Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 99-106).

Diss. med. dent. Zürich. / Literaturverz.

Background: In September 2005, scientific journals began requiring trial protocol registration to increase transparency and accountability. Objective: My primary objectives were: develop a database of linked protocols and publications for surgical randomized control trials (RCTs); estimate the proportion published; and determine the proportion exhibiting selective outcome reporting. Methods: A systematic search of the clinicaltrials.gov database was conducted identifying surgical RCTs, completed between 2006 and 2012. Protocols were linked with publications. Primary outcomes were compared. Results: We identified a cohort of 743 surgical RCT protocols. The proportion of registered trials which published their primary results was 0.49 (n=364). The proportion of selective outcome reporting was estimated to be 0.244, significantly lower than the previous estimate (p<0.001). Conclusion: More than half of the completed surgical RCTs were unpublished, and one quarter of those published selectively reported their primary outcome. This supports the notion that significant bias is present in the surgical literature.

Patient-reported outcomes (PROs) produce meaningful information about patient-perceived health status reported directly by patients. Routine collection of PROs data is particularly important in chronic conditions, such as heart failure (HF). Major cardiovascular societies and regulatory agencies encouraged PRO inclusion in randomized controlled trials (RCTs), but PROs remain underutilized as a key outcome in these studies. In this systematic review, we aimed to evaluate temporal trends and explore trial characteristics associated with PRO inclusion in HF RCTs published in high-impact medical journals. We also assessed the quality of PRO reporting against the Consolidated Standards of Reporting Trials PRO extension. We found that over half of HF RCTs included a PRO. The proportion of RCTs with PROs increased significantly since 2000. A number of RCT characteristics such as multicentre; medium-sized (n = 51-250 participants); trials coordinated in Central and South America; and that tested health services, devices or surgery, exercise and rehabilitation interventions were independently associated with higher odds of PRO inclusion. The quality of PRO reporting was modest, with better reporting in RCTs with PROs a primary or co-primary endpoint. Consistent PRO inclusion and high-quality reporting are necessary to increase the utility of these findings by patients, clinicians, and health care policy makers. / Thesis / Master of Science (MSc)

Background and Objectives: Missing participant data are likely to bias the results of randomized control trials (RCTs) when the reason for missingness is associated with status on the outcome of interest. Unlike dichotomous MPD in RCTs, which have been thoroughly investigated, knowledge regarding continuous MPD in RCTs is much more limited. Our objectives were 1) using an adapted checklist, to assess the reporting quality of simulation studies comparing methods to deal with continuous MPD; 2) identify optimal methods proposed by biostatisticians and tested in simulations studies for continuous MPD in RCTs; 3) evaluate how authors report MPD, and how they plan and conduct analyses to deal with MPD in RCTs. Methods: We conducted two systematic surveys. The first identified methods papers published till 2015 January that compared statistical approaches to deal with continuous MPD in RCTs using at least one simulation. In this sample, we considered both the quality of reporting and the results. The second survey identified a representative sample of individual RCTs published in 2014 in core journals reporting the results of at least one continuous variable addressing a patient-important outcome. Results and conclusion: Our survey identified important limitations in reporting quality of simulation studies that compared statistical approaches to deal with continuous MPD, particularly in the reporting of simulation procedures. Only one of 60 studies reported the random number generator used and none reported starting seeds or failures during simulation. Less then half reported software used to perform simulation (41.7%) or analysis (48.3%), and only 4 (5%) reported justification of number of simulations. When facing continuous MPD in RCTs, results of simulation studies demonstrate that trialists seeking optimal approaches may choose robust regression or mixed models and avoid using last observation caring forward. Continuous MPD frequently occurs in RCTs and the extent is typically substantial (median greater than 10%). Methods sections in trial reports typically do not provide adequate detail on how they dealt with MPD in their primary analysis. Among methods actually implemented to deal with MPD, most authors use only available data, thus excluding MPD from the analysis. Seldom do investigators apply statistical approaches to impute or taking into account of MPD nor conduct sensitivity analysis to address the impact of it. A comprehensive knowledge synthesis summarizing current available statistical approaches and its relative merits, as well as the current used methods in RCTs provide clear implications on how the practise of using methods to handle continuous MPD should shift in individual RCTs. Trialists should use mixed models and robust regressions and avoid using last observation caring forward method. / Thesis / Doctor of Philosophy (PhD)

