Same-Day Ileostomy Closure Discharge Reduces Costs without Compromising Outcomes: An Economic Analysis.

OBJECTIVE: This study aims to assess the costs of a Same-Day Discharge Enhanced Recovery Pathway (SDD) for diverting loop ileostomy closure compared to a standard institutional enhanced recovery protocol (ERP). SUMMARY BACKGROUND DATA: Every year, 50,155 patients in the United States undergo temporary stoma reversal. While ambulatory stoma closure has shown promise, widespread adoption remains slow. This study builds on previous research, focusing on the costs of a novel SDD protocol introduced in 2020. METHODS: A retrospective case-control study was conducted at Mayo Clinic, Rochester, Minnesota, and Mayo Clinic, Jacksonville, Florida, comparing patients undergoing same-day discharge diverting loop ileostomy closure (SDD) from August 2020 to February 2023 to those in a matched cohort receiving standard inpatient ERP. Patients were matched based on age, sex, ASA score, surgery period, and hospital. Primary outcomes included direct hospitalization and additional costs in the 30 days post-discharge. RESULTS: The SDD group (n=118) demonstrated a significant reduction in median index episode hospitalization and 30-day post-operative costs compared to the inpatient group (n=236), with savings of $4,827 per patient. Complication rates were similar, and so were readmission and reoperation rates. CONCLUSIONS: Implementation of the SDD for diverting loop ileostomy closure is associated with substantial cost savings without compromising patient outcomes. The study advocates for a shift towards same-day discharge protocols, offering economic benefits and potential improvements in healthcare resource utilization.

Adapting a Financial Incentives Intervention for Smoking Cessation With Alaska Native Families: Phase 1 Qualitative Research to Inform the Aniqsaaq (To Breathe) Study.

INTRODUCTION: Alaska Native and American Indian (ANAI) peoples in Alaska currently experience a disproportionate burden of morbidity and mortality from tobacco cigarette use. Financial incentives for smoking cessation are evidence-based, but a family-level incentive structure has not been evaluated. We used a community-based participatory research and qualitative approach to culturally adapt a smoking cessation intervention with ANAI families. AIMS AND METHODS: We conducted individual, semistructured telephone interviews with 12 ANAI adults who smoke, 12 adult family members, and 13 Alaska Tribal Health System stakeholders statewide between November 2022 and March 2023. Through content analysis, we explored intervention receptivity, incentive preferences, culturally aligned recruitment and intervention messaging, and future implementation needs. RESULTS: Participants were receptive to the intervention. Involving a family member was viewed as novel and aligned with ANAI cultural values of commitment to community and familial interdependence. Major themes included choosing a family member who is supportive and understanding, keeping materials positive and encouraging, and offering cash and noncash incentives for family members to choose (eg, fuel, groceries, activities). Participants indicated that messaging should emphasize family collaboration and that cessation resources and support tips should be provided. Stakeholders also reinforced that program materials should encourage the use of other existing evidence-based cessation therapies (eg, nicotine replacement, counseling). CONCLUSIONS: Adaptations, grounded in ANAI cultural strengths, were made to the intervention and recruitment materials based on participant feedback. Next steps include a beta-test for feasibility and a randomized controlled trial for efficacy. IMPLICATIONS: This is the first study to design and adapt a financial incentives intervention promoting smoking cessation among ANAI peoples and the first to involve the family system. Feedback from this formative work was used to develop a meaningful family-level incentive structure with ANAI people who smoke and family members and ensure intervention messaging is supportive and culturally aligned. The results provide qualitative knowledge that can inform future family-based interventions with ANAI communities, including our planned randomized controlled trial of the intervention.

Association between nintedanib adherence trajectory and healthcare use among idiopathic pulmonary fibrosis patients.

