Background : The majority of patients with Crohn’s Disease (CD) will be hospitalized and receive surgery for their disease. Hospitalizations and surgical procedures account for the majority of the direct costs of CD. Purpose : Our objective was to use population-based administrative data from the province of Quebec, Canada, to estimate the effectiveness of infliximab therapy in reducing CD-related surgery, hospitalization and health care resource consumption in subjects with CD. Methods : We obtained patient level prescription data, physician billing claims and hospitalization data from the Régie de l'Assurance Maladie du Québec (RAMQ) a Canadian provincial health care provider. Subjects who were enrolled in the system for a minimum of two years and who received prescription drug benefits for each year they participated in the study were identified as being affected by CD using a validated algorithm. For each subject treated with infliximab, up to two closely matched comparison subjects were selected using propensity score methods. We compared time to first CD-related intra-abdominal surgery and hospitalization as well as total hospitalized days and physician visits between infliximab users and non-users. Results : We were able to match 319 (77%) out of the 414 infliximab users to comparison subjects using propensity score matching; 300 were matched to two infliximab non-users and 19 were matched to one non-user to create 619 matched-pair sets. Subjects who received infliximab therapy had a significantly reduced risk of experiencing a CD-related intra-abdominal surgery (HR=0.674, 95%CI 0.533-0.853, p=0.001), any hospitalization (HR=0.753, 95%CI 0.619-0.917 p=0.005), and CD-related hospitalization (HR=0.726, 95%CI 0.565-0.934 p=0.013). Infliximab users experienced lower rates of hospitalized days (RateR=0.6418, 95%CI 0.4399-0.9362; P=0.021) and gastroenterologist visits (RateR=0.810, 95% CI 0.700-0.937; P=0.005). Infliximab users and non-users had similar rates of non-gastroenterologist physician visits (RateR=0.928, 95% CI 0.851-1.057; P=0.262). Conclusion : Infliximab therapy was associated with significant reductions in CD-related intra-abdominal surgeries, hospitalizations, hospitalized days and gastroenterologist visits. Our results confirm the population-based effectiveness of infliximab beyond the ideal conditions of clinical trials.

No description available.

Serious safety concerns have been raised recently about the use of second generation antipsychotics (SGAs), in young patients. In this population based study, utilization of antipsychotics use in the youth population of Manitoba between 1996 and 2011 was determined. Rates of adverse events (diabetes, hypertension, EPS) were compared among the users of SGAs. School enrolment and high school completion rates were evaluated for young users. Databases from the Population Health Research Data Repository, housed at the Manitoba Centre of Health Policy were accessed. Increased utilization (prevalence: 2.3 to 9 per 1,000 persons; incidence: 1.2 to 2.7 per 1,000 between 2001 and 2011) of SGAs was observed in the youth population of MB. The most common diagnosis recorded were Attention Deficit Hyperactivity Disorder (56.8%), Conduct Disorders (38%) and Mood Disorders (22.7%). Olanzapine therapy seemed to be associated with a higher risk of hypertension compared to risperidone users (HR: 2.52, 95% CI: 1.20 – 5.29). Risperidone users seemed to be at higher risk of EPS than quetiapine users (HR: 0.46, 95% CI: 0.26 – 0.82). School enrolment of SGAs users appeared to be comparable to those reported for the general population. High school completion rates may be lower than those of the general population.

