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These collections showcase journal articles, preprints, book chapters, and other publications and presentations produced by faculty, postdocs, and researchers at UMass Chan Medical School, including a dedicated collection for research on COVID-19 and related viruses.

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  • Francis Fontan (1929-2018): Pioneer pediatric cardiac surgeon

    Huynh, Elisah; Chernick, Rebecca E.; Desai, Manisha S. (2022-09-07)
    Up until the mid-1900s, tricuspid atresia - a birth defect of the tricuspid valve, was once categorized as a "death sentence." The challenge of achieving positive health outcomes for affected patients was compounded by a hesitancy to operate on children. The main concern was safely administering anesthesia to young patients who were going through a strenuous operation that was often poorly tolerated. Despite these assumed limitations, Francis Fontan, a pediatric cardiothoracic surgeon at the Hospital of Tondu in Bordeaux, was able to redirect blood flow from the superior and inferior vena cava to the pulmonary arteries in 1971, which elucidated the process of advancing clinical practice in medicine. With the support of mentors and a firm belief in this new technique, Fontan pioneered his eponymous procedure and ultimately paved the way for modern cardiovascular surgical techniques that helped to prolong the life of those with single functioning ventricles. The aim of this study is to examine the genesis and the evolution of the Fontan procedure to elucidate the process of advancing clinical practice in medicine by utilizing personal interviews, Fontan's works, associated primary and secondary sources in the context of 20th century cardiothoracic surgery and innovations.
  • Examining Pregnant Veterans' Acceptance and Beliefs Regarding the COVID-19 Vaccine

    Mattocks, Kristin M.; Kroll-Desrosiers, Aimee R.; Moore Simas, Tiffany A.; Bastian, Lori A; Marteeny, Valerie; Walker, Lorrie; Sheahan, Kate; Elwy, A Rani (2022-08-30)
    Background: Pregnant persons have received mixed messages regarding whether or not to receive COVID-19 vaccines as limited data are available regarding vaccine safety for pregnant and lactating persons and breastfeeding infants. Objective: The aims of this study were to examine pregnant Veteran's acceptance of COVID-19 vaccines, along with perceptions and beliefs regarding vaccine safety and vaccine conspiracy beliefs. Design and participants: We conducted a cross-sectional survey of pregnant Veterans enrolled in VA care who were taking part in an ongoing cohort study at 15 VA medical centers between January and May 2021. Main measures: Pregnant Veterans were asked whether they had been offered the COVID-19 vaccine during pregnancy, and whether they chose to accept or refuse it. Additional questions focused on perceptions of COVID-19 vaccine safety and endorsements of vaccine knowledge and conspiracy beliefs. Logistic regression was utilized to examine predictors of acceptance of a vaccine during pregnancy. Key results: Overall, 72 pregnant Veterans were offered a COVID-19 vaccine during pregnancy; over two-thirds (69%) opted not to receive a vaccine. Reasons for not receiving a vaccine included potential effects on the baby (64%), side effects for oneself (30%), and immunity from a past COVID-19 infection (12%). Those who received a vaccine had significantly greater vaccine knowledge and less belief in vaccine conspiracy theories. Greater knowledge of vaccines in general (aOR: 1.78; 95% CI: 1.2-2.6) and lower beliefs in vaccine conspiracies (aOR: 0.76; 95% CI: 0.6-0.9) were the strongest predictors of acceptance of a COVID-19 vaccine during pregnancy. Conclusions: Our study provides important insights regarding pregnant Veterans' decisions to accept the COVID-19 vaccine, and reasons why they may choose not to accept the vaccine. Given the high endorsement of vaccine conspiracy beliefs, trusted healthcare providers should have ongoing, open discussions about vaccine conspiracy beliefs and provide additional information to dispel these beliefs.
  • International Controlled Study of Revascularization and Outcomes Following COVID-Positive Mechanical Thrombectomy

