Clearance While Upright on Initial Diuretic Renography Predicts the Need for Surgery in Children With Congenital Hydronephrosis.

OBJECTIVE: To improve the predictive ability of diuretic renography (DR) for surgical intervention in children with congenital hydronephrosis (CH) and concern for ureteropelvic junction obstruction. METHODS: Children with CH born between 2007 and 2021 who underwent initial DR prior to 6months of life, had both clearance while upright (CUP) and T ½ reported, and did not have immediate surgical intervention after the first DR were retrospectively evaluated for surgical intervention during the period of clinical observation. Once the optimal cut-points were identified for CUP and T ½, they were used to calculate the sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: In total 65 patients were included in the final analysis with 33 (50.8%) undergoing surgical intervention (pyeloplasty) and 32 (49.2%) still on observation at last follow-up. The optimal cut-points for predicting surgical intervention were 28.1 minutes for T ½ and 22.4% for CUP. Applying the CUP cut-point of 22.4% we achieved a sensitivity of 60.6% (95% CI: 43.9-77.3), specificity of 96.9% (95% CI: 90.1-100.0), positive predictive value of 95.2% (95% CI: 86.1-100.0), and negative predictive value of 70.5% (95% CI: 57.0-83.9). CONCLUSION: A low CUP accurately predicts surgical intervention in children with CH who are initially observed. Although there is no singular measure on DR that can with absolute certainty predict future clinical course, our data do suggest there is utility in incorporating CUP (if <22.4%) into the decision process. Further research is necessary to help guide the management of children with intermediate CUP values.

Laser Epilation as an Adjunct to Standard Care in Reducing Pilonidal Disease Recurrence in Adolescents and Young Adults: A Randomized Clinical Trial.

Importance: Recurrence continues to be a significant challenge in the treatment and management of pilonidal disease. Objective: To compare the effectiveness of laser epilation (LE) as an adjunct to standard care vs standard care alone in preventing recurrence of pilonidal disease in adolescents and young adults. Design, Setting, and Participants: This was a single-institution, randomized clinical trial with 1-year follow-up conducted from September 2017 to September 2022. Patients aged 11 to 21 years with pilonidal disease were recruited from a single tertiary children's hospital. Intervention: LE and standard care (improved hygiene and mechanical or chemical depilation) or standard care alone. Main Outcomes and Measures: The primary outcome was the rate of recurrence of pilonidal disease at 1 year. Secondary outcomes assessed during the 1-year follow-up included disability days, health-related quality of life (HRQOL), health care satisfaction, disease-related attitudes and perceived stigma, and rates of procedures, surgical excisions, and postoperative complications. Results: A total of 302 participants (median [IQR] age, 17 [15-18] years; 157 male [56.1%]) with pilonidal disease were enrolled; 151 participants were randomly assigned to each intervention group. One-year follow-up was available for 96 patients (63.6%) in the LE group and 134 (88.7%) in the standard care group. The proportion of patients who experienced a recurrence within 1 year was significantly lower in the LE treatment arm than in the standard care arm (-23.2%; 95% CI, -33.2 to -13.1; P < .001). Over 1 year, there were no differences between groups in either patient or caregiver disability days, or patient- or caregiver-reported HRQOL, health care satisfaction, or perceived stigma at any time point. The LE group had significantly higher Child Attitude Toward Illness Scores (CATIS) at 6 months (median [IQR], 3.8 [3.4-4.2] vs 3.6 [3.2-4.1]; P = .01). There were no differences between groups in disease-related health care utilization, disease-related procedures, or postoperative complications. Conclusions and Relevance: LE as an adjunct to standard care significantly reduced 1-year recurrence rates of pilonidal disease compared with standard care alone. These results provide further evidence that LE is safe and well tolerated in patients with pilonidal disease. LE should be considered a standard treatment modality for patients with pilonidal disease and should be available as an initial treatment option or adjunct treatment modality for all eligible patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03276065.

Assessing Alternative Approaches for Wound Closure in a National Pediatric Learning Health System.

