Osteogenesis imperfecta (OI) is a heterogeneous disease of connective tissue, the cardinal symptom being fractures and severity ranging from mild to lethal. Dominant mutations in collagen I, encoded by COL1A1 and COL1A2, cause >90% of cases. To delineate genotype-phenotype correlations and pharmaco-genetic response, collagen I was sequenced in 150 unrelated Swedish families and clinical data were collected in Paper I. Mutation type, gene affected, and N- to C-terminal location correlated with phenotype and severity. Bisphosphonate response assessed by calculated yearly change in lumbar spine bone mineral density (BMD) was inversely related to age and BMD at treatment initiation. Mutations associated with a more severe phenotype exhibited an increased response after 2 years; however, all types of OI responded well. To investigate the effect of naturally occurring variations in collagen I, the only common coding single nucleotide polymorphism (rs42524 in COL1A2) was genotyped in 2004 healthy men in Paper II. Heterozygous genotype was associated with decreased BMD and an increased risk of stroke. An adolescent with repeated fractures despite a markedly high BMD harbored a unique C-terminal procollagen cleavage-site mutation in COL1A1, which motivated extensive investigations in concert with a similar COL1A2 case in Paper III. The probands were found to have impaired procollagen processing, incorporation of collagen with retained C-propeptide in matrix and increased mineral to matrix ratio, which demonstrates that C-propeptide cleavage is crucial to normal bone mineralization and structure. Bisphosphonate therapy has insufficient effect in OI, and as classical OI is a dominant disorder severe cases would benefit from silencing of the mutated allele. In Paper IV and V small interfering RNAs (siRNAs) were used to allele-specifically target primary human bone cells heterozygous for I) a coding polymorphism in COL1A2 and II) insertion/deletions in the 3’UTR of COL1A1 and COL1A2. Results were promising with altered allele ratios and decreased mRNA levels in the predicted fashion. To summarize, this thesis found that collagen I is crucial to bone and connective tissue and that collagen I mutations create markedly diverse phenotypes. Age, BMD and pharmaco-genetic effects influence the response to bisphosphonate therapy in individuals with OI; however, novel approaches are needed. Utilizing allele-specific siRNAs may be a way forward in the treatment of severe OI.

Les objectifs de ce travail étaient d’évaluer la prévalence vie entière des traitements à visée psychotrope et les caractéristiques associées à cet usage dont l’adéquation avec l’existence de troubles psychiatriques. Les travaux ont été réalisés à partir des données issues de l’enquête Santé Mentale en Population Générale sur un échantillon de 36 785 adultes représentatifs de la population générale française. Un tiers des sujets a rapporté avoir fait usage d’au moins un traitement psychotrope au cours de la vie. L’inadéquation diagnostic-traitement est retrouvée dans le sens « usage en l’absence de trouble psychiatrique » aussi bien que dans le sens « absence d’usage en présence de trouble identifié ». Ainsi, seul un tiers des sujets avec un diagnostic de trouble dépressif récurrent a fait usage d’un traitement antidépresseur ou thymorégulateur. Concernant l’utilisation de traitements alternatifs, seuls 1,3 % des personnes rapportent un usage de traitement homéopathique à visée psychotrope. Ces traitements sont principalement utilisés par des personnes présentant un trouble anxieux en association avec un traitement psychotrope conventionnel. Des études ultérieures documentant l’ensemble des traitements à visée psychotrope utilisé dans le traitement des symptômes psychiques permettraient d’affiner les résultats sur l’adéquation diagnostic-traitement et d’estimer le nombre de sujets évitant le recours aux traitements conventionnels par l’utilisation d’alternatives thérapeutiques. / The aims of this work were to assess the lifetime prevalence of psychotropic drug use and the characteristics associated with use, particularly the congruence with psychiatric diagnoses. The studies were performed using the database from the survey Mental Health in the General Population including 36 785 persons representative of the French general population. One out of three subjects reported a lifetime use of psychotropic treatment. The non-congruence between diagnosis and psychotropic drug was observed in the pattern “use without psychiatric disorders” as well as in the pattern “no use with psychiatric disorders”. So, only one out of three persons with recurrent major depressive disorder reported having used an antidepressant or a mood stabilizer. Regarding complementary and alternative medicine use, only 1,3% of persons reported use of homeopathic treatment for psychiatric symptoms. These treatments were mainly used by persons with anxiety symptoms in association with conventional psychotropic drugs. Further studies assessing the all the treatments used for psychiatric symptoms would allow to refine the results on the congruence between diagnosis and psychotropic drug and to estimate the number of persons avoiding use of conventional psychotropic drugs by using complementary and alternative medicine.

