French Healthcare Databases Research Articles

Signal detection of drugs associated with obstructive and central sleep apnoea

We aim to discover new safety signals of drug-induced sleep apnoea (SA), a global health problem affecting approximately 1 billion people worldwide.We first conducted a series of sequence symmetry analyses (SSA) in a cohort composed from all patients who received a first SA diagnosis or treatment between 2006 and 2018 in the Echantillon Généraliste des Bénéficaires (EGB), a random sample of the French healthcare database. We used two primary outcomes to estimate the sequence ratio (SR) for all drug classes available in France: a sensitive one (diagnosis or treatment of SA) and a specific one (Positive Airway Pressure (PAP) therapy). We then performed disproportionality analyses using the “Bayesian neural network method” on all cases of sleep apnoea (MedDRA high level term) reported up to November 2023 in the World Health Organisation (WHO) pharmacovigilance database.Among the 728,167 individuals, 46,193 had an incident diagnosis or treatment for SA and 17,080 had started an incident treatment by PAP therapy. Fifty-eight drug classes had a significant SR, with 7 considered highly plausible: opium alkaloids and derivatives, benzodiazepine derivatives, other centrally acting agents, other anxiolytics, carbamic acid esters, quinine and derivatives and antivertigo preparations; with consistent signals found for the first 3 drug classes in the disproportionality analysis.In this signal detection study, we found that opioids, benzodiazepines (but not Z-drugs) and myorelaxing agents are associated with the onset or aggravation of SA. Moreover, a new safety signal for antivertigo preparations such as betahistine emerged and needs to be further explored.

Hydroxychloroquine and Cardiovascular Events in Patients With Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) predisposes individuals to early cardiovascular (CV) events. While hydroxychloroquine is thought to mitigate CV risk factors, its protective role against CV events, particularly arterial ones, remains to be confirmed. To evaluate the association between hydroxychloroquine and the risk of myocardial infarction (MI), stroke, and other thromboembolic events (OTEs) in patients with SLE. This cohort study using a nested case-control design was conducted within the National French Healthcare Database (SNDS), which represents 99% of the French population, from 2010 to 2020. Participants were the cohort of all patients with SLE recorded in the SNDS. Patients with SLE experiencing CV events during the study period were the case group; those without CV events were controls. The analysis period was from February 2022 to September 2023. Hydroxychloroquine use within 365 days prior to the index date, defined as current (within 90 days), remote (91-365 days), or no exposure within the previous 365 days. Outcomes of interest were MI, stroke, and OTE, analyzed individually and as a composite outcome (primary analysis). Controls were matched to patients with CV events by age, sex, time since SLE onset and entry into the SNDS database, index date, prior antithrombotic and CV medication, chronic kidney disease, and hospitalization. Multivariable conditional logistic regression was performed using hydroxychloroquine exposure as the main independent variable. The SLE cohort included 52 883 patients (mean [SD] age, 44.23 [16.09] years; 45 255 [86.6%] female; mean [SD] follow-up, 9.01 [2.51] years), including 1981 patients with eligible CV events and 16 892 matched control patients. There were 669 MI events, 916 stroke events, and 696 OTEs in the individual outcome studies. For current exposure to hydroxychloroquine, the adjusted odds were lower for composite CV events (odds ratio [OR], 0.63; 95% CI, 0.57-0.69) as well as for MI (OR, 0.72; 95% CI, 0.60-0.85), stroke (OR, 0.69; 95% CI, 0.60-0.81), and OTEs (OR, 0.58; 95% CI, 0.49-0.69) individually compared with no hydroxychloroquine exposure within 365 days. In this nationwide cohort study of patients with SLE, a protective association was found between the current use of hydroxychloroquine and the occurrence of CV events, but not between remote use of hydroxychloroquine and CV outcomes, highlighting the value of continuous hydroxychloroquine treatment in patients with SLE.

Development and validation of a code-based algorithm using in-hospital medical records to identify patients with pulmonary arterial hypertension in a French healthcare database.

