Building a collaborative cloud platform to accelerate heart, lung, blood, and sleep research.

Research increasingly relies on interrogating large-scale data resources. The NIH National Heart, Lung, and Blood Institute developed the NHLBI BioData CatalystⓇ (BDC), a community-driven ecosystem where researchers, including bench and clinical scientists, statisticians, and algorithm developers, find, access, share, store, and compute on large-scale datasets. This ecosystem provides secure, cloud-based workspaces, user authentication and authorization, search, tools and workflows, applications, and new innovative features to address community needs, including exploratory data analysis, genomic and imaging tools, tools for reproducibility, and improved interoperability with other NIH data science platforms. BDC offers straightforward access to large-scale datasets and computational resources that support precision medicine for heart, lung, blood, and sleep conditions, leveraging separately developed and managed platforms to maximize flexibility based on researcher needs, expertise, and backgrounds. Through the NHLBI BioData Catalyst Fellows Program, BDC facilitates scientific discoveries and technological advances. BDC also facilitated accelerated research on the coronavirus disease-2019 (COVID-19) pandemic.

Acute Cardiac Events During COVID-19-Associated Hospitalizations.

BACKGROUND: COVID-19 is associated with cardiac complications. OBJECTIVES: The purpose of this study was to estimate the prevalence, risk factors, and outcomes associated with acute cardiac events during COVID-19-associated hospitalizations among adults. METHODS: During January 2021 to November 2021, medical chart abstraction was conducted on a probability sample of adults hospitalized with laboratory-confirmed SARS-CoV-2 infection identified from 99 U.S. counties in 14 U.S. states in the COVID-19-Associated Hospitalization Surveillance Network. We calculated the prevalence of acute cardiac events (identified by International Classification of Diseases-10th Revision-Clinical Modification codes) by history of underlying cardiac disease and examined associated risk factors and disease outcomes. RESULTS: Among 8,460 adults, 11.4% (95% CI: 10.1%-12.9%) experienced an acute cardiac event during a COVID-19-associated hospitalization. Prevalence was higher among adults who had underlying cardiac disease (23.4%; 95% CI: 20.7%-26.3%) compared with those who did not (6.2%; 95% CI: 5.1%-7.6%). Acute ischemic heart disease (5.5%; 95% CI: 4.5%-6.5%) and acute heart failure (5.4%; 95% CI: 4.4%-6.6%) were the most prevalent events; 0.3% (95% CI: 0.1%-0.5%) experienced acute myocarditis or pericarditis. Risk factors varied by underlying cardiac disease status. Patients with ≥1 acute cardiac event had greater risk of intensive care unit admission (adjusted risk ratio: 1.9; 95% CI: 1.8-2.1) and in-hospital death (adjusted risk ratio: 1.7; 95% CI: 1.3-2.1) compared with those who did not. CONCLUSIONS: Acute cardiac events were common during COVID-19-associated hospitalizations, particularly among patients with underlying cardiac disease, and are associated with severe disease outcomes. Persons at greater risk for experiencing acute cardiac events during COVID-19-associated hospitalizations might benefit from more intensive clinical evaluation and monitoring during hospitalization.

Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection.

The continuous evolution of SARS-CoV-2 variants complicates efforts to combat the ongoing pandemic, underscoring the need for a dynamic platform for the rapid development of pan-viral variant therapeutics. Oligonucleotide therapeutics are enhancing the treatment of numerous diseases with unprecedented potency, duration of effect, and safety. Through the systematic screening of hundreds of oligonucleotide sequences, we identified fully chemically stabilized siRNAs and ASOs that target regions of the SARS-CoV-2 genome conserved in all variants of concern, including delta and omicron. We successively evaluated candidates in cellular reporter assays, followed by viral inhibition in cell culture, with eventual testing of leads for in vivo antiviral activity in the lung. Previous attempts to deliver therapeutic oligonucleotides to the lung have met with only modest success. Here, we report the development of a platform for identifying and generating potent, chemically modified multimeric siRNAs bioavailable in the lung after local intranasal and intratracheal delivery. The optimized divalent siRNAs showed robust antiviral activity in human cells and mouse models of SARS-CoV-2 infection and represent a new paradigm for antiviral therapeutic development for current and future pandemics.

