Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
MethodsX ; 7: 100796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32322541

RESUMO

Users of newly marketed drugs often differ from the patients included in randomized clinical trials, and from patients prescribed similar drugs. Cohorts of such users may be compared using propensity score adjustment, or similar user cohorts may be built using high-dimensional propensity score matching in large population databases. One such database is SNDS, the French nationwide claims and hospitalization database, which covers 99 % of the French population. It has yet been rarely used. To study the comparative effectiveness and safety in secondary coronary prevention of ticagrelor, compared to clopidogrel or prasugrel, we identified in SNDS patients who were dispensed any of the three antiplatelet agents of interest (± aspirin) within a month after discharge from hospital for acute coronary syndrome (ACS) and followed them one year for recurrence of ACS, stroke, acute bleeding, or death. High-dimensional propensity scores were developed to identify matched cohorts. Drug performances were also compared in the whole population using adjustment on the same parameters. Here we describe the database that was used, and the methods developed for the high-dimensional propensity score matching, resulting in standardized mean differences between the matched populations of less than 2 % for all of the 500+ variables included in the model. •This study was done in a newly available large-scale claims database, which may differ from other population databases, by it size and exhaustiveness•The methods elaborate on standard high-dimensional propensity scores as adapted to this claims database.

3.
Br J Haematol ; 189(5): 931-942, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32130726

RESUMO

Childhood chronic immune thrombocytopenic purpura (cITP) is a rare disease. In severe cases, there is no evidence for the optimal therapeutic strategy. Our aim was to describe the real-life management of non-selected children with cITP at diagnosis. Since 2004, patients less than 18 years old with cITP have been enrolled in the national prospective cohort, OBS'CEREVANCE. From 1990 to 2014, in 29 centres, 392 children were diagnosed with cITP. With a median follow-up of six years (2·0-25), 45% did not need second-line therapy, and 55% (n = 217) received one or more second lines, mainly splenectomy (n = 108), hydroxychloroquine (n = 61), rituximab (n = 61) or azathioprine (n = 40). The overall five-year further second-line treatment-free survival was 56% [95% CI 49·5-64.1]. The use of splenectomy significantly decreased over time. Hydroxychloroquine was administered to children with positive antinuclear antibodies, more frequently older and girls, and reached 55% efficacy. None of the patients died. Ten years after the initial diagnosis, 55% of the 56 followed children had achieved complete remission. Children with cITP do not need second-line treatments in 45% of cases. Basing the treatment decision on the pathophysiological pathways is challenging, as illustrated by ITP patients with positive antinuclear antibodies treated with hydroxychloroquine.

4.
Am J Cardiovasc Drugs ; 20(1): 81-103, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31254174

RESUMO

BACKGROUND: Clinical trials have indicated that the direct-acting oral anticoagulants dabigatran and rivaroxaban have better risk/benefit profiles than do vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation (NVAF). OBJECTIVE: Our objective was to compare the 1-year real-life risk of major clinical events with dabigatran or rivaroxaban versus VKAs for NVAF. METHODS: This was a high-dimensional propensity score (hdPS)-matched cohort study of new users of dabigatran, rivaroxaban or VKAs for NVAF in the French national healthcare systems database in 2013 followed-up for 1 year [22]. Hazard ratios (HRs) with 95% confidence intervals (CIs) for clinical events and death were determined during exposure. RESULTS: In 2013, a total of 103,101 new anticoagulant users had definite NVAF: 44,653 VKA, 27,060 dabigatran, and 31,388 rivaroxaban. In matched populations, HRs were as follows for dabigatran versus VKAs (20,489 per group): stroke and systemic embolism (SSE) 0.75 (95% CI 0.63-0.88), clinically relevant bleeding (CRB) 0.58 (95% CI 0.51-0.66), hemorrhagic stroke (HS) 0.22 (95% CI 0.14-0.36), gastrointestinal bleeding (GIB) 0.98 (95% CI 0.80-1.19), acute coronary syndrome (ACS) 0.79 (95% CI 0.65-0.95), death 0.74 (95% CI 0.67-0.82), composite (any of the above) 0.71 (95% CI 0.66-0.76). For matched rivaroxaban versus VKA (23,053 per group) HRs were as follows: SSE 0.98 (95% CI 0.85-1.14), CRB 0.83 (95% CI 0.75-0.92), HS 0.65 (95% CI 0.49-0.87), GIB 1.08 (95% CI 0.90-1.30), ACS 0.84 (95% CI 0.71-1.00), death 0.77 (95% CI 0.71-0.84), composite 0.84 (95% CI 0.79-0.89). Numbers needed to treat to observe one fewer death were 49 ± 0.05 with dabigatran or rivaroxaban versus VKAs. CONCLUSION: Consistent with results from clinical trials and other observational studies, dabigatran and rivaroxaban were at least as effective and safer than VKAs for the prevention of thromboembolic events in NVAF over 1 year in the French population. STUDY REGISTRATION: European Medicines Agency EUPAS 13017 (www.encepp.eu) Clinicaltrials.gov id NCT02785354.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Dabigatrana/efeitos adversos , Dabigatrana/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Rivaroxabana/efeitos adversos , Rivaroxabana/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Sistemas de Dados , Feminino , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragia Gastrointestinal/tratamento farmacológico , Humanos , Masculino , Pontuação de Propensão , Vitamina K/antagonistas & inibidores
5.
Handb Exp Pharmacol ; 260: 433-451, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31768750

