Publications by authors named "Lamiae Grimaldi-Bensouda"

42 Publications

Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus in Adults Admitted to Intensive Care Units: Protocol for a Double-Blind, Multicenter Randomized Controlled Trial.

JMIR Res Protoc 2021 Feb 24;10(2):e22511. Epub 2021 Feb 24.

Centre Hospitalier Poissy Saint Germain en Laye, Poissy, France.

Background: Generalized convulsive status epilepticus (GCSE) is a frequent medical emergency. GCSE treatment focuses on the administration of benzodiazepines followed by a second-line antiepileptic drug (AED). Despite this stepwise strategy, GCSE is not controlled in one-quarter of patients and is associated with protracted hospitalization, high mortality, and long-term disability. Valproic acid (VPA) is an AED with good tolerability and neuroprotective properties.

Objective: This study aims to demonstrate that administration of VPA as an adjuvant for first- and second-line treatment in GCSE can improve outcomes.

Methods: A multicenter, double-blind, randomized controlled trial was conducted, comparing VPA with a placebo in adults admitted to intensive care units (ICUs) for GCSE in France. GCSE was diagnosed by specifically trained ICU physicians according to standard criteria. All patients received standard of care, including a benzodiazepine and a second-line AED (not VPA), at the discretion of the treating medical team. In the intervention arm, VPA was administered intravenously at a loading dose of 30 mg/kg over 15 minutes, followed by a continuous infusion of 1 mg/kg/hour over the next 12 hours. In the placebo group, an identical intravenous administration of 0.9% saline was used. The primary outcome was the proportion of patients discharged alive from the hospital by day 15. Secondary outcomes were frequency of refractory and super refractory GCSE, ICU-related morbidity, adverse events related to VPA, and cognitive dysfunction at 3 months. Statistical analyses will be performed according to the intent-to-treat principle.

Results: The first patient was randomized on February 18, 2013, and the last patient was randomized on July 7, 2018. Of 248 planned patients, 98.7% (245/248) were enrolled across 20 ICUs. At present, data management is still ongoing, and all parties involved in the trial remain blinded.

Conclusions: The Valproic Acid as an Adjuvant Treatment for Generalized Convulsive Status Epilepticus (VALSE) trial will evaluate whether the use of VPA as an adjuvant for first- and second-line treatment in GCSE improves outcomes.

Trial Registration: ClinicalTrials.gov NCT01791868; https://clinicaltrials.gov/ct2/show/NCT01791868.

International Registered Report Identifier (irrid): DERR1-10.2196/22511.
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http://dx.doi.org/10.2196/22511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946594PMC
February 2021

Impact of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Hypertensive Patients with COVID-19 (COVIDECA Study).

Am J Cardiol 2021 Feb 20. Epub 2021 Feb 20.

Department of Cardiology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Centre de référence des cardiomyopathies et des troubles du rythme cardiaque héréditaires ou rares, Université de Versailles-Saint Quentin (UVSQ), Boulogne-Billancourt, France; INSERM U-1018, CESP, Epidémiologie clinique, UVSQ, Université de Paris Saclay, Villejuif, France. Electronic address:

Effect of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) among hypertensive patients with coronavirus disease 2019 (COVID-19) is debated. The aim of the COVIDECA study was to assess the outcome of ACEI and ARB among hypertensive patients presenting with COVID-19. We reviewed from the Assistance Publique-Hôpitaux de Paris healthcare record database all patients presenting with confirmed COVID-19 by RT-PCR. We compared hypertensive patients with ACEI or ARB and hypertensive patients without ACEI and ARB. Among 13,521 patients presenting with confirmed COVID-19 by RT-PCR, 2,981 hypertensive patients (mean age: 78.4 ± 13.6 years, 1,464 men) were included. Outcome of hypertensive patients was similar whatever the use or non-use of ACEI or ARB: admission in ICU (13.4% in patients with ACEI or ARB versus 14.8% in patients without ACEI/ARB, p = 0.35), need of mechanical ventilation (5.5% in patients with ACEI or ARB vs 6.3% in patients without ACEI/ARB, p = 0.45), in-hospital mortality (27.5% in patients with ACEI or ARB vs 26.7% in patients without ACEI/ARB, p = 0.70). In conclusion, the use of ACEI and ARB remains safe and can be maintained in hypertensive patients presenting with COVID-19.
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http://dx.doi.org/10.1016/j.amjcard.2021.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895710PMC
February 2021

Decongestant use and the risk of myocardial infarction and stroke: a case-crossover study.

Sci Rep 2021 Feb 18;11(1):4160. Epub 2021 Feb 18.

Normandie Université, Université Caen Normandie, CHU Caen Normandie, Inserm U1237, Caen, France.

Pharmacovigilance reports of cerebral and cardiovascular events in those who use decongestants have triggered alerts related to their use. We aimed to assess the risk of stroke and myocardial infarction (MI) associated with the use of decongestants. We conducted a nested case-crossover study of patients with incident stroke and MI identified in France between 2013 and 2016 in two systematic disease registries. Decongestant use in the three weeks preceding the event was assessed using a structured telephone interview. Conditional logistic multivariable models were used to estimate the odds of incident MI and stroke, also accounting for transient risk factors and comparing week 1 (index at-risk time window, immediately preceding the event) to week 3 (reference). Time-invariant risk factors were controlled by design. In total, 1394 patients with MI and 1403 patients with stroke, mainly 70 years old or younger, were interviewed, including 3.2% who used decongestants during the three weeks prior to the event (1.0% definite exposure in the index at-risk time window, 1.1% in the referent time window; adjusted odds ratio (aOR), 0.78; 95%CI, 0.43-1.42). Secondary analysis yielded similar results for individual events (MI/stroke). We observed no increased risk of MI or stroke for patients 70 years of age and younger without previous MI or stroke who used decongestants.
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http://dx.doi.org/10.1038/s41598-021-83718-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893034PMC
February 2021

Eculizumab as an emergency treatment for adult patients with severe COVID-19 in the intensive care unit: A proof-of-concept study.

EClinicalMedicine 2020 Nov 5;28:100590. Epub 2020 Nov 5.

Department of Intensive Care, Hôpital Raymond Poincaré (APHP), Laboratory of Infection & Inflammation - U1173, School of Medicine Simone Veil, University Versailles Saint Quentin - University Paris Saclay, INSERM, Garches, France.

Background: Complement pathway inhibition may provide benefit for severe acute respiratory illnesses caused by viral infections such as COVID-19. We present results from a nonrandomized proof-of-concept study of complement C5 inhibitor eculizumab for treatment of severe COVID-19.

