Effect of epinephrine on survival after cardiac arrest: a systematic review and meta-analysis.

The use of epinephrine is currently recommended as a treatment option for patients with cardiac arrest. The primary objective of this systematic review was to determine if epinephrine use during cardiac arrest is associated with improved survival to hospital discharge. MEDLINE, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, International Pharmaceutical Abstracts, and Biological Abstracts (BIOSIS Previews), and bibliographies of previous systematic reviews. Studies involving patients with cardiac arrest that compared epinephrine to no epinephrine (or placebo) with regard to survival to hospital discharge or 30-day survival. Randomized controlled trials (RCTs) and observational studies were included. The results were stratified into three groups: 1) RCTs, 2) observational studies with unadjusted data (observational-U), and 3) observational studies with adjusted data using multivariate analysis (observational-A). There were a total of 10 studies included in the systematic review and nine studies were included in the meta-analysis. The association between epinephrine use and survival to hospital discharge, grouped by study type was not significant for RCTs (OR 2.33, 95% CI 0.85 to 6.40; p=0.10; I2=0.00%) or observational-U studies (OR 1.17, 95% CI 0.67 to 2.07; p=0.58; I2=76.68%). But epinephrine was associated with decreased survival in observational-A studies (OR 0.43, 95% CI 0.40 to 0.48; P<0.01; I2=0.00%). Epinephrine use during cardiac arrest is not associated with improved survival to hospital discharge. Observational studies with a lower-risk for bias suggest that it may be associated with decreased survival.

A meta-analysis of the efficacy of intraperitoneal cisplatin for the front-line treatment of ovarian cancer.

Ovarian cancer is the fourth leading cause of cancer death among women in the United States. First-line chemotherapy offered to patients with ovarian cancer generally consists of an intravenous (IV) platinum plus taxane regimen and has remained virtually unchanged for the past 10 years. A number of recently completed phase III randomized trials in the United States have reported improved progression-free survival (PFS) and/or overall survival (OS) with the intraperitoneal (IP) administration of cisplatin. The purpose of this study was to pool the published data to perform a meta-analysis of randomized trials of IP cisplatin in the initial chemotherapy treatment of ovarian cancer patients. This study was initiated to obtain a more valid estimate of the therapeutic impact of IP treatment for these patients. A search strategy was initiated that searched published findings of randomized trials of IP cisplatin therapy from multiple sources from January 1990 through January 2006. Six randomized trials of 1716 ovarian cancer patients were identified and included in this analysis. The pooled hazard ratio (HR) for PFS of IP cisplatin as compared to IV treatment regimens is 0.792 (95% CI: 0.688-0.912, P= 0.001), and the pooled HR for OS is 0.799 (95% CI: 0.702-0.910, P= 0.0007). These findings strongly support the incorporation of an IP cisplatin regimen to improve survival in the front-line treatment of stage III, optimally debulked ovarian cancer.

Pharmacists' attitudes toward diabetes and their involvement in diabetes education.

OBJECTIVE: To determine the relationship between pharmacists' attitudes toward diabetes and their involvement in diabetes patient education in the community setting. METHODS: Registered pharmacists in Arizona were mailed surveys regarding their attitudes toward diabetes and their involvement in diabetes patient education. Attitudes were measured using the Diabetes Attitude Scale (DAS); the types of educational skills evaluated were based on those recommended by the American Diabetes Association's Standards of Medical Care. RESULTS: Pharmacists' attitudes were significantly positive toward the need for special training for diabetes care, the importance of tight glycemic control, the team approach to care, and the preference for diabetes education in an outpatient setting (p < 0.001). The majority of the time, pharmacists provided basic patient education (52%) rather than intermediate or advanced patient education (26% and 27%, respectively). There was a negative correlation between the attitude that diabetes is a difficult disease to treat and pharmacists' involvement in diabetes patient education (p < 0.05). This indicates that, although pharmacists believe that diabetes is a treatable disease, they infrequently provide diabetes patient education. CONCLUSIONS: Overall, pharmacists had positive attitudes toward diabetes. These attitudes did not correlate with the degree of their involvement in diabetes patent education. More diabetes patient education through community pharmacists is needed.

Establishing the internal and external validity of experimental studies.

