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Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Au cours des dernières années, le développement des connaissances au niveau de l’étiologie de la maladie ainsi que l’arrivée de nouveaux médicaments et de lignes directrices guidant la pratique clinique sont susceptibles d’avoir entraîné une meilleure gestion de la polyarthrite rhumatoïde (PAR) et de l’ostéoporose, une comorbidité fréquente chez ces patients. Dans cette thèse, trois questions de recherche sont étudiées à l’aide des banques de données administratives québécoises (RAMQ, MED-ÉCHO). Une première étude documente l’utilisation des médicaments pour la PAR au Québec. À ce jour, il s’agit de la seule étude canadienne à rapporter les tendances d’utilisation des DMARD (disease-modifying antirheumatic drug) biologiques depuis leur introduction dans la pratique clinique. Au cours de la période à l’étude (2002-2008), l’utilisation de DMARD (synthétiques et biologiques) a augmenté légèrement dans la population atteinte de PAR (1,9%, 95% CI : 1,1 - 2,8). Cependant, malgré la présence de recommandations cliniques soulignant l’importance de commencer un traitement rapidement, et la couverture de ces traitements par le régime général d’assurance médicaments, les résultats démontrent une initiation sous-optimale des DMARD chez les patients nouvellement diagnostiqués (probabilité d’initiation à 12 mois : 38,5%). L’initiation de DMARD était beaucoup plus fréquente lorsqu’un rhumatologue était impliqué dans la provision des soins (OR : 4,31, 95% CI : 3,73 - 4,97). Concernant les DMARD biologiques, le facteur le plus fortement associé avec leur initiation était l’année calendrier. Chez les sujets diagnostiqués en 2002, 1,2 sur 1 000 ont initié un DMARD biologique moins d’un an après leur diagnostic. Pour ceux qui ont été diagnostiqués en 2007, le taux était de 13 sur 1 000. Les résultats démontrent que si la gestion pharmacologique de la PAR s’est améliorée au cours de la période à l’étude, elle demeure tout de même sous-optimale. Assurer un meilleur accès aux rhumatologues pourrait, semble-t-il, être une stratégie efficace pour améliorer la qualité des soins chez les patients atteints de PAR. Dans une deuxième étude, l’association entre l’utilisation des DMARD biologiques et le risque de fractures ostéoporotiques non vertébrales chez des patients PAR âgés de 50 ans et plus a été rapportée. Puisque l’inflammation chronique résultant de la PAR interfère avec le remodelage osseux et que les DMARD biologiques, en plus de leur effet anti-inflammatoire et immunosuppresseur, sont des modulateurs de l’activité cellulaire des ostéoclastes et des ostéoblastes pouvant possiblement mener à la prévention des pertes de densité minérale osseuse (DMO), il était attendu que leur utilisation réduirait le risque de fracture. Une étude de cas-témoin intra-cohorte a été conduite. Bien qu’aucune réduction du risque de fracture suivant l’utilisation de DMARD biologiques n’ait pu être démontrée (OR : 1,03, 95% CI : 0,42 - 2,53), l’étude établit le taux d’incidence de fractures ostéoporotiques non vertébrales dans une population canadienne atteinte de PAR (11/1 000 personnes - années) et souligne le rôle d’importants facteurs de risque. La prévalence élevée de l’ostéoporose dans la population atteinte de PAR justifie que l’on accorde plus d’attention à la prévention des fractures. Finalement, une troisième étude explore l’impact de la dissémination massive, en 2002, des lignes directrices du traitement de l’ostéoporose au Canada sur la gestion pharmacologique de l’ostéoporose et sur les taux d’incidence de fractures ostéoporotiques non vertébrales chez une population de patients PAR âgés de 50 ans et plus entre 1998 et 2008. Étant donné la disponibilité des traitements efficaces pour l’ostéoporose depuis le milieu des années 1990 et l’évolution des lignes directrices de traitement, une réduction du taux de fractures était attendue. Quelques études canadiennes ont démontré une réduction des fractures suivant une utilisation étendue des médicaments contre l’ostéoporose et de l’ostéodensitométrie dans une population générale, mais aucune ne s’est attardée plus particulièrement sur une population adulte atteinte de PAR. Dans cette étude observationnelle utilisant une approche de série chronologique, aucune réduction du taux de fracture après 2002 (période suivant la dissémination des lignes directrices) n’a pu être démontrée. Cependant, l’utilisation des médicaments pour l’ostéoporose, le passage d’ostéodensitométrie, ainsi que la provision de soins pour l’ostéoporose en post-fracture ont augmenté. Cette