RESUMO

At the time of their marketing authorization, the effects of drugs and especially their efficacy have been mostly studied in randomized controlled clinical trials (RCT), comparing them to placebo or to existing drugs. However, RCT are by nature limited in their extent, and the often stringent inclusion and exclusion criteria destined to provide for homogeneous study populations reduce the generalizability of RCT results.The post-authorization evaluation of drugs (pharmacoepidemiology or real-world evidence (RWE)) covers the description of drug utilization and population risks or benefits of these drugs after they have been marketed and provided to their target populations. Though field studies have existed for a long time, modern pharmacoepidemiology has been made possible essentially by the emergence of large population databases compiled from claims data or electronic health records. The methods can be exposure or disease-based cohorts or event-driven case-based studies, tailored to the specific questions to be answered. They rely on scrupulous analysis and execution of impeccable methodology, to ensure the most reliable results possible.Pharmacoepidemiology requires knowledge of the pharmacology of drugs, of the clinical aspects of diseases and disease management, and of the epidemiological methods that can apply.


Assuntos
Farmacoepidemiologia/tendências , Bases de Dados Factuais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Therapie ; 74(6): 557-567, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31623850

RESUMO

The discovery and quantification of adverse drug reactions has long relied on the careful analysis of spontaneously reported cases. Causality assessment (imputation) was a fundamental feature of individual case report analysis. This was complemented by analysis of aggregated cases, and of disproportionality analyses in spontaneous reports databases. In the absence of more specific information sources, these have resulted in the discovery of many new adverse reactions, altering drug information. It has led to the withdrawal from the market of many drugs, but its use for risk quantification remains fraught with uncertainty. The recent access to population-wide claims or electronic health records databases have confirmed for spontaneous reporting a predominant role in hypothesis generation for serious adverse drug reactions, notably those that result in hospital admission or death. In these cases, the events are identifiable at the population level, and can be quantified precisely using the tools of modern pharmacoepidemiology, to generate specific benefit-risk analyses. Spontaneous reporting remains irreplaceable in signal and alert generation in drug safety, despite its inherent limitations. For signal strengthening and assessment, more systematic and quantitative methods should be sought, such as claims databases for reactions resulting in hospital admissions.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos/organização & administração , Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Sistemas de Notificação de Reações Adversas a Medicamentos/tendências , Coleta de Dados/métodos , Coleta de Dados/normas , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Registros Eletrônicos de Saúde/organização & administração , Registros Eletrônicos de Saúde/estatística & dados numéricos , Humanos , Segurança do Paciente , Farmacoepidemiologia/métodos , Farmacoepidemiologia/tendências
7.
Br J Clin Pharmacol ; 85(11): 2524-2539, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31318059

RESUMO

AIMS: To estimate the incidence of direct oral anticoagulant drug (DOAC) use in patients with nonvalvular atrial fibrillation and to describe user and treatment characteristics in 8 European healthcare databases representing 6 European countries. METHODS: Longitudinal drug utilization study from January 2008 to December 2015. A common protocol approach was applied. Annual period incidences and direct standardisation by age and sex were performed. Dose adjustment related to change in age and by renal function as well as concomitant use of potentially interacting drugs were assessed. RESULTS: A total of 186 405 new DOAC users (age ≥18 years) were identified. Standardized incidences varied from 1.93-2.60 and 0.11-8.71 users/10 000 (2011-2015) for dabigatran and rivaroxaban, respectively, and from 0.01-8.12 users/10 000 (2012-2015) for apixaban. In 2015, the DOAC incidence ranged from 9 to 28/10 000 inhabitants in SIDIAP (Spain) and DNR (Denmark) respectively. There were differences in population coverage among the databases. Only 1 database includes the total reference population (DNR) while others are considered a population representative sample (CPRD, BIFAP, SIDIAP, EGB, Mondriaan). They also varied in the type of drug data source (administrative, clinical). Dose adjustment ranged from 4.6% in BIFAP (Spain) to 15.6% in EGB (France). Concomitant use of interacting drugs varied between 16.4% (SIDIAP) and 70.5% (EGB). Cardiovascular comorbidities ranged from 25.4% in Mondriaan (The Netherlands) to 82.9% in AOK Nordwest (Germany). CONCLUSION: Overall, apixaban and rivaroxaban increased its use during the study period while dabigatran decreased. There was variability in patient characteristics such as comorbidities, potentially interacting drugs and dose adjustment. (EMA/2015/27/PH).


