The movement towards the provision of evidence-based services has become increasingly important to psychological practice (CPA Task Force on Evidence-Based Practice of Psychological Treatments, 2012; Levant, 2005). One of the key components of this movement is the summarizing and dissemination of important findings to key stakeholders for interventions using techniques such as meta-analysis. Meta-analyses are typically based on reviews of the published literature on a particular topic, but increasingly researchers are acknowledging the importance of examining and including unpublished, grey literature in their reviews in presenting an accurate picture of a body of literature (Hopewell, McDonald, Clarke, & Egger, 2008; McAuley, Pham, Tugwell, & Moher, 2000). However, the inclusion of grey literature in meta-analyses and reviews remains controversial (Coad, Hardicre, & Devitt, 2006; Martin, Perez, Sacristan, & Alvarez, 2005; Seymour, 2010). A number of reviews of behavioural parenting interventions have been conducted. The body of literature in this area continues to grow quickly, and recent meta-analyses in this area have examined only subsets of the literature, thus necessitating an overall examination of all available literature in this area: published and unpublished. The present meta-analysis synthesized the results of 42 published and 6 unpublished behavioural parenting intervention studies conducted between 1966 and 2011. In the first manuscript, treatment efficacy was examined with respect to three different outcomes (parent behaviour, child behaviour, and parent adjustment). I also examined the differential effects of six moderator variables in two categories: child characteristics (child formal diagnostic status and child age) and methodological characteristics (overall quality, comparison group, experimenter allegiance, and publication status). In the second manuscript, I examined both the advantages and challenges of including grey literature in meta-analyses, and explored the use of an innovative search program. I also explored the influence of the inclusion of grey literature on outcomes, including whether effect sizes, sample homogeneity, and publication bias indices are affected by the inclusion of grey literature. Results of the present study confirm the efficacy of behavioural parenting interventions on parent behaviour, child behaviour, and parent adjustment outcomes. Further, I extend the knowledge base through the inclusion of recent reports, grey literature, searches of basic search engines such as Google and Yahoo, and the examination of previously unexplored moderator variables. My results underline the importance of consistent reporting practices in the field and their impact on the availability of evidence for policy-makers, administrators, researchers, clinicians and consumers. I also discuss the implications of these findings for the provision of evidence-based services for parents, knowledge translation, and grey literature.

Class of 2008 Abstract / Objectives: 1) To determine if data on weight change in the placebo arm of RCT's for weight loss were available, and 2) to conduct a pilot meta-analysis to estimate the average weight change in the placebo arm. Methods: Four randomized placebo controlled trials of rimonabant for weight loss were retrieved. A draft data extraction form was developed to record weight loss and demographic data. Potential for bias was assessed on design issues related to withdrawals, blinding, allocation procedure, adherence, and manufacturer influence. Based on available data, a forest plot was constructed and heterogeneity was assessed. The a priori alpha level was 0.05. Results: The placebo groups from all studies were similar. The pooled data indicated that individuals in the placebo arm lost an average of 3.3 kg, p < 0.001. One study had a significantly greater completion rate than the other studies. Participants were prescribed a hypocaloric diet and were instructed to increase physical activity but no data were reported on calories consumed or amount of physical activity. Weight loss of 5% ranged from 15-20% of participants. There was potential for bias relating to reported adherence, allocation concealment process, and manufacturer funding. Conclusions: Participants in the placebo arm of rimonabant trials lost an average of 3.3 kg, which was statistically significant. Little can be learned about weight loss in the placebo arm because no data on calories consumed, amount of exercise, or hunger were reported. Information from other RCT's is needed to provide additional data and to confirm the findings.

