Faculty Bibliography

CONTEXT/BACKGROUND:Metyrapone and ketoconazole, frequently used steroidogenesis inhibitors for treatment of Cushing syndrome, can be associated with side effects and limited efficacy. Osilodrostat is a CYP11B1 and CYP11B2 inhibitor, with unknown effects on other steroidogenic enzymes. OBJECTIVE:To compare the effects of osilodrostat, metyrapone, and ketoconazole on adrenal steroidogenesis, and pituitary adenoma cells in vitro. METHODS:HAC15 cells, 17 primary human adrenocortical cell cultures, and pituitary adenoma cells were incubated with osilodrostat, metyrapone, or ketoconazole (0.01 to 10 µM). Cortisol and ACTH were measured using chemiluminescence immunoassays, and steroid profiles by liquid chromatography-mass spectrometry. RESULTS:In HAC15 cells, osilodrostat inhibited cortisol production more potently (IC50: 0.035 µM) than metyrapone (0.068 µM; P < 0.0001), and ketoconazole (0.621 µM; P < 0.0001). IC50 values of osilodrostat and metyrapone for basal cortisol production varied with a 25- and 18-fold difference, respectively, with comparable potency. Aldosterone production was inhibited more potently by osilodrostat vs metyrapone and ketoconazole. Osilodrostat and metyrapone treatment resulted in strong inhibition of corticosterone and cortisol, 11-deoxycortisol accumulation, and modest effects on adrenal androgens. No pituitary-directed effects of osilodrostat were observed. CONCLUSIONS:Under our study conditions, osilodrostat is a potent cortisol production inhibitor in human adrenocortical cells, comparable with metyrapone. All steroidogenesis inhibitors showed large variability in sensitivity between primary adrenocortical cultures. Osilodrostat might inhibit CYP11B1 and CYP11B2, in some conditions to a lesser extent CYP17A1 activity, and a proximal step in the steroidogenesis. Osilodrostat is a promising treatment option for Cushing syndrome, and in vivo differences with metyrapone are potentially driven by pharmacokinetic differences.

This paper presents the results of the literature review conducted for the working group topic on inflammation, infection, exposure, and the human microbiome. Infection and chronic inflammation can elevate risk for cardiovascular disease and cancer. Environmental exposures common among South Asian (SA) subgroups, such as arsenic exposure among Bangladeshis and particulate matter air pollution among taxi drivers, also pose risks. This review explores the effects of exposure to arsenic and particulate matter, as well as other infections common among SAs, including human papillomavirus (HPV) and hepatitis B/C infection. Emerging research on the human microbiome, and the effect of microbiome changes on obesity and diabetes risk among SAs are also explored.

PURPOSE/UNASSIGNED:Housing status can become compromised in the wake of financial hardship for some patients with cancer and become a source of disparity. This qualitative study describes the types of housing issues experienced by patients with cancer and survivors of cancer in New York City. METHODS/UNASSIGNED:Semistructured interviews were conducted with a volunteer sample of 21 patients with cancer or survivors of cancer treated in New York City who reported housing needs in the period after diagnosis through survivorship. Nine supplemental interviews were conducted with cancer and housing key informants. Conventional content analysis was conducted on transcripts to create a codebook describing types of housing needs. RESULTS/UNASSIGNED:Patients and survivors most commonly had breast (n = 9) and blood (n = 4) cancers and ranged from recently diagnosed to many years posttreatment. Twenty-nine distinct housing-related issues were identified, which were grouped into the following six major categories: housing costs (eg, rent, mortgage), home loss, doubled up or unstable housing, housing conditions, accessibility (eg, stairs, proximity to amenities), and safety. Issues were often interrelated. Housing needs sometimes predated cancer diagnosis. Other issues newly emerged in the wake of cancer-related physical limitations and disruption to finances. Needs ranged in severity and caused patients and survivors considerable burden during a difficult period of poor health and financial strain. CONCLUSION/UNASSIGNED:This study contributes depth to current understandings of housing needs among patients with cancer and survivors by providing detailed disaggregated descriptions. We recommend increasing availability of services responsive to these needs and exploring promising options such as patient navigation and legal services. Findings also highlight the importance of creative solutions addressing ecologic-level factors such as housing affordability.