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Uso de Medicamentos/estatística & dados numéricos , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/farmacocinética , Fibrilação Atrial/mortalidade , Dabigatrana/administração & dosagem , Dabigatrana/farmacocinética , Bases de Dados Factuais/estatística & dados numéricos , Dinamarca , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , França , Alemanha , Humanos , Estudos Longitudinais , Masculino , Metaloporfirinas , Pessoa de Meia-Idade , Países Baixos , Pirazóis/administração & dosagem , Pirazóis/farmacocinética , Piridonas/administração & dosagem , Piridonas/farmacocinética , Rivaroxabana/administração & dosagem , Rivaroxabana/farmacocinética , Fatores Sexuais , Espanha , Reino Unido , Adulto Jovem
8.
Clin Colorectal Cancer ; 18(1): e150-e162, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30630730

RESUMO

BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Their real-life evaluation is insufficient, especially in elderly and frail patients. The aim was to describe use, safety, and effectiveness of targeted therapies in first-line mCRC treatment according to age. PATIENTS AND METHODS: Two field cohorts of patients initiating bevacizumab or cetuximab for first-line mCRC were pooled. Patients characteristics, use, and safety were compared between younger and elderly patients (<75 vs. ≥75 years). Two-year overall survival (OS) and progression-free survival (PFS) were estimated in both age groups using the Kaplan-Meier method adjusted on factors associated with death or progression identified with Cox multivariate modeling. RESULTS: Eight hundred patients (n = 411, 51.4% bevacizumab) were included: 498 (62.3%) male, median age 64 years, 118 (14.8%) Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2. Elderly patients (n = 126, 15.8%) were more often treated with 5-fluorouracil alone than younger. Severe adverse events were equivalent across age groups. ECOG-PS ≥1, abnormal hemoglobin, and abnormal alkaline phosphatases were associated with a higher risk of death; OS adjusted on these factors was similar between elderly and younger patients. ECOG-PS ≥1, lung metastases, abnormal hemoglobin, and abnormal creatinine clearance were associated with a higher risk of progression or death; PFS adjusted on these factors was similar across groups. CONCLUSION: Despite treatment adaptations, elderly patients could benefit from targeted therapies as younger without safety warning.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Terapia de Alvo Molecular , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Estudos de Coortes , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Resultado do Tratamento
9.
Atherosclerosis ; 281: 98-106, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30658197

RESUMO

BACKGROUND AND AIMS: We aimed to compare the effectiveness of ticagrelor vs. clopidogrel or prasugrel on recurrence of acute coronary syndromes (ACS) in real-life conditions, as requested by regulatory authorities at the time of marketing. METHODS: We performed a cohort study in SNDS, the French national healthcare database. All patients with a hospital admission for ACS in 2013 were followed one year. Patients on ticagrelor, clopidogrel or prasugrel were matched 1:1 using age, gender, index ACS type, and high-dimensional propensity scores (hdPS). Outcomes were ACS, stroke, all-cause death, and major bleeding, compared within matched groups using Cox proportional hazards models analysis during treatment. RESULTS: 54,048 ACS were hospitalized in 2013. At discharge, 19,796 were dispensed clopidogrel, 8242 prasugrel, and 13,916 ticagrelor. Per group, 9224 ticagrelor vs. clopidogrel, 6752 ticagrelor vs. prasugrel, and 4676 prasugrel vs. clopidogrel patients were matched. Compared to clopidogrel, ticagrelor was associated with a lower hazard ratio of death 0.73 [0.59-0.90] and composite criterion (0.88, 95% CI [0.79-0.99] but not ACS 0.92 [0.80-1.06], stroke (0.96 [017-5.53]) or major bleeding (1.02 [0.82-1.26]). Prasugrel was not different from ticagrelor or clopidogrel for any outcome, in matched patients. CONCLUSIONS: Ticagrelor in real-life conditions in matched populations was associated with a lower risk of all-cause death than clopidogrel, and a lower risk of composite outcome, as in the main pivotal clinical trial. Ticagrelor and prasugrel were not different, nor were prasugrel and clopidogrel.


