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      Prescription medicine use by pedestrians and the risk of injurious road traffic crashes: A case-crossover study

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          While some medicinal drugs have been found to affect driving ability, no study has investigated whether a relationship exists between these medicines and crashes involving pedestrians. The aim of this study was to explore the association between the use of medicinal drugs and the risk of being involved in a road traffic crash as a pedestrian.

          Methods and findings

          Data from 3 French nationwide databases were matched. We used the case-crossover design to control for time-invariant factors by using each case as its own control. To perform multivariable analysis and limit false-positive results, we implemented a bootstrap version of Lasso. To avoid the effect of unmeasured time-varying factors, we varied the length of the washout period from 30 to 119 days before the crash. The matching procedure led to the inclusion of 16,458 pedestrians involved in an injurious road traffic crash from 1 July 2005 to 31 December 2011. We found 48 medicine classes with a positive association with the risk of crash, with median odds ratios ranging from 1.12 to 2.98. Among these, benzodiazepines and benzodiazepine-related drugs, antihistamines, and anti-inflammatory and antirheumatic drugs were among the 10 medicines most consumed by the 16,458 pedestrians. Study limitations included slight overrepresentation of pedestrians injured in more severe crashes, lack of information about self-medication and the use of over-the-counter drugs, and lack of data on amount of walking.

          Conclusions

          Therapeutic classes already identified as impacting the ability to drive, such as benzodiazepines and antihistamines, are also associated with an increased risk of pedestrians being involved in a road traffic crash. This study on pedestrians highlights the necessity of improving awareness of the effect of these medicines on this category of road user.

          Abstract

          In a case-crossover study, Mélanie Née and colleagues examines the association between use of presciption medicine by pedestrians and risk of injurious road traffic crashes.

          Author summary

          Why was this study done?
          • Pedestrians account for 22% of the world’s road traffic deaths.

          • Medicines have the potential to impair the ability of all road users, including pedestrians.

          • To our knowledge, no study so far has investigated the association between consumption of medicinal drugs and risk of road traffic injury as a pedestrian.

          What did the researchers do and find?
          • We matched French nationwide databases with data on road traffic crashes (collected by police officers) and data on medicine delivery (collected by the national healthcare insurance system).

          • We identified 16,458 pedestrians involved in an injurious road traffic crash between 1 July 2005 and 31 December 2011. Among them, 6,584 were included in our analyses.

          • Several classes of medicine were associated with an increased risk of a pedestrian being involved in a road traffic crash.

          • The most commonly consumed medicines associated with an increased risk of crash included benzodiazepines and benzodiazepine-related drugs, antihistamines, and anti-inflammatory and antirheumatic drugs.

          What do these findings mean?
          • Increased awareness of the risks of medicine use for pedestrians is important as the risks of medicines in road safety have hitherto been thought to concern drivers only.

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          Most cited references46

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          Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort.

          The Diabetes Control and Complications Trial (DCCT) demonstrated the powerful impact of glycemic control on the early manifestations of microvascular complications. Contemporary prospective data on the evolution of macrovascular and late microvascular complications of type 1 diabetes are limited. The Epidemiology of Diabetes Interventions and Complications (EDIC) study is a multicenter, longitudinal, observational study designed to use the well-characterized DCCT cohort of > 1,400 patients to determine the long-term effects of prior separation of glycemic levels on micro- and macrovascular outcomes. Using a standardized annual history and physical examination, 28 EDIC clinical centers that were DCCT clinics will follow the EDIC cohort for 10 years. Annual evaluation also includes resting electrocardiogram. Doppler ultrasound measurements of ankle/arm blood pressure, and screening for nephropathy. At regular intervals, a timed 4-h urine is collected, lipid profiles are obtained, and stereoscopic fundus photographs are taken. In addition, dual B-mode Doppler ultrasound scans of the common and internal carotid arteries will be performed at years 1 and 6 and at study end. Written informed consent was obtained from 96% of the DCCT subjects. The participants, compared with nonparticipants, tended to have better glycemic control at the completion of the DCCT and were more likely to have their diabetes care provided by DCCT personnel. The EDIC baseline measurement stratified by sex delineates multiple cardiovascular disease risk factor differences such as age (older in men), waist-to-hip ratio (higher in men). HDL cholesterol (lower in men), hypertension (more prevalent in men), and maximum intimal-medial thickness of common and internal carotid arteries (thicker in men). Of the original conventional treatment group, 69% have changed to continuous subcutaneous insulin infusion or multiple daily injections. Although the mean HbA1c difference between the intensive and conventional treatment groups narrowed at EDIC years 1 and 2, HbA1c remained significantly lower in the intensive group. Of all expected clinic visits, 95% were completed, and the quality of EDIC data is very similar to that observed in the DCCT. Although obvious problems exist in extended follow-up studies of completed clinical trials, these are balanced by the value of continued systematic observation of the DCCT cohort. In contrast to other epidemiologic studies, EDIC will provide 1) definitive data on type 1 as distinct from type 2 diabetes; 2) reliance on prospective rather than on cross-sectional analysis; 3) long-term follow-up in a large population; 4) consistent use of objective, reliable measures of outcomes and glycemia; and 5) observation of patients from before the onset of complications.
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            The effects of type 1 diabetes on cognitive performance: a meta-analysis.