Methods: All patients ( = 80) with confirmed SARS-CoV-2 infection and severe COVID-19 admitted to our intensive care unit between March 10 and May 5, 2020 were included. Forty-five patients were treated with standard care and 35 with standard care plus eculizumab through expanded-access emergency treatment. The prespecified primary outcome was day-15 survival. Clinical laboratory values and biomarkers, complement levels, and treatment-emergent serious adverse events (TESAEs) were also assessed.

Findings: At day 15, estimated survival was 82.9% (95% CI: 70.4%‒95.3%) with eculizumab and 62.2% (48.1%‒76.4%) without eculizumab (log-rank test,  = 0.04). Patients treated with eculizumab experienced a significantly more rapid decrease in lactate, blood urea nitrogen, total and conjugated bilirubin levels and a significantly more rapid increase in platelet count, prothrombin time, and in the ratio of arterial oxygen tension over fraction of inspired oxygen versus patients treated without eculizumab. Eculizumab-associated changes in complement levels, laboratory values, and biomarkers were consistent with terminal complement inhibition, reduced hypoxia, and decreased inflammation. TESAEs of special interest occurring in >5% of patients treated with/without eculizumab were ventilator-associated pneumonia (51%/24%), bacteremia (11%/2%), gastroduodenal hemorrhage (14%/16%), and hemolysis (3%/18%).

Interpretation: Findings from this proof-of-concept study suggest eculizumab may improve survival and reduce hypoxia in patients with severe COVID-19. Randomized studies evaluating the efficacy and safety of this treatment approach are needed.

Funding: Programme d'Investissements d'Avenir: ANR-18-RHUS60004.
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http://dx.doi.org/10.1016/j.eclinm.2020.100590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644240PMC
November 2020

The systematic case-referent method.

Therapie 2019 Apr 26;74(2):199-207. Epub 2018 Oct 26.

London School of Hygiene and Tropical Medicine, LA Risk Research, London EC1R 5BD, United Kingdom.

The systematic case-referent method is a special case-referent design originally developed for pharmacoepidemiologic research purposes. It consists in the systematic collection of series of incident cases of various disorders and the assembling of a general reference pool, from which "controls" are secondarily selected to be matched to specific cases. Both series are collected independently from each other and with no a priori hypothesis to be investigated. The reference pool can be either general or limited to a subpopulation, representative of the source population of the cases. Based on clinical recruitment of cases and referents, the design allows a very high specificity of diagnosis and documentation of clinical variables. All cases and referents are systematically documented on all treatments received before the incidence of the cases or before identification of referents. This documentation is done preferentially using objective sources assembled independently (linkage to claims data, medical records, pharmacy records, prescription records, hospital discharge letters). It can be completed with patients' interviews using standardised research tools, in particular for over-the-counter drug use and self-medication, and for the documentation of adherence to treatment and specific time-windows of exposure. Likewise, all cases and all referents are systematically documented on a series of risk factors, which are common to most epidemiological studies and are not hypothesis-dependent. Whenever the documentation of a confounding factor specific to the disease at hand is necessary, additional questionnaires can be applied to all or a sample of patients. The method has been successfully implemented for the pharmacoepidemiologic study of myocardial infarction, stroke, lupus, multiple sclerosis, rheumatoid arthritis, Guillain Barré syndrome, idiopathic thrombocytopenic purpura, type 1 diabetes mellitus, suicide attempts, breast cancer, and other disorders, for the analysis of the risk or preventing action of NSAIDs, statins, antiplatelet agents, anticoagulants, insulins, vaccines and other drugs.
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http://dx.doi.org/10.1016/j.therap.2018.09.073DOI Listing
April 2019

Clinical and economic burden of severe asthma: A French cohort study.

Respir Med 2018 11 2;144:42-49. Epub 2018 Oct 2.

Bichat Hospital, AP-HP, Inserm U1152 & Paris-Diderot Medical School, 46 Rue Henri Huchard, 75877, Paris, France.

Objective: To describe the clinical and economic burden of severe asthma in France over 12 months.

Methods: Data were retrieved from the observational, prospective "Cohorte Obstruction Bronchique et Asthme" (COBRA) cohort, which has enrolled nearly 1000 asthma patients since 2007 from throughout France. Patients undergoing treatment with GINA step-4 or 5 medications uninterruptedly for 12 months (thus defining "severe asthma") were identified and their clinical data used to describe the clinical burden of asthma (exacerbations, symptoms outside exacerbations, and level of asthma control). Patients' utilization of healthcare resources was described and used to estimate the direct medical costs incurred to treat severe asthma.

Results: 155 patients were included in the present study. Over the 12-month period of interest, 128 (83%) patients experienced at least one asthma exacerbation, 22 (14%) patients were hospitalized for asthma, 133 (86%) patients experienced continuous symptoms outside exacerbations, and 77 (50%) patients experienced important limitations in daily life activities. The median number of asthma-related drugs used was 4. The mean estimated annual asthma-related cost was 8,222 euros (standard deviation, SD = 11,886), including 7,229 euros (SD = 11,703) for controller medications.

Conclusion: Symptoms outside exacerbation periods are highly prevalent in severe asthma patients, for whom the main driver of medical costs is controller medication.
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http://dx.doi.org/10.1016/j.rmed.2018.10.002DOI Listing
November 2018

Dronedarone, amiodarone and other antiarrhythmic drugs, and acute liver injuries: a case-referent study.

Int J Cardiol 2018 Sep;266:100-105

Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité, Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.

Background: Spontaneous reports of acute liver injuries (ALI) in patients taking dronedarone triggered an EMA alert in 2011. This study aimed to assess the risk of ALI for class III antiarrhythmic drugs controlling for the use of other potential ALI-inducing drugs.

Methods: Between 2010 and 2014, consecutive ALI cases (≥50 years-old) were identified across Germany. ALI was defined as a new increase in at least one of the transaminases ≥3 times the upper limit of normal (ULN) or ≥2 ULN if alkaline phosphatase, with ("definite" case) or without ("biochemical" case) suggestive signs/symptoms of ALI, excluding other liver diseases. Recruited community controls were matched to cases on gender, age and inclusion date. Exposure to antiarrhythmic drugs and co-medication up to 2 years before ALI onset was informed by patients and confirmed by physicians' prescriptions. Adjusted Odds Ratios (aOR) were obtained from conditional multivariable logistic regressions, adjusted for a multivariate disease risk score and co-medication.

