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Introduction Use of the 13-valent pneumococcal conjugate vaccine in nonimmunocompromised adults aged ≥65 years is controversial. Higher-valency conjugate vaccines (15-valent and 20-valent ) are under development; their potential cost effectiveness in older adults is unknown, particularly when potential indirect (herd immunity) effects from childhood vaccination are considered. Methods A Markov model estimated the cost effectiveness of current U.S. recommendations and alternative strategies using currently available and in-development pneumococcal conjugate vaccines in seniors. Separately, strategies using a hypothetical 20-valent vaccine adding the 7 most common disease-causing non–13-valent vaccine serotypes were considered. Sensitivity analyses were performed and alternative scenarios were examined. Data were gathered and the analyses were performed in 2020. Results In analyses considering only existing and in-development vaccines, sole 20-valent vaccine use cost $172,491/quality-adjusted life year gained compared with current U.S. recommendations under baseline assumptions (equal serotype effectiveness and no childhood vaccination indirect effects). Strategies using 15-valent vaccine were more costly and less effective. When 13-valent/20-valent vaccines were assumed ineffective against pneumococcal serotype 3 and 15-valent vaccine was fully effective, 15-valent vaccine cost $237,431/quality-adjusted life year gained. With indirect effects considered, 15-valent or 20-valent vaccine cost >$449,000/quality-adjusted life year gained. When adding hypothetical 20-valent vaccine under baseline assumptions, hypothetical 20-valent vaccine cost $139,348/quality-adjusted life year gained. Conclusions In-development pneumococcal conjugate vaccines may be economically unreasonable in older adults, regardless of serotype effectiveness assumptions, particularly when considering potential indirect effects from use of those vaccines in children. Adult vaccines containing high-risk serotypes not contained in childhood vaccines may be more promising.

Background Currently it remains difficult to identify patients most likely to benefit from radiotherapy (RT) for ductal carcinoma-in-situ (DCIS), thus leading to wide variation in practice patterns. The genomic risk assessment tool DCISionRT (PreludeDX) has been validated to prognosticate recurrence risk and predict RT benefit. We aimed to study the cost-effectiveness analysis comparing DCIS treatments based on DCISionRT testing to traditional clinicopathologic risk factors. Patients and Methods A Markov state transition model was constructed to perform a cost-effectiveness analysis comparing breast-conserving surgery with or without RT using DCISionRT testing vs. traditional clinicopathologic risk factors. Clinical parameters were obtained from clinical trial data and cross-validation studies. Cost data were based on 2019 Medicare reimbursement. Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained comparing DCIS treatments using DCISionRT testing to traditional clinicopathologic risk factors and evaluated with a willingness-to-pay threshold of US$100,000 per QALY gained. To account for uncertainty, 1-way and probabilistic sensitivity analyses were performed. Results Base case analysis showed that DCIS management using DCISionRT testing was a cost-effective strategy, resulting in an ICER of $74,331 per QALY gained compared to clinicopathology-based treatment. Model results were sensitive to a variation of the proportion of genomic-high, low-risk patients receiving RT in DCISionRT testing strategy, and changes in DCISionRT testing cost. Conclusion DCISionRT testing could potentially be a cost-effective strategy compared to traditional decision making for DCIS treatments, optimizing RT benefit based on an accurate recurrence risk assessment.

Introduction Central line-associated bloodstream infections (CLABSIs) lead to significant morbidity and mortality in children with intestinal failure (IF). Ethanol lock prophylaxis (ELP) greatly reduces CLABSI frequency with minimal side effects. However, in the United States, a recently approved orphan drug designation for dehydrated alcohol has greatly increased 70% ethanol cost from about $10/day to $1000/day. We examined the cost-effectiveness of ELP in relation to these changes. Methods We simulated a previously developed IF Markov model over 1 year. Costs were measured in 2020 US dollars and effectiveness in quality-adjusted life-years (QALYs). CLABSI rate with and without ELP was estimated from the largest available comparative observational study. The primary outcome was incremental cost-effectiveness ratio (ICER) between treatments. Secondary outcomes included CLABSI frequency. Sensitivity analyses on all model parameters were performed. Results In the base model, children with IF not using ELP accumulated $131,815 in costs and 0.32 QALYs per patient compared with $437,884 and 0.33 QALYs per patient in those using ELP. The ICER was nearly $17 million/QALY gained. ELP resulted in a 40% reduction in CLABSI frequency. ELP became cost-effective at $68/day and cost-saving at $63/day. Sensitivity analysis identified no other plausible parameter variation to reach the benchmark of $100,000/QALY gained. Conclusions At the current price, ELP is not cost-effective for CLABSI prevention in children with IF in the United States. This study highlights the critical need for the approval of an affordable lock therapy option to prevent CLABSIs in these children.

OBJECTIVE: Patient–oncologist therapeutic alliance is a foundation of quality cancer care, although there is limited research demonstrating its relationship with patient outcomes. We investigated the relationship between therapeutic alliance and patient quality of life with a secondary goal of determining whether the association varied by patients’ baseline level of psychological distress. METHODS: Cross-sectional analysis of baseline data from a randomized clinical trial of 672 patients with advanced cancer participating in a primary palliative care intervention trial. Patients completed baseline self-reported measures of therapeutic alliance (The Human Connection Scale, range: 16–64), overall quality of life (Functional Assessment of Cancer Therapy—Palliative Care, range: 0–184), and psychological distress (Hospital Anxiety and Depression Scale, range: 0–42). First, we determined the relationship between therapeutic alliance and quality of life using multivariable regression adjusting for confounders. We then examined if psychological distress was an effect modifier in this relationship by adding interaction effects of depression and anxiety symptoms on therapeutic alliance into the regression model. RESULTS: Patients reported high levels of therapeutic alliance (56.4 ± 7.4) and moderate quality of life (130.3 ± 25.5). Stronger therapeutic alliance was associated with better quality of life after adjusting for other confounding factors (β = 3.7, 95% confidence interval = 2.1, 5.3, p < 0.01). The relationship between therapeutic alliance and quality of life was generally consistent regardless of psychological distress. CONCLUSIONS: Collaborative, trusting relationships between patients with advanced cancer and their oncologists are associated with better patient quality of life. Future research should investigate the causal, longitudinal nature of these relationships.

Biliary atresia (BA) is the leading indication to perform a pediatric liver transplantation (LT). Timely hepatoportoenterostomy (HPE) attempts to interrupt the natural history and allow for enteric bile flow; however, most patients who are treated with HPE require LT by the age of 10 years. We determined the cost-effectiveness of foregoing HPE to perform primary LT (pLT) in children with BA compared with standard-of-care HPE management. A Markov model was developed to simulate BA treatment over 10 years. Costs were measured in 2018 US dollars and effectiveness in life-years (LYs). The primary outcome was incremental cost-effectiveness ratio (ICER) between treatments. Model parameters were derived from the literature. In the base model, we assumed similar LT outcomes after HPE and pLT. Sensitivity analyses on all model parameters were performed, including a scenario in which pLT led to 100% patient and graft survival after LT. Children undergoing HPE accumulated $316,692 in costs and 8.17 LYs per patient. Children undergoing pLT accumulated $458,059 in costs and 8.24 LYs per patient, costing $1,869,164 per LY gained compared with HPE. With parameter variation over plausible ranges, only post-HPE and post-LT costs reduced the ICER below a typical threshold of $100,000 per LY gained. On probabilistic sensitivity analysis, 93% of iterations favored HPE at that threshold. With 100% patient and graft survival after pLT, pLT cost $283,478 per LY gained. HPE is more economically favorable than pLT for BA. pLT is unfavorable even with no graft or patient loss. The ability to predict those patients who may experience high costs after HPE or low costs after LT may help identify those patients for whom pLT could be considered.

