French Database Research Articles

SLC4A3 anion exchanger mutations associated to sudden death : short or long QT syndrome?

Abstract Introduction SLC4A3 gene codes for an (Cl-/HCO3-) exchanger present on the surface of cardiomyocytes (AE3 channel) is involved in maintaining the physiological acid-base gradient of the cardiomyocyte at rest. Loss of function of the SLC4A3 gene leading to an increase in intracellular pH has. been reported to be responsible for short QT syndrome (SQT). Methods The aim of our study was to characterize the genotype-phenotype relationships of SLC4A3 mutations identified in the French databases (Paris, Nantes and Lyon) in patients with sudden death. Through systematic exome sequencing we identified 3 new SLC4A3 variants in 3 families with a history of sudden death in two universitary hospitals. Results Family 1. The c.3209G>C variant (p.Gly1070Ala) in the SLC4A3 gene was identified in a 7-yo boy with VF at sleep but admitted in encephalic death. EKG showed short QT (QTc 280ms). Clinical examination, blood tests, TTE and autopsy were normal. There was no family history of sudden death. His mother had EKG evidence of SQT and was carrier the SLC4A3 mutation. She was implanted with an ICD. His two older brothers and the rest of the family had no mutation or pathological ECG and were asymptomatic. Family 2. The c.1027C>T (p.Arg343Cys) mutation in the SLC4A3 gene was identified in a 29-year-old man who presented with sudden death at sleep (VF). Clinical examination, blood tests, TTE and autopsy were normal. A maternal uncle died suddenly while sleeping. His two brothers (30 and 27 yo) are both carriers of the SLC4A3 mutation and exhibit SQT (QTc 320 and 330 ms respectively). TEE, Holter monitoring and stress test were normal in both. Both brothers were treated with hydroquinidine. Over a 2-year follow-up they had no symptom nor AF. Family 3. The c.1022C>G (p.Thr341Arg) mutation was identified in the SLC4A3 gene in a 54-yoman who presented with VF during shower but admitted in encephalic death. There was no family history of sudden death. Clinical examination, blood tests and echocardiography as well as coronary angiogram were normal. The initial ECG showed a prolonged QT interval (QTc 520 ms). QTc decreased to 480 ms in the 48 following hours. His parents and his sister as well as his 18 yo daughter have normal QTc values. We are awaiting the genetic results. Conclusion Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 has been recently reported to cause short QT syndrome but it seems that in rare cases it may also be responsible for LQTS. Further patients are needed to confirm these data. In order to understand the underlying electrophysiological mechanisms, we plan to characterize the cellular impact of these new mutations through IPS.

Association of fluoroquinolones with the risk of spontaneous pneumothorax: nationwide case–time–control study

IntroductionFluoroquinolones can cause severe collagen-associated adverse effects, potentially impacting the pulmonary connective tissue. We investigated the association between fluoroquinolones and spontaneous pneumothorax.MethodsA case–time–control study was performed using the nationwide French...

Academic impact of French Hip & Knee Surgery Society (SFHG): A bibliometric analysis