étude démontre que malgré des années de disponibilité de traitements efficaces et d’investissement dans le développement et la promotion de lignes directrices de traitement, l’effet bénéfique au niveau de la réduction des fractures ne s’est toujours pas concrétisé dans la population atteinte de PAR, au cours de la période à l’étude. Ces travaux sont les premiers à examiner, à l’aide d’une banque de données administratives, des sujets atteints de PAR sur une période s’étalant sur 11 ans, permettant non seulement l’étude des changements de pratique clinique suivant l’apparition de nouveaux traitements ou bien de nouvelles lignes directrices, mais également de leur impact sur la santé. De plus, via l’étude des déterminants de traitement, les résultats offrent des pistes de solution afin de combler l’écart entre la pratique observée et les recommandations cliniques. Enfin, les résultats de ces études bonifient la littérature concernant la qualité des soins pharmacologiques chez les patients PAR et de la prévention des fractures. / Over the past two decades, progresses in the understanding of disease etiology, the arrival of new drugs, and the development of clinical practice guidelines may have led to a better pharmacological management of rheumatoid arthritis (RA) and osteoporosis, a common comorbidity. In this thesis, three research questions were investigated using well characterized administrative databases (RAMQ and MED-ECHO). A first study documented RA drug use in the province of Quebec. To this date, this is the only Canadian study to report on patterns of biologic DMARD use since their introduction in clinical practice. Over our study time horizon (2002-2008), the use of any DMARDs (synthetic and biologic) slightly increased in the overall RA population (1.9%, 95% CI: 1.1-2.8). However, despite clinical practice guidelines stressing the importance of early treatment, and the reimbursement of treatments by the Quebec drug plan, the results demonstrated suboptimal DMARD initiation in newly diagnosed RA (probability at 12 months: 38.5%), though DMARD initiation increased when rheumatologists were overseeing care (OR: 4.31, 95%CI: 3.73-4.97). For biologic DMARDs, the strongest predictor of initiation was the calendar year of study entry. Of subjects newly diagnosed in 2002, 1.2 in 1000 had a biologic initiated within one year, while for those newly diagnosed in 2007, it was 13.0 in 1000. The results showed that the pharmacological management of RA is improving over time, but remains below expectations. Ensuring better access to rheumatologists should be an area of focus in order to enhance the quality of RA care. A second study reported on biologic DMARD use and the risk of non-vertebral osteoporotic fractures in RA patients aged ≥50 years. Because chronic inflammation in RA interferes with bone remodeling and biologic DMARDs, in addition to their anti-inflammatory and immunosuppressive effects, are modulators of the cellular activity of osteoblasts and osteoclasts possibly leading to the preservation of bone mineral density (BMD), it was believed that their use may reduce the risk of fractures. A nested-case control study was conducted. Although a reduction in the risk of fractures subsequent to biologic DMARD use could not be demonstrated (OR: 1.03, 95% CI: 0.42-2.53), the study established the incidence rate of non-vertebral osteoporotic fractures in a Canadian RA population (11/1000 person-years) and highlighted some important risk factors. The high prevalence of osteoporosis in the RA population justifies that more attention be paid to preventing fractures. Finally, a third study investigated the impact of the 2002 Canadian osteoporosis guidelines on the pharmacological management of osteoporosis and on the rates of non-vertebral osteoporotic fractures in a RA population aged ≥50 years between 1998 and 2008. With the availability of effective osteoporosis treatments since the mid 90s, and the evolving clinical practice guidelines, a reduction in the rate of fractures was expected. Some Canadian studies have shown reductions in the rate of fractures following broader use of osteoporosis drugs and BMD testing in a general adult population, but none have specifically investigated the impact in RA. In this observational study using a time series approach, no reduction in the rate of fractures after 2002 (post guidelines dissemination) could be demonstrated. However, the use of osteoporosis drugs, BMD testing, and provision of post fracture osteoporosis care improved. This study demonstrated that years of availability of effective preventive measures and investments