Faculty Bibliography

A primary service provided by home care is medication management. Issues with medication management at home place older adults at high risk for hospital admission, readmission, and adverse events. This study sought to understand medication management challenges from the home care provider perspective. A qualitative secondary data analysis approach was used to analyze program evaluation interview data from an interprofessional educational intervention study designed to decrease medication complexity in older urban adults receiving home care. Directed and summative content analysis approaches were used to analyze data from 90 clinician and student participants. Medication safety issues along with provider-provider communication problems were central themes with medication complexity. Fragmented care coordination contributed to medication management complexity. Patient-, provider-, and system-level factors influencing medication complexity and management were identified as contributing to both communication and coordination challenges.

Inactivating mutations in SMARCA4 (BRG1), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16^INK4a-deficient profile associated with positive responses to CDK4/6 inhibitors. Thus, our findings indicate that CDK4/6 inhibitors, approved for a breast cancer subtype addicted to CDK4/6 activation, could be repurposed to treat SCCOHT. Moreover, our study suggests a novel paradigm whereby critically low oncogene levels, caused by loss of a driver tumor suppressor, may also be exploited therapeutically.

Caucasian Americans (CA) compared with African Americans (AA) have a twofold increased incidence of multiple myeloma (MM) and have an earlier age of diagnosis. However, there is sparse information regarding underlying biological differences across racial/ethnic groups. We characterized genetic alterations using a targeted next-generation sequencing assay called myTYPE, developed at MSKCC, allowing capture of somatic mutations, IgH translocations, gains/losses, and hyperdiploidy. Samples were obtained from the NIH Plasma Cell Dyscrasia Racial Disparity Cohort. In total, 68 patient samples were successfully sequenced and manually curated based on well-established databases. Of the 68 patient samples (47 CA, 21 AA), 84% had at least one type of genomic alteration. Importantly, the IgH translocation, t(11;14), was observed more frequently in the AA group (0 vs. 29%, p = 0.001). Known oncogenic somatic non-synonymous mutations were found in 18 genes and indels in 2 genes. KRAS mutations were the most common mutation found in 16% of patients followed by NRAS and BRAF mutations. TP53 somatic mutations appeared to be more common in CA but lacked significance. This proof-of-principle study indicates the presence of varying underlying tumor biology between racial groups and supports the need of future prospective trials to capture these molecular characteristics.

OBJECTIVE:Persons living with HIV (PLWH) well-treated on antiretroviral therapies remain at risk for ensuing arterial disease. We investigated the relationship between adipose depots and biomarkers of arterial injury and inflammation to gain insight into the link between body composition and CVD risk. DESIGNS/METHODS/UNASSIGNED:155 HIV-infected and 70 non-HIV-infected individuals were well-phenotyped for body composition. Adipose depots were assessed via single-slice abdominal CT. Circulating markers of arterial disease and generalized inflammation [lipoprotein-associated phospholipase A2 (LpPLA2), oxidized LDL (oxLDL), high sensitivity cardiac troponin T (hs-cTnT), high sensitivity C reactive protein (hsCRP)] were evaluated. RESULTS:Despite similar BMI and visceral adipose tissue (VAT), HIV-infected individuals had significantly lower subcutaneous adipose tissue (SAT, 199[126,288] vs. 239[148,358]cm, P = .04) compared to non-HIV-infected individuals. Among HIV-infected individuals, reduced SAT inversely correlated with LpPLA2 (ρ = -0.19, P = .02) and hs-cTnT (ρ = -0.24, P = .004), whereas increased VAT significantly and positively related to LpPLA2 (ρ = 0.25, P = .003), oxLDL (ρ = 0.28, P = .0005), hs-cTnT (ρ = 0.28, P = .0007), and hsCRP (ρ = 0.32, P =  < .0001). Similar analyses among the non-HIV-infected individuals revealed significant relationships between SAT and LpPLA2 (ρ = -0.24, P = .05), as well as VAT and LpPLA2 (ρ = 0.37, P = .002), oxLDL (ρ = 0.24, P = .05), and hsCRP (ρ = 0.29, P = .02). In modeling performed among the HIV group, simultaneously controlling for VAT, SAT, age, and relevant HIV-related parameters, reduced SAT was an independent predictor of LpPLA2 (P = .04) and hs-cTnT (P = .005) and increased VAT was an independent predictor of LpPLA2 (P = .001), oxLDL (P = .02), hs-cTnT (P = .04), and hsCRP (P = .04) CONCLUSION:: Fat redistribution phenotypes, characterized by SAT loss and/or VAT accumulation, may be linked to arterial injury and inflammation in HIV.

