Efficacy of sustained knowledge translation (KT) interventions in chronic disease management in older adults: Systematic review and meta-analysis of complex interventions

BACKGROUND: Chronic disease management (CDM) through sustained knowledge translation (KT) interventions ensures long-term, high-quality care. We assessed implementation of KT interventions for supporting CDM and their efficacy when sustained in older adults. METHODS: Design: Systematic review with meta-analysis engaging 17 knowledge users using integrated KT. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) including adults (\u3e 65 years old) with chronic disease(s), their caregivers, health and/or policy-decision makers receiving a KT intervention to carry out a CDM intervention for at least 12 months (versus other KT interventions or usual care). INFORMATION SOURCES: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from each database\u27s inception to March 2020. OUTCOME MEASURES: Sustainability, fidelity, adherence of KT interventions for CDM practice, quality of life (QOL) and quality of care (QOC). Data extraction, risk of bias (ROB) assessment: We screened, abstracted and appraised articles (Effective Practice and Organisation of Care ROB tool) independently and in duplicate. DATA SYNTHESIS: We performed both random-effects and fixed-effect meta-analyses and estimated mean differences (MDs) for continuous and odds ratios (ORs) for dichotomous data. RESULTS: We included 158 RCTs (973,074 participants [961,745 patients, 5540 caregivers, 5789 providers]) and 39 companion reports comprising 329 KT interventions, involving patients (43.2%), healthcare providers (20.7%) or both (10.9%). We identified 16 studies described as assessing sustainability in 8.1% interventions, 67 studies as assessing adherence in 35.6% interventions and 20 studies as assessing fidelity in 8.7% of the interventions. Most meta-analyses suggested that KT interventions improved QOL, but imprecisely (36 item Short-Form mental [SF-36 mental]: MD 1.11, 95% confidence interval [CI] [- 1.25, 3.47], 14 RCTs, 5876 participants, I CONCLUSIONS: KT intervention sustainability was infrequently defined and assessed. Sustained KT interventions have the potential to improve QOL and QOC in older adults with CDM. However, their overall efficacy remains uncertain and it varies by effect modifiers, including intervention type, chronic disease number, comorbidities, and participant age. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018084810

No role for initial severity on the efficacy of antidepressants: results of a multi-meta-analysis

Introduction: During the last decade, a number of meta-analyses questioned the clinically relevant efficacy of antidepressants. Part of the debate concerned the method used in each of these meta-analyses as well as the quality of the data set. Materials and methods: The Kirsch data set was analysed with a number of different methods, and eight key questions were tackled. We fit random effects models in both Bayesian and frequentist statistical frameworks using raw mean difference and standardised mean difference scales. We also compare between-study heterogeneity estimates and produce treatment rank probabilities for all antidepressants. The role of the initial severity is further examined using meta-regression methods. Results: The results suggest that antidepressants have a standardised effect size equal to 0.34 which is lower but comparable to the effect of antipsychotics in schizophrenia and acute mania. The raw HDRS difference from placebo is 2.82 with the value of 3 included in the confidence interval (2.21-3.44). No role of initial severity was found after partially controlling for the effect of structural (mathematical) coupling. Although data are not definite, even after controlling for baseline severity, there is a strong possibility that venlafaxine is superior to fluoxetine, with the other two agents positioned in the middle. The decrease in the difference between the agent and placebo in more recent studies in comparison to older ones is attributed to baseline severity alone. Discussion: The results reported here conclude the debate on the efficacy of antidepressants and suggest that antidepressants are clearly superior to placebo. They also suggest that baseline severity cannot be utilized to dictate whether the treatment should include medication or not. Suggestions like this, proposed by guidelines or institutions (e.g. the NICE), should be considered mistaken

Besieged : Malta 1565

The sixteenth century Mediterranean has often been described as ‘a battleground’ between the two great empires of Catholic Spain in the West and the Muslim Ottomans in the East. It was a century during which the two great empires gave evidence of their formidable might. Before the rise of the Habsburg kings, Charles V and Philip II, the Catholic Kings of Spain, Ferdinand and Isabella, who were responsible for the unification of Spain, played as vital a part in creating the Spanish Empire as did the Ottoman sultans before the fall of Constantinople in 1453.peer-reviewe

Prevalence, impact and treatment of generalised anxiety disorder in bipolar disorder : A systematic review and meta-analysis

Publisher Copyright: © 2016, BMJ Publishing Group. All rights reserved.Question Recent data suggest that anxiety disorders are as often comorbid with bipolar disorder (BD) as with unipolar depression; however, less attention has been paid to comorbidity of anxiety disorders with BD. Generalised anxiety disorder (GAD) is one of the most prevalent anxiety disorders that is highly comorbid with other mental disorders. We carried out a systematic review and meta-analysis to assess the degree of comorbidity between GAD and BD. Study selection and analysis We searched for all studies, which included primary data concerning the existence of GAD in patients with BD. The literature search strategy, selection of publications and the reporting of results have been conducted with PRISMA guidelines. The meta-analysis calculated prevalence estimates using the variance-stabilising Freeman-Tukey double arcsine transformation. We applied the inverse variance method using both fixed-effects and random-effects models to estimate summary effects for all combined studies. Heterogeneity was assessed and measured with Cochran’s Q and I2 statistics, respectively. Findings The current meta-analysis analysed data from 28 independent studies and a total of 2975 patients from point prevalence studies and 4919 patients from lifetime studies. The overall random-effects point prevalence of GAD in patients with BD was 12.2% (95% CI 10.9% to 13.5%) and the overall random-effects lifetime estimate was 15.1% (95% CI 9.7% to 21.5%). Both estimates reported significant heterogeneity (94.0% and 94.7%, respectively). Conclusions Published studies report prevalence rates with high heterogeneity and consistently higher than those typically reported in the general population. It is believed that comorbid GAD might be associated with a more severe BD course and increased suicidality, and it is unknown how best to treat such conditions. The current meta-analysis confirms that GAD is highly prevalent in BD and the rate is higher in comparison to those in the general population.publishersversionPeer reviewe

