Symptoms in patients receiving dialysis are common and associated with impaired quality of life. Symptoms are a top research priority because effective therapies are lacking and even with appropriate diagnosis and treatment, residual symptoms often persist. Clinical trials in the setting of kidney disease are challenging to conduct and as a result, nephrology lags behind other specialties regarding the degree to which clinical trials inform the care of patients with kidney disease, including those receiving dialysis. The studies in this thesis inform the design of randomized controlled trials with regards to run-in periods and the treatment of symptoms in patients with kidney disease. Chapter 2 describes a meta-epidemiologic study of the frequency, setting and purposes of run-in periods in parallel randomized controlled trials of self-administered medications for chronic diseases in adults. Chapter 3 is a study within a trial of an international randomized controlled trial that compares spironolactone to placebo for the prevention of cardiovascular morbidity and mortality in dialysis. It compares the ability of a 3-week study visit in addition to a 7-week study visit during an active-run-in period to identify and exclude participants with non-adherence. Chapter 4 is a protocol for a randomized placebo controlled crossover trial of low fixed dose pharmacologic therapy for restless legs syndrome in hemodialysis that includes a placebo run-in period for adherence and tolerability. Chapter 5 is a survey of Canadian nephrologists regarding the use of cannabinoids for symptom management in patients with kidney disease and support for their use in clinical trials. / Thesis / Doctor of Philosophy (PhD)

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<p> Challenges to the diagnostic accuracy of standardized tests of language can make the utility of these measures on their own, problematic. Consequently, this research program uses tools of conversational analysis to study the speech of preschoolers and young adults.</p> <p> In the first of three studies we examine, from a purely data-driven approach, how conversational measures relate to one another and compare with WPPSI-III expressive and receptive vocabulary scores in assessing preschoolers' language. Mean length of utterance (MLU) was found to be the only conversation measure strongly related to WPPSI-III language scores. However, other conversation measures constituted reasonably stable factors that may have utility for children's language assessment.</p> <p> The second study uses the same sample of children to investigate what features of language best predict behavioural and emotional problems and whether conversation measures provide better prediction of these symptoms than standardized scores. Results indicated that conversation measures of language significantly improved prediction of Child Behavior Checklist (CBCL C-TRF) DSM-oriented and syndrome scales beyond that accounted for by WPPSI GLC scores.</p> <p> Finally, the third study uses conversational analysis to study the role of disfluencies in the speech of young adults with and without autism spectrum disorders (ASDs) to determine whether these features of speech serve listener or speaker-oriented functions. Individuals with ASD were observed to produce fewer filled pause words (ums and uhs) and revisions than controls, but more silent pauses. Filled-pause words, therefore, appear to be listener-oriented features of speech.</p> <p> Taken together, findings of this program of research highlight the importance of using conversational analysis as an alternative or in addition to standardized tests of language as well as inform what specific measures of language are best suited for this purpose.</p> / Thesis / Doctor of Philosophy (PhD)

No description available.

No description available.

No description available.

No description available.