Results: 252 cases and 1081 matched controls were included (59.1% females; mean age: 64 years). Exposure to class III antiarrhythmic drugs was 4.0% in cases and 1.5% in controls, aOR = 3.6 (95% CI: 1.6-8.4). Associations with exposure to dronedarone and amiodarone were respectively 3.1 (95% CI: 0.7-14. 8) and 5.90 (1.7-20.0). Restricting the analysis to definite or severe ALI cases did not change these results.

Conclusions: Class III antiarrhythmic drugs were associated with ALI, amiodarone displaying the highest risk, and results were robust to case definitions. Continued vigilance is needed for patients taking these drugs.
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http://dx.doi.org/10.1016/j.ijcard.2018.04.007DOI Listing
September 2018

Effectiveness of new antiplatelets in the prevention of recurrent myocardial infarction.

Heart 2018 10 13;104(19):1583-1592. Epub 2018 Mar 13.

Pharmacoepidemiology, Analytica LA-SER, London, UK.

Objective: To compare ticagrelor and prasugrel with clopidogrel for recurrent fatal and non-fatal myocardial infarction (reMI) in real-life conditions.

Methods: Case-referent study using the Pharmacoepidemiological General Research eXtension (PGRx)-acute coronary syndrome (ACS) registry. Cases were patients with reMI from a cohort with index ACS or external to the cohort (same sites). Referents from the cohort, without recurrent event, were matched on index ACS type and date, age and sex with reMI cases. Multivariate conditional logistic regression assessed the OR (95% CI) for reMI associated with ticagrelor and prasugrel vs clopidogrel, adjusted for aspirin use and cardiovascular risk factors.

Results: 1047 cases and 2234 matched referents were included. Compared with clopidogrel, ticagrelor and prasugrel were associated with respective ORs of 0.65 (95% CI 0.52 to 0.81) and 0.71 (95% CI 0.53 to 0.96) for reMI occurrence. ORs for ticagrelor and prasugrel vs clopidogrel were: 0.50 (95% CI 0.38 to 0.67) and 0.66 (95% CI 0.45 to 0.95), 0.39 (95% CI 0.24 to 0.62) and 0.44 (95% CI 0.26 to 0.75), 0.63 (95% CI 0.43 to 0.92) and 1.20 (95% CI 0.69 to 2.07), 1.11 (95% CI 0.72 to 1.72) and 0.82 (95% CI 0.44 to 1.54) when index ACS was a first MI, a first ST-elevated MI (STEMI), a first non-STEMI and a recurrent ACS, respectively, and 0.63 (95% CI 0.45 to 0.87) and 0.77 (95% CI 0.41 to 1.45) for patients aged ≥70  years.

Conclusions: This real-world study showed a significant reduction of reMI with new antiplatelets compared with clopidogrel, ticagrelor being associated with a greater decrease of risk notably for first, either STEMI or non-STEMI. The larger magnitude of effect may be attributed to potential residual confounding or higher effectiveness compared with efficacy reported in trials (EMA Post Authorisation Study Registry Number EUPAS5905).
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http://dx.doi.org/10.1136/heartjnl-2017-312534DOI Listing
October 2018

Effect of an Institutional Medication Adherence Program for Long-Acting Injectable Risperidone on Adherence and Psychiatric Hospitalizations: Evidence from a Prospective Cohort Study.

J Popul Ther Clin Pharmacol 2017 05 30;24(2):e61-e70. Epub 2017 May 30.

Analytica LASER, Paris, France.

Background: Long-acting injectable (LAI) atypical antipsychotics are associated with improved adherence and reduced relapse rates in schizophrenia but reminder-based interventions may further improve outcomes.

Objectives: To assess an institutional medication adherence program's (IMAP) effectiveness on adherence and psychiatric hospitalizations among schizophrenia patients taking risperidone LAI (RLAI).

Methods: Between 2009 and 2010, we recruited patients meeting DSM-IV criteria for schizophrenia treated with RLAI receiving outpatient care from psychiatric centres in France. The IMAP consisted of calling patients 48 hours prior to their scheduled RLAI injections and within 3 days of a missed appointment. Centres applying the IMAP to ≥50% of scheduled patient injections were deemed compliant. Patients were followed up to one year for adherence (≥80% of scheduled RLAI injections received within 5 days of the scheduled date) and psychiatric hospitalizations.

Results: Among 506 patients recruited from 36 centres, the hospitalization rate was 32.5 per 100 person-years. 15 centres treating 243 patients were IMAP compliant and 21 centres treating 263 patients were not. IMAP compliance was associated with lower psychiatric hospitalization rates (crude RR: 0.64 [95% CI: 0.44-0.93]; adjusted RR: 0.78 [95% CI: 0.47-1.27]). Nearly 75% of patients were adherent to RLAI. While patient adherence had little impact on hospitalization rates (adjusted RR: 0.92 [95% CI: 0.59-1.44]), IMAP compliance was more effective among non-adherent (adjusted RR: 0.45 [95% CI: 0.16-1.28]) than adherent (adjusted RR: 0.88 [95% CI: 0.51-1.53]) patients.

Conclusions: IMAPs may improve patient adherence and reduce psychiatric hospitalizations, particularly among patients with difficulties adhering to LAI antipsychotics.
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http://dx.doi.org/10.22374/1710-6222.24.2.7DOI Listing
May 2017

Correlates and predictors of antipsychotic drug polypharmacy in real-life settings: Results from a nationwide cohort study.

Schizophr Res 2018 02 27;192:213-218. Epub 2017 May 27.

LASER, 3 rue de l'Arrivée, 75015, Paris, France; CESP, INSERM U1018, Maison des adolescents, 97 boulevard de Port-Royal, 75005 Paris, France. Electronic address:

Reasons for using antipsychotic polypharmacy (APP) in routine clinical practice, despite a potentially unfavorable risk-benefit ratio, are poorly understood. This research aimed to determine (1) if severe courses of schizophrenia were associated with APP and (2) if a schizophrenia-related acute event would predict a switch to APP in the short term. Observational prospective data (at baseline and 6months) were drawn from a French nationwide cohort ("Cohorte Générale Schizophrénie"), which included 1859 inpatients and outpatients with schizophrenia. APP was defined as the prescription of ≥2 antipsychotic drugs (there being different active substances). Early-onset schizophrenia, legal guardianship, higher lifetime maximal severity of illness and comorbid antisocial personality were used as proxies for severe courses of schizophrenia. Schizophrenia-related acute events included hospitalization and recent suicide attempts. Logistic regression models were used to determine (1) whether the use of APP at baseline (vs. monotherapy) was associated with a severe course of schizophrenia or not, independent of acute events, and (2) if a switch to APP at 6months (vs. remaining on monotherapy) was associated with acute events, independent of severe courses of schizophrenia. Increased odds of APP use at baseline were independently associated with legal guardianship (OR=1.6; 95%CI=1.3, 2.0) and higher lifetime maximum severity of illness (OR=1.3; 95%CI=1.2, 1.5). A switch to APP at 6months was predicted by a hospitalization occurring since baseline (OR=6.1; 95%CI=3.9, 9.4). In routine clinical practice, APP is more likely prescribed to patients with severe courses of illness, possibly indicating the difficulty to manage these patients.
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http://dx.doi.org/10.1016/j.schres.2017.05.015DOI Listing
February 2018

Risk of autoimmune diseases and human papilloma virus (HPV) vaccines: Six years of case-referent surveillance.

