Faculty Bibliography

Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous glucagon-like peptide-1 (GLP-1). We hypothesized that genetic variation in the gene encoding the GLP-1 receptor (GLP1R) could affect the metabolic response to DPP-4 inhibition. To evaluate the relationship between the GLP1R rs6923761 variant (G-to-A nucleic acid substitution) and metabolic responses, we performed mixed meal studies in individuals with type 2 diabetes mellitus and hypertension after 7-day treatment with placebo and the DPP-4 inhibitor sitagliptin. This analysis is a substudy of NCT02130687. The genotype frequency was 13:12:7 GG:GA:AA among individuals of European ancestry. Postprandial glucose excursion was significantly decreased in individuals carrying the rs6923761 variant (GA or AA) as compared with GG individuals during both placebo (P = 0.001) and sitagliptin treatment (P = 0.045), while intact GLP-1 levels were similar among the genotype groups. In contrast, sitagliptin lowered postprandial glucose to a greater degree in GG as compared with GA/AA individuals (P = 0.035). The relationship between GLP1R rs6923761 genotype and therapies that modulate GLP-1 signalling merits study in large populations.

INTRODUCTION: The COVID-19 pandemic overwhelmed New York City hospitals. Shortages of ventilators and sedatives prompted tracheostomy earlier than recommended by professional societies. The objective of this study was to determine the impact of percutaneous dilational tracheostomy (PDT) in COVID-19 patients on critical care capacity.
METHOD(S): This is a single-institution prospective case series of SARS-CoV-2 infected patients undergoing PDT from April 1-June 4, 2020 with follow-up through June 25, 2020 at a public tertiary care center. Clinical data were obtained through medical record review. Mechanically ventilated COVID-19 patients were screened for intervention based on the following criteria: >= 6 days of intubation with further need for mechanical ventilation, a fractional inspired oxygen concentration of <= 60%, positive end expiratory pressure <=12, no significant organ dysfunction except acute kidney injury, and minimal pressor requirements. The main outcomes measured were change in 48-hour periprocedural sedative/analgesia requirements, liberation from the ventilator, rate of transfer from the ICU, decannulation, PDT-related complications, and in-hospital survival.
RESULT(S): Fifty-five patients met PDT criteria and underwent PDT a median of 13 days from intubation. Patient characteristics are found in Table 1. Intravenous midazolam equivalents, fentanyl equivalents and cisatracurium equivalents were significantly reduced post- PDT (Table 2). Thirty-five patients were transferred from the ICU and liberated from the ventilator. Median time from PDT to ventilator liberation and ICU discharge was 10 and 12 days respectively. Decannulation occurred in 45.5% and 52.7% were discharged from acute inpatient care. Median follow-up for the study was 62 days. Four patients had bleeding complications postoperatively and 11 died during the study period. Older age was associated with increased odds of complication (OR 1.12, 95% CI 1.04, 1.23) and death (OR=1.15, 95% CI 1.05, 1.30).
CONCLUSION(S): Mechanically ventilated COVID-19 patients undergoing PDT using standard criteria improves ventilator and medication utilization in areas strained by the SARS-CoV-2 pandemic. Long term outcomes after PDT in this population deserve further study

