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BACKGROUND: This study aimed to use natural language processing to predict the presence of intra-abdominal injury using unstructured data from electronic medical records. METHODS: This was a random-sample retrospective observational cohort study leveraging unstructured data from injured patients taken to one of 9 acute care hospitals in an integrated health system between 2015 and 2021. Patients with International Classification of Diseases External Cause of Morbidity codes were identified. History and physical, consult, progress, and radiology report text from the first 8 hours of care were abstracted. Annotator dyads independently annotated encounters' text files to establish ground truth regarding whether intra-abdominal injury occurred. Features were extracted from text using natural language processing techniques, bag of words, and principal component analysis. We tested logistic regression, random forests, and gradient boosting machine to determine accuracy, recall, and precision of natural language processing to predict intra-abdominal injury. RESULTS: A random sample of 7,000 patient encounters of 177,127 was annotated. Only 2,951 had sufficient information to determine whether an intra-abdominal injury was present. Among those, 84 (2.9%) had an intra-abdominal injury. The concordance between annotators was 0.989. Logistic regression of features identified with bag of words and principal component analysis had the best predictive ability, with an area under the receiver operating characteristic curve of 0.9, recall of 0.73, and precision of 0.17. Text features with greatest importance included "abdomen," "pelvis," "spleen," and "hematoma." CONCLUSION: Natural language processing could be a screening decision support tool, which, if paired with human clinical assessment, can maximize precision of intra-abdominal injury identification.
Subject(s)
Abdominal Injuries , Electronic Health Records , Natural Language Processing , Humans , Electronic Health Records/statistics & numerical data , Retrospective Studies , Abdominal Injuries/diagnosis , Abdominal Injuries/epidemiology , Female , Male , Middle Aged , Adult , Aged , Young AdultABSTRACT
Objectives: The COVID-19 pandemic was disruptive for trainees and may have affected career decisions for some learners. This study examined the impact of the pandemic on emergency medicine (EM) resident perceptions of their mental health, perceptions of personal safety, and career choice regret. Methods: This was a cross-sectional survey study administered following the 2021 American Board of Emergency Medicine In-Training Examination (ITE). Survey measures included suicidal ideation (SI), COVID concerns in terms of infection prevention and control (IPC) training, COVID risk to self and/or COVID risk to family, and COVID-related career regret. COVID concerns were compared by gender and race/ethnicity using Pearson's chi-square tests. Multivariable logistic regression models were used to test the association between SI and COVID concerns, resident characteristics, and program characteristics. Results: A total of 6980 out of 8491 EM residents (82.2%) from 244 programs completed the survey. Only 1.1% of participants reported insufficient training in COVID IPC practices. Participants were concerned about COVID risk to themselves (40.3%) and to their families (63.3%) due to their job roles. These concerns were more common among women or nonbinary (vs. men); all other races/ethnicities (vs. non-Hispanic Whites); senior residents (vs. PGY-1, PGY-2 residents); and residents who were married or in relationships (vs. single or divorced). A total of 6.1% of participants reported that COVID made them reconsider choosing EM as their career. Career regret in this cohort was higher than that in the proportion (3.2%) expressing career regret in the 2020 ITE (p < 0.001). Career regret was more common among women or nonbinary (vs. men); all other races/ethnicities (vs. non-Hispanic Whites); and senior residents (vs. PGY-1, PGY-2 residents). The overall SI rate was 2.6%, which did not differ from that of the 2020 sample of EM residents (2.5%, p = 0.88). Conclusions: Many EM residents reported concerns about COVID risks to themselves and their families. Although the rate of SI remained unchanged, more EM residents reported career regret during the COVID pandemic.
