. Eliminating the 23% unable to decide, 47/62 or 76% (CI 63%, 86% expressed a distributional preference. With a smaller distributional discrepancy, indecision increased, with 35% of respondents having no preference and the remainder split almost evenly between the two programs. Other scenarios showed that health officials' pro-youth biases were only slightly larger than their distributional preferences and that distributional preferences were magnified when combined with minor differences in average ages of beneficiaries. CONCLUSIONS: A substantial minority of health care decision-makers had difficulty choosing between programs with similar overall gains and distributional differences--a result consistent with the utilitarian assumptions of cost-effectiveness analysis. However, when distributional differences were large, decision-makers clearly favored large gains for a few beneficiaries rather than small gains for many. Policy analysts should explicitly weigh distributional issues along with aggregate health gains when addressing resources allocation problems.

OBJECTIVE: To determine the value of conjunctival pallor in ruling in or ruling out the presence of severe anemia (hemoglobin < or = 90 g/L) and to determine the interobserver agreement in assessing this sign. DESIGN: Patients were prospectively assessed for pallor by at least one of three observers. All observations were made without information of the patient's hemoglobin value or of another observer's assessment. SETTING: Tertiary-care, university-affiliated teaching hospital. PATIENTS: Three hundred and two medical and surgical inpatients. MEASUREMENTS AND MAIN RESULTS: Likelihood ratios (LRs) calculated for conjunctival pallor present, borderline, and absent were as follows: pallor present, LR 4.49 (95% confidence interval [CI] 1.80, 10.99); pallor borderline, LR 1.80 (95% CI 1.18, 2.62); pallor absent, LR 0.61 (95% CI 0.44, 0.80). Kappa scores of interobserver agreement between paired observers were 0.75 and 0.54. CONCLUSIONS: The presence of conjunctival pallor, without other information suggesting anemia, is reason enough to perform a hemoglobin determination. The absence of conjunctival pallor is not likely to be of use in ruling out severe anemia. With well-defined criteria, interobserver agreement is good to very good.

The population-based dialysis rate in Ontario more than doubled between 1981 and 1992; yet there is concern about over-loaded facilities, delayed treatment and denial of dialysis through nonreferral and implicit rationing. A working party involving several stakeholders has been established in Ontario to address these issues. However, clinical policy making concerning dialysis services is impeded in all provinces by a lack of information. The causes of the moderately large variations in dialysis rates from province to province remain unclear. The exact extent and risks of delayed therapy have not been well defined. Dialysis protocols vary inexplicably among centres, and cost data on different methods of providing dialysis are limited. Many steps could be taken in Ontario and other provinces to generate a better information base for planning and managing dialysis services. Predialysis clinics with outreach programs could help to ensure equitable access to this life-saving therapy. Criteria for choosing modes and intensities of renal-replacement therapy must be reviewed. In areas of clear disagreement and uncertainty, patients could be randomly assigned to different protocols and outcomes studied. In areas of agreement, the criteria should be standardized. Advance directives may help ascertain patients' wishes concerning the initiation or continuation of dialysis, and more accurate data on prognosis of different patient subgroups would aid in early identification of patients in a hopelessly deteriorating situation. Last, studies comparing the "output" (e.g., hours on hemodialysis) per dollar of different dialysis units and modalities are also needed to ensure that all facilities are opening efficiently without compromising patient outcomes.

OBJECTIVE: To describe the prevalence and content of long-term care facility policies regarding the use of life-sustaining treatments (cardiopulmonary resuscitation (CPR), artificial hydration and nutrition, dialysis, antibiotics for life-threatening infections, transfer to acute care hospital) and advance directives in Canada. DESIGN: Cross-sectional mailed survey. SETTING: Canadian long-term care facilities with 25 beds or more listed in the 1991-92 Directory of Long Term Care Centres in Canada. Institutions listed as, "general hospitals,""psychiatric hospitals,""children's treatment centres,""group homes," or as purely residential facilities were excluded. PARTICIPANTS: Chief Executive Officers or their designates. MAIN OUTCOME MEASURES: Respondents' self-reports regarding the existence of life-sustaining treatment or advance directive policies and content analysis of the policies themselves. RESULTS: Of 1472 long-term care facilities, 1021 (69%) responded. Of these, 344 (34%) institutions had 397 policies regarding the use of life-sustaining treatments or advance directives. Three hundred twenty facilities (31%) had 349 do-not-resuscitate (DNR) policies (40% on CPR alone and 60% on CPR plus other life-sustaining treatments). Seventeen institutions (2%) each had one policy addressing life-sustaining treatments other than CPR, and 31 institutions (3%) each had one policy addressing advance directives. Of the 397 policies, 171 (43%) required routine discussion with all patients, 156 (39%) mentioned futility, 331 (83%) indicated that the competent patient had the right to make a decision about life-sustaining treatment, 265 (67%) indicated that the family of the incompetent patient had this right, 27 policies (7%) mentioned conflict resolution, 378 (95%) had an explicit requirement for recording the decision, 10 (3%) required explicit communication of the decision to the competent patient, 10 (3%) required such communication to the family of the incompetent patient, 260 (66%) required updating of the decision, and 213 (54%) mentioned rescinding or changing the decision. CONCLUSIONS: Only one-third of Canadian long-term care facilities have do-not-resuscitate policies, and even fewer have policies on advance directives or life-sustaining treatments other than CPR. The policies themselves could be improved by encouraging routine advance discussions, scrutinizing the use of the futility standard, stipulating procedures for conflict resolution, and explicitly requiring communication of the decision to competent patients or substitute decision makers of incompetent patients.