            To investigate the exact nature and magnitude of cognitive impairments in patients with type 1 diabetes and the possible association with other disease variables, such as recurrent episodes of hypoglycemia and metabolic control. MedLine and PsycLit search engines were used to identify studies on cognitive performance in patients with type 1 diabetes. Effect sizes (Cohen's d), which are the standardized differences between the experimental and the control group, were calculated. In the meta-analysis, a combined d value was calculated, expressing the magnitude of associations across studies. A total of 33 studies were identified that met the inclusion criteria. Compared with nondiabetic control subjects, the type 1 diabetic group demonstrated a significantly lowered performance on the following cognitive domains: intelligence (d = -0.7), speed of information processing (d = -0.3), psychomotor efficiency (d = -0.6), visual (d = -0.4) and sustained attention (d = -0.3), cognitive flexibility (d = -0.5), and visual perception (d = -0.4). Lowered cognitive performance in diabetic patients appeared to be associated with the presence of microvascular complications but not with the occurrence of severe hypoglycemic episodes or with poor metabolic control. In patients with type 1 diabetes, cognitive dysfunction is characterized by a slowing of mental speed and a diminished mental flexibility, whereas learning and memory are spared.The magnitude of the cognitive deficits is mild to moderate, but even mild forms of cognitive dysfunction might hamper everyday activities since they can be expected to present problems in more demanding situations.
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              Least squares after model selection in high-dimensional sparse models

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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: VisualizationRole: Writing – review & editing
                Role: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: SoftwareRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: VisualizationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                18 July 2017
                July 2017
                : 14
                : 7
                : e1002347
                Affiliations
                [1 ] Institut de Santé Publique, d’Epidémiologie et de Développement (ISPED), Université de Bordeaux, Bordeaux, France
                [2 ] Team IETO, Bordeaux Population Health Research Center, UMR U1219, INSERM, Université de Bordeaux, Bordeaux, France
                [3 ] Team Biostatistique, Bordeaux Population Health Research Center, UMR U1219, INSERM, Université Bordeaux, Bordeaux, France
                [4 ] Service d’Information Médicale, Pôle de Santé Publique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
                [5 ] Team Pharmacoepidemiology, Bordeaux Population Health Research Center, UMR U1219, INSERM, Université Bordeaux, Bordeaux, France
                [6 ] Pharmacologie Medicale, Pôle de Santé Publique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
                [7 ] Centre d’Investigation Clinique Bordeaux, INSERM CIC 1401, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
                [8 ] Université de Lyon, Lyon, France
                [9 ] UMRESTTE, UMR T9405, l’Institut Français des Sciences et Technologies des Transports, de l’Aménagement et des Réseaux (IFSTTAR), Bron, France
                [10 ] UMRESTTE, Université Lyon 1, Lyon, France
                University of Toronto, CANADA
                Author notes

                I have read the journal's policy and the authors of this manuscript have the following competing interests: EL is a member of the Editorial Board of PLOS Medicine.

                Author information
                http://orcid.org/0000-0001-7016-501X
                http://orcid.org/0000-0002-3004-8051
                http://orcid.org/0000-0002-3307-049X
                http://orcid.org/0000-0001-8031-7400
                Article
                PMEDICINE-D-16-03479
                10.1371/journal.pmed.1002347
                5515401
                28719606
                c199678d-2390-48f4-9dff-89de3f35b8b4
                © 2017 Née et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 October 2016
                : 7 June 2017
                Page count
                Figures: 3, Tables: 3, Pages: 19
                Funding
                The CESIR-A project was supported by the French Direction de la sécurité et de la circulation routières (DSCR) and the French National Institute of Health and Medical Research (Equipe INSERM). The present study is part of the Drugs Systematized Assessment in real-liFe Environment (DRUGS-SAFE) research program funded by the French Medicines Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM); grants received for the year 2015: 900,000 euros. Employees of ANSM participated in data collection. The funders had no role in study design and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Public and Occupational Health
                Safety
                Traffic Safety
                Social Sciences
                Sociology
                Criminology
                Police
                People and Places
                Population Groupings
                Professions
                Police
                Engineering and Technology
                Civil Engineering
                Transportation Infrastructure
                Roads
                Engineering and Technology
                Transportation
                Transportation Infrastructure
                Roads
                Biology and Life Sciences
                Nutrition
                Diet
                Alcohol Consumption
                Medicine and Health Sciences
                Nutrition
                Diet
                Alcohol Consumption
                Social Sciences
                Economics
                Health Economics
                Health Insurance
                Medicine and Health Sciences
                Health Care
                Health Economics
                Health Insurance
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognition
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antidepressants
                Research and Analysis Methods
                Database and Informatics Methods
                Custom metadata
                Access to the French national healthcare insurance database, the police reports and the national police database of injurious crash have been respectively provided by the French National Health Insurance (CNAMTS), Agira-TransPV and the National Interministerial Road Safety Observatory (ONISR). Access to the national healthcare insurance database and matching with other datasources requires the authorization of the Health Data Institute (Institut des données de santé [IDS]) and the French Data Protection Authority (Commission nationale de l’informatique et des libertés [CNIL]). More information can be found at http://www.institut-des-donnees-de-sante.fr/etudes-recherches or email requests to: ieto.bphu1219@ 123456u-bordeaux.fr .

                Medicine
                Medicine

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