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OBJECTIVES: The objective of this thesis is to explore the effectiveness and safety of common pharmacotherapeutic options used for the management of patent ductus arteriosus (PDA) in preterm infants. METHODS: Following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidance, article 1 develops the protocol to conduct the systematic review and network meta-analysis to answer the research question. Article 2 details the actual methods implemented to conduct the network meta-analysis and presents the results in the form of network plots, league tables, rank heat maps, rankograms and forest plots. RESULTS: Article 1 suggests the need to conduct a Bayesian random-effects network meta-analysis of randomized controlled trials (RCTs) as the analysis would involve multiple treatments with potentially both direct and indirect comparisons. Article 1 also a priori defines potential effect modifiers and statistical strategies to control for the same. In article 2, the results of the meta-analysis show that in 68 RCTs that included 4802 infants, 14 different variations of indomethacin, ibuprofen or acetaminophen were used. Oral high-dose ibuprofen was associated with a significantly higher odds of PDA closure compared with standard-dose intravenous ibuprofen (Odds Ratio [OR], 3.59; 95% Credible Interval [CrI],1.64-8.17) and intravenous indomethacin (OR, 2.35; 95% CrI,1.08-5.31). Oral high-dose ibuprofen ranked the best option for PDA closure (SUCRA [surface under the cumulative ranking curve],0.89 [SD, 0.12]) and to prevent surgical PDA ligation (SUCRA,0.98 [SD, 0.08]). There was no significant difference in the odds of mortality, necrotizing enterocolitis or intra-ventricular hemorrhage with use of placebo or no treatment compared with any of the other treatment modalities. CONCLUSION: This thesis suggests that oral high-dose ibuprofen could be the best treatment option for closure of a hemodynamically significant PDA. Placebo or no treatment for a hemodynamically significant PDA may not increase morbidity and mortality. / Thesis / Master of Science (MSc) / The following thesis explores the effectiveness and safety of commonly used drugs for the treatment of a heart condition in premature infants called the patent ductus arteriosus (PDA). Article 1 outlines the protocol for the systematic review and network meta-analysis designed to evaluate the effectiveness and safety of indomethacin, ibuprofen and acetaminophen for the treatment of PDA in preterm infants. Article 2 provides in detail the results of the network meta-analysis that examined all eligible randomized controlled trials that compared intravenous or oral formulations of indomethacin, ibuprofen or acetaminophen compared against to other or placebo for the treatment of a PDA that may be harmful for a premature infant based on certain clinical and echocardiographic criteria set by the clinicians and researchers. Overall, this body of work suggests that a higher dose of oral ibuprofen is the best treatment for PDA in premature infants.

Background: Carpal Tunnel Syndrome (CTS) is a condition affecting wrists and hands, causing pain, tingling, and numbness. Despite the high prevalence of CTS and the existence of several diagnostic tools, there is no consensus over a diagnostic gold standard test. Thesis Objectives: To conduct a systematic review of diagnostic test accuracy of clinical scales, questionnaires and hand symptom diagrams/maps for the diagnosis of CTS in people suspected with this condition; and to do a cognitive interviewing qualitative study of the Kamath and Stothard questionnaire, a diagnostic tool for CTS, to identify and resolve potential sources of error. Methods: In the first study, we searched MEDLINE, CINAHL, and Embase databases keywords related to diagnostic accuracy and clinical tests of CTS. In the second study, we interviewed clinicians and people diagnosed with CTS and other upper extremity conditions. We recorded, and content analyzed their opinion on comprehensiveness and comprehensibility of Kamath and Stothard questionnaire. Results: Twenty-one articles met the eligibility criteria of the systematic review, of which nine were on the diagnostic accuracy of hand symptom diagrams and twelve assessed the diagnostic accuracy of clinical scales and questionnaires for the diagnosis of CTS. Positive likelihood ratios (LRs) to diagnose or rule in CTS ranged from 0.94 for Boston carpal tunnel questionnaire to 10.5 for CTS-6 scale, and negative LRs to rule out CTS ranged from 1.05 to 0.05 for the same diagnostic tools. In the cognitive interviewing study, we categorized the areas of uncertainty in the participants’ responses into five themes: clarity and comprehension (51%), relativeness (38%), inadequate response definition (3.75%), perspective modifiers (3.75%), and a reference point (2.5%). Conclusions: Very few high-quality studies exist on the diagnostic accuracy of CTS-6, Kamath and Stothard questionnaire, Bland questionnaire, and Katz and Stirrat’s hand symptom diagram. By doing cognitive interviews, we identified options for potential improvement in the wording of the Kamath and Stothard questionnaire. Future studies should assess the diagnostic properties of the proposed modified questionnaire, and high-quality studies are warranted to assist in deciding on ruling in or out CTS. / Thesis / Master of Science (MSc) / Carpal tunnel syndrome is a condition affecting the hands, causing feelings of burning pain, pins and needles, heaviness and/or lack of sensation. This condition is very common among people who do manual work and can make them unable to do their jobs and daily living tasks. Early diagnosis of carpal tunnel syndrome is very important in starting an appropriate plan of treatment. The best diagnostic test for carpal tunnel syndrome is still uncertain. In the first study, we collected studies of the questionnaires and hand maps that exist for the diagnosis of carpal tunnel syndrome. We then tried to summarize the information that assists clinicians in making a diagnostic decision. In the second study, we interviewed people about their opinion of a questionnaire that is used in hand clinics to diagnose carpal tunnel syndrome. We concluded that more studies with high quality are needed to confidently decide which diagnostic test is best. Also, we revised a questionnaire that is currently used, and we hope that these revisions make the questionnaire more relecant and understandable for people.

