Underdetection of cases of COVID-19 in France threatens epidemic control.

As countries in Europe gradually relaxed lockdown restrictions after the first wave, test-trace-isolate strategies became critical to maintain the incidence of coronavirus disease 2019 (COVID-19) at low levels1,2. Reviewing their shortcomings can provide elements to consider in light of the second wave that is currently underway in Europe. Here we estimate the rate of detection of symptomatic cases of COVID-19 in France after lockdown through the use of virological3 and participatory syndromic4 surveillance data coupled with mathematical transmission models calibrated to regional hospitalizations2. Our findings indicate that around 90,000 symptomatic infections, corresponding to 9 out 10 cases, were not ascertained by the surveillance system in the first 7 weeks after lockdown from 11 May to 28 June 2020, although the test positivity rate did not exceed the 5% recommendation of the World Health Organization (WHO)5. The median detection rate increased from 7% (95% confidence interval, 6-8%) to 38% (35-44%) over time, with large regional variations, owing to a strengthening of the system as well as a decrease in epidemic activity. According to participatory surveillance data, only 31% of individuals with COVID-19-like symptoms consulted a doctor in the study period. This suggests that large numbers of symptomatic cases of COVID-19 did not seek medical advice despite recommendations, as confirmed by serological studies6,7. Encouraging awareness and same-day healthcare-seeking behaviour of suspected cases of COVID-19 is critical to improve detection. However, the capacity of the system remained insufficient even at the low epidemic activity achieved after lockdown, and was predicted to deteriorate rapidly with increasing incidence of COVID-19 cases. Substantially more aggressive, targeted and efficient testing with easier access is required to act as a tool to control the COVID-19 pandemic. The testing strategy will be critical to enable partial lifting of the current restrictive measures in Europe and to avoid a third wave.

Clinical presentation, course, and prognosis of patients with mixed connective tissue disease: A multicenter retrospective cohort.

OBJECTIVES: The objective of this study is to better characterize the features and outcomes of a large population of patients with mixed connective tissue disease (MCTD). METHODS: We performed an observational retrospective multicenter cohort study in France. Patients who fulfilled at least one diagnostic criterion set for MCTD and none of the criteria for other differentiated CTD (dCTD) were included. RESULTS: Three hundred and thirty patients (88% females, median [interquartile range] age of 35 years [26-45]) were included. The diagnostic criteria of Sharp or Kasukawa were met by 97.3% and 93.3% of patients, respectively. None met other classification criteria without fulfilling Sharp or Kasukawa criteria. After a median follow-up of 8 (3-14) years, 149 (45.2%) patients achieved remission, 92 (27.9%) had interstitial lung disease, 25 (7.6%) had pulmonary hypertension, and 18 (5.6%) died. Eighty-five (25.8%) patients progressed to a dCTD, mainly systemic sclerosis (15.8%) or systemic lupus erythematosus (10.6%). Median duration between diagnosis and progression to a dCTD was 5 (2-11) years. The presence at MCTD diagnosis of an abnormal pattern on nailfold capillaroscopy (odds ratio [OR] = 2.44, 95% confidence interval [95%CI] [1.11-5.58]) and parotid swelling (OR = 3.86, 95%CI [1.31-11.4]) were statistically associated with progression to a dCTD. Patients who did not progress to a dCTD were more likely to achieve remission at the last follow-up (51.8% vs. 25.9%). CONCLUSIONS: This study shows that MCTD is a distinct entity that can be classified using either Kasukawa or Sharp criteria, and that only 25.8% of patients progress to a dCTD during follow-up.

Incidence of serious respiratory tract infections and associated characteristics in a population exposed to immunosuppressive therapies: a register-based population study.

