Maternal and neonatal outcomes according to the timing of diagnosis of hyperglycaemia in pregnancy: a nationwide cross-sectional study of 695,912 deliveries in France in 2018.

AIMS/HYPOTHESIS: We aimed to assess maternal-fetal outcomes according to various subtypes of hyperglycaemia in pregnancy. METHODS: We used data from the French National Health Data System (Système National des Données de Santé), which links individual data from the hospital discharge database and the French National Health Insurance information system. We included all deliveries after 22 gestational weeks (GW) in women without pre-existing diabetes recorded in 2018. Women with hyperglycaemia were classified as having overt diabetes in pregnancy or gestational diabetes mellitus (GDM), then categorised into three subgroups according to their gestational age at the time of GDM diagnosis: before 22 GW (GDM<22); between 22 and 30 GW (GDM22-30); and after 30 GW (GDM>30). Adjusted prevalence ratios (95% CI) for the outcomes were estimated after adjusting for maternal age, gestational age and socioeconomic status. Due to the multiple tests, we considered an association to be statistically significant according to the Holm-Bonferroni procedure. To take into account the potential immortal time bias, we performed analyses on deliveries at ≥31 GW and deliveries at ≥37 GW. RESULTS: The study population of 695,912 women who gave birth in 2018 included 84,705 women (12.2%) with hyperglycaemia in pregnancy: overt diabetes in pregnancy, 0.4%; GDM<22, 36.8%; GDM22-30, 52.4%; and GDM>30, 10.4%. The following outcomes were statistically significant after Holm-Bonferroni adjustment for deliveries at ≥31 GW using GDM22-30 as the reference. Caesarean sections (1.54 [1.39, 1.72]), large-for-gestational-age (LGA) infants (2.00 [1.72, 2.32]), Erb's palsy or clavicle fracture (6.38 [2.42, 16.8]), preterm birth (1.84 [1.41, 2.40]) and neonatal hypoglycaemia (1.98 [1.39, 2.83]) were more frequent in women with overt diabetes. Similarly, LGA infants (1.10 [1.06, 1.14]) and Erb's palsy or clavicle fracture (1.55 [1.22, 1.99]) were more frequent in GDM<22. LGA infants (1.44 [1.37, 1.52]) were more frequent in GDM>30. Finally, women without hyperglycaemia in pregnancy were less likely to have preeclampsia or eclampsia (0.74 [0.69, 0.79]), Caesarean section (0.80 [0.79, 0.82]), pregnancy and postpartum haemorrhage (0.93 [0.89, 0.96]), LGA neonate (0.67 [0.65, 0.69]), premature neonate (0.80 [0.77, 0.83]) and neonate with neonatal hypoglycaemia (0.73 [0.66, 0.82]). Overall, the results were similar for deliveries at ≥37 GW. Although the estimation of the adjusted prevalence ratio of perinatal death was five times higher (5.06 [1.87, 13.7]) for women with overt diabetes, this result was non-significant after Holm-Bonferroni adjustment. CONCLUSIONS/INTERPRETATION: Compared with GDM22-30, overt diabetes, GDM<22 and, to a lesser extent, GDM>30 were associated with poorer maternal-fetal outcomes.

Choice of Systemic Drugs for the Management of Moderate-to-severe Psoriasis: A Cross-country Comparison Based on National Health Insurance Data.

Current management of moderate-to-severe psoriasis may be heterogeneous between European countries, probably due to differences in the organization of care. The aim of this study was to compare the utilization of systemic treatments for psoriasis between 2 coun-tries. All adults with psoriasis who were registered in the French (SNDS) and the Dutch (VEKTIS) national health insurance databases between 2012 and 2016 were eligible for inclusion. In France, 105,035 (15%) of 684,156 patients and, in the Netherlands, 37,405 (28.6%) of 130,822 patients received at least a systemic agent. In France, the proportion of patients treated with systemic agents was constant, while the type of drugs dispensed shifted from non-biological to biological agents. In the Netherlands, the first systemic treatment was methotrexate and, in France, acitretin. In France, the choice of the first biologic was much more variable than it was in the Netherlands, where a large proportion of patients were dispensed ustekinumab. This study highlights discrepancies between France and the Netherlands concerning the choice of first non-biologic agent and first biologic agent for patients with psoriasis. These discrepancies may be due to differences in the healthcare systems between the 2 countries.

