COVID-19 patient experiences in prehospital pathways: a processual approach using life-events calendar method and state sequence analysis shows detrimental delays.

OBJECTIVES: To our best knowledge, no study in France has comprehensively investigated the prehospital history of patients admitted for severe cases of COVID-19. 'Patients' voice is an excellent means to capture data on primary care pathways.We aimed to identify clusters of COVID-19 hospitalised patients with similar prehospital symptom sequences, and to test whether these clusters were associated with a higher risk of poor clinical outcomes. DESIGN: Cross-sectional online survey using life-event calendars. SETTING: All patients hospitalised for COVID-19 between September 2020 and May 2021 in the Infectious Disease Departments in Nice and in Marseilles in France. PARTICIPANTS: 312 patients responded to the survey. MAIN OUTCOME MEASURES: From the day of symptom onset to the day of hospitalisation, we defined a symptom sequence as the time-ordered vector of the successive symptom grades (grade 1, grade 2, grade 3). State sequence analysis with optimal matching was used to identify clusters of patients with similar symptom sequences. Multivariate logistic regressions were performed to test whether these clusters were associated with admission to intensive care unit (ICU) and COVID-19 sequelae after hospitalisation. RESULTS: Three clusters of symptom sequences were identified among 312 complete prehospital pathways. A specific group of patients (29%) experienced extended symptoms of severe COVID-19, persisting for an average duration of 7.5 days before hospitalisation. This group had a significantly higher probability of being admitted to ICU (adjusted OR 2.01). They were less likely to know a loved one who was a healthcare worker, and more likely to have a lower level of education. Similarly, this group of patients, who were more likely to have previously visited the emergency room without exhibiting severe symptoms at that time, may have been inclined to postpone reassessment when their health worsened.Their relatives played a decisive role in their hospitalisation. CONCLUSION AND RELEVANCE: This study highlights the negative impact of delayed hospitalisation on the health outcomes of French patients with severe COVID-19 symptoms during the first wave and underscores the influence of socioeconomic factors, such as lower education levels and limited connections to the medical field, on patients' experiences.

Geographical access to hemodialysis: an analysis of patient choices / Accès géographique à l'hémodialyse : une analyse sur les choix des patients

Introduction: Patients do not always go to the facility closest to their home. Description: A study was carried out in Provence-Alpes Côtes d'Azur (PACA) on patients' preferences to mobilize the hemodialysis offer. Methods: The data were extracted from the REIN Registry. Potential access was compared with actual access. A survey was carried out among a sample of patients travelling an additional distance of more than 25 km. Results: About a quarter of the patients did not travel to the nearest facility. Of these, 16.3% travelled an additional distance of over 25 km. Patients' choices were determined by the relationship of trust with the team that first set up dialysis, followed by their desire to be followed in a multi-purpose facility. Discussion: While distance remained the decisive factor, human factors were cited in the majority of cases to explain the bypass. Conclusion: The links between the first team and the next one should be strengthened.

Introduction: Les patients ne se rendent pas toujours dans l'établissement le plus proche de leur domicile. Description: Une étude a été réalisée en Provence-Alpes Côtes d'Azur (PACA) sur les préférences des patients à mobiliser l'offre d'hémodialyse. Méthodes: Les données ont été extraites du Registre REIN. L'accès potentiel a été comparé à l'accès réalisé. Une enquête a été effectuée auprès d'un échantillon de patients parcourant une distance supplémentaire supérieure à 25 km. Résultats: Environ un quart des patients ne se rendait pas dans la structure la plus proche. Parmi eux, 16,3 % parcouraient un trajet supplémentaire supérieur à 25 km. Les choix des patients étaient déterminés par la relation de confiance avec l'équipe de la première mise en place de dialyse, puis par le souhait d'être suivis dans une structure polyvalente. Discussion: Si la distance restait le facteur décisif, les facteurs humains étaient majoritairement cités. Conclusion: Il faudrait renforcer les liens entre la première équipe et celle qui prend la suite.

Effect of comorbidities on healthcare expenditures for patients on kidney replacement therapy considering the treatment modality and duration in a French cohort.