IntroductionThe French Hip & Knee Surgery Society (SFHG) brings together French-speaking hip and knee expert surgeons. There has been an exponential growth of orthopaedic surgical activity over the last decade and hip and knee surgery clinical research has had a similar growth. Despite this, the SFHG's contribution to the orthopaedic literature remains poorly known. To answer this question, we conducted a bibliometric study using data from the national SIGAPS database between 2013 and 2022 to determine: (1) the number of publications produced by SFHG members, (2) the proportion of articles produced by SFHG members in relation to French orthopaedic production, (3) impact markers for articles produced by SFHG member surgeons, (4) collaboration networks between SFHG member surgeons. HypothesisThe number of articles produced by SFHG member surgeons will represent a significant proportion of French scientific output in orthopaedics. Material and methodThe analysis was carried out by cross-referencing the SFHG membership list with the French database of the “Système d'interrogation, de gestion, d'analyse des publications scientifiques” (SIGAPS) and the InCites platform. Among the 189 SFHG members, we identified a list of 183 SIGAPS identifiers in the national database, corresponding to 127 distinct individuals with publications over the period 2013–2022. Several indicators were studied: number of publications; SIGAPS score for the different WoS categories; number and percentage of publications in the top1% and top10%. ResultsOf SFHG's 189 members, 127 have been identified by the SIGAPS database as “publishers”. Over the last decade, 2306 articles have been published by SFHG members. The number of publications has risen steadily, from 203 publications in 2013 to 261 publications in 2022. All SIGAPS categories were represented. Most articles were published in rank D (n = 719; 31.2%) C (n = 552; 23.9%) and B (n = 549; 23.8%) journals. Authors were in first (n = 624) or last position (n = 730) in 58.7% of publications. Orthopaedics (1,639; 71.1%), Surgery (1,124; 48.7%) and Sports surgery (335; 14.5%) were the most frequently observed topics. Orthopaedics & Traumatology: Surgery & Research is the most popular journal for SFHG members' articles, with 655/2306 articles published over the last decade, representing a 32.2% market share. Of the 2160 publications indexed on the Web of Science, 1807 (83.7%) had a French corresponding author. 31 articles (1.4%) were in the Top 1% of most-cited articles worldwide, and 310 were in the Top 10% of most-cited articles worldwide (14.5%). DiscussionSFHG is a major player in orthopaedic research in France. In 2022, it accounted for 19% of the annual volume of French scientific publications in the field of orthopaedics and traumatology. Level of evidenceIV; Retrospective study without control group.

Impact of the COVID-19 health crisis on psychotropic drug use in children and adolescents in France

BackgroundIn 2019, the world faced a pandemic brought about by a severe acute respiratory infection caused by SARS-CoV-2 virus. The spread of this virus has profoundly affected societies, particularly in terms of their economic, human and social dimensions, as well as their healthcare systems. Several restrictive measures (reduced social interaction, periodic school closures,…) had to be taken to contain the spread of the virus. These measures have had an impact on the psychological well-being of both adults and children. The aim of this study was to assess the changes in psychotropic drugs prescriptions for children and adolescents living in Limousin, a French region, over the period 2018 to 2021.MethodsThe consumption of psychotropic drugs was studied using a national database of drug reimbursement. These data were extracted and supplied from the nationwide French reimbursement healthcare system database (SNDS). The following therapeutic classes were studied: N05A (antipsychotics), N05B (anxiolytics), N05C (hypnotics and sedatives), N06A (antidepressants) and N06B (psychostimulants). Data were collected for insured persons under the age of 18 who received at least one reimbursement for a psychotropic drug between 2018 and 2021.ResultsOver a 4-year period, 7949 patients under the age of 18 were included with an average age of 12.1 years and a sex ratio of 0.97 M/F. The number of patients increased from 2018 to 2021, as did the number of reimbursements. We observed a statistically significant difference of means of patients reimbursed per week for on five therapeutic classes, with the greatest difference in 2021 (p < 0.0001). An increase in the number of patients of between + 20.7% and + 689% was observed, depending on the drug classes studied. Comparisons between the COVID-19 and pre-COVID-19 periods showed a significantly higher COVID average for psychotropic drugs reimbursements in general and individually for all classes except psychostimulants.ConclusionThe results show a significant increase in the consumption of psychotropic drugs among youth. The increase in psychotropic drug use was continuous and progressive throughout the pandemic. All five classes were increased, but particularly anxiolytics and antidepressants. The COVID-19 context may have been at the origin of a deterioration in the mental health of children and adolescents, or of a heightened awareness of psychiatric care among young people.

