Faculty Bibliography

BACKGROUND:Numerous clinical trials have been initiated to find effective treatments for COVID-19. These trials have often been initiated in regions where the pandemic has already peaked. Consequently, achieving full enrollment in a single trial might require additional COVID-19 surges in the same location over several years. This has inspired us to pool individual patient data (IPD) from ongoing, paused, prematurely-terminated, or completed randomized controlled trials (RCTs) in real-time, to find an effective treatment as quickly as possible in light of the pandemic crisis. However, pooling across trials introduces enormous uncertainties in study design (e.g., the number of RCTs and sample sizes might be unknown in advance). We sought to develop a versatile treatment efficacy assessment model that accounts for these uncertainties while allowing for continuous monitoring throughout the study using Bayesian monitoring techniques. METHODS:We provide a detailed look at the challenges and solutions for model development, describing the process that used extensive simulations to enable us to finalize the analysis plan. This includes establishing prior distribution assumptions, assessing and improving model convergence under different study composition scenarios, and assessing whether we can extend the model to accommodate multi-site RCTs and evaluate heterogeneous treatment effects. In addition, we recognized that we would need to assess our model for goodness-of-fit, so we explored an approach that used posterior predictive checking. Lastly, given the urgency of the research in the context of evolving pandemic, we were committed to frequent monitoring of the data to assess efficacy, and we set Bayesian monitoring rules calibrated for type 1 error rate and power. RESULTS:The primary outcome is an 11-point ordinal scale. We present the operating characteristics of the proposed cumulative proportional odds model for estimating treatment effectiveness. The model can estimate the treatment's effect under enormous uncertainties in study design. We investigate to what degree the proportional odds assumption has to be violated to render the model inaccurate. We demonstrate the flexibility of a Bayesian monitoring approach by performing frequent interim analyses without increasing the probability of erroneous conclusions. CONCLUSION:This paper describes a translatable framework using simulation to support the design of prospective IPD meta-analyses.

BACKGROUND AND AIMS/OBJECTIVE:Opioid overdose is a leading cause of death during the immediate time after release from jail or prison. Most jails in the United States do not provide methadone and buprenorphine treatment for opioid use disorder (MOUD), and research in estimating its impact in jail settings is limited. We aimed to test the hypothesis that in-jail MOUD is associated with lower overdose mortality risk post-release. DESIGN, SETTING AND PARTICIPANTS/METHODS:Retrospective, observational cohort study of 15 797 adults with opioid use disorder who were released from New York City jails to the community in 2011-17. They experienced 31 382 incarcerations and were followed up to 1 year. MEASUREMENTS/METHODS:The primary outcomes were death caused by accidental drug poisoning and all-cause death. The exposure was receipt of MOUD (17 119 events) versus out-of-treatment (14 263 events) during the last 3 days before community reentry. Covariates included demographic, clinical, behavioral, housing, healthcare utilization, and legal characteristics variables. We performed multivariable, mixed-effect Cox regression analysis to test association between in-jail MOUD and deaths. FINDINGS/RESULTS:A majority were male (82%) and their average age was 42 years. Receiving MOUD was associated with misdemeanor charges, being female, injection drug use, and homelessness. During 1 year post-release, 111 overdose deaths occurred, and crude death rates were 0.49 and 0.83 per 100 person-years for in-jail MOUD and out-of-treatment groups, respectively. Accounting for confounding and random effects, in-jail MOUD was associated with lower overdose mortality risk (adjusted hazard ratio = 0.20, 95% CI = 0.08-0.46), and all-cause mortality risk (adjusted hazard ratio = 0.22, 95% CI = 0.11-0.42) for the first month post-release. CONCLUSIONS:Methadone and buprenorphine treatment for opioid use disorder during incarceration was associated with an 80% reduction in overdose mortality risk for the first month post-release.

Background: Integrative medicine (IM) is a growing subspecialty among the American healthcare system, but little is known about geographical and sociodemographic variability in access to services. Objective: To better understand access to IM healthcare services, we aim to: 1.) document the number of IM providers within the hospital service area (HSA) of various hospitals across the United States (US) and, 2.) explore the relationship between age, income, and race as predictors of the number of IM providers. Methods: We conducted an environmental scan to document the number of IM providers including naturopathic, acupuncture, chiropractic, and massage therapy providers within the HSA of 16 US hospitals using state and national search databases. We examined predictors of the number of providers per HSA using population and demographic data from the U.S. Census Bureau. Search database quality was evaluated using the Center for Disease Control and Prevention Clear Communication Index. Results: The number of IM providers varied from 11.6 "“ 67.4 providers/100,000 persons. Massage therapists were the most prevalent (n = 13.8/100,000), followed by chiropractors (n = 5.2/100,000), acupuncturists (n = 4.6/100,000), and naturopathic physicians (n =.5/100,000). Higher average household income and population >65 years old were associated with more IM providers within an HSA (Rate Ratio (RR) 4.22, 95% CI 1.49-12.01; and 1.14, 1.05 - 1.24, respectively). In addition, the quality of publicly available search databases varied widely among US states (4.84 - 8.00/10), but less so among IM provider types (6.21 - 7.57/10). Conclusions: The high variability in number of IM providers and search database quality among various HSAs across the US warrants further investigation into factors influencing access to services. Our findings regarding income and older adult population raise concern for inequitable access to care, but are also promising when considering the increasing demand for healthcare services among the older adult population.

