Health Equity and Decentralized Trials.

This Viewpoint discusses the proliferation of decentralized clinical trials during the COVID-19 pandemic and the need for rigorous studies to inform whether decentralized approaches promote or prevent access to clinical trials for people facing health disparities.

Activated CD8 T-cell hepatitis in children: a single institution experience

Background: Pediatric acute liver failure is a rare and serious life-threatening situation, principally for the 30 to 50% of children in whom the etiology of their liver failure is unclear or indeterminate. Treating these patients is challenging, requiring constant assessment over time with regular evaluation for possible liver transplantation. Children with pediatric acute liver failure of undetermined etiology have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. Emerging evidence suggests that a subgroup of patients with indeterminate pediatric acute liver failure have clinical, laboratory, and liver biopsy features of immune dysregulation with a dense infiltration of CD8 T cells. Method(s): In 2022, we received percutaneous liver biopsies from three children with acute hepatic dysfunction that showed an increased number of lymphocytes including CD8 T cells. For each case, routine H&E stains with levels, special stains and immunostains were performed. The first biopsy was from an 18-month-old male who presented with COVID infection, pancytopenia, elevated transaminases, and synthetic liver dysfunction (elevated INR). The second was from a 9-year-old female with a history of elevated liver enzymes with no clear cause. The third case was from a 2-year-old male with elevated liver enzymes, coagulopathy, and cholestasis. Result(s): The three cases showed similar histopathologic findings;an acute liver injury pattern with lobular architectural disarray, giant cell formation, reactive changes, single cell necrosis, cholestasis and marked mixed lymphocytic infiltrates. The infiltrates were predominantly composed of CD8-positive T-lymphocytes with scattered neutrophils, eosinophils and rare plasma cells. Portal areas were mildly expanded with mild bile ductular proliferation and mild to moderate lymphocytic infiltrates. Immunostains for CD8 demonstrated that the infiltrates were predominantly composed of CD8-positive T-lymphocytes. All three patients received steroids and responded to treatment evidenced by normalization of liver enzymes and function. Conclusion(s): Dense hepatic CD8 T-cell infiltration is a major finding inactivated CD8 T-cell hepatitis. However, the percentage distribution of lymphocyte subtypes in the setting of hepatitis is not well established, and CD8 T-cell infiltration has also been described in cases of drug-induced hypersensitivity reactions, viral hepatitis, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome, as well as autoimmune hepatitis. Further investigation is needed to better understand the diagnostic criteria in this disease.

Design of a multi-institutional neurocognitive discovery study in adult congenital heart disease (MINDS-ACHD).

BACKGROUND: Neurocognitive dysfunction (NCD) is a common comorbidity among children with congenital heart disease (CHD). However, it is unclear how underlying CHD and its sequelae combine with genetics and acquired cardiovascular and neurological disease to impact NCD and outcomes across the lifespan in adults with CHD. METHODS: The Multi-Institutional Neurocognitive Discovery Study in Adults with Congenital Heart Disease (MINDS-ACHD) is a partnership between the Pediatric Heart Network (PHN) and the Adult Alliance for Research in Congenital Cardiology (AARCC) that examines objective and subjective neurocognitive function and genetics in young ACHD. This multicenter cross-sectional pilot study is enrolling 500 young adults between 18 and 30 years with moderate or severe complexity CHD at 14 centers in North America. Enrollment includes 4 groups (125 participants each): (1) d-looped Transposition of the Great Arteries (d-TGA); (2) Tetralogy of Fallot (TOF); (3) single ventricle (SV) physiology; and (4) "other moderately or severely complex CHD." Participants complete the standardized tests from the NIH Toolbox Cognitive Battery, the NeuroQoL, the Hospital Anxiety and Depression Scale, and the PROMIS Global QoL measure. Clinical and demographic variables are collected by interview and medical record review, and an optional biospecimen is collected for genetic analysis. Due to the COVID-19 pandemic, participation may be done remotely. Tests are reviewed by a Neurocognitive Core Laboratory. CONCLUSIONS: MINDS-ACHD is the largest study to date characterizing NCD in young adults with moderate or severely complex CHD in North America. Its results will provide valuable data to inform screening and management strategies for NCD in ACHD and improve lifelong care.

