Operations (management) warp speed: Rapid deployment of hospital‐focused predictive/prescriptive analytics for the COVID‐19 pandemic

At the onset of the COVID‐19 pandemic, hospitals were in dire need of data‐driven analytics to provide support for critical, expensive, and complex decisions. Yet, the majority of analytics being developed were targeted at state‐ and national‐level policy decisions, with little availability of actionable information to support tactical and operational decision‐making and execution at the hospital level. To fill this gap, we developed a multi‐method framework leveraging a parsimonious design philosophy that allows for rapid deployment of high‐impact predictive and prescriptive analytics in a time‐sensitive, dynamic, data‐limited environment, such as a novel pandemic. The product of this research is a workload prediction and decision support tool to provide mission‐critical, actionable information for individual hospitals. Our framework forecasts time‐varying patient workload and demand for critical resources by integrating disease progression models, tailored to data availability during different stages of the pandemic, with a stochastic network model of patient movements among units within individual hospitals. Both components employ adaptive tuning to account for hospital‐dependent, time‐varying parameters that provide consistently accurate predictions by dynamically learning the impact of latent changes in system dynamics. Our decision support system is designed to be portable and easily implementable across hospital data systems for expeditious expansion and deployment. This work was contextually grounded in close collaboration with IU Health, the largest health system in Indiana, which has 18 hospitals serving over one million residents. Our initial prototype was implemented in April 2020 and has supported managerial decisions, from the operational to the strategic, across multiple functionalities at IU Health.

Access to Health Care Improves COVID-19 Vaccination and Mitigates Health Disparities Among Medicare Beneficiaries.

BACKGROUND: COVID-19 disproportionately impacts the elderly, particularly racial/ethnic minorities and those with low socioeconomic status (SES). These latter groups may also have higher vaccine hesitancy. We aim to evaluate if access to care improves COVID-19 vaccination rates and improves health disparities. METHODS: We conducted a retrospective cohort study of Medicare patients receiving care in a high-touch capitated network across ten states. We collected type and date of COVID-19 vaccine and demographic and clinical data from the inpatient and outpatient electronic health records and socioeconomic status from the US census. Our primary outcome was completing vaccination using logistic regression. RESULTS: Our cohort included 93,224 patients enrolled in the network during the study period. Sixty nine percent of all enrolled patients completed full vaccination. Those who completed vaccination did it with Pfizer (46%), Moderna (49%), and Jannsen (4.6%) vaccines. In adjusted models, we found that the following characteristics increased the odds of being vaccinated: being male, increasing age, BMI, and comorbidities, being Black or Hispanic, having had the flu vaccine in 2020, and increasing number of office primary care visits. Living in a neighborhood with higher social deprivation and having dual Medicaid/Medicare enrollment decreased the odds of completing full vaccination. CONCLUSIONS: Increasing office visit in a high-touch primary care model is associated with higher vaccination rates among elderly populations who belong to racial/ethnic minorities or have low socioeconomic status. However, lower SES and Medicaid populations continue to have difficulty in completing vaccination. KEY POINTS: • High COVID-19 vaccination rates of minorities enrolled in Medicare can be achieved. • Lower socioeconomic status is associated with completing vaccination. • Increasing office visits can lead to higher vaccination rates.

Ex Vivo and In Vivo CD46 Receptor Utilization by Species D Human Adenovirus Serotype 26 (HAdV26).

Human adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HIV-1. However, its primary receptor portfolio remains controversial, potentially including sialic acid, coxsackie and adenovirus receptor (CAR), integrins, and CD46. We and others have shown that Ad26 can use CD46, but these observations were questioned on the basis of the inability to cocrystallize Ad26 fiber with CD46. Recent work demonstrated that Ad26 binds CD46 with its hexon protein rather than its fiber. We examined the functional consequences of Ad26 for infection in vitro and in vivo. Ectopic expression of human CD46 on Chinese hamster ovary cells increased Ad26 infection significantly. Deletion of the complement control protein domain CCP1 or CCP2 or the serine-threonine-proline (STP) region of CD46 reduced infection. Comparing wild-type and sialic acid-deficient CHO cells, we show that the usage of CD46 is independent of its sialylation status. Ad26 transduction was increased in CD46 transgenic mice after intramuscular (i.m.) injection but not after intranasal (i.n.) administration. Ad26 transduction was 10-fold lower than Ad5 transduction after intratumoral (i.t.) injection of CD46-expressing tumors. Ad26 transduction of liver was 1,000-fold lower than that ofAd5 after intravenous (i.v.) injection. These data demonstrate the use of CD46 by Ad26 in certain situations but also show that the receptor has little consequence by other routes of administration. Finally, i.v. injection of high doses of Ad26 into CD46 mice induced release of liver enzymes into the bloodstream and reduced white blood cell counts but did not induce thrombocytopenia. This suggests that Ad26 virions do not induce direct clotting side effects seen during coronavirus disease 2019 (COVID-19) vaccination with this serotype of adenovirus. IMPORTANCE The human species D Ad26 is being investigated as a low-seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection and its role in virus biology, vaccine efficacy, and, importantly, vaccine safety.