Two new approaches for the visualisation of models for network meta-analysis

Abstract Background Meta-analysis is a useful tool for combining evidence from multiple studies to estimate a pooled treatment effect. An extension of meta-analysis, network meta-analysis, is becoming more commonly used as a way to simultaneously compare multiple treatments in a single analysis. Despite the variety of approaches available for presenting fitted models, ascertaining an intuitive understanding of these models is often difficult. This is especially challenging in large networks with many different treatments. Here we propose two visualisation methods, so that network meta-analysis models can be more easily interpreted. Methods Our methods can be used irrespective of the statistical model or the estimation method used and are grounded in network analysis. We define three types of distance measures between the treatments that contribute to the network. These three distance measures are based on 1) the estimated treatment effects, 2) their standard errors and 3) the corresponding p-values. Then, by using a suitable threshold, we categorise some treatment pairs as being “close” (short distances). Treatments that are close are regarded as “connected” in the network analysis theory. Finally, we group the treatments into communities using standard methods for network analysis. We are then able to identify which parts of the network are estimated to have similar (or different) treatment efficacy and which parts of the network are better identified. We also propose a second method using parametric bootstrapping, where a heat map is used in the visualisation. We use the software R and provide the code used. Results We illustrate our new methods using a challenging dataset containing 22 treatments, and a previously fitted model for this data. Two communities of treatments that appear to have similar efficacy are identified. Furthermore using our methods we can identify parts of the network that are better (and less well) identified. Conclusions Our new visualisation approaches may be used by network meta-analysts to gain an intuitive understanding of the implications of their fitted models. Our visualisation methods may be used informally, to identify the most salient features of the fitted models that can then be reported, or more formally by presenting the new visualisation devices within published reports

Dexamethasone versus betamethasone for preterm birth: a systematic review and network meta-analysis

Objective: This study aimed to evaluate the comparative clinical effectiveness and safety of dexamethasone vs betamethasone for preterm birth. Data Sources: The sources searched were MEDLINE, EMBASE, Cochrane Library, LILACS, ClinicalTrials.gov, and International Clinical Trials Registry Platform without language restrictions until October 2019 in addition to the reference lists of included studies. Field experts were also contacted. Study Eligibility Criteria: Randomized or quasi-randomized controlled trials comparing any corticosteroids against each other or against placebo at any dose for preterm birth were included in the study. Methods: Three researchers independently selected and extracted data and assessed the risk of bias of the included studies by using Early Review Organizing Software and Covidence software. Random-effects pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcomes were chorioamnionitis, endometritis or puerperal sepsis, neonatal death, respiratory distress syndrome, and neurodevelopmental disability. Results: A total of 45 trials (11,227 women and 11,878 infants) were included in the study. No clinical or statistical difference was found between dexamethasone and betamethasone in neonatal death (odds ratio, 1.05; 95% confidence interval, 0.62–1.84; moderate-certainty evidence), neurodevelopmental disability (odds ratio, 1.03; 95% confidence interval, 0.80–1.33; moderate-certainty evidence), intraventricular hemorrhage (odds ratio, 1.04; 95% confidence interval, 0.56–1.78); low-certainty evidence), or birthweight (+5.29 g; 95% confidence interval, −49.79 to 58.97; high-certainty evidence). There was no statistically significant difference, but a potentially clinically important effect was found between dexamethasone and betamethasone in chorioamnionitis (odds ratio, 0.70; 95% confidence interval, 0.45–1.06; moderate-certainty evidence), fetal death (odds ratio, 0.81; 95% confidence interval, 0.24–2.41; low-certainty evidence), puerperal sepsis (odds ratio, 2.04; 95% confidence interval, 0.72–6.06; low-certainty evidence), and respiratory distress syndrome (odds ratio, 1.34; 95% confidence interval, 0.96–2.11; moderate-certainty evidence). Meta-regression, subgroup, and sensitivity analyses did not reveal important changes regarding the main analysis. Conclusion: Corticosteroids have proven effective for most neonatal and child-relevant outcomes compared with placebo or no treatment for women at risk of preterm birth. No important difference was found on neonatal death, neurodevelopmental disability, intraventricular hemorrhage, and birthweight between corticosteroids, and there was no statistically significant difference, but a potentially important difference was found in chorioamnionitis, fetal death, endometritis or puerperal sepsis, and respiratory distress syndrome. Further research is warranted to improve the certainty of evidence and inform health policies.Fil: Ciapponi, Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Klein, Karen. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Colaci, Daniela. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Organizacion Mundial de la Salud; ArgentinaFil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Deegan, Allie. University of New York; Estados UnidosFil: Veroniki, Areti Angeliki. University of Ioannina; Grecia. St. Michael’s Hospital. Li Ka Shing Knowledge Institute; CanadáFil: Florez, Ivan D.. Universidad de Antioquia; Colombia. Mc Master University; Canad