Use of the French national health insurance information system for research in the field of mental health: Systematic review and perspectives.

PURPOSE: This systematic review registered in PROSPERO (CRD42021225296) aimed to describe the use of the French national health insurance information system, which covers the entire French population (67 million inhabitants), for research in the field of mental health. METHODS: Three electronic databases and a journal hand-search identified 15 265 articles from January 1, 2003 (year of creation of the database) to October 31, 2020. Studies of any design were eligible for inclusion provided that they (i) made use of at least one component of the French health insurance database and (ii) focused on a topic in near and far connection with the field of mental health in France. Database used, design and methods, study period, population, key findings, and type of use for medical research were described. RESULTS: A total of 152 studies were included in the review analysis. There was an increase in the number of published articles over time throughout the studied period. Studies focusing on adults (n = 139) largely outnumbered those focusing on children and adolescents (n = 11). Pharmacoepidemiological studies were by far the most frequent (n = 123), followed by methodological studies (n = 23), epidemiological studies (n = 17), and health economics studies (n = 3). The most studied psychotropic drugs were antidepressants (n = 27), anxiolytics (n = 27), and opioids (n = 25) while fewer studies focused on methylphenidate (n = 6) and on mood stabilizers (n = 5). Few studies specifically focused on psychiatric disorders, mainly depression (n = 4), suicide (n = 4), and psychotic disorders (n = 3). CONCLUSION: This systematic review highlighted a relatively poor exploitation of the Système national des données de santé database in the field of psychiatric research with regard to the great possibilities it offers, with a clear lag in certain fields such as epidemiological or health economics studies and in specific populations, in particular children and adolescents.

The value of a health insurance database to conduct pharmacoepidemiological studies in oncology.

Some concerns have emerged about the evidence of benefits on survival outcomes or quality of life of new anticancer drugs. In parallel, the decreased cancer mortality leads to an increased number of patients exposed to cancer treatment-related consequences. In this context, pharmacoepidemiology is crucial to assess anticancer drug use, effectiveness and safety in real life conditions. We aimed to describe strengths, limitations and considerations associated with the use of the French national health insurance database (système national des données de santé [SNDS]) to conduct pharmacoepidemiological studies in oncology. The SNDS represents a powerful tool in pharmacoepidemiology owing to its extensive coverage, accurate description and quantification of drug exposure and individual data on patients. The main limitations of this database ensue from the administrative nature resulting in technical difficulties in its management and gaps in availability of data. Another limitation is the lack of accurate identification of diseases, comorbidities or outcomes and potential confounding with notably the lack of data regarding cancer stage, prognosis or risk factors. Finally, the accurate identification of the nature of chemotherapy received by patients is sometimes complex. To minimize these limitations, several approaches and statistical methods could be used as highlighted by national or international initiatives. First, the SNDS may be linked with cancer registry or clinical data. Then, several data sources could be combined using meta-analytical methods. The development of methodological tools and the use of standardized methods are crucial to enhance the quality of studies that can impact clinical practice and guide public decision. Pharmacoepidemiological approaches and pharmacovigilance represent an important cornerstone in oncology for signal detection or long-term follow up of cancer patients. In this context, validated methods to identify cancer patients and to describe chemotherapy regimens within these data should be promoted and remain too scarce despite international guidelines. Moreover, limits and strength of each data sources should be systematically discussed according to the research question. Optimized and framed use of claims database represents a future challenge in onco-pharmacoepidemiology.

Is there overuse of proton pump inhibitors in B-cell non-Hodgkin lymphomas? A cohort study based on the French health insurance database in the Midi-Pyrénées region.

