Faculty Bibliography

The geographic availability of pre-exposure prophylaxis (PrEP) providers is one important factor that significantly affects PrEP uptake. While most previous studies have employed spatial accessibility in static residential neighborhood definitions or self-reported healthcare accessibility, we examined the associations of the objectively measured geographic density of PrEP services with current PrEP use, using global positioning system (GPS) among sexual minority men (SMM) in New York City. 250 HIV-negative SMM participated in a 2-week GPS monitoring (January 2017-January 2018). Geographic PrEP density was measured as total numbers of PrEP providers in (1) individual activity space defined as daily path area of GPS points, (2) residential street network buffers and (3) census tract and ZIP code of residential locations. Geographic PrEP density within GPS-based activity space was positively associated with current PrEP use (prevalence ratio for 50-m activity space = 1.10, 95% confidence interval: [1.02, 1.18]). PrEP provider counts in residential buffer areas and administrative neighborhoods were not associated with PrEP use. Although it is not generalizable beyond New York City, our finding suggests the importance of daily mobility pattern in HIV prevention and PrEP implementation strategies.

OBJECTIVE:To review the frequency as well as the pros and cons of telephone and video-enabled telemedicine during the first 9 months of the Coronavirus disease 2019 (COVID-19) pandemic as experienced by safety net providers across New York State (NYS). METHODS:Analysis of visits to 36 community health centers (CHCs) in NYS by modality (telephone vs video) from February to November 2020. Semi-structured interviews with 25 primary care, behavioral health, and pediatric providers from 8 CHCs. FINDINGS:In the week following the NYS stay-at-home order, video and telephone visits rose from 3.4 and 0% of total visits to 14.9 and 22.3%. At its peak, more than 60% of visits were conducted via telemedicine (April 2020) before tapering off to about 30% of visits (August 2020). Providers expressed a strong preference for video visits, particularly for situations when visual assessments were needed. Yet, more visits were conducted over telephone than video at all points throughout the pandemic. Video-specific advantages included enhanced ability to engage patients and use of visual cues to get a comprehensive look into the patient's life, including social supports, hygiene, and medication adherence. Telephone presented unique benefits, including greater privacy, feasibility, and ease of use that make it critical to engage with key populations and as a backup for when video was not an option. CONCLUSIONS:Despite challenges, providers reported positive experiences delivering care remotely using both telephone and video during the COVID-19 pandemic and believe both modalities are critical for enabling access to care in the safety net.

Poverty-related disparities appear early in life in cognitive, language, and social-emotional development, and in growth, especially obesity, and have long-term consequences across the life course. It is essential to develop effective strategies to promote healthy behaviors in pregnancy and the early years of parenthood that can mitigate disparities. Primary preventive interventions within the pediatric primary care setting offer universal access, high engagement, and population-level impact at low cost. While many families in poverty or with low income would benefit from preventive services related to both development and growth, most successful interventions have tended to focus on only one of these domains. In this manuscript, we suggest that it may be possible to address both development and growth simultaneously and effectively. In particular, current theoretical models suggest alignment in mechanisms by which poverty can create barriers to parent-child early relational health (i.e., parenting practices, creating structure, and parent-child relationship quality), constituting a final common pathway for both domains. Based on these models and related empirical data, we propose a strength-based, whole child approach to target common antecedents through positive parenting and prevent disparities in both development and growth; we believe this approach has the potential to transform policy and practice. Achieving these goals will require new payment systems that make scaling of primary prevention in health care feasible, research funding to assess efficacy/effectiveness and inform implementation, and collaboration among early childhood stakeholders, including clinicians across specialties, scientists across academic disciplines, and policy makers.