Importance: Evidence from randomized controlled trials (RCTs) is required to guide treatment of critically ill children. Unfortunately such evidence is not always available. Objectives: To describe the RCT research enterprise in pediatric critical care — the evidence and the process of creating it, along with problems and some solutions. Methods: To meet these objectives I undertook a series of 5 related studies. First a scoping review to describe the output of the research enterprise. Second, a social network analysis of coauthorship patterns to describe the community of researchers who produce this evidence. Third, a survey to investigate the importance of RCTs in clinicians’ decision-making. Fourth, a survey of trialists to identify barriers and facilitators of high quality RCTs. Fifth, a qualitative interview study to identify acceptable, feasible and effective strategies to improve the evidence available from RCTs in pediatric critical care. Results and conclusions: The number of RCTs in pediatric critical care is increasing but there is a preponderance of small, single-centred RCTs focusing on laboratory or physiological outcomes that are often stopped early because of feasibility problems or futility. The research community is highly fragmented and highly clustered. Experienced trialists identified approaches to improve the pediatric critical care research enterprise, including building a sense of community and ensuring key training and relevant practical experiences for new investigators. Because of the barriers that researchers face and their ethical obligation to undertake trials that are feasible and make a meaningful contribution to advancing the care of critically ill children, individuals and groups must take an active role in building a healthy research community. Only by changing how we function as a research community can we train the next generation of investigators and undertake the type of trials needed to improve the care of critically ill children. / Thesis / Doctor of Philosophy (PhD) / Evidence from randomized controlled trials (RCTs) is required to guide treatment of critically ill children. Unfortunately such evidence is not always available. My objectives in this thesis are to describe the RCT research enterprise in pediatric critical care — the evidence and the process of creating it, along with problems and some solutions. To meet these objectives I undertook a series of 5 related studies: to identify and describe the RCTs, describe how researchers collaborate, understand how clinicians use RCTs, identify barriers and facilitators of conducting high quality RCTs, and understand how we can improve the evidence available from RCTs in pediatric critical care. We found that the number of RCTs is increasing but there are opportunities to improve the methods, outcome measures, and quality of reporting. We identified strategies that researchers can adopt to facilitate the rigorous RCTs that are needed to improve the care of critically ill children.

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 1999. / Typescript. Bibliography: leaves 82-110.

