Faculty Bibliography

In the original paper, we used the variable "URBRUR08," from the 2008 survey wave as a measure of childhood urbanicity. Upon further investigation we realized that this variable actually measured Beale urban-rural code during the respondent's adulthood.  Thus, we reran our analysis of the pseudo-heritability of childhood urbanicity using the variable. The original results hold such that even with the first 20 principal components held constant, childhood urban-rural status appears to be ~20% "heritable" in GREML models-a figure that is actually higher than the original estimate reported in the paper (14% controlling for 25 PCs, 15% controlling for 10 PCs, and 29% controlling for two PCs). Meanwhile, the heritabilities of the other phenotypes-height, BMI and education-still do not change when they are residualized on childhood urbanicity. In other words, the original results of the paper do not change.

PURPOSE/OBJECTIVE:The IGF and mTOR-pathways are considered as potential targets for therapy in patients with adrenocortical carcinoma (ACC). This study aims to describe the IGF pathway in ACC and to explore the response to the combined treatment with the IGF1R/IR inhibitor linsitinib, and mTOR inhibitors (sirolimus and everolimus) in in vitro models of ACC. METHODS:The protein expression level of IGF2, IGF1R and IGF2R was evaluated by immunohistochemistry in 17 human ACCs and the mRNA expression level of IGF1, IGF2, IGF1R, IR isoforms A and B, IGF2R, IGF-Binding-Proteins[IGFBP]-1, 2, 3 and 6 was evaluated by RT-qPCR in 12 samples. In H295R and HAC15 ACC cell lines the combined effects of linsitinib and sirolimus or everolimus on cell survival were evaluated. RESULTS:A high protein expression of IGF2, IGF1R and IGF2R was observed in 82, 65 and 100% of samples, respectively. A high relative expression of IGF2 mRNA was found in the majority of samples. The mRNA levels of the IRA were higher than that of IRB and IGF1R in the majority of samples (75%). Linsitinib inhibits cell growth in the H295R and HAC15 cell lines and, combined with sirolimus or everolimus, linsitinib showed a significant additive effect. CONCLUSIONS:In addition to IGF2 and IGF1R, ACC express IGF2R, IRA and several IGFBPs, suggesting that the interplay between the different components of the IGF pathway in ACC could be more complex than previously considered. The addition of mTOR inhibitors to linsitinib may have stronger antiproliferative effects than linsitinib alone.

BACKGROUND:Reducing costs while increasing or maintaining quality is crucial to delivering high value care. OBJECTIVE:To assess the impact of a hospital value-based management programme on cost and quality. DESIGN/METHODS:Time series analysis of non-psychiatric, non-rehabilitation, non-newborn patients discharged between 1 September 2011 and 31 December 2017 from a US urban, academic medical centre. INTERVENTION/METHODS:NYU Langone Health instituted an institution-wide programme in April 2014 to increase value of healthcare, defined as health outcomes achieved per dollar spent. Key features included joint clinical and operational leadership; granular and transparent cost accounting; dedicated project support staff; information technology support; and a departmental shared savings programme. MEASUREMENTS/METHODS:Change in variable direct costs; secondary outcomes included changes in length of stay, readmission and in-hospital mortality. RESULTS:The programme chartered 74 projects targeting opportunities in supply chain management (eg, surgical trays), operational efficiency (eg, discharge optimisation), care of outlier patients (eg, those at end of life) and resource utilisation (eg, blood management). The study cohort included 160 434 hospitalisations. Adjusted variable costs decreased 7.7% over the study period. Admissions with medical diagnosis related groups (DRG) declined an average 0.20% per month relative to baseline. Admissions with surgical DRGs had an early increase in costs of 2.7% followed by 0.37% decrease in costs per month. Mean expense per hospitalisation improved from 13% above median for teaching hospitals to 2% above median. Length of stay decreased by 0.25% per month relative to prior trends (95% CI -0.34 to 0.17): approximately half a day by the end of the study period. There were no significant changes in 30-day same-hospital readmission or in-hospital mortality. Estimated institutional savings after intervention costs were approximately $53.9 million. LIMITATIONS/CONCLUSIONS:Observational analysis. CONCLUSION/CONCLUSIONS:A systematic programme to increase healthcare value by lowering the cost of care without compromising quality is achievable and sustainable over several years.