Assuntos
Síndrome Coronariana Aguda/terapia , Clopidogrel/uso terapêutico , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Prevenção Secundária , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Demandas Administrativas em Assistência à Saúde , Idoso , Clopidogrel/efeitos adversos , Pesquisa Comparativa da Efetividade , Bases de Dados Factuais , França/epidemiologia , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Recidiva , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
10.
Therapie ; 74(2): 271-277, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30477749

RESUMO

Non-steroidal anti-inflammatory drugs (NSAIDs) are reversible inhibitors of cyclo-oxygenase (COX), mainly used for the symptomatic relief of pain, whether traumatic, infectious, episodic or rheumatologic. Use for the long-term relief of inflammation is waning with the emergence of specific biotherapies. Their effects are related to potency, dosage, and pharmacokinetic or galenic considerations. Adverse reactions are mostly related to COX inhibition, and to the relative COX1 and COX2 inhibition. Over the years have resulted in the withdrawal of some NSAIDs. The most common adverse reactions are: gastrointestinal (COX1) which have declined over time with the emergence of more COX1 sparing drugs and gastroprotection; renal, with an impact on renal function and sodium extraction that is associated with hypertension, heart failure exacerbation, and stress-related renal failure; allergic skin reactions; increased transaminases and acute liver injury which may be idiosyncratic or immunoallergic; increased risk of acute coronary syndromes, initially associated with high-dose long-term use of COX2 specific inhibitors in controlled clinical trials, though more recently there have been indications from poorly controlled observational studies that they could occur with most NSAIDs. Event rates in patients with no overt coronary heart disease are vanishingly low, and the real magnitude of the issue in the treatment of common pain is still unknown. Considering their purely symptomatic effects, they should be used at the lowest possible dose for the shortest possible time, based on the symptomatic relief of pain or fever.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Inibidores de Ciclo-Oxigenase/administração & dosagem , Dor/tratamento farmacológico , Farmacoepidemiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase/efeitos adversos , Inibidores de Ciclo-Oxigenase/farmacologia , Relação Dose-Resposta a Droga , Febre/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico
11.
Br J Clin Pharmacol ; 85(2): 432-441, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30423205

RESUMO

AIMS: We compared the 1-year safety and effectiveness of dabigatran 110 mg (D110) or 150 mg (D150) twice daily to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation. METHODS: New user cohort study of patients dispensed D110 or D150 vs. VKA in 2013 for nonvalvular atrial fibrillation, followed 1 year in the French Système National des Données de Santé (66 million persons). D110 and D150 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing and high-dimensional propensity score. Hazard ratios [HR (95% confidence intervals)] for stroke and systemic embolism (SSE), major bleeding (MB) and death were computed using Cox proportional hazards or Fine and Gray models during exposure. RESULTS: In 14 442 matched D110 and VKA patients, mean age 79, 49% male, 91% with CHA2 DS2 -VASc ≥2 and 8% with HAS-BLED score >3, incidence rates of SSE were 1.9% and 2.6% person-years [HR 0.69 (0.56-0.84)], MB 1.8% and 2.9% [0.62 (0.51-0.76)], death 7.2% and 8.6% [0.84 (0.76-0.94)]. In 8389 matched D150 and VKA patients, mean age 67, 67% male, 65% with CHA2 DS2 -VASC ≥2; < 5% HAS-BLED >3, incidence rates were for SSE 1.4% and 1.9% [0.76 (0.56-1.04)], MB 0.6% and 1.9% [0.30 (0.20-0.46)], death 1.6% and 3.6% [0.46 (0.35-0.59)]. Numbers needed to treat to observe one fewer death were 78 for D110, 88 for D150. CONCLUSION: In real life D110 and D150 were at least as effective, and safer than VKA.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/administração & dosagem , Vitamina K/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Dabigatrana/efeitos adversos , Relação Dose-Resposta a Droga , Embolia/epidemiologia , Embolia/etiologia , Embolia/prevenção & controle , Feminino , Seguimentos , França/epidemiologia , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
12.
Clin Pharmacol Ther ; 105(6): 1439-1455, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30499605

