Treatment patterns of patients with HR+/HER2- metastatic breast cancer receiving CDK4/6 inhibitor-based regimens: a cohort study in the French nationwide healthcare database.

PURPOSE: To assess real-world treatment patterns in patients diagnosed with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC) who received cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with an aromatase inhibitor (AI) or fulvestrant at first line. METHODS: Patient characteristics, treatment history, and outcomes data were extracted from the French 'Système National des Données de Santé' (SNDS) database for patients diagnosed with HR+/HER2- mBC between January 2014 and June 2019 and who received combination therapy with a CDK4/6 inhibitor and endocrine therapy. Kaplan-Meier methodology was used to assess time to next treatment (TTNT) and time to treatment discontinuation (TTTD). RESULTS: The cohort comprised 6061 patients including 4032 patients who received CDK4/6 inhibitors + AIs and 2029 patients who received CDK4/6 inhibitors + fulvestrant. Median follow-up was 13.5 months (IQR 9.5-18.1). The median TTTD of first line treatment with CDK4/6 inhibitors + AIs and CDK4/6 inhibitors + fulvestrant was 17.3 months (95% CI 16.8-17.9) and 9.7 months (95% CI 9.0-10.2), respectively. Chemotherapy was the most common second line therapy. Median TTTD of subsequent treatment lines was progressively shorter following first line treatment with CDK4/6 inhibitors + AIs (2nd line: 4.6 months (95% CI 4.4-4.9) and with CDK4/6 inhibitors + fulvestrant (2nd line: 4.7 months (95% CI 4.3-5.1). TTNT was longer than TTTD across lines of therapy. CONCLUSION: This real-world analysis confirms the effectiveness of CDK4/6 inhibitor-based regimens in French patients and highlights the frequent use of chemotherapy as second line therapy.

Incidence of stroke, subsequent clinical outcomes and health care resource utilization in people with type 2 diabetes: a real-world database study in France: "INSIST" study.

BACKGROUND: People with type 2 diabetes (T2D) are at elevated risk of cardiovascular disease (CVD) including stroke, yet existing real-world evidence (RWE) on the clinical and economic burden of stroke in this population is limited. The aim of this cohort study was to evaluate the clinical and economic burden of stroke among people with T2D in France. METHODS: We conducted a retrospective RWE study using data from the nationally representative subset of the French Système National des Données de Santé (SNDS) database. We assessed the incidence of stroke requiring hospitalization between 2012 and 2018 among T2D patients. Subsequent clinical outcomes including CVD, stroke recurrence, and mortality were estimated overall and according to stroke subtype (ischemic versus hemorrhagic). We also examined the treatment patterns for glucose-lowering agents and CVD agents, health care resource utilization and medical costs. RESULTS: Among 45,331 people with T2D without baseline history of stroke, 2090 (4.6%) had an incident stroke requiring hospitalization. The incidence of ischemic stroke per 1000 person-years was 4.9-times higher than hemorrhagic stroke (6.80 [95% confidence interval (CI) 6.47-7.15] versus 1.38 [1.24-1.54]). During a median follow-up of 2.4 years (interquartile range 0.6; 4.4) from date of index stroke, the rate of CVD, stroke recurrence and mortality per 1000 person-years was higher among hemorrhagic stroke patients than ischemic stroke patients (CVD 130.9 [107.7-159.0] versus 126.4 [117.2-136.4]; stroke recurrence: 86.7 [66.4-113.4] versus 66.5 [59.2-74.6]; mortality 291.5 [259.1-327.9] versus 144.1 [134.3-154.6]). These differences were not statistically significant, except for mortality (adjusted hazard ratio 1.95 [95% CI 1.66-2.92]). The proportion of patients prescribed glucagon-like peptide-1 receptor agonists increased from 4.2% at baseline to 6.6% during follow-up. The proportion of patients prescribed antihypertensives and statins only increased slightly following incident stroke (antihypertensives: 70.9% pre-stroke versus 76.7% post-stroke; statins: 24.1% pre-stroke versus 30.0% post-stroke). Overall, 68.8% of patients had a subsequent hospitalization. Median total medical costs were €12,199 (6846; 22,378). CONCLUSIONS: The high burden of stroke among people with T2D, along with the low proportion of patients receiving recommended treatments as per clinical guidelines, necessitates a strengthened and multidisciplinary approach to the CVD prevention and management in people with T2D.

Design and validation of algorithms to identify venous thromboembolism in the French National Healthcare Database.

