Faculty Bibliography

OBJECTIVE:To determine the prevalence and risk factors for inappropriate discharge on proton pump inhibitor (PPI) therapy started in the intensive care unit (ICU) for stress ulcer prophylaxis. PATIENTS AND METHODS/METHODS:This was a retrospective cohort study of adults initiated on treatment with a PPI in any of 9 affiliated ICUs from January 1, 2014, to December 31, 2018. Patients were excluded if they had an appropriate long-term PPI indication. Logistic regression modeling was used to identify characteristics associated with discharge on treatment with an inappropriate PPI. RESULTS:Of 24,751 patients admitted to an ICU, 4127 were initiated on treatment with a new PPI, with 2467 (60%) lacking a long-term PPI indication. Of these 2467, a total of 1122 (45%) were continued on PPI therapy after transfer to the floor and 668 (27%) were discharged on PPI therapy. On multivariable analysis, risk factors for inappropriate discharge on PPI therapy included having an upper endoscopy (adjusted odds ratio [aOR], 1.70; 95% CI, 1.08-2.66), admission to the surgical compared with medical ICU (aOR, 2.03; 95% CI, 1.32-3.10), and discharge to a nursing home or rehabilitation facility (aOR, 1.43; 95% CI, 1.04-1.96; and aOR, 2.29; 95% CI, 1.62-3.24, respectively). CONCLUSION/CONCLUSIONS:Among patients started on treatment with a PPI in the ICU without an indication for outpatient PPI use, 27% (668 of 2467) were nonetheless discharged on PPI therapy. Medically complex and surgical ICU patients are at increased risk for receiving PPIs without appropriate documented indications, and careful review of medication lists at discharge should occur in these high-risk groups.

Background: Forensic odontology, a branch of dentistry includes identification of individuals in various crime scenes, natural calamities, and mass disasters. The identification is possible because every individual body is unique and so is our tongue due to its morphological variations. The primary objective of the study was to assess the morphological features of the tongue and its use in sex determination.
Method(s): The study included a sample size of 100 individuals (50 males and 50 females) in the age range of 20-50 years old. Photographs were taken of front and side view of the tongue; visual inspection was done and lastly impressions of the tongue were made with help of alginate and then poured with the help of dental stone. IBM SPSS statistics 20.0 (IBM Corporation, Armonk, NY, USA) was used for the analyses of the data. Microsoft word and Excel were used to generate graphs, tables etc. Females presented with triangular shape, presence of shallow fissures more commonly and a sharp lingual apex of tongue. Males presented with rectangular shape, presence of deep fissure/absence of fissures more commonly and septate/ sharp lingual apex of the tongue.
Conclusion(s): Tongue exhibits various unique characteristics and can be used in sex determination.
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Introduction: Patients with inflammatory bowel disease (IBD) have a 2-to 3-fold greater risk of venous thromboembolism (VTE) than the general population, with increased risk during hospitalization. However, recent evidence suggests that this increased risk persists post-discharge. As such, we aimed to determine the cost-effectiveness of post-discharge VTE prophylaxis among hospitalized patients with IBD.
Method(s): A decision tree was used to compare inpatient prophylaxis alone versus 4 weeks of postdischarge VTE prophylaxis with rivaroxaban 10 mg/day. Our primary outcome was quality-adjusted life years (QALYs) over one year, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (in 2020 $US), incremental cost-effectiveness ratios (ICERs), and number needed to treat (NNT) to prevent one VTE and VTE death were calculated. Deterministic 1-way and probabilistic analyses were performed to assess uncertainty within the model.
Result(s): Four-week post-discharge prophylaxis with rivaroxaban resulted in 1.68 higher QALYs per 1000 persons and an incremental cost of $185,778 per QALY as compared to no postdischarge prophylaxis (see Table). The NNT to prevent a single VTE was 78 individuals, while the NNT to prevent a single VTE-related death was 3190 individuals. One-way sensitivity analyses showed that higher baseline VTE risk>4.5% or decreased cost of rivaroxaban <=$280 can reduce the ICER to<$100,000/QALY (see Figure, Tornado Diagram showing main drivers of the ICER). Probabilistic sensitivity analyses favored post-discharge prophylaxis in 30.5% of iterations
Conclusion(s): Four weeks of post-discharge VTE prophylaxis results in higher QALYs as compared to inpatient prophylaxis alone, and can prevent one post-discharge VTE among 78 patients with IBD. As such, post-discharge VTE prophylaxis in patients with IBD should be considered in a case-by-case scenario considering VTE risk profile, costs, and patient preference