J Autoimmun 2017 May 9;79:84-90. Epub 2017 Feb 9.

LASER Europe Ltd, London, 66 Chiltern St, London W1U 4JT, United Kingdom; Department of Epidemiology, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK.

Background: Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization.

Objectives: To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France.

Methods: Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11-25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barré syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008-2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations.

Results: With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41-0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results.

Conclusion: Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.
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http://dx.doi.org/10.1016/j.jaut.2017.01.005DOI Listing
May 2017

Risk of autoimmune diseases and human papilloma virus (HPV) vaccines: Six years of case-referent surveillance.

J Autoimmun 2017 May 9;79:84-90. Epub 2017 Feb 9.

LASER Europe Ltd, London, 66 Chiltern St, London W1U 4JT, United Kingdom; Department of Epidemiology, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK.

Background: Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization.

Objectives: To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France.

Methods: Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11-25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barré syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008-2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations.

Results: With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41-0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results.

Conclusion: Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.
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http://dx.doi.org/10.1016/j.jaut.2017.01.005DOI Listing
May 2017

Model-observational bridging study on the effectiveness of ezetimibe on cardiovascular morbidity and mortality in France: A population-based study.

J Clin Lipidol 2016 Nov - Dec;10(6):1379-1388. Epub 2016 Sep 7.

LASER Europe, London, United Kingdom; Conservatoire national des arts et métiers (CNAM), Paris, France. Electronic address:

Background: To evaluate the real-life impact of ezetimibe on cardiovascular (CV) morbidity and mortality in France.

Objective: To estimate the number of non-fatal and fatal CV events that could be prevented and corresponding number of patients needed to treat (NNT) with ezetimibe to prevent one CV event over 5 years.

Methods: Non-interventional 48-month follow-up cohort conducted in hypercholesterolemic patients starting on ezetimibe <3 months at study entry, either as monotherapy or combined with statins. Prediction modeling using discrete event simulation with calibrated Framingham CV risk equations was applied to data from pivotal clinical trials on ezetimibe and real-life data derived from the cohort.

Results: A total of 3215 patients in the cohort accumulated 9314 person-years of follow-up for an average of 2.9 years. Mean age was 61.5 (standard deviation [SD] = 10.7), 54.6% were males, and 27.0% had a history of CV disease. Baseline LDL-cholesterol averaged 4.1 mmol/L (159 mg/dL; SD = 1.0) and HDL-C 1.6 mmol/L (62 mg/dL; SD = 0.5). LDL-C decreased in the first 12 months in ezetimibe-LLT (lipid-lowering therapy) initiators, switchers (monotherapy), and combination therapy with a statin by respectively 21.3%, 6.4%, and 29.1%. The corresponding predicted rate reductions of CV events (non-fatal and fatal) compared to no treatment or to a statin (combination therapy) were respectively 8, 2, and 12 per 1000 patients treated over 5 years, with a global NNT of 143 patients over 5 years.

Conclusion: These results, accounting for observed CV event rates, risk factors evolution over time and adherence to treatment in real life, were consistent with those from clinical trials.
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http://dx.doi.org/10.1016/j.jacl.2016.08.015DOI Listing
October 2017

Childhood immune thrombocytopenia: A nationwide cohort study on condition management and outcomes.

Pediatr Blood Cancer 2017 Jul 1;64(7). Epub 2016 Dec 1.

French Reference Center for Rare Diseases and Autoimmune Cytopenias of Childhood (CEREVANCE), Pellegrin Hospital, Bordeaux, France.

Objectives: Nationwide prospective cohort study exploring (i) the factors associated with treatment initiation (vs. watchful waiting) in children with primary immune thrombocytopenia (ITP) followed in routine clinical practice and (ii) the predictors of chronicity at 12 months.

Procedure: Between 2008 and 2013, 23 centers throughout France consecutively included 257 children aged 6 months-18 years and diagnosed with primary ITP over a 5-year period. Data on ITP clinical features along with medical management were collected at baseline and 12 months. Multivariate logistic regressions were used to determine (i) and (ii) as defined above, providing odds ratio (OR) with 95% confidence interval (95% CI).

Results: One hundred thirty-seven (53%) children were males, median age was 4.6 years, median platelet count was 7 × 109/l, and 214 (81%) patients initiated medication. Factors independently associated with treatment initiation included platelet counts <10 × 109/l (P < 0.0001) and mucocutaneous bleeding symptoms at baseline (P < 0.001). At 12 months, data were available for 211 (82%) children, of whom 160 (74%) had recovered. Predictors of chronicity included female gender (OR = 2.2; 95% CI = 1.0-4.8), age ≥10 years (OR = 2.6; 95% CI = 1.1-6.0), and platelet counts ≥10 × 10 /l (OR = 3.2; 95% CI = 1.5-6.9).

Conclusions: In routine clinical practice, the decision to apply a watchful waiting strategy seems to be driven by platelet counts even in the absence of bleeding symptoms, resulting in treatment being initiated in more than 80% of the children surveyed. Overall, younger children with ITP showed good prognosis, with lower platelet counts and, to a lesser extent, male gender predicting more favorable outcomes.
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http://dx.doi.org/10.1002/pbc.26389DOI Listing
July 2017

Immune thrombocytopenia in adults: a prospective cohort study of clinical features and predictors of outcome.

Haematologica 2016 09 26;101(9):1039-45. Epub 2016 May 26.

Centre de Référence des Cytopénies Auto-Immunes de l'Adulte, Service de Médecine Interne, CHU Henri Mondor, Créteil, France.