Pulmonary arterial hypertension (PAH) is a rare and severe disease for which most of the evidence about prognostic factors, evolution and treatment efficacy comes from cohorts, registries and clinical trials. We therefore aimed to develop and validate a new PAH identification algorithm that can be used in the French healthcare database "Système National des Données de Santé (SNDS)". We developed and validated the algorithm using the Grenoble Alpes University Hospital medical charts. We first identified PAH patients following a previously validated algorithm, using in-hospital ICD-10 (10th revision of the International Statistical Classification of Diseases) codes, right heart catheterisation procedure and PAH-specific treatment dispensing. Then, we refined the latter with the exclusion of chronic thromboembolic pulmonary hypertension procedures and treatment, the main misclassification factor. Second, we validated this algorithm using a gold standard review of in-hospital medical charts and calculated sensitivity, specificity, positive and negative predictive value (PPV and NPV) and accuracy. Finally, we applied this algorithm in the French healthcare database and described the characteristics of the identified patients. In the Grenoble University Hospital, we identified 252 unique patients meeting all the algorithm's criteria between 1 January 2010 and 30 June 2022, and reviewed all medical records. The sensitivity, specificity, PPV, NPV and accuracy were 91.0%, 74.3%, 67.9%, 93.3% and 80.6%, respectively. Application of this algorithm to the SNDS yielded the identification of 9931 patients with consistent characteristics compared to PAH registries. Overall, we propose a new PAH identification algorithm developed and adapted to the French specificities that can be used in future studies using the French healthcare database.

Use of the French National Health Data System (SNDS) in pharmacoepidemiology: A systematic review in its maturation phase

The French National Health Data System (SNDS) comprises healthcare data that cover 99% of the population (over 67 million individuals) in France. The aim of this study was to present an overview of published pharmacoepidemiological studies using the SNDS in its maturation phase. We conducted a systematic literature review of original research articles in the Pubmed and EMBASE databases from January 2012 until August 2018. A total of 316 full-text articles were included, with an annual increase over the study period. Only 16 records were excluded after screening because they did not involve the SNDS but other French healthcare databases. The study design was clearly reported in only 66% of studies of which 57% were retrospective cohorts and 22% cross-sectional studies. The reported study objectives were drug utilization (65%), safety (22%) and effectiveness (9%). Almost all ATC groups were studied but the most frequent ones concerned the nervous system in 149 studies (49%), cardiovascular system drugs in 104 studies (34%) and anti-infectives for systemic use in 50 studies (16%). The SNDS is of growing interest for studies on drug use and safety, which could be conducted more in specific populations, including children, pregnant women and the elderly, as these populations are often not included in clinical trials.

Evolution of the profiles of new psychotropic drug users before and during the COVID-19 crisis: an original longitudinal approach through multichannel sequence analysis using the French health-care database.

The COVID-19 pandemic has had a substantial impact on mental health. An increase in the use of anxiolytic, hypnotic, and antidepressant drugs has been highlighted in France, but with no information at the individual level (trajectories) or concerning patient characteristics. The objective of this study was to describe the profile of new psychotropic drug users since the beginning of the pandemic. We formed two historical cohorts using the Pays-de-la-Loire regional component of the National Health Data System (SNDS): a "COVID-19 crisis cohort" (2020-2021) and a "control cohort" (2018-2019). We analyzed reimbursements for psychotropic medications (anxiolytics, antidepressants, hypnotics, mood stabilizers, and antipsychotics) using a multichannel sequence analysis and performed clustering analysis of sequences. The proportion of new consumers of psychotropic drugs was higher in the COVID-19 crisis cohort (18.0%) than that in the control cohort (16.0%). In the COVID-19 cohort, three clusters of psychotropic drug users were identified, whereas four clusters were identified in the control cohort. A time lag in treatment initiation was observed in the COVID-19 crisis cohort (September) compared with the control cohort (July). This study is one of the first to analyze the profile of psychotropic treatment users during the COVID-19 crisis. Our analysis sheds light on changes in patterns of psychotropic drug use during the COVID-19 pandemic, possibly associated with changes in prescribing conditions and mental health conditions during the crisis. This study also provides an example of the application of an innovative longitudinal analysis methodology in the field of pharmacoepidemiology.