Surgical management of atrioesophageal fistula after catheter ablation of atrial fibrillation: A French nationwide study

ObjectiveThe study objective was to assess the efficacity of different surgical strategies for atrioesophageal fistula after catheter ablation of atrial fibrillation. MethodsBetween January 2010 and April 2023, all patients with a diagnosis of atrioesophageal fistula or pericardo-esophageal fistula after catheter ablation of atrial fibrillation were analyzed retrospectively from the French database EPITHOR. Patients without surgical management were excluded. ResultsEighteen patients were included, 15 with atrioesophageal fistula and 3 with pericardo-esophageal fistula. Median follow-up was 89.5 days with an overall survival of 50%. Five patients underwent esophageal stenting, 2 as a bridge-to-esophagectomy with 50% of survival and 3 in association with esophagus and left atrial direct repair with 66% survival. Primary esophageal repair with flap coverage was performed in 8 patients with 25% survival, most of them with sepsis and neurological failure. Seven patients had an esophagectomy with 71% survival, only 2 of them having a neurological failure. Among them, 5 patients underwent a restorative surgery and are still alive. Four patients had a retrosternal colon interposition, and 1 patient had an esogastric anastomosis. Risk factors for death were neurological failure (hazard ratio [HR], 4.91, 95% CI, 0.95-25.22; P = .0057) in univariate analysis and sepsis (HR, 6.25, 95% CI, 1.17-33.3; P = .032) in multivariate analysis. Esophagectomy tended to offer a survival benefit (HR, 0.163, 95% CI, 0.019-1.340; P = .092). The use of cardiopulmonary bypass did not significantly impact survival (HR, 1.953, 95% CI, 0.392-9.719; P = .413). ConclusionsAggressive surgical strategies for managing atrioesophageal fistula are mandatory to offer the best chance of survival.

Stroke but no hospital admission: Lost opportunity for whom?

To counter the spread of COVID-19, the French government imposed several stringent social and political measures across its entire population. We hereto assess the impact of these political decisions on healthcare access in 2020, focusing on patients who suffered from an ischemic stroke. We divide our analysis into four distinct periods: the pre-COVID-19 pandemic period, the lockdown period, the "in-between" or transitional period, and the shutdown period. Our methodology involves utilizing a retrospective dataset spanning 2019-2020, an exhaustive French national hospital discharge diagnosis database for stroke inpatients, integrated with income information from the reference year of 2019. The results reveal that the most affluent were more likely to forgo medical care, particularly in heavily affected areas. Moreover, the most disadvantaged exhibited even greater reluctance to seek care, especially in the most severely impacted regions. The data suggest a loss of opportunity for less severely affected patients to benefit from healthcares during this lockdown period, regardless of demographic, location, and socioeconomic determinants. Furthermore, our analysis reveals a notable discrepancy in healthcare-seeking behavior, with less affluent patients and seniors (over 75 years old) experiencing slower rates of return to healthcare access compared to pre-pandemic levels. This highlights a persistent gap in healthcare accessibility, particularly among socioeconomically disadvantaged groups, despite the easing of COVID-19 restrictions.

Early Maintenance Treatment Initiation and Relapse Risk Mitigation After a First Event of MOGAD in Adults: The MOGADOR2 Study.

Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes. Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method. We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%. The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk. This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.

Descriptive epidemiology of 399 histologically confirmed newly diagnosed meningeal solitary fibrous tumours and haemangiopericytomas in France: 2006-2015.

Meningeal solitary fibrous tumour (SFT) and haemangiopericytoma (HPC) are uncommon tumours that have been merged into a single entity in the last 2021 WHO Classification of Tumors of the Central Nervous System. To describe the epidemiology of SFT/HPC operated in France and, to assess their incidence. We processed the French Brain Tumour Database (FBTDB) to conduct a nationwide population-based study of all histopathologically confirmed SFT/HPC between 2006 and 2015. Our study included 399 SFT/HPC patients, operated in France between 2006 and 2015, in one of the 46 participating neurosurgical centres. The incidence reached 0.062, 95%CI[0.056-0.068] for 100,000 person-years. SFT accounted for 35.8% and, HPC for 64.2%. The ratio of SFT/HPC over meningioma operated during the same period was 0.013. SFT/HPC are about equally distributed in women and men (55.9% vs. 44.1%). For the whole population, mean age at surgery was 53.9 (SD ± 15.8) years. The incidence of SFT/HPC surgery increases with the age and, is maximal for the 50-55years category. Benign SFT/HPC accounted for 65.16%, SFT/HPC of uncertain behaviour for 11.53% and malignant ones for 23.31%. The number of resection progresses as the histopathological behaviour became more aggressive. 6.7% of the patients with a benign SFT/HPC had a second surgery vs.16.6% in case of uncertain behaviour and, 28.4% for malignant SFT/HPC patients. Meningeal SFT and HPC are rare CNS mesenchymal tumours which both share common epidemiological characteristics, asserting their merging under a common entity. SFT/HPC incidence is less that one case for 1 billion per year and, for around 100 meningiomas-like tumours removed, one SFT/HPC may be diagnosed. SFT/HPC are equally distributed in women and men and, are mainly diagnosed around 50-55years. The more aggressive the tumour, the higher the probability of recurrence.

