French National Healthcare Database Research Articles

Association of early follow-up visits with reduced hospital readmissions of newborns: a French population-based data-linkage study.

Newborn care guidelines recommend assessments within a week of discharge from maternity care. However, the optimal timing and effectiveness to prevent neonatal hospital readmission are debated. This study aimed to determine the association between early follow-up visits (EFVs) within threedays of postpartum discharge and hospital readmission of newborns up to 15days of life. This population-based data-linkage study used data from the French National Health Care Database. "Healthy" singleton term infants with a gestational age (GA) of ≥36weeks, born between January 1, 2017, and November 30, 2018, in Southern France, were included. A multivariate regression analysis was performed. Among the 67,359 included infants, 1519 (2.25%) were hospitalized. The principal causes of hospitalization were infectious diseases (42.4%) and jaundice or growth/nutrition disorders (36.1%). Hospitalized infants were more likely to be born to young and socioeconomically deprived mothers, to be male (54.4% vs. 50.6%, P < 0.001), or born early (GA < 38weeks; 28.5% vs. 20.5%, P < 0.001). They received 6% less EFVs than non-hospitalized infants (63.7% vs. 67.8%, P < 0.001). The multivariable regression logistic analysis revealed that infants who received EFVs had 13% lower odds of being hospitalized than infants without EFVs, with an adjusted odds ratio of 0.87 (95% confidence interval=0.78-0.96; P < 0.01). EFVs within threedays were associated with a 13% reduction in the rate of neonatal hospital readmission. Therefore, EFVs should be implemented to improve infant health and reduce healthcare costs.

114P Epidemiology and therapeutic outcomes of patients with spinal muscular atrophy: results from a 12-year real-world study based on the French National Healthcare database (SNDS)

114P Epidemiology and therapeutic outcomes of patients with spinal muscular atrophy: results from a 12-year real-world study based on the French National Healthcare database (SNDS)

Avelumab as second-line or later treatment in patients with metastatic Merkel cell carcinoma: Analysis of real-world outcomes in France using the CARADERM database linked to the French national healthcare database

AimAvelumab has been approved worldwide for treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. This study evaluated outcomes in patients with mMCC in France who received avelumab as second-line or later (2L+) treatment in routine clinical practice. MethodsThis retrospective, noninterventional study evaluated all patients diagnosed with mMCC using two databases: CARADERM (French national database of rare dermatological cancers) and SNDS (national healthcare database), identified via probabilistic linkage. Eligible patients initiated avelumab as 2L+ treatment between August 2016 and December 2019 and were followed for 24 months. The primary endpoint was overall survival (OS) at 24 months. ResultsOverall, 180 patients who received 2L+ avelumab were identified (112 from CARADERM, 68 after SNDS linkage). Median age at diagnosis was 74.0 years and 177 (98.3 %) had received chemotherapy alone as first-line treatment. Median follow-up was 13.1 months. Median OS from start of avelumab was 14.6 months (95 % CI, 9.9–21.3) in the overall population, 15.9 months (95 % CI, 8.6–28.3) in CARADERM patients, and 13.3 months (95 % CI, 6.7–19.1) in non-CARADERM patients. OS rates at 12 and 24 months were 53.8 % (95 % CI, 46.2 %−60.8 %) and 40.5 % (95 % CI, 33.2 %−47.6 %), respectively. In evaluable patients (CARADERM database), median progression-free survival was 3.6 months (95 % CI, 2.7–7.5) and the objective response rate was 55.3 % (95 % CI, 45.3–65.4), including complete response in 31.9 %. ConclusionsReal-world outcomes with 2L+ avelumab treatment for mMCC are consistent with clinical trial findings, supporting the recommendation of avelumab as a standard of care.

Survival After Newly-Diagnosed High-Grade Glioma Surgery: What Can We Learn From the French National Healthcare Database?