Total shoulder arthroplasty in France: An analysis of trends between 2009 and 2019 and projections to the year 2070

BackgroundOver the past decades, total shoulder arthroplasty (TSA) procedures have steadily increased in the United States and Europe. In France, the number of shoulder surgeries rose by 24.5% between 2012 and 2018, but no study has yet analyzed TSA trends based on patient characteristics. Therefore, the aim of our study was to use the French healthcare database to (1) analyze growth trends based on the patient's sex, age, and comorbidity profile and (2) estimate the most appropriate incidence rate (IR) projections to the year 2070. HypothesisWe hypothesize that in France, the upward trends are different for each sex and age group. Materials and methodsThis study was conducted in France from 2009 to 2019 based on the French healthcare database (SNDS), which contains all nationwide procedures. Patients were analyzed by sex, age group (<65 years, 65–74 years, ≥75 years), and comorbidity profile (4 levels). IR trends per 100,000 population were inferred by patient age, sex, and comorbidity using data from the French hospital discharge database (PMSI) and population forecasts and censuses from the French National Institute of Statistics and Economic Studies (INSEE). Linear, Poisson, logistic, and Gompertz projection models were created to forecast IRs to the year 2070. ResultsBetween 2009 and 2019, there was a sharper increase in IR in males (+155%; from 6.0 to 15.3) than in females (+118%; from 16.2 to 35.3) across all age groups. This increase was most significant in those younger than 65 years (+112%; from 2.3 to 4.9), in both males (+129%; from 2.1 to 4.8) and females (+99%; from 2.5 to 5.0). From 2012 to 2019, the proportion of patients with mild comorbidities increased by +92% (from 5,435 to 10,410 TSAs, i.e., from 56% to 61% of total procedures), unlike the other comorbidity profiles. All the projections modeled the data from 2009 to 2019 with minor deviations. However, the logistic projection was the most likely, with a 45% increase in the IR for the overall population by 2070 (from 17,175 to 25,338 TSAs), which will start to plateau in 2050. ConclusionThe IR has risen sharply in the overall population, as in all age, sex, and comorbidity categories, with the most significant growth seen in the<65 and 65–74 age groups and a shift toward patients with milder comorbidities. According to our projections, the IR will continue to be more significant in older patients, except for males, for whom the IR for those 65 to 74 years old will exceed that of those 75 and older around 2030. In the longer term, the IRs follow a logistic trend, reaching a plateau around 2050. Therefore, an increase in healthcare burden is to be expected to meet the growing demand for TSAs. Level of evidenceIV; Descriptive epidemiological study.

Two-Year Results on Real-World Fenestrated or Branched Endovascular Repair for Complex Aortic Abdominal Aneurysm in France.

To describe and compare mid-term outcomes from 2 real-world data collection efforts on fenestrated and branched endovascular aortic repair (fbEVAR) for complex abdominal aortic aneurysms (AAAs) in France and to evaluate the potential of health care databases for long-term post-market surveillance (PMS) and continued reimbursement approval. Two real-world studies were conducted in France: a retrospective health care database study (SNDS) and a prospective clinical study. In the SNDS study, data from implantation and/or hospital stays occurring during follow-up were extracted for all patients treated with the study devices from April 2012 to December 2018. In the clinical study, high-risk patients undergoing fbEVAR with the study devices were enrolled consecutively at 15 sites in France from December 2016 to November 2018. Data from 1073 patients were extracted from SNDS and compared with analogous variables from 186 patients in the clinical study. Most demographic details were similar between studies (SNDS vs clinical: mean age, 71.9 vs 71.8 years; men, 91.0% vs 89.8%), as was 30-day mortality (SNDS: 5.5%, clinical: 4.3%). Patients received custom-made fenestrated or branched devices (SNDS: 80.7%, clinical: 96.2%) or CE-marked Zenith Fenestrated devices (SNDS: 19.3%, clinical: 3.8%). Initial or technical success was above 94% for both studies. Two-year freedom from all-cause mortality was 80.0% (SNDS) and 85.1% (clinical study). Two-year freedom from aneurysm-related mortality was 93.8% (SNDS) and 94.6% (clinical study). Detailed imaging outcomes were not captured within SNDS; however, information on secondary procedures to restore patency was available and used as a surrogate measure for secondary interventions. Two-year freedom from secondary interventions was 73% for the SNDS study. In the clinical study, at 2 years, aneurysm stability or shrinkage was observed in 92.3% of patients, freedom from target vessel primary patency loss was above 95% for all visceral target vessels, and freedom from secondary interventions was 79.1%. Real-world outcomes from the SNDS and clinical study suggest positive mid-term outcomes in high-risk populations following fbEVAR for complex AAAs. The similarities between these studies suggest that the use of health care databases may be an alternative to prospective clinical studies for long-term follow-up and PMS. Positive results following endovascular repair of complex abdominal aortic aneurysms are observed from data extracted from both the French health care database and a post-market clinical study despite initial high-risk patient status and diverse center experience. These outcomes parallel more rigorously designed studies and suggest that with careful study design, real-world data collections have high translatable value to add to the clinical understanding of fenestrated and branched endovascular aortic repair (fbEVAR).

