Ce travail présente le développement d’une nouvelle approche pharmacoépidémiologique, reposant sur les bases de données de l'assurance maladie, permettant de caractériser et d’estimer le détournement d’usage de médicaments psychoactifs. Cette approche utilisant la méthode de classification, regroupe, a posteriori, les sujets en différents sous-groupes, menant à l’identification, la caractérisation et la quantification de différents profils de comportement dont le comportement déviant. Nous avons appliqué cette méthode sur plusieurs médicaments. Pour chaque médicament, nous avons inclus l'ensemble des sujets affiliés au régime général des régions PACA et Corse ayant eu un remboursement. Leurs délivrances ont été suivies sur 9 mois. Après une analyse descriptive, une méthode de classification est appliquée, suivie d’une analyse des différents sous-groupes.Un premier travail a permis de confirmer l'importance du détournement d'usage d'une molécule émergente, le clonazépam (publication n°1). Ensuite nous avons adapté notre méthode afin de pouvoir suivre l'évolution sur plusieurs années de ce détournement (publication n°2). Nous avons appliqué cette méthode pour souligner l’existence, sur plusieurs années, du détournement d'usage du méthylphénidate (publication n°3). Notre équipe avait également développé une autre méthode pour estimer la polyprescription (publication n°4). Enfin, nous avons appliqué de façon conjointe ces deux méthodes (publication n°5). La méthode de classification est de plus en plus utilisée afin de surveiller l'évolution du détournement d'usage de médicaments et commencent à être intégrés au système français de surveillance de l’abus de médicament.aux cotés des autres outils pharmacoépidémiologiques plus traditionnels (OSIAP, OPPIDUM, OPEMA, ASOS, DRAMES). / This work presents the development of a new pharmacoepidemiologic method. This methodallows to estimate abuse of psychoactive prescription drugs in real life using prescriptiondatabase. The method is based on a cluster analysis which is a statistical method used todetermine, a posteriori, different subgroups of subjects. According the subgroups’characteristics, we can determine and estimate different behaviours whose subjects with adeviant behaviour. It assesses the rate of subjects with a deviant behaviour among all thesubjects that obtain the drug from a pharmacy.We used this method on several prescription drugs. For each prescription drug, we includedall individuals, affiliated to the French health reimbursement system of two southern Franceareas (Provence-Alpes-Côte-d’Azur and Corsica), who have had a prescription drugreimbursed during the first weeks of the year. Their deliveries have been monitored over a 9month-period. After a descriptive analysis, a clustering method has been used. The fourquantitative variables used to establish profiles of consumers were : number of differentprescribers, number of different pharmacies, number of dispensings and quantity dispensed(DDD). Finally, the characteristics of different subgroups have been presented, especiallythose with a deviant behavior.The first study using this method allows to confirm and assess the magnitude of the abuseliability of an emerging prescription drug as clonazepam (publication n°1). Then we adapt thismethod in order to follow the abuse evolution during several years. In the second publicationon clonazepam, we identified that the proportion of deviant subjects has increased between2001 and 2006 (from 0.86% to 1.38%). We also applied this method to estimatemethylphenidate abuse during several years (from 2005 to 2008) (publication n°3).Methylphenidate abuse is already describe in other countries whereas few data are available inFrance. This study estimates the proportion of subjects with a deviant behaviour (from 0.5%9in 2005 and in 2006 to 2.0% in 2007 and 1.2% in 2008) and assesses its evolution since theapplication of a specific regulation.Our research team has also developed an other method using prescription database : thedoctor shopping indicator which measures the quantity obtained by doctor shopping amongthe overall quantity reimbursed (publication n°4). The objective of the last publication is toanalyze and compare results from those two methods applied to High Dosage Buprenorphine,a product well-known to be diverted in France.Actually, clustering method is more and more used on prescription drugs in order to assesstheir abuse. The results obtained by this method begin to be included in the other postmarketing surveillance of CNS drugs (OSIAP, OPPIDUM, OPEAM, ASOS, DRAMES)which are used by French public health authorities.

The research presented in this dissertation harnesses two secondary data sources, administrative databases of patient-level healthcare data and adverse event (AE) data reported in randomized clinical trials (RCTs), to assess the relationship between intravenous immune globulin (IVIg) and the risk of clinically serious thromboembolic adverse events (TEEs). Since 2013, IVIg products have carried a boxed warning concerning TEE risk, a determination supported by numerous case reports, a large claims-based risk assessment, and laboratory evaluations of the thrombogenecity of IVIg products. Questions remain concerning the magnitude of the risk overall and across subgroups of IVIg users. Taken together, our results are compatible with the conclusion that the absolute risk of TEE following IVIg use is likely to be low overall. While these results are reassuring, a clinically meaningful elevation in risk cannot be ruled out in certain patient sub-groups, such as older adults and others with a high baseline risk of TEE. A limitation of our research is that differences in TEE risk across products could not be evaluated with sufficient statistical power.