PURPOSE: This paper aims to introduce an algorithm designed to identify Venous Thromboembolism (VTE) in the French National Healthcare Database (SNDS) and to estimate its positive predictive value. METHODS: A case-identifying algorithm was designed using SNDS inpatient and outpatient encounters, including hospital stays with discharge diagnoses, imaging procedures and drugs dispensed, of French patients aged at least 18 years old to whom baricitinib or Tumor Necrosis Factor Inhibitors (TNFi) were dispensed between September 1, 2017, and December 31, 2018. An intra-database validation study was then conducted, drawing 150 cases identified as VTE by the algorithm and requesting four vascular specialists to assess them. Patient profiles used to conduct the case adjudication were reconstituted from de-identified pooled and formatted SNDS data (i.e., reconstituted electronic health records-rEHR) with a 6-month look-back period prior to the supposed VTE onset and a 12-month follow-up period after. The positive predictive value (PPV) with its 95% confidence interval (95% CI) was calculated as the number of expert-confirmed VTE divided by the number of algorithm-identified VTE. The PPV and its 95% CI were then recomputed among the same patient set initially drawn, once the VTE-identifying algorithm was updated based on expert recommendation. RESULTS: For the 150 patients identified with the first VTE-identifying algorithm, the adjudication committee confirmed 92 cases, resulting in a PPV of 61% (95% CI = [54-69]). The final VTE-identifying algorithm including expert suggestions showed a PPV of 92% (95% CI = [86-98]) with a total of 87 algorithm-identified cases, including 80 retrieved from the 92 confirmed by experts. CONCLUSION: The identification of VTE in the SNDS is possible with a good PPV.

Potentially avoidable hospitalizations and associated factors among older people in French Guiana using the French National Health Data System.

Knowing the prevalence of potentially avoidable hospitalizations (PAHs) and the factors associated with them is essential if preventive action is to be taken. Studies on PAHs mainly concern adults, and very few have been carried out in South America. To the best of our knowledge, there has been no study on PAHs in French Guiana, particularly among older adults. This case-control study aimed to estimate the prevalence of PAHs in the Guianese population aged over 65 and to analyze their associated factors. We used the 2017-2019 data from the French National Health Service database (Système National des Données de Santé). The patients were age- and sex-matched 1 : 3 with controls without any PAH in 2019. Factors associated with PAHs were investigated through two conditional logistic regression models [one including the Charlson comorbidity index (CCI) and one including each comorbidity of the CCI], with calculation of the adjusted odds ratio (aOR) and 95% confidence interval (CI). The PAH incidence was 17.4 per 1000 inhabitants. PAHs represented 6.6% of all hospitalizations (45.6% related to congestive heart failure or hypertension). A higher CCI was associated with PAHs [aOR 2.2 (95% CI: 1.6, 3.0) and aOR 4.8 (95% CI: 2.4, 9.9) for 1-2 and ≥3 comorbidities, respectively, versus 0], as was immigrant health insurance status [aOR 2.3 (95% CI: 1.3, 4.2)]. Connective tissue disease, chronic pulmonary disease, congestive heart failure, diabetes, and peripheral vascular disease were comorbidities associated with an increased risk of PAHs. While the prevention of PAHs among immigrants is probably beyond the reach of the Guianese authorities, primary care and a public health policy geared toward prevention should be put in place for the French Guianese population suffering from cardiovascular disease in order to reduce PAHs.

Health status and comorbidities of adult patients with phenylketonuria (PKU) in France with a focus on early-diagnosed patients - A nationwide study of health insurance claims data.