INTRODUCTION: Our objective was to perform a feasibility study using real-world data from a learning health system (LHS) to describe current practice patterns of wound closure and explore differences in outcomes associated with the use of tissue adhesives and other methods of wound closure in the pediatric surgical population to inform a potentially large study. METHODS: A multi-institutional cross-sectional study was performed of a random sample of patients <18 y-old who underwent laparoscopic appendectomy, open or laparoscopic inguinal hernia repair, umbilical hernia repair, or repair of traumatic laceration from January 1, 2019, to December 31, 2019. Sociodemographic and operative characteristics were obtained from 6 PEDSnet (a national pediatric LHS) children's hospitals and OneFlorida Clinical Research Consortium (a PCORnet collaboration across 14 academic health systems). Additional clinical data elements were collected via chart review. RESULTS: Of the 692 patients included, 182 (26.3%) had appendectomies, 155 (22.4%) inguinal hernia repairs, 163 (23.6%) umbilical hernia repairs, and 192 (27.8%) traumatic lacerations. Of the 500 surgical incisions, sutures with tissue adhesives were the most frequently used (n = 211, 42.2%), followed by sutures with adhesive strips (n = 176, 35.2%), and sutures only (n = 72, 14.4%). Most traumatic lacerations were repaired with sutures only (n = 127, 64.5%). The overall wound-related complication rate was 3.0% and resumption of normal activities was recommended at a median of 14 d (interquartile ranges 14-14). CONCLUSIONS: The LHS represents an efficient tool to identify cohorts of pediatric surgical patients to perform comparative effectiveness research using real-world data to support medical and surgical products/devices in children.

Inequities in the Diagnosis of Pediatric Appendicitis in Tertiary Children's Hospitals and the Consequences of Delayed Diagnosis.

INTRODUCTION: Missed diagnosis (MD) of acute appendicitis is associated with increased risk of appendiceal perforation. This study aimed to investigate whether racial/ethnic disparities exist in the diagnosis of pediatric appendicitis by comparing rates of MD versus single-encounter diagnosis (SED) between racial/ethnic groups. METHODS: Patients 0-18 y-old admitted for acute appendicitis from February 2017 to December 2021 were identified in the Pediatric Health Information System (PHIS). International Classification of Diseases, 10th Revision, Clinical Modification diagnosis codes for Emergency Department visits within 7 d prior to diagnosis were evaluated to determine whether the encounter represented MD. Generalized mixed models were used to assess the association between MD and patient characteristics. A similar model assessed independent predictors of perforation. RESULTS: 51,164 patients admitted for acute appendicitis were included; 50,239 (98.2%) had SED and 925 (1.8%) had MD. Compared to non-Hispanic White patients, patients of non-Hispanic Black (odds ratio 2.5, 95% confidence interval 2.0-3.1), Hispanic (2.1, 1.8-2.5), and other race/ethnicity (1.6, 1.2-2.1) had higher odds of MD. There was a significant interaction between race/ethnicity and imaging (P < 0.0001). Among patients with imaging, race/ethnicity was not significantly associated with MD. Among patients without imaging, there was an increase in strength of association between race/ethnicity and MD (non-Hispanic Black 3.6, 2.7-4.9; Hispanic 3.3, 2.6-4.1; other 2.0, 1.4-2.8). MD was associated with increased risk of perforation (2.5, 2.2-2.8). CONCLUSIONS: Minority children were more likely to have MD. Future efforts should aim to mitigate the risk of MD, including implementation of algorithms to standardize the workup of abdominal pain to reduce potential consequences of implicit bias.

Association of the Affordable Care Act Medicaid Expansion With Secondary Overtriage among Young Adult Trauma Patients.

BACKGROUND: Previous work has shown that the Affordable Care Act (ACA) Medicaid expansion decreased the uninsured rate and improved some trauma outcomes among young adult trauma patients, but no studies have investigated the impact of ACA Medicaid expansion on secondary overtriage, namely the unnecessary transfer of non-severely injured patients to tertiary trauma centers. METHODS: Statewide hospital inpatient and emergency department discharge data from two Medicaid expansion and one non-expansion state were used to compare changes in insurance coverage and secondary overtriage among trauma patients aged 19-44 y transferred into a level I or II trauma center before (2011-2013) to after (2014-quarter 3, 2015) Medicaid expansion. Difference-in-difference (DD) analyses were used to compare changes overall, by race/ethnicity, and by ZIP code-level median income quartiles. RESULTS: Medicaid expansion was associated with a decrease in the proportion of patients uninsured (DD: -4.3 percentage points; 95% confidence interval (CI): -7.4 to -1.2), an increase in the proportion of patients insured by Medicaid (DD: 8.2; 95% CI: 5.0 to 11.3), but no difference in the proportion of patients who experienced secondary overtriage (DD: -1.5; 95% CI: -4.8 to 1.8). There were no differences by race/ethnicity or community income level in the association of Medicaid expansion with secondary overtriage. CONCLUSIONS: In the first 2 y after ACA Medicaid expansion, insurance coverage increased but secondary overtriage rates were unchanged among young adult trauma patients transferred to level I or II trauma centers.