The carbon footprint of French hospital ophthalmology consultations.

France carbon footprint, with 604 million tons of CO2 equivalent (CO2eq) annual emissions, far exceeds the worldwide scientific specifications to not exceed 2 °C of warming in 2100. The healthcare sector is one of the biggest contributors to greenhouse gas emissions. The aim of this study is to quantify and evaluate the carbon footprint of the consultation activity of an ophthalmology department at a single institution in France. The perimeter of the investigation included consultations and excluded the surgeries and the hospitalisation. We calculated the carbon footprint of a single day of practice in our scope of investigation. We included consumption of energy, patient travel, staff travel, pharmaceutics and medical devices purchases, computer hardware, biomedical equipment/exam materials, and waste. We used the official French public database of emission factors: Base Empreinte® of the Environmental and Energy Management Agency of France. The carbon footprint of a single day of our department was estimated at 1 688.65 kgCO2eq. It represents an average of 9.28 kgCO2eq per patient. Energy consumption contributed for 114.80 kgCO2eq (6.8%), travel for 1324.76 kgCO2eq (78.4%), pharmaceutics and medical devices for 208.33 kgCO2eq (12.3%), equipment for 14.38 kgCO2eq (0.9%) and waste for 26.38 kgCO2eq (1.6%). This study highlights the importance of patient travels, and possibly pharmaceutics, in the carbon footprint of hospital ophthalmology practice in France. More studies are needed to establish it at the national or international scale, as well as more carbon footprint analyses on products, especially those of high prices, to increase the accuracy of these studies.

Impact of new drug releases on heart failure management and hospitalizations in France: A repeated cross-sectional study between 2014 and 2023

Real-life data on the impact of sacubitril-valsartan and sodium-glucose cotransporter type 2 (SGLT-2) inhibitors on heart failure (HF) in France is lacking. Using French health insurance databases, we examined the ten-year evolution in HF medication use, focusing on SGLT-2 inhibitors and sacubitril/valsartan, and incidence of HF hospitalizations during the same period. We conducted a repeated cross-sectional study using medical-administrative data from French health insurance databases between 2014 and 2023. These included "OpenMedic" for outpatient medication reimbursements and "ScanSanté" for annual hospitalization data. Medications were classified using ATC codes, and hospitalizations were identified using ICD-10 codes. Statistical analyses encompassed annual rates of users and boxes dispensed for HF medications, along with HF, ischemic heart disease and ischemic stroke hospitalization rates. Prevalence of SGLT-2 inhibitors and sacubitril-valsartan use was also studied regionally, with direct standardization by age and sex, with the French population as the standard population. Between 2014 and 2023, HF drug use increased significantly, with beta-blockers and ACE inhibitors/ARBs leading in prevalence of use. ARNi and SGLT-2 inhibitors, introduced later, showed remarkable rises: +506% and +3766% in users since their market introduction, respectively. Meanwhile, HF hospitalizations slightly increased by +3.6% between 2016 and 2019, followed by a notable decline of -12.5% during 2019-2023, coinciding with the introduction of SGLT-2 inhibitors. In contrast, hospitalizations for ischemic heart disease rose by 11.6% over the period 2016-2019 and by +5.2% over the period 2019-2023, and hospitalizations for ischemic stroke rose by 8.2% over the period 2016-2019 and declined by -0.6% over the period 2019-2023. We observed regional disparities in SGLT-2 inhibitors use, with prevalence ranging from 0.9% in Bretagne to 1.5% in Hauts-de-France. The data suggests a temporal correlation between the increase in SGLT-2 inhibitors use and the decline in HF hospitalizations since 2019. More studies are needed to measure real life effectiveness of SGLT-2 inhibitors in heart failure.