    Dmytriw, Adam A.; Kuhn, Anna L.; Puri, Ajit S.; Jabbour, Pascal (2022-07-12)
    BACKGROUND: Previous studies suggest that the mechanisms and outcomes in COVID-19-associated stroke differ from those with non-COVID-19 strokes, but there is limited comparative evidence focusing on these populations. Therefore, we aimed to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study of consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (mTICI 3), COVID-19 was associated with lower odds of complete revascularization [OR=0.33; 95% CI=0.23-0.48; p < 0.001], which persisted on multivariable modelling with adjustment for other predictors [aOR=0.30; 95% CI=0.12-0.77; p=0.012]. Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and suffered higher morbidity/mortality rates.
  • COVID-19: a gray swan's impact on the adoption of novel medical technologies

    Dunlap, Denise; Santos, Roberto S.; Lilly, Craig M.; Teebagy, Sean; Hafer, Nathaniel S.; Buchholz, Bryan O.; McManus, David D. (2022-07-08)
    The COVID-19 pandemic offers a unique context and opportunity to investigate changes in healthcare professional perceptions towards the adoption of novel medical technologies, such as point-of-care technologies (POCTs). POCTs are a nascent technology that has experienced rapid growth as a result of COVID-19 due to their ability to increase healthcare accessibility via near-patient delivery, including at-home. We surveyed healthcare professionals before and during COVID-19 to explore whether the pandemic altered their perceptions about the usefulness of POCTs. Our network analysis method provided a structure for understanding this changing phenomenon. We uncovered that POCTs are not only useful for diagnosing COVID-19, but healthcare professionals also perceive them as increasingly important for diagnosing other diseases, such as cardiovascular, endocrine, respiratory, and metabolic diseases. Healthcare professionals also viewed POCTs as facilitating the humanization of epidemiology by improving disease management/monitoring and strengthening the clinician-patient relationship. As the accuracy and integration of these technologies into mainstream healthcare delivery improves, hurdles to their adoption dissipate, thereby encouraging healthcare professionals to rely upon them more frequently to diagnose, manage, and monitor diseases. The technological advances made in POCTs during COVID-19, combined with shifting positive perceptions of their utility by healthcare professionals, may better prepare us for the next pandemic.
  • The Impact of the COVID-19 Pandemic on the Clubhouse Model

    McKay, Colleen E.; Corcoran, Joel D (2022-06-29)
    The COVID-19 pandemic posed challenges to the traditional Clubhouse Model of Psychosocial Rehabilitation (Clubhouse). The COVID-19 pandemic forced many Clubhouses around the world to rapidly pivot from face-to-face services and support programs at the Clubhouse to hybrid or virtual services. The Clubhouse community quickly mobilized to establish new structures to maintain connections with Clubhouse members and provide them with essential supports. This brief describes adaptations that Clubhouses made during the COVID-19 pandemic. We also describe supports offered by Clubhouse International to inform their international network about innovative approaches and best practices for Clubhouses during the COVID-19 pandemic.
  • Design and Preliminary Findings of Adherence to the Self-Testing for Our Protection From COVID-19 (STOP COVID-19) Risk-Based Testing Protocol: Prospective Digital Study

    Herbert, Carly; Broach, John P.; Gerber, Ben S.; Fahey, Nisha; Orvek, Elizabeth Aaker; Lazar, Peter; Ferranto, Julia M.; Noorishirazi, Kamran; Valpady, Shivakumar; Shi, Qiming; et al. (2022-06-16)
    BACKGROUND: Serial testing for SARS-CoV-2 is recommended to reduce spread of the virus; however, little is known about adherence to recommended testing schedules and reporting practices to health departments. OBJECTIVE: The Self-Testing for Our Protection from COVID-19 (STOP COVID-19) study aims to examine adherence to a risk-based COVID-19 testing strategy using rapid antigen tests and reporting of test results to health departments. METHODS: STOP COVID-19 is a 12-week digital study, facilitated using a smartphone app for testing assistance and reporting. We are recruiting 20,000 participants throughout the United States. Participants are stratified into high- and low-risk groups based on history of COVID-19 infection and vaccination status. High-risk participants are instructed to perform twice-weekly testing for COVID-19 using rapid antigen tests, while low-risk participants test only in the case of symptoms or exposure to COVID-19. All participants complete COVID-19 surveillance surveys, and rapid antigen results are recorded within the smartphone app. Primary outcomes include participant adherence to a risk-based serial testing protocol and percentage of rapid tests reported to health departments. RESULTS: As of February 2022, 3496 participants have enrolled, including 1083 high-risk participants. Out of 13,730 tests completed, participants have reported 13,480 (98.18%, 95% CI 97.9%-98.4%) results to state public health departments with full personal identifying information or anonymously. Among 622 high-risk participants who finished the study period, 35.9% showed high adherence to the study testing protocol. Participants with high adherence reported a higher percentage of test results to the state health department with full identifying information than those in the moderate- or low-adherence groups (high: 71.7%, 95% CI 70.3%-73.1%; moderate: 68.3%, 95% CI 66.0%-70.5%; low: 63.1%, 59.5%-66.6%). CONCLUSIONS: Preliminary results from the STOP COVID-19 study provide important insights into rapid antigen test reporting and usage, and can thus inform the use of rapid testing interventions for COVID-19 surveillance.
  • Surgical Triage and Timing for Patients with COVID: A Guidance Statement from the Society of Thoracic Surgeons