BACKGROUND: Immunosuppressive therapies are associated with a risk of infections. Nevertheless, their incidence in this population remains unclear. This study aims to determine the incidence of serious respiratory tract infections (SRI) in a population exposed to immunosuppressive therapies. METHODS: Data from a representative sample of the French healthcare claims from 01/01/2014 to 12/31/2019 were analyzed. Exposure to immunosuppressive therapy was defined by the dispensation of drugs through community pharmacies or in hospitals. SRI diagnosis was based on ICD-10 codes from hospitalization records. A cohort analysis was performed to estimate standardized SRI incidence rates. A nested case-control analysis within this cohort was used to study the characteristics associated with SRI. RESULTS: We identified 24,122 individuals exposed to immunosuppressive therapies, among which 1,559 developed SRI, resulting in a standardized incidence rate of 1,398 per 100,000 person-years. In this population, the risk of SRI was associated with a history of cancer (OR 2.68, 95% Confidence Intervals (CI) 2.24-3.21; p < 0.001), chronic respiratory disease (2.62, 95%CI 2.17-3.16; p < 0.001), end-stage renal failure (2.38, 95%CI 1.37-4.13; p = 0.003), neurodegenerative diseases (1.52, 95%CI 1.07-2.17; p = 0.026), diabetes (1.44, 95%CI 1.14-1.82; p < 0.001), psychiatric diseases (1.27, 95%CI 1.06-1.52; p < 0.001), and cardiovascular diseases (1.26, 95%CI 1.04-1.52; p = 0.002). Compared to corticosteroids alone, the risk of SRI was lower in individuals treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) only (0.44, 95%CI 0.25-0.78; p < 0.001). CONCLUSION: In the population exposed to immunosuppressive therapies, a history of chronic disease is associated with an increased risk of SRI. This risk is lower in those receiving csDMARD alone than corticosteroids alone.

General practitioners and palliative care practices: a better knowledge of specific services is still needed.

BACKGROUND: France allows deep sedation for pain relief, but not for euthanasia. In anticipation of an increase in home-based palliative care, the role of general practitioners is central to the design of outpatient palliative care services. This study aimed to describe the knowledge, attitudes, and practices of general practitioners in mainland France regarding palliative and end of life care. METHODS: This was a national descriptive cross-sectional study within the Sentinelles network. Self-report questionnaires were distributed to general practitioners between November 2020 and November 2021. A descriptive analysis was carried out. RESULTS: Out of the 123 participating general practitioners, 84% had received academic training in palliative care (n = 104). While a significant majority (69%) expressed comfort in pain management, only a quarter (25%) declared that they were competent at indicating deep and continuous sedation for pain relief. Awareness of outpatient palliative care facilities close to their place of practice such as hospitalization at home was over 97% (n = 117/120). Awareness of hospital facilities, including identified palliative care beds on hospital wards and palliative care units, was lower (75% (n = 59/79) and 86% (n = 86/100), respectively). CONCLUSIONS: Our results suggest that French general practitioners are reasonably aware of palliative care resources available. However, there is room for improvement, particularly in understanding hospital-based facilities. Furthermore, a quarter of the general practitioners expressed discomfort with deep and continuous sedation for pain relief, highlighting the need for increased training in this specific aspect of palliative and end of life care.

Dysregulation of neutrophil oxidant production and interleukin-1-related cytokines in granulomatosis with polyangiitis.

OBJECTIVES: Neutrophils play a key role in ANCA-associated vasculitis, both as targets of autoimmunity and facilitators of vascular damage. In granulomatosis with polyangiitis (GPA), data regarding the production of reactive oxygen species (ROS) in neutrophils are unclear. Further, recent data suggests that ROS production could have an anti-inflammatory effect through the regulation of the inflammasome and IL-1-related cytokines. We aimed to analyse the ROS production in neutrophils from patients with GPA and investigate its association with IL-1-related cytokines and the autoantigen proteinase 3 (PR3). METHODS: Seventy-two GPA patients with disease flare were included in the NEUTROVASC prospective cohort study. ROS production was evaluated in whole blood of patients with active GPA and compared with the same patients in remission or healthy controls. Associations between ROS production, PR3 membrane expression on neutrophils, serum levels of IL-1-related cytokines as well as inflammasome-related proteins were analyzed. RESULTS: We observed a robust defect in ROS production by neutrophils from patients with active GPA compared with healthy controls, independent of glucocorticoid treatment. Serum levels of IL-1-related cytokines were significantly increased in GPA patients, particularly in patients with kidney involvement, and levels of these cytokines returned to normal after patients achieved remission. Further, inflammasome-related proteins were significantly dysregulated in the cytosol of neutrophils as well as the serum from GPA patients. CONCLUSION: Our data suggests that ROS production and regulation of the inflammasome in neutrophils from patients with GPA are disturbed and may be a potential therapeutic target. CLINICAL TRIAL REGISTRATION NUMBER: NCT01862068, clinicaltrials.gov, https://www.clinicaltrials.gov.