Primary Care Patients' and Staff's Perceptions of Self-Rooming as Alternative to Waiting Rooms.

PURPOSE: Most patients are escorted to exam rooms (escorted rooming) although patients directing themselves to their exam room (self-rooming) saves patient and staff time while increasing patient satisfaction. This study assesses patient and staff perceptions after pragmatic implementation of self-rooming. METHODS: In October-December 2020, we surveyed patients and staff in 25 primary care clinics after our institution expanded self-rooming from 4 specially built clinics during the COVID-19 pandemic. Semi-structured surveys asked about rooming process used, rooming process preferred, and perceptions of self-rooming compared with escorted rooming. RESULTS: Most patients (n = 1,561) preferred self-rooming (86%), especially among patients aged <65 years and in family medicine clinics. Few patients felt less welcomed (10.6%), less cared about (6.8%), more isolated (15.6%), more lost/confused (7.6%), or more frustrated (3.2%) with self-rooming compared with escorted rooming. Early-adopter clinics that implemented self-rooming ≤2016 had even lower rates of patients feeling more isolated, lost/confused, or frustrated with self-rooming compared with escorted rooming.Over one-half of staff (n = 241; 180 clinical, 61 nonclinical) preferred self-rooming (59%) and thought most patients liked self-rooming (65.8%), especially among clinical staff and in early adopter clinics (≤2016). Few staff reported worse waiting times for patients (12.4%), medical assistants (MAs) (15.9%), and clinicians (16.4%) or worse crowding in waiting areas (1.7%) and hallways (10.1%). Unlike patient-reported confusion (7.6%), most staff thought self-rooming led to more patient confusion (63.8%), except in early-adopter clinics (44.4%). CONCLUSIONS: Self-rooming is a patient-centered innovation that is also acceptable to staff. We demonstrated that pragmatic implementation is feasible across primary care without expensive technology or specially designed buildings.

Education increases COVID-19 vaccine uptake among people in Canadian federal prisons in a prospective randomized controlled trial: The EDUCATE study.

Education is key to behavioural adoption and acceptability of health interventions. We evaluated the impact of an educational intervention administered 1:1 to individuals incarcerated in four Canadian federal prisons on COVID-19 vaccine uptake. Eligible individuals (those who had refused all COVID-19 vaccines) were randomized 2:1 to receive the educational intervention or not (control group); those who received the intervention completed questionnaires assessing COVID-19 vaccine-related knowledge, attitudes, and beliefs pre- and post-educational intervention. The primary and secondary outcome measures were COVID-19 vaccine uptake and vaccine confidence, respectively. Between May 3 and September 9, 2022, 202 participants were randomized to receive the intervention, of whom 127 (63 %) agreed to participate. Participants who were randomized to the intervention had higher COVID-19 vaccine uptake vs. the control group (5 % vs 1 %, p = 0.046). COVID-19 vaccine-related knowledge, attitudes, and beliefs improved post-intervention. Education increases COVID-19 vaccine uptake and confidence among people in Canadian federal correctional facilities.

Affective domain predictors of PharmD student pursuit of and successful matching for postgraduate pharmacy residency training.

PURPOSE: A study was conducted to identify significant associations between affective domain (AD) features identified using the Birkman Method assessment and students' likelihood to pursue and to successfully match for postgraduate residency training (PGRT), while controlling for demographic and academic variables known to impact PGRT match rates. METHODS: A retrospective analysis of 3 graduating classes of PharmD students from 2 colleges of pharmacy was performed. Data points such as PGRT match results, PGRT pursuit, student demographics, academic performance information, and AD data from the Birkman assessment were analyzed. Regression analysis was used to identify statistically significant associations between demographic, academic performance, and AD variables with both pursuit of PGRT and successful matching for PGRT. RESULTS: Data from 503 students were evaluated, with 211 (42%) pursuing PGRT. A variety of AD variables were significantly associated with pursuing PGRT and matching for PGRT. Two groups of actionable variables emerged: (1) variables associated with a lesser likelihood of pursuing PGRT but a greater likelihood of successful matching, and (2) variables associated with a greater likelihood of pursuing PGRT and a lesser likelihood of successful matching. CONCLUSION: Early identification of students' AD features along with specific interventions to promote PGRT pursuit in those less likely to pursue but more likely to match, as well as interventions to promote successful matching in students most likely to pursue but less likely to match for PGRT, is a strategy for possibly optimizing PharmD student career path planning and PGRT match success that merits further evaluation.

