RESUMO
AIMS: To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse subject to treatment (ARRt) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real-life setting. METHODS: A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between 1 July 2015 and 12 December 2017, with 4.5 years of database history and 1-3.5 years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional propensity score. Negative binomial regression and a logistic regression model were used to estimate the relative risk (RR ± [95% CI]) of ARRt and the odds ratio (OR ± [95% CI]) of disability progression, respectively. RESULTS: Overall, 9304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF-IMM patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARRt compared to IMM (RR 0.72 [0.61-0.86]) and TERI (0.81 [0.68-0.96]) and did not show any significant difference when compared with FTY. The risk of the progression of MS-specific disability was not significantly different for any matched cohorts. CONCLUSION: DMF is associated with lower risk of treated relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM).
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Estudos de Coortes , Fumarato de Dimetilo/uso terapêutico , Cloridrato de Fingolimode/uso terapêutico , Humanos , Fatores Imunológicos , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Diagnosis performances of case-identifying algorithms developed in healthcare database are usually assessed by comparing identified cases with an external data source. When this is not feasible, intra-database validation can present an appropriate alternative. OBJECTIVES: To illustrate through two practical examples how to perform intra-database validations of case-identifying algorithms using reconstituted Electronic Health Records (rEHRs). METHODS: Patients with 1) multiple sclerosis (MS) relapses and 2) metastatic castration-resistant prostate cancer (mCRPC) were identified in the French nationwide healthcare database (SNDS) using two case-identifying algorithms. A validation study was then conducted to estimate diagnostic performances of these algorithms through the calculation of their positive predictive value (PPV) and negative predictive value (NPV). To that end, anonymized rEHRs were generated based on the overall information captured in the SNDS over time (e.g. procedure, hospital stays, drug dispensing, medical visits) for a random selection of patients identified as cases or non-cases according to the predefined algorithms. For each disease, an independent validation committee reviewed the rEHRs of 100 cases and 100 non-cases in order to adjudicate on the status of the selected patients (true case/ true non-case), blinded with respect to the result of the corresponding algorithm. RESULTS: Algorithm for relapses identification in MS showed a 95% PPV and 100% NPV. Algorithm for mCRPC identification showed a 97% PPV and 99% NPV. CONCLUSION: The use of rEHRs to conduct an intra-database validation appears to be a valuable tool to estimate the performances of a case-identifying algorithm and assess its validity, in the absence of alternative.
Assuntos
Registros Eletrônicos de Saúde , Recidiva Local de Neoplasia , Algoritmos , Bases de Dados Factuais , Atenção à Saúde , Humanos , MasculinoRESUMO
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 TratamentoRESUMO
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 Narcóticos/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Acetaminofen/administração & dosagem , Adolescente , Adulto , Idoso , Analgésicos não Narcóticos/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 JovemRESUMO
AIMS: This study aimed to describe the real-life incidence of bleeding, arterial thrombotic events and death during vitamin K antagonist (VKA) treatment in atrial fibrillation (AF). METHODS: This was a cohort study in Echantillon Généraliste de Bénéficiaires, the 1/97 sample of the French national healthcare claims and hospitalization database, of new VKA users with definite or probable AF and no other indication, and of patients without AF, from 2007 to 2011. Prespecified outcomes were all-cause death, hospitalization for bleeding, arterial thrombotic event (ATE), or acute coronary syndrome (ACS) or any of the above (composite outcome). RESULTS: Of 8894 new VKA users, 3345 had probable or certain AF, 51.7% were male, mean age was 75.1 years, 87.1% had a CHA2 DS2 -VASc score ≥ 2 and 11.6% a HAS-BLED score > 3. Among AF patients, during VKA exposure the incidence rate of bleeding was 2.8 [95% confidence interval (CI) 2.2, 3.4] per 100 patient-years, including 0.6 (95% CI 0.3, 0.8) cerebral, 1.0 (95% CI 0.7, 1.3) digestive and 1.4 (95% CI 1.0, 1.7) other bleeds. There were 1.6 (95% CI 1.2, 2.0) ACS, 1.5 (95% CI 1.1, 1.8) ATE and 3.8 (95% CI 3.2, 4.4) deaths per 100 patient-years. The incidence rate of the composite outcome was 9.1 per 100 patient-years (95% CI 8.2, 10.0). When patients stopped VKA, bleeding decreased (RR 0.67, 95% CI 0.43, 1.04)), but death or thrombosis increased (RR 3.06, 95% CI 2.46, 3.81 and 1.75, 95% CI 1.14, 2.70, respectively). During VKA exposure non-AF patients had similar rates of bleeding, but fewer deaths, ACS and ischaemic events. CONCLUSIONS: Real-life rates for bleeding, arterial thrombotic events, ACS and deaths in AF patients treated with VKA were similar to those observed in clinical trials.
