Faculty Bibliography

Background Angiotensin receptor neprilysin inhibitors (ARNI) reduce mortality and hospitalization for patients with heart failure. However, relatively high copayments for ARNI may contribute to suboptimal adherence, thus potentially limiting their benefits. Methods and Results We conducted a retrospective cohort study within a large, multi-site health system. We included patients with: ARNI prescription between November 20, 2020 and June 30, 2021; diagnosis of heart failure or left ventricular ejection fraction ≤40%; and available pharmacy or pharmacy benefit manager copayment data. The primary exposure was copayment, categorized as $0, $0.01 to $10, $10.01 to $100, and >$100. The primary outcome was prescription fill nonadherence, defined as the proportion of days covered <80% over 6 months. We assessed the association between copayment and nonadherence using multivariable logistic regression, and nonbinarized proportion of days covered using multivariable Poisson regression, adjusting for demographic, clinical, and neighborhood-level covariates. A total of 921 patients met inclusion criteria, with 192 (20.8%) having $0 copayment, 228 (24.8%) with $0.01 to $10 copayment, 206 (22.4%) with $10.01 to $100, and 295 (32.0%) with >$100. Patients with higher copayments had higher rates of nonadherence, ranging from 17.2% for $0 copayment to 34.2% for copayment >$100 (P<0.001). After multivariable adjustment, odds of nonadherence were significantly higher for copayment of $10.01 to $100 (odds ratio [OR], 1.93 [95% CI, 1.15-3.27], P=0.01) or >$100 (OR, 2.58 [95% CI, 1.63-4.18], P<0.001), as compared with $0 copayment. Similar associations were seen when assessing proportion of days covered as a proportion. Conclusions We found higher rates of not filling ARNI prescriptions among patients with higher copayments, which persisted after multivariable adjustment. Our findings support future studies to assess whether reducing copayments can increase adherence to ARNI and improve outcomes for heart failure.

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

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.

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

Background. CAB+RPV LA is a complete regimen for treatment of virologically suppressed people with HIV (PWH). As an injectable therapeutic administered by a healthcare provider (HCP), CAB+RPV LA may alleviate challenges with adherence to daily oral therapy and reduce fear of HIV status disclosure with oral treatment. Real world perspectives from HCPs and PWH are needed to enable successful delivery of this treatment in US healthcare settings. Methods. BEYOND is a 2 year prospective, observational, real-world study of utilization, outcomes, and experience of PWH initiating CAB+RPV LA across 30 US sites. HCPs at participating sites (treaters, injectors, drug acquisition/reimbursement staff) completed surveys at site activation (Sep 2021-Feb 2022; with follow-up surveys planned at 6, 12, 24 months) evaluating experiences to date with implementation of CAB+RPV LA at their sites. Results. HCPs from 24 sites responded to the initial survey (Table 1). 75% ofHCPs estimated that >=25% of their PWH are eligible for CAB+RPV LA, and 71% of sites are proactively discussing the regimen with >=25% of PWH. The majority (79%) of treaters reported they were extremely/very positive about administering CAB+RPV LA. Over 90% of injectors reported a positive overall opinion about administering CAB+RPV LA, and 86% reported the injections were easy to administer.Most (87%) HCPs reported injection visits taking <=45 minutes, including waiting time. Over 95% of sites have patient reminder systems; 86% will manually identify missed injections and all reported manual follow up by site staff. All sites utilizing the injection education video on the external HCP website (n=15/15) found it helpful and 94% (n=16/17) utilizing reimbursement specialists found them to be helpful. In their experience to date, most clinics reported only needing to increase coordination with the pharmacy team and add injection training to implement CAB+RPV LA. The most frequently reported benefits of implementing CAB+RPV LAbyHCPs included assurance of patient adherence and patient engagement in their HIV treatment (Table 2). Conclusion. Early real-world data from US HCPs in this study indicates interest in and anticipated uptake of CAB+RPV LA at their sites, positive overall opinion, and multiple benefits of administering the CAB+RPV LA regimen to PWH

BACKGROUND AND AIM/OBJECTIVE:Emerging data showed patients with chronic inflammatory disorders, including inflammatory bowel disease, are more likely to develop atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. This article aims to review the evidence of those associations. METHODS:PubMed was searched from inception to January 2022 using the keywords, including inflammatory bowel diseases, Crohn's disease, ulcerative colitis, atherosclerotic cardiovascular disease, coronary artery disease, cardiovascular disease, atrial fibrillation, heart failure, and premature coronary artery disease. Relevant literature, including retrospective/prospective cohort studies, clinical trials, meta-analyses, and guidelines were reviewed and summarized. RESULTS:Both ulcerative colitis and Crohn's disease are associated with an increased risk of atherosclerotic cardiovascular diseases, cerebrovascular accidents, premature coronary artery disease, and atrial fibrillation. Ulcerative colitis is associated with an increased risk of heart failure. The increased atrial fibrillation occurred during inflammatory bowel disease flares and persistent activity, but not during periods of remission. Hypotheses for the mechanism underlying the association of inflammatory bowel disease and atherosclerotic cardiovascular diseases include shared risk factors (i.e., obesity, diabetes, smoking, diet) and pathophysiology (gut microbiome dysfunction), or adverse effects from inflammatory bowel disease itself or its treatment (i.e., chronic inflammation, dyslipidemia, thrombocytosis, steroids). CONCLUSION/CONCLUSIONS:Inflammatory bowel disease is associated with an increased risk of atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. A multidisciplinary team with gastroenterologists and cardiologists is needed to optimize the care for patients with inflammatory bowel disease and associated cardiac diseases.

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.

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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