PURPOSE: Providers have cited fear of taking away hope from patients as one of the principal reasons for deferring advance care planning (ACP). However, research is lacking on the relationship between ACP and hope. We sought to investigate the potential association between ACP and hope in advanced cancer. METHODS: This is a cross-sectional analysis of baseline data from a primary palliative care intervention trial. All patients had advanced solid cancers. Three domains of ACP were measured using validated questions to assess discussion with oncologists about end-of-life (EOL) planning, selection of a surrogate decision maker, and completion of an advance directive. Hope was measured using the Hearth Hope Index (HHI). Multivariable regression was performed, adjusting for variables associated with hope or ACP. RESULTS: A total of 672 patients were included in this analysis. The mean age was 69.3 ± 10.2 years; 54% were female, and 94% were White. Twenty percent of patients (132 of 661) reported having a discussion about EOL planning, 51% (342 of 668) reported completing an advance directive, and 85% (565 of 666) had chosen a surrogate. There was no difference in hope between patients who had and had not had an EOL discussion (adjusted mean difference in HHI, 0.55; P = .181 for adjusted regression), chosen a surrogate (adjusted HHI difference, 0.31; P = .512), or completed an advance directive (adjusted HHI difference, 0.11; P = .752). CONCLUSION: In this study, hope was equivalent among patients who had or had not completed 3 important domains of ACP. These findings do not support concerns that ACP is associated with decreased hope for patients with advanced cancer.

Hip fractures are associated with significant morbidity and mortality in smokers with lung disease, but whether lung-specific factors are associated with fracture risk is unknown. Our goal was to determine whether lung-specific factors associate with incident hip fracture and improve risk discrimination of traditional fracture risk models in smokers. The analysis consisted of a convenience sample of 9187 current and former smokers (58,477 participant follow-up years) participating in the Genetic Epidemiology of chronic obstructive pulmonary disease (COPD) longitudinal observational cohort study. Participants were enrolled between 2008 and 2011 with follow-up data collection through July 2018. Traditional risk factors associated with incident hip fracture (n = 361) included age, female sex, osteoporosis, prevalent spine and hip fracture, rheumatoid arthritis, and diabetes. Lung-specific risk factors included post-bronchodilator percent forced expiratory volume in 1 s (FEV1 %) predicted (OR, 0.95; 95% CI, 0.92-0.99 for each 10% increase), Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification (OR, 1.09; 95% CI, 1.002-1.19 for each higher stage), presence of CT-determined emphysema (OR, 1.34; 95% CI, 1.06-1.69), symptom scores (OR, 1.10; 95% CI, 1.03-1.19 for each higher unit score), 6-min walk distance (OR, 0.92; 95% CI, 0.90-0.95 for each 30-m increase), body mass index, airflow obstruction, dyspnea, and exercise (BODE) index (OR, 1.07; 95% CI, 1.01-1.13 for each higher unit score), total exacerbations (OR, 1.13; 95% CI, 1.10-1.16 per exacerbation), and annual exacerbations (OR, 1.37; 95% CI, 1.21-1.55 per exacerbation). In multivariable modeling, age, black race, osteoporosis, prevalent hip and spine fracture, rheumatoid arthritis, and diabetes were associated with incident hip fracture. The presence of emphysema, 6-min walk distance, and total number of exacerbations added to traditional models improved risk discrimination (integrated discrimination improvement [IDI] values 0.001 [95% CI, 0.0003-0.002], 0.001 [95% CI, 0.0001-0.002], and 0.008 [95% CI, 0.003-0.013], corresponding to relative IDIs of 12.8%, 6.3%, and 34.6%, respectively). These findings suggest that the incorporation of lung-specific risk factors into fracture risk assessment tools may more accurately predict fracture risk in smokers. © 2020 American Society for Bone and Mineral Research.

Background Children with chronic intestinal failure have a high prevalence of anemia, commonly from iron deficiency, leading to frequent blood transfusions. No current guideline exists for iron supplementation in these children. In this analysis, we evaluate the effectiveness and the cost-effectiveness of using parenteral, enteral, and no iron supplementation to reduce blood transfusions. Methods We created a microsimulation model of pediatric intestinal failure over a 1-year time horizon. Model outcomes included cost (US dollars), blood transfusions received, and hemoglobin trend. Strategies tested included no supplementation, daily enteral supplementation, and monthly parenteral supplementation. We estimated parameters for the model using an institutional cohort of 55 patients. Model parameters updated each 1-month cycle using 2 regressions. A multivariate mixed-effects linear regression estimated hemoglobin values at the next month based on data from the prior month. A mixed-effects logistic regression on hemoglobin predicted the probability of receiving a blood transfusion in a given month. Results Compared with no supplementation, both enteral and parenteral iron supplementation reduced blood transfusions required per patient by 0.3 and 0.5 transfusions per year, respectively. Enteral iron cost $34 per avoided blood transfusion. Parenteral iron cost an additional $6600 per avoided blood transfusion compared with enteral iron. Conclusions We found both parenteral and enteral iron to be effective at reducing blood transfusions. The cost of enteral iron makes it the desired choice in patients who can tolerate it. Future work should aim to identify which subpopulations of patients may benefit most from one strategy over the other.

Background/objectives Recently revised vaccination recommendations for US adults, aged 65 years and older, include both 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13), with PCV13 now recommended for immunocompetent older people based on shared decision making. The public health impact and cost-effectiveness of this recommendation or of pneumococcal vaccine uptake improvement interventions are unclear. Design Markov decision analysis. Setting and participants Hypothetical 65-year-old general and black population cohorts. Intervention Current pneumococcal vaccination recommendations for US older people, an alternative policy omitting PCV13 in immunocompetent older people, and vaccine uptake improvement programs. Results The current pneumococcal vaccination recommendation was the most effective strategy, but afforded slight public health benefits compared to an alternative (PPSV23 for all older people plus PCV13 for the immunocompromised) and cost greater than $750 000 per quality-adjusted life-year (QALY) gained in either population group with a vaccine uptake improvement program (absolute uptake increase = 12.3%; cost = $1.78/eligible patient) in place. The alternative strategy was more economically favorable, but cost greater than $100 000/QALY in either population, with or without an uptake intervention. Results were robust in sensitivity analyses; however, in black older people, the alternative strategy with an uptake program was most likely to be favored in probabilistic sensitivity analyses at a $150 000/QALY gained threshold. Conclusion Current pneumococcal vaccination recommendations for US older people are economically unfavorable compared to an alternative strategy omitting PCV13 in the immunocompetent. The alternative recommendation with an uptake improvement program may be economically reasonable in black population analyses and could be worth considering as a population-wide recommendation if mitigating racial disparities is a priority. J Am Geriatr Soc 68:1271-1278, 2020.

Background Adults with short bowel syndrome have a high mortality and significant morbidity due to unsuccessful attempts at rehabilitation that necessitate chronic use of parenteral nutrition (PN). Teduglutide is a novel therapy that promotes intestinal adaptation to improve rehabilitation but with a price >$400,000/y. Objective The current study evaluated the cost-effectiveness of using teduglutide in US adult patients with short bowel syndrome. Methods A Markov model evaluated the costs (in US dollars) and effectiveness (in quality-adjusted life years, or QALYs) of treatment compared with no teduglutide use, with a presumed starting age of 40 y. Parameters were obtained from published data or estimation. The primary effect modeled was the increased likelihood of reduced PN days per week when using teduglutide, leading to greater quality of life and lower PN costs. Sensitivity analyses were performed on all model parameters. Results In the base scenario, teduglutide cost $949,910/QALY gained. In 1-way sensitivity analyses, only reducing teduglutide cost decreased the cost/QALY gained to below the typical threshold of $100,000/QALY gained. Specifically, teduglutide cost would need to be reduced by >65% for it to reach the threshold value. Probabilistic sensitivity analysis favored no teduglutide use in 80% of iterations at a $100,000/QALY threshold. However, teduglutide therapy was cost-saving in 13% of model iterations. Conclusions Teduglutide does not meet a traditional cost-effectiveness threshold as treatment for PN reduction in adult patients with short bowel syndrome compared with standard intestinal rehabilitation. Subpopulations that demonstrate maximum benefit could be cost-saving, and complete nonuse could lead to financial loss. Teduglutide becomes economically reasonable only if its cost is substantially reduced.