Assuntos
Síndrome Coronariana Aguda/epidemiologia , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Bases de Dados Factuais , Hemorragia/epidemiologia , Trombose/epidemiologia , Vitamina K/antagonistas & inibidores , Síndrome Coronariana Aguda/induzido quimicamente , Idoso , Fibrilação Atrial/mortalidade , Feminino , França/epidemiologia , Hemorragia/induzido quimicamente , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Trombose/induzido quimicamenteRESUMO
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 OTCâ vs. 53 for POM; 93% OTCâ 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-IdadeRESUMO
OBJECTIVE: Estimate the effect of lifestyle adjustment activities in patients with metabolic syndrome treated by prescribed balneotherapy. METHODS: Observational pilot cohort study with 12-month follow-up after multidimensional lifestyle training (physical, dietary, educational) during 3-week standard stay in the spa town of Eugénie-les-Bains. RESULTS: Of 145 eligible patients, 97 were included; 63 were followed and analysable. At inclusion all had ≥3 National cholesterol education program-Adult treatment panel III (NCEP-ATPIII) criteria defining metabolic syndrome, 76.2% were female, mean age was 61.2 years. At the end of follow-up (median:10.4 months, Inter-Quartile Range: [6.7;11.4]), 48 of these 63 patients (76.2%) no longer had metabolic syndrome (95%CI [65.7;86.7]). These 48 patients without metabolic syndrome at the end of follow-up represented 49.5% of the 97 included (95%CI [39.5;59.4]). CONCLUSIONS: Future studies of lifestyle interventions taking advantage of the spa environment can be expected to find least one third of patients free of metabolic syndrome at the end of 12-month follow-up in the intervention group.
Assuntos
Balneologia , Estâncias para Tratamento de Saúde , Estilo de Vida , Síndrome Metabólica/terapia , Adulto , Idoso , Antropometria , Glicemia/análise , Pressão Sanguínea , Terapia Combinada , Dieta Redutora , Terapia por Exercício , Feminino , Seguimentos , Humanos , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/dietoterapia , Pessoa de Meia-Idade , Motivação , Educação de Pacientes como Assunto , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Redução de PesoRESUMO
Although drugs for osteoporosis have been demonstrated to be effective in reducing fracture risk in placebo-controlled clinical trials, data on effectiveness in real-world practice is limited. Data from the French national health insurance claims database (SNDS) were used to follow five cohorts of women aged ≥55 years after initiating treatment for ≥6 months with either denosumab, zoledronic acid, oral bisphosphonates, raloxifene, or teriparatide in 2014-2016. Fracture incidence was compared within each cohort between the 3 months following initiation (baseline fracture risk) and the 12month, 18month, and 24 month postinitiation periods. Data are presented as incidence rate ratios (IRRs) with their 95% confidence intervals (CIs)s. Overall, 67,046 women were included in the denosumab cohort, 52,914 in the oral bisphosphonate cohort, 41,700 in the zoledronic acid cohort, 11,600 in the raloxifene cohort, and 7510 in the teriparatide cohort. The baseline vertebral fracture rate ranged from 1.74 per 1000 person years (PY) in the raloxifene cohort to 34.75PY in the teriparatide cohort, and the baseline hip fracture rate from 0.70PY in the raloxifene cohort to 10.52PY in the zoledronic acid cohort. Compared with the baseline fracture rate, vertebral fractures involving hospitalization were significantly reduced in the 3-24-month postinitiation period with denosumab (IRR 0.6; 95% CI, 0.5-0.7), zoledronic acid (IRR 0.4; 95% CI, 0.3-0.4), teriparatide (IRR 0.3; 95% CI, 0.2-0.5), and oral bisphosphonates (IRR 0.6; 95% CI, 0.4-0.8). Hip fracture incidence was reduced with denosumab (IRR 0.8; 95% CI, 0.6-0.9), but higher for oral bisphosphonates (IRR 1.7; 95% CI, 1.2-2.3); no significant change in hip fracture rate was observed for zoledronic acid, teriparatide, or raloxifene. A reduction in nonvertebral, non-hip fracture incidence was observed only in the denosumab cohort (IRR 0.8; 95% CI, 0.7-0.9). These findings indicate that treatment with osteoporosis drugs is effective in the real-world setting. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