    Grant, Michael C.; Lother, Sylvain A.; Engelman, Daniel T.; Hassan, Ansar; Atluri, Pavan; Moosdorf, Rainer; Hayanga, J Awori.; Merritt-Genore, HelenMari; Chatterjee, Subhasis; Firstenberg, Michael S.; et al. (2022-05-21)
    The coronavirus disease 2019 (COVID-19) pandemic continues to disrupt the provision of cardiac procedural services due to overwhelming interval surges in COVID-19 cases and the associated crisis of cardiac intervention deferment. Despite the availability of widespread testing, highly efficacious vaccines, and intensive public health efforts, the pandemic is entering its third year where new SARS-CoV-2 variants have increased the likelihood that patients scheduled for cardiac intervention will contract COVID-19 in the perioperative period. The Society of Thoracic Surgeons (STS) Workforce on Critical Care, the Workforce on Adult Cardiac and Vascular Surgery and the Canadian Society of Cardiac Surgeons have developed this document, endorsed by the STS and affirmed by the Society of Cardiovascular Angiography and Interventions and the Canadian Association of Interventional Cardiology, to provide guidance for cardiac procedure deferment and intervention timing for preoperative patients diagnosed with COVID-19. This document is intended for the perioperative cardiac surgical team and outlines the present state of the pandemic, the impact of COVID-19 on intervention outcome, and offers a recommended algorithm for individualized cardiac procedure triage and timing.
  • COVID-19: The Impact on Internal Medicine Resident Training

    Garcia, Odalys Estefania. Lara; Sawalha, Khalid; Al-Akchar, Mohammad (2022-05-20)
    The novel coronavirus disease 2019 (COVID-19) pandemic has impacted the lives of physicians at all levels. The workloads and working hours have increased tremendously which affected the time spent on administrative and academic duties. The COVID-19 pandemic imposed a lot of challenges on academic institutions in term of providing quality of care to patients and maintaining the quality of education for trainee. Herein, we discuss the challenges and impact of the pandemic on residents training.
  • LGBTQ+ Health Research Guides: A Cross-institutional Pilot Study of Usage Patterns

    Stevens, Gregg A.; Fajardo, Francisco J.; Morris, Martin; Berry, Jessica; Parker, Robin M. N.; McLean, Katie D. (2022-05-06)
    Objectives: Multiple authors have recommended that health sciences libraries use research guides to promote LGBTQ+ health information, connect with their users and the community, and improve health equity. However, little is known about LGBTQ+ health guide usage patterns and whether such guides really meet the information needs of their users. Based on usage patterns from LGBTQ+ health research guides, we assessed the types of LGBTQ+ health information of greatest interest to health sciences library users and how, if appropriate, these guides might be revised to be more relevant to user needs. Methods: The data for LGBTQ+ health research guides of five health sciences libraries (three in the United States and two in Canada) were studied. Usage data were retrieved for a three year period (July 2018-June 2021). Two separate factors were chosen for analysis: monthly guide usage over time and the individual types of resources used. Monthly usage was studied by generating line graphs in Excel with trendlines to calculate overall guide usage trends. To determine the most sought-after types of resources by users, clicks for individual resources were categorized by type and focus using open coding in Google Sheets. Results: Overall guide usage was mixed, with some libraries’ guides trending upward over time and others downward. Analysis of the resource links showed that links to local and community health resources were among the most heavily clicked (64.11% of clicks), as were resources designed to help patients find healthcare providers and services (53.23%). Links to library-owned resources, such as books, journals, and databases, were generally clicked less (2.44%), as were links aimed at healthcare professionals (11.36%). Conclusions: The usage statistics for the guides were relatively low. However, the size of the LGBTQ+ community is relatively low compared to the general population and therefore LGBTQ+ health can be considered a category of minority health. We argue that the importance of providing quality LGBTQ+ health information outweighs any concerns of large-scale usage, and that providing such guides promotes health equity. The higher usage numbers for local resources supports the idea that guides are most useful when they link users to services and providers in their own communities. This suggests a best practice for librarians to focus on local resources and collaborations, and on consumer health resources, when creating and editing these guides.
  • Tocilizumab in patients hospitalised with COVID-19 pneumonia: Efficacy, safety, viral clearance, and antibody response from a randomised controlled trial (COVACTA)