Society for Vascular Surgery appropriate use criteria for management of intermittent claudication.

The Society for Vascular Surgery appropriate use criteria (AUC) for the management of intermittent claudication were created using the RAND appropriateness method, a validated and standardized method that combines the best available evidence from medical literature with expert opinion, using a modified Delphi process. These criteria serve as a framework on which individualized patient and clinician shared decision-making can grow. These criteria are not absolute. AUC should not be interpreted as a requirement to administer treatments rated as appropriate (benefit outweighs risk). Nor should AUC be interpreted as a prohibition of treatments rated as inappropriate (risk outweighs benefit). Clinical situations will occur in which moderating factors, not included in these AUC, will shift the appropriateness level of a treatment for an individual patient. Proper implementation of AUC requires a description of those moderating patient factors. For scenarios with an indeterminate rating, clinician judgement combined with the best available evidence should determine the treatment strategy. These scenarios require mechanisms to track the treatment decisions and outcomes. AUC should be revisited periodically to ensure that they remain relevant. The panelists rated 2280 unique scenarios for the treatment of intermittent claudication (IC) in the aortoiliac, common femoral, and femoropopliteal segments in the round 2 rating. Of these, only nine (0.4%) showed a disagreement using the interpercentile range adjusted for symmetry formula, indicating an exceptionally high degree of consensus among the panelists. Post hoc, the term "inappropriate" was replaced with the phrase "risk outweighs benefit." The term "appropriate" was also replaced with "benefit outweighs risk." The key principles for the management of IC reflected within these AUC are as follows. First, exercise therapy is the preferred initial management strategy for all patients with IC. Second, for patients who have not completed exercise therapy, invasive therapy might provide net a benefit for selected patients with IC who are nonsmokers, are taking optimal medical therapy, are considered to have a low physiologic and technical risk, and who are experiencing severe lifestyle limitations and/or a short walking distance. Third, considering the long-term durability of the currently available technology, invasive interventions for femoropopliteal disease should be reserved for patients with severe lifestyle limitations and a short walking distance. Fourth, in the common femoral segment, open common femoral endarterectomy will provide greater net benefit than endovascular intervention for the treatment of IC. Finally, in the infrapopliteal segment, invasive intervention for the treatment of IC is of unclear benefit and could be harmful.

SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity.

The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants of concern (VoCs) and the long-term threat of emerging coronaviruses. Here, we design and characterize four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of the prefusion SARS-CoV-2 spike (S), S1, and receptor-binding domain (RBD). These immunogens induce robust S binding, ACE2 inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2. A spike-ferritin nanoparticle (SpFN) vaccine elicits neutralizing titers (ID50 > 10,000) following a single immunization, whereas RBD-ferritin nanoparticle (RFN) immunogens elicit similar responses after two immunizations and also show durable and potent neutralization against circulating VoCs. Passive transfer of immunoglobulin G (IgG) purified from SpFN- or RFN-immunized mice protects K18-hACE2 transgenic mice from a lethal SARS-CoV-2 challenge. Furthermore, S-domain nanoparticle immunization elicits ACE2-blocking activity and ID50 neutralizing antibody titers >2,000 against SARS-CoV-1, highlighting the broad response elicited by these immunogens.

Impact of coronavirus of 2019 on the delivery of pharmacy services to patients with cancer: An international survey of oncology pharmacy practitioners.

