EXPLORING THE GENOME-WIDE GENETIC OVERLAP BETWEEN ANXIETY AND FEAR DISORDERS

: Background: Twin studies have consistently shown a high genetic overlap amongst anxiety disorders and depression. Some research has also identified modest genetic specificity to fear-based anxiety disorders not shared with general anxiety. Identifying the genetic variants shared amongst all anxiety disorders or specific to one or more requires large sample sizes. Measuring anxiety disorders in large cohorts typically involves in-depth symptom-based diagnoses or minimally phenotyped single-item self-report diagnoses. A trade-off exists between maximising sample size and the level of detail in the phenotyping. Aims: First, to explore genetic correlations between generalised anxiety disorder (GAD) and the fear disorders (panic disorder, agoraphobia, specific phobia and social phobia) using a combination of in-depth and minimal phenotyping. Second, to compare the results from using minimal phenotyping of the anxiety disorders to that of in-depth phenotyping. Methods: We will use two case-only samples for analyses: the Genetic Links to Anxiety and Depression (GLAD) Study (∼N = 18,000) and the Australian Genetics of Depression Study (AGDS) (∼18,000). In addition, we will use three studies that provide both cases and controls: the COVID-19 Psychiatric and Neurological Genetics (COPING) study (N = ∼10,000), the QSkin study (N = ∼18,000) and the UK Biobank (N = ∼157,366). We will conduct three independent sets of case-control anxiety disorder genome-wide association studies (GWAS) before meta-analysing all five samples together (expected N cases ∼53,000, N controls ∼160,000). Results from GWAS meta-analyses of lifetime anxiety disorder, GAD, and fear-based disorders will be used to explore genetic correlations across anxiety disorders and depression and a wide range of complex traits. As sensitivity analyses, we will explore genetic correlations between anxiety phenotypes assessed using minimally phenotyped single-item diagnoses versus in-depth symptom-based diagnoses. Results: We hypothesise that the anxiety disorders will have a SNP-based heritability of approximately 15%. We also hypothesise that GAD and fear-based disorders will be moderately to highly genetically correlated, with some genetic variants that are specific to the fear disorders [1]. Disclosure: Nothing to disclose.

DIARRHEA, ELEVATED AST, AND ELEVATION OF INFLAMMATORYRELATED BIOMARKERS IS A PREDICTOR FOR MORTALITY IN MINORITY HOSPITALISED COVID-19 PATIENTS

Background and Aims: Initial reports on US COVID-19 showed different outcomes in different races. In this study, we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. Methods: We analyzed data from hospitalized COVID- 19 patients (n=5,852) from 8 hospitals. Demographics, comorbidities, symptoms and laboratory data were collected. Results: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and dead patients' mean ages were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, and EA were 14.8%, 7.3%, and 16.3%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation, respiratory failure, shortness of breath (SOB) (p<0.01), fatigue (p=0.04), diarrhea (p=0.02), and increased AST (p<0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had a higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables were age (over 45 years old), male sex, EA, patients hospitalized in Indiana, Michigan, Georgia, and District of Columbia. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP, and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID- 19 death in our cohort. Conclusion: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, predictors of mortality include male gender, diarrhea, elevated AST, comorbidities, respiratory symptoms and failure, and elevation of inflammatory- related biomarkers. These findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to a high frequency of comorbidities and older age among AA.

Long-Term Results of a Novel, Externally-Powered, Spinal Cord Stimulator for Chronic Pain (AUS nPower study)

