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Background & aim We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19. Methods From August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates. Results The overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT-qPCR were 72% (95%CI 62%–81%), 99% (95% CI95%–100%), 99% (95%CI 93%–100%), and 78% (95%CI 70%–85%), 0.28 (95%CI 0.21–0.39), and 72 (95%CI 10–208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%–99%), TSO > 4 days 100% (95%CI 54%–100%), and asymptomatic 100% (95%CI 78–100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed. Conclusions This study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.

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Purposes Following a hospitalization for COPD, dual and triple therapies were compared in terms of persistence and relations with outcomes (exacerbations, health care resource use and costs). Methods This was a historical observational database study. All patients aged ≥45 hospitalized for COPD between 2007 and 2015 were identified in a 1/97th random sample of French claims data. Patients receiving dual therapy within 60 days after hospitalization were compared to patients receiving triple therapy, after propensity score matching on disease severity. Results Of the 3,089 patients hospitalized for COPD, 1,538 (49.8%) received either dual or triple therapy in the 2 months following inclusion, and 1,500 (48.6%) had at least 30 days of follow-up available; 846 (27.4%) received dual therapy, and 654 (21.2%) received triple therapy. After matching, the number of exacerbations was 2.4 per year in the dual vs 2.3 in the triple group (p=0.45). Among newly treated patients (n=206), persistence at 12 months was similar in the dual and triple groups (48% vs 41%, respectively, p=0.37). As compared to patients on dual therapy, more patients on triple therapy received oral corticosteroids (49.1 vs 40.4%, p=0.003) or were hospitalized for any reason (67% vs 55.8%, p=0.0001) or for COPD (35.3 vs 25.1%, p=0.0002) during follow-up. Cost of care was higher for patients on triple than for those on dual therapy (€11,877.1 vs €9,825.1, p=0.01). Conclusion Following hospitalizations for COPD, patients on dual and triple therapy experienced recurrent exacerbations, limited adherence to therapies and high cost of care. Patients on triple therapy appeared more severe than those on dual therapy, as reflected by exacerbations and health care resource use.

BackgroundDiagnosing SARS CoV-2 infection with certainty is essential for appropriate case management. We investigated the combination of rapid antigen detection (RAD) and RT-qPCR assays in a stepwise procedure to optimize the detection of COVID-19.MethodsFrom August 2020 to November 2020, 43,399 patients were screened in our laboratory for COVID-19 diagnostic by RT-qPCR using nasopharyngeal swab. Overall, 4,691 of the 43,399 were found to be positive, and 200 were retrieved for RAD testing allowing comparison of diagnostic accuracy between RAD and RT-qPCR. Cycle threshold (Ct) and time from symptoms onset (TSO) were included as covariates.ResultsThe overall sensitivity, specificity, PPV, NPV, LR-, and LR+ of RAD compared with RT- qPCR were 72% (95%CI 62%–81%), 99% (95% CI95%–100%), 99% (95%CI 93%–100%), and 78% (95%CI 70%–85%), 0.28 (95%CI 0.21-0.39), and 72 (95%CI 10-208) respectively. Sensitivity was higher for patients with Ct ≤ 25 regardless of TSO: TSO ≤ 4 days 92% (95%CI 75%–99%), TSO > 4 days 100% (95%CI 54%–100%), and asymptomatic 100% (95%CI 78-100%). Overall, combining RAD and RT-qPCR would allow reducing from only 4% the number of RT-qPCR needed.ConclusionThis study highlights the risk of misdiagnosing COVID-19 in 28% of patients if RAD is used alone. Thus, negative results from RAD needs to be confirmed by RT-qPCR prior to making treatment decisions. A stepwise analysis that combines RAD and RT-qPCR would be an efficient screening procedure for COVID-19 detection and may facilitate the control of the outbreak.

