RESUMO
PURPOSE: Baclofen is widely used off-label for alcohol use disorders (AUD) in France, despite its uncertain efficacy and safety, particularly at high doses. This study was designed to evaluate the safety of this off-label use compared to the main approved drugs for AUD (acamprosate, naltrexone, nalmefene). METHODS: This cohort study from the French Health Insurance claims database included patients, aged 18 to 70 years, with no serious comorbidity (assessed by the Charlson score) initiating baclofen or approved drugs for AUD between 2009 and 2015. The risk of hospitalisation or death associated with baclofen, at variable doses over time (from low doses <30 mg/day to high doses ≥180 mg/day), compared to approved drugs, was evaluated by a Cox model adjusted to sociodemographic and medical characteristics. RESULTS: The cohort included 165 334 patients, 47 614 of whom were exposed to baclofen. Patients exposed to baclofen differed from those treated with approved drugs in terms of sociodemographic and medical characteristics (more females, higher socioeconomic status, fewer hospitalisations for alcohol-related problems), but these differences tended to fade at higher doses of baclofen. Baclofen exposure was significantly associated with hospitalisation (hazard ratio [HR] = 1.13 [95%CI: 1.09-1.17]) and death (HR = 1.31 [95%CI: 1.08-1.60]). The risk increased with dose, reaching 1.46 [1.28-1.65] for hospitalisation and 2.27 [1.27-4.07] for death at high doses. Similar results were in patients with a history of hospitalisation for alcohol-related problems. CONCLUSIONS: This study raises concerns about the safety of baclofen for AUD, particularly at high doses, with higher risks of hospitalisation and mortality than approved drugs.
Assuntos
Dissuasores de Álcool/administração & dosagem , Alcoolismo/tratamento farmacológico , Baclofeno/efeitos adversos , Hospitalização/estatística & dados numéricos , Uso Off-Label , Acamprosato/administração & dosagem , Acamprosato/efeitos adversos , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Adulto , Idoso , Dissuasores de Álcool/efeitos adversos , Alcoolismo/mortalidade , Baclofeno/administração & dosagem , Bases de Dados Factuais/estatística & dados numéricos , Relação Dose-Resposta a Droga , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Naltrexona/análogos & derivados , Medição de Risco , Fatores SocioeconômicosRESUMO
Guillain-Barré syndrome (GBS) is potentially life threatening and typically occurs after an infection. No detailed information is available concerning the epidemiological characteristics of GBS in France. We estimated age- and sex-specific incidence rates (IRs) based on a French nationwide hospital discharge database. All patients hospitalized for GBS between 2008 and 2013 were identified by International Classification of Diseases-10 code G61.0 as principal diagnosis. Patients previously hospitalized for GBS in 2006 and 2007 were excluded. Sensitivity analyses were performed by considering alternative case definitions, based on more restrictive sets of codes. A total of 9,391 patients were identified, leading to an overall crude IR of 2.42 per 100,000 person-years (world standardized IR = 2.00). IRs increased with age, reaching a peak in the 70-79-year age group. IR was 46% higher in men than in women, and 44% higher in winter than in summer. In children, the highest IR was observed at the age of 2 years. These patterns were not modified by the use of alternative case definitions. This French nationwide study showed similar GBS epidemiological patterns in adults to those reported in other countries. We also report a childhood incidence peak around the age of 2 years, as previously observed in Latin American and Chinese populations.