Comparison of Stroke Recurrence, Cardiovascular Events, and Death Among Patients With Pregnancy-Associated vs Non–Pregnancy-Associated Stroke

Women with pregnancy-associated stroke might have different risks of stroke recurrence, including during subsequent pregnancies, and other cardiovascular events due to pregnancy-specific stroke risk factors, such as gestational hypertension, preeclampsia, or gestational diabetes. To estimate the rate of stroke recurrence, cardiovascular hospitalization, and death in women with pregnancy-associated stroke compared with women with non-pregnancy-associated stroke. This cohort study included all women aged 15 to 49 years in France who were affiliated with the general scheme of French health care insurance (94% of women) and had a first hospitalization for stroke between January 1, 2010, and December 31, 2018. Women were followed up until December 31, 2020, with the registration of stroke recurrence, hospitalization for cardiovascular conditions, and death. Data were from the French health care database Système National des Données de Santé. Statistical analyses were conducted between December 2021 and September 2022. Pregnancy status at the time of stroke. Poisson regressions were used to estimate incidence rates of these events with 95% CIs. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) of each event during the follow-up for women with a pregnancy-associated stroke vs women with a non-pregnancy-associated stroke. Among women aged between 15 and 49 years between 2010 and 2018 and living in France, 1204 had a pregnancy-associated stroke at a mean (SD) age of 31.5 (5.8) years, and 31 697 had a non-pregnancy-associated stroke at a mean age of 39.6 (8.2) years. Among the 1204 women with a pregnancy-associated stroke, the incidence rate was 11.4 (95% CI, 9.0-14.3) per 1000 person-years, with 2 recurrent events during a subsequent pregnancy. Compared with women with non-pregnancy-associated stroke, women with pregnancy-associated stroke had lower risks of ischemic stroke (adjusted HR, 0.53; 95% CI, 0.36-0.77), cardiovascular events (adjusted HR, 0.58; 95% CI, 0.49-0.69), and death (adjusted HR, 0.42; 95% CI, 0.22-0.79). In contrast, the risk of recurrent intracerebral hemorrhage and cerebral venous thrombosis did not differ significantly, whereas the risks of venous thromboembolism (HR, 2.02; 95% CI, 1.14-3.58) and acute coronary syndrome with ST-segment elevation (HR, 3.93; 95% CI, 1.10-14.0) were increased. In this cohort study, although the risks of ischemic stroke, overall cardiovascular events, and mortality were lower after a pregnancy-associated stroke than after a non-pregnancy-associated stroke, the risks of venous thromboembolism and acute coronary syndrome with ST-segment elevation were higher. Recurrent stroke during a subsequent pregnancy remained rare.

Drug-drug interactions of protein kinase inhibitors in chronic myeloid leukaemia patients: a study using the French health insurance database.

The introduction of protein kinase inhibitors (PKIs) for chronic myeloid leukaemia (CML) has considerably improved prognosis of the disease but has also demonstrated a great potential for drug-drug interactions. Using the French health insurance databases, we aim to investigate the frequency, identify the associated factors, and describe the potential consequences of potential drug-drug interactions (pPKI-DIs) between PKIs and concurrent medications in CML. A retrospective cohort study has been performed among patients with CML identified in the French healthcare database from 2011 to 2014. A pPKI-DI is defined as the presence of drugs listed as "interacting" on the same day as PKI dispensing (co-dispensing), or in its coverage period (co-medication) during the first year of follow-up. The list of interacting drugs is based on the summary of products characteristics (SPC) and Thesaurus of interactions. We performed specific nested case-control comparisons to investigate the association between PKI-DI and each of the three potential outcomes (death, hospitalisation for adverse drug reactions and switch to another PKI). We included 3,480 patients; 1,429 (41%) had a co-dispensing pPKI-DI and 2,153 (62%) had a co-medication pPKI-DI. 50% of the pPKI-DIs were "to be taken into account" and 17% were "not recommended". The PKI with the most interactions was imatinib, and additional common drug classes included statins, benzodiazepines and proton pump inhibitors. Multivariate analysis demonstrated that the use of a higher number of additional drugs, comorbidities at baseline, high number of prescribers and higher ages were potential risk factors. Nilotinib and dasatinib showed a tendency towards a higher risk of pPKI-DI compared to imatinib. Despite the fact that some PKI-DIs were potentially clinically relevant, we did not find any significant association with death, hospitalisation for adverse drug reactions and switching. These findings should increase awareness to help reduce the prevalence of PKI-drug interactions, and thereby ensure better management of CML patients.