INTRODUCTION: The coronavirus of 2019 pandemic has necessitated vast and rapid changes in the way oncology pharmacy services are delivered around the world. METHODS/AIMS: An international survey of oncology pharmacists and technicians was conducted via the International Society of Oncology Pharmacy Practitioners and collaborating global pharmacy organisations to determine the impact that the coronavirus of 2019 has had on pharmacy service delivery, pharmacy practitioners and oncology practice. RESULTS: The survey received 862 responses from 40 different countries from September to October 2020. The majority of respondents were pharmacists (n = 841, 97.6%), with 24% involved in the direct care of patients with the coronavirus of 2019. Of the survey participants, 55% increased their time working remotely, with remote activities including dispensing, patient assessment/follow-up and attending multi-disciplinary rounds. Respondents reported a 72% increase in the use of technology to perform remote patient interaction activities and that participation in educational meetings and quality improvement projects was reduced by 68% and 44%, respectively. Workforce impacts included altered working hours (50%), cancelled leave (48%) and forced leave/furloughing (30%). During the pandemic, respondents reported reduced access to intensive care (19%) and anti-cancer (15%) medications. In addition, 39% of respondents reported reduced access to personal protective equipment, including N95 masks for chemotherapy compounding. Almost half of respondents (49%) reported that cancer treatments were delayed or intervals were altered for patients being treated with curative intent. A third of practitioners (30%) believed that patient outcomes would be adversely impacted by changes to pharmacy services. Sixty-five percent of respondents reported impacts on their mental health, with 12% utilising support services. CONCLUSION: The coronavirus of 2019 pandemic has altered the way oncology pharmacy services are delivered. These results demonstrate the adaptability of the oncology pharmacy profession and highlight the importance of formal evaluation of the varied practice models to determine the evidence-based practices that enhance pharmacy services and, thus, should be reinstated as soon as practical and reasonable.

VIRAL AND ANTIBODY TESTING FOR CORONAVIRUS DISEASE 2019 (COVID-19): FACTORS ASSOCIATED WITH POSITIVITY IN ELECTRONIC HEALTH RECORDS FROM THE UNITED STATES (preprint)

Background. Insufficient information on SARS-CoV-2 testing results exists in clinical practice from the United States. Methods. We conducted an observational retrospective cohort study using Optum(R) de-identified COVID-19 electronic health records from the United States to characterize patients who received a SARS-CoV-2 viral or antibody test between February 20, 2020 and July 10, 2020. We assessed temporal trends in testing and positivity by demographic and clinical characteristics; evaluated concordance between viral and antibody tests; and identified factors associated with positivity via multivariable logistic regression. Results. Our study population included 891,754 patients. Overall positivity rate for SARS-CoV-2 was 9% and 12% for viral and antibody tests, respectively. Positivity rate was inversely associated with the number of individuals tested and decreased over time across regions and race/ethnicities. Among patients who received a viral test followed by an antibody test, concordance ranged from 90%-93% depending on the duration between the two tests which is notable given uncertainties related to specific viral and antibody test characteristics. The following factors increased the odds of viral and antibody positivity in multivariable models: male, Hispanic or non-Hispanic Black and Asian, uninsured or Medicaid insurance, Northeast residence, dementia, diabetes, and obesity. Charlson Comorbidity Index was negatively associated with test positivity. We identified symptoms that were positively associated with test positivity, as well as, commonly co-occurring symptoms / conditions. Pediatric patients had reduced odds of a positive viral test, but conversely had increased odds of a positive antibody test. Conclusions. This study identified sociodemographic and clinical factors associated with SARS-CoV-2 testing and positivity within routine clinical practice from the United States.

Assessing the Influence of COVID-19 on the Shortwave Radiative Fluxes Over the East Asian Marginal Seas.

The Coronavirus Disease 2019 (COVID-19) pandemic led to a widespread reduction in aerosol emissions. Using satellite observations and climate model simulations, we study the underlying mechanisms of the large decreases in solar clear-sky reflection (3.8 W m-2 or 7%) and aerosol optical depth (0.16 W m-2 or 32%) observed over the East Asian Marginal Seas in March 2020. By separating the impacts from meteorology and emissions in the model simulations, we find that about one-third of the clear-sky anomalies can be attributed to pandemic-related emission reductions, and the rest to weather variability and long-term emission trends. The model is skillful at reproducing the observed interannual variations in solar all-sky reflection, but no COVID-19 signal is discerned. The current observational and modeling capabilities will be critical for monitoring, understanding, and predicting the radiative forcing and climate impacts of the ongoing crisis.