Prevalence and bleeding risk associated with the concomitant use of direct oral anticoagulants and antiarrhythmic drugs in patients with atrial fibrillation, based on the French healthcare insurance database.

PURPOSE: Pharmacokinetic interactions exist between apixaban or rivaroxaban, and CYP3A4 and P-glycoprotein inhibitors such as amiodarone, verapamil and diltiazem. We aimed to estimate the prevalence of exposure to this drug-drug association (DDA) and to assess the bleeding risk associated in patients with atrial fibrillation (AF). METHODS: We conducted a cohort study using a representative 1/97th sample of the French healthcare insurance database between 2014 and 2019. Patients with AF receiving apixaban or rivaroxaban were included and followed-up until hospitalization for bleeding, death, discontinuation of apixaban or rivaroxaban, exposure to strong CYP3A4 inhibitor, or until December 31st 2019, whichever came first. Primary outcome was hospitalization for bleeding registered as primary diagnosis. The association between the exposure to the DDA and hospitalization for bleeding was evaluated as a time-dependent variable in Cox model. RESULTS: Between 2014 and 2019, the AF population under apixaban or rivaroxaban represented 10,392 patients. During the study period, the annual average prevalence of DDA exposure in this population was 38.9%. Among the 10,392 patients, 223 (2.1%) were hospitalized for bleeding, of which 75 (33.6%) received the association and 148 (66.4%) received apixaban or rivaroxaban alone. There was no association between DDA exposure and risk of hospitalization for bleeding (aHR = 1.19, [95% CI: 0.90, 1.58]). Age (HR 1.03 [1.02, 1.05]) and male gender (HR 1.72 [1.28, 2.30]) were associated with an increased risk of hospitalization for bleeding. CONCLUSION: Exposure to antiarrhythmic drugs was not associated with an increased risk of hospitalization for bleeding in patients with AF under rivaroxaban or apixaban.

Pertussis surveillance results from a French general practitioner network, France, 2017 to 2020.

IntroductionIn France, three complementary surveillance networks involving hospitals and paediatrician practices currently allow pertussis surveillance among infants (<1 year old) and children (1-12 years old). Data on incidences among adolescents (13-17 years old) and adults (≥ 18 years) are scarce. In 2017, a sentinel surveillance system called Sentinelles network, was implemented among general practitioners (GPs).AimThe purpose of Sentinelles network is to assess pertussis incidence, monitor the cases' age distribution and evaluate the impact of the country's vaccination policy. We present the results from the first 4 years of this surveillance.MethodsGPs of the French Sentinelles network reported weekly numbers of epidemiologically or laboratory-confirmed cases and their characteristics.ResultsA total of 132 cases were reported over 2017-2020. Estimated national incidence rates per 100,000 inhabitants were 17 (95% confidence interval (CI): 12-22) in 2017, 10 (95% CI: 6-14) in 2018, 15 (95% CI: 10-20) in 2019 and three (95% CI: 1-5) in 2020. The incidence rate was significantly lower in 2020 than in 2017-2019. Women were significantly more affected than men (83/132; 63% of women, p = 0.004); 66% (87/132) of cases were aged 15 years or over (median age: 31.5 years; range: 2 months-87 years). Among 37 vaccinated cases with data, 33 had received the recommended number of doses for their age.ConclusionsThese results concur with incidences reported in other European countries, and with studies showing that the incidences of several respiratory diseases decreased in 2020 during the COVID-19 pandemic. The results also suggest a shift of morbidity towards older age groups, and a rapid waning of immunity after vaccination, justifying to continue this surveillance.