The information needed to determine the internal and external validity of an experimental study is discussed. Internal validity is the degree to which a study establishes the cause-and-effect relationship between the treatment and the observed outcome. Establishing the internal validity of a study is based on a logical process. For a research report, the logical framework is provided by the report's structure. The methods section describes what procedures were followed to minimize threats to internal validity, the results section reports the relevant data, and the discussion section assesses the influence of bias. Eight threats to internal validity have been defined: history, maturation, testing, instrumentation, regression, selection, experimental mortality, and an interaction of threats. A cognitive map may be used to guide investigators when addressing validity in a research report. The map is based on the premise that information in the report evolves from one section to the next to provide a complete logical description of each internal-validity problem. The map addresses experimental mortality, randomization, blinding, placebo effects, and adherence to the study protocol. Threats to internal validity may be a source of extraneous variance when the findings are not significant. External validity is addressed by delineating inclusion and exclusion criteria, describing subjects in terms of relevant variables, and assessing generalizability. By using a cognitive map, investigators reporting an experimental study can systematically address internal and external validity so that the effects of the treatment are accurately portrayed and generalization of the findings is appropriate.

Cost-effectiveness of regional poison control centers.

BACKGROUND: Poison exposures are a significant public health concern. Despite the impact that regional poison control centers have on reducing morbidity and mortality associated with poison exposures, they are facing a serious financial crisis today resulting in an increased emphasis on their economic justification. METHODS: Using decision-analysis techniques, the cost-effectiveness of the treatment of poison exposures with the services of a regional poison control center compared with treatment without access to any poison control center was evaluated. The relative cost-effectiveness was modeled based on 2 outcomes (morbidity and mortality) for each of 4 typical poison exposures. Additionally, analyses were conducted to test the sensitivity of the cost-effectiveness ratios to outcome probability, average inpatient and emergency department costs, and proportion of poison exposures treated on site by the regional poison control center. A societal perspective was adopted. RESULTS: The regional poison control center was substantially more cost-effective than the treatment of poison exposures without the services of a regional poison control center for both outcomes (morbidity and mortality) in each of the poison exposures considered. The results of the sensitivity analyses demonstrated that the outcomes of the decision analyses do not change regardless of the type of poison exposure, outcome considered, clinical outcome probabilities, average inpatient and emergency department costs, and proportion of poison-exposure cases treated on site by a regional poison control center. CONCLUSIONS: The regional poison control center is consistently more cost-effective in the treatment of poison exposures with an average cost-effectiveness ratio (cost per successful outcome) approximately half of that achieved without the services of a regional poison control center. Finally, significant cost savings to society are realized for each additional successful outcome obtained with a regional poison control center.

National survey of hospital-based pharmacokinetic services.

The status of pharmacokinetic services in the nation's hospitals was studied. A questionnaire was mailed in February 1995 to all 252 respondents to ASHP's 1994 national survey of hospital-based pharmaceutical services who indicated the provision of pharmacokinetic services in their institution. Ninety-eight completed questionnaires were returned (40.2% response rate). The pharmacokinetic services provided required an average of 19.1 person-hours per week, tended to be provided by staff pharmacists, were managed by the pharmacy department, tended to be most focused on aminoglycosides and vancomycin, required an average of 60 notes in patient charts per month, and relied on both computers and calculators for deriving values. There was little contact with patients during the consultation process. Drug concentration measurements tended to be scheduled by service providers, but confidence in the accuracy of the timing of dose administration and blood sampling was limited. Respondents believed that the services tended to be supported by other hospital personnel and that they were successful. There was very little expectation that the workload for providing pharmacokinetic services would increase in the near future. A national survey of hospital-based pharmacokinetic services showed that it took 19 hours per week on average to provide the services, that the focus was on aminoglycosides and vancomycin, and that the services were perceived to be supported by other departments.

Impact of clerkship students on pharmacy-site output.

The development of a theory-based method of estimating the impact of pharmacy clerkship students on clerkship sites is described. A job-analysis approach was used to estimate the impact of pharmacy clerkship activities on the clerkship sites. Two models--an employee model and a nonemployee model--of the student-preceptor relationship were used to evaluate clerkship student activities. Pairs of clerkship students and their preceptors were interviewed about student activities and supervision. Activities were assigned three-digit codes expressing (1) the level of preceptor supervision required, (2) the necessity of the activity to the functioning of the site, and (3) the complexity and amount of patient contact involved. The fit of each activity to the models was determined, and the impact of the clerkship students on a composite clerkship site was estimated. Twelve pairs of clerkship students and preceptors were interviewed. Degree of required supervision was the primary determinant in assigning an activity to a model. Student activities that fit the employee model were determined to have the greatest potential for having a positive or negative impact on the clerkship site. Performance of nonemployee-model activities could represent a net loss to the site because of the demand on preceptors' time. A method of categorizing and evaluating the value of specific student activities at pharmacy clerkship sites was useful in estimating student impact on the productivity of the site.