Real-life impact of uncontrolled severe asthma on mortality and healthcare use in adolescents and adults: findings from the retrospective, observational RESONANCE study in France

ObjectiveTo characterise uncontrolled severe asthma and compare the disease burden with the general and asthmatic populations.DesignRetrospective observational study using a national sample of a French healthcare database (Echantillon Généraliste des...

Real-life omalizumab exposure and discontinuation in a large nationwide population-based study of paediatric and adult asthma patients

This real-life study aimed to assess omalizumab treatment patterns in adult and paediatric asthma patients, and to describe asthma control and healthcare resource use (HCRU) at omalizumab initiation and discontinuation. The French healthcare database system (Système National des Données de Santé (SNDS)) was used to identify asthma patients aged ≥6 years who initiated omalizumab for at least 16 weeks from 2009 to 2019. We examined omalizumab treatment patterns using dispensation records. We identified 16 750 adults and 2453 children initiating omalizumab. Median treatment persistence before discontinuation (TSTOP) was 51.2 (95% CI 49.3-53.4) months in adults and 53.7 (95% CI 50.6-56.4) months in children. At 2 years of omalizumab exposure, rate of hospitalisation for asthma decreased by 75% and use of oral corticosteroids (OCS) by 30%, in adults and children. Among adults who discontinued omalizumab while asthma was controlled, 70%, 39% and 24% remained controlled and did not resume omalizumab at 1, 2 and 3 years after discontinuation, respectively. These proportions were higher in children (76%, 44% and 33%, respectively). Over 2 years of follow-up after discontinuation, HCRU remained stable in adults and children, notably rate of hospitalisations for asthma (none before TSTOP, 1.3% and 0.6% at 2 years) and use of OCS (in adults and children, respectively: 20.0% and 20.2% before TSTOP, 33.3% and 24.6% at 2 years). This is the first large-scale study describing omalizumab real-life exposure patterns in adult and paediatric asthma patients in France with >10 years of follow-up. We showed the long-term maintenance of low HCRU in adults and children who discontinued omalizumab while asthma was controlled, notably for OCS use and hospitalisations for asthma.

Trends of influenza vaccination coverage in pregnant women: a ten-year analysis from a French healthcare database

Pregnant women have a high risk of severe influenza, associated with obstetrical complications. The World Health Organization (WHO) has recommended influenza vaccination for all pregnant women since 2012. The vaccination coverage remains low worldwide, and in Europe, due to a lack of proposition from the health care providers, and a high refusal rate from the women. The primary aim of this study was to estimate the influenza vaccination coverage (IVC) in a population of pregnant women in France, and to analyse its evolution from 2009 to 2018. The secondary objective was to describe the vaccinated population and to find determinants associated with the vaccination. This retrospective cohort study is based on the EGB French health care database, a representative sample of the French population containing data from the health insurance system. All pregnant women who delivered medically or spontaneously over the 2009–2018 period were included. In the 2009–2018 period, only 1.2% pregnant women were vaccinated against influenza (n = 875/72,207; 95% CI 1.14–1.30). The IVC slightly increased after the 2012 WHO recommendation, from 0.33 to 1.79% (p < 0.001) but remained extremely low (4.1% in 2018). Women younger than 25 years old had a low coverage (0.6%) whereas women over 35 years old were more likely to get the influenza vaccine (1.7%; OR: 2.82, 95% CI 2.14–3.71). The vaccination behavior was not influenced by multifetal pregnancy or parity, but socio-economically deprived women were less likely to be vaccinated (OR: 0.81, 95% CI: 0.67–0.98). Women with pre-existing medical conditions had an overall higher vaccination rate (2.5%; OR: 2.32, 95% CI: 1.94–2.77). The vaccine was mainly prescribed by family physicians (58%). Influenza vaccination in pregnant women in France remains very low, particularly in younger, healthy women, and measures such as information campaigns towards pregnant women and studies of the knowledge, attitudes, and practices of the health care professionals need to be undertaken to improve the coverage.

Association Between Exposure to Effervescent Paracetamol and Hospitalization for Acute Heart Failure: A Case-Crossover Study.

