Faculty Bibliography

Background/Purpose: Patients with immune mediated inflammatory disorders (IMIDs) have an inherently heightened susceptibility to infection and may be considered high risk for developing COVID-19. While data regarding the COVID-19 vaccine's immunogenicity in an immunocompetent adult population is rapidly emerging, the ability of IMID patients to adequately respond to these vaccines is not known. Here, we investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with IMIDs on immunomodulatory treatment Methods: Patients with immune mediated inflammatory disorders (IMIDs) have an inherently heightened susceptibility to infection and may be considered high risk for developing COVID-19. While data regarding the COVID-19 vaccine's immunogenicity in an immunocompetent adult population is rapidly emerging, the ability of IMID patients to adequately respond to these vaccines is not known. Here, we investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with IMIDs on immunomodulatory treatment.
Result(s): The NY cohort baseline characteristics are found in Table 1. The Erlangen cohort consisted of 182 healthy subjects, 11 subjects with IMID receiving TNFi monotherapy, and 20 subjects with IMID on MTX monotherapy. In both cohorts, healthy individuals and those with IMID not on MTX were similar in age, while those IMID patients receiving MTX were generally older. In the NY cohort, of the healthy participants, 96.3% demonstrated adequate humoral immune response. Patients with IMID not on MTX achieved a similar rate of high antibody response rate (91.8%), while those on MTX had a lower rate of adequate humoral response (75.0%) (Figure 1A). This remains true even after the exclusion of patients who had evidence of prior COVID-19 infection (P= 0.014). Of note, 3 out of the 4 IMID patients receiving rituximab did not produce an adequate response. Similarly, in the Erlangen validation cohort, 98.3% of healthy controls, 90.9% of patients with IMID receiving TNFi monotherapy, and 50.0% receiving MTX monotherapy achieved adequate immunogenicity (Figure 1B). These differences remain significant when combining the cohorts, using a stricter definition of adequate response, and in a subgroup analysis by age. Cellular response was also analyzed in a subgroup of the NY cohort before and after second vaccination. Activated CD8+ T cells (CD8+ T cells expressing Ki67 and CD38) and the granzyme B-producing subset of these activated CD8+ T cells, were induced in immunocompetent adults and those with IMID not on MTX, but not induced in patients receiving MTX (Figure 2).
Conclusion(s): In two independent cohorts of IMID patients, MTX, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking MTX to increase the chances of immunization efficacy against SARS-CoV-2, as has been demonstrated for other viral vaccines

Increasing evidence supports a link between maternal prenatal cannabis use and altered neural and physiological development of the child. However, whether cannabis use relates to altered human brain development prior to birth, and specifically, whether maternal prenatal cannabis use relates to connectivity of fetal functional brain systems, remains an open question. The major objective of this study was to identify whether maternal prenatal cannabis exposure (PCE) is associated with variation in human brain hippocampal functional connectivity prior to birth. Prenatal drug toxicology and fetal fMRI data were available in a sample of 115 fetuses [43 % female; mean age 32.2 weeks (SD = 4.3)]. Voxelwise hippocampal connectivity analysis in a subset of age and sex-matched fetuses revealed that PCE was associated with alterations in fetal dorsolateral, medial and superior frontal, insula, anterior temporal, and posterior cingulate connectivity. Classification of group differences by age 5 outcomes suggest that compared to the non-PCE group, the PCE group is more likely to have increased connectivity to regions associated with less favorable outcomes and to have decreased connectivity to regions associated with more favorable outcomes. This is preliminary evidence that altered fetal neural connectome may contribute to neurobehavioral vulnerability observed in children exposed to cannabis in utero.

Evaluation of alopecia often includes laboratory testing for ferritin, thyroid stimulating hormone, vitamin D, and zinc as previous studies have found associations between non-scarring alopecia and vitamin deficiencies. These studies are limited by small sample sizes, and subsequent analyses showed conflicting results. This study aims to explore laboratory abnormalities in non-scarring alopecia and examine whether supplementation is associated with increased hair growth. A total of 131 patients completed at least two visits by a hair specialist at NYU’s Faculty Group Practice. They had quantitative hair measurements taken at each visit and laboratory tests performed at the first visit. There were 20 (15.3%) patients with abnormal lab results. The most common vitamin deficiency was ferritin (6.5%). Forty-two (32%) patients received supplementations that specifically addressed their vitamin or hormone deficiency. Multivariate regression analysis showed that supplementation did not significantly impact hair density or diameter (P=0.73; P=0.96, respectively). Baseline hair density and diameter were positively associated with change in hair density and diameter, respectively (standardized coefficient [β] 0.57, P<0.01; β 0.61, P<0.01). The number of prescribed oral medications was negatively associated with change in hair diameter (β -6.60, P=0.04). Limitations of this study include the single-center, retrospective design and the short followup interval. However, our findings suggest that vitamin supplementation may not lead to improved outcomes in non-scarring alopecia, thus limiting the utility of laboratory testing. Additional large-scale prospective studies are needed to improve our management of alopecia. J Drugs Dermatol. 2021;20(7):807-809. doi:10.36849/JDD.5886.

