Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Performances of statistical methods for the detection of seasonal influenza epidemics using a consensus-based gold standard.

Influenza epidemics are monitored using influenza-like illness (ILI) data reported by health-care professionals. Timely detection of the onset of epidemics is often performed by applying a statistical method on weekly ILI incidence estimates with a large range of methods used worldwide. However, performance evaluation and comparison of these algorithms is hindered by: (1) the absence of a gold standard regarding influenza epidemic periods and (2) the absence of consensual evaluation criteria. As of now, performance evaluations metrics are based only on sensitivity, specificity and timeliness of detection, since definitions are not clear for time-repeated measurements such as weekly epidemic detection. We aimed to evaluate several epidemic detection methods by comparing their alerts to a gold standard determined by international expert consensus. We introduced new performance metrics that meet important objective of influenza surveillance in temperate countries: to detect accurately the start of the single epidemic period each year. Evaluations are presented using ILI incidence in France between 1995 and 2011. We found that the two performance metrics defined allowed discrimination between epidemic detection methods. In the context of performance detection evaluation, other metrics used commonly than the standard could better achieve the needs of real-time influenza surveillance.

The economic burden of urinary tract infections in women visiting general practices in France: a cross-sectional survey.

BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections. Despite this burden, there are few studies of the costs of UTIs. The objective of this study was to determine the costs of UTIs in women over 18 years of age who visit general practitioners in France. METHODS: The direct and indirect costs of clinical UTIs were estimated from societal, French National Health Insurance and patient perspectives. The study population was derived from a national cross-sectional survey entitled the Drug-Resistant Urinary Tract Infection (Druti). The Druti included every woman over 18 years of age who presented with symptoms of UTI and was conducted in France in 2012 and 2013 to estimate the annual incidence of UTIs due to antibiotic-resistant Enterobacteriaceae in women visiting general practitioners (GPs) for suspected UTIs. RESULTS: Of the 538 women included in Druti, 460 were followed over 8 weeks and included in the cost analysis. The mean age of the women was 46 years old. The median cost of care for one episode of a suspected UTI was €38, and the mean cost was €70. The annual societal cost was €58 million, and €29 million of this was reimbursed by the French National Health Insurance system. In 25 % of the cases, the suspected UTIs were associated with negative urine cultures. The societal cost of these suspected UTIs with negative urine cultures was €13.5 million. No significant difference was found between the costs of the UTIs due to antibiotic-resistant E. coli and those due to wild E. coli (p = 0.63). CONCLUSION: In the current context in which the care costs are continually increasing, the results of this study suggests that it is possible to decrease the cost of UTIs by reducing the costs of suspected UTIs and unnecessary treatments, as well as limiting the use of non-recommended tests.

Physician practices in requesting stool samples for patients with acute gastroenteritis, France, August 2013-July 2014.

A better understanding of physician practices in requesting stool samples for patients with acute gastroenteritis (AG) is needed to more accurately interpret laboratory-based surveillance data. A survey was conducted in General Practitioners (GPs) between August 2013 and July 2014 to estimate the proportion of stool samples requested for patients with AG and to identify factors associated with GP requests for a stool sample. National health insurance (NHI) data together with surveillance data from a French Sentinel GP network were also used to estimate the proportion of stool samples requested. This proportion was estimated at 4·3% in the GP survey and 9·1% (95% confidence interval 8·7-9·6) using NHI data. Multivariate analysis indicated that the ratio of stool samples requested was almost five times higher in patients with bloody diarrhoea and 10-20 times higher in patients with a long duration of illness before consultation. Laboratory-based surveillance data underestimates the actual burden of disease as fewer than one in 10 AG cases consulting their GP will be requested to submit a stool sample for laboratory testing. This underestimation varies by pathogen as stool samples are more frequently requested for severe illness.

Incidence and hospitalisation rates of Lyme borreliosis, France, 2004 to 2012.

Lyme borreliosis (LB) has become a major concern recently, as trends in several epidemiological studies indicate that there has been an increase in this disease in Europe and America over the last decade. This work provides estimates of LB incidence and hospitalisation rates in France. LB data was obtained from the Sentinelles general practitioner surveillance network (2009­2012) and from the Programme de Médicalisation des Systèmes d'Information (PMSI) data processing centre for hospital discharges (2004­09). The yearly LB incidence rate averaged 42 per 100,000 inhabitants (95% confidence interval (CI): 37­48), ranging from 0 to 184 per 100,000 depending on the region. The annual hospitalisation rate due to LB averaged 1.55 per 100,000 inhabitants (95% CI: 1.42­1.70). Both rates peaked during the summer and fall and had a bimodal age distribution (5­10 years and 50­70 years). Healthcare providers should continue to invest attention to prompt recognition and early therapy for LB, whereas public health strategies should keep promoting use of repellent, daily checks for ticks and their prompt removal.