    Rosas, Ivan O.; Brau, Norbert; Waters, Michael; Go, Ronaldo C.; Malhotra, Atul; Hunter, Bradley D.; Bhagani, Sanjay; Skiest, Daniel; Savic, Sinisa; Douglas, Ivor S.; et al. (2022-04-28)
    Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated. Methods: Adults in Europe and North America hospitalised with COVID-19 (N = 452) between April 3, 2020 and May 28, 2020 were randomly assigned (2:1) to double-blind intravenous tocilizumab or placebo and assessed for efficacy and safety through day 60. Assessments included mortality, time to hospital discharge, SARS-CoV-2 viral load in nasopharyngeal swab and serum samples, and neutralising anti-SARS-CoV-2 antibodies in serum. ClinicalTrials.gov registration: NCT04320615. Findings: By day 60, 24.5% (72/294) of patients in the tocilizumab arm and 25.0% (36/144) in the placebo arm died (weighted difference -0.5% [95% CI -9.1 to 8.0]), and 67.0% (197/294) in the tocilizumab arm and 63.9% (92/144) in the placebo arm were discharged from the hospital. Serious infections occurred in 24.1% (71/295) of patients in the tocilizumab arm and 29.4% (42/143) in the placebo arm. Median time to negative reverse transcriptase-quantitative polymerase chain reaction result in nasopharyngeal/oropharyngeal samples was 15.0 days (95% CI 14.0 to 21.0) in the tocilizumab arm and 21.0 days (95% CI 14.0 to 28.0) in the placebo arm. All tested patients had positive test results for neutralising anti-SARS-CoV-2 antibodies at day 60. Interpretation: There was no mortality benefit with tocilizumab through day 60. Tocilizumab did not impair viral clearance or host immune response, and no new safety signals were observed. Future investigations may explore potential biomarkers to optimize patient selection for tocilizumab treatment and combination therapy with other treatments.
  • “I felt isolated”: Patients’ Hospitalization Experiences During the COVID-19 Pandemic

    Nancy Morris; Patrick, Julia (2022-04-25)
    Purpose: The purpose of this Qualitative Descriptive study was to describe the experience of hospitalized adults during the pandemic who did not have COVID-19. Specific Aims: The specific aims of the study were to: Describe the hospital experience, including but not limited to, interactions with hospital staff, visitation, isolation, physical and emotional stressors, and the environment. Identify perceived comfort needs during hospitalization and perceptions of the nurse’s role in providing comforting interventions. Examine the ability to achieve physical, psychospiritual, sociocultural, and environmental comfort during hospitalization despite the required infection control measures. Framework: This study was guided by Kolcaba’s Theory of Comfort (1994). Design: This was a qualitative descriptive study. Semi-structured interviews were conducted. Interview questions focused on the overall hospital experience, the nurse’s role in their experience, comfort needs, and the experience of having comfort needs met during the hospitalization. Results: Twenty participants took part in this study. Conventional content analysis revealed five main themes. The themes are: I don’t expect the hospital to be comfortable, I was always tense, Wanting human connection, Communication is important, and Nurses are busy. Conclusion: The findings identified a need for targeting education, research, and policy development to improve patient comfort (physical, psycho-spiritual, sociocultural, and environmental). This is important as we look toward improving the overall patient experience during hospitalization.
  • Reducing stroke by screening for undiagnosed atrial fibrillation in elderly individuals (GUARD-AF): Rationale and design of the GUARD-AF randomized trial of screening for atrial fibrillation with a 14-day patch-based continuous ECG monitor