Oral anticoagulants and risk of acute liver injury in patients with nonvalvular atrial fibrillation: a propensity-weighted nationwide cohort study.

Insufficient real-world data on acute liver injury (ALI) risk associated with oral anticoagulants (OACs) exist in patients with nonvalvular atrial fibrillation (NVAF). Using the French national healthcare databases, a propensity-weighted nationwide cohort study was performed in NVAF patients initiating OACs from 2011 to 2016, considering separately those (1) with no prior liver disease (PLD) as main population, (2) with PLD, (3) with a history of chronic alcoholism. A Cox proportional hazards model was used to estimate the hazard ratio with 95% confidence interval (HR [95% CI]) of serious ALI (hospitalised ALI or liver transplantation) during the first year of treatment, for each non-vitamin K antagonist (VKA) oral anticoagulant (NOAC: dabigatran, rivaroxaban, apixaban) versus VKA. In patients with no PLD (N = 434,015), only rivaroxaban new users were at increased risk of serious ALI compared to VKA initiation (adjusted HR: 1.41 [1.05-1.91]). In patients with chronic alcoholism history (N = 13,173), only those initiating dabigatran were at increased risk of serious ALI compared to VKA (2.88 [1.74-4.76]) but an ancillary outcome suggested that differential clinical follow-up between groups might partly explain this association. In conclusion, this study does not suggest an increase of the 1-year risk of ALI in NOAC versus VKA patients with AF.

Annual rate of newly treated atrial fibrillation by age and gender in France, 2010-2016.

Few studies are available on atrial fibrillation (AF) burden at a whole country scale. The objective was to estimate the rate of AF patients newly treated with oral anticoagulants (OAC) in France each year between 2010 and 2016 and to describe age and gender differences. We used the French national health data system. For each year between 2010 and 2016, we identified patients aged over 20 initiating OAC. OAC indicated for the treatment of AF was determined by hospitalization diagnoses, specific procedures and registered long-term disease status, or a multiple imputation process for patients with no recorded information as to why they initiated OAC. Among the 421,453 individuals initiating OAC treatment in 2016, the estimated number of newly treated AF patients was 210,131, women accounting for 46%, patients under 65 years old 17%, and 21.4% of patients living in most deprived area. Age-standardized rates reached 400/100,000 inhabitants. Approximately 19% of patients were recently hospitalized for heart failure and 7% for stroke. Age-standardized rates increased by 35% over the study period in both genders, with a marked increase in patients under 55 (+ 41%) and those over 85 years old (+ 60%). Annual rates of AF patients newly treated with OAC increased by 35% between 2010 and 2016. Important differences in rates were observed according to age, gender and the deprivation level of the living area.

Oral anticoagulation therapy use in patients with atrial fibrillation after the introduction of non-vitamin K antagonist oral anticoagulants: findings from the French healthcare databases, 2011-2016.

OBJECTIVES: To describe (i) the trend in oral anticoagulant (OAC) use following the introduction of non-vitamin K antagonist oral anticoagulant (NOAC) therapy for stroke prevention in atrial fibrillation (AF) patients and (ii) the current patterns of use of NOAC therapy in new users with AF in France. DESIGN: (i) Repeated cross-sectional study and (ii) population-based cohort study. SETTING: French national healthcare databases (50 million beneficiaries). PARTICIPANTS: (i) Patients with identified AF in 2011, 2013 and 2016 and (ii) patients with AF initiating OAC therapy in 2015-2016. PRIMARY AND SECONDARY OUTCOME MEASURES: (i) Trend in OAC therapy use in patients with AF and (ii) patterns of use of NOAC therapy in new users with AF. RESULTS: Between 2011 and 2016, use of OAC therapy moderately increased (+16%), while use of antiplatelet therapy decreased (-22%) among all patients with identified AF. In 2016, among the 1.1 million AF patients, 66% used OAC therapy and were more likely to be treated by vitamin K antagonist (VKA) than NOAC therapy, including patients at higher risk of stroke (63.5%), while 33% used antiplatelet therapy. Among 192 851 new users of OAC therapy in 2015-2016 with identified AF, NOAC therapy (66.3%) was initiated more frequently than VKA therapy, including in patients at higher risk of stroke (57.8%). Reduced doses were prescribed in 40% of NOAC new users. Several situations of inappropriate use at NOAC initiation were identified, including concomitant use of drugs increasing the risk of bleeding (one in three new users) and potential NOAC underdosing. CONCLUSIONS: OAC therapy use in patients with AF remains suboptimal 4 years after the introduction of NOACs for stroke prevention in France and improvement in appropriate prescribing regarding NOAC initiation is needed. However, NOAC therapy is now the preferred drug class for initiation of OAC therapy in patients with AF, including in patients at higher risk of stroke.

