Faculty Bibliography

The dynamics of viral load (VL) of the 2019 novel coronavirus (severe acute respiratory syndrome coronavirus 2) and its association with different clinical parameters remain poorly characterized in the US patient population. Herein, we investigate associations between VL and parameters, such as severity of symptoms, disposition (admission versus direct discharge), length of hospitalization, admission to the intensive care unit, length of need for oxygen support, and overall survival in a cohort of 205 patients from a tertiary care center in New York City. VL was determined using quantitative PCR and log10 transformed for normalization. Univariate and multivariate regression models were used to test these associations. We found that diagnostic viral load is significantly lower in hospitalized patients than in patients not hospitalized (log10 VL = 3.3 versus 4.0; P = 0.018) after adjusting for age, sex, race, body mass index, and comorbidities. Higher VL was associated with shorter duration of the symptoms in all patients and hospitalized patients only and shorter hospital stay (coefficient = -2.02, -2.61, and -2.18; P < 0.001, P = 0.002, and P = 0.013, respectively). No significant association was noted between VL, admission to intensive care unit, length of oxygen support, and overall survival. Our findings suggest a higher shedding risk in less symptomatic patients, an important consideration for containment strategies in severe acute respiratory syndrome coronavirus 2. Furthermore, we identify a novel association between viral load and history of cancer. Larger studies are warranted to validate our findings.

OBJECTIVE:D-cycloserine (DCS) promotes consolidation of extinction learning. This study extends earlier work by examining whether DCS can enhance cognitive behavioral therapy (CBT) for delusions. METHODS:Adults reporting moderate or greater delusions were randomly assigned to receive 50 mg of DCS or placebo prior to 10 weekly CBT sessions. The primary outcome was change in severity of delusions measured with the Psychotic Symptom Rating Scale delusion subscale (PSYRATS-D). Secondary outcomes included persistence of response at 3 and 6 month follow-up and the effects of DCS on memory consolidation and cognitive flexibility. Fifty-eight participants were randomized and 44 completed the trial. RESULTS:The DCS and placebo groups did not differ in change from baseline to end of CBT on PSYRATS-D, nor did DCS improve memory consolidation or cognitive flexibility compared to placebo. However, at the 3 month follow-up visit (week 24), 47% of participants who completed treatment with DCS reported a 20% or greater decrease on PSYRATS-D compared to 15% in the placebo group (p = .04). Change in distress across CBT sessions interacted with treatment group to predict change from baseline to week 24 in PSYRATS-D total score (p = .03) such that response at week 24 was greatest in DCS-treated participants who experienced a decrease in distress during CBT sessions. CONCLUSIONS:DCS augmentation of CBT did not improve delusions compared to placebo during treatment; however, DCS was associated with a higher response rate at 3-month follow-up. DCS may produce a delayed therapeutic effect, associated with successful CBT sessions, but this finding requires replication.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.ajpath.2020.07.001. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Sixteen million caregivers currently provide care to more than 5 million persons living with dementia (PLWD) in the United States. Although this population is growing and highly complex, evidence-based management remains poorly integrated within healthcare systems. Therefore, the National Institute on Aging IMPACT Collaboratory was formed to build the nation's ability to conduct embedded pragmatic clinical trials (ePCTs) for PLWD and their caregivers. The pilot core of the IMPACT Collaboratory seeks to provide funds for upward of 40 pilots for ePCTs to accelerate the testing of nonpharmacologic interventions with the goal that these pilots lead to full-scale ePCTs and eventually the embedding of evidence-based care into healthcare systems. The first two challenges for the pilot core in building the pilot study program were (1) to develop a transparent, ethical, and open nationwide process for soliciting, reviewing, and selecting pilot studies; and (2) to begin the process of describing the necessary components of a pilot study for an ePCT. During our initial funding cycle, we received 35 letters of intent, of which 17 were accepted for a full proposal and 14 were submitted. From this process we learned that investigators lack knowledge in ePCTs, many interventions lack readiness for an ePCT pilot study, and many proposed studies lack key pragmatic design elements. We therefore have set three key criteria that future pilot studies must meet at a minimum to be considered viable. We additionally discuss key design decisions investigators should consider in designing a pilot study for an ePCT. J Am Geriatr Soc 68:S14-S20, 2020.