Introduction :Les anticoagulants oraux soulèvent des problématiques majeures en termes de risque hémorragique et de bon usage. L’informatisation du dossier médical offre la possibilité d’accéder à de grandes bases de données que l’on peut exploiter de manière automatisée. L’objectif de ce travail est de montrer comment la réutilisation de données peut permettre d’étudier des problématiques liées aux anticoagulants et accompagner une démarche d’assurance de la qualité des soins. MéthodesCe travail a été réalisé sur les données informatisées (97 355 séjours) d’un centre hospitalier général. Pour chaque séjour nous disposons des données diagnostiques, biologiques, médicamenteuses, administratives et des courriers de sortie. Ce travail est organisé autour de 3 axes :Axe I. L’objectif est d’évaluer la qualité de la détection des facteurs pouvant majorer l’effet anticoagulant des antivitamines K (AVK), à l’aide de règles développées au cours de du projet européen PSIP (convention de subvention n° 216130). Une revue des cas sur une année a permis de calculer la valeur prédictive positive et la sensibilité des règles. Axe II. Nous avons réalisé une étude de cohorte historique sur les données de 2007 à 2012 pour déterminer les éléments majeurs impliqués dans l’élévation du risque hémorragique sous AVK dans la réalité clinique. Les cas étaient les séjours présentant une élévation de l’INR au-delà de 5, les témoins n’en présentaient pas. Axe III. Nous avons mis la réutilisation de données au service de l’étude de la qualité des prescriptions. D’une part nous avons évalué le suivi des recommandations de traitement du risque thromboembolique dans la fibrillation atriale (FA) chez la personne âgée, d’autre part nous avons étudié les modalités de prescription des anticoagulants oraux directs (AOD).Résultats : Axe I : La valeur prédictive positive des règles de détection des facteurs favorisant l’élévation de l’INR sous AVK est de 22,4%, leur sensibilité est de 84,6%. Les règles les plus contributives sont les règles de détection d’un syndrome infectieux et de l’administration d’amiodarone. Axe II : Les facteurs majeurs d’élévation du risque hémorragique sous AVK mis en évidence par l’étude de cohorte sont le syndrome infectieux, le cancer, l’hyprotidémie et l’insuffisance hépatique. Axe III : Le taux de suivi des recommandations dans la fibrillation atriale chez le sujet âgé est de 47.8%. Seuls 45% des patients reçoivent des anticoagulants oraux, 22,9% ne reçoivent aucun traitement antithrombotique et 32,1% reçoivent des antiagrégants plaquettaires. Les AOD sont quant à eux prescrits à des posologies inadaptées chez 15 à 31,4% des patients, respectivement pour le dabigatran et le rivaroxaban. Ces erreurs sont principalement des sous-dosages en AOD dans la FA de la personne âgée (82.6%). Discussion : L’informatisation des dossiers médicaux a permis la constitution de grandes bases de données médico-administratives, qui peuvent être utilisées à des fins variées comme nous le montrons dans ce travail. Dans le premier axe nous avons montré que des systèmes d’aide à la décision à base de règles permettent de caractériser les facteurs impliqués dans les surdosages en AVK avec une bonne sensibilité mais avec une faible valeur prédictive positive. Le second axe a montré que l’on pouvait utiliser ces données à des fins exploratoires pour identifier les facteurs liés à l’élévation de l’INR chez les patients recevant des AVK en pratique réelle. Le troisième axe montre que les systèmes