Prevalence of long COVID in the general adult population according to different definitions and sociodemographic and infection characteristics. A nationwide random sampling survey in France in autumn 2022.

OBJECTIVES: Long COVID has been recognized since early 2020, but its definition is not unanimous, which complicates epidemiological assessments. This study estimated the prevalence of long COVID based on several definitions and severity thresholds in the adult population of mainland France and examined variations according to sociodemographic and infection characteristics. METHODS: A cross-sectional survey using random sampling was conducted in August-November 2022. Participants declaring SARS-CoV-2 infection were assessed for infection dates and context, post-COVID symptoms (from a list of 31, with onset time, daily functioning impact, and alternative diagnosis), and perceived long COVID. Long COVID prevalence was estimated according to the WHO, National Institute for Health and Care Excellence, United States National Centre for Health Statistics, and United Kingdom Office for National Statistics definitions. RESULTS: Of 10 615 participants, 5781 (54.5%) reported SARS-CoV-2 infection, with 123-759 (1.2-13.4%) having long COVID, depending on the definition. The prevalence of WHO post-COVID condition (PCC) was 4.0% (95% CI: 3.6-4.5) in the overall population and 8.0% (95% CI: 7.0-8.9) among infected individuals. Among the latter, the prevalence varied from 5.3% (men) to 14.9% (unemployed) and 18.6% (history of hospitalization for COVID-19). WHO-PCC overlapped poorly with other definitions (kappa ranging from 0.18 to 0.59) and perceived long COVID (reported in only 43% of WHO-PCC). DISCUSSION: Regardless of its definition, long COVID remains a significant burden in the French adult population that deserves surveillance, notably for forms that strongly impact daily activities. More standardized definitions will improve integrated surveillance of, and better research on, long COVID.

Urine concentration impairment in sickle cell anemia: genuine nephrogenic diabetes insipidus or osmotic diuresis?

The urine concentration impairment responsible for hyposthenuria in sickle cell nephropathy is currently thought to be a consequence of renal medulla lesions, which lead to nephrogenic diabetes insipidus. The objective of the present study was to investigate the mechanism of hyposthenuria in patients with sickle cell anemia. We performed an observational study of patients with homozygous SS sickle cell anemia and data available on the fasting plasma antidiuretic hormone (ADH) concentration. A total of 55 patients were analyzed. The fasting plasma ADH values ranged from 1.2 to 15.4 pg/mL, and 82% of the patients had elevated ADH values and low fasting urine osmolality (<505 mosmol/kgH2O). Plasma ADH was positively associated with plasma tonicity and natremia (P < 0.001). None of the patients experienced polyuria and fasting free water clearance was negative in all cases, thus, ruling out nephrogenic diabetes insipidus. The tertile groups did not differ with regard to fasting urine osmolality, plasma renin level, mGFR, or several hemolysis biomarkers. The negative fasting free water clearance in all cases and the strong association between 24-h osmolal clearance and 24-h diuresis favors the diagnosis of osmotic diuresis due to an impaired medullary gradient, rather than lesions to collecting tubule.NEW & NOTEWORTHY The urine concentration impairment in sickle cell anemia is an osmotic diuresis related to an impaired renal medullary gradient leading to an ADH plateau effect. The fasting plasma ADH was high in the context of a basic state of close-to-maximal urine concentration probably driven by short nephrons maintaining a cortex-outer medullary gradient (about 400 milliosmoles). The patients had a low daily osmoles intake without evidence of thirst dysregulation so no one experienced polyuria.

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.