The Impact of Race and Ethnicity on Surgical Risk and Outcomes Following Palatoplasty: An Analysis of the NSQIP Pediatric Database.

OBJECTIVE: To determine how race and ethnicity affect palatoplasty 30-day outcomes. DESIGN: Retrospective review. PATIENTS/SETTING: The 2012 to 2019 National Surgical Quality Improvement Program (NSQIP) Pediatric database was used to identify patients ≤ 2 years who underwent primary palatoplasty. We compared demographics, comorbidities, and 30-day outcomes among different racial and ethnic groups. Logistic regression was used to determine independent risk factors for adverse events. MAIN OUTCOME MEASURES: Increased risk for adverse events and postoperative surgical outcomes, including complications, readmission, and prolonged length of stay. RESULTS: A total of 8537 patients were identified in the database. African-American patients had the highest proportion of premature infants and infants with a BMI < 15% at the time of repair. Asian patients underwent palatoplasty at a later age compared to other races (12.7 months vs 11.7-12.1 months). Postoperatively, the odds of a complication were significantly higher in Asian patients (aOR = 1.73, 95% CI: 1.17-2.57) and other/unknown patients (aOR = 1.40, 95% CI: 1.05-1.86), but not among African American (aOR = 1.02, 95% CI: 0.70-1.47) or Hispanic (aOR = 0.93, 95% CI: 0.69-1.26) patients. Other/unknown patients were more likely to require postoperative ventilation (aOR = 2.34, 95% CI: 1.38-3.95). The odds of readmission were highest in Asian and other/unknown patients. African American, Hispanic, and other/unknown patients were more likely than Caucasian patients to be hospitalized > 2 days postoperatively. CONCLUSION: This study highlights ethnic differences in presentation and 30-day outcomes following palatoplasty. Further evaluation of disparities in cleft care should be performed to improve healthcare access and surgical outcomes.

Perioperative outcomes in minimally-invasive versus open surgery in infants undergoing repair of congenital anomalies.

BACKGROUND: This study compared perioperative outcomes among infants undergoing repair of congenital anomalies using minimally invasive (MIS) versus open surgical approaches. METHODS: The ACS NSQIP Pediatric (2013-2018) was queried for patients undergoing repair of any of the following 9 congenital anomalies: congenital lung lesion (LL), mediastinal mass (MM), congenital malrotation (CM), anorectal malformation (ARM), Hirschsprung disease (HD), congenital diaphragmatic hernia (CDH), tracheoesophageal fistula (TEF), hepatobiliary anomalies (HB), and intestinal atresia (IA). Inverse probability of treatment weights (IPTW) derived from propensity scores were utilized to estimate risk-adjusted association between surgical approach and 30-day outcomes. RESULTS: 12,871 patients undergoing congenital anomaly repair were included (10,343 open; 2528 MIS). After IPTW, MIS was associated with longer operative time (difference; 95% CI) (16 min; 9-23) and anesthesia time (13 min; 6-21), but less postoperative ventilation days (-1.0 days; -1.4- -0.6) and shorter postoperative length of stay (-1.4 days; -2.4- -0.3). MIS repairs had decreased risk of any surgical complication (risk difference: -6.6%; -9.2- -4.0), including hematologic complications (-7.3%; -8.9- -5.8). There was no significant difference in risk of complication when hematologic complications were excluded (RD -2.3% [-4.7%, 0.1%]). There were no significant differences in the risk of unplanned reoperation (0.4%; -1.5-2.2) or unplanned readmission (0.2%; -1.2-1.5). CONCLUSIONS: MIS repair of congenital anomalies is associated with improved perioperative outcomes when compared to open. Additional studies are needed to compare long-term functional and disease-specific outcomes. MINI-ABSTRACT: In this propensity-weighted multi-institutional analysis of nine congenital anomalies, minimally invasive surgical repair was associated with improved 30-day outcomes when compared to open surgical repair. LEVEL OF EVIDENCE: III.

Impact of Medicaid expansion on young adult firearm and motor vehicle crash trauma patients.

