Indiana University-Purdue University Indianapolis (IUPUI) / Observational studies offer unique advantages over randomized clinical trials (RCTs) in many situations where RCTs are not feasible or suffer from major limitations such as insufficient sample sizes and narrowly focused populations. Because observational data are relatively easy and inexpensive to access, and contain rich and comprehensive demographic and medical information on large and representative populations, they have played a major role in the assessment of the effectiveness and safety of medical interventions. However, observational data also have the challenges of higher rates of missing data and the confounding effect. My proposal is on the development of three statistical methods to address these challenges. The first method is on the refinement and extension of a multiply robust (MR) estimation procedure that simultaneously accounts for the confounding effect and missing covariate process, where we derived the asymptotic variance estimator and extended the method to the scenario where the missing covariate is continuous. The second method focuses on the improvement of estimation precision in an RCT by a historical control cohort. This was achieved through augmenting the conventional effect estimator with an extra mean zero (approximately) term correlated with the conventional effect estimator. In the third method, we calibrated the hidden database bias of an electronic medical records database and utilized an empirical Bayes method to improve the accuracy of the estimation of the risk of acute myocardial infarction associated with a drug by borrowing information from other drugs.

Bakgrund: När sjukvården till stor del förlitar sig på medicinsk teknik och läkemedelsbehandling är det lätt att omvårdnadsåtgärder som syftar till att förebygga och lindra lidande inte ges tillräckligt utrymme. Intensivvårdsdelirium är ett förhållandevis outforskat område inom barnintensivvården. Idag finns inga riskskattningsinstrument översatta till svenska.   Syfte: Syftet var att studera barns beteenden när de vårdades på en barnintensivvårdsavdelning. Dessutom undersöktes om dessa beteenden kunde användas för att besvara frågor från ett engelskspråkigt riskskattningsinstrument för delirium.   Metod: Studien utfördes som en fokuserad etnografisk observationsstudie där sju patienter på en barnintensivvårdsavdelning observerades under tre timmar vardera. Utifrån observationernas fältanteckningar gjordes en innehållsanalys med fokus på manifest innehåll. I ett andra steg utfördes en deduktiv analys där kategorierna från fältanteckningarna jämfördes mot frågor från riskskattningsinstrumentet för delirium.   Resultat: Innehållsanalysen av fältanteckningarna resulterade i åtta kategorier som representerade barnens beteende under observationerna: reagerar på vårdhandling, förmedlar fysiska behov, förmedlar smärta, svarar på fråga, sysselsätter sig själv, stimuleras av underhållning, uppmärksammar omgivningen och väcks av stimuli. Den deduktiva innehållsanalysen visade att fyra av de åtta frågorna från riskskattningsinstrumentet kunde besvaras med hjälp av kategorierna.   Slutsats: Urvalet bestod av en homogen subgrupp där inga beteenden med tydlig koppling till risk för delirium kunde observeras. Miljörelaterade riskfaktorer för delirium i form av frekventa vårdhandlingar, höga ljud och störd sömn förekom. Trots att denna grupp patienter inte visade tecken på delirium kan förebyggande av dessa störningar leda till minskat vårdlidande. Barnintensivvården kan ytterligare minska vårdlidande genom att öka föräldrarnas möjligheter att vara hos sitt sjuka barn dygnet runt. / Background: Nursing and preventive measures may be overlooked when health care in large relies on medical technology and medical treatment. Intensive care delirium is a relatively unexplored area in pediatric intensive care. There are currently no risk assessment tools translated to Swedish.   Aim: The objective was to study children's behaviour when they were cared for in a pediatric intensive care unit. In addition, it was questioned whether these behaviours where able to answer questions originating from an English language risk assessment tool for delirium.   Method: Using focused ethnographic observation seven patients were observed during three hours each. Content analysis was performed on the field notes from the observations with focus on manifest content. As a second step, a deductive analysis compared the categories with questions from the risk assessment tool for delirium.   Findings: The content analysis of field notes resulted in eight categories which represented the children’s behavior during the observations: reacting to care, expressing physical needs, expressing pain, answering question, occupying oneself, stimulated by entertainment, observing the surroundings and awakened by stimulus. The deductive analysis showed that four of the eight questions from the risk assessment tool could be answered with the categories.   Conclusion: The selection consisted of a homogenous subgroup where no obvious behaviors related to risk of delirium was observed. Environmental risk factors for delirium such as frequent care related interventions, loud noise and disturbed sleep where observed. Despite that, prevention of these disturbances could reduce health care related suffering even though this group of patients did not show signs of delirium. Pediatric intensive care units can further reduce healthcare related suffering by enabling families to be present with their sick child during all hours of the day and night.