PURPOSE/OBJECTIVE:To examine how the choice of neighborhood food environment definition impacts the association with diet. METHODS:) and relative measures (i.e., percentage of all food stores or restaurants); and various buffer distances, including administrative units (census tract) and empirically-derived buffers ("classic" network, "sausage" network) tailored to community type (higher-density urban, lower-density urban, suburban/small town, rural). Using generalized estimating equations, we estimated the association between each geospatial measure and DIS, controlling for individual- and neighborhood-level sociodemographics. RESULTS:The choice of buffer-based measure did not change the direction or magnitude of associations with DIS. Effect estimates derived from administrative units were smaller than those derived from tailored empirically-derived buffer measures. Substantively, a 10% increase in the percentage of fast food restaurants using a "classic" network buffer was associated with a 6.3 (SE=1.17) point higher DIS (p<0.001). The relationship between the percentage of supermarkets and DIS, however, was null. We observed high correlation coefficients between buffer-based density measures of supermarkets and fast food restaurants (r=0.73-0.83), which made it difficult to estimate independent associations by food outlet type. CONCLUSIONS:Researchers should tailor buffer-based measures to community type in future studies, and carefully consider the theoretical and statistical implications for choosing relative (vs. absolute) measures.

Objective/UNASSIGNED:To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Methods/UNASSIGNED:Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. Results/UNASSIGNED:Although healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. Conclusions/UNASSIGNED:In two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines. KEY MESSAGES/UNASSIGNED:These results suggest that patients on methotrexate may need alternate vaccination strategies such as additional doses of vaccine, dose modification of methotrexate, or even a temporary discontinuation of this drug. Further studies will be required to explore the effect of these approaches on mRNA vaccine immunogenicity.

OBJECTIVE:Posttraumatic stress disorder and prolonged grief disorder (PGD) arise following major life stressors and may share some overlapping symptomatology. This study aimed to examine the presence and response to treatment of posttraumatic stress symptoms (PTSS) in bereaved adults with a primary diagnosis of PGD. METHODS:A randomized controlled trial of 395 adults with PGD (defined as an Inventory of Complicated Grief score ≥ 30 plus confirmation on structured clinical interview) randomly assigned participants to either complicated grief treatment (CGT) with citalopram, CGT plus placebo, citalopram, or placebo between March 2010 and September 2014. This secondary analysis examined the presence of PTSS (per the Davidson Trauma Scale) at baseline and change in PTSS with treatment using longitudinal mixed-effects regression and examined the role of violent compared to nonviolent deaths (loss type). RESULTS:High levels of PTSS were present at baseline, regardless of loss type, and were associated with increased functional impairment (P < .001). CGT with placebo demonstrated efficacy for PTSS compared to placebo in both threshold (OR = 2.71; 95% CI, 1.13-6.52; P = .026) and continuous (P < .001; effect size d = 0.47) analyses, and analyses were suggestive of a greater effect for CGT plus citalopram compared to citalopram alone (threshold analysis: OR = 2.84; 95% CI, 1.20-6.70; P = .017; continuous analysis: P = .053; d = 0.25). In contrast, citalopram did not differ from placebo, and CGT plus citalopram did not differ from CGT plus placebo. CONCLUSIONS:Bereavement-related PTSS are common in bereaved adults with PGD in the context of both violent and nonviolent death and are associated with poorer functioning. CGT shows efficacy for PTSS, while the antidepressant citalopram does not. TRIAL REGISTRATION:: ClinicalTrials.gov identifier: NCT01179568.