BACKGROUND: This study aimed at evaluating the health status and healthcare consumption of ≥16-year-old patients with phenylketonuria (PKU), with a focus on early-diagnosed patients. METHODS: This retrospective observational study used health insurance claims data from the French SNDS (Système National des Données de Santé) database. Patients with PKU were identified between 2006 and 2018 by ICD-10 diagnosis codes E70.0 (classic PKU) or E70.1 (other causes of hyperphenylalaninemia). They were matched to controls by age, sex, and region. Patients with early-diagnosed PKU were defined as patients born after implementation of nationwide newborn screening in France in 1972. Outcomes were analyzed for the year 2018. RESULTS: Overall, 3549 patients with PKU were identified on January 1st, 2018. Of those, 3469 patients could be matched to 17,170 controls without PKU. Of these patients, 2175 were at least 16 years old and suffered significantly more than controls from specific comorbidities of interest - osteoporosis (28.7% vs 19.8%, p < 0.0001), hypertension (20.9% vs 17.0%, p < 0.0001), hypercholesterolemia (12.8% vs 8.3%, p < 0.0001), diabetes (7.8% vs 4.7%, p < 0.0001), obesity (4.2% vs 1.3%, p < 0.0001), ischemic heart diseases (4.8% vs 2.0%, p < 0.0001), and depression (10.3% vs 8.2%, p = 0.0011). Prescriptions for many medications were also more frequent in patients with PKU than controls. Among ≥16-year-old patients, 1528 were categorized as early-diagnosed. Osteoporosis (0.3% vs 0.01%, p = 0.0035), chronic renal failure (0.6% vs 0.1%, p = 0.0020), hypertension (4.0% vs 2.7%, p = 0.0063), and obesity (2.5% vs 0.8%, p < 0.0001) were significantly more prevalent in early-diagnosed adult patients compared with matched controls. In total, 28.6% of ≥16-year-old patients with PKU and 40.4% of early-diagnosed patients with PKU received dietary amino-acid supplements. Sapropterin was prescribed to 5.0% and 7.0% patients, respectively. CONCLUSION: The results indicate that PKU is associated with a significantly higher comorbidity risk along with increased pharmaceutical prescriptions in adulthood. The comorbidity burden is less distinct in early-diagnosed patients but still present. Few patients are treated specifically for PKU in adulthood. Healthcare of patients with PKU should include prevention and management of comorbidities and especially target PKU-specific treatment adherence and consistent care in specialized medical centers in adulthood.

Health status and comorbidities of adult patients with late-diagnosed phenylketonuria (PKU) born before the newborn screening in France - A nationwide study of health insurance claims data.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism. When diagnosed late, it causes developmental delay or severe irreversible intellectual disability. This study aimed at evaluating the health status and healthcare consumption of late-diagnosed PKU patients in France. METHODS: This retrospective observational study used health insurance claims data from the French SNDS (Système National des Données de Santé) database, which contains data from over 66 million French inhabitants. Patients with PKU were identified between 2006 and 2018 by ICD-10 diagnosis codes E70.0 / E70.1 documented as a chronic condition (affection de longue durée - ALD) or in the inpatient setting. Patients with PKU were matched to controls by age, sex, and region. Patients with late-diagnosed PKU were defined as patients born before the nationwide implementation of newborn screening in France in 1972. Outcomes were analyzed for the year 2018. RESULTS: In total, 3549 patients with PKU were identified in the database on January 1st, 2018. Of those, 3469 patients could be matched to 17,170 controls without PKU. Of these, 2175 patients were at least 16 years old of whom 647 patients were categorized as late-diagnosed. The late-diagnosed PKU patients suffered significantly more often from hypertension (60.9% vs. 50.4%, p < 0.0001), hypercholesterolemia (41.7% vs. 26.9%, p < 0.0001), diabetes (24.4% vs. 14.1%, p < 0.0001), depression (20.6% vs. 13.8%, p < 0.0001), ischemic heart disease (16.1% vs. 6.6%, p < 0.0001), obesity (7.9% vs. 2.5%, inpatient diagnoses only, p < 0.0001), and chronic kidney disease (5.2% vs. 1.3%, inpatient diagnoses only, p < 0.0001) compared with their non-PKU controls. Consequently, significantly more patients with late-diagnosed PKU received medication to treat comorbidities associated with the nervous (82.6% vs 77.0%; p = 0.0021) and cardiovascular system (69.5% vs 58.0%; p < 0.0001). Overall, only 3.4% of patients with late-diagnosed PKU received dietary amino-acid supplements and 0.7% received sapropterin. CONCLUSION: The results indicate that PKU is associated with a significantly higher risk of comorbidities along with increased pharmaceutical prescriptions in patients with late-diagnosed PKU, compared with non-PKU controls. The increased risk of comorbidities was more pronounced than in patients with early-diagnosed PKU, as shown in previous research, but these patients are older than those with early-diagnosed PKU. Only few late-diagnosed patients were treated specifically for PKU. Patients with late-diagnosed PKU should be referred to specialized centers to prevent and manage comordities and introduce PKU-specific treatment when it is possible.

Impact of direct-acting antiviral treatment for hepatitis C on cardiovascular diseases and extrahepatic cancers.

