Faculty Bibliography

BACKGROUND/UNASSIGNED:Nonadherence to antihypertensive medications remains a persistent problem that leads to preventable morbidity and mortality. Behavioral economic strategies represent a novel way to improve antihypertensive medication adherence, but remain largely untested especially in vulnerable populations which stand to benefit the most. The Behavioral Economics Trial To Enhance Regulation of Blood Pressure (BETTER-BP) was designed in this context, to test whether a digitally-enabled incentive lottery improves antihypertensive adherence and reduces systolic blood pressure (SBP). DESIGN/UNASSIGNED:BETTER-BP is a pragmatic randomized trial conducted within 3 safety-net clinics in New York City: Bellevue Hospital Center, Gouveneur Hospital Center, and NYU Family Health Centers - Park Slope. The trial will randomize 435 patients with poorly controlled hypertension and poor adherence (<80% days adherent) in a 2:1 ratio (intervention:control) to receive either an incentive lottery versus passive monitoring. The incentive lottery is delivered via short messaging service (SMS) text messages that are delivered based on (1) antihypertensive adherence tracked via a wireless electronic monitoring device, paired with (2) a probability of lottery winning with variable incentives and a regret component for nonadherence. The study intervention lasts for 6 months, and ambulatory systolic blood pressure (SBP) will be measured at both 6 and 12 months to evaluate immediate and durable lottery effects. CONCLUSIONS/UNASSIGNED:BETTER-BP will generate knowledge about whether an incentive lottery is effective in vulnerable populations to improve antihypertensive medication adherence. If successful, this could lead to the implementation of this novel strategy on a larger scale to improve outcomes.

Objectives UpRi is a first-in-class NaPi2b ADC with a novel scaffold-linker-payload that enables high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a sodium-dependent phosphate transporter protein broadly expressed in high-grade serous ovarian cancer (HGSOC), with limited expression in healthy tissues. Interim data from the Phase 1b expansion cohort of heavily pretreated patients with recurrent HGSOC has been reported. These data demonstrated clinically meaningful activity, notably in patients with NaPi2b-high tumors (TPS>=75). Effective and well-tolerated treatments for PROC remains an unmet medical need. The standard of care, singleagent chemotherapy, has limited efficacy, significant toxicities, and short duration of response. UPLIFT was designed as a single- arm Ph2 registrational trial for UpRi monotherapy in PROC. Methods UPLIFT is enrolling patients with PROC with up to 4 prior LoT. Prior bevacizumab is required for patients with 1-2 prior LoT only; it's not required for patients with 3-4 prior LoT. Patients may enroll regardless of NaPi2b expression; <= Grade 2 peripheral neuropathy is permitted. Primary platinum refractory patients are excluded. UPLIFT will enroll ~180 patients globally, including ~100 patients with high NaPi2b expression. UpRi is dosed IV at 36 mg/ m2 up to ~80 mg dose maximum Q4W. Baseline tumor samples (fresh or archived) will be collected for central analysis of NaPi2b expression. The primary endpoint is ORR in NaPi2b-high expressing patients. The cut-off for high NaPi2b expression is TPS>=75. Secondary endpoints include ORR in the overall population, duration of response, and safety. UPLIFT is conducted in collaboration with ENGOT (ENGOT-ov67) and GOG (GOG-3048). NCT03319628 Results trialinprogress Conclusions trialinprogress

Objectives GEN-1, an IL-12 DNA plasmid formulated with a synthetic carrier is being evaluated with neoadjuvant platinumtaxane chemotherapy (NACT) in patients with advanced epithelial ovarian cancer. OVATION 2 is a multi-center, randomized, open-label phase I/II study evaluating the safety, antitumor activity, and immunological response to GEN-1 at a dose of 100 mg/m2 intraperitoneal (IP) actively enrolling at 20 centers in USA and Canada. Methods Up to 130 patients will be randomized 1:1 to receive either NACT plus GEN-1 or NACT alone. The phase I portion will evaluate safety in at least 6 patients administered in 8 weekly infusions starting at cycle 1 week 2 in combination with three 21-day cycles of carboplatin AUC 6 with paclitaxel 175 mg/m2 (PC). Following interval cytoreductive surgery an additional 9 weekly GEN-1 IP infusions starting at cycle 4 week 1 with three 21-day cycles of PC. If no dose limiting toxicities are found, then the study will continue into the phase II portion. To evaluate biological activity a subgroup of patients will have tumor tissue at initial biopsy/laparoscopy collected and at interval cytoreductive surgery. Tissue will be analyzed for the density of CD8, FoxP3, IDO-1, PD-1, and PDL-1 cells. Blood, peritoneal fluid/wash will be collected before and after treatment in a subgroup of patients to quantify for levels of IFN-g. The primary endpoint is PFS. Results Trial in progress: there are no available results at the time of submission. Conclusions Trial in progress: there are no available conclusions at the time of submission