Estimation of influenza-attributable burden in primary care from season 2014/2015 to 2018/2019, France.

Influenza viruses cause seasonal epidemics whose intensity varies according to the circulating virus type and subtype. We aim to estimate influenza-like illness (ILI) incidence attributable to influenza viruses in France from October 2014 to May 2019. Physicians participating in the French Sentinelles network reported the number of patients with ILI seen in consultation and performed nasopharyngeal swabs in a sample of these patients. The swabs were tested by RT-PCR for the presence of influenza viruses. These clinical and virological data were combined to estimate ILI incidence attributable to influenza viruses by subtypes and age groups. Influenza incidence rates over seasons ranged from 1.9 (95% CI, 1.9; 2.0) to 3.4% (95% CI, 3.2; 3.6) of the population. Each season, more than half of ILI cases were attributable to influenza. Children under 15 years were the most affected, with influenza incidence rates ranging from 3.0 (95% CI, 2.8;3.3) to 5.7% (95% CI, 5.3;6.1). Co-circulation of several (sub)types of influenza viruses was observed each year, except in 2016/2017 where A(H3N2) viruses accounted for 98.0% of the influenza cases. Weekly ILI incidences attributable to each influenza virus (sub)type were mostly synchronized with ILI incidence, except in 2014/2015 and 2017/2018, where incidence attributable to type B viruses peaked few weeks later. The burden of medically attended influenza among patients with ILI is significant in France, varying considerably across years and age groups. These results show the importance of influenza surveillance in primary care combining clinical and virological data.

Incidence and severity of pertussis hospitalisations in infants aged less than 1 year in 37 hospitals of six EU/EEA countries, results of PERTINENT sentinel pilot surveillance system, December 2015 to December 2018.

IntroductionPERTINENT is a pilot active surveillance system of infants hospitalised with pertussis in six European Union/European Economic Area countries (37 hospitals, seven sites).AimThis observational study aimed to estimate annual pertussis incidence per site from 2016 to 2018 and respective trends between 2017 and 2018. Pertussis cases were described, including their severity.MethodsWe developed a generic protocol and laboratory guidelines to harmonise practices across sites. Cases were hospitalised infants testing positive for Bordetella pertussis by PCR or culture. Sites collected demographic, clinical, laboratory data, vaccination status, and risk/protective factors. We estimated sites' annual incidences by dividing case numbers by the catchment populations.ResultsFrom December 2015 to December 2018, we identified 469 cases (247 males; 53%). The median age, birthweight and gestational age were 2.5 months (range: 0-11.6; interquartile range (IQR): 2.5), 3,280 g (range: 700-4,925; IQR: 720) and 39 weeks (range: 25-42; IQR: 2), respectively. Thirty cases (6%) had atypical presentation either with cough or cyanosis only or with absence of pertussis-like symptoms. Of 330 cases with information, 83 (25%) were admitted to intensive care units including five deceased infants too young to be vaccinated. Incidence rate ratios between 2018 and 2017 were 1.43 in Czech Republic (p = 0.468), 0.25 in Catalonia (p = 0.002), 0.71 in France (p = 0.034), 0.14 in Ireland (p = 0.002), 0.63 in Italy (p = 0.053), 0.21 in Navarra (p = 0.148) and zero in Norway.ConclusionsIncidence appeared to decrease between 2017 and 2018 in all but one site. Enhanced surveillance of hospitalised pertussis in Europe is essential to monitor pertussis epidemiology and disease burden.

Use of the French healthcare insurance database to estimate the prevalence of exposure to potential drug-drug interactions.