Background Solid tumors comprise >90% of cancers. Metastatic colorectal cancer, non-small cell lung cancer, and pancreatic cancer are among the leading causes of cancer-related mortality (5-year overall survival: 14%, 6%, and 3%, respectively). 1Chimeric antigen receptor (CAR) T-cell therapy demonstrated clinical outcomes in hematologic malignancies.2 3 However, translating engineered T-cell therapies to solid tumors proves difficult due to a lack of tumor-specific targets that discriminate cancer cells from normal cells. In previous studies, the use of a carcinoembryonic antigen T-cell receptors and mesothelin CARs both resulted in dose-limiting on-target, off-tumor toxicities.4 5 TmodTM CAR T-cell therapy addresses these challenges by leveraging dual receptors to create a robust AND NOT signal integrator capable of killing tumor cells, while leaving healthy cells intact (figure 1).6 Tmod platform technology is a versatile system that may be applied to T cells and natural killer cells in autologous and allogeneic settings. HLA LOH offers a definitive tumor versus normal discriminator target for CAR T-cell therapy.6 7 The 2 receptors comprise an activator that recognizes an antigen present on the surface of normal and tumor cells and a blocker that recognizes a second surface antigen from an allele lost only in tumor cells. HLA LOH has been observed in ~13% across all solid tumors and up to 33% of pancreatic cancers.8 New technologies have shown higher HLA LOH rates; however, it is unclear whether patients with HLA LOH in their primary tumor tissues are at higher risk for recurrence. BASECAMP-1 is an observational study with key objectives: 1) To determine and identify patients with somatic HLA LOH eligible for Tmod CAR T-cell therapy, and 2) Subsequent leukapheresis and manufacturing feasibility for future Tmod CAR T-cell trials. Methods BASECAMP-1 (NCT04981119) patient eligibility has 2 parts (figure 2): 1) Patients will be initially screened to identify germline HLA-A*02 heterozygosity by central nextgeneration sequencing (NGS). If HLA-A*02 heterozygosity is confirmed, primary archival tumor tissue will be analyzed by xT-Onco NGS testing9 to determine if somatic tumor HLAA* 02 LOH is present; 2) If the tumor demonstrates HLAA* 02 LOH and the patient screens eligible, the patient will undergo leukapheresis. Patients enrolled in the study who undergo leukapheresis will be evaluated for safety 7 days post-leukapheresis and followed for relapsed status. Banked T cells will be available for subsequent autologous Tmod CAR T-cell therapy at the time of relapse

PURPOSE:We examined the demographic and clinicopathological parameters associated with the time to convert from active surveillance to treatment among men with prostate cancer. MATERIALS AND METHODS:A multi-institutional cohort of 7,279 patients managed with active surveillance had data and biospecimens collected for germline genetic analyses. RESULTS:Of 6,775 men included in the analysis, 2,260 (33.4%) converted to treatment at a median followup of 6.7 years. Earlier conversion was associated with higher Gleason grade groups (GG2 vs GG1 adjusted hazard ratio [aHR] 1.57, 95% CI 1.36-1.82; ≥GG3 vs GG1 aHR 1.77, 95% CI 1.29-2.43), serum prostate specific antigen concentrations (aHR per 5 ng/ml increment 1.18, 95% CI 1.11-1.25), tumor stages (cT2 vs cT1 aHR 1.58, 95% CI 1.41-1.77; ≥cT3 vs cT1 aHR 4.36, 95% CI 3.19-5.96) and number of cancerous biopsy cores (3 vs 1-2 cores aHR 1.59, 95% CI 1.37-1.84; ≥4 vs 1-2 cores aHR 3.29, 95% CI 2.94-3.69), and younger age (age continuous per 5-year increase aHR 0.96, 95% CI 0.93-0.99). Patients with high-volume GG1 tumors had a shorter interval to conversion than those with low-volume GG1 tumors and behaved like the higher-risk patients. We found no significant association between the time to conversion and self-reported race or genetic ancestry. CONCLUSIONS:A shorter time to conversion from active surveillance to treatment was associated with higher-risk clinicopathological tumor features. Furthermore, patients with high-volume GG1 tumors behaved similarly to those with intermediate and high-risk tumors. An exploratory analysis of self-reported race and genetic ancestry revealed no association with the time to conversion.