SINgapore GERiatric intervention study to reduce physical frailty and cognitive decline (SINGER)-pilot: A feasibility study.

INTRODUCTION: The SINGER pilot randomized controlled trial aims to examine the feasibility and acceptability of the Finnish Geriatric Intervention Study (FINGER) multi-domain lifestyle interventions compared to Singaporean adaptations. METHODS: Seventy elderly participants were recruited and randomized into FINGER (n = 36) or SINGER (n = 34) interventions; involving physical exercise, cognitive training, diet, and vascular risk factors management, for 6 months. RESULTS: Both intervention groups were equally feasible and acceptable with participants completing at least 80% of the interventions. Body strength improved in both groups (Pupper body = .04, P lower body = .06, P core = .05). More participants in the SINGER group attained good blood pressure control at month-6 compared to FINGER (41% vs 19%; P = .06). DISCUSSION: This study is the first to compare the feasibility of multi-domain interventions adapted to local culture with the FINGER interventions. The findings will be utilized for a larger study to provide evidence for the efficacy of multi-domain lifestyle interventions in preventing cognitive decline.

Operations (Management) warp speed: Rapid deployment of hospital-focused predictive/prescriptive analytics for the COVID-19 pandemic

At the onset of the COVID-19 pandemic, hospitals were in dire need of data-driven analytics to provide support for critical, expensive, and complex decisions. Yet, the majority of analytics being developed were targeted at state- and national-level policy decisions, with little availability of actionable information to support tactical and operational decision making and execution at the hospital level. To fill this gap, we developed a multi-method framework leveraging a parsimonious design philosophy that allows for rapid deployment of high-impact predictive and prescriptive analytics in a time-sensitive, dynamic, data-limited environment, such as a novel pandemic. The product of this research is a workload prediction and decision support tool to provide mission-critical, actionable information for individual hospitals. Our framework forecasts time-varying patient workload and demand for critical resources by integrating disease progression models, tailored to data availability during different stages of the pandemic, with a stochastic network model of patient movements among units within individual hospitals. Both components employ adaptive tuning to account for hospital-dependent, time-varying parameters that provide consistently accurate predictions by dynamically learning the impact of latent changes in system dynamics. Our decision support system is designed to be portable and easily implementable across hospital data systems for expeditious expansion and deployment. This work was contextually grounded in close collaboration with IU Health, the largest health system in Indiana, which has 18 hospitals serving over one million residents. Our initial prototype was implemented in April 2020 and has supported managerial decisions, from the operational to the strategic, across multiple functionalities at IU  Health. This article is protected by copyright. All rights reserved

Impact of Covid-19 pandemic on lifestyle in a middle-aged and elderly population

Background Mandated lockdowns and restricted activity in response to the COVID-19 pandemic has affected our everyday life1. Seniors, in particular, have been affected due to higher morbidity and mortality2. The World-Wide-FINGERS-SARS-CoV-2 survey is part of an international project, consisting of members of the World-Wide FINGERS (WW-FINGERS) Network for dementia risk reduction and prevention3. The study aims to measure the direct and indirect effects of the outbreak in midlife and older age. Preliminary results of this ongoing study is focused on lifestyle changes. Method The survey commenced in September 2020.Participants aged 45 and above were recruited from existing research cohorts, memory clinic patients and community subjects. Sociodemographic factors, health related information, impact on lifestyle and behavior as well as personality factors were collected through three modalities: self-administered online survey, telephone survey and in person with research staff. Result At present, 167 non-demented participants were included in the current preliminary analysis. Majority of the participants were Chinese (83.2%), aged 65 and above (59.3%), male (58.1%), with at least secondary education (80.8%). The survey found that 61.6% of the participants reported decreased contact with friends and relatives, with 22.2% reporting an increase in loneliness. Approximately one-third of the participants reported a decrease in physical activity (35.9%) and an increase in food intake (30.5% in snacking habits;25.1% in fruits consumption). Approximately half of the participants reported increase in usage of internet and digital services to keep in contact with family and friends. Conclusion The COVID-19 pandemic has produced measurable impacts on lifestyle-related behavior of individuals. The decrease in social interaction and increase in loneliness during the pandemic due to government directive, along with concerns of contracting the virus highlight the importance of digital services for and digital literacy in older adults to keep them connected and supported remotely.

