Effectiveness of mid-regional pro-adrenomedullin, compared to other biomarkers (including lymphocyte subpopulations and immunoglobulins), as a prognostic biomarker in COVID-19 critically ill patients: New evidence from a 15-month observational prospective study.

Background: Mid-regional pro-adrenomedullin (MR-proADM), an endothelium-related peptide, is a predictor of death and multi-organ failure in respiratory infections and sepsis and seems to be effective in identifying COVID-19 severe forms. The study aims to evaluate the effectiveness of MR-proADM in comparison to routine inflammatory biomarkers, lymphocyte subpopulations, and immunoglobulin (Ig) at an intensive care unit (ICU) admission and over time in predicting mortality in patients with severe COVID-19. Methods: All adult patients with COVID-19 pneumonia admitted between March 2020 and June 2021 in the ICUs of a university hospital in Italy were enrolled. MR-proADM, lymphocyte subpopulations, Ig, and routine laboratory tests were measured within 48 h and on days 3 and 7. The log-rank test was used to compare survival curves with MR-proADM cutoff value of >1.5 nmol/L. Predictive ability was compared using the area under the curve (AUC) and 95% confidence interval (CI) of different receiver-operating characteristic curves. Results: A total of 209 patients, with high clinical severity [SOFA 7, IQR 4-9; SAPS II 52, IQR 41-59; median viral pneumonia mortality score (MuLBSTA)-11, IQR 9-13] were enrolled. ICU and overall mortality were 55.5 and 60.8%, respectively. Procalcitonin, lactate dehydrogenase, D-dimer, the N-terminal prohormone of brain natriuretic peptide, myoglobin, troponin, neutrophil count, lymphocyte count, and natural killer lymphocyte count were significantly different between survivors and non-survivors, while lymphocyte subpopulations and Ig were not different in the two groups. MR-proADM was significantly higher in non-survivors (1.17 ± 0.73 vs. 2.31 ± 2.63, p < 0.0001). A value of >1.5 nmol/L was an independent risk factor for mortality at day 28 [odds ratio of 1.9 (95% CI: 1.220-3.060)] after adjusting for age, lactate at admission, SOFA, MuLBSTA, superinfections, cardiovascular disease, and respiratory disease. On days 3 and 7 of the ICU stay, the MR-proADM trend evaluated within 48 h of admission maintained a correlation with mortality (p < 0.0001). Compared to all other biomarkers considered, the MR-proADM value within 48 h had the best accuracy in predicting mortality at day 28 [AUC = 0.695 (95% CI: 0.624-0.759)]. Conclusion: MR-proADM seems to be the best biomarker for the stratification of mortality risk in critically ill patients with COVID-19. The Ig levels and lymphocyte subpopulations (except for natural killers) seem not to be correlated with mortality. Larger, multicentric studies are needed to confirm these findings.

The Impact of COVID-19 Pandemic on Psychiatric Rehabilitation in Residential Facilities: Perspectives of Staff and Residents.

The coronavirus pandemic imposed significant changes in the care of patients in psychiatric residential facilities, especially during lockdown periods. The aim of this study was to assess the impact of the pandemic on patients and staff of psychiatric residential facilities (RFs). This cross-sectional survey was conducted between 30 June and 30 July 2021 and involved 31 RFs located in the province of Verona (Italy). In total, 170 staff members and 272 residents participated in this study. Staff showing clinically significant symptoms of anxiety, depression and burnout were, respectively, 7.7%, 14.2% and 6%. Staff were concerned about the risk that COVID-19 infection might spread among residents (67.6%) and that residents could not receive an acceptable service due to service reconfiguration because of the pandemic (50.3%). Residents found it very unpleasant not to be permitted to attend family members (85.3%), and not to be allowed to engage in outdoor activities due to the restrictions (84%). Both staff and residents agree that the main problematic areas for the residents was the interdiction to meet family members or friends and the interdiction to outdoor activities, whereas problems related to the COVID-19 infection were considered by the staff members as more frequently problematic than reported by residents. The COVID-19 pandemic had a significant impact on the rehabilitation care and recovery journeys of the residents of psychiatric RFs. Therefore, sustained, and careful attention is needed to ensure that the rehabilitation needs of people with severe mental disorders are not neglected in time of pandemics. Supplementary Information: The online version contains supplementary material available at 10.1007/s40737-023-00343-6.

Changes in emergency psychiatric consultations in time of COVID-19: a retrospective observational study in the Verona Academic Hospital over the two pandemic years 2020-2021.