PURPOSE: Drug-drug interactions (DDIs) require monitoring in an aging population with increasing polypharmacy exposure. We aimed to estimate the prevalence of exposure to potential DDIs using the French healthcare insurance system database, for six DDIs with various clinical relevance: angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs (ARBs-ACEIs + NSAIDs), antiplatelet agents and NSAIDs (AAP + NSAIDs), serotonergic drugs and tramadol (SD + T), statins and macrolides (S + M), oral anticoagulant and NSAIDs (OAC + NSAIDs), and colchicine and macrolides (C + M). METHODS: We used exhaustive healthcare data from a 1/97th random sample of the population covered by the French health insurance system (EGB) between 2006 and 2016. Exposure to a DDI was defined as overlapping exposure to two interacting drugs. The prevalence of exposure was estimated by year. RESULTS: Prevalence of exposure in 2016 was estimated at 3.7% for ARBs-ACEIs + NSAIDs, 1.5% for AAP + NSAIDs, 0.76% for SD + T, 0.36% for S + M, 0.24% for AOC + NSAIDs, and 0.02% for C + M. In 26% to 58% of episodes of exposure, the two interacting drugs were prescribed by the same physician and dispensed by the same pharmacy the same day. Between 2006 and 2016, the yearly prevalence was increasing for SD + T and for DDIs involving NSAIDs, and it was decreasing for those involving macrolides. CONCLUSION: Exposures to potential DDIs in France are not uncommon with a high proportion resulting from a co-prescription by the same physician. Monitoring the prevalence of exposure to DDIs is needed to implement prevention measures. Administrative data enable this surveillance in large and representative cohorts.

Determinants and risk factors of gastroenteritis in the general population, a web-based cohort between 2014 and 2017 in France.

BACKGROUND: Although it is rarely fatal in developed countries, acute gastroenteritis (AGE) still induces significant morbidity and economic costs. The objective of this study was to identify factors associated with AGE in winter in the general population. METHODS: A prospective study was performed during winter seasons from 2014 to 2015 to 2016-2017. Participants filled an inclusion survey and reported weekly data on acute symptoms. Factors associated with having at least one AGE episode per winter season were analyzed using the generalized estimating equations (GEE) approach. RESULTS: They were 13,974 participants included in the study over the three seasons. On average, 8.1% of participants declared at least one AGE episode during a winter season. People over 60 declared fewer AGE episodes (adjusted OR (aOR) = 0.76, 95% CI [0.64; 0.89]) compared to individuals between 15 and 60 years old, as well as children between 10 and 15 (aOR = 0.60 [0.37; 0.98]). Overweight (aOR = 1.25 [1.07; 1.45]) and obese (aOR = 1.47 [1.19; 1.81]) individuals, those having frequent cold (aOR = 1.63 [1.37; 1.94]) and those with at least one chronic condition (aOR = 1.35 [1.16; 1.58]) had more AGE episodes. Living alone was associated with a higher AGE episode rate (aOR = 1.31 [1.09; 1.59]), as well as having pets at home (aOR = 1.23 [1.08; 1.41]). CONCLUSIONS: Having a better knowledge of AGE determinants will be useful to adapt public health prevention messages.

Management in primary care at the time of a suicide attempt and its impact on care post-suicide attempt: an observational study in the French GP sentinel surveillance system.

BACKGROUND: We aimed to describe primary care management at the time of a suicide attempt (SA) and after the SA. METHODS: An observational (cross-sectional) study was conducted among 166 sentinel GPs within France (a non-gatekeeping country) between 2013 and 2017 for all GP's patients who attempted suicide. MEASUREMENTS: frequency of patients 1) managed by the GP at the time of the SA, 2) addressed to an emergency department (ED), 3) without care at the time of the SA, and 4) managed by the GP after the SA and factors associated with GP management at the time of and after the SA. RESULTS: Three hundred twenty-one SAs were reported, of which N = 95 (29.6%) were managed by the GP at the time of the SA, N = (70.5%) were referred to an ED, and N = (27.4%) remained at home. Forty-eight (14.9%) patients did not receive any care at the time of the SA and 178 (55.4%) were managed directly by an ED. GPs were more likely to be involved in management of the patient at the time of the SA if they were younger (39.2% for patients < 34 years old; 22.9% for those 35 to 54 years old, and 30.3% for those more than 55 years old p = 0.02) or the SA involved a firearm or self-cutting (51.9%) versus those involving drugs (23.7%); p = 0.006). After the SA, GPs managed 174 patients (54.2%), more often (60%) when they provided care at home at the time of the SA, p = 0.04; 1.87 [1.07; 3.35]. No other factor was associated with management by GPs after the SA. CONCLUSIONS: The study faced limitations: data were not available for patients managed solely by specialists during their SA and results may not be generalisable to countries with a stronger gatekeeping system. We concluded that GPs are involved in the management of patients at the time of a SA for a third of patients. EDs are the major provider of care at that time. Half patients consulted GPs after the SA and connections between GPs and ED upon discharge should be improved.