Background Symptomatic hypocalcemia is a common complication of total thyroidectomy. Management strategies include responsive treatment initiation for symptoms or prevention by routine or parathyroid hormone-directed calcium supplementation. The comparative cost-effectiveness of even the most often utilized strategies is unclear. Methods A Markov cohort model was created to compare routine supplementation with calcium alone (RS), postoperative parathyroid hormone-based selective supplementation with calcium and calcitriol (SS), and no supplementation (NS) in asymptomatic patients. Patients could remain asymptomatic or develop symptomatic hypocalcemia, managed with outpatient oral supplementation or intravenous calcium infusion and administered either inpatient or outpatient. Effectiveness was measured in quality-adjusted life years. Sensitivity analyses were performed to test model parameter assumptions. Results RS was the preferred strategy, costing $329/patient and resulting in 0.497 quality-adjusted life years, which was only marginally better compared to SS ($373 for 0.495 quality-adjusted life years). NS was most costly at $4,955 for 0.491 quality-adjusted life years. Preference for RS over SS was sensitive to the probability of developing symptoms and the probability of symptom treatment with intravenous supplementation. On probabilistic sensitivity analysis, RS was preferred in 75.4% of scenarios. Conclusion After total thyroidectomy, a preventative calcium supplementation strategy should be strongly considered. In this data-driven theoretical model, RS was the least costly option and resulted in an incremental gain in quality-adjusted life years.

INTRODUCTION: In US adults aged

Introduction Tradeoffs exist between efforts to increase influenza vaccine uptake, including early season vaccination, and potential decreased vaccine effectiveness if protection wanes during influenza season. U.S. older adults increasingly receive vaccination before October. Influenza illness peaks vary from December to April. Methods A Markov model compared influenza likelihood in older adults with (1) status quo vaccination (August–May) to maximize vaccine uptake or (2) vaccination compressed to October–May (to decrease waning vaccine effectiveness impact). The Centers for Disease Control and Prevention data were used for influenza incidence and vaccination parameters. Prior analyses showed that absolute vaccine effectiveness decreased by 6%–11% per month, favoring later season vaccination. However, compressed vaccination could decrease overall vaccine uptake. Influenza incidence was based on average monthly incidence with earlier and later peaks also examined. Influenza strain distributions from two seasons were modeled in separate scenarios. Sensitivity analyses were performed to test result robustness. Data were collected and analyzed in 2018. Results Compressed vaccination would avert ≥11,400 influenza cases in older adults during a typical season if it does not decrease vaccine uptake. However, if compressed vaccination decreases vaccine uptake or there is an early season influenza peak, more influenza can result. In probabilistic sensitivity analyses, compressed vaccination was never favored if it decreased absolute vaccine uptake by >5.5% in any scenario; when influenza peaked early, status quo vaccination was favored. Conclusions Compressed vaccination could decrease waning vaccine effectiveness and decrease influenza cases in older adults. However, this positive effect is negated when early season influenza peaks occur and diminished by decreased vaccine uptake that could occur with shortening the vaccination season.

In the U.S., pneumococcal polysaccharide vaccine (PPSV23) uptake among high-risk adults aged

Background The COVID-19 pandemic is causing declines in childhood immunization rates. We examined potential COVID-19-related changes in pediatric 13-valent pneumococcal conjugate vaccine (PCV13) use, subsequent impact on childhood and adult pneumococcal disease rates, and how those changes might affect the favorability of PCV13 use in non-immunocompromised adults aged ≥65 years. Methods A Markov model estimated pediatric disease resulting from decreased PCV13 use in children aged 53% increase in pneumococcal disease was required to favor PCV13 use in non-immunocompromised seniors at a $200,000 per quality-adjusted life-year gained threshold, which corresponded to absolute decreases in pediatric PCV13 vaccination of >50% over a 2-year period. In sensitivity analyses, senior PCV13 vaccination was unfavorable if absolute decreases in pediatric PCV13 receipt were within plausible ranges, despite model assumptions favoring PCV13 use in seniors. Conclusion COVID-19-related decreases in pediatric PCV13 use would need to be both substantial and prolonged to make heightened PCV13 use in non-immunocompromised seniors economically favorable.

Background Pneumococcal vaccination policy for US adults is evolving, but previous research has shown that programs to increase vaccine uptake are economically favorable, despite parameter uncertainty. Using value of information (VOI) analysis and prior analyses, we examine the value of further research on vaccine uptake program parameters. Methods In US 50–64-year-olds, current vaccine recommendations with and without an uptake program were analyzed. In older adults, current recommendations and an alternative strategy (polysaccharide vaccine for all, adding conjugate vaccine only for the immunocompromised) with and without uptake programs were examined. Uptake program parameters were derived from a clinical trial (absolute uptake increase 12.3% [range 0–25%], per-person cost $1.78 [range $0.70–$2.26]), with other parameters obtained from US databases. VOI analyses incorporated probabilistic sensitivity analysis outputs into R-based regression techniques. Results In 50–64-year-olds, an uptake program cost $54,900/QALY gained compared to no uptake program. For ages ≥65, the program cost $287,000/QALY gained with the alternative strategy and $765,000/QALY with current recommendations. In younger adults, population-level expected value of perfect information (EVPI) was $59.7 million at $50,000/QALY gained and $2.8 million at $100,000/QALY gained. In older adults, EVPI values ranged from ~$1 million to $34.5 million at $100,000 and $200,000/QALY thresholds. The population expected value of partial perfect information (EVPPI) for combined uptake program cost and uptake improvement parameters in the younger population was $368,700 at $50,000/QALY and $43,900 at $100,000/QALY gained thresholds. In older adults, population EVPPI for vaccine uptake program parameters was $0 at both thresholds, reaching a maximum value of $445,000 at a $225,000/QALY threshold. Other model parameters comprised larger components of the global EVPI. Conclusion VOI results do not support further research on pneumococcal vaccine uptake programs in adults at commonly cited US cost-effectiveness benchmarks. Further research to reduce uncertainty in other aspects of adult pneumococcal vaccination is justifiable.

Background PEG-asparaginase is critical in pediatric acute lymphoblastic leukemia (ALL) therapy but is highly immunogenic. Severe allergic reactions lead to substitution of further PEG-asparaginase with Erwinia. Erwinia is associated with more frequent dosing, increased expense, and limited availability. Premedication may reduce rates of allergic reactions. Procedures This Markov model evaluated the cost-effectiveness of three strategies: premedication plus therapeutic drug monitoring (TDM), TDM alone, and no premedication or TDM. We modeled two scenarios: a standard-risk (SR) B-ALL patient receiving two asparaginase doses and a high-risk (HR) patient receiving seven asparaginase doses. The model incorporated costs of asparaginase, premedication, TDM and clinic visits, and lost parental wages associated with each additional Erwinia dose. We incorporated a five-year time horizon with a societal perspective. Outcomes were Erwinia substitutions avoided and differences in quality-adjusted life years (QALYs). Probabilistic and one-way sensitivity analyses evaluated model uncertainty. Results In both scenarios, premedication was the least costly strategy. In SR and HR scenarios, premedication with monitoring resulted in 8% and 7% fewer changes to Erwinia compared with monitoring alone and 3% and 2% fewer changes compared with no premedication/monitoring, respectively. Premedication resulted in the most QALYs gained in the SR patients. Individual variation of model inputs did not change premedication/monitoring favorability for either scenario. In probabilistic sensitivity analyses, premedication/monitoring was favored in >87% of iterations in both scenarios. Conclusion Compared with other strategies, premedication use and asparaginase level monitoring in children with B-ALL is potentially cost-saving.

Clostridioides difficile is a leading cause of nosocomial infection responsible for significant morbidity and mortality with limited options for therapy. Secreted C. difficile toxin B (TcdB) is a major contributor to disease pathology, and select TcdB-specific Abs may protect against disease recurrence. However, the high frequency of recurrence suggests that the memory B cell response, essential for new Ab production following C. difficile reexposure, is insufficient. We therefore isolated TcdB-specific memory B cells from individuals with a history of C. difficile infection and performed single-cell deep sequencing of their Ab genes. Herein, we report that TcdB-specific memory B cell–encoded antibodies showed somatic hypermutation but displayed limited isotype class switch. Memory B cell–encoded mAb generated from the gene sequences revealed low to moderate affinity for TcdB and a limited ability to neutralize TcdB. These findings indicate that memory B cells are an important factor in C. difficile disease recurrence., The C. difficile toxin-specific human memory B cell repertoire encodes low-affinity, non-neutralizing antibodies.