This prospective observational cohort study aimed to explore the clinical features of incident immune thrombocytopenia in adults and predictors of outcome, while determining if a family history of autoimmune disorder is a risk factor for immune thrombocytopenia. All adults, 18 years of age or older, recently diagnosed with immune thrombocytopenia were consecutively recruited across 21 hospital centers in France. Data were collected at diagnosis and after 12 months. Predictors of chronicity at 12 months were explored using logistic regression models. The association between family history of autoimmune disorder and the risk of developing immune thrombocytopenia was explored using a conditional logistic regression model after matching each case to 10 controls. One hundred and forty-three patients were included: 63% female, mean age 48 years old (Standard Deviation=19), and 84% presented with bleeding symptoms. Median platelet count was 10×10(9)/L. Initial treatment was required in 82% of patients. After 12 months, only 37% of patients not subject to disease-modifying interventions achieved cure. The sole possible predictor of chronicity at 12 months was a higher platelet count at baseline [Odds Ratio 1.03; 95%CI: 1.00, 1.06]. No association was found between outcome and any of the following features: age, sex, presence of either bleeding symptoms or antinuclear antibodies at diagnosis. Likewise, family history of autoimmune disorder was not associated with incident immune thrombocytopenia. Immune thrombocytopenia in adults has been shown to progress to a chronic form in the majority of patients. A lower platelet count could be indicative of a more favorable outcome.
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http://dx.doi.org/10.3324/haematol.2016.146373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5060020PMC
September 2016

Homeopathic medical practice for anxiety and depression in primary care: the EPI3 cohort study.

BMC Complement Altern Med 2016 May 4;16:125. Epub 2016 May 4.

INSERM U657, University Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076, Bordeaux, France.

Background: The purpose of the study was to compare utilization of conventional psychotropic drugs among patients seeking care for anxiety and depression disorders (ADDs) from general practitioners (GPs) who strictly prescribe conventional medicines (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho).

Methods: This was one of three epidemiological cohort studies (EPI3) on general practice in France, which included GPs and their patients consulting for ADDs (scoring 9 or more in the Hospital Anxiety and Depression Scale, HADS). Information on all medication utilization was obtained by a standardised telephone interview at inclusion, 1, 3 and 12 months.

Results: Of 1562 eligible patients consulting for ADDs, 710 (45.5 %) agreed to participate. Adjusted multivariate analyses showed that GP-Ho and GP-Mx patients were less likely to use psychotropic drugs over 12 months, with Odds ratio (OR) = 0.29; 95 % confidence interval (CI): 0.19 to 0.44, and OR = 0.62; 95 % CI: 0.41 to 0.94 respectively, compared to GP-CM patients. The rate of clinical improvement (HADS <9) was marginally superior for the GP-Ho group as compared to the GP-CM group (OR = 1.70; 95 % CI: 1.00 to 2.87), but not for the GP-Mx group (OR = 1.49; 95 % CI: 0.89 to 2.50).

Conclusions: Patients with ADD, who chose to consult GPs prescribing homeopathy reported less use of psychotropic drugs, and were marginally more likely to experience clinical improvement, than patients managed with conventional care. Results may reflect differences in physicians' management and patients' preferences as well as statistical regression to the mean.
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http://dx.doi.org/10.1186/s12906-016-1104-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4855343PMC
May 2016

The IMI PROTECT project: purpose, organizational structure, and procedures.

Pharmacoepidemiol Drug Saf 2016 Mar;25 Suppl 1:5-10

Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, the Netherlands.

The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) initiative was a collaborative European project that sought to address limitations of current methods in the field of pharmacoepidemiology and pharmacovigilance. Initiated in 2009 and ending in 2015, PROTECT was part of the Innovative Medicines Initiative, a joint undertaking by the European Union and pharmaceutical industry. Thirty-five partners including academics, regulators, small and medium enterprises, and European Federation of Pharmaceuticals Industries and Associations companies contributed to PROTECT. Two work packages within PROTECT implemented research examining the extent to which differences in the study design, methodology, and choice of data source can contribute to producing discrepant results from observational studies on drug safety. To evaluate the effect of these differences, the project applied different designs and analytic methodology for six drug-adverse event pairs across several electronic healthcare databases and registries. This papers introduces the organizational structure and procedures of PROTECT, including how drug-adverse event and data sources were selected, study design and analyses documents were developed, and results managed centrally.
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http://dx.doi.org/10.1002/pds.3933DOI Listing
March 2016

Calcium channel blockers and cancer: a risk analysis using the UK Clinical Practice Research Datalink (CPRD).

BMJ Open 2016 Jan 8;6(1):e009147. Epub 2016 Jan 8.

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada.

Objective: The evidence of an association between calcium channel blockers (CCBs) and cancer is conflicting. The objective of the present study was to evaluate the risk of cancer (all, breast, prostate and colon cancers) in association with exposure to CCB.

Methods: This is a population-based cohort study in patients exposed to CCBs from across the UK, using two comparison cohorts: (1) patients with no exposure to CCB (non-CCB) matched on age and gender and (2) unmatched patients unexposed to CCB and at least one other antihypertensive (AHT) prescription. Cancer incidence rates computed in the exposed and the two unexposed groups were compared using HRs and 95% CIs obtained from multivariate Cox regression analyses.

Results: Overall, 150,750, 557,931 and 156,966 patients were included, respectively, in the CCB, non-CCB and AHT cohorts. Crude cancer incidence rates per 1000 person-years were 16.51, 15.75 and 10.62 for the three cohorts, respectively. Adjusted HRs (CI) for all cancers comparing CCB, non-CCB and AHT cohorts were 0.88 (0.86 to 0.89) and 1.01 (0.98 to 1.04), respectively. Compared to the AHT cohort, adjusted HRs (CI) for breast, prostate and colon cancer for the CCB cohort were 0.95 (0.87 to 1.04), 1.07 (0.98 to 1.16) and 0.89 (0.81 to 0.98), respectively. Analyses by duration of exposure to CCB did not show excess risk.

Conclusions: This large population-based study provides strong evidence that CCB use is not associated with an increased risk of cancer. The analyses yielded robust results across all types of cancer and different durations of exposure to CCBs.
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http://dx.doi.org/10.1136/bmjopen-2015-009147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716173PMC
January 2016

Utilization of psychotropic drugs by patients consulting for sleeping disorders in homeopathic and conventional primary care settings: the EPI3 cohort study.

Homeopathy 2015 Jul 10;104(3):170-5. Epub 2015 Jun 10.