BACKGROUND: Although inverse associations have been found between medication adherence and healthcare use and spending outcomes in many clinical settings, no studies to date have examined these relationships for patients with idiopathic pulmonary fibrosis (IPF) initiating nintedanib. We build on our prior study that used group-based trajectory modeling (GBTM) to compare inpatient hospitalization and medical care spending outcomes between groups of patients with different nintedanib adherence trajectories. METHODS: This analysis used 100% Medicare data and included beneficiaries with IPF who initiated nintedanib during 10/01/2014-12/31/2018. The sample consisted of community-dwelling older adults (≥ 66 years) with continuous coverage in Medicare Parts A (inpatient care), B (outpatient care) and D (prescription drugs) for one year before (baseline) and after (follow-up) initiating nintedanib. Patients were assigned to the GBTM-derived adherence trajectory group closest to their own nintedanib adherence experience. All-cause and IPF-related hospitalization events and total medical spending were measured during the follow-up period. Unadjusted and adjusted regression models were estimated to compare outcomes between patients in different nintedanib adherence trajectories. RESULTS: Among the 1,798 patients initiating nintedanib, the mean age was 75.4 years, 61.1% were male, and 91.1% were non-Hispanic white. The best-fitting GBTM had five adherence trajectories: high adherence, moderate adherence, high-then-poor adherence, delayed-poor adherence, and early-poor adherence. All-cause hospitalizations and total all-cause medical spending were higher among patients in the high-then-poor, delayed-poor and early-poor adherence trajectories than those in the high adherence trajectory. For example, adjusted total all-cause medical spending was $4,876 (95% CI: $1,470 to $8,282) higher in the high-then-poor adherence trajectory, $3,639 (95% CI: $1,322 to $5,955) higher in the delayed-poor adherence trajectory and $3,907 (95% CI: $1,658 to $6,156) higher in the early-poor adherence trajectory compared with the high adherence trajectory. IPF-related hospitalizations and medical care spending were higher among those in the high-then-poor adherence trajectory compared with those in the high adherence trajectory. CONCLUSIONS: Poor adherence to nintedanib was associated with all-cause hospitalizations and medical costs. Therefore, improved adherence programs, such as support programs, can be implemented to reduce economic burden.

Cost-effectiveness of Adjuvant Pembrolizumab After Nephrectomy for High-risk Renal Cell Carcinoma: Insights for Patient Selection From a Markov Model.

PURPOSE: The KEYNOTE-564 trial demonstrated that adjuvant pembrolizumab after nephrectomy for clear cell renal cell carcinoma decreased the risk of disease progression and potentially overall mortality as well. Herein, we used a Markov model to weigh the costs, toxicities, and efficacy of pembrolizumab to further investigate its utility. MATERIALS AND METHODS: Decision-analytic Markov modeling was used to conduct a cost-utility analysis of adjuvant pembrolizumab versus observation after nephrectomy for high-risk clear cell renal cell carcinoma, using data from KEYNOTE-564 to inform model probabilities. Primary outcomes were quality-adjusted life years, Medicare costs, and incremental cost-effectiveness ratios. The willingness-to-pay threshold utilized was $100,000/quality-adjusted life year. RESULTS: At 5 years, adjuvant treatment with pembrolizumab resulted in 0.3 additional quality-adjusted life years at an additional cost of $99,484 relative to observation. Pembrolizumab was found not to be cost-effective at a 5-year time horizon (incremental cost-effectiveness ratio=$326,534). On sensitivity analysis, pembrolizumab became cost-effective if its per cycle cost was <$5,064 (base=$10,278) or its 5-year progression benefit was >18.8% (base 9%). Upon simulation, pembrolizumab was cost-effective for 29% of patients at 5 years. Specifically, we found that pembrolizumab would be cost-effective at 5 years for patients with at least a 59% 5 year risk of progression, which corresponds to a Mayo Progression-free Survival Score ≥10. CONCLUSIONS: At current prices, adjuvant pembrolizumab was found to be cost-effective only for the highest risk subset of clear cell renal cell carcinoma patients 5 years after treatment, including patients with complete metastasectomy, regional lymph node involvement, or ≥7cm pT3 tumors with sarcomatoid features. Longer-term trial data, including overall survival results, are necessary to confirm these extrapolations.

Extreme Risk of Sudden Cardiac Death within Three Months after Revascularization in Patients with Ischemic Left Ventricular Systolic Dysfunction.

Background: The risk of sudden cardiac death (SCD) after coronary revascularization in patients with left ventricular (LV) systolic dysfunction has not been characterized completely. This study aims to evaluate the incidence and time course of SCD after revascularization in such patients. The determinants of SCD within 3 months after revascularization were also assessed. Methods: A cohort study of patients with reduced ejection fraction (EF ≤ 40%), who underwent revascularization was performed. The incidence of SCD was estimated to account for the competing risk of deaths due to other causes. Results: 2317 patients were enrolled. With a median follow-up of 3.5 years, 162 (32.1%) of the 504 deaths were due to SCD. The risk of SCD was highest in the first 3 months after revascularization, with an incidence rate of 0.37%/month. The event rate decreased to 0.12%/month, 0.08%/month, 0.09%/month, 0.14%/month, and 0.19%/month at 3-6 months, 6-12 months, 1-3 years, 3-5 years, and 5-10 years, respectively. A history of ventricular tachycardia/ventricular fibrillation (hazard ratio [HR], 5.55; 95% confidence interval [CI], 1.33-23.19; p = 0.019) and triple vessel disease (HR, 3.90; 95% CI, 1.38-11.05; p = 0.010) were associated with the risk of SCD within 3 months. However, preoperative EF (in 5% increments) was not predictive (HR per 5% increase, 0.98; 95% CI, 0.62-1.55; p = 0.935). Conclusions: For patients with LV dysfunction, the risk of SCD was the highest during the first 3 months after revascularization. Further risk classification and treatment strategy are warranted. Clinical Trial Registration: The name of the registry: Coronary Revascularization in Patients with Ischemic Heart Failure and Prevention of Sudden Cardiac Death. Registration number: ChiCTR2100044378.