Meta-analysis of the use of low-dose beta-adrenergic blocking therapy in idiopathic or ischemic dilated cardiomyopathy.

We concluded that low-dose beta-adrenergic blocking agents are beneficial in the treatment of patients with ischemic or idiopathic cardiomyopathy. Low-dose beta blockers appear to improve NYHA functional class and LVEF.

Treatment of resistant atrial fibrillation. A meta-analysis comparing amiodarone and flecainide.

BACKGROUND: Chronic atrial fibrillation (AF) is a common arrhythmia with significant morbidity and mortality. Maintenance of normal sinus rhythm (NSR) can be achieved with antiarrhythmic drug therapy. The antiarrhythmic effects of amiodarone hydrochloride and flecainide acetate in patients with resistant chronic AF have been investigated separately in several small studies. This investigation compared amiodarone to flecainide in maintaining NSR in patients with resistant chronic AF. METHODS: Studies using amiodarone or flecainide in the treatment of patients with chronic AF refractory to class I antiarrhythmic drugs or sotalol hydrochloride were identified. The results of six trials of amiodarone (200 to 400 mg/d, 315 patients) and two trials of flecainide (200 to 300 mg/d, 163 patients) were aggregated using meta-analytic techniques. The percentages of patients taking amiodarone or flecainide and remaining in NSR at 3 and 12 months were compared relative to results for quinidine, which were acquired from a meta-analysis of quinidine used as first-line therapy for AF. RESULTS: After 3 and 12 months of treatment with amiodarone, 217 (72.6%) of 299 patients and 64 (59.8%) of 107 patients, respectively, remained in NSR. These percentages were significantly greater (P < .0001) than those for quinidine (70% and 50%, respectively). For flecainide, the percentage of patients remaining in NSR was significantly lower (P < .0001) than for quinidine: 79 (48.5%) and 56 (34%) of 163 patients, respectively. The aggregated percentages of patients requiring withdrawal of amiodarone and flecainide were similar: 9.5% and 8.6%, respectively. Mortality and proarrhythmia could not be assessed. CONCLUSION: This analysis suggests that low-dose amiodarone is more efficacious and equally well tolerated when compared with flecainide in the management of chronic, drug-resistant AF.

Medication management issues for adolescents with asthma.

Issues related to medication use by teens with asthma were studied. Adolescents 13-17 years old who were receiving drug therapy for asthma were recruited to participate in focus groups. Facilitators asked open-ended questions, and the discussion was recorded and coded for content. Participants were asked to complete questionnaires covering attitudes and beliefs, family issues, and communication with physicians and pharmacists. Of 28 teens participating in the focus groups, 26 returned completed questionnaires. The teens considered themselves compliant with medication therapy. They said they talked more to physicians than to pharmacists and received more oral and written information from the physicians. Focus group responses indicated that teens wanted complete responsibility for taking their medications and experienced conflict with adults--parents, teachers, school nurses, and physicians--about medication use. The teens were concerned about adverse effects and the cost of medications and wanted more information about asthma and its treatment. The teens did not disobey their parents or physicians by refusing to take their medications, and peers did not have a negative influence on the teens' asthma management. The primary medication issue for this group of adolescents was managing their medication to control their asthma in spite of inappropriate rules or behavior by adults.

Fluid delivery from infusion-pump syringes.

Fluid-delivery rates of five small-volume infusion-pump syringes were compared. The study consisted of a comparison of the infusion-pump syringes in their respective infusion pumps (1) set for continuous delivery at 1 mL/hr, (2) set for continuous delivery at 3 mL/hr, and (3) set to deliver 1-mL bolus volumes during continuous delivery at 4 mL/hr. The Life-care prefilled 30-mL syringe (Abbott), the DBL 30-mL syringe no. 770205 (DBL Inc.), and the Pump-Jet 30-mL syringe no. 1931 (International Medication Systems) were tested in the Lifecare PCA Plus II infusion pump no. 4100 (Abbott). The 30-mL Pump-Jet syringe no. 1911 (International Medication Systems) and the DBL 30-mL syringe no. 709700 (DBL Inc.) were tested in the Stratofuse PCA infusion pump (Baxter). The infusion pumps were set to deliver fluid continuously at 1 mL/hr for 30 hours, and the solutions were collected separately and weighed. The procedure was repeated with the infusion rate set at 3 mL/hr for 10 hours. For the third part of the study, each syringe was tested to deliver 1-mL boluses with 0, 5, 15, and 25 mL removed from the syringe. The solutions were collected and weighed before and after each bolus was delivered. The volume of solution collected was calculated by using the specific gravity of the solution. The syringes delivered significantly different volumes during the first hour of infusion at both the 1- and 3-mL/hr rates. Differences also existed across time for most of the syringes. Bolus volumes varied greatly after infusion of 0 or 5 mL of fluid but were acceptable for the remainder of the infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

The production model as a basis for conducting economic evaluations of regional poison control centers.