BACKGROUND: The Affordable Care Act Medicaid expansion has increased insurance coverage and reduced some disparities in care and outcomes among trauma patients, but its impact on subsets of trauma patients with particular mechanisms of injury are unclear. This study evaluated the association of the Affordable Care Act Medicaid expansion with insurance coverage, trauma care, and outcomes among young adults hospitalized for firearm- or motor vehicle crash-related injuries. MATERIALS AND METHODS: We used statewide hospital discharge data from 5 Medicaid expansion and 5 nonexpansion states to compare changes in insurance coverage and outcomes among firearm and motor vehicle crash trauma patients aged 19-44 from before (2011-2013) to after (2014-2017) Medicaid expansion. We examined difference in differences overall, by race/ethnicity, and by zip-code-level median income quartile. RESULTS: Medicaid expansion was associated with a decrease in the proportion of young adult motor vehicle crash and firearm trauma patients who were uninsured (motor vehicle crash: difference in differences - 12.7 percentage points, P < .001; firearm: difference in differences - 30.7 percentage points, P < .001). Medicaid expansion was also associated with increases in the percentage of patients discharged to any rehabilitation (motor vehicle crash: difference in differences 1.78 percentage points, P = .001; firearm: difference in differences 2.07 percentage points, P = .02) and inpatient rehabilitation (motor vehicle crash: difference in differences 1.21 percentage points, P = .001; firearm: difference in differences 1.58 percentage points, P = .002). Among patients with firearm injuries, Medicaid expansion was associated with a reduction in in-hospital mortality (difference in differences - 1.55 percentage points, P = .002). CONCLUSION: In its first 4 years, the Affordable Care Act Medicaid expansion increased insurance coverage and access to rehabilitation among young adults hospitalized for firearm- or motor vehicle crash-related injuries while reducing inpatient mortality among firearm trauma patients.

Quantifying Upper Aerodigestive Sequelae in Esophageal Atresia/Tracheoesophageal Fistula Neonates.

OBJECTIVES: We examined rates of upper aerodigestive tract (UADT) procedures in a multi-institutional cohort of neonates with esophageal atresia/tracheoesophageal fistula (EA/TEF) to estimate secondary UADT pathology. METHODS: A retrospective cohort study was performed using a previously-validated population of patients with EA/TEF within the Pediatric Health Information System (PHIS) between 2007 and 2015. ICD-9/10-CM codes for aerodigestive procedures were examined from 2007 to 2020: 1) diagnostic direct laryngoscopy and/or bronchoscopy (DLB), 2) DLB with intervention, 3) tracheostomy, 4) gastrostomy, 5) fundoplication, 6) aortopexy, 7) laryngotracheoplasty, and 8) esophageal dilation. Associations between procedures and demographics, length of gestation, and weight were estimated using generalized linear mixed models. RESULTS: We identified 2,509 patients with EA/TEF from 47 hospitals, 56.7% male and 43.3% female. Median length of stay for the first admission was 24 days (interquartile range: 12-55). Of these patients, 1,943 (77.4%) had at least one aerodigestive procedure within 14 admissions. Specifically, 1,635 (65.2%) underwent diagnostic DLB, 85 (3.4%) DLB with intervention, 167 (6.7%) tracheostomy, 1,043 (41.2%) gastrostomy, 211 (11.0%) fundoplication, 52 (2.1%) aortopexy, 161 (6.4%) laryngotracheoplasty, and 207 (8.3%) esophageal dilation. Preterm gestation increased odds of tracheostomy (adjusted odds ratio (OR) 2.4, 95% confidence interval (CI) 1.5-3.7), gastrostomy (OR 2.1, CI 1.7-2.7), fundoplication (OR 1.7, CI 1.1-2.4), aortopexy (OR 5.8, CI 2.1-16.1), and esophageal dilation (OR 2.0, CI 1.4-3.0). Very low birth weight (<1,500 g) increased odds of gastrostomy (OR 2.5, CI 1.6-3.8). CONCLUSION: Patients with EA/TEF frequently have aerodigestive sequelae. This work helps quantify aerodigestive needs in neonates with EA/TEF, suggesting early otolaryngology evaluation in their care. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:695-700, 2022.

Association of the Affordable Care Act Medicaid Expansion with Trauma Outcomes and Access to Rehabilitation among Young Adults: Findings Overall, by Race and Ethnicity, and Community Income Level.