Statins for primary prevention and rhabdomyolysis: A nationwide cohort study in France.

AIMS: The purpose of this study was to investigate the risk of rhabdomyolysis in subjects initiating statin therapy for primary prevention of cardiovascular disease, focusing on the type of statin, dose and time since initiation. METHODS AND RESULTS: A nationwide cohort study using French hospital discharge and claims databases was performed, studying subjects from the general population 40-75 years in 2009, with no history of cardiovascular disease and no lipid-lowering drugs during the preceding three-year period, followed for up to seven years. The primary outcome was hospitalization for rhabdomyolysis. Event-free survival analysis and case-time-control analysis were both performed, separately by gender. The cohort included 8,236,667 subjects, 969,460 of whom initiated a lipid-lowering drug for cardiovascular disease primary prevention. During 18,407,391 person-months exposed to statins, 168 events were observed, corresponding to an incidence of rhabdomyolysis of 1.10 per 10,000 person-years (1.54 in men vs 0.81 in women); 10/168 cases were fatal, and 18/168 and 57/168 cases occurred during the first month and first trimester of treatment, respectively. Survival analysis did not reveal any increased overall risk (hazard ratio = 1.02 (0.83-1.25) in men and 0.76 (0.60-0.96) in women). However, exposure to high-potency statins was associated with an increased risk in men (hazard ratio = 1.93 (1.27-2.94)). Rosuvastatin 20 mg (in men and women) and simvastatin 40 mg (in men) were associated with hazard ratios > 5. Case-time-control analyses showed similar patterns of risk. Drug interactions did not appear to significantly contribute to rhabdomyolysis events in this study. CONCLUSION: Although the overall risk of statin-associated rhabdomyolysis in the context of primary prevention was not increased, the first months of treatment and the use of high-potency statins represent at-risk situations, which require appropriate monitoring, especially in men.

Non-bleeding Adverse Events with the Use of Direct Oral Anticoagulants: A Sequence Symmetry Analysis.

INTRODUCTION: Postmarketing pharmacovigilance reports have raised concerns about non-bleeding adverse events associated with direct oral anticoagulants (DOACs), but only limited results are available from large claims databases. OBJECTIVE: The aim of this study was to assess the potential association between DOAC initiation and the onset of four types of non-bleeding adverse events by sequence symmetry analysis (SSA). METHODS: SSA was performed using nationwide data from the French National Healthcare databases (Régime Général, 50 million beneficiaries) to assess a cohort of 386,081 DOAC new users for the first occurrence of four types of non-bleeding outcomes: renal, hepatic, skin outcomes identified by using hospitalization discharge diagnoses, and gastrointestinal outcomes by using medication reimbursement. Asymmetry in the distribution of each investigated outcome occurring before and after initiation of DOAC therapy was used to test the association between DOAC therapy and these outcomes. SSA inherently controls for time-constant confounders, and adjusted sequence ratios were computed after correcting for temporal trends. Negative (glaucoma) and positive (bleeding, depressive disorders) control outcomes were used and analyses were replicated on a cohort of 310,195 patients initiating a vitamin K antagonist (VKA). RESULTS: This study demonstrated the expected positive association between either DOAC or VKA therapy and hospitalised bleeding and initiation of antidepressant therapy, while no association was observed between either DOAC or VKA therapy and initiation of antiglaucoma medications. For DOAC therapy, signals were the associations with hepatic outcomes, including acute liver injury [for the 3-month time window, aSR3 = 2.71, 95% confidence interval (CI) 1.79-4.52]; gastrointestinal outcomes, including initiation of drugs for constipation and antiemetic drugs (aSR3 = 1.31, 95% CI 1.27-1.36; and 1.17, 95% CI 1.12-1.22, respectively); and kidney diseases (aSR3 = 1.33, 95% CI 1.29-1.37). CONCLUSION: Results of this nationwide study suggest that DOACs are associated with rare but severe liver injury and more frequent gastrointestinal disorders. A low risk of kidney injury with DOAC therapy can also not be excluded.

