Faculty Bibliography

Background/Purpose: Psoriatic arthritis (PsA) is a complex immune-mediated disease. Beyond its deleterious effects in the skin and joints, PsA can lead to decreased quality of life, increased psychosocial stress, and is associated with high levels of depression and anxiety. However, little is known about the effects of mental health on disease activity and severity. This may be especially important in PsA where up to half of patients have residual symptoms (i.e., pain, fatigue) despite effective immunomodulatory therapies. The objective of this study was to characterize the prevalence of psychiatric comorbidities and their impact on PsA outcomes in an urban, academic, combined clinic setting.
Method(s): Consecutive adult patients meeting CASPAR criteria (n=537) were prospectively recruited at the NYU Psoriatic Arthritis Center and followed for up to 2 years. All data was obtained from clinical visits using a standardized EPIC template. Depression was defined as patient-reported depression and/or use of anti-depressant medications.
Result(s): The cohort was 53% male, mostly Caucasian (79.7%) and had an average age of 49 years. Within our population, 23% had depression, 18% anxiety, and 4% ADHD (Table 1). At the initial visit, patients with depression were more likely to be female, older, and have concomitant anxiety compared to those without depression. Moreover, compared to their nondepressed counterparts, patients with depression had similar swollen joint counts (SJCs), tender joint counts (TJCs) and RAPID3 scores, as well as a lower percent body surface area (BSA). However, at the subsequent timepoints, while other outcomes remained similar between the groups, patients with depression had a higher TJC (Figure 1). When adjusting for age, sex, race, medication use, and comorbidities, the rate ratio (RR) of TJC in patients with depression vs. without depression was 1.23 (95%CI 0.78, 1.94, p=0.79) at baseline (Figure 2). This ratio was even higher at year 1 (RR 1.47, 95%CI 0.91, 2.35, p=0.19) and year 2 (RR 1.75, 95%CI 0.97, 3.14, p=0.07), nearing significance. In the adjusted models for SJC, BSA, and RAPID3, this pattern was not seen.
Conclusion(s): High rates of depression and anxiety in this cohort expand upon previously reported data. While most patients improve over time, TJC is significantly higher in those who carry a diagnosis of depression whereas SJC and BSA are similar in patients with and without depression. This may reflect differences in how patients with depression perceive their disease and may lead to difficulty in achieving low disease activity/remission by composite score measures. Therefore, addressing depression, along with inflammatory symptoms, should be considered, especially in those with residual pain. Further work is needed to understand if intervening on depression could help improve PsA outcomes

Insufficient physical activity and obesity are associated with an increased risk of cancer recurrence and death in breast cancer survivors. Sex steroid hormones may mediate these associations. This study tested the hypothesis that exercise and diet, as compared to control, favorably change sex steroid hormones. This analysis of data from a subset of participants in a 2 × 2 factorial trial compares 269 postmenopausal breast cancer survivors who were insufficiently physically active and had overweight or obesity and were randomized to one of four treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. Secondary sex steroid hormone endpoints included estradiol, sex hormone-binding globulin (SHBG), and testosterone. Treatment effects were quantified using a mixed model for repeated measures. Compared to control, exercise alone did not significantly change estradiol (-1.9%; 95% CI: -12.6, 8.8), SHBG (2.4%; 95% CI: -9.9, 14.6), or testosterone (1.2%; 95% CI: -12.2, 14.5). Compared to control, diet alone did not significantly change estradiol (-7.8%; 95% CI: -17.6, 1.9), SHBG (8.2%; 95% CI: -4.2, 20.6), or testosterone (-0.8%; 95% CI: -13.6, 12.0). Compared to control, exercise plus diet did not significantly change estradiol (-6.3%; 95% CI: -16.3, 3.6), SHBG (8.8%; 95% CI: -4.0, 21.7), or testosterone (-5.3%; 95% CI: -18.0, 7.4). In postmenopausal breast cancer survivors who were insufficiently physically active and had overweight or obesity, randomization to exercise alone, diet alone, or exercise plus diet did not statistically significantly change sex steroid hormone concentrations at week 52.

BACKGROUND:In 2021, Delta became the predominant SARS-CoV-2 variant worldwide. While vaccines have effectively prevented COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occurred. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contributed to increased rates of breakthrough infections compared to unvaccinated controls. METHODS:We studied SARS-CoV-2 variant distribution, dynamics, and adaptive selection over time in relation to vaccine status, phylogenetic relatedness of viruses, full genome mutation profiles, and associated clinical and demographic parameters. FINDINGS/RESULTS:We show a steep and near-complete replacement of circulating variants with Delta between May and August 2021 in metropolitan New York. We observed an increase of the Delta sublineage AY.25 (14% in vaccinated, 7% in unvaccinated), its spike mutation S112L, and AY.44 (8% in vaccinated, 2% in unvaccinated) with its nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthrough infections increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals. INTERPRETATION/CONCLUSIONS:We observed a modest adaptation of Delta genomes in breakthrough infections in New York, suggesting an improved genomic framework to support Delta's epidemic growth in times of waning vaccine protection despite limited impact on vaccine escape. FUNDING/BACKGROUND:The study was supported by NYU institutional funds. The NYULH Genome Technology Center is partially supported by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.