No / Reactivity to assessment has attracted recent attention in the brief alcohol intervention literature. This systematic review sought to examine the nature of change in alcohol consumption over time in control groups in brief intervention studies. Primary studies were identified from existing reviews published in English language, peer-reviewed journals between 1995 and 2005. Change in alcohol consumption and selected study-level characteristics for each primary study were extracted. Consumption change data were pooled in random effects models and meta-regression was used to explore predictors of change. Eleven review papers reported the results of 44 individual studies. Twenty-six of these studies provided data suitable for quantitative study. Extreme heterogeneity was identified and the extent of observed reduction in consumption over time was greater in studies undertaken in Anglophone countries, with single gender study participants, and without special targeting by age. Heterogeneity was reduced but was still substantial in a sub-set of 15 general population studies undertaken in English language countries. The actual content of the control group procedure itself was not predictive of reduction in drinking, nor were a range of other candidate variables including setting, the exclusion of dependent drinkers, the collection of a biological sample at follow-up, and duration of study. Further investigations may yield novel insights into the nature of behaviour change with potential to inform brief interventions design.

Yes / Background: medication-related problems occur frequently when older patients are discharged from hospital. Interventions to support medication use have been developed; however, their effectiveness in older populations are unknown. This review evaluates interventions that support successful transitions of care through enhanced medication continuity. Methods: a database search for randomised controlled trials was conducted. Selection criteria included mean participant age of 65 years and older, intervention delivered during hospital stay or following recent discharge and including activities that support medication continuity. Primary outcome of interest was hospital readmission. Secondary outcomes related to the safe use of medication and quality of life. Outcomes were pooled by random-effects meta-analysis where possible. Results: twenty-four studies (total participants=17,664) describing activities delivered at multiple time points were included. Interventions that bridged the transition for up to 90 days were more likely to support successful transitions. The meta-analysis, stratified by intervention component, demonstrated that self-management activities (RR 0.81 [0.74, 0.89]), telephone followup (RR 0.84 [0.73, 0.97]) and medication reconciliation (RR 0.88 [0.81, 0.96]) were statistically associated with reduced hospital readmissions. Conclusion: our results suggest that interventions that best support older patients’ medication continuity are those that bridge transitions; these also have the greatest impact on reducing hospital readmission. Interventions that included self management, telephone follow-up and medication reconciliation activities were most likely to be effective; however, further research needs to identify how to meaningfully engage with patients and caregivers to best support post-discharge medication continuity. Limitations included high subjectivity of intervention coding, study heterogeneity and resource restrictions. / National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant PB-PG-0317-20010).

Assessment of risk of bias in the included randomized controlled trials (RCTs) has become an essential step in systematic reviews, which informs the decision of whether to rate down certainty of evidence due to risk of bias applying the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Many instruments exist for rating risk of bias in RCTs; however, even those most commonly used that developed by the Cochrane group, suffer from limitations. In particular, the revised Cochrane instrument, while reflecting methodological advances, sacrificed simplicity and practicability. The objective of this thesis is to use rigorous methodology to develop a simple-structured RCT risk of bias instrument that is easy for systematic review authors to use. The thesis begins with a chapter introducing the background and the structure of the thesis. The thesis subsequently describes a systematic survey of existing RCT risk of bias instruments for their included items, through which we collected potential candidate items for the new instrument. We then present a summary of empirical evidence investigating how the possible risk of bias issues influence the estimates of intervention effects in RCTs, which assisted with the item selection for the new instrument. Then, this thesis describes the detailed process for instrument development and providing the new instrument. This thesis ends with a chapter summarizing key findings, discussing strengths and limitations, and exploring directions for future research. / Thesis / Doctor of Philosophy (PhD)

