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Background Understanding modifiable surgical risk factors is essential for preoperative optimization. We evaluated the association between smoking and complications following major gastrointestinal surgery. Methods Patients who underwent elective colorectal, pancreatic, gastric, or hepatic procedures were identified in the 2017 ACS NSQIP dataset. The primary outcome was 30-day death or serious morbidity (DSM). Secondary outcomes included pulmonary complications, wound complications, and readmission. Multivariable logistic regression was used to evaluate the association between smoking and these outcomes. Results A total of 46,921 patients were identified, of whom 7,671 (16.3%) were smokers. Smoking was associated with DSM (23.2% vs. 20.4%, OR 1.15 [1.08–1.23]), wound complications (13.0% vs. 10.4%, OR 1.24 [1.14–1.34]), pulmonary complications (4.9% vs 2.9%, OR 1.93 [1.70–2.20]), and unplanned readmission (12.6% vs. 11%, OR 1.14 [95% CI 1.06–1.23]). Conclusions Smoking is associated with complications following major gastrointestinal surgery. Patients who smoke should be counseled prior to surgery regarding risks.

Summary Background The Food and Drug Administration has approved several pharmacotherapies for the treatment of obesity. This study assesses the cost‐effectiveness of six pharmacotherapies and lifestyle intervention for people with mild obesity (body mass indices [BMIs] 30 to 35). Methods A microsimulation model was constructed to compare seven weight loss strategies plus no treatment: intensive lifestyle intervention, orlistat, phentermine, phentermine/topiramate, lorcaserin, liraglutide, and semaglutide. Weight loss, quality‐of‐life scores, and costs were estimated using clinical trials and other published literature. Endpoints included costs, quality‐adjusted life years (QALYs), and incremental cost‐effectiveness ratios (ICERs) with a willingness‐to‐pay (WTP) threshold of $100 000/QALY. Results were analysed at 1‐, 3‐, and 5‐year time horizons. Results At each of the three follow‐up periods, phentermine was the cost‐effective strategy, with ICERs of $46 258/QALY, $20 157/QALY, and $17 880/QALY after 1, 3, and 5 years, respectively. Semaglutide was the most effective strategy in the 3‐ and 5‐year time horizons, with total QALYs of 2.224 and 3.711, respectively. However, the ICERs were prohibitively high at $1 437 340/QALY after 3 years and $576 931/QALY after 5 years. Deterministic and probabilistic sensitivity analyses indicated these results were robust. Conclusions Phentermine is the cost‐effective pharmacologic weight‐loss strategy. Although semaglutide is the most effective, it is not cost‐effective because of its high price.