Thesis (MCur)--Stellenbosch University, 2011. / ENGLISH ABSTRACT: Background: Misoprostol, a prostaglandin E1 analogue with its uterotonic properties has entered as an integral part of management of the third stage of labour, helping to prevent postpartum haemorrhage (PPH). Objective: To assess evidence on the effectiveness of misoprostol compared to a placebo for the prevention and treatment of postpartum haemorrhage. Methods: Databases searched included; MEDLINE, Google Scholar and Cochrane Central Register of Controlled Trials (CENTRAL). Other sources were also searched. All articles were screened for methodological quality by two reviewers independently by standardized instrument. Data was entered in Review Manger 5.1 software for analysis. Results: Three Misoprostol studies were included (2346 participants), Oral (2 trials) and sublingual (1 trial). Misoprostol has shown not to be effective in reducing PPH (RR 0.65: 95% CI 0.40-1.06). Only one trial reported on need for blood transfusion (RR 0.14; 95% CI 0.02-1.15). Misoprostol use is associated with significant increases in shivering (RR 2.75; 95% CI 2.26-3.34) and pyrexia (RR 5.34; 95% CI 2.86-9.96) than with placebo. No maternal deaths were reported in included trials. Compared to placebo, misoprostol was coupled with less hysterectomies and additional used of uterotonics (RR 0.45; 95%CI 0.21-0.96) compared to placebo. Conclusion: Results of this review shows that the use of misoprostol in combination with some components of active management was not associated with any significant reduction in incidence of PPH. However oral administration showed a significant reduction in incidence of PPH. For its use for treatment of postpartum haemorrhage, there is a need for research focus in optimal dose and route of administration for a clinically significant effect and acceptable side effects. / AFRIKAANSE OPSOMMING: Agtergrond: Misoprostol, 'n prostaglandien E1 analoog met sy uterotonic eienskappe het ingeskryf as' n integrale deel van die bestuur van die derde stadium van kraam, help postpartum bloeding (PPH) te voorkom. Doelwit: Om bewyse oor die effektiwiteit van Misoprostol in vergelyking met 'n placebo vir die voorkoming en behandeling van postpartum bloeding te evalueer. Metodes: Databases gesoek ingesluit, Medline, CINHAL, Google Scholar en Cochrane Sentrale Register van gecontroleerde studies (Sentraal). Ander bronne is ook deursoek. Alle artikels is gekeur vir die metodologiese kwaliteit deur twee beoordelaars onafhanklik deur die gestandaardiseerde instrument. Data is opgeneem in Review Manger 5.1 sagteware vir ontleding. Hoof Resultate: Drie Misoprostol studies were ingesluit (2346 deelnemers). Mondeling (2 proe) en sublinguale (1 verhoor). Misoprostol het getoon nie doeltreffend te wees in die vermindering van PPH (RR 0,65: 95% CI 0,40-1,06). Slegs een verhoor berig oor die noodsaaklikheid vir 'n bloedoortapping (RR 0,14, 95% CI 0,02-1,15). Misoprostol gebruik word geassosieer met 'n aansienlike toename in bewing (RR 2,75, 95% CI 2,26- 3,34) en koors (RR 5,34, 95% CI 2,86-9,96) as met' n placebo. Geen moederlike sterftes is aangemeld in proewe. In vergelyking met placebo, was Misoprostol tesame met minder hysterectomies en addisionele gebruik van uterotonics (RR 0,45, 95% CI,21-,96) in vergelyking met placebo. Gevolgtrekking: Resultate van hierdie studie toon dat die gebruik van Misoprostol in kombinasie met 'n paar komponente van aktiewe bestuur is wat nie verband hou met' n beduidende afname in die voorkoms van PPH. Vir die gebruik vir die behandeling van postpartum bloeding, daar is 'n behoefte vir navorsing fokus in die optimale dosis en die roete van administrasie vir' n klinies beduidende uitwerking en aanvaarbare neweeffekte.

Fibromialgia é caracterizada por dor crônica músculo-esquelética difusa, distúrbio do sono, fadiga e humor depressivo ou ansiedade. Cinqüenta e oito mulheres com fibromialgia foram alocadas aleatoriamente e divididas em dois grupos: o primeiro (n=34), tratadas duas vezes por semana com acupuntura perfazendo total de 20 sessões, medicadas com antidepressivos tricíclico e utilizando caminhada, exercícios e relaxamento 2 vezes por semana. O segundo grupo (n=24) recebeu o mesmo tratamento exceto a acupuntura. A avaliação da dor foi realizada através da escala visual analógica (EVA), número de pontos dolorosos (NPD), do índice miálgico (IM) e um questionário SF36 para a qualidade de vida. As avaliações foram feitas antes, após, seis meses, um ano e dois anos depois da primeira avaliação. Foram realizadas por profissionais que desconheciam o grupo ao qual a paciente pertencia. No final das vinte sessões, as pacientes que receberam a acupuntura apresentaram melhora significante nas medidas de dor (EVA, NPD e IM) e em cinco sub-escalas do SF36 em relação ao grupo controle. Após seis meses o grupo de acupuntura apresentou resultado melhor do que o controle em relação ao NPD e ao IM e em uma sub-escala do SF36. Após um ano o grupo de acupuntura mostrou melhora sobre o grupo controle somente em uma sub-escala do SF36. Depois de dois anos do início do tratamento com acupuntura não houve diferença significativa entre os dois grupos em todas as medidas pesquisadas. A associação da acupuntura ao tratamento usual para fibromialgia mostrou-se benéfica para dor e qualidade de vida, mas somente por três meses após o tratamento. / Fibromyalgia is characterized by chronic widespread pain, disturbed sleep, fatigue and psychological distress. The aim of this study was to evaluate the effect of acupuncture as a treatment for this condition. Fifty-eight women diagnosed with fibromyalgia were randomly allocated to two groups. One group received acupuncture (n=34) twice a week for 20 sessions in addition to tricyclic antidepressants and exercises. The control group (n=24) received only tricyclic antidepressants and exercises. Patients rated their pain intensity using a visual analogue scale (VAS). A blinded assessor evaluated the number of fibromyalgia tender points (TePsN) and the pressure pain threshold over the 18 fibromyalgia tender points (PPT18). The same assessor also evaluated quality of life (QoL) using SF-36. These evaluations were done prior to treatments, at the end of the 20 sessions, and again at six months, one year and two years after the first evaluation. At the end of the 20 sessions, patients who had received acupuncture were significantly better than those who had not in all measures of pain (VAS, TePsN, PPT18) and in five subscales of SF-36. After six months, the acupuncture group was significantly better than the control group in some measures of pain (TePsN and PPT18) and in one subscale of SF-36. After one year, the acupuncture group showed significant advantage in only one subscale of SF-36; at two years there were no significant differences between the two groups on all outcome measures. The addition of acupuncture to usual treatment for fibromyalgia is beneficial for pain and quality of life, but only in the first six months.