Erector Spinae Plane Block With Liposomal Bupivacaine: Analgesic Adjunct in Adult Pectus Surgery.

INTRODUCTION: Pain management may be challenging in patients undergoing pectus excavatum (PE) bar removal surgery. To enhance recovery, opioid sparing strategies with regional anesthesia including ultrasound-guided erector spinae plane block (ESPB) have been implemented. The purpose of this study was to evaluate the safety and efficacy of bilateral ESPB with a liposomal bupivacaine/traditional bupivacaine mixture as part of an enhanced patient recovery pathway. MATERIALS AND METHODS: A retrospective review of adult patients who underwent PE bar removal from January 2019 to December 2020 was performed. Perioperative data were reviewed and recorded. Patients who received ESPB were compared to historical controls (non-ESPB patients). RESULTS: A total of 202 patients were included (non-ESPB: 124 patients; ESPB: 78 patients). No adverse events were attributed to ESPB. Non-ESPB patients received more intraoperative opioids (milligram morphine equivalents; 41.8 ± 17.0 mg versus 36.7 ± 17.1, P = 0.05) and were more likely to present to the emergency department within 7 d postoperatively (4.8% versus 0%, P = 0.05) when compared to ESPB patients. No significant difference in total perioperative milligram morphine equivalents, severe pain in postanesthesia care unit (PACU), time from PACU arrival to analgesic administration, PACU length of stay, or postprocedure admission rates between groups were observed. CONCLUSIONS: In patients undergoing PE bar removal surgery, bilateral ESPB with liposomal bupivacaine was performed without complications. ESPB with liposomal bupivacaine may be considered as an analgesic adjunct to enhance recovery in patients undergoing cardiothoracic procedures but further prospective randomized clinical trials comparing liposomal bupivacaine to traditional local anesthetics with and without indwelling nerve catheters are necessary.

Cost-effectiveness of Myomectomy versus Hysterectomy in Women with Uterine Fibroids.

STUDY OBJECTIVE: Increasing evidence suggests that hysterectomy to treat uterine fibroids (UFs), even with ovarian conservation (OC), is associated with a 33% increased risk of coronary artery disease (CAD). We sought to compare the cost-effectiveness of various treatment approaches for UFs to understand the trade-offs among development of CAD vs new fibroids. DESIGN: We developed a Markov model to include women with UFs who no longer desired pregnancy. The outcomes of interest were quality-adjusted life-years (QALYs) and total treatment costs. We conducted sensitivity analyses to test the effect of uncertain model inputs. SETTING: Health system perspective. PATIENTS: A hypothetical cohort of 10 000 40-year-old women. INTERVENTIONS: Myomectomy, hysterectomy with OC, and hysterectomy without OC. MEASUREMENTS AND MAIN RESULTS: Myomectomy was the best-value strategy, costing US$528 217 and providing 19.38 QALYs. Neither hysterectomy with OC nor hysterectomy without OC was found to be cost-effective, assuming a willingness-to-pay threshold of $100 000 per QALY gain as hysterectomy with OC provided more benefit than myomectomy at an average cost of $613 144 to gain one additional QALY. The sensitivity analyses showed that if the risk of new symptomatic UFs that required treatment after myomectomy was more than 13%, annually (base case, 3.6%), or the quality of life after myomectomy was less than 0.815 (base case, 0.834), then myomectomy would no longer be cost-effective, under a willingness-to-pay amount of US$100 000. CONCLUSION: Myomectomy is an optimal treatment of UFs compared with hysterectomy among women aged 40 years. The increased risk of CAD after hysterectomy and its associated costs and the effects on morbidity and quality of life made hysterectomy a costlier and less effective long-term strategy.

Comparative cost-effectiveness of neoadjuvant chemotherapy regimens for muscle-invasive bladder cancer: Results according to VESPER data.