This survey study examines the frequency, types, and sources of perceived workplace mistreatment and the prevalence of suicidal ideation among emergency medicine residents in the US., Key Points Question What is the prevalence of workplace mistreatment and suicidal thoughts among emergency medicine residents? Findings In this survey study of 7680 emergency medicine residents, 45.1% reported exposure to some type of workplace mistreatment (eg, discrimination, abuse, or harassment) and 2.5% reported having suicidal thoughts during the most recent academic year. The prevalence of workplace mistreatment and suicidal thoughts was similar by gender and race/ethnicity. Meaning The findings suggest that educational interventions are warranted to reduce workplace mistreatment and ensure emergency medicine residents’ well-being during training., Importance The prevalence of workplace mistreatment and its association with the well-being of emergency medicine (EM) residents is unclear. More information about the sources of mistreatment might encourage residency leadership to develop and implement more effective strategies to improve professional well-being not only during residency but also throughout the physician’s career. Objective To examine the prevalence, types, and sources of perceived workplace mistreatment during training among EM residents in the US and the association between mistreatment and suicidal ideation. Design, Setting, and Participants In this survey study conducted from February 25 to 29, 2020, all residents enrolled in EM residencies accredited by the Accreditation Council for Graduate Medical Education (ACGME) who participated in the 2020 American Board of Emergency Medicine computer-based In-training Examination were invited to participate. A multiple-choice, 35-item survey was administered after the examination asking residents to self-report the frequency, sources, and types of mistreatment experienced during residency training and whether they had suicidal thoughts. Main Outcomes and Measures The types and frequency of workplace mistreatment and the sources of the mistreatment were identified, and rates of self-reported suicidality were obtained. Multivariable logistic regression models were used to examine resident and program characteristics associated with suicidal thoughts. Results Of 8162 eligible EM residents, 7680 (94.1%) responded to at least 1 question on the survey; 6503 (79.7%) completed the survey in its entirety. A total of 243 ACGME-accredited residency programs participated, and 1 did not. The study cohort included 4768 male residents (62.1%), 2698 female residents (35.1%), 4919 non-Hispanic White residents (64.0%), 2620 residents from other racial/ethnic groups (Alaska Native, American Indian, Asian or Pacific Islander, African American, Mexican American, Native Hawaiian, Puerto Rican, other Hispanic, or mixed or other race) (34.1%), 483 residents who identified as lesbian, gay, bisexual, transgender, queer, or other (LGBTQ+) (6.3%), and 5951 residents who were married or in a relationship (77.5%). Of the total participants, 3463 (45.1%) reported exposure to some type of workplace mistreatment (eg, discrimination, abuse, or harassment) during the most recent academic year. A frequent source of mistreatment was identified as patients and/or patients’ families; 1234 respondents (58.7%) reported gender discrimination, 867 (67.5%) racial discrimination, 282 (85.2%) physical abuse, and 723 (69.1%) sexual harassment from patients and/or family members. Suicidal thoughts occurring during the past year were reported by 178 residents (2.5%), with similar prevalence by gender (108 men [2.4%]; 59 women [2.4%]) and race/ethnicity (113 non-Hispanic White residents [2.4%]; 65 residents from other racial/ethnic groups [2.7%]). Conclusions and Relevance In this survey study, EM residents reported that workplace mistreatment occurred frequently. The findings suggest common sources of mistreatment for which educational interventions may be developed to help ensure resident wellness and career satisfaction.

OBJECTIVES: The 2015 updated American Thyroid Association (ATA) guidelines recommended the option of the following: 1) active surveillance (AS) of some small DTC, 2) performance of less extensive surgery for low-risk DTC, and 3) more selective administration of radioactive iodine (RAI). We sought patient perspectives regarding these changes. METHODS: A on-line 34-item survey was distributed to thyroid cancer patient advocacy organizations and members of the ATA to distribute to patients. Data were collected on demographic and treatment information, opinions about the guideline changes, and patient experience with DTC. Patients were asked “what-if” scenarios on core topics, including AS, extent of surgery, and indications for RAI. RESULTS: Survey responses were analyzed from 1,546 patients with previously treated DTC: 96% had a total thyroidectomy, and 76% underwent treatment with RAI. Response rate is unknown given the method of distribution. If no change in overall cancer outcome, 39% of respondents would have considered a lobectomy over total thyroidectomy; 35% would have opted for AS; and 41% would have chosen to forego RAI. 64% of respondents wanted more time with their clinicians when making decisions about extent of operation. 58% of patients experienced significant side effects with RAI treatment, and 30% felt that the risks of treatment were not well explained. 80% felt that AS would not be overly burdensome, and preservation of quality of life was the main reason cited for choosing AS. CONCLUSIONS: Patient perspective regarding choice in management of low-risk DTC varies widely and a large proportion of DTC patients would change aspects of their care if oncologic outcomes were equivalent.