A top 5 list for French general practice.

BACKGROUND: Medical overuse is an issue that has recently gained attention. The "Choosing Wisely" campaign invited each specialty in each country to create its own top five lists of care procedures with a negative benefit-risk balance to promote dialogue between patients and physicians. This study aims to create such a list for French general practice. METHODS: A panel of general practitioners (GPs) suggested care procedures that they felt ought to be prescribed less. Using the Delphi method, a short list of those suggestions was selected. Systematic literature reviews were performed for each item on the short list. The results were presented to the panel to assist with the final selection of the top five list. RESULTS: The panel included 40 GPs. The list includes: i/ antibiotics prescription for acute bronchitis, nasopharyngitis, otitis media with effusion, or uncomplicated influenza, ii/ systematic prostate specific antigen testing in men older than 50, iii/ prescription of cholinesterase inhibitors for mild cognitive impairment and for Alzheimer's disease and memantine for Alzheimer's disease, iv/ statins prescription in primary prevention of cardio-vascular risk in older patients, and v/ benzodiazepine or benzodiazepine-like agents prescription for generalised anxiety, insomnia, and for all indications in older patients. CONCLUSIONS: This study resulted in a French top five list in general practice using a panel of GPs. All the items selected have a negative risk-benefit balance and are frequently prescribed by French general practitioners. This list differs from other top five lists for general practice, reflecting the local medical culture.

Excess cases of influenza-like illnesses synchronous with coronavirus disease (COVID-19) epidemic, France, March 2020.

Several French regions where coronavirus disease (COVID-19) has been reported currently show a renewed increase in ILI cases in the general practice-based Sentinelles network. We computed the number of excess cases by region from 24 February to 8 March 2020 and found a correlation with the number of reported COVID-19 cases so far. The data suggest larger circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the French population than apparent from confirmed cases.

The French Society of Internal Medicine's Top-5 List of Recommendations: a National Web-Based Survey.

BACKGROUND: The international project "Choosing Wisely" aims to target unnecessary and potentially harmful examinations and treatments. OBJECTIVE: To define the French Internal Medicine Top-5 list. DESIGN: Based on a review of existing Top-5 lists and personal experience, a working group of the French National Society of Internal Medicine selected 27 diagnostic and therapeutic procedures. They were submitted through a national web-based survey to French internists who rated from 1 to 5 the perceived frequency, uselessness, and risk of each procedure. A composite score was calculated as the unweighted addition of the three scores. PARTICIPANTS: Four hundred thirty internists answered the web-based survey (14% of all French internists including residents). All the French regions and status of the profession were represented. KEY RESULTS: For the 27 submitted procedures, the mean score (± SD) was 3.25 (± 0.48) for frequency, 3.10 (± 0.43) for uselessness, and 2.63 (± 0.84) for risk. The Top-5 list obtained with the composite score was as follows: 1. Do not prescribe long-term treatment with proton pump inhibitors without regular reevaluation of the indication 2. Do not administer preventive treatments (e.g., for dyslipidemia, hypertension…) in elderly people with dementia when potential risks outweigh the benefits 3. Do not administer hypnotic medications as first-line treatment for insomnia 4. Do not treat with an anticoagulant for more than 3 months a patient with a first venous thromboembolism occurring in the setting of a major transient risk factor 5. Do not screen for Lyme disease without an exposure history or related clinical examination findings We found that the composite score was strongly correlated to the risk score (rs = 0.88, p < 10-5) and not to the frequency (rs = 0.06, p = 0.75) or uselessness score (rs = 0.17, p = 0.38). CONCLUSIONS: This Top-5 list provides an opportunity to discuss appropriate use of health care practices in internal medicine.