End-stage kidney disease (ESKD) is associated with a substantial economic burden. In France, the cost of care for such patients represents 2.5% of the total French healthcare expenditures but serves less than 1% of the population. These patients' healthcare expenditures are high because of the specialized and complex treatment needed as well as the presence of multiple comorbidities. This study aims to describe and assess the effect of comorbidities on healthcare expenditures (direct medical cost and non-medical costs including transportation and compensatory allowances) for patients with ESKD in France while considering the modality and duration of renal replacement therapy (RRT). This study included adults who started RRT for the first time between 2012 and 2014 in France and were followed for 5 years. Generalized linear models were built to predict mean monthly cost (MMC) by integrating first the time duration in the cohort, then patient characteristics and finally the duration of use of each treatment modalities. Comorbidities with the highest effect on MMC were inability to walk (+ 1435€), active cancer (+ 593€), HIV positivity (+ 507€) and diabetes (+ 396€). These effects vary according to age or treatment modalities. This study confirms the importance of considering patient characteristics, comorbidities and type of RRT when assessing healthcare expenditures for patients with ESKD.

Pre-Hospital Management of Patients with COVID-19 and the Impact on Hospitalization.

Background and Objectives: During the COVID-19 pandemic, patient care was mainly organized around the hospital. Pre-hospital care has, to our knowledge, never been evaluated. We aimed to study the impact of pre-hospital pathways on hospitalization during the last part of the pandemic. Materials and Methods: This was a monocentric, retrospective analysis of prospectively collected medical records. Data from patients admitted to our institute between 1 February and 7 March 2022 were analyzed. The primary outcomes were defined as the number of hospitalizations, resuscitations, and deaths at the time of interview and in the subsequent 30 days. The main explanatory variables were times from onset of symptoms to care, age, gender, News2 score, comorbidities, and pre-hospital pathways and their duration. Results: Three pre-hospital pathways were identified: a pathway in which the patient consults a general practitioner for a test (PHP1); a pathway in which the patient consults for care (PHP2); and no pre-hospital pathway and direct admission to hospital (PHP3). Factors independently associated with outcome (hospitalization) were being male (OR 95% CI; 2.21 (1.01-4.84), p = 0,04), News2 score (OR 95% CI; 2.04 (1.65-2.51), p < 0.001), obesity (OR 95% CI; 3.45 (1.48-8.09), p = 0.005), D-dimers > 0.5 µg/mL (OR 95% CI; 3.45 (1.47-8.12), p = 0.005), and prolonged time from symptoms to hospital care (PHP duration) (OR 95% CI; 1.07 (1.01-1.14), p = 0.03). All things being equal, patients with a "PHP2" pre-hospital pathway had a higher probability of hospitalization compared to those with a "PHP3" pre-hospital pathway (OR 95% CI; 4.31 (1.48-12.55), p = 0.007). Conclusions: Along with recognized risk factors such as gender, News 2 score, and obesity, the patient's pre-hospital pathway is an important risk factor associated with hospitalization.

Developing and Validating an Individual-Level Deprivation Index for Children's Health in France.

BACKGROUND: Deprivation generates many health inequalities. This has to be taken in account to enhance appropriate access to care. This study aimed to develop and validate a pediatric individual-level index measuring deprivation, usable in clinical practice and in public health. METHODS: The French Individual Child Deprivation Index (FrenChILD-Index) was designed in four phases: item generation then reduction using the literature review and expert opinions, and index derivation then validation using a cross-sectional study in two emergency departments. During these last two phases, concordance with a blinded evaluation by an expert enabled us to determine thresholds for two levels of moderate and severe deprivation. RESULTS: The generation and reduction phases retained 13 items. These were administered to 986 children for the derivation and validation phases. In the validation phase, the final 12 items of the FrenChILD-Index showed for moderate deprivation (requiring single specific care for deprived children) a sensitivity of 96.0% [92.6; 98.7] and specificity of 68.3% [65.2; 71.4]. For severe deprivation (requiring a multidisciplinary level of care), the sensitivity was 96.3% [92.7; 100] and specificity was 91.1% [89.2; 92.9]. CONCLUSIONS: The FrenChILD-Index is the first pediatric individual-level index of deprivation validated in Europe. It enables clinical practice to address the social determinants of health and meet public health goals.

Caregiver Burden Is Reduced by Social Support Services for Non-Dependent Elderly Persons: Pre-Post Study of 569 Caregivers.

