Faculty Bibliography

Background/UNASSIGNED:SARS-CoV-2 antigen-based tests are well-calibrated to infectiousness and have a critical role to play in the COVID-19 public health response. We report the development and performance of a unique lateral flow immunoassay (LFA). Methods/UNASSIGNED:Combinations of several monoclonal antibodies targeting multiple antigenic sites on the SARS-CoV-2 nucleocapsid protein (NP) were isolated, evaluated, and chosen for the development of a LFA termed CoV-SCAN (BioMedomics, Inc.). Clinical point-of-care studies in symptomatic and asymptomatic individuals were conducted to evaluate positive predictive agreement (PPA) and negative predictive agreement (NPA) with RT-PCR as comparator. Results/UNASSIGNED:In laboratory testing, CoV-SCAN detected 14 recombinant N-proteins of SARS-CoV-2 variants with sensitivity in the range of 0.2-3.2 ng/mL, and 10 authentic SARS-CoV-2 variants with sensitivity in the range of 1.6-12.5 TCID50/swab. No cross reactivity was observed with other human coronaviruses or other respiratory pathogens. In clinical point-of-care testing on 148 individuals over age 2 with symptoms of ≤5 days, PPA was 87.2% (CI 95: 78.3-94.8%) and NPA was 100% (CI 95: 94.2-100%). In another 884 asymptomatic individuals, PPA was 85.7% (CI 95: 42.1-99.6%) and 99.7% (99.0-99.9%). Overall, CoV-SCAN detected over 97.2% of specimens with CT values <30 and 93.8% of nasal swab specimens with the Omicron variant, even within the first 2 days after symptom onset. Conclusions/UNASSIGNED:The unique construction of CoV-SCAN using two pairs of monoclonal antibodies has resulted in a test with high performance that remains durable across multiple variants in both laboratory and clinical evaluations. CoV-SCAN should identify almost all individuals harboring infectious SARS-CoV-2. Summary/UNASSIGNED:Unique construction of a point-of-care rapid antigen test using two pairs of monoclonal antibodies has led to good performance that remained durable across multiple variants in laboratory and clinical evaluations. Test should identify almost all individuals harboring infectious SARS-CoV-2.

BACKGROUND AND PURPOSE/OBJECTIVE:Non-alcoholic fatty liver disease (NAFLD) is one of the metabolic disturbances associated with liver cell inflammation. Nigella sativa (N.sativa) is a widely used medicinal plant known for its anti-inflammatory, antimicrobial, antioxidant, and hepato-protective properties. This study aimed to assess the effect of supplementation of N. sativa oil on plasma levels of adiponectin, leptin, and blood pressure (BP) in patients diagnosed with NAFLD. MATERIALS AND METHODS/METHODS:This randomized, double-blind, placebo-controlled clinical trial was conducted on 44 NAFLD patients. Participants were randomly assigned to two groups (n = 22/group); the experimental group received 1000 mg of N. sativa oil per day, while the control group received a placebo for eight weeks. The primary outcome measures were serum levels of adiponectin, leptin, and systolic and diastolic blood pressure measured at the baseline and the end of the intervention. RESULTS:After eight weeks of supplementation with N. sativa oil, no statistically significant differences were found in serum levels of adiponectin (p = 0.40), leptin (p = 0.89), systolic BP (p = 0.13), and diastolic BP (p = 0.09) between the two groups. Furthermore, after supplementation with N. sativa, no significant changes were observed in leptin (p = 0.07), adiponectin (p = 0.13), systolic BP (p = 0.82), and diastolic BP (p = 0.38) within the two groups. CONCLUSION/CONCLUSIONS:These results indicate that administration of N. sativa oil 1000 mg/day for 8 weeks has no favorable effect on cardiometabolic measures in NAFLD patients. Further studies with higher dosage over a longer period are needed to investigate whether this effect is dose- and time-dependent.