BACKGROUND: Low-income young adults disproportionately experience traumatic injury and poor trauma outcomes. This study aimed to evaluate the effects of the Affordable Care Act's Medicaid expansion, in its first 4 years, on trauma care and outcomes in young adults, overall and by race, ethnicity, and ZIP code-level median income. STUDY DESIGN: Statewide hospital discharge data from 5 states that did and 5 states that did not implement Medicaid expansion were used to perform difference-in-difference (DD) analyses. Changes in insurance coverage and outcomes from before (2011-2013) to after (2014-2017) Medicaid expansion and open enrollment were examined in trauma patients aged 19 to 44 years. RESULTS: Medicaid expansion was associated with a decrease in the percentage of uninsured patients (DD -16.5 percentage points; 95% CI, -17.1 to -15.9 percentage points). This decrease was larger among Black patients but smaller among Hispanic patients than White patients. It was also larger among patients from lower-income ZIP codes (p < 0.05 for all). Medicaid expansion was associated with an increase in discharge to inpatient rehabilitation (DD 0.6 percentage points; 95% CI, 0.2 to 0.9 percentage points). This increase was larger among patients from the lowest-compared with highest-income ZIP codes (p < 0.05). Medicaid expansion was not associated with changes in in-hospital mortality or readmission or return ED visit rates overall, but was associated with decreased in-hospital mortality among Black patients (DD -0.4 percentage points; 95% CI, -0.8 to -0.1 percentage points). CONCLUSIONS: The Affordable Care Act Medicaid expansion, in its first 4 years, increased insurance coverage and access to rehabilitation among young adult trauma patients. It also reduced the socioeconomic disparity in inpatient rehabilitation access and the disparity in in-hospital mortality between Black and White patients.

How Long-Term Acute Care Hospitals Can Play an Important Role in Controlling Carbapenem-Resistant Enterobacteriaceae in a Region: A Simulation Modeling Study.

Typically, long-term acute care hospitals (LTACHs) have less experience in and incentives to implementing aggressive infection control for drug-resistant organisms such as carbapenem-resistant Enterobacteriaceae (CRE) than acute care hospitals. Decision makers need to understand how implementing control measures in LTACHs can impact CRE spread regionwide. Using our Chicago metropolitan region agent-based model to simulate CRE spread and control, we estimated that a prevention bundle in only LTACHs decreased prevalence by a relative 4.6%-17.1%, averted 1,090-2,795 new carriers, 273-722 infections and 37-87 deaths over 3 years and saved $30.5-$69.1 million, compared with no CRE control measures. When LTACHs and intensive care units intervened, prevalence decreased by a relative 21.2%. Adding LTACHs averted an additional 1,995 carriers, 513 infections, and 62 deaths, and saved $47.6 million beyond implementation in intensive care units alone. Thus, LTACHs may be more important than other acute care settings for controlling CRE, and regional efforts to control drug-resistant organisms should start with LTACHs as a centerpiece.

The Potential Clinical and Economic Value of a Human Papillomavirus Primary Screening Test That Additionally Identifies Genotypes 31, 45, 51, and 52 Individually.

BACKGROUND: Although current human papillomavirus (HPV) genotype screening tests identify genotypes 16 and 18 and do not specifically identify other high-risk types, a new extended genotyping test identifies additional individual (31, 45, 51, and 52) and groups (33/58, 35/39/68, and 56/59/66) of high-risk genotypes. METHODS: We developed a Markov model of the HPV disease course and evaluated the clinical and economic value of HPV primary screening with Onclarity (BD Diagnostics, Franklin Lakes, NJ) capable of extended genotyping in a cohort of women 30 years or older. Women with certain genotypes were later rescreened instead of undergoing immediate colposcopy and varied which genotypes were rescreened, disease progression rate, and test cost. RESULTS: Assuming 100% compliance with screening, HPV primary screening using current tests resulted in 25,194 invasive procedures and 48 invasive cervical cancer (ICC) cases per 100,000 women. Screening with extended genotyping (100% compliance) and later rescreening women with certain genotypes averted 903 to 3163 invasive procedures and resulted in 0 to 3 more ICC cases compared with current HPV primary screening tests. Extended genotyping was cost-effective ($2298-$7236/quality-adjusted life year) when costing $75 and cost saving (median, $0.3-$1.0 million) when costing $43. When the probabilities of disease progression increased (2-4 times), extended genotyping was not cost-effective because it resulted in more ICC cases and accrued fewer quality-adjusted life years. CONCLUSIONS: Our study identified the conditions under which extended genotyping was cost-effective and even cost saving compared with current tests. A key driver of cost-effectiveness is the risk of disease progression, which emphasizes the need to better understand such risks in different populations.

