Steven J. Bernstein

Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy.

Context Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients. Clinicians use a variety of contrast agents to reduce the risk for contrast-induced nephropathy, including N-acetylcysteine, theophylline, fenoldopam, dopamine, furosemide, mannitol, and bicarbonate. Contribution Although all of the agents included in this analysis reduced the risk for contrast-induced nephropathy, this meta-analysis of 33 trials involving 3622 patients found the strongest evidence for the effectiveness of N-acetylcysteine, mannitol, and theophylline when compared with periprocedural hydration alone. Caution Available studies examined laboratory end points (such as an increase in serum creatinine levels) rather than clinical end points (such as dialysis or death). The Editors Contrast-induced nephropathy, defined as an increase in serum creatinine greater than 25% or 44.2 mol/L (>0.5 mg/dL) within 3 days of intravascular contrast administration in the absence of an alternative cause, is the third most common cause of new acute renal failure in hospitalized patients (1, 2). Contrast-induced nephropathy develops in 0% to 10% of patients with normal renal function (3). However, the incidence may be as high as 25% in patients with preexisting renal impairment or certain risk factors, such as diabetes, congestive heart failure, advanced age, and concurrent administration of nephrotoxic drugs (3). Large doses of intravenous contrast and use of high-osmolar contrast agents in patients with renal impairment also increase the risk for contrast-induced nephropathy (46). High-osmolar contrast agents are more rarely used now. The risk difference between iso-osmolar agents, such as iodixanol, and low-osmolar agents, such as iopamidol, ioxaglate, or iohexol, is less clear (79). Most episodes of contrast-induced nephropathy are not detected clinically because patients are asymptomatic. However, contrast-induced nephropathy may increase the risk for renal failure and is associated with dialysis, prolonged hospital stay, increased health care costs, potentially irreversible reduction in renal function, and death (10). Use of preprocedural fluids and low-osmolar or iso-osmolar contrast agents has been shown to decrease the risk for contrast-induced nephropathy (1113). These measures suffice for many patients; however, the risk is reduced but not eliminated in some patientseven when iso-osmolar contrast is used (14, 15). Other studies have evaluated the use of N-acetylcysteine, theophylline, fenoldopam, and other agents as preventive strategies in contrast-induced nephropathy; the results have been heterogeneous and are difficult to compare across the different treatment strategies. Given the widespread use of iodinated intravascular contrast agents, an improved understanding of the potential value of these agents has important patient safety and cost implications. We conducted a meta-analysis of the literature to quantify the effects of individual strategies on the prevention of contrast-induced nephropathy and to facilitate comparison of preventive effects across strategies. Methods Study Search Strategy We performed a computerized search by using standard meta-analytic techniques (16) to identify relevant articles in MEDLINE (from 1966 through 3 November 2006), EMBASE (1980 through November 2006), PubMed, Web of Knowledge (Current Contents Connect, Web of Science, BIOSIS Previews, and ISI Proceedings for the latest 5 years), and the Cochrane Library databases. For the MEDLINE search, we used the following combination of keywords: [renal failure or kidney failure to include all subheadings] and [contrast media or iopamidol or iodine or ioxaglic acid or iodine compounds or iohexol or urography or drug hyper sensitivity or tomography, X ray computed or diatrizoate] and [hydration or fluid therapy or water or dehydration or skin or nutritional support or body water] and [clinical trial or randomized, controlled trial] and [prospective trial or prospective studies or clinical trials] and [adult or middle aged or aged] and [N-Acetylcysteine or acetylcysteine] or [theophylline] or [mannitol] or [dopamine] or [fenoldopam] or [bicarbonate]. For the PubMed, Cochrane Library Database, and Web of Knowledge searches, we used the search words renal failure, contrast medium, hydration, randomized, controlled trial, N acetyl cysteine, Theophylline, Mannitol, Fenoldopam, Dopamine and Bicarbonate. We included English-, French-, German-, Spanish- and Italian-language studies and clinical trials and excluded review articles and nonhuman studies. We combined this strategy with a manual search of reference lists from identified articles. Study Selection We included a study if 1 of the treatment groups received N-acetylcysteine, theophylline, fenoldopam, iloprost, statin, dopamine, trimetazidine, bicarbonate, ascorbic acid, furosemide, or mannitol. Criteria for inclusion were randomized, controlled trials that compared treatment with control; used intravenous iodinated contrast; explicitly defined contrast-induced nephropathy; and sufficiently reported data to construct a 22 table and calculate the primary effect measure (relative risk reduction). Where data were missing, we contacted the original authors for the relevant information. Data Extraction One reviewer examined the abstracts to determine whether the study met the inclusion and exclusion criteria. Two reviewers separately abstracted complete articles according to a standardized form for studies meeting criteria. Abstracted information included patient characteristics (mean age, proportion of men and patients with diabetes mellitus or hypertension, and mean baseline creatinine level), type of radiologic or cardiologic imaging, inclusion and exclusion criteria, type of contrast media and dose used, periprocedural hydration, specific definition of contrast-induced nephropathy, prophylactic agent dose and route, and serum creatinine level at baseline and at 48 hours after contrast injection. Analysis of Renoprotective Agents The primary outcome was the development of contrast-induced nephropathy, defined as an absolute increase in baseline serum creatinine greater than 44.2 mol/L (>0.5 mg/dL) or a relative increase greater than 25% at 48 hours after contrast injection. For trials missing this datum, we contacted the original authors to get the number of patients with this outcome. We calculated individual study relative risks and 95% CIs before aggregation. Subsequently, we obtained overall and subgroup summary risk ratios by random-effects modeling of the binary data from the multiple 22 tables. We used the method of DerSimonian and Laird (17), with the estimate of heterogeneity taken from the inverse variance fixed-effect model. We used the metan module in Stata, version 9.0 (Stata, College Station, Texas), to perform data synthesis. We performed subgroup evaluation of each therapeutic regimen. In studies comparing 2 dosage regimens of the same intervention with a single control group (1820), we considered the same-study dosage groups as representing a single intervention to avoid double-counting of shared control observations. When we identified only 1 study that examined a given therapy, we assigned that study to a group termed other and pooled data from all such studies together. This group included 1 study each on the use of iloprost; trimetazidine; mannitol; bicarbonate; ascorbic acid; and combinations of furosemide, dopamine, and mannitol and furosemide and dopamine. We used relative risk ratios to estimate the treatment effects. Assessment of Methodological Quality Criteria for quality assessment included concealment of allocation, similarity of both groups at baseline regarding prognostic indicators, eligibility criteria, blinding of patient, blinding of care provider, blinding of outcome assessor, point estimates and measures of variability for the primary outcome measure, and inclusion of an intention-to-treat analysis (21). Any disagreements in abstracted data between the reviewers were adjudicated by a third reviewer. We explored potential heterogeneity in estimates of treatment efficacy attributable to each quality criterion by using meta-regression. Assessment of Heterogeneity We used Forest plots to visualize the extent of heterogeneity among studies. We also examined I 2, a standard test for heterogeneity that measures the degree of inconsistency across studies. I 2 values, which range from 0% to 100%, describe the proportion of variation in treatment effect estimates that is due to genuine variation rather than sampling error (22). A value of 0% indicates no observed heterogeneity. Higgins and colleagues (22) suggest describing I 2 values of 25%, 50%, and 75% as low, moderate, and high, respectively. We obtained the group-specific and overall I 2 as standard output of the metan program. We performed an Egger precision-weighted linear regression test as a statistical test of funnel plot asymmetry and publication bias (23). All statistical analyses were performed with Stata. Results Study Identification Our initial search yielded 619 citations and references. We excluded 531 studies on the basis of our criteria, including nonclinical trials; trials not conducted on humans; trials not reported in English, French, German, Spanish, or Italian; trials reporting only nonnephropathy outcomes; and trials using nonclinical outcome measures, leaving 88 studies that met the inclusion criteria (Figure 1). We reviewed abstracts from the 88 articles and excluded an additional 23 trials, including nonrandomized clinical trials; trials not conducted on humans; trials not reported in English, French, German, Spanish, or Italian; trials reporting only nonnephropathy outcomes; and trials that used nonclinical outcome measures, leaving 65 studies for full publication review. The full articles were then reviewed, and a further 24 studies were excluded for reasons similar to t