Background: Inappropriate use of medications (IUM), in particular inappropriate prescribing and non-adherence to prescribed medications, are important causes of drug-related morbidities (DRMs). They are increasing problems with the ageing populations and the growing burden of chronic conditions. However, research is needed on the association of IUMs with DRMs in outpatient settings and in the general population. Aim: The aim of this thesis is to estimate and analyse the burden of potentially inappropriate prescriptions (PIPs) in the elderly and non-adherence to long-term medications among adults across care settings, and to investigate how IUM is associated to DRMs. Methods: A meta-analysis summarised the previous evidence on the percentage of adverse drug reactions (ADRs) associated to IUM across healthcare settings (Study I). From a cohort in the general population, using medical records and register data, the prevalence of PIPs in the elderly and its association with ADRs were estimated retrospectively (Study II). From the same cohort, the factors associated with refill non-adherence to antihypertensive therapy, considering the use of multiple medications, and the association between non-adherence and sub-therapeutic effects (STEs) were investigated (Study III). A survey assessed the refill behaviour to antihypertensive, lipid lowering and oral antidiabetic medications (undersupply, adequate supply and oversupply), and its association with perceived ADRs and STEs (Study IV). Results: IUM was the cause 52% and 45% of ADRs occurring in adult outpatients and inpatients respectively. Across healthcare settings, 46% of the elderly refilled PIPs over a 6-month period; PIPs were considered the cause of 30% of all ADRs; and the elderly who were prescribed PIPs had increased odds to experience ADRs (OR 2.47, 95% CI 1.65-3.69). In total, 35% was nonadherent to the full multidrug therapy and 13% was non-adherent to any medication (complete non-adherence).  Sociodemographic factors (working age and lower income) were associated with non-adherence to any medication, while clinical factors (use of specialised care, use of multiple medications, and being a new user) with non-adherence to the full multidrug therapy. STEs were associated with non-adherence to any medication a month prior to a healthcare visit (OR 3.27, 95% CI 1.27-8.49), but not with long-term measures of non-adherence. Among survey respondents, 22% of the medications were oversupplied and 12% were undersupplied. Inadequate refill behaviour was not associated with reporting ADRs or STEs (p<0.05). Conclusions: A large proportion of ADRs occurring in hospital is caused by IUM, but more knowledge is needed in other settings. PIPs are common in the elderly general population and associated with ADRs. Therefore decreasing PIPs could contribute towards ADR prevention. Considering the use of multiple medications may help to better understand the factors associated with non-adherence to a multidrug therapy for tailoring the interventions to patient needs. Monitoring the adherence prior to a healthcare visit may facilitate interpreting STEs. Yet, the absence of an association between long-term measures of refill non-adherence with clinical and perceived DRMs suggest the need to enhance the knowledge of this association in clinical practice. In summary, this thesis shows a significant potential for improvements of medication use and outcomes.