Nationwide trends over 10 years in epidemiology and management of pancreatic ductal adenocarcinoma: A real-world study from the French administrative database

Background & aimsSignificant progress has been made in the management of pancreatic ductal adenocarcinoma (PDAC) in recent years. In this population-based study, we aimed to compare incidence, therapeutic strategies, and survival outcomes of PDAC patients in France over a decade. MethodsThis study was performed using a nationwide French database. All patients receiving care for PDAC during years 2009, 2014 and 2018 were included. Treatment modalities and survival outcomes were analyzed. ResultsA total of 8143/8771/10494 patients were considered in 2009/2014/2018, respectively. Incidence increased mainly among patients aged >60 years. In localized PDAC, the proportion of patients receiving best supportive care (BSC) only decreased at 43.6/36.4/32.4 % and 27.8/29.1/34.3 % received chemo(radio)therapy alone. The rate of upfront surgery remained stable while 3/8/18 % of operated patients received neoadjuvant therapy. Median overall survival (OS) was 7.0/7.9/8.5 months in the overall population. Among treated patients, 1-year OS was 61.4/67.7/68.8 % and 30.3/36.3/38.8 % for localized and metastatic PDAC, respectively. ConclusionsThis study confirms the rising incidence of PDAC. Improved outcomes were seen in localized PDAC, with a wider use of chemotherapy and neoadjuvant strategies, and in treated metastatic patients. A modest survival gain was seen overall, hindered by the still high rate of patients receiving BSC only.

Machine learning based on functional principal component analysis to quantify the effects of the main drivers of wheat yields

Assessing the response of crop yield to year-to-year climate variability at the field scale is often done using process-based models and regression techniques. Although powerful, these tools rely on strong assumptions and can lead to substantial prediction errors. In this study, we investigate the use of a flexible machine learning algorithm combining Functional Principal Component Analysis and Random Forest, to relate field scale wheat yield to local daily climate variables. Instead of computing seasonal, monthly or any other arbitrary time-frame climate averages, climate time series are decomposed by Functional Principal Component Analysis into a few data-driven basis functions, called Principal Curves, in order to summarize the dynamic of key climate variables by a limited number of interpretable components. Scores associated to these components are then used as inputs of a Random Forest algorithm for yield prediction and for analysing important factors responsible for yield variability. To evaluate our approach, we use a French national database including wheat yield data as well as climate and management practice data for 298 farm fields from 2011 to 2016 in four main producing regions. Depending on the regions, our approach can explain from 62 % to 81 % of the yield variability when both agronomic and climate variables are included, down to 56–81 % when ignoring agronomic variables and 51–74 % when ignoring climate variables. Based on a year-by-year cross-validation, RMSE ranges from 0.5 t ha−1 to 2.1 t ha−1 in non-extreme years (2012–2015). However, prediction error can reach 3.6 t ha−1 in case of exceptional weather conditions, such as those experienced in 2016 in Northern France. We find that this new approach performs in most cases better than the same machine learning algorithm using the usual time averages of climate variables, without the need to choose an arbitrary time-frame. We then show how important patterns in weather time series can be identified and how their effects on yield can be interpreted using the proposed modelling framework.