BACKGROUND: During the first months of the COVID-19 pandemic, local health authorities in most Italian regions prescribed a reduction of ordinary outpatient and community mental health care. The aim of this study was to assess the impact of the COVID-19 pandemic on access to the emergency departments (ED) for psychiatric consultation in the pandemic years 2020 and 2021 compared to 2019. METHODS: This is a retrospective study conducted by using routinely collected administrative data of the two EDs of the Verona Academic Hospital Trust (Verona, Italy). All ED psychiatry consultations registered from 01.01.2020 to 31.12.2021 were compared with those registered in the pre-pandemic year (01.01.2019 to 31.12.2019). The association between each recorded characteristic and the year considered was estimated by chi-square or Fisher's exact test. RESULTS: A significant reduction was observed between 2020 and 2019 (-23.3%) and between 2021 and 2019 (-16.3%). This reduction was most evident in the lockdown period of 2020 (-40.3%) and in the phase corresponding to the second and third pandemic waves (-36.1%). In 2021, young adults and people with diagnosis of psychosis showed an increase in requests for psychiatric consultation. CONCLUSIONS: Fear of contagion may have been an important factor in the overall reduction in psychiatric consultations. However, psychiatric consultations for people with psychosis and for young adults increased. This finding underlines the need for mental health services to implement alternative outreach strategies aimed to support, in times of crisis, these vulnerable segments of the population.

Effectiveness of a Mindful Compassion Care Program in reducing burnout and psychological distress amongst frontline hospital nurses during the COVID-19 pandemic: a study protocol for a randomized controlled trial.

BACKGROUND: Recent studies have shown that nurses have been more affected by the COVID-19 pandemic than any other group of hospital workers in terms of anxiety, depression, and burnout. Several clinical studies had previously demonstrated the effectiveness of mindfulness and compassion interventions in reducing burnout and emotional distress amongst healthcare professionals. METHODS AND ANALYSIS: A parallel-group randomized controlled trial will assess the feasibility, acceptability, and efficacy of a mindfulness and compassion-focused programme on frontline nurses who had been working during the COVID-19 pandemic. Seventy-two participants will be recruited from Verona University Hospital Trust (Veneto Region, north-east Italy) and will be divided equally into an intervention group and a control group. Primary outcome will be assessed using the Emotional Exhaustion subscale of the Maslach Burnout Inventory General Survey (MBI-GS). Secondary outcomes will be measured by the Cynicism and Professional Efficacy subscales of the MBI-GS, the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder (GAD-7), the Insomnia Severity Index (ISI), the Impact of Stressful Events (IES-R), the Perceived Stress Scale (PSS), the Five Facet Mindfulness Questionnaire (FFMQ), and the Forms of Self-Criticising/attacking and Self-Reassuring Scale (FSCRS). DISCUSSION: The study aims to fill a gap in the literature and present a scientifically validated intervention for those healthcare professionals most exposed to the stressful conditions of working during the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov; Identifier: NCT05308537.

Development and psychometric validation of new questionnaires assessing experienced discrimination and internalised stigma among people with Covid-19.

AIMS: To develop and validate two new standardised measures assessing, respectively, experienced discrimination (Covid-19 Experienced DISCrimination scale, CEDISC) and internalised stigma (COvid-19 INternalised Stigma scale, COINS) in people who had been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or had developed coronavirus disease 2019 (Covid-19) disease. METHODS: Both the CEDISC and the COINS were developed in Italian and tested for ease of use, comprehension, acceptability, the relevance of items and response options within a focus group session. Online cross-sectional validation survey was conducted among adults infected with SARS-CoV-2 or who developed Covid-19 disease, members of a closed Facebook discussion group in Italy. Exploratory factor analysis (EFA) with Promax oblique rotation; the Kaiser-Meyer-Olkin (KMO) measure of sampling adequacy and the Bartlett's test of sphericity were used to assess the suitability of the sample for factor analysis. Reliability was assessed as internal consistency using Cronbach's alpha and as test-retest reliability using weighted kappa and intraclass correlation coefficient (ICC). Precision was examined by Kendall's tau-b coefficient. RESULTS: Overall, 579 participants completed the CEDISC, 519 also completed the COINS, 155 completed the retest for both scales after two weeks. The 12 items of the CEDISC converged over a 2-factor solution ('social life' and 'close relations') accounting for 49.2% of the variance (KMO = 0.894; Bartlett's test p < 0.001); the 13 items of the COINS converged over a 3-factor solution ('self-perception', 'close relations' and 'social life') accounting for 67.7% (KMO = 0.827; Bartlett's test p < 0.001). Cronbach's α was 0.848 for the CEDISC, and 0.837 for the COINS. The CEDISC showed three items (25%) with kappa between 0.61 and 0.80 and seven (58.4%) between 0.41 and 0.60, with only two items scoring 0.21 and 0.40; the COINS had ten items (76.9%) with kappa ranging from 0.41 to 0.60, and three items below 0.31. ICC was 0.906 (95% CI, 0.871-0.932) for the, CEDISC and 0.860 (95% CI, 0.808-0.898) for the COINS. Kendall's tau-b ranged from 0.360 to 0.556 (p < 0.001) for the CEDISC and from 0.290 to 0.606 (p < 0.001) for the COINS. CONCLUSIONS: Both the CEDISC and the COINS are two valid and reliable scales to be used in studies examining the role of stigma and discrimination of people infected with SARS-CoV-2 and Covid-19 patients, and in research evaluating interventions designed to mitigate stigma in this population.