Objective: To evaluate the consumption of analgesics in Lithuania in the year 2005 – 2007. Material and methods: The data on sales of analgesics drugs in Lithuanian over a 3-year period (2005 – 2007) were obtained from Softdent database. Data were calculated by defined daily dose (DDD) methodology and expressed in DDDs per 1000 inhabitants per day. Results: The total analgesic drugs consumption increased by 16.55% in a 3-year period (2005 – 2007): from 58.37 DDDs/1000 inhabitants/day to 68.03 DDDs/1000 inhabitants/day. Diclofenac (ATC M01A) seemed to be the most highly consumed drug in Lithuania in the three-year period. Diclofenac (M01A) price/DDD is only 0.28 Lt. For these reasons diclofenac was more often used than other painkillers. The second most used agent for pain control was glucosamine (6.38 DDDs/1000 inhabitants/day in 2005), which is used for the treatment of osteoarthritis and, along with new products, its popularity increased sharply. Its consumption grew by 29.80% and achieved 8.28 DDDs/1000 inhabitants/day in 2007. Glucosamine value (Price/DDD) is 1.39 Lt, while paracetamol - 0.59 Lt. Glucosamine is OTC drug so people can buy it easily without control. Maybe for this reasons the usage of glucosamine is enough high. Ibuprofen has regained its popularity after the problems with coxibs. In 2005, the consumption of ibuprofen (4.42 DDDs/1000 inhabitants/day) grew rapidly once again, reached 7.26 DDDs/1000 inhabitants/day in 2007 and showed 64.25% increase... [to full text] / Tikslas. Įvertinti analgetikų vartojimo tendencijas Lietuvoje 2005 – 2007 m. Metodai. Duomenys apie analgetikų pardavimą Lietuvoje 2005 – 2007 metais rinkti iš UAB „Softdent" duomenų bazės. Vaistai buvo klasifikuojami pagal anatominę terapinę cheminę (ATC) klasifikaciją. Vaistų suvartojimas buvo vertinamas pagal apibrėžtos dienos dozės (DDD – angl. defined daily dose) metodiką, o duomenys pateikiami apibrėžta dienos doze tūkstančiui gyventojų. Rezultatai. Lietuvoje per trejus metus (2005 – 2007) analgetikų vartojimas padidėjo 16.55%: nuo 58.37 iki 68.03 DDD/tūkstančiui gyventojų. Daugiausiai buvo suvartojama diklofenako (ATC grupė M01A), tai galėjo būtų dėl tam tikrų priežasčių: diklofenako vieno DDD kaina tik 0.28 lito. Antroje vietoje pagal suvartojimą – gliukozaminas, kuris vartojamas osteoartritui gydyti. Jo suvartojimas išaugo 29.80% ir 2007 m. pasiekė 8.28 DDD/tūkstančiui gyventojų. Gliukozamino vieno DDD vertė 1.39 Lt, kai paracetamolio – 0.59 Lt. Gliukozaminas yra bereceptis vaistas, taigi žmonėms jis legvai prieinamas. Galbūt dėl šių priežasčių gliukozamino suvartojama gana daug. Ibuprofenas susigrąžino savo populiarumą: 2005 metais jo suvartojimas pradėjo vėl sparčiai didėti, 2007 metais pasiekė 7.26 DDD/tūkstančiui gyventojų, ir parodė 64.25% augimą. Nimesulido vartojimas dramatiškai išaugo ir 2007 metais pasiekė 4.91 DDD/tūkstančiui gyventojų. Jo vieno DDD vertė 1.69 Lt, kai paracetamolio ir kitų analgetikų ši vertė nesiekė 1 Lt. Airijoje nimesulidas buvo... [toliau žr. visą tekstą]

Pharmacoepidemiological analyses are needed as a background for evaluation of drug use and for making cost-effective priorities. Drug sales and prescription databases provide useful tools for analysis of drug consumption and expenditures. In this essay, an analysis of the sales and prescribing of proton pump inhibitors (PPIs), drugs used for acid related gastric disorders, are presented. Since 1996, the consumption of PPIs in Norway has increased by approximately 10 % per year, with esomeprazole as the most commonly used drug. An increasing number of individuals are using these drugs with considerable costs for the reimbursement schemes, e.g., in 2006 more than 450 million NOK. Verified reflux oesophagitis is the predominant indication for reimbursement prescribing. There are, however, indications of an overprescribing of PPIs. The prescribing in Norway is different from Denmark and Sweden, both regarding choice of drug and level of consumption. The prevalence of PPI use increased with age, reaching a maximum of nearly 12 % in the age groups 70-79 and 80-89 years of age. A considerable proportion is long-term users (&gt; 2 years). These groups have a high risk of polypharmacy treatment. Even though the PPIs have been on the market for many years, negative effects associated with long term use are being discussed and need to be further explored. Attention should be focused on the rational use of PPIs and not only on the reduction of costs for PPI therapy. / Farmakoepidemiologiske analyser er nødvendige som bakgrunn for å evaluere legemiddelbruk og gjøre kostnads-effektivitets