Statins are cholesterol-lowering medications with immunologic properties. To assess the role of statins on incident immune-mediated conditions, a modified case-cohort study was performed using administrative databases from the Midwest Veterans Administration (VA) region. A comparison sub-cohort was formed by randomly sampling 10,000 subjects with medical and pharmacy benefits during fiscal year (FY) 2002. Cases were identified by inpatient or outpatient medical claims using International Classification of Disease, Ninth Revision (ICD-9) codes between FY 2003-2004. All subjects needed at least one year of medical claims and at least one pharmacy claim. The incident cases (n=28,642) included non-mutually exclusive groups of immune-mediated (n=2,327), infectious (n=8,221), and non-immunologic (n=10,730) diagnoses. Demographic and medical variables were obtained from FY 2001-2004, and pharmacologic data from FY 2002-2004. Cox proportional hazards regression modeling was used to estimate hazard ratios for the current statin use (within the last 180 days) and former statin use, compared to non-users, including time-dependant variables for demographic factors, comorbidity as measured by Elixhauser and Chronic Disease Score variables, medications, and visit rates after initiating statins. Current statin use was associated with decreased diagnoses rates of psoriasis; rheumatoid arthritis; inflammatory bowel diseases, including ulcerative colitis and Crohn disease; diffuse connective tissue diseases, including systemic lupus erythematosus; ankylosing spondylitis; bacterial pneumonia; urinary tract infection; cellulitis; sepsis; candidiasis; osteomyelitis; and tuberculosis. Former statin use was also associated with increased rates of polymyalgia rheumatica, sepsis, and osteomyelitis. Statin use was not associated with other spondylitis, multiple sclerosis, thyroiditis, sarcoidosis, temporal arteritis, influenza, shingles, histoplasmosis, or pyelonephritis. Although current statin use appeared protective for some study conditions, selection bias, misclassification, healthy user effects, adherence bias, confounding by indication, and surveillance bias were considered as possible explanations of the study findings.

This multi-method study provides detailed information about the friendships of 87 children with ADHD (77.0% boys) and 46 comparison children (73.9% boys) between the ages of 7 and 13. The methods used in the study included parent and teacher ratings, self-report measures, and direct observation of friends’ dyadic behaviours in three structured analogue tasks. Results indicated that, in contrast with comparison children, children with ADHD had friends with high levels of ADHD and oppositional symptoms; they perceived fewer positive features and more negative features, and were less satisfied in their friendships. Observational data indicated that children with ADHD performed both more legal and more illegal manoeuvres than comparison children in a fast-paced competitive game. While negotiating with their friends, children with ADHD made more insensitive and self-centred proposals than comparison children. In dyads consisting of one child with ADHD and one typically developing child, children with ADHD were often more controlling than their non-diagnosed friends. Globally, these results were robust and did not seem to be affected by age differences, ADHD subtypes, comorbidities, and medication status. Given the increased recognition of ADHD in adolescence and adulthood as well as the fact that negative peer reputation in childhood very strongly predicts mental-health status by early adulthood, this research may lead to the discovery of meaningful ways to help people with ADHD achieve improved mental health and happiness over their lifespan.

This multi-method study provides detailed information about the friendships of 87 children with ADHD (77.0% boys) and 46 comparison children (73.9% boys) between the ages of 7 and 13. The methods used in the study included parent and teacher ratings, self-report measures, and direct observation of friends’ dyadic behaviours in three structured analogue tasks. Results indicated that, in contrast with comparison children, children with ADHD had friends with high levels of ADHD and oppositional symptoms; they perceived fewer positive features and more negative features, and were less satisfied in their friendships. Observational data indicated that children with ADHD performed both more legal and more illegal manoeuvres than comparison children in a fast-paced competitive game. While negotiating with their friends, children with ADHD made more insensitive and self-centred proposals than comparison children. In dyads consisting of one child with ADHD and one typically developing child, children with ADHD were often more controlling than their non-diagnosed friends. Globally, these results were robust and did not seem to be affected by age differences, ADHD subtypes, comorbidities, and medication status. Given the increased recognition of ADHD in adolescence and adulthood as well as the fact that negative peer reputation in childhood very strongly predicts mental-health status by early adulthood, this research may lead to the discovery of meaningful ways to help people with ADHD achieve improved mental health and happiness over their lifespan.

