Dementia, infections and vaccines: 30 years of controversy.

This paper reports the proceedings of a virtual meeting convened by the European Interdisciplinary Council on Ageing (EICA), to discuss the involvement of infectious disorders in the pathogenesis of dementia and neurological disorders leading to dementia. We recap how our view of the infectious etiology of dementia has changed over the last 30 years in light of emerging evidence, and we present evidence in support of the implication of infection in dementia, notably Alzheimer's disease (AD). The bacteria and viruses thought to be responsible for neuroinflammation and neurological damage are reviewed. We then review the genetic basis for neuroinflammation and dementia, highlighting the genes that are currently the focus of investigation as potential targets for therapy. Next, we describe the antimicrobial hypothesis of dementia, notably the intriguing possibility that amyloid beta may itself possess antimicrobial properties. We further describe the clinical relevance of the gut-brain axis in dementia, the mechanisms by which infection can move from the intestine to the brain, and recent findings regarding dysbiosis patterns in patients with AD. We review the involvement of specific pathogens in neurological disorders, i.e. SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV1), and influenza. Finally, we look at the role of vaccination to prevent dementia. In conclusion, there is a large body of evidence supporting the involvement of various infectious pathogens in the pathogenesis of dementia, but large-scale studies with long-term follow-up are needed to elucidate the role that infection may play, especially before subclinical or clinical disease is present.

Anticipating need for intensive care in the healthcare trajectory of patients with chronic disease: A qualitative study among specialists.

INTRODUCTION: We investigated the reflections and perceptions of non-ICU physicians about anticipating the need for ICU admission in case of acute decompensation in patients with chronic disease. METHODS: We performed a qualitative multicentre study using semi-structured interviews among non-ICU specialist physicians. The interview guide, developed in advance, focused on 3 questions: (1) What is your perception of ICU care? (2) How do you think advance directives can be integrated into the patient's healthcare goals? and (3) How can the possibility of a need for ICU admission be integrated into the patient's healthcare goals? Interviews were recorded, transcribed and analysed by thematic analysis. Interviews were performed until theoretical saturation was reached. RESULTS: In total, 16 physicians (8 women, 8 men) were interviewed. The main themes related to intensive care being viewed as a distinct specialty, dispensing very technical care, and with major human and ethical challenges, especially regarding end-of-life issues. The participants also mentioned the difficulty in anticipating an acute decompensation, and the choices that might have to be made in such situations. The timing of discussions about potential decompensation of the patient, the medical culture and the presence of advance directives are issues that arise when attempting to anticipate the question of ICU admission in the patient's healthcare goals or wishes. CONCLUSION: This study describes the perceptions that physicians treating patients with chronic disease have of intensive care, notably that it is a distinct and technical specialty that presents challenging medical and ethical situations. Our study also opens perspectives for actions that could promote a pluridisciplinary approach to anticipating acute decompensation and ICU requirements in patients with chronic disease.

A qualitative study of the perceptions and experiences of healthcare providers caring for critically ill patients during the first wave of the COVID-19 pandemic: A PsyCOVID-ICU substudy.

BACKGROUND: Intensive care unit (ICU) staff have faced unprecedented levels of stress, in the context of profound upheaval of their working environment due to the COVID-19 pandemic. We explored the perceptions of frontline ICU staff about the first wave of the COVID-19 pandemic, and how this experience impacted their personal and professional lives. METHODS: In a qualitative study as part of the PsyCOVID-ICU project, we conducted semi-structured interviews with a random sample of nurses and nurses' aides from 5 centres participating in the main PsyCOVID study. Interviews were recorded and fully transcribed, and analysed by thematic analysis. RESULTS: A total of 18 interviews were performed from 13 August to 6 October 2020; 13 were nurses, and 5 were nurses' aides. Thematic analysis revealed three major themes, namely: (1) Managing the home life; (2) Conditions in the workplace; and (3) the meaning of their profession. CONCLUSION: In this qualitative study investigating the experiences and perceptions of healthcare workers caring for critically ill patients during the first COVID-19 wave in France, the participants reported that the crisis had profound repercussions on both their personal and professional lives. The main factors affecting the participants were a fear of contamination, and the re-organisation of working conditions, against a background of a media "infodemic".