BACKGROUND: The VESPER trial demonstrated improved progression-free (PFS) and (preliminarily) overall survival (OS) with six cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVACx6) versus four cycles of gemcitabine and cisplatin (GCx4) before radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC), but with increased toxicity. This study compares the cost-effectiveness of these regimens. METHODS: A cost-effectiveness analysis of neoadjuvant ddMVACx6 and GCx4 was performed using a decision-analytic Markov model with 5-year, 10-year, and lifetime horizons. Probabilities were derived from reported VESPER data. Utility values were obtained from the literature. Primary outcomes were effectiveness measured in quality-adjusted life years (QALY) and incremental cost-effectiveness ratio (ICER) with a willingness to pay threshold of $100,000 per QALY. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of the model. RESULTS: At 5 years, ddMVACx6 improved QALYs by 0.30 at an additional cost of $16,100, rendering it cost-effective relative to GCx4 (ICER: $53,284/QALY). Additionally, probabilistic sensitivity analysis found ddMVACx6 to be cost-effective in 79% and 81% of microsimulations at10-year and lifetime horizons, respectively. One-way sensitivity analysis demonstrated a minimum difference in 5-year progression of 0.9% and progression mortality of 0.7% between ddMVACx6 and GCx4 was necessary for ddMVACx6 to remain cost-effective. CONCLUSIONS: Neoadjuvant ddMVACx6 was more cost-effective than GCx4 for MIBC. These data, together with the improved PFS and (albeit preliminary) OS noted in VESPER, support use of this regimen in appropriate candidates for neoadjuvant chemotherapy before RC. LAY SUMMARY: We performed a benefit-to-cost analysis using evidence from a randomized controlled trial that compared two different chemotherapy treatments before bladder removal for bladder cancer that had invaded into the bladder muscle. Despite being more expensive and having a greater likelihood of toxicity, six cycles of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin was more cost-effective (or had higher value) than four cycles of gemcitabine and cisplatin.

Evaluating educational interventions to increase breast density awareness among Latinas: A randomized trial in a Federally Qualified Health Center.

BACKGROUND: The objective of this randomized trial was to evaluate the short-term effect of bilingual written and interpersonal education regarding mammographic breast density (MBD). METHODS: Latinas aged 40 to 74 years who were presenting for screening mammography were recruited and randomized 1:1:1 to receive a letter with their mammogram and MBD results (usual care [UC]), a letter plus a brochure (enhanced care [ENH]), or a letter plus a brochure and telephonic promotora education (interpersonal care [INT]). Surveys were administered at enrollment (T0 ) and 2 weeks to 6 months after intervention delivery (T1 ). Differences were assessed with χ2 , Kruskal-Wallis, and McNemar tests and pairwise comparisons as appropriate. INT metrics and audio recordings were analyzed with descriptive statistics and qualitative content analysis. RESULTS: Between October 2016 and October 2019, 943 of 1108 Latina participants (85%) completed both surveys. At T1 , INT participants were more likely (P < .001) to report seeing their MBD results in the letter (70.2%) than UC (53.1%) or ENH participants (55.1%). The percentage of INT women who reported speaking with a provider about MBD (29.0%) was significantly greater (P < .001) than the percentage of UC (14.7%) or ENH participants (15.6%). All groups saw significant (P < .001) but nondifferential improvements in their knowledge of MBD as a masking and risk factor. In the INT group, the promotora delivered education to 77.1% of the 446 participants randomized to INT and answered questions at 28.3% of the encounters for an average of $4.70 per participant. CONCLUSIONS: Among Latinas in a low-resource setting, MBD knowledge may increase with written or interpersonal education, but with modest investment, interpersonal education may better improve MBD awareness and prompt patient-provider discussions.

Out-of-Pocket Cost Burden Associated With Contemporary Management of Advanced Prostate Cancer Among Commercially Insured Patients.