This study aimed to assess the overall survival (OS) of patients after high-grade glioma (HGG) resection and to search for associated prognostic factors. A random sample of ad hoc cases was extracted from the French medico-administrative national database, Système National des Données de Santé (SNDS). We solely considered the patients who received chemoradiotherapy with temozolomide (TMZ/RT) after HGG surgery. Statistical survival methods were implemented. A total of 1,438 patients who had HGG resection at 58 different institutions between 2008 and 2019 were identified. Of these, 34.8% were female, and the median age at HGG resection was 63.2 years (interquartile range [IQR], 55.6-69.4 years). Median OS was 1.69 years (95% confidence interval [CI], 1.63-1.76), i.e., 20.4 months. Median age at death was 65.5 years (IQR, 58.5-71.8). OS at 1, 2, and 5 years was 78.5% (95% CI, 76.4-80.7), 40.3% (95% CI, 37.9-43), and 11.8% (95% CI, 10.2-13.6), respectively. In the adjusted Cox regression, female gender (HR=0.71; 95% CI, 0.63-0.79; p<0.001), age at HGG surgery (HR=1.02; 95% CI, 1.02-1.03; p<0.001), TMZ treatment over 6 months after HGG surgery (HR=0.36; 95% CI, 0.32-0.4; p<0.001), bevacizumab (HR=1.22; 95% CI, 1.09-1.37; p<0.001), and redo surgery (HR=0.79; 95% CI, 0.67-0.93; p=0.005) remained significantly associated with the outcome. The SNDS is a reliable source for studying the outcome of HGG patients. OS is better in younger patient, female gender, and those who complete concomitant chemoradiotherapy. Redo surgery for HGG recurrence was also associated with prolonged survival.

WED-455 Sex disparities in initiation of direct-acting antivirals for hepatitis C treatment: data from the French national healthcare database (2014–2022, ANRS FANTASIO 2 study)

WED-455 Sex disparities in initiation of direct-acting antivirals for hepatitis C treatment: data from the French national healthcare database (2014–2022, ANRS FANTASIO 2 study)

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

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. 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. 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. The identification of VTE in the SNDS is possible with a good PPV.

Clinical care pathways of patients with biliary tract cancer: A French nationwide longitudinal cohort study

BackgroundAlthough the incidence of BTC is raising, national healthcare strategies to improve care lack. We aimed to explore patient clinical care pathways and strategies to improve biliary tract cancer (BTC) care. MethodsWe analysed the French National Healthcare database of all BTC inpatients between January 1, 2017 and December 31, 2021. Multinomial logistic regression adjusted odds ratios (aOR) were used to identify healthcare organisation factors that influenced access to curative care both overall and in a longitudinal sensibility analysis using optimal matching and hierarchical ascending classification to detect a subgroup of curative-care patients with a high survival over a two-year period. ResultsA total of 19,825 new BTC patients and three clinical care pathways (CCP) were identified: ‘Palliative care’ (PC-CCP), ‘Non-curative Care’ (NCC-CCP) and ‘Curative Care’ (CC-CCP) involving 7669 (38.7%), 7721 (38.9%) and 4435 (22.4%) patients respectively. Out of 1200 centers involved in BTC treatment, 84%, 11% and 5% were of low- (<15 patients/year), medium- (15–30 patients/year) and high-volume (>30 patients/year) respectively. Among patient, tumor and hospital factors, BTC management in academic (aOR: 2.32; 95%CI: 1.98–2.71), private (2.51; 2.22–2.83), semi-private (2.25; 1.91–2.65) and in high- (2.09; 1.81–2.42) or medium-volume (1.49; 1.33–1.68) centers increased probability to CC-CCP. These results were maintained in a longitudinal cluster of 2363 (53%) CC-CCP patients presenting a higher two-year survival compared with the rest [96.4% (95.1; 97.6) vs. 38.8% (36.3; 41.4), log-rank p < 0.001]. ConclusionsAmong factors subject to healthcare policy improvement, the volume and type of centers managing BTC strongly influenced access to curative care.

Dementia and glaucoma: Results from a Nationwide French Study between 2006 and 2018.

Glaucoma is the leading cause of irreversible blindness worldwide. The brain and eye share many characteristics, so the eye may provide an easy-access window on brain processes. The aim of the study was to evaluate the link between glaucoma as well as intraocular pressure (IOP)-lowering drops load and all-cause dementia. This was a nested case-control study based on the French national healthcare database from 1 January 2006 to 31 December 2018in individuals aged ≥60 years. We compared cases of incident all-cause dementia with 1:5 controls matched by date of case diagnosis (index date), age, sex, and income. We set a 5-year exposure to glaucoma period ending 2 years before the index date (lag-time period to avoid protopathic bias). The main outcome was glaucoma defined with hospitalization related to POAG and/or dispensations of IOP-lowering drops. The secondary outcome was the IOP-lowering drops load. In total, 4810 incident all-cause dementia and 24 050 matched controls were analysed (median [IQR] age 82 [10] years; 66.6% women). The prevalence of glaucoma was 14.0% in controls and cases. Risk of all-cause dementia was not associated with glaucoma (crude OR, 1.02; 95% CI [0.93-1.11]; p = 0.7; adjusted OR, 0.99; 95% CI [0.91-1.09]; p = 0.9) or IOP-lowering drops load (p = 0.2). The present study in general population ≥60 years old in France did not find any association between glaucoma and incident all-cause dementia.