BACKGROUND:Poor adherence to antihypertensive medications is a significant contributor to the racial gap in rates of blood pressure (BP) control among Latino adults, as compared to Black and White adults. While multi-level interventions (e.g., those aiming to influence practice, providers, and patients) have been efficacious in improving medication adherence in underserved patients with uncontrolled hypertension, the translation of these interventions into routine practice within "real world" safety-net primary care settings has been inadequate and slow. This study will fill this evidence-to-practice gap by evaluating the effectiveness of practice facilitation (PF) as a practical and tailored strategy for implementing Advancing Medication Adherence for Latinos with Hypertension through a Team-based Care Approach (ALTA), a multi-level approach to improving medication adherence and BP control in 10 safety-net practices in New York that serve Latino patients. METHODS AND DESIGN/METHODS:We will conduct this study in two phases: (1) a pre-implementation phase where we will refine the PF strategy, informed by the Consolidated Framework for Implementation Research, to facilitate the implementation of ALTA into routine care at the practices; and (2) an implementation phase during which we will evaluate, in a stepped-wedge cluster randomized controlled trial, the effect of the PF strategy on ALTA implementation fidelity (primary outcome), as well as on clinical outcomes (secondary outcomes) at 12 months. Implementation fidelity will be assessed using a mixed methods approach based on the five core dimensions outlined by Proctor's Implementation Outcomes Framework. Clinical outcome measures include BP control (defined as BP< 130/80 mmHg) and medication adherence (assessed using the proportion of days covered via pharmacy records). DISCUSSION/CONCLUSIONS:The study protocol applies rigorous research methods to identify how implementation strategies such as PF may work to expedite the translation process for implementing evidence-based approaches into routine care at safety-net practices to improve health outcomes in Latino patients with hypertension, who suffer disproportionately from poor BP control. By examining the barriers and facilitators that affect implementation, this study will contribute knowledge that will increase the generalizability of its findings to other safety-net practices and guide effective scale-up across primary care practices nationally. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03713515, date of registration: October 19, 2018.

OBJECTIVE:To determine whether a smartphone application (app) with an electronic headache diary and a progressive muscle relaxation (PMR) intervention is feasible and acceptable to people presenting to the Emergency Department (ED) with migraine. METHODS:This single arm prospective study assessed feasibility by actual use of the app and acceptability by satisfaction with the app. We report preliminary data on change in migraine disability and headache days. RESULTS:The 51 participants completed PMR sessions on a mean of 13 ± 19 (0,82) days for the 90-day study period, lasting a median of 11 min (IQR 6.5, 17) each. Median number of days of diary use was 34 (IQR 10, 77). Diaries were completed at least twice a week in half of study weeks (337/663). Participants were likely (≥4/5 on a 5-point Likert scale) to recommend both the app (85%) and PMR (91%). MIDAS scores significantly decreased by a mean of 38 points/participant (p < 0.0001). More frequent PMR use was associated with a higher odds of headache free days (p = 0.0148). CONCLUSION/CONCLUSIONS:Smartphone-based PMR introduced to patients who present to the ED for migraine is feasible and acceptable. More frequent users have more headache free days. Future work should focus on intervention engagement.

INTRODUCTION/BACKGROUND:Although hand temperature and electromyograph biofeedback have evidence for migraine prevention, to date, no study has evaluated heartrate variability (HRV) biofeedback for migraine. METHODS:2-arm randomized trial comparing an 8-week app-based HRV biofeedback (HeartMath) to waitlist control. Feasibility/acceptability outcomes included number and duration of sessions, satisfaction, barriers and adverse events. Primary clinical outcome was Migraine-Specific Quality of Life Questionnaire (MSQv2). RESULTS:There were 52 participants (26/arm). On average, participants randomized to the Hearthmath group completed 29 sessions (SD = 29, range: 2-86) with an average length of 6:43 min over 36 days (SD = 27, range: 0, 88) before discontinuing. 9/29 reported technology barriers. 43% said that they were likely to recommend Heartmath to others. Average MSQv2 decreases were not significant between the Heartmath and waitlist control (estimate = 0.3, 95% CI = -3.1 - 3.6). High users of Heartmath reported a reduction in MSQv2 at day 30 (-12.3 points, p = 0.010) while low users did not (p = 0.765). DISCUSSION/CONCLUSIONS:App-based HRV biofeedback was feasible and acceptable on a time-limited basis for people with migraine. Changes in the primary clinical outcome did not differ between biofeedback and control; however, high users of the app reported more benefit than low users.

Teacher interactions around instructional practices have been a topic of study for a long time. Previous studies concerning such interactions have focused on questions pertaining to cross-sectional networks. In fact, very few studies have considered longitudinal networks and still fewer have employed longitudinal network models to study changes in such interactions. We analyse teachers"™ advice-seeking networks, observed annually between 2010 and 2013, in schools within a district where several initiatives were implemented starting in 2011. We assess whether formal structures, teaching assignment and leadership position, and teacher characteristics, gender and experience, are associated with advice-seeking ties, and the extent to which these associations change over time. To analyse the advice-seeking networks, we implement a Bayesian longitudinal latent space network model with covariates and random sender-receiver effects. Within the Bayesian framework, we address practical aspects of a principled network analysis such as missing ties and yearly immigration and emigration of teachers. Goodness of model fit assessment is conducted using posterior predictive checks. Our results demonstrate that while some of the associations between observed covariates and teachers"™ interactions varied in 2011, most were otherwise stable. In 2011, we found decreases in the associations with same grade assignment, leadership position, and teaching in the same school.