Use of tramadol and the risk of bleeding complications in patients on oral anticoagulants: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to determine whether tramadol intake increases the risk of bleeding in patients receiving oral anticoagulants. METHODS: This systematic review was registered on PROSPERO, CRD42022327230. We searched PubMed and Embase up to 14 April 2022, and references and citations of included studies were screened. Comparative and non-comparative studies exploring bleeding complications among adult patients on oral anticoagulants and tramadol were included. Risk of bias was assessed using an adaptation of the Drug Interaction Probability Scale for case reports and case series and the Newcastle-Ottawa Scale for comparative studies. A meta-analysis was performed for the risk of serious bleeding (leading to hospitalisation or death) associated with tramadol in patients on vitamin K antagonists. RESULTS: A total of 17 studies were included: 1 case series, 12 case reports, 2 case-control studies and 2 cohort studies. Most of the studies described tramadol-vitamin K antagonists' concomitant use; one case-control study also assessed dabigatran and rivaroxaban; one case report involved dabigatran. Among case reports/series, a total of 33 patients had a bleeding complication while using tramadol and an oral anticoagulant. The 4 comparative studies reported an increased bleeding risk during tramadol and vitamin K antagonist intake which was statistically significant in one study; the pooled risk ratio of serious bleeding was 2.68 [95% CI: 1.45 to 4.96; p < 0.001]. CONCLUSION: This systematic review confirms an association between tramadol use and risk of bleeding in patients on vitamin K antagonists. Evidence is too limited to assess whether this risk extends to patients on direct oral anticoagulants, and further studies are needed.

Role of non-invasive methods in detecting liver impairment in familial Mediterranean fever adult patients with persistent hepatic cytolysis.

Familial Mediterranean fever (FMF) patients may have hepatic cytolysis, although its origin is not formally elucidated. We aimed to evaluate liver involvement in familial Mediterranean fever (FMF) using non-invasive methods. All adult FMF patients harboring two non-ambiguous mutations of the MEFV gene with hepatic cytolysis were identified in a French tertiary adult center for FMF. Liver impairment was explored with FibroMax (a non-invasive method to estimate hepatic steatosis, necrosis, inflammation and fibrosis) and liver ultrasound. Among 520 FMF adult patients, 43 had persistent hepatic cytolysis and 20 patients were included (11 women, median age at inclusion: 49.5 years). According to the FibroMax results, patients were classified as having steatosis, fibrosis, and possible or definite nonalcoholic steato-hepatitis in 10 (50%), 9 (45%) and 7 (35%) of cases, respectively. The score of steatosis did not seem associated with the usual metabolic risk factors. No significant association was found between the cumulated dose of colchicine and any of the scores included in FibroMax. In adult FMF patients with persistent hepatic cytolysis, steatosis is the first cause to consider even in the absence of usual metabolic risk factors, suggesting other mechanisms. Colchicine did not seem to be involved in this toxicity.

'Involve me and I learn': an experiential teaching approach to improve dyspnea awareness in medical residents.

BACKGROUND: Dyspnea is a frightening and debilitating experience. It attracts less attention than pain ('dyspnea invisibility'), possibly because of its non-universal nature. We tested the impact of self-induced experimental dyspnea on medical residents. MATERIALS AND METHODS: During a teaching session following the principles of experiential learning, emergency medicine residents were taught about dyspnea theoretically, observed experimental dyspnea in their teacher, and personally experienced self-induced dyspnea. The corresponding psychophysiological reactions were described. Immediate and 1-year evaluations were conducted to assess course satisfaction (overall 0-20 grade) and the effect on the understanding of what dyspnea represents for patients. RESULTS: Overall, 55 emergency medicine residents participated in the study (26 men, median age 26 years). They were moderately satisfied with previous dyspnea teaching (6 [5-7] on a 0-10 numerical rating scale [NRS]) and expressed a desire for an improvement in the teaching (8 [7-9]). Immediately after the course they reported improved understanding of patients' experience (7 [6-8]), which persisted at 1 year (8 [7-9], 28 respondents). Overall course grade was 17/20 [15-18], and there were significant correlations with experimental dyspnea ratings (intensity: r = 0.318 [0.001-0.576], p = 0.043; unpleasantness: r = 0.492 [0.208-0.699], p = 0.001). In multivariate analysis, the only factor independently associated with the overall course grade was 'experiential understanding' (the experimental dyspnea-related improvement in the understanding of dyspneic patients' experience). A separate similar experiment conducted in 50 respiratory medicine residents yielded identical results. CONCLUSIONS: This study suggests that, in advanced medical residents, the personal discovery of dyspnea can have a positive impact on the understanding of what dyspnea represents for patients. This could help fight dyspnea invisibility.

Vegetarian and Vegan Diets: Beliefs and Attitudes of General Practitioners and Pediatricians in France.