PURPOSE: Out-of-pocket costs represent an important component of financial toxicity and may impact patients' receipt of care. Herein, we evaluated patient-level factors associated with out-of-pocket costs for contemporary advanced prostate cancer treatment options. MATERIALS AND METHODS: We identified all commercially insured men receiving treatment for advanced prostate cancer between 2007 and 2019 within the OptumLabs Data Warehouse®. Patients were categorized into 3 treatment groups: androgen deprivation monotherapy, novel hormonal therapy, and nonandrogen systemic therapy. The primary outcome was out-of-pocket costs in the first year of treatment. The associations of treatment and patient variables with out-of-pocket costs were assessed using multivariable regression models. All costs were adjusted to reflect 2019 U.S. dollars using the Consumer Price Index. RESULTS: In a cohort of 13,409 men 81% (n = 10,926) received androgen deprivation monotherapy, 6% (n = 832) novel hormonal therapy, and 12% (n = 1,651) nonandrogen systemic therapy. Mean treatment-related out-of-pocket costs in the first year were $165, $4,236, and $994 for androgen deprivation monotherapy, novel hormonal therapy, and nonandrogen systemic therapy, respectively. The adjusted difference in annual treatment-related out-of-pocket costs for novel hormonal therapy and nonandrogen systemic therapy were $2,581 (95% CI: $1,923-$3,240) and $752 (95% CI: $600-$903) higher than androgen deprivation monotherapy, respectively. Patient characteristics associated (P < .05) with higher treatment-related out-of-pocket costs included older age (65-74 years), Black race, lower comorbidity scores, and lower household income. CONCLUSIONS: Patients receiving novel hormonal therapy for advanced prostate cancer had substantially higher treatment-related out-of-pocket costs. In addition to raising awareness among prescribers, these data support the inclusion of treatment associated financial toxicity in shared decision making for advanced prostate cancer and call attention to subgroups of patients particularly vulnerable to financial toxicity.

Cost-effectiveness of the anti-fibrotics for the treatment of idiopathic pulmonary fibrosis in the United States.

BACKGROUND: The anti-fibrotic medications nintedanib and pirfenidone were approved in the United States for use in patients with idiopathic pulmonary fibrosis several years ago. While there is a growing body of evidence surrounding their clinical effectiveness, these medications are quite expensive and no prior cost-effectiveness analysis has been performed in the United States. METHODS: A previously published Markov model performed in the United Kingdom was replicated using United States data to project the lifetime costs and health benefits of treating idiopathic pulmonary fibrosis with: (1) symptom management; (2) pirfenidone; or (3) nintedanib. For the cost-effectiveness analysis, strategies were ranked by increasing costs and then checked for dominating treatment strategies. Then an incremental cost-effectiveness ratio was calculated for the dominant therapy. RESULTS: The anti-fibrotic medications were found to cost more than $110,000 per year compared to $12,291 annually for symptom management. While pirfenidone was slightly more expensive than nintedanib and provided the same amount of benefit, neither medication was found to be cost-effective in this U.S.-based analysis, with an average cost of $1.6 million to gain one additional quality-adjusted life year over symptom management. CONCLUSIONS: Though the anti-fibrotics remain the only effective treatment option for patients with idiopathic pulmonary fibrosis and the data surrounding their clinical effectiveness continues to grow, they are not considered cost-effective treatment strategies in the United States due to their high price.

Cost comparison and complication profiles of superior capsular reconstruction, lower trapezius transfer, and reverse shoulder arthroplasty for irreparable rotator cuff tears.

BACKGROUND: Irreparable rotator cuff tears (IRCTs) pose treatment challenges both clinically and financially. As cost-effectiveness initiatives are prioritized, value-based health care delivery models are becoming increasingly common. The purpose of this study was to perform a comprehensive analysis of the cost, complications, and readmission rates of 3 common surgical treatment options for IRCTs: superior capsular reconstruction (SCR), arthroscopically assisted lower trapezius tendon transfer (LTTT), and reverse shoulder arthroplasty (RSA). METHODS: Between 2018 and 2020, 155 patients who underwent shoulder surgery at a single institution for IRCT with minimal to no arthritis were identified. Procedures performed included 20 SCRs, 47 LTTTs, and 88 RSAs. A cost analysis was designed to include a period of 60 days preoperatively, the index surgical hospitalization, and 90 days postoperatively, including costs of any readmission or reoperation. RESULTS: Mean standardized costs were as follows: preoperative evaluation SCR $507, LTTT $507, and RSA $730; index surgical hospitalization SCR $19,675, LTTT $15,722, and RSA $16,077; and postoperative care SCR $655, LTTT $686, and RSA $404. Significant differences were observed in the index surgical costs (P < .001), with SCR incurring an additional average cost of $3953 and $3598 compared with LTTT and RSA, respectively. The 90-day complication, reoperation, and readmission rates were 0%, 0%, and 0% in the SCR group; 2.1%, 0%, and 0% in the LTTT group; and 3.4%, 0%, and 1.1% in the RSA group, respectively. With the numbers available, differences among the 3 surgical procedures with respect to complication (P = .223), reoperation (P = .999), and readmission rates (P = .568) did not reach statistical significance. CONCLUSIONS: The mean standardized costs for the treatment of 3 common IRCT procedures inclusive of 60-day workup and 90-day postoperative recovery were $16,915, $17,210, and $20,837 for LTTT, RSA (average added cost $295), and SCR (average added cost $3922), respectively. This information may provide surgeons and institutions with cost-related information that will become increasingly relevant with the expansion of value-based surgical reimbursements.