Sex disparities in the utilization of nurse-assisted peritoneal dialysis: a mediation analysis using data from the REIN registry.

This study was carried out to evaluate the association between patient sex and the proportion of nurse-assisted peritoneal dialysis (PD) at dialysis initiation and to explore whether sex disparities in nurse-assisted PD utilization was explained by predialysis care and/or by social deprivation using mediation analysis. This was a retrospective study using data from the Renal Epidemiology and Information Network (REIN) registry linked to the French National Healthcare Database (SNDS) of incident patients between 1 January 2017 and 30 June 2018. A regression logistic was used for statistical analysis. A mediation analysis explored the direct effect of sex on nurse-assisted PD proportion and the indirect effect through the European Deprivation Index (EDI), and the number of general practitioner (GP) and nephrologist visits before dialysis initiation. Among 1706 patients on PD, there were 637 women (37.3%) and 1069 men (62.7%). Nurse-assisted PD proportion was 332/610 (54.4%) for women vs 464/1036 (44.8%) for men. In the multivariable analysis women were more likely to be treated by nurse-assisted PD {odds ratio (OR) 1.92 [95% confidence interval (CI) 1.46-2.52]}. Nurse-assisted PD was associated with the median number of GP visits [OR 1.44 (95% CI 1.11-1.86)] and with the median number of nephrologist visits [OR 0.59 (95% CI 0.46-0.76)]. The mediation analysis showed a direct effect of sex on nurse-assisted PD [OR 1.90 (95% CI 1.80-2.01)] and an indirect effect through the median number of GP visits [OR 1.05 (95% CI 1.04-1.06], the median number of nephrologist visits [OR 1.02 (95% CI 1.02-1.03)] and quintile 5 of the EDI [OR 1.03 (95% CI 1.02-1.03)]. Women were more frequently treated by nurse-assisted PD than men. Differences between women and men in predialysis care and social deprivation could explain the greater utilization of nurse-assisted PD among women.

Deleterious association between proton pump inhibitor and protein kinase inhibitor exposure and survival for patients with lung cancer: A nationwide cohort study

IntroductionPrevious studies have identified an interaction between protein kinase inhibitors (PKIs) and proton pump inhibitors (PPIs) in patients with lung cancer. This type of interaction may reduce the efficacy of PKIs. However, the effect of PKI-PPI interaction on patient mortality remains controversial. This study set out to determine the impact of PKI-PPI interaction on overall survival for lung cancer patients. Materials and methodsThis study was conducted using data from the French National Health Care Database from January 1, 2011 to December 31, 2021. We identified patients with: (i) an age equal to or greater than 18 years; (ii) lung cancer; and (iii) at least one reimbursement for one of the following drugs: erlotinib, gefitinib, afatinib and osimertinib. Patients were followed-up between the first date of PKI reimbursement and either December 31, 2021 or if they died, the date on which death occurred. The cumulative exposure to PPI duration during PKI treatment was calculated as the ratio between the number of concomitant exposure days to PKI and PPI and the number of exposure days to PKI. A survival analysis using a Cox proportional hazards model was then performed to assess the risk of death following exposure to a PKI-PPI interaction. Results34,048 patients received at least one reimbursement for PKIs of interest in our study: 26,133 (76.8 %) were exposed to erlotinib; 3,142 (9.2 %) to gefitinib; 1,417 (4.2 %) to afatinib; and 3,356 (9.9 %) to osimertinib. Patients with concomitant exposure to PKI-PPI interaction during 20 % or more of the PKI treatment period demonstrated an increased risk of death (HR, 1.60 [95 % CI, 1.57–1.64]) compared to other patients. When this cut-off varied from 10 % to 80 %, the estimated HR ranged from 1.46 [95 % CI, 1.43–1.50] to 2.19 [95 % CI, 2.12–2.25]. Discussion/ConclusionIn our study, an elevated risk of death was observed in patients exposed to PKI-PPI interaction. Finally, we were able to identify a dose-dependent effect for this interaction. This deleterious effect of osimertinib and PPI was revealed for the first time in real life conditions.