Assuntos
Síndrome de Guillain-Barré/epidemiologia , Alta do Paciente/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Bases de Dados Factuais/estatística & dados numéricos , Feminino , França/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estações do Ano , Adulto JovemRESUMO
BACKGROUND: The most used score to measure comorbidity is the Charlson index. Its application to a health care administrative database including International Classification of Diseases, 10th edition (ICD-10) codes, medical procedures, and medication required studying its properties on survival. Our objectives were to adapt the Charlson comorbidity index to the French National Health Insurance database to predict 1-year mortality of discharged patients and to compare discrimination and calibration of different versions of the Charlson index. METHODS: Our cohort included all adults discharged from a hospital stay in France in 2010 registered in the French National Health Insurance general scheme. The pathologies of the Charlson index were identified through ICD-10 codes of discharge diagnoses and long-term disease, specific medical procedures, and reimbursement of specific medications in the past 12 months before inclusion. RESULTS: We included 6,602,641 subjects at the date of their first discharge from medical, surgical, or obstetrical department in 2010. One-year survival was 94.88%, decreasing from 98.41% for Charlson index of 0-71.64% for Charlson index of ≥5. With a discrimination of 0.91 and an appropriate calibration curve, we retained the crude Cox model including the age-adjusted Charlson index as a 4-level score. CONCLUSIONS: Our study is the first to adapt the Charlson index to a large health care database including >6 million of inpatients. When mortality is the outcome, we recommended using the age-adjusted Charlson index as 4-level score to take into account comorbidities.
Assuntos
Comorbidade , Registros Eletrônicos de Saúde/estatística & dados numéricos , Mortalidade , Risco Ajustado/métodos , Adulto , Idoso , Feminino , França , Humanos , Revisão da Utilização de Seguros/estatística & dados numéricos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
AIM: To quantify and describe the population starting treatment with baclofen for alcohol dependence during the period 2007-2013 in France. METHODS: The French national health insurance (système national d'information inter-régimes de l'Assurance maladie [SNIIRAM]) and French hospital discharge (programme de médicalisation des systèmes d'information [PMSI]) databases were used to identify the population starting treatment with baclofen, determine the algorithm of baclofen use, define patient characteristics and their treatment. RESULTS: About 200,000 subjects initiated baclofen therapy between 2007 and 2013, for alcohol dependence in 52.0% of cases. In 2013, this population was predominantly male (62.3%), with a mean age of 50.1 years, the first prescriber was a general practitioner in 58.9% of cases, they continued their treatment 6 months after their initiation in 48.8% of cases and one half of these subjects consumed at least 57.0 mg of baclofen daily. CONCLUSIONS: The use of baclofen for alcohol dependence increased considerably since 2008, with more than 34,000 new users and more than 9,000 general practitioners as first prescribers in 2013.
Assuntos
Dissuasores de Álcool/uso terapêutico , Alcoolismo/tratamento farmacológico , Baclofeno/uso terapêutico , Bases de Dados Factuais , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos , Feminino , França/epidemiologia , Humanos , Masculino , Medicina , Programas Nacionais de Saúde/estatística & dados numéricos , Doenças do Sistema Nervoso/tratamento farmacológico , Alta do Paciente/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricosRESUMO
Cervical cancer screening in young women may lead to the detection of lesions with a high potential for spontaneous regression and no benefit of surgery. French guidelines recommend initiating cervical cancer screening by the Pap test from the age of 25 years. To date, no French nationwide study has assessed cervical cancer screening in young women and the related subsequent work-up and surgical procedures among screen-positive women. Using data from the French national healthcare databases (around 50 million beneficiaries), annual and 3-year Pap test screening rates were calculated among women aged 15-24 years between 2007 and 2013. Cervical excisional procedures were assessed during the 15-month period following a first Pap test in women aged 20-24 years in 2007 and 2012. About 10% of the almost six million women aged 15-65 years with at least one annual Pap test were under the age of 25, mainly women aged 20-24 years, in whom the 3-year screening coverage was 35.5% in 2013. In screened women aged 20-24 years, human papillomavirus testing rates increased markedly over the study period (+105%) and surgical management became less conservative with an increased rate of both conization (+16.5%) and other excisional treatments (+74.5%). Nevertheless, because of the overall decrease in screening coverage, the absolute yearly number of women who underwent conization decreased from 1974 to 1766 between 2007 and 2012. Higher adherence to guidelines is needed to reduce the burden of surgical treatment that is potentially associated with adverse obstetric outcomes among women under the age of 25 years.