We investigated whether effervescent paracetamol, as an important source of nondietary sodium and fluid load, is associated with a transient increase in the risk of hospitalization for acute heart failure (AHF). We conducted a unidirectional case-crossover study using data from the 1 in 97th representative sample from the French health care database. Subjects aged ≥18 years, hospitalized for AHF during the 2014-2016 period, were included. Exposure to effervescent paracetamol was compared between a risk period (ie, 15 days immediately before admission for AHF) and 3 earlier 15-day control periods, to test a possible trigger effect of effervescent paracetamol intake on AHF. Adjusted odds ratios (aORs) were estimated with a conditional logistic regression. We identified 4301 patients hospitalized for AHF. We found that 5.7% of AHF subjects were exposed to effervescent paracetamol during the risk period, as compared with 4.1% during the control periods (aOR, 1.56 [95% confidence interval [CI], 1.27-1.90]; P < .001). This association was also found in the subgroup of subjects with hypertension (aOR, 1.45 [95%CI, 1.13-1.87]; P = .004, n = 2648) and in the subgroup of subjects aged ≥83 years (aOR, 1.70 [95%CI: 1.28-2.24], P < .001, n = 2238). A similar analysis, considering exposure to noneffervescent paracetamol, did not support the existence of an indication bias likely to explain the association observed for effervescent paracetamol. This study suggests an association between effervescent paracetamol and admission for AHF and should be confirmed with other complementary study designs.

Incidence and risk of cancer among multiple sclerosis patients: A matched population-based cohort study.

Studies have not yet found conclusive results on the risk of cancer in patients with multiple sclerosis (MS). This study aimed to compare the incidence of all cancers and of specific types of cancer between MS patients and the general population by age and by sex. All prevalent MS patients identified between 2008 and 2014 in the nationwide French health care database (Système National des Données de Santé) and without history of malignancy were included in a cohort study and followed up until cancer occurrence, date of death, or 31 December 2015, whichever came first. MS patients were matched based on sex and year of birth to non-MS controls from the general population without cancer before index date. Incidence rate was reported per 100,000 person-years (PY), and risk of cancer was estimated by type of cancer, age, and sex using a Cox model (hazard ratio [HR] and its 95% confidence interval [CI]). Overall, 576 cancers per 100,000 PY were observed in MS patients versus 424 per 100,000 PY in the control population. The risk of cancer was higher among MS patients than among population controls whether considered overall (HR = 1.36, 95% CI = 1.29-1.43) or for prostate (HR = 2.08, 95% CI = 1.68-2.58), colorectal and anal (HR = 1.35, 95% CI = 1.16-1.58), trachea, bronchus, and lung (HR = 2.36, 95% CI = 1.96-2.84), and to a lesser extent, breast cancer (HR = 1.12, 95% CI = 1.03-1.23). MS patients were associated with increased risk of cancer compared to population controls.

Impact of transcatheter aortic valve implantations on temporal trend in pacemaker implantations over the last decade using the French National Healthcare database

Transcatheter aortic valve implantation (TAVI) has emerged in 2010's for high-risk patients. Permanent pacemaker implantation (PPMI) is a common complication after TAVI procedure. There are no data on the eventual impact of TAVI on PPMI temporal trends, at a nationwide scale. First, to evaluate whether PPMI have increased in France during the period 2008–2018, and secondly to evaluate the extent to which those post-TAVI PPMI could explain such potential increase. We used the Échantillon Généraliste de Bénéficiaires (EGB), the 1/97th randomly selected sample of the French healthcare database to identify patients with PPMI and TAVI performed between 2008 and 2018. The number of observed PPMI, O, in the period 2013–2018 (TAVI period) was compared with the expected number of PPMI, E, calculated by using 2008–2012 (pre-TAVI period) incidence rates. We computed the standardized incidence ratio (SIR) of the observed number of PPMI to the expected number of PPMI (O/E), with 95% confidence intervals (CIs). We evaluated the contribution of post-TAVI PPMI in the overall number of excess cases of PPMI (O-E) for the period 2013–2018. The EGB included more than 500,000 individuals each year with an increasing part of octogenarians (> 80 years) (4.7% in 2008; 5.9% in 2018). By removing the effect of age, the PPMI annual rate remained stable, except for octogenarians: 546 in 2008 to 676 per 100,000 inhabitants in 2018, especially after 2012 with a significant SIR = 1.06 (95% CI: 1.01–1.12). In this group of octogenarians, 72% of the increase appeared to be related to post-TAVI PPMI. Between 2008 and 2018 in France, the incidence of PPMI significantly increased only among octogenarians. Post-TAVI PPMI could explain more than 70% of this increase.