Comparison of juvenile and adult myasthenia gravis in a French cohort with focus on thymic histology

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle fatigability due to acetylcholine receptor (AChR) autoantibodies. To better characterize juvenile MG (JMG), we analyzed 85 pre- and 132 post-pubescent JMG (with a cutoff age of 13) compared to 721 adult MG patients under 40 years old using a French database. Clinical data, anti-AChR antibody titers, thymectomy, and thymic histology were analyzed. The proportion of females was higher in each subgroup. No significant difference in the anti-AChR titers was observed. Interestingly, the proportion of AChR+ MG patients was notably lower among adult MG patients aged between 30 and 40 years, at 69.7%, compared to over 82.4% in the other subgroups. Thymic histological data were examined in patients who underwent thymectomy during the year of MG onset. Notably, in pre-JMG, the percentage of thymectomized patients was significantly lower (32.9% compared to more than 42.5% in other subgroups), and the delay to thymectomy was twice as long. We found a positive correlation between anti-AChR antibodies and germinal center grade across patient categories. Additionally, only females, particularly post-JMG patients, exhibited the highest rates of lymphofollicular hyperplasia (95% of cases) and germinal center grade. These findings reveal distinct patterns in JMG patients, particularly regarding thymic follicular hyperplasia, which appears to be exacerbated in females after puberty.

Greenhouse gas emissions of environmentally sustainable diets: Insights from the Icelandic National Dietary Survey 2019–2021

BackgroundHealth authorities are increasingly integrating environmental sustainability considerations into food-based dietary guidelines. However, concerns persist about the accuracy of the data used to assess environmental impacts, as well as the extent to which these guidelines are followed in practice. AimTo compare dietary greenhouse gas (GHG) emissions estimates using different top-down and bottom-up life cycle assessment (LCA) databases; and to estimate GHG emissions of food consumption within the ranges set for meat and dairy in recently proposed environmentally sustainable diets. MethodsDietary GHG emissions were estimated for participants in the 2019–2021 Icelandic National Dietary Survey (n = 822) using three publicly available LCA databases from Denmark, the US, and France. GHG emissions among participants whose consumption was aligned with the EAT-Lancet diet, the 2021 Danish food-based dietary guidelines and the 2023 Nordic Nutrition Recommendations were also quantified. ResultsThe mean dietary GHG emissions among participants were 6.3, 6.1, and 6.1 kg CO2-eq/day based on the Danish (top-down), US (bottom-up), and French (bottom-up) databases, respectively. The relative ranking of foods was also consistent across all three databases. For example, the relative contribution of total CO2-eq (% range for the three databases) was highest for red meat (39–51%), followed by dairy (10–17%) and beverages (9–13%). The contribution from plant-based foods (6–10%), seafood (4–11%), and poultry/eggs (<5%) was modest. The dietary habits of most participants (86%) were outside the ranges for meat and dairy consumption as set by the three sustainable diets. However, participants reporting consumption within the ranges for meat and dairy had mean GHG emissions ranging between 4.2 and 4.7 kg CO2-eq/day, depending on the diet. In comparison, the mean for participants not adhering to the sustainable diets was 7.7 kg CO2-eq/day. These results are higher than those reported in other Nordic and European studies, likely due to high consumption of lamb, beef, and dairy, and low consumption of plant-based food. ConclusionAll three LCA databases provided similar estimates for total dietary GHG emissions and relative ranking of different food groups. Based on current dietary habits in Iceland, adherence to environmentally sustainable diets would lead to a substantial reduction in dietary GHG emissions.

Public Health Impact and Cost-Effectiveness Analysis of 4-Component Meningococcal Serotype B Vaccination for Infants in France.

In France, meningococcal serogroup B (MenB) is the most common serogroup causing invasive meningococcal disease (IMD) in infants and young children. Our objective was to illustrate the impact of model choices on health outcomes and the cost-effectiveness of infant vaccination with the multicomponent meningococcal serogroup B vaccine (4CMenB) versus no vaccine in France. A previously published dynamic transmission-based cost-effectiveness model was adapted for the French context using updated, French-specific demographic, epidemiological, and cost data. IMD incidence and long-term sequelae were derived through analysis of French healthcare and surveillance databases. A collective perspective over a 100-year time horizon was adopted, with a discount rate of 2.5%, reduced to 1.5% after the first 30 years. Deterministic and probabilistic sensitivity and scenario analyses were performed. In the base case analysis, infant vaccination with 4CMenB avoided 3101 MenB IMD cases in infants aged <1 year (-54%) and 6845 cases in all age groups (-21%). The estimated incremental cost-effectiveness ratio was €316,272/quality-adjusted life-year (QALY) but was highly sensitive to the types of sequelae included, MenB incidence, vaccine effectiveness parameters, and consideration of life-expectancy in IMD survivors (range: €65,272/QALY to €493,218/QALY). Using economic models compliant with French methodology guidelines, 4CMenB does not seem cost-effective; however, results are sensitive to model choices and 4CMenB immunization is an effective strategy to prevent MenB IMD cases and to improve quality of life and economic burden associated with MenB IMD treatment, especially with regard to long-term sequelae.

