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.

Background Potentially Inappropriate Medications (PIMs) and polypharmacy are widely used indicators of suboptimal prescribing for older people. The aim of this study was to describe the changes in the prevalence of PIMs and polypharmacy among people aged 75 years and over between 2011 and 2019 in France. Methods PIMs and polypharmacy were assessed among people aged 75 years and over every two years between 2011 and 2019 using the French health insurance data system. Sixteen PIM criteria from the 2015 Beers and STOPP lists were assessed. Polypharmacy (5 to 9 drugs) and hyper-polypharmacy (≥10 drugs) were defined based on the average number of drugs dispensed per quarter. The Annual Percent Change (APC) and 95%CI were assessed using linear regression models after standardization of the prevalence on age and sex. Results The study population included 5,777,645 individuals over 75 years old in 2011 and 6,328,155 in 2019. The prevalence of PIMs decreased from 49.6 to 39.6% over the study period (APC: − 1.19% [− 1.35;-1.04]). Of the sixteen indicators assessed, the prevalence of thirteen decreased between 2011 and 2019. Benzodiazepines were the most frequent PIMs (34.7% in 2011 to 26.9% in 2019), followed by anticholinergic drugs (12.1% in 2011 to 8.3% in 2019), oral non-steroidal anti-inflammatory drugs (11.4 to 7.8%), and PIMs related to antihypertensive drugs (7.4 to 6.0%). Overall, women and individuals aged 85 years and older were more likely to receive PIMs. The prevalence of hyper-polypharmacy decreased from 30.5 to 25.9% over the study period. Conclusion This study, which is the first to assess the change in prevalence of PIMs and polypharmacy over time from comprehensive health data in France, highlights that PIMs and hyper-polypharmacy declined between 2011 and 2019. However, PIMs remains frequent for older people and often involves benzodiazepines.

An indirect consequence of the improved long-term survival seen in patients with breast cancer (BC) is the increased risk of hematologic malignant neoplasms (HM). This study aimed to analyze the role of postoperative treatment for BC in the development of subsequent HM. Using the French National Health Data System, we examined the HM risks in patients diagnosed with an incident primary breast cancer between 2007 and 2015, who underwent surgery as first-line treatment for BC. Main outcomes were acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), multiple myeloma (MM), Hodgkin’s lymphoma or non-Hodgkin’s lymphoma (HL/NHL), and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL). Analyses were censored at HM occurrence, death, loss to follow up, or December 2017. The risk of each type of HM was compared according to the initial postoperative treatment of breast cancer. Of a total of 324,056 BC survivors, 15.5% underwent surgery only, 46.7% received radiotherapy after surgery, 4.3% received chemotherapy after surgery, and 33.5% received all three modalities. Overall, 2236 cases of hematologic malignancies occurred. Compared to the surgery alone group, AML was significantly increased after surgery plus radiation (aHR, 1.5; 95% CI, 1.0–2.1), surgery plus chemotherapy (aHR, 2.1; 95% CI, 1.2–3.6) and all modalities (aHR, 3.3; 95% CI, 2.3–4.7). MDS was significantly increased after surgery plus chemotherapy (aHR, 1.7; 95% CI, 1.1–2.5) or after all modalities (aHR, 1.4; 95% CI, 1.1–1.8). HL/NHL were significantly increased only in the radiotherapy and surgery group (aHR, 1.3; 95% CI, 1.0–1.6). A nonsignificant increase of ALL/LL (aHR, 1.8; 95% CI, 0.6–3.5) was noted after chemotherapy and with all three modalities (aHR, 1.4; 95% CI, 0.7–2.8). Our population based study revealed increased risks of various HM associated with postoperative BC treatment. The added benefit of chemotherapy and radiation therapy should take into consideration these long-term complications.

Financial support: The study was performed at EPIPHARE in cooperation with clinicians. No external funding was received.

Key Points Question Which hematologic malignant neoplasm types are more prone to develop after breast cancer diagnosis? Findings In this cohort study of 439 704 French women, breast cancer survivors with an incident breast cancer diagnosis had statistically significantly higher standardized incidence rate ratios of acute myeloid leukemia and myelodysplastic syndrome compared with women in the general population. A slight increase in the incidence of multiple myeloma and acute lymphoblastic leukemia was noted. Meaning This study sugests that acute myeloid leukemia, myelodysplastic syndrome, and acute lymphoblastic leukemia occur more frequently among breast cancer survivors than among women in the general population; continuous monitoring and further investigations into the underlying mechanisms of hematologic malignant neoplasms are necessary.