To reduce unnecessary laboratory testing, a three-phase intervention was designed by students to decrease serum folate laboratory testing in the inpatient setting. These included an educational phase, a personalized feedback phase, and the uncoupling of orders in the electronic medical record. Average monthly serum folate ordering decreased by 87% over the course of the intervention, from 98.4 orders per month at baseline to 12.7 per month in the last phase of the intervention. In the segmented regression analysis, joint ordering of folate and vitamin B12 significantly decreased during the intervention ([INCREMENT]slope = -4.22 tests/month, p = .0089), whereas single ordering of vitamin B12 significantly increased ([INCREMENT]slope = +5.6 tests/month; p < .001). Our intervention was successful in modifying ordering patterns to decrease testing for a deficiency that is rare in the U.S. population.

OBJECTIVE:To characterize the prevalence of tobacco, alcohol, and drug use and the acceptability of screening in university health centers. PARTICIPANTS/METHODS:Five hundred and two consecutively recruited students presenting for primary care visits in February and August, 2015, in two health centers. METHODS:Participants completed anonymous substance use questionnaires in the waiting area, and had the option of sharing results with their medical provider. We examined screening rates, prevalence, and predictors of sharing results. RESULTS:Past-year use was 31.5% for tobacco, 67.1% for alcohol (>4 drinks/day), 38.6% for illicit drugs, and 9.2% for prescription drugs (nonmedical use). A minority (43.8%) shared screening results. Sharing was lowest among those with moderate-high risk use of tobacco (OR =0.37, 95% CI 0.20-0.69), alcohol (OR =0.48, 95% CI 0.25-0.90), or illicit drugs (OR =0.38, 95% CI 0.20-0.73). CONCLUSIONS:Screening can be integrated into university health services, but students with active substance use may be uncomfortable discussing it with medical providers.

During 2014-2016, the largest outbreak of Ebola virus disease (EVD) in history occurred in West Africa. The New York City Department of Health and Mental Hygiene (DOHMH) worked with health care providers to prepare for persons under investigation (PUIs) for EVD in New York City. From July 1, 2014, through December 29, 2015, we classified as a PUI a person with EVD-compatible signs or symptoms and an epidemiologic risk factor within 21 days before illness onset. Of 112 persons who met PUI criteria, 74 (66%) sought medical care and 49 (44%) were hospitalized. The remaining 38 (34%) were isolated at home with daily contact by DOHMH staff members. Thirty-two (29%) PUIs received a diagnosis of malaria. Of 10 PUIs tested, 1 received a diagnosis of EVD. Home isolation minimized unnecessary hospitalization. This case study highlights the importance of developing competency among clinical and public health staff managing persons suspected to be infected with a high-consequence pathogen.

Despite improvements in the management of in-hospital cardiac arrest over the past decade, in-hospital cardiac arrest continues to be associated with poor prognosis. This has led to the development of rapid response systems, hospital-wide efforts to improve patient outcomes by centering on prompt identification of decompensating patients, expert clinical management, and continuous quality improvement of processes of care. The rapid response system may include cardiac arrest teams, which are centered on identification and treatment of patients with in-hospital cardiac arrest. However, few evidence-based guidelines exist to guide the formation of such teams, and the degree of their variation across the United States has not been well described.

Objectives: To identify predictors of pulmonary hypertension (PHT) and the predictive value of PHT for rehospitalization among patients with heart failure with reduced ejection fraction (HFrEF). Methods: A retrospective study of 351 hospitalized patients with heart failure (HF). Patients 18 years and above with HFrEF secondary to non-ischemic cardiomyopathy were reviewed. Patients with coronary artery disease, preserved ejection fraction and other secondary causes of PHT apart from HF were excluded. PHT as a predictor of 30-day and six-month re-admission was assessed as well as important possible predictors of PHT. Cox regression analysis, multiple linear regression as well as other statistical tools were employed as deemed appropriate. Results: Thirty-seven (37) and 99 patients were re-hospitalized within 30 days and 6 months after discharge for decompensated HF, respectively. After Cox regression analysis, higher hemoglobin reduced the odds of rehospitalization for decompensated HF (p = 0.015) within 30 days after discharge while higher pulmonary artery systolic pressure (PASP) (p = 0.002) and blood urea nitrogen (BUN) (p = 0.041) increased the odds of rehospitalization within 6 months of discharge. The predictors of the PHT among patients with HFrEF after multiple linear regression were low BMI (p = 0.027), increasing age (p = 0.006) and increased left atrial diameter (LAD) on echocardiography (p = 0.0001). Conclusion: Patients with HFrEF have a high predisposition to developing PHT if at admission, they have low BMI, dilated left atrium or are older. Patients with one or more of these attributes may need more intensive therapy to reduce the risk of developing PHT and in turn reduce readmission rates.