Prevalence and severity of cognitive dysfunction in patients referred for transcatheter aortic valve implantation (TAVI): clinical and cognitive impact at 1 year.

AIM: We estimated the proportion and severity of cognitive disorders in an unselected population of patients referred for transcatheter aortic valve implantation (TAVI). Second, we describe clinical and cognitive outcomes at 1 year. METHODS: Eligible patients were aged ≥ 70 years, with symptomatic aortic stenosis and an indication for TAVI. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive dysfunction (CD), defined as no CD if score ≥ 26, mild CD if 18-25; moderate CD if 10-18, and severe CD if < 10. We assessed survival and in-hospital complications at 6 months and 1 year. RESULTS: Between June 2019 and October 2020, 105 patients were included; 21 (20%) did not undergo TAVI, and thus, 84 were analyzed; median age 85 years, 53.6% females, median EuroScore 11.5%. Median MoCA score was 22 (19-25); CD was excluded in 18 (21%), mild in 50 (59.5%), moderate in 15 (19%) and severe in 1. Mean MoCA score at follow-up was 21.9(± 4.69) and did not differ significantly from baseline (21.79 (± 4.61), p = 0.73). There was no difference in success rate, in-hospital complications, or death across CD categories. CONCLUSION: The clinical course of patients with mild or moderate CD is not different at 1 year after TAVI compared to those without cognitive dysfunction.

Mental Health Support for Hospital Staff during the COVID-19 Pandemic: Characteristics of the Services and Feedback from the Providers.

French authorities created mental health support services to accompany HCWs during the pandemic. We aimed to obtain feedback from staff providing these mental health support services within French hospitals to identify positive and negative features and avenues for improvement. A mixed-methods study was performed between 1 April and 30 June 2020. We contacted 77 centres to identify those providing mental health support services. We developed a questionnaire containing questions about the staff providing the service (quantitative part), with open questions to enable feedback from service providers (qualitative part). Of the 77 centres, 36 had mental health support services; 77.8% were created specifically for the epidemic. Services were staffed principally by psychologists, mainly used a telephone platform, and had a median opening time of 8 h/day. Thirty-seven professionals provided feedback, most aged 35-49 years. For 86.5%, it was their first time providing such support. Median self-reported comfort level was 8 (interquartiles 3-10), and 95% would do it again. Respondents reported (i) difficulties with work organisation, clinical situations, and lack of recognition and (ii) a desire for training. This study suggests that mental health support needs to be adapted to the needs of HCWs, both in terms of the content of the service and the timing of delivery.

A qualitative study of reinforcement workers' perceptions and experiences of working in intensive care during the COVID-19 pandemic: A PsyCOVID-ICU substudy.

PURPOSE: During the COVID pandemic, many hospitals had to mobilize reinforcement healthcare workers, especially in intensive care (ICUs). We investigated the perceptions and experiences of reinforcement workers deployed to ICUs, and the impact of deployment on their personal and professional lives. METHODS: For this qualitative study, a random sample of 30 reinforcement workers was drawn from 4 centres participating in the larger PsyCOVID-ICU study. Individual semi-structured interviews were held, recorded, transcribed and analyzed by thematic analysis. RESULTS: Thirty interviews were performed from April to May 2021 (22 nurses, 2 anesthesiology nurses, 6 nurses' aides). Average age was 36.8±9.5 years; 7 participants had no ICU experience. Four major themes emerged, namely: (1) Difficulties with integration, especially for those with no ICU experience; (2) lack of training; (3) difficulties with management, notably a feeling of insufficient communication; (4) Mental distress relating to the unusual work and fear of contaminating their entourage. CONCLUSION: Healthcare workers deployed as reinforcements to ICUs at the height of the pandemic had a unique experience of the crisis, and identified important gaps in organisation and preparation. They also suffered from a marked lack of training, given the stakes in the management of critically ill patients in the ICU.