Inflammatory disorders associated with trisomy 8-myelodysplastic syndromes: French retrospective case-control study.

OBJECTIVE: We report cases of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) with trisomy 8 associated with inflammatory and autoimmune diseases (IADs). METHOD: Data for 21 patients with trisomy 8-MDS/MPN and IADs were analyzed and compared to 103 patients with trisomy 8-MDS/MPN without IADs. RESULTS: The median age of MDS/MPN patients with IADs was 67 [59-80]. The IADs were Behçet's-like disease in 11 (52%) patients, inflammatory arthritis in 4 (19%) and Sjögren's syndrome, autoimmune hemolytic anemia, aseptic abscess, periarteritis nodosa, Sweet's syndrome and unclassified vasculitis in one patient each. Overall, 17/21 (81%) patients with IADs received treatment (88% with steroids), with complete and partial response in 7/17 (35%) and 8/17 (47%), respectively. The effect of MDS treatment on IADs could be assessed in seven patients receiving azacytidine: five achieved remission and two partial response. As compared with the 103 trisomy 8-MDS/MPN cases without IADs, those with IADs were more often non-European (P = 0.005) and had poor karyotype (P < 0.001). We found no difference in overall survival or acute myeloid leukemia progression between trisomy 8-associated MDS/MPN with and without IADs. CONCLUSION: The spectrum of IADs associated with trisomy 8-positive MDS/MPN is dominated by Behçet's-like disease. Steroid therapy is effective, but mostly sparing therapies are necessary. Azacytidine could be an effective alternative.

Cross-validation of an algorithm detecting acute gastroenteritis episodes from prescribed drug dispensing data in France: comparison with clinical data reported in a primary care surveillance system, winter seasons 2014/15 to 2016/17.

BACKGROUND: This study compares an algorithm to detect acute gastroenteritis (AG) episodes from drug dispensing data to the validated data reported in a primary care surveillance system in France. METHODS: We used drug dispensing data collected in a drugstore database and data collected by primary care physicians involved in a French surveillance network, from season 2014/15 to 2016/17. We used an adapted version of an AG discrimination algorithm to identify AG episodes from the drugstore database. We used Pearson's correlation coefficient to evaluate the agreement between weekly AG signals obtained from the two data sources during winter months, in the overall population, by specific age-groups and by regions. RESULTS: Correlations between AG signals for all ages were 0.84 [95%CI 0.69; 0.92] for season 2014/15, 0.87 [95%CI 0.75; 0.93] for season 2015/16 and 0.94 [95%CI 0.88; 0.97] for season 2016/17. The association between AG signals estimated from two data sources varied significantly across age groups in season 2016/17 (p-value < 0.01), and across regions in all three seasons studied (p-value < 0.01). CONCLUSIONS: There is a strong agreement between the dynamic of AG activity estimated from drug dispensing data and from validated primary care surveillance data collected during winter months in the overall population but the agreement is poorer in several age groups and in several regions. Once automated, the reuse of drug dispensing data, already collected for reimbursement purposes, could be a cost-efficient method to monitor AG activity at the national level.

Estimate of male urethritis incidences in France between 2007 and 2017 with a specific focus on Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis infections.