à base de règles peuvent aussi être utilisés pour identifier des prescriptions inappropriées à des fins d’amélioration de la qualité des soins. Dans le domaine de l’anticoagulation ce travail ouvre des perspectives innovantes en vue de l’amélioration de la qualité des soins. / Introduction :Oral anticoagulants raise major issues in terms of bleeding risk and appropriate use. The computerization of medical records offers the ability to access large databases that can be explored automatically. The objective of this work is to show how routinely collected data can be reused to study issues related to anticoagulants in a supportive approach to quality of care.MethodsThis work was carried out on the electronic data (97,355 records) of a community hospital. For each inpatient stay we have diagnostic, biological, drug and administrative data, and the discharge letters. This work is organized around three axes:Axis I. The objective is to evaluate the accuracy of the detection of factors that may increase the anticoagulant effect of vitamin K antagonists (VKA), using rules developed in the PSIP european project (grant agreement N° 216130). A case review on one year enabled the calculation of the positive predictive value and sensitivity of the rules. Axis II. We conducted a cohort study on data from 2007 to 2012 to determine the major elements involved in raising the risk of bleeding related to VKA in clinical reality. Cases were the stays with an elevation of the INR beyond 5, the controls did not have.Axis III. We made data reuse serve a study of the quality of the prescriptions. On the one hand we assessed treatment of the thromboembolic risk recommendations in atrial fibrillation (AF) in the elderly, on the other hand we investigated the prescription of direct oral anticoagulants.Results : Axis I : The positive predictive value of the rules intended to detect the factors favoring the elevation of INR in case of treatment with VKA is 22.4%, the sensitivity is 84.6%. The main contributive rules are the ones intended to detect an infectious syndrome and amiodarone.Axis II : The major factor increasing the INR with VKA treatment highlighted by the cohort study are infectious syndrome, cancer, hepatic insufficiency and hypoprotidemia. The recommendations compliance rate in atrial fibrillation in the elderly is 47.8%. Only 45% of patients receive oral anticoagulants, 22.9% do not receive antithrombotic treatment at all and 32.1% received platelet aggregation inhibitors. Direct oral anticoagulants are prescribed at inadequate dosages in 15 to 31.4% of patients, respectively for dabigatran and rivaroxaban. These errors are mainly underdosages in the elderly with atrial fibrillation (82.6%).Discussion : The computerization of medical records has led to the creation of large medical databases, which can be used for various purposes as we show in this work. In the first work axis we have shown that rule-based decision support systems detect the contributing factors for VKA overdose with a good sensitivity but a low positive predictive value. The second line shows that we could use the data for exploratory purposes to identify factors associated with increased INR in patients receiving VKA in “real life practice”. The third line shows that the rule-based systems can also be used to identify inappropriate prescribing for the purpose of improving the quality of care. In the field of anticoagulation this work opens up innovative perspectives for improving the quality of care.