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BACKGROUND: An enriching learning environment is integral to resident wellness and education. Integrated vascular (VS) and general surgery (GS) residents share 18 months of core GS rotations during the postgraduate years 1-3 (PGY1-3); differences in their experiences may help identify practical levers for change. METHODS: We used a convergent mixed-methods design. Cross-sectional surveys were administered after the 2020 American Board of Surgery In-Training Examination and Vascular Surgery In-Training Examination, assessing eight domains of the learning environment and resident wellness. Multivariable logistic regression models identified factors associated with thoughts of attrition between categorical PGY1-3 residents at 57 institutions with both GS and VS programs. Resident focus groups were conducted during the 2022 Vascular Annual Meeting to elicit more granular details about the experience of the learning environment. Transcripts were analyzed using inductive and deductive logics until thematic saturation was achieved. RESULTS: Surveys were completed by 205 VS and 1198 GS PGY1-3 residents (response rates 76.8% for VS and 82.5% for GS). After adjusting for resident demographics, PGY level, and program type, GS residents were more likely than their VS peers to consider leaving their programs (odds ratio [OR]: 2.61, 95% confidence interval [CI]: 1.37-4.99). This finding did not persist after adjusting for differences in perceptions of the learning environment, specifically: GS residents had higher odds of mistreatment (OR: 1.99, 95% CI: 1.36-2.90), poorer work-life integration (OR: 2.88, 95% CI: 1.41-5.87), less resident camaraderie (OR: 3.51, 95% CI: 2.26-5.45), and decreased meaning in work (OR: 2.94, 95% CI: 1.80-4.83). Qualitative data provided insight into how the shared learning environment was perceived differently: (1) vascular trainees expressed that early specialization and a smaller, more invested faculty allow for an apprenticeship model with early operative exposure, hands-on guidance, frequent feedback, and thus early skill acquisition (meaning in work); (2) a smaller program is conducive to closer relationships with co-residents and faculty, increasing familiarity (camaraderie and work-life integration); and (3) due to increased familiarity with program leadership, vascular trainees feel more comfortable reporting mistreatment, allowing for prompt responses (mistreatment). CONCLUSIONS: Despite sharing a learning environment, VS and GS residents experience training differently, contributing to differential thoughts of attrition. These differences may be attributable to intrinsic features of the integrated training paradigm that are not easily replicated by GS programs, such as smaller program size and higher faculty investment due to early specialization. Alternative strategies to compensate for these inherent differences should be considered (eg, structured operative entrustment programs and faculty incentivization).
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STUDY OBJECTIVE: The influence of workplace mistreatment on the well-being and career satisfaction of emergency medicine residents is unknown. This study examined the relationships between burnout, career choice regret, and workplace mistreatment in a national sample of emergency medicine residents. METHODS: This was a secondary analysis of a survey study on the prevalence of workplace mistreatment among emergency residents. Residents who reported emotional exhaustion or depersonalization at least once per week were considered to have burnout. Residents who reported dissatisfaction with their decision to become an emergency physician were considered to have career choice regret. Respondents also reported the type (discrimination, abuse, sexual harassment) and frequency of mistreatment over the academic year. Multivariable logistic regression, adjusting for program characteristics, was used to examine resident characteristics associated with burnout and career choice regret, with the frequency of mistreatment as a covariate. RESULTS: Of the 8,162 eligible residents, 7,680 (94.1 %) participated. About a third of respondents reported burnout (2,188 of 6,902, 31.7%), whereas a minority (224 of 6,923, 3.2%) reported career choice regret. Of the 7,087 responses on mistreatment frequency, 2,117 (29.9%) reported "a few times per year," and 1,296 (18.3%) reported "a few times per month or more." Compared with residents who never experienced mistreatment, residents who reported increasing frequencies of mistreatment were associated with having burnout-from mistreatment a few times per year (OR [odds ratio],1.6; 99% CI [confidence interval], 1.3 to 1.9) to a few times per month or more (OR, 3.3; 99% CI, 2.7 to 4.1). Compared with residents without burnout, residents who reported burnout were associated with having career choice regret (OR, 11.3; 99% CI, 7.0 to 18.1). After adjusting for burnout, there were no significant relationships between the frequency of mistreatment and career choice regret. CONCLUSIONS: Workplace mistreatment is associated with burnout, but not career choice regret, among emergency medicine residents. Efforts to address workplace mistreatment may improve emergency medicine residents' professional well-being.