Studies suggest a decreasing trend in the consumption of meat products and a growing interest in vegetarian diets. Medical support may be relevant, especially when switching to a vegan diet. Our objective was to describe the beliefs and attitudes of primary care physicians toward vegetarian diets. A cross-sectional survey was conducted among general practitioners and pediatricians thorough a questionnaire including socio-demographic characteristics, specific care to vegetarians, and the risks and benefits of vegetarian diets according to physicians. Out of the 177 participating physicians, 104 (59%) have seen at least one vegetarian patient in consultation in the last three months. Half of the physicians declared that they would dissuade their patients from switching to a vegan diet (n = 88, 51%) and 14% (n = 24) from switching to an ovo-lacto-vegetarian (OLV) diet. Most physicians (n = 141, 88%) did not feel informed enough about these diets. Physicians thought that the most frequent deficiencies for OLV and vegan diets were iron (76% and 84%, respectively) and protein (45% and 79%, respectively). These results highlight the fact that French primary care physicians feel concerned by this subject and need more information on these diets. Specific recommendations would be useful to support their practice and relationship with vegetarians.

Immediate consequences and solutions used to maintain medical education during the COVID-19 pandemic for residents and medical students: a restricted review.

BACKGROUND: The COVID-19 outbreak has dramatically impacted medical education, both bedside and academic teaching had to be adapted to comply with the reorganisation of care and social distancing measures. OBJECTIVES: To overview the impact of the pandemic on medical education, including the pedagogical responses adopted and their assessment by medical students and residents. MATERIAL AND METHODS: This restricted systematic review was performed using Rayyan QCRI, to select observational or interventional articles and field experience reports assessing the impact of the COVID-19 pandemic on medical education for medical students and residents. Study design, study population, geographical origin, use of an educational tools (including softwares and social media), their type and assessment, were recorded. For studies evaluating a specific tool the Medical Education Research Study Quality Instrument (MERSQI) was used to assess study quality. RESULTS: The literature search identified 1480 references and 60 articles were selected. Most articles focused on residents (41/60; 69%), and half (30/60; 50%) involved surgical specialties. Online courses were the most frequently used pedagogical tool (52/60; 88%). Simulation tools were used more frequently in articles involving surgical specialties (15/29; 52%) compared with medical specialties (2/14; 12%) (p=0.01). Only four studies reported the assessment of pedagogical tools by medical students, their MERSQI scores ranged from 5.5/18 to 9.0/18. CONCLUSION: Medical education was highly impacted by the COVID-19 pandemic particularly in surgical specialties. Online courses were the most frequently attempted solution to cope with social distancing constraints. Medical students' assessment of pedagogical tools was mostly positive, but the methodological quality of those studies was limited.

Risk of Bleeding Associated With Nonsteroidal Anti-inflammatory Drug Use in Patients Exposed to Antithrombotic Therapy: A Case-Crossover Study.

Concomitant nonsteroidal anti-inflammatory drug (NSAIDs) and antithrombotic drug use is associated with an increased risk of bleeding, mainly gastrointestinal. The goal of this study was to quantify the transient increase in the risk of hospitalization for bleeding associated with NSAID use in patients treated with antiplatelet agents or anticoagulants. We performed a unidirectional case-crossover study using the EGB (Échantillon généraliste de bénéficiaires), a permanent random sample of the French nationwide health database. Patients receiving antithrombotic therapy and hospitalized for bleeding between 2009 and 2017 were included. We compared their NSAID exposure during a 15-day hazard window immediately before hospital admission to 3 earlier 15-day control windows. The risk of hospitalization for bleeding associated with the recent use of NSAIDs was estimated using conditional logistic regression to estimate odds ratios (ORs). During the study period, 33 patients treated with anticoagulants and 253 treated with antiplatelet agents received NSAIDs and were included in the case-crossover analysis. We found an increased risk of hospitalization for gastrointestinal bleeding after exposure to NSAIDs, with an adjusted OR of 3.59 (95%CI, 1.58-8.17) in patients receiving anticoagulant therapy and 1.44 (95%CI, 1.07-1.94) in patients receiving antiplatelet therapy. The risk of nongastrointestinal bleeding was also increased after exposure to NSAIDs with an adjusted OR of 2.72 (95%CI, 1.23-6.04) in patients exposed to anticoagulant therapy. The risk of gastrointestinal and nongastrointestinal bleeding increases after NSAID use in patients treated with anticoagulants, while the risk of gastrointestinal bleeding increases, but to a lesser extent in those treated with antiplatelets.