Dissemination of misinformation through social media is a major societal issue. Bladder cancer is the second most common urological cancer in the world, but there are limited data on the quality of bladder cancer information on social networks. Our objective was to characterize the quality of information and presence of misinformation about bladder cancer on YouTube, the most commonly used social media platform. We reviewed the first 150 YouTube videos about "bladder cancer" using two validated instruments for consumer health information and assessed the videos for the presence of misinformation. The videos had a median of 2288 views (range, 14-511 342), but the overall quality of information was moderate to poor in 67%, based on scores of 1-3 out of 5 on the validated DISCERN instrument. A moderate to high amount of misinformation was present in 21% of videos and reached 1 289 314 viewers. Commercial bias was apparent in 17% of videos, which reached 324 287 viewers. From a networking perspective, comments sections in the videos were sometimes used to request medical advice (20%), provide medical advice to others (9%), or give support (19%). In conclusion, YouTube is a widely used source of information and advice about bladder cancer, but much of the content is of poor quality. PATIENT SUMMARY: A large quantity of content about bladder cancer is available on YouTube. Unfortunately, much of the content is of moderate to poor quality and presents a risk of exposure to misinformation.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Electronic dance music (EDM) party attendees who use ecstasy (3,4-methylenedioxymethamphetamine [MDMA], Molly) are at high risk for ingesting adulterant drugs, but little is known regarding trends in exposure. We sought to determine whether adulteration has shifted in recent years. METHODS:Adults entering EDM events at nightclubs and dance festivals in NYC were surveyed in 2016 and 2019. We tested hair samples from a subsample of those reporting past-year ecstasy use using ultra-high performance liquid chromatography-tandem mass spectrometry. Differences in unreported drug exposure and suspected adulteration were compared between 2016 (n = 90) and 2019 (n = 72). RESULTS:MDMA detection was stable at 72-74%. We detected decreases in unreported use of methamphetamine (from 22.2% to 5.6% [P = .003], an 74.8% decrease), new psychoactive substances (from 31.1% to 2.8% [P < .001], a 91.0% decrease), and synthetic cathinones in particular (from 27.8% to 2.8% (P < .001, an 89.9% decrease). Unreported ketamine exposure increased from 18.9% to 34.7% (P = .022, an 83.6% increase). We also detected decreases in participants' suspicion of their ecstasy being adulterated with methamphetamine (from 20.0% to 5.6% [P = .010], an 72.0% decrease) and "bath salts" (synthetic cathinones, from 8.9% to 1.4% [P = .044], an 84.3% decrease). DISCUSSION AND CONCLUSIONS/CONCLUSIONS:Unknown exposure to adulterants among people who use ecstasy in the EDM scene is shifting. Monitoring of exposure to adulterants is needed to inform harm reduction. SCIENTIFIC SIGNIFICANCE/CONCLUSIONS:This was among the first studies to examine unintentional exposure to drugs over time in this population and unintentional exposure to synthetic cathinones in particular appears to be declining. (Am J Addict 2020;00:00-00).

BACKGROUND:Thirty years after the Mangled Extremity Severity Score (MESS) was developed, advances in vascular, trauma and orthopedic surgery have rendered the sensitivity of this score obsolete. A significant number of patients receive amputation during subsequent admissions, which are often missed in the analysis of amputation at the index admission. We aimed to identify risk factors for and predict amputation on initial admission or within 30 days of discharge (peritraumatic amputation or PTA). STUDY DESIGN/METHODS:The Nationwide Readmission Database for 2016 and 2017 was used in our analysis. Factors associated with PTA were identified. We used XGBoost, Random Forest, and Logistic Regression methods to develop a framework for machine learning (ML) based prediction models for PTA. RESULTS:We identified 1098 adult patients with traumatic lower extremity fracture and arterial injuries, 206 underwent amputation. 176 (85.4%) underwent amputation during the index admission and 30 (14.6%) underwent amputation within a 30-day readmission period. After identifying factors associated with PTA, we constructed machine learning models based on Random Forest, XGBoost, and Logistic Regression to predict PTA. We discovered that Logistic regression had the most robust predictive ability, with an accuracy of 0.88, sensitivity of 0.47, and specificity of 0.98. We then built on the Logistic Regression by the NearMiss algorithm, increasing sensitivity to 0.71, but decreasing accuracy to 0.74 and specificity to 0.75. CONCLUSIONS:ML-based prediction models combined with sampling algorithms (such as the NearMiss algorithm in this study), can help identify patients with traumatic arterial injuries at high risk for amputation and guide targeted intervention in the modern age of vascular surgery.

PURPOSE/OBJECTIVE:To identify, appraise, and assess clinical practice guidelines informing patient counseling on female age-related fertility decline. METHODS:Searched electronic database records from January 1, 2006, to September 10, 2018, and professional society websites. The search terms included iterations of "guideline," "counseling," "preconception," "age-related fertility decline," and "reproductive life planning." English-language professional organization guidelines addressing patient counseling on age-specific reproductive health topics were included. Assessed the methodological quality of included guidelines using the AGREE II instrument. Guidelines were categorized as high quality or low quality based on AGREE II scores. Extracted age-specific reproductive health recommendations of high-quality guidelines. RESULTS:The search identified 2918 records. Nineteen records addressed counseling on age-related fertility decline; only 6 focused only on reproductive aging, with the remaining 13 covering related topics. Eleven met criteria for high quality. All high-quality guidelines had high "rigor of development" scores on AGREE II. Ten high-quality guidelines stated an age at which female fertility declines, ranging from 30 to "late 30s." One recommended a specific age at which patients should be counseled. Five of eleven high-quality guidelines did not discuss the obstetric and perinatal risks of advanced maternal age. CONCLUSIONS:Few high-quality guidelines address counseling on female age-related fertility decline, and existing guidance on reproductive aging counseling is inconsistent and incomplete. Greater rigor of development and incorporation of age-specific counseling recommendations into clinical practice guidelines could lead to improved patient anticipatory guidance and more informed reproductive choices.