Background : The majority of patients with Crohn’s Disease (CD) will be hospitalized and receive surgery for their disease. Hospitalizations and surgical procedures account for the majority of the direct costs of CD. Purpose : Our objective was to use population-based administrative data from the province of Quebec, Canada, to estimate the effectiveness of infliximab therapy in reducing CD-related surgery, hospitalization and health care resource consumption in subjects with CD. Methods : We obtained patient level prescription data, physician billing claims and hospitalization data from the Régie de l'Assurance Maladie du Québec (RAMQ) a Canadian provincial health care provider. Subjects who were enrolled in the system for a minimum of two years and who received prescription drug benefits for each year they participated in the study were identified as being affected by CD using a validated algorithm. For each subject treated with infliximab, up to two closely matched comparison subjects were selected using propensity score methods. We compared time to first CD-related intra-abdominal surgery and hospitalization as well as total hospitalized days and physician visits between infliximab users and non-users. Results : We were able to match 319 (77%) out of the 414 infliximab users to comparison subjects using propensity score matching; 300 were matched to two infliximab non-users and 19 were matched to one non-user to create 619 matched-pair sets. Subjects who received infliximab therapy had a significantly reduced risk of experiencing a CD-related intra-abdominal surgery (HR=0.674, 95%CI 0.533-0.853, p=0.001), any hospitalization (HR=0.753, 95%CI 0.619-0.917 p=0.005), and CD-related hospitalization (HR=0.726, 95%CI 0.565-0.934 p=0.013). Infliximab users experienced lower rates of hospitalized days (RateR=0.6418, 95%CI 0.4399-0.9362; P=0.021) and gastroenterologist visits (RateR=0.810, 95% CI 0.700-0.937; P=0.005). Infliximab users and non-users had similar rates of non-gastroenterologist physician visits (RateR=0.928, 95% CI 0.851-1.057; P=0.262). Conclusion : Infliximab therapy was associated with significant reductions in CD-related intra-abdominal surgeries, hospitalizations, hospitalized days and gastroenterologist visits. Our results confirm the population-based effectiveness of infliximab beyond the ideal conditions of clinical trials.

The safety of antipsychotic use in elderly persons has recently been questioned. The incidence of adverse events (AEs) (extrapyramidal syndromes (EPS), cerebrovascular and cardiac events, and all-cause mortality) in the elderly users of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) was compared. Risks of AEs in antipsychotic-exposed persons and non-exposed individuals were also assessed. A population-based retrospective cohort study was conducted in the elderly Manitoba residents who received their first antipsychotic medication between April 1, 2000 and March 31, 2007. Cox proportional hazards models were built to compare risks of AEs in FGA and SGA users, as well as in non-exposed subjects. SGAs were associated with a lower risk of all-cause mortality (adjusted HR 0.683, 95% CI 0.577–0.809) and a higher risk of myocardial infarction (1.614 [1.024–2.543]) compared to FGAs. No significant differences between FGAs and SGAs were found for cerebrovascular events, cardiac arrhythmia and congestive heart failure (CHF) but a higher incidence of EPS was observed for FGAs compared to risperidone. Both FGA and SGA users were at a higher risk of cerebrovascular events (FGAs 1.415 [1.114–1.797]; SGAs 1.611 [1.388–1.869]) and CHF (FGAs 1.228 [0.893–1.689]; SGAs 1.242 [1.003–1.536]) compared to non-exposed subjects. Only FGA-users were at a higher risk of death compared to non-exposed subjects (FGAs 1.387 [1.065–1.805]; SGAs 0.824 [0.708–0.959]). Both FGA and risperidone use were associated with a higher risk of EPS (FGAs 3.503 [2.271–5.403]; risperidone 1.733 [1.214–2.472]). Both classes of antipsychotics might lead to potentially life-threatening AEs. Neither FGAs nor SGAs seem to have a superior overall safety profile. Antipsychotic pharmacotherapy should be prescribed in elderly persons after careful consideration of all risks and benefits.

The safety of antipsychotic use in elderly persons has recently been questioned. The incidence of adverse events (AEs) (extrapyramidal syndromes (EPS), cerebrovascular and cardiac events, and all-cause mortality) in the elderly users of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) was compared. Risks of AEs in antipsychotic-exposed persons and non-exposed individuals were also assessed. A population-based retrospective cohort study was conducted in the elderly Manitoba residents who received their first antipsychotic medication between April 1, 2000 and March 31, 2007. Cox proportional hazards models were built to compare risks of AEs in FGA and SGA users, as well as in non-exposed subjects. SGAs were associated with a lower risk of all-cause mortality (adjusted HR 0.683, 95% CI 0.577–0.809) and a higher risk of myocardial infarction (1.614 [1.024–2.543]) compared to FGAs. No significant differences between FGAs and SGAs were found for cerebrovascular events, cardiac arrhythmia and congestive heart failure (CHF) but a higher incidence of EPS was observed for FGAs compared to risperidone. Both FGA and SGA users were at a higher risk of cerebrovascular events (FGAs 1.415 [1.114–1.797]; SGAs 1.611 [1.388–1.869]) and CHF (FGAs 1.228 [0.893–1.689]; SGAs 1.242 [1.003–1.536]) compared to non-exposed subjects. Only FGA-users were at a higher risk of death compared to non-exposed subjects (FGAs 1.387 [1.065–1.805]; SGAs 0.824 [0.708–0.959]). Both FGA and risperidone use were associated with a higher risk of EPS (FGAs 3.503 [2.271–5.403]; risperidone 1.733 [1.214–2.472]). Both classes of antipsychotics might lead to potentially life-threatening AEs. Neither FGAs nor SGAs seem to have a superior overall safety profile. Antipsychotic pharmacotherapy should be prescribed in elderly persons after careful consideration of all risks and benefits.