Invasive fungal infection incidence and risk factors in patients receiving ibrutinib in real-life settings: A nationwide population-based cohort study.

Data on the risk of invasive fungal infections (IFI) with ibrutinib treatment are scarce. This study aimed to determine IFI incidence and risk factors in ibrutinib-treated patients in real-life settings. We constituted a cohort of ibrutinib incident users in the French National Healthcare Database. All patients ≥18 years with a first dispensing of ibrutinib between 21 November 2014 and 31 December 2019 were included. Patients were followed from the cohort entry date until IFI, ibrutinib discontinuation, death, or 31 December 2020, whichever came first. The cumulative incidence function method was used to estimate the probability of IFI accounting for competing risk of death. A multivariate cause-specific Cox proportional hazards model was used to assess independent IFI risk factors. Among 6937 ibrutinib-treated patients, 1-year IFI cumulative incidence was 1.3%, with invasive aspergillosis being the most frequent. Allogenic or autologous stem cell transplantation (ASCT) (hazard ratio [HR] 3.59, 95% confidence interval [1.74; 7.41]), previous anticancer treatment (HR 2.12, CI 95% [1.34; 3.35]) and chronic respiratory disease (HR 1.66, [1.03; 2.67]) were associated with higher risk of IFI. Besides neutropenia and corticosteroids, use of anti-CD20 agents was significantly more frequent in patients having experienced IFI (HR 3.68, [1.82; 7.45]). In addition to patients with ASCT history, severe neutropenia or treated with corticosteroids, our findings support active surveillance of IFIs in those with chronic respiratory disease, previously treated, or treated with anti-CD20 agents in combination with ibrutinib. Further studies are needed to optimise IFI prophylaxis in these patient subgroups.

Cervical cancer screening pathways in France in 2015–2021, a nationwide study based on medico-administrative data

To better document cervical cancer screening (CCS) pathways, the purpose of our study was to examine CCS pathways among women who had undergone a screening test (opportunistic or organised programme), based on real-life data over a 7-year period. This study used data from the French national health care database (SNDS), which covers almost 100 % of the French population of around 66 million inhabitants. Data from 2015 to 2021 were extracted. More than one quarter (27 %) of women who were at least 25 years old in 2015 and up to 65 years old in 2021 were not screened over the 2015–2021 period. Compared to women who had undergone screening at least once, women who were not screened were older (36 % vs. 23 % in the 50–59 years age group in 2015) and lived in the most deprived urban areas (21 % vs 16 % for less and most deprived respectively). 57 % of women underwent screening within recommended intervals, 13 % of women were under-screened, and 30 % were overscreened. Overall, our study identified that, in 2021, women who participated in the French organised screening programme were less likely to be screened within the recommended interval over the 7-year period. These analyses need to be continued over time in order to assess whether the programme helps reintegrate women into the screening process.

Direct-Acting Antivirals and the Risk of Arrhythmias and Conduction Disorders in Patients with Chronic Hepatitis C: A French Nationwide Cohort Study.

To quantify the risk of arrhythmias and conduction disorders (ACD) in patients receiving direct-acting antiviral (DAA) therapy for hepatitis C. All individuals aged 18 to 85 years old treated with DAAs between 01 January 2014 and 31 December 2021 were selected from the French national healthcare database (SNDS). Individuals with a history of ACD were excluded. The primary outcome was the incidence of hospitalization or medical procedure for ACD. Marginal structural models were used to adjust for age, sex, medical comorbidities, and concomitant medications. After analyzing 87,589 individuals (median age, 52 years; 60% male) from 01 January 2014 to 31 December 2021, 2131 hospitalizations or medical procedures for ACD were observed over 672,572 person-years (PY) of follow-up. The incidence of ACD was 245/100,000 PY [95% confidence interval (CI), 228-263/100,000 PY] before DAA and 375/100,000 PY (95% CI 355-395/100,000 PY) after DAA exposure (rate ratio 1.53; 95% CI 1.40-1.68; P < 0.001). The risk of ACD was increased after DAA exposure, compared with the pre-DAA period (adjusted hazard ratio,1.66; 95% CI 1.43-1.93; P < 0.001). The increase in ACD risk was similar among individuals treated with sofosbuvir-based and sofosbuvir-free regimens. Of the 1398 ACD detected after DAA exposure, 30% were hospitalizations for atrial fibrillation, 25% were medical procedures for ACD, and 15% were hospitalizations for atrioventricular blocks. A significant increase in the risk of ACD was observed in the population-level cohort of individuals treated with DAAs, regardless of the regimen. Further research is needed to identify patients at risk of ACD, determine cardiac monitoring strategies, and evaluate the need for Holter monitoring after DAA therapy.