BACKGROUND: Informal care provided by family caregivers (FCGs) to elderly persons is associated with a high risk of burden and poor health status. Social support services (3S) for the elderly persons were characterized by assistance in various activities of daily living. This study aimed to analyze the impact of 3S on the burden of FCGs of elderly persons living in the community and identify factors associated with changes in their burden. METHODS: This pre-post study was performed in the southeast of France: FCGs of non-dependent elderly persons still living at home who received a 3S were consecutively included. FCG burden was assessed with the Mini-Zarit scale before the setting up of the 3S (pre-3S) and 6 months after (post-3S). RESULTS: A total of 569 FCGs were included in the study. Mean age of the FCGs was 62.9 years old (±13.3), 67% were women, 61.2% were children or stepchildren. Burden was present for 81% of FCGs. In most cases, 3S targeted household chores (95.8%); 59.8% of elderly persons and their FCGs were fully satisfied. The improvement in burden was greater for FCGs perceiving less obstacles post-3S in helping elderly persons (OR = 4.083) but also for FCGs fully satisfied with the 3S (OR = 2.809) and for FCGs whose perceived health status had improved post-3S (OR = 2.090). CONCLUSIONS: FCGs of non-dependent elderly persons experience a burden similar to those of dependent elderly persons. The implementation of a 3S in daily life helps to reduce their burden.

Family Caregiver's Loneliness and Related Health Factors: What Can Be Changed?

Background: Loneliness is a public health issue that may affect the entire population. Loneliness is associated with depression, sleep disorders, fatigue, and increased risk of obesity and diabetes. Risk factors for loneliness include having a poor social network and poor physical and mental health. The main objective was to study factors related to loneliness of family caregivers caring for independent older people. Methods: We performed a non-interventional observational cross-sectional study in south-eastern France. Family caregivers caring for people aged 70 and over and living at home were included. These older people were independent, without long-term conditions, and had applied for professional social assistance for daily living. Data were collected through a questionnaire, administered face-to-face or by telephone. Loneliness and perceived health status were measured through a single-question. Burden was assessed through the Mini-Zarit Scale, and frailty was measured through the Gerontopole Frailty Screening Tool. Results: Of the 876 family caregivers included, 10% felt lonely often or always. They reported more physical and mental health issues than those who did not feel loneliness (p < 0.001). Family caregivers with loneliness were more likely to be looking after a parent and were twice as likely to have a moderate to severe burden (OR = 2.6). They were more likely to feel anxious (OR = 5.6), to have sleep disorders (OR = 2.4), to be frail (OR = 2), and to view the status of their health as poor or bad (OR = 2). Conclusions: Loneliness has a negative impact on health, causes frailty, and places a burden on family caregivers. Means must be implemented to anticipate the consequences of the loneliness felt by family caregivers, notably by orienting them towards the relevant services.

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-ß are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.

Validation of the Computerized Pediatric Triage Tool, pediaTRI, in the Pediatric Emergency Department of Lenval Children's Hospital in Nice: A Cross-Sectional Observational Study.

Introduction: A reliable pediatric triage tool is essential for nurses working in pediatric emergency departments to quickly identify children requiring priority care (high-level emergencies) and those who can wait (low-level emergencies). In the absence of a gold standard in France, the objective of our study was to validate our 5-level pediatric triage tool -pediaTRI- against the reference tool: the Pediatric Early Warning Score (PEWS) System. Materials and Methods: We prospectively included 100,506 children who visited the Pediatric Emergency Department at Lenval Children's Hospital (Nice, France) in 2016 and 2017. The performance of pediaTRI to identify high-level emergencies (severity levels 1 and 2) was evaluated in comparison with a PEWS ≥ 4/9. Data from 2018-19 was used as an independent validation cohort. Results: pediaTRI agreed with the PEWS score for 84,896 of the patients (84.5%): 15.0% (14.8-15.2) of the patients were over-triaged and 0.5% (0.5-0.6) under-triaged compared with the PEWS score. pediaTRI had a sensitivity of 76.4% (74.6-78.2), a specificity of 84.7% (84.4-84.9), and positive and negative likelihood ratios of 5.0 (4.8-5.1) and 0.3 (0.3-0.3), respectively, for the identification of high-level emergencies. However, the positive likelihood ratios were lower for patients presenting with a medical complaint [4.1 (4.0-4.2) v 10.4 (7.9-13.7 for trauma), and for younger children [1.2 (1.1-1.2) from 0 to 28 days, and 1.9 (1.8-2.0) from 28 days to 3 months]. Conclusion: pediaTRI has a moderate to good validity to triage children in a Pediatric Emergency Department with a tendency to over-triage compared with the PEWS system. Its validity is lower for younger children and for children consulting for a medical complaint.

Who Were Hospitalized Deceased Patients from COVID-19 During the First Year of Pandemic? Retrospective Analysis of 1104 Deceased Patients in South of France.