Background: Significant racial and ethnic disparities exist in the community in underprescribing analgesics for pain and overprescribing antipsychotics for behavioral symptoms in persons with dementia. In hospice these drugs are commonly used to provide comfort, but little is known about prescription patterns in minoritized populations. We aimed to identify prescribing patterns in minoritized racial and ethnic groups among persons with living advanced dementia in home hospice.
Method(s): A cross-sectional study of 6,874 participants with advanced dementia from eight hospices across the United States. Demographics, antipsychotic (typical, atypical) and analgesic (opioid, non-opioid) prescriptions at admission, days of prescription use in hospice and length of stay were collected from electronic records. Descriptive statistics were calculated and hurdle regression models estimated to examine the association between race/ethnicity and prescription rates for each drug (days of drug use per 100 person-days).
Result(s): Participants were 10.7% Black, 34.8% Hispanic, 51.1% white, and 3.3% from other racial and ethnic groups. On admission, Hispanics and Blacks had similar rates of antipsychotic prescription that were lower than whites (11.9% & 12.3% vs 16.8%) and Hispanics had substantially lower non-opioid analgesic prescription vs Blacks and whites (23.3% vs 36.0% & 37.3%); During the hospice stay, Hispanics were prescribed antipsychotics (atypical RR =1.03, 95 % CI: 1.02-1.04; typical RR:1.04, 95% CI: 1.01-1.07) and analgesics (opioid RR =1.03, 95% CI: 1.02-1.04; non-opioid RR = 1.03, 95% CI = 1.02-1.03) for more days than whites. Blacks were prescribed analgesics (opioid RR =1.09, 95% CI 1.08-1.11; non-opioid RR = 1.01, 95% CI: 1-1.02) for more days than whites.
Conclusion(s): Disparities in analgesic and antipsychotic use on admission amongst Blacks and Hispanics were found, yet hospice narrowed this gap significantly. While less likely to be prescribed opioids, Blacks and Hispanics had more person days on analgesics overall. However, there was divergence in antipsychotic use over time between groups that requires further investigation given the controversial role of antipsychotics in management of dementia symptoms

INTRODUCTION/BACKGROUND:Effective communication is essential to good health care, and hearing loss disrupts patient-provider communication. For the more than 2 million veterans with severe hearing loss, communication is particularly challenging in noisy health care environments such as emergency departments. The purpose of this qualitative study was to describe patient and provider perspectives of feasibility and potential benefit of providing a hearing assistance device, a personal amplifier, during visits to an emergency department in an urban setting affiliated with the Department of Veterans Affairs. METHODS:This qualitative descriptive study was conducted in parallel with a randomized controlled study. We completed a semistructured interview with 11 veterans and 10 health care providers to elicit their previous experiences with patient-provider communication in the ED setting and their perspectives on hearing screening and using the personal amplifier in the emergency department. Interview data were analyzed using content analysis and Atlas.ti V8.4 software (Scientific Software Development GmbH, Berlin, Germany). RESULTS:The veteran sample (n = 11) had a mean age of 80.3 years (SD = 10.2). The provider sample included 7 nurses and 3 physicians. In the ED setting, hearing loss disrupts patient-provider communication. Screening for hearing loss in the emergency department was feasible except in urgent/emergent cases. The use of the personal amplifier made communication more effective and less effortful for both veterans and providers. DISCUSSION/CONCLUSIONS:Providing the personal amplifier improved the ED experience for veterans and offers a promising intervention that could improve health care quality and safety for ED patient populations.