Primary vaginal cancer is rare, comprising 1% to 2% of gynecologic malignancies and 20% of all malignancies involving the vagina. More frequently, the vagina is involved secondarily by direct invasion from malignancies originating in adjacent organs or by metastases from other pelvic or extrapelvic primary malignancies. Data on the use of imaging in vaginal cancer are sparse. Insights are derived from the study of imaging in cervical cancer and have reasonable generalizability to vaginal cancer due to similar tumor biology. Given the trend toward definitive chemoradiation for both cancers in all but early stage lesions, principles of postchemoradiation tumor response evaluation are largely analogous. Accordingly, many of the recommendations outlined here are informed by principles translated from the literature on cervical cancer. For pretreatment assessment of local tumor burden and in the case of recurrent vaginal cancer, MRI is the preferred imaging modality. PET/CT has demonstrated utility for the detection of nodal metastatic and unexpected distant metastatic disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Introduction: Tracheostomy in COVID-19 patients is a controversial and difficult clinical decision. A recent COVID-19 Severity Score (CSS) was validated to identify high-risk patients requiring hospitalization. We hypothesized that the CSS would be associated with survival in patients considered for tracheostomy.
Method(s): We reviewed 77 mechanically ventilated COVID-19 patients evaluated for percutaneous dilational tracheostomy (PDT) from March-June 2020 at a public tertiary care center. Decision for PDT was based on clinical judgment of the screening surgeons. The CSS was retrospectively calculated using mean biomarker values from admission to time of PDT consult. Primary end point was survival to discharge. The Youden index identified an optimal CSS cut point for survival.
Result(s): Mean CSS for 42 survivors vs 35 nonsurvivors was significantly different (CSS 52 vs 66; p = 0.003). The Youden index returned an optimal CSS of 55 (area under the curve 0.7; 95% CI, 43 to 72). Median CSS was 40 (interquartile range 27 to 49) in the Low CSS (<55 group) and 72 (interquartile range 66 to 93) in the high CSS (>= 55) group (Fig. 1a). Eighty-seven percent of low CSS patients underwent PDT, with 74% survival, and 61% of high CSS patients underwent PDT with only 41% surviving (Fig. 1b). Patients with high CSS had 77% lower odds of survival (odds ratio 0.2; 95% CI, 0.1 to 0.7).
Conclusion(s): Higher CSS was associated with decreased survival to discharge in patients evaluated for PDT, with a score > 55 predictive of mortality. The novel CSS can be a useful adjunct in determining which COVID-19 patients will benefit from tracheostomy. Further prospective validation of this tool is warranted. [Formula presented]
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BACKGROUND:Drugs like ecstasy, cocaine, and counterfeit prescription pills can contain fentanyl. We examined knowledge about potential adulteration/contamination of such drugs among people attending electronic dance music (EDM) parties. METHODS:Adults in New York City were surveyed entering randomly selected EDM parties during the summers of 2018 (n=1,029) and 2019 (n=559). Surveys assessed perceptions that: 1) ecstasy/Molly can contain adulterants more dangerous than MDMA, 2) cocaine can contain fentanyl, and 3) prescription pills from non-pharmacy sources can contain fentanyl. We compared prevalence of perceptions between 2018 and 2019. RESULTS:Prevalence of agreeing that cocaine can contain fentanyl increased from 42.1% to 58.6%, a 39.2% increase (p=.003). Increases in agreement were not significant regarding ecstasy potentially containing adulterants (55.0% vs. 59.0%) and non-pharmacy prescription drugs potentially containing fentanyl (46.8% vs. 52.9%). Those reporting past-year ecstasy use in particular reported increased agreement that ecstasy can be adulterated (from 52.9% to 80.0%, a 51.2% increase; p<.001) and those reporting past-year cocaine use reported increased agreement that cocaine can be adulterated (from 48.2% to 70.7%, a 46.7% increase; p=.016). CONCLUSIONS:Knowledge of potential adulteration or contamination of commonly used drugs in this high-risk scene is increasing. Continued education about possible drug contents is needed.