INSERM U657, University of Bordeaux Segalen, 146 Rue Léo Saignat, 33076 Bordeaux, France. Electronic address:

Background: Utilization of sedative hypnotic drugs for sleeping disorders (SD) raises concerns, particularly among older people. This study compared utilization of conventional psychotropic drugs for SD among patients seeking care from general practitioners (GPs) who strictly prescribe conventional medications (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho).

Methods: This was a French population-based cohort study of GPs and their patients consulting for SD, informed through the Pittsburgh sleep quality index (PSQI) questionnaire. Information on psychotropic drugs utilization was obtained from a standardized telephone interview at inclusion, one, three and 12 months.

Results: 346 patients consulting for SD were included. Patients in the GP-Ho group experienced more often severe SD (41.3%) than patients in the GP-CM group (24.3%). Adjusted multivariate analyses showed that patients who chose to be managed by GP-Ho were less likely to use psychotropic drugs over 12 months as opposed to the GP-CM group, with Odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.14 to 0.42. Patients in the GP-Mx group also used less psychotropic drugs but the result was not statistically significant (OR = 0.67; 95% CI: 0.39-1.16). Rates of clinical improvement of the SD did not differ between groups.

Conclusions: Patients with SD who chose to consult GPs certified in homeopathy consumed less psychotropic drugs and had a similar evolution of their condition to patients treated with conventional medical management. This result may translate in a net advantage with reduction of adverse events related to psychotropic drugs.
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http://dx.doi.org/10.1016/j.homp.2015.05.002DOI Listing
July 2015

Management of upper respiratory tract infections by different medical practices, including homeopathy, and consumption of antibiotics in primary care: the EPI3 cohort study in France 2007-2008.

PLoS One 2014 19;9(3):e89990. Epub 2014 Mar 19.

Pasteur Institute, Paris, France; Faculty of Medicine, University of Paris-Ile de France Ouest, Guyancourt, Paris, France.

Background: Prescribing of antibiotics for upper respiratory tract infections (URTI) varies substantially in primary care.

Objectives: To describe and compare antibiotic and antipyretic/anti-inflammatory drugs use, URTI symptoms' resolution and occurrence of potentially-associated infections in patients seeking care from general practitioners (GPs) who exclusively prescribe conventional medications (GP-CM), regularly prescribe homeopathy within a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho).

Method: The EPI3 survey was a nationwide population-based study of a representative sample of 825 GPs and their patients in France (2007-2008). GP recruitment was stratified by self-declared homeopathic prescribing preferences. Adults and children with confirmed URTI were asked to participate in a standardized telephone interview at inclusion, one-, three- and twelve-month follow up. Study outcomes included medication consumption, URTI symptoms' resolution and potentially-associated infections (sinusitis or otitis media/externa) as reported by patients. Analyses included calibration to account for non-respondents and groups were compared using multivate analyses adjusting for baseline differences with a propensity score.

Results: 518 adults and children with URTI (79.3% rhinopharyngitis) were included (36.9% response rate comparable between groups). As opposed to GP-CM patients, patients in the GP-Ho group showed significantly lower consumption of antibiotics (Odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.27-0.68) and antipyretic/anti-inflammatory drugs (OR = 0.54, 95% CI: 0.38-0.76) with similar evolution in related symptoms (OR = 1.16, 95% CI: 0.64-2.10). An excess of potentially-associated infections (OR = 1.70, 95% CI: 0.90-3.20) was observed in the GP-Ho group (not statistically significant). No difference was found between GP-CM and GP-Mx patients.

Conclusion: Patients who chose to consult GPs certified in homeopathy used less antibiotics and antipyretic/anti-inflammatory drugs for URTI than those seen by GPs prescribing conventional medications. No difference was observed in patients consulting GPs within mixed-practice. A non-statistically significant excess was estimated through modelling for associated infections in the GP-Ho group and needs to be further studied.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089990PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960096PMC
December 2014

The risk of systemic lupus erythematosus associated with vaccines: an international case-control study.

Arthritis Rheumatol 2014 Jun;66(6):1559-67

LA-SER and Conservatoire National des Arts et Métiers, Paris, France.

Objective: Studies have suggested that systemic lupus erythematosus (SLE) may be triggered by vaccinations. We undertook this study to investigate the relationship between vaccination and onset of SLE.

Methods: This international case-control study was conducted between April 2008 and June 2012 in 36 specialist referral centers (34 in France and 2 in Quebec, Canada) and recruited patients ≤60 years old recently diagnosed as having either definite SLE (meeting ≥4 American College of Rheumatology [ACR] criteria including at least 1 immunologic criterion) or probable SLE (meeting 3 ACR criteria including at least 1 immunologic criterion). Controls were recruited from general practice settings through a closely monitored protocol and matched to patients by age, sex, region of residence, and date of recruitment. Vaccinations and other potential risk factors for SLE were assessed using a standardized telephone interview. We compared proportions of patients and controls who were vaccinated 12 and 24 months before the index date (date of first clinical symptom presented by the patient) using odds ratios (ORs) from conditional logistic regression.

Results: We assessed 105 patients (89 with definite SLE and 16 with probable SLE) and 712 controls. Twenty-two of the 105 patients (21.0%) and 181 of the 712 controls (25.4%) had received at least 1 vaccination within 24 months before the index date (adjusted OR 0.9 [95% confidence interval 0.5-1.5]). The proportions of patients and controls vaccinated within the previous 12 months were also similar.

Conclusion: Our study showed no association between exposure to vaccination and risk of developing SLE.
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http://dx.doi.org/10.1002/art.38429DOI Listing
June 2014

Characteristics of patients consulting their regular primary care physician according to their prescribing preferences for homeopathy and complementary medicine.

Homeopathy 2014 Jan;103(1):51-7

INSERM U657, University of Bordeaux Segalen, Bordeaux, France. Electronic address:

Background: Homeopathic care has not been well documented in terms of its impact on patients' utilization of drugs or other complementary and alternative medicines (CAM). The objective of this study was to describe and compare patients who visit physicians in general practice (GPs) who prescribe only conventional medicines (GP-CM), regularly prescribe homeopathy within a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho).

Material And Methods: The EPI3-LASER study was a nationwide observational survey of a representative sample of GPs and their patients from across France. Physicians recorded their diagnoses and prescriptions on participating patients who completed a self-questionnaire on socio-demographics, lifestyle, quality of life Short Form 12 (SF-12) and the complementary and alternative medicine beliefs inventory (CAMBI).