External validation of prognostic scores for COVID-19: a multicenter cohort study of patients hospitalized in Greater Paris University Hospitals.

PURPOSE: The Coronavirus disease 2019 (COVID-19) has led to an unparalleled influx of patients. Prognostic scores could help optimizing healthcare delivery, but most of them have not been comprehensively validated. We aim to externally validate existing prognostic scores for COVID-19. METHODS: We used "COVID-19 Evidence Alerts" (McMaster University) to retrieve high-quality prognostic scores predicting death or intensive care unit (ICU) transfer from routinely collected data. We studied their accuracy in a retrospective multicenter cohort of adult patients hospitalized for COVID-19 from January 2020 to April 2021 in the Greater Paris University Hospitals. Areas under the receiver operating characteristic curves (AUC) were computed for the prediction of the original outcome, 30-day in-hospital mortality and the composite of 30-day in-hospital mortality or ICU transfer. RESULTS: We included 14,343 consecutive patients, 2583 (18%) died and 5067 (35%) died or were transferred to the ICU. We examined 274 studies and found 32 scores meeting the inclusion criteria: 19 had a significantly lower AUC in our cohort than in previously published validation studies for the original outcome; 25 performed better to predict in-hospital mortality than the composite of in-hospital mortality or ICU transfer; 7 had an AUC > 0.75 to predict in-hospital mortality; 2 had an AUC > 0.70 to predict the composite outcome. CONCLUSION: Seven prognostic scores were fairly accurate to predict death in hospitalized COVID-19 patients. The 4C Mortality Score and the ABCS stand out because they performed as well in our cohort and their initial validation cohort, during the first epidemic wave and subsequent waves, and in younger and older patients.

Hemodynamic and biological correlates of glomerular hyperfiltration in sickle cell patients before and under renin-angiotensin system blocker.

Glomerular hyperfiltration alone or associated with albuminuria is a well-known feature of sickle cell associated nephropathy. Though, glomerular hyperfiltration is currently considered to be related to a high renal plasma flow and chronic hemolysis, cardiac output influence on measured glomerular filtration rate (mGFR) have not been investigated so far. Thirty seven homozygous sickle cell patients (SCA) from the RAND study investigated before and under angiotensin converting enzyme inhibitor (ACEI) were included. Both mGFR and cardiac index (CI) were high (> 110 ml/min/1.73 m2 and > 3.5 l/m2 in 81% and 97% of cases) with low systemic vascular resistance (SVR) (< 700 dynes/s/cm-5) in 38% of cases. mGFR association with CI and SVR were significant at baseline (respectively ρ: 0.44, p = 0.008 and ρ: - 0.37, p = 0.02) and under ACEI (p = 0.007 and 0.01 respectively), in accordance with previous data showing that hyperfiltration was linked to an increased glomerular perfusion and a glomerulomegaly rather than increased capillary hydrostatic pressure. Of notice, after adjustment on CI, mGFR remained associated with reticulocyte count and albuminuria under ACEI (p = 0.006 and 0.02 respectively). Our results suggest that hyperfiltration is tightly linked to an increased cardiac output which may account for an increased renal blood flow. Chronic hemolysis could be a relevant factor accounting for hyperfiltration potentially acting on glomerular enlargement which appears as a key factor. Our data suggest that cardiac output assessment is a relevant tool in the routine management and monitoring of SCA nephropathy.

Risk factors for CKD stage II onset in a prospective cohort of homozygous sickle cell adults.