Three-Month Follow-up Study of Mental Health Outcomes After a National COVID-19 Lockdown: Comparing Patients With Mood or Anxiety Disorders Living in an Area With a Higher Versus Lower Infection Incidence.

Objective: The COVID-19 pandemic and the related containment measures can represent a traumatic experience, particularly for populations living in high incidence areas and individuals with mental disorders. The aim of this study was to prospectively examine posttraumatic stress disorder (PTSD), anxiety, and depressive symptoms since the end of the first COVID-19 pandemic wave and Italy's national lockdown in subjects with mood or anxiety disorders living in 2 regions with increasing pandemic incidence.Methods: 102 subjects with a DSM-5 anxiety or mood disorder were enrolled from June to July 2020 and assessed at baseline (T0) and after 3 months (T1) with the Impact of Event Scale-Revised, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-Item, and Work and Social Adjustment Scale. At T1, subjects were also assessed by means of the Trauma and Loss Spectrum Self-Report for PTSD.Results: At T0, subjects from the high COVID-19 incidence area showed higher levels of traumatic symptoms than those from the low COVID-19 incidence area (P < .001), with a decrease at T1 with respect to T0 (P = .001). Full or partial DSM-5 PTSD related to the COVID-19 pandemic emerged in 23 subjects (53.5%) from the high COVID-19 incidence area and in 9 (18.0%) from the low COVID-19 incidence area (P < .001).Conclusions: Subjects with mood or anxiety disorders presented relevant rates of PTSD, depressive, and anxiety symptoms in the aftermath of the lockdown, and in most cases these persisted after 3 months. The level of exposure to the pandemic emerged as a major risk factor for PTSD development. Further long-term studies are needed to follow up the course of traumatic burden.

The Sustained Psychological Impact of the COVID-19 Pandemic on Health Care Workers One Year after the Outbreak-A Repeated Cross-Sectional Survey in a Tertiary Hospital of North-East Italy.

This study aimed to evaluate the mental health outcomes of health care workers (HCWs) of the Verona academic hospital trust (Italy) one year after the outbreak of COVID-19 and to identify predicted risk factors. A web-based survey was conducted from mid-April to mid-May 2021 on hospital workers one year after the first evaluation performed during the lock-down phase of the COVID-19 pandemic. Post-traumatic stress, general anxiety, depression, and burnout were assessed by using, respectively, the impact of event scale (IES-R), the self-rating anxiety scale (SAS), the patient health questionnaire (PHQ-9) and the Maslach burnout inventory-general survey (MBI-GS). Multivariate logistic regression analysis was performed to identify factors associated with each of the four mental health outcomes one year after the COVID-19 outbreak. A total of 1033 HCWs participated. The percentage of HCWs scoring above the cut-off increased from 2020 to 2021 in all of the outcome domains (anxiety, 50.1% vs. 55.7, p < 0.05; depression, 26.6% vs. 40.6%, p < 0.001; burnout, 28.6% vs. 40.6%, p < 0.001; chi-square test), with the exception of post-traumatic distress. There was also an increase when stratifying by occupation and workplace, with a greater increase for depression and burnout. Multivariate analysis revealed that, one year after the COVID-19 outbreak, nurses were at the greatest risk of anxiety and depression, whereas residents were at the greatest risk of burnout (in terms of low professional efficacy). Working in intensive care units was associated with an increased risk of developing severe emotional exhaustion and a cynical attitude towards work.