BACKGROUND:The World Trade Center (WTC) attacks on 11 September 2001 created a hazardous environment with known and suspected carcinogens. Previous studies have identified an increased risk of prostate cancer in responder cohorts compared with the general male population. OBJECTIVES:To estimate the length of time to prostate cancer among WTC rescue/recovery workers by determining specific time periods during which the risk was significantly elevated. METHODS:Person-time accruals began 6 months after enrolment into a WTC cohort and ended at death or 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. New York State was the comparison population. We used Poisson regression to estimate hazard ratios and 95% CIs; change points in rate ratios were estimated using profile likelihood. RESULTS:The analytic cohort included 54 394 male rescue/recovery workers. We observed 1120 incident prostate cancer cases. During 2002-2006, no association with WTC exposure was detected. Beginning in 2007, a 24% increased risk (HR: 1.24, 95% CI 1.16 to 1.32) was observed among WTC rescue/recovery workers when compared with New York State. Comparing those who arrived earliest at the disaster site on the morning of 11 September 2001 or any time on 12 September 2001 to those who first arrived later, we observed a positive, monotonic, dose-response association in the early (2002-2006) and late (2007-2015) periods. CONCLUSIONS:Risk of prostate cancer was significantly elevated beginning in 2007 in the WTC combined rescue/recovery cohort. While unique exposures at the disaster site might have contributed to the observed effect, screening practices including routine prostate specific antigen screening cannot be discounted.

BACKGROUND:World Trade Center (WTC)-exposed responders may be eligible to receive no-cost medical monitoring and treatment for certified conditions, including cancer. The survival of responders with cancer has not previously been investigated. METHODS:This study compared the estimated relative survival of WTC-exposed responders who developed cancer while enrolled in two WTC medical monitoring and treatment programs in New York City (WTC-MMTP responders) and WTC-exposed responders not enrolled (WTC-non-MMTP responders) to non-responders from New York State (NYS-non-responders), all restricted to the 11-southernmost NYS counties, where most responders resided. Parametric survival models estimated cancer-specific and all-cause mortality. Follow-up ended at death or on December 31, 2016. RESULTS:From January 1, 2005 to December 31, 2016, there were 2,037 cancer cases and 303 deaths (248 cancer-related deaths) among WTC-MMTP responders, 564 cancer cases, and 143 deaths (106 cancer-related deaths) among WTC-non-MMTP responders, and 574,075 cancer cases and 224,040 deaths (158,645 cancer-related deaths) among the NYS-non-responder population. Comparing WTC-MMTP responders with NYS-non-responders, the cancer-specific mortality hazard ratio (HR) was 0.72 (95% confidence interval [CI] = 0.64-0.82), and all-cause mortality HR was 0.64 (95% CI = 0.58-0.72). The cancer-specific HR was 0.94 (95% CI = 0.78-1.14), and all-cause mortality HR was 0.93 (95% CI = 0.79-1.10) comparing WTC-non-MMTP responders to the NYS-non-responder population. CONCLUSIONS:WTC-MMTP responders had lower mortality compared with NYS-non-responders, after controlling for demographic factors and temporal trends. There may be survival benefits from no-out-of-pocket-cost medical care which could have important implications for healthcare policy, however, other occupational and socioeconomic factors could have contributed to some of the observed survival advantage.

BACKGROUND:A recent study of World Trade Center (WTC)-exposed firefighters and emergency medical service workers demonstrated that elevated thyroid cancer incidence may be attributable to frequent medical testing, resulting in the identification of asymptomatic tumors. We expand on that study by comparing the incidence of thyroid cancer among three groups: WTC-exposed rescue/recovery workers enrolled in a New York State (NYS) WTC-medical monitoring and treatment program (MMTP); WTC-exposed rescue/recovery workers not enrolled in an MMTP (non-MMTP); and the NYS population. METHODS:Person-time began on 9/12/2001 or at enrollment in a WTC cohort and ended at death or on 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. We used Poisson regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for MMTP and non-MMTP participants. NYS rates were used as the reference. To estimate potential changes over time in WTC-associated risk, change points in RRs were estimated using profile likelihood. RESULTS:The thyroid cancer incidence rate among MMTP participants was more than twice that of NYS population rates (RR = 2.31; 95% CI = 2.00-2.68). Non-MMTP participants had a risk similar to NYS (RR = 0.96; 95% CI = 0.72-1.28). We observed no change points in the follow-up period. CONCLUSION/CONCLUSIONS:Our findings support the hypothesis that no-cost screening (a benefit provided by WTC-MMTPs) is associated with elevated identification of thyroid cancer. Given the high survival rate for thyroid cancer, it is important to weigh the costs and benefits of treatment, as many of these cancers were asymptomatic and may have been detected incidentally.