RESUMO

Dabigatran and rivaroxaban at standard or reduced doses have been compared to warfarin in nonvalvular atrial fibrillation (NVAF), but not to each other. This was a new user study of standard dose and reduced dose dabigatran or rivaroxaban for NVAF in the French healthcare database, matched on gender, age, date of first dispensing, and high-dimensional propensity score, followed 2 years. Hazard ratios (HRs; 95% confidence intervals (CI)) of stroke or systemic embolism (SSE), major bleeding (MB), or death were computed. In matched standard-dose patients (8,290 per arm), mean age 67 years, HRs for dabigatran vs. rivaroxaban were SSE 0.92 (95% CI = 0.67-1.26), MB 0.59 (95% CI = 0.39-0.90), and death 0.84 (95% CI = 0.65-1.11). In reduced-dose patients (7,639 per arm), mean age 80 years, HRs for dabigatran vs. rivaroxaban were SSE 0.73 (95% CI = 0.59-0.94), MB 0.74 (95% CI = 0.57-0.96), and death 0.95 (95% CI = 0.83-1.09). In conclusion, at either dose, dabigatran had similar or better effectiveness than rivaroxaban but lower bleeding risk. Death rates were not different.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Dabigatrana/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Rivaroxabana/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico , Estudos de Coortes , Dabigatrana/efeitos adversos , Bases de Dados Factuais/tendências , Relação Dose-Resposta a Droga , Inibidores do Fator Xa/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Rivaroxabana/efeitos adversos , Resultado do Tratamento , Adulto Jovem
13.
Drug Saf ; 41(11): 1049-1058, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29797240

RESUMO

INTRODUCTION: Non-steroidal anti-inflammatory drugs are associated with a dose and duration-dependent coronary risk. There is little information concerning analgesic-dose ibuprofen, among the most widely used drugs worldwide. OBJECTIVE: Our objective was to measure the risks of acute coronary syndrome (ACS) after dispensing of ibuprofen, versus paracetamol. METHODS: Propensity score 1:2-matched cohorts of ibuprofen or paracetamol treatment episodes (TEs) in Echantillon Généraliste de Bénéficiaires (EGB), the 1/97 sample of Système National des Données de Santé (SNDS), the French nationwide claims database, from 2009 to 2014, were compared. Outcomes were hospital admissions for ACS during the 3 months after the dispensing of ibuprofen or paracetamol. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated overall and stratified on low-dose aspirin dispensing. RESULTS: A total of 315,269 ibuprofen TEs in 168,400 persons were matched to 630,457 paracetamol TEs in 395,952 patients. Event rates were 50-100 times higher in low-dose aspirin users (27 vs 0.28 per 1000 patient years). Overall there was no difference in risk of ACS at 3 months (HR 0.94, 95% CI 0.74-1.20) despite a transient increase in the first 2 weeks in ibuprofen users (HR 1.70, 95% CI 1.11-2.59). In the stratified analysis, this short-term risk was only found in aspirin users (5% of population, HR 1.84, 95% CI 1.24-3.24), but not in non-aspirin users (HR 1.09, 95% CI 0.40-2.94). CONCLUSIONS: There was no evidence for an increased risk of ACS in patients dispensed ibuprofen compared to paracetamol.


Assuntos
Acetaminofen/efeitos adversos , Síndrome Coronariana Aguda/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Ibuprofeno/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Adulto Jovem
14.
Pharmacoepidemiol Drug Saf ; 26(8): 954-962, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28544284

RESUMO

The French health care system is based on universal coverage by one of several health care insurance plans. The SNIIRAM database merges anonymous information of reimbursed claims from all these plans, linked to the national hospital-discharge summaries database system (PMSI) and the national death registry. It now covers 98.8% of the French population, over 66 million persons, from birth (or immigration) to death (or emigration), making it possibly the world's largest continuous homogeneous claims database. The database includes demographic data; health care encounters such as physician or paramedical visits, medicines, medical devices, and lab tests (without results); chronic medical conditions (ICD10 codes); hospitalisations with ICD10 codes for primary, linked and associated diagnoses, date and duration, procedures, diagnostic-related groups, and cost coding; date but currently not cause of death. The power of the database is correlatively great, and its representativeness is near perfect, since it essentially includes the whole country's population. The main difficulty in using the database, beyond its sheer size and complexity, is the administrative process necessary to access it. Recent legislative advances are making this easier. EGB (Echantillon Généraliste de Bénéficiaires) is the 1/97th random permanent representative sample of SNIIRAM, with planned 20-year longitudinal data (10 years at this time). Access time is 1 to 3 months, but its power is less (780 000 subjects). This is enough to study common issues with older drugs but may be limited for new products or rare events.