The psychological impact of COVID-19 among primary care physicians in the province of Verona, Italy: a cross-sectional study during the first pandemic wave.

BACKGROUND: Among healthcare professionals working with COVID-19 patients, general practitioners (GPs) are under considerable pressure and may develop adverse mental health outcomes. OBJECTIVES: To assess mental health outcomes on GPs working during the COVID-19 pandemic and to explore their associations with personal characteristics and features of GP practices. METHODS: Observational cross-sectional study conducted on a sample of GPs working in Verona province (Italy) during the first pandemic wave. Participants were invited to complete a web-based form addressing socio-demographic and work-related information, previous practice organization, practice re-organization during the COVID-19 pandemic, and a set of measures for post-traumatic stress (IES-R), anxiety (SAS), depression (PHQ-9), and burnout (MBI-GS). RESULTS: A total of 215 GPs (38.3% of the eligible population) participated. Overall, 44.7% reported COVID-19-related traumatic events; among these, 35.9% (95% CI, 26%‒46%) developed symptoms of post-traumatic distress. Furthermore, 36% (95% CI, 29%‒43%) reported symptoms of anxiety, 17.9% (95% CI, 12%‒23%) symptoms of at least moderate depression, and 25.4% (95% CI, 19%‒32%) symptoms of burnout. Multivariate regressions showed that being quarantined or admitted for COVID-19 was associated with all the mental health outcomes considered. Being female, working in rural settings, and having less professional experience were associated with higher anxiety and depression. The ability to diagnose COVID-19 increased self-perceived professional efficacy, thus contributing to burnout reduction. CONCLUSION: The high prevalence of adverse mental health outcomes among GPs during the pandemic highlights the importance of timely interventions in this population and promoting targeted preventive actions in the event of future healthcare crises.

Effects of Steroids and Tocilizumab on the Immune Response Profile of Patients with COVID-19-Associated ARDS Requiring or Not Veno-Venous Extracorporeal Membrane Oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a life-saving rescue therapy in patients with Acute Respiratory Distress Syndrome (ARDS). ECMO has been associated with development of lymphocytopenia that is also common in COVID-19. Hyperinflammation may complicate SARS-CoV-2 pneumonia, prompting therapy with steroids and immunomodulatory drugs. We aimed to evaluate the association of therapies such as steroids and Tocilizumab with trajectories of the total leukocytes, lymphocyte subpopulation count, and inflammatory and fibrinolysis markers in COVID-19-related ARDS, requiring or not VV-ECMO support. The association of the trajectories of the leukocytes, lymphocyte subpopulation count, and inflammatory and fibrinolysis markers with treatment with steroids (Steroids), Tocilizumab (Tocilizumab), both drugs (Steroids + Tocilizumab), and absence of treatment (No Treatment) were analyzed using mixed effects regression models, where ECMO was considered as a potential effect modifier. One hundred and thirty-nine leukocyte and eighty-one lymphocyte subpopulation counts were obtained from thirty-one patients who required (VV-ECMO, N = 13) or not (no VV-ECMO, N = 18) extracorporeal support. In both groups, treatment with Steroids + Tocilizumab was independently associated with a significant reduction of 46% and 67% in total lymphocytes, 22% and 60% in CD3+, and 61% and 91% in CD19+ (B lymphocytes) compared to those obtained without treatment, respectively. In the no VV-ECMO group, Tocilizumab was associated with a 79% increase in total lymphocytes and with a reduction in procalcitonin compared to no treatment. CD45+, CD3+CD4+ (Th cell), CD3+CD8+, CD4+/CD8+, the NK cell subpopulation, neutrophils, monocytes, and basophils were significantly reduced by Steroids + Tocilizumab without an effect modification by VV-ECMO support. In critically ill COVID-19 patients with ARDS, concomitant therapies with steroids and Tocilizumab, beside mitigating the inflammation and fibrinolysis, could reduce the total leukocyte, lymphocyte, and subpopulation count. Moreover, the effect of Tocilizumab in increasing the total lymphocytes and reducing procalcitonin might be blunted by VV-ECMO.

Real-life study on the pharmacokinetic of remdesivir in ICU patients admitted for severe COVID-19 pneumonia.

