Background: Postpartum depression (PPD) is a complex mental health disorder that affects women during their childbearing years. It is a serious medical condition that occurs in approximately 13–20% of women after birth and has an adverse effect on both the mother and the infant. Certain dietary deficiencies in a pregnant or postnatal woman’s diet may cause postnatal depression. It is unclear whether Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are effective for treating or preventing PPD. Objectives: To assess the best available evidence to date regarding the effect of n-3 PUFAs on the etiology, prevention and treatment of postnatal depression. Methods: A systematic review and narrative synthesis was conducted in order to address the gaps in knowledge. For the systematic review, a broad search of electronic databases of published quantitative literature was conducted. Quality appraisal was performed using the tools produced by the effective public health practice project (EPHPP). The narrative synthesis consists of four elements: 1) developing a theory; 2) developing a preliminary synthesis; 3) exploring relationships in the data; 4) assessing the robustness of the synthesis. Results: Out of 181 potential articles, a total of 17 studies met the inclusion criteria. The overwhelming majority of the studies found that n-3 PUFAs had no association with PPD evaluations versus only few ones observed a beneficial effect of n-3 PUFAs supplementation on depressive symptoms. Significant heterogeneity was observed among included studies which can be explained by dissimilar study designs, differences in study duration, time period of measurement and number of participants, and in varied dosages and types of supplemental n-3 PUFAs. Conclusions: Overall, This systematic review and narrative synthesis failed to find a significant positive association between n-3 PUFAs intake and PPD. However further investigation of the specific molecular mechanisms underlying the function of n-3 PUFAs in the brain and the factors related to the pathophysiological nature of depression is warranted.

Background: With usual supplementation practices, most children are Vitamin D Deficient (VDD) following Congenital Heart Disease (CHD) surgery and alternative regimens need consideration. Methods/Results: i) A systematic review identified 88 pediatric trials of high dose vitamin D. Studies evaluating the Institute of Medicine (IOM) Tolerable Upper Intake Level (UL) did not rapidly normalize levels, while loading therapy (≥ 40000 IU) did so within 3 days. Hypercalcemia occurred more often with doses above 400000 IU. ii) A double blind RCT was designed to determine whether pre-operative administration of the IOM UL can prevent post-operative VDD. Results after the first 30 participants completed study procedures demonstrated it was possible to recruit (1.8 patients per month) and complete study procedures (i.e. blood collection). Unfortunately few participants (45%) received more than 30 doses of study drug. Conclusion: Prevention of post-operative VDD in the majority of CHD patients will require alternatives to the IOM recommendations.

Objective Postpartum hemorrhage (PPH) is a major cause of maternal mortality world-wide; misoprostol is a relatively cheap, easily administered, and an efficient medication to be given after the delivery of the baby to prevent PPH, thus posing it as a first choice in resource-poor communities. The aim of this study is to answer questions regarding the most appropriate dose (400 µg versus 600 µg), effect of labour settings (community or clinical), and management of labour on misoprostol effectiveness and safety in preventing PPH. Methods We developed a search strategy and conducted a search within five key databases. Two reviewers screened the articles for predefined inclusion/exclusion criteria, quality, and performed data extraction. Discrepancy was dealt with by reaching consensus. In article 1, we only included randomized controlled trials, we performed a random-effects Bayesian network meta-analysis comparing 400 µg to 600 µg misoprostol over five outcomes of interest: blood loss ≥500 ml, blood loss ≥1000 ml, using additional uterotonics, shivering, and pyrexia. In article 2, we included any experimental trial, we performed a random effects model meta-analysis, pooling the incidence of PPH from each misoprostol arm. Subsequently, a meta-regression model was performed on identified potential effect-modifiers, including clinical settings and labour management. Results Of 444 identified records, 46 trials met the inclusion/exclusion criteria in article 1, and 56 trials in article 2. The odds ratio (OR) of misoprostol 400 µg vs. 600 µg for bleeding ≥ 500 ml is 0.86 [95% Credible Intervals: 0.46 − 1.54], for bleeding ≥ 1000 ml the OR is 0.83 [95% CrI 0.54 – 1.26], for additional uterotonics is 0.75 [95% CrI 0.40 – 1.40], for pyrexia and shivering an OR of 0.57 [95% CrI 0.15 – 2.18] and 0.63 [95% CrI 0.29 – 1.31] respectively. The overall incidence of PPH was 6.62 per 100 pregnancies (95%CI 4.71 per 100 – 8.53 per 100). Labour settings and other aspects of active management of labour had no statistically significant effect on the incidence of post-partum hemorrhage. Conclusion We found no difference between the administration of misoprostol 400 µg or 600 µg for the prevention of PPH and side effects of misoprostol, as well as no effect of labour settings and management of labour on misoprostol effectiveness.