RESUMO
PURPOSE: To determine healthcare claim patterns associated using nonsteroidal anti-inflammatory drugs (NSAIDs) for rheumatoid arthritis (RA). METHODS: The CADEUS study randomly identified NSAID users within the French health insurance database. One-year claims data were extracted, and NSAID indication was obtained from prescribers. Logistic regression was used in a development sample to identify claim patterns predictive of RA and models applied to a validation sample. Analyses were stratified on the dispensation of immunosuppressive agents or specific antirheumatism treatment, and the area under the receiver operating characteristic curve was used to estimate discriminant power. RESULTS: NSAID indication was provided for 26,259 of the 45,217 patients included in the CADEUS cohort; it was RA for 956 patients. Two models were constructed using the development sample (n = 13,143), stratifying on the dispensation of an immunosuppressive agent or specific antirheumatism treatment. Discriminant power was high for both models (AUC > 0.80) and was not statistically different from that found when applied to the validation sample (n = 13,116). CONCLUSIONS: The models derived from this study may help to identify patients prescribed NSAIDs who are likely to have RA in claims databases without medical data such as treatment indication.
Assuntos
Anti-Inflamatórios não Esteroides , Artrite Reumatoide/tratamento farmacológico , Revisão de Uso de Medicamentos/métodos , Revisão da Utilização de Seguros , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/epidemiologia , Revisão de Uso de Medicamentos/estatística & dados numéricos , Feminino , França , Humanos , Revisão da Utilização de Seguros/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Farmacoepidemiologia , Adulto JovemRESUMO
BACKGROUND: Quadruple therapy using a single capsule formulation of bismuth, metronidazole and tetracycline (BMT; Pylera®), associated with omeprazole for the eradication of Helicobacter pylori, represents the reintroduction of bismuth in France after 40 years. OBJECTIVE: To describe the real-life patterns of use of BMT following a request from the French health authorities. METHODS: Patients with a first BMT dispensing (index date, ID), with one year of data before and after ID, were identified in the French nationwide claims database 1/97 sample. Misuse of BMT was defined as dispensing>1 pack of BMT at ID or absence of a diagnostic test in the preceding year. RESULTS: In total, 540 patients were included. Prescribers were gastroenterologists (n=243; 45%) and general practitioners (n=160; 30%). A proton pump inhibitor was co-dispensed to 504 patients (96%). Ten patients (2%) had contraindications to BMT. Fifty-nine patients (11%) met the misuse criteria: ten (2%) were dispensed>1 pack of BMT and 49 (9%) had not had a diagnostic test for H. pylori in the previous year. During follow-up, 27 patients (5%) required retreatment (treatment failure). CONCLUSION: In this real-life study, most patients were dispensed only one pack of BMT, consistent with recommendations. Misuse related principally to the absence of prior diagnostic test for H. pylori.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Bismuto/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Resultado do TratamentoRESUMO
