Faculty Bibliography

BACKGROUND/UNASSIGNED:Effective management of alcohol withdrawal syndrome during hospitalization is paramount to patient safety and quality care. NYC Health + Hospitals initiated a quality improvement project to pilot an electronic health record (EHR) integrated, nurse-driven CIWA-Ar symptom-triggered protocol, including recommendations for medications for alcohol use disorder (MAUD), in medical and surgical units at 3 public hospitals. OBJECTIVE/UNASSIGNED:To describe implementation processes and to report related implementation outcomes (appropriateness, feasibility, and adoption) of the updated CIWA-Ar protocol in a safety net hospital setting. METHODS/UNASSIGNED:NYC Health + Hospitals implemented a standardized CIWA-Ar symptom-triggered, nurse-driven EHR protocol on March 15, 2022. The protocol included order sets, practice advisories, task lists, and reminders for assessments and orders. We measured nursing perspectives on feasibility and appropriateness at 6 months via a survey. We measured provider adoption as the proportion of admissions with a CIWA-Ar protocol ordered among admissions that triggered a recommendation, and MAUD use as the proportion of admissions with a MAUD order during hospitalization among all patients with a protocol ordered. RESULTS/UNASSIGNED:= .249). CONCLUSIONS/UNASSIGNED:The CIWA-Ar protocol was appropriate, feasible, and adopted at NYC public hospitals. Quality improvements to ensure protocol fidelity with benzodiazepine dosing and MAUD prescribing are needed.

OBJECTIVE:In Nigeria, adolescents and young adults (AYA) who engage in multiple sexual partnerships, transactional sex, and needle-sharing are eligible for preexposure prophylaxis (PrEP) and are prioritized for HIV testing. AYA with PrEP-eligible behaviors should be using facility-based HIV testing services. We examined associations between these behaviors and facility-based HIV testing among AYA aged 14-24 years. DESIGN/METHODS:A longitudinal analysis of a stepped-wedge trial. METHODS:Using Innovative Tools to Expand Youth-friendly HIV Self-Testing (I-TEST) data, we fit generalized linear models using generalized estimating equations. We used a two-stage weighted approach to generalize I-TEST estimates to all AYA in Nigeria. RESULTS:Of 1429 trial participants, the median age was 20 years (IQR: 18-22), 50.3% were female, and 69.4% reported secondary education as highest level of education completed. Recent facility-based HIV testing uptake was higher among AYA with one [unadjusted risk difference: 11.7%, 95% confidence interval (95% CI): 8.1-15.2], two [11% (5.3, 16.8)], and three or more sexual partners in the past 3 months [17.3% (10.5, 24)], compared to AYA with no recent sexual partners. AYA who engaged in transactional sex had higher facility-based testing uptake [14.7% (9.8, 19.5)] than AYA who never engaged in transactional sex. AYA who shared needles had lower facility-based testing uptake [-3.3% (-6.7, 0.2)] than AYA with no needle-sharing history. The trial and generalized estimates were in the same direction. CONCLUSION/CONCLUSIONS:While facility-based testing may reach AYA who engaged in multiple sexual partnerships or transactional sex, AYA who shared needles may require more tailored HIV testing approaches.

BACKGROUND:Intensive care unit (ICU) staffing models increasingly use advanced practice providers (APPs), with unclear implications for clinical practice patterns. Sedation strategy is a modifiable determinant of clinical outcomes that might differ by staffing model. METHODS:This retrospective cohort study evaluated adults admitted to two medical ICUs in a quaternary teaching hospital, whose staffing differed only by APPs or residents. Patients requiring invasive ventilation for at least 48 h were included. The primary outcome was association of staffing model with sedative exposure during the first week of mechanical ventilation. Time to extubation and vital status at discharge were also assessed. RESULTS:Of 337 included patients, 96 % received continuous sedation on the day of intubation. Admission to the APP ICU was associated with significantly lower benzodiazepine exposure (adjusted OR 0.63; 95 % CI 0.40-0.99; p = 0.04) and higher propofol exposure (adjusted OR 1.73; 95 % CI 1.07-2.79; p = 0.03) on day of intubation. Cumulative benzodiazepine and opioid exposures over the first week after intubation were significantly less, and cumulative propofol exposure significantly more in the APP ICU despite similar sedation depth achieved between ICUs. Receipt of propofol on the first day was associated with shorter time to extubation (adjusted HR 1.45, 95 % CI 1.07-1.98; p = 0.02) and lower in-hospital mortality (adjusted OR 0.55, 95 % CI 0.33-0.93; p = 0.02). CONCLUSION/CONCLUSIONS:Patients admitted to an APP-staffed ICU were more likely to have sedation management reflective of best practice, and this practice was associated with shorter time to extubation and lower mortality.