Subject(s)
Burnout, Professional , Emergency Medicine , Internship and Residency , Humans , United States/epidemiology , Burnout, Professional/epidemiology , Burnout, Professional/psychology , Emotions , Surveys and Questionnaires , WorkplaceABSTRACT
To characterize nonrespondents to a national survey about trainee well-being, examine response patterns to questions of sensitive nature, and assess how nonresponse biases prevalence estimates of mistreatment and well-being. Background: Surgical trainees are at risk for burnout and mistreatment, which are discernible only by self-report. Therefore, prevalence estimates may be biased by nonresponse. Methods: A survey was administered with the 2018 and 2019 American Board of Surgery In-Training Examinations assessing demographics, dissatisfaction with education and career, mistreatment, burnout, thoughts of attrition, and suicidality. Responders in 2019 were characterized as survey "Completers," "Discontinuers" (quit before the end), and "Selective Responders" (selectively answered questions throughout). Multivariable logistic regression assessed associations of respondent type with mistreatment and well-being outcomes, adjusting for individual and program characteristics. Longitudinal survey identifiers linked survey responses for eligible trainees between 2018 and 2019 surveys to further inform nonresponse patterns. Results: In 2019, 6956 (85.6%) of 8129 eligible trainees initiated the survey, with 66.5% Completers, 17.5% Discontinuers, and 16.0% Selective Responders. Items with the highest response rates included dissatisfaction with education and career (93.2%), burnout (86.3%), thoughts of attrition (90.8%), and suicidality (94.4%). Discontinuers and Selective Responders were more often junior residents and racially/ethnically minoritized than Completers. No differences were seen in burnout and suicidality rates between Discontinuers, Selective Responders, and Completers. Non-White or Hispanic residents were more likely to skip questions about racial/ethnic discrimination than non-Hispanic White residents (21.2% vs 15.8%; odds ratio [OR], 1.35; 95% confidence interval [CI], 1.19-1.53), particularly when asked to identify the source. Women were not more likely to omit questions regarding gender/gender identity/sexual orientation discrimination (OR, 0.91; 95% CI, 0.79-1.04) or its sources (OR, 1.02; 95% CI, 0.89-1.16). Both Discontinuers and Selective Responders more frequently reported physical abuse (2.5% vs 1.1%; P = 0.001) and racial discrimination (18.3% vs 13.6%; P < 0.001) on the previous survey (2018) than Completers. Conclusions: Overall response rates are high for this survey. Prevalence estimates of burnout, suicidality, and gender discrimination are likely minimally impacted by nonresponse. Nonresponse to survey items about racial/ethnic discrimination by racially/ethnically minoritized residents likely results in underestimation of this type of mistreatment.
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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.
Subject(s)
Digestive System Surgical Procedures , Digestive System Surgical Procedures/adverse effects , Elective Surgical Procedures/adverse effects , Humans , Patient Readmission , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Smoking/adverse effects , Smoking/epidemiologyABSTRACT
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 United States 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 vascular trainees (47.3%) and was more common in female trainees (n = 63 [48.5%] reporting monthly or more frequently) compared with 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 with male trainees (n = 50 [16.2%]; P = .002). After controlling for race/ethnicity, postgraduate year, program type, and geography, female trainees were less likely to report burnout (odds ratio [OR], 0.49; 95% confidence interval [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 one-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.
Subject(s)
Burnout, Professional/epidemiology , Internship and Residency/statistics & numerical data , Surgeons/psychology , Vascular Surgical Procedures/education , Burnout, Professional/prevention & control , Burnout, Professional/psychology , Career Choice , Cross-Sectional Studies , Female , Humans , Male , Prevalence , Risk Factors , Sex Factors , Suicidal Ideation , Surgeons/education , Surveys and Questionnaires/statistics & numerical data , United States/epidemiology , Vascular Surgical Procedures/psychologyABSTRACT
The cost of testing can be a substantial contributor to hepatitis C virus (HCV) elimination program costs in many low- and middle-income countries such as Georgia, resulting in the need for innovative and cost-effective strategies for testing. Our objective was to investigate the most cost-effective testing pathways for scaling-up HCV testing in Georgia. We developed a Markov-based model with a lifetime horizon that simulates the natural history of HCV, and the cost of detection and treatment of HCV. We then created an interactive online tool that uses results from the Markov-based model to evaluate the cost-effectiveness of different HCV testing pathways. We compared the current standard-of-care (SoC) testing pathway and four innovative testing pathways for Georgia. The SoC testing was cost-saving compared to no testing, but all four new HCV testing pathways further increased QALYs and decreased costs. The pathway with the highest patient follow-up, due to on-site testing, resulted in the highest discounted QALYs (123 QALY more than the SoC) and lowest costs ($127,052 less than the SoC) per 10,000 persons screened. The current testing algorithm in Georgia can be replaced with a new pathway that is more effective while being cost-saving.