prioriteringer. Databaser med informasjon om salg og forskrivning av legemidler er nyttige redskaper for slike analyser. I denne oppgaven presenteres en analyse av salgs- og forskrivningsdata for protonpumpehemmere, en legemiddelgruppe som brukes ved syrerelaterte gasterointestinale sykdommer. Forbruket av protonpumpehemmere i Norge har siden 1996 økt med 10 % per år, med esomeprazol som vanligste legemiddel. Et økende antall personer bruker disse legemidlene. Utgiftene for det offentlige trygdesystemet er omfattende, mer enn 450 millioner NOK i 2006. Verifisert spiserørbetennelse er den dominerende årsak til forskrivning angitt på reseptene. Det er indikasjoner på en for høy forskrivning av protonpumpehemmere. Forskrivningen i Norge er forskjellig fra Danmark og Sverige, både med hensyn på valg av legemiddel og forbruksnivå. Prevalens for bruk av protonpumpehemmere øker med alder og når et maksimum på nær 12 % av befolkningen i aldersgruppene 70-79 og 80-89 år. En betydelig andel bruker legemidlene over lengre tid (&gt; 2 år). Dette er grupper som bruker mange legemidler samtidig (polyfarmasi). Selv om protonpumpehemmerne har vært på markedet i mange år, diskuteres fortsatt negative følger av langtidsbruk og det er behov for å studere bruken nærmere. Oppmerksomheten bør rettes mot rasjonell bruk av disse legemidlene, ikke bare hvordan utgiftene til dem skal kunne reduseres. / <p>ISBN 978-91-85721-14-6</p>

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

L'asthme est un problème de Santé publique au niveau mondial. Il touche environ 10% des enfants et des adultes en France, avec des conséquences socio-économiques importantes. L'asthme est une maladie respiratoire chronique obstructive complexe, caractérisée par une hétérogénéité phénotypique et une expression clinique variable au cours du temps. Les essais contrôlés randomisés restent la référence pour évaluer l'efficacité et la sécurité des médicaments. Néanmoins, les études pharmaco-épidémiologiques, nécessaires pour compléter les résultats des essais contrôlés randomisés, restent encore limitées dans l'asthme. Cette thèse en pharmaco-épidémiologie, s'appuyant sur deux cohortes françaises complémentaires, avait pour objectif d’améliorer la compréhension de la qualité de la prise en charge thérapeutique de l'asthme en population. Les objectifs spécifiques étaient d'étudier: 1) les bénéfices à long terme des corticoïdes inhalés dans l'asthme, 2) le ratio « traitements de fond/traitements des pathologies respiratoires obstructives », défini à partir des données médico-administratives, et ses fluctuations au cours du temps chez les sujets âgés, et 3) la polymédication dans l'asthme du sujet âgé.L'efficacité à court terme des corticoïdes inhalés a largement été démontrée mais leurs bénéfices à long terme ont rarement été étudiés. Nous avons estimé les effets à long terme des corticoïdes inhalés sur 245 adultes asthmatiques participant à l'étude EGEA. L'application d'une méthode par score de propension pour prendre en compte le biais d'indication n’a pas permis de mettre en évidence un bénéfice à long terme des corticoïdes inhalés utilisés au long cours sur la santé respiratoire. Un bénéfice potentiel de l’exposition aux corticoïdes inhalés au long cours a toutefois été observé sur l’évolution de la fonction respiratoire. Plusieurs indicateurs de qualité de prise en charge de l’asthme, basés principalement sur des bases de données administratives américaines, ont été proposés dans l'enfance et à l'âge adulte. Cependant, la pertinence de tels indicateurs n'a pas été spécifiquement étudiée dans des populations plus âgées et leurs fluctuations au cours du temps n'ont jamais été caractérisées. Notre étude menée auprès de 4328 femmes asthmatiques âgées de l'étude Asthma-E3N a montré que le ratio « traitements de fond/traitements des pathologies respiratoires obstructives », défini à partir des bases de données médico-administratives, est un indicateur pertinent pour identifier les sujets âgés à risque de mauvais contrôle de la maladie. De plus, l’étude de la variation à long terme du ratio a permis d’identifier des groupes de femmes asthmatiques présentant un risque élevé d’asthme non contrôlé à terme. La population âgée souffre fréquemment de multimorbidité, conduisant à la polymédication et potentiellement à une réponse altérée au traitement. L’impact des comorbidités et de leurs traitements reste inconnu. Nous avons appliqué une méthode intégrative à partir des bases de données de remboursements des médicaments chez les femmes asthmatiques de l'étude Asthma-E3N. Le « Pharmacome » a confirmé