Modeling the Cost of Teleneonatology from the Health System Perspective.

Introduction: Teleneonatology (TN) allows remote neonatologists to provide real-time audio-video telemedicine support to community hospitals when neonates require advanced resuscitation or critical care. Currently, there are no published economic evaluations of U.S. TN programs. Objective: To evaluate the cost of TN from the perspective of the health care system. Methods: We constructed a decision tree comparing TN to usual care for neonates born in hospitals without a neonatal intensive care unit (NICU) who require consultation. Our outcome of interest was total cost per patient, which included the incremental cost of a TN program, the cost of medical transport, and the cost of NICU or non-NICU hospitalization. We performed threshold sensitivity analyses where we varied each parameter to determine whether the base-case finding reverted. Results: For neonates requiring consultation after birth in a hospital without a NICU, TN was less costly ($16,878) than usual care ($28,047), representing a cost-savings of $11,168 per patient. Sensitivity analyses demonstrated that at least one of the following conditions would need to be met for TN to no longer be cost saving compared to usual care: transfer rate with usual care <12% (base-case = 82%), TN reducing the odds of transfer by <8% (base-case = 52%), or TN cost exceeding $12,989 per patient (base-case = $1,821 per patient). Conclusions: Economic modeling from the health system perspective demonstrated that TN was cost saving compared to usual care for neonates requiring consultation following delivery in a non-NICU hospital. Understanding the cost savings associated with TN may influence organizational decisions regarding implementation, diffusion, and retention of these programs.

Comparative Cost Effectiveness of Reflux-Based and Reflux-Independent Strategies for Barrett's Esophagus Screening.

INTRODUCTION: Minimally invasive tests for Barrett's esophagus (BE) detection have raised the prospect of broader nonreflux-based testing. Cost-effectiveness studies have largely studied men aged 50 years with chronic gastroesophageal reflux disease (GERD) symptoms. We evaluated the comparative cost effectiveness of BE screening tests in GERD-based and GERD-independent testing scenarios. METHODS: Markov modeling was performed in 3 scenarios in 50 years old individuals: (i) White men with chronic GERD (GERD-based); (ii) GERD-independent (all races, men and women), BE prevalence 1.6%; and (iii) GERD-independent, BE prevalence 5%. The simulation compared multiple screening strategies with no screening: sedated endoscopy (sEGD), transnasal endoscopy, swallowable esophageal cell collection devices with biomarkers, and exhaled volatile organic compounds. A hypothetical cohort of 500,000 individuals followed for 40 years using a willingness to pay threshold of $100,000 per quality-adjusted life year (QALY) was simulated. Incremental cost-effectiveness ratios (ICERs) comparing each strategy with no screening and comparing screening strategies with each other were calculated. RESULTS: In both GERD-independent scenarios, most non-sEGD BE screening tests were cost effective. Swallowable esophageal cell collection devices with biomarkers were cost effective (<$35,000/QALY) and were the optimal screening tests in all scenarios. Exhaled volatile organic compounds had the highest ICERs in all scenarios. ICERs were low (<$25,000/QALY) for all tests in the GERD-based scenario, and all non-sEGD tests dominated no screening. ICERs were sensitive to BE prevalence and test costs. DISCUSSION: Minimally invasive nonendoscopic tests may make GERD-independent BE screening cost effective. Participation rates for these strategies need to be studied.

A model-based cost-effectiveness analysis of pharmacogenomic panel testing in cardiovascular disease management: preemptive, reactive, or none?