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 & inibidoresRESUMO
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 JovemRESUMO
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 JovemRESUMO
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 JovemRESUMO
BACKGROUND: Imatinib has dramatically improved the prognosis of advanced gastrointestinal stromal tumours (GISTs). Clinical trial data showed that patients with trough imatinib plasma concentrations (Cmin) below 1100 ng/ml (quartile 1) had shorter time to progression, but no threshold has been defined. The main objective of this study was to investigate in advanced GIST whether a Cmin threshold value associated with a longer progression-free survival (PFS) could be specified. This would be the first step leading to therapeutic drug monitoring of imatinib in GIST. PATIENTS AND METHODS: Advanced GIST patients (n=96) treated with imatinib 400 mg/d (41 stomach, 34 small bowel, and 21 other primary site localisations) were prospectively included in this real-life setting study. Routine plasma level testing imatinib (Cmin) and clinical data of were recorded prospectively. RESULTS: Small bowel localisation was associated with an increased relative risk of progression of 3.09 versus stomach localisation (p=0.0255). Mean Cmin (±standard deviation) was 868 (±536) ng/ml with 75% inter-individual and 26% intra-patient variability. A Cmin threshold of 760 ng/ml defined by log-rank test was associated with longer PFS for the whole population (p=0.0256) and for both stomach (p=0.043) and small bowel (p=0.049) localisations when analysed separately. Multivariate Cox regression analysis found that Cmin above 760 ng/ml was associated with 65% reduction risk of progression (p=0.0271) in the whole population independently of the anatomical localisation. CONCLUSION: Concentration of imatinib significantly influences duration of tumour control treatment in GIST patients with a Cmin threshold of 760 ng/ml associated with prolonged PFS in real-life setting.
Assuntos
Antineoplásicos/farmacocinética , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Mesilato de Imatinib/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/metabolismo , Progressão da Doença , Monitoramento de Medicamentos , Feminino , Tumores do Estroma Gastrointestinal/sangue , Humanos , Mesilato de Imatinib/metabolismo , Intestino Delgado/química , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estômago/química , Resultado do TratamentoRESUMO
The aims of the present study were to assess the prevalence and comorbidity of psychiatric disorders in subjects with intentional drug overdose and to explore whether there were gender differences in prevalence and comorbidity. A standardized psychiatric evaluation was performed in 100 randomly selected subjects, 18 years old and older, with intentional drug overdose referred to an emergency department. The prevalences of psychiatric morbidity and comorbidity were very high in both genders: 88% presented with at least one psychiatric diagnosis, and three-quarters presented with comorbid psychiatric disorders. Affective and anxiety disorders were the most prevalent diagnoses. One patient out of three presented with alcohol or substance misuse. Compared to females, males suffered five times more often from substance misuse and three times more often from psychotic syndrome and were three times less likely to present with anxiety disorder. When subjects are referred to hospital for intentional drug overdose, medical management should systematically involve a psychiatric assessment in order to identify not only affective and anxiety disorders, but also alcohol and substance misuse, due to the high prevalence of these disorders, especially in male subjects.