Assuntos
Conização/estatística & dados numéricos , Detecção Precoce de Câncer/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Colo do Útero/virologia , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Feminino , França/epidemiologia , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Incidência , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Teste de Papanicolaou/normas , Teste de Papanicolaou/estatística & dados numéricos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal/normas , Esfregaço Vaginal/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Whether human papillomavirus (HPV) vaccination could induce or trigger autoimmune diseases (AID) has been questioned, and potentially contributes to low immunization coverage in France. This study evaluated the association between HPV vaccination and the risk of AID using routinely collected data sources. METHODS: All girls aged 13-16years between 2008 and 2012, covered by the general health insurance scheme and without history of HPV vaccination or AID, were included and followed using French nationwide databases. Fourteen neurological, rheumatological, haematological, gastrointestinal or endocrine AID, were identified from ICD-10 codes allocated to hospital stays and long-term illnesses or by marker drugs. Their incidence was compared between girls exposed and non-exposed to HPV vaccination, using a Cox model adjusted for inclusion year, geographic area, socio-economic indicators, healthcare use level and other immunizations. RESULTS: Among 2,252,716 girls, 37% received HPV vaccine and 4,096 AID occurred during a mean follow-up time of 33months. The incidence of AID was not increased after exposure to HPV vaccination, except for Guillain-Barré syndrome (GBS) (incidence rate of 1.4 among exposed [20 cases] versus 0.4 per 100,000 PY among unexposed [23 cases]; adjusted HR: 3.78 [1.79-7.98]). This association persisted across numerous sensitivity analyses and was particularly marked in the first months following vaccination. Under the hypothesis of a causal relationship, this would result in 1-2 GBS cases attributable to HPV vaccine per 100,000 girls vaccinated. CONCLUSIONS: Our study provides reassuring results regarding the risk of AID after HPV vaccination, but an apparently increased risk of GBS was detected. Further studies are warranted to confirm this finding.
Assuntos
Doenças Autoimunes/etiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/efeitos adversos , Adolescente , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/epidemiologia , Estudos de Coortes , Bases de Dados Factuais , Feminino , Seguimentos , França/epidemiologia , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/etiologia , Humanos , Incidência , Estudos Longitudinais , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Modelos de Riscos Proporcionais , Fatores de Risco , Neoplasias do Colo do Útero/prevenção & controle , VacinaçãoRESUMO
BACKGROUND AND AIM: According to guidelines, diabetic patients with high cardiovascular risk should receive a statin. Despite this consensus, fibrate monotherapy is commonly used in this population. We assessed the frequency and clinical consequences of the use of fibrates for primary prevention in patients with diabetes and high cardiovascular risk. DESIGN: Retrospective cohort study based on nationwide data from the medical and administrative databases of French national health insurance systems (07/01/08-12/31/09) with a follow-up of up to 30 months. METHODS: Lipid-lowering drug-naive diabetic patients initiating fibrate or statin monotherapy were identified. Patients at high cardiovascular risk were then selected: patients with a diagnosis of diabetes and hypertension, and > 50 (men) or 60 (women), but with no history of cardiovascular events. The composite endpoint comprised myocardial infarction, stroke, amputation, or death. RESULTS: Of the 31,652 patients enrolled, 4,058 (12.8%) received a fibrate. Age- and gender-adjusted annual event rates were 2.42% (fibrates) and 2.21% (statins). The proportionality assumption required for the Cox model was not met for the fibrate/statin variable. A multivariate model including all predictors was therefore calculated by dividing data into two time periods, allowing Hazard Ratios to be calculated before (HR < 540) and after 540 days (HR > 540) of follow-up. Multivariate analyses showed that fibrates were associated with an increased risk for the endpoint after 540 days: HR < 540 = 0.95 (95% CI: 0.78-1.16) and HR > 540 = 1.73 (1.28-2.32). CONCLUSION: Fibrate monotherapy is commonly prescribed in diabetic patients with high cardiovascular risk and is associated with poorer outcomes compared to statin therapy.