la polymédication dans cette population et a mis en évidence les liens entre les médicaments. En appliquant une méthode de classification sur les classes thérapeutiques des médicaments utilisés, nous avons identifié trois profils de femmes asthmatiques présentant un niveau de risque différent de mauvais contrôle de la maladie.En conclusion, les données médico-administratives représentent une source pertinente pour identifier les patients à haut risque de mauvais pronostic d’asthme au niveau populationnel. Notre travail en pharmaco-épidémiologie apporte une nouvelle approche sur l’évaluation de la prise en charge thérapeutique de l’asthme et sur l’interrelation entre les médicaments de l’asthme et les autres médicaments, proxies de comorbidités. Nos résultats sont d’une importance particulière, en raison du fardeau mondial de l’asthme........ / : Asthma is a worldwide non-communicable disease affecting around 10% of children and adults in France, with substantial socio-economic impacts. This is a complex chronic respiratory disease characterized by phenotypic heterogeneity and fluctuations of clinical expression over time. Randomized controlled trials (RCT) remain the gold standard to assess medication efficacy and safety. Nevertheless, pharmacoepidemiological studies have a helpful design to complement RCT findings, but are still limited in asthma. This thesis in pharmacoepidemiology, relying on two complementary French cohorts, aimed to add information on the assessment of the quality of asthma therapeutic management in real life. Specific aims were to investigate: i) the long-term benefits of inhaled corticosteroids in asthma, ii) the controller-to-total asthma medication ratio and its fluctuations over time in the elderly, and iii) the polymedication in elderly asthma.The short-term efficacy of inhaled corticosteroids on asthma has been largely established, but their long-term benefits have rarely been assessed. We estimated the long-term effects of inhaled corticosteroids on 245 adults with persistent asthma who participated to the EGEA study. Applying a propensity score method to take into account the indication bias did not offer evidence of a statistical significant long-term benefit of ICS used regularly or continuously over twelve years on respiratory health. However, a trend for benefits of long-term ICS exposure was observed on lung function evolution. Asthma therapeutic management in the elderly relies on studies performed in younger populations, postulating that its efficacy is similar in this specific population. Some quality of care markers, mainly based on US drug administrative databases, have been proposed in childhood and adulthood with asthma. However, the relevance of such asthma medication ratios has been poorly addressed in older populations, and its fluctuations over time have never been characterized. Our study, conducted among 4,328 elderly women with ever asthma from the Asthma-E3N study and using drug administrative databases, showed that the controller-to-total asthma medication ratio is also relevant in the elderly and identified specific patterns of fluctuations of the ratio significantly associated with the subsequent risk for poor asthma-related outcomes. The elderly population frequently suffers from multimorbidity, leading to polymedication and potential altered response to treatment. To which extent asthma-related comorbidities and their treatments impact on asthma phenotypes and medications remains unknown. Therefore, we applied an integrative method on a drug administrative database to characterize the medication network in elderly women with asthma from the Asthma-E3N study. The medication network (“Pharmacome”) in elderly asthma confirmed the complexity of therapeutic management in this population and highlighted links between medications. Applying a clustering method on drug use among participants with asthma, we identified three clusters of individuals characterized by their profiles of treatment use, which showed different risk levels for subsequent poor asthma characteristics (uncontrolled asthma, asthma attacks/exacerbations, impaired health-related quality of life).In conclusion, our findings are both of public health and clinical interests. Claims data are relevant to identify patients at high risk for poor asthma prognosis at the population level. Our work in pharmacoepidemiology, relying on health administrative databases, provides new insights into the assessment of asthma therapeutic management and the inter-relationship between asthma medications and medications for comorbid conditions......