Practices and activities among healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection working in different healthcare settings-ten Emerging Infections Program sites, April-November 2020.

Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.

The Landscape of Candidemia During the Coronavirus Disease 2019 (COVID-19) Pandemic.

BACKGROUND: The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 coinfection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis. METHODS: We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention's Emerging Infections Program during April-August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher's exact tests. RESULTS: Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid-organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 coinfection, whereas intensive care unit-level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All-cause in-hospital fatality was 2 times higher among those with COVID-19 (62.5%) than without (32.1%). CONCLUSIONS: One-quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19.

Substance abuse and neurotransmission.

The number of people who suffer from a substance abuse disorder has continued to rise over the last decade; particularly, the number of drug-related overdose deaths has sharply increased during the COVID-19 pandemic. Converging lines of clinical observations, supported by imaging and neuropsychological performance testing, have demonstrated that substance abuse-induced dysregulation of neurotransmissions in the brain is critical for development and expression of the addictive properties of abused substances. Recent scientific advances have allowed for better understanding of the neurobiological processes that mediates drugs of abuse and addiction. This chapter presents the past classic concepts and the recent advances in our knowledge about how cocaine, amphetamines, opioids, alcohol, and nicotine alter multiple neurotransmitter systems, which contribute to the behaviors associated with each drug. Additionally, we discuss the interactive effects of HIV-1 or COVID-19 and substance abuse on neurotransmission and neurobiological pathways. Finally, we introduce therapeutic strategies for development of pharmacotherapies for substance abuse disorders.

Risk Factors for SARS-CoV-2 Infection Among US Healthcare Personnel, May-December 2020.

To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case-control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living.

Clinical Trends Among U.S. Adults Hospitalized With COVID-19, March to December 2020 : A Cross-Sectional Study.

BACKGROUND: The COVID-19 pandemic has caused substantial morbidity and mortality. OBJECTIVE: To describe monthly clinical trends among adults hospitalized with COVID-19. DESIGN: Pooled cross-sectional study. SETTING: 99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET). PATIENTS: U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020. MEASUREMENTS: Monthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100 000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients. RESULTS: Among 116 743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100 000 persons), ICU admission (20.2 per 100 000 persons), and death (11.7 per 100 000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18 508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December. LIMITATION: COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country. CONCLUSION: Rates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

COVID-19-Associated Hospitalizations Among Health Care Personnel - COVID-NET, 13 States, March 1-May 31, 2020.

Health care personnel (HCP) can be exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), both within and outside the workplace, increasing their risk for infection. Among 6,760 adults hospitalized during March 1-May 31, 2020, for whom HCP status was determined by the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), 5.9% were HCP. Nursing-related occupations (36.3%) represented the largest proportion of HCP hospitalized with COVID-19. Median age of hospitalized HCP was 49 years, and 89.8% had at least one underlying medical condition, of which obesity was most commonly reported (72.5%). A substantial proportion of HCP with COVID-19 had indicators of severe disease: 27.5% were admitted to an intensive care unit (ICU), 15.8% required invasive mechanical ventilation, and 4.2% died during hospitalization. HCP can have severe COVID-19-associated illness, highlighting the need for continued infection prevention and control in health care settings as well as community mitigation efforts to reduce transmission.

Characteristics and Maternal and Birth Outcomes of Hospitalized Pregnant Women with Laboratory-Confirmed COVID-19 - COVID-NET, 13 States, March 1-August 22, 2020.

Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19) (1,2). The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) (3) collects data on hospitalized pregnant women with laboratory-confirmed SARS-CoV-2, the virus that causes COVID-19; to date, such data have been limited. During March 1-August 22, 2020, approximately one in four hospitalized women aged 15-49 years with COVID-19 was pregnant. Among 598 hospitalized pregnant women with COVID-19, 54.5% were asymptomatic at admission. Among 272 pregnant women with COVID-19 who were symptomatic at hospital admission, 16.2% were admitted to an intensive care unit (ICU), and 8.5% required invasive mechanical ventilation. During COVID-19-associated hospitalizations, 448 of 458 (97.8%) completed pregnancies resulted in a live birth and 10 (2.2%) resulted in a pregnancy loss. Testing policies based on the presence of symptoms might miss COVID-19 infections during pregnancy. Surveillance of pregnant women with COVID-19, including those with asymptomatic infections, is important to understand the short- and long-term consequences of COVID-19 for mothers and newborns. Identifying COVID-19 in women during birth hospitalizations is important to guide preventive measures to protect pregnant women, parents, newborns, other patients, and hospital personnel. Pregnant women and health care providers should be made aware of the potential risks for severe COVID-19 illness, adverse pregnancy outcomes, and ways to prevent infection.

Hospitalization Rates and Characteristics of Children Aged <18 Years Hospitalized with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, March 1-July 25, 2020.

Most reported cases of coronavirus disease 2019 (COVID-19) in children aged <18 years appear to be asymptomatic or mild (1). Less is known about severe COVID-19 illness requiring hospitalization in children. During March 1-July 25, 2020, 576 pediatric COVID-19 cases were reported to the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system that collects data on laboratory-confirmed COVID-19-associated hospitalizations in 14 states (2,3). Based on these data, the cumulative COVID-19-associated hospitalization rate among children aged <18 years during March 1-July 25, 2020, was 8.0 per 100,000 population, with the highest rate among children aged <2 years (24.8). During March 21-July 25, weekly hospitalization rates steadily increased among children (from 0.1 to 0.4 per 100,000, with a weekly high of 0.7 per 100,000). Overall, Hispanic or Latino (Hispanic) and non-Hispanic black (black) children had higher cumulative rates of COVID-19-associated hospitalizations (16.4 and 10.5 per 100,000, respectively) than did non-Hispanic white (white) children (2.1). Among 208 (36.1%) hospitalized children with complete medical chart reviews, 69 (33.2%) were admitted to an intensive care unit (ICU); 12 of 207 (5.8%) required invasive mechanical ventilation, and one patient died during hospitalization. Although the cumulative rate of pediatric COVID-19-associated hospitalization remains low (8.0 per 100,000 population) compared with that among adults (164.5),* weekly rates increased during the surveillance period, and one in three hospitalized children were admitted to the ICU, similar to the proportion among adults. Continued tracking of SARS-CoV-2 infections among children is important to characterize morbidity and mortality. Reinforcement of prevention efforts is essential in congregate settings that serve children, including childcare centers and schools.

Pulmonary embolism in acute medicine: a case-based review incorporating latest guidelines in the COVID-19 era.

Pulmonary embolism remains an important cause of morbidity and mortality in the UK, particularly following the outbreak of the novel coronavirus 2019 (COVID-19), where those infected have an increased prevalence of venous thromboembolic events. The pathophysiology in COVID-19 patients is thought to relate to a thromboinflammatory state within the pulmonary vasculature, triggered by the infection, but other risk factors such as reduced mobility, prolonged immobilisation and dehydration are likely to contribute. Several societies have released comprehensive guidelines emphasising the importance of risk stratification in patients with acute pulmonary embolism. They advocate the use of clinically validated risk scores in conjunction with biochemical and imaging results. Patients with mild disease can now be managed in the outpatient setting and with newly developed therapies, such as catheter-directed thrombolysis, becoming available in more centres, treatment options for those with more severe disease are also expanding. This article presents four theoretical but realistic cases, each diagnosed with acute pulmonary embolism, but differing in levels of severity. These demonstrate how the guidelines can be applied in a clinical setting, with particular focus on risk stratification and management.