Insights From Rapid Deployment of a “Virtual Hospital” as Standard Care During the COVID-19 Pandemic

Background: Pandemics disrupt traditional health care operations by overwhelming system resource capacity but also create opportunities for care innovation. Objective: To describe the development and rapid deployment of a virtual hospital program, Atrium Health hospital at home (AH-HaH), within a large health care system. Design: Prospective case series. Setting: Atrium Health, a large integrated health care organization in the southeastern United States. Patients: 1477 patients diagnosed with coronavirus disease 2019 (COVID-19) from 23 March to 7 May 2020 who received care via AH-HaH. Intervention: A virtual hospital model providing proactive home monitoring and hospital-level care through a virtual observation unit (VOU) and a virtual acute care unit (VACU) in the home setting for eligible patients with COVID-19. Measurements: Patient demographic characteristics, comorbid conditions, treatments administered (intravenous fluids, antibiotics, supplemental oxygen, and respiratory medications), transfer to inpatient care, and hospital outcomes (length of stay, intensive care unit [ICU] admission, mechanical ventilation, and death) were collected from electronic health record data. Results: 1477 patients received care in either the AH-HaH VOU or VACU or both settings, with a median length of stay of 11 days. Of these, 1293 (88%) patients received care in the VOU only, with 40 (3%) requiring inpatient hospitalization. Of these 40 patients, 16 (40%) spent time in the ICU, 7 (18%) required ventilator support, and 2 (5%) died during their hospital admission. In total, 184 (12%) patients were ever admitted to the VACU, during which 21 patients (11%) required intravenous fluids, 16 (9%) received antibiotics, 40 (22%) required respiratory inhaler or nebulizer treatments, 41 (22%) used supplemental oxygen, and 24 (13%) were admitted as an inpatient to a conventional hospital. Of these 24 patients, 10 (42%) required ICU admission, 1 (3%) required a ventilator, and none died during their hospital admission. Limitation: Generalizability is limited to patients with a working telephone and the ability to comply with the monitoring protocols. Conclusion: Virtual hospital programs have the potential to provide health systems with additional inpatient capacity during the COVID-19 pandemic and beyond. Primary Funding Source: Atrium Health.

Spatial Inequities in COVID-19 Testing, Positivity, Confirmed Cases, and Mortality in 3 U.S. Cities: An Ecological Study: Annals of Internal Medicine: Vol 174, No 7

Background: Preliminary evidence has shown inequities in coronavirus disease 2019 (COVID-19)–related cases and deaths in the United States. Objective: To explore the emergence of spatial inequities in COVID-19 testing, positivity, confirmed cases, and mortality in New York, Philadelphia, and Chicago during the first 6 months of the pandemic. Design: Ecological, observational study at the ZIP code tabulation area (ZCTA) level from March to September 2020. Setting: Chicago, New York, and Philadelphia. Participants: All populated ZCTAs in the 3 cities. Measurements: Outcomes were ZCTA-level COVID-19 testing, positivity, confirmed cases, and mortality cumulatively through the end of September 2020. Predictors were the Centers for Disease Control and Prevention Social Vulnerability Index and its 4 domains, obtained from the 2014–2018 American Community Survey. The spatial autocorrelation of COVID-19 outcomes was examined by using global and local Moran I statistics, and estimated associations were examined by using spatial conditional autoregressive negative binomial models. Results: Spatial clusters of high and low positivity, confirmed cases, and mortality were found, co-located with clusters of low and high social vulnerability in the 3 cities. Evidence was also found for spatial inequities in testing, positivity, confirmed cases, and mortality. Specifically, neighborhoods with higher social vulnerability had lower testing rates and higher positivity ratios, confirmed case rates, and mortality rates. Limitations: The ZCTAs are imperfect and heterogeneous geographic units of analysis. Surveillance data were used, which may be incomplete. Conclusion: Spatial inequities exist in COVID-19 testing, positivity, confirmed cases, and mortality in 3 large U.S. cities. Primary Funding Source: National Institutes of Health.