BACKGROUND:The American Board of Internal Medicine Foundation's Choosing Wisely campaign has resulted in a vast number of recommendations to reduce low-value care. Implementation of these recommendations, in conjunction with patient input, remains challenging. OBJECTIVE:To create updated Society of Hospital Medicine Adult Hospitalist Choosing Wisely recommendations that incorporate patient input from inception. DESIGN AND PARTICIPANTS/METHODS:This was a multi-phase study conducted by the Society of Hospital Medicine's High Value Care Committee from July 2017 to January 2020 involving clinicians and patient advocates. APPROACH/METHODS:Phase 1 involved gathering low-value care recommendations from patients and clinicians across the USA. Recommendations were reviewed by the committee in phase 2. Phase 3 involved a modified Delphi scoring in which 7 committee members and 7 patient advocates voted on recommendations based on strength of evidence, potential for patient harm, and relevance to either hospital medicine or patients. A patient-friendly script was developed to allow advocates to better understand the clinical recommendations. KEY RESULTS/RESULTS:A total of 1265 recommendations were submitted by clinicians and patients. After accounting for similar suggestions, 283 recommendations were categorized. Recommendations with more than 10 mentions were advanced to phase 3, leaving 22 recommendations for the committee and patient advocates to vote upon. Utilizing a 1-5 Likert scale, the top combined recommendations were reducing use of opioids (4.57), improving sleep (4.52), minimizing overuse of oxygen (4.52), reducing CK-MB use (4.50), appropriate venous thromboembolism prophylaxis (4.43), and decreasing daily chest x-rays (4.43). CONCLUSIONS:Specific voting categories, along with the use of patient-friendly language, allowed for the successful co-creation of recommendations.

BACKGROUND:Human grayanotoxin poisoning is distinctly uncommon in North America, as the predominant source of human exposure is honey made by bees pollinating rhododendron species in the Mediterranean. We present a case of confirmed grayanotoxin poisoning from honey imported from Turkey. CASE REPORT/METHODS:A 61-year-old man developed nausea, lightheadedness, and lost consciousness. Onset was 30 min after the ingestion of honey that was brought to the United States from Turkey. Emergency medical services found him bradycardic, hypotensive, and unresponsive. He was treated with atropine, saline, and oxygen, at which point his heart rate and blood pressure improved, and he regained consciousness. A similar episode several days earlier was followed by a brief unrevealing hospitalization. He was again hospitalized, and had a normal echocardiogram, telemetric monitoring, and complete laboratory studies. Grayanotoxins I and III were subsequently identified in the patient's blood, urine, and honey. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Grayanotoxins are diterpenoids found in rhododendron species, whose clinical effects span multiple organ systems including gastrointestinal, cardiac, and neurologic. Treatment is largely supportive, and a good response to atropine and intravenous fluids has been described. Laboratory confirmation of grayanotoxins is not available in a short enough turnaround time to be clinically useful during immediate management, but confirmatory testing may obviate further unnecessary evaluation. Grayanotoxins are likely to remain a rare source of poisoning in North America, but recurrent bradycardia without alternative etiology should prompt a thorough exposure history, which may reveal, as in this case, a treatable toxicologic etiology.

INTRODUCTION:Racial discrimination has been consistently linked to various health outcomes and health disparities, including studies associating racial discrimination with patterns of racial disparities in adverse pregnancy outcomes. To expand our knowledge, this systematic review and meta-analysis assesses all available evidence on the association between self-reported racial discrimination and adverse pregnancy outcomes. METHODS:statistic. RESULTS:Of 13 597 retrieved records, 24 articles were included. Studies included cohort, case-control and cross-sectional designs and were predominantly conducted in the USA (n=20). Across all outcomes, significant positive associations (between experiencing racial discrimination and an adverse pregnancy event) and non-significant associations (trending towards positive) were reported, with no studies reporting significant negative associations. The overall pooled odds ratio (OR) for preterm birth was 1.40 (95% CI 1.17 to 1.68; 13 studies) and for small for gestational age it was 1.23 (95% CI 0.76 to 1.99; 3 studies). When excluding low-quality studies, the preterm birth OR attenuated to 1.31 (95% CI 1.08 to 1.59; 10 studies). Similar results were obtained across sensitivity and subgroup analyses, indicating a significant positive association. CONCLUSION:These results suggest that racial discrimination has adverse impacts on pregnancy outcomes. This is supported by the broader literature on racial discrimination as a risk factor for adverse health outcomes. To further explore this association and underlying mechanisms, including mediating and moderating factors, higher quality evidence from large ethnographically diverse cohorts is needed.