BACKGROUND:There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS:We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS:Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS:We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

Introduction: Oral cancer remains prevalent, despite being largely preventable. The widespread use of technology at chairside, combined with advances in electronic health record (EHR) capabilities, present opportunities to improve oral cancer screening by dentists, especially for disadvantaged patients with severe health needs. Design and methods: Using a mixed-methods approach, we will evaluate the feasibility and acceptability of integrating a telementoring component into the identification of oral lesions using the following 3 methods: 1) administering provider surveys that consist of a checklist of 10 key components of the intervention based on process, and asking the dental provider subjects if each one was covered; 2) conducting semi-structured interviews informed by the Consolidated Framework for Implementation Research and the Implementation Outcomes Framework with dental resident subjects to assess specific barriers to sustaining the intervention and strategies for addressing these barriers to facilitate integration of the intervention into the routine workflow of the dental clinics; and 3) administering brief exit interviews with patient subjects regarding the acceptability of the intervention to assess satisfaction with the use of intra-oral cameras at chairside to screen for and refer patients with oral lesions and identification of these oral lesions via EHR and secure e-mail tele-mentoring with an oral pathology expert. Expected impact of the study for public health: If successful, then later clinical trials will maximize the external validity of the intervention and facilitate the widespread implementation and dissemination of the model for the teaching of dentists and residents, with the ultimate goal of improving patient care.

BACKGROUND:First-line PD-inhibition in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer represents a novel clinical setting, with uncertainty concerning second-line outcomes. Specifying second-line treatment and outcomes will provide guidance in this new sequence. We performed a retrospective chart review to document the outcomes of these patients treated at our institution. PATIENTS AND METHODS/METHODS:Our cohort consisted of 43 patients with advanced urothelial cancer receiving first-line checkpoint inhibition. Baseline factors, programmed death-ligand 1 (PD-L1) status, treatments, and outcomes during and beyond the first line were obtained. Response was scored using Response Evaluation Criteria in Solid Tumors, version 1.1 criteria. Log rank tests were used to compare outcomes in prognostic subgroups, and outcome associations with PD-L1 status were analyzed with Fisher exact tests. RESULTS:A total of 43 patients received first-line atezolizumab or pembrolizumab from June 2014 until June 2018. The median age was 76.8 years, and the population was 74% male, with 60% having visceral metastases. Reasons for cisplatin ineligibility were Eastern Cooperative Oncology Group performance status 2%, 30%; renal insufficiency, 44%, and both, 21%. First-line objective response rate (ORR) was 30%, and complete response was 14%. The median overall survival was 11.7 months. Of 29 patients progressing, 17 received second-line treatment (most commonly, gemcitabine/carboplatin [10 patients]). The second-line response rate was 33%, and the ORR was 11%. The second-line median overall survival was 6.2 months. No association was found between PD-L1 status and outcomes. CONCLUSION/CONCLUSIONS:Outcomes with first-line immunotherapy are consistent with historical outcomes. The ORR after first-line checkpoint inhibition falls short of historical comparators; however, the response rate compares favorably to those of chemotherapies used in previous second-line regimens. The older age and poorer performance status may have contributed to second-line outcomes.

Atypical response patterns following immune checkpoint blockade (ICB) in Hodgkin lymphoma (HL) led to the concept of continuation of treatment beyond progression (TBP); however, the longitudinal benefit of this approach is unclear. We therefore performed a retrospective analysis of 64 patients treated with ICB - 20 who received TBP (TBP cohort) and 44 who stopped ICB at initial progression (non-TBP cohort). The TBP cohort received ICB for a median of 4.7 months after initial progression and delayed subsequent treatment by a median of 6.6 months. Despite receiving more prior lines of therapy, the TBP cohort achieved longer progression-free survival with post-ICB treatment (median 17.5m vs 6.1m, p=0.035) and longer time-to-subsequent treatment failure (TTSTF), defined as time from initial ICB progression to failure of subsequent treatment (median 34.6m vs 9.9m, p=0.003). With the limitations of a retrospective study, these results support the clinical benefit of TBP with ICB for selected patients.