Background Infections are the leading cause of therapy-related mortality in pediatric patients with acute myeloid leukemia (AML). Although effectiveness of levofloxacin antibacterial prophylaxis in oncology patients is recognized, its cost-effectiveness is unknown. This study evaluated epidemiologic data regarding levofloxacin use and the cost-effectiveness of this strategy as the cost per bacteremia episode, intensive care unit (ICU) admission, and death avoided in children with AML. Procedure A retrospective cohort study using the Pediatric Health Information System (PHIS) database compared demographic and clinical characteristics and receipt of levofloxacin prophylaxis in children with AML admitted for chemotherapy from January 1, 2014, through December 31, 2018. We then developed a decision analysis model in this population that compared costs associated with bacteremia, ICU admission, or death secondary to bacteremia to levofloxacin prophylaxis cost from a healthcare perspective. Time horizon is one chemotherapy cycle. Probabilistic and one-way sensitivity analyses evaluated model uncertainty. Results Prophylaxis cost $8491 per bacteremia episode prevented compared with an average added hospital cost of $119 478. Prophylaxis cost $81 609 per ICU admission avoided, compared with an average added hospital cost of $94 181. Prophylaxis cost $220 457 per death avoided. In sensitivity analysis, at a willingness-to-pay threshold of $100 000 per bacteremia episode avoided, prophylaxis remained cost-effective in 94.6% of simulations. Prophylaxis use was more common in recent years in patients with relapsed disease and with chemotherapy regimens considered more intensive. Conclusion Prophylaxis is cost-effective in preventing bacterial infections in patients with AML. Findings support increased use in patients considered at high risk of bacterial infection secondary to myelosuppression.

Objective: Antimicrobial prophylaxis for children with vesicoureteral reflux (VUR) reduces recurrences of urinary tract infection (UTI) but requires daily antimicrobials for extended periods. We used a cost-utility model to evaluate whether the benefits of antimicrobial prophylaxis outweigh its risks and, if so, to investigate whether the benefits and risks vary according to grade of VUR. Methods: We compared the cost per quality-adjusted life-year (QALY) gained in four treatment strategies in children aged

Background Warfarin use for stroke prevention in atrial fibrillation (AF) patients with chronic kidney disease is debated. Apixaban was shown to be safer than warfarin, with superior reduction in the risk of stroke, systemic embolism, mortality, and major bleeding irrespective of kidney function. Objectives To evaluate the cost-utility of apixaban compared with warfarin in AF patients at different levels of kidney function. Methods A Markov model was used to estimate the cost effectiveness of apixaban compared with warfarin in AF patients at three levels of kidney function: estimated glomerular filtration rate (eGFR) of more than 80 ml/min, 50 to 80 ml/min, and 50 ml/min or less. Event rates and associated utilities were obtained from previous literature. The model adopted the US health care system perspective, with hospitalization costs extracted from the Healthcare and Utilization Project. Treatment costs were obtained from official price lists. Univariate and probabilistic sensitivity analyses were performed to evaluate the robustness of results. Results Apixaban was a dominant treatment strategy compared with warfarin in AF patients with eGFR levels of 50 ml/min or less and 50 to 80 ml/min. In patients with an eGFR of more than 80 ml/min, apixaban was cost-effective compared with warfarin, costing $6307 per quality-adjusted life-year gained. Results were consistent assuming anticoagulant discontinuation after major bleeding events. Compared with dabigatran and rivaroxaban, apixaban was the only cost-effective anticoagulant strategy relative to warfarin in both mild and moderate renal impairment settings. Conclusions Apixaban is a favorably cost-effective alternative to warfarin in AF patients with normal kidney function and potentially cost-saving in those with renal impairment.

Introduction In 2012 the American Urological Association released asymptomatic microhematuria guidelines that resulted in criticisms of overtreatment and improper risk stratification, particularly in women. Specifically, concerns have been raised regarding overtreatment in low risk female patients. Evaluating trade-offs between cost and effectiveness can provide valuable insight into the applicability of these guidelines in different patient populations. Methods We used a decision analysis model to estimate the cost-effectiveness of a microhematuria evaluation according to the 2012 guidelines, using varying strategies according to whether confirmatory urinalysis was obtained and stratifying by sex. Where applicable, model parameter values were from prospective observational trials. Costs were estimated based on U.S. databases. Results Up-front evaluation costs 20% more than confirmatory evaluation ($792.76 vs $662.65). When considering costs per quality adjusted life-year, up-front evaluation costs $125,105 per quality adjusted life-year gained in the overall population. When stratified by sex, up-front evaluation costs $94,777 per quality adjusted life-year gained in male patients and $390,954 per quality adjusted life-year gained in female patients. At a cost-effectiveness threshold of $100,000 per quality adjusted life-year, up-front evaluation is cost-effective in male but not in female patients or the overall population compared to a delayed evaluation. Conclusions Up-front microhematuria evaluation may be economically justifiable in men but not in women or in the overall population. Sex specific risk stratification and confirmatory urinalyses may have a role in populations with a lower risk of urinary tract malignancy.

Gene therapy provides a potential phenotypic cure for hemophilia, yet the cost of this novel treatment is high, tempering enthusiasm and raising questions regarding cost vs benefit. To evaluate the cost-effectiveness of gene therapy treatment of severe hemophilia A compared with prophylaxis with factor VIII (FVIII), we developed a Markov state-transition model to estimate the costs and effectiveness of severe hemophilia A treatment strategies from a United States health care system perspective. Quality-adjusted life-years (QALYs) were the effectiveness measure. In the base case, hypothetical cohorts of 30-year-old patients received gene therapy or FVIII prophylaxis. We obtained model probabilities and utilities from the literature and costs from Medicare reimbursement data. One-way and probabilistic sensitivity analyses were performed to test the robustness of results. Over a 10-year time horizon, total per-person gene therapy strategy costs were $1.0M and resulted in 8.33 QALYs, whereas prophylaxis cost $1.7M and resulted in 6.62 QALYs. Thus, gene therapy dominated prophylaxis (costs less and was more effective). Gene therapy remained dominant unless initial costs exceeded $1.6M and were$100 000 per 1 QALY gained compared with prophylaxis if initial costs were$1.7M. Results were not sensitive to variation of all other parameters over clinically plausible ranges. In a probabilistic sensitivity analysis simultaneously varying all parameters 3000 times over parameter distributions, gene therapy was dominant in 92% of model iterations. Treatment of severe hemophilia A with gene therapy is likely to be cost-saving or cost-effective compared with FVIII prophylaxis.

Objective To better understand the role of B cells, the potential mechanisms responsible for their aberrant activation, and the production of autoantibodies in the pathogenesis of Sjogren's syndrome (SS), this study explored patterns of selection pressure and sites of N-glycosylation acquired by somatic mutation (acN-glyc) in the IgG variable (V) regions of antibody-secreting cells (ASCs) isolated from the minor salivary glands of patients with SS and non-SS control patients with sicca symptoms. Methods A novel method to produce and characterize recombinant monoclonal antibodies (mAb) from single cell-sorted ASC infiltrates was applied to concurrently probe expressed genes (all heavy- and light-chain isotypes as well as any other gene of interest not related to immunoglobulin) in the labial salivary glands of patients with SS and non-SS controls. V regions were amplified by reverse transcription-polymerase chain reaction, sequenced, and analyzed for the incidence of N-glycosylation and selection pressure. For specificity testing, the amplified regions were expressed as either the native mAb or mutant mAb lacking the acN-glyc motif. Protein modeling was used to demonstrate how even an acN-glyc site outside of the complementarity-determining region could participate in, or inhibit, antigen binding. Results V-region sequence analyses revealed clonal expansions and evidence of secondary light-chain editing and allelic inclusion, of which neither of the latter two have previously been reported in patients with SS. Increased frequencies of acN-glyc were found in the sequences from patients with SS, and these acN-glyc regions were associated with an increased number of replacement mutations and lowered selection pressure. A clonal set of polyreactive mAb with differential framework region 1 acN-glyc motifs was also identified, and removal of the acN-glyc could nearly abolish binding to autoantigens. Conclusion These findings support the notion of an alternative mechanism for the selection and proliferation of some autoreactive B cells, involving V-region N-glycosylation, in patients with SS.