Risk of pacemaker implantation after radiotherapy for breast cancer: A study based on French nationwide health care database sample.

BackgroundAmong cardiac complications of breast cancer radiotherapy (BC RT), there are very limited data on arrhythmia and conduction disorders, in particular severe cases requiring permanent pacemaker implantation (PPMI). Therefore, this exploratory study aimed to evaluate the risk of PPMI for BC patients treated with RT, compared with the general population and with BC patients not treated with RT.MethodsThe study was performed on a 1/97 representative sample of the French health care database (EGB database). Adult women with a first BC treated with or without RT between 2008 and 2016 were included, followed until 2018, and de novo PPMI were identified. We compared the PPMI incidence in BC cohort relative to the general population with standardized incidence ratio (SIR) and evaluated the risk of PPMI in RT patients compared to patients without RT with a competing risk survival analysis.ResultsA total of 3853 BCE patients were included. Among BC patients treated with RT, 28 PPMI cases were observed compared with 13 expected cases, corresponding to a SIR of 2.18 [95% CI: 1.45–3.06]. For BC patients not treated with RT, the SIR was 1.01 [95% CI: 0.40–1.90]. Patients treated with RT showed a borderline significant higher risk of PPMI compared with those not treated with RT (subdistribution Hazard Ratio = 2.08, 95% CI 0.87–4.97, p = 0.09).ConclusionsOur exploratory findings indicate that, over the last decade in France, BC patients treated with RT appeared to be at higher risk of PPMI than general population. Further studies are needed to expand on this topic.

Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France (the PROGRESS study)

BackgroundThere is a paucity of data on the epidemiology, survival estimates and healthcare resource utilisation and associated costs of patients with progressive fibrosing interstitial lung disease (PF-ILD) in France. An algorithm for extracting claims data was developed to indirectly identify and describe patients with PF-ILD in the French national administrative healthcare database.MethodsThe French healthcare database, the Système National des Données de Santé (SNDS), includes data related to ambulatory care, hospitalisations and death for 98.8% of the population. In this study, algorithms based on age, diagnosis and healthcare consumption were created to identify adult patients with PF-ILD other than idiopathic pulmonary fibrosis between 2010 and 2017. Incidence, prevalence, survival estimates, clinical features and healthcare resource usage and costs were described among patients with PF-ILD.ResultsWe identified a total of 14,413 patients with PF-ILD. Almost half of them (48.1%) were female and the mean (± standard deviation) age was 68.4 (± 15.0) years. Between 2010 and 2017, the estimated incidence of PF-ILD ranged from 4.0 to 4.7/100,000 person-years and the estimated prevalence from 6.6 to 19.4/100,000 persons. The main diagnostic categories represented were exposure-related ILD other than hypersensitivity pneumonitis (n = 3486; 24.2%), idiopathic interstitial pneumonia (n = 3113; 21.6%) and rheumatoid arthritis-associated ILD (n = 2521; 17.5%). Median overall survival using Kaplan–Meier estimation was 3.7 years from the start of progression. During the study, 95.2% of patients had ≥ 1 hospitalisation for respiratory care and 34.3% were hospitalised in an intensive care unit. The median (interquartile range) total specific cost per patient during the follow-up period was €25,613 (10,622–54,287) and the median annual cost per patient was €18,362 (6856–52,026), of which €11,784 (3003–42,097) was related to hospitalisations. Limitations included the retrospective design and identification of cases through an algorithm in the absence of chest high-resolution computed tomography scans and pulmonary function tests.ConclusionsThis large, real-world, longitudinal study provides important insights into the characteristics, epidemiology and healthcare resource utilisation and costs associated with PF-ILD in France using a comprehensive and exhaustive database, and provides vital evidence that PF-ILD represents a high burden on both patients and healthcare services.Trial registration ClinicalTrials.gov, NCT03858842. ISRCTN, ISRCTN12345678. Registered 3 January 2019—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03858842

The Economic Burden of Severe Osteoporotic Fractures in the French Healthcare Database: The FRACTOS Study.