Background One of the major challenges in treating OSA is to achieve adequate CPAP adherence. Telemonitoring has the potential to provide individualized management and early recognition of problems during treatment. Research Question What is the effect of a multimodal telemonitoring intervention on treatment adherence, quality of life, and functional status in symptomatic patients with OSA and low cardiovascular risk? Study Design and Methods In a multicenter, randomized controlled trial, patients newly diagnosed with OSA were randomly assigned to multimodal telemonitoring for 6 months vs usual care (UC). Telemonitoring consisted of built-in electronic alert algorithms for early adjustment of CPAP treatment in case of side effects, leaks, or persistent residual events. The primary outcome was CPAP adherence (in hours per night). Secondary outcomes included daily symptoms such as fatigue and sleepiness, and quality of life measured by using self-reported questionnaires. Results A total of 206 patients with OSA and a median age of 50.6 years (interquartile range [IQR], 42.1; 58.1 years) were included in the study; they were predominantly male (63%) with a median BMI of 30.6 kg/m2 (IQR, 26.8; 35.1 kg/m2) and a median apnea-hypopnea index of 45.2 events/h (IQR, 34.0; 60.0 events/h). Of these, 102 received UC and 104 received telemonitoring. After 6 months of treatment, CPAP adherence was similar in the two groups when assessed either by mean duration of usage (4.73 ± 2.48 h per night in the telemonitoring group and 5.08 ± 2.44 h per night in the UC group; P = .30) or in percentage of patients adherent to treatment (> 4 h usage per night, > 70% nights; 64% in the telemonitoring group vs 72% in the UC group; P = .24). There was no significant difference between the groups in effect size of improvement in fatigue and sleepiness. Interpretation In patients with severe OSA and low cardiovascular risk, multimodal telemonitoring did not increase CPAP adherence. For both the telemonitoring and UC groups, similar improvements in daytime symptoms were achieved. Trial Registry ClinicalTrials.gov; No.: 01796769; URL: www.clinicaltrials.gov

Background: One of the major challenges in treating obstructive sleep apnea (OSA) is to achieve adequate continuous positive airway pressure (CPAP) adherence. We determined the effect of a multimodal telemonitoring intervention on CPAP adherence, quality of life and functional status in symptomatic OSA patients with low cardiovascular risk. Study Design and Methods: In a multicenter, randomized controlled trial, newly diagnosed OSA patients were randomly assigned to multimodal telemonitoring(TM) for 6 months vs usual care (UC). TMconsisted ofbuilt-in electronic alert algorithms for early adjustment of CPAP treatment in case of side effects, leaks or persistent residual events.The outcomesincluded CPAP adherence, daily symptoms such as fatigue and sleepiness, and quality of life. Results: Of 206 OSA patients aged 50.6 [42.1;58.1] (median [IQR]) years;predominantly male (63%) with body mass index of 30.6 [26.8;35.1] kg/m2and an AHI of 45.2 [34.0;60.0] events/hour) 102 received UC and 104 TM. After 6 months of treatment, CPAPadherence was similar in the two groups when assessed either by mean duration of usage (4.73±2.48 hours/night in the TM group and 5.08±2.44 hours/night in the UC group, p=0.30) or in % of patients adherent to treatment (over 4 hours usage/night, > 70% nights; 64% in TM vs 72% in UC, p=0.24). There was no significant difference between the groups in effect size of improvement in fatigue and sleepiness. Interpretation: In severe OSA patients with low cardiovascular risk, multimodal telemonitoring did not increase CPAP adherence. For both TM and UC groups similar improvements in daytime symptoms were achieved.