Advancements in chromatographic separation are critical to in-depth top-down proteomics of complex intact protein samples. Reversed-phase liquid chromatography is the most prevalent technique for top-down proteomics. However, in cases of high complexities and large dynamic ranges, 1D-RPLC may not provide sufficient coverage of the proteome. To address these challenges, orthogonal separation techniques are often combined to improve the coverage and the dynamic range of detection. In this study, a “salt-free” high-pH RPLC was evaluated as an orthogonal dimension of separation to conventional low-pH RPLC with top-down MS. The RPLC separations with low-pH conditions (pH=2) and high-pH conditions (pH=10) were compared to confirm the good orthogonality between high-pH and low-pH RPLC’s. The offline 2D RPLC-RPLC-MS/MS analyses of intact E. coli samples were evaluated for the improvement of intact protein identifications as well as intact proteoform characterizations. Compared to the 163 proteins and 328 proteoforms identified using a 1D RPLC-MS approach, 365 proteins and 886 proteoforms were identified using the 2D RPLC-RPLC top-down MS approach. Our results demonstrate that the 2D RPLC-RPLC top-down approach holds great potential for in-depth top-down proteomics studies by utilizing the high resolving power of RPLC separations and by using mass spectrometry compatible buffers for easy sample handling for online MS analysis.

Context: Intervention fidelity is a critical component of behavioral research that has received inadequate attention in palliative care studies. With increasing focus on the need for palliative care models that can be widely disseminated and delivered by non-specialists, rigorous yet pragmatic strategies for training interventionists and maintaining intervention fidelity are needed. Objectives: (1) Describe components of a plan for interventionist training and monitoring and maintaining intervention fidelity as part of a primary palliative care trial (CONNECT) and (2) present data about perceived training effectiveness and delivery of key intervention content. Methods: Post-training evaluations, visit checklists, and visit audio-recordings. Results: Data were collected from June, 2016 through April, 2017. We include procedures for (1) identification, training and certification of oncology nurses as CONNECT interventionists; (2) monitoring intervention delivery; and (3) maintaining intervention quality. All nurses (N = 14) felt prepared to deliver key competencies after a 3-day in-person training. As assessed via visit checklists, interventionists delivered an average of 94% (SD 13%) of key content for first intervention visits and 85% (SD 14%) for subsequent visits. As assessed via audio-recordings, interventionists delivered an average of 85% (SD 8%) of key content for initial visits and 85% (SD 12%) for subsequent visits. Conclusion: We present a 3-part strategy for training interventionists and monitoring and maintaining intervention delivery in a primary palliative care trial. Training was effective in having nurses feel prepared to deliver primary palliative care skills. As assessed via nursing checklists and visit audio-recordings, intervention fidelity was high. Keywords: Oncology nursing, Primary palliative care, Intervention fidelity, CONNECT

Background Annual influenza vaccination is a key to preventing widespread influenza infections. Recent reports of influenza vaccine effectiveness (VE) indicate that vaccination in prior years may reduce VE in the current season, suggesting vaccine interference. The purpose of this study is to evaluate the potential effect of repeat influenza vaccinations in the presence of vaccine interference. Methods Using literature-based parameters, an age-structured influenza equation-based transmission model was used to determine the optimal vaccination strategy, while considering the effect of varying levels of interference. Results The model shows that, even in the presence of vaccine interference, revaccination reduces the influenza attack rate and provides individual benefits. Specifically, annual vaccination is a favored strategy over vaccination in alternate years, as long as the level of residual protection is less than 58% or vaccine interference effect is minimal. Furthermore, the negative impact of vaccine interference may be offset by increased vaccine coverage levels. Conclusions Even in the presence of potential vaccine interference, our work provides a population-level perspective on the potential merits of repeated influenza vaccination. This is because repeat vaccination groups had lower attack rates than groups that omitted the second vaccination unless vaccine interference was at very high, perhaps implausible, levels.

Drug-coated balloons (DCBs) may increase durability of endovascular treatment of superficial femoral artery (SFA) disease while avoiding stent-related risks. The purpose of this study was to use meta-analytic data of DCB studies to compare the cost-effectiveness of potential SFA treatments: DCB, drug-eluting stent (DES), plain old balloon angioplasty (POBA), or bare-metal stent (BMS).A search for randomized controlled trials comparing DCB with POBA for treatment of SFA disease was performed. Hazard ratios were extracted to account for the time-to-event primary outcome of target lesion revascularization. Odds ratios were calculated for the secondary outcomes of primary patency (PP) and major amputation. Incorporating pooled data from the meta-analysis, cost-effectiveness analysis, assuming a payer perspective, used a decision model to simulate patency at 1 year and 2 years for each index treatment modality: POBA, BMS, DCB, or DES. Costs were based on current Medicare outpatient reimbursement rates.Eight studies (1352 patients) met inclusion criteria for meta-analysis. DCB outperformed POBA with respect to target lesion revascularization over time (pooled hazard ratio, 0.41; P .001). Risk of major amputation at 12 months was not significantly different between groups. There was significantly improved 1-year PP in the DCB group compared with POBA (pooled odds ratio, 3.30; P .001). In the decision model, the highest PP at 1 year was seen in the DES index therapy strategy (79%), followed by DCB (74%), BMS (71%), and POBA (64%). With a baseline cost of $9259.39 per patent limb at 1 year in the POBA-first group, the incremental cost per patent limb for each other strategy compared with POBA was calculated: $14,136.10/additional patent limb for DCB, $38,549.80/limb for DES, and $59,748,85/limb for BMS. The primary BMS option is dominated by being more expensive and less effective than DCB. Compared directly with DCB, DES costs $87,377.20 per additional patent limb at 1 year. Based on the projected PP at 1 year in the decision model, the number needed to treat for DES compared with DCB is 20. At current reimbursement, the use of more than two DCBs per procedure would no longer be cost-effective compared with DES. At 2 years, DCB emerges as the most cost-effective index strategy with the lowest overall cost and highest patency rates over that time horizon.Current data and reimbursements support the use of DCB as a cost-effective strategy for endovascular intervention in the SFA; any additional effectiveness of DES comes at a high price. Use of more than one DCB per intervention significantly decreases cost-effectiveness.

Introduction Decreased live attenuated influenza vaccine (LAIV) effectiveness in the U.S. prompted the Advisory Committee on Immunization Practices in August 2016 to recommend against this vaccine’s use. However, overall influenza uptake increases when LAIV is available and, unlike the U.S., LAIV has retained its effectiveness in other countries. These opposing countercurrents create a dilemma. Methods To examine the potential consequences of the decision to not recommend LAIV, which may result in decreased influenza vaccination coverage in the U.S. population, a Markov decision analysis model was used to examine influenza vaccination options in U.S. children aged 2–8 years. Data were compiled and analyzed in 2016. Results Using recently observed low LAIV effectiveness values, fewer influenza cases will occur if LAIV is not used compared with having LAIV as a vaccine option. However, having the option to use LAIV may be favored if LAIV effectiveness returns to prior levels or if the absence of vaccine choice substantially decreases overall vaccine uptake. Conclusions Continued surveillance of LAIV effectiveness and influenza vaccine uptake is warranted, given their importance in influenza vaccination policy decisions.

Objective To perform a cost-minimization study comparing the supraorbital and endoscopic endonasal (EEA) approach with or without craniotomy for the resection of olfactory groove meningiomas (OGMs). Methods We built a decision tree using probabilities of gross total resection (GTR) and cerebrospinal fluid (CSF) leak rates with the supraorbital approach versus EEA with and without additional craniotomy. The cost (not charge or reimbursement) at each “stem” of this decision tree for both surgical options was obtained from our hospital's finance department. After a base case calculation, we applied plausible ranges to all parameters and carried out multiple 1-way sensitivity analyses. Probabilistic sensitivity analyses confirmed our results. Results The probabilities of GTR (0.8) and CSF leak (0.2) for the supraorbital craniotomy were obtained from our series of 5 patients who underwent a supraorbital approach for the resection of an OGM. The mean tumor volume was 54.6 cm 3 (range, 17–94.2 cm 3 ). Literature-reported rates of GTR (0.6) and CSF leak (0.3) with EEA were applied to our economic analysis. Supraorbital craniotomy was the preferred strategy, with an expected value of $29,423, compared with an EEA cost of $83,838. On multiple 1-way sensitivity analyses, supraorbital craniotomy remained the preferred strategy, with a minimum cost savings of $46,000 and a maximum savings of $64,000. Probabilistic sensitivity analysis found the lowest cost difference between the 2 surgical options to be $37,431. Conclusion Compared with EEA, supraorbital craniotomy provides substantial cost savings in the treatment of OGMs. Given the potential differences in effectiveness between approaches, a cost-effectiveness analysis should be undertaken.