Orientadores: Marilisa Berti de Azevedo Barros, Priscila Maria Stoless Bergamo Francisco / Dissertação (mestrado) - Universidade Estadual de Campinas. Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-15T23:33:51Z (GMT). No. of bitstreams: 1 Costa_KarenSarmento_M.pdf: 5997477 bytes, checksum: 6d2ec607090eb98273bd84354bf2baba (MD5) Previous issue date: 2010 / Resumo: Os medicamentos tem sido considerados instrumentos terapêuticos fundamentais que produzem curas, prolongam a vida e retardam o surgimento de complicações associadas a doenças, sendo responsáveis por parte significativa da melhoria da qualidade e expectativa de vida da população. São vários os fatores que influenciam o uso de medicamentos, entre eles se destacam os aspectos demográficos, sócio-econômicos e culturais da população e as políticas governamentais para o setor e o mercado farmacêutico. Analisar o padrão de utilização e os fatores associados a esse uso justifica-se devido ao crescente consumo dos medicamentos e o alto investimento do Estado com a Política de Assistência Farmacêutica no país. Os inquéritos de saúde são instrumentos importantes para obter informações relativas a utilização de medicamentos pelos diferentes segmentos sociais da população. O objetivo do presente estudo e analisar a prevalência da utilização de medicamentos segundo variáveis demográficas, sócio-econômicas e de comportamentos relacionadas a saúde da população, identificando os fatores associados ao uso. Trata-se de um estudo transversal, cujos dados foram obtidos do inquérito ISA-SP. A população de estudo e residente da área urbana de Campinas, com idade igual ou superior a 18 anos. A amostragem foi realizada em múltiplos estágios, estratificada e por conglomerados. O período recordatorio do uso de medicamentos foi os 3 dias anteriores a realização da entrevista. Utilizou-se a classificação ATC para a codificação dos medicamentos. As estimativas de prevalência e as analises de regressão consideraram as ponderações relativas ao desenho amostral, utilizando o software STATA 8.0. Utilizou-se o teste qui-quadrado para verificar a associação estatística entre a variável dependente e as variáveis independentes. Foram estimadas razoes de prevalência ajustadas por sexo e idade e respectivos IC 95% utilizando regressão múltipla de Poisson. Foi desenvolvido um modelo hierárquico de regressão múltipla de Poisson para ajuste de variáveis de confundimento. A prevalência global do uso de medicamentos foi de 48,5%. Observou-se que mulheres referiram maior consumo de medicamentos que os homens e que a media de medicamentos aumentou com a idade em ambos os sexos. Apos ajuste por idade e sexo, observa-se que as variáveis religião, renda, numero de doenças crônicas, presença de morbidade nos últimos 15 dias e transtorno mental comum permaneceram significativamente associadas ao uso de medicamentos. No modelo hierarquizado final verificou-se consumo significativamente maior de medicamentos nas pessoas no sexo feminino, nas idades de 40 anos ou mais, renda familiar superior a 4 salários mínimos, religião evangélica, morbidade referida nos últimos 15 dias e apresentando doenças crônicas (uma a duas, três ou mais). Os medicamentos mais consumidos foram os que atuam no sistema cardiovascular, sistema nervoso e fitoterápicos. O perfil de utilização de medicamentos em Campinas encontra-se dentro dos parâmetros observados em outros estudos. Os resultados podem subsidiar ações da Política de Assistência Farmacêutica, visando a ampliação do acesso e a promoção do uso racional de medicamentos. / Abstract: The drugs have been considered key therapeutic tools that produce healing, prolong life and delay the onset of complications associated with diseases, accounting for a significant part of improving the quality and life expectancy of the population. There are several factors influencing the use of drugs, among them stand out the demographic, socioeconomic and cultural population and government policies for the sector and the pharmaceutical market. To analyze the pattern of use and factors associated with such use is justified due to the increasing consumption of drugs and the high investment from the State Pharmaceutical Assistance Policy in the country. Health surveys are important tools for information concerning the use of drugs by different social segments of the population. The aim of this study is to analyze the prevalence of use of medicines according to demographic, socioeconomic and health-related behaviors of the population, identifying the factors associated with use. This is a cross-sectional study with data obtained from the survey ISA-SP. The study population is resident in the urban area of Campinas, aged over 18 years. Sampling was performed in multiple stages, stratified by conglomerates. The recall period of drug use was the three days prior to the interview. We used the ATC classification for the coding of medicines. The prevalence estimates and regression analysis considered the weights from the sample design, using STATA 8.0. We used the chi-square test to verify the statistical association between the dependent and independent variables. We estimated adjusted prevalence ratios by sex and age and their respective 95% using Poisson multiple regression. We developed a hierarchical model of Poisson multiple regression to adjust for confounders. The overall prevalence of drug use was 48.5%. It was observed that women reported higher consumption of drugs than men and that the mean number of medications increased with age in both sexes. After adjusting for age and sex, it is observed that the variables of religion, income, number of chronic diseases, presence of morbidity in the last 15 days and common mental disorder remained significantly associated with drug use. In the final hierarchical model was found significantly higher consumption of medicines in people in females, ages 40 years or more family income than 4 minimum wages, evangelical religion, reported morbidity in the last 15 days and presenting chronic diseases (one two, three or more). Most frequently consumed drugs were acting on the cardiovascular system, nervous system and herbal medicines. The profile of drug utilization in Campinas is within the parameters observed in other studies. The results can support the actions of Pharmaceutical Policy, aimed at expanding access and promoting rational drug use. / Mestrado / Epidemiologia / Mestre em Saude Coletiva