The potential economic value of a therapeutic Chagas disease vaccine for pregnant women to prevent congenital transmission.

BACKGROUND: Currently, there are no solutions to prevent congenital transmission of Chagas disease during pregnancy, which affects 1-40% of pregnant women in Latin America and is associated with a 5% transmission risk. With therapeutic vaccines under development, now is the right time to determine the economic value of such a vaccine to prevent congenital transmission. METHODS: We developed a computational decision model that represented the clinical outcomes and diagnostic testing strategies for an infant born to a Chagas-positive woman in Mexico and evaluated the impact of vaccination. RESULTS: Compared to no vaccination, a 25% efficacious vaccine averted 125 [95% uncertainty interval (UI): 122-128] congenital cases, 1.9 (95% UI: 1.6-2.2) infant deaths, and 78 (95% UI: 66-91) DALYs per 10,000 infected pregnant women; a 50% efficacious vaccine averted 251 (95% UI: 248-254) cases, 3.8 (95% UI: 3.6-4.2) deaths, and 160 (95% UI: 148-171) DALYs; and a 75% efficacious vaccine averted 376 (95% UI: 374-378) cases, 5.8 (95% UI: 5.5-6.1) deaths, and 238 (95% UI: 227-249) DALYs. A 25% efficacious vaccine was cost-effective (incremental cost-effectiveness ratio <3× Mexico's gross domestic product per capita, <$29,698/DALY averted) when the vaccine cost ≤$240 and ≤$310 and cost-saving when ≤$10 and ≤$80 from the third-party payer and societal perspectives, respectively. A 50% efficacious vaccine was cost-effective when costing ≤$490 and ≤$615 and cost-saving when ≤$25 and ≤$160, from the third-party payer and societal perspectives, respectively. A 75% efficacious vaccine was cost-effective when ≤$720 and ≤$930 and cost-saving when ≤$40 and ≤$250 from the third-party payer and societal perspectives, respectively. Additionally, 13-42 fewer infants progressed to chronic disease, saving $0.41-$1.21 million to society. CONCLUSION: We delineated the thresholds at which therapeutic vaccination of Chagas-positive pregnant women would be cost-effective and cost-saving, providing economic guidance for decision-makers to consider when developing and bringing such a vaccine to market.

The Potential Economic Value of a Zika Vaccine for a Woman of Childbearing Age.

INTRODUCTION: With Zika vaccine candidates under development and women of childbearing age being the primary target population, now is the time to map the vaccine (e.g., efficacy and duration of protection) and vaccination (e.g., cost) characteristic thresholds at which vaccination becomes cost effective, highly cost effective, and cost saving. METHODS: A Markov model was developed (to represent 2019 circumstances, US$ and INT$, Region of the Americas) to simulate a woman of childbearing age and the potential risk and clinical course of a Zika infection. RESULTS: Compared with no vaccination, vaccination was cost effective (incremental cost-effectiveness ratio: US$1,254-$82,900/disability-adjusted life years averted) when the risk of infection was ≥0.05%-0.08% (varying with country income), vaccine efficacy was ≥25%, and vaccination cost was US$1-$7,500 (INT$5-$10,000 depending on country income level). Vaccination was dominant (i.e., saved costs and provided beneficial health effects) when the infection risk was ≥0.1% for a vaccine efficacy ≥75% and when the infection risk was ≥0.5% for a vaccine efficacy ≥25%, for scenarios where vaccination conferred a 1-year duration of protection and cost ≤$200. In some cases, the vaccine was cost effective when the risk was as low as 0.015%, the cost was as high as $7,500 (INT$10,000), the efficacy was as low as 25%, and the duration of protection was 1 year. CONCLUSIONS: The thresholds at which vaccination becomes cost effective and cost saving can provide targets for Zika vaccine development and implementation.

Economic value of a therapeutic Chagas vaccine for indeterminate and Chagasic cardiomyopathy patients.