Background Evidence supports two methods for preventing dental caries lesions in children: pit and fissure sealants (PFS) and fluoride varnishes (FV). The aim of this study was to compare the cost-effectiveness of these two strategies in preventing dental caries lesions on the occlusal surface of the first permanent molar in children. Methods A Markov model was used to simulate the progression of dental caries on the occlusal surface of the first permanent molar in a hypothetical cohort of children over a 9-year period. Transition probabilities were extracted from the published literature and costs were calculated from a payer's perspective. Two scenarios were evaluated based on the probability of replacing a failed PFS. Sensitivity analysis was performed to test the robustness of the model. Results Over the 9-year study period PFS were less expensive and more effective than FV in preventing occlusal dental caries lesions. For the base case scenario the probability of replacing a failed PFS was 100 percent and the Incremental Cost-Effectiveness Ratio (ICER) for PFS was $156.87 per first episode of caries lesion averted. For the second scenario, the probability of replacing a failed PFS was lowered to 50 percent. Here, the ICER dropped to $113.00 per first episode of caries lesion averted and remained the dominant strategy. Conclusion PFS should be the preferred method for the prevention of dental caries lesion on the occlusal surface of the first permanent molar, especially in children who are at high risk and have barriers of access to dental care.

The addition of specialty palliative care to standard oncology care improves outcomes for patients with advanced cancer and their caregivers, but many lack access to specialty care services. Primary palliative care-meaning basic palliative care services provided by clinicians who are not palliative care specialists-is an alternative approach that has not been rigorously evaluated.A cluster randomized, controlled trial of the CONNECT (Care management by Oncology Nurses to address supportive care needs) intervention, an oncology nurse-led care management approach to providing primary palliative care for patients with advanced cancer and their family caregivers, is currently underway at 16 oncology practices in Western Pennsylvania. Existing oncology nurses are trained to provide symptom management and emotional support, engage patients and families in advance care planning, and coordinate appropriate care using evidence-based care management strategies. The trial will assess the impact of CONNECT versus standard oncology care on patient quality of life (primary outcome), symptom burden, and mood; caregiver burden and mood; and healthcare resource use.This trial addresses the need for more accessible models of palliative care by evaluating an intervention led by oncology nurses that can be widely disseminated in community oncology settings. The design confronts potential biases in palliative care research by randomizing at the practice level to avoid contamination, enrolling patients prior to informing them of group allocation, and conducting blinded outcome assessments. By collecting patient, caregiver, and healthcare utilization outcomes, the trial will enable understanding of the full range of a primary palliative care intervention's impact.

Objectives Current National Comprehensive Cancer Network (NCCN) guidelines support systemic therapy based on mutational status in stage IV non-small cell lung cancer (NSCLC), with stereotactic body radiation therapy (SBRT) reserved for oligoprogression. We aimed to evaluate the cost-effectiveness of the routine addition of SBRT to upfront therapy in stage IV NSCLC by mutational subgroup. Materials and methods A Markov state transition model was constructed to perform a cost-effectiveness analysis comparing SBRT plus maintenance therapy with maintenance therapy alone for oligometastatic NSCLC. Three hypothetical cohorts were analyzed: epidermal growth factor receptor or anaplastic lymphoma kinase mutation-positive, programmed death ligand-1 expressing, and mutation-negative group. Clinical parameters were obtained largely from clinical trial data, and cost data were based on 2018 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness to pay threshold of $100,000 per QALY gained. Results SBRT plus maintenance therapy was not cost-effective at a $100,000/QALY gained threshold, assuming the same survival for both treatments, resulting in an incremental cost effectiveness ratio of $564,186 and $299,248 per QALY gained for the epidermal growth factor receptor or anaplastic lymphoma kinase positive and programmed death ligand-1 positive cohorts, respectively. Results were most sensitive to the cost of maintenance therapy. A large overall survival gain with SBRT could potentially result in upfront SBRT becoming cost-effective. For the mutation-negative cohort, upfront SBRT was nearly cost-effective, costing $128,424 per QALY gained. Conclusion Adding SBRT to maintenance therapy is not a cost-effective strategy for oligometastatic NSCLC compared with maintenance therapy alone for mutation-positive groups. However, this should be validated via randomized trials.

Background: Broadly protective, long-lasting universal influenza vaccines are under development in response to low-moderate seasonal vaccine effectiveness, frequent genetic changes in circulating viruses and extended turnaround for vaccine manufacture. Because a long-lasting vaccine might be less effective than a seasonal vaccine that has been matched to current circulating strains, the public health impact of its introduction should be evaluated. Methods: A modified agent-based model (ABM) examined multi-year effects of a universal vaccine among 18 to 49-year-olds, given in Year 1 only. The proportion of vaccinated 18 to 49-year-olds who received universal vaccine was varied from 0% to 100%. Model parameters were drawn from US databases and the medical literature. Outcomes were 4-year cumulative and annual influenza cases as well as annual cases averted/100,000 population for 3 age groups, 0–17 years, 18–49 years and 50+ years. Results: In Year 1 when universal vaccine was given to 50% or 100% of all vaccinated 18 to 49-year-olds, more influenza cases occurred, compared to no universal vaccine, but fewer cases occurred in Years 2–4 as overall protection increased. Cumulative averted cases over 4 years in 18 to 49-year-olds were 892/100,000 and 1,687/100,000 population for the 50% and 100% universal vaccine for 18 to 49-year-olds scenarios, respectively, with additional benefits to children and older adults through indirect effects. Conclusions: In ABM, the universal vaccine with a conservative VE estimate given once to 18 to 49-year-olds reduced influenza cases among all age groups in Years 2–4 following its introduction. Reduced influenza burden may occur sooner if VE of universal vaccines exceeds that assumed in these models.

Detecting autoimmune diseases at an early stage is crucial for effective treatment and disease management to slow disease progression and prevent irreversible organ damage. In many autoimmune diseases, disease-specific autoantibodies are produced by B cells in response to soluble autoantigens due to defects in B cell tolerance mechanisms. Autoantibodies accrue early in disease development, and several are so disease-specific they serve as classification criteria. In this study, we established a high-throughput, sensitive, intact serum autoantibody analysis platform based on the optimization of a one dimensional ultra-high-pressure liquid chromatography top-down mass spectrometry platform (1D UPLC-TDMS). This approach has been successfully applied to a 12 standard monoclonal antibody antigen-binding fragment (Fab) mixture, demonstrating the feasibility to separate and sequence intact antibodies with high sequence coverage and high sensitivity. We then applied the optimized platform to characterize total serum antibody Fabs in a systemic lupus erythematosus (SLE) patient sample and compared it to healthy control samples. From this analysis, we show that the SLE sample has many dominant antibody Fab-related mass features unlike the healthy controls. To our knowledge, this is the first top-down demonstration of serum autoantibody pool analysis. Our proposed approach holds great promise for discovering novel serum autoantibody biomarkers that are of interest for diagnosis, prognosis, and tolerance induction, as well as improving our understanding of pathogenic autoimmune processes.

Anthrax vaccine adsorbed (AVA) is a significant line of defense against bioterrorist attack from Bacillus anthracis spores. However, in a subset of individuals, this vaccine may produce a suboptimal quantity of anti-protective antigen (PA), antibodies that are poorly neutralizing, and/or antibody titers that wane over time, necessitating annual boosters. To study individuals with such poor responses, we examine the properties of anti-PA in a subset of vaccinated individuals that make significant quantities of antibody but are still unable to neutralize toxin. In this cohort, characterized by poorly neutralizing antibody, we find that increased IgG4 to IgG1 subclass ratios, low antibody avidity, and insufficient antibody targeting domain 4 associate with improper neutralization. Thus, future vaccines and vaccination schedules should be formulated to improve these deficiencies.

Introduction Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2–8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014–2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. Methods An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2–8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2–8 years receive LAIV and IIV, respectively. Analyses were performed in 2014–2015. Results Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2–8 years, whereas IIV would not be preferred. However, when 2014–2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. Conclusions The cost effectiveness of influenza vaccination in children aged 2–8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV.