BACKGROUND: In a context of increasing use of Nucleic Acid Amplification Test, diagnoses of Neisseria gonorrhoeae and Chlamydia trachomatis infections among men increased in Europe and USA since 2007. We aimed to describe trends in the incidence of male urethritis in France between 2007 and 2017. METHODS: We analysed male urethritis clinical cases reported by the French GPs' Sentinelles network. RESULTS: GPs reported 1944 cases of male urethritis during the study period. The estimated annual incidence rates in men aged 15 years and older remained stable between 226 cases per 100,000 seen in 2007 and 196 in 2017 (P value = 0.9). A third-generation cephalosporin with macrolide or tetracycline was prescribed in 17.5% of cases in 2009 (27/154) and 32.4% in 2017 (47/145) (P value = 0.0327). CONCLUSIONS: The incidence rates for adult male urethritis diagnosed in primary care have remained stable since 2007 in France in contrast with the increasing trend of Neisseria gonorrhoeae and Chlamydia trachomatis infections based on microbiological surveillance. Using stable clinical definition for male urethritis seems essential to follow correctly epidemiological dynamic.

Factors associated with influenza-like-illness: a crowdsourced cohort study from 2012/13 to 2017/18.

BACKGROUND: Influenza generates a significant societal impact on morbidity, mortality, and associated costs. The study objective was to identify factors associated with influenza-like-illness (ILI) episodes during seasonal influenza epidemics among the general population. METHODS: A prospective study was conducted with the GrippeNet.fr crowdsourced cohort between 2012/13 and 2017/18. After having completed a yearly profile survey detailing socio-demographic, lifestyle and health characteristics, participants reported weekly data on symptoms. Factors associated with at least one ILI episode per influenza epidemic, using the European Centre for Disease Prevention and Control case definition, were analyzed through a conditional logistic regression model. RESULTS: From 2012/13 to 2017/18, 6992 individuals participated at least once, and 61% of them were women (n = 4258). From 11% (n = 469/4140 in 2013/14) to 29% (n = 866/2943 in 2012/13) of individuals experienced at least one ILI during an influenza epidemic. Factors associated with higher risk for ILI were: gender female (OR = 1.29, 95%CI [1.20; 1.40]), young age (< 5 years old: 3.12 [2.05; 4.68]); from 5 to 14 years old: 1.53 [1.17; 2.00]), respiratory allergies (1.27 [1.18; 1.37]), receiving a treatment for chronic disease (1.20 [1.09; 1.32]), being overweight (1.18 [1.08; 1.29]) or obese (1.28 [1.14; 1.44]), using public transport (1.17 [1.07; 1.29]) and having contact with pets (1.18 [1.09; 1.27]). Older age (≥ 75 years old: 0.70 [0.56; 0.87]) and being vaccinated against influenza (0.91 [0.84; 0.99]) were found to be protective factors for ILI. CONCLUSIONS: This ILI risk factors analysis confirms and further completes the list of factors observed through traditional surveillance systems. It indicates that crowdsourced cohorts are effective to study ILI determinants at the population level. These findings could be used to adapt influenza prevention messages at the population level to reduce the spread of the disease.

Population perception of mandatory childhood vaccination programme before its implementation, France, 2017.

BackgroundVaccination policy in France was previously characterised by the coexistence of eight recommended and three mandatory vaccinations for children younger than 2 years old. These 11 vaccines are now mandatory for all children born after 1 January 2018.AimTo study the French population's opinion about this new policy and to assess factors associated with a positive opinion during this changing phase.MethodsA cross-sectional survey about vaccination was conducted from 16 November-19 December 2017 among the GrippeNet.fr cohort. Data were weighted for age, sex and education according to the French population. Univariate and multivariate analyses were performed to identify factors associated with a favourable opinion on mandatory vaccines' extension and defined in the '3Cs' model by the World Health Organization Strategic Advisory Group of Experts working group on vaccine hesitancy.ResultsOf the 3,222 participants (response rate 50.5%) and after adjustment, 64.5% agreed with the extension of mandatory vaccines. It was considered a necessary step by 68.7% of the study population, while 33.8% considered it unsafe for children and 56.9% saw it as authoritarian. Factors associated with a positive opinion about the extension of mandatory vaccines were components of the confidence, complacency and convenience dimensions of the '3Cs' model.ConclusionsIn our sample, two thirds of the French population was in favour of the extension of mandatory vaccines for children. Perception of vaccine safety and benefits were major predictors for positive and negative opinions about this new policy.