Remdesivir is one of the most encouraging treatments against SARS-CoV-2 infection. After intravenous infusion, RDV is rapidly metabolized (t1/2 = 1 h) within the cells to its active adenosine triphosphate analogue form (GS-443902) and then it can be found in plasma in its nucleoside analogue form (GS-441524). In this real-life study, we describe the remdesivir and GS-441524 concentrations at three time points in nine ICU patients, through a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. The observed data confirmed the very rapid conversion of RDV to its metabolite and the quite long half-life of GS-441524. The mean Cmin , Cmax and AUC0-24 , were < 0.24 ng/mL and 122.3 ng/mL, 2637.3 ng/mL and 157.8 ng/mL, and 5171.2 ng*h/mL and 3676.5 ng*h/ml, respectively, for RDV and GS-441524. Three out of nine patients achieved a Cmax  > 2610 ng/mL and 140 ng/mL and AUC0-24  > 1560 ng*h/mL and 2230 ng*h/mL for RDV and GS-441524, respectively. The mean t1/2 value for GS-441524 was 26.3 h. Despite the low number of patients, these data can represent an interesting preliminary report on the variability of RDV and GS-441524 concentrations in a real-life ICU setting.

ECMO Support and Operator Safety in the Context of COVID-19 Outbreak: A Regional Center Experience.

Since the beginning of the COVID-19 emergency, the referral Intensive Care Unit for the Extracorporeal Membrane Oxygenation (ECMO) support of Piedmont Region (Italy), in cooperation with infectious disease specialists, perfusionists and cardiac surgeons, developed a protocol to guarantee operator safety during invasive procedures, among which the ECMO positioning or inter-hospital transport. The use of powered air-purifying respirators, filtering facepiece particles (FFP) 2-3 masks, protective suits, disposable sterile surgical gowns, and two pairs of sterile gloves as a part of a protocol seemed effective and feasible for trained healthcare workers and allow all the complex activities connected with the positioning of the ECMO support to be completed effectively. The simulation training on donning and doffing procedures and the presence of a dedicated team member to verify the compliance with the safety procedure effectively reassured operators and likely reduced the risk of self-contamination. From 1 March to 31 December 2020, we used the procedure in 35 severe acute respiratory distress syndrome (ARDS) patients and one acute respiratory failure caused by neoplastic total tracheal obstruction, all positive to COVID-19, to be connected to veno-venous ECMO in peripheral hospitals and centralized for ECMO management. This preliminary experience seems to confirm that the use of ECMO during COVID-19 outbreaks is feasible and the risks associated with its positioning and management are sustainable for the health-care workers and safe for patients.

Levels of burn-out among healthcare workers during the COVID-19 pandemic and their associated factors: a cross-sectional study in a tertiary hospital of a highly burdened area of north-east Italy.

OBJECTIVE: To determine burn-out levels and associated factors among healthcare personnel working in a tertiary hospital of a highly burdened area of north-east Italy during the COVID-19 pandemic. DESIGN: Observational study conducted from 21 April to 6 May 2020 using a web-based questionnaire. SETTING: Research conducted in the Verona University Hospital (Veneto, Italy). PARTICIPANTS: Out of 2195 eligible participants, 1961 healthcare workers with the full range of professional profiles (89.3%) completed the survey. PRIMARY OUTCOME MEASURE: Levels of burn-out, assessed by the Maslach Burnout Inventory-General Survey (MBI-GS). Multivariable logistic regression analysis was performed to identify factors associated with burn-out in each MBI-GS dimension (emotional exhaustion, EX; professional efficacy, EF; cynicism, CY). RESULTS: Overall, 38.3% displayed high EX, 46.5% low EF and 26.5% high CY. Burn-out was frequent among staff working in intensive care units (EX 57.0%; EF 47.8%; CY 40.1%), and among residents (EX 34.9%; EF 63.9%; CY 33.4%) and nurses (EX 49.2%; EF 46.9%; CY 29.7%). Being a resident increased the risk of burn-out (by nearly 2.5 times) in all the three MBI subscales and being a nurse increased the risk of burn-out in the EX dimension in comparison to physicians. Healthcare staff directly engaged with patients with COVID-19 showed more EX and CY than those working in non-COVID wards. Finally, the risk of burn-out was higher in staff showing pre-existing psychological problems, in those having experienced a COVID-related traumatic event and in those having experienced interpersonal avoidance in the workplace and personal life. CONCLUSIONS: Burn-out represents a great concern for healthcare staff working in a large tertiary hospital during the COVID-19 pandemic and its impact is more burdensome for front-line junior physicians. This study underlines the need to carefully address psychological well-being of healthcare workers to prevent the increase of burn-out in the event of a new COVID-19 healthcare emergency.