BackgroundPD1/L1 Immune Checkpoint Inhibitors (ICI) have significantly improved long-term outcome in about 20% of advanced Non Small Cells Lung Cancer (NSCLC) patients (pts), but 80% present primary or secondary resistance. The PIONeeR project (NCT03493581) aims to predict the response/resistance to PD1/L1 ICIs in advanced NSCLC pts through a comprehensive agnostic multiparametric and longitudinal biomarkers assessment. Data presented here are a focus on the quantification of tumor infiltration by lymphocytes, their activation as potential markers of the resistance to treatment by ICI.MethodsAdvanced NSCLC pts with available archived tumor tissue at screening visit (VS), treated with standard PD1/L1 ICIs (nivolumab, pembrolizumab or atezolizumab), alone (2nd line or more) or combined with chemotherapy (1st line), were re-biopsied at 6 weeks (V2) of treatment. PD1/L1 ICIs overall response rate (ORR) was assessed by RECIST 1.1 every 6 weeks. The multiplex IHC test ”Immunoscore® CR T Cells Exhaustion” (IS TCE) quantifies cytotoxic lymphocytes expressing three checkpoints: PD1, LAG3, TIM3, extrapolating their exhaustion status, both in the stroma and parenchyma. The unsupervised neural-network-based machine learning algorithm SOM (Self-Organizing Maps) was used to classify samples based on the 27 IS TCE variables. Statistical significance of survival differences between groups was evaluated using the log-rank test.ResultsAmong the first 100 pts, (male (64%), smokers (91,8%), ConclusionsIS TCE test may help stratifying and predicting responders to anti PD1/L1 therapy through checkpoint expressing lymphocytes quantification and spatial distribution. Additional tests performed on the PIONeeR cohort to explore other aspects of the immune response to cancer should complete these results.AcknowledgementsThis work is supported by French National Research Agency (ANR-17-RHUS-0007), a partnership of AMU, APHM, AstraZeneca, Centre Léon Bérard, CNRS, HalioDx, ImCheck Therapeutics, Innate Pharma, Inserm, Institut Paoli Calmettes and sponsored by AP HM. Drug supply is funded by AstraZeneca. Special thanks to patients and families.Trial RegistrationNCT03493581Ethics ApprovalThe study is conducted in accordance with Good Clinical Practice and the French applicable regulatory requirements (Public Health Code, article L.1121-1/La loi n° 2012–300 du 5 mars 2012 relative aux recherches impliquant la personne humaine (dite loi Jardé), the applicable subject privacy requirements, and the ethical principles that are outlined in the Declaration of Helsinski. The study was approved by the French Ethic Committee, CPP Ouest II - Angers, ref. CPP: 2028/08, Ref ANSM (French competent authority) 2018020500208, 2018072600120, 2019083000148. Freely given written informed consent was signed and obtained from each individual participating in the study, before any study specific procedure was undertaken and after the provision of information about the study by the investigator during a physician-patient consultation and sufficient time for reflection.

Introduction: COPD dual (inhaled corticosteroids (ICS) + long-acting beta2-agonists (LABA) or LABA + long-acting muscarinic antagonist (LAMA)) and triple (ICS + LABA+ LAMA) therapies have been compared in clinical trials but not yet in real-life conditions. Aims: To compare dual and triple therapies in patients hospitalized for COPD, on exacerbations, healthcare resource use, costs and persistence. Methods: All patients aged 45 and over, hospitalized for COPD between 2007 and 2015, were included, using the EGB (Echantillon Generaliste de Beneficiaires, 1/97e random sample of the French claims database SNIIRAM). Patients on dual therapy within 60 days after hospitalization were compared with patients on triple therapy, after propensity score matching on disease severity. Results: Out of 3,089 patients included, 926 received dual and 1,017 triple therapy. After matching, the number of exacerbations was 2.4 per year in the dual group vs 2.3 in the triple group (p=0.45). The persistence of newly treated patients (n=206) was low in both matched groups: 48% in the dual group vs 41% in the triple group. As compared to patients on any dual therapy, more patients under triple therapy received oral corticosteroids (49.1 vs 40.4%, p=0.003) and were hospitalized for any causes (67 vs 55.8%, p=0.0001) and for COPD (35.3 vs 25.1%, p=0.0002). Triple therapy patients had a higher total annual cost than dual therapy patients (€11,877.1 vs €9,825.1, p=0.009). Conclusion: Patients hospitalized for COPD experienced recurrent hospitalizations and oral CS therapy, especially when under triple therapy, besides high cost of treatments and poor adherence to both dual and triple therapies.