OBJECTIVE: Burnout and suicidality are known risks for vascular surgeons above other surgical subspecialties, with surgical trainees at risk for exposure to factors that increase burnout. This study aimed to inform initiatives to improve wellness by assessing the prevalence of hazards in vascular training (mistreatment, duty hour violations) and the rates of wellness outcomes (burnout, thoughts of attrition/specialty change/suicide). We hypothesized that mistreatment and duty hour violations would predispose trainees to increased burnout. METHODS: We performed a cross-sectional study of residents and fellows enrolled in accredited U.S. vascular surgery training programs using a voluntary, confidential survey administered during the 2020 Vascular Surgery In-Training Examination. The primary outcome assessed was burnout symptoms reported on a weekly basis or more frequently. The rates of wellness outcomes were measured. The association of mistreatment and duty hours with the primary outcome was modeled with multivariable logistic regression. RESULTS: A total of 475 residents and fellows who were enrolled in one of 120 vascular surgery training programs completed the survey (84.2% response rate). Of 408 trainees completing burnout survey items, 182 (44.6%) reported symptoms of burnout. Fewer trainees reported thoughts of attrition (n = 42 [10.0%], specialty change (n = 35 [8.4%]), or suicide (n = 22 [4.9%]). Mistreatment was reported by 191 (47.3%) vascular trainees and was more common in female trainees (n = 63 [48.5%] reporting monthly or more frequently) compared to male trainees (n = 51 [18.6%], p < .001). Duty-hour violations were also more commonly reported by female trainees (n = 31 [21.4%] reporting 3+ months in violation) compared to male trainees (n = 50 [16.2%], p = .002). After controlling for race/ethnicity, post-graduate year, program type, and geography, female trainees were less likely to report burnout (odds ratio [OR] 0.49, 95% CI 0.28 – 0.86). Trainees experiencing mistreatment monthly or more were three times more likely to report burnout (OR 3.09, 95% CI 1.78 – 5.39). Frequency of duty hour violations also increased the odds of reporting burnout (1-2 months in violation OR 2.09, 95% CI 1.17 – 3.73; 3+ months in violation OR 3.95, 95% CI 2.24 – 6.97). CONCLUSIONS: Nearly half of vascular surgery trainees reported symptoms of burnout, which was associated with frequency of mistreatment and duty hour violations. Interventions to improve well-being in vascular surgery must be tailored to the local training environment to address trainee experiences that contribute to burnout.

Background: BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based BRAFV600E assay ...

Background Expectant mothers who are beneficiaries of TRICARE (universal insurance to United States Armed Services members and their dependents) can choose to receive care within direct (salary-based) or purchased (fee-for-service) care systems. We sought to compare frequency of intrapartum obstetric procedures and outcomes such as severe acute maternal morbidity (SAMM) and common postpartum complications between direct and purchased care systems within TRICARE. Methods TRICARE (2006-2010) claims data were used to identify deliveries. Patient demographics, frequency of types of delivery (noninstrumental vaginal, cesarean, and instrumental vaginal), comorbid conditions, SAMM, and common postpartum complications were compared between the two systems of care. Multivariable models adjusted for patient clinical/demographic factors determined the odds of common complications and SAMM complications in purchased care compared with direct care. Results A total of 440 138 deliveries were identified. Compared with direct care, purchased care had higher frequency (30.9% vs 25.8%, P

Objective To assess relative clinical and economic performance of the revised American Thyroid Association (ATA) thyroid cancer guidelines compared to current standard of care. Background Diagnosis of thyroid cancer in the United States has tripled whereas mortality has only marginally increased. Most patients present with small papillary carcinomas and have historically received at least a total thyroidectomy as a treatment. In 2015, the ATA released the revised guidelines recommending an option for active surveillance (AS) of small papillary thyroid carcinoma and thyroid lobectomy for larger unifocal tumors. Methods We created a Markov microsimulation model to evaluate the performance of the ATA's 2015 guidelines compared to the ATA's 2009 guidelines. We modeled a cohort of simulated patients with demographic and thyroid nodule characteristics representative of those presenting clinically in the United States. Outcome measures include life expectancy, quality-adjusted life years, costs, and frequency of surgical adverse events. Results In our base case analysis, the ATA 2015 strategy dominates the ATA 2009 strategy. The ATA 2015 strategy delivers greater discounted average quality-adjusted life years (13.09 vs 12.43) at a lower discounted average cost ($14,752 vs $20,126). Deaths due to thyroid cancer under the 2015 strategy are higher than the 2009 strategy but this is offset by a reduction in surgical deaths, leading to greater average life expectancy under the ATA 2015 strategy. The optimal strategy is sensitive to patients who experience a greater decrement in quality of life while undergoing AS. Conclusions The ATA 2015 Guidelines represent a cost-effective strategy regarding AS and extent of surgery.