A intercalação de espécies de interesse biológico e terapêutico em Hidróxidos Duplos Lamelares (HDLs) vem se mostrando uma estratégia interessante para a obtenção de sistemas de armazenamento ou carregadores de drogas. No presente trabalho foram investigadas rotas sintéticas e parâmetros experimentais para a intercalação dos ânions derivados dos fármacos ácido mefenâmico e piroxicam em HDL de Mg2+ e Al3+. Os sólidos foram caracterizados por difratometria de raios X, análises elementar e térmica, microscopia eletrônica de varredura e espectroscopia no infravermelho e Raman. Os difratogramas de raios X dos materiais híbridos HDL-mefenamato isolados por co-precipitação (pH=9-9,5) mostram, além de fase do tipo HDL, alguns picos finos e de baixa intensidade que podem estar relacionados com a presença de um sal de mefenamato. Os melhores resultados foram obtidos empregando uma relação molar ânion/Al3+ =1. Nos processos de reconstituição e troca iônica, os picos finos não são observados. Os espectros vibracionais mostram que o ácido mefenâmico está na forma desprotonada e intacto. Os ânions mefenamato se arranjam em uma bicamada no espaço interlamelar (d003 ~21-22 Å). Os híbridos HDL-piroxicamato obtidos por co-precipitação são constituídos de pelo menos duas fases. À medida que a razão ânion/Al3+ diminui, observa-se o aumento na formação de fase HDL. / Intercalation of biological and therapeutical species into Layered Double Hydroxides (LDHs) has been shown an interesting strategy to get drug storage or drug carrier systems. In this work it were investigated synthetic routes and experimental parameters for intercalation of anions derived from mefenamic acid and piroxicam drugs into LDH of Mg2+ and Al3+ composition. The isolated solids were characterized by X-ray diffractometry, elemental and thermal analysis, scanning electron microscopy and infrared and Raman spectroscopies. Besides LDH phase, XRD patterns of LDH-mefenamate hybrid materials isolated by coprecipitation (pH=9-9.5) show some narrow and low intensity peaks that can be related to a mefenamate salt phase. Improved data were obtained using an anion/Al3+ molar ratio equal 1. When employing reconstruction and ion exchange methods, narrow peaks are no observed. Vibrational spectra indicate that mefenamic acid is deprotonated and integral between the layers. Guest anions are arranged in a bylayer in the interlayer space (d003 ~21-22 Å). LDH-piroxicamate hybrid materials obtained by coprecipitation are constituted by at least two phases. An increase in LDH phase formation it is observed when the molar ratio anion/Al3+ decreases.

A intercalação de espécies de interesse biológico e terapêutico em Hidróxidos Duplos Lamelares (HDLs) vem se mostrando uma estratégia interessante para a obtenção de sistemas de armazenamento ou carregadores de drogas. No presente trabalho foram investigadas rotas sintéticas e parâmetros experimentais para a intercalação dos ânions derivados dos fármacos ácido mefenâmico e piroxicam em HDL de Mg2+ e Al3+. Os sólidos foram caracterizados por difratometria de raios X, análises elementar e térmica, microscopia eletrônica de varredura e espectroscopia no infravermelho e Raman. Os difratogramas de raios X dos materiais híbridos HDL-mefenamato isolados por co-precipitação (pH=9-9,5) mostram, além de fase do tipo HDL, alguns picos finos e de baixa intensidade que podem estar relacionados com a presença de um sal de mefenamato. Os melhores resultados foram obtidos empregando uma relação molar ânion/Al3+ =1. Nos processos de reconstituição e troca iônica, os picos finos não são observados. Os espectros vibracionais mostram que o ácido mefenâmico está na forma desprotonada e intacto. Os ânions mefenamato se arranjam em uma bicamada no espaço interlamelar (d003 ~21-22 Å). Os híbridos HDL-piroxicamato obtidos por co-precipitação são constituídos de pelo menos duas fases. À medida que a razão ânion/Al3+ diminui, observa-se o aumento na formação de fase HDL. / Intercalation of biological and therapeutical species into Layered Double Hydroxides (LDHs) has been shown an interesting strategy to get drug storage or drug carrier systems. In this work it were investigated synthetic routes and experimental parameters for intercalation of anions derived from mefenamic acid and piroxicam drugs into LDH of Mg2+ and Al3+ composition. The isolated solids were characterized by X-ray diffractometry, elemental and thermal analysis, scanning electron microscopy and infrared and Raman spectroscopies. Besides LDH phase, XRD patterns of LDH-mefenamate hybrid materials isolated by coprecipitation (pH=9-9.5) show some narrow and low intensity peaks that can be related to a mefenamate salt phase. Improved data were obtained using an anion/Al3+ molar ratio equal 1. When employing reconstruction and ion exchange methods, narrow peaks are no observed. Vibrational spectra indicate that mefenamic acid is deprotonated and integral between the layers. Guest anions are arranged in a bylayer in the interlayer space (d003 ~21-22 Å). LDH-piroxicamate hybrid materials obtained by coprecipitation are constituted by at least two phases. An increase in LDH phase formation it is observed when the molar ratio anion/Al3+ decreases.