p. 1-127 / Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-04-25T19:07:36Z No. of bitstreams: 1 99999999999qqq.pdf: 1226981 bytes, checksum: 67831b3311099f69a1ec51212bc4c811 (MD5) / Approved for entry into archive by Maria Creuza Silva(mariakreuza@yahoo.com.br) on 2013-05-04T17:25:42Z (GMT) No. of bitstreams: 1 99999999999qqq.pdf: 1226981 bytes, checksum: 67831b3311099f69a1ec51212bc4c811 (MD5) / Made available in DSpace on 2013-05-04T17:25:42Z (GMT). No. of bitstreams: 1 99999999999qqq.pdf: 1226981 bytes, checksum: 67831b3311099f69a1ec51212bc4c811 (MD5) Previous issue date: 2008 / Introdução: A relação entre fatores determinantes e utilização de medicamentos prescritos e não prescritos na população pediátrica é pouco estudada, apesar de se reconhecer os problemas existentes nessa área. Objetivo: Descrever o perfil de utilização e determinar os fatores associados ao uso de medicamentos prescritos e não prescritos em crianças em Salvador, Bahia, Brasil. Métodos: Foi realizado um inquérito domiciliar de base populacional, no período de fevereiro a maio de 2006, em que estudou-se crianças provenientes de domicílios selecionados através de micro-regiões representativas de Salvador. O consumo de medicamentos prescritos e não prescritos nos 15 dias anteriores à entrevista foi considerado à variável dependente. Foram considerados três grupos de variáveis exploratórias: socioeconômicas, estado de saúde e indicadores de uso de serviços de saúde. A análise ajustada foi conduzida através de uma regressão logística multinomial seguindo um modelo hierárquico. Resultados: Das 1382 crianças, 663 (48%) haviam consumido pelo menos um medicamento nos últimos 15 dias: 267 (40,3%) referidas pela mãe haviam consumido medicamentos prescritos e 396 (59,7%) consumiram medicamentos não prescritos. Os grupos farmacológicos entre os prescritos mais consumidos foram analgésicos/antitérmicos (42,3%), antibacterianos sistêmicos (21,3%) e antiasmáticos (16,5%). Os grupos farmacológicos não prescritos mais consumidos foram analgésicos/antitérmicos (65,2%), antitussígenos (15,7%) e vitaminas (9,3%). Após ajustamento por variáveis de confusão, as seguintes variáveis apresentaram associações positivas com o uso de medicamentos prescritos: idade (4-5 e 6 anos), autopercepção de saúde ruim/muito ruim, presença de doença crônica, interrupção de atividades por problemas de saúde, número de consultas médicas, recebeu atendimento de saúde independente de estar doente e relato de gastos com medicamentos. O uso de medicamentos não prescritos apresentou associação negativa com mães de cor da pele negra e associação positiva com idade (4-5 anos), sexo feminino, idade materna (30-39 anos), autopercepção de saúde ruim/muito ruim, interrupção de atividades por problemas de saúde e relato de gastos com medicamentos. Conclusões: Os resultados apontam para a necessidade de programas para otimizar o acesso e racionalização do uso de medicamentos entre crianças no Brazil. / Salvador

Background and Aims: Type 2 diabetes mellitus (T2DM) is a chronic progressive condition characterised by hyperglycaemia due to insulin deficiency with or without insulin resistance. The prevalence of diabetes is increasing rapidly worldwide and it has a significant burden on health care resources with estimated costs of up to 10% of health expenditure in the UK. With an ageing population, people are now living longer with diabetes which consequently leads to increased multimorbidity and polypharmacy. Some previous studies have not assessed the effect of demographic or geographic factors (such as age, gender, UK nation and social deprivation) on the incidence and prevalence of T2DM in the UK over the past decade. In addition, detailed reports on the patterns of comorbidities in T2DM patients are sparse. Patients with T2DM are at a two-fold higher risk for cardiovascular (CV) disease. Some earlier studies assessing the CV risk associated with available therapies have been inconclusive in determining the preferred regimens. This thesis aimed to: i) assess the incidence and prevalence of T2DM in the UK; ii) investigate and compare mortality risk between T2DM patients and patients without diabetes and explore if it explains the observed prevalence rates; iii) examine the patterns of comorbidities in T2DM patients and matched comparators without diabetes; and iv) assess the comparative CV risk associated with second-line diabetes therapies. Methods: All the studies in this thesis used data from the UK Clinical Practice Research Datalink. Access to linked national hospitalisation, deprivation and mortality data was obtained for the individual studies. Annual overall and gender-specific incidence and prevalence of T2DM were calculated for the study period 2004-2014. Rates were standardised by age bands, gender, neighbourhood social deprivation, and UK nation and expressed per 10,000 person-years (PYRs) with 95% confidence intervals (95% CI). For the mortality analysis, T2DM patients (cases) were matched to patients without diabetes (controls) on age, gender and general practice. Annual mortality rates for the matched T2DM and patients without diabetes were calculated and compared. Cox regression analysis was used