<p>Objective: We compared the performance of PLUS to that ofthe Cochrane Trial Registry (CCTR), Medline and EMBASE for locating studies added during an update of Cochrane Systematic reviews. We investigated the effect of excluding studies not found in PLUS on meta-analysis results.</p> <p>Study Design and Setting: A sample of new studies in updated Cochrane Systematic Reviews was used to establish a reference standard. Searches were performed for each study in PLUS, CCTR, Medline and EMBASE. Where a primary study was not indexed in PLUS, we examined the effect on the review of excluding the study. We compared the result of each selected meta-analysis including only new studies obtained in PLUS to the result using only those not found in PLUS (non-PLUS) via ratio of odds ratios (ROR). The sensitivity of Hedges filters for randomized trials was measured.</p> <p>Results: Ninety-eight updated reviews were identified and 87 included a meta-analysis suitable for calculation of RORs. The relative recall rates for PLUS, CCTR, Medline and EMBASE were 23%, 95%, 90% and 86%, respectively. PLUS contained all new studies for 13 of74 reviews. No statistically significant difference between PLUS and non-PLUS new studies was found when RORs were pooled across 39 reviews (ROR 0.929; 95% CI, 0.79-1.093). Nineteen updated reviews had no new studies indexed in PLUS. Hedges filters for Medline demonstrated 99.4% sensitivity to detect new trials.</p> <p>Conclusions: PLUS included less than a quarter of the new studies in Cochrane Review updates but the majority of reviews in our sample appeared unaffected by the use of PLUS as a sole source of literature. This may be because PLUS captures the most important studies although no predictors of PLUS retrieval performance were found. Reviewers should consider adopting PLUS and Hedges filters to keep their reviews up to date.</p> / Master of Science (MS)

<p>This thesis is based on 32 semi-structured phenomenological interviews conducted at a large Canadian ambulatory cancer centre serving 2.3 million people in Ontario. The primary objective of this program of study was to explore cancer care employees' perceptions of a Quality of Work-Life (QWL) Project where they were the subjects of research and their perceptions of clinical research where patients were the subjects of research. Three secondary objectives were to explore: (a) perceptions of the participatory approach to research from the perspective of employees on the steering committee of the QWL Project; (b) perceptions of the QWL Survey from the perspective of employees who completed the survey; and (c) perceptions of clinical trials from the perspective of nurses and radiation therapists who treated trial patients Findings had important implications for the conduct of workplace and clinical research in a cancer care environment. Some of the main findings included: (a) It may be difficult to conduct participatory research in a work environment given that power and a hierarchy of relationships interfere with employees being considered equal; (b) Many QWL issues presented by employees were not captured in the QWL Survey. QWL researchers need to ensure that QWL measures are pertinent to a particular worksite and encompass all meaningful QWL issues of a given work environment; (c) Ethical concerns associated with clinical trials suggested that the clinical trials department should review trial procedures; (d) Workload concerns associated with clinical trials implied that employees should be credited for their present involvement in trials; and (e) Clinical research was perceived to be more important than the QWL Project, party due to the perception that patient interests outweighed those of employees. In general, employees' perceptions of clinical and workplace research suggested that identification with the cancer centre as a clinical research organization contributed significantly to employees' QWL.</p> / Doctor of Philosophy (PhD)

<p>Hydrocephalus is a common condition of childhood. Attempts to measure the health status of children with hydrocephalus have traditionally relied on surgical outcomes, non-specific generic health outcomes, or very specific neuropsychological measures. This work describes the development of a new disease-specific health status outcome measure for children with hydrocephalus--called the Hydrocephalus Outcome Questionnaire (HOQ). This work begins with a discussion of several methodological issues relevant to health status measurement, highlighting certain points of controversy. This is followed by a review of the methodology and the results of various stages of development of this new health status measure. This includes the stages of concept development, item generation, item reduction, reliability testing, and validity testing. The final section describes the use of some different approaches to providing interpretability to the new outcome measure. This work was approved by the Research Ethics Board at the Hospital for Sick Children, Toronto. The result of this work was the 60-item Hydrocephalus Outcome Questionnaire. It demonstrated very good psychometric properties and was well received by the parents of children with hydrocephalus, who are the primary respondents. It is hoped that this will serve a useful role as a much-needed outcome measure for pediatric hydrocephalus.</p> / Doctor of Philosophy (PhD)