Avelumab as second-line or later (2L+) treatment in patients (pts) with metastatic Merkel cell carcinoma (mMCC): Analysis of real-world outcomes in France using the CARADERM registry and the French national healthcare database.

9537 Background: Avelumab, an anti–PD-L1 antibody, has been approved in multiple countries for the treatment of mMCC based on the results of the pivotal phase 2 JAVELIN Merkel 200 trial (NCT02155647). In pts who received avelumab as 2L+ treatment in the trial (part A), median overall survival (OS) was 12.6 months and median progression-free survival (PFS) was 2.7 months. The French health technology assessment agency requested the collection of real-world data from pts with mMCC from a comprehensive registry; data are reported here. Methods: This retrospective, noninterventional, real-world study evaluated all pts with mMCC in France using combined data from 2 databases: CARADERM (French national database of rare dermatological cancers) and Système National des Données de Santé (SNDS; national healthcare database). For this analysis, eligible pts were diagnosed with mMCC and initiated 2L+ avelumab outside of a clinical trial between August 2016 and December 2019. Pts were followed for 24 months after initiation of avelumab. Probabilistic linkage was performed to identify pts registered in both databases. OS and PFS were analyzed using Kaplan-Meier methodology. Safety data were not collected. Results: A total of 180 pts who received 2L+ avelumab were identified, data were obtained for 112 pts from the CARADERM database and for 68 additional pts after SNDS linkage. Median age at diagnosis was 74.0 years, 66.7% were male, and 98.3% received chemotherapy as first-line treatment. Median follow-up was 13.1 months. 79.5% of CARADERM database pts had discontinued avelumab; the most common reasons specified were progressive disease (36.4%), complete response (17.0%), and death (13.6%). Median OS was 14.6 months (95% CI, 9.9-21.3 months) overall; in CARADERM database pts, median OS was 15.9 months (95% CI, 8.6-28.3 months) vs 13.3 months (95% CI, 6.7-19.1 months) in non-CARADERM database pts. 12- and 24-month OS rates in the overall population were 53.8% (95% CI, 46.2%-60.8%) and 40.5% (95% CI, 33.2%-47.6%), respectively. In CARADERM database pts (data not available in non-CARADERM database pts), median PFS was 3.6 months (95% CI, 2.7-7.5 months), and the objective response rate was 55.3% (95% CI, 45.3%-65.4%), including complete response in 31.9%. Median duration of response was 39.3 months (95% CI, 24.3 months-not estimable). Conclusions: In this real-world study of national data from France, outcomes with avelumab as 2L+ treatment for mMCC were similar to those observed in part A of the JAVELIN Merkel 200 trial. These findings confirm the effectiveness of avelumab in pts with mMCC that have progressed following first-line systemic treatment in routine clinical practice.

Clustering of prostate cancer healthcare pathways in the French National Healthcare database.

Healthcare pathways of patients with prostate cancer are heterogeneous and complex to apprehend using traditional descriptive statistics. Clustering and visualization methods can enhance their characterization. Patients with prostate cancer in 2014 were identified in the French National Healthcare database (Système National des Données de Santé-SNDS) and their data were extracted with up to 5 years of history and 4 years of follow-up. Fifty-one-specific encounters constitutive of prostate cancer management were synthesized into four macro-variables using a clustering approach. Their values over patient follow-ups constituted healthcare pathways. Optimal matching was applied to calculate distances between pathways. Partitioning around medoids was then used to define consistent groups across four exclusive cohorts of incident prostate cancer patients: Hormone-sensitive (HSPC), metastatic hormone-sensitive (mHSPC), castration-resistant (CRPC), and metastatic castration-resistant (mCRPC). Index plots were used to represent pathways clusters. The repartition of macro-variables values-surveillance, local treatment, androgenic deprivation, and advanced treatment-appeared to be consistent with prostate cancer status. Two to five clusters of healthcare pathways were observed in each of the different cohorts, corresponding for most of them to relevant clinical patterns, although some heterogeneity remained. For instance, clustering allowed to distinguish patients undergoing active surveillance, or treated according to cancer progression risk in HSPC, and patients receiving treatment for potentially curative or palliative purposes in mHSPC and mCRPC. Visualization methods combined with a clustering approach enabled the identification of clinically relevant patterns of prostate cancer management. Characterization of these care pathways is an essential element for the comprehension and the robust assessment of healthcare technology effectiveness.