Many practicing health care providers find themselves ill-prepared to meet the complex care needs of older adults. The Geriatric Certificate Program (GCP) represents a collaborative partnership leveraging existing educational courses, with new courses developed to fill existing education gaps, aimed at improving quality of care for older adults. This paper describes the GCP and examines its impact on knowledge, skills, clinical practice, as well as confidence, comfort, and competence in providing geriatric care. Upon program completion, all graduates (N = 146; 100%) completed an online evaluation survey. The majority of graduates reported (5-point scale: 1 = much less now; 5 = much more now) being more confident (88%), comfortable (83%), and competent (89%) to provide optimal geriatric care than prior to the program. The GCP provides a significant opportunity for health care providers to build their capacity for the care of older adults. Key lessons learned in implementing the GCP and suggestions for further development are discussed.

Sugar-sweetened beverages (SSBs) increase risk of cardiometabolic disease. Young people consume the largest amounts of SSBs and have experienced the greatest relative gains in obesity in the past several decades. There is evidence of addictive properties of both caffeine and sugar, the primary ingredients in SSBs, but little research into such properties of SSBs in naturally occurring consumption patterns. Thus, in this exploratory study, we sought to examine potentially addictive properties of SSBs during a 3-day SSB cessation intervention in overweight and obese adolescents who typically consume ≥3 SSBs daily. Participants (n = 25) were aged 13-18 years, mostly female (72%), and African American (56%) or Hispanic (16%) with a BMI≥95th percenttile (76%). Withdrawal symptoms and SSB craving were assessed approximately 1-week apart, during both regular SSB consumption and a 3-day period of SSB cessation in which participants were instructed to drink only plain milk and water. During SSB cessation, adolescents reported increased SSB cravings and headache and decreased motivation, contentment, ability to concentrate, and overall well-being (uncorrected Ps < 0.05). After controlling the false discovery rate, changes in motivation, craving, and well-being remained significant (corrected Ps < 0.05). Using 24-hr recalls and drink journals, participants reported lower total daily consumption of sugar (-80 g) and added sugar (-16 g) (Ps < 0.001) during cessation. This study provides preliminary evidence of withdrawal symptoms and increased SSB cravings during cessation in a diverse population of overweight or obese adolescents.

Rationale: Mandatory influenza vaccination for all hospital employees is increasingly common, and was a policy at NYU Langone Health System (NYC, Winthrop, Lutheran) in 2017. Employees applying for exemption based on prior allergic reaction underwent evaluation by an allergist. We assessed the success of mandating the vaccine and whether allergic evaluation increased vaccination rates. Method(s): Prior reaction history, skin testing, and outcomes of evaluation were reviewed from charts. Primary outcomes were total vaccination rate and outcomes of those that applied for exemption. Result(s): A total of 39,146 of 39,558 employees (98.9%) received vaccination without evaluation. Of 39,558 employees, 419 (0.01%) applied for exemption; 73 sought exemption based on prior allergic reaction. Exemption was granted to 303 employees for other reasons. Egg-free vaccine was administered to 38/73 (52%) who reported egg allergy. The remaining 35 underwent allergy evaluation; 15 were granted exemption while 20 (57%) were vaccinated. At Winthrop, 46 employees applied for medical exemption due to allergy; 45 (97%) were ultimately vaccinated. Eight employees with reported vaccine allergy were evaluated. Four received the vaccine without testing, while four were skin tested. One patient developed a generalized rash with skin testing and was granted exemption. The other three successfully received influenza vaccine via graded challenge. Institution-wide, 99.04% (39,182 of 39,558) of employees received the vaccine. Conclusion(s): Mandating flu vaccination is by itself an effective method to ensure compliance (98.9%). Allergy evaluation increased the vaccination rate in those applying for an exemption due to allergy, with only 15/73 (20%) granted exemption.