Agency for Healthcare Research and Quality.

BACKGROUND: Sexual dysfunction (SD) is prevalent in patients with major depressive disorder (MDD) and is also associated with second-generation antidepressants (SGAD) which are commonly used to treat the condition. Evidence indicates underreporting of SD in efficacy studies. SD associated with antidepressant treatment is a serious side effect that may lead to early termination of treatment and worsening of quality of life. OBJECTIVES: To systematically assess the harms of SD associated with SGAD in adult patients with MDD by drug type. METHODS: We retrieved English-language abstracts from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012 as well as from reference lists of pertinent review articles and grey literature searches. Two independent reviewers identified randomized controlled trials (RCTs) of at least six weeks' duration and observational studies with at least 1,000 participants. STUDY SELECTION: Reviewers abstracted data on study design, conduct, participants, interventions, outcomes and method of SD ascertainment, and rated risk of bias. A senior reviewer checked and confirmed extracted data and risk of bias ratings. ANALYSES: Random effects network meta-analysis using Bayesian methods for data from head-to-head trials and placebo-controlled comparisons; descriptive analyses calculating weighted mean rates from individual trials and observational studies. RESULTS/ SYNTHESIS: Data from sixty-three studies of low and moderate risk of bias (58 RCTs, five observational studies) with more than 26,000 patients treated with SGAD were included. Based on network meta-analyses of 66 pairwise comparisons from 37 RCTs, most comparisons showed a similar risk of sexual dysfunction among included SGAD. Credible intervals, however, were wide and included differences that would be considered clinically relevant. We observed three main patterns: Bupropion had a statistically significantly lower risk of sexual dysfunction than some other SGAD, and both escitalopram, and paroxetine showed a statistically significantly higher risk of sexual dysfunction than some other SGAD. We found reporting of harms related to sexual dysfunction inconsistent and insufficient in some trials. LIMITATIONS: Most trials were conducted in highly selected populations. Search was restricted to English-language only. CONCLUSION AND IMPLICATIONS: Because of the indirect nature of the comparisons, the often wide credible intervals, and the high variation in magnitude of 2 outcome, we rated the overall strength of evidence with respect to our findings low. The current degree of evidence does not allow a precise estimate of comparative risk of sexual dysfunction associated with a specific antidepressant. In the absence of such evidence, clinicians need to be aware of SD as a common adverse event and should discuss patients' preferences before initiating antidepressant therapy.

1 Structured Abstract:Purpose: We aimed to systematically review published empirical research on leadership as a determinant for the implementation of evidence-based practice (EBP) and to investigate leadership conceptualization and operationalization in this field. Design/methodology/approach: A systematic review with narrative synthesis was conducted. Relevant bibliographic databases and reference lists of pertinent review articles were searched. To be included, a study had to involve empirical research and refer to both leadership and EBP in health care. Study quality was assessed with a structured instrument based on study design. Findings: A total of 17 studies were included. Leadership was mostly viewed as a modifier for implementation success, acting through leadership support. Yet, there was definitional imprecision as well as conceptual inconsistency and studies seemed to inadequately address situational and contextual factors. Although referring to an organizational factor, the concept was mostly analysed at the individual or group level. Research limitations/implications:The concept of leadership in implementation science seems to be not fully developed. It is unclear whether attempts to tap the concept of leadership in available instruments truly capture and measure the full range of the diverse leadership elements at various levels. Research in implementation science would benefit from a better integration of research findings from other disciplinary fields. Once a more mature concept has been established, researchers in implementation science could proceed to further elaborate operationalization and measurement. Originality/value Although the relevance of leadership in implementation science has been acknowledged, the conceptual base of leadership in this field has received only limited attention. KeywordsLeadership, Conceptualization, Measurement, Evidence-based practice, Systematic review 2 BackgroundDespite widespread acceptance of the importance of implementing evidence-based practice (EBP) and the use of findings from scientific research in clinical practice, many patients still do not receive treatments with proven effectiveness or may receive care that is of little benefit or harmful (Dopson et al., 2002, Greenhalgh et al., 2004, Oxman et al., 1995. Implementation science has emerged as a vital interdisciplinary research field to address the challenges associated with the gap identified between the production and use of evidence in various settings. Explanations for this gap have largely focused on the characteristics of the individual provider, such as limited access to research, poor confidence in identifying and critically appraising evidence and perceived time restrictions to integrate research into clinical practice (Rycroft-Malone, 2008, Estabrooks et al., 2003, Squires et al., 2011.However, within the field of implementation science, there has been increasing recognition of the role of the organizational context in the implementation of EBP (Durlak and DuPre, 2008, Greenhalgh et al.,...

Available evidence currently shows no clear differences between the two formulations and therefore we cannot recommend a first choice. However, if adherence or compliance with one medication is an issue, then clinicians and patients should consider the alternative medication. If adherence or costs are a problem with one formulation, consideration of the other formulation to provide an adequate treatment trial is reasonable.