The French health care system is based on universal coverage by one of several health care insurance plans. The SNIIRAM database merges anonymous information of reimbursed claims from all these plans, linked to the national hospital-discharge summaries database system (PMSI) and the national death registry. It now covers 98.8% of the French population, over 66 million persons, from birth (or immigration) to death (or emigration), making it possibly the world's largest continuous homogeneous claims database. The database includes demographic data; health care encounters such as physician or paramedical visits, medicines, medical devices, and lab tests (without results); chronic medical conditions (ICD10 codes); hospitalisations with ICD10 codes for primary, linked and associated diagnoses, date and duration, procedures, diagnostic-related groups, and cost coding; date but currently not cause of death. The power of the database is correlatively great, and its representativeness is near perfect, since it essentially includes the whole country's population. The main difficulty in using the database, beyond its sheer size and complexity, is the administrative process necessary to access it. Recent legislative advances are making this easier. EGB (Echantillon Généraliste de Bénéficiaires) is the 1/97th random permanent representative sample of SNIIRAM, with planned 20-year longitudinal data (10 years at this time). Access time is 1 to 3 months, but its power is less (780 000 subjects). This is enough to study common issues with older drugs but may be limited for new products or rare events.

Keywordsdrug-related risks, over-the-counter nonsteroidal anti-inflammatory drugs, prescription nonsteroidal anti-inflammatory drugs, usage patterns AIMSMost risks of nonsteroidal anti-inflammatory drugs (NSAIDs) are pharmacological, dose and duration dependent. Usage patterns of prescription-only (POM) or 'over-the-counter (OTC)' NSAIDs may influence risks, but are not commonly described. METHODSThe Echantillon Généraliste de Bénéficiaires database, the permanent 1/97 representative sample from the French national healthcare insurance systems, was queried over 2009-2010 to identify usage patterns, concomitant chronic diseases and cardiovascular medication in OTC and POM NSAID users. RESULTSOver 2 years, 229 477 of 526 108 patients had at least one NSAID dispensation; 44 484 patients (19%) were dispensed only OTC NSAIDs (93% ibuprofen) and 121 208 (53%) only POM NSAIDs. The OTC users were younger (39.9 vs. 47.4 years old) and more often female (57 vs. 53%); 69% of OTC users and 49% of POM users had only one dispensation. A mean of 14.6 defined daily doses (DDD) were dispensed over 2 years for OTC vs. 53 for POM; 93% OTC vs. 60% POM patients bought ≤ 30 DDD over 2 years, and 1.5 vs. 12% bought ≥ 90 DDD. Chronic comorbidities were found in 19% of OTC users vs. 28% of POM users; 24 vs. 37% had at least one dispensation of a cardiovascular drug over the 2 years.

AIMSThe aim of the present study was to describe the real-life usage patterns of paracetamol. METHODSThe Echantillon Généraliste de Bénéficiaires (EGB) database, the permanent 1/97 representative sample from the French national healthcare insurance system, was searched in 2011 to identify usage patterns, concomitant chronic diseases and use of cardiovascular medication in users prescribed single-ingredient (SP) and combination (CP) paracetamol, representing 85% of all sales. RESULTSOf 526 108 subjects aged ≥15 years in the EGB, 268 725 (51%) had paracetamol dispensed on ≥1 occasion; of these, 207 707 (77%) were dispensed only SP and 61 018 (23%) received CP with or without SP. SP users were younger (48.3 years vs. 50.5 years), and 57% of SP users vs. 58% of CP users were female. Chronic comorbidities were more common in CP than SP users. SP users had, on average, 3.4 dispensings per year vs. 5.0 for CP users, for 36 defined daily doses (DDD, 3 g) of SP vs. 53 DDD per year for CP; 49% SP users bought 14 DDD or fewer; 15% bought >60 DDD. Use of paracetamol increased with age from about 16 DDD per year in 15-30-yearolds to over 90 DDD per year in patients above the age of 75; 53% of patients ≤60 years bought fewer than 14 DDD per year, whereas 55% of those >60 bought more than 30 DDD per year. More than half the dispensings exceeded the legal per-box limit of 8 g. CONCLUSIONSOver 50% of the French adult population were dispensed paracetamol at least once over the course of a year, generally for shortterm use. Considering recent misgivings on the real efficacy and safety of paracetamol, such widespread use might have important public health consequences. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Although paracetamol is used mostly in mild-to-moderate pain conditions and in chronic arthritis, and its usage pattern might be derived from these indications, there are few or no studies of actual usage patterns and drug exposure or burden. WHAT THIS STUDY ADDS• Over 50% of all adults in the database were dispensed paracetamol at least once in 2011.• The median amount of paracetamol dispensed over 1 year was seven defined daily doses (or 21 g), and this increased with age.• Only 15% of subjects received more than 60 days' worth of paracetamol in a year. British Journal of Clinical PharmacologyBr J Clin Pharmacol (2016) 82 498-503 498

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Results are ambiguous: long-term exposure seemed associated with an increased risk of myocardial infarction or stroke with high-dose rofecoxib, and perhaps diclofenac, but less with other NSAIDs. In other studies, little or no increase in risk was associated with exposures shorter than 30 days. Since most NSAIDs are rarely used long term, there is little information on risks associated with long-term use. The relative risks or odds ratios associated with most drugs are mostly well below 2.

At doses below the maximal daily OTC dose and for durations associated with OTC usage, there was no clear association with increased CV risk.

induced regulatory action, drug-induced hospital admissions and burden of care. • studies based on clinical identification of hospitalized cases rarely include more than a few hundred cases. • The EPIHAM study provides information on the drugs associated with the greatest burden of ALI, and drugs with the highest individual associated risk, over the whole French population over 5 years. Most of these drugs are well known to be able to cause liver injury.

There was no evidence for an increased risk of ACS in patients dispensed ibuprofen compared to paracetamol.