Concussions are diffuse injuries that affect areas of the brain responsible for a person's physical, cognitive, and emotional health. Although concussions were once thought only to present transient symptoms, mounting evidence suggests potential for long-term neurological impairments. The deleterious effects of concussion can be from a single, high severity impact event or the accumulation of lower severity impacts. Clinical changes that can result from concussion include an elevated symptom presentation and changes in gait, or an individual's walking pattern. It is not well understood if similar deficits result after an accumulation of subconcussive impacts. The majority of research on human tolerance to head injury has been based on American football, using helmet-mounted sensors in male athletes. Limited studies have attempted to quantify biomechanical tolerance in women, despite the sex-specific nature of presentation and outcome of concussion. Biomechanical, physiologic, and psychosocial factors differ between males and females, likely contributing to this difference. The research presented in this dissertation was aimed at describing sex-specific outcomes of subconcussion in a matched cohort of male and female athletes to gain a better sense of unhelmeted, sex-specific tolerance to head impacts. On-field data were collected from collegiate rugby players using instrumented mouthguards. Rugby involves high energy, frequent head impacts, does not require protective headgear, and is played the same for both men and women. The females in our study sustained fewer impacts per session than the males, but their impacts had similar linear acceleration magnitudes. The kinematics of the concussive male impacts were higher than the kinematics of the concussive female impacts. Both sexes reported concussion-like symptoms in the absence of diagnosed concussion during a season. Females reported more symptoms with a higher severity in-season compared to males after subconcussive and concussive impacts. Female athletes saw deficits in cadence, double support time, gait speed, and stride length post-concussion. The majority of athletes improved in their dual-task gait assessment by the end of the season, suggesting there may not be a negative effect on gait after an accumulation of subconcussive impacts. This work assessed the biomechanics of head impacts and concussions of this population, and evaluated changes in symptom presentation through weekly graded symptom surveys and dual-task gait assessments both after a concussion and as an effect of subconcussive impacts. Understanding the sex-specific clinical effects of head impacts is critical, and can provide insight into concussion diagnostic, management, and prevention tools that are appropriate and effective. / Doctor of Philosophy / Concussions are injuries that affect many areas of the brain, including those responsible for a person's physical, cognitive, and emotional health. Although concussions were once thought only to present transient symptoms, mounting evidence suggests potential for long-term neurological impairments. The harmful effects of concussion can be from a single, high intensity impact event or the build-up of lower intensity impacts. Clinical changes that can result from concussion include an elevated symptom presentation and changes in gait, or an individual's walking pattern. It is not well understood if similar side effects result after an accumulation of subconcussive impacts. The majority of research on human tolerance to head injury has been based on American football, using helmet-mounted sensors in male athletes. Limited studies have attempted to quantify concussion tolerance in women, despite the differences in men and women's symptoms and recovery time after a concussion. Female's neck strength, hormones, and increased honesty in reporting concussion differ from males, likely contributing to this difference. The research presented in this dissertation was aimed at describing how sex affects the results of subconcussion in a group of male and female athletes to gain a better sense of unhelmeted, sex-specific tolerance to head impacts. On-field data were collected from collegiate rugby players using sensor-embedded mouthguards. Rugby involves high energy, frequent head impacts, does not require protective headgear, and is played the same by both men and women. The females in our study sustained fewer impacts per session than the males, but their impacts were similar in magnitude. The impact energies of the concussive male impacts were higher than those of the concussive female impacts. Both sexes reported concussion-like symptoms in the absence of diagnosed concussion during a season. Females reported more symptoms with a higher severity in-season compared to males after subconcussive and concussive impacts. Female athletes had a slower walking pace and walking speed, a shorter stride length, and spent more time with both feet on the ground post-concussion. The majority of athletes improved in their dual-task gait assessment by the end of the season, suggesting there may not be a negative effect on gait after an accumulation of subconcussive impacts. This work assessed the biomechanics of head impacts and concussions of this population, and evaluated changes in symptom presentation through weekly graded symptom surveys and dual-task gait assessments both after a concussion and as an effect of subconcussive impacts. Understanding the sex-specific clinical effects of head impacts is critical, and can provide insight into concussion diagnostic, management, and prevention tools that are appropriate and effective.

Chronic kidney disease (CKD) is a multifaceted health problem with both physical and psychological manifestations. Increased symptom burden is associated with higher risk of mortality, decreased treatment adherence, and impaired quality of life. Despite the recognition of the importance of symptoms, the symptoms and mental health of individuals with CKD remain poorly understood in terms of their measurement, epidemiology and associated service use. The chapters in this dissertation aim to inform these knowledge gaps. Chapter 2 focusses on the symptom burden of patients receiving maintenance hemodialysis treatment and uses exploratory analyses to identify intra-dialytic symptom clusters associated with prolonged dialysis treatment recovery time. Chapters 3 and 4 are population-based studies examining mental health and addictions service utilization in patients with CKD using administrative data in Ontario, Canada. Chapter 3 is a cross-sectional study evaluating the prevalence of individuals with a history of mental health and addiction service use by levels of kidney function. Chapter 4 is a retrospective cohort study evaluating the rates of mental health and addiction service use over time in patients with CKD. Together, these chapters provide further understanding of how symptoms of dialysis and mental health and addiction service use may be measured in this patient population. They also inform considerations for the design of future symptom management and system-level mental health strategies in CKD. / Thesis / Doctor of Philosophy (PhD)