Development of an algorithm to identify pregnancy episodes and related outcomes in health care claims databases: An application to antiepileptic drug use in 4.9 million pregnant women in France.

PURPOSE: Access to claims databases provides an opportunity to study medication use and safety during pregnancy. We developed an algorithm to identify pregnancy episodes in the French health care databases and applied it to study antiepileptic drug (AED) use during pregnancy between 2007 and 2014. METHODS: The algorithm searched the French health care databases for discharge diagnoses and medical procedures indicative of completion of a pregnancy. To differentiate claims associated with separate pregnancies, an interval of at least 28 weeks was required between 2 consecutive pregnancies resulting in a birth and 6 weeks for terminations of pregnancy. Pregnancy outcomes were categorized into live births, stillbirths, elective abortions, therapeutic abortions, spontaneous abortions, and ectopic pregnancies. Outcome dates and gestational ages were used to calculate pregnancy start dates. RESULTS: According to our algorithm, live birth was the most common pregnancy outcome (73.9%), followed by elective abortion (17.2%), spontaneous abortion (4.2%), ectopic pregnancy (1.1%), therapeutic abortion (1.0%), and stillbirth (0.4%). These results were globally consistent with French official data. Among 7 559 701 pregnancies starting between 2007 and 2014, corresponding to 4 900 139 women, 6.7 per 1000 pregnancies were exposed to an AED. The number of pregnancies exposed to older AEDs, comprising the most teratogenic AEDs, decreased throughout the study period (-69.4%), while the use of newer AEDs increased (+73.4%). CONCLUSIONS: We have developed an algorithm that allows identification of a large number of pregnancies and all types of pregnancy outcomes. Pregnancy outcome and start dates were accurately identified, and maternal data could be linked to neonatal data.

Comparison of Treatment Persistence with Dabigatran or Rivaroxaban versus Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients: A Competing Risk Analysis in the French National Health Care Databases.

BACKGROUND: Direct oral anticoagulants (DOACs) have been proposed as a more convenient alternative to vitamin K antagonists (VKAs), which are commonly associated with poor treatment persistence in non-valvular atrial fibrillation (nv-AF). METHODS: Using data from the French national health care databases (Régime Général, 50 million beneficiaries), a cohort study was conducted to compare the 1-year non-persistence rates in nv-AF patients initiating dabigatran (N=11,141) or rivaroxaban (N=11,126) versus VKA (N=11,998). Treatment discontinuation was defined as a switch between oral anticoagulant (OAC) classes or a 60-day gap with no medication coverage, with the additional criterion of no reimbursement for international normalized ratio monitoring during this gap for VKA patients. Considering death as a competing risk, differences between 1-year discontinuation rates were used to compare each DOAC versus VKA. The 95% confidence intervals (CIs) were estimated via bootstrapping. Baseline patient characteristics were adjusted using inverse probability of treatment weighting. Subgroup analyses considered DOAC dose at initiation, age, risk of stroke, and bleeding. RESULTS: Adjusted 1-year discontinuation rates were higher for dabigatran than for VKA new users (36.8% vs 30.2%; difference: 6.6% [95% CI, 5.5-7.6]) and for rivaroxaban versus VKA new users (33.4% vs 30.4%; 3.0% [1.9-4.1]). Similar differences were found in all subgroup analyses, except in dabigatran and rivaroxaban patients <75 years (dabigatran vs VKA: 0.3% [-1.4 to 1.8]; rivaroxaban vs VKA: -2.6% [-4.3 to -0.9]) and dabigatran 150 mg new users (-1.1% [-3.1 to 0.7]). Consistent results were obtained when considering both switches between OAC classes and death as competing risks of treatment discontinuation. CONCLUSION: Results from this nationwide cohort study showed high non-persistence levels with all OACs and suggest that persistence with both dabigatran and rivaroxaban therapy is not better than persistence with VKA therapy. Hospitalizations for bleeding among non-persistent patients were unlikely to explain these high non-persistence rates.

Adherence with direct oral anticoagulants in nonvalvular atrial fibrillation new users and associated factors: a French nationwide cohort study.