Intensive Behavioural Intervention (IBI) is one of the most widely used treatments for children with an autism spectrum disorder (ASD). While IBI has been recognized as the treatment of choice for very young children with an ASD, its sensible use among school age children is a matter of dispute. The aim of this thesis was to determine the clinical effectiveness of IBI, as compared with no treatment or treatment-as-usual, for the management of cognitive functioning and adaptive skills in preschool and school age children with an ASD, as well as to examine predictors of treatment response. Peer-reviewed, English language publications were identified using MEDLINE, EMBASE, PsychINFO, CINAHL, and ERIC from 1995 to September 1, 2014. Grey literature and reference lists of published papers were also searched for relevant records. Retrieved citations were screened by two independent reviewers, and data extraction was performed by a single reviewer with verification by a second reviewer. The methodological quality and procedural fidelity of included studies was assessed by one reviewer, and a subset of included studies were pooled in a random-effects meta-analysis using the standardized mean difference (SMD) effect size. A total of 24 unique studies were selected for inclusion in this review, comprising a total of 1,816 participants. Findings revealed that IBI improves full-scale IQ (SMD ES = 0.66, 95% CI 0.46 to 0.85, p<0.00001; 13 studies) and adaptive skills (SMD ES = 0.57, 95% CI 0.33 to 0.82, p<0.00001; 12 studies) in preschool and school age children with an ASD, with seemingly higher clinical benefits in children aged under 4 years at intake. Better outcomes with IBI are predicted by children’s relatively younger age, increased cognitive and adaptive ability, as well as a milder severity of symptoms at treatment entry. Results warrant careful interpretation in light of several methodological limitations and inadequate monitoring of procedural fidelity.

Type 2 diabetes mellitus (T2DM) continues to be a national challenge for Canadians. African and Caribbean Immigrants are among the most affected groups and those at risk of developing comorbidities and related complications. It continues to prove challenging to treat T2DM for the affected individuals. Effectively treating the disease can help mitigate risk factors for related comorbidities and complications while improving the quality of life for those affected. There is increasing research, outside of Canada, showing the evidence for the effectiveness of culturally sensitive and adapted interventions to immigrant patients affected with T2DM. In light of the effectiveness of such interventions in many industrialized nations, a systematic review (SR) can offer the best evidence for the scope and consideration of such treatment approaches in Canada. This SR aimed to determine whether community-based diabetic interventions in Canada, are culturally sensitive to African and Caribbean minorities living with type II diabetes. A narrative synthesis was employed to report the effect of interventions seeking to affect outcomes of T2DM patients in Canada. Of the 63 articles included for full review, 60 were excluded for not meeting the criteria of having the target population explicitly identified and also not having any mention of cultural sensitivity. Three articles were included for the final review because the target population was explicitly identified. The final results showed that all interventions were found not to be culturally sensitive to African and Caribbean T2DM patients in Canada. Our results suggest a lack in Canadian literature. To the best of our knowledge, this is the very first systematic review on this subject matter in Canada. This review provides dependable information and recommendations to researchers, educators, clinicians, and policy makers for future research with T2DM African and Caribbean patients in Canada. RÉSUMÉ Le diabète de type 2 demeure un défi national pour les Canadiens. Les immigrants d’origine d’Afrique et des Caraïbes sont parmi les groupes les plus frappés et l'un des plus à risque de développer des troubles comorbides et de complications liées au diabète. Traiter le diabète continue à poser un défi chez les personnes affectées. Traiter efficacement cette maladie peut contribuer à réduire des principaux facteurs de risque quant aux troubles comorbides et complications, tout en améliorant la qualité de vie chez les personnes affectées. Un nombre grandissant de recherche, hors du Canada, démontrent avec des preuves concluantes que les interventions sensibles et culturellement adaptées aux immigrants affectés par le diabète sont efficaces. Étant donné l'efficacité de ces interventions dans nombreux pays industrialisés, une revue systématique peut nous offrir la meilleure preuve pour l'envergure relative à ce genre de traitement au Canada. La présente étude méthodique vise à déterminer si les interventions contre le diabète, en milieu communautaires au Canada, sont culturellement adaptées aux minorités ethniques d’origines d’Afrique et des Caraïbes souffrant de diabète de type II. Une synthèse narrative a été utilisée afin de signaler les effets des interventions par rapport aux résultats des patients souffrant du diabète de type 2. Parmi les 63 articles considérés pour une évaluation complète, 60 ont été exclus car ni la population cible ou la mention de la sensibilité culturelle n’a été explicitement identifiée. Trois articles ont été inclus pour l’évaluation finale car la population cible fut explicitement identifiée. Aucune des interventions n’est culturellement sensible aux patients Africains et Caribéen affecté par le diabète de type 2. Nos résultats démontrent un écart dans la littérature Canadienne. A ce que nous sachons, cette revue systématique est la première qui touche à cette question au Canada. Cette revue fournie des données fiables et recommandations qui permettront aux chercheurs, enseignants, cliniciens, et aux décideurs en matière de politiques de santé pour des recherches futures auprès des patients Africains et Caribéen souffrants du diabète de type 2 au Canada.