Despite major advances in medical therapies and prevention strategies, the risk of cardiovascular complications in patients with both type I and type II diabetes remains substantially elevated. In 2019, the American Heart Association sought applications for a Strategically Focused Research Network on Cardiometabolic Health and Type 2 Diabetes. In 2020, 4 centers were named, including Brigham and Women's Hospital, Johns Hopkins University, New York University, and the University of Iowa. These centers performed basic, translational, and clinical studies to provide insights to explain the over 2-fold risk of cardiovascular complications in diabetes. Clinical studies and studies in cells and animals aimed to uncover new mechanisms responsible for disease development. Studies using human populations sought to uncover new biomarkers to prognosticate risk. In this review, we discuss several key issues and current and developing methods to understand why diabetes drives atherosclerotic cardiovascular disease and heart failure. Both human data and experimental models are considered. We integrate a review of these topics with work from the Strategically Focused Research Network and conclude with suggestions for identifying novel risk factors and future experimental research.

ObjectivePatients with systemic lupus erythematosus (SLE) often have concomitant fibromyalgia (FM) or similar symptoms including chronic pain, fatigue, or depression. This study explored whether Patient-Reported Outcomes Measurement Information System (PROMIS) measures provide richer information than 2016 American College of Rheumatology (ACR) FM criteria survey.MethodsPatients with SLE in our convenience cohort were categorized into groups: (1) concurrent FM chronic pain, (2) concurrent non-FM chronic pain, and (3) no chronic pain using 2016 ACR FM Survey. Based on PROs in the FM Survey, we captured comparable PROMIS measures (e.g., depression, fatigue). Associations by pain group were tested using Kruskal-Wallis rank sum test, Shapiro-Wilk normality test, chi-squared test, or Fisher's exact test. Violin plots explored differences across groups.ResultsThe cohort (n = 181) included 31 patients with FM pain, 23 with non-FM chronic pain, and 127 with no chronic pain. Median PROMIS symptom scores (fatigue, sleep disturbance, pain intensity and interference, depression) were highest and cognitive function lowest in the FM group, despite 13% being in remission. There were significant differences on 4 PROMIS measures (cognitive function, fatigue, pain intensity, pain interference) between FM pain and non-FM pain groups (p < .02), the former being worse. There were no significant differences in SLE Disease Activity Index (SLEDAI) score.ConclusionSLE patients with non-FM chronic pain have similar symptoms to FM compared with SLE patients without chronic pain; however, symptoms are not as severe as those meeting FM criteria. PROMIS measures may be used to classify severity more precisely for disease categorization and management.

This study aims to define the efficacy of pregabalin in treating neuropathic pain in diabetic peripheral neuropathy (DPN), both as a monotherapy and in combination with other drugs that are commonly used to treat DPN in a clinical setting. Thus, physicians are able to make more informed decisions when choosing drugs to relieve DPN. Studies found on PubMed and Embase were evaluated for the role of pregabalin in DPN pain management, as well as its efficacy in comparison to other treatments. Search terms included "pregabalin," "diabetic," "peripheral," "neuropathy," and "pain." Experimental groups varied from amitriptyline, duloxetine, carbamazepine, venlafaxine, and Xiaoketongbi Formula (XF). Pregabalin was shown to have no difference when compared to amitriptyline; however, longer treatment regimens should be performed. Duloxetine is more effective at lower dosages, but pregabalin is more effective at higher dosages. Additionally, pregabalin was found to be more effective than carbamazepine and venlafaxine. Surprisingly, XF was found to be as effective as pregabalin, demonstrating a potential role of herbal treatments. Combination therapies did not have a significant advantage over pregabalin monotherapy in treating DPN. In terms of adverse effects, pregabalin was more tolerated among patients, though side effects were generally mild. Pregabalin remains an effective option for DPN pain management and is considered noninferior to current monotherapies and combination therapies.

This article provides a focused update to the clinical practice guideline on the treatment and management of patients with coronavirus disease 2019 (COVID-19), developed by the Infectious Diseases Society of America. The guideline panel presents a recommendation on the use of abatacept in hospitalized adults with severe or critical COVID-19. The recommendation is based on evidence derived from a systematic literature review and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.

