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The Patient-Reported Outcomes Measurement Information System (PROMIS) has developed item banks, short forms and computer-adaptive tests (CATs) to help standardize measurement for important patient reported outcome (PRO) domains. These tools have the potential to revolutionize outcome measurement in clinical research through greater assessment precision while reducing response burden. Perceived implementation challenges include the need for CAT software, mobile technology and internet access. Here, we present preliminary results examining the feasibility of using PROMIS tools within a large, multi-center clinical trials consortium. The assessment of 10 PROMIS domains was incorporated into the longitudinal data collection of six ongoing orthopaedic trauma clinical trials for participants being evaluated at 3, 6 and 12 months following an orthopaedic injury. Twelve-month assessments included both CAT assessments as well as completion of full item banks for a subset of domains. Data were collected for 1,000 trauma patients at 43 trauma centers using a custom-built application which included an interface with our primary data capture system. Paper short forms were available as backup instruments and used infrequently. Six and 12-month study assessments were conducted for 83% and 77% of patients, respectively. It was feasible to use PROMIS tools in a large multi-center, trauma orthopaedics research setting. The ability to efficiently assess a wide spectrum of domains is critically important to the successful completion of future large-scale trials.

This chapter offers guidance to defining the scope and study design of a cost-effectiveness analysis. As mentioned earlier, healthcare involves many stakeholders ranging from payers, to providers, to integrated health systems, to patients, and ultimately to society as a whole. Economic models can range in their measurement of costs and effectiveness depending on the perspective of these stakeholders. We will explore how these perspectives impact the design and calculation of different economic model parameters. We will also highlight basic types of economic models (i.e., decision trees and Markov chains) which are used to simulate the impacts of vaccines on different types of static or time-dependent health outcomes, as well as accumulate costs and effectiveness measures.

The transaction price for branded drugs in the United States often varies widely by the eventual payer, a fact that can complicate research and policy discussions surrounding drug pricing. We combine publicly-available data on branded drug prices from a host of sources—prices paid by Medicare (Parts B and D), the Veterans Affairs Administration (VA), those included in the Federal Supply Schedule (FSS), invoice prices paid by pharmacies described in National Average Drug Acquisition Costs (NADAC), list prices, and payments ultimately received by drug makers—to illustrate how prices vary across the U.S. market and how these relationships changed from 2010 to 2019. We document large variation across payers and find VA prices are generally the lowest, averaging nearly 50% below list prices during our study period, which is meaningfully lower than the average prices manufacturers ultimately receive. Some net prices, like those in Part D and average payments received by manufacturers, have diverged substantially from list prices in the last decade and are now much closer to the published VA and FSS prices. In part, this reflects unexpected net price increases among published VA and FSS prices that is worthy of future study.

To describe the uptake and out-of-pocket (OOP) costs of Basaglar, the first long-acting insulin biosimilar, in a commercially insured population in the United States.Retrospective analysis of commercial pharmacy claims and pharmacy co-payment offsets.We assessed Basaglar uptake by examining trends in the composition of the long-acting insulin market in the United States from 2014 to 2018. As patient demographics and plan type may be important determinants of biosimilar uptake, we also assessed characteristics of all long-acting insulin users by drug. We examined Basaglar OOP costs by assessing mean OOP costs per claim for users of Basaglar and other long-acting insulins, overall and by plan type, and the number and source of co-payment offsets for Basaglar and other insulin glargine products from Basaglar market entry through 2018. We used multivariate linear models to examine the relationship between Basaglar OOP expenditures and insurer-negotiated amounts, overall and by plan type.Basaglar experienced a rapid uptake. However, there was no evidence that Basaglar users had lower OOP costs than reference product (Lantus) users.Given our results and the approval of the first interchangeable biosimilar, we recommend the empirical evaluation of biosimilar cost savings to patients and insurers prior to promoting their automatic substitution.