INTRODUCTION: Following the first year of the COVID-19 pandemic, a complete analysis of the characteristics of the deceased hospitalized patients was performed, to identify factors related to premature mortality and to compare patient profiles according to the epidemic periods. METHODS: Retrospective analysis of 1104 deceased patients in two University Hospitals in South-eastern France, between March 1, 2020 and March 12, 2021 from Hospital's electronic medical records was performed. RESULTS: Mean age was 80 years (± 11.1) and 10% of the deceased were younger than 65 years with specific comorbidities, e.g., genetic conditions, metastatic cancer, or massive obesity. Among the three clusters identified, two clusters (75% of deceased patients) include very elderly patients with numerous comorbidities, and differ by their proportion of dependent institutionalized patients. The third cluster is made up of younger patients with fewer but severe comorbidities. Deceased patients' profiles varied according to the epidemic periods: during the first period (March-June 2020), more patients were institutionalized. The second period (September-December2020) coincided with a higher mortality rate. CONCLUSIONS: This study confirmed that most patients hospitalized and dying from COVID-19 were frail, i.e., elderly and/or highly comorbid and that the small proportion of young patients had severe comorbidities.

Work environment and mental health in nurse assistants, nurses and health executives: Results from the AMADEUS study.

AIM: This study aimed to explore work environment and mental health in nurse assistants, nurses and health executives in a national large-scale study. BACKGROUND: We have data for physicians but not for other health care workers categories. METHODS: A total of 6935 participants were recruited between May and June 2021 by professional mailings and professional networks. RESULTS: All professional categories reported high rates of high psychological demand (>90%), low social support (>60%), burnout (50% to 60%), exposure to potentially morally injurious events (>40%) and depression (approximately 30%). Surgery nurses reported the highest exposure to potentially morally injurious events. Major depression was identified in approximately 30% of participants in all categories, but less than 10% reported consuming antidepressants. A total of 31% to 49% of participants reported sleep disorders and 16% to 21% reported consuming regularly hypnotics. Physicians reported high hazardous drinking behaviour and nurse assistant high smoking rates. CONCLUSIONS AND IMPLICATIONS FOR NURSING MANAGEMENT: Our results suggest that preventing burnout and depression in health care workers is a priority. To reach this goal, nursing managers could develop some interventions to reduce psychological demand and increase personal accomplishment and social support between colleagues, and prevent sustained bullying at the workplace and health risk behaviours. These interventions should be further developed and evaluated.

The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies.

SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-ß are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.

Evaluation of compliance with early postbirth follow-up and unnecessary visits to the paediatric emergency department: a prospective observational study at the Lenval Children's Hospital in Nice.

OBJECTIVE: To evaluate compliance with the French National Authority for Health's (Haute Autorité de Santé, HAS) postbirth follow-up recommendations for newborns attending our paediatric emergency department (PED) and identify risk factors associated with non-compliance and unnecessary emergency department utilisation. DESIGN: Prospective, single centre. SETTING: Fourth biggest PED in France in terms of attendance (CHU-Lenval). PATIENTS: 280 patients of whom 249 were included in the statistical analysis. MAIN OUTCOME MEASURES: The primary outcome of this study was the evaluation of compliance of the care pathway for newborns consulting at the PED with respect to the French postbirth follow-up recommendations. Secondary outcome was the assessment of whether the visit to the PED was justified by means of PED reception software and two postconsultation interviews RESULTS: 77.5% (193) of the newborns had non-compliant care pathways and 43% (107) of PED visits were unnecessary. Risk factors associated with a non-compliance regarding the HAS's postbirth follow-up recommendations were: unnecessary visit to the PED (OR 2.0, 95% CI 1.1 to 3.9), precariousness (OR 2.8, 95% CI 1.4 to 6.2), birth in a public maternity hospital (OR 2.5, 95% CI 1.3 to 4.8) and no information about HAS's postbirth follow-up recommendations on discharge from maternity ward (OR 11.4, 95% CI 5.8 to 23.3). Risk factors for unnecessary PED visits were: non-compliant care pathway (OR 2.0, 95% CI 1.1 to 3.9) and a first medical visit at a PED (OR 1.8, 95% CI 1.1 to 3.1). CONCLUSION: Postbirth follow-up may lead to decrease unnecessary emergency department visits unnecessary emergency department visits. TRIAL REGISTRATION NUMBER: The study bears the clinical trial number NCT02863627.

[Influence of the work environment on burn-out and depression in nurses]. / Influence de l'environnement de travail sur le burn-out et la dépression des infirmiers.

Burn out is defined as a state of psychological exhaustion in the face of an unfavourable work environment. In the health sector, this includes, among other things, an excessive care burden, the lack of autonomy or control over work, the vicious circle of absenteeism, the lack of support, moral and sexual harassment, discrimination or the Covid-19 health crisis. Burn-out also increases the risk of depression among care workers.