Background Clinical Care Pathways (CCPs) are a form of organized care processes and mutual decision making regarding select patient groups in a specific context. Their aim is to enhance care quality, patient satisfaction, and outcomes while optimizing safety and resource utilization. CCPs are poorly characterized in the Canadian context, with a few examples of successful programs but no organizational framework. Aims & Methods Through an interview series and qualitative descriptive content analysis, this thesis attempts to discern neurosurgeon perspectives on CCPs, important content and processes, and barriers to CCP development. Through a retrospective case control study, for operative patients at one Canadian center, a second project describes characteristics of entry to neurosurgical care for the purpose of understanding system inputs and subsequent CCP development. Results Interviewed neurosurgeons describe a positive sentiment toward CCPs overall, with nuanced understanding coalescing between numerous perspectives. Respondents described CCPs heterogeneously, but overall recognized their structure. Current care barriers were identified. Numerous existing informal or partial CCPs were discussed. CCPs are noted to have specific essential elements in their design. Retrospective review of care entry from July through December 2022 analyzed 654 operative cases and 2135 regional urgent consult requests. This analysis revealed differences in care entry dependent on disease entity, referral characteristics, patient characteristics, and patient acuity. Conclusions Design and development of CCPs is an emerging practice in the Canadian neurosurgical context. Numerous institutions and groups are presently developing their local CCPs. This analysis serves as a preliminary structure of CCP design, with an example retrospective analysis of the care entry component at a local institution. / Thesis / Master of Science (MSc) / Clinical Care Pathways (CCPs) are processes describing how to care for a group of patients, from diagnosis through treatment and follow-up. Interviewed surgeons suggested that while significant barriers exist, such as resource limitations and prolonged wait times, CCP implementation would improve care. These pathways need to be evidence based, expert led, collect data, and contain a team from multiple specialties. CCPs should be uniquely built for certain disease groups such as spine, trauma, or oncology. Review of care entry at a specialized neurosurgical center suggested that care capacity is currently very strained. Wait times from assessment to surgery are lengthy. Many surgeries are happening as emergency cases, and some emergency cases would likely be done in a scheduled fashion, if resources were available for this. Similar reviews of referral sources can assist an institution to plan, in an informed way, for current and future needs for neurosurgery patients. This type of study serves as an example, when constructing a CCP, of how one can analyze system inputs.

<p>Multi-faceted interventions that include some form of a clinical information system have been shown to improve primary care physicians' management of chronic diseases. The objective of this pilot study was to assess the feasibility of a cluster randomized controlled trial of a multi-faceted intervention, which includes a clinical information system, to improve the management of the chronic disease of tobacco use by physicians. Feasibility was assessed with respect to the use of a measurement tool (Smoking Status Identification Card) and use of a new smoking cessation management module in the clinical information system.</p> <p>Letters of invitation were sent out to the 65 primary care physicians (in 38 primary care practices) who were subscribed to the web-based clinical information system (P-PROMPT CDMS). Five physicians from 5 primary care practices agree.d to participate, who were stratified and then randomized to the intervention (2 primary care practices) or control group (3 primary care practices).</p> <p>Following the 12-week study period, SSIC completion reached the 90% threshold success criterion in 2 of the 5 primary care practices (one each from the intervention and control group). The intervention group demonstrated basic use of the new smoking cessation management module that reached 21.9% and 19.0% in each of the respective practices, which was below the 30% threshold success criterion. A preliminary evaluation of physician delivery of smoking cessation counselling demonstrated a trend to a higher percentage of Ministry of Health and Long-Term Care (MOHLTC) physician service billing codes submitted among the physicians in the intervention group, which may be indicative of greater smoking cessation counselling.</p> <p>It is concluded that a randomized controlled trial to test a multi-faceted intervention is not feasible with the current study design. Significant modifications to the current study design are required that can potentially be tested prior to progression to a larger trial.</p> / Master of Science (MS)