This multi-method study provides detailed information about the friendships of 87 children with ADHD (77.0% boys) and 46 comparison children (73.9% boys) between the ages of 7 and 13. The methods used in the study included parent and teacher ratings, self-report measures, and direct observation of friends’ dyadic behaviours in three structured analogue tasks. Results indicated that, in contrast with comparison children, children with ADHD had friends with high levels of ADHD and oppositional symptoms; they perceived fewer positive features and more negative features, and were less satisfied in their friendships. Observational data indicated that children with ADHD performed both more legal and more illegal manoeuvres than comparison children in a fast-paced competitive game. While negotiating with their friends, children with ADHD made more insensitive and self-centred proposals than comparison children. In dyads consisting of one child with ADHD and one typically developing child, children with ADHD were often more controlling than their non-diagnosed friends. Globally, these results were robust and did not seem to be affected by age differences, ADHD subtypes, comorbidities, and medication status. Given the increased recognition of ADHD in adolescence and adulthood as well as the fact that negative peer reputation in childhood very strongly predicts mental-health status by early adulthood, this research may lead to the discovery of meaningful ways to help people with ADHD achieve improved mental health and happiness over their lifespan.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23810号 / 医博第4856号 / 新制||医||1058(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 高橋 淳, 教授 伊佐 正, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

This multi-method study provides detailed information about the friendships of 87 children with ADHD (77.0% boys) and 46 comparison children (73.9% boys) between the ages of 7 and 13. The methods used in the study included parent and teacher ratings, self-report measures, and direct observation of friends’ dyadic behaviours in three structured analogue tasks. Results indicated that, in contrast with comparison children, children with ADHD had friends with high levels of ADHD and oppositional symptoms; they perceived fewer positive features and more negative features, and were less satisfied in their friendships. Observational data indicated that children with ADHD performed both more legal and more illegal manoeuvres than comparison children in a fast-paced competitive game. While negotiating with their friends, children with ADHD made more insensitive and self-centred proposals than comparison children. In dyads consisting of one child with ADHD and one typically developing child, children with ADHD were often more controlling than their non-diagnosed friends. Globally, these results were robust and did not seem to be affected by age differences, ADHD subtypes, comorbidities, and medication status. Given the increased recognition of ADHD in adolescence and adulthood as well as the fact that negative peer reputation in childhood very strongly predicts mental-health status by early adulthood, this research may lead to the discovery of meaningful ways to help people with ADHD achieve improved mental health and happiness over their lifespan.

Hip fractures are common injuries with devastating consequences, including high rates of morbidity and mortality. The purpose of my thesis was to lay the foundation for further research which can fully explore: i) the epidemiology of morbidity and mortality following hip fracture; ii) risk factors for poor outcomes following hip fracture; iii) causes and pathways to mortality following hip fracture; iv) secondary prevention of morbidity and mortality following hip fracture; and v) potential interventions to improve outcomes following hip fracture. To this end, I will first detail the design, execution, results, and ‘lessons learned’ of a prospective observational pilot cohort study that recruited 100 consecutive patients aged ≥18 years presenting with a hip fracture to the Juravinski Hospital and Cancer Centre of the Hamilton Health Sciences. The primary aim of this pilot study was to assess the feasibility of a larger prospective international cohort study. Second, I will present a systematic review and meta-analysis of a promising intervention that consisted of multi-disciplinary (specifically geriatrician-led) co-management of hip fracture patients. This intervention has previously been shown to reduce mortality and length of stay following hip fracture. The meta-analysis presented will determine the effectiveness of this intervention in reducing the incidence, duration, and severity of delirium—a common condition following hip fracture. / Thesis / Master of Science (MSc)

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