Although the U.S. National Academy of Sciences concluded that anthrax vaccine adsorbed (AVA) has an adverse event (AE) profile similar to those of other adult vaccines, 30 to 70% of queried AVA vaccinees report AEs. AEs appear to be correlated with certain demographic factors, but the underlying immunologic pathways are poorly understood. We evaluated a cohort of 2,421 AVA vaccinees and found 153 (6.3%) reported an AE. Females were more likely to experience AEs (odds ratio [OR] = 6.0 [95% confidence interval {CI} = 4.2 to 8.7]; P < 0.0001). Individuals 18 to 29 years of age were less likely to report an AE than individuals aged 30 years or older (OR = 0.31 [95% CI = 0.22 to 0.43]; P < 0.0001). No significant effects were observed for African, European, Hispanic, American Indian, or Asian ancestry after correcting for age and sex. Additionally, 103 AEs were large local reactions (LLRs), whereas 53 AEs were systemic reactions (SRs). In a subset of our cohort vaccinated 2 to 12 months prior to plasma sample collection ( n = 75), individuals with LLRs ( n = 33) had higher protective-antigen (PA)-specific IgE levels than matched, unaffected vaccinated individuals ( n = 50; P < 0.01). Anti-PA IgE was not associated with total plasma IgE, hepatitis B-specific IgE, or anti-PA IgG in individuals who reported an AE or in matched, unaffected AVA-vaccinated individuals. IP-10 was also elevated in sera of individuals who developed LLRs ( P < 0.05). Individuals reporting SRs had higher levels of systemic inflammation as measured from C-reactive protein ( P < 0.01). Thus, LLRs and SRs are mediated by distinct pathways. LLRs are associated with a vaccine-specific IgE response and IP-10, whereas SRs demonstrate increased systemic inflammation without a skewed cytokine profile.

Purpose To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases. Methods and Materials A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account for model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Results In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm). Conclusions If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data.

Background Long-acting beta agonists (LABA) and leukotriene receptor antagonists (LTRA) are the major add-on treatments in older adults with persistent asthma when inhaled corticosteroids (ICS) fail to achieve adequate asthma control. Objectives To evaluate the cost-utility of ICS + LABA treatment compared with ICS + LTRA treatment in older adults with asthma. Methods A Markov model was used to estimate the incremental costs and quality-adjusted life expectancy associated with ICS + LABA treatment versus ICS + LTRA treatment in older adults with asthma in the United States from the health system perspective. The HCUPnet 2010 national statistics were used to extract the costs associated with asthma and cardiovascular hospitalizations, and inpatient mortality associated with these events. Event probabilities were predicted using Medicare 2009-2010 claims for older adults with asthma. Treatment costs were estimated on the basis of average wholesale drug price listings, and utility estimates were extracted from the literature. To account for uncertainty, one-way sensitivity analysis and probabilistic sensitivity analysis were performed. Results The model predicted that, compared with ICS + LTRA treatment, ICS + LABA treatment costs $5,823 more while gaining 0.03 quality-adjusted life-years (QALYs), resulting in an incremental cost-effectiveness ratio of $209,090 per QALY. Hospitalization probabilities and posthospitalization utilities were the most influential parameters in the one-way sensitivity analysis. Probabilistic uncertainty analysis using Monte-Carlo simulations showed that the probabilities that ICS + LTRA treatment is cost-effective compared with ICS + LABA treatment are 77% and 62% at $50,000 and $100,000 per QALY gained willingness-to-pay thresholds, respectively. Conclusions The cost-effectiveness of ICS + LABA treatment is economically unfavorable in older adults when compared with LTRA as add-on treatment.

Background Interferon-free hepatitis C treatment regimens are effective but very costly. The cost-effectiveness, budget, and public health impacts of current Medicaid treatment policies restricting treatment to patients with advanced disease remain unknown. Objectives To evaluate the cost-effectiveness of current Medicaid policies restricting hepatitis C treatment to patients with advanced disease compared with a strategy providing unrestricted access to hepatitis C treatment, assess the budget and public health impact of each strategy, and estimate the feasibility and long-term effects of increased access to treatment for patients with hepatitis C. Methods Using a Markov model, we compared two strategies for 45- to 55-year-old Medicaid beneficiaries: 1) Current Practice—only advanced disease is treated before Medicare eligibility and 2) Full Access—both early-stage and advanced disease are treated before Medicare eligibility. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die each year. Morbidity was reduced after successful treatment. We calculated the incremental cost-effectiveness ratio and compared the costs and public health effects of each strategy from the perspective of Medicare alone as well as the Centers for Medicare & Medicaid Services perspective. We varied model inputs in one-way and probabilistic sensitivity analyses. Results Full Access was less costly and more effective than Current Practice for all cohorts and perspectives, with differences in cost ranging from $5,369 to $11,960 and in effectiveness from 0.82 to 3.01 quality-adjusted life-years. In a probabilistic sensitivity analysis, Full Access was cost saving in 93% of model iterations. Compared with Current Practice, Full Access averted 5,994 hepatocellular carcinoma cases and 121 liver transplants per 100,000 patients. Conclusions Current Medicaid policies restricting hepatitis C treatment to patients with advanced disease are more costly and less effective than unrestricted, full-access strategies. Collaboration between state and federal payers may be needed to realize the full public health impact of recent innovations in hepatitis C treatment.

Objective To assess the cost-effectiveness of an online adaptation of the diabetes prevention program (ODPP) lifestyle intervention. Methods ODPP was a before–after evaluation of a weight loss intervention comprising 16 weekly and 8 monthly lessons, incorporating behavioral tools and regular, brief, web-based individualized counseling in an overweight/obese cohort (mean age 52, 76% female, 92% white, 28% with diabetes). A Markov model was developed to estimate ODPP cost effectiveness compared with usual care (UC) to reduce metabolic risk over 10 years. Intervention costs and weight change outcomes were obtained from the study; other model parameters were based on published reports. In the model, diabetes risk was a function of weight change with and without the intervention. Results Compared to UC, the ODPP in our cohort cost $14,351 and $29,331 per quality-adjusted life-year (QALY) gained from the health care system and societal perspectives, respectively. In a hypothetical cohort without diabetes, the ODPP cost $7777 and $18,263 per QALY gained, respectively. Results were robust in sensitivity analyses, but enrolling cohorts with lower annual risk of developing diabetes (≤ 1.8%), enrolling fewer participants (≤ 15), or increasing the hourly cost (≥$91.20) or annual per-participant time (≥ 1.45 h) required for technical support could increase ODPP cost to >$20,000 per QALY gained. In probabilistic sensitivity analyses, ODPP was cost-effective in 20–58% of model iterations using an acceptability threshold of $20,000, 73–92% at $50,000, and 95–99% at $100,000 per QALY gained. Conclusions The ODPP may offer an economical approach to combating overweight and obesity.

Background Patients with venous thromboembolism (VTE) require access to comprehensive physician and pharmacy benefits to prevent recurrence and hemorrhage. Prior to 2006, Massachusetts provided these benefits through a program restricted to safety net hospitals called Free Care. Providing portable health insurance through Massachusetts health reform could improve outcomes for uninsured with VTE but its cost-effectiveness is unknown.

Human antibodies consist of a heavy chain and one of two possible light chains, kappa (κ) or lambda (λ). Here we tested how these two possible light chains influence the overall antibody response to polysaccharide and protein antigens by measuring light chain usage in human monoclonal antibodies from antibody secreting cells obtained following vaccination with Pneumovax23. Remarkably, we found that individuals displayed restricted light chain usage to certain serotypes and that lambda antibodies have different specificities and modes of cross-reactivity than kappa antibodies. Thus, at both the monoclonal (7 kappa, no lambda) and serum levels (145 μg/mL kappa, 2.82 μg/mL lambda), antibodies to cell wall polysaccharide were nearly always kappa. The pneumococcal reference serum 007sp was analyzed for light chain usage to 12 pneumococcal serotypes for which it is well characterized. Similar to results at the monoclonal level, certain serotypes tended to favor one of the light chains (14 and 19A, lambda; 6A and 23F, kappa). We also explored differences in light chain usage at the serum level to a variety of antigens. We examined serum antibodies to diphtheria toxin mutant CRM197 and Epstein-Barr virus protein EBNA-1. These responses tended to be kappa dominant (average kappa-to-lambda ratios of 4.52 and 9.72 respectively). Responses to the influenza vaccine were more balanced with kappa-to-lambda ratio averages having slight strain variations: seasonal H1N1, 1.1; H3N2, 0.96; B, 0.91. We conclude that antigens with limited epitopes tend to produce antibodies with restricted light chain usage and that in most individuals, antibodies with lambda light chains have specificities different and complementary to kappa-containing antibodies.