EE625 Economic and Clinical Burden of Worsening Heart Failure Patients With Reduced Ejection Fraction: French National Healthcare Database Analysis (SNDS)

EE625 Economic and Clinical Burden of Worsening Heart Failure Patients With Reduced Ejection Fraction: French National Healthcare Database Analysis (SNDS)

Incidence of heart failure following exposure to a protein kinase inhibitor, a French population-based study.

Pharmacovigilance signals of heart failure (HF) following exposure to protein kinase inhibitors (PKIs) have been detected in recent years. Our aim was to identify the PKIs most frequently associated with the development of HF. Using the French National Healthcare Database, all patients newly exposed to a PKI between January 2011 and June 2014 were followed up for 18 months. Specific hospitalization diagnosis and long-term HF-related disease codes were used to identify HF patients. HF incidence rate ratios (IRRs) were measured and adjusted hazard ratios (aHRs) were estimated using a Cox model. Sensitivity analyses were performed to limit the potential indication and competitive risk bias. Thirteen PKIs were studied. Among the 49 714 new PKI users registered during the study period, the mean IRR of HF was 3.38 per 100 person-years, with a median time to onset of 155 days. We found a significant increase in the incidence of HF for six medicinal products: pazopanib (aHR = 2.42, 95% confidence interval [CI] 1.67-3.52), dasatinib (aHR = 2.22, 95% CI 1.42-3.44), ruxolitinib (aHR = 2.11, 95% CI 1.69-2.64), crizotinib (aHR = 1.71, 95% CI 1.07-2.72), everolimus (aHR = 1.45, 95% CI 1.26-1.67) and vemurafenib (aHR = 1.37, 95% CI 1.01-1.86). Sensitivity analyses were consistent with our primary analysis. The current study provides knowledge on HF following exposure to a PKI. Additional studies could confirm these results for dasatinib, everolimus, pazopanib and ruxolitinib, and particularly for the two medicinal products with results slightly above the significance threshold, namely, crizotinib and vemurafenib, in our sensitivity analyses.

Total knee arthroplasty in France: Male-driven rise in procedures in 2009–2019 and projections for 2050

BackgroundThe number of Total Knee Arthroplasty (TKA) procedures has been rising steadily for several decades in Europe and the USA. The increase varies in pace across countries, with a gradual climb in northern and central Europe, a slowing in the USA, and an exponential surge in the UK. In France, a 32.2% rise in the number of TKA and unicompartmental knee arthroplasty procedures was documented between 2012 and 2018. However, no study has focussed specifically on changes in both TKA procedures and the features of TKA patients. The objective of this study was to use the French national healthcare database to evaluate (1) increases in TKA procedures according to sex and age, (2) whether TKA is being performed at increasingly younger ages, (3) whether the comorbidity profile at TKA is changing, and (4) whether the TKA incidence rate will stabilise in the future, with a projection for 2050. HypothesisIn France, the number of TKA procedures is rising in both males and females but the pace of the increases differs between sexes. Material and methodThis study used data collected in France in 2009–2019, separately for different age groups and for males and females, in the French national healthcare database (Système national des données de santé, SNDS) that collects information on all surgical procedures performed nationwide. Based on information about the TKA procedures, we determined (1) the TKA incidence rates with their time trends and (2) indirectly, the comorbidity profiles of the patients at TKA. Linear, Poisson, and logistic models were built to predict incidence rates in 2030, 2040, and 2050. ResultsBetween 2009 and 2019, the TKA incidence rate showed a steeper increase in males than in females (from 71.2 to 122.9 [+73%] vs. 124.2 to 181.0 [+46%], respectively). Although this increase was replicated in all age groups, it was sharper in patients younger than 65 years, in both males and females (from 20.9 to 37.9 [+82%] and 33.6 to 51.3 [+53%], respectively). During the study period, the number and proportion of patients increased in the group with mild comorbidities (from 40 093 to 67 430 TKAs, i.e., from 53.1% to 65.7% of all TKAs) but not in the other comorbidity groups. All projection models were validated. Nonetheless, the most likely scenario, provided by the logistic model, is a 33% rise by 2050 in both males and females (i.e., to 151 575 TKA procedures) with a plateau starting around 2030. ConclusionAlthough the increase in TKA procedures is more marked in males than in females, the trends are similar in both sexes, with a sharper rise in the group younger than 65 years and a shift toward patients with milder comorbidities. In the longer term, incidence rate trends follow logistic dynamics, with a plateau starting around 2030. To meet the increasing demand, a corresponding development in relevant healthcare resources must be planned. Level of evidenceIV, descriptive epidemiological study.