[Prevention of pertussis in newborns: Should pregnant women be vaccinated at each pregnancy?] / Prévention de la coqueluche chez le nouveau-né : faut-il vacciner les femmes enceintes à chaque grossesse ?

Pertussis is a respiratory disease that can be fatal at all ages but especially in infants before their mandatory vaccination. Recent epidemiological data shows a decrease in the number of pertussis cases, but a resurgence cannot be excluded in the coming years due to the cyclic evolution of the disease and the loosening of hygiene measures. Two approaches are used to protect infants before their vaccination: vaccination of the mother during pregnancy and vaccination of all the infant's close relatives (cocooning). The vaccination of the mother during pregnancy is more effective. The uncertain risk of chorioamniotitis associated with vaccination during pregnancy is insufficient to question this strategy.

[Suicide prevention: How to act?] / Prévention du suicide : comment agir ?

Although being complex, suicide is a phenomenon considered as preventable, and its prevention has been made as a public health priority. Some interventions to prevent suicide have been evaluated, such as the education of the healthcare workers, especially in the suicidal assessment (suicidal risk and suicidal emergency/dangerousness), the diagnosis and management of common mental disorders, the care provided after a suicide attempt, the restriction access to common means of suicide, the use of websites to educate the public, or the appropriate reports of suicide in media. Other interventions, even not rigorously evaluated, are implemented in France as in many parts of the world. It is the case of interventions among identified high-risk groups. To be efficient, prevention programs should simultaneously include different strategies targeting several known risk factors for suicide. Clinicians play a crucial role in the suicide prevention strategies.

Initial risk perception and feeling of preparedness of primary care physicians regarding the COVID-19 pandemic in Belgium, France and Spain in February 2020.

BACKGROUND: The knowledge of risk perceptions in primary care could help health authorities to manage epidemics. METHODS: A European multi-center cross-sectional study was conducted in France, Belgium and Spain to describe the perceptions, the level of anxiety and the feeling of preparedness of primary healthcare physicians towards the COVID-19 infection at the beginning of the pandemic. The factors associated with the feeling of preparedness were studied using multivariate logistic regressions. RESULTS: A total of 511 physicians participated to the study (response rate: 35.2%). Among them, only 16.3% (n=82) were highly anxious about the pandemic, 50.6% (n=254) had the feeling to have a high level of information, 80.5% (n=409) found the measures taken by the health authorities suitable to limit the spread of COVID-19, and 45.2% (n=229) felt prepared to face the epidemic. Factors associated with feeling prepared were: being a Spanish practitioner (adjusted OR=4.34; 95%CI [2.47; 7.80]), being a man (aOR=2.57, 95%CI [1.69; 3.96]), finding the measures taken by authorities appropriate (aOR=1.72, 95%CI [1.01; 3.00]) and being highly informed (aOR=4.82, 95%CI [2.62; 9.19]). CONCLUSIONS: Regarding the dramatic evolution of the pandemic in Europe in the weeks following the study, it appears that information available at this time and transmitted to the physicians could have given a wrong assessment of the spread and the severity of the disease. It seems essential to better integrate the primary care physicians into the information, training and protection channels. A comparison between countries could help to select the most effective measures in terms of information and communication.

Pertussis incidence among adolescents and adults surveyed in general practices in the Paris area, France, May 2008 to March 2009.

Since the introduction in 1998 of an adolescent pertussis vaccine booster (for persons aged 11-13 years) in France, the incidence of pertussis in adolescents and adults has been unknown. We therefore undertook a study to estimate the incidence of pertussis in these population groups and to evaluate the feasibility of a real-time electronic surveillance system for pertussis in general practices in France. The general practitioners selected for the study were located in Paris and the surrounding area. Polymerase chain reaction (PCR) or measurement of anti-pertussis toxin IgG levels by enzyme-linked immunosorbent assay (ELISA) was used to confirm the infection. Among the 204 patients enrolled in the study, 46 (23%) were diagnosed as having pertussis: 21 were confirmed cases, 24 were clinical cases and one was an epidemiological case. The median age of the 204 patients was 44 years and 134 (66%) were female. The median duration of the patients' cough at enrolment was 24 days. No clinical difference was observed between those with and without a pertussis diagnosis. The incidence of pertussis was estimated to be 145 (95% confidence interval: 121-168) per 100,000 population based on the results from the 10-month study period (calculated for 12 months). Problems in sample collection were identified: pertussis sentinel surveillance cannot be developed without training the staff of medical laboratories who take the biological samples. French health authorities were alerted and training procedures were developed.