PURPOSE: The impact of direct-acting antivirals (DAAs) on extrahepatic complications in chronic hepatitis C (CHC) patients remains poorly described. We estimated the association of DAAs with cardiovascular events and extrahepatic cancers. METHODS: The prospective ANRS CO22 HEPATHER cohort was enriched with individual data until December 2018 from the French Health Insurance Database (SNDS). CHC patients were enrolled between August 2012 and December 2015 in 32 French hepatology centers. A total of 8148 CHC adults were selected. Cardiovascular events (stroke, acute coronary syndrome, pulmonary embolism, heart failure, arrhythmias and conduction disorders [ACD], peripheral arterial disease [PAD]) and extrahepatic solid cancers were derived from the SNDS. Associations between DAAs and extrahepatic events were estimated using marginal structural models, with adjustments for clinical confounders. RESULTS: Analyses of 12 905 person-years of no DAA exposure and 22 326 person-years following DAA exposure showed a decreased risk of PAD after DAA exposure (hazard ratio [HR], 0.54; 95% CI, 0.33-0.89), a beneficial effect of DAAs on overall cardiovascular outcomes in patients with advanced fibrosis (aHR, 0.58; 95% CI, 0.42-0.79), and an increased risk of ACD (hazard ratio [HR], 1.46; 95% CI, 1.04-2.04), predominant after the first year following DAA initiation. There was no association between DAAs and extrahepatic cancer risk (HR, 1.23; 95% CI, 0.50-3.03). CONCLUSIONS: DAAs were not associated with extrahepatic cancer development or reduction. They were associated with a decreased risk of PAD and an increased risk of ACD, supporting long-term cardiac monitoring after DAA therapy.

Pressure ulcer prevention devices in the management of older patients at risk after hospital discharge: an SNDS study.

OBJECTIVE: Our aim was to measure the effectiveness of home healthcare pressure ulcer (PU) prevention devices (PUPDs) for at-risk patients after hospital discharge in France. METHOD: We conducted a retrospective analysis of PU-associated hospitalisations based on the French medico-administrative database (Système National des Données de Santé, SNDS), which covers the entire French population. All adults >70 years of age, hospitalised from 1 July to 31 December 2015, and equipped with a medical bed at home, were included. Follow-up was for a maximum of 18 months. Propensity score matching allowed the comparison of PUPD equipped and non-equipped groups (No-PUPD), considering sociodemographic characteristics and other factors. RESULTS: The study included 43,078 patients. Of this population, 54% were PUPD patients and 46% No-PUPD. After matching, PUPD patients had significantly fewer PUs than No-PUPD patients (5.5% versus 8.9%, respectively; p<0.001). The adoption of PUPD reduced by 39% the risk of a PU in hospital. Patients equipped within the first 30 days at home after hospitalisation had fewer PUs than those equipped later (4.8% versus 5.9%, respectively). The estimated PUPD use costs represented 1% of total healthcare expenditure per patient during the study period. CONCLUSION: The study results demonstrated the effectiveness of the adoption of mattress toppers or prevention mattresses in reducing PU occurrence in patients aged >70 years of age. A short delay in PUPD delivery appeared to have a real impact in the medical setting. Future research on a larger population might provide more evidence on the appropriate support and timeframe to choose based on risk assessment.

Therapeutic management and outcome of patients with advanced systemic mastocytosis treated with midostaurin: A comprehensive real-life study in the French national healthcare database.

Advanced Systemic Mastocytosis (Adv-SM) is rare and has a poor prognosis. Midostaurin (Rydapt® ) is one of the few treatments for Adv-SM in Europe. The study aims were to describe the characteristics of patients treated with midostaurin, their treatment modalities, outcomes, and serious events requiring hospitalization. This retrospective observational study was conducted using the French National Healthcare Database (SNDS) and included adult Adv-SM patients treated with midostaurin between 01-01-2012 and 09-30-2018. Kaplan-Meier method was used to assess survival and treatment duration. Eighty-one patients were included: 37 with Aggressive Systemic Mastocytosis (SM) (46%), 31 with SM with an Associated Hematological Neoplasm (38%), and 4 with Mast Cell Leukemia (5%). The SM subtype was undetermined in 9 patients (11%). The median age was 67 years; 64% of patients were male. Over the mean follow-up of 11.4 months, median midostaurin treatment duration was 8.4 months and 28 patients (35%) were still under treatment at the end of the study. One-year and 5-year overall survival rates estimated since the time of diagnosis were 83% and 56%, respectively. Twelve serious events (among those frequently reported during clinical trials and compassionate use) requiring hospitalization were identified; a causal association with Adv-SM treatment could neither be excluded nor established. In this first real-life study on patients treated with midostaurin for Adv-SM, the patients' characteristics, their management, treatment discontinuation, and survival were in line with previous results (compassionate use and clinical trials).

Overall Survival Among Chemotherapy-Naive Patients With Castration-Resistant Prostate Cancer Under Abiraterone Versus Enzalutamide: A Direct Comparison Based on a 2014-2018 French Population Study (the SPEAR Cohort).