Les progrès continus de la recherche scientifique dans le domaine de la santé ont entraîné une augmentation de l'espérance et de la qualité de vie. Ainsi, le développement de nouveaux médicaments et des dispositifs médicaux a permis d'améliorer les conditions sanitaires et la prise en charge des patients au prix d'une inflation des dépenses de santé. Ces évolutions ont eu pour conséquences d'inciter les états à mettre en place des procédures d'évaluation de l'efficacité et de la gestion des risques liés à ces nouvelles approches thérapeutiques. Plus récemment, les restrictions budgétaires liées à la crise économique dans de nombreux pays de l'OCDE ont contraint les états à diminuer la part de leur budget consacré à la santé. Cette situation les a conduits à mettre en place des politiques de santé basées sur l'optimisation des ressources.En ce sens, l'évaluation médico-économique et la pharmaco-épidémiologie constituent pour les acteurs de santé et pour les décideurs politiques un outil d'analyse décisionnelle particulièrement légitime. Ils sont aujourd'hui de plus en plus intégrés dans les réflexions sur les stratégies de soins et dans la mise en place des programmes de santé. L'objectif de notre travail de recherche a été à travers deux projets, d'étudier l'intérêt de l'évaluation médico-économique et de la pharmaco-épidémiologie en chirurgie pédiatrique. Ainsi, dans une première partie plus théorique, une synthèse des différentes études de pharmaco-économie, de pharmaco-épidémiologie a été conduite et un état des lieux des études d'évaluation médico-économiques dans la chirurgie de l'enfant a été réalisé. Dans une seconde partie plus pratique, les deux projets concernant la chirurgie pédiatrique sont présentés :- Le projet 1 (pharmaco-économie) présente l'évaluation et l'analyse coût-efficacité dutraitement du reflux vésico-urétéral de grade modéré chez l'enfant.- Le projet 2 (pharmaco-épidémiologie) est une étude multicentrique prospective surl'épidémiologie de l'invagination intestinale aiguë de moins de 1 an (EPIstudy) / The continuing progress of scientific research in the field of health have led to increasingexpectancy and quality of life. Thus, the development of new medicines and medical deviceshave improved the health conditions and treatment of patients at the cost of inflation inhealth spending. These developments have effects for encouraging states to implementprocedures of effectiveness assessment and management of risks associated with these newtherapeutic approaches.More recently, budget cuts due to the economic crisis in many OECD countries havecompelled states to reduce the proportion of their budgets on health. This led them todevelop health policies based on resource optimization.In this sense, the health econoic evaluation and pharmacoepidemiology are for healthcarestakeholders and policy makers a tool for decisional analysis. They are now increasingly integrated into reflection on care strategies and the implementation of health programs. The objective of our research has been through two projects, to study the interest of the health economic evaluations and pharmacoepidemiology in pediatric surgery. Thus, in a first, theoretical part, it is a synthesis of various studies of pharmaco-economics, pharmacoepidemiology was conducted and an inventory of economic evaluation studies in pediatric surgery was performed. In the second part more convenient, both projects are presented in pediatric surgery :- Project 1 (pharmacoeconomic) presents evaluation and cost-effectiveness analysis oftreatment of moderate grade of vesicoureteral reflux in children.- Project 2 (Parmacoepidemiology) is a prospective multicenter study of theepidemiology of acute intussusception among infants (EPIstudy)

La recherche scientifique vise à produire des connaissances objectives, tandis que l'éthique s'intéresse à la réalisation des valeurs. Malgré l'éloignement de ces deux domaines, cette thèse vise à montrer de quelle façon sciences et valeurs se forment et s'informent mutuellement. <br />Ce travail s'appuie sur une étude de cas, celui de la constitution de fichiers de données à caractère personnel par les épidémiologistes, et vise à éclaire les problèmes éthiques et épidémiologiques que suscitent ces fichiers. Une approche historique permet de retracer l'émergence en France de la loi du 1er juillet 1994 qui encadre – c'est-à-dire à la fois permet et contraint – de telles pratiques à finalité scientifique. Les notions directrices du questionnement éthique sur la recherche avec l'être humain (mesures invasives, respect des personnes, consentement, respect du secret médical) sont alors retravaillées sous un jour nouveau. <br />L'épidémiologie est une science située à mi-chemin entre clinique et santé publique, entre action et recherche, et elle se révèle profondément hétérogène dans ses pratiques. Une approche de terrain, centrée sur l'activité évaluatrice du Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le Domaine de la Santé (CCTIRS), a permis d'analyser les normes de qualité scientifique en ce domaine. <br />Questionner philosophiquement la mise à l'épreuve de la scientificité de l'épidémiologie dans le cadre des normes de confidentialité conduit (1) à raviver le problème de la démarcation science/non-science et (2) à souligner le rôle que certaines valeurs constitutives de l'intentionnalité scientifique ont à jouer dans le partage entre l'authentique et l'inauthentique en matière de recherche.