Background: There is currently a paucity of data on urethral-related outcomes in metoidioplasty and phalloplasty gender affirming surgery (MaPGAS) with urethral lengthening (UL)and vaginectomy.
Method(s): A systematic review was performed utilizing MEDLINE, Web of Science, Cochrane Library, Europe PMC, OSF Preprints, and EMBASE. Methodologic quality was scored using Methodological Index for Non-Randomized Studies (MINORS) criteria. Four independent reviewers performed the article evaluation, data extraction, and methodologic quality assessment. Primary outcomes included standing to urinate/pee (STP), penile length, glanular meatus, urethral stricture, fistula, and flap necrosis. Results were summarized qualitatively with descriptive statistics.
Result(s): A total of 2,881 articles of which 11 retrospective reviews of 13 cohorts met criteria; 4.3/16 average (avg) MINORS score. Six metoidioplasty cohorts had an average penile length of 6 cm, 74% reported successful STP, and a quarter developed stricture or fistula. Phalloplasty cohorts included radial forearm flap (RF) and Anterolateral Thigh flap (ALT). Of the 4 RF studies nearly a third developed a stricture or fistula and only one study reported 99% STP with a glanular meatus. Three ALT studies reported no length but had 80-90% STP with a glanular meatus and a quarter with stricture or fistula.
Conclusion(s): Urethral complications in MaPGAS-UL in a cohort with prior vaginectomy are common and variably reported. Patient centered outcome measures as well as clearly defined outcome metrics created in partnership with community members are needed.
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Despite the many clerkship models of medical education, all can be considered a form of experiential learning. Experiential learning is a complex pedagogical approach involving the development of cognitive skills in an environment with a unique culture with multiple stakeholders, which may impact learner motivation, confidence, and other noncognitive drivers of success. Students may delay the transition to the clerkship year for myriad reasons, and the intricate nature of experiential learning suggested this may impact student performance. This retrospective, observational study investigated the impact of clerkship postponement by measuring subsequent clerkship performance. Pre-clerkship and third-year clerkship performance were analyzed for three cohorts of students (classes of 2018, 2019, and 2020, N = 274) where students had the option to delay the start of their clerkship year. A mixed analysis of variance (ANOVA) and paired t-tests were conducted to compare academic performance over time among students who did and did not delay. Across three cohorts of students, 12% delayed the start of the clerkship year (N = 33). Regardless of prior academic performance, these students experienced a significant reduction in clerkship grades compared to their non-delaying peers. Delaying the start of the clerkship year may have negative durable effects on future academic performance. This information should be kept in mind for student advisement.

Background. HIV-associated wasting (i.e., progressive, involuntary weight loss with both fat and lean tissue loss; HIVAW) is an under-appreciated AIDS-defining illness; the 2012-2018 period prevalence was reported as 18% in a recent claims study in the United States. We aimed to assess the association between incident HIVAW/ low weight and all-cause mortality in the era of modern combination antiretroviral therapy (ART). Methods. In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort, PWH without (a) any prior HIVAW/low weight, (b) malignancy within 3 years, and (c) opportunistic infection within 1 year who were active in care between 2016 and 2020 were followed through death, loss to follow-up, or study end (31OCT2021). HIVAW/low weight included a wasting or low BMI/underweight diagnosis (ICD codes, title search) or BMI < 20 kg/m2. Hazard ratios (HR) and 95% confidence intervals (CI) for the association between time-dependent incident HIVAW/low weight (exposure) and all-cause mortality (outcome) were estimated with extended Cox regression models. The adjusted model included age at baseline, race, ethnicity, and time-dependent covariates (log10 viral load, Veterans Aging Cohort Study [VACS] Mortality Index score). Viral load and VACS score were included as surrogate markers for ART use and comorbidities, respectively. Linear and quadratic terms of continuous variables were included. Results. Of 67,119 PWH without prior HIVAW/low weight in OPERA, 62,314 (93%) PWH had non-missing covariate data and were included in the models; baseline characteristics did not differ between the full and model study populations (Table 1). Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of incident HIVAW/low weight and 1,354 (2%) deaths. In the adjusted model, PWH who experienced incident HIVAW/low weight had a significantly increased risk of death over follow-up than those who did not experience HIVAW/low weight (HR: 1.96; 95% CI: 1.68, 2.27) (Table 2). Conclusion. In this analysis of 62,314 PWH in care, incident HIVAW/low weight was associated with twice the risk for all-cause mortality in the modern ART era. Particular attention needs to be paid to HIVAW/low weight among PWH to restore health and potentially reduce the risk of death

