Causal inference to formalize responsibility analyses in road safety epidemiology

Journées GDR/SFB, BORDEAUX, FRANCE, 05-/10/2017 - 06/10/2017The last few decades have seen the Structural Causal Model framework provide valuable tools to assess causal effects from observational data. In this article, we briefly review recent results regarding the recoverability of causal effects from selection biased data, and apply them to the case of responsibility analyses in road safety epidemiology. Our objective is to formally determine whether causal effects can be unbiasedly estimated through this type of analyses, when available data are restricted to severe accidents, as it is commonly the case in practice. However, because speed has a direct effect on the severity of the accident, we show that the causal odds-ratio of exposures that influence speed, such as alcohol, is not estimable. We present numerical results to illustrate our arguments, the magnitude of the bias and to discuss some recent results from real data

Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions

Objective: The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown. Methods: HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (,8), medium (8-9), or high (.9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up. Results: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58). Conclusions: We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions

[Cancer and HIV infection.]

International audienceAvec l'arrivée des nouvelles combinaisons antirétrovirales, l'incidence des cancers classant SIDA a fortement diminué et l'incidence des cancers ne définissant pas le SIDA est désormais plus élevée. les cancers dont le risque est augmenté avec l'immunodépression sont le plus souvent associés à une infection virale. Dans le contexte de l'infection à VIH, certains virus pourraient avoir un effet oncogène directement ou via un processus de facilitation, l'immunodépression limitant la capacité de l'hôte de contrôler précocement l'expansion tumorale ou la réplication virale. Les taux de survie après un diagnostic de cancer sont significativement plus faibles chez les personnes vivant avec le VIH que dans la population générale posant la question de la sévérité de leur présentation, et aussi celle de leur prise en charge

[Cancer and HIV infection.]

International audienceAvec l'arrivée des nouvelles combinaisons antirétrovirales, l'incidence des cancers classant SIDA a fortement diminué et l'incidence des cancers ne définissant pas le SIDA est désormais plus élevée. les cancers dont le risque est augmenté avec l'immunodépression sont le plus souvent associés à une infection virale. Dans le contexte de l'infection à VIH, certains virus pourraient avoir un effet oncogène directement ou via un processus de facilitation, l'immunodépression limitant la capacité de l'hôte de contrôler précocement l'expansion tumorale ou la réplication virale. Les taux de survie après un diagnostic de cancer sont significativement plus faibles chez les personnes vivant avec le VIH que dans la population générale posant la question de la sévérité de leur présentation, et aussi celle de leur prise en charge

Prise en charge tardive des sujets séropositifs pour le virus de l'immunodéficience humaine

Dans les pays industrialisés, depuis 1996, l accès aux multithérapies antirétrovirales a considérablement amélioré le pronostic clinique des patients séropositifs pour le virus de l immunodéficience humaine (VIH). Cependant, les patients pris en charge tardivement, à un stade immuno-clinique avancé de l infection, ont une espérance de vie plus courte. Cette thèse a étudié, chez les patients inclus dans la base de données hospitalière française sur l infection à VIH (ANRS CO4-FHDH), la fréquence de la prise en charge tardive, ses caractéristiques socio-démographiques et son influence sur la survie. Plus d un tiers des patients était pris en charge tardivement à leur inclusion dans la cohorte en 1997-2002. La prise en charge tardive était associée à une surmortalité, très importante lors des 6 premiers mois du suivi et persistante jusqu à 4 ans après l inclusion. Parmi les patients suivis en 1999, 8,5% n étaient pas revus à un an dans la base actualisée en 2001 et ceci pourrait influencer nos résultats. Parmi les facteurs associés à la perte de vue, le plus important était une durée de diagnostic inférieure à un an. Nous avons recherché le statut vital des patients perdus de vue en 1999 lors l actualisation de FHDH à la mi-2006 puis par croisement avec les données de Mortalité 2000-CépiDc. Après actualisation, le taux de perte de vue à 1 an était de 7,5% et 5,4% des patients n avaient jamais été revus depuis 1999 parmi lesquels 29,8% étaient décédés selon les données de Mortalité 2000-CépiDc. Les analyses effectuées après correction du statut vital confirment la surmortalité associée à la prise en charge tardive et sa persistance à distance de l inclusion dans la cohorte.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Integrating expert’s knowledge constraint of time dependent exposures in structure learning for Bayesian networks

International audienc

Effect of bariatric surgery on cancer risk: results from an emulated target trial using population-based data