in the development and promotion of clinical practice guidelines have not yet translated into further reduction in the rate of fractures in our RA population over our study time horizon. This body of work is the first to examine, using healthcare administrative data, subjects with RA over a period of 11 years, allowing not only to study the changes in clinical practice following the introduction of new treatments and guidelines, but also to capture the impact on health. In addition, by studying predictors of treatment, the results provide good insights in terms of solutions to fill the gap between the observed clinical practice and guideline recommendations. Finally, the results of these studies substantiate the literature regarding the quality of RA care and the prevention of fractures.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

Background: According to the United Nations AIDS Reference Group (2010) and World Health Organization (2010:2), approximately 33 million people in the world had HIV/AIDS in 2009 of which 2.6 million were children. More than 30 million of these individuals resided in low– and middle–income countries. South–Africa had the highest prevalence of HIV/AIDS in the world with an estimated 5.2 million patients in 2009 (Statistics South Africa, 2010:2). Although the prevalence of human immunodeficiency virus (HIV) infection among children is reported to be high, little is known about other medication administrated concomitantly with their antiretroviral drugs. Objective: The general objective of this study was to investigate possible changes in the medicine prescribing patterns of HIV/AIDS and non–HIV/AIDS children. Methods: A quantitative, retrospective drug utilisation review was performed utilising medicine claims data of a South African pharmacy benefit management company. Data for a four–year period (Jan 1, 2005 to Dec 31, 2008) were analysed. The study population consisted of all children <=12 years divided into those receiving ARVs (designated HIV positive) and those without (designated HIV negative). Descriptive statistics such as average mean, standard deviation, t–test, d–values, and two way frequency tables were used to describe the results. Data were analysed using the Statistical Analysis System ® SAS 9.1 ® programme. Results: The study population (children <= 12 years) represented 16.2% (n = 197 323) of the total population in 2005, 15.4% (n = 193 346) in 2006, 15.6% (n = 142 049) in 2007 and 13.3% (n = 98 939) in 2008. Children with HIV/AIDS represented 0.2% (n = 197 323) of the study population in 2005 and increased to 0.4% (n = 98 939) in 2008, whereas the percentage of children without HIV/AIDS decreased from 99.8% (n = 197 323) in 2005 to 99.6% (n = 98 939) in 2008. The total number of HIV/AIDS children that also received other medication concomitantly with their ARVs increased from 96.5% (n = 402) in 2005 to 97.2% (n = 427) in 2008. Males with HIV/AIDS who used other medication represented 52.6% (n = 388) in 2005 and increased to 53.3% in 2008 while female HIV/AIDS patients represented 47.4% in 2005 and decreased to 46.7% in 2008. Prescriptions containing three ARV items represented 69.5% (n = 2 969) of the total number of prescriptions received by HIV/AIDS patients in 2005 and decreased to 67.7% in 2008. The combination of lamivudine, nevirapine and stavudine were the three products that appeared most frequently on prescriptions for HIV/AIDS children in the age group 0 <= 1 years and 1 <= 5 years from 2005 to 2008. In the age group 5 <= 12 years the combination most frequently prescribed was lamivudine, nevirapine and zidovudine. HIV positive children received 6.2 ± 4.62 prescriptions for other medication (non–ARVs) per year during 2005 compared to HIV negative children with 3.9 ± 3.71 (p < 0.0001, d = 0.5). In 2008 HIV positive children received 6.4 ± 5.02 prescriptions per year compared to HIV negative patients who received 4.36 ± 4.05 prescriptions (p < 0.0001, d = 0.5) in 2008. HIV negative children received more central nervous system items, endocrine items and autacoids than HIV positive children, whereas HIV positive children received more respiratory system agents, dermatological, ear, nose throat and antimicrobials items. Conclusion: The study showed that HIV positive children received significantly more prescriptions for other medication per year compared to their HIV negative counterparts. The top pharmacological groups mostly prescribed to both groups were respiratory agents, antimicrobials, analgesics, dermatological and ear, nose and throat items. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2012.