Introduction: Thromboprophylaxis recommendations for hospitalized cancer are based on trials done for the general medically patients, as there are no randomized clinical trials(RCTs) looking at thromboprophylaxis in medically ill patients with cancer. Methods: To determine if thromboprophylaxis is safe and effective to prevent VTE these patients, a Systematic Review(SR) was done. A survey was performed to assess: clinical equipoise, trial design and minimally clinically important difference(MCID) for a potential trial. Lastly, a pilot study for an RCT was designed. Results: The pooled RR of VTE was 0.91 (95%CI:0.21 to 4.0;I2:68%) among hospitalized cancer patients receiving thromboprophylaxis compared to placebo. 63.9% believe there is clinical equipoise and 58.3% would consider participating in a RCT comparing different agents/dosing. The MCID for absolute reduction in symptomatic VTE between two arms was 2% and for “acceptable” increase in major bleeding events was 1%. Conclusion: The risk-benefit ratio of current doses of thromboprophylaxis administered to hospitalized cancer patients is unclear and additional RCTs are necessary.

Depuis une dizaine d’années, la thérapeutique de pulpotomie totale est proposée dans la littérature pour le traitement pérenne de l’inflammation pulpaire des dents permanentes matures. De nombreuses publications de type essai clinique, étude de cohorte, série de cas ou revue systématique rapportent des résultats convergents qui placent la pulpotomie totale comme une alternative au traitement endodontique conventionnel. Cependant, la procédure reste peu enseignée, la variabilité méthodologique des études, les influences potentielles des fabricants de matériaux et les interprétations dogmatiques peuvent constituer un frein à la diffusion de cette thérapeutique. Des arguments complémentaires semblent nécessaires pour que les cliniciens, les enseignants et les chercheurs puissent appuyer leurs pratiques de soins, d’enseignements et de recherches selon la démarche fondée sur la preuve. Cette thèse constitue une démarche réflexive essentielle à la compréhension des phénomènes qui régissent la guérison à long terme de l’inflammation pulpaire et aux choix méthodologiques qui permettront d’évaluer cette guérison. Ce travail interroge les données bibliographiques pour argumenter les trois questions suivantes : 1°) Pourquoi et comment la pulpotomie totale peut-elle être considérée comme une thérapeutique de l’inflammation pulpaire ; 2°) Quelles procédures doit-on respecter et quels matériaux peut-on utiliser pour considérer la pulpotomie totale comme une thérapeutique à part entière ? 3°) Quels critères peut-on utiliser pour évaluer le succès d’une pulpotomie totale sur dents permanentes ? Ce travail bibliographique est complété par une étude expérimentale au cours de laquelle la fiabilité et la stabilité d’un guide de lecture des images radiologiques ont été vérifiées afin de proposer un outil de formation susceptible d’être appliqué lors de l’évaluation des résultats de la pulpotomie totale. / Full pulpotomy is a therapeutic in which the coronal pulp portion is removed surgically followed by the capping of the remaining radicular pulp. During the last decade, this therapeutic has been reinvestigated as a definitive treatment of pulp pathologies in mature permanent teeth. Converging datas from published studies suggested that full pulpotomy could be recognized as an alternative to root canal treatment. Furthermore, few clinical trials and a meta analysis aimed to evaluate the effect of initial pulp state or pulp capping material on the success of this treatment. However, large variations in the methodology of the studies, potential influence of laboratories of materials and endodontic dogmas are the major obstacles to the promotion of this therapeutic. An evidence-based approach is necessary because incorporates the best evidence in making decisions. This strategy will help clinicians, teachers and researchers to include full pulpotomy in a daily practice This thesis consists to question the scientific literature in order to answer three following questions: 1) Why and how the full pulpotomy should be considered as a treatment of pulp pathologies ? 2) Which procedures could be applied for full pulpotomy ? 3) Which criteria’s could be used to evaluate the outcomes of full pulpotomy ? These literature reviews are completed with an experimental study about an enriched version of a practical guide for the interpretation of PAI score. Its reliability and reproducibility were verified among French undergraduate students. This practical guide will be a useful tool in evaluation of outcomes in endodontics.