Subject(s)
Hepatitis C/diagnosis , Adult , Antiviral Agents/therapeutic use , Cost-Benefit Analysis , Female , Georgia (Republic)/epidemiology , Hepacivirus/isolation & purification , Hepatitis C/drug therapy , Hepatitis C/economics , Hepatitis C/epidemiology , Humans , Male , Markov Chains , Mass Screening/economics , Microbiological Techniques/economics , Quality-Adjusted Life YearsABSTRACT
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.
Subject(s)
Emergency Medicine/statistics & numerical data , Health Personnel/psychology , Internship and Residency/statistics & numerical data , Occupational Stress/psychology , Racism/psychology , Sexism/psychology , Sexual Harassment/psychology , Adult , Cohort Studies , Female , Health Personnel/statistics & numerical data , Humans , Male , Occupational Stress/epidemiology , Prevalence , Racism/statistics & numerical data , Sexism/statistics & numerical data , Sexual Harassment/statistics & numerical data , Surveys and Questionnaires , United States/epidemiology , Young AdultABSTRACT
OBJECTIVE: To understand patient perspective regarding recommended changes in the 2015 American Thyroid Association (ATA) guidelines. Specifically, in regard to active surveillance (AS) of some small differentiated thyroid cancer (DTC), performance of less extensive surgery for low-risk DTC, and more selective administration of radioactive iodine (RAI). METHODS: An online survey was disseminated to thyroid cancer patient advocacy organizations and members of the ATA to distribute to the patients. Data were collected on demographic and treatment information, 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 1546 patients with DTC: 1478 (96%) had a total thyroidectomy, and 1167 (76%) underwent RAI. If there was no change in the overall cancer outcome, 606 (39%) of respondents would have considered lobectomy over total thyroidectomy, 536 (35%) would have opted for AS, and 638 (41%) would have chosen to forego RAI. Moreover, (774/1217) 64% of respondents wanted more time with their clinicians when making decisions about the extent of surgery. A total of 621/1167 of patients experienced significant side effects with RAI, and 351/1167 of patients felt that the risks of treatment were not well explained. 1237/1546 (80%) of patients felt that AS would not be overly burdensome, and quality of life was the main reason cited for choosing AS. CONCLUSION: Patient perspective regarding choice in the 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.
Subject(s)
Iodine Radioisotopes , Thyroid Neoplasms , Humans , Iodine Radioisotopes/therapeutic use , Quality of Life , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/surgery , ThyroidectomyABSTRACT
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.
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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.