Introduction: Crohn's disease (CD) carries a major healthcare burden, costing over $10 billion a year in the United States. Strictures are a common complication of CD, emerging in over half of patients after 20 years from diagnosis, and requiring invasive interventions such as surgery which further increases healthcare costs. Endoscopic balloon dilation (EBD) has emerged as an alternative intervention in managing CD strictures. We determined the cost-effectiveness of EBD versus resection surgery for patients with short (<4-5cm) anastomotic or primary small or large bowel strictures.
Method(s): A microsimulation state-transition model simulated the benefits and risks of EBD and bowel resection surgery for patients with primary or anastomotic strictures due to CD. Our base case was a 40-year-old patient with CD who developed a stricture. Strategies included EBD or surgery as a patient's first procedure, after which they were allowed to receive either procedure based on probabilities of subsequent intervention derived from the literature. Our primary outcome was qualityadjusted life years (QALYs) over ten years, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (in 2021 $US) and incremental cost-effectiveness ratios (ICER) were calculated. Deterministic 1-way and probabilistic analyses assessed model uncertainty.
Result(s): The EBD strategy cost $19,822 and resulted in 6.18 QALYs while the surgery strategy cost $41,358 and resulted in 6.37 QALYs. Surgery had an ICER of $113,332 per QALY, making EBD a cost-effective strategy. The median number of EBDs was 6 in the EBD strategy and 0 in the surgery strategy. The median number of surgeries was 2 in the surgery strategy and 1 in the EBD strategy. Of individuals who initially received EBD, 50.4% underwent subsequent surgery. One-way sensitivity analyses showed that the probabilities of requiring repeated interventions, surgery mortality (, 0.6%), and quality of life after interventions were the most influential parameters in our model. Probabilistic sensitivity analyses favored EBD in 50.9% of iterations.
Conclusion(s): EBD, when feasible, is a cost-effective strategy for managing CD primary or anastomotic strictures. Sensitivity analyses show that differences in patient risk and quality of life after intervention can impact cost-effectiveness. The decision between EBD or surgery should be made considering cost-effectiveness, patient risks, and quality of life preferences