INTRODUCTION/BACKGROUND:Standardized incidence rates of multiple myeloma (MM) are higher among males than females, suggesting that male sex is an important risk factor for MM, which may affect disease etiology, pathogenesis, and clinical presentation. METHODS:The association of sex with the prevalence of clinical features and chromosomal abnormalities was evaluated among 850 patients with newly diagnosed MM enrolled in the Integrative Molecular And Genetic Epidemiology (IMAGE). Risk estimates were calculated using prevalence odds ratios (OR) and corresponding 95% CIs from logistic regression adjusted for confounders. RESULTS:Male patients with newly diagnosed MM by comparison with females, were more likely to have International Staging System stage III disease (odds ratio [OR] = 2.05; 95% CI, 1.22-3.46; p = .007), high serum monoclonal protein (≥3 g/dL; OR = 1.72; 95% CI, 1.15-2.56; p = .008), κ light chain disease (OR = 1.60; 95% CI, 1.11-2.30; p = .01), and more end-organ damage (OR = 1.24; 95% CI, 1.02-1.50; p = .03) including impaired renal function (OR = 1.71; 95% CI, 1.12-2.61; p = .01) and lytic lesions (OR = 1.97; 95% CI, 1.01-3.85; p = .05) and were less likely to have osteopenia (OR = 0.59; 95% CI, 0.36-0.98; p = .04) and light chain only disease (OR = 0.63; 95% CI, 0.41-0.95; p = .03) after adjusting for race, age, body mass index, education, income, smoking, and alcohol use. Significant interactions of age on the association of male sex with the prevalence of involved to uninvolved free light chain ratio ≥100 (p = .01) and any copy number abnormality (p = .04) were also observed. CONCLUSION/CONCLUSIONS:These novel findings suggest that male patients with newly diagnosed MM have a greater tumor burden.

Many chemotherapies are effective against cancers that display high levels of genome instability by disrupting or overwhelming the DNA damage response (DDR) to induce cell death. PARP inhibitors (PARPi) exploit this vulnerability by stalling DNA repair, particularly in homologous recombination-deficient cancer cells. Although PARPi are now used to treat BRCA1/2-mutated cancers such as ovarian and breast cancers, they are still limited to a narrow range of clinical indications and are susceptible to acquired resistance. Here, we introduce "DNA damage chemical inducers of proximity" (DD-CIPs), bivalent molecules that rewire the mechanism of action of conventional PARPi. The DD-CIPs function through chemically induced proximity between PARP1/2 and the chromatin remodeling protein, BRD4. From a candidate library of DD-CIPs, we identified DD-CIP1, which induces the DDR and apoptosis in cancer cells at two-digit nanomolar concentrations. Further optimization yielded DD-CIP2, which induces tumor cell death at nanomolar concentrations across diverse blood and solid cancer cells, including cancer types that are insensitive to PARPi. Using small-cell lung cancer (SCLC) as a model, we found that DD-CIP2 triggers DDR, cell cycle arrest, and apoptosis in vitro, leading to antitumor efficacy without substantial toxicity in preclinical SCLC xenograft models at well-tolerated doses. Our findings demonstrate that DD-CIPs may provide an opportunity to address the limitations of traditional PARPi and establish chemical-induced proximity as a strategy for modulating the DDR in cancer.

Disruption of ribosome biogenesis triggers nucleolar stress, a conserved cellular response that activates p53. We previously demonstrated that depletion of Nucleolar Complex Protein 1 (Noc1) in Drosophila wing imaginal discs impairs rRNA maturation and ribosome assembly, resulting in elevated p53 levels and apoptosis, hallmarks of nucleolar stress. The Drosophila p53 gene produces four mRNA isoforms, yet their individual contributions to nucleolar stress responses remain poorly understood. Using newly designed isoform-specific qPCR primers, we found that although all p53 isoforms exhibit moderate transcriptional changes following Noc1 reduction, the truncated isoform p53E is robustly and preferentially upregulated. Notably, p53E lacks the N-terminal transactivation domain and has been reported to negatively regulate p53-induced apoptosis in specific tissues. Furthermore, our analyses indicate that γ-H2AV accumulation arises from caspase-dependent apoptosis rather than primary genomic lesions, suggesting the activation of a p53-dependent stress pathway distinct from canonical genotoxic pathways. Together, these findings suggest that p53E may be part of a novel mechanism activated during nucleolar stress, providing insight into how cells adapt to defects in ribosome biogenesis.