Subject(s)
Cost-Benefit Analysis , Practice Guidelines as Topic , Thyroid Neoplasms/surgery , Thyroid Nodule/surgery , Thyroidectomy/economics , Thyroidectomy/methods , Female , Humans , Life Expectancy , Male , Markov Chains , Middle Aged , Quality-Adjusted Life Years , Thyroid Neoplasms/mortality , Thyroid Nodule/mortality , United StatesABSTRACT
BACKGROUND: The effectiveness and cost-effectiveness of using neoadjuvant FOLFIRINOX (nFOLFIRINOX) for patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA PDAC) are unknown. Our objective was to determine whether nFOLFIRINOX is more effective or cost-effective for patients with BR/LA PDAC compared with upfront resection surgery and adjuvant gemcitabine plus capecitabine (GEM/CAPE) or gemcitabine monotherapy (GEM). MATERIALS AND METHODS: We performed a decision-analysis to assess the value of nFOLFIRINOX versus GEM/CAPE or GEM using a mathematical simulation model. Model transition probabilities were estimated using published and institutional clinical data. Model outcomes included overall and disease-free survival, quality-adjusted life-years (QALYs), cost in U.S. dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analyses explored the uncertainty of model assumptions. RESULTS: Model results found median overall survival (34.5/28.0/22.0 months) and disease-free survival (15.0/14.0/13.0 months) were better for nFOLFIRINOX compared with GEM/CAPE and GEM. nFOLFIRINOX was the optimal strategy on an efficiency frontier, resulting in an additional 0.35 life-years, or 0.30 QALYs, at a cost of $46,200/QALY gained compared with GEM/CAPE. Sensitivity analysis found that cancer recurrence and complete resection rates most affected model results, but were otherwise robust. Probabilistic sensitivity analyses found that nFOLFIRINOX was cost-effective 92.4% of the time at a willingness-to-pay threshold of $100,000/QALY. CONCLUSION: Our modeling analysis suggests that nFOLFIRINOX is preferable to upfront surgery for patients with BR/LA PDAC from both an effectiveness and cost-effectiveness standpoint. Additional clinical data that further define the long-term effectiveness of nFOLFIRINOX are needed to confirm our results. IMPLICATIONS FOR PRACTICE: Increasingly, neoadjuvant FOLFIRINOX has been used for borderline resectable and locally advanced pancreatic cancer with the goal of rendering them resectable and decreasing risk of recurrence. Despite many efforts to show the benefits of neoadjuvant over adjuvant therapies, clinical evidence to guide this decision is largely lacking. Decision-analytic modeling can provide a methodologic platform that integrates the best available data to quantitatively explore clinical decisions by simulating a hypothetical clinical trial. This modeling analysis suggests that neoadjuvant FOLFIRINOX is preferable to upfront surgery and adjuvant therapies by various outcome metrics including quality-adjusted life years, overall survival, and incremental cost-effectiveness ratio.
Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Pancreatic Ductal/drug therapy , Decision Support Techniques , Neoadjuvant Therapy/mortality , Neoplasm Recurrence, Local/drug therapy , Pancreatic Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/surgery , Female , Fluorouracil/therapeutic use , Follow-Up Studies , Humans , Irinotecan/therapeutic use , Leucovorin/therapeutic use , Male , Middle Aged , Models, Statistical , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Oxaliplatin/therapeutic use , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Prognosis , Survival RateABSTRACT
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.
Subject(s)
Adenocarcinoma/diagnosis , Diagnostic Tests, Routine/methods , Early Detection of Cancer/methods , Esophageal Neoplasms/diagnosis , Adenocarcinoma/mortality , Esophageal Neoplasms/mortality , Europe , Female , Humans , Male , Middle Aged , Survival Analysis , United StatesABSTRACT
Hürthle 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.
Subject(s)
Chromosome Aberrations , DNA, Mitochondrial/genetics , Mutation , Thyroid Neoplasms/genetics , DNA Copy Number Variations , Haploidy , Humans , Neoplasm Metastasis , Telomerase/genetics , Thyroid Neoplasms/pathology , Exome SequencingABSTRACT
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.
Subject(s)
Computer Simulation , Diet Therapy/methods , Eosinophilic Esophagitis/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Humans , Infant , Male , Middle Aged , Treatment Outcome , Young AdultABSTRACT
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 was reported. The objective of this study was to assess the correlation of BRAFV600E circulating tumor RNA levels with surgical and medical treatment. METHODS: Circulating BRAFV600E levels were assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma with known BRAFV600E mutation undergoing BRAFV600E-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 BRAFV600E analysis before and after treatment. Testing characteristics were assessed and positivity criteria optimized. Changes in blood BRAFV600E values were assessed and compared to clinical characteristics and response to therapy. RESULTS: In a murine model of anaplastic thyroid carcinoma with BRAFV600E mutation, blood BRAFV600E RNA correlated with tumor volume in animals treated with BRAFi. In tissue BRAFV600E-positive (n = 36) patients undergoing initial surgery for PTC, blood BRAFV600E 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 BRAFV600E declined following therapy and corresponded with radiographic evidence of partial response or stable disease. CONCLUSIONS: This study shows the correlation of blood BRAFV600E levels in response to treatment in both an established animal model of thyroid cancer and in patients with BRAFV600E-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.