Background/UNASSIGNED:Dynamic nutrition education strategies may help prepare physicians to provide nutrition guidance to patients. Activity/UNASSIGNED:We pilot tested a nutrition-focused iBook chapter with a group of medical students and residents (June 2017) through pre and post-test Qualtrics surveys. Results/UNASSIGNED:All 29 respondents recognized the role of nutrition in medical care. Two-thirds reported some nutrition training in their medical education; nearly 90% reported this training was inadequate. Few (17%) reported reading scholarly nutrition articles; 84% reported they would recommend the iBook to their peers. Conclusions/UNASSIGNED:An iBook is a resource that could be used to teach nutrition to medical trainees.

Prolonged remission of hypercortisolism with steroidogenesis inhibitors has been described in patients with ectopic adrenocorticotropic hormone (ACTH) syndrome. The anti-proliferative and pro-apoptotic effect of ketoconazole in human cancer cells was previously suggested. The aim of this study was to explore the effects of ketoconazole on ACTH-producing and non-ACTH-producing neuroendocrine tumor (NET) cell lines. The effects of ketoconazole alone, and in combination with somatostatin analogs, were evaluated in two human cell lines: DMS-79 (ectopic ACTH-producing small cell lung carcinoma) and BON-1 (human pancreatic NET). Total DNA measurement, apoptosis, cell cycle, chromogranin A (CgA)/proopiomelanocortin (POMC) expression by qRT-PCR, serotonin, CgA, and ACTH secretion assays were performed. In both cell lines, ketoconazole significantly suppressed cell growth and colony formation in a dose and time-dependent manner. The effect in DMS-79 was primarily cytotoxic, while it was more apoptotic in BON-1 cells. Ketoconazole also induced increase in G0/G1 phase in both cell lines and arrest in phase G2/M of BON-1 cells. Ketoconazole did not affect the secretion of serotonin, CgA, ACTH, or the mRNA expression of CgA and POMC. Decreased serotonin secretion was observed after the combination treatment with pasireotide. These results suggest a direct effect of ketoconazole on cell proliferation, apoptosis, and cell cycle in both ACTH- and non-ACTH-producing NET cells.

BACKGROUND AND PURPOSE/OBJECTIVE:Cardiac biomarkers may help identify stroke mechanisms and may aid in improving stroke prevention strategies. There is limited data on the association between these biomarkers and acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). We hypothesized that cardiac biomarkers (cardiac troponin and left atrial diameter [LAD]) would be associated with the presence of LVO. METHODS:Data were abstracted from a single center prospective AIS database over 18 months and included all patients with AIS with CT angiography of the head and neck. The presence of LVO was defined as proximal LVO of the internal carotid artery terminus, middle cerebral artery (M1 or proximal M2), or basilar artery. Univariate analyses and predefined multivariable models were performed to determine the association between cardiac biomarkers (positive troponin [troponin ≥0.1 ng/mL] and LAD on transthoracic echocardiogram) and LVO adjusting for demographic factors (age and sex), risk factors (hypertension, diabetes, hyperlipidemia, history of stroke, congestive heart failure, coronary heart disease, and smoking), and atrial fibrillation (AF). RESULTS:We identified 1234 patients admitted with AIS; 886 patients (71.8%) had vascular imaging to detect LVO. Of those with imaging available, 374 patients (42.2%) had LVO and 207 patients (23.4%) underwent thrombectomy. There was an association between positive troponin and LVO after adjusting for age, sex and other risk factors (adjusted OR 1.69 [1.08-2.63], P = .022) and this association persisted after including AF in the model (adjusted OR 1.60 [1.02-2.53], P = 0.043). There was an association between LAD and LVO after adjusting for age, sex, and risk factors (adjusted OR per mm 1.03 [1.01-1.05], P = 0.013) but this association was not present when AF was added to the model (adjusted OR 1.01 [0.99-1.04], P = .346). Sensitivity analyses using thrombectomy as an outcome yielded similar findings. CONCLUSIONS:Cardiac biomarkers, particularly serum troponin levels, are associated with acute LVO in patients with ischemic stroke. Prospective studies are ongoing to confirm this association and to test whether anticoagulation reduces the risk of recurrent embolism in this patient population.

