RESUMEN
BACKGROUND: Available treatments for Parkinson's disease (PD) are only partially or transiently effective. Identifying existing molecules that may present a therapeutic or preventive benefit for PD (drug repositioning) is thus of utmost interest. OBJECTIVE: We aimed at detecting potentially protective associations between marketed drugs and PD through a large-scale automated screening strategy. METHODS: We implemented a machine learning (ML) algorithm combining subsampling and lasso logistic regression in a case-control study nested in the French national health data system. Our study population comprised 40,760 incident PD patients identified by a validated algorithm during 2016 to 2018 and 176,395 controls of similar age, sex, and region of residence, all followed since 2006. Drug exposure was defined at the chemical subgroup level, then at the substance level of the Anatomical Therapeutic Chemical (ATC) classification considering the frequency of prescriptions over a 2-year period starting 10 years before the index date to limit reverse causation bias. Sensitivity analyses were conducted using a more specific definition of PD status. RESULTS: Six drug subgroups were detected by our algorithm among the 374 screened. Sulfonamide diuretics (ATC-C03CA), in particular furosemide (C03CA01), showed the most robust signal. Other signals included adrenergics in combination with anticholinergics (R03AL) and insulins and analogues (A10AD). CONCLUSIONS: We identified several signals that deserve to be confirmed in large studies with appropriate consideration of the potential for reverse causation. Our results illustrate the value of ML-based signal detection algorithms for identifying drugs inversely associated with PD risk in health-care databases. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Asunto(s)
Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/diagnóstico , Estudios de Casos y Controles , Aprendizaje Automático , Algoritmos , Sustancias ProtectorasRESUMEN
BACKGROUND AND OBJECTIVES: Despite the potentially devastating effects of pregnancy-related stroke, few studies have examined its incidence by type of stroke. We aimed to study the nationwide incidence rates and recent temporal trends for all types of pregnancy-related stroke and to compare these incidences with stroke incidence in nonpregnant women. METHODS: We conducted a study of 6,297,698 women aged 15-49 years who gave birth in France between 2010 and 2018 with no history of stroke before pregnancy by collecting data from the French National Health Insurance Information System database. Poisson regression was used to estimate the incidence by types of strokes for the different pregnancy periods and the incidence rate ratio of stroke in pregnant vs nonpregnant French women. RESULTS: Among the 6,297,698 women, 1,261 (24.0 per 100,000 person-years) experienced a first ever stroke during, antepartum peripartum, or the first 6 weeks of postpartum. Of the pregnancy-related strokes, 42.9% were ischemic (IS), 41.9% were hemorrhagic (with similar proportion of intracerebral and subarachnoid hemorrhage), and 17.4% were cerebral venous thrombosis (CVT). Compared with nonpregnant women, incidence rates of stroke were similar during pregnancy for IS (adjusted incidence risk ratio [IRR] 0.9 [0.8-1.1]), slightly higher for all hemorrhagic strokes (IRR 1.4 [1.2-1.8]), and considerably increased for CVT (IRR 8.1 [6.5-10.1]). Pregnancy-related stroke incidence rose between 2010 and 2018 for IS and HS but was stable for CVT. DISCUSSION: The risk of pregnancy-related CVT was more than 8-fold higher than that observed in nonpregnant women. The incidence of pregnancy-related IS and HS is increasing over time, and efforts should be made for prevention considering treatable cardiovascular risk factors and hypertensive disorders in pregnant women.
Asunto(s)
Trombosis Intracraneal , Complicaciones Cardiovasculares del Embarazo , Accidente Cerebrovascular , Hemorragia Subaracnoidea , Femenino , Humanos , Incidencia , Trombosis Intracraneal/complicaciones , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Hemorragia Subaracnoidea/complicacionesRESUMEN
AIMS: Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and foetal morbidity and mortality. We aimed to estimate the impact of HDP on the onset of chronic hypertension in primiparous women in the first years following childbirth. METHODS AND RESULTS: This nationwide cohort study used data from the French National Health Data System (SNDS). All eligible primiparous women without pre-existing chronic hypertension who delivered between 2010 and 2018 were included. Women were followed up from six weeks post-partum until onset of hypertension, a cardiovascular event, death, or the study end date (31 December 2018). The main outcome was a diagnosis of chronic hypertension. We used Cox models to estimate hazard ratios (HRs) of chronic hypertension for all types of HDP. Overall, 2 663 573 women were included with a mean follow-up time of 3.0 years. Among them, 180 063 (6.73%) had an HDP. Specifically 66 260 (2.16%) had pre-eclampsia (PE) and 113 803 (4.27%) had gestational hypertension (GH). Compared with women who had no HDP, the fully adjusted HRs of chronic hypertension were 6.03 [95% confidence interval (CI) 5.89-6.17] for GH, 8.10 (95% CI 7.88-8.33) for PE (all sorts), 12.95 (95% CI 12.29-13.65) for early PE, 9.90 (95% CI 9.53-10.28) for severe PE, and 13.17 (95% CI 12.74-13.60) for PE following GH. Hypertensive disorders of pregnancy exposure duration was an additional risk factor of chronic hypertension for all PE subgroups. Women with HDP consulted a general practitioner or cardiologist more frequently and earlier. CONCLUSION: Hypertensive disorders of pregnancy exposure greatly increased the risk of chronic hypertension in the first years following delivery.