BACKGROUND Out-of-network charges during hospital care can result in unexpected or surprise bills for the patient. The aim of this study was to ascertain the frequency of out-of-network (OON) billing by the primary orthopaedic surgeon for commonly performed elective, inpatient procedures: total hip arthroplasty (THA), total knee arthroplasty (TKA), anterior cervical diskectomy and fusion (ACDF), and posterior lumbar fusion (PLF). METHODS Patients undergoing TKA, THA, one-level ACDF, and one-level PLF from 2010 to 2018 were queried using a commercially insured claims database with Current Procedural Terminology codes. The in-network (IN) versus OON status of the primary surgeon's submitted charges and the payor's reimbursement was recorded for each case. All costs were adjusted for inflation and reported in terms of 2018 real dollars. Bivariate analyses were performed. RESULTS Among the 549,868 elective orthopaedic cases, 6.7% were billed as OON by the primary orthopaedic surgeon: 6.1% TKA cases, 6.5% THA, 9.9% ACDF, and 8.5% PLF. From 2010 to 2018, a declining trend was seen in proportion of cases billed as OON by orthopaedic surgeons (P < 0.001 for each case). Mean reimbursement for claims paid as OON was 2.6 times higher than claims paid at the IN rate (range: 1.5 to 3.1 times higher; P < 0.001). The mean OON payments were higher by $1,284 for TKA, $2,516 for THA, $10,097 for ACDF, and $15,104 for PLF compared with mean IN payments (P < 0.001 for each). Compared with health maintenance organization-type plans, preferred provider organization-type plans reimbursed a greater percentage of the submitted claims at the OON rate (14.3% versus 44.5%, P < 0.001). CONCLUSION OON billing by the orthopaedic surgeon for TKA, THA, ACDF, and PLF is an uncommon and declining phenomenon. LEVEL OF EVIDENCE IV.

BACKGROUND Fractures in late life are highly consequential for health, services use, and spending. Little is known about trends in extremity fracture hospitalizations among older adults in the United States. DESIGN Retrospective longitudinal cohort study. SETTING The 2003-2017 National Inpatient Sample (NIS), a representative sample of U.S. community hospitals. PARTICIPANTS Hospitalized adults aged 65 and older with a diagnosis of upper or lower extremity fracture. MEASUREMENTS Incidence of extremity fracture hospitalization and mortality, using NIS discharge and trend weights, and population denominators derived from the U.S. Census Bureau. Incidence was reported separately for men and women by age, fracture diagnosis, and injury mechanism. Weighted linear regression was used to test for significant trends over time. RESULTS Incidence of extremity fracture hospitalizations declined in both women (15.7%, p trend

// Taylor R. Cushman 1 , Vivek Verma 2 , Rahul Khairnar 3 , Joseph Levy 3 , Charles B. Simone 2nd 4 and Mark V. Mishra 4 1 Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 2 Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, USA 3 Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA 4 Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA Correspondence to: Vivek Verma, email: vivek333@gmail.com Keywords: prostate cancer; stereotactic body radiation therapy; stereotactic ablative radiation therapy; hypofractionation; toxicities Received: April 17, 2019 Accepted: August 05, 2019 Published: September 24, 2019 ABSTRACT Background: Despite the increasing worldwide utilization of stereotactic body radiation therapy (SBRT) for prostate cancer, there are no known summative data regarding its safety and efficacy. To address this knowledge gap, we conducted a PRISMA-guided systematic review and meta-analysis of prospective prostate SBRT trials. Results: Fourteen trials with a total of 2,038 patients were included. Median follow-up was 37 months (range 6-55 months). Most patients had cT1-T2a, Gleason ≤7 disease with median pre-treatment PSAs of 5–10; 1,042 (51%) were low-risk, 744 (37%) were intermediate-risk, 158 (8%) were high-risk, and the remainder were unreported. Doses ranged from 33.5–50.0 Gy, most typically in 5 fractions, with nearly all studies delivering nondaily fractionation with some type of daily image guidance. Outcomes were converted into counts at the end of one year. The pooled rate of FFBF was 98% [95% confidence interval, 97–98%]. The pooled rate of late grade ≥3 gastrointestinal and genitourinary toxicities were 1% [0–5%] and 2% [1–3%], respectively. Methods: PubMed and Google Scholar were queried for prospective studies evaluating survival and/or toxicity outcomes in SBRT (≤5 fractions) for localized prostate cancer. Pooled rates of freedom from biochemical failure (FFBF) and late grades ≥3 gastrointestinal (GI) and genitourinary (GU) toxicities were assessed. Meta-analysis of proportions was logit transformed and pooled using generalized linear mixed models (both fixed and random effects) and subsequently back transformed to standard proportions. Conclusions: Despite the lack of long-term follow-up and heterogeneity of the available evidence, prostate SBRT affords appropriate biochemical control with few high-grade toxicities. These data have implications for ongoing worldwide utilization of prostate SBRT as well as ongoing prospective investigations.