    Singer, Daniel E.; Atlas, Steven J.; Go, Alan S.; Lopes, Renato D.; Lubitz, Steven A.; McManus, David D.; Revkin, James H.; Mills, Donna; Crosson, Lori A.; Lenane, Judith C.; et al. (2022-04-25)
    BACKGROUND: Screening for atrial fibrillation (AF) is attractive because AF independently raises the risk of ischemic stroke, this risk is largely reversible by long-term oral anticoagulant therapy (OAC), and many patients with AF remain undiagnosed and untreated. Recent trials of one-time brief screening for AF have not produced a significant increase in the proportion of patients diagnosed with AF. Trials of longer-term screening have demonstrated an increase in AF diagnoses, primarily paroxysmal AF. To date, however, no trials have demonstrated that screening for AF results in lower rates of stroke. Clinical practice guidelines conflict in their level of support for screening for AF. METHODS: The GUARD-AF individually randomized trial is designed to test whether screening for AF in individuals age 70 years or greater using a 2-week single-lead electrocardiographic patch monitor can identify patients with undiagnosed AF and lead to treatment with OAC, resulting in a reduced rate of stroke in the screened population. The trial's efficacy end point is hospitalization for stroke (either ischemic or hemorrhagic) and the trial's safety end point is hospitalization for a bleeding event. End points will be ascertained via Medicare claims or electronic health records at 2.5 years after study start. Enrollment is based in primary care practices and the OAC decision for screen-detected cases is left to the patient and their physician. The initial planned target sample size was 52,000, with 26,000 allocated to either screening or to usual care. RESULTS: Trial enrollment was severely hampered by the novel coronavirus disease 2019 (COVID-19) pandemic and stopped at a total enrollment of 11,931 participants. Of 5,965 randomized to the screening arm, 5,713 patients (96%) returned monitors with analyzable results. Incidence of screen-detected and clinically detected AF and associated stroke and bleeding outcomes will be ascertained. CONCLUSIONS: GUARD-AF is the largest AF screening randomized trial using a longer-term patch-based continuous electrocardiographic monitor. The results will contribute important information on the yield of patch-based AF screening, the "burden" of AF detected (percent time in AF, longest episode), and physicians' OAC decisions as a function of AF burden. GUARD-AF's stroke and bleed results will contribute to pooled trial analyses of AF screening, thereby informing future studies and guidelines.
  • Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of concern

    Li, Maggie; Gerber, Jonathan M.; Sullivan, David J. (2022-04-20)
    The ongoing evolution of SARS-Co-V2 variants to omicron severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. Covid-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The FDA currently allows outpatient CCP for the immunosuppressed. Viral specific antibody levels in CCP can range ten- to hundred-fold between donors unlike the uniform viral specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-delta/pre-omicron donor units obtained before March 2021, 20 post-delta COVID-19/post-vaccination units and one pre-delta/pre-omicron hyperimmunoglobulin preparation for variant specific virus (vaccine-related isolate (WA-1), delta and omicron) neutralization correlated to Euroimmun S1 IgG antibody levels. We observed a 2- to 4-fold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to delta or omicron, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-delta COVID-19/post-vaccination units and the hyperimmunoglobulin effectively neutralized all three variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.
  • Application of Abbott ID NOW in the emergency department for SARS-CoV-2 detection: A medical center's perspective