[Evaluation of ambulance transport relevance of dialysis patients in the PACA region (France), and estimation of savings by the Health Insurance]. / Évaluation de la pertinence des transports par ambulance des patients dialysés en région PACA, et estimation des économies réalisables par l'Assurance maladie.

INTRODUCTION: Patient transport represents the second largest item of cost of dialysis after hospitalization. A significant proportion of patients transported by ambulance are self-sufficient for walking. DESCRIPTION: A study was carried out in the PACA region (France) to analyse the profile of patients transported by ambulance and self-sufficient for walking and then to evaluate the savings for the Health Insurance. METHODS: A triangulation of data was carried out using data from haemodialysis patients recorded in the French REIN Registry in 2017 and data from two surveys: one of a sample of patients transported by ambulance and autonomous in walking, and the other of 62 nephrologists. RESULTS: The data from the REIN register allowed us to estimate that 44 % of patients transported by ambulance are self-sufficient for walking. Our study allowed us to estimate that 2/3 of patients transported by ambulance, self-sufficient for walking, have a reason for being transported by ambulance; for the third without a reason, the health insurance savings would amount to €2 million per year with a reclassification of their transport as seated transport. The survey of prescribers showed that there are exemptions justified by a temporary deterioration in health and/or housing conditions, but also by the lack of seated transport. CONCLUSION: One third of the patients, transported by ambulance and self-sufficient for walking, would have an inappropriate transport. This would be explained by the fluctuating state of health of the patients and would also linked to the lack of seated transportation. Savings are possible and depend in part on improved management of the supply.

Colorectal cancer screening by fecal immunochemical test or colonoscopy in France: how many people are actually covered? Focus on the Provence-Alpes-Côte d'Azur region.

BACKGROUND: Colorectal cancer (CRC) screening with fecal immunochemical test (FIT) remains low in France, particularly in the Provence-Alpes-Côte-d'Azur (PACA) region. The aim of this study was to compare insured persons (50-74 years) who had FIT and/or colonoscopy in PACA with the general French population. METHODS: FIT and colonoscopy rates were calculated according to SP-France and National Health Data System data. RESULTS: The rate of FIT in 2016-2017 was lower in PACA than in France (25.6 vs. 29.1%, P < 0.001). Conversely, in 2013-2017, the rate of colonoscopy in the past 5 years was higher in PACA than in France (23.1 vs. 20.1%, P < 0.001). Total rate for FIT within 2 years and/or colonoscopy within 5 years was 46.0% in PACA vs. 46.5% in France (P < 0.001). Overuse was higher for diagnostic (1.21) than therapeutic colonoscopies (1.05). Therapeutic colonoscopy occurred more with FIT than without (47.88 vs. 38.7%, P < 0.001). According to USA criteria, persons with FIT within 2 years and/or sigmoidoscopy and/or colonoscopy within 10 years was 59.4% in PACA vs. 54.7% in France (P < 0.001). CONCLUSION: Low participation in FIT in France must be improved to increase the rate of therapeutic colonoscopies and reduce the incidence of CRC. The higher colonoscopy rate in PACA could explain the lower CRC mortality. Efforts should be focused on the more than 40% of French insured who are not screened by either FIT or colonoscopy.

Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients.

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.

[An exploratory study of hospital stakeholders' perceptions on the introduction of advanced practice nurses]. / Étude exploratoire de la perception des parties prenantes hospitalières vis-à-vis de l'implantation des infirmiers en pratique avancée.

Introduction : One solution proposed by the authorities to address public health issues is to deploy a new category of professionals with a greater range of skills : advanced practice nurses (APNs). The literature identifies the complexity of the deployment projects of these professionals. The PEPPA model approved by the International Council of Nurses is the reference model for the introduction of APNs. The objectives of this study were to explore various stakeholders' perceptions on the introduction of APNs into health institutions, in order to propose recommendations to support the institutions.Method : A multicenter qualitative study was conducted in France's Provence-Alpes-Côte d'Azur region with physicians, managers, nurses, patients, and advanced practice students.Results : APNs are beneficial for patients and the health system, but their introduction into health institutions brings with it risks, primarily linked to their integration. APN introduction projects need to be well planned and should prioritize their integration.Discussion : Results consistent with the PEPPA model identified seven recommendations to facilitate the successful introduction of APNs into hospitals.Conclusion : This work needs to be continued with studies related to the out-of-hospital setting and the evaluation of the successfulness of APNs' introduction.

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-ß. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-ß do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.

Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis.

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.