Background: Inverse-probability-of-treatment-weighted estimation (IPTW) of marginal structural models was proposed to adjust for time-varying confounders that are influenced by prior treatment use. It is unknown whether pharmacoepidemiologic studies that applied IPTW conformed to the recommendations proposed by methodological studies. In addition, no previous study has compared the performance of different analytic strategies adopted in IPTW analyses. Objectives: This project aims 1) to review the reporting practice of pharmacoepidemiologic studies that applied IPTW, 2) to compare the validity and precision of several approaches to constructing weight, 3) to use IPTW to estimate the effectiveness of glucosamine and chondroitin in treating osteoarthritis. Methods: We systematically retrieved pharmacoepidemiologic studies that were published in 2012 and applied IPTW to estimate the effect of a time-varying treatment. Under a variety of simulated scenarios, we assessed the performance of four analytic approaches what were commonly used in studies conducting IPTW analyses. Finally, using data from Osteoarthritis Initiative, we applied IPTW to estimate the long-term effectiveness of glucosamine and chondroitin on treating knee osteoarthritis. Results: The practice of reporting use of IPTW in pharmacoepidemiologic studies was suboptimal. The majority of reviewed studies did not report that the positivity assumption was assessed, and several studies used unstablized weights or did not report that the stabilized weights were used. With data simulation, we found that intention-to-treat analyses underestimated the actual treatment effect when there was non-null treatment effect and treatment non-adherence. This underestimation was linearly correlated with adherence levels. As-treated analyses that took into account the complex mechanism of treatment use generated approximately unbiased estimates without sacrificing the estimate precision when the treatment effect was non-null. Finally, after adjustment for potential confounders with marginal structural models, we found no clinically meaningful benefits of glucosamine/chondroitin in relieving knee pain, stiffness and physical function or slowing joint space narrowing. Conclusions: It may be prudent to develop best practices of reporting the use of IPTW. Studies performing intention-to-treat analyses should report the levels of adherence after treatment initiation, and studies performing as-treated analyses should take into the complex mechanism of treatment use in weight construction.