Introduction: A novel spinal cord stimulation (SCS) system with a battery-free micro-implantable pulse generator (mIPG;Nalu Medical, Inc. CA, USA) is available for the treatment of intractable chronic pain. The system utilizes an external power source that bi-directionally communicates with the mIPG (∼1.5 cc volume). Methods: A prospective, multi-center clinical study was initiated to confirm the safety and performance of this novel system, in the treatment of trunk and limb intractable chronic pain. Specifically, subjects with leg(s) and/or back pain, meeting eligibility criteria were recruited and consented into the study. Subjects underwent a SCS trial utilizing a menu of therapy options, including tonic and the novel pulsed stimulation pattern (PSP) therapy. Eligible subjects received the permanent implant and were followed-up for up to 12-months from activation. Due to global COVID-19 restrictions, subjects were moved into a long-term follow-up (LTFU) phase, with study visits planned every 6-months, for an additional 2-years from their last visit. This reports on the long-term clinical and functional (depression, activities of daily living, overall change in quality of life) outcomes. The study was approved by an independent Ethics Committee and conducted in compliance with local regulations. Results: Twenty-five (25) intractable chronic back and/or leg pain subjects, using the PSP therapy, passed a screening and trial phase with ≥50% pain reduction in leg(s) and/or back and moved into the long-term implant phase of the study. Of these 25 subjects, 13 subjects have currently completed an average of 22-months follow-up;the average pain reduction was 73% (n=12) in the leg and 64% (n=11) in the back, from baseline to this time point. The responder rate (≥50% pain relief) was 92% in the leg (11/12) and 64% (7/11) in the back. In addition, all subjects wore the external power source via an adhesive clip and rated both its average comfort and ease of use as <1 on an 11-point scale (0=Very Comfortable, 10=Very Uncomfortable;0=Very Easy, 10=Very Difficult). The average percent improvement on the Beck’s Depression Inventory (BDI) was 40% (n=13) from screening to 22-months;the average improvement in Oswestry Disability Index (ODI) was 34% (n=13) at this time point. Sixty-nine percent (69%;9/13) of subjects indicated “very much improved” on the Patient Global Impression of Change. Conclusion: These results continue to demonstrate the favorable performance of this novel, battery-free, externally-powered micro-implantable SCS through 22-months post implantation. Further investigation is warranted to confirm these preliminary findings. Disclosure: Paul Verrills, FAFMM GDMM (Hons) MM (Pain Medicine) FIPP AMA: Abbott: Consulting Fee: Self, Abbott: Speakers Bureau: Self, Nalu: Ownership Interest - Future Stock Options: Self, Nalu: Contracted Research: Self, Nevro: Contracted Research: Self, Saluda: Contracted Research: Self, Nalu: Speakers Bureau: Self, Biotronik: Consulting Fee: Self, Presidio: Contracted Research: Self, John Salmon, MBBS: None, Dan Bates, MBBS: None, James Yu, MD: None, Bruce Mitchell, MD: None, Neels Du Toit, MBChB: None, Matthew Green, MD: None, Murray Taverner, MBBS: None, Vahid Mohabbati, MD: None, Peter Staats, MBA,MD: Saluda Medical: Consulting Fee: Self, Grunenthal: Royalty:, Medtronic: Fees for Non-CME/CE Services (e.g. advisor):, electroCore: Employee:, SPR therapeutics: Ownership Interest:, Nalu: Fees for Non-CME/CE Services (e.g. advisor):, Gary Heit, MD, PhD: Nalu Medical Inc: Consultant: Self, Robert Levy, MD, PhD: Nalu: Ownership Interest:, Saluda: Ownership Interest:, James Makous, PhD: Nalu Medical: Consulting Fee:, Nalu Medical: Ownership Interest:

Varied Institutional Responses to COVID-19: An Investigation of US Colleges' and Universities' Reopening Plans for Fall 2020

The authors investigate coronavirus disease 2019 (COVID-19) risk factors, suitability of online instruction, politics, and institutions' finances as rationales guiding instructional delivery decisions for fall 2020, after COVID-19's emergence. Contributions include estimating multinomial logit regressions with mode of delivery as a categorical variable, integrating resource dependence and crisis response as theoretical frames, and introducing new predictor variables, including a measure of local residential access to broadband Internet. Findings suggest that county populations, local political preferences, and the percentage of revenue derived from auxiliary enterprises were consistent predictors of delivery mode. Political parties of an institution's governor and congressional representative were predictive of delivery mode for institutions in the lowest tercile of endowment per student but not for institutions in the highest tercile. Bottom-tercile institutions substituted from online to in-person reopening as reliance on revenue from auxiliary enterprises increased, but top-tercile institutions appeared only to substitute from hybrid to in-person or from online to hybrid delivery as revenue from auxiliary enterprises or tuition and fees increased.

