Faculty Bibliography

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Hippocampal volume loss is prominent in first episode schizophrenia (FES) and has been associated with poor clinical outcomes and with BDNF genotype; antidepressants are believed to reverse hippocampal volume loss via release of BDNF. In a 12-month, placebo-controlled add-on trial of the antidepressant, citalopram, during the maintenance phase of FES, negative symptoms were improved with citalopram. We now report results of structural brain imaging at baseline and 6 months in 63 FES patients (34 in citalopram group) from the trial to assess whether protection against hippocampal volume loss contributed to improved negative symptoms with citalopram. Hippocampal volumetric integrity (HVI) did not change significantly in the citalopram or placebo group and did not differ between treatment groups, whereas citalopram was associated with greater volume loss of the right CA1 subfield. Change in cortical thickness was associated with SANS change in 4 regions (left rostral anterior cingulate, right frontal pole, right cuneus, and right transverse temporal) but none differed between treatment groups. Our findings suggest that minimal hippocampal volume loss occurs after stabilization on antipsychotic treatment and that citalopram's potential benefit for negative symptoms is unlikely to result from protection against hippocampal volume loss or cortical thinning.

BACKGROUND:Sleep difficulties are common among older adults, and clinical management of sleep difficulties commonly includes sleep medication (pharmacological and non-pharmacological). Our research examines sleep medication use and incident dementia over 8 years using nationally representative data from older adults ages 65 years and older in the United States. METHODS:We used data collected from the National Health and Aging Trends Study (NHATS), a nationally-representative longitudinal study of Medicare beneficiaries. Routine sleep medication use (pharmacological and non-pharmacological) was defined as use "most nights" or "every night." Participants were screened for dementia with validated instruments that assessed memory, orientation, and executive function. We conduct prospective analyses to examine the relationship between routine sleep medication use and incident dementia using Cox proportional hazards modeling and estimated survival curves. Analyses controlled for age, sex, marital status, education, and chronic conditions. RESULTS:Among respondents at baseline (n = 6373), most participants (21%) were age 70-74 years of age. Participants were 59% female and the sample comprised non-Hispanic White (71%). At baseline, 15% of our study sample reported using sleep medication routinely, which is representative of 4.6 million older adults in the US. Covariate adjusted proportional hazard models revealed that routinely using sleep medication was associated with incident dementia (HR = 1.30, 95%CI: 1.10 to 1.53, p < 0.01). CONCLUSIONS:Our study observed, in a nationally representative study of older adults in the US across 8 years of data that 15% of older adults report routinely using sleep medication, yet routine use of sleeping medication was associated with incident dementia across the follow-up interval. Future research may examine behavioral approaches to improving sleep among older adults.

OBJECTIVE:To evaluate the acceptability of a community health worker (CHW) intervention designed to improve the oral health of low-income, urban Chinese immigrant adults. BACKGROUND:Given that both dental caries and periodontitis are behaviourally mediated, biofilm-based diseases that are largely preventable with attention to regular oral hygiene practices and preventive dental visits, strategies to arrest or even heal carious lesions and high-quality maintenance care and plaque control without the need to resort to aerosol-generating surgical approaches are evidence-based best practices. Older immigrants have poorer oral health than older US-born natives, motivating the need for delivery of more effective and affordable services to this vulnerable population. MATERIALS AND METHODS/METHODS:CHWs were trained by the NYU College of Dentistry dental hygienist faculty members using dental models and flip charts to instruct patients on proper brushing and flossing techniques. In addition, they discussed the presented oral health promotion information one-on-one with patients, addressed any expressed concerns and encouraged prevention of oral conditions through regular dental visits and brushing with fluoride toothpaste. RESULTS:More than 98% of the 74 older Chinese adult participants strongly agreed/agreed that the CHWs helped them to improve how they take care of their health, the CHWs answered their questions and concerns, the information and topics were informative, and the in-person demonstrations were helpful in improving oral health. CONCLUSION/CONCLUSIONS:The health of all communities depends on access to comprehensive care, including oral health care, in the wake of COVID-19. CHW interventions are acceptable to and may reach marginalised and immigrant communities.