Objectives To evaluate the cost-effectiveness of abusive head trauma detection strategies in emergency department settings with and without rapid magnetic resonance imaging (rMRI) availability. Study design A Markov decision model estimated outcomes in well-appearing infants with high-risk chief complaints. In an emergency department without rMRI, we considered 3 strategies: clinical judgment, universal head computed tomography (CT) scan, or the Pittsburgh Infant Brain Injury Score (PIBIS) with a CT scan. In an emergency department with rMRI for brain availability, we considered additional strategies: universal rMRI, universal rMRI with a CT scan, PIBIS with rMRI, and PIBIS with rMRI followed by a CT scan. Correct diagnosis eliminated future risk; missed abusive head trauma led to reinjury risk with associated poor outcomes. Cohorts were followed for 1 year from a healthcare perspective. One-way and probabilistic sensitivity analyses were performed. The main outcomes evaluated in this study were abusive head trauma correctly identified and incremental cost per quality-adjusted life-year. Results Without rMRI availability, PIBIS followed by a CT scan was the most cost-effective strategy. Results were sensitive to variation of CT scan-induced cancer parameters and abusive head trauma prevalence. When rMRI was available, universal rMRI followed by a confirmatory CT scan cost $25 791 to gain 1 additional quality-adjusted life-year compared with PIBIS followed by rMRI with a confirmatory CT scan. In both models, clinical judgement was less effective than alternative strategies. Conclusions By applying CT scans to a more targeted population, PIBIS decreases radiation exposure and is more effective for the identification of abusive head trauma compared with clinical judgment. When rMRI is available, universal rMRI with a CT scan is more effective than PIBIS and is economically favorable.

BACKGROUND: Changing pneumococcal disease epidemiology due to childhood vaccination has prompted re-examination of US adult pneumococcal vaccination policies, as have considerations of greater pneumococcal disease incidence and higher prevalence of conditions that increase risk in underserved minority populations. Prior analyses suggest routine pneumococcal vaccination at age 50 could be considered, which could disproportionately benefit underserved populations. METHODS: A Markov cohort model estimated the cost-effectiveness of US pneumococcal vaccination policies in hypothetical 50-year-old underserved minority and general population cohorts. Strategies included receiving one or both available pneumococcal vaccines based on age- or chronic condition-specific criteria. US databases and medical literature data calibrated pneumococcal illness incidence, vaccine serotype distributions, age- and race-specific chronic condition distributions, and costs. Black population data were used as a proxy for underserved minorities. We took a US healthcare perspective, discounting at 3%/year. One-way and probabilistic sensitivity analyses were performed and scenarios modeling differing vaccine assumptions were examined. RESULTS: In both black and general population 50-year-olds, giving both pneumococcal vaccines to all 50-year-olds prevented the most disease, but cost >$250,000 per quality adjusted life year (QALY) gained. Current CDC recommendations (both vaccines for the immunocompromised, polysaccharide vaccine for other high-risk conditions) were economically favorable in either population when analyses assumed polysaccharide vaccine was ineffective against nonbacteremic pneumococcal pneumonia (NBP). If polysaccharide vaccine is effective against NBP or if less complex age-based vaccination recommendations result in increased vaccine uptake, giving polysaccharide vaccine to all 50-year-olds cost

Background and Objectives “Universal” vaccines that could have multistrain and multiyear effectiveness are being developed. Their potential cost-effectiveness in geriatric populations is unknown. Research Design and Methods A Markov model estimated effects of a theoretical universal influenza vaccine compared with available seasonal vaccines in hypothetical cohorts of U.S. 65+-year olds followed over a 5-year time horizon to capture potential multiyear protection. Outcomes included costs per quality-adjusted life-year gained and influenza cases avoided. Results Using hypothetical universal vaccine parameter values (cost $100, vaccine effectiveness 39%, uptake 64%, effectiveness duration 5 years), universal vaccine was less costly than seasonal influenza vaccination strategies. High-dose trivalent influenza vaccine, compared with universal vaccine, gained 0.0028 quality-adjusted life-years and cost $82 more, or $28,700 per quality-adjusted life-year gained. Other seasonal vaccines were not favorable economically. Five-year influenza risk with universal vaccination was 32.3% under base case assumptions, compared with

BACKGROUND: Racial disparities in U.S. adult pneumococcal vaccination rates persist despite reduced barriers to access. Consequently, racial and ethnic minorities experience pneumococcal disease at higher rates than whites. This study examined prevalence of high risk conditions and pneumococcal hospitalizations among U.S. black and non-black populations aged ≥50 years. METHODS: National Health Interview Survey, National Center for Health Statistics and National Inpatient Sample data were used to create black and non-black population cohorts, determine risk factors for pneumococcal disease (pneumococcal vaccine indications) and assess the impact of pneumococcal hospitalization. Each racial cohort was segmented into groups based on the presence of immunocompromising or other pneumococcal high-risk conditions. Persons without those conditions were separated into smokers (also a pneumococcal vaccine indication) and nonsmokers. Mortality was estimated from NCHS life table data. NIS data provided length of stay and costs (calculated from cost to charge ratios) for admissions related to pneumococcal disease including bacteremia, meningitis and nonbacteremic pneumonia. RESULTS: There were similar proportions of immunocompromised (

Background Patients undergoing posterior spinal fusion surgery can lose a substantial amount of blood. This can prolong operative time and require transfusion of allogeneic blood components, which increases the risk of infection and can be the harbinger of serious complications. Does a saline-irrigated bipolar radiofrequency hemostatic sealer (RFHS) help reduce transfusion requirements? Methods In an observational cohort study, we compared transfusion requirements in 30 patients undergoing surgery for adult spinal deformity using the RFHS with that of a historical control group of 30 patients in which traditional hemostasis was obtained with bipolar electrocautery and matched them for blood loss–related variables. Total expense to the hospital for the RFHS, laboratory expenses, and blood transfusions was used for cost calculations. The incremental cost-effectiveness ratio was calculated using the number of blood transfusions avoided as the effectiveness payoff. Results Using a multivariable linear regression model, we found that only estimated blood loss (EBL) was an independent significant predictor of transfusion requirement in both groups. We evaluated the variables of age, EBL, time duration of surgery, preoperative hemoglobin, hemoglobin nadir during surgery, body mass index, length of stay, and number of levels operated on. Mean EBL was greater in the control group (2201 vs. 1416 mL, P = 0.0099). The number of transfusions also was greater in the control group (14.5 vs. 6.5, P = 0.0008). In the cost-effectiveness analysis, we found that the RFHS cost $108 more (compared with not using the RFHS) to avoid 1 unit of blood transfusion. Conclusions The cost-effectiveness analysis revealed that if we are willing to pay $108 to avoid 1 unit of blood transfusion, the use of the RFHS is a reasonable choice to use in open surgery for adult spinal deformity.

Background and Objectives Obesity rates in adults ≥65 years have increased more than other age groups in the last decade, elevating risk for chronic disease and poor physical function, particularly in underserved racial and ethnic minorities. Effective, sustainable lifestyle interventions are needed to help community-based older adults prevent or delay mobility disability. Design, baseline recruitment, and implementation features of the Mobility and Vitality Lifestyle Program (MOVE UP) study are reported. Research Design and Methods MOVE UP aimed to recruit 26 intervention sites in underserved areas around Allegheny County, Pennsylvania and train a similar number of community health workers to deliver a manualized intervention to groups of approximately 12 participants in each location. We adapted a 13-month healthy aging/weight management intervention aligned with several evidence-based lifestyle modification programs. A nonrandomized, pre–post design was used to measure intervention impact on physical function performance, the primary study endpoint. Secondary outcomes included weight, self-reported physical activity and dietary changes, exercise self-efficacy, health status, health-related quality of life, and accelerometry in a subsample. Results Of 58 community-based organizations approached, nearly half engaged with MOVE UP. Facilities included neighborhood community centers (25%), YMCAs (25%), senior service centers (20%), libraries (18%), senior living residences (6%), and churches (6%). Of 24 site-based cohorts with baseline data completed through November 2017, 21 community health workers were recruited and trained to implement the standardized intervention, and 287 participants were enrolled (mean age 68 years, 89% female, 33% African American, other, or more than one race). Discussion and Implications The MOVE UP translational recruitment, training, and intervention approach is feasible and could be generalizable to diverse aging individuals with obesity and a variety of baseline medical conditions. Additional data regarding strategies for program sustainability considering program cost, organizational capacity, and other adaptations will inform public health dissemination efforts.