Mechanical Ventilation in COVID-19 Patients: Insights into the Role of Age and Frailty from a Multicentre Observational Study.

In patients with COVID-19, frailty has been shown to better predict outcomes than age alone. We investigated factors associated with mechanical ventilation (MV) during hospitalization for COVID-19 among older adults in a multicentre study during the first two waves in Italy. Using data from the FRACOVID project, we included consecutive patients admitted to the participating centres during the first and second waves. We recorded sociodemographics, comorbidities, time since symptom onset, ventilatory support at admission, and chest X-ray findings. Frailty was assessed using a frailty index (FI). Results are reported as hazard ratios (HR) with 95%CI. 1,344 patients were included; 487 females (36.2%), median age 68 (56; 79) years; 52.4% had hypertension, 10.6% had chronic obstructive pulmonary disease, 15.2% were obese. Median FI was 0.088 (0.03, 0.20), and 67% had bilateral consolidations at admission. Median time since symptom onset was 7 days (4, 10). During hospitalization, 47 patients (3.6%, 95%CI 0.33-13.6%) received MV. Multivariable Cox regression analysis found that the likelihood of intubation decreased with increasing age (HR 0.945 (95%CI 0.921-0.969), p<0.0001), while heart rate >110bpm (HR 3.429 (95%CI 1.583-7.429), p=0.0018), and need for continuous positive airway pressure (CPAP) at admission (HR 2.626 (95%CI 1.330-5.186), p=0.0054) were significantly associated with a greater likelihood of intubation. Older patients are less likely to receive intubation, while those with heart rate >110 bpm and need for CPAP at admission are more likely to receive MV during hospitalization for COVID-19.

Risk and protective factors for the possible development of post-traumatic stress disorder among intensive care professionals in France during the first peak of the COVID-19 epidemic Factores de riesgo y factores protectores para el posible desarrollo de un trastorno de estrés postraumático en profesionales de cuidados intensivos en Francia durante la primera ola de la pandemia por la COVID-19 在 COVID-19 疫情第一个高峰期间, 法国重症监护专业人员可能发生创伤后应激障碍的风险和保护因素

Background Intensive care units (ICU) are among the healthcare services most affected by the COVID-19 crisis. Stressors related to insecurity, unpredictability, patient death and family distress are significant, and put healthcare workers (HCWs) at high risk of post-traumatic stress disorder (PTSD). The aims of this study were to measure the prevalence of post-traumatic stress disorder in HCWs and to identify risk factors and protective factors during the epidemic in France. Methods During the first peak of the epidemic (from 22 April to 13 May 2020), we assessed sources of stress (PS-ICU scale), mental health (GHQ-12) and coping strategies (Brief-COPE). Three months later (03 June to 6 July 2020), PTSD was assessed using the IES-R scale, with additional questions about sources of support. Data were collected using self-report questionnaires administered online. Results Among 2153 professionals who participated in the study, 20.6% suffered from potential PTSD, mostly intrusion symptoms. Risk factors for the development of PTSD were having experienced additional difficult events during the crisis, having a high level of psychological distress, a high level of perceived stress related to the workload and human resources issues, the emotional burden related to the patient and family, and stressors specific to COVID-19 during the first peak of the crisis. The use of positive thinking coping strategies decreased the relationship between perceived stress and the presence of PTSD, while social support seeking strategies increased the relationship. Finally, the HCWs preferred to use support from colleagues, relatives and/or a psychologist, and very few used the telephone hotlines. Conclusion The epidemic has had a strong traumatic impact on intensive care HCWs. Given the risk of PTSD, we need to consider implementing easily-accessible support services that focus on positive thinking coping strategies, during and after the crisis. HIGHLIGHTS The risk of PTSD is high among intensive care professionals. Perceived stress and psychological distress during the first peak of crisis increased the likelihood of subsequent PTSD. Support for professionals should be easily available and focused on positive thinking strategies.