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

We used plasma neuronal extracellular vesicles to examine how neuronal insulin signaling proteins relate cross-sectionally to brain structure in nondemented older adults with varying levels of cortical amyloid. Extracellular vesicles enriched for neuronal origin by anti-L1CAM immunoabsorption were isolated from plasma of Atherosclerosis Risk in Communities-Positron Emission Tomography study participants (n = 88; mean age: 77 years [standard deviation: 6]). Neuronal extracellular vesicle levels of phosphorylated insulin signaling cascade proteins were quantified. Brain volume and white matter hyperintensity (WMH) volume were assessed using 3T magnetic resonance imaging. After adjusting for demographic variables and extracellular vesicle marker Alix, higher levels of a neuronal insulin signaling composite measure were associated with lower WMH and greater temporal lobe volume. Secondary analyses found the levels of downstream protein kinases involved in cell survival (p70S6K) and tau phosphorylation/neuroinflammation (GSK-3β) to be most strongly associated with WMH and temporal lobe volume, respectively. Associations between neuronal insulin signaling and lower WMH volume were attenuated in participants with elevated cortical amyloid. These results suggest that enhanced neuronal proximal insulin signaling is associated with preserved brain structure in nondemented older adults.

BACKGROUND:There is no commonly accepted comprehensive framework for describing the practical specifics of external support for practice change. Our goal was to develop such a taxonomy that could be used by both external groups or researchers and health care leaders. METHODS:The leaders of 8 grants from Agency for Research and Quality for the EvidenceNOW study of improving cardiovascular preventive services in over 1500 primary care practices nationwide worked collaboratively over 18 months to develop descriptions of key domains that might comprehensively characterize any external support intervention. Combining literature reviews with our practical experiences in this initiative and past work, we aimed to define these domains and recommend measures for them. RESULTS:The taxonomy includes 1 domain to specify the conceptual model(s) on which an intervention is built and another to specify the types of support strategies used. Another 5 domains provide specifics about the dose/mode of that support, the types of change process and care process changes that are encouraged, and the degree to which the strategies are prescriptive and standardized. A model was created to illustrate how the domains fit together and how they would respond to practice needs and reactions. CONCLUSIONS:This taxonomy and its use in more consistently documenting and characterizing external support interventions should facilitate communication and synergies between 3 areas (quality improvement, practice change research, and implementation science) that have historically tended to work independently. The taxonomy was designed to be as useful for practices or health systems managing change as it is for research.

BACKGROUND:Sodium bicarbonate therapy (SBT) is currently indicated for the management of a variety of acute drug poisonings. However, SBT effects on serum potassium concentrations may lead to delayed QTc prolongation (DQTP), and subsequent risk of adverse cardiovascular events (ACVE), including death. Emergency department (ED)-based studies evaluating associations between SBT and ACVE are limited; thus, we aimed to investigate the association between antidotal SBT, ECG changes, and ACVE. METHODS:This was a secondary data analysis of a consecutive cohort of ED patients with acute drug overdose over 3 years. Demographic and clinical data as well as SBT bolus dosage and infusion duration were collected, and outcomes were compared with an unmatched consecutive cohort of patients with potential indications for SBT but who did not receive SBT. The primary outcome was the occurrence of ACVE, and secondary outcomes were delayed QTc (Bazett) prolongation (DQTP), and death. Propensity score and multivariable adjusted analyses were conducted to evaluate associations between adverse outcomes and SBT administration. Planned subgroup analysis was performed for salicylates, wide QRS (> 100 ms), and acidosis (pH < 7.2). RESULTS:Out of 2365 patients screened, 369 patients had potential indications for SBT, of whom 31 (8.4%) actually received SBT. In adjusted analyses, SBT was found to be a significant predictor of ACVE (aOR 9.35, CI 3.6-24.1), DQTP (aOR 126.7, CI 9.8-1646.2), and death (aOR 11.9, CI 2.4-58.9). Using a propensity score model, SBT administration was associated with ACVE (OR 5.07, CI 1.8-14.0). Associations between SBT and ACVE were maintained in subgroup analyses of specific indications for sodium channel blockade (OR 21.03, CI 7.16-61.77) and metabolic acidosis (OR: 6.42, 95% CI: 1.20, 34.19). CONCLUSION/CONCLUSIONS:In ED patients with acute drug overdose and potential indications for SBT, administration of SBT as part of routine clinical care was an independent, dose-dependent, predictor of ACVE, DQTP, and death. This study was not designed to determine whether the SBT or acute overdose itself was causative of ACVE; however, these data suggest that poisoned patients receiving antidotal SBT require close cardiovascular monitoring.