Rates of esophageal adenocarcinoma (EAC) have increased rapidly in the United States and much of western Europe, and 5-year survival continues to be poor.1 Prevention and early detection efforts for EAC have focused on identifying persons with EAC precursor state, Barrett's esophagus, but the survival benefit has been disappointingly low.

Background: BRAF(V600E) is the most common mutation in papillary thyroid carcinoma (PTC) and can be associated with aggressive disease. Previously, a highly sensitive blood RNA-based BRAF(V600E) assay was reported. The objective of this study was to assess the correlation of BRAF(V600E) circulating tumor RNA levels with surgical and medical treatment. Methods: Circulating BRAF(V600E) levels were assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma with known BRAF(V600E) mutation undergoing BRAF(V600E)-inhibitor (BRAFi) treatment, and (ii) in 111 patients enrolled prior to thyroidectomy (n = 86) or treatment of advanced recurrent or metastatic PTC (n = 25). Blood samples were drawn for BRAF(V600E) analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood BRAF(V600E) values were assessed and compared to clinical characteristics and response to therapy. Results: In a murine model of anaplastic thyroid carcinoma with BRAF(V600E) mutation, blood BRAF(V600E) RNA correlated with tumor volume in animals treated with BRAFi. In tissue BRAF(V600E)-positive (n = 36) patients undergoing initial surgery for PTC, blood BRAF(V600E) levels declined postoperatively (median 370.0–178.5 fg/ng; p = 0.002). In four patients with metastatic or poorly differentiated thyroid carcinoma receiving targeted therapies, blood BRAF(V600E) declined following therapy and corresponded with radiographic evidence of partial response or stable disease. Conclusions: This study shows the correlation of blood BRAF(V600E) levels in response to treatment in both an established animal model of thyroid cancer and in patients with BRAF(V600E)-positive tumors with all stages of disease. This assay represents an alternative biomarker in patients with positive thyroglobulin antibodies, and tumors, which do not express thyroglobulin.

Summary Hurthle cell carcinoma of the thyroid (HCC) is a form of thyroid cancer recalcitrant to radioiodine therapy that exhibits an accumulation of mitochondria. We performed whole-exome sequencing on a cohort of primary, recurrent, and metastatic tumors, and identified recurrent mutations in DAXX, TP53, NRAS, NF1, CDKN1A, ARHGAP35, and the TERT promoter. Parallel analysis of mtDNA revealed recurrent homoplasmic mutations in subunits of complex I of the electron transport chain. Analysis of DNA copy-number alterations uncovered widespread loss of chromosomes culminating in near-haploid chromosomal content in a large fraction of HCC, which was maintained during metastatic spread. This work uncovers a distinct molecular origin of HCC compared with other thyroid malignancies.

Background Thyroid cancer affects over ½ million people in the U.S. and the incidence of thyroid cancer has increased worldwide at a rate higher than any other cancer, while survival has remained largely unchanged. The aim of this research was to develop, calibrate and verify a mathematical disease model to simulate the natural history of papillary thyroid cancer, which will serve as a platform to assess the effectiveness of clinical and cancer control interventions. Methods Herein, we modeled the natural pre-clinical course of both benign and malignant thyroid nodules with biologically relevant health states from normal to detected nodule. Using established calibration techniques, optimal parameter sets for tumor growth characteristics, development rate, and detection rate were used to fit Surveillance Epidemiology and End Results (SEER) incidence data and other calibration targets. Results Model outputs compared to calibration targets demonstrating sufficient calibration fit and model validation are presented including primary targets of SEER incidence data and size distribution at detection of malignancy. Additionally, we show the predicted underlying benign and malignant prevalence of nodules in the population, the probability of detection based on size of nodule, and estimates of growth over time in both benign and malignant nodules. Conclusions This comprehensive model provides a dynamic platform employable for future comparative effectiveness research. Future model analyses will test and assess various clinical management strategies to improve patient outcomes related to thyroid cancer and optimize resource utilization for patients with thyroid nodules.