Randomised trials of complex interventions are typically designed, conducted, and analysed as if they are drug trials. Although there are many parallels there are also a number of important distinctions, which are seldom considered when designing individual trials. One of these concerns the involvement of therapists in delivering psychotherapy. Systematic reviews and meta-analyses provide an opportunity for exploring the full range and complexity of issues encountered in realistically complex situations. The first objective of the thesis was therefore to develop a conceptual framework for understanding the role of the therapist in trial designs. It was addressed by a review of the psychotherapy and statistical literatures structured according to the broad concepts of precision, internal and external validity and refined on the basis of a systematic methodological review of Cochrane reviews meta-analysing trials involving psychotherapy. The second objective was then to review, adapt, illustrate and compare methods for meta-analysing psychotherapy trials with nested designs. Methods for meta-analysing ICC estimates, absolute and standardised mean differences were adapted to allow for heteroscedasticity between treatments at the therapist- and patient- levels. These were illustrated using the example of counselling in primary care, with comparisons being made between aggregate and one-step approaches to the meta-analysis of individual-patient-data.It was argued that the therapist has two roles in randomised trials. Firstly, they are one component of a multi-component intervention, and are thus a potential treatment variable. Second, the nesting of patients within therapists creates an additional level in the design, so the therapist is also an experimental unit. The inability to conceal or randomise allocations leads to observational components within the trial design and to heteroscedasticity which deserves more attention. Characterising complex interventions, like psychotherapy, with more than one treatment variable could facilitate greater understanding of their components, how they interact, which are important, to what extent, and for whom. It also brings what is currently referred to as process research into the remit of trials, enabling a more complete evaluation of the causal effects. The broad concept of multiple experimental units makes cluster-randomised, longitudinal, multi-centre, crossover, therapist- and group-based intervention trials special cases of a more general class of multilevel trial. All involve clustering effects; their nature and the appropriate statistical model varying according to the design. Methods were proposed for the meta-analysis of continuous outcome data for two-level nested designs. A general approach was adopted, where possible, to incorporate methods covering cluster-randomised trials and the Behrens-Fisher problem. It was clear that this is a relatively untouched methodological area in need of further exploration. For the same reasons as it became necessary to summarise clinical research, it is recommended that systematic methodological reviews be carried out on a larger scale in future.

Organizational development and change (ODC) is a broad field because change occurs in all organizations, occurs at multiple organizational levels, consists of numerous interventions, and can impact multiple outcomes. Many ODC efforts attempt to examine the effectiveness of their initiatives, yet fail to account for the quality, or rigor of their methods. The purpose of this paper is to examine how methodological rigor and intervention implementation quality impact ODC outcomes. The results indicate that overall methodological rigor is not a significant predictor of organizational change outcomes; however, several individual rigor criteria exhibit predictive power. Implementation quality is a significant predictor of organizational outcomes, but in a negative direction.

The present meta-analytic study estimated the overall effectiveness of child therapy interventions using CCPT methodology and explored the relationships between study characteristics and treatment effects. Fifty-two studies between 1995 and the present were included based on the following criteria: (a) the use of CCPT methodology, (b) the use of control or comparison repeated measure design, (c) the use of standardized psychometric assessment, and (d) clear reports of effect sizes or sufficient information for effect size calculation. Hierarchical linear modeling (HLM) techniques were utilized to estimate the overall effect size for the collected studies and explore relationships between effect sizes and study characteristics. Dependent variable included 239 effect sizes, and independent variables included 22 study characteristics. The mean age of all child participants in the collected studies was 6.7. In 15 studies, the majority of participants were Caucasian. An equal number of studies were made up of non-Caucasian participants, including 3 with majority African American, 4 with majority Hispanic/Latino participants, 5 with majority Asian/Asian American participants, and 3 with other ethnic populations. Study collection included 33 studies with majority of boys and 11 studies with majority of girls. HLM analysis estimated a statistically significant overall effect size of 0.47 for the collected studies (p < 0.001). This result indicated that the overall improvement from pre to post treatment demonstrated by children in experimental groups was approximately 1/2 standard deviation better than by children in control groups. A statistically significant amount (49.2%) of between-study variance was found (p < 0.001), indicating the heterogeneity among the 52 studies Statistically significant relationships were found between effect sizes and study characteristics including child age, child ethnicity, clinical level of referral, treatment integrity, presenting issue, source of data, population, and caregiver involvement. Effect size findings for CCPT and its moderators should be interpreted in light of the specific, and perhaps more rigorous statistical analysis method (HLM) and effect size calculation formula used for the present study, particularly in comparison to previous meta-analytic findings. Overall findings support CCPT's beneficial treatment effect. Specifically, CCPT can be considered a developmentally and culturally responsive effective mental health intervention across presenting issues.

