Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Effective dose of nefopam in 80% of patients (ED80): a study using the continual reassessment method

What is already known about this subjectDixon's up-and-down technique allows the calculation of the median effective dose (ED50) of a drug with a limited number of patients.However, it is not possible to calculate the effective dose in more than 50%, i.e. in 80% or 90% (ED80 or ED90) of the patients with this technique.What this study addsWe used the continual reassessment method, which is a Bayesian method to determine ED80, the dose of nefopam relieving pain in 80% of postoperative patients. The ED80 was close to 60 mg, higher than the usual dose of 20 mg

Efficacious switching from subcutaneous to intravenous tocilizumab in patients with non-infectious non-anterior uveitis

Abstract Purpose The efficacy of tocilizumab in refractory chronic noninfectious uveitis has been previously reported, but no data comparing intravenous and subcutaneous tocilizumab in uveitis are available. Results We report a case series of patients with chronic noninfectious uveitis with incomplete efficacy of subcutaneous tocilizumab, improved after switching to intravenous routes. Improvement of visual acuity was observed with intravenous tocilizumab for all patients. Half of the patients could stop corticosteroids. Rapid efficacy of intravenous tocilizumab was observed, between 2 and 3 months. Conclusion In uveitis, tocilizumab administration could be optimized by a switching from a subcutaneous to an intravenous administration route

Development and validation of a questionnaire assessing fears and beliefs of patients with knee osteoarthritis: the Knee Osteoarthritis Fears and Beliefs Questionnaire (KOFBeQ).

ObjectiveWe aimed to develop a questionnaire assessing fears and beliefs of patients with knee OA.DesignWe sent a detailed document reporting on a qualitative analysis of interviews of patients with knee OA to experts, and a Delphi procedure was adopted for item generation. Then, 80 physicians recruited 566 patients with knee OA to test the provisional questionnaire. Items were reduced according to their metric properties and exploratory factor analysis. Reliability was tested by the Cronbach α coefficient. Construct validity was tested by divergent validity and confirmatory factor analysis. Test-retest reliability was assessed by the intra-class correlation coefficient (ICC) and the Bland and Altman technique.Results137 items were extracted from analysis of the interview data. Three Delphi rounds were needed to obtain consensus on a 25-item provisional questionnaire. The item-reduction process resulted in an 11-item questionnaire. Selected items represented fears and beliefs about daily living activities (3 items), fears and beliefs about physicians (4 items), fears and beliefs about the disease (2 items), and fears and beliefs about sports and leisure activities (2 items). The Cronbach α coefficient of global score was 0.85. We observed expected divergent validity. Confirmation factor analyses confirmed higher intra-factor than inter-factor correlations. Test-retest reliability was good, with an ICC of 0.81, and Bland and Altman analysis did not reveal a systematic trend.ConclusionsWe propose an 11-item questionnaire assessing patients' fears and beliefs concerning knee OA with good content and construct validity

Comparison of conventional immunosuppressive drugs versus anti-TNF-α agents in non-infectious non-anterior uveitis

International audienceObjective: To compare the efficacy and safety of Disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α agents in patients with non-infectious non-anterior uveitis.Methods: Single center retrospective study including adult patients with non-infectious intermediate, posterior or pan-uveitis. Outcomes were compared between patients treated with DMARDs or anti-TNF-α agents. The primary outcome was treatment failure or occurrence of serious adverse events. Treatment failure was determined by ophthalmologic criteria.Results: Seventy-three patients were included, mostly female (52%). Among them, 39 were treated with DMARDs and 34 with anti-TNF-α agents. The main uveitis causes were idiopathic (30%), birdshot chorio-retinopathy (25%), sarcoidosis (16%) and Behçet's disease (14%). The primary outcome was observed in 56% of patients treated with anti-TNF-α agents versus 59% of patients treated with DMARDs (p = 0.82). Median time to observe the primary outcome was 16 months (anti-TNF-α group) versus 21 months (p = 0.52). There was no significant difference between the two groups in terms of treatment failure, corticosteroid sparing effect, visual acuity improvement or adverse events. Earlier control of ocular inflammation was achieved with anti-TNF-α agents than with DMARDs (p = 0.006). In relapsing patients, anti-TNF-α agents allowed better corticosteroid sparing (p = 0.06).Conclusion: DMARDs could still be used as first-line therapy for non-infectious non-anterior uveitis after corticosteroid therapy. However, anti-TNF-α agents could be proposed as an alternative in cases of severe inflammation or initial high level of steroid dependency