Multicenter preclinical studies have been suggested as a method to improve potential clinical translation of preclinical work by testing reproducibility and generalizability of findings. In these studies, multiple independent laboratories collaboratively conduct a research experiment using a shared protocol. The use of a multicenter design in preclinical experimentation is a recent approach and only a handful of these studies have been published. In this thesis, I aimed to provide insight into preclinical multicenter studies by 1) systematically synthesizing all published preclinical multicenter studies; and 2) exploring the experiences of, barriers and enablers to, and the extent of collaboration within preclinical multicenter studies. In Part One, I conducted a systematic review of preclinical multicenter studies. The database searches identified 3150 citations and 13 studies met inclusion criteria. The multicenter design was applied across a diverse range of diseases including stroke, heart attack, and traumatic brain injury. The median number of centers was 4 (range 2-6) and the median sample size was 133 (range 23-384). Most studies had lower risk of bias and higher completeness of reporting than typically seen in single-centered studies. Only five of the thirteen studies produced results consistent with previous single-center studies, highlighting a central concern of preclinical research: irreproducibility and poor generalizability of findings from single laboratories. In Part Two, I performed semi-structured interviews with researchers who have been involved in a preclinical multicenter study. Braun and Clarkes’ thematic analysis was used to identify emerging themes, and the extent of collaboration was evaluated using an established theory of collaboration developed by Wood and Gray. Twelve researchers from 6 studies were interviewed. Most participants indicated that funding and the culture of the scientific community were barriers, and that established relationships and transparency with collaborators were enablers to multicenter studies. Some participants felt that a harmonized protocol was optimal, while others stated that variability in the protocol across sites was more appropriate. Most participants indicated that multicenter studies had a purpose and place in preclinical research. My findings also suggest that multicenter preclinical studies may provide a method to robustly assess therapies prior to considering clinical translation. These insights will allow for more effective planning and execution of future preclinical multicenter projects and may support the development of best practices and guidelines.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第22835号 / 社医博第111号 / 新制||社医||11(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 佐藤 俊哉, 教授 川上 浩司, 教授 木村 剛 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

Background: Construct validity refers to the degree to which tests that claim to measure a “construct” (i.e., an inferred concept that is intangible regarding an individual’s health or internal state such as a disease, or postulated attribute) are truly reflective of that specific construct. It is suggested that construct validity is an important concept in preclinical research, as it may help reduce misinterpretations of study results allowing for better ability to predict the success of clinical translation of preclinical studies. However, there is a lack of empirical evidence to confirm its impact on preclinical research efficacy. Objectives: (I) Conduct a scoping review of the construct validity literature as it relates to the design of in vivo animal studies. (II) Conduct an overview of systematics reviews evaluating the application and reporting of construct validity within systematic reviews of in vivo animal studies. Methods: For the scoping review, we searched Embase, MEDLINE, and Google Scholar. Eligibility criteria was intentionally broad as we included any article that mentioned construct validity in preclinical in vivo research. Further review of citations was performed on eligible studies that provided substantial discussion on construct validity. For the overview, we searched MEDLINE, Embase, and TOXLINE for systematic reviews of preclinical in vivo interventions. The outcomes of interest were the prevalence of systematic reviews that mentioned construct validity and the prevalence of reviews that assessed construct validity. Results: The literature searches for the scoping and overview yielded 3657 and 2356 articles, respectively. After screening 372 and 444 met inclusion criteria for the scoping and overview. Six codes were generated (theory; mechanism; matches the human condition; measures what it reports to; experimental conditions; and outcomes) from the content analysis for the definition of construct validity. Of the 444 systematic reviews, seven mentioned construct validity, but only three used the term construct validity directly. None of the systematic reviews assessed construct validity. Discussion/Conclusion: Construct validity was not defined uniformly among studies suggesting it is not clearly understood. There was limited reporting on construct validity in systematic reviews and entirely no assessment of it; this may reflect a lack of awareness of this concept. Future research should aim to find a consensus on the definition of construct validity in order to develop tools and frameworks to help researchers assess construct validity.