Vascular surgery triage during the coronavirus disease 2019 pandemic.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a marked increase in hospital usage, medical resource scarcity, and rationing of surgical procedures. This has created the need for strategies to triage surgical patients. We have described our experience using the American College of Surgeons (ACS) COVID-19 guidelines for triage of vascular surgery patients in an academic surgery practice. METHODS: We used the ACS guidelines as a framework to direct the triage of vascular surgery patients during the COVID-19 pandemic. We retrospectively analyzed the results of this triage during the first month of surgical restriction at our hospital. Patients undergoing surgery were identified by reviewing the operating room schedule. We reviewed the electronic medical records (EMRs) and assigned an ACS category, condition, and tier class to each completed surgery. Surgeries that were postponed during the same period were identified from a prospectively maintained list. We reviewed the EMRs for all postponed surgeries and assigned an ACS category, condition, and tier class to each surgery. We reviewed the EMRs for all postponed procedures to identify any adverse events related to the treatment delay. RESULTS: We performed 69 surgeries in 52 patients during the study period. All surgeries were performed to treat emergent, urgent, or time-sensitive elective diagnoses. Of the 69 surgeries, 47 (68%) were from tier 3 and 22 (32%) from tier 2b. We did not perform any surgeries from tier 1 or 2a. We postponed surgery for 66 patients during the same period, of which 36 (55%) were from tier 1, 22 (33%) from tier 2a, 5 (8%) from tier 2b, and 3 (5%) could not be assigned a tier class. No tier 3 surgeries were postponed. Of the 66 patients, 3 (4.5%) experienced an adverse event that could be attributed to the treatment delay. CONCLUSIONS: The ACS triage guidelines provided an effective method to decrease vascular surgical volumes during the COVID-19 pandemic without an increase in patient morbidity. We believe the clinical utility of the guidelines would be strengthened by incorporating the SURGCON/VASCCON (surgical activity condition/vascular activity condition) threat level alert system.

Outpatient clinical pharmacy practice in the face of COVID-19 at a cancer center in New York City.

PURPOSE: With the rapid spread of COVID-19 in New York City since early March 2020, innovative measures were needed for clinical pharmacy specialists to provide direct clinical care safely to cancer patients. Allocating the workforce was necessary to meet the surging needs of the inpatient services due to the COVID-19 outbreak, which had the potential to compromise outpatient services. We present here our approach of restructuring clinical pharmacy services and providing direct patient care in outpatient clinics during the pandemic. DATA SOURCES: We conducted a retrospective review of electronic clinical documentation involving clinical pharmacy specialist patient encounters in 9 outpatient clinics from March 1, 2020 to May 31, 2020. The analysis of the clinical pharmacy specialist interventions and the impact of the interventions was descriptive. DATA SUMMARY: As hospital services were modified to handle the surge due to COVID-19, select clinical pharmacy specialists were redeployed from the outpatient clinics or research blocks to COVID-19 inpatient teams. During these 3 months, clinical pharmacy specialists were involved in 2535 patient visits from 9 outpatient clinics and contributed a total of 4022 interventions, the majority of which utilized telemedicine. The interventions provided critical clinical pharmacy care during the pandemic and omitted 199 in-person visits for medical care. CONCLUSION: The swift transition to telemedicine allowed the provision of direct clinical pharmacy services to patients with cancer during the COVID-19 pandemic.

Making lemonade from SARS coronavirus-2 lemons: Transitioning a smoking cessation trial to a virtual platform.

Clinical trials represent an essential component of improving treatment for substance use disorders (SUD). The SARS coronavirus-2 pandemic disrupted our ongoing clinical trial of smoking cessation and forced us to rapidly implement changes to assure participants access to ongoing counseling and monitoring via telephone calls and/or video chat sessions. Our experiences suggest that this pandemic will lead to changes for both future clinical trial participants and project staff. While challenges remain, it will be important to assessing the impact of these changes with regard to participant experiences and treatment outcomes.