Abiraterone acetate (ABI) and enzalutamide (ENZ) are considered to be clinically relevant comparators among chemotherapy-naive patients with castration-resistant prostate cancer. No clinical trials comparing overall survival with ABI versus ENZ in a head-to-head approach have been published so far. A few observational studies with low power suggested a potential benefit of ENZ. We used the French National Health Data System to compare overall survival of new users of ABI and ENZ among chemotherapy-naive patients with castration-resistant prostate cancer in 2014-2017, followed through 2018 (the SPEAR cohort, a 2014-2018 cohort study). With an intent-to-treat approach, a survival analysis was performed, estimating hazard ratios for overall survival with the inverse probability weighted Cox model method. Among 10,308 new users, 64% were treated with ABI and 36% with ENZ. The crude mortality rate was 25.2 per 100 person-years (95% confidence interval (CI): 24.4, 26.0) for ABI and 23.7 per 100 person-years (95% CI: 22.6, 24.9) for ENZ. In the weighted analysis, ENZ was associated with better overall survival compared with ABI (hazard ratio = 0.90 (95% CI: 0.85, 0.96) with a median overall survival of 31.7 months for ABI and 34.2 months for ENZ). When restricting to 2015-2017 new users, the effect estimate shifted up to a hazard ratio of 0.93 (95% CI: 0.86, 1.01).

Epidemiologic study of patients with psoriatic arthritis in a real-world analysis: a cohort study of the French health insurance database.

OBJECTIVE: PsA is a chronic inflammatory arthritis with heterogeneous disease manifestations. Data on the prevalence of PsA in adults differ widely depending on the study and the country. This study aimed to estimate the prevalence and incidence of PsA in France, characterize comorbidities associated to PsA and identify prescribed treatments. METHODS: This nationwide cohort study involved the administrative healthcare database (Système National des Données de Santé) of the French health insurance scheme linked to the national hospital discharge database. All adults with PsA registered in the database and identified with a specific International Classification of Diseases, 10th revision code (M07) were included between 1 January 2015 and 31 December 2018. RESULTS: A total of 63 598 patients were identified as having PsA [55.9 years (s.d. 14.4), 45.6% males]. The prevalence of PsA was estimated at 0.1% and the incidence at 8.4 per 100 000 person-years in the general population. The most common comorbidities were hypertension, diabetes, chronic obstructive pulmonary disease and dyslipidaemia. The prevalence of treatment with conventional synthetic DMARDs (csDMARDs), biological or biosimilar DMARDs (b/bsDMARDs) and apremilast for PsA was 25.9% (16 453), 30.4% (19 325) and 3.5% (2231), respectively. Overall, 8966 (14.1%) patients were new users of csDMARDs, 8311 (13.1%) were new users of b/bsDMARDs and 1529 (7.4%) were new users of apremilast. The most common first-line csDMARD was methotrexate (70.9%) and the most frequent first-line b/bsDMARD was adalimumab (30.8%). CONCLUSION: Our results lead to a better understanding of PsA. Results were similar to those from other published studies using other data sources, which highlights the reliability of insurance databases for studies.

Survival and treatment patterns of patients with relapsed or refractory multiple myeloma in France - a cohort study using the French National Healthcare database (SNDS).

Over the past decade, several drugs have been approved for the treatment of relapsed or refractory multiple myeloma (RRMM). This retrospective study, using the French National Healthcare database (SNDS), describes the treatment patterns and outcomes of patients with RRMM treated in real-world clinical practice in France. Patients were adults, with a diagnosis of multiple myeloma, who initiated second-line (2L) treatment approved for use in France between 2014 and 2018; this included bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide, or pomalidomide. Data were analyzed overall, by first-line (1L) autologous stem cell transplant (ASCT) status and by lenalidomide treatment status at 2L. In total, 12987 patients with RRMM were included in the study (mean age 69.5 years); 27% received an ASCT at 1L, and 30% received a lenalidomide-sparing regimen at 2L. Overall, and among the ASCT and non-ASCT subgroups, most patients received a bortezomib-based regimen at 1L, whereas lenalidomide-based regimens were most common at 2L. Among patients who received a lenalidomide-sparing regimen at 2L, this was most often a proteasome inhibitor-based regimen. Mortality rate was 26.1/100 person-years, and median (95% confidence interval) survival from 2L initiation was 32.4 (31.2-33.6) months. Survival differed by various factors, shorter survival was reported in the non-ASCT group, those receiving a lenalidomide-sparing regimen at 2L, older patients (≥ 70 years), and those with multiple comorbidities. This analysis provides insight into the real-world use of approved novel MM treatments and highlights an ongoing unmet need to improve outcomes, particularly for selected patient groups.