PURPOSE: Pharmacogenomics (PGx) studies how inherited genetic variations in individuals affect drug absorption, distribution, and metabolism. PGx panel testing can potentially help improve efficiency and accuracy in individualizing therapy. This study compared the cost-effectiveness between preemptive PGx panel testing, reactive PGx panel testing and usual care (no testing) in cardiovascular disease management. METHODS: We developed a decision analytic model from the US payer's perspective for a hypothetical cohort of 10,000 patients ≥45 years old, using a short-term decision tree and long-term Markov model. The testing panel included the following gene-drug pairs: CYP2C19-clopidogrel, CYP2C9/VKORC1-warfarin, and SLCO1B1-statins with 30 test-return days. Costs were reported in 2019 US dollars and effectiveness was measured in quality-adjusted life years (QALYs). The primary outcome was incremental cost-effectiveness ratio (ICER = ΔCost/ΔQALY), assuming 3% discount rate for costs and QALYs. Scenario and probabilistic sensitivity analyses were performed to assess the impact of demographics, risk level, and follow-up timeframe. RESULTS: Preemptive testing was found to be cost-effective compared with usual care (ICER $86,227/QALY) at the willingness-to-pay threshold of $100,000/QALY while reactive testing was not (ICER $148,726/QALY). Sensitivity analyses suggested that our cost-effectiveness results were sensitive to longer follow-up, and the age group 45-64 years. CONCLUSION: Compared with usual care, preemptive PGx panel testing was cost-effective in cardiovascular disease management.

Cost-Effectiveness Analysis of Pembrolizumab for Bacillus Calmette-Guérin-Unresponsive Carcinoma In Situ of the Bladder.

PURPOSE: Patients with bacillus Calmette-Guérin-unresponsive carcinoma in situ are treated with radical cystectomy or salvage intravesical chemotherapy. Recently, pembrolizumab was approved for bacillus Calmette-Guérin-unresponsive carcinoma in situ. MATERIALS AND METHODS: We used a decision-analytic Markov model to compare pembrolizumab, salvage intravesical chemotherapy (with gemcitabine-docetaxel induction+monthly maintenance) and radical cystectomy for patients with bacillus Calmette-Guérin-unresponsive carcinoma in situ who are radical cystectomy candidates (index patient 1) or are unwilling/unable to undergo radical cystectomy (index patient 2). The model used a U.S. Medicare perspective with a 5-year time horizon. One-way and probabilistic sensitivity analyses were performed. Incremental cost-effectiveness ratios were compared using a willingness to pay threshold of $100,000/quality-adjusted life year. RESULTS: For index patient 1, pembrolizumab was not cost-effective relative to radical cystectomy (incremental cost-effectiveness ratios $1,403,008/quality-adjusted life year) or salvage intravesical chemotherapy (incremental cost-effectiveness ratios $2,011,923/quality-adjusted life year). One-way sensitivity analysis revealed that pembrolizumab only became cost-effective relative to radical cystectomy with a >93% price reduction. Relative to radical cystectomy, salvage intravesical chemotherapy was cost-effective for time horizons <5 years and nearly cost-effective at 5 years (incremental cost-effectiveness ratios $118,324/quality-adjusted life year). One-way sensitivity analysis revealed that salvage intravesical chemotherapy became cost-effective relative to radical cystectomy if risk of recurrence or metastasis at 2 years was less than 55% or 5.9%, respectively. For index patient 2, pembrolizumab required >90% price reduction to be cost-effective (incremental cost-effectiveness ratios $1,073,240/quality-adjusted life year). Pembrolizumab was cost-effective in 0% of 100,000 microsimulations in probabilistic sensitivity analyses for both index patients. CONCLUSIONS: At its current price, pembrolizumab is not cost-effective for bacillus Calmette-Guérin-unresponsive carcinoma in situ relative to radical cystectomy or salvage intravesical chemotherapy. Although gemcitabine-docetaxel is not cost-effective relative to radical cystectomy at 5 years, further studies may validate its cost-effectiveness if recurrence and metastasis thresholds are met.

Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis with Severe Kidney Disease.

BACKGROUND: Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX). METHODS: A retrospective cohort study of MPO- or PR3-ANCA-positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m2). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared. RESULTS: Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC (n=161) or RTX (n=64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P=0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P=0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P=0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P=0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P=0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P=0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P=0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P=0.330). CONCLUSIONS: The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.

Cost and clinical outcomes of postoperative intensive care unit versus general floor management in head and neck free flap reconstructive surgery patients.

PURPOSE: To compare clinical, surgical, and cost outcomes in patients undergoing head and neck free-flap reconstructive surgery in the setting of postoperative intensive care unit (ICU) against general floor management. METHODS: Retrospective analysis of head and neck free-flap reconstructive surgery patients at a single tertiary academic medical center. Clinical data was obtained from medical records. Cost data was obtained via the Mayo Clinic Rochester Cost Data Warehouse, which assigns Medicare reimbursement rates to all professional billed services. RESULTS: A total of 502 patients were included, with 82 managed postoperatively in the ICU and 420 on the general floor. Major postoperative outcomes did not differ significantly between groups (Odds Ratio[OR] 1.54; p = 0.41). After covariate adjustments, patients managed in the ICU had a 3.29 day increased average length of hospital stay (Standard Error 0.71; p < 0.0001) and increased need for take-back surgery (OR 2.35; p = 0.02) when compared to the general floor. No significant differences were noted between groups in terms of early free-flap complications (OR 1.38;p = 0.35) or late free-flap complications (Hazard Ratio 0.81; p = 0.61). Short-term cost was $8772 higher in the ICU (range = $5640-$11,903; p < 0.01). Long-term cost did not differ significantly. CONCLUSION: Postoperative management of head and neck oncologic free-flap patients in the ICU does not significantly improve major postoperative outcomes or free-flap complications when compared to general floor care, but does increase short-term costs. General floor management may be appropriate when cardiopulmonary compromise is not present.