To identify the significant inputs, activities, and outputs of a regional poison control center, a production model is described and its potential application to the conduct of economic evaluations delineated. The model can help the researcher identify the significant inputs (costs) incurred through the provision of poison control center services. These inputs directly influence the activities that the poison center is capable of undertaking. Activities undertaken by a poison center are intermediate steps between the inputs and outputs, and serve to convert the various inputs into associated outputs. They form the basis for determining the outputs produced by the poison center services. The outputs derived from poison center services provide the conceptual framework for assessing the effectiveness of a poison center in an economic analysis. Also described are potential applications of the production model in conducting poison center cost-effectiveness and cost-benefit analyses.

Empiric long-term amiodarone prophylaxis following myocardial infarction. A meta-analysis.

BACKGROUND: The prophylactic administration of amiodarone following acute myocardial infarction has been investigated in several small trials. This study combined the results of these small trials in a meta-analysis to determine the effects of prophylactic low-dose amiodarone on mortality following acute myocardial infarction. METHODS: Four prospective, randomized, placebo-controlled trials, which investigated the prophylactic administration of low-dose amiodarone (200 to 400 mg/d) to patients after acute myocardial infarction, were selected from the current literature according to strict inclusion criteria. A total of 1140 patients, 566 in the amiodarone-treated group and 574 in the placebo-treated group, were included in the analysis. Sudden cardiac death, cardiac mortality, and total mortality were the end points of interest. In addition, the effect of impaired left ventricular function (ejection fraction, < 45%) on total mortality was assessed. Data were aggregated by using the Mantel-Haenszel method to obtain final summary statistics for these end points. RESULTS: Patients treated with low-dose amiodarone exhibited a lower incidence of sudden cardia death (3.1%) and total mortality (6.1%) when compared with patients treated with placebo (6.9% and 11.2%, respectively; both P < .01; and 95% confidence interval [CI], 0.011 to 0.065 and 0.013 to 0.082, respectively). There was no significant difference between the amiodarone- and placebo-treated groups with respect to cardiac mortality (2.6% vs 3.7%, respectively; P = .26; and 95% CI, -0.012 to 0.032). For patients with a left ventricular ejection fraction of less than 45%, total mortality was 5.5% in the amiodarone-treated group and 9.4% in the placebo-treated group (P = .30; CI, -0.023 to 0.101). CONCLUSIONS: Although further data from ongoing large, randomized trials are needed, this meta-analysis suggests that the prophylactic administration of low-dose amiodarone to patients following acute myocardial infarction reduces the incidence of both sudden cardiac death and total mortality. The benefits of low-dose amiodarone may be limited to patients with preserved left ventricular function.

Crossover design in pharmacy research.

OBJECTIVE: Reports of pharmacy research using crossover designs were reviewed to determine if the studies adequately consider interaction effects and use appropriate statistical analyses. DATA SOURCES: All crossover studies published in DICP, The Annals of Pharmacotherapy during 1988 and 1989 were analyzed. STUDY SELECTION: Reports of crossover studies were included only if at least two treatments were applied in a different order to two or more groups of subjects. DATA EXTRACTION: The principal characteristics of crossover studies and the critical design variables were listed and each study analyzed according to these variables. The critical design variables included consideration of period, sequence, and carryover effects as well as the presentation of data by groups and the use of multivariate statistical analysis. The analysis was conducted independently by each author and conflicts were discussed until consensus was obtained. RESULTS: A total of 11 crossover studies were identified: 6 were bioavailability trials, 3 were treatment comparisons, and 2 had multiple objectives. The possibility of period, sequence, or carryover effects was less with bioavailability studies than with treatment comparisons. Only 1 study presented data by group and only 4 studies used multivariate analysis. CONCLUSIONS: The crossover design appears more appropriate for bioavailability trials than for treatment trials in pharmacy research. Analysis of data from crossover designs could be improved by presenting the data for each treatment group and using multivariate statistical analysis.