RATIONALE, AIMS, AND OBJECTIVES/UNASSIGNED:There are well-documented barriers that have limited widespread, sustained adoption of screening and brief intervention for risky substance use in health care settings. In order to better inform implementation efforts, this study evaluates whether patient characteristics, screening results, and implementation success indicators differed between two clinical setting types: primary care and emergency. METHODS:Patients presenting to an emergency or primary care setting were screened for risky substance use (n = 41 567). Patients with a positive screen were further assessed for psychosocial, health, and substance use problems (n = 1604). Differences in patient characteristics between primary care and emergency settings were examined using chi-square and t tests. Multilevel logistic regression was used to examine whether setting type predicted screening results. Site-level indicators of implementation success were calculated (percentage prescreens completed, percentage full screens completed, and percentage refused services) for all patient visits (n = 78 656). RESULTS:As compared with primary care patients, emergency patients had more severe substance use patterns and screening scores, were more likely to use a variety of illicit drugs, and reported more psychosocial issues. In logistic regression models, setting type did not predict whether patients screened positive; however, it did predict screening into a higher vs lower risk category such that emergency patients were more likely to be in a higher risk category. Emergency settings had lower indicators of implementation success (eg, 14% lower prescreen completion rate) as compared with primary care settings on some implementation measures. CONCLUSIONS:This evaluation found important differences in patient characteristics and screening and implementation results between primary care and emergency settings. Health care organizations and administrators implementing screening and brief intervention should attend to setting differences that could affect implementation and clinical care.

Control of symptoms related to hormonal hypersecretion by functioning neuroendocrine tumors (NETs) is challenging. New therapeutic options are required. Since novel in vitro tumor models seem to better mimic the tumor in vivo conditions, we aimed to study the effect of somatostatin and dopamine receptor agonists (octreotide and cabergoline, respectively) and novel somatostatin-dopamine chimeric multi-receptor drugs (BIM-065, BIM-23A760) using 2D (monolayer) and 3D (spheroids) cultures.

BACKGROUND:Patients with chronic conditions routinely see multiple outpatient providers, who may or may not communicate with each other. Gaps in information across providers caring for the same patient can lead to harm for patients. However, the exact causes and consequences of healthcare fragmentation are not understood well enough to design interventions to address them. OBJECTIVE:We sought to elicit patients' and providers' views on the causes and consequences of healthcare fragmentation. DESIGN AND PARTICIPANTS:We conducted a qualitative study with focus groups of patients and, separately, of providers (attending physicians and nurse practitioners) at an academic hospital-based primary care practice in New York City in June-August 2017. Patient participants were English-speaking adults with ≥ 2 chronic conditions. APPROACH:Each focus group lasted 1 h and asked the same two questions: "Why do you think some patients receive care from many different providers and others do not?" and "What do you think happens as a result of patients receiving care from many different providers?" Data collection continued until a point of data saturation was reached. Thematic analysis was used to identify themes and subthemes. KEY RESULTS:We conducted 6 focus groups with a total of 46 participants (25 patients and 21 providers). Study participants identified 41 unique causes of fragmentation, which originate from 4 different levels of the healthcare system (patient, provider, healthcare organization, and healthcare environment); most causes were not related to medical need. Participants also identified 24 unique consequences of fragmentation, of which 3 were desirable and 21 were undesirable. CONCLUSIONS:The results of this study offer a granular roadmap for how to decrease healthcare fragmentation. The large number and severity of negative consequences (including medical errors, misdiagnosis, increased cost, and provider burnout) underscore the urgent need for interventions to address this problem directly.

Introduction/UNASSIGNED:Despite a decline, smoking rates have remained high, especially in communities with lower income, education, and limited insurance options. Evidence shows that physician-initiated counseling on smoking cessation is effective and saves lives, and that specific skills are needed to appropriately lead this type of patient-physician communication. Residency is a critical moment for future physicians and may be the optimal time to learn, practice, and refine this skillset. Unannounced Standardized Patients (USPs) have been found to be effective, incognito evaluators of resident practices. Methods/UNASSIGNED:This study introduced rigorously trained actors (USPs) into two urban, safety-net clinics to assess resident ability to engage, activate, and counsel a pre-contemplative smoker. A complementary chart review assessed appropriate documentation in the patient's electronic health record (EHR) and its relationship to counseling style and prescribing practices. Results/UNASSIGNED:Resident scores (% well done) on patient education and engagement were low (33% and 23%, respectively). Residents who coupled cessation advice with an open discussion style activated their patients more than those who solely advised cessation across all comparable measures. On EHR documentation, residents who accurately documented smoking history were more likely to directly advise their patient to quit smoking when compared to residents who did not document (t(97) = 2.828, p = .006, Cohen's D = 0.56). Conclusions/UNASSIGNED:Results highlight the need to reinforce training in patient-centered approaches including motivational interviewing, counseling, and shared decision-making. Future research should focus on the effects of smokers in pre-contemplation on physician counseling style and examine the relationship between medical training and provider communication to guide interventions.