The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults: A Response-Adaptive, Randomized Clinical Trial: Annals of Internal Medicine: Vol 174, No 2

Background: Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences. Objective: To compare the effects of 4 doses of vitamin D3 supplements on falls. Design: 2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333) Setting: 2 community-based research units. Participants: 688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L. Intervention: 200 (control), 1000, 2000, or 4000 IU of vitamin D3 per day. During the dose-finding stage, participants were randomly assigned to 1 of the 4 vitamin D3 doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose. Measurements: Time to first fall or death over 2 years (primary outcome). Results: During the dose-finding stage, the primary outcome rates were higher for the 2000- and 4000-IU/d doses than for the 1000-IU/d dose, which was selected as the best dose (posterior probability of being best, 0.90). In the confirmatory stage, event rates were not significantly different between participants with experience receiving the best dose (events and observation time limited to the period they were receiving 1000 IU/d; n = 308) and those randomly assigned to receive 200 IU/d (n = 339) (hazard ratio [HR], 0.94 [95% CI, 0.76 to 1.15]; P = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46]). Limitations: The control group received 200 IU of vitamin D3 per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached. Conclusion: In older persons with elevated fall risk and low serum 25-(OH)D levels, vitamin D3 supplementation at doses of 1000 IU/d or higher did not prevent falls compared with 200 IU/d. Several analyses raised safety concerns about vitamin D3 doses of 1000 IU/d or higher. Primary Funding Source: National Institute on Aging.

Characteristics of COVID-19 in Homeless Shelters: A Community-Based Surveillance Study: Annals of Internal Medicine: Vol 174, No 1

Background: Homeless shelters are a high-risk setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission because of crowding and shared hygiene facilities. Objective: To investigate SARS-CoV-2 case counts across several adult and family homeless shelters in a major metropolitan area. Design: Cross-sectional, community-based surveillance study. (ClinicalTrials.gov: NCT04141917) Setting: 14 homeless shelters in King County, Washington. Participants: A total of 1434 study encounters were done in shelter residents and staff, regardless of symptoms. Intervention: 2 strategies were used for SARS-CoV-2 testing: routine surveillance and contact tracing (“surge testing”) events. Measurements: The primary outcome measure was test positivity rate of SARS-CoV-2 infection at shelters, determined by dividing the number of positive cases by the total number of participant encounters, regardless of symptoms. Sociodemographic, clinical, and virologic variables were assessed as correlates of viral positivity. Results: Among 1434 encounters, 29 (2% [95% CI, 1.4% to 2.9%]) cases of SARS-CoV-2 infection were detected across 5 shelters. Most (n = 21 [72.4%]) were detected during surge testing events rather than routine surveillance, and most (n = 21 [72.4% {CI, 52.8% to 87.3%}]) were asymptomatic at the time of sample collection. Persons who were positive for SARS-CoV-2 were more frequently aged 60 years or older than those without SARS-CoV-2 (44.8% vs. 15.9%). Eighty-six percent of persons with positive test results slept in a communal space rather than in a private or shared room. Limitation: Selection bias due to voluntary participation and a relatively small case count. Conclusion: Active surveillance and surge testing were used to detect multiple cases of asymptomatic and symptomatic SARS-CoV-2 infection in homeless shelters. The findings suggest an unmet need for routine viral testing outside of clinical settings for homeless populations. Primary Funding Source: Gates Ventures.

Synopsis of the 2020 U.S. Department of Veterans Affairs/U.S. Department of Defense Clinical Practice Guideline: The Diagnosis and Management of Hypertension in the Primary Care Setting

Description: In January 2020, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the diagnosis and management of hypertension in the primary care setting. Methods: The VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included a multidisciplinary panel of practicing clinician stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions in collaboration with the ECRI Institute, which systematically searched and evaluated the literature from 15 December 2013 to 25 March 2019 and developed and rated recommendations by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: This synopsis summarizes key features of the guideline in several key areas: the measurement of blood pressure, the definition of hypertension, target treatment goals, and nonpharmacologic and pharmacologic treatment of essential and resistant hypertension.

Safety and Efficacy of Checkpoint Inhibition in Patients With Melanoma and Preexisting Autoimmune Disease: A Cohort Study: Annals of Internal Medicine: Vol 174, No 5