Tocilizumab for the treatment of birdshot uveitis that failed interferon alpha and anti-tumor necrosis factor-alpha therapy: two cases report and literature review

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Spontaneous remission of fully symptomatic visceral leishmaniasis

International audienceBackground: Visceral leishmaniasis (VL), i.e., infection with Leishmania sp. associated with high fever, weight loss, massive splenomegaly and markedly altered laboratory parameters, is generally fatal if untreated. The possibility of transient spontaneous remission of fully symptomatic visceral leishmaniasis (VL) has been mentioned but, to our knowledge) has never been documented. Case presentation: We report the first documented history of a patient with overt, confirmed VL experiencing a complete remission in the absence of any anti-leishmanial therapy. The diagnosis of VL at the time of the self-resolving episode was strongly suspected based on clinical presentation and presence of antileishmanial antibody, then unequivocally confirmed years later by the presence of an amastigote on a stored smear and the positive quantitative PCR with Leishmania-specific primers from the material scraped from this same slide Conclusion: This report demonstrates that complete spontaneous remission may occur in patients with overt, fully symptomatic VL. VL should therefore be considered in cases of self-resolving or relapsing episodes of fever of unknown origin. Confirmation should be based on both serological tests and specific PCR on a blood sample

The gap between practice and guidelines in the choice of first-line disease modifying antirheumatic drug in early rheumatoid arthritis: results from the ESPOIR cohort.

International audienceOBJECTIVE: To compare rheumatologists' prescription for first disease modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA) in real-life settings with 2 clinical practice guidelines (CPG), the French Society of Rheumatology/STPR 2004 and EULAR/ESCISIT 2007, and thus assess the gap between practices and guidelines. Method. ESPOIR was a French multicenter cohort study of 813 patients with early arthritis between 2002 and 2005. "Definite" and "probable" RA were defined according to ACR criteria and the level of diagnostic certainty. The objectives were to assess conformity between the observed first-line DMARD prescribed for those patients and the DMARD recommended in the guidelines; and to conduct a mail survey of patients' usual rheumatologists to investigate the reasons for their nonconformity with guidelines. RESULTS: In total 627 patients with definite or probable RA were identified. Conformity rates were 58% for STPR guidelines and 54% for EULAR guidelines. At 6 months, 83 (34%) patients with early RA did not receive any DMARD. Main determinants associated with conformity to guidelines were disease activity and presence of severity-predictive factors. The main reason leading to a discrepancy between guidelines and daily practice appeared to be diagnostic uncertainty, i.e., the difficulty to reliably assess RA diagnosis as early as the first visits to the rheumatologist. CONCLUSION: There is a substantial gap between CPG and rheumatologists' daily practice concerning the first DMARD to prescribe in early RA. This is explained mainly by diagnostic uncertainty. More attention should be paid in future guidelines to the diagnostic difficulties of early RA

Early referral to the rheumatologist for early arthritis patients: evidence for suboptimal care. Results from the ESPOIR cohort

International audienceOBJECTIVE: To assess the time to access a rheumatologist (TTAR) by early arthritis (EA) patients participating in a nationwide incidental cohort (ESPOIR) and compare it with European League Against Rheumatism (EULAR) recommendations, which recommends rapid referral, ideally within 6 weeks, to a rheumatologist for patients presenting with EA. METHODS: Eight hundred and thirteen patients with EA were included in the cohort between 2002 and 2005. The inclusion criteria were 18-70 years old, two or more swollen joints, symptom duration from 6 weeks to 6 months and possible RA diagnosis. TTAR was defined as the time between the first synovitis and first visit to a rheumatologist. TTAR and satisfaction of the EULAR guidelines were investigated by multiple linear and logistic regressions. RESULTS: Mean TTAR was 76 days; only 46.2% of patients were seen by a rheumatologist within the EULAR-recommended time frame. Patients' patterns of accessing medical care substantially affected access to specialized care: mean TTAR was 58 days for patients who directly scheduled an appointment with the rheumatologist and 78 days for those referred by their general practitioner (P < 0.0007). Only 57.2 and 44.5%, respectively, were able to consult a rheumatologist within 6 weeks. Multivariate analysis confirmed the significant impact of indirect access on TTAR, after adjustment for EA characteristics and medical density in the region. CONCLUSIONS: Significant disparities were identified in the care of EA patients in terms of early access to a rheumatologist. More effort is needed to optimize the physicians' knowledge about EA and to improve the efficiency of medical networks