Assuntos
Bases de Dados Factuais , Assistência à Saúde/métodos , Revisão da Utilização de Seguros , Farmacoepidemiologia/métodos , Bases de Dados Factuais/estatística & dados numéricos , Assistência à Saúde/estatística & dados numéricos , Feminino , França/epidemiologia , Humanos , Revisão da Utilização de Seguros/estatística & dados numéricos , Masculino , Programas Nacionais de Saúde/estatística & dados numéricos , Farmacoepidemiologia/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos
15.
Br J Clin Pharmacol ; 82(2): 498-503, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27059520

RESUMO

AIMS: The aim of the present study was to describe the real-life usage patterns of paracetamol. METHODS: The Echantillon Généraliste de Bénéficiaires (EGB) database, the permanent 1/97 representative sample from the French national healthcare insurance system, was searched in 2011 to identify usage patterns, concomitant chronic diseases and use of cardiovascular medication in users prescribed single-ingredient (SP) and combination (CP) paracetamol, representing 85% of all sales. RESULTS: Of 526 108 subjects aged ≥15 years in the EGB, 268 725 (51%) had paracetamol dispensed on ≥1 occasion; of these, 207 707 (77%) were dispensed only SP and 61 018 (23%) received CP with or without SP. SP users were younger (48.3 years vs. 50.5 years), and 57% of SP users vs. 58% of CP users were female. Chronic comorbidities were more common in CP than SP users. SP users had, on average, 3.4 dispensings per year vs. 5.0 for CP users, for 36 defined daily doses (DDD, 3 g) of SP vs. 53 DDD per year for CP; 49% SP users bought 14 DDD or fewer; 15% bought >60 DDD. Use of paracetamol increased with age from about 16 DDD per year in 15-30-year-olds to over 90 DDD per year in patients above the age of 75; 53% of patients ≤60 years bought fewer than 14 DDD per year, whereas 55% of those >60 bought more than 30 DDD per year. More than half the dispensings exceeded the legal per-box limit of 8 g. CONCLUSIONS: Over 50% of the French adult population were dispensed paracetamol at least once over the course of a year, generally for short-term use. Considering recent misgivings on the real efficacy and safety of paracetamol, such widespread use might have important public health consequences.


Assuntos
Acetaminofen/uso terapêutico , Analgésicos não Entorpecentes/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Acetaminofen/administração & dosagem , Adolescente , Adulto , Idoso , Analgésicos não Entorpecentes/administração & dosagem , Comorbidade , Bases de Dados Factuais , Uso de Medicamentos/estatística & dados numéricos , França , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/tendências , Adulto Jovem
16.
Br J Clin Pharmacol ; 77(5): 887-95, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24102791

RESUMO

AIMS: Most risks of nonsteroidal anti-inflammatory drugs (NSAIDs) are pharmacological, dose and duration dependent. Usage patterns of prescription-only (POM) or 'over-the-counter (OTC)' NSAIDs may influence risks, but are not commonly described. METHODS: The Echantillon Généraliste de Bénéficiaires database, the permanent 1/97 representative sample from the French national healthcare insurance systems, was queried over 2009-2010 to identify usage patterns, concomitant chronic diseases and cardiovascular medication in OTC and POM NSAID users. RESULTS: Over 2 years, 229 477 of 526 108 patients had at least one NSAID dispensation; 44 484 patients (19%) were dispensed only OTC NSAIDs (93% ibuprofen) and 121 208 (53%) only POM NSAIDs. The OTC users were younger (39.9 vs. 47.4 years old) and more often female (57 vs. 53%); 69% of OTC users and 49% of POM users had only one dispensation. A mean of 14.6 defined daily doses (DDD) were dispensed over 2 years for OTC vs. 53 for POM; 93% OTC vs. 60% POM patients bought ≤ 30 DDD over 2 years, and 1.5 vs. 12% bought ≥ 90 DDD. Chronic comorbidities were found in 19% of OTC users vs. 28% of POM users; 24 vs. 37% had at least one dispensation of a cardiovascular drug over the 2 years. CONCLUSIONS: Most of the use of NSAIDs appears to be short term, especially for OTC-type NSAIDs, such as ibuprofen. The validity of risk estimates for NSAIDs extrapolated from clinical trials or from observational studies not including OTC-type usage may need to be revised.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Medicamentos sem Prescrição/uso terapêutico , Adolescente , Adulto , Idoso , Uso de Medicamentos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade
17.
Br J Clin Pharmacol ; 70(3): 418-28, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20716243