Small-Sized Neural Network for Detecting COVID-19 from Chest X-rays

COVID-19 is a highly contagious infection that has now reached almost all countries in the world infecting over 33M and killing 1M people as of the time of writing. Therefore, it is essential to diagnose it early so that health care professionals can prevent the chance of a person spreading the virus. Because the disease often presents with respiratory symptoms, one method for detecting it is by radiology examination using chest radiography. Healthcare professionals examine the chest X-ray for abnormalities that are characteristics of those infected with COVID-19, which must be distinguished from other conditions with similar presentation such as pneumonia. This requires significant expertise, which may not be available in all parts of the world, so computer assisted diagnosis would be highly beneficial. We propose a deep neural network for extracting those abnormalities as features and classifying the infection. In this study, we examine the efficiency of small-sized deep neural network tailored for the detection of COVID-19 infection from chest X-ray (CXR) images. We designed a modified version of SqueezeNet and Capsule Network and show that even with a relatively small number of free parameters, it can achieve a competitive result while having modest hardware requirements. We use a modified version of fire modules to ensure better convergence. For our Capsule network, we used fire modules as two of its upper layers. To our knowledge, this is the first time that a fire module has been used in conjunction with capsules. Without any pretraining or transfer learning, our SqueezeNet was able to achieve an accuracy of 94.8 %, sensitivity of 88.0 %, and specificity of 98.4%. Additionally, our CapsNet achieved an accuracy of 93.8 %, sensitivity of 88.0 %, and specificity of 96.9 %. © 2020 IEEE.

COVID-19-related anxieties: Impact on duty to care among nurses.

BACKGROUND: Duty to care is integral to nursing practice. Personal obligations that normally conflict with professional obligations are likely amplified during a public health emergency such as COVID-19. Organizations can facilitate a nurse's ability to fulfill the duty to care without compromising on personal obligations. RESEARCH AIM: The study aimed to explore the relationships among duty to care, perception of supportive environment, perceived stress, and COVID-19-specific anxieties in nurses working directly with COVID-19 patients. RESEARCH DESIGN: The study design was a cross-sectional descriptive study using an online survey. It was conducted at an ANCC Magnet® designated 385-bed acute care teaching hospital located in a suburban area. PARTICIPANTS AND RESEARCH CONTEXT: Included in this study were 339 medical surgical nurses working directly with COVID-19 patients during the early phase of the pandemic. ETHICAL CONSIDERATIONS: The study was reviewed by the institution's clinical research committee and determined to be exempt. A survey invitation letter with a voluntary implied consent agreement was sent to participants with a description of the research study attached to the anonymous survey. RESULTS: Nurses with specific COVID-19-related anxieties were more likely to agree that it was ethical to abandon the workplace during a pandemic. CONCLUSIONS: Organizations can and ought to mitigate the negative effects of COVID-19 on duty to care in future pandemics and healthcare emergencies by incorporating several recommendations derived from this study.

Assessment of twenty-two SARS-CoV-2 rapid antigen tests against SARS-CoV-2: A laboratory evaluation study (preprint)

Background Rapid antigen testing is widely used as a way of scaling up population-level testing. To better inform antigen test deployment in Australia, we evaluated 22 commercially available antigen tests, including an assessment of culture infectivity. Methods Analytical sensitivity was evaluated against SARS-CoV-2 B.1.617.2 (Delta), reported as TCID50/mL, cycle threshold (Ct) value and viral load (RNA copies/mL). Specificity was assessed against non-SARS-CoV-2 viruses. Clinical sensitivity and correlation with cell culture infectivity was assessed using the Abbott PanBio COVID-19 Ag test. Results Nineteen kits consistently detected SARS-CoV-2 antigen equivalent to 1.3x10^6 copies/mL (5.8x10^3 TCID50/mL). Specificity for all kits was 100%. Compared to RT-PCR the Abbott PanBio COVID-19 Ag test was 52.6% (95% CI, 41.6% to 63.3%) sensitive, with a 50% detection probability for infectious cell culture at 5.9 log10 RNA copies/mL (95% CI, 5.3 to 6.5 log10 copies/mL). Antigen test sensitivity was 97.6% (95% CI, 86.3% to 100.0%) compared to positive infectious in cell culture. Conclusions Antigen test positivity correlated with positive viral culture, suggesting antigen test results may determine SARS-CoV-2 transmission risk. Sensitivity varied considerably between test kits and highlights the need for ongoing systematic post-market evaluation, providing valuable information to help guide antigen test selection and deployment.