Efficacy and safety of aripiprazole in the acute treatment of schizophrenia in Chinese patients with risperidone as an active control: a randomized trial. Cost-effectiveness of olanzapine vs. aripiprazole in the treatment of schizophrenia. Staged diabetes management. Toward an integrated model of diabetes care. Appraising the evidence: applying sex- and gender-based analysis (SGBA) to Cochrane systematic reviews on cardiovascular diseases. Inhaled zanamivir versus rimantadine for the control of influenza in a highly vaccinated long-term care population. Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics. Recursive cumulative meta-analysis: a diagnostic for the evolution of total randomized evidence from group and individual patient data. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study.
Asian populations may differ from other races in response to antipsychotics. Studies of aripiprazole in Asian populations are scarce. This study aimed to investigate the efficacy, safety, and tolerability of aripiprazole in Chinese patients with acute schizophrenia or schizoaffective disorder.
                This 4-week, double-blind, randomized, parallel study was conducted in 5 medical centers in Taiwan between March 2004 and January 2005. A total of 83 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomly assigned (with a randomization ratio of 3:2) to 15 mg/day of aripiprazole (N = 49) or 6 mg/day of risperidone (N = 34). Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores and Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement scale scores. Extrapyramidal symptoms (EPS), weight gain, serum prolactin level, QTc interval, and self-reported adverse events were assessed as measures of safety and tolerability.
                Both the aripiprazole and risperidone groups showed statistical improvement from baseline in PANSS total, PANSS positive, PANSS negative, and CGI-S scores at study endpoint (all p < .001). Significant improvement was noted in the first week of treatment for both treatment groups. There were no significant differences in efficacy measures between treatment groups. Aripiprazole showed significantly less EPS liability as assessed by the Simpson-Angus Scale (p < .005) and less serum prolactin level elevation (p < .001) than risperidone. Both groups showed mild weight gain. No patients showed clinically significant QTc interval prolongation in this study.
                Compared with risperidone 6 mg/day, aripiprazole 15 mg/day has comparable efficacy and favorable safety and tolerability profiles in the short-term treatment of Chinese patients with acute schizophrenia. In this group of Chinese patients, the overall response to aripiprazole did not differ from that of white patients.
                ClinicalTrials.gov identifier NCT00283179. Information about the cost-effectiveness of aripiprazole relative to other atypical antipsychotics in the treatment of patients with schizophrenia is limited. This information is needed to better inform drug formulary managers and population-based health care decision makers. The objective of this study was to compare the cost-effectiveness of olanzapine to aripiprazole in the treatment of schizophrenia from the perspective of public payers in the United States.
                Data for this post-hoc analysis came from a 28-week double-blind, randomized trial of individuals with schizophrenia who were treated with olanzapine or aripiprazole (clinicaltrial.gov identifier NCT00088049). Two-thirds (67.7%) of the patients were male and the patients' mean age was 37.6 years. Utilities were calculated based on previously published methods using the Positive and Negative Syndrome Scale (PANSS) and treatment-emergent adverse events. Treatment costs were calculated based on previously published methods and were inflated to 2008 US dollars. A mixed model was used to compare outcomes on utilities. Propensity score-adjusted analysis of covariance was used for the cost analysis.
                Olanzapine treatment was associated with statistically significantly greater total utility scores relative to aripiprazole (0.78 vs. 0.76; p = 0.024) and lower total treatment costs ($22,831 vs. $24,749; p = 0.013), although medication acquisition cost was significantly higher for olanzapine than aripiprazole ($3524 vs. $2637; p < 0.001). An incremental cost-effectiveness ratio was not calculated because olanzapine was found to be the dominant choice (i.e., greater effectiveness and lower total costs).
                This cost-effectiveness analysis is the first to use patient-level data from a randomized, double-blind study comparing olanzapine and aripiprazole in the treatment of patients with schizophrenia. Olanzapine was found to be a dominant cost-effective choice, as it was associated with greater effectiveness at lower total costs relative to aripiprazole. This paper introduces a new and innovative approach to diabetes management in the primary-care setting. Staged diabetes management (SDM) represents a four-year effort to develop and test a data-based approach to diabetes management that could be easily adapted to a variety of health-care settings in which diabetes management is principally under the direction of primary-care physicians was limited access to specialists. After testing under controlled circumstances at the International Diabetes Center (Minneapolis, MN), SDM was subjected to substantial field trials under conditions that represent the scope and variety of primary-care practices in diabetes. The following represents the work of several investigators who independently undertook a review of SDM. To examine the use of sex- and gender-based analysis (SGBA) in systematic reviews of cardiovascular health in order to strengthen the evidence base for clinical practice and policy.
                To determine the current status of SGBA in systematic reviews, an appraisal tool was developed by the research team and applied by an independent reviewer to a random sample of 38 Cochrane systematic reviews. The sample was drawn from reviews addressing interventions for cardiovascular diseases (CVD). A random sample of Cochrane reviews in cardiovascular health was selected from the Cochrane Library, Issue 3, 2001, to Issue 3, 2007. The main outcome measure was the number of reviews that included analysis of sex or gender or both.
                Our findings showed that SGBA was generally absent in the sampled reviews. Data were rarely disaggregated by sex; only 2 of 38 reviews reported any sex or gender research gaps. Only one quarter of the reviews included a rationale as to why any subgroup analyses by sex were or were not completed. None of the 38 reviews met all of the appraisal tool criteria. As well, we found that where sex or gender was mentioned, the terms were used interchangeably.
