Faculty Bibliography

This Special Issue of the International Journal of Environmental Research and Public Health is dedicated to increasing the scientific information available about the long-term effects of exposure to the 2001 World Trade Center disaster [...].

BACKGROUND:We compared outcomes in inpatients and outpatients, pre-COVID-19, who were infected with either coronavirus or influenza. METHODS:Using deidentified electronic health records data from the Geisinger-Regeneron partnership, we compared patients with RT-PCR-positive tests for the 4 common coronaviruses (229E, HKU1, NL63, OC43) or influenza (A and B) from June 2016 to February 2019. RESULTS:Overall, 52 833 patients were tested for coronaviruses and influenza. For patients ≥21 years old, 1555 and 3991 patient encounters had confirmed positive coronavirus and influenza tests, respectively. Both groups had similar intensive care unit (ICU) admission rates (7.2% vs 6.1%, P = .12), although patients with coronavirus had significantly more pneumonia (15% vs 7.4%, P < .001) and higher death rate within 30 days (4.9% vs 3.0%, P < .001). After controlling for other covariates, coronavirus infection still had a higher risk of death and pneumonia than influenza (odds ratio, 1.64 and 2.05, P < .001), with no significant difference in ICU admission rates. CONCLUSIONS:Common coronaviruses cause significant morbidity, with potentially worse outcomes than influenza. Identifying a subset of patients who are more susceptible to poor outcomes from common coronavirus infections may help plan clinical interventions in patients with suspected infections.

PURPOSE OF REVIEW/OBJECTIVE:Cardiovascular disease (CVD) is highly associated with obesity and cardiometabolic dysfunction. This review will focus on three novel therapies that have been identified for potential treatment of obesity and its associated CVD risk factors. RECENT FINDINGS/RESULTS:Intermittent fasting (IF) studies in animal models have shown improvements in cardiometabolic factors, including improved glucose metabolism, reduced inflammation, and reduced blood pressure. However, there is still a lack of prospective human trials to support results from animal-based studies and observational data. Studies of ketogenic diets in humans have produced mixed effects in CVD risk factors. It has been shown that the ketogenic diet (KD) increases low-density lipoprotein cholesterol (LDL-C) but decreases triglycerides. Additionally, implementation of KD in rodent studies have demonstrated increased insulin resistance and glucose intolerance. Bariatric surgery is a useful tool to help patients with obesity lose significant amounts of weight while alleviating CVD risk factors such as hypertension, LDL-C levels, triglyceride levels, and diabetes. The type of procedure influences degree of improvement in weight and CVD risk factors, yet complications remain possible. IF and bariatric surgery offer potential for weight loss and treatment of CVD risk factors. Negative cardiovascular effects of KD have been noted and should be considered before recommending this diet to patients, particularly those with established cardiovascular disease.

BACKGROUND:Advances in genetics and sequencing technologies are enabling the identification of more individuals with inherited cancer susceptibility who could benefit from tailored screening and prevention recommendations. While cancer family history information is used in primary care settings to identify unaffected patients who could benefit from a cancer genetics evaluation, this information is underutilized. System-level population health management strategies are needed to assist health care systems in identifying patients who may benefit from genetic services. In addition, because of the limited number of trained genetics specialists and increasing patient volume, the development of innovative and sustainable approaches to delivering cancer genetic services is essential. METHODS:We are conducting a randomized controlled trial, entitled Broadening the Reach, Impact, and Delivery of Genetic Services (BRIDGE), to address these needs. The trial is comparing uptake of genetic counseling, uptake of genetic testing, and patient adherence to management recommendations for automated, patient-directed versus enhanced standard of care cancer genetics services delivery models. An algorithm-based system that utilizes structured cancer family history data available in the electronic health record (EHR) is used to identify unaffected patients who receive primary care at the study sites and meet current guidelines for cancer genetic testing. We are enrolling eligible patients at two healthcare systems (University of Utah Health and New York University Langone Health) through outreach to a randomly selected sample of 2780 eligible patients in the two sites, with 1:1 randomization to the genetic services delivery arms within sites. Study outcomes are assessed through genetics clinic records, EHR, and two follow-up questionnaires at 4 weeks and 12 months after last genetic counseling contactpre-test genetic counseling. DISCUSSION/CONCLUSIONS:BRIDGE is being conducted in two healthcare systems with different clinical structures and patient populations. Innovative aspects of the trial include a randomized comparison of a chatbot-based genetic services delivery model to standard of care, as well as identification of at-risk individuals through a sustainable EHR-based system. The findings from the BRIDGE trial will advance the state of the science in identification of unaffected patients with inherited cancer susceptibility and delivery of genetic services to those patients. TRIAL REGISTRATION/BACKGROUND:BRIDGE is registered as NCT03985852 . The trial was registered on June 6, 2019 at clinicaltrials.gov .