BACKGROUND: Therapeutic vaccines to prevent Chagas disease progression to cardiomyopathy are under development because the only available medications (benznidazole and nifurtimox) are limited by their efficacy, long treatment course, and side effects. Better understanding the potential clinical and economic value of such vaccines can help guide development and implementation. METHODS: We developed a computational Chagas Markov model to evaluate the clinical and economic value of a therapeutic vaccine given in conjunction with benznidazole in indeterminate and chronic Chagas patients. Scenarios explored the vaccine's impact on reducing drug treatment dosage, duration, and adverse events, and risk of disease progression. RESULTS: When administering standard-of-care benznidazole to 1000 indeterminate patients, 148 discontinued treatment and 219 progressed to chronic disease, resulting in 119 Chagas-related deaths and 2293 DALYs, costing $18.9 million in lifetime societal costs. Compared to benznidazole-only, therapeutic vaccination administered with benznidazole (25-75% reduction in standard dose and duration), resulted in 37-111 more patients (of 1000) completing treatment, preventing 11-219 patients from progressing, 6-120 deaths, and 108-2229 DALYs (5-100% progression risk reduction), saving ≤$16,171 per patient. When vaccinating determinate Kuschnir class 1 Chagas patients, 10-197 fewer patients further progressed compared to benznidazole-only, averting 11-228 deaths and 144-3037 DALYs (5-100% progression risk reduction), saving ≤$34,059 per person. When vaccinating Kuschnir class 2 patients, 13-279 fewer progressed (279 with benznidazole-only), averting 13-692 deaths and 283-10,785 DALYs (5-100% progression risk reduction), saving ≤$89,759. Therapeutic vaccination was dominant (saved costs and provided health benefits) with ≥ 5% progression risk reduction, except when only reducing drug treatment regimen and adverse events, but remained cost-effective when costing <$200. CONCLUSIONS: Our study helps outline the thresholds at which a therapeutic Chagas vaccine may be cost-effective (e.g., <5% reduction in preventing cardiac progression, 25% reduction in benznidazole treatment doses and duration) and cost-saving (e.g., ≥5% and 25%, respectively).

What Is the Value of Different Zika Vaccination Strategies to Prevent and Mitigate Zika Outbreaks?

BACKGROUND: While the 2015-2016 Zika epidemics prompted accelerated vaccine development, decision makers need to know the potential economic value of vaccination strategies. METHODS: We developed models of Honduras, Brazil, and Puerto Rico, simulated targeting different populations for Zika vaccination (women of childbearing age, school-aged children, young adults, and everyone) and then introduced various Zika outbreaks. Sensitivity analyses varied vaccine characteristics. RESULTS: With a 2% attack rate ($5 vaccination), compared to no vaccination, vaccinating women of childbearing age cost $314-$1664 per case averted ($790-$4221/disability-adjusted life-year [DALY] averted) in Honduras, and saved $847-$1644/case averted in Brazil, and $3648-$4177/case averted in Puerto Rico, varying with vaccination coverage and efficacy (societal perspective). Vaccinating school-aged children cost $718-$1849/case averted (≤$5002/DALY averted) in Honduras, saved $819-$1609/case averted in Brazil, and saved $3823-$4360/case averted in Puerto Rico. Vaccinating young adults cost $310-$1666/case averted ($731-$4017/DALY averted) in Honduras, saved $953-$1703/case averted in Brazil, and saved $3857-$4372/case averted in Puerto Rico. Vaccinating everyone averted more cases but cost more, decreasing cost savings per case averted. Vaccination resulted in more cost savings and better outcomes at higher attack rates. CONCLUSIONS: When considering transmission, while vaccinating everyone naturally averted the most cases, specifically targeting women of childbearing age or young adults was the most cost-effective.

The economic value of identifying and treating Chagas disease patients earlier and the impact on Trypanosoma cruzi transmission.