Background: Because immune checkpoint inhibition (ICI) can cause immune-related adverse events (irAEs) mimicking immunologic diseases, patients with preexisting autoimmune disease (AID) have been excluded from clinical trials. Objective: To evaluate the safety and efficacy of ICI in patients with advanced melanoma with and without AID. Design: Nationwide cohort study. Setting: The Netherlands. Patients: 4367 patients with advanced melanoma enrolled in the Dutch Melanoma Treatment Registry (DMTR) between July 2013 and July 2018 and followed through February 2019. Measurements: Patient, clinical, and treatment characteristics; irAEs of grade 3 or higher; treatment response; and survival. Results: A total of 415 patients (9.5%) had AID, categorized as rheumatologic AID (n = 227), endocrine AID (n = 143), inflammatory bowel disease (IBD) (n = 55), or “other” (n = 8). Of these, 228 patients (55%) were treated with ICI (vs. 2546 [58%] without AID); 87 were treated with anti–cytotoxic T lymphocyte–associated protein 4 (CTLA-4), 187 with anti–programmed cell death 1 (PD-1), and 34 with the combination. The incidences of irAEs of grade 3 or higher in patients with AID were 30% (95% CI, 21% to 41%) with anti–CTLA-4, 17% (CI, 12% to 23%) with anti–PD-1, and 44% (CI, 27% to 62%) with combination therapy; for patients without AID, the incidences were 30% (CI, 27% to 33%) (n = 916), 13% (CI, 12% to 15%) (n = 1540), and 48% (CI, 43% to 53%) (n = 388), respectively. Patients with AID more often discontinued anti–PD-1 treatment because of toxicity than patients without AID (17% [CI, 12% to 23%] vs. 9% [CI, 8% to 11%]). Patients with IBD were more prone to anti–PD-1–induced colitis (6/31 = 19% [CI, 7% to 37%]) than patients with other AIDs (3% [CI, 0% to 6%]) and patients without AID (2% [CI, 2% to 3%]).The objective response rate was similar in patients with versus without AID who were treated with anti–CTLA-4 (10% [CI, 5% to 19%] vs. 16% [CI, 14% to 19%]), anti–PD-1 (40% [CI, 33% to 47%] vs. 44% [CI, 41% to 46%]), or the combination (39% [CI, 20% to 59%] vs. 43% [CI, 38% to 49%]). Survival did not differ between patients with and those without AID (median, 13 months [CI, 10 to 16 months] vs. 14 months [CI, 13 to 15 months]). Limitation: Information was limited on AID severity and immunosuppressive treatment. Conclusion: Response to ICI with anti–CTLA-4, anti–PD-1, or their combination for advanced melanoma and overall incidence of any irAEs of grade 3 or higher were similar in patients with and without preexisting AID. However, severe colitis and toxicity requiring early discontinuation of treatment occurred more frequently among patients with preexisting IBD, warranting close follow-up. Primary Funding Source: The Netherlands Organization for Health Research and Development.

Dynamics and Correlation Among Viral Positivity, Seroconversion, and Disease Severity in COVID-19: A Retrospective Study: Annals of Internal Medicine: Vol 174, No 4

Background: The understanding of viral positivity and seroconversion during the course of coronavirus disease 2019 (COVID-19) is limited. Objective: To describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and disease severity. Design: Retrospective cohort study. Setting: 3 designated specialty care centers for COVID-19 in Wuhan, China. Participants: 3192 adult patients with COVID-19. Measurements: Demographic, clinical, and laboratory data. Results: Among 12 780 reverse transcriptase PCR tests for severe acute respiratory syndrome coronavirus 2 that were done, 24.0% had positive results. In 2142 patients with laboratory-confirmed COVID-19, the viral positivity rate peaked within the first 3 days. The median duration of viral positivity was 24.0 days (95% CI, 18.9 to 29.1 days) in critically ill patients and 18.0 days (CI, 16.8 to 19.1 days) in noncritically ill patients. Being critically ill was an independent risk factor for longer viral positivity (hazard ratio, 0.700 [CI, 0.595 to 0.824]; P < 0.001). In patients with laboratory-confirmed COVID-19, the IgM-positive rate was 19.3% in the first week, peaked in the fifth week (81.5%), and then decreased steadily to around 55% within 9 to 10 weeks. The IgG-positive rate was 44.6% in the first week, reached 93.3% in the fourth week, and then remained high. Similar antibody responses were seen in clinically diagnosed cases. Serum inflammatory markers remained higher in critically ill patients. Among noncritically ill patients, a higher proportion of those with persistent viral positivity had low IgM titers (<100 AU/mL) during the entire course compared with those with short viral positivity. Limitation: Retrospective study and irregular viral and serology testing. Conclusion: The rate of viral PCR positivity peaked within the initial few days. Seroconversion rates peaked within 4 to 5 weeks. Dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity. Low IgM titers (<100 AU/mL) are an independent risk factor for persistent viral positivity. Primary Funding Source: None.

Vaccination-Induced Bursitis: Technique Matters

Thromboembolic Findings in COVID-19 Autopsies: Pulmonary Thrombosis or Embolism?

Primary Care Panel Size: How You Measure Makes a Difference