Examining the Adaptation of the Fama-French Three-Factor and Five-Factor Models in the US Market

The adaptability of the Fama-French three-factor and five-factor models in distinct markets is currently a key research topic. Some researchers are investigating whether the FF3FM and FF5FM are reasonable frameworks for explaining excess returns in stock markets by testing them with data from different markets. This paper mainly explores the adaptability of FF3FM and FF5FM in the US stock market, and adds CAPM to the comparison. This article uses the daily factors’ data and the daily average value weighted returns in 6 portfolios formed on size and book-to-market in the Kenneth French database website to construct a linear regression model to study the explanatory power of FF3FM and FF5FM in the US stock market. In order to determine whether these factors are parts of an effective asset pricing model, this paper assesses the efficacy, robustness, and reliability of factors in explaining asset returns using the Durbin-Watson test, the correlation matrix, and the sub-period analysis, which also confirm whether these factors have statistical significance, economic significance, and stability. It is found that the explanatory power of FF5FM is stronger than that of FF3FM in the US stock market. While both profitability and investment factors have relatively modest explanatory power, size and value factors offer significant explanatory power for stock returns.

Descriptive epidemiology of 30,223 histopathologically confirmed meningiomas in France: 2006-2015.

Meningioma is one of the most common neoplasm of the central nervous system. To describe the epidemiology of meningioma operated in France and, to assess grading and histopathological variability among the different neurosurgical centres. We processed the French Brain Tumour Database (FBTDB) to conduct a nationwide population-based study of all histopathologically confirmed meningiomas between 2006 and 2015. 30,223 meningiomas cases were operated on 28,424 patients, in 61 centres. The average number of meningioma operated per year in France was 3,022 (SD ± 122). Meningioma was 3 times more common in women (74.1% vs. 25.9%). The incidence of meningioma increased with age and, mean age at surgery was 58.5 ± 13.9 years. Grade 1, 2, and 3 meningiomas accounted for 83.9%, 13.91% and, 2.19% respectively. There was a significant variability of meningioma grading by institutions, especially for grade 2 which spanned from 5.1% up to 22.4% (p < 0.001). Moreover, the proportion of grade 2 significantly grew over the study period (p < 0.001). There was also a significant variation in grade 1 subtypes diagnosis among the institutions (p < 0.001). 89.05% of the patients had solely one meningioma surgery, 8.52% two and, 2.43% three or more. The number of surgeries was associated to the grade of malignancy (p < 0.001). The incidence of meningioma surgery increased with age and, peaked at 58.5 years. They were predominantly benign with meningothelial subtype being the most common. However, there was a significant variation of grade 1 subtypes diagnosis among the centres involved. The proportion of grade 2 meningioma significantly grew over the study time, on contrary to malignant meningioma proportion, which remained rare and, stable over time around 2%. Likewise, there was a significant variability of grade 2 meningioma rate among the institutions.

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

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

Factors associated with high costs of patients with metabolic dysfunction-associated steatotic liver disease: an observational study using the French CONSTANCES cohort