BACKGROUND: The World Health Organization's 2020 Goals for Chagas disease include access to antiparasitic treatment and care of all infected/ill patients. Policy makers need to know the economic value of identifying and treating patients earlier. However, the economic value of earlier treatment to cure and prevent the Chagas' spread remains unknown. METHODS: We expanded our existing Chagas disease transmission model to include identification and treatment of Chagas disease patients. We linked this to a clinical and economic model that translated chronic Chagas disease cases into health and economic outcomes. We evaluated the impact and economic outcomes (costs, cost-effectiveness, cost-benefit) of identifying and treating different percentages of patients in the acute and indeterminate disease states in a 2,000-person village in Yucatan, Mexico. RESULTS: In the absence of early treatment, 50 acute and 22 new chronic cases occurred over 50 years. Identifying and treating patients in the acute stage averted 0.5-5.4 acute cases, 0.6-5.5 chronic cases, and 0.6-10.8 disability-adjusted life years (DALYs), saving $694-$7,419 and $6,976-$79,950 from the third-party payer and societal perspectives, respectively. Treating in the indeterminate stage averted 2.2-4.9 acute cases, 6.1-12.8 chronic cases, and 11.7-31.1 DALYs, saving $7,666-$21,938 from the third-party payer perspective and $90,530-$243,068 from the societal perspective. Treating patients in both stages averted ≤9 acute cases and ≤15 chronic cases. Identifying and treating patients early was always economically dominant compared to no treatment. Identifying and treating patients earlier resulted in a cumulative cost-benefit of $7,273-$224,981 at the current cost of identification and treatment. CONCLUSIONS: Even when identifying and treating as little as 5% of cases annually, treating Chagas cases in the acute and indeterminate stages reduces transmission and provides economic and health benefits. This supports the need for improved diagnostics and access to safe and effective treatment.

Estimated Cost to a Restaurant of a Foodborne Illness Outbreak.

OBJECTIVES: Although outbreaks of restaurant-associated foodborne illness occur periodically and make the news, a restaurant may not be aware of the cost of an outbreak. We estimated this cost under varying circumstances. METHODS: We developed a computational simulation model; scenarios varied outbreak size (5 to 250 people affected), pathogen (n = 15), type of dining establishment (fast food, fast casual, casual dining, and fine dining), lost revenue (ie, meals lost per illness), cost of lawsuits and legal fees, fines, and insurance premium increases. RESULTS: We estimated that the cost of a single foodborne illness outbreak ranged from $3968 to $1.9 million for a fast-food restaurant, $6330 to $2.1 million for a fast-casual restaurant, $8030 to $2.2 million for a casual-dining restaurant, and $8273 to $2.6 million for a fine-dining restaurant, varying from a 5-person outbreak, with no lost revenue, lawsuits, legal fees, or fines, to a 250-person outbreak, with high lost revenue (100 meals lost per illness), and a high amount of lawsuits and legal fees ($1 656 569) and fines ($100 000). This cost amounts to 10% to 5790% of a restaurant's annual marketing costs and 0.3% to 101% of annual profits and revenue. The biggest cost drivers were lawsuits and legal fees, outbreak size, and lost revenue. Pathogen type affected the cost by a maximum of $337 000, the difference between a Bacillus cereus outbreak (least costly) and a listeria outbreak (most costly). CONCLUSIONS: The cost of a single foodborne illness outbreak to a restaurant can be substantial and outweigh the typical costs of prevention and control measures. Our study can help decision makers determine investment and motivate research for infection-control measures in restaurant settings.

The potential economic burden of Zika in the continental United States.

BACKGROUND: As the Zika virus epidemic continues to spread internationally, countries such as the United States must determine how much to invest in prevention, control, and response. Fundamental to these decisions is quantifying the potential economic burden of Zika under different scenarios. METHODOLOGY/PRINCIPLE FINDINGS: To inform such decision making, our team developed a computational model to forecast the potential economic burden of Zika across six states in the US (Alabama, Florida, Georgia, Louisiana, Mississippi, and Texas) which are at greatest risk of Zika emergence, under a wide range of attack rates, scenarios and circumstances. In order to accommodate a wide range of possibilities, different scenarios explored the effects of varying the attack rate from 0.01% to 10%. Across the six states, an attack rate of 0.01% is estimated to cost $183.4 million to society ($117.1 million in direct medical costs and $66.3 million in productivity losses), 0.025% would result in $198.6 million ($119.4 million and $79.2 million), 0.10% would result in $274.6 million ($130.8 million and $143.8 million) and 1% would result in $1.2 billion ($268.0 million and $919.2 million). CONCLUSIONS: Our model and study show how direct medical costs, Medicaid costs, productivity losses, and total costs to society may vary with different attack rates across the six states and the circumstances at which they may exceed certain thresholds (e.g., Zika prevention and control funding allocations that are being debated by the US government). A Zika attack rate of 0.3% across the six states at greatest risk of Zika infection, would result in total costs that exceed $0.5 billion, an attack rate of 1% would exceed $1 billion, and an attack rate of 2% would exceed $2 billion.