Patients suffering from B-cell non-Hodgkin lymphomas (B-NHL) have an increased likelihood of being exposed to proton pump inhibitors (PPIs), related to several factors which have been reported in the literature. PPIs are among the drugs most likely to be prescribed inappropriately. Consequently, B-NHL patients could be particularly at risk of inappropriate PPI prescription, with potential adverse drug reactions. We aimed to evaluate the incidence of PPIs use and to identify factors associated with PPIs initiation during the active treatment phase of B-NHL. We conducted a new-user cohort study using regional data from the French national health insurance database in the Midi-Pyrénées region (southwestern France). Incident B-NHL patients were selected according to an algorithm of selection, validated with data from a cancer registry. Our study revealed that 48.9% (95% confidence interval [CI]: 45.2-52.6) of patients initiated PPIs during chemotherapy after B-NHL diagnosis. According to information available in the SNDS, recommended indications for PPI prescriptions were identified in 21.1% of cases. Median duration of treatment was 65.3 days (CI: 35-112). Determinants of PPIs initiation were peptic ulcer disease, gastroprotection (appropriate or not) for medications considered at risk (NSAIDs, glucocorticoids and anticoagulants), age, nonfollicular lymphoma, polypharmacy, gastroenterologists' consultations and being hospitalized in a university hospital. Around 50% of patients initiated PPI treatment during the chemotherapy phase with only one-fifth identified as appropriate prescriptions and with long durations of treatment in most cases. Given this background, appropriate PPI prescription should be promoted in B-NHL to avoid potential inappropriate chronic use and related adverse events.

Infectious risk of biological drugs vs. traditional systemic treatments in moderate-to-severe psoriasis: a cohort analysis in the French insurance database.

The aim of this study was to compare the infectious risk between a group of psoriasis patients treated by biological drugs (BD) and a group treated by traditional systemic treatments (TST). We built a retrospective observational cohort study from the French health insurance database in the Midi-Pyrénées area (2.9 million inhabitants, southwest of France) using data from 01/01/2010 to 12/31/2013. We compared the infectious risk between 'exposed' patients treated with BD (adalimumab, etanercept, infliximab, or ustekinumab) and 'unexposed' patients treated by TST (phototherapy, acitretin, methotrexate, or cyclosporine). We realized a survival analysis on the first infectious event, defined as an anti-infective drug delivery or a hospital diagnosis of infection. We selected 101 'exposed' and 788 'unexposed' patients. In our multivariate Cox model, 'exposure' did not seem to decrease the time frame of the first infectious event compared with 'nonexposure' (HR = 0.94, P = 0.62). Among all treatment, the safest seemed to be ustekinumab while the least safe was etanercept. We found factors statistically associated with the risk of infection: gender (female vs. male), economic deprivation, chronic hepatitis B or C, history of cancer, at least one infectious event, and the number of different drugs during the 6-month period before the study. We did not find any difference of infective risk between the BD and the TST. This result enhances the recent PSONET registries conclusions.

Validation of an algorithm identifying incident primary immune thrombocytopenia in the French national health insurance database.

OBJECTIVES: To evaluate the accuracy of an algorithm identifying newly diagnosed immune thrombocytopenia (ITP) patients in the French national health insurance database (SNIIRAM). METHODS: The source of data was the SNIIRAM of Midi-Pyrenees region (southwest of France, three million inhabitants). Data of patients with at least one ITP code (D69.3 code of the International Classification of Disease, version 10) were extracted between January 1, 2012, and December 31, 2014. We used an algorithm that identifies newly diagnosed primary ITPs. Medical charts of incident ITPs were reviewed. Positive predictive values (PPVs) of identification of true, incident, and primary ITP cases were estimated. RESULTS: Of the 168 patients selected, 161 were true ITP cases yielding a PPV of 95.8% (95% confidence interval-95% CI: 92.8-98.8). Among them, 128 were truly incident according to symptom onset date and 134 according to the diagnosis date yielding PPVs of 79.5% (95% CI: 73.2-85.7) and 83.2% (95% CI: 77.4-89.0), respectively. Median time between estimated diagnosis date by the algorithm and true diagnosis date was 0 days (interquartile range: 0 to 15). CONCLUSIONS: This study showed a very good PPV of this algorithm identifying incident primary ITP patients in the SNIIRAM.

Overview of drug data within French health insurance databases and implications for pharmacoepidemiological studies.