Resume Introduction Le diagnostic et le traitement de la BPCO sont sous-optimaux chez de nombreux malades, ce qui peut etre deletere pour leur devenir. Objectifs Decrire les modalites de prise en charge pneumologique des patients atteints de BPCO selon leur stade de severite. Methodes Etude observationnelle transversale realisee en France metropolitaine en 2006-2007, aupres de 515 medecins pneumologues repartis sur le territoire national, devant recruter chacun 5 BPCO stables. Resultats L’observatoire a inclus 2 494 patients (âge moyen 67 ans, 78% d’hommes) dont pres de 50% de BPCO severes ou tres severes (Stades III ou IV de la classification GOLD). A l’inclusion, 93,2% des patients avaient un traitement medicamenteux, le plus souvent un bronchodilatateur (91,2%, hors nebulisations) et/ou un corticosteroide inhale (73,7%). Une rehabilitation respiratoire etait rapportee au cours des deux annees precedentes ou prevue chez 26,9% des patients. Si la frequence des explorations et traitements augmentait avec la severite de la maladie, il existait un fort recouvrement entre les stades. Conclusions Les decisions d’explorations et de traitements des pneumologues ne peuvent etre expliquees par la seule severite des malades atteints de BPCO. Des efforts doivent porter sur l’identification des autres caracteristiques des malades associees a ces decisions, afin d’aider a l’elaboration des recommandations a venir.

This study aimed to investigate factors associated with analgesic use of morphine in end-of-life care. French general practitioners (GPs) and oncologists (N = 719) were asked whether they would prescribe morphine asfirst-line therapy to patients with terminal lung cancer suffering from dyspnea associated with cough and great anxiety. Overall, 54 percent of oncologists and 40percent of GPs stated that they would prescribe morphine in the presented case. This prescriptive attitude correlated with physicians’ age, professional back-ground, communication skills, and attitude toward terminally ill patients. The findings of this study indicate that improving analgesic use of opioids in end-of-life care is not only a matter of enhancing technical skills acquired through training or experience but also a matter of improving communication and empathy between physicians and patients.

In 1999, the French Parliament established a “right to palliative care”, which reactivated public debate about euthanasia. In order to investigate jointly physicians’ attitude toward palliative care and euthanasia, we conducted a cross-sectional survey of a national sample of French GPs, oncologists, and neurologists. Overall, 917 physicians participated in the survey. Significant proportions of respondents, especially among GPs and neurologists, considered that palliative sedation and withdrawing life-sustaining treatments (WLST) were euthanasia. Multivariate analysis showed that the physicians who had special medical training in palliative care, and those who distinguish palliative sedation and WLST from euthanasia were more likely to oppose legalisation of euthanasia. Thus, French physicians’ attitude to the legalisation of euthanasia is strongly influenced by whether or not they distinguish palliative care from euthanasia. Improved palliative care requires better training of the entire medical profession, and clearer guidelines about which end-of-life care practices are legally and ethically acceptable.

Background Secondary or reactive hemophagocytic syndrome is frequently related to viral infections and is named Virus-Associated Hemophagocytic Syndrome (VAHS). Cytomegalovirus (CMV) has been associated with hemophagocytic syndrome in healthy subjects, patients with inflammatory bowel diseases rheumatologic diseases, and transplant recipients. CMV and hepatitis B virus (HBV) can be sexually transmitted. However, co-infection with these viruses has never been reported and the clinical follow-up after acute HBV–CMV infection is not known. Objectives To report on the first case of a VAHS related to acute CMV and HBV co-infection probably acquired after sexual contact. Study design A 47-year-old woman, with no past medical history, complaining of severe asthenia, pneumonia, myalgia, and high fever, was hospitalized for the first time on July 5, 2008. During 20 days, her CMV viral load and HBV DNA were monitored. Results Ten days after her hospitalization, all signs and symptoms worsened. Twenty days after hospitalization, the patient had a natural recovery from acute HBV infection and a rapid clearance of CMV infection. Three weeks later, the patient was discharged without any complaints. Conclusion This report points out the etiological role of CMV and HBV co-infection in VAHS due to probable sexual transmission.

To evaluate opinion of physicians about the legalization of euthanasia according to their professional characteristics, their attitudes toward morphine, their attitudes toward communication with end-of-life patients, and their perception of specific types of terminal care.Univariate and multivariate analyses were carried out from data collected among 1.000 general practitioners, oncologists, neurologists and HIV specialists (French cross-sectional survey on palliative care, 2002).42.5% of physicians agreed with the statement that euthanasia should be legalized as it is already the case in the Netherlands. Inadequate prescription of morphine and calling terminal sedation as active euthanasia were associated with a favorable opinion toward legalization of euthanasia.Specific training on pain management and terminal sedation would help physicians to have a better view of the problem of euthanasia.