Results: A total of 6379 patients (participation rate 73.1%) recruited from 804 GP practices participated in this survey. Patients attending a GP-Ho were slightly more often female with higher education than in the GP-CM group and had markedly healthier lifestyle. They did not differ greatly in their comorbidities or quality of life but exhibited large differences in their beliefs in holistic medicine and natural treatments, and in their attitude toward participating to their own care. Similar but less striking observations were made in patients of the GP-Mx group.

Conclusion: Patients seeking care with a homeopathic GP did not differ greatly in their socio-demographic characteristics but more so by their healthier lifestyle and positive attitude toward CAM. Further research is needed to explore the directionality of those associations and to assess the potential economic benefits of homeopathic management in primary care.
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http://dx.doi.org/10.1016/j.homp.2013.09.001DOI Listing
January 2014

Bridging differences in outcomes of pharmacoepidemiological studies: design and first results of the PROTECT project.

Curr Clin Pharmacol 2014 May;9(2):130-8

Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082 3508 TB Utrecht, The Netherlands.

Background: Observational pharmacoepidemiological (PE) studies on drug safety have produced discrepant results that may be due to differences in design, conduct and analysis.

Purpose: The pharmacoepidemiology work-package (WP2) of the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) project aims at developing, testing and disseminating methodological standards for design, conduct and analysis of pharmacoepidemiological studies applicable to different safety issues using different databases across European countries. This article describes the selection of the safety issues and the description of the databases to be systematically studied.

Methods: Based on two consensus meetings and a literature search, we selected five drug-adverse event (AE) pairs to be evaluated in different databases. This selection was done according to pre-defined criteria such as regulatory and public health impact, and the potential to investigate a broad range of methodological issues.

Results: The selected drug-AE pairs are: 1) inhaled long-acting beta-2 agonists and acute myocardial infarction; 2) antimicrobials and acute liver injury; 3) antidepressants and/or benzodiazepines and hip fracture; 4) anticonvulsants and suicide/suicide attempts; and 5) calcium channel blockers and malignancies. Six European databases, that will be used to evaluate the drug-AE pairs retrospectively, are also described.

Conclusion: The selected drug-AE pairs will be evaluated in PE studies using common protocols. Based on consistencies and discrepancies of these studies, a framework for guiding methodological choices will be developed. This will increase the usefulness and reliability of PE studies for benefit-risk assessment and decision-making.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083447PMC
http://dx.doi.org/10.2174/1574884708666131111211802DOI Listing
May 2014

Real-life effectiveness of statins in the prevention of first acute coronary syndrome in France: a prospective observational study.

Int J Cardiol 2013 Nov 7;169(4):271-5. Epub 2013 Sep 7.

LA-SER, France; Conservatoire national des arts et métiers, France; Equipe d'accueil Pharmacoépidémiologie et Maladies Infectieuses, Pasteur Institute, France. Electronic address:

Background: Evidence on the real effectiveness of statins on acute coronary syndrome (ACS) incidence is scarce. We assessed the effectiveness of real-life statins on the risk of first non-fatal ACS in a low-cardiovascular-risk country.

Methods: Systematic case-control study was conducted in 60 cardiology centres and 371 general practices from across France. A total of 2238 cases with first ACS within 1 month from recruitment and 2238 controls without history of ACS were included; controls were matched to ACS cases on sex, age, frequency of visits to GPs, date of recruitment and personal history of chronic diseases. Statin exposure and risk factors were documented through patient telephone interviews and validated against medical records. The index date was the date of ACS for cases. Adjusted odds ratios (OR) of first ACS and statin use were estimated by multiple conditional logistic regression models controlled for risk factors and propensity score for statin exposure.

Results: Statin use was associated with lower ACS risk, with an adjusted matched OR of 0.67; 95% confidence interval (CI): 0.56 to 0.79 for current use (within 2 months) and 0.73; 95% CI: 0.62 to 0.86 for any use within 24 months [atorvastatin: 0.83 (0.63-1.10), fluvastatin: 0.75 (0.43-1.30), pravastatin: 0.98 (0.72-1.34), rosuvastatin: 0.49 (0.35-0.68) and simvastatin: 0.62 (0.46-0.84)]. The preventive effect of statins on non-fatal ACS reached its maximum after one to four years of use.

Conclusion: A similar magnitude of effect for statin use was observed in real life, as compared to randomised clinical trials in France.
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http://dx.doi.org/10.1016/j.ijcard.2013.08.127DOI Listing
November 2013

Risk of breast cancer by individual insulin use: an international multicenter study.

Diabetes Care 2014 15;37(1):134-43. Epub 2013 Aug 15.

Corresponding author: Lamiae Grimaldi-Bensouda,

OBJECTIVE Several studies have been published in 2009 suggesting a possible association between insulin glargine and increased risk of malignancies, including breast cancer. The objective of this study was to assess the relation between the individual insulins (glargine, aspart, lispro, and human insulin) and development of breast cancer. RESEARCH DESIGN AND METHODS Seven hundred seventy-five incident cases of primary invasive or in situ carcinoma breast cancer occurring in women with diabetes from 92 centers in the U.K., Canada, and France were matched to a mean of 3.9 diabetic community control subjects (n = 3,050; recruited from 580 general practices) by country, age, recruitment date, and diabetes type and management. The main risk model was a multivariate conditional logistic regression model with case/control status as the dependent variable and individual insulin use, 8 years preceding the index date, as the independent variable, controlling for past use of any insulin, oral antidiabetes drugs, reproductive factors, lifestyle, education, hormone replacement therapy and history of contraceptive use, BMI, comorbidities, diabetes duration, and annual number of physician visits. Glargine was also compared with every other insulin by computing all ratios using the variance-covariance matrix of logistic model parameters. RESULTS Adjusted odds ratios of breast cancer for each type of insulin versus no use of that insulin were 1.04 (95% CI 0.76-1.44) for glargine, 1.23 (0.79-1.92) for lispro, 0.95 (0.64-1.40) for aspart, and 0.81 (0.55-1.20) for human insulin. Two-by-two comparisons found no difference between glargine and the different types of insulins. Insulin dosage or duration of use and tumor stage did not change the results. CONCLUSIONS This international study found no difference in the risk of developing breast cancer in patients with diabetes among the different types of insulin with short- to mid-term duration of use. Longer-term studies would be of interest.
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http://dx.doi.org/10.2337/dc13-0695DOI Listing
August 2015

Does omalizumab make a difference to the real-life treatment of asthma exacerbations?: Results from a large cohort of patients with severe uncontrolled asthma.

Chest 2013 Feb;143(2):398-405

Department of Epidemiology, London School of Hygiene & Tropical Medicine, London, England; LA-SER Europe Ltd, London, England.