PURPOSE: Direct oral anticoagulants (DOACs) have been promoted in patients with nonvalvular atrial fibrillation (nv-AF) as a more convenient alternative to vitamin K antagonists. We estimated 1-year dabigatran and rivaroxaban adherence rates in nv-AF patients and assessed associations between baseline patient characteristics and nonadherence. METHODS: This cohort study included OAC-naive nv-AF patients with no contraindications to OAC, who initiated dabigatran and rivaroxaban, using nationwide data from French national health care databases. One-year adherence was defined by the proportion of days covered of 80% or more over a fixed 1-year period after treatment initiation. Associations between nonadherence and baseline patient characteristics were assessed using multivariate logistic regression models. RESULTS: The population was composed of 11 141 dabigatran (women: 48%; mean age: 74 ± 10.7 y; ≥80 y: 34.9%) and 11 126 rivaroxaban (46.5%; 74 ± 10.9 y; 34.8%) new users. One-year adherence was 53.3% in dabigatran-treated and 59.9% in rivaroxaban-treated patients, consistent with numerous subgroup analyses. A switch to vitamin K antagonist was observed in 14.5% of dabigatran and 11.7% of rivaroxaban patients; 10.2% and 5.9% of patients switched to another DOAC, respectively; and 4.3% of patients died in the 2 cohorts. In patients who did not die or switch during the follow-up, 1-year adherence was 69.6% in dabigatran-treated and 72.3% in rivaroxaban-treated patients. Having concomitant ischemic heart diseases was associated with an increased risk of nonadherence in the 2 cohorts. CONCLUSION: In this real-life study, 1-year adherence to DOAC is poor in nv-AF new users. Despite the introduction of DOAC, adherence to OACs may remain a significant challenge in AF patients.

Identifying atrial fibrillation in outpatients initiating oral anticoagulants based on medico-administrative data: results from the French national healthcare databases.

PURPOSE: Identifying atrial fibrillation (AF) in outpatients treated with oral anticoagulants (OACs) from claims databases is challenging when the outpatient indication is not available, as OACs are also prescribed for deep vein thrombosis/pulmonary embolism (DVT/PE) that may be treated in the ambulatory setting. An algorithm was developed to identify AF in outpatients initiating OAC from medico-administrative data. METHODS: Among patients initiating OAC in 2013 in the French healthcare databases, those treated for orthopaedic indications were excluded. Patients with a history of AF or DVT/PE directly identified from available medical data, mainly hospital discharge diagnoses, were considered to be 'confirmed AF or DVT/PE patients'. Demographics of these patients and their healthcare utilization data prior to OAC initiation were then included in a logistic regression model discriminating AF versus DVT/PE indications. The final model selected, comparing c-index, provided an algorithm identifying AF from among initially unclassified patients assumed to be either AF or DVT/PE outpatients. RESULTS: Among 256 418 patients initiating OAC, 37 388 were excluded; 61 329 AF and 59 859 DVT/PE patients were directly identified, leaving 88 488 unclassified patients. The final model (c-index: 0.93) included demographics, cardiologist prescriber, hospitalization for stroke, use of antiarrhythmics/beta-blockers/antihypertensive drugs and undergoing a Holter/echocardiography procedure, thyroid function tests, but no D-dimer tests. With a specificity of 95% (sensitivity: 65%), 41% of the unclassified patients were assumed to be AF outpatients. Similar results were obtained on 250 159 new users in 2014. CONCLUSION: This algorithm combining inpatient and outpatient claims data performed relatively well to identify AF outpatients initiating OAC. Copyright © 2017 John Wiley & Sons, Ltd.

Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012.

AIMS/HYPOTHESIS: The aim of this study was to assess the risk of adverse perinatal outcomes in gestational diabetes mellitus (GDM) in a large national cohort. METHODS: All deliveries taking place after 22 weeks in France in 2012 were included by extracting data from the hospital discharge database and the national health insurance system. The diabetic status of mothers was determined by the use of glucose-lowering agents and by hospital diagnosis. Outcomes were analysed according to the type of diabetes and, in the GDM group, whether or not diabetes was insulin-treated. RESULTS: The cohort of 796,346 deliveries involved 57,629 (7.24%) mothers with GDM. Mother-infant linkage was obtained for 705,198 deliveries. The risks of adverse outcomes were much lower with GDM than with pregestational diabetes. After limiting the analysis to deliveries after 28 weeks to reduce immortal time bias, the risks of preterm birth (OR 1.3 [95% CI 1.3, 1.4]), Caesarean section (OR 1.4 [95% CI 1.4, 1.4]), pre-eclampsia/eclampsia (OR 1.7 [95% CI 1.6, 1.7]), macrosomia (OR 1.8 [95% CI 1.7, 1.8]), respiratory distress (OR 1.1 [95% CI 1.0, 1.3]), birth trauma (OR 1.3 [95% CI 1.1, 1.5]) and cardiac malformations (OR 1.3 [95% CI 1.1, 1.4]) were increased in women with GDM compared with the non-diabetic population. Higher risks were observed in women with insulin-treated GDM than those with diet-treated GDM. After limiting the analysis to term deliveries, an increased risk of perinatal mortality was observed. After excluding women suspected to have undiagnosed pregestational diabetes, the risk remained moderately increased only for those with diet-treated GDM (OR 1.3 [95% CI 1.0, 1.6]). CONCLUSIONS/INTERPRETATION: GDM is associated with a moderately increased risk of adverse perinatal outcomes, which is higher in insulin-treated GDM than in non-insulin-treated GDM for most outcomes.