Importance/UNASSIGNED:Recently, the benefit of adding daratumumab to the proteasome inhibitor-based, 3-drug combination of bortezomib, lenalidomide, and dexamethasone for patients with newly diagnosed multiple myeloma who underwent high-dose melphalan chemotherapy and autologous hemopoietic cell transplant was assessed. Here, we examine the addition of daratumumab to the second-generation proteasome inhibitor-based, 3-drug combination of carfilzomib, lenalidomide, and dexamethasone. Objective/UNASSIGNED:To assess the safety and effectiveness of carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy for patients with newly diagnosed multiple myeloma, in the absence of high-dose melphalan chemotherapy and autologous hemopoietic cell transplant. Design, Setting, and Participants/UNASSIGNED:Clinical and correlative pilot study at the Memorial Sloan Kettering Cancer Center in New York, New York. Patients with newly diagnosed multiple myeloma were enrolled between October 1, 2018, and November 15, 2019. The median follow-up from start of treatment was 20.3 months (95% CI, 19.2-21.9 months). Interventions/UNASSIGNED:Eight 28-day cycles with intravenous carfilzomib, 20/56 mg/m2 (days 1, 8, and 15); oral lenalidomide, 25 mg, (days 1-21); dexamethasone, 40 mg weekly, orally or intravenously (cycles 1-4), and 20 mg after cycle 4; and intravenous daratumumab, 16 mg/kg (days 1, 8, 15, and 22 [cycles 1-2]; days 1 and 15 [cycles 3-6]; and day 1 [cycles 7 and 8]). Main Outcomes and Measures/UNASSIGNED:The primary end point was the minimal residual disease (MRD) rate, in the absence of high-dose melphalan chemotherapy and autologous hemopoietic cell transplant. Secondary end points included determining safety and tolerability, evaluating rates of clinical response per the International Myeloma Working Group, and estimating progression-free survival (PFS) and overall survival (OS) rates. Results/UNASSIGNED:Forty-one evaluable patients were enrolled (median age, 59 years; range, 30-70 years); 25 (61%) were female, and 20 (49%) had high-risk multiple myeloma. The primary end point (MRD negativity in the bone marrow; 10-5 sensitivity) was achieved in 29 of 41 patients (71%; 95% CI, 54%-83%), and therefore the trial was deemed successful. Median time to MRD negativity was 6 cycles (range, 1-8 cycles). Secondary end points of the overall response rate and the very good partial response or complete response rate were 100% (41 of 41 patients) and 95% (39 of 41 patients), respectively. At 11 months of the median follow-up, the 1-year PFS rate and the OS rate were 98% (95% CI, 93%-100%) and 100%, respectively. Most common (≥2 patients) grade 3 or 4 adverse events were neutropenia (12 patients [27%]), rash (4 patients [9%]), lung infection (3 patients [7%]), and increased alanine aminotransferase level (2 patients [4%]). There were no deaths. Conclusions and Relevance/UNASSIGNED:In this nonrandomized clinical trial, carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy was associated with high rates of MRD negativity in patients with newly diagnosed multiple myeloma and high rates of PFS.

Thoracic aortic calcium(TAC) is an important marker of extracoronary atherosclerosis with established predictive value for all-cause mortality. We sought to explore the predictive value of TAC for stroke mortality, independent of the more established coronary artery calcium (CAC) score. The CAC Consortium is a retrospectively assembled database of 66,636 patients aged ≥18 years with no previous history of cardiovascular disease, baseline CAC scans for risk stratification, and follow-up for 12 ± 4 years. CAC scans capture the adjacent thoracic aorta, enabling assessment of TAC from the same images. TAC was available in 41,066 (62%), and was primarily analyzed as present or not present. To account for competing risks for nonstroke death, we utilized multivariable-adjusted Fine and Gray competing risk regression models adjusted for traditional cardiovascular risk factors and CAC score. The mean age of participants was 53.8 ± 10.3 years, with 34.4% female. There were 110 stroke deaths during follow-up. The unadjusted subdistribution hazard ratio (SHR) for stroke mortality in those who had TAC present compared with those who did not was 8.80 (95% confidence interval [CI]: 5.97, 12.98). After adjusting for traditional risk factors and CAC score, the SHR was 2.21 (95% CI:1.39,3.49). In sex-stratified analyses, the fully adjusted SHR for females was 3.42 (95% CI: 1.74, 6.73) while for males it was 1.55 (95% CI: 0.83, 2.90). TAC was associated with stroke mortality independent of CAC and traditional risk factors, more so in women. The presence of TAC appears to be an independent risk marker for stroke mortality.

OBJECTIVE:The aim of the study was to determine the main factors contributing to hospital readmissions and their potential preventability after a coronavirus disease 2019 (COVID-19) hospitalization at 2 New York City hospitals. METHODS:This was a retrospective study at 2 affiliated New York City hospitals located in the Upper East Side and Lower Manhattan neighborhoods. We performed case reviews using the Hospital Medicine Reengineering Network framework to determine potentially preventable readmissions among patients hospitalized for COVID-19 between March 3, 2020 (date of first case) and April 27, 2020, and readmitted to either of the 2 hospitals within 30 days of discharge. RESULTS:Among 53 readmissions after hospitalization for COVID-19, 44 (83%) were deemed not preventable and 9 (17%) were potentially preventable. Nonpreventable readmissions were mostly due to disease progression or complications of COVID-19 (37/44, 84%). Main factors contributing to potentially preventable readmissions were issues with initial disposition (5/9, 56%), premature discharge (3/9, 33%), and inappropriate readmission (1/9, 11%) for someone who likely did not require rehospitalization. CONCLUSIONS:Most readmissions after a COVID-19 hospitalization were not preventable and a consequence of the natural progression of the disease, specifically worsening dyspnea or hypoxemia. Some readmissions were potentially preventable, mostly because of issues with disposition that were directly related to challenges posed by the ongoing COVID-19 pandemic. Clinicians should be aware of challenges with disposition related to circumstances of the COVID-19 pandemic.