OBJECTIVE:To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes. METHODS:We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders. RESULTS:Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001). CONCLUSIONS:Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

Importance:Hip and knee arthroplasty are the most common inpatient surgical procedures for Medicare beneficiaries in the US, with substantial variation in cost and quality. Whether remote monitoring incorporating insights from behavioral science might help improve outcomes and increase value of care remains unknown. Objective:To evaluate the effect of activity monitoring and bidirectional text messaging on the rate of discharge to home and clinical outcomes in patients receiving hip or knee arthroplasty. Design, Setting, and Participants:Randomized clinical trial conducted between February 7, 2018, and April 15, 2019. The setting was 2 urban hospitals at an academic health system. Participants were patients aged 18 to 85 years scheduled to undergo hip or knee arthroplasty with a Risk Assessment and Prediction Tool score of 6 to 8. Interventions:Eligible patients were randomized evenly to receive usual care (n = 153) or remote monitoring (n = 147). Those in the intervention arm who agreed received a wearable activity monitor to track step count, messaging about postoperative goals and milestones, pain score tracking, and connection to clinicians as needed. Patients assigned to receive monitoring were further randomized evenly to remote monitoring alone or remote monitoring with gamification and social support. Remote monitoring was offered before surgery, began at hospital discharge, and continued for 45 days postdischarge. Main Outcomes and Measures:The primary outcome was discharge status (home vs skilled nursing facility or inpatient rehabilitation). Prespecified secondary outcomes included change in average daily step count and rehospitalizations. Results:A total of 242 patients were analyzed (124 usual care, 118 intervention); median age was 66 years (interquartile range, 58-73 years); 78.1% were women, 45.5% were White, 43.4% were Black; and 81.4% in the intervention arm agreed to receive monitoring. There was no significant difference in the rate of discharge to home between the usual care arm (57.3%; 95% CI, 48.5%-65.9%) and the intervention arm (56.8%; 95% CI, 47.9%-65.7%) and no significant increase in step count in those receiving remote monitoring plus gamification and social support compared with remote monitoring alone. There was a statistically significant reduction in rehospitalization rate in the intervention arm (3.4%; 95% CI, 0.1%-6.7%) compared with the usual care arm (12.2%; 95% CI, 6.4%-18.0%) (P = .01). Conclusions and Relevance:In this study, the remote monitoring program did not increase rate of discharge to home after hip or knee arthroplasty, and gamification and social support did not increase activity levels. There was a significant reduction in rehospitalizations among those receiving the intervention, which may have resulted from goal setting and connection to the care team. Trial Registration:ClinicalTrials.gov Identifier: NCT03435549.

PURPOSE/OBJECTIVE:To present the results of a survey of the Zoster Eye Disease Study (ZEDS) investigators regarding barriers to the enrollment of study participants and approaches to overcome them. METHODS:ZEDS is a multicenter randomized clinical trial supported by the National Eye Institute to determine whether prolonged suppressive valacyclovir reduces the complications of herpes zoster ophthalmicus (HZO), relative to placebo. Enrollment of study participants is currently far below expectations. An institutional review board-approved anonymous internet survey was conducted of ZEDS investigators to study their experiences and opinions regarding barriers to enrollment and various approaches to overcome them. RESULTS:The overall survey response rate was 54% (79/145). Only 29% (23/79) agreed that it is easy to enroll study participants. Regarding patient barriers, 69% (55/79) agreed that HZO patients want to be treated with antiviral medication and 69% (54/78) agreed that HZO patients on antivirals do not want to be randomized. Regarding personal barriers facing investigators, 91% (72/79) agreed that antivirals are effective and 100% that the research questions ZEDS is designed to answer are very important. Fewer than 30% of respondents believed that steps taken to increase enrollment have been very helpful. Over half (54%, 42/78) believed that advertising on social media would be moderately or very effective. CONCLUSIONS:Belief among ZEDS investigators that antivirals are effective, and the preference of patients to be treated with antivirals rather than be randomized in ZEDS, are major barriers to enrollment. New approaches to overcoming barriers are necessary to develop an evidence-based standard of care for treatment of HZO.