Orientadores: Andre Deeke Sasse, Carmen Silvia Passos Lima / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T13:13:47Z (GMT). No. of bitstreams: 1 Duarte_IgorLemos_M.pdf: 729678 bytes, checksum: 3da7b8934fdc3f3c7776ad13bc0dbd2b (MD5) Previous issue date: 2015 / Resumo: Pacientes com câncer de mama localmente avançado são de alto risco para recidiva após ressecção cirúrgica com intuito curativo. Muitos estudos têm sido realizados na tentativa de se descobrir alguma intervenção adjuvante capaz de reduzir este risco. No entanto, há, na literatura atual, controvérsias no que tange a melhor estratégia terapêutica neste cenário. Discordância entre intensidade de dose e densidade de dose ainda permeiam o tema. O objetivo desta revisão sistemática foi avaliar o exato papel da quimioterapia em dose densa nas pacientes portadoras de câncer de mama local. Foram comparados os efeitos da quimioterapia em dose densa com quimioterapia convencional em pacientes com câncer de mama localizado ou loco-regionalmente avançado. Os desfechos clínicos avaliados foram sobrevida global (SG), sobrevida livre de doença (SLD) e toxicidades severas. A análise dos dados extraídos foi realizada no programa estatístico Review Manager 5.0 (RevMan 5; Cochrane Collaboration Software). As diferentes estratégias de tratamento adjuvante foram avaliadas em conjunto e separadamente. Quatro estudos (3418 pacientes) foram incluídos. A metanálise demonstrou que quimioterapia em dose densa pode melhorar a sobrevida livre de doença (3356 pacientes; HR 0,83; 95% IC 0,73-0,95; p 0,0005), independente do status de expressão hormonal. Não houve benefício em sobrevida global (3356 pacientes, HR 0,86; IC 95% 0,73-1,01; p 0,006), independente do status de receptor hormonal (SG no subgrupo hormônio positivo HR 0,94; 95% IC 0,74-1,21; SG no subgrupo hormônio negativo HR 0,78; IC 95% 0,62-0,99; p 0,28). Regimes em dose densa causaram pequeno aumento em mucosite, porem sem impacto em eventos cardíacos, leucemia ou mielodisplasia. Em conclusão, a quimioterapia adjuvante em dose densa pode melhora sobrevida livre de doença em pacientes com câncer de mama localizado com pouco impacto na segurança. Entretanto não há claro benefício em sobrevida global. Novas pesquisas podem indicar se há algum impacto em sobrevida global, não verificada atualmente em função do tamanho da amostra, e possivelmente qual grupo de pacientes teria maior benefício / Abstract: Patients with locally advanced breast cancer are at high risk for recurrence after surgical resection with curative intent. Many studies have been conducted in an attempt to discover some adjuvant intervention can reduce this risk. However, there is, in the current literature, controversies regarding the best therapeutic strategy in this scenario. Disagreement between dose intensity and dose density still permeate the theme. The aim of this systematic review was to assess the exact role of dose dense chemotherapy in patients with local breast cancer. The effects of dose dense chemotherapy with conventional chemotherapy in patients with localized breast cancer or loco-regionally advanced were compared. The clinical endpoints were overall survival (OS), disease-free survival (DFS) and severe toxicities. The extracted data was performed in Review Manager 5.0 (RevMan 5, Cochrane Collaboration Software) statistical program. The different strategies of adjuvant treatment were evaluated together and separately. Four studies (3418 patients) were included. The meta-analysis showed that dose dense chemotherapy in improvements can free survival (3356 patients, HR 0,83, 95% CI 0,73 to 0,95, p 0,0005), regardless of the status of hormone expression. There was no benefit in overall survival with chemotherapy dose dense (3356 patients, HR 0,86, 95% CI 0,73 ? 1:01, p 0,006), independent of hormone receptor status d (SG subgroup hormone positive HR 0,94, 95% CI 0,74 ? 1:21, SG in the subgroup negative hormone HR 0,78, 95% CI 0,62 ? 0.99, p 0:28). Regimes in dense dose caused small increase in mucositis, however no impact on cardiac events, leukemia or myelodysplasia. DD adjuvant chemotherapy may improve disease-free survival in patients with early breast cancer with little impact on safety. However there is no clear benefit in overall survival. New research may indicate whether there is any impact on overall survival, not currently seen as a function of sample size, and that group of patients will benefit most / Mestrado / Clinica Medica / Mestre em Clinica Medica

Recent advances in global gene expression measurement and the development of large- scale public repositories for storage of such data have made a wealth of information available to researchers. While one gene expression study may lack sufficient replicates to make statistically significant pronouncements, the combination of studies through meta-analysis can yield results with a much greater likelihood of accuracy. In order to combine multiple sets of data, one must first address the issue of cross-comparison between global gene expression platforms, as well as resolve the issue of repeated measures (multiple probes representing the same gene) within each platform. In this work, I present computational methods for probe reannotation and scoring and for redundant probe consolidation that together allow for greatly improved access to data for meta-analysis. I also present an example of the application of these methods, in the analysis of the gene expression regulated by estrogen across multiple cell types. Estrogen, a steroid hormone, interacts with its receptors to regulate gene transcription in both direct and indirect manners. Estrogen has the effect of increasing proliferation in some tissues, while inhibiting proliferation or increasing apoptosis in others. How estrogen achieves these highly divergent results remains unclear. Through meta-analysis of gene expression experiments across multiple cell types, I show that patterns of estrogen regulation in many tissues involve the same key genes and pathways, including cell cycle, p53 signaling, and TGF&beta; signaling pathways. However, regulation in different cell types can result from regulation of different genes, or the same genes regulated in different directions. Many patterns of gene regulation support known physiological consequences of estrogen on these tissues. In particular, genes promoting proliferation are upregulated in uterus and certain breast and ovarian cancer cell lines. One gene, thrombospondin-1, is up-regulated in eleven out of nineteen cell types and may be a key player in regulating proliferation in re- sponse to estrogen. Results in other cell types are unexpected. Most notably, neither genes promoting nor inhibiting proliferation are differentially regulated upon estrogen treatment in vascular smooth muscle cells, despite estrogen inhibiting proliferation of these cells.