    Fan, Shu-Ling Liang (2022-04-16)
    Testing for SARS-CoV-2 is crucial to tracking and controlling the pandemic. In particular, rapid testing in settings such as the emergency department (ED) could improve time to diagnosis and promote proper infection control measures. Early in the COVID-19 pandemic, we implemented the Abbott ID NOW COVID-19 method for screening symptomatic ED patients. However, due to concerns of suboptimal sensitivity, samples with a negative result were reflexed to the lab for confirmatory testing by the TaqPath COVID-19 Combo RT-PCR method. This study analyzed 6773 ID NOW results from April 2020 to September 2020 in the ED, of which 10% (n = 673) were positive and reported directly. The rest 90% (n = 6100) were negative and reflexed to RT-PCR. Among them, 3% (n = 175) turned positive on RT-PCR while 97% (n = 5925) of the results were consistently negative. The cycle threshold (Ct) values of the false-negative samples (n = 175) showed 90% (n = 158) of them with relatively low viral loads (Ct > /= 30) with median Ct value at 35, while a number of samples (n = 17) had low Ct values (Ct < 30) and no clear explanation for false-negative results. Our study demonstrates that the Abbott ID NOW, despite it's sensitivity limitations, was capable of providing near real-time results for 10% of symptomatic patients presenting to the ED allowing for improved management and workflow. However, our study findings emphasize the need to reflex negative specimens to a higher sensitivity method when prevalence is high and false-negative results are intolerable.
  • An artificial intelligence deep learning platform achieves high diagnostic accuracy for Covid-19 pneumonia by reading chest X-ray images

    Li, Dongguang; Li, Shaoguang (2022-04-15)
    The coronavirus disease of 2019 (Covid-19) causes deadly lung infections (pneumonia). Accurate clinical diagnosis of Covid-19 is essential for guiding treatment. Covid-19 RNA test does not reflect clinical features and severity of the disease. Pneumonia in Covid-19 patients could be caused by non-Covid-19 organisms and distinguishing Covid-19 pneumonia from non-Covid-19 pneumonia is critical. Chest X-ray detects pneumonia, but a high diagnostic accuracy is difficult to achieve. We develop an artificial intelligence-based (AI) deep learning method with a high diagnostic accuracy for Covid-19 pneumonia. We analyzed 10,182 chest X-ray images of healthy individuals, bacterial pneumonia. and viral pneumonia (Covid-19 and non-Covid-19) to build and test AI models. Among viral pneumonia, diagnostic accuracy for Covid-19 reaches 99.95%. High diagnostic accuracy is also achieved for distinguishing Covid-19 pneumonia from bacterial pneumonia (99.85% accuracy) or normal lung images (100% accuracy). Our AI models are accurate for clinical diagnosis of Covid-19 pneumonia by reading solely chest X-ray images.
  • The Impact of COVID-19 on Self-Reported Substance Use, Well-Being, and Functioning Among United States Veterans: A Cross-Sectional Study

    Reilly, Erin D.; Chamberlin, Elizabeth S.; Duarte, Brooke A.; Harris, J. Irene; Shirk, Steven D.; Kelly, Megan (2022-04-11)
    As the COVID-19 pandemic sweeps the globe, many veterans with substance use issues have faced the closure of treatment facilities, mandates to shelter in place, and social distancing measures. To better understand their pandemic experiences, substance use changes, and functioning, a survey was nationally administered to a sample of United States veterans reporting substance use issues during the pandemic. The purpose of this cross-sectional online survey for veterans (N = 409) was to report on COVID-19 experiences, safety behaviors, and infection experiences while also investigating the relationship among addictive behaviors, mental and physical health, and COVID-19 impact. Measures also assessed specific substance use concerns, pandemic-related loneliness, and functioning. Though few veterans reported personally receiving a confirmed COVID-19 medical diagnosis (10.5%), the impact of pandemic stressors was evident, with a majority reporting anxiety related to contracting COVID-19 (61.4%) or fear of a family member or close friend contracting COVID-19 (58.7%). Participants reported increased use of alcohol (45.3%), sedatives (36.6%), inhalants (35.7%), tobacco (35.0%), and cannabis (34.9%), attributed specifically to the pandemic. Regression analyses revealed that even when controlling for the contribution of problematic substance use issues, negative pandemic impacts and self-reported COVID-19 related loneliness were related to more impaired physical and mental health functioning during the pandemic. Findings from this sample of veterans with addiction issues add to the growing literature suggesting unique and adverse effects of COVID-19 stressors on functioning while also revealing specific pandemic impacts for this group.
  • Acute ischaemic stroke associated with SARS-CoV-2 infection in North America

    Dmytriw, Adam A.; Kuhn, Anna L.; Puri, Ajit S. (2022-04-01)
    BACKGROUND: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS < /=2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age > 60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p < 0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. CONCLUSION: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality.
  • Medicinal Plant Extracts and Natural Compounds for the Treatment of Cutaneous Lupus Erythematosus: A Systematic Review

