Use of proton pump inhibitors in adults in France: a nationwide drug utilization study.

PURPOSE: Proton pump inhibitor (PPI) drugs are approved for the management of gastric acid-related diseases, mainly treatment of gastroesophageal reflux disease, treatment of nonsteroidal anti-inflammatory drugs (NSAID)-related gastrointestinal complications and prevention in at-risk patients, Helicobacter pylori eradication, and treatment of ulcers. PPIs are one of the most commonly prescribed drug class worldwide, and off-label use is widespread. The aim of this study was to describe outpatient PPI use of the whole adult population in France, based on the French National Health Data System (SNDS). METHODS: All individuals aged 18 years or older, with at least one dispensing for PPI between January 1, 2015 and December 31, 2015, were identified as PPI users. PPI users were considered as new users if they received no dispensing for PPI in the prior year. New users were followed until treatment discontinuation or up to 1 year, whichever occurred first. Characteristics of new users and of their PPI treatment were described, overall and separately by treatment indication. RESULTS: In total, 15,388,419 PPI users were identified in 2015 (57.0% women; mean age 57.0 years), accounting for 29.8% of the French adult population. Of them, 7,399,303 were new PPI users; mean treatment duration was 40.9 days, and 4.1% received a continuous PPI therapy lasting more than 6 months (10.2% among new users > 65 years versus 2.4% among those 18-65 years). For 53.5% of new users, indication for PPI therapy was a co-prescription with NSAID; in this indication, the large majority of patients (79.7%) had no measurable risk factor supporting a systematic prophylactic co-prescription of PPI. A proportion of 32.4% of new users did not have any identified comedication or inpatient diagnosis supporting an indication for PPI therapy; among them, only a small proportion (7.3% overall, and 8.4% of patients aged > 65 years) underwent a procedure investigating the digestive tract at the time of PPI initiation. CONCLUSION: The results of this study suggest PPI overuse in France, not always in line with the French guidelines. In particular, inappropriate co-prescription with NSAID was frequent. Efforts should be made to limit PPI treatment to appropriate indications and durations.

Is There a Cardiotoxicity Associated With Metallic Head Hip Prostheses? A Cohort Study in the French National Health Insurance Databases.

BACKGROUND: There are four distinguishable types of THA devices in wide use, as defined by the femoral and acetabular bearing surfaces: metal-on-polyethylene (MoP), ceramic-on-polyethylene (CoP), metal-on-metal (MoM), and ceramic-on-ceramic (CoC). Metallic head THAs (MoP and MoM) can potentially induce cardiac toxicity because cobalt species, generated at the head-neck trunnion, and in the case of MoM devices, at the articular surface as well, can be absorbed systemically. However, studies have provided inconsistent results. QUESTIONS/PURPOSES: The purpose of this study was to assess the risk of dilated cardiomyopathy (DCM) or heart failure (HF) associated with metallic head THAs using data from the French national health insurance databases. METHODS: Between 2008 and 2011 in France, 399,968 patients ≥ 55 years had a first THA. A total of 127,481 were excluded after we applied the exclusion criteria regarding arthroplasty and 17,137 as a result of a history of DCM/HF, recorded in the French national health insurance reimbursement databases, between January 1, 2006, and the date of inclusion. The final cohort included 255,350 individuals (43% men; mean age 72 ± 9 years). Of them, 93,581 (37%) had been implanted with MoP, 58,095 (23%) with CoP, 11,298 (4%) with MoM, and 92,376 (36%) with CoC THAs. Patients were followed until December 2015. Patients with incident DCM/HF were identified by a new entitlement to the long-term disease scheme or a first hospitalization with a diagnosis of DCM or HF. MoP and CoP THAs are generally implanted in old patients, whereas MoM and CoC are mostly indicated in young, active male patients. Thus, to consider the specific indications of the bearing couples, analyses were separately performed in two distinct subcohorts, one comprising patients with MoP or CoP and one comprising patients with MoM or CoC THA. In each subcohort, the DCM/HF risk was compared between patients with metallic head versus nonmetallic head THAs (MoP versus CoP, MoM versus CoC). Hazard ratios (adjusted HRs) of incident DCM/HF were estimated using Cox models adjusted for baseline sex, age, THA characteristics (fixation technique with cement, use of a modular femoral neck), and comorbidities at baseline. Cox models were stratified by sex and age. RESULTS: The crude incidence of DCM/HF per 100 person-years was 2.4 in patients with MoP, 1.8 with CoP, 1.2 with MoM, and 1.1 with CoC THAs. Overall, metallic head THAs were associated with a slight increase in DCM/HF risk (MoP versus CoP: adjusted HR, 1.08; 95% confidence interval [CI], 1.05-1.12; p < 0.001; MoM versus CoC: adjusted HR, 1.11; 95% CI, 1.03-1.19; p = 0.007). In the MoM-CoC subcohort, the risk tended to be more pronounced with MoM versus CoC THAs in women (MoM versus CoC: adjusted HR, 1.20; 95% CI, 1.07-1.35; p = 0.002) and patients aged ≥ 75 years (MoM versus CoC: adjusted HR, 1.16; 95% CI, 1.04-1.29; p = 0.009). CONCLUSIONS: Metallic head THAs were associated with a slightly increased DCM/HF risk, especially with MoM in women and older patients. Some caveats should be mentioned: severity of DCM or HF was not available and residual confounding cannot be ruled out despite considering many covariates. Our findings suggest that cardiac function should be regularly monitored in patients with metallic head THAs. Further investigations should be planned on large international cohorts. LEVEL OF EVIDENCE: Level III, therapeutic study.