SARS-CoV-2 Disrupts Proximal Elements in the JAK-STAT Pathway.

SARS-CoV-2 can infect multiple organs, including lung, intestine, kidney, heart, liver, and brain. The molecular details of how the virus navigates through diverse cellular environments and establishes replication are poorly defined. Here, we generated a panel of phenotypically diverse, SARS-CoV-2-infectible human cell lines representing different body organs and performed longitudinal survey of cellular proteins and pathways broadly affected by the virus. This revealed universal inhibition of interferon signaling across cell types following SARS-CoV-2 infection. We performed systematic analyses of the JAK-STAT pathway in a broad range of cellular systems, including immortalized cells and primary-like cardiomyocytes, and found that SARS-CoV-2 targeted the proximal pathway components, including Janus kinase 1 (JAK1), tyrosine kinase 2 (Tyk2), and the interferon receptor subunit 1 (IFNAR1), resulting in cellular desensitization to type I IFN. Detailed mechanistic investigation of IFNAR1 showed that the protein underwent ubiquitination upon SARS-CoV-2 infection. Furthermore, chemical inhibition of JAK kinases enhanced infection of stem cell-derived cultures, indicating that the virus benefits from inhibiting the JAK-STAT pathway. These findings suggest that the suppression of interferon signaling is a mechanism widely used by the virus to evade antiviral innate immunity, and that targeting the viral mediators of immune evasion may help block virus replication in patients with COVID-19. IMPORTANCE SARS-CoV-2 can infect various organs in the human body, but the molecular interface between the virus and these organs remains unexplored. In this study, we generated a panel of highly infectible human cell lines originating from various body organs and employed these cells to identify cellular processes commonly or distinctly disrupted by SARS-CoV-2 in different cell types. One among the universally impaired processes was interferon signaling. Systematic analysis of this pathway in diverse culture systems showed that SARS-CoV-2 targets the proximal JAK-STAT pathway components, destabilizes the type I interferon receptor though ubiquitination, and consequently renders the infected cells resistant to type I interferon. These findings illuminate how SARS-CoV-2 can continue to propagate in different tissues even in the presence of a disseminated innate immune response.

Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets.

Non-human primate models will expedite therapeutics and vaccines for coronavirus disease 2019 (COVID-19) to clinical trials. Here, we compare acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old rhesus macaques, baboons and old marmosets. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies, and both age groups recovered in two weeks. Baboons had prolonged viral RNA shedding and substantially more lung inflammation compared with macaques. Inflammation in bronchoalveolar lavage was increased in old versus young baboons. Using techniques including computed tomography imaging, immunophenotyping, and alveolar/peripheral cytokine response and immunohistochemical analyses, we delineated cellular immune responses to SARS-CoV-2 infection in macaque and baboon lungs, including innate and adaptive immune cells and a prominent type-I interferon response. Macaques developed T-cell memory phenotypes/responses and bystander cytokine production. Old macaques had lower titres of SARS-CoV-2-specific IgG antibody levels compared with young macaques. Acute respiratory distress in macaques and baboons recapitulates the progression of COVID-19 in humans, making them suitable as models to test vaccines and therapies.

Tackling challenges in care of Alzheimer's disease and other dementias amid the COVID-19 pandemic, now and in the future.

We have provided an overview on the profound impact of COVID-19 upon older people with Alzheimer's disease and other dementias and the challenges encountered in our management of dementia in different health-care settings, including hospital, out-patient, care homes, and the community during the COVID-19 pandemic. We have also proposed a conceptual framework and practical suggestions for health-care providers in tackling these challenges, which can also apply to the care of older people in general, with or without other neurological diseases, such as stroke or parkinsonism. We believe this review will provide strategic directions and set standards for health-care leaders in dementia, including governmental bodies around the world in coordinating emergency response plans for protecting and caring for older people with dementia amid the COIVD-19 outbreak, which is likely to continue at varying severity in different regions around the world in the medium term.