Osteoporosis carries a high medical, economic, and societal burden principally because of the risk of severe fractures. The objective of this cost-of-illness study was to describe health resource utilization and associated costs in all patients aged ≥50 years hospitalized for a severe osteoporotic fracture over a 6-year period (2009 to 2014) in France. Data were extracted from the French national healthcare database (SNDS) on all health care resource utilization between the index date (date of hospitalization for first fracture during the enrollment period) and study end (December 31, 2016) or until the patient died. Costing was restricted to direct costs and determined from the payer perspective. Variables related to costs were identified through multivariate logistic regression analysis. A total of 356,895 patients were included (median follow-up 39.1 months). In the year after the index fracture, 36,622 patients (10.5%) were rehospitalized for a fracture-related reason. Only 18,474 (5.3%) underwent bone densitometry and 58,220 (16.7%) received a specific treatment. The total annual per capita osteoporosis-related cost in the year after the index severe osteoporotic fracture was €18,040 (from €8598 for multiple ribs to €21,085 for hip fracture) of which €17,905 was incurred by fracture-related costs. The cost incurred by management of osteoporosis was €135. Over years 2 to 5, the mean annual per capita costs of fracture treatment (€806, mostly attributable to the treatment of refractures) continued to dominate those of osteoporosis management (€99). Total annual cost of care was €1260 million (year 2014). Variables associated with higher cost were older age, male sex, site of fracture, a history of prior osteoporotic fracture, and the number of refracture events. The 5-year cost of severe osteoporotic fractures to the French health care system is high and mostly attributable to the treatment of refractures. Improved fracture prevention measures in patients with osteoporosis is crucial to reduce the economic burden of the disease. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Consequences of the new zolpidem prescription regulations: a cohort study from the French national healthcare database.

To determine changes in the prevalence of zolpidem consumption since the change in the regulations of prescription. Formulations containing zolpidem were subject to the regulations of narcotics by the French decree of April 7, 2017. Longitudinal cohort study using data from the representative French healthcare database. The main outcome was the prevalence of oral hypnotic drug reimbursement before and after April 2017. The secondary outcome was the change in prescription habits for zolpidem since the decree in long-term users and excessive users. A total of 81,174 individuals had at least one hypnotic drug reimbursement; among, whom 2143 had at least one reimbursement of zolpidem. Before the decree, 26% had at least one reimbursement of zolpidem, whereas it dropped to 18.4% after the decree. Among the 545 long-term users, the reimbursement of zolpidem was discontinued after the decree for 60.4% and 24.2% retained zolpidem as a treatment. The main replacement drug was zopiclone for 6.4% of them. Among the 1598 excessive users, the reimbursement of zolpidem was stopped after the decree for 16.5% and 56.3% retained zolpidem as a treatment. The main replacement drug was zopiclone for 12.1% of them. The French decree had a major impact on the reimbursement of oral zolpidem. Indeed, prescription of the hypnotic was discontinued for half of the long-term users of zolpidem, and just over one-sixth of the excessive users discontinued the prescription of zolpidem after the decree.

Geographical Disparities of Outcomes of Hepatocellular Carcinoma in France: The Heavier Burden of Alcohol Compared to Hepatitis C

Data on alcohol-related HCC are limited. Our aim was to describe the incidence, management, and prognosis of alcohol compared to Hepatitis C (HCV)-related HCC at a national level. Incident cases of HCC were identified in French healthcare databases between 2009 and 2012 and analyzed retrospectively. Demographic data, type, location, and annual HCC-caseload of the hospitals where patients were first managed were retrieved. Survival of incident cases was computed from the time of diagnosis and adjusted for potential confounding variables. The study population included 14,060 incident cases of alcohol and 2581 HCV-related HCC. Alcohol-related HCC was more frequent than HCV-related HCC (29.37 and 5.39/100,000 adults/year, respectively) with an heterogeneous distribution on the French territory. The optimal treatment was less frequently curative (20.5% vs 35.9%; p < 0.001), and survival was significantly shorter (9.5 [9.0-10.0] versus 16.8 [15.5-18.7] months p < 0.001) in alcohol compared to HCV-related HCC, with marked variations between regions for a given risk factor. In multivariable analysis in the whole study population, curative treatment was a strong predictor of survival (adjusted HR 0.28 [0.27-0.30] months p < 0.001). Being managed at least once in a teaching hospital during follow-up was independently associated with receiving a curative treatment and survival. In France, incidence of alcohol-related HCC is high and prognosis is poor compared to HCV-related HCC, with marked variations between regions. These results should guide future health policy initiatives pertaining to HCC care. Importantly, increasing patient' referral in expert centers could increase chances to receive curative treatment and improve outcomes.