Asunto(s)
Hipertensión Inducida en el Embarazo , Preeclampsia , Estudios de Cohortes , Femenino , Humanos , Hipertensión Inducida en el Embarazo/diagnóstico , Hipertensión Inducida en el Embarazo/epidemiología , Periodo Posparto , Preeclampsia/epidemiología , Embarazo , Factores de RiesgoRESUMEN
AIMS: Tobacco smoking is a major risk factor for many cardiovascular diseases. In France, the daily smoking prevalence is among the highest in high-income European countries. This study estimated the number of hospitalizations for cardiovascular diseases attributable to smoking in France in 2015, and the number of stays that could have been avoided if there had been 10% less current smokers or if the prevalence of current smokers had been 20%. METHODS: Age- and sex-specific attributable fractions were calculated by combining relative risks extracted from the literature with the prevalence of smoking estimated in the 2014 Health Barometer, a national representative survey. These fractions were applied to hospitalization stays with a primary diagnosis for a cardiovascular disease whose risk is known to increase with smoking. RESULTS: In France in 2015, 250,813 hospital stays (95% uncertainty interval=234,869-269,807) related to a cardiovascular condition were estimated as attributable to smoking. This represented 21% of all stays for a cardiovascular condition. Ischemic heart disease accounted for the largest share of smoking-related stays (39%). If the number of current smokers had been 10% lower or if the prevalence of smoking in the population had dropped to below 20%, 5867 stays and 25,911 stays, respectively, would have been prevented. CONCLUSIONS: In France, a large number of hospital stays for cardiovascular disease are attributable to tobacco smoking. A 10% reduction in smoking would avoid nearly 6000 hospital stays per year; more than 25,000 annual hospital stays if only 20% of the French population smoked.
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Enfermedades Cardiovasculares , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Femenino , Francia/epidemiología , Hospitalización , Humanos , Masculino , Factores de Riesgo , Fumar/efectos adversos , Fumar/epidemiología , Fumar Tabaco/efectos adversos , Fumar Tabaco/epidemiologíaRESUMEN
Hypertensive disorders of pregnancy (HDP) are one of the leading causes of maternal and fetal morbidity and mortality. We aimed to estimate the prevalence of each HDP in France and to study their associations. All pregnant women who delivered in France between 2010 and 2018 were included in a cohort and followed during their pregnancy and 6 weeks of postpartum. Each HDP occurring during the follow-up was identified. Prevalence of each HDP and cumulative incidence by gestational age were estimated. Incidence rate ratio (IRR) and 95% confidence interval (CI) for preeclampsia among women with preexisting or gestational hypertension (GH) were estimated using Poisson regression and adjusted for age were estimated. Between 2010 and 2018, 6 302 810 deliveries were included. HDP complicated 7.4% of pregnancies. Preeclampsia and GH complicated 2.0% and 4.2% of pregnancies, respectively. Most of preeclampsia cases occurred without a prior HDP. HELLP syndrome represented 10.4% of preeclampsia cases. Compared to nulliparous pregnancies without HDP prior preeclampsia, the age-adjusted IRR of preeclampsia was 6.2 [95% CI: 6.1-6.4] in nulliparous pregnancies with preexisting hypertension and 2.9 [95% CI: 2.8-3.0] in nulliparous pregnancies with GH. In France, HDP occurred in 7.4% of all pregnancies. Women with preexisting chronic hypertension are at high risk to present preeclampsia during pregnancy. Preeclampsia complicated 2.0% of pregnancies in France. Tailoring management of women according to the HDP is a major challenge to avoid complications related to these disorders.
Asunto(s)
Síndrome HELLP , Hipertensión Inducida en el Embarazo , Preeclampsia , Estudios de Cohortes , Femenino , Humanos , Hipertensión Inducida en el Embarazo/epidemiología , Preeclampsia/epidemiología , Embarazo , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: The terrorist attacks in Paris and Nice in 2015 and 2016 generated widespread emotional stress in France. Given that acute emotional stress is a well-known trigger for cardiovascular disease, we investigated whether these attacks had any short-term impact on hospitalizations for acute cardiovascular disease in France. METHODS: Annual hospital discharge data from 2009 to 2016 were extracted from the French Hospital Discharge Database. All hospitalizations with a primary diagnosis of acute coronary syndrome, heart failure, or stroke were selected. Generalized additive Poisson models were used to differentiate "unusual" variations in daily hospitalization numbers in the 15 days following the attacks from the expected background hospitalization rate. RESULTS: The average daily number of hospitalizations was 396.4 for acute coronary syndrome, 598.6 for heart failure, and 334.6 for stroke. The daily mean number of hospitalizations for heart failure and stroke was higher in the 15 days following each attack compared with the reference periods. However, multivariate analysis showed no significant variation in the risk of hospitalization in the days following the attacks. INTERPRETATION: Watching events unfold on television, no matter how dramatic, was not a sufficiently potent trigger for cardiovascular disease, although it may have led to an increase in hospitalizations for stress or anxiety. The 2015 and 2016 terrorist attacks do not seem to have had any measurable short-term impact on hospitalizations for cardiovascular disease either in the Paris and Nice regions or in the rest of France.