Background. In-vitro neutralizing antibody (Ab) titers correlated with ~250 IU/ mL Spike Ig Ab level for the Delta COVID-19 variant, establishing the 2021 French and Swiss cutoff for booster guidance. In a New York City healthcare clinic where those guidelines were adopted, we aimed to quantify vaccination responses in HIV + and HIV- individuals to assess the utility of quantifying antibodies to guide booster timing. Methods. Adults who were fully vaccinated against SARS-CoV-2 virus (i.e., 2 Pfizer, 2 Moderna or 1 J&J vaccine) were included if >1 Roche SARS-CoV-2 Semi-Quant Spike Ig Ab test was performed >21 days after vaccination and before any booster (through 03DEC2021). Vaccine response was assessed at the first Ab test and considered adequate (>250 IU/mL) or inadequate (low: >=51 to <=250 IU/ mL; no response: < 51 IU/mL). The rate of Ab decline was estimated with linear regression, using all sequential Ab tests over the first 6 months between vaccination and boosting. Analyses were stratified by vaccine type, HIV status and CD4 count in HIV+ ( >200 cells/muL cutoff). Results. Out of 1979 patients, 869 completed their primary vaccinations, of whom 825 (95%) had >=1 eligible Ab test (HIV+: 512; HIV-: 313; Table). Overall, 83% had an adequate immune response to vaccination (Pfizer: 82%, Moderna: 94%, J&J: 51%), with similar findings regardless of HIV status and CD4 count (Figure 1). In those with >=2 Ab tests within six months between vaccination and boosting, Ab levels declined at a rate of 91 IU/mL per month (95% CI: -138, -44). While some variation was observed, rates of Ab decay were generally consistent across vaccine, HIV status and CD4 count strata (Figure 2). Only 1/7 breakthrough COVID-19 infections occurred post booster (6 days later Conclusion. In the pre-omicron era, primary COVID immunization with a mRNA vaccine generally yielded adequate Ab responses, although inadequate responses were observed in 19% of Pfizer, 6% of Moderna, and 49% of J&J vaccine recipients. Ab levels decreased at an average rate of 91 IU/mL per month after primary immunization. Variability in vaccine responses and Ab declines show the utility of measuring spike Ig Ab levels rather than using empiric time frames for booster guidance. Omicron-specific quantitative IgG neutralization levels must be established to inform preventative care

BACKGROUND:Reducing unnecessary routine laboratory testing is a Choosing Wisely® recommendation, and new areas of overuse were noted during the COVID-19 pandemic. OBJECTIVE:To reduce unnecessary repetitive routine laboratory testing for patients with COVID-19 during the pandemic across a large safety net health system. DESIGNS, SETTINGS AND PARTICIPANTS/UNASSIGNED:This quality improvement initiative was initiated by the System High-Value Care Council at New York City Health + Hospitals (H + H), the largest public healthcare system in the United States consisting of 11 acute care hospitals. INTERVENTION/METHODS:four overused laboratory tests in noncritically ill hospitalized patients with COVID-19 were identified: C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and procalcitonin. A two-pronged electronic health record intervention was implemented consisting of (1) nonintrusive, informational nudge statements placed on selected order sets, and (2) a forcing function of one consecutive day limit on ordering. MAIN OUTCOME AND MEASURES/METHODS:The average of excess tests per encounter days (ETPED) for each of four target laboratory testing only in patients with COVID-19. OBJECTIVE:Interdisciplinary System High-Value Care Council identified four overused laboratory tests (inflammatory markers) in noncritically ill hospitalized patients with COVID-19: C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and procalcitonin. Within an 11-hospital safety net health system, a two-pronged electronic health record intervention was implemented consisting of (1) nonintrusive, informational nudge statements placed on selected order sets, and (2) a forcing function of one consecutive day limit on ordering. The preintervention period (March 16, 2020 to January 24, 2021) was compared to the postintervention period (January 25, 2021 to March 22, 2022). RESULTS:Time series linear regression showed decreases in CRP (-17.9%, p < .05), ferritin (-37.6%, p < .001), and LDH (-30.1%, p < .001). Slope differences were significant (CRP, ferritin, and LDH p < 0.001; procalcitonin p < 0.05). Decreases were observed across weekly averages: CRP (-19%, p < .01), ferritin (-37.9%, p < .001), LDH (-28.7%, p < .001), and procalcitonin (-18.4%, p < .05). CONCLUSION/CONCLUSIONS:This intervention was associated with reduced routine inflammatory marker testing in non-intensive care unit COVID-19 hospitalized patients across 11 hospitals. Variation was high among individual hospitals.