BACKGROUND/OBJECTIVES/OBJECTIVE:Little is known about trajectories of recovery 12-months after hospitalization for severe COVID. METHODS:We conducted a prospective, longitudinal cohort study of patients with and without neurological complications during index hospitalization for COVID-19 from March 10, 2020-May 20, 2020. Phone follow-up batteries were performed at 6- and 12-months post-COVID symptom onset. The primary 12-month outcome was the modified Rankin Scale (mRS) comparing patients with or without neurological complications using multivariable ordinal analysis. Secondary outcomes included: activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA) and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. Changes in outcome scores from 6 to 12-months were compared using non-parametric paired-samples sign test. RESULTS:Twelve-month follow-up was completed in N=242 patients (median age 65, 64% male, 34% intubated during hospitalization) and N=174 completed both 6- and 12-month follow-up. At 12-months 197/227 (87%) had ≥1 abnormal metric: mRS>0 (75%), Barthel<100 (64%), t-MoCA≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%) and poor sleep (10%). 12-month mRS scores did not differ significantly among those with (N=113) or without (N=129) neurological complications during hospitalization after adjusting for age, sex, race, pre-COVID mRS and intubation status (adjusted OR 1.4, 95% CI0.8-2.5), though those with neurological complications had higher fatigue scores (T-score 47 vs 44, P=0.037). Significant improvements in outcome trajectories from 6- to 12-months were observed in t-MoCA scores (56% improved, median difference 1 point, P=0.002), and Neuro-QoL anxiety scores (45% improved, P=0.003). Non-significant improvements occurred in fatigue, sleep and depression scores in 48%, 48% and 38% of patients, respectively. Barthel and mRS scores remained unchanged between 6 and 12-months in >50% of patients. DISCUSSION/CONCLUSIONS:At 12-months post-hospitalization for severe COVID, 87% of patients had ongoing abnormalities in functional, cognitive or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a prior history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurological complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6- to 12-months. These results may not be generalizable to those with mild/moderate COVID.

Despite considerable progress, smoking remains the leading preventable cause of death in the United States. To address the considerable health and economic burden of tobacco use, the development of improved tobacco control and treatment interventions is critical. By combining elements of economics and psychology, behavioral economics provides a framework for novel solutions to treat smokers who have failed to quit with traditional smoking cessation interventions. The full range of behavioral economic principles, however, have not been widely utilized in the realm of tobacco control and treatment. Given the need for improved tobacco control and treatment, the limited use of other behavioral economic principles represents a substantial missed opportunity. For this reason, we sought to describe the principles of behavioral economics as they relate to tobacco control, highlight potential gaps in the behavioral economics tobacco research literature, and provide examples of potential interventions that use each principle.

Background/UNASSIGNED:To examine the feasibility and acceptability of integrating a tele-mentoring component into the identification of oral lesions at the dental clinics of a Federally Qualified Health Center network. Design and Methods/UNASSIGNED:General Practice Residency faculty and residents completed research ethics courses and trained dentists to use intra-oral cameras at chairside to photograph oral lesions of patients at routine dental visits. These images were then uploaded into the patient electronic health records (EHRs) with attendant descriptions and an oral surgeon was notified, who reviewed the charts, placed his observations in the EHR, and communicated his findings via secure e-mail to the involved residents, who in turn contacted their patients regarding follow-up actions. Feasibility was assessed via checklists completed by provider participants and semi-structured interviews. Acceptability was assessed via brief exit interviews completed by patient participants. Results/UNASSIGNED:All 12 of the dentist participants reported that they had successfully provided the tele-mentoring intervention, and that the process (from EHR data entry to interaction with the oral surgeon over findings to patient referral) was clear and straightforward. Of 39 patient participants, most strongly agreed or agreed that the use of an intra-oral camera by their dentists helped them to better understand oral cancer screening (94.9%) and that dentists answered their questions about oral cancer and were able to provide them with resources (94.8%). Conclusions/UNASSIGNED:Findings support further implementation research into adapting tele-mentoring using intra-oral cameras for training dental residents to detect and identify oral lesions and educating patients about oral cancer across settings.