RESUMO

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Determining bacterial aetiology of acute sinusitis is difficult without employing invasive procedures. Most episodes of acute sinusitis resolve spontaneously. Antibiotics have demonstrated efficacy for the treatment of acute bacterial sinusitis in clinical trials yet little is known of their effectiveness in real-life treatment settings. WHAT THIS STUDY ADDS: Most cases of untreated acute sinusitis resolved spontaneously. Antibiotics were more effective when given within the first 10 days of treatment. This had no effect on later recurrence. Patients with poor oro-dental condition or recent antibiotic use may derive the most benefit from an antibiotic prescription and this should be considered by prescribers. The antibiotics used were found to be equally effective. Existing recommendations to identify acute sinusitis with high probability of bacterial origin, such as the French recommendations, fever or duration of symptoms fail to identify patients in whom antibiotics are more effective. AIMS: To assess the effectiveness of antibiotics in acute bacterial sinusitis. METHODS: This was a prospective cohort study with 2 months follow-up of 5640 patients with acute sinusitis included by a random sample from 1174 GPs and 120 ENT specialists. Main outcomes were short-term initial success, defined as the absence of prescription of (another) antibiotic or sinus lavage within 10 days, and lack of recurrence between the 11th and 60th day, after initial success. RESULTS: Initial success was found in 88.7% (95% CI 85.1, 91.4%) of patients without antibiotic prescription at inclusion and 96.2% (95% CI 95.7, 96.7%) of patients prescribed antibiotics. The 10 day adjusted hazard ratio (HR) for treatment failure (new antibiotic prescription or sinus drainage) with initial antibiotics compared with no antibiotics was 0.30 (95% CI 0.21, 0.42) with no difference between antibiotics. Antibiotics were more effective in patients with poor oro-dental condition (HR 0.04, 95% CI 0.01, 0.20) and in patients who had already used antibiotics during the previous 2 months (HR 0.09, 95% CI 0.03, 0.28). For patients without failure at 10 days, recurrence between the 11th and 60th day was similar whether or not they had initially been prescribed an antibiotic, 94.1% (95% CI 93.4, 94.7%) and 93.4% (95%CI 90.3, 95.5%), respectively. CONCLUSION: Most acute sinusitis cases not prescribed antibiotics resolve spontaneously. Antibiotics reduced by 3.3-fold the risk of failure within 10 days, without impact on later recurrence. The greatest benefit of antibiotics was found for patients with poor oro-dental condition or with antibiotic use within the previous 2 months.


Assuntos
Sinusite/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Feminino , França , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estatística como Assunto , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Br J Clin Pharmacol ; 67(1): 118-24, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19133061

RESUMO

AIM: The aim of this study was to compare patterns of utilization of NSAIDs for musculoskeletal disorders (MSD) by occupation in a general employed population. METHODS: This was a secondary analysis of the CADEUS cohort study on 5651 actively employed patients, who submitted at least one claim for the reimbursement of a NSAID dispensation for a MSD between August 2003 and July 2004, in the French National Healthcare Insurance database. Questionnaires were sent to prescribing physicians to obtain diagnoses and the medical history, and to patients for their occupation, height and weight and smoking status. Multivariate logistic regression was used to study the determinants of a heavy use of NSAIDs defined as 'over four dispensations in one year with less than two months between any two'. RESULTS: Factors associated with heavy use of NSAIDs were age (Odds ratio (OR): 1.8 (ten years), 95% confidence interval (CI): 1.6-1.9), osteoarthritis (versus back pain) (OR: 1.8, 95% CI: 1.5-2.1), body mass index (superior to 30) (OR: 1.8, 95% CI: 1.5-2.2), and occupation (blue collar versus white collar workers) (OR: 1.4, 95% CI: 1.2-1.6). Blue collar workers also had a 20% higher prevalence of 5-year history of dyspepsia. No difference was observed between sexes or in the use of COX-2 selective inhibitors between occupations. CONCLUSION: Factors associated with occupational constraints that contribute to the severity of MSDs, may explain the heavier use of NSAIDs among blue collar workers in spite of a concurrent and past medical history of adverse reactions to this type of medication.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Revisão de Uso de Medicamentos , Doenças Musculoesqueléticas/tratamento farmacológico , Doenças Profissionais/tratamento farmacológico , Ocupações , Adulto , Fatores Etários , Idoso , Métodos Epidemiológicos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Prescrições , Distribuição por Sexo , Adulto Jovem
19.
Antivir Ther ; 9(4): 615-25, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15456093