Cyproterone acetate and meningioma: a nationwide-wide population based study.

BACKGROUND: The study the characteristics of surgical meningiomas in female patients who took CPA and to compare this population to a non-CPA control group. MATERIALS AND METHODS: We processed the French Système National des Données de Santé (SNDS) database to retrieve appropriate cases operated between 2007 and 2017. RESULTS: 1 101 female patients (3.8%) who used to take CPA and underwent a meningioma surgery were extracted from a nationwide population based cohort of 28 924 patients. Median age at CPA prescription was 42 years IQR[36.7-48.9]. The median time between CPA start and surgery was 5.5 years IQR[3.1-7.9]. The median age at surgery was significantly lower in patients who were treated by CPA (47 years, IQR[42-54) compared to the non-CPA population (61 years, IQR[51-70], p < 0.001). Median CPA dose was 40 g, IQR[19-72]. There was a strong correlation between CPA dose and duration (r = 0.58, 95%CI[0.54-0.62], p < 0.001). Middle skull base was the most common (39%) location with a anterior skull base insertion being also far more common compared to the usual population with 21.9% of the tumour. This skull base predominance of CPA-associated meningioma is highly significant (p < 0.001). Increased CPA dose raised the risk of having multiple meningioma surgeries (p < 0.001) and multiple meningioma locations (p < 0.001). Tumour grading was not modified by CPA treatment (p = 0.603). Benign or grade I meningioma accounting for 92%, atypical or grade II for 6.1% and malignant or grade III for 1.9%. CONCLUSION: In the past 10 years, a significant number of CPA-induced meningiomas have been removed, modifying the global pyramid of age at surgery for female patients. These tumours occur well before the usual age and are preferentially located on the anterior and middle skull base.

Antibiotic prescriptions and risk factors for antimicrobial resistance in patients hospitalized with urinary tract infection: a matched case-control study using the French health insurance database (SNDS).

BACKGROUND: Antibiotic resistance is increasing among urinary pathogens, resulting in worse clinical and economic outcomes. We analysed factors associated with antibiotic-resistant bacteria (ARB) in patients hospitalized for urinary tract infection, using the comprehensive French national claims database. METHODS: Hospitalized urinary tract infections were identified from 2015 to 2017. Cases (due to ARB) were matched to controls (without ARB) according to year, age, sex, infection, and bacterium. Healthcare-associated (HCAI) and community-acquired (CAI) infections were analysed separately; logistic regressions were stratified by sex. RESULTS: From 9460 cases identified, 6468 CAIs and 2855 HCAIs were matched with controls. Over a 12-months window, the risk increased when exposure occurred within the last 3 months. The following risk factors were identified: antibiotic exposure, with an OR reaching 3.6 [2.8-4.5] for men with CAI, mostly associated with broad-spectrum antibiotics; surgical procedure on urinary tract (OR 2.0 [1.5-2.6] for women with HCAI and 1.3 [1.1-1.6] for men with CAI); stay in intensive care unit > 7 days (OR 1.7 [1.2-2.6] for men with HCAI). Studied co-morbidities had no impact on ARB. CONCLUSIONS: This study points out the critical window of 3 months for antibiotic exposure, confirms the impact of broad-spectrum antibiotic consumption on ARB, and supports the importance of prevention during urological procedures, and long intensive care unit stays.

Empirical assessment of case-based methods for identification of drugs associated with acute liver injury in the French National Healthcare System database (SNDS).

PURPOSES: Drug induced acute liver injury (ALI) is a frequent cause of liver failure. Case-based designs were empirically assessed and calibrated in the French National claims database (SNDS), aiming to identify the optimum design for drug safety alert generation associated with ALI. METHODS: All cases of ALI were extracted from SNDS (2009-2014) using specific and sensitive definitions. Positive and negative drug controls were used to compare 196 self-controlled case series (SCCS), case-control (CC), and case-population (CP) design variants, using area under the receiver operating curve (AUC), mean square error (MSE) and coverage probability. Parameters that had major impacts on results were identified through logistic regression. RESULTS: Using a specific ALI definition, AUCs ranged from 0.78 to 0.94, 0.64 to 0.92 and 0.48 to 0.85, for SCCS, CC and CP, respectively. MSE ranged from 0.12 to 0.40, 0.22 to 0.39 and 1.03 to 5.29, respectively. Variants adjusting for multiple drug use had higher coverage probabilities. Univariate regressions showed that high AUCs were achieved with SCCS using exposed time as the risk window. The top SCCS variant yielded an AUC = 0.93 and MSE = 0.22 and coverage = 86%, with 1/7 negative and 13/18 positive controls presenting significant estimates. CONCLUSIONS: SCCS adjusting for multiple drugs and using exposed time as the risk window performed best in generating ALI-related drug safety alert and providing estimates of the magnitude of the risk. This approach may be useful for ad-hoc pharmacoepidemiology studies to support regulatory actions.