Assuntos
Transtornos de Ansiedade/epidemiologia , Transtornos Psicóticos/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Adolescente , Adulto , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Comorbidade , Feminino , Humanos , Masculino , Prevalência , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Estudos de Amostragem , Distribuição por Sexo , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/psicologiaAssuntos
Catárticos/uso terapêutico , Laxantes/uso terapêutico , Automedicação/estatística & dados numéricos , Idoso , Catárticos/administração & dosagem , Estudos Transversais , Feminino , França , Humanos , Laxantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Farmácias , Inquéritos e QuestionáriosRESUMO
The correct use of inhalation devices is an inclusion criterion in many comparative studies. However, patients can make errors, thus compromising the effectiveness of their own inhaler. The aim of the study is to evaluate inhaler use by patients with chronic obstructive pulmonary disease (COPD) [n = 984]. General practitioners assessed inhalation technique, using a specific checklist previously established for each inhaler model (Aerolizer, Autohaler, Diskus, a pressurised metered-dose inhaler (pMDI) or a Turbuhaler). A total of 24% of the patients using a pMDI did not make an error compared with 34-40% of those using breath-actuated devices. The frequency of critical errors varied according to the device: 11.5-14.9% of the subjects using an Aerolizer, Autohaler or Diskus versus 37.4% and 38.1% of the patients using a pMDI and a Turbuhaler, respectively. The proper use of the Turbuhaler is often overestimated (24.7%) compared with the pMDI (2.1%). The development of educational programmes for patients and prescribers is needed to improve the management of COPD.
Assuntos
Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Erros de Medicação , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Anti-tumour necrosis factor (TNF) agents, through their intense immunoregulatory effect, have been suspected to increase the risk of malignant lymphoma. However, the classical epidemiological approaches conducted over about the last 10 years have not totally succeeded in addressing the question of a causal or artifactual association. Therefore, the analysis of a substantial set of case reports, although usually considered as poorly generalizable to the general population, could be particularly informative. Two main sources of case reports in postmarketing settings are available; publications in medical journals and reports to pharmacovigilance systems. OBJECTIVE: The aim of the study was to compare the characteristics of case reports from both these sources in order to understand whether they provided the same information for the investigation of the causal link between lymphoma and anti-TNF agents. METHODS: All case reports of malignant lymphoma in patients treated with an anti-TNF agent published in MEDLINE and all reports to the French pharmacovigilance system up to 1 February 2010 were identified. Cases of malignant lymphoma identified in postmarketing surveillance from both sources were compared regarding the following variables: age, sex, anti-TNF agent involved, indication for use, type of lymphoma, prior or concomitant immunosuppressive drugs and time to onset of lymphoma. RESULTS: A total of 81 published case reports and 61 cases reported to the French pharmacovigilance system were compared. In published reports, patients were younger (p = 0.03) and more frequently receiving a first anti-TNF treatment (p = 0.03), particularly infliximab (p = 0.03). Conversely, in the pharmacovigilance system reports, a succession of different anti-TNFs (p = 0.03) and adalimumab (p < 0.0001) were more frequently reported. Lymphomas in patients treated with anti-TNF agents for Crohn's disease were more prevalent in published cases than in pharmacovigilance reports (p < 0.0001), and in particular involved hepatosplenic T-cell lymphoma. Conversely, rheumatoid arthritis was the main indication for anti-TNF agents in pharmacovigilance reports (p = 0.01). Time to onset was markedly shorter in published cases (median 12 months) than in pharmacovigilance reports (median 30 months; p = 0.0001). CONCLUSIONS: Characteristics of published cases and those reported to the French pharmacovigilance system differed markedly for all characteristics tested, except sex and the use of prior or concomitant immunosuppressive drugs. Published case reports favoured convincing arguments for drug causation whereas cases reported to the pharmacovigilance system were more disparate but could describe more accurately the reality of lymphoma occurrence in this particular population. These results argue for the use of the pharmacovigilance reports when case reports are used to investigate the causal link between lymphoma and anti-TNF agents at the population level. Data from cases notified to the French pharmacovigilance system did not indicate an increased risk of lymphoma during the early phase of anti-TNF treatment. To confirm this hypothesis, a study combining pharmacovigilance reports from several countries, or, if feasible, a cohort study both with a large sample size and a long duration of follow-up would be required.