Proton Pump Inhibitor Use and Risk of Serious Infections in Young Children.

Importance: Proton pump inhibitor (PPI) use may lead to infections through alteration of the microbiota or direct action on the immune system. However, only a few studies were conducted in children, with conflicting results. Objective: To assess the associations between PPI use and serious infections in children, overall and by infection site and pathogen. Design, Setting, and Participants: This nationwide cohort study was based on the Mother-Child EPI-MERES Register built from the French Health Data System (SNDS). We included all children born between January 1, 2010, and December 31, 2018, who received a treatment for gastroesophageal reflux disease or other gastric acid-related disorders, namely PPIs, histamine 2 receptor antagonists, or antacids/alginate. The index date was defined as the first date any of these medications was dispensed. Children were followed up until admission to the hospital for serious infection, loss of follow-up, death, or December 31, 2019. Exposure: PPI exposure over time. Main Outcomes and Measures: Associations between serious infections and PPI use were estimated by adjusted hazard ratios (aHRs) and 95% CIs using Cox models. PPI use was introduced as time-varying. A 30-day lag was applied to minimize reverse causality. Models were adjusted for sociodemographic data, pregnancy characteristics, child comorbidities, and health care utilization. Results: The study population comprised 1 262 424 children (median [IQR] follow-up, 3.8 [1.8-6.2] years), including 606 645 who received PPI (323 852 male [53.4%]; median [IQR] age at index date, 88 [44-282] days) and 655 779 who did not receive PPI (342 454 male [52.2%]; median [IQR] age, 82 [44-172] days). PPI exposure was associated with an increased risk of serious infections overall (aHR, 1.34; 95% CI, 1.32-1.36). Increased risks were also observed for infections in the digestive tract (aHR, 1.52; 95% CI, 1.48-1.55); ear, nose, and throat sphere (aHR, 1.47; 95% CI, 1.41-1.52); lower respiratory tract (aHR, 1.22; 95% CI, 1.19-1.25); kidneys or urinary tract (aHR, 1.20; 95% CI, 1.15-1.25); and nervous system (aHR, 1.31; 95% CI, 1.11-1.54) and for both bacterial (aHR, 1.56; 95% CI, 1.50-1.63) and viral infections (aHR, 1.30; 95% CI, 1.28-1.33). Conclusions and Relevance: In this study, PPI use was associated with increased risks of serious infections in young children. Proton pump inhibitors should not be used without a clear indication in this population.

Use of Proton Pump Inhibitors and Risk of Pancreatic Cancer: A Nationwide Case-Control Study Based on the French National Health Data System (SNDS).

BACKGROUND: Only a few studies investigated the association between proton pump inhibitor (PPI) use and pancreatic cancer, with inconsistent results. Moreover, these studies had a number of methodologic limitations. Our objective was to assess this association in a nationwide case-control study. METHODS: We used the French National Health Data System (SNDS), covering 99% of the French population since 2006. Incident cases of pancreatic cancer, identified between 2014 and 2018, were matched with up to four controls on year of birth, sex, frequency of hospitalization within 8 years prior to index date, and department of residence. Associations between PPIs and pancreatic cancer were estimated using conditional logistic regression models adjusted for sociodemographic characteristics, risk factors of pancreatic cancer (including diabetes mellitus, tobacco-related diseases, and morbid obesity), and other comorbidities. RESULTS: A total of 23,321 cases of pancreatic cancer (mean age, 69.8 years; 51.7% males) and 75,937 matched controls were included. Overall, 77.8% of cases and 75.5% of controls were PPI ever users. Ever (vs. never) PPI use was associated with an increased risk of pancreatic cancer [adjusted OR (aOR) = 1.05, 95% confidence interval (CI), 1.01-1.09]. A dose-response relationship was observed [1-30 cumulative defined daily dose (cDDD): aOR = 0.92, 95% CI, 0.87-0.97; 31-180 cDDD: aOR = 1.05, 95% CI, 1.00-1.11; 181-1,080 cDDD: aOR = 1.18, 95% CI, 1.12-1.24; >1,080 cDDD: aOR = 1.17, 95% CI, 1.10-1.23]. CONCLUSIONS: On the basis of these findings, a slight increase in the risk of pancreatic cancer associated with high cumulative doses of PPIs cannot be excluded. IMPACT: Given the overuse of PPIs, efforts should be continued to limit treatments to appropriate indications and durations.

Working conditions and psychotropic drug use: cross-sectional and prospective results from the French national SIP study.

Prospective studies exploring the associations between a large range of occupational factors and psychotropic drug use among national samples of workers are seldom. This study investigates the cross-sectional and prospective associations between occupational factors, including a large set of psychosocial work factors, and psychotropic drug use in the national French working population. The study sample comprised 7542 workers for the cross-sectional analysis and 4213 workers followed up for a 4-year period for the prospective analysis. Psychotropic drug use was measured within the last 12 months and defined by the use of antidepressants, anxiolytics or hypnotics. Three groups of occupational factors were explored: classical and emergent psychosocial work factors, working time/hours and physical work exposures. Weighted Poisson regression analyses were performed to adjust for covariates. In the cross-sectional analysis, psychological demands, low social support and hiding emotions were associated with psychotropic drug use. Job insecurity for men and night work for women were associated with psychotropic drug use. In the prospective analysis, hiding emotions and physical exposure were predictive of psychotropic drug use. Dose-response associations were observed for the frequency/intensity of exposure and repeated exposure to occupational factors. This study underlines the role of psychosocial work factors, including emergent factors, in psychotropic drug use. Prevention policies oriented toward psychosocial work factors comprehensively may be useful to reduce this use.