Introdução: Muitos pacientes com zumbido também apresentam algum grau de perda auditiva associada e o uso de próteses auditivas pode ser uma boa opção para melhorar ambos os sintomas. Porém, na prática clínica, a oclusão do meato acústico externo pelo molde da prótese auditiva pode até piorar o zumbido em alguns casos. A literatura apresenta poucos estudos sobre a real influência da ventilação do molde da prótese auditiva na percepção do zumbido. Objetivo: avaliar a resposta do zumbido à prótese auditiva retro-auricular com dois tipos de ventilação no molde (molde aberto e ventilação de alívio) em pacientes com perda auditiva neurossensorial simétrica após um mês de uso. Métodos: 50 pacientes atendidos no Grupo de Pesquisa em Zumbido com zumbido bilateral e perda auditiva neurossensorial simétrica de grau leve a severo foram submetidos a um ensaio clínico randomizado cego crossover. Destes, 26 pacientes iniciaram o ensaio utilizando próteses auditivas com molde aberto (ventilação de 4mm) e 24 iniciaram usando molde com ventilação de alívio (ventilação de 1mm). Após 30 dias de teste com o primeiro tipo de molde e um período de wash-out (15 dias), o tipo de molde foi trocado e o segundo molde foi usado por mais 30 dias. O zumbido foi avaliado de modo qualitativo (classificado em melhora, inalterado e piora) e quantitativo (variação de 0 a 10 de uma escala numérica). Resultados: A melhora do zumbido foi observada em 82% dos casos com pelo menos um tipo de molde e não houve diferença significante na diminuição do incômodo com o zumbido nas avaliações qualitativa e quantitativa com ambos os moldes. Apesar disto, 66% dos pacientes preferiram o molde aberto. Conclusão: A curto prazo, a melhora do zumbido por meio da prótese auditiva em pacientes com perda auditiva neurossensorial simétrica de grau leve a severo não depende do tamanho da ventilação do molde auricular / Introduction: Most tinnitus patients also have some degree of associated hearing loss, and the use of hearing aids is an option to improve both symptoms. In daily practice, the occlusion of the external meatus by the earmold during hearing aids fitting may enhance the tinnitus perception. However, the literature lacks studies about the real influence of the earmold ventilation on tinnitus perception. Objective: to evaluate the tinnitus response to the BTE hearing aids using two types of ventilation (open mold and relief ventilation) in patients with symmetric sensorineural hearing loss after one month usage. Methods: 50 patients attended in our Tinnitus Clinic who presented bilateral tinnitus and mild to severe symmetric sensorineural hearing loss underwent a randomized blind crossover clinical trial. Among them, 26 first used BTE hearing aids with open molds (4mm ventilation) and 24 first used hearing aids with relief ventilation mold (1mm ventilation). After 30 days using the first mold and a 15-day wash-out period, the type of earmold was changed in a crossover way and the second mold was used for another 30-day-period. Tinnitus evaluation was performed by a qualitative way (classified in improvement, unchanged and worsening) and by a quantitative way (variation of a numeric scale from 0 to 10). Results: Tinnitus improvement was observed by 82% of the patients with at least one type of earmold and there was no significant difference in the decrease of tinnitus discomfort by both, quantitative and qualitative evaluation. Despite the similar tinnitus control, 66% of the patients preferred to acquire the hearing aids with open mold. Conclusion: In a short-term evaluation, the tinnitus improvement by the use of hearing aids in patients with mild to severe symmetric sensorineural hearing loss does not depend on the size of earmold ventilation