Notre thèse de pharmacie clinique est une contribution à l'optimisation de l'efficience du traitement antirétroviral (TAR) par des méthodes de modélisation en Côte d'Ivoire. La première étude a été consacrée à une modélisation de la réponse antirétrovirale par taxonomie des trajectoires de taux de CD4 en utilisant un modèle de méta-apprentissage des trajectoires d'indicateurs biomédicaux. Ce modèle appliqué à la taxonomie des trajectoires des taux de CD4 a montré son intérêt dans la mise en évidence de classes distinctes de patients avec des caractéristiques particulières justifiant et/ou déterminant le profil particulier de méta-trajectoires de leur marqueur immunologique au cours du traitement. La deuxième tâche a consisté en une évaluation de l'impact de principaux déterminants des méta-trajectoires de taux de CD4 sur divers types de réponse immunologique à partir d'un modèle explicatif avec une équation de régression logistique. Les réponses immunologiques considérées ont été exprimées en termes d'absence de gain de CD4, de gain sub-optimal et de gain optimal de CD4 à différentes périodes de suivi du TAR. Enfin l'évaluation de l'efficience des stratégies antirétrovirales de première ligne en Côte d'Ivoire, a été abordée dans la dernière partie avec un modèle pharmaco-économique. Nous avons effectué une étude préliminaire ouvrant des perspectives pour encourager la mise en oeuvre d'évaluations pharmaco-économiques complètes par modélisation en Côte d'Ivoire. Elle a permis de mettre en exergue les parties méthodologiques pouvant être sujettes à caution dans une étude de modélisation pharmaco-économique des TAR de première ligne dans un contexte de ressources limitées

The global anti-dyslipidemic market grew by 19% from 2000 to 2001, achieving sales of over $21 billion (Smith, 2004: 2). This market is currently well sewed by a number of effective and well-tolerated treatments. Lipid-lowering drugs are considered as the first choice drugs in control of dyslipidemias and they are well tolerated by most patients. As with many drug therapies, there should be a balance between the benefits of cholesterol lowering agents, increased medication cost and the overall risk of adverse drug reactions. According to Ballesteros (2001: 514), hypolipidemic drugs are consumed on a large scale and most consumers are elderly. This warrants a study of expenditure incurred because of inadequate prescribing of these agents. The general objective of this study was to determine the utilisation and cost of hypolipidemic drugs in the private health care environment in South Africa. A quantitative retrospective drug utilisation review was performed using a medicine claims database. Data for twenty-four consecutive months (May 1, 2001 to April 30, 2003) were used to determine and compare the utilisation patterns and cost of drugs associated with the management of dyslipidemia a year before (1st May 2001 to 30 April 2002) and a year after (1st May 2002 to 30 April 2003) the implementation of a medicine reference price system (MPL). Data analysis was done by calculating the average value, the standard deviation, effect size, and cost-prevalence indices. The results of this study revealed that hypolipidemic drugs constituted 2.70% (n = 21820911) and 2.78% (n =27277825) of the total number of all medicine items for the first and the second study years respectively. On the other hand, the total cost of all hypolipidemic drugs accounted for 6.33% (n= R3 097 604 602) and 6.23 % (n= R 4 053 280 295) of the total cost of all medicine items claimed during the first and the second study years respectively. The prevalence of generic hypolipidemic drugs accounted for 0.89% (n=589036) and 4.88% (n=759675) of the total number of hypolipidemic drugs claimed during the first and second study year respectively. Innovator drugs, on the other hand, constituted 99.1 1% (n=589036) and 95.11% (n=759675) of the total number of hypolipidemic drugs claimed during the first and second study years respectively. It was found that R23 694.5 and R603 277.36 could have been saved for generic bezafibrate and generic simvastatin respectively if they had been sold at ME'L prices. The total cost of generic hypolipidemic drugs accounted for 0.60% and 2.94%. The total cost of innovator hypolipidemic drugs