Systematic review of the evidence on the cost-effectiveness of pharmacogenomics-guided treatment for cardiovascular diseases.

PURPOSE: To examine the evidence on the cost-effectiveness of implementing pharmacogenomics (PGx) in cardiovascular disease (CVD) care. METHODS: We conducted a systematic review using multiple databases from inception to 2018. The titles and abstracts of cost-effectiveness studies on PGx-guided treatment in CVD care were screened, and full texts were extracted. RESULTS: We screened 909 studies and included 46 to synthesize. Acute coronary syndrome and atrial fibrillation were the predominantly studied conditions (59%). Most studies (78%) examined warfarin-CYP2C9/VKORC1 or clopidogrel-CYP2C19. A payer's perspective was commonly used (39%) for cost calculations, and most studies (46%) were US-based. The majority (67%) of the studies found PGx testing to be cost-effective in CVD care, but cost-effectiveness varied across drugs and conditions. Two studies examined PGx panel testing, of which one examined pre-emptive testing strategies. CONCLUSION: We found mixed evidence on the cost-effectiveness of PGx in CVD care. Supportive evidence exists for clopidogrel-CYP2C19 and warfarin-CYP2C9/VKORC1, but evidence is limited in other drug-gene combinations. Gaps persist, including unclear explanation of perspective and cost inputs, underreporting of study design elements critical to economic evaluations, and limited examination of PGx panel and pre-emptive testing for their cost-effectiveness. This review identifies the need for further research on economic evaluations of PGx implementation.

Cost-Effectiveness of Maintenance bacillus Calmette-Guérin for Intermediate and High Risk Nonmuscle Invasive Bladder Cancer.

PURPOSE: While guidelines support the use of maintenance bacillus Calmette-Guérin for patients with intermediate and high risk nonmuscle invasive bladder cancer, in an era of bacillus Calmette-Guérin shortage we explored the cost-effectiveness of maintenance bacillus Calmette-Guérin. MATERIALS AND METHODS: A Markov model compared the cost-effectiveness of maintenance bacillus Calmette-Guérin to surveillance after induction bacillus Calmette-Guérin for intermediate/high risk nonmuscle invasive bladder cancer from a U.S. Medicare perspective. Five-year oncologic outcomes, toxicity rates and utility values were extracted from the literature. Univariable and multivariable sensitivity analyses were conducted. A willingness to pay threshold of $100,000 per quality adjusted life year was considered cost-effective. RESULTS: At 5 years mean costs per patient were $14,858 and $13,973 for maintenance bacillus Calmette-Guérin and surveillance, respectively, with quality adjusted life years of 4.046 for both, making surveillance the dominant strategy. On sensitivity analysis full dose and 1/3 dose maintenance bacillus Calmette-Guérin became cost-effective if the absolute reduction in 5-year progression was greater than 2.1% and greater than 0.76%, respectively. On further sensitivity analysis full dose and 1/3 dose maintenance bacillus Calmette-Guérin became cost-effective when maintenance bacillus Calmette-Guérin toxicity equaled surveillance toxicity. In multivariable sensitivity analyses using 100,000 Monte-Carlo microsimulations, full dose and 1/3 dose maintenance bacillus Calmette-Guérin was cost-effective in 17% and 39% of microsimulations, respectively. CONCLUSIONS: Neither full dose nor 1/3 dose maintenance bacillus Calmette-Guérin appears cost-effective for the entire population of patients with intermediate/high risk nonmuscle invasive bladder cancer. These data support prioritizing maintenance bacillus Calmette-Guérin for the subset of patients with high risk nonmuscle invasive bladder cancer most likely to experience progression, in particular those who tolerated induction bacillus Calmette-Guérin well. Overall, our findings support the American Urological Association policy statement to allocate bacillus Calmette-Guérin for induction rather than maintenance therapy during times of bacillus Calmette-Guérin shortage.