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:The emergency department (ED) is a critical juncture in the care of persons living with dementia (PLwD), as they have a high rate of hospital admission, ED revisits, and subsequent inpatient stays. We examine ED disposition of PLwD compared with older adults with non-dementia chronic disease as well as healthcare utilization and survival. METHODS:Medicare claims data were used to identify community-dwelling older adults 66+ years old from 34 hospitals with either Alzheimer's disease/Alzheimer's disease related dementias (AD/ADRD) or a non-AD/ADRD chronic condition between January 1, 2014, and December 31, 2018. We compared ED disposition at the index visit, as well as healthcare utilization and mortality in the 12 months following an index ED visit, and adjusted for age, gender, and risk of mortality. RESULTS:There were 29,626 patients in the AD/ADRD sample, and 317,046 in the comparison sample. The AD/ADRD sample was older (82.4 years old [SD: 8.2] vs. 76.0 years old [SD: 7.7]) and had more female patients (59.9% vs. 54.7%). The AD/ADRD sample was more likely to experience ED disposition to acute care (OR 1.039, p < 0.001, 95% CI 1.029-1.050), to have an ED revisit (OR 1.077, p < 0.001, 95% CI 1.066-1.087), and an inpatient stay in the subsequent 12 months (OR 1.085, p < 0.001, 95% CI 1.075-1.095). ED disposition to hospice was low in both samples (0.2%). AD/ADRD patients had a higher risk of mortality (OR 1.099, p < 0.001, 95% CI 1.091-1.107) and high short-term mortality (31.9% within 12 months) than those without AD/ADRD (15.3% within 12 months). CONCLUSIONS:PLwD who visit the ED have high short-term mortality. Despite this, disposition to acute care, ED revisits, and inpatient stays, rather than hospice, remain the predominant mode of care delivery. Transition directly from the ED to hospice for PLwD is rare.

To determine whether an opt-out approach is effective for referral to treatment for tobacco use, we designed a clinical reminder for nurses in a primary care setting that provides a referral for patients who smoke cigarettes. We will use a two-arm, cluster-randomized design to assign nurses at the VA New York Harbor Healthcare System to test which mode of referral (opt-in vs opt-out) is more effective. All patients will be referred to evidence-based treatment for tobacco cessation including counseling from the New York State Quitline, and VetsQuit, a text messaging-based system for tobacco cessation counseling. We will measure patient engagement with the referral both in the short and long term to determine if referral modality had an impact on tobacco cessation treatment. We will also measure nurse engagement with the referral before, during, and after the implementation of the reminder to determine whether an opt-out approach is cost effective at the health system level. At the conclusion of this project, we expect to have developed and tested an opt-out system for increasing tobacco cessation treatment for Veterans in VA primary care and to have a thorough understanding of factors associated with implementation. Trial Registration:Clinicaltrials.govIdentifierNCT03477435.

Importance:Identifying which patients with COVID-19 are likely to benefit from COVID-19 convalescent plasma (CCP) treatment may have a large public health impact. Objective:To develop an index for predicting the expected relative treatment benefit from CCP compared with treatment without CCP for patients hospitalized for COVID-19 using patients' baseline characteristics. Design, Setting, and Participants:This prognostic study used data from the COMPILE study, ie, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) evaluating CCP vs control in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. A combination of baseline characteristics, termed the treatment benefit index (TBI), was developed based on 2287 patients in COMPILE using a proportional odds model, with baseline characteristics selected via cross-validation. The TBI was externally validated on 4 external data sets: the Expanded Access Program (1896 participants), a study conducted under Emergency Use Authorization (210 participants), and 2 RCTs (with 80 and 309 participants). Exposure:Receipt of CCP. Main Outcomes and Measures:World Health Organization (WHO) 11-point ordinal COVID-19 clinical status scale and 2 derivatives of it (ie, WHO score of 7-10, indicating mechanical ventilation to death, and WHO score of 10, indicating death) at day 14 and day 28 after randomization. Day 14 WHO 11-point ordinal scale was used as the primary outcome to develop the TBI. Results:A total of 2287 patients were included in the derivation cohort, with a mean (SD) age of 60.3 (15.2) years and 815 (35.6%) women. The TBI provided a continuous gradation of benefit, and, for clinical utility, it was operationalized into groups of expected large clinical benefit (B1; 629 participants in the derivation cohort [27.5%]), moderate benefit (B2; 953 [41.7%]), and potential harm or no benefit (B3; 705 [30.8%]). Patients with preexisting conditions (diabetes, cardiovascular and pulmonary diseases), with blood type A or AB, and at an early COVID-19 stage (low baseline WHO scores) were expected to benefit most, while those without preexisting conditions and at more advanced stages of COVID-19 could potentially be harmed. In the derivation cohort, odds ratios for worse outcome, where smaller odds ratios indicate larger benefit from CCP, were 0.69 (95% credible interval [CrI], 0.48-1.06) for B1, 0.82 (95% CrI, 0.61-1.11) for B2, and 1.58 (95% CrI, 1.14-2.17) for B3. Testing on 4 external datasets supported the validation of the derived TBIs. Conclusions and Relevance:The findings of this study suggest that the CCP TBI is a simple tool that can quantify the relative benefit from CCP treatment for an individual patient hospitalized with COVID-19 that can be used to guide treatment recommendations. The TBI precision medicine approach could be especially helpful in a pandemic.