to examine the effect of important covariates on the risk for all-cause mortality in the matched cohort and calculate hazard ratios (HR) and 95% CI. The multimorbidity profile in T2DM cases and matched controls, registered in English general practices, were also examined. Annual prevalence rates of 18 physical and mental health comorbidities were determined between 2004 and 2014 using linked primary care and hospitalisation records. For the CV risk analysis, patients prescribed a second-line medication after greater than or equal to90days of metformin monotherapy between 1998 and 2011 were identified. Using a retrospective cohort study design, inverse probability of treatment-weighted time-varying Cox regression models were used to estimate HRs and 95% CI for developing a major CV event (myocardial infarction, stroke, acute coronary syndrome, unstable angina, coronary revascularisation, or CV death) associated with second-line therapies after adjusting for clinically important CV risk factors. Results: The prevalence of T2DM nearly doubled from 320.62 (95% CI: 318.83; 322.41) in 2004 to 526.36 per 10,000 PYR (95% CI: 523.81; 528.91) in 2014, whereas the incidence was relatively stable with overall rate of 43.07 per 10,000 PYR (95% CI: 40.06; 46.09). Gender-specific incidence and prevalence rates were markedly higher in men than women. Between 2004 and 2014, the prevalence increased from 380.31 (95% CI: 377.48; 383.13) to 625.45 (95% CI: 621.37; 629.52) in men and from 268.56 (95% CI: 266.22; 270.90) to 437.28 (95% CI: 433.94; 440.62) in women. Overall, older individuals, men, and residents in the most deprived locations were more likely to have T2DM. Wales and Northern Ireland had higher prevalence rates than the other UK nations. In the all-cause mortality analysis, 20,312 (11.5%) patients with T2DM died, as compared with 79,951 (9.1%) controls. The adjusted survival model showed that patients with T2DM were at significantly greater risk for mortality in comparison with patients without diabetes (HR: 1.26, 95% CI: 1.20; 1.32). Mortality rates decreased over time in both cases and controls. The multimorbidity study showed that comorbidities were more prevalent in patients diagnosed with T2DM in comparison with patients without diabetes. The number of patients with two comorbidities increased between 2004 and 2014. The prevalence of cardiovascular disease (CVD) in T2DM patients was double that of matched control patients. DPP-4 inhibitors, thiazolidinediones and sulphonylureas add-on therapies to metformin were the most commonly-prescribed second-line therapies. The time-varying survival models showed that DPP-4 inhibitors (HR: 0.78, 95% CI: 0.55; 1.11) and thiazolidinediones (HR: 0.68, 95% CI: 0.54; 0.85) add-on therapies were associated with lower risk for major CVD compared to sulphonylurea add-on therapy when all added to initial metformin. Conclusions: The prevalence of T2DM is increasing rapidly in the UK. Patients with T2DM are at significantly greater risk for mortality than patients without diabetes. However, with the declining mortality rates over the past decade, patients are now living longer to develop comorbidities. CVD was the most prevalent comorbidity in T2DM cases in comparison with people without diabetes. This is important as CVD is the main cause of mortality in patients with T2DM. Thiazolidinedione combination with metformin was associated with significantly lower CV risk in comparison with sulphonylurea add-on therapies to metformin. Lower, but non-statistically significant, risks were also found with DPP-4 inhibitors add-on therapies. These real-world findings add to the existing knowledge on the epidemiology of T2DM, provide novel insight on the patterns of multimorbidity in these patients and clinically relevant evidence on the CV risk associated with commonly-prescribed second-line regimens. Future larger studies are needed to confirm the observed CV benefits associated with antidiabetic therapies.

Introdução: Nos últimos anos, o consumo de medicamentos tem aumentado em todo o mundo e também no Brasil. Investigar este consumo numa determinada população é relevante para a gestão da política de medicamentos e o gerenciamento dos recursos em saúde, pois serve como ferramenta no planejamento de ações de prevenção e promoção de saúde. Objetivo: Descrever a prevalência e a tendência de consumo de medicamentos por intermédio da dispensação numa Farmácia Pública Municipal no período de oito anos. Metodologia: Trata-se de um estudo descritivo, retrospectivo, baseado em dados secundários obtidos por meio dos relatórios de dispensação de medicamentos do sistema informatizado da Farmácia Pública Municipal de Glorinha (RS) no período de 2008 a 2015. A população do estudo constitui-se de todos os usuários que tiveram pelo menos um medicamento da Relação Municipal de Medicamentos. As variáveis demográficas foram sexo e idade. Para fins de análise, os medicamentos foram categorizados no primeiro (Grupo Anatômico – GA), segundo (Grupo Terapêutico Principal – GTP) e quinto nível (Substância Química – SQ) da classificação Anatomical Therapeutic Chemical (ATC) e seu consumo analisado pela Dose Diária Definida (DDD) por 1.000 