Suboptimal Statin Adherence and Discontinuation in Primary and Secondary Prevention Populations

AbstractOBJECTIVES: To compare statin nonadherence and discontinuation rates of primary and secondary prevention populations and to identify factors that may affect those suboptimal medication-taking behaviors. DESIGN: Retrospective cohort utilizing pharmacy claims and administrative databases. SETTING: A midwestern U.S. university-affiliated hospital and managed care organization (MCO). PATIENTS: Non-Medicaid MCO enrollees, 18 years old and older, who filled 2 or more statin prescriptions from January 1998 to November 2001; 2,258 secondary and 2,544 primary prevention patients were identified. MEASUREMENTS: Nonadherence was assessed by the percent of days without medication (gap) over days of active statin use, a measurement known as cumulative multiple refill-interval gap (CMG). Discontinuation was identified by cessation of statin refills prior to the end of available pharmacy claims data. RESULTS: On average, the primary and secondary groups went without medication 20.4% and 21.5% of the time, respectively (P=.149). Primary prevention patients were more likely to discontinue statin therapy relative to the secondary prevention cohort (relative risk [RR], 1.24; 95% confidence interval [CI], 1.08 to 1.43). Several factors influenced nonadherence and discontinuation. Fifty percent of patients whose average monthly statin copayment was <

When Do Patients and Their Physicians Agree on Diabetes Treatment Goals and Strategies, and What Difference Does It Make?