Empirical assessment of case-based methods for drug safety alert identification in the French National Healthcare System database (SNDS): Methodology of the ALCAPONE project.

OBJECTIVES: To introduce the methodology of the ALCAPONE project. BACKGROUND: The French National Healthcare System Database (SNDS), covering 99% of the French population, provides a potentially valuable opportunity for drug safety alert generation. ALCAPONE aimed to assess empirically in the SNDS case-based designs for alert generation related to four health outcomes of interest. METHODS: ALCAPONE used a reference set adapted from observational medical outcomes partnership (OMOP) and Exploring and Understanding Adverse Drug Reactions (EU-ADR) project, with four outcomes-acute liver injury (ALI), myocardial infarction (MI), acute kidney injury (AKI), and upper gastrointestinal bleeding (UGIB)-and positive and negative drug controls. ALCAPONE consisted of four main phases: (1) data preparation to fit the OMOP Common Data Model and select the drug controls; (2) detection of the selected controls via three case-based designs: case-population, case-control, and self-controlled case series, including design variants (varying risk window, adjustment strategy, etc.); (3) comparison of design variant performance (area under the ROC curve, mean square error, etc.); and (4) selection of the optimal design variants and their calibration for each outcome. RESULTS: Over 2009-2014, 5225 cases of ALI, 354 109 MI, 12 633 AKI, and 156 057 UGIB were identified using specific definitions. The number of detectable drugs ranged from 61 for MI to 25 for ALI. Design variants generated more than 50 000 points estimates. Results by outcome will be published in forthcoming papers. CONCLUSIONS: ALCAPONE has shown the interest of the empirical assessment of pharmacoepidemiological approaches for drug safety alert generation and may encourage other researchers to do the same in other databases.

Suicide mortality in people with mental disorders: a register-based study in north France.

INTRODUCTION: Suicide is very common among people with mental disorders. In addition, suicide mortality rates are stable in this group, while they are decreasing in the general population. METHODS: The vital statuses of adult inpatients admitted to French psychiatry departments in 2008-2009 were researched in death databases on 31 December 2013. Suicide probability was calculated using a Kaplan-Meier analysis, and standardized mortality ratios (SMRs) were calculated in relation to the population of the study area. RESULTS: Among the 13,979 patients included in the study, (7416 men and 6563 women; mean age 43.6 ± 14.6 years), 1454 died in total, among whom 286 died by suicide an average of 4.9 years after the date of their enrolment. The cumulative probability of suicide was 0.8% at 1 year, 1.3% at 2 years and 2.5% at 6 years. The SMR value, which was 1492 for the whole group of patients and was twice as high in women (2494) as in men (1220), decreased with age (from 2078 in patients aged 18-34 years to 1278 in patients aged 75 years or more). DISCUSSION: Our study confirms that suicide mortality is higher in inpatients admitted to French psychiatry units than in the general population and advocates specific prevention programmes for this group.

[Risk of incarceration of persons undergoing psychiatric care. A retrospective longitudinal study on the French department of Oise using information from a psychiatric hospital discharge database]. / Le risque d'incarcération des personnes suivies en psychiatrie. Une étude longitudinale rétrospective dans le département français de l'Oise à partir du Recueil d'informations médicalisé en psychiatrie.