Beta-blockers and non-steroidal anti-inflammatory drugs (NSAIDs) are often avoided in asthma over risk of bronchospasm which may vary according to drug selectivity and duration of administration. This thesis attempts to quantify the risk of beta-blocker and NSAID exposure in asthma by synthesising clinical trial evidence and conducting observational studies using linked electronic medical records. As part of this thesis, three systematic reviews of clinical trials were conducted evaluating: the prevalence of aspirin-exacerbated respiratory disease (AERD); risk of selective NSAIDs/COX-2 inhibitors in people with AERD; and risk of acute beta-blocker exposure in people with asthma. Electronic primary care data from the Clinical Practice Research Datalink (CPRD) was used to define a cohort of people with active asthma, measure the prevalence of beta-blocker and NSAID prescribing, and perform a series of nested case control studies evaluating asthma death, asthma hospitalisation and primary care asthma exacerbations (PCAE). A self-controlled case-series was performed for PCAE as well. Based upon work in this thesis, the prevalence of AERD in people with asthma was around 9%. Selective NSAIDs triggered respiratory symptoms in 8% of people with AERD whilst no significant changes in lung function or symptoms occurred with COX-2 inhibitors. Acute non-selective beta-blocker exposure caused a significant mean fall in FEV1 of 10%, a significant increase in respiratory symptoms in around 1 in 13 and a non-significant increase in falls in FEV1 of ≥20% in around 1 in 9. Acute selective beta-blocker exposure caused a significant mean fall in FEV1 of 7%, significant falls in FEV1 of ≥20% in around 1 in 8 and a non-significant increase in respiratory symptoms in around 1 in 33. The prevalence of selective beta-blocker prescribing in asthma rose by around 200% over the 12 year period whilst the prevalence of non-selective beta-blocker prescribing rose by around 90%. Changing trends in NSAID prescribing occurred over the 12 year period with COX-2 inhibitors now rarely prescribed. Using the nested case control design, both incident and high-dose non-selective beta-blocker exposure was associated with significantly increased risk of asthma morbidity (hospitalisation and PCAE). In contrast, no significant increased risk of asthma morbidity occurred with any type of selective beta-blocker exposure. Consistent findings were seen for PCAE using the self-controlled case series. No significantly increased risk was seen with different oral NSAIDs apart from weak evidence of an association between asthma death and non-selective NSAID exposure which is unlikely to be causal. Significant numbers of people with asthma are prescribed beta-blockers and NSAIDs. Evidence from clinical trials and observational studies demonstrate that non-selective beta-blockers significantly increase asthma morbidity with risk appearing to vary according to dose and duration of administration. Although selective beta-blockers have the potential to cause significant changes in lung function, no significant increase in asthma morbidity was observed in observational studies. Although around 9% of asthmatics may be susceptible to NSAIDs, no strong evidence was found to suggest that the current practice of NSAID prescribing increases asthma morbidity. At the same time, COX-2 inhibitors are infrequently prescribed despite apparently being well tolerated by people with AERD.

Our knowledge of a drug’s potential for harm is incomplete at the time of drug licensing leaving residual questions about the long-term safety and effectiveness of drugs in the ‘real world’. Pharmacoepidemiologic research can contribute to the study of the unintended effects of drugs. The central aims of this dissertation were to create new knowledge about drug-related harm in the postmarketing environment using pharmacoepidemiologic methods and larged linked databases, and understand how various types of design and analytic strategies can be applied to reduce bias and threats to internal validity when studying drug harm. The aims of the thesis were achieved by performing three studies. The first study examined elderly individuals hospitalized with bradycardia and identified an association with recent initiation of cholinesterase inhibitor therapy (adjusted odds-ratio 2.13, 95% confidence interval 1.29 to 3.51). The second study examined the measurement properties of administrative diagnostic codes for subtrochanteric and femoral shaft fractures and found the positive predictive value and sensitivity of the codes to be reasonably good (90% and 81%, respectively). This study was linked to the third study which explored the association between long-term bisphosphonate use and subtrochanteric or femoral shaft fractures in postmenopausal women and found an increased risk of these unusual fractures in women with greater than 5 years of bisphosphonate use. The research performed as part of this thesis provides an example of the types of new knowledge about drug-related harm that can be generated using pharmacoepidemiologic designs and analytic strategies. The pharmacoepidemiologic studies will play an important and dynamic role in the larger evolving focus on post-marketing drug safety and effectiveness as new data sources become increasingly available and and the methods within the pharmacoepidemiologic discipline become more sophisticated and refined.