Background: Compared with typically developing children, children with special needs often struggle with academic and social aspects of school, though certain factors can improve their academic and social developmental trajectory. The objective of this investigation was to explore the association between the developmental health of children with special needs at school-entry, as measured by the Early Development Instrument (EDI), and neighborhood-level SES. To date, the EDI has only been validated for use in typically developing children. Hence, a secondary objective of this investigation was to explore the psychometric properties of the EDI for children with special needs. Methods: The data for this investigation were from the Pan-Canadian database of children’s developmental health at school entry. The psychometric properties of the EDI, including item and domain characteristics, factor structure, and construct validity, were tested for children with special needs. Hierarchical generalized linear models was used to model the association between EDI domain scores and a custom neighborhood SES index. Results: A total of 29,841 (69.8% male) and 29,520 (69.7% male) children with special needs were available for the investigation on the psychometric properties of the EDI and the relationship between EDI outcomes and SES, respectively. The psychometric performance of the EDI in children with special needs was similar to its performance in typically developing children. The EDI was subsequently used to explore the association between developmental outcomes and neighborhood socioeconomic status (SES). All EDI domains were positively correlated with SES, indicating that children in high SES neighborhoods have better developmental outcomes at school entry than those in lower SES neighborhoods. Conclusions: The results of this investigation draw attention to the potential impact of contextual factors on children’s health and have implications for policy development and service planning. These results also indicate that the EDI performs similarly in children with special needs and typically developing children, thus enabling its more extensive use for this population. / Thesis / Master of Science (MSc) / Background: Compared with typically developing children, children with special needs often struggle with academic and social aspects of school, though certain factors can improve their academic and social developmental trajectory. The objective of this investigation was to explore the association between the developmental health of children with special needs at school-entry, as measured by the Early Development Instrument (EDI), and neighborhood-level SES. To date, the EDI has only been validated for use in typically developing children. Hence, a secondary objective of this investigation was to explore the psychometric properties of the EDI for children with special needs. Methods: The data for this investigation were from the Pan-Canadian database of children’s developmental health at school entry. The psychometric properties of the EDI, including item and domain characteristics, factor structure, and construct validity, were tested for children with special needs. Hierarchical generalized linear models was used to model the association between EDI domain scores and a custom neighborhood SES index. Results: A total of 29,841 (69.8% male) and 29,520 (69.7% male) children with special needs were available for the investigation on the psychometric properties of the EDI and the relationship between EDI outcomes and SES, respectively. The psychometric performance of the EDI in children with special needs was similar to its performance in typically developing children. The EDI was subsequently used to explore the association between developmental outcomes and neighborhood socioeconomic status (SES). All EDI domains were positively correlated with SES, indicating that children in high SES neighborhoods have better developmental outcomes at school entry than those in lower SES neighborhoods. Conclusions: The results of this investigation draw attention to the potential impact of contextual factors on children’s health and have implications for policy development and service planning. These results also indicate that the EDI performs similarly in children with special needs and typically developing children, thus enabling its more extensive use for this population.

<p>Human atherosclerosis is a disease of the blood vessel wall caused by an interplay between inflammatory, thrombotic, and lipid factors. A contributing or causal role for infection in that inflammatory response was first proposed in the 19th century, and with the advent of more sophisticated diagnostic techniques, a new search for a microbiologic etiology of human atherosclerosis has been rekindled. In this thesis, I examine methods for investigating whether infections contribute to human atherosclerotic cardiovascular disease. I explore three different technologies: serology (measuring antibody), inflammatory markers (as risk markers and as surrogates for infections), and the direct measurement of bacterial or viral DNA in the bloodstream. I examine three different study designs: cross-sectional, case-control, and cohort. Chlamydia pneumoniae , an obligate intracellular bacterium, is the primary focus of these studies. In addition, cytomegalovirus and other infections are included as controls, with the a priori expectation that these other infections would not be related to cardiovascular disease. We found a relationship between cardiovascular disease and C. pneumoniae antibody status in a small case-control study, but found no independent association in a large, prospective study. Inflammatory markers were measured in the prospective study, and were associated with cardiovascular events, yet no clear association between inflammation and infection was found. However, in developing methods for directly detecting bacterial and viral DNA in the bloodstream, we found that serology itself was not associated with current detection of bacterial DNA. Furthermore, we found a strong relationship between C. pneumoniae and smoking, and conclude that future studies need to examine the interaction between infection, inflammation, and smoking status.</p> / Doctor of Philosophy (PhD)

Chronic non-cancer pain (CNCP) is a complex phenomenon that affects multiple dimensions of daily life. Optimal therapies for managing CNCP must, then, demonstrate clinically important benefits that go beyond reductions in pain and adverse events. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has recommended that clinical trialists who are evaluating treatments for chronic pain consider reporting treatment effects across nine patient-important outcome domains. This thesis begins with an investigation of the extent to which clinical trials evaluating the effects of opioids for CNCP report IMMPACT-recommended core outcome domains. Further, it explores optimal therapeutic strategies for specific CNCP conditions; specifically, it features a systematic review of randomized controlled trials of all pharmacological and non-pharmacological therapies for central post-stroke pain, as well as a plan for a network meta-analysis of all therapies for all chronic neuropathic pain syndromes. Chronic pain is also a common reason for disability, and this thesis concludes with a retrospective cohort study focused on identifying predictors of claim duration following acceptance for disability benefits among Canadian workers. / Thesis / Doctor of Philosophy (PhD)