    Lubov, Janet E.; Jamison, Aisha S.; Baltich Nelson, Becky; Amudzi, Alice A.; Haas, Kelly N. (2022-03-31)
    Cutaneous lupus erythematosus (CLE) is a group of autoimmune connective tissue disorders that significantly impact quality of life. Current treatment approaches typically use antimalarial medications, though patients may become recalcitrant. Other treatment options include general immunosuppressants, highlighting the need for more and more targeted treatment options. The purpose of this systematic review was to identify potential compounds that could be repurposed for CLE from natural products since many rheumatologic drugs are derived from natural products, including antimalarials. This study was registered with PROSPERO, the international prospective register of systematic reviews (registration number CRD42021251048). We comprehensively searched Ovid Medline, Cochrane Library, and Scopus databases from inception to April 27th, 2021. These terms included cutaneous lupus erythematosus; general plant, fungus, bacteria terminology; selected plants and plant-derived products; selected antimalarials; and JAK inhibitors. Our search yielded 13,970 studies, of which 1,362 were duplicates. We screened 12,608 abstracts, found 12,043 to be irrelevant, and assessed 565 full-text studies for eligibility. Of these, 506 were excluded, and 59 studies were included in the data extraction. The ROBINS-I risk of bias assessment tool was used to assess studies that met our inclusion criteria. According to our findings, several natural compounds do reduce inflammation in lupus and other autoimmune skin diseases in studies using in vitro methods, mouse models, and clinical observational studies, along with a few randomized clinical trials. Our study has cataloged evidence in support of potential natural compounds and plant extracts that could serve as novel sources of active ingredients for the treatment of CLE. It is imperative that further studies in mice and humans are conducted to validate these findings.
  • Whole-genome sequencing reveals that variants in the Interleukin 18 Receptor Accessory Protein 3'UTR protect against ALS

    Eitan, Chen; Werneburg, Sebastian; Schafer, Dorothy P.; Brown, Robert H. Jr.; Hornstein, Eran (2022-03-31)
    The noncoding genome is substantially larger than the protein-coding genome but has been largely unexplored by genetic association studies. Here, we performed region-based rare variant association analysis of > 25,000 variants in untranslated regions of 6,139 amyotrophic lateral sclerosis (ALS) whole genomes and the whole genomes of 70,403 non-ALS controls. We identified interleukin-18 receptor accessory protein (IL18RAP) 3' untranslated region (3'UTR) variants as significantly enriched in non-ALS genomes and associated with a fivefold reduced risk of developing ALS, and this was replicated in an independent cohort. These variants in the IL18RAP 3'UTR reduce mRNA stability and the binding of double-stranded RNA (dsRNA)-binding proteins. Finally, the variants of the IL18RAP 3'UTR confer a survival advantage for motor neurons because they dampen neurotoxicity of human induced pluripotent stem cell (iPSC)-derived microglia bearing an ALS-associated expansion in C9orf72, and this depends on NF-kappaB signaling. This study reveals genetic variants that protect against ALS by reducing neuroinflammation and emphasizes the importance of noncoding genetic association studies.
  • Multisystem inflammatory syndrome in children (MIS-C) possibly secondary to COVID-19 mRNA vaccination

    Wangu, Zoon; Swartz, Hannah; Doherty, Meaghan (2022-03-30)
    Multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 is a postinfectious condition identified during the COVID-19 pandemic with specific Centers for Disease Control and Prevention and WHO criteria. Theoretical concerns have been raised whether MIS-C might also occur after COVID-19 vaccination, as the pathogenesis of MIS-C is not yet entirely understood. We present a woman in her late teens who developed MIS-C after having received two doses of Pfizer BioNTech COVID-19 vaccine 12 weeks prior, in the setting of documented anti-spike SARS-CoV-2 IgG positive, antinucleocapsid SARS-CoV-2 IgG negative, and multiple negative surveillance SARS-CoV-2 PCRs done in the 12-week period prior to development of MIS-C. While vaccination remains safe and critical in controlling the pandemic, it may be considered as a potential trigger for MIS-C in patients with no history of infection. Further surveillance is necessary to determine whether MIS-C will emerge as a confirmed adverse event after COVID-19 vaccination.

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