INTRODUCTION: Compared to the general population, persons with mental disorders are overrepresented in prison. In a study carried out in Picardy (northern France) in 2017, a quarter of those entering prison had had contact with a psychiatric service prior to their incarceration. Since to our knowledge no work on this subject has been published in France, we conducted a retrospective study, the main objective of which was to propose an estimate measure of incarceration likelihood in people with mental disorders. METHODS: Using data from a psychiatric hospital discharge database (Recueil d'informations médicalisé en psychiatrie, RimP), we searched for patients aged 18 and older who had received psychiatric care (except for those who were incarcerated at baseline) at the Oise psychiatric hospital in 2015-2016 and identified those who had also been registered by the psychiatric care tool (DSP) in liaison with the same hospital. As a marker of incarceration, registration was the event to be investigated. Survival analyses (Kaplan-Meier), first simple and then stratified by age, gender, past history, main diagnosis and intensity of care outside of prison were carried out to calculate likelihood of incarceration. A multivariate Cox model was used in order to identify the factors associated with incarceration. RESULTS: Among the 25,029 patients monitored in the Oise psychiatric hospital in 2015-2016, 126 had experienced incarceration during the 12 months following their inclusion in the study, i.e. an incarceration probability of 0.45% (95 % confidence interval: 0.37-0.55%). The incarcerated patients were younger (36.6 years in average versus 44.7-Pt-test<0.0001), more often male (96.8% versus 43.7% - P<0.0001), and had a more frequent history of detention (11.1% versus 0.6% - P <0.0001) and psychiatric care (20.6% versus 10.1% - P<0.0001) than the general population. The probability of incarceration at 12 months for the population followed in the psychiatry unit was 3.2 times higher than the detention rate of the general population in Oise over the same period. CONCLUSION: Our study confirms the pronouncedly high incarceration rate of people with mental disorders. Scheduled to begin in 2020, coding in the RimP of a single nationwide patient identifier for all the procedures and stays described will allow the generalized measurement by means of the proposed indicator throughout France.

Twelve complete chloroplast genomes of wild peanuts: great genetic resources and a better understanding of Arachis phylogeny.

BACKGROUND: The cultivated peanut (Arachis hypogaea) is one of the most important oilseed crops worldwide, however, its improvement is restricted by its narrow genetic base. The highly variable wild peanut species, especially within Sect. Arachis, may serve as a rich genetic source of favorable alleles to peanut improvement; Sect. Arachis is the biggest taxonomic section within genus Arachis and its members also include the cultivated peanut. In order to make good use of these wild resources, the genetic bases and the relationships of the Arachis species need first to be better understood. RESULTS: Here, in this study, we have sequenced and/or assembled twelve Arachis complete chloroplast (cp) genomes (eleven from Sect. Arachis). These cp genome sequences enriched the published Arachis cp genome data. From the twelve acquired cp genomes, substantial genetic variation (1368 SNDs, 311 indels) has been identified, which, together with 69 SSR loci that have been identified from the same data set, will provide powerful tools for future explorations. Phylogenetic analyses in our study have grouped the Sect. Arachis species into two major lineages (I & II), this result together with reports from many earlier studies show that lineage II is dominated by AA genome species that are mostly perennial, while lineage I includes species that have more diverse genome types and are mostly annual/biennial. Moreover, the cultivated peanuts and A. monticola that are the only tetraploid (AABB) species within Arachis are nested within the AA genome species-dominated lineage, this result together with the maternal inheritance of chloroplast indicate a maternal origin of the two tetraploid species from an AA genome species. CONCLUSION: In summary, we have acquired sequences of twelve complete Arachis cp genomes, which have not only helped us better understand how the cultivated peanut and its close wild relatives are related, but also provided us with rich genetic resources that may hold great potentials for future peanut breeding.

Reduced risk of cancer among low-dose aspirin users: Data from French health care databases.

PURPOSE: The effect of chronic use of low-dose aspirin (LDA) on overall cancer is still unclear owing to many controversial results and methodological limitations of studies. This study aimed to assess the effect of LDA use on overall cancer incidence among the French population. METHODS: We conducted a 10-year historical cohort study using the permanent sample of the French national health care databases: the Système National des Données de Santé (SNDS). We used data for 111 025 individuals aged 50 to 80 years at study entry (January 1, 2006) without prevalent cancer or LDA use. Individuals were followed until the earliest of cancer incidence, death from any cause, exit from the database, or end of the study on December 31, 2015. We estimated the effect of LDA on cancer incidence by using a dynamic model to account for the competing risk of death in the presence of time-dependent exposure and risk factors. RESULTS: LDA use was associated with reduced 10-year risk of cancer (subdistribution hazard ratio [SHR] 0.81 [95% CI 0.77-0.86]). The SHRs were 0.88 [0.82-0.94] for men and 0.93 [0.85-1.02] for women. Moreover, each additional year of LDA use was associated with reduced 10-year risk of cancer (SHR 0.93 [0.92-0.95]). LDA use was also associated with reduced 10-year risk of death (SHR 0.86 [0.82-0.91]). CONCLUSIONS: This is the first population-based study to demonstrate a protective effect of LDA on overall cancer incidence and to account for the main methodological issues of previous observational studies.