habitantes por dia. Resultados: A população do estudo foi 9.967 pessoas, sendo o maior percentual do sexo feminino (52,8%) e a faixa etária mais prevalente de 0 a 9 anos (16,2%). O consumo pelas mulheres é maior que os homens em todas as faixas etárias. Em relação ao consumo de medicamentos dispensados por usuário por ano: os GA mais prevalentes foram sistema nervoso (22,1%) e sistema cardiovascular (19,5%); os GTP mais prevalentes foram anti-inflamatórios e antirreumáticos (11,3%) e analgésicos (10,5%) e as SQ mais consumidas foram ibubrofeno (11,3%) e paracetamol (9,9%). Quanto à quantidade de unidades farmacêuticas dispensadas por ano: os GA mais prevalentes foram sistema (43,1%) e sistema nervoso (26,7%); os GTP mais prevalentes foram os agentes com ação no sistema renina-angiotensina (18,0%) e psicoanalépticos (10,8%) e as SQ mais consumidas foram captopril (8,9%) e enalapril (7,9%). Sobre o total da DDD (DDD/1.000 habitantes/dia): os GA de maior consumo foram os medicamentos do sistema cardiovascular (47,6%) e do sistema nervoso (15,3%); os GTP mais utilizados foram os medicamentos com ação no sistema renina-angiotensina (22,7%) e os diuréticos (10,3%) e as SQ mais utilizadas foram enalapril (14,7%) e omeprazol (9,6%). Dentre os medicamentos disponibilizados foi observado um maior decréscimo de dispensação nos seguintes grupos terapêuticos principais: ação no sistema renina-angiotensina (93,0%), na diabetes (82,4%) e os diuréticos (79,0%). Conclusões: Apesar da ampliação do acesso da população aos medicamentos pelas políticas públicas vigentes de Assistência Farmacêutica, a expressiva e crescente prevalência de consumo e a sua utilização de forma não racional causa preocupação. Dentro deste contexto, o profissional farmacêutico desempenha um papel relevante na compreensão e enfrentamento do problema e, desta forma, pode também contribuir na elaboração de estratégias para educação em saúde e para o uso racional de medicamentos na população por intermédio de estudos na área de Farmacoepidemiologia. / Introduction: In recent years, the consumption of medicinal products has increased worldwide and also in Brazil. Investigating this consumption in a given population is relevant for the management of health resources, as it serves as a tool in the planning of health preventive and promotion actions. Objectives: Describing the prevalence and trend of the consumption of medicinal products through the dispensing procedure at a Municipal Public Pharmacy over a period of eight years. Methodology: This is a descriptive, retrospective study, based on secondary data obtained through the reports of dispensing procedures of medicines from the computerized system of the Municipal Public Pharmacy in Glorinha (RS), from 2008 to 2015. The studied population consisted of all users who got at least one medication from the Municipal Medication List. Demographic variables were sex and age. For the purposes of analysis, the medicinal products were categorized in the first (Anatomical Group – AG), second (Therapeutic Subgroup – TS) and fifth level (Chemical Substance – CS) of the Anatomical Therapeutic Chemical (ATC) classification, and its consumption analyzed by the Defined Daily Dose DDD (1,000 inhabitants per day). Results: The studied population was 9,967 people, the highest percentage being female (52.8%) ant the most prevalent age group that of 0 to 9 years old (16.2%). Consumption by women is greater than men in all age groups. Respecting the consumption of medicines dispensed to users per year: the most prevalent AG were nervous system (22.1%) and cardiovascular system (19.5%); the most prevalent TS were antiinflammatory and antirheumatic (11.3%) and analgesics (10.5%), and the most commonly consumed CS were ibuprofen (11.3%), and acetaminophen (9.9%). Regarding the quantity of pharmaceutical units dispensed per year: the most prevalent AG were cardiovascular system (43.1%) and nervous system (26.7%); the most prevalent TS were agents action on the renin angiotensin system (18.0%) and psychoanalytics (10.8%), and the most commonly used CS were captopril (8.9%) and enalapril (7.9%). About the total DDD (DDD/1,000 inhabitants/day): the most consumed AG were the cardiovascular system medications (47.6%) and the nervous system (15.3%); the most used TS were the medicines with action in the renin angiotensin system (22.7%) and the diuretics (10.3%) and the most used CS were enalapril (14.7%) and omeprazole (9.6%). Among the medicinal products available, a greater decrease in the following main therapeutic groups was observed: action in the renin angiotensin system (93.0%), diabetes (82.4%) and diuretics (79.0%). Conclusions: Despite the increasing access of the population to medication by the current public policies of Pharmaceutical Assistance, the expressive and growing prevalence of consumption and its use of form non-rational causes concern. Within this context, the pharmacy professional plays a relevant role in understanding and coping with the problem and, in this way, can also contribute in the elaboration of strategies for health education and for the rational use of medicines in the population through studies in the area of Pharmacoepidemiology.