Background: According to the United Nations AIDS Reference Group (2010) and World Health Organization (2010:2), approximately 33 million people in the world had HIV/AIDS in 2009 of which 2.6 million were children. More than 30 million of these individuals resided in low– and middle–income countries. South–Africa had the highest prevalence of HIV/AIDS in the world with an estimated 5.2 million patients in 2009 (Statistics South Africa, 2010:2). Although the prevalence of human immunodeficiency virus (HIV) infection among children is reported to be high, little is known about other medication administrated concomitantly with their antiretroviral drugs. Objective: The general objective of this study was to investigate possible changes in the medicine prescribing patterns of HIV/AIDS and non–HIV/AIDS children. Methods: A quantitative, retrospective drug utilisation review was performed utilising medicine claims data of a South African pharmacy benefit management company. Data for a four–year period (Jan 1, 2005 to Dec 31, 2008) were analysed. The study population consisted of all children <=12 years divided into those receiving ARVs (designated HIV positive) and those without (designated HIV negative). Descriptive statistics such as average mean, standard deviation, t–test, d–values, and two way frequency tables were used to describe the results. Data were analysed using the Statistical Analysis System ® SAS 9.1 ® programme. Results: The study population (children <= 12 years) represented 16.2% (n = 197 323) of the total population in 2005, 15.4% (n = 193 346) in 2006, 15.6% (n = 142 049) in 2007 and 13.3% (n = 98 939) in 2008. Children with HIV/AIDS represented 0.2% (n = 197 323) of the study population in 2005 and increased to 0.4% (n = 98 939) in 2008, whereas the percentage of children without HIV/AIDS decreased from 99.8% (n = 197 323) in 2005 to 99.6% (n = 98 939) in 2008. The total number of HIV/AIDS children that also received other medication concomitantly with their ARVs increased from 96.5% (n = 402) in 2005 to 97.2% (n = 427) in 2008. Males with HIV/AIDS who used other medication represented 52.6% (n = 388) in 2005 and increased to 53.3% in 2008 while female HIV/AIDS patients represented 47.4% in 2005 and decreased to 46.7% in 2008. Prescriptions containing three ARV items represented 69.5% (n = 2 969) of the total number of prescriptions received by HIV/AIDS patients in 2005 and decreased to 67.7% in 2008. The combination of lamivudine, nevirapine and stavudine were the three products that appeared most frequently on prescriptions for HIV/AIDS children in the age group 0 <= 1 years and 1 <= 5 years from 2005 to 2008. In the age group 5 <= 12 years the combination most frequently prescribed was lamivudine, nevirapine and zidovudine. HIV positive children received 6.2 ± 4.62 prescriptions for other medication (non–ARVs) per year during 2005 compared to HIV negative children with 3.9 ± 3.71 (p < 0.0001, d = 0.5). In 2008 HIV positive children received 6.4 ± 5.02 prescriptions per year compared to HIV negative patients who received 4.36 ± 4.05 prescriptions (p < 0.0001, d = 0.5) in 2008. HIV negative children received more central nervous system items, endocrine items and autacoids than HIV positive children, whereas HIV positive children received more respiratory system agents, dermatological, ear, nose throat and antimicrobials items. Conclusion: The study showed that HIV positive children received significantly more prescriptions for other medication per year compared to their HIV negative counterparts. The top pharmacological groups mostly prescribed to both groups were respiratory agents, antimicrobials, analgesics, dermatological and ear, nose and throat items. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2012.

Text in English / The rationale for the study was to investigate the symbiotic connection of trauma and addiction. The focus is on childhood trauma and the turn to addictive practices to quell the memories and experiences endured as children. Chapter One discusses the methodology regarding the approach of the study and includes an introductory literature review of the phenomena. Additional literature is included in the ensuing chapters. A personal account of the motivation behind the research is chronicled in Chapter Two. In this chapter, I share with the readers my personal experiences around trauma and addiction in my family of origin. The notion of the blending of trauma and addiction is the focus of Chapter Three. It includes the approach to treatment of trauma and addiction as well as addiction counsellor training in the South African context. The storied lives of the participants and their experiences of trauma and addiction are encapsulated in Chapter Four. Finally, Chapter Five rounds off the study with the analyses of the narratives of the unique individuals who contributed to this research undertaking. / Psychology / M.A. (Psychology)