BACKGROUND:Telemedicine as a mode of health care work has grown dramatically during the COVID-19 pandemic; the impact of this transition on clinicians' after-hours electronic health record (EHR)-based clinical and administrative work is unclear. OBJECTIVE:This study assesses the impact of the transition to telemedicine during the COVID-19 pandemic on physicians' EHR-based after-hours workload (ie, "work outside work") at a large academic medical center in New York City. METHODS:We conducted an EHR-based retrospective cohort study of ambulatory care physicians providing telemedicine services before the pandemic, during the acute pandemic, and after the acute pandemic, relating EHR-based after-hours work to telemedicine intensity (ie, percentage of care provided via telemedicine) and clinical load (ie, patient load per provider). RESULTS:A total of 2129 physicians were included in this study. During the acute pandemic, the volume of care provided via telemedicine significantly increased for all physicians, whereas patient volume decreased. When normalized by clinical load (ie, average appointments per day by average clinical days per week), telemedicine intensity was positively associated with work outside work across time periods. This association was strongest after the acute pandemic. CONCLUSIONS:Taking physicians' clinical load into account, physicians who devoted a higher proportion of their clinical time to telemedicine throughout various stages of the pandemic engaged in higher levels of EHR-based after-hours work compared to those who used telemedicine less intensively. This suggests that telemedicine, as currently delivered, may be less efficient than in-person-based care and may increase the after-hours work burden of physicians.

BACKGROUND:The Revised Illness Perception Questionnaire (IPQ-R) measures individuals' unique perceptions of their illness. While psychometric properties of the IPQ-R have been demonstrated in many disease populations, its content validity has not been extensively studied in non-dialysis chronic kidney disease (CKD). Unique features of CKD (e.g., few symptoms in early stages) may impact the measurement of illness perceptions. The purpose of this study was to explore the IPQ-R content validity in a sample of CKD patients. METHODS:Thirty-one participants completed the IPQ-R and were interviewed regarding their subscale scores (timeline, consequences, personal control, treatment control, coherence, cyclical, and emotions). Participants' agreement with their scores was tallied and assessed qualitatively for themes related to the content validity of the measure. RESULTS:Individual participant agreement with their subscale scores averaged 79% (range: 29-100%). Subscale agreement varied: timeline (100%), consequences, coherence, and emotion (83% each), cyclical (75%), personal control (65%), and treatment control (64%). A qualitative exploration of disagreement responses revealed concerns with the relevance and comprehensibility of personal control and treatment control. CONCLUSIONS:Some IPQ-R subscales may pose content validity concerns in the non-dialysis CKD population. Item modification for comprehensibility (personal control) and relevance (treatment control) should be considered. Future studies should explore the impact of a patient's symptom experience on IPQ-R validity, especially in populations like CKD with a higher proportion of asymptomatic patients.