accounted for 99.40% and 97.06% of the total cost of hypolipidemic drugs claimed during the first (n=R 196 076 050) and second (n=R 252 919 285) study year respectively. With respect to the prescribed daily dose, it was found that most prescriptions for individual hypolipidemic drugs did not conform to the defined daily dose. It was, however, found that most prescriptions whose prescribed daily dose was for one tablet once daily and whose strength was similar to the defined daily dose conformed to the defined daily dose. The conclusion is that there was an insignificant difference in both the prevalence and cost of hypolipidemic drugs a year before and after the implementation of MPL. It was further concluded that increased utilisation of generic hypolipidemic medicine items a year after the implementation of the MPL, could have been brought about by the introduction of generic simvastatin into the market as opposed to the implementation of the MPL. Recommendations for further studies will be formulated. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2005.

"Diabetes mellitus" refers to a spectrum of conditions, which all present with hyperglycaemia as a common medical finding. Diabetes was once thought of as a single disease, but according to Setter et a/. (2000:378), it includes a heterogeneous group of disorders that are secondary to various genetic predispositions and precipitating factors. Type 1 diabetes mellitus (DM) accounts for 10 to 15% of all cases of diabetes mellitus and is clinically characterised by hyperglycaemia and a propensity to diabetic keto-acidosis. Its control requires chronic insulin treatment. Although it may occur at any age, it most commonly develops in childhood or adolescence and is the predominant type of diabetes mellitus diagnosed before age 30 (Beers & Berkow, 2004). Type 2 DM is usually the type diagnosed in patients older than 30 years of age. It is also commonly associated with obesity (Berkow, 1992:1108). The objective of this study was to review the usage and cost of antidiabetic drugs and to determine the influence of the pricing regulations on the cost of these drugs. This research can be classified as retrospective and quantitative. Data were obtained from a prescription claims database, and the study population consisted of all the antidiabetic prescriptions for the year 1 January 2004 to 31 December 2004. The one-year period was divided into three study periods, namely January to April, May to August and September to December. Firstly diabetes mellitus was investigated in order to understand the disease and to determine the prevalence and treatment thereof. It was found that diabetes mellitus is a heterogeneous disorder acquired from both genetic and environmental factors and that education for the general population, and in particular for the patients, is the key to preventing and controlling diabetes and reducing the complications arising from it. Secondly managed health care, pharmaco-economics and a drug utilisation review were investigated in order to understand these concepts. The influence of the South African Government on health care was discussed, including the new pricing regulations of medicine in South Africa. Thirdly, the utilisation patterns of antidiabetic drugs were reviewed, analysed and interpreted. It was determined that the oral antidiabetic agents are relatively less expensive than the insulins and that they are prescribed more frequently, and secondly that the biguanides presented almost half (49.4%, n = 116 138) of all the oral antidiabetic agents. It was also determined that the average cost of the oral antidiabetic drugs was between 21 .O% and 28.0% lower in 2004 than in 1996 - an indication that, despite inflation, the antidiabetic drugs were less expensive in 2004 than eight years ago in 1996. It was also calculated that the total cost savings in antidiabetic medication could have been R1 448 682.26 if the lower price of antidiabetic agents had been implemented during the period January to April. And finally it was also determined that further substantial "cost savings" could have been possible if all the innovator antidiabetic products had been substituted for less expensive generic antidiabetic products. Abstract / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2006.