[The use of venous catheter : Which ones to choose, how to prevent their complications?] / Utilisation des cathéters veineux : lesquels choisir, comment prévenir leurs complications ?

Intravenous catheters are multiple and essential for daily practice. They are also responsible for high morbidity and mortality. Simple or echo-guided peripheral venous catheters, midlines, PICCline, tunneled or non-tunneled central venous catheters, and implantable venous access device are currently at our disposal. Thus, catheter selection, duration and indications for use, and prevention and treatment of complications vary according to the situation. The objective of this update is to provide the clinician with an overview of knowledge and rules of good practice on the use of catheters.

[HIV prevention with PrEP: Challenges and prospects]. / Prévenir le VIH par la PrEP : enjeux et perspectives.

Pre-exposure prophlaxis (PrEP) is the use of antiretroviral drugs by uninfected people to prevent human immunodeficiency virus (HIV) infection. PrEP is used by people who are at substantial risk of being exposed to HIV. Numerous clinical trials have confirmed its effectiveness in reducing HIV acquisition and PrEP has been approved and allowed in several countries including France. However, PrEP uptake remains low as concerns about increase in sexual risk behaviour with PrEP use in the wake of a growing epidemic of sexually transmitted infections, and fear of drug resistance have been expressed. As a result, the difference between the proportion of people on PrEP and the proportion of people who would be very likely to use PrEP if they could access it -otherwise known as the PrEP gap- remains high. Nowadays, studies continue to explore long-term effects of PrEP as well as expand the array of available technologies and regimens.

[Pseudohyperkalemia and thrombocytosis]. / Pseudo-hyperkaliémie et thrombocytose.

INTRODUCTION: Hyperkalemia is common in medicine and requires rapid management. Besides the easily evoked causes such as renal failure, adrenal insufficiency, cell lysis or iatrogenic causes, false or pseudo-hyperkalemia should not be forgotten. OBSERVATIONS: Three patients (1 man, 2 women, aged 78, 84, 88) were managed for thrombocytosis (between 1306 and 2404 G/L) and non-symptomatic hyperkalemia (between 6.1 and 7.7mmol/L) are reported. Kalemia on blood collected in heparin tube was normal (4.4-4.6mmol/L). Therefore, no specific treatment for this pseudohyperkalemia was required. CONCLUSION: The combination of thrombocytosis and non-symptomatic hyperkalemia should suggest the diagnosis of pseudohyperkalemia and should prompt for a control of kalemia on blood collected in heparin tube. The recognition of this diagnosis is important in order to avoid unnecessary and potentially deleterious treatment of hyperkalemia.

[Characteristics of patients admitted from emergency units in 18 internal medicine departments and organisation of these departments: A cross sectional study from SNFMI (SiFMI study group) in 2015]. / Caractéristiques des patients admis en médecine interne dans 18 hôpitaux français en aval des urgences et organisation de ces services : enquête transversale de la SNFMI (groupe d'étude SiFMI) en 2015.

INTRODUCTION: Patients admitted from emergency units represent a large portion of the population in internal medicine departments. The aim of this study is to identify characteristics of patients and organization of these departments. METHODS: Between June 29th and July 26th 2015, voluntary internal medicine departments from the SiFMI group prospectively filled anonymized internet forms to collect data of each patients admitted in their ward from emergency units, during seven consecutive days. RESULTS: Three hundred and sixty-five patients from emergency departments were admitted in 18 internal medicine inpatients departments, totalling 1100 beds and 33,530 annual stays, 56% of them for emergency units inpatients. Mean age was 68 years, 54% were women, mean Charlson score was 2.6 and 44% of the patients took at least three drugs. Main causes of hospitalization were infectious (29%) and neurological (17%) diseases. Mean length of stay was 9.2 days. The medical team was composed by a median value of 4,5 [2,75-6,25] senior full-time equivalents, 86% were internists. Each department except one received residents, two third of them were from general medicine. CONCLUSION: This study highlights a high organizational variability among internal medicine departments and patients, and sets internal medicine as a specialty with a great capacity to achieve an integrative/comprehensive management of patients and to offer a comprehensive basis for physicians in training.