Background & aimsDespite its high prevalence in the western world metabolic dysfunction-associated steatotic liver disease (MASLD) does not benefit from targeted pharmacological therapy. We measured healthcare utilisation and identified factors associated with high-cost MASLD patients in France.MethodsThe prevalent population with MASLD (including non-alcoholic steatohepatitis) in the CONSTANCES cohort, a nationally representative sample of 200,000 adults aged between 18 and 69, was linked to the French centralised national claims database (SNDS). Study participants were identified by the fatty liver index (FLI) over the period 2015–2019. MASLD individuals were classified according as “high-cost” (above 90th percentile) or “non-high cost” (below 90th percentile). Factors significantly associated with high costs were identified using a multivariate logistic regression model.ResultsA total of 14,437 predominantly male (69%) participants with an average age of 53 ± SD 12 years were included. They mainly belonged to socially deprived population groups with co-morbidities such as diabetes, high blood pressure, mental health disorders and cardiovascular complications. The average expenditure was €1860 ± SD 4634 per year. High-cost MASLD cost €10,863 ± SD 10,859 per year. Conditions associated with high-cost were mental health disorders OR 1.79 (1.44–2.22), cardiovascular diseases OR 1.54 (1.21–1.95), metabolic comorbidities OR 1.50 (1.25–1.81), and respiratory disease OR 1.50 (1.11–2.00). The 10% high-cost participants accounted for 58% of the total national health care expenditures for MASLD.ConclusionOur results emphasize the need for comprehensive management of the comorbid conditions which were the major cost drivers of MASLD.Graphical

Evaluation of a machine-learning model based on laboratory parameters for the prediction of acute leukaemia subtypes: a multicentre model development and validation study in France

Acute leukaemias are life-threatening haematological cancers characterised by the infiltration of transformed immature haematopoietic cells in the blood and bone marrow. Prompt and accurate diagnosis of the three main acute leukaemia subtypes (ie acute lymphocytic leukaemia [ALL], acute myeloid leukaemia [AML], and acute promyelocytic leukaemia [APL]) is of utmost importance to guide initial treatment and prevent early mortality but requires cytological expertise that is not always available. We aimed to benchmark different machine-learning strategies using a custom variable selection algorithm to propose an extreme gradient boosting model to predict leukaemia subtypes on the basis of routine laboratory parameters. This multicentre model development and validation study was conducted with data from six independent French university hospital databases. Patients aged 18 years or older diagnosed with AML, APL, or ALL in any one of these six hospital databases between March 1, 2012, and Dec 31, 2021, were recruited. 22 routine parameters were collected at the time of initial disease evaluation; variables with more than 25% of missing values in two datasets were not used for model training, leading to the final inclusion of 19 parameters. The performances of the final model were evaluated on internal testing and external validation sets with area under the receiver operating characteristic curves (AUCs), and clinically relevant cutoffs were chosen to guide clinical decision making. The final tool, Artificial Intelligence Prediction of Acute Leukemia (AI-PAL), was developed from this model. 1410 patients diagnosed with AML, APL, or ALL were included. Data quality control showed few missing values for each cohort, with the exception of uric acid and lactate dehydrogenase for the cohort from Hôpital Cochin. 679 patients from Hôpital Lyon Sud and Centre Hospitalier Universitaire de Clermont-Ferrand were split into the training (n=477) and internal testing (n=202) sets. 731 patients from the four other cohorts were used for external validation. Overall AUCs across all validation cohorts were 0·97 (95% CI 0·95-0·99) for APL, 0·90 (0·83-0·97) for ALL, and 0·89 (0·82-0·95) for AML. Cutoffs were then established on the overall cohort of 1410 patients to guide clinical decisions. Confident cutoffs showed two (0·14%) wrong predictions for ALL, four (0·28%) wrong predictions for APL, and three (0·21%) wrong predictions for AML. Use of the overall cutoff greatly reduced the number of missing predictions; diagnosis was proposed for 1375 (97·5%) of 1410 patients for each category, with only a slight increase in wrong predictions. The final model evaluation across both the internal testing and external validation sets showed accuracy of 99·5% for ALL diagnosis, 98·8% for AML diagnosis, and 99·7% for APL diagnosis in the confident model and accuracy of 87·9% for ALL diagnosis, 86·3% for AML diagnosis, and 96·1% for APL diagnosis in the overall model. AI-PAL allowed for accurate diagnosis of the three main acute leukaemia subtypes. Based on ten simple laboratory parameters, its broad availability could help guide initial therapies in a context where cytological expertise is lacking, such as in low-income countries. None.