Burnout is a psychological syndrome characterized by feelings of exhaustion, cynicism, and inefficacy, and is particularly prevalent in surgical specialties. Despite the widespread recognition that burnout is the result of exposure to chronic job stressors, research on burnout among physicians has primarily focused on individual correlates and solutions to this issue. We also have a limited understanding of what kinds of interventions have become available to physicians following the pandemic and what the most effective options are for those in independent practice. Thus, this thesis serves to fill a gap in the literature on physician burnout by using a validated organizational framework to identify the organizational drivers of burnout among surgeons and McMaster and update the literature on the state of burnout interventions in medicine. The first chapter explores the state of the literature on physician burnout, with a specific focus on surgical specialties and the theoretical gaps that exist in this field. Chapters two through four describe the design and findings of a mixed methods study exploring surgeons’ experiences with burnout and the workplace stressors associated with its symptoms. Chapter five consists of a systematic review and meta-analysis evaluating the effectiveness of interventions for physician burnout and provides a methodological critique of the available studies in this field. Finally, chapter six integrates the finding from the quantitative and qualitative strand of the mixed methods study while considering the findings in reference to available interventions. The findings presented in this thesis provide tangible recommendations to McMaster’s Department of Surgery on how to improve burnout symptoms with specific reference to the role of payment structures, tensions among leadership positions, patient care burden, moral injury, workplace incivility, and gender inequity. It also highlights opportunities for future intervention development focusing on health system stressors and organizational structures. / Dissertation / Doctor of Philosophy (PhD) / Burnout is a condition that results from issues in the workplace and is extremely common among physicians. Although we generally know where burnout comes from, what causes burnout tends to take different forms in different medical specialties and workplaces. Given the negative effects that burnout has on both physicians and the quality of patient care they are able to provide, it is important that we identify the specific stressors leading to burnout within different medical settings and identify effective interventions for the problems they face. Using a range of evaluation methods, including surveys, interviews, and reviews of the current research on this subject, this thesis looked to identify issues leading to burnout among surgeons at McMaster University, and provide specific recommendations on how to address them.

Yes / Social media comprises communication websites that facilitate relationship forming between users from diverse backgrounds, resulting in a rich social structure. User generated content encourages inquiry and decision-making. Given the relevance of social media to various stakeholders, it has received significant attention from researchers of various fields, including information systems. There exists no comprehensive review that integrates and synthesises the findings of literature on social media. This study discusses the findings of 132 papers (in selected IS journals) on social media and social networking published between 1997 and 2017. Most papers reviewed here examine the behavioural side of social media, investigate the aspect of reviews and recommendations, and study its integration for organizational purposes. Furthermore, many studies have investigated the viability of online communities/social media as a marketing medium, while others have explored various aspects of social media, including the risks associated with its use, the value that it creates, and the negative stigma attached to it within workplaces. The use of social media for information sharing during critical events as well as for seeking and/or rendering help has also been investigated in prior research. Other contexts include political and public administration, and the comparison between traditional and social media. Overall, our study identifies multiple emergent themes in the existing corpus, thereby furthering our understanding of advances in social media research. The integrated view of the extant literature that our study presents can help avoid duplication by future researchers, whilst offering fruitful lines of enquiry to help shape research for this emerging field.

Yes / People worldwide are largely engaged and attached with the web 2.0 technology and Social media platforms. By the same token, businesses start looking at such technologies as effective mechanisms to interact more with their customers. Equally, the related issues of social media marketing have been also the focus of attention for academics and researchers to expand the current understanding about such phenomena over the marketing area. Accordingly, the main aim of this study is to systematically examine and review the current studies that have conducted over the related area of social media and marketing. By reviewing approximately 144 articles, the researchers were able to provide an overview of the main themes and trends covered by the relevant literature such as the role of social media on advertising, the electronic word of mouth, customers’ relationship management, and firms’ brands and performance. In this review, it has also studied the most common research approaches adopted to examine the related issues of social media marketing. Further discussion is also introduced followed by an explanation of the current review limitations and recommended directions to be examined by future studies.