10 discontinued by the end of follow-up (3.9 years), whereas 50% of those who paid >

ACC/AHA guidelines for ambulatory electrocardiography: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography): Developed in collaboration with the North American Society for Pacing and Electrophysiology

10 but ≤

Impact of a pharmacist-facilitated hospital discharge program: a quasi-experimental study.

20 and >

ACC/AHA guidelines for ambulatory electrocardiography: Executive summary and recommendations: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the Guidelines for Ambulatory Electrocardiography): Developed in Collaboration with the North American Society for Pacing and Electrophysiology

20 discontinued by 2.2 and 1.0 years, respectively (RR, 1.39 and 4.30 relative to <

The Appropriateness of Recommendations for Hysterectomy

10 copay, respectively). CONCLUSIONS: Statin nonadherence and discontinuation was suboptimal and similar across prevention categories. Incremental efforts, including those that decrease out-of-pocket pharmaceutical expenditures, should focus on improving adherence in high-risk populations most likely to benefit from statin use.

MEASURING THE NECESSITY OF MEDICAL PROCEDURES

BACKGROUND: For patients with chronic illnesses, it is hypothesized that effective patient-provider collaboration contributes to improved patient self-care by promoting greater agreement on patient-specific treatment goals and strategies. However, this hypothesis has not been tested in actual encounters of patients with their own physicians.OBJECTIVE: To assess the extent to which patients with type 2 diabetes agree with their primary care providers (PCPs) on diabetes treatment goals and strategies, the factors that predict agreement, and whether greater agreement is associated with better patient self-management of diabetes.DESIGN: One hundred twenty-seven pairs of patients and their PCPs in two health systems were surveyed about their top 3 diabetes treatment goals (desired outcomes) and strategies to meet those goals. Using several measures to evaluate agreement, we explored whether patient characteristics, such as education and attitudes toward treatment, and patient-provider interaction styles, such as shared decision making, were associated with greater agreement on treatment goals and strategies. We then examined whether agreement was associated with higher patient assessments of their diabetes care self-efficacy and self-management.RESULTS: Overall, agreement on top treatment goals and strategies was low (all κ were less than 0.40). In multivariable analyses, however, patients with more education, greater belief in the efficacy of their diabetes treatment, and who shared in treatment decision making with their providers were more likely to agree with their providers on treatment goals or strategies. Similarly, physician reports of having discussed more content areas of diabetes self-care were associated with greater agreement on treatment strategies. In turn, greater agreement on treatment goals and strategies was associated both with higher patient diabetes care self-efficacy and assessments of their diabetes self-management.CONCLUSION: Although patients and their PCPs in general had poor agreement on goals and strategies for managing diabetes, agreement was associated with higher patient self-efficacy and assessments of their diabetes self-management. This supports the hypothesis that enhancing patient-provider agreement on both overall treatment goals and specific strategies to meet these goals may lead to improved patient outcomes.

Missed Opportunities for Type 2 Diabetes Mellitus Screening Among Women With a History of Gestational Diabetes Mellitus

A meter drive circuit includes a signal input circuit through which an input signal is applied to a peak hold circuit for producing an output signal which indicates an instantaneous peak value of the input signal and which is held for a predetermined time, a sample and hold circuit for sampling the level of the output signal of the peak hold circuit, and holding the sampled level, and a signal level indicator connected to the sample and hold circuit to provide an indication of the sampled level.

Quality of life of patients with chronic stable angina before and four years after coronary revascularisation compared with a normal population

BACKGROUND Medication discrepancies are common at hospital discharge and can result in adverse events, hospital readmissions, and emergency department visits. Our objectives were to characterize medication discrepancies at hospital discharge and test the effects of a pharmacist intervention on health care utilization following discharge. METHODS We used a prospective, alternating month quasi-experimental design to compare outcomes of patients receiving the intervention (n = 358) with controls (n = 366). All patients were discharged to home and were at high risk for medication-related problems following discharge because of the number or types of medications they were prescribed, multiple medication changes during hospitalization, or problems managing medications. The intervention consisted of medication therapy assessment, medication reconciliation, screening for adherence concerns, patient counseling and education, and postdischarge telephone follow-up. The primary outcomes were 14-day and 30-day readmission rates and emergency department visits within 72 hours of discharge. Medication discrepancies occurring at discharge were also characterized. RESULTS Medication discrepancies at discharge were identified in 33.5% of intervention patients and 59.6% of control patients (P < .001). Although all discrepancies were resolved in the intervention group prior to discharge, readmission rates did not differ significantly between groups at 14 days (12.6% vs 11.5%; P = .65) and 30 days (22.1% vs 18%; P = .17), nor did emergency department visits (2.8% vs 2.2%, respectively; P = .60). CONCLUSION While our intervention improved the quality of patient discharge by identifying and reconciling medication discrepancies at discharge, there was no effect on postdischarge health care resource utilization.