Despite the growing number of genome-wide association studies (GWASs), it remains unclear to what extent gene-by-gene and gene-by-environment interactions influence complex traits in humans. The magnitude of genetic interactions in complex traits has been difficult to quantify because GWASs are generally underpowered to detect individual interactions of small effect. Here, we develop a method to test for genetic interactions that aggregates information across all trait-associated loci. Specifically, we test whether SNPs in regions of European ancestry shared between European American and admixed African American individuals have the same causal effect sizes. We hypothesize that in African Americans, the presence of genetic interactions will drive the causal effect sizes of SNPs in regions of European ancestry to be more similar to those of SNPs in regions of African ancestry. We apply our method to two traits: gene expression in 296 African Americans and 482 European Americans in the Multi-Ethnic Study of Atherosclerosis (MESA) and low-density lipoprotein cholesterol (LDL-C) in 74K African Americans and 296K European Americans in the Million Veteran Program (MVP). We find significant evidence for genetic interactions in our analysis of gene expression; for LDL-C, we observe a similar point estimate, although this is not significant, most likely due to lower statistical power. These results suggest that gene-by-gene or gene-by-environment interactions modify the effect sizes of causal variants in human complex traits.

BACKGROUND:Point-of-care ultrasound (POCUS) is rapidly becoming ubiquitous across healthcare specialties. This is due to several factors including its portability, immediacy of results to guide clinical decision-making, and lack of radiation exposure to patients. The recent growth of handheld ultrasound devices has improved access to ultrasound for many clinicians. Few studies have directly compared different handheld ultrasound devices among themselves or to cart-based ultrasound machines. We conducted a prospective observational study comparing four common handheld ultrasound devices for ease of use, image quality, and overall satisfaction. Twenty-four POCUS experts utilized four handheld devices (Butterfly iQ+â„¢ by Butterfly Network Inc., Kosmosâ„¢ by EchoNous, Vscan Airâ„¢ by General Electric, and Lumifyâ„¢ by Philips Healthcare) to obtain three ultrasound views on the same standardized patients using high- and low-frequency probes. RESULTS:Data were collected from 24 POCUS experts using all 4 handheld devices. No single ultrasound device was superior in all categories. For overall ease of use, the Vscan Airâ„¢ was rated highest, followed by the Lumifyâ„¢. For overall image quality, Lumifyâ„¢ was rated highest, followed by Kosmosâ„¢. The Lumifyâ„¢ device was rated highest for overall satisfaction, while the Vscan Airâ„¢ was rated as the most likely to be purchased personally and carried in one's coat pocket. The top 5 characteristics of handheld ultrasound devices rated as being "very important" were image quality, ease of use, portability, total costs, and availability of different probes. CONCLUSIONS:In a comparison of four common handheld ultrasound devices in the United States, no single handheld ultrasound device was perceived to have all desired characteristics. POCUS experts rated the Lumifyâ„¢ highest for image quality and Vscan Airâ„¢ highest for ease of use. Overall satisfaction was highest with the Lumifyâ„¢ device, while the most likely to be purchased as a pocket device was the Vscan Airâ„¢. Image quality was felt to be the most important characteristic in evaluating handheld ultrasound devices.

BACKGROUND:In 2021, Delta became the predominant SARS-CoV-2 variant worldwide. While vaccines have effectively prevented COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occurred. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contributed to increased rates of breakthrough infections compared to unvaccinated controls. METHODS:We studied SARS-CoV-2 variant distribution, dynamics, and adaptive selection over time in relation to vaccine status, phylogenetic relatedness of viruses, full genome mutation profiles, and associated clinical and demographic parameters. FINDINGS/RESULTS:We show a steep and near-complete replacement of circulating variants with Delta between May and August 2021 in metropolitan New York. We observed an increase of the Delta sublineage AY.25 (14% in vaccinated, 7% in unvaccinated), its spike mutation S112L, and AY.44 (8% in vaccinated, 2% in unvaccinated) with its nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthrough infections increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals. INTERPRETATION/CONCLUSIONS:We observed a modest adaptation of Delta genomes in breakthrough infections in New York, suggesting an improved genomic framework to support Delta's epidemic growth in times of waning vaccine protection despite limited impact on vaccine escape. FUNDING/BACKGROUND:The study was supported by NYU institutional funds. The NYULH Genome Technology Center is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.