Prevalence of renal impairment is increasing with aging in sickle cell anemia (SCA) patients, and is responsible for a high morbidity and mortality. However, sickle cell nephropathy's natural course remains mostly unknown. We conducted a prospective observational cohort study aimed to identify risk factors for CKD stage II in a cohort of SCA patients. Baseline clinical and biological parameters were collected. Renal parameters were updated at each visit. Risk factors were analyzed using the Cox model. Five-hundred and thirty-five SCA patients were included with a median follow-up of 5.33 (IQR:2.10-8.13) years. Median age was 22 (IQR:19-30) years old. Glomerular hyperfiltration was detected in 299 (55.9%) patients, microalbuminuria and macroalbuminuria in 180 (34%) and 67 (12.7%) patients respectively. During follow up, CKD stage II onset was detected in 39 patients (7.3%). Risk factors for CKD stage II after adjustment on baseline eGFR and age were macroalbuminuria HR: 3.89 [95% CI: 1.61;9.43], diastolic blood pressure (DBP) above 70 mm Hg HR: 2.02 [1.02-3.971], LDH (for 100 IU/L increase) HR: 1.28 [1.12;1.48] and tricuspid regurgitation velocity >2.5 m/sec HR: 2.89 [1.20-6.99]. Multivariate analysis also found age as a strong independent risk factor with HR: (per year increase) 1.13 [1.09;1.16] and a 13.3-fold increase above 30 years (p < 0.001). Our results show a high incidence of CKD stage II with aging, with a strong significant risk increase after 30-years-old, and pinpoint baseline DBP, macroalbuminuria and increased LDH as independent risk factors raising the issue of optimal blood pressure targets for SCA patients.

International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers.

Approximately 20% of patients diagnosed with a phaeochromocytoma or paraganglioma carry a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. When a pathogenic SDHx mutation is identified in an affected patient, genetic counselling is proposed for first-degree relatives. Optimal initial evaluation and follow-up of people who are asymptomatic but might carry SDHx mutations have not yet been agreed. Thus, we established an international consensus algorithm of clinical, biochemical and imaging screening at diagnosis and during surveillance for both adults and children. An international panel of 29 experts from 12 countries was assembled, and the Delphi method was used to reach a consensus on 41 statements. This Consensus Statement covers a range of topics, including age of first genetic testing, appropriate biochemical and imaging tests for initial tumour screening and follow-up, screening for rare SDHx-related tumours and management of elderly people who have an SDHx mutation. This Consensus Statement focuses on the management of asymptomatic SDHx mutation carriers and provides clinicians with much-needed guidance. The standardization of practice will enable prospective studies in the near future.

Psychosocial risk factors for increased emergency hospital utilization by sickle cell disease patients: a systematic review protocol.

OBJECTIVE: To assess psychosocial risk factors for increased emergency hospital utilization by sickle cell patients. INTRODUCTION: Emergency hospital utilization by sickle cell disease patients is high but heterogeneous between patients and in a given patient over time. Psychosocial factors affect emergency hospital utilization and are a possible target to improve the management of sickle cell disease. INCLUSION CRITERIA: This review will include all original quantitative studies evaluating the impact of psychosocial risk factors on emergency hospital utilization by sickle cell disease patients. There will be no language restriction. METHODS: PubMed, Embase, CINAHL, PubPsych, LiSSa, and Web of Science will be searched using a peer-reviewed search strategy. Study selection and extraction of data will be performed independently by two authors. Discrepancies will be solved by consensus or, if needed, by a third author. The authors will assess study quality, as well as perform a narrative synthesis of included studies, and where possible, meta-analyses with evaluation of heterogeneity and publication bias. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019140435.

[Discrepancies in medical textbooks and their impact on medical school students]. / Discordances entre les référentiels des collèges d'enseignants en médecine et leur impact sur les étudiants en médecine.

BACKGROUND: Textbooks endorsed by national medical specialty societies and colleges are used as official references for faculty and national examinations. Oncology is transdisciplinary, practiced and taught by oncologists but also by other specialists. We aimed at identifying discrepancies between chapters on cancers in different official specialty textbooks and evaluating their impact on students. MATERIAL AND METHODS: Volunteer 6th-year medical students of the Sorbonne University faculty were paired and asked to list the discrepancies between all official specialty textbooks addressing a given cancer and then individually asked to evaluate the impact of discrepancies on their learning experience. RESULTS: In March 2018, the 17 cancers listed in the French medical school education program were addressed in 14 official specialty textbooks (2 to 4 textbooks/cancer). Out of a class of 390 students, 78 volunteered and were paired; each cancer was analyzed by 3 pairs of students (1 or 2 cancers/pair); 154 discrepancies were reported (range: 4-18 per cancer). Discrepancies induced doubt and anxiety in students; 85% considered that harmonization should be achieved for all topics of the national medical school program. CONCLUSIONS: Discrepancies between official textbook are frequent, generate anxiety in students and impact learning experience.