Parkinson disease (PD) is the second most common neurodegenerative disease worldwide, with estimates suggesting that PD prevalence and incidence will increase with aging populations. Therapeutic options and clinical guidelines for PD have significantly changed over the past 15 years; however, pharmacoepidemiology data in PD are lacking, especially regarding adverse effects of non-ergot dopamine agonists (DAs) and outcomes associated with anticholinergic burden. The objectives of this doctoral research are threefold: 1) examine patterns of antiparkinson drug use in relation to clinical guideline publication, drug availability, and emerging safety concerns; 2) determine whether PD patients treated with non-ergot DAs are at increased risk of adverse cardiovascular or cerebrovascular outcomes; and 3) determine whether anticholinergic burden is associated with adverse outcomes in PD. Specific research questions were investigated using epidemiological methods and electronic health data from Cerner Health Facts®, an electronic medical record database that stores time-stamped patient records for more than 300 Cerner subscribing facilities across the United States. Findings from this work are reported in a series of manuscripts, all of which have been published. Key findings include: 1) DA use began declining in 2007, from 34% to 27% in 2012. The decline followed publication of the American Academy of Neurology’s practice parameter refuting levodopa toxicity, pergolide withdrawal, and pramipexole label revisions; 2) heart failure was the only adverse cardiovascular or cerebrovascular outcome that demonstrated a significant association with non-ergot DA use, mainly pramipexole; and 3) anticholinergic burden in PD was associated with the diagnosis of fracture and delirium, and significantly increased the risk of emergency department visit and readmission post inpatient discharge. Reported antiparkinson prescribing trends suggest that safety and best practice information may be communicated effectively in PD. Although findings warrant replication, individuals with PD and independent risk factors for or a history of heart failure may benefit from limited use of pramipexole. Similarly, individuals with PD may benefit from substituting non-PD medications with anticholinergic effects for equally effective non-anticholinergic agents. Additional pharmacovigilance studies are needed to better understand health risks and the impact of population health interventions in PD.

<p>Background</p> <p>Adults with cerebral palsy (CP) may have special health care considerations related to an increased prevalence of risk factors for chronic diseases. In particular, disability-related sedentary time may increase the risk of cardiovascular disease and the related major adverse cardiovascular events (MACE) in this population.</p> <p>Methods</p> <p>Part I: A systematic review of major databases, trial registries, and conference abstracts identified randomized trials and observational studies exploring the prevalence and evaluating the prevention of MACE and risk factors for MACE in adults with CP. Title and abstract, data extraction, and quality of reporting assessment were completed in duplicate.</p> <p>Part II: A secondary analysis of Canadian census data evaluated the crude and adjusted risk of stroke in adults with CP and compared the crude risk with other Canadian adults with spinal cord injury, acquired brain injury, and epilepsy. All risks were reported as an odds ratio (OR) with 95% confidence intervals.</p> <p>Results</p> <p>Part I: 2281 unique articles were screened to provide 10 cross-sectional studies. No studies evaluated any interventions for MACE or risk factors for MACE. The most common risk factor studied was obesity. Two studies showed an increased in death due to circulatory diseases.</p> <p>Part II: Crude risk of stroke to CP was OR=12.5 (12.2-12.9). Mediation effects or multicollinearity was not observed. The adjusted risk of stroke was OR=7.9 (1.8-34.2). Elevated crude risk of stroke was also noted in patients with acquired brain injury (OR=16.2 [16.0-16.5]), spinal cord injury (OR=6.1 [6.0-6.3]), and epilepsy (OR=6.2 [6.0-6.3]).</p> <p>Conclusions</p> <p>This thesis provides a preliminary overview of the risk of MACE in adults with CP and hypothesis generating evidence for further research in this population. A prospective cohort study is urgently needed assess the implications of these findings. Adults with CP should minimize exposure to modifiable risk factors as much as possible.</p> / Master of Science (MSc)

<p> Meta-analysis is a statistical method to summarize the overall evidence of effects on intervention by systematically combining outcomes from available studies in the literature which are homogeneous in research methodology and research interest. The objective of this project is to evaluate the treatment effects of preoperative aspirin on bleeding and other cardiovascular outcomes from 11 randomized control trials (RCT) and 19 observational (non-RCT) studies. Both Bayesian meta-analysis and classical (frequentist) meta-analysis were applied to continuous and binary outcomes, and the results were compared.</p> <p> The robustness of the Bayesian approach is assessed by examining the performances of different likelihood functions and priors. We also discuss strategies on dealing with zero-event studies for binary outcomes, and the implementation of multiple imputation (MI) technique to missing data for continuous outcomes.</p> <p> Most results of primary analysis agree between the Bayesian and classical approaches. We suggest that the final conclusion of a meta-analysis should be based on the comparison of the results from both Bayesian and classical approaches.</p> / Thesis / Master of Science (MSc)