Covariate adjustment of cumulative incidence functions for competing risks data using inverse probability of treatment weighting.

In observational studies without random assignment of the treatment, the unadjusted comparison between treatment groups may be misleading due to confounding. One method to adjust for measured confounders is inverse probability of treatment weighting. This method can also be used in the analysis of time to event data with competing risks. Competing risks arise if for some individuals the event of interest is precluded by a different type of event occurring before, or if only the earliest of several times to event, corresponding to different event types, is observed or is of interest. In the presence of competing risks, time to event data are often characterized by cumulative incidence functions, one for each event type of interest. We describe the use of inverse probability of treatment weighting to create adjusted cumulative incidence functions. This method is equivalent to direct standardization when the weight model is saturated. No assumptions about the form of the cumulative incidence functions are required. The method allows studying associations between treatment and the different types of event under study, while focusing on the earliest event only. We present a SAS macro implementing this method and we provide a worked example.

Comparison of the short-term risk of bleeding and arterial thromboembolic events in nonvalvular atrial fibrillation patients newly treated with dabigatran or rivaroxaban versus vitamin K antagonists: a French nationwide propensity-matched cohort study.

BACKGROUND: The safety and effectiveness of non-vitamin K antagonist (VKA) oral anticoagulants, dabigatran or rivaroxaban, were compared with VKA in anticoagulant-naive patients with nonvalvular atrial fibrillation during the early phase of anticoagulant therapy. METHODS AND RESULTS: With the use of the French medico-administrative databases (SNIIRAM and PMSI), this nationwide cohort study included patients with nonvalvular atrial fibrillation who initiated dabigatran or rivaroxaban between July and November 2012 or VKA between July and November 2011. Patients presenting a contraindication to oral anticoagulants were excluded. Dabigatran and rivaroxaban new users were matched to VKA new users by the use of 1:2 matching on the propensity score. Patients were followed for up to 90 days until outcome, death, loss to follow-up, or December 31 of the inclusion year. Hazard ratios of hospitalizations for bleeding and arterial thromboembolic events were estimated in an intent-to-treat analysis using Cox regression models. The population was composed of 19 713 VKA, 8443 dabigatran, and 4651 rivaroxaban new users. All dabigatran- and rivaroxaban-treated patients were matched to 16 014 and 9301 VKA-treated patients, respectively. Among dabigatran-, rivaroxaban-, and their VKA-matched-treated patients, 55 and 122 and 31 and 68 bleeding events and 33 and 58 and 12 and 28 arterial thromboembolic events were observed during follow-up, respectively. After matching, no statistically significant difference in bleeding (hazard ratio, 0.88; 95% confidence interval, 0.64-1.21) or thromboembolic (hazard ratio, 1.10; 95% confidence interval, 0.72-1.69) risk was observed between dabigatran and VKA new users. Bleeding (hazard ratio, 0.98; 95% confidence interval, 0.64-1.51) and ischemic (hazard ratio, 0.93; 95% confidence interval, 0.47-1.85) risks were comparable between rivaroxaban and VKA new users. CONCLUSIONS: In this propensity-matched cohort study, our findings suggest that physicians should exercise caution when initiating either non-VKA oral anticoagulants or VKA in patients with nonvalvular atrial fibrillation.

Higher prevalence of breathlessness in elderly exposed to indoor aldehydes and VOCs in a representative sample of French dwellings.