Le nalméfène représente une option nouvelle dans le traitement de l’alcoolodépendance. Cette molécule a reçu une AMM européenne en 2013 pour réduire la consommation d’alcool des patients adultes ayant une consommation à risque élevé selon la classification de l’OMS (i.e. plus de 60 g d'alcool par jour pour les hommes, ou plus de 40 g par jour pour les femmes). Toutefois, les avis dans la littérature divergent quant à son intérêt. Nous avons donc souhaité réévaluer le rapport bénéfice-risque de cette molécule en appliquant des méthodes appartenant au domaine de la méta-recherche. Une première méta-analyse des essais randomisés contrôlés comparant le nalméfène par voie orale à un placebo nous a permis de mettre en évidence des tailles d’effet faibles sur les critères de consommation, avec un possible biais d’attrition dans les études. Dans une seconde méta-analyse en réseau évaluant l’efficacité, dans l’indication de réduction des consommations, du nalméfène à d’autres traitements également utilisés dans la prise en charge de l’alcoolodépendance, nous avons conclu à l’absence de preuve de haut niveau de l’efficacité des traitements pharmacologiques pour contrôler la consommation d'alcool chez les patients non abstinents souffrant de troubles liés à l’usage. Enfin, nous avons montré, à travers la réalisation d’un grand nombre de méta analyses, que les choix méthodologiques faits dans les essais randomisés contrôlés évaluant le nalméfène et la naltrexone dans la prise en charge de l’addiction à l’alcool entraînaient une variation substantielle de l’estimation de l’efficacité de ces deux traitements, phénomène également appelé « vibration de l’effet » des traitements. / Nalmefene is a new option in the treatment of alcohol dependence. It was approved by the European Medicines Agency to help reduce alcohol consumption in adults who consume more than 60 g of alcohol per day (for men) or more than 40 g per day (for women). However, researchers’ opinions on the interest of the drug are divided. We therefore planned direct and network meta-analyses to enable an objective reappraisal of the efficacy of nalmefene. A first meta-analysis of randomized controlled trials comparing oral nalmefene with placebo showed small effect sizes on consumption criteria with a possible attrition bias in the studies. In a second network meta-analysis evaluating the comparative efficacy of nalmefene to control drinking with other treatments also used in the management of alcohol dependence, we concluded that there was no high-grade evidence for pharmacological treatment to control drinking in non-abstinent patients with alcohol use disorders. Finally, we explored the vibration of effects in a large number of overlapping indirect meta-analyses comparing nalmefene versus naltrexone to reduce alcohol consumption. We demonstrated that the methodological choices made in randomized controlled trials resulted in a substantial variation in the effect sizes of these two treatments.

Objectives: A number of primary empirical studies report strong and positive relationships between information and communication technology (ICT) and second language (L2) learning outcomes. However, these strong relationships were not observed in recent meta-analysis studies associated with ICT and L2 learning outcomes. This meta-analysis study aims to iterate the evaluation of effectiveness of ICT integrated L2 classrooms. Method: Initially, a study search and screening of the digital database were conducted to include quantitative studies exploring the use of ICT for L2 skills in classroom contexts with an experimental design. Then essential statistics from included studies were retrieved and coded. Standardized mean difference of comparison groups across included studies were calculated as the unit of analysis. Finally, a random effects model was used to pool mean effects sizes calculated from included studies. Heterogeneity test, subgroup analysis and publication bias were assessed for implication of study variation and reliability. Results: After a systematic study search and screening, 30 experimental studies were included for this meta-analysis, which yielded 43 effect sizes based on comparison groups across included studies. Results showed a large effect size in favor of technology-integrated instruction with substantial between-groups heterogeneity. Additionally, nine moderating variables were identified, covering substantial, methodological and reporting features. Results also updated the current information on the state of methodological practice in the L2 research domain and suggested that the reliability of instruments used for measurements were overlooked and might lead to an overestimation of effect size. Conclusion: The current meta-analysis provided an updated evaluation of the ICT integrated L2 classrooms, supporting the effectiveness of integrating technologies into L2 instruction (with the exception of L2 pragmatics). Both theoretical and methodological maturation were observed in the research domain, as well as methodological limitations which might impact the precision of effect size. More research is needed to explore more specific topics, as well as methodological imperfections in ICT integrated L2 classrooms. / Graduate

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