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-10-13T18:19:07Z No. of bitstreams: 1 arisegarciadesiqueiragalil.pdf: 700408 bytes, checksum: bda59712c26407e09b49f3dd136c52b2 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-10-22T13:00:41Z (GMT) No. of bitstreams: 1 arisegarciadesiqueiragalil.pdf: 700408 bytes, checksum: bda59712c26407e09b49f3dd136c52b2 (MD5) / Made available in DSpace on 2016-10-22T13:00:41Z (GMT). No. of bitstreams: 1 arisegarciadesiqueiragalil.pdf: 700408 bytes, checksum: bda59712c26407e09b49f3dd136c52b2 (MD5) Previous issue date: 2008-02-15 / Introdução: A insuficiência cardíaca (IC) tem alta morbimortalidade que decorre de fatores causais e refratariedade ao tratamento. A doença renal crônica (DRC) e a anemia têm se associado a pior prognóstico em pacientes com IC grave, especialmente os hospitalizados. Há, porém, poucos estudos que avaliem a prevalência e as conseqüências da DRC e da anemia em pacientes com IC acompanhados ambulatorialmente. Objetivos: Avaliar a prevalência da DRC e anemia e o impacto de desfechos cardiovasculares em portadores de IC sistólica estágios B e C. Pacientes e Métodos: Foram estudados pacientes adultos, com idade >18 anos e diagnóstico de IC sistólica e com fração de ejeção (EF) ≤45%, selecionados do ambulatório do Serviço de Hipertensão, Diabetes e Obesidade do SUS de Juiz de Fora e acompanhados por 12 meses. A anemia foi definida como hemoglobina <12,0g/dl nas mulheres e <13,0g/dl nos homens. A reserva de ferro foi considerada adequada quando índice de saturação da transferrina encontrava-se ≥20% e a ferritina ≥100ηg/dl. A filtração glomerular foi estimada pela fórmula do estudo MDRD e a DRC foi definida como proposto pelo K/DOQI da National Kidney Foundation americana. Considerou-se com desfechos cardiovasculares (CV) a ocorrência de hospitalização e/ou morte decorrente da IC. Os dados demográficos, de exame físico e laboratorial foram obtidos do prontuário dos pacientes. Resultados: Foram avaliados 83 pacientes, com idade média de 62,7±12 anos, sendo 56,6% do sexo feminino. A média da fração de ejeção (FE) foi de 37,8+7,9% e a maioria dos indivíduos (60,2%) estava no estágio C. A prevalência de anemia foi de 24,09%; 30,30% no estágio B e 20% no estágio C. A prevalência de DRC foi elevada, presente em 49,4% da amostra, 42,4% no estágio B da IC e 54% no estágio C. Todos os pacientes com anemia tinham reserva de ferro normal e 68,6% apresentavam DRC concomitante. Os desfechos CV ocorreram em 26,5% da amostra. Na estratificação dos pacientes nos estágios B e C da IC e presença ou não de DRC, evidenciou que 100% e 64,7% apresentaram desfechos, respectivamente. Na análise multivariada, após ajustes para fatores prognósticos no período basal, o diagnóstico de DRC aumentou em 3,6 vezes a possibilidade de desfechos (IC 95%1,04-12,67, p=0,04), enquanto os níveis mais elevados de sódio sérico (R 0,807, IC95%0,862-0,992, p=0,03) e da fração de ejeção (R 0,925, IC95% 0,862-0,942, p= 0,03) se mostraram protetores. Conclusão: Na coorte de pacientes estudada, composta de pacientes com IC estágios B e C, a ocorrência de anemia foi compatível com a observada em outros estudos e com tendência de se associar com menor filtração glomerular. A DRC foi prevalente e independentemente se associou a maior risco de hospitalizações e mortes secundárias à descompensação cardíaca, especialmente nos pacientes assintomáticos. / Introduction: Chronic heart failure (CHF) has a high morbidity and mortality which are consequent to etiologic factors and no response to treatment. Anemia and chronic kidney disease (CKD) have been associated to worse outcome in patients with severe hospitalized CHF. So far, there is few studies that assessed the prevalence and the consequences of anemia and CKD in outpatients with CHF. Aim: To study the prevalence of CKD and anemia and the impact of CV end points in patients with systolic CHF followed in an outpatient clinic. Methods: This is prospective cohort study, dealing with adult patients older than 18 years of age and diagnosis of systolic CHF and ejection fraction (EF) ≤45%, selected from the Hypertension, Diabetes and Obesity Outpatient Clinic of SUS of Juiz de Fora. Anemia was defined as hemoglobin <12,0g/dL in women and <13g/dL in men and women after the menopause. Normal iron store was defined when transferring saturation index was >20% and/or ferritin >100ηg/dL. The glomerular filtration rate was estimated from serum creatinine usinf the MDRD study formula, and CKD was defined as suggested by the K/DOQI of National Kidney Foundation. CV endpoints were defined as death or hospitalization due to CHF, in 12 months follow up. Demographic and clinical date were obtained from the patients’ charts. Results: Eight three patients were studied, the mean age was 62.7±12 years, and 56.6% were female. The EF was 37,8+7,9%, and the majority of the patients had stage C CHF (60,2%). The prevalence of anemia was 24,1%; 30,3% in stage B and 50% in stage C. CKD was diagnosed in 49.4% of the patients, 42,4% of the stage B and 54% in the stage C. All patients with anemia had normal iron storage, and 68,6% had concomitant CKD. Cardiovascular endpoints were observed in 26.5% of the patients. When the sample was stratified in stages B and C of CHF and presence or absence of CKD, it was found that 100% and 64.7% had CV endpoints, respectively. After adjustments for all other prognostic factors at baseline, it was observed that the diagnosis of CKD increased in 3.6 folds the hazard of CV endpoints (CI 95% 1,04-12,67, p=0,04), whereas higher ejection fraction (R 0,925, IC 95% 0,862-0,942, p= 0,03) and serum sodium (R 0,807, IC 95% 0,862-0,992, p=0,03) were protectors. Conclusion: In this cohort of outpatients with CHF stages B and C, the occurrence of anemia was low and frequently associated with concomitant CKD. On the other hand, CKD was prevalent and independently associated with heightened risk for hospitalization and death secondary of cardiovascular causes, mainly in asymptomatic patients.