Symptomatic spinal disorders affect a large proportion of the population and are associated with substantial morbidity, social burden, and economic impact. Spine surgery interventions can provide excellent results in carefully selected patients whose symptoms fail to improve with non-operative management, but an evidence-based approach is paramount to optimize outcomes and rigorous standards of health research methodology are critical to avoid misleading conclusions. This thesis aimed to investigate and apply modern innovations in health research methodology to the field of spine surgery. It consists of seven chapters divided between three sections: randomized controlled trials, observational studies, and systematic reviews and meta-analyses. By applying the findings of each chapter, clinicians, researchers, and other evidence users can advance the credibility of future research and enhance the care of patients with spinal disorders. / Thesis / Doctor of Philosophy (PhD)

Finite mixture modeling is a useful statistical technique for clustering individuals based on patterns of responses. The fundamental idea of the mixture modeling approach is to assume there are latent clusters of individuals in the population which each generate their own distinct distribution of observations (multivariate or univariate) which are then mixed up together in the full population. Hence, the name mixture comes from the fact that what we observe is a mixture of distributions. The goal of this model-based clustering technique is to identify what the mixture of distributions is so that, given a particular response pattern, individuals can be clustered accordingly. Commonly, finite mixture models, as well as the special case of latent class analysis, are used on data that inherently involve repeated measures. The purpose of this dissertation is to extend the finite mixture model to allow for the number of repeated measures to be incorporated and contribute to the clustering of individuals rather than measures. The dimension of the repeated measures or simply the count of responses is assumed to follow a truncated Poisson distribution and this information can be incorporated into what we call a dimension informative finite mixture model (DIMM). The outline of this dissertation is as follows. Paper 1 is entitled, "Dimension Informative Mixture Modeling (DIMM) for questionnaire data with an informative number of repeated measures." This paper describes the type of data structures considered and introduces the dimension informative mixture model (DIMM). A simulation study is performed to examine how well the DIMM fits the known specified truth. In the first scenario, we specify a mixture of three univariate normal distributions with different means and similar variances with different and similar counts of repeated measurements. We found that the DIMM predicts the true underlying class membership better than the traditional finite mixture model using a predicted value metric score. In the second scenario, we specify a mixture of two univariate normal distributions with the same means and variances with different and similar counts of repeated measurements. We found that that the count-informative finite mixture model predicts the truth much better than the non-informative finite mixture model. Paper 2 is entitled, "Patterns of Physical Activity in the Northern Manhattan Study (NOMAS) Using Multivariate Finite Mixture Modeling (MFMM)." This is a study that applies a multivariate finite mixture modeling approach to examining and elucidating underlying latent clusters of different physical activity profiles based on four dimensions: total frequency of activities, average duration per activity, total energy expenditure and the total count of the number of different activities conducted. We found a five cluster solution to describe the complex patterns of physical activity levels, as measured by fifteen different physical activity items, among a US based elderly cohort. Adding in a class of individuals who were not doing any physical activity, the labels of these six clusters are: no exercise, very inactive, somewhat inactive, slightly under guidelines, meet guidelines and above guidelines. This methodology improves upon previous work which utilized only the total metabolic equivalent (a proxy of energy expenditure) to classify individuals into inactive, active and highly active. Paper 3 is entitled, "Complex Drug Use Patterns and Associated HIV Transmission Risk Behaviors in an Internet Sample of US Men Who Have Sex With Men." This is a study that applies the count-informative information into a latent class analysis on nineteen binary drug items of drugs consumed within the past year before a sexual encounter. In addition to the individual drugs used, the mixture model incorporated a count of the total number of drugs used. We found a six class solution: low drug use, some recreational drug use, nitrite inhalants (poppers) with prescription erectile dysfunction (ED) drug use, poppers with prescription/non-prescription ED drug use and high polydrug use. Compared to participants in the low drug use class, participants in the highest drug use class were 5.5 times more likely to report unprotected anal intercourse (UAI) in their last sexual encounter and approximately 4 times more likely to report a new sexually transmitted infection (STI) in the past year. Younger men were also less likely to report UAI than older men but more likely to report an STI.