Importance/UNASSIGNED:Close remote monitoring of patients following discharge for heart failure (HF) may reduce readmissions or death. Objective/UNASSIGNED:To determine whether remote monitoring of diuretic adherence and weight changes with financial incentives reduces hospital readmissions or death following discharge with HF. Design, Setting, and Participants/UNASSIGNED:The Electronic Monitoring of Patients Offers Ways to Enhance Recovery (EMPOWER) study, a 3-hospital pragmatic trial, randomized 552 adults recently discharged with HF to usual care (n = 280) or a compound intervention (n = 272) designed to inform clinicians of diuretic adherence and changes in patient weight. Patients were recruited from May 25, 2016, to April 8, 2019, and followed up for 12 months. Investigators were blinded to assignment but patients were not. Analysis was by intent to treat. Interventions/UNASSIGNED:Participants randomized to the intervention arm received digital scales, electronic pill bottles for diuretic medication, and regret lottery incentives conditional on the previous day's adherence to both medication and weight measurement, with $1.40 expected daily value. Participants' physicians were alerted if participants' weights increased 1.4 kg in 24 hours or 2.3 kg in 72 hours or if diuretic medications were missed for 5 days. Alerts and weights were integrated into the electronic health record. Participants randomized to the control arm received usual care and no further study contact. Main Outcomes and Measures/UNASSIGNED:Time to death or readmission for any cause within 12 months. Results/UNASSIGNED:Of the 552 participants, 290 were men (52.5%); 291 patients (52.7%) were Black, 231 were White (41.8%), and 16 were Hispanic (2.9%); mean (SD) age was 64.5 (11.8) years. The mean (SD) ejection fraction was 43% (18.1%). Each month, approximately 75% of participants were 80% adherent to both medication and weight measurement. There were 423 readmissions and 26 deaths in the control group and 377 readmissions and 23 deaths in the intervention group. There was no significant difference between the 2 groups for the combined outcome of all-cause inpatient readmission or death (unadjusted hazard ratio, 0.91; 95% CI, 0.74-1.13; P = .40) and no significant differences in all-cause inpatient readmission or observation stay or death, all-cause cardiovascular readmission or death, time to first event, and total all-cause deaths. Participants in the intervention group were slightly more likely to spend fewer days in the hospital. Conclusions and Relevance/UNASSIGNED:In this randomized clinical trial, there was no reduction in the combined outcome of readmission or mortality in a year-long intensive remote monitoring program with incentives for patients previously hospitalized for HF. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT02708654.

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved. A Bayesian-adaptive individual patient data meta-analysis was implemented. Outpatients aged ≥50 years and symptomatic for ≤7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution.

PURPOSE/OBJECTIVE:The purpose of this study was to describe the rationale and design of the Zoster Eye Disease Study (ZEDS). METHODS:ZEDS is a National Eye Institute-supported randomized clinical trial designed to determine whether 1 year of suppressive valacyclovir in patients with herpes zoster ophthalmicus (HZO) reduces complications because there is currently no high-quality evidence to support its use. Eligible patients are 18 years and older, immunocompetent, have a history of a typical rash at disease onset, and have had a record of active epithelial or stromal keratitis or iritis within 1 year before enrollment. Exclusion criteria include estimated glomerular filtration rate less than 45 or pregnancy. The primary endpoint is the time to first occurrence of new or worsening dendriform epithelial keratitis, stromal keratitis without or with ulceration, endothelial keratitis, or iritis due to HZO during 12 months of study treatment requiring prespecified treatment changes. The study has 80% power to detect a 30% difference between treatment groups, with a 30% rate of endpoints by 1 year assumed among controls. Secondary and exploratory questions include whether there is a persistent treatment benefit during the 6 months after treatment, whether development of postherpetic neuralgia varies by treatment group, and whether vaccinations against herpes zoster affect study outcomes and coronavirus disease 19 status. RESULTS:Over approximately 4 years, over 400 study participants have been enrolled. CONCLUSIONS:ZEDS aims to provide scientific evidence on whether suppressive valacyclovir treatment improves outcomes in HZO and should become the standard of care.

INTRODUCTION/BACKGROUND:There is evidence that supports the association of dense tumor infiltrating lymphocyte (TILs) with an increased risk of ipsilateral recurrence in ductal carcinoma in situ (DCIS). However, the association of cellular composition of DCIS immune microenvironment with the histopathologic parameters and outcome is not well understood. METHODS:We queried our institutional database for patients with pure DCIS diagnosed between 2010 and 2019. Immunohistochemical studies for CD8, CD4, CD68, CD163, and FOXP3 were performed and evaluated in the DCIS microenvironment using tissue microarrays. Statistical methods included Fisher's exact test for categorical variables and the two-sample t-test or the Wilcoxon Rank-Sum test for continuous variables. RESULTS:The analytic sample included 67 patients. Median age was 62 years (range = 53 to 66) and median follow up was 6.7 years (range = 5.3 to 7.8). Thirteen patients had ipsilateral recurrence. Of all the clinicopathologic variables, only the DCIS size and TIL density were significantly associated with recurrence (p = 0.023 and 0.006, respectively). After adjusting for age and TIL density, only high CD68 (>50) and high CD68/CD163 ratio (>0.46) correlated with ipsilateral recurrence (p = 0.026 and 0.013, respectively) and shorter time to recurrence [hazard ratio 4.87 (95% CI: 1.24-19, p = 0.023) and 10.32 (95% CI: 1.34-80, p = 0.025), respectively]. CONCLUSIONS:macrophage density and CD68/CD163 ratio also predict a shorter time to recurrence.