Risk and protective factors for the possible development of post-traumatic stress disorder among intensive care professionals in France during the first peak of the COVID-19 epidemic.

Background: Intensive care units (ICU) are among the healthcare services most affected by the COVID-19 crisis. Stressors related to insecurity, unpredictability, patient death and family distress are significant, and put healthcare workers (HCWs) at high risk of post-traumatic stress disorder (PTSD). The aims of this study were to measure the prevalence of post-traumatic stress disorder in HCWs and to identify risk factors and protective factors during the epidemic in France. Methods: During the first peak of the epidemic (from 22 April to 13 May 2020), we assessed sources of stress (PS-ICU scale), mental health (GHQ-12) and coping strategies (Brief-COPE). Three months later (03 June to 6 July 2020), PTSD was assessed using the IES-R scale, with additional questions about sources of support. Data were collected using self-report questionnaires administered online. Results: Among 2153 professionals who participated in the study, 20.6% suffered from potential PTSD, mostly intrusion symptoms. Risk factors for the development of PTSD were having experienced additional difficult events during the crisis, having a high level of psychological distress, a high level of perceived stress related to the workload and human resources issues, the emotional burden related to the patient and family, and stressors specific to COVID-19 during the first peak of the crisis. The use of positive thinking coping strategies decreased the relationship between perceived stress and the presence of PTSD, while social support seeking strategies increased the relationship. Finally, the HCWs preferred to use support from colleagues, relatives and/or a psychologist, and very few used the telephone hotlines. Conclusion: The epidemic has had a strong traumatic impact on intensive care HCWs. Given the risk of PTSD, we need to consider implementing easily-accessible support services that focus on positive thinking coping strategies, during and after the crisis.

Antecedentes: Las unidades de cuidados intensivos (UCIs) se encuentran dentro de los servicios de salud más comprometidos por la crisis de la COVID-19. Los factores estresantes asociados a la inseguridad, la impredecibilidad, el fallecimiento de pacientes y la angustia familiar son considerables y colocan a los trabajadores de salud (TS) en un alto riesgo de trastorno de estrés postraumático (TEPT). Los objetivos de este estudio fueron el determinar la prevalencia del trastorno por estrés postraumático en TS e identificar los factores de riesgo y los factores protectores durante la epidemia en Francia.Métodos: Durante la primera ola de la epidemia (del 22 de abril al 13 de mayo del 2020) evaluamos fuentes de estrés (mediante la escala de percepción de factores estresantes en la UCI; PS-ICU en sus siglas en inglés), salud mental (mediante el cuestionario de salud general de 12 ítems; GHQ-12 en sus siglas en inglés) y estrategias de afrontamiento (mediante el inventario de la orientación del afrontamiento ante los problemas experimentados; Brief-COPE en sus siglas en inglés). Tres meses después (del 3 de junio al 6 de julio del 2020) se evaluó el TEPT mediante la escala de impacto del evento (IES-R en sus siglas en inglés) y con preguntas adicionales respecto a las fuentes de soporte. Se recolectó la información mediante cuestionarios de autoreporte realizados en línea.Resultados: De los 2.153 profesionales que participaron en el estudio, 20,6% padecían un potencial TEPT, predominando los síntomas intrusivos. Los factores de riesgo para el desarrollo del TEPT fueron el haber experimentado eventos difíciles adicionales durante la crisis, el tener un nivel elevado de angustia psicológica, un nivel alto de estrés percibido asociado a la carga laboral y a situaciones asociadas a los recursos humanos, la carga emocional relacionada al paciente y su familia, y los factores estresantes específicos de la COVID-19 durante la primera ola de la crisis. El uso del pensamiento positivo como estrategia de afrontamiento disminuía la relación entre el estrés percibido y la presencia del TEPT, mientras que las estrategias relacionadas con la búsqueda de soporte social incrementaban esta relación. Finalmente, los TS preferían emplear el soporte brindado por sus colegas, familiares y/o un psicólogo, mientras que muy pocos preferían el uso de líneas telefónicas de crisis.Conclusión: La epidemia ha tenido un fuerte impacto traumático sobre los TS de las UCIs. Dado el riesgo de TEPT, se necesita considerar la implementación de servicios de apoyo de fácil acceso que se enfoquen en el empleo del pensamiento positivo como estrategia de afrontamiento, tanto durante como después de la crisis.