Background & Aims Elimination diets are effective treatments for eosinophilic esophagitis (EoE), but foods that activate esophagitis are identified empirically, via a process that involves multiple esophagogastroduodenoscopies (EGDs). No optimized approach has been developed to identify foods that activate EoE. We aimed to compare clinical strategies to provide data to guide treatment. Methods We developed a computer-based simulation model to determine promising empiric elimination strategies based on reported prevalence values for foods that activate EoE. We conducted a review, searching PubMed through October 1, 2017, for prospective and retrospective studies of EoE and diet. Each patient in our simulated cohort was assigned a profile comprising as many as 12 foods known to induce EoE, including dairy, wheat, eggs, soy, nuts, seafood, beef, corn, chicken, potato, pork, and/or rice. To balance the strategy success rate with the number of EGDs required for food identification, we applied an efficiency frontier approach. Strategies on the frontier were the most efficient, requiring fewer EGDs for higher or equivalent success rates relative to their comparable, neighboring strategies. Results In all simulations, we found the 1,4,8-food and 1,3-food strategies to be the most efficient in identifying foods that induce EoE, resulting in the highest rate of the correct identification of food triggers balanced by the number of EGDs required to complete the food elimination strategy. Both strategies begin with elimination of dairy; if EoE remission is not achieved, the 1,3 diet proceeds to eliminate wheat and eggs in addition to dairy, and the 1,4,8 strategy removes wheat, eggs, dairy, and soy. In the case of persistent EoE after the second round of food elimination, the 1,3-food strategy terminates, whereas the 1,4,8-food diet eliminates corn, chicken, beef, and pork. The 1,4,8-food diet resulted in correct identification of foods that activated esophagitis in 76.68% of patients, with a mean of 4.13 EGDs and a median of 6 EGDs. The 1,3-food strategy identified foods that activated esophagitis in 42.76% of patients, with a mean of 3.36 EGDs and a median of 2 EGDs required. Conclusions In this modeling analysis, we found the 1,4,8-food and 1,3-food elimination strategies to be the most efficient in detection of foods that induce EoE in patients. However, the ideal elimination strategy will vary based on clinical priorities. Additional research on specific foods that induce EoE are needed to confirm the predictions of this model.

4117 Background: With the advent of more effective therapies for metastatic pancreatic ductal adenocarcinoma (PDAC), efforts to incorporate these agents, such as FOLFIRINOX, into the neoadjuvant setting are increasing. However, the efficacy and cost-effectiveness of using neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced PDAC are unknown. We performed a decision analysis to assess the value of neoadjuvant FOLFIRINOX versus upfront surgery and adjuvant therapy. Methods: We developed a mathematical simulation model to evaluate the efficacy and cost-effectiveness of neoadjuvant FOLFIRINOX compared to upfront surgery and adjuvant therapy. We used published and institutional data as inputs to inform model development. Model outcomes included overall and disease-free survival, net benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. We used deterministic and probabilistic sensitivity analyses to explore the uncertainty of model assumptions. Results: Model estimated median overall survival (29 vs 23 months) and disease-free survival (14 vs 13 months) were better for neoadjuvant strategy compared with upfront surgery. Neoadjuvant strategy resulted in an additional 0.68 life-years gained, or 0.57 QALYs, at a cost of $59,000/QALY gained. Sensitivity analysis found that cancer recurrence rates affected model results the most. Our findings were otherwise robust with respect to changes in other model parameters, including chemotherapy toxicity, surgical complications and cancer mortality. Probabilistic sensitivity analyses showed that neoadjuvant strategy was cost-effective 80% of the time with a willingness-to-pay threshold of $100,000/QALY. Conclusions: Our model results demonstrate that neoadjuvant strategy is preferable to upfront surgery for patients with borderline resectable or locally advanced PDAC from both an efficacy and cost-effectiveness standpoint. Additional clinical data are needed to further define the long-term effectiveness of neoadjuvant FOLFIRINOX to confirm our results.