Background: Omalizumab has been shown to decrease the risk of hospitalization or ED visits in patients with uncontrolled severe allergic asthma compared with placebo. This longitudinal study observed the conditions under which omalizumab is prescribed in real-life settings and assessed whether its use as an add-on therapy alongside standard treatments decreases the risk of severe asthmatic exacerbations.

Methods: A cohort of adult patients with uncontrolled severe asthma despite optimal treatment with inhaled and oral corticosteroids and a long-acting b 2 -agonist but no treatment with omalizumab upon entry was assembled. Risk of hospitalization or ED visits for asthma exacerbation was assessed using the Andersen-Gill extension of the Cox model for repeated events, controlling for age, sex, smoking history, BMI, gastroesophageal reflux, allergic status, allergic rhinitis, treatment, and hospitalization or ED visits for asthma in the 2 months prior to omalizumab treatment.

Results: Overall, 163 physicians recruited 767 patients, of whom 374 took omalizumab at least once (mean observation period, 20.4 months). Omalizumab use was associated with an adjusted relative risk of 0.57 (95% CI, 0.43-0.78) for hospitalization or ED visits for asthma. In users of omalizumab, the adjusted relative risk of hospitalization or ED visits for asthma during omalizumab treatment vs nontreatment periods was 0.40 (95% CI, 0.28-0.58).

Conclusions: Add-on omalizumab is associated with a significantly decreased risk of hospitalization or ED visits in patients with uncontrolled severe asthma in real-life practice.
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http://dx.doi.org/10.1378/chest.12-1372DOI Listing
February 2013

Agreement between patients' self-report and medical records for vaccination: the PGRx database.

Pharmacoepidemiol Drug Saf 2013 Mar 14;22(3):278-85. Epub 2013 Jan 14.

LA-SER, Paris, France.

Purpose: Patients' self-reported vaccine exposure (PS) may be subject to memory errors and other biases. Physicians' prescription records and other medical records (MR) do not capture noncompliance with vaccination. This study compared PS with MR for influenza, 23-valent pneumococcal, and human papillomavirus (HPV) vaccines.

Methods: The Pharmacoepidemiologic General Research Extension (PGRx) database uses a network of over 300 general practitioners across France, who systematically recruit an age- and sex-stratified sample of patients (≥ 14 years old), without reference to their diagnoses or prescriptions. Patients received a structured telephone interview, combined with an interview guide listing vaccines commonly given. Patients' self-reported vaccination in the 3 years before their recruitment was compared with medical records kept by the physician or the patient.

Results: Concordance between PS and MR was assessed for 7613 patients for whom both sources of information were available. Agreement within 3 years before the recruitment date was substantial for influenza vaccines (prevalence and bias-adjusted kappa [PABAK] = 0.74, sensitivity PS relative to MR 81.5%) and high for 23-valent pneumococcal vaccines (PABAK = 0.98, sensitivity PS 49.6) and HPV vaccines (PABAK = 0.92, sensitivity PS 91.6). In adjusted analyses, agreement varied with sociodemographic and health-related factors, particularly for influenza and 23-valent pneumococcal vaccines.

Conclusions: The PGRx method for drug exposure assessment is a new tool in pharmacoepidemiology that shows substantial to high agreement between PS and MR for exposure to various vaccines. Our finding of high agreement between PS and MR for HPV vaccination status in young women is a significant addition to the literature.
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http://dx.doi.org/10.1002/pds.3401DOI Listing
March 2013

Who seeks primary care for sleep, anxiety and depressive disorders from physicians prescribing homeopathic and other complementary medicine? Results from the EPI3 population survey.

BMJ Open 2012 22;2(6). Epub 2012 Nov 22.

Equipe d'accueil "Pharmacoépidémiologie et maladies infectieuses", Institut Pasteur, Paris, France.

Objectives: To describe and compare patients seeking treatment for sleep, anxiety and depressive disorders (SADD) from physicians in general practice (GPs) with three different practice preferences: strictly conventional medicine (GP-CM), mixed complementary and conventional medicine (GP-Mx) and certified homeopathic physicians (GP-Ho).

Design And Setting: The EPI3 survey was a nationwide, observational study of a representative sample of GPs and their patients, conducted in France between March 2007 and July 2008.

Participants: 1572 patients diagnosed with SADD.

Primary And Secondary Outcomes: The patients' attitude towards complementary and alternative medicine; psychotropic drug utilisation.

Results: Compared to patients attending GP-CM, GP-Ho patients had healthier lifestyles while GP-Mx patients showed similar profiles. Psychotropic drugs were more likely to be prescribed by GP-CM (64%) than GP-Mx (55.4%) and GP-Ho (31.2%). The three groups of patients shared similar SADD severity.

Conclusion: Our results showed that patients with SADD, while differing principally in their sociodemographic profiles and conventional psychotropic prescriptions, were actually rather similar regarding the severity of SADD in terms of comorbidities and quality of life. This information may help to better plan resource allocation and management of these common health problems in primary care.
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http://dx.doi.org/10.1136/bmjopen-2012-001498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532988PMC
February 2013

A case-control study to assess the risk of immune thrombocytopenia associated with vaccines.

Blood 2012 Dec 24;120(25):4938-44. Epub 2012 Oct 24.

LA-SER, 10 Place de Catalogne, Paris, France.

The cause of immune thrombocytopenia (ITP) remains unknown. Studies have suggested immunizations as possible triggering factors of ITP through molecular mimicry. This case-control study explored potential associations between adult ITP and various routinely administered vaccines. A network of internal medicine and hematology centers across France recruited 198 incident (ie, newly diagnosed) cases of ITP between April 2008 and June 2011. These cases were compared with 878 age- and sex-matched controls without ITP recruited in general practice. Information on vaccination was obtained from patients' standardized telephone interviews. Sixty-six of 198 cases (33.3%) and 303 of 878 controls (34.5%) received at least 1 vaccine within the 12 months before the index date. We found no evidence of an increase in ITP after vaccination in the previous 6 or 12 months (adjusted odds ratio [OR] for the previous 12 months = 1.0; 95% confidence interval, 0.7-1.4). When the 2-month time window was used, higher ORs were observed for all vaccines (OR = 1.3). This increase was mainly attributable to the vaccination against diphtheria-tetanus-pertussis-poliomyelitis (OR = 1.5) and was not statistically significant. The results of the present study show that in an adult population, the exposure to common vaccines is on average not associated with an observable risk of developing ITP.
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http://dx.doi.org/10.1182/blood-2012-05-431098DOI Listing
December 2012