RESUMO

OBJECTIVES: To compare the antiviral efficacy of a salvage therapy combining lopinavir and amprenavir with 200 mg/d or 400 mg/d ritonavir, together with nucleoside reverse transcriptase inhibitors, over a 26-week period in HIV-infected patients in whom multiple antiretroviral regimens had failed. DESIGN: Phase IIb, randomized, open-label, multicentre trial. Patients were eligible if they had <500 CD4+ cells/mm3 and >4 log10 copies/ml HIV-RNA after treatment with at least two protease inhibitors (PIs) and one non-nucleoside reverse transcriptase inhibitor. RESULTS: At baseline (n=37), the median CD4+ cell count was 207/mm3 and the median plasma HIV-1 RNA level was 4.7 log10 copies/ml; the median number of PI mutations was seven and the median decrease in phenotypic susceptibility to lopinavir and amprenavir was 9.7 and 2.6, respectively. The mean number of antiretrovirals received prior to randomization was 7.7. The fall in the median HIV-1 RNA level at week 26 was -1.4 log10 copies/ml in the 200 mg/d ritonavir group and -2.5 log10 copies/ml in the 400 mg/d group (P=0.02). Viral load fell below 50 copies/ml in 32% and 61% of patients, respectively (P=0.07). After adjustment for the ritonavir dose, a smaller number of PI mutations was the only baseline characteristic associated with a better virological response at week 26. Amprenavir concentrations were significantly lower in presence of lopinavir. The lopinavir inhibitory quotient at week 6 correlated weakly with the change in the HIV-RNA level at week 26. CONCLUSION: Combination of amprenavir, lopinavir and 400 mg/d ritonavir shows significant virological efficacy without increased toxicity in HIV-infected patients in whom multiple antiretroviral regimens have failed.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1 , Pirimidinonas/uso terapêutico , Ritonavir/uso terapêutico , Terapia de Salvação , Sulfonamidas/uso terapêutico , Adulto , Idoso , Carbamatos , Esquema de Medicação , Quimioterapia Combinada , Feminino , França , Furanos , Infecções por HIV/sangue , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Lopinavir , Masculino , Pessoa de Meia-Idade , Pirimidinonas/administração & dosagem , RNA Viral/sangue , Ritonavir/administração & dosagem , Sulfonamidas/administração & dosagem , Carga Viral
20.
Clin Pharmacol Ther ; 75(4): 310-23, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15060509

RESUMO

OBJECTIVE: This pharmacokinetic study was designed to characterize interactions between amprenavir and the lopinavir-ritonavir combination in patients infected with human immunodeficiency virus in whom previous antiretroviral therapy had failed. METHODS: Twenty-seven patients included in a randomized clinical trial (ANRS [National Agency for AIDS Research] Protocol 104) participated in this study. They were randomized to receive ritonavir at a dose of either 100 mg twice daily or 200 mg twice daily. For the first 2 weeks of therapy, they were randomly assigned to receive lopinavir (400 mg twice daily) and ritonavir (100 mg twice daily), amprenavir (600 mg twice daily) plus ritonavir (100 mg twice daily), lopinavir (400 mg twice daily) and ritonavir (100 mg twice daily) plus additional ritonavir (100 mg twice daily), or amprenavir (600 mg twice daily) plus ritonavir (200 mg twice daily). From week 3 onward, all patients received amprenavir plus lopinavir-ritonavir with or without an additional ritonavir dose (100 mg twice daily). The pharmacokinetics of the 3 drugs was studied in weeks 2 and 6 of therapy. RESULTS: Median amprenavir concentrations decreased by 54% (P =.004) when lopinavir was added to the amprenavir-ritonavir regimen. Lopinavir weakly displaced amprenavir from plasma proteins: The average unbound fraction of amprenavir was 0.089 in week 2 and 0.114 in week 6 (P =.03), but this did not fully account for the observed interaction. Increasing the ritonavir dose did not affect the amprenavir concentration. The relationship between lopinavir and ritonavir concentrations fitted a maximum effect (E(max)) model;the average concentration of ritonavir that yielded a lopinavir concentration of 8119 ng/mL (50% of E(max)) was 602 ng/mL (coefficient of variation, 22%). There was a significant relationship between the lopinavir inhibitory quotient and the virologic response in week 2 (P =.005). CONCLUSION: Lopinavir markedly decreases the amprenavir concentration during amprenavir and lopinavir-ritonavir combination therapy. The inhibitory quotients were more predictive of the short-term virologic response than was the level of drug exposure.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Pirimidinonas/administração & dosagem , Ritonavir/administração & dosagem , Terapia de Salvação , Sulfonamidas/administração & dosagem , Administração Oral , Adulto , Disponibilidade Biológica , Carbamatos , Relação Dose-Resposta a Droga , Esquema de Medicação , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Seguimentos , Furanos , Infecções por HIV/diagnóstico , Humanos , Lopinavir , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Probabilidade , Pirimidinonas/farmacocinética , Medição de Risco , Ritonavir/farmacocinética , Índice de Gravidade de Doença , Método Simples-Cego , Estatísticas não Paramétricas , Sulfonamidas/farmacocinética , Taxa de Sobrevida , Resultado do Tratamento , Carga Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA