Mental health and wellbeing of health and aged care workers in Australia, May 2021 - June 2022: a longitudinal cohort study.

OBJECTIVES: To assess the mental health and wellbeing of health and aged care workers in Australia during the second and third years of the coronavirus disease 2019 (COVID-19) pandemic, overall and by occupation group. DESIGN, SETTING, PARTICIPANTS: Longitudinal cohort study of health and aged care workers (ambulance, hospitals, primary care, residential aged care) in Victoria: May-July 2021 (survey 1), October-December 2021 (survey 2), and May-June 2022 (survey 3). MAIN OUTCOME MEASURES: Proportions of respondents (adjusted for age, gender, socio-economic status) reporting moderate to severe symptoms of depression (Patient Health Questionnaire-9, PHQ-9), anxiety (Generalized Anxiety Disorder scale, GAD-7), or post-traumatic stress (Impact of Event Scale-6, IES-6), burnout (abbreviated Maslach Burnout Inventory, aMBI), or high optimism (10-point visual analogue scale); mean scores (adjusted for age, gender, socio-economic status) for wellbeing (Personal Wellbeing Index-Adult, PWI-A) and resilience (Connor Davidson Resilience Scale 2, CD-RISC-2). RESULTS: A total of 1667 people responded to at least one survey (survey 1, 989; survey 2, 1153; survey 3, 993; response rate, 3.3%). Overall, 1211 survey responses were from women (72.6%); most respondents were hospital workers (1289, 77.3%) or ambulance staff (315, 18.9%). The adjusted proportions of respondents who reported moderate to severe symptoms of depression (survey 1, 16.4%; survey 2, 22.6%; survey 3, 19.2%), anxiety (survey 1, 8.8%; survey 2, 16.0%; survey 3, 11.0%), or post-traumatic stress (survey 1, 14.6%; survey 2, 35.1%; survey 3, 14.9%) were each largest for survey 2. The adjusted proportions of participants who reported moderate to severe symptoms of burnout were higher in surveys 2 and 3 than in survey 1, and the proportions who reported high optimism were smaller in surveys 2 and 3 than in survey 1. Adjusted mean scores for wellbeing and resilience were similar at surveys 2 and 3 and lower than at survey 1. The magnitude but not the patterns of change differed by occupation group. CONCLUSION: Burnout was more frequently reported and mean wellbeing and resilience scores were lower in mid-2022 than in mid-2021 for Victorian health and aged care workers who participated in our study. Evidence-based mental health and wellbeing programs for workers in health care organisations are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12621000533897 (observational study; retrospective).

Evaluating the impact of alcohol minimum unit pricing on deaths and hospitalisations in Scotland: a controlled interrupted time series study.

BACKGROUND: Since May 1, 2018, every alcoholic drink sold in Scotland has had minimum unit pricing (MUP) of £0·50 per unit. Previous studies have indicated that the introduction of this policy reduced alcohol sales by 3%. We aimed to assess whether this has led to reductions in alcohol-attributable deaths and hospitalisations. METHODS: Study outcomes, wholly attributable to alcohol consumption, were defined using routinely collected data on deaths and hospitalisations. Controlled interrupted time series regression was used to assess the legislation's impact in Scotland, and any effect modification across demographic and socioeconomic deprivation groups. The pre-intervention time series ran from Jan 1, 2012, to April 30, 2018, and for 32 months after the policy was implemented (until Dec 31, 2020). Data from England, a part of the UK where the intervention was not implemented, were used to form a control group. FINDINGS: MUP in Scotland was associated with a significant 13·4% reduction (95% CI -18·4 to -8·3; p=0·0004) in deaths wholly attributable to alcohol consumption. Hospitalisations wholly attributable to alcohol consumption decreased by 4·1% (-8·3 to 0·3; p=0·064). Effects were driven by significant improvements in chronic outcomes, particularly alcoholic liver disease. Furthermore, MUP legislation was associated with a reduction in deaths and hospitalisations wholly attributable to alcohol consumption in the four most socioeconomically deprived deciles in Scotland. INTERPRETATION: The implementation of MUP legislation was associated with significant reductions in deaths, and reductions in hospitalisations, wholly attributable to alcohol consumption. The greatest improvements were in the four most socioeconomically deprived deciles, indicating that the policy is positively tackling deprivation-based inequalities in alcohol-attributable health harm. FUNDING: Scottish Government.

A cell-free platform to measure coronavirus membrane fusion

Here we present a protocol to measure coronavirus-mediated membrane fusion, an essential event in coronavirus-cell entry. The approach uses nanoluciferase (Nluc) "HiBiT”-tagged corona virus-like particles (VLPs) and Nluc "LgBiT” – containing extracellular vesicles (EVs) as proxies for virus and cell, respectively. VLP-EV membrane fusion allows HiBiT and LgBiT to combine into measurable Nluc, which signifies virus fusion with target cell membranes. We highlight assay utility with methods to assess coronavirus-mediated fusion and its inhibition by antibodies and antiviral agents. Graphical Publisher's note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

The increasing significance of disease severity in a burden of disease framework.

Recent estimates have reiterated that non-fatal causes of disease, such as low back pain, headaches and depressive disorders, are amongst the leading causes of disability-adjusted life years (DALYs). For these causes, the contribution of years lived with disability (YLD) - put simply, ill-health - is what drives DALYs, not mortality. Being able to monitor trends in YLD closely is particularly relevant for countries that sit high on the socio-demographic spectrum of development, as it contributes more than half of all DALYs. There is a paucity of data on how the population-level occurrence of disease is distributed according to severity, and as such, the majority of global and national efforts in monitoring YLD lack the ability to differentiate changes in severity across time and location. This raises uncertainties in interpreting these findings without triangulation with other relevant data sources. Our commentary aims to bring this issue to the forefront for users of burden of disease estimates, as its impact is often easily overlooked as part of the fundamental process of generating DALY estimates. Moreover, the wider health harms of the COVID-19 pandemic have underlined the likelihood of latent and delayed demand in accessing vital health and care services that will ultimately lead to exacerbated disease severity and health outcomes. This places increased importance on attempts to be able to differentiate by both the occurrence and severity of disease.

A cell-free platform to measure coronavirus membrane fusion.

Here we present a protocol to measure coronavirus-mediated membrane fusion, an essential event in coronavirus cell entry. The approach uses nanoluciferase (Nluc) "HiBiT"-tagged corona virus-like particles (VLPs) and Nluc "LgBiT"-containing extracellular vesicles (EVs) as proxies for virus and cell, respectively. VLP-EV membrane fusion allows HiBiT and LgBiT to combine into measurable Nluc, which signifies virus fusion with target cell membranes. We highlight assay utility with methods to assess coronavirus-mediated fusion and its inhibition by antibodies and antiviral agents. For complete details on the use and execution of this protocol, please refer to Qing et al. (2021),1 Qing et al. (2022),2 and Marcink et al. (2022).3.

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.

Direct impact of COVID-19 by estimating disability-adjusted life years at national level in France in 2020.

BACKGROUND: The World Health Organization declared a pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), on March 11, 2020. The standardized approach of disability-adjusted life years (DALYs) allows for quantifying the combined impact of morbidity and mortality of diseases and injuries. The main objective of this study was to estimate the direct impact of COVID-19 in France in 2020, using DALYs to combine the population health impact of infection fatalities, acute symptomatic infections and their post-acute consequences, in 28 days (baseline) up to 140 days, following the initial infection. METHODS: National mortality, COVID-19 screening, and hospital admission data were used to calculate DALYs based on the European Burden of Disease Network consensus disease model. Scenario analyses were performed by varying the number of symptomatic cases and duration of symptoms up to a maximum of 140 days, defining COVID-19 deaths using the underlying, and associated, cause of death. RESULTS: In 2020, the estimated DALYs due to COVID-19 in France were 990 710 (1472 per 100 000), with 99% of burden due to mortality (982 531 years of life lost, YLL) and 1% due to morbidity (8179 years lived with disability, YLD), following the initial infection. The contribution of YLD reached 375%, assuming the duration of 140 days of post-acute consequences of COVID-19. Post-acute consequences contributed to 49% of the total morbidity burden. The contribution of YLD due to acute symptomatic infections among people younger than 70 years was higher (67%) than among people aged 70 years and above (33%). YLL among people aged 70 years and above, contributed to 74% of the total YLL. CONCLUSIONS: COVID-19 had a substantial impact on population health in France in 2020. The majority of population health loss was due to mortality. Men had higher population health loss due to COVID-19 than women. Post-acute consequences of COVID-19 had a large contribution to the YLD component of the disease burden, even when we assume the shortest duration of 28 days, long COVID burden is large. Further research is recommended to assess the impact of health inequalities associated with these estimates.

Estradiol and Dihydrotestosterone Levels in COVID-19 Patients.

OBJECTIVE: To determine differences in plasma sex hormone levels in male and female coronavirus disease 2019 (COVID-19) patients and healthy volunteers (HVs) because cell entry of severe acute respiratory syndrome coronavirus 2 occurs via the angiotensin-converting enzyme 2 receptor which is downregulated by 17ß-estradiol. PATIENTS AND METHODS: Citrated plasma samples were collected from 101 patients with COVID-19 upon presentation to the emergency department and from 40 HVs between November 1, 2020, and May 30, 2021. Plasma 17ß-estradiol and 5α-dihydrotestosterone (DHT) levels were measured using enzyme-linked immunosorbent assay (pg/mL). Data are presented as median and quartiles (IQR). Wilcoxon rank sum test with a P value less than .05 was considered significant. RESULTS: Patients with COVID-19 (median age, 49 years) included 51 males and 50 females (25 postmenopausal). Hospital admission was required for 58.8% of male patients (n = 30) and 48.0% of female patients (n = 24) (66.7% postmenopausal, n = 16) Healthy volunteers (median age, 41 years) included 20 males and 20 females (9 postmenopausal). Female patients with COVID-19 were found to have decreased 17ß-estradiol levels (18.5 [IQR, 10.5-32.3] pg/mL; 41.4 [IQR, 15.5-111.0] pg/mL, P=.025), and lower 17ß-estradiol to DHT ratios (0.073 [IQR, 0.052-0.159] pg/mL; 0.207 [IQR, 0.104-0.538] pg/mL, P=.015) than female HVs. Male patients with COVID-19 were found to have decreased DHT levels (302.8 [IQR, 249.9-470.8] pg/mL; 457.2 [IQR, 368.7-844.3] pg/mL, P=.005), compared with male HVs. Levels of DHT did not differ between female patients with COVID-19 and female HVs, whereas 17ß-estradiol levels did not differ between male patients with COVID-19 and male HVs. CONCLUSION: Sex hormone levels differ between patients with COVID-19 and HVs, with sex-specific patterns of hypogonadism in males and females. These alterations may be associated with disease development and severity.

Patient hesitancy in perioperative clinical trial enrollment during the COVID-19 pandemic.

The COVID-19 pandemic has caused tremendous disruptions to non-COVID-19 clinical research. However, there has been little investigation on how patients themselves have responded to clinical trial recruitment during the COVID-19 pandemic. To investigate the effect of the COVID-19 pandemic on rates of patient consent to enrollment into non-COVID-19 clinical trials, we carried out a cross-sectional study using data from the Nitric Oxide/Acute Kidney Injury (NO/AKI) and Minimizing ICU Neurological Dysfunction with Dexmedetomidine-Induced Sleep (MINDDS) trials. All patients eligible for the NO/AKI or MINDDS trials who came to the hospital for cardiac surgery and were approached to gain consent to enrollment were included in the current study. We defined "Before COVID-19" as the time between the start of the relevant clinical trial and the date when efforts toward that clinical trial were deescalated by the hospital due to COVID-19. We defined "During COVID-19" as the time between trial de-escalation and trial completion. 5,015 patients were screened for eligibility. 3,851 were excluded, and 1,434 were approached to gain consent to enrollment. The rate of consent to enrollment was 64% in the "Before COVID-19" group and 45% in the "During COVID-19" group (n = 1,334, P<0.001) (RR = 0.70, 95% CI 0.62 to 0.80, P<0.001). Thus, we found that rates of consent to enrollment into the NO/AKI and MINDDS trials dropped significantly with the onset of the COVID-19 pandemic. Patient demographic and socioeconomic status data collected from electronic medical records and patient survey data did not shed light on possible explanations for this observed drop, indicating that there were likely other factors at play that were not directly measured in the current study. Increased patient hesitancy to enroll in clinical trials can have detrimental effects on clinical science, patient health, and patient healthcare experience, so understanding and addressing this issue during the COVID-19 pandemic is crucial.

A Report of Disseminated Histoplasmosis in an Immunocompromised Patient Following Covid-19 Infection

INTRODUCTION: Histoplasmosis results from spore inhalation of Histoplasma capsulatum, an endemic fungus in the soil of the Ohio and Mississippi River Valleys of the United States. While the majority of infections with H. capsulatum are asymptomatic and self-limited, immunosuppressed patients may develop severe, disseminated disease. Few reports have described disseminated histoplasmosis following SARS-CoV-2 (COVID-19) infection such as described in this case. DESCRIPTION: A 69-year-old female was evaluated for shortness of breath. Her medical history was significant for rheumatoid arthritis on methotrexate and recent COVID-19 infection treated with dexamethasone. Initial CT-angiography of the chest showed patchy bilateral ground glass opacities. She had leukopenia with white blood cell count of 1.3 K/uL and elevated procalcitonin of 5.88 ng/mL. Broad spectrum empiric antibiotics were initiated. On day 6, the patient decompensated and required ICU transfer. Urine histoplasma antigen, M and H precipitin bands, and serum galactomannan antigen returned positive. Amphotericin B was initiated. The patient underwent bronchoscopy with bronchoalveolar lavage showing atypical reactive macrophages with rare intracellular organisms suspicious for fungi. Repeat CT of the chest, abdomen, and pelvis showed extensive bilateral ground glass opacities, bilateral pulmonary calcifications consistent with granulomas, and calcifications in the spleen and liver. On hospital day 10, the patient required intubation due to hypoxemic respiratory failure. Despite appropriate antifungal therapy, she had worsening encephalopathy, leukocytosis, erythema nodosum, and renal failure. She passed away on day 19. DISCUSSION: This case highlights the development of disseminated histoplasmosis in an immunocompromised adult following COVID-19 infection. It was not until treatment with high dose glucocorticoids that the patient developed disseminated disease and declined. It is important to be aware of the impact that the COVID-19 pandemic has on the emergence of infectious disease and the role its treatment plays in immune suppression. Disseminated histoplasmosis is a consideration for immunocompromised patients in high risk, H. capsulatum endemic areas who are being treated for COVID-19 with high doses of steroids for prolonged periods.

Harnessing the Electronic Medical Record to Improve the Utilization of Ultrasound Screening for Abdominal Aortic Aneurysms.

PURPOSE: The US Preventive Services Task Force recommends one-time ultrasound screening to detect abdominal aortic aneurysms (AAAs) in male smokers. Despite this recommendation, AAA screening is still underutilized. The aim of this study was to determine the effectiveness of an electronic medical record (EMR) automated ordering program in increasing AAA screening at an integrated health care system. METHODS: This study was a retrospective chart review of patients who underwent ultrasound screening for AAA from January 1, 2016, to December 31, 2021, at a geographically isolated integrated health care system. An automated ordering system was implemented in a stepwise fashion within our EMR beginning in March 2019. The number of ultrasound studies and the incidence of AAA were compared between manual referral and EMR automated ordering periods. RESULTS: A total of 4,176 patients met the inclusion criteria for this study, among whom 148 aneurysms were identified. There was an increase in the average number of monthly screening ultrasound studies performed during the automated ordering period compared with the manual referral period (105 vs 16.3 studies, P < .001). The incidence of AAA was lower in the automated ordering period compared with the manual referral period (3.2% vs 5.3%, P = .013). CONCLUSIONS: An EMR automated ordering program can increase the number of screening ultrasound studies performed for AAA, which may help clinicians identify more high-risk aneurysms requiring urgent repair.

Implementation of a Virtual Asynchronous Scribe Program to Reduce Physician Burnout.

GOAL: Administrative burden is one of many potential root causes of physician burnout. Scribe documentation assistance can reduce this burden. However, traditional in-person scribe services are challenged by consistent staffing because the model requires the physical presence of a scribe and limits the team to a single individual. In addition, in-person scribes cannot provide the flexible support required for virtual care encounters, which can now pivot geographically and temporally. To respond to these challenges, our health network implemented an asynchronous virtual scribe model and evaluated the program's impact on clinician perceptions of burnout across multiple outpatient specialties. METHODS: Using a mixed-methods, pre-/postdesign, this evaluation measured the impact of an asynchronous virtual scribe program on physician burnout. Physicians were given the Professional Fulfillment Index tool (to self-assess their mental state) and free-text comment surveys before virtual scribe initiation and again at 3-, 6-, and 12-month intervals after program implementation. Descriptive statistics of survey results and qualitative review of free-text entries were analyzed for themes of facilitation and barriers to virtual scribe use. PRINCIPAL FINDINGS: Of 50 physician participants in this study, 42 (84%) completed the preintervention survey and 15 (36%) completed all 4 surveys; 25 participants (50%) discontinued scribe use after 12 months. Burnout levels-as defined by dread, exhaustion, lack of enthusiasm, decrease in empathy, and decrease in colleague connection-all trended toward improvement during this study. Importantly, quality, time savings, burnout, and productivity moved in positive directions as well. PRACTICAL APPLICATION: The cost burden to physicians and the COVID-19 pandemic inhibited the continued use of asynchronous virtual medical scribes. Nevertheless, those who continued in the program have reported positive outcomes, which indicates that the service can be a viable and effective tool to reduce physician burnout.

Asynchronous Telehealth.

Asynchronous telehealth provides a viable option for improving access in a convenient and timely manner to patients seeking care as well as for physicians seeking subspecialty consultation. Access to technology, clear guidelines, standards, and expectations is required for this innovation to function well. Limitations in access due to patient and technology factors is an area that requires attention. Positive impact on access and quality has been demonstrated. Rapid development continues and was enhanced with the Sars-CoV-2 pandemic.

Severity of previous infection enhances immune response to COVID-19 vaccination

Hybrid immunity from vaccination following recovery from infection with SARS-CoV- 2 is stronger than immunity induced by infection or vaccination alone. To test whether infection severity influenced the strength of subsequent vaccine-induced immune responses against SARS-CoV- 2, we measured humoral and cellular immune responses following recovery from infection, vaccine dose 1 and vaccine dose 2 in 35 persons experiencing COVID-19 of varying severity. Humoral immunity was assessed by ELISA and cellular immunity by ELISpot, intracellular flow cytometry and 51Cr cytotoxicity assays. Responses were compared between groups recovered from either asymptomatic/mild infection (n = 14) or moderate/ severe infection (n = 21). The group with moderate or severe infection had stronger humoral and cellular immune responses against SARS-CoV- 2 at all time points. Most subjects experienced robust increases in humoral and cellular immunity against SARS-CoV- 2 spike (S) protein following first vaccination. Quantitative responses to second vaccination were marginal in both groups, but the group with moderate or severe infection maintained stronger responses. Polyfunctional IFN-γ + IL-2+ CD8+ T cell responses were greater in the moderate/severe group following second vaccination and those with SARS-CoV- 2 spike (S)-specific IL-2 + CD8+ T cells generated strong anti-S cytotoxic T lymphocyte (CTL) responses following in vitro stimulation. Scanning with S peptide matrices indicated recognition of between 1 and 5 epitopes by CTL from persons recovered from moderate/severe COVID-19. As these epitopes are generally conserved across SARS-CoV- 2 variants, induction of S-specific central memory CD8+ T cells by infection and/or vaccination may provide broad protection against subsequent severe illness.

Burden of Disease of COVID-19: Strengthening the Collaboration for National Studies.

Objectives: Quantifying the combined impact of morbidity and mortality is a key enabler to assessing the impact of COVID-19 across countries and within countries relative to other diseases, regions, or demographics. Differences in methods, data sources, and definitions of mortality due to COVID-19 may hamper comparisons. We describe efforts to support countries in estimating the national-level burden of COVID-19 using disability-adjusted life years. Methods: The European Burden of Disease Network developed a consensus methodology, as well as a range of capacity-building activities to support burden of COVID-19 studies. These activities have supported 11 national studies so far, with study periods between January 2020 and December 2021. Results: National studies dealt with various data gaps and different assumptions were made to face knowledge gaps. Still, they delivered broadly comparable results that allow for interpretation of consistencies, as well as differences in the quantified direct health impact of the pandemic. Discussion: Harmonized efforts and methodologies have allowed for comparable estimates and communication of results. Future studies should evaluate the impact of interventions, and unravel the indirect health impact of the COVID-19 crisis.

Re-engineering the Cypriot General Healthcare System for Syndemics.

To date in Cyprus, there is no dedicated "Quality Improvement" body or Public Health authority. The long-awaited general healthcare system (known as GeSy or GHS) has been completed, mid-stream of the COVID-19 pandemic. A recently proposed resilience plan in response to the lessons learnt from the pandemic was put forward by the Government of the Republic of Cyprus to strengthen the capacity of the GHS and support public health defense. The negotiator of GeSy and Health Minister 2015-2018 also provided his view that the health system needs a holistic transformation of service provision. Recognizing failures and thinking from a syndemogenesis perspective how the envisioned patient-centric healthcare delivery can be achieved, we propose that the public health response could also be linked to a politico-economic one in shielding GeSy. We make such case for a syndemic strategy (simultaneous management of COVID-19 and pre-existing epidemics on the island) and the development of the five-district model where each main district hospital is to complement the activities of the GHS through developing: 1. A training Center for training and sharing of best practices for COVID-19 and other public emergencies. 2. A public health body. 3. A quality improvement institute. 4. A commissioning center on planning and streamlining healthcare services. 5. A clinical trial platform. The rationale is based on the management literature and use of existing resources and capabilities for transforming the GeSy and generating value.