Adherence to opioid agonist therapy predicts uptake of direct-acting antivirals in people who use drugs: results from the French national healthcare database (the ANRS FANTASIO study)

BackgroundOpioid agonist therapy (OAT) is associated with reduced injection, reduced HCV transmission, and more opportunities to initiate hepatitis C virus (HCV) treatment in people who use drugs (PWUD). We aimed to study the extent to which adherence to OAT was predictive of increased uptake of direct-acting antivirals (DAA) in PWUD with chronic HCV infection.MethodsUsing the French national healthcare system database, we targeted PWUD (i.e. with a history of OAT) who had chronic HCV infection and were eligible for DAA during 2014–2016. Adherence to OAT was computed as a time-varying variable expressing the proportion of days covered by OAT receipt, over any six-month interval before DAA receipt. We used a Cox proportional hazards model to estimate the association between adherence to OAT and the rate of DAA uptake after adjustment for age, sex, alcohol use disorder, socioeconomic status, and liver disease severity.ResultsAmong the 22,615 persons included in the ANRS FANTASIO study, 3438 (15.2%) initiated DAA during the study period. After multivariable adjustment, adherence to OAT was associated with a higher rate of DAA initiation. However, this association was not linear, and only individuals on OAT for 20% or more of the time in the previous six-month period had a higher rate of DAA initiation (adjusted hazard ratio [95% confidence interval]: 1.28 [1.18–1.38]). Other variables associated with DAA initiation were male sex, older age, cirrhosis or liver cancer, and higher socioeconomic status.ConclusionsAdherence to OAT is a major predictor of DAA initiation in PWUD living with chronic HCV infection in France. Our results also suggest that even moderate adherence to OAT can facilitate DAA uptake. Adequate HCV training for OAT prescribers together with interventions to ensure adherence to OAT will help improve DAA initiation rates and reach HCV elimination goals.

Healthcare costs of a telemonitoring programme for heart failure: indirect deterministic data linkage analysis.

We aim to evaluate the costs associated with healthcare resource consumption for chronic heart failure (HF) management in patients allocated to telemonitoring versus standard of care (SC). OSICAT-ECO involved 745 patients from the OSICAT trial (NCT02068118) who were successfully linked to the French national healthcare database through an indirect deterministic data linkage approach. OSICAT compared a telemonitoring programme with SC follow-up in adults hospitalized for acute HF≤12months. Healthcare resource costs included those related to hospital and ambulatory expenditure for HF and were restricted to direct costs determined from the French health data system over 18months of follow-up. Most of the total costs (69.4%) were due to hospitalization for HF decompensation, followed by ambulatory nursing fees (11.8%). During 18-month follow-up, total costs were 2% lower in the telemonitoring versus the SC group, due primarily to a 21% reduction in nurse fees. Among patients with NYHA class III/IV, a 15% reduction in total costs (€3131 decrease) was observed over 18-month follow-up in the telemonitoring versus the SC group, with the highest difference in hospital expenditure during the first 6months, followed by a shift in costs from hospital to ambulatory at 12months. HF hospitalization and ambulatory nursing fees represented most of the costs related to HF. No benefit was observed for telemonitoring versus SC with regard to cost reductions over 18months. Patients with severe HF showed a non-significant 15% reduction in costs, largely related to hospitalization for HF decompensation, nurse fees, and medical transport.