The effect of frailty on in-hospital and medium-term mortality of patients with COronaVIrus Disease-19: the FRACOVID study.

BACKGROUND: Older people hospitalized for COVID-19 are at highest risk of death. Frailty Assessment can detect heterogeneity in risk among people of the same chronological age. We investigated the association between frailty and in-hospital and medium-term mortality in middle-aged and older adults with COVID-19 during the first two pandemic waves. METHODS: This study is an observational multicenter study. We recorded sociodemographic factors (age, sex), smoking status, date of symptom onset, biological data, need for supplemental oxygen, comorbidities, cognitive and functional status, in-hospital mortality. We calculated a Frailty Index (FI) as the ratio between deficits presented and total deficits considered for each patient (theoretical range 0-1). We also assessed the Clinical Frailty Scale (CFS). Mortality at follow-up was ascertained from a regional registry. RESULTS: In total, 1344 patients were included; median age 68 years (Q1-Q3, 56-79); 857 (64%) were men. Median CFS score was 3 (Q1-Q3 2-5) and was lower in younger vs. older patients. Median FI was 0.06 (Q1-Q3 0.03-0.09) and increased with increasing age. Overall, 244 (18%) patients died in-hospital and 288 (22%) over a median follow-up of 253 days. FI and CFS were significantly associated with risk of death. In two different models using the same covariates, each increment of 0.1 in FI increased the overall hazard of death by 35% (HR=1.35, 95%CI 1.23-1.48), similar to the hazard for each increment of CFS (HR=1.37, 95%CI 1.25-1.50). CONCLUSIONS: Frailty, assessed with the FI or CFS, predicts in-hospital and medium-term mortality and may help estimate vulnerability in middle-aged and older COVID-19 patients.

Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic.

BACKGROUND: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. METHODS: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. RESULTS: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11. CONCLUSION: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).

Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose to venous thromboembolism. We determined factors independently associated with computed tomography pulmonary angiography (CTPA)-confirmed pulmonary embolism (PE) in hospitalised severe COVID-19 patients. METHODS: Among all (n=349) patients hospitalised for COVID-19 in a university hospital in a French region with a high rate of COVID-19, we analysed patients who underwent CTPA for clinical signs of severe disease (oxygen saturation measured by pulse oximetry ≤93% or breathing rate ≥30 breaths·min-1) or rapid clinical worsening. Multivariable analysis was performed using Firth penalised maximum likelihood estimates. RESULTS: 162 (46.4%) patients underwent CTPA (mean±sd age 65.6±13.0 years; 67.3% male (95% CI 59.5-75.5%). PE was diagnosed in 44 (27.2%) patients. Most PEs were segmental and the rate of PE-related right ventricular dysfunction was 15.9%. By multivariable analysis, the only two significant predictors of CTPA-confirmed PE were D-dimer level and the lack of any anticoagulant therapy (OR 4.0 (95% CI 2.4-6.7) per additional quartile and OR 4.5 (95% CI 1.1-7.4), respectively). Receiver operating characteristic curve analysis identified a D-dimer cut-off value of 2590 ng·mL-1 to best predict occurrence of PE (area under the curve 0.88, p<0.001, sensitivity 83.3%, specificity 83.8%). D-dimer level >2590 ng·mL-1 was associated with a 17-fold increase in the adjusted risk of PE. CONCLUSION: Elevated D-dimers (>2590 ng·mL-1) and absence of anticoagulant therapy predict PE in hospitalised COVID-19 patients with clinical signs of severity. These data strengthen the evidence base in favour of systematic anticoagulation, and suggest wider use of D-dimer guided CTPA to screen for PE in acutely ill hospitalised patients with COVID-19.