In this study, we aimed to provide an updated overview of drug data contained in the French health insurance database (SNIIRAM) and its associated national representative sample (EGB). This study identified most common problems concerning drug data: (i) change in level of coverage of drugs of interest (drug no more eligible for reimbursement or no more prescription-only), (ii) break in patients' eligibility (in connection with change of healthcare plan or patients' identifier), and (iii) technical and regulatory issues. We provide a brief checklist to enable a structured identification of these issues. The impact of gap in drug data availability on study validity will depend on the research question, drug, setting, and population of interest. The French health insurance database and associated sample are valuable resources for pharmacoepidemiological research. There is a need to pursue further methodological and validation studies to promote accurate and transparent use of French health insurance databases for pharmacoepidemiology.

Acute pain management for patients under opioid maintenance treatment: what physicians do in emergency departments?

The aim of this study was to analyze the current practices on acute pain management of patients under opioid maintenance treatment (OMT), that is, buprenorphine or methadone. A total of 706 physicians were solicited through a national network to answer a survey about pain perception and analgesic strategies. Among the prescribers, 323 (46%) answered the survey: 131 (40%) physicians estimated that patients under OMT when exposed to an acute painful event feel more pain than other patients and 170 (53%) estimated that the patients felt the same amount of pain. Use of WHO step 1 analgesics was reported by 283 (88%) prescribers [264 (82%) prescribers reported use of paracetamol and 178 (55%) reported use of NSAIDs]. Among the second-line analgesic drugs, the WHO step 3 analgesics (mainly morphine) were the most commonly reported [221 physicians (68%)]. Overall, the results demonstrate the misconceptions of physicians on the pain tolerance of patients under OMT. Clinical studies and evidence-based guidelines are necessary to improve the therapeutic strategies for such patients in an emergency setting.

Non-steroidal anti-inflammatory drugs (NSAIDs) and hypertension treatment intensification: a population-based cohort study.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to antagonize the effects of antihypertensive drugs, and these associations can lead to an increase in arterial blood pressure. However, the impact of NSAIDs on hypertension treatment management in large-scale populations remains poorly evaluated. We examined whether the introduction of NSAID into the treatment regimen would induce an intensification of hypertension treatment (defined as the introduction of a new antihypertensive drug). METHODS: We conducted a cohort study involving 5,710 hypertensive subjects included in the French health insurance system database who had been treated and stabilized with their antihypertensive therapy and not exposed to any NSAID between 1 April 2005 and 1 April 2006. The maximum follow-up duration was 4 years. RESULTS: Adjusted hazard ratios (HR) for hypertension treatment intensification were 1.34 [95 % confidence interval (CI) 1.05-1.71] for NSAIDs in general, 1.79 (95 % CI 1.15-2.78) for diclofenac and 2.02 (95 % CI:1.09-3.77) for piroxicam. There were significant interactions between NSAIDs and angiotensin converting enzyme inhibitors (ACEIs; HR 4.09, 95 % CI 2.02-8.27) or angiotensin receptor blockers (ARBs; HR 3.62, 95 % CI 1.80-7.31), but not with other antihypertensive drugs. CONCLUSIONS: Exposure to NSAIDs leads to an intensification of hypertension treatment, especially in patients treated with ACEIs or ARBs. Renin-angiotensin system blockers should be avoided whenever NSAIDs are prescribed.

The importance of drug-drug interactions as a cause of adverse drug reactions: a pharmacovigilance study of serotoninergic reuptake inhibitors in France.