Impact of glucocorticoid-induced adverse events on adherence in patients receiving long-term systemic glucocorticoid therapy.

BACKGROUND: Factors influencing adherence to long-term (i.e. ≥ 3 months) systemic glucocorticoid therapy are poorly understood. OBJECTIVE: To evaluate the relationship between glucocorticoid-induced adverse events and therapeutic adherence in patients on long-term glucocorticoid treatment. METHODS: A cross-sectional survey was conducted in three departments of dermatology/internal medicine between April and September 2008. Patients were asked to provide data regarding symptoms they attributed to glucocorticoids, and adherence to treatment was measured using the four-item Morisky-Green adherence scale. Logistic regression analyses were used to assess the association between reported adverse events and adherence to glucocorticoids. RESULTS: A total of 255 questionnaires were completed and analysed [women 78%; median age 48 years (interquartile range (IQR) 34-65); connective tissue diseases 59%; median duration of treatment 24 months (IQR 8-72); median daily dose 10 mg (IQR 6-20)]. Among these 255 patients, 199 (78%) reported themselves as 'good adherents' and 56 (22%) as 'poor adherents' to treatment. Poor adherence was associated with younger age [odds ratio (OR) 0·97, 95% confidence interval (CI) 0·95-0·99, per increasing year; P < 0·01], presence of glucocorticoid-induced epigastralgia (OR 4·02, 95% CI 2·00-8·09; P < 0·01) and presence of glucocorticoid-induced morphological changes (OR 2·49, 95% CI 1·19-5·21; P = 0·02). Moreover, patients with poor adherence were likely to report concomitantly poor adherence to dietary advice associated with glucocorticoid therapy (OR 2·44, 95% CI 1·12-5·26; P = 0·02). CONCLUSIONS: As with other chronic therapies, the presence of glucocorticoid-induced adverse events is associated with an altered self-reported adherence to glucocorticoids. Patients who report epigastric pain or morphological changes that they associate with glucocorticoid therapy are particularly at risk of poor adherence. Adherence to dietary advice associated with glucocorticoid therapy may be an indirect measure of treatment adherence.

Micro and macro population effects in disease transmission: the case of varicella.

Profiles of varicella-zoster virus (VZV) seroprevalence have shown large variability in European countries in which vaccination has not been implemented. Differences in micro and macro population structures (e.g. household and municipality, respectively) may explain such variability, which is the focus of a population-based study of varicella in 12,000 children from 7800 French households in Corsica. The cumulative incidence was 89% at age 11 years, as the median age at infection was 5 years in first-born children, but decreased to 3.9 years in younger siblings. Hazard of infection in households increased as the first-born child initially enrolled in primary school. Age at infection was higher in less populated areas. Household attack rates increased with age (55% in <6 months, >90% in >3 years) and household secondary attack rate was approximately 70%. Several levels of population structure independently affect age at varicella infection.

[An abscessed granulomatous prostatitis]. / Une prostatite granulomateuse abcédée.

INTRODUCTION: Prostatic abscesses are usually diagnosed in the setting of bacterial prostatitis. Rarely, they reveal or complicate granulomatous prostatitis. CASE REPORT: A 55-year-old man was admitted for acute urinary retention. Urine culture was sterile, with leukocyturia > 106/ml. After failure of antibiotic therapy with cefotaxime, CT scan revealed a necrotic prostatic collection and a nodular non-necrotic tissular lesion in the left upper lung lobe. Trans-rectal drainage of the prostatic lesion and lung biopsies revealed granuloma with multinucleated giant cells (without mycobacteria). The diagnosis of granulomatosis with polyangiitis was confirmed by high level of anti-proteinase 3 antibodies. Treatment with steroids and rituximab resulted in apyrexia, regression of the inflammatory syndrome and clinical manifestations. CONCLUSION: The diagnosis of granulomatosis with polyangiitis should be considered in the presence of a non-infectious granulomatous prostatitis with systemic involvement.

[A tularemia mimicking lymphoma]. / Une tularémie mimant un lymphome.