                Despite increasing evidence over the past decade documenting that sex and gender frequently matter in CVD, this study demonstrated that SGBA was rarely considered in systematic reviews. We suggest this omission has important implications for assuring the quality of research and of evidence-based policy and practice and for achieving equitable health outcomes for women and men. To build a robust evidence base for future work in cardiovascular health, we propose that the methodologies of systematic reviews and of SGBA be refined and synchronized to enhance the collection, synthesis, and analysis of evidence for decision making. Despite vaccination, influenza commonly causes morbidity and mortality in institutional settings. Influenza control with rimantadine and amantadine is limited by emergence and transmission of drug-resistant influenza A variants, ineffectiveness against influenza B, and toxicity. This study evaluated the efficacy and tolerability of zanamivir versus rimantadine for influenza outbreak control in long-term care facilities.
                This double-blind, randomized, controlled study prospectively enrolled nursing home residents for 3 influenza seasons (1997 to 2000). Vaccine was offered to all subjects. Following influenza outbreak declaration, subjects were randomized to inhaled zanamivir 10 mg or standard of care (rimantadine 100 mg for influenza A or placebo for influenza B) once daily for 14 days. The proportion of randomized subjects developing symptomatic, laboratory-confirmed influenza during prophylaxis was the primary endpoint.
                Of 482 randomizations (238 zanamivir, 231 rimantadine, 13 placebo), 96% of subjects were elderly or had high-risk conditions; over 90% were vaccinated. Symptomatic, laboratory-confirmed influenza occurred in 3% of zanamivir subjects and 8% of rimantadine subjects during chemoprophylaxis (P = .038; additional protective efficacy for zanamivir over rimantadine = 61%). Since only 25 subjects were randomized during 2 influenza B outbreaks and none developed influenza, the influenza B data were excluded from further analysis. Zanamivir was well tolerated and unassociated with emergence of resistant virus; rimantadine-resistant variants were common.
                This is the first prospective, controlled study demonstrating effectiveness of chemoprophylaxis for influenza outbreak control. Zanamivir prevents symptomatic, laboratory-confirmed influenza more effectively than rimantadine, is unassociated with resistant virus, and has a favorable safety profile. Zanamivir is an appropriate alternative for influenza outbreak control among institutionalized vaccinated elderly. In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome.
                The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug.
                Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings.
                Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies. Meta-analyses of randomized evidence may include published, unpublished, and updated data in an ongoing estimation process that continuously accommodates more data. Synthesis may be performed either with group data or with meta-analysis of individual patient data (MIPD). Although MIPD with updated data is considered the gold standard of evidence, there is a need for a careful study of the impact different sources of data have on a meta-analysis and of the change in the treatment effect estimates over sequential information steps. Unpublished data and late-appearing data may be different from early-appearing data. Updated information after the end of the main study follow-up may be affected by cross-overs, missing information, and unblinding. The estimated treatment effect may thus depend on the completeness and updating of the available evidence. To address these issues, we present recursive cumulative meta-analysis (RCM) as an extension of cumulative metaanalysis. Recursive cumulative meta-analysis is based on the principle of recalculating the results of a cumulative meta-analysis with each new or updated piece of information and focuses on the evolution of the treatment effect as a more complete and updated picture of the evidence becomes available. An examination of the perturbations of the cumulative treatment effect over sequential information steps may signal the presence of bias or heterogeneity in a meta-analysis. Recursive cumulative meta-analysis may suggest whether there is a true underlying treatment effect to which the meta-analysis is converging and how treatment effects are sequentially altered by new or modified evidence. The method is illustrated with an example from the conduct of an MIPD on acyclovir in human immunodeficiency virus infection. The relative strengths and limitations of both metaanalysis of group data and MIPD are discussed through the RCM perspective. Switching patients from one antipsychotic to another can lead to tolerability problems or transient symptom exacerbations. It is important to compare switching strategies to determine which methods produce the best possible patient outcomes.
                To investigate the efficacy, safety and tolerability of three dosing strategies for switching chronic, stable patients with schizophrenia from current oral antipsychotic monotherapy to once-daily oral aripiprazole monotherapy.
                Patients in this 8-week, open-label, outpatient study were randomized to: 1). immediate initiation of 30 mg/day aripiprazole with simultaneous immediate discontinuation of current antipsychotic; 2). immediate initiation of 30 mg/day aripiprazole while tapering off current antipsychotic over 2 weeks; or 3). up-titrating aripiprazole to 30 mg/day over 2 weeks, while simultaneously tapering off current antipsychotic. Efficacy assessments included PANSS, CGI-S, and CGI-I scores. Safety assessments included: adverse events (AEs) recording, evaluation of extrapyramidal symptoms (EPS), vital signs, ECG, and clinical laboratory tests.
                Efficacy with aripiprazole was maintained during the study with numerical improvements compared with baseline in all three groups. The overall incidence of AEs was broadly comparable across all groups, and AEs were generally mild to moderate in severity and time-limited. Discontinuations due to AEs were comparable across the groups. No deterioration in EPS occurred in any group. The reduction in body weight and plasma prolactin levels following switch to aripiprazole were comparable across the three groups.
                Any of the three strategies evaluated can be used safely for switching patients to aripiprazole from antipsychotic monotherapy. Furthermore, patients' symptoms may continue to improve after switching to aripiprazole.
Information on all comparisons are of limited quality, are incomplete and problematic to apply clinically. Aripiprazole is an antipsychotic drug with a variant but not absent adverse effect profile. Long-term data are sparse and there is considerable scope for another update of this review as new data emerges from the many Chinese studies as well as from ongoing larger, independent pragmatic trials.