PURPOSE: To quantify the importance of drug-drug interactions (DDIs) in the occurrence of adverse drug reactions (ADRs) reported with serotoninergic reuptake inhibitors in a pharmacovigilance database. METHODS: All spontaneous reports of ADRs registered in 2008 by the Midi-Pyrénées PharmacoVigilance Centre that contained mention of one of the serotoninergic reuptake inhibitor (SRI) antidepressants marketed in France were reviewed. DDIs were identified according to the French National Drug Formulary (Vidal) and the interaction supplement of the French independent drug bulletin La Revue Prescrire. ADRs explained by DDIs were characterised. RESULTS: Among the 2,101 spontaneous reports recorded, 177 involved at least one SRI antidepressant. Among the 156 ADRs with at least one theoretical DDI, 41% (95% confidence interval 34-49%) could be explained by a DDI. The most frequent antidepressant involved in DDIs was escitalopram, followed by fluoxetine and citalopram. Among the 65 ADRs related to DDIs, 37 (52.9%) were "serious", mainly bleedings, confusion and falls, hyponatremia and serotoninergic syndromes. The most frequent drug interactions occurred with psychotropics (antipsychotics, benzodiazepines, among others), followed by antithrombotic agents (antagonists of vitamin K, antiplatelets), diuretics and angiotensin II antagonists. The group with ADRs related to DDIs was older than the group with ADRs not related to DDIs. ADRs were threefold more "serious" in the case of DDIs. CONCLUSION: Around 40% of ADRs reported with SRIs were related to DDIs. Most of these occurred after association with psychotropics, antithrombotics, or diuretics, especially in the elderly.

Case ascertainment and estimated incidence of drug-induced long-QT syndrome: study in Southwest France.

AIMS: The aim of this study was to investigate the incidence and reporting rate of drug-induced long-QT syndrome (LQTS) in France [defined by evidence of torsades de pointes (TdP), QT prolongation and exposure to a relevant drug] and to assess feasibility of case collection for drug-induced LQTS. METHODS: A retrospective population-based study was carried out in Southwest France in five institutions: three main hospitals, one private clinic and one cardiac emergency unit, searched from 1 January 1999 to 1 January 2005 (population coverage of 614 000). The study population consisted of 861 cases with International Classification of Diseases-10 diagnostic codes for ventricular tachycardia (I147.2), ventricular fibrillation (I149.0) and sudden cardiac death (I146.1) from hospital discharge summaries, supplemented by cases reported to national or regional pharmacovigilance systems, and voluntary reporting by physicians, validated according to internationally defined criteria for drug-induced LQTS. RESULTS: Of 861 patients coded with arrhythmias or sudden cardiac death, there were 40 confirmed surviving acquired cases of drug-induced LQTS. We estimated that the incidence of those who survive to reach hospital drug-induced LQTS is approximately 10.9 per million annually in France (95% confidence interval 7.8, 14.8). CONCLUSIONS: Many cases of drug-induced LQTS may not survive before they reach hospital, as the reporting rate for drug-induced LQTS identified through the cardiology records and also reported to pharmacovigilance systems for the Midi-Pyrenees area is 3/40 (7.5%). Using the methods outlined it is possible to assemble cases to study genetic susceptibility to drug-induced LQTS and adapt these methods more widely.

Drug counselling in pregnancy: an opinion survey of French community pharmacists.

PURPOSE: The aim of the present study was to determine whether community pharmacists recommend appropriate medications and give valid information to pregnant women. METHODS: A total of 163 community pharmacists randomly selected in the Midi-Pyrénées area were interviewed by means of an open questionnaire. Ten scenarios were proposed concerning back pain, headache, coughs and sore-throats, fever, constipation, nausea, dyspepsia, 'venous insufficiency', allergic rhinitis and insomnia. RESULTS: Out of the total, 130 pharmacists accepted to answer. Out of them 94.5% reported advising homeopathy, especially for coughs and allergy. They often advised medication for pain, fever, nose and oropharynx disorders, 'venous insufficiency', dyspepsia or constipation. By contrast, they referred the women to the general practitioner for nausea and vomiting or back pain. Advice without drug dispensation was given for gastrointestinal disorders or 'venous insufficiency'. Phytotherapy only concerned 0.5-2% of the answers except for anxiety and sleep disturbances (59%), 'venous disorders'(17%) and sore-throat (9%). Pharmacists' answers were sometimes inappropriate involving (1) pharmacologically illogical advice, (2) drugs for which neither clinical nor experimental data are available and (3) drugs potentially harmful in pregnancy. CONCLUSIONS: The present study shows that French community pharmacists do not always give appropriate advice to pregnant women. As primary health care providers, pharmacists have to improve counselling regarding drug use in pregnancy.