The purpose of this study was to explore respiratory health effects of indoor exposures to aldehydes and volatile organic compounds (VOCs) in elderly living in a population-based representative sample of French dwellings and to compare them to the rest of the occupants of the dwellings. Twenty VOCs were objectively measured in 490 main dwellings. The respiratory conditions were assessed through a standardized questionnaire in 1012 inhabitants aged over 15 years, 144 of whom were aged over 65 years. Generalized estimating equations (GEE) were used to model the relationship between respiratory health outcomes and air pollutants concentrations using the median value of the distribution to define elevated exposure. Similar levels of indoor air pollutants were found in elderly and others. However, associations between breathlessness and living in dwellings with elevated concentrations of toluene and o-xylene respectively were statistically significant in elderly but not in the rest of the population (adjusted odds ratios (AOR(95% confidence interval) = 3.36(1.13, 9.98) and 2.85(1.06, 7.68) in elderly vs. 0.91(0.59, 1.39) and 0.79( 0.47, 1.34) in the others respectively). A more pronounced effect of n-decane on past year breathlessness was observed in case of poor ventilation in the dwellings. Our results showed a higher risk of breathlessness in elderly exposed to indoor air pollution than in the rest of the exposed population. Further investigations are needed to confirm whether this is related to frailty in elderly.

Estimating the health effects of exposure to multi-pollutant mixture.

PURPOSE: Air pollution constitutes a major public health concern because of its ubiquity and of its potential health impact. Because individuals are exposed to many air pollutants at once that are highly correlated with each other, there is a need to consider the multi-pollutant exposure phenomenon. The characteristics of multiple pollutants that make statistical analysis of health-related effects of air pollution complex include the high correlation between pollutants prevents the use of standard statistical methods, the potential existence of interaction between pollutants, the common measurement errors, the importance of the number of pollutants to consider, and the potential nonlinear relationship between exposure and health. METHODS: We made a review of statistical methods either used in the literature to study the effect of multiple pollutants or identified as potentially applicable to this problem. We reported the results of investigations that applied such methods. RESULTS: Eighteen publications have investigated the multi-pollutant effects, 5 on indoor pollution, 10 on outdoor pollution, and 3 on statistical methodology with application on outdoor pollution. Some other publications have only addressed statistical methodology. CONCLUSIONS: The use of Hierarchical Bayesian approach, dimension reduction methods, clustering, recursive partitioning, and logic regression are some potential methods described. Methods that provide figures for risk assessments should be put forward in public health decisions.

Quantitative assessments of indoor air pollution and respiratory health in a population-based sample of French dwellings.

BACKGROUND: Various volatile organic compounds (VOCs) have been related to respiratory health effects, but have generally been assessed individually without taking into account the fact that such pollutants are highly correlated to one other. AIMS: We investigated the effects of exposure to various VOC, and considered their combined effect on adult asthma and rhinitis. METHOD: A national cross-sectional representative survey conducted by the Indoor Air Quality Observatory objectively assessed 20 VOCs in 490 main dwellings in France. A standardized questionnaire determined the prevalence of asthma and rhinitis among 1012 inhabitants of the dwellings (≥ 15 years). Marginal models for binary outcome were used to relate VOCs exposure to asthma and rhinitis, controlling for potential confounders. A global score representing the number of VOCs in each dwelling with an elevated concentration (using the 3(rd) quartile value of the distribution as a threshold value) was then derived as a measure of the combined effect of VOCs. Specific scores were built using a similar approach, grouping VOCs by family. RESULTS: Asthma (8.6%) was significantly associated with N-undecane and 1,2,4-trimethylbenzene and rhinitis (38.3%) with ethylbenzene, trichloroethylene, m/p- and o-xylene. The global VOC score was associated with a significant risk of asthma and rhinitis (odds ratio (OR) of 1.40 and 1.22, respectively, for 5 additional VOCs with high exposure level). Both specific scores for aromatic hydrocarbons and aliphatic hydrocarbons were associated with a significantly risk of asthma (OR=1.12; 95% confidence interval (CI): 1.01-1.24 and OR=1.41; 95% CI=1.03-1.93, respectively). The specific VOC score for halogenated hydrocarbons was associated with a significant risk of rhinitis (OR=1.28; 95% CI: 1.07-1.54). CONCLUSION: We have shown that high concentrations of VOCs in homes were associated with an increasing prevalence of asthma and rhinitis in adults.