INTRODUCTION: Adenopathies are a frequent cause of recourse in internal medicine. When histological analysis reveals the presence of granuloma, multiple infectious or non-infectious etiologies are considered. If diagnoses of lymphoma, sarcoidosis or tuberculosis are easily mentioned, tularemia should also be considered in the differential diagnosis. OBSERVATION: A 54-year-old patient had a fever at the evening with night sweats and a cough resistant to two lines of antibiotics. A thoraco-abdomino-pelvic CT scan revealed hilar and mediastinal adenopathies that appeared hypermetabolic with PET-TDM, as well as pulmonary nodules. A PCR performed on lymph node biopsy and serology allowed the diagnosis of tularemia. The evolution was favourable after antibiotic treatment. CONCLUSION: The association of fever, night sweats, altered general state and mediastinal adenopathies should be considered as a diagnosis of tularemia. Ganglionic biopsy, combined with molecular biology techniques and serology, can confirm the diagnosis.

[Cerebral infarction and tuberculosis: case report and literature review]. / Infarctus cérébral et tuberculose : rapport d'un cas et analyse de la littérature.

INTRODUCTION: Although tuberculous meningitis is an uncommon presentation of tuberculosis, it still remains one of the deadliest forms of this disease. In this context, the occurrence of a cerebral infarct is an aggravating factor. OBSERVATION: A 48-year-old Asian man presented himself in the emergency room for dysarthria and dysphagia of progressive onset. Cerebral CT showed a recent ischemic defect of the right internal capsule. Lumbar puncture showed meningitis with low sugar levels. Pulmonary micronodules on the thoracic CT suggested tuberculosis, which was confirmed by a broncho-alveolar lavage. Anti-tuberculosis treatment and early corticosteroid resulted in an improvement of the patient's state. CONCLUSION: Cerebral infarctions in patients with tuberculous meningitis are events that cannot be underestimated in terms of frequency or severity. Their poor prognosis is partly the result of insufficiently defined management, which combines anti-tuberculosis treatment and early corticosteroid therapy.

[Association between psychiatric comorbidities and hospital length of stay in post-emergency internal medicine patients]. / Association des comorbidités psychiatriques avec la durée de séjour des patients en médecine interne d'aval des urgences.

INTRODUCTION: Patients with psychiatric disorders suffer from a higher rate of somatic disorders than those without psychiatric disorder, often inappropriately managed. Our study aimed to describe patients with psychiatric comorbidity in post-emergency internal medicine units and to compare their length of hospital stay to patients without psychiatric disease. METHODS: This French cross sectional study used the data warehouse of the greater Paris hospitals. It included, all patients hospitalized through the emergency department in 9 internal medicine departments during the year 2017. Psychiatric disorders and the burden of somatic disorders (Charlson score) were determined through diagnostic coding. Charlson score and hospital length of stay were compared between patients with and without psychiatric comorbidity. RESULTS: In total, 8981 hospital stays (8001 patients) were included, 1867 (21%) with psychiatric comorbidity. After adjusting for age, gender, hospital and main diagnosis, the Charlson score was on average 0.68 higher in the psychiatric comorbidity group (P<0.001) and the length of hospital stay was 30% higher after further adjustment on the Charlson score (P<0.001). These differences were consistent for each main diagnosis. CONCLUSION: Patients with psychiatric comorbidity are frequent in post-emergency internal medicine wards. They experience longer hospital stays, only partly related with a higher burden of somatic disorders. Special attention should be paid to this vulnerable population.

Early estimates of 2009 pandemic influenza A(H1N1) virus activity in general practice in France: incidence of influenza-like illness and age distribution of reported cases.

In the end of August 2009, an unusually elevated level of influenza-like illness (ILI) activity was reported to the French Sentinel Network. We quantified the observed excess in ILI cases in France during summer 2009 and characterised age patterns in reported cases. An excess of cases has been observed since 5 July, with a time increasing trend. The cumulated estimated excess number of ILI cases was 269,935 [179,585; 316,512], corresponding to 0.5% French population over the period. Compared to the same period in the past years, relative cumulated incidence was greater among young subjects and lower among subjects over 65 years old. Compared to past epidemics, the relative cumulated incidence was greater in children less than 5 years old. This excess of cases may reflect the current spread of the A(H1N1) virus in France, subject to the following limitations: estimates were based on clinical cases consulting a GP; large media coverage may have led to a non specific increase in consultation rates.