International audienceAbstract Background The impact of weight loss induced by bariatric surgery on cancer occurrence is controversial. To study the causal effect of bariatric surgery on cancer risk from an observational database, a target-trial emulation technique was used to mimic an RCT. Methods Data on patients admitted between 2010 and 2019 with a diagnosis of obesity were extracted from a national hospital discharge database. Criteria for inclusion included eligibility criteria for bariatric surgery and the absence of cancer in the 2 years following inclusion. The intervention arms were bariatric surgery versus no surgery. Outcomes were the occurrence of any cancer and obesity-related cancer; cancers not related to obesity were used as negative controls. Results A total of 1 140 347 patients eligible for bariatric surgery were included in the study. Some 288 604 patients (25.3 per cent) underwent bariatric surgery. A total of 48 411 cancers were identified, including 4483 in surgical patients and 43 928 among patients who did not receive bariatric surgery. Bariatric surgery was associated with a decrease in the risk of obesity-related cancer (hazard ratio (HR) 0.89, 95 per cent c.i. 0.83 to 0.95), whereas no significant effect of surgery was identified with regard to cancers not related to obesity (HR 0.96, 0.91 to 1.01). Conclusion When emulating a target trial from observational data, a reduction of 11 per cent in obesity-related cancer was found after bariatric surgery

Trend of antibiotic consumption and its association with influenza-like illnesses in France between 2004 and 2018

International audienceAbstract Background Antibiotic consumption has been reported to be driven by the treatment of respiratory tract infections. Our objectives were to describe the trend of antibiotic consumption in France compared with that of other European countries; to describe the evolution of each antibiotic class in France; and to explore the relationship between antibiotic consumption and incidence of influenza-like illnesses. Methods In this observational study, antibiotic consumption was reported as defined daily doses per 1000 inhabitants per day in the community and hospital sectors in descriptive and graphical formats, using data from the European Surveillance of Antimicrobial Consumption Network database. The total consumption and the consumption of different classes of antibiotics in France according to time and influenza-like illnesses were studied using multiple linear regression models. Results The total consumption of antibiotics in France was constant over the 15 years. It was driven by the community sector (92.8%) and was higher than the consumption of other European Union countries (P-value < 0.001). The beta-lactam penicillins were the most consumed antibiotic class and the only class that increased with time. The multiple linear regression models showed a positive correlation between antibiotic consumption in the community sector and incidence of influenza-like illnesses [B = 0.170, 95% CI (0.088–0.252)]. Similar significant results were shown between other antibiotic classes used in the management of influenza-like illnesses (other beta-lactams, and macrolides, lincosamides and streptogramins) and influenza-like illnesses. Conclusion Our results suggest that antibiotics used in the management of respiratory tract infections might be involved in the irrational use of antibiotics

Estimating causal effects of time-dependent exposures on a binary endpoint in a high-dimensional setting

Abstract Background Recently, the intervention calculus when the DAG is absent (IDA) method was developed to estimate lower bounds of causal effects from observational high-dimensional data. Originally it was introduced to assess the effect of baseline biomarkers which do not vary over time. However, in many clinical settings, measurements of biomarkers are repeated at fixed time points during treatment and, therefore, this method needs to be extended. The purpose of this paper is to extend the first step of the IDA, the Peter Clarks (PC)-algorithm, to a time-dependent exposure in the context of a binary outcome. Methods We generalised the so-called “PC-algorithm” to take into account the chronological order of repeated measurements of the exposure and proposed to apply the IDA with our new version, the chronologically ordered PC-algorithm (COPC-algorithm). The extension includes Firth’s correction. A simulation study has been performed before applying the method for estimating causal effects of time-dependent immunological biomarkers on toxicity, death and progression in patients with metastatic melanoma. Results The simulation study showed that the completed partially directed acyclic graphs (CPDAGs) obtained using COPC-algorithm were structurally closer to the true CPDAG than CPDAGs obtained using PC-algorithm. Also, causal effects were more accurate when they were estimated based on CPDAGs obtained using COPC-algorithm. Moreover, CPDAGs obtained by COPC-algorithm allowed removing non-chronological arrows with a variable measured at a time t pointing to a variable measured at a time t´ where t´ < t. Bidirected edges were less present in CPDAGs obtained with the COPC-algorithm, supporting the fact that there was less variability in causal effects estimated from these CPDAGs. In the example, a threshold of the per-comparison error rate of 0.5% led to the selection of an interpretable set of biomarkers. Conclusions The COPC-algorithm provided CPDAGs that keep the chronological structure present in the data and thus allowed to estimate lower bounds of the causal effect of time-dependent immunological biomarkers on early toxicity, premature death and progression