Introduction: Cytotoxic drugs are hampered by limited efficacy. Hence, a personalized treatment approach matching chemotherapy with appropriate patients remains an unmet need. Genomic heterogeneity creates an opportunity to discern key genomic aberrations and pathways that confer resistance and response to standard treatment options. We conducted a study using the Cellworks Computational Omics Biology Model (CBM) to identify novel genomic biomarkers associated with response among Non-Small Cell Lung Cancer (NSCLC) patients receiving platinum-based treatments.
Method(s): 104 NSCLC patients who received platinum-based chemotherapy were selected from TCGA: platinum-etoposide (N=18), platinum-gemcitabine (N=20), platinum-vinorelbine (N=31), platinum-paclitaxel (N=21), and platinum-docetaxel (N=14). Mutation and CNV from each case served as input for the CBM to generate a patient-specific protein network-map based on PubMed and other resources. Biomarkers unique to each patient were identified within protein network-maps. Drug impact on the disease network was biosimulated to determine efficacy score by measuring the effect of chemotherapy on the cell growth score, a composite of cell proliferation, viability, apoptosis, metastasis, DNA damage and other cancer hallmarks. Effectively, the mechanism of action of each drug was mapped to each patient's genome and biological consequences determined response.
Result(s): Among the 104 patients, 74 were responders (R) and 30 non-responders (NR), determined using compete and partial response based on RECIST criteria (Figure 1). The CBM predicted clinical response with 73% sensitivity and 77% specificity. Cellworks CBM identified novel biomarkers responsible for platinum-based combination therapy response as mentioned below. +Etoposide: 13q-del, RB1-del, MBD1-del, LIG4-del, ERCC5-del, ATP7B-del +Gemcitabine: AKT3-amp, MAPKAP2-amp, TAP1-del +Vinorelbine: TET2-del/LOF, TRIB3-amp, SLX4-del +Paclitaxel: KLF4-del, SNCG-del, RAC1-amp/GOF +Docetaxel: BCL2L1-amp, HMGA1-amp, NSD1-del, SLC22A7-amp, FSIP1-del These genes contributed to drug efficacy by impacting various pathways, including DNA repair, oxidative-stress, methylation machinery, spindle formation, and mitotic-catastrophe. The aberration frequency of these genes was high among the responders within each subgroup and was very low in non-responders. Additionally, a model of clinical outcome versus the linear and quadratic function of efficacy score, drug combination and the interaction of both showed that efficacy score provides predictive information above and beyond the choice of drug combination alone (likelihood ratio chi-sq = 35.56, df=13, p-value = 0.0007). [Formula presented]
Conclusion(s): This pilot study highlights how the Cellworks CBM biosimulation platform can help identify patients for therapy response prediction. By using novel biomarkers, a CBM-informed decision tree can be employed to identify the optimal drug combination for platinum-based therapy. We suggest that this approach be validated prospectively in a larger patient cohort. Keywords: Cancer Therapy Biosimulation, Multi-omics Therapy Biosimulation, Personalized Cancer Therapy
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Introduction: Non-alcoholic fatty liver disease (NAFLD) is present in 36-70% of women with polycystic ovary syndrome (PCOS). Both are highly prevalent in subjects with obesity. Androgen overproduction in PCOS promotes a pro-apoptotic environment and may contribute to NAFLD. Our objective was to examine the association between PCOS and NAFLD diagnosis and if PCOS is an independent predictor of advanced fibrosis in patients with NAFLD.
Method(s): In a single-center retrospective analysis of electronic medical records, 625 adult patients ( .18 years old) with a diagnosis of NAFLD from 2018-2019 were divided into 3 cohorts: a female study group with PCOS, female control group without PCOS, and a male control cohort, age-matched to the study group. PCOS diagnosis was based on established PCOS society criteria. Our primary outcome was to assess the stage of liver fibrosis, as defined by histology, Fibroscan, MR elastography, NAFLD fibrosis score (NFS), by the age of initial diagnosis. Additionally, demographic, laboratory and clinical parameters were analyzed to compare the three cohorts. Demographics were analyzed using ANOVA, Pearson's chi-squared, and Kruskal-Wallis methods. Linear regression modeling NAFLD score as a function of age of diagnosis was performed.
Result(s): A total of 625 subjects with NAFLD were seen. Of these, 21 met criteria for the female NAFLD/PCOS study group, 525 in the female NAFLD only control group, and 79 age-matched male subjects with NAFLD. The NAFLD/PCOS females study group were significantly younger than the other two cohorts at time of diagnosis of NAFLD, had the highest BMI of 38.4, highest AST/ALT ratio of 0.92, lowest albumin value of 4.03, highest percentage of patients with physical signs of the male cohort was associated with a 0.7 reduction in NFS compared to women with NAFLD only. Females with NAFLD demonstrate significant difference in the mean NFS and mean age of diagnosis compared to the other 2 groups, while females with both versus males with NAFLD did not (Image 1).
Conclusion(s): Females with PCOS significantly demonstrated NAFLD at an earlier age supported by positive physical and radiological signs, and worse NFS vs. males at the time of initial NAFLD diagnosis.

BACKGROUND:Implicit bias instruction is becoming more prevalent across the continuum of medical education. Little guidance exists for faculty on recognizing and debriefing about implicit bias during routine clinical encounters. OBJECTIVE:To assess the impact and feasibility of single seminars on implicit bias and the approach to its management in clinical settings. METHODS:Between September 2016 and November 2017, the authors delivered five departmental/divisional grand rounds across three different academic medical centers in New York, USA. Instruction provided background information on implicit bias, highlighted its relevance to clinical care, and discussed proposed interventions. To evaluate the impact of instruction participants completed a twelve-item retrospective pre-intervention/post-intervention survey. Questions related to comfort and confidence in recognizing and managing implicit bias, debriefing with learners, and role-modeling behaviors. Participants identified strategies for recognizing and managing potentially biased events through free text prompts. Authors qualitatively analyzed participants' identified strategies. RESULTS:We received 116 completed surveys from 203 participants (57% response rate). Participants self-reported confidence and comfort increased for all questions. Qualitative analysis resulted in three themes: looking inward, looking outward, and taking action at individual and institutional levels. CONCLUSION/CONCLUSIONS:After a single session, respondents reported increased confidence and comfort with the topic. They identified strategies relevant to their professional contexts which can inform future skills-based interventions. For healthcare organizations responding to calls for implicit bias training, this approach has great promise. It is feasible and can reach a wide audience through usual grand rounds programming, serving as an effective early step in such training.