Background The COVID-19 pandemic led to large-scale cancellation and deferral of elective surgeries. We quantified volume declines, and subsequent recoveries, across all hospitals in Maryland. Materials and Methods Data on elective inpatient surgical volumes were assembled from the Maryland Health Service Cost Review Commission for years 2019-2020. The data covered all hospitals in the state. We compared the volume of elective inpatient surgeries in the second (Q2) and fourth quarters (Q4) of 2020 to those same quarters in 2019. Analysis was stratified by patient, hospital, and service characteristics. Results Surgical volumes were 55.8% lower in 2020 Q2 than in 2019 Q2. Differences were largest for orthopedic surgeries (74.3% decline), those on Medicare (61.4%), and in urban hospitals (57.3%). By 2020 Q4, volumes for most service lines were within 15% of volumes in 2019 Q4. Orthopedic surgery remained most affected (44.5% below levels in 2019 Q4) and Plastic Surgery (21.9% lower). Conclusions COVID-19 led to large volume declines across hospitals in Maryland followed by a partial recovery. We observed large variability, particularly across service lines. These results can help contextualize case-specific experiences and inform research studying potential health effects of these delays and cancellations.

This study compares revenue of Maryland hospitals in March-July 2020 vs historical trends and assesses whether rate increases for inpatient and outpatient services that were permitted to offset pandemic-related decines in revenues were associated with changes to state hospital revenue.

Objective The purpose of this study was to characterize outpatient physical therapy (OPT) use following tibial fractures and examine the variability of OPT attendance, time of initiation, number of visits, and length of care by patient, injury, and treatment factors. In the absence of clinical guidelines, results will guide future efforts to optimize OPT following tibial fractures. Methods This study used 2016 to 2017 claims from the IBM MarketScan Commercial Claims Research Database. The cohort included 9079 patients with International Classification of Diseases: Tenth Revision (ICD-10) diagnosis codes for tibial fractures. Use in the year following initial fracture management was determined using Current Procedural Terminology codes. Differences in use were examined using χ2 tests, t tests, and Kruskal-Wallace tests. Results Sixty-seven percent of patients received OPT the year following fracture. OPT attendance was higher in female patients, in patients with 1 or no major comorbidity, and in the western United States. Attendance was higher in patients with upper tibial fractures, moderate-severity injuries, and treatment with external fixation and in patients discharged to an inpatient rehabilitation facility. Patients started OPT on average [SD] 50 [52.6] days after fracture and attended 18 [16.1] visits over the course of 101 [86.4] days. The timing of OPT, the number of visits attended, and the length of OPT care varied by patient, injury, and treatment-level factors. Conclusions One-third of insured patients do not receive OPT following tibial fracture. The timing of OPT initiation, the length of OPT care, and the number of visits attended by patients with tibial fractures were highly variable. Further research is needed to standardize referral and prescription practices for OPT following tibial fractures. Impact OPT use varies based on patient, injury, and treatment-level factors following tibial fractures. Results from this study can be used to inform future efforts to optimize rehabilitation care for patients with tibial fractures.

Background Assessment of drug costs for cost-effectiveness analyses (CEAs) in the United States is not straightforward because the prices paid for drugs are not publicly available and differ between payers. CEAs have relied on list prices that do not reflect the rebates and discounts known to be associated with these purchases. Objectives To review available cost measures and propose a novel strategy that is transparent, consistent, and applicable to all CEAs taking a US health care sector perspective or a societal payer's perspective. Methods We propose using the National Average Drug Acquisition Cost (NADAC), the Veterans Affairs Federal Supply Schedule (VAFSS), and their midpoint as the upper bound, lower bound, and base case, respectively, to estimate net drug prices for various payers. We compare this approach with wholesale acquisition cost (WAC), the most common measure observed in our literature review. The minimum WAC is used to provide the most conservative comparison. Results Our sample consists of 1436 brand drugs and 1599 generic drugs. On average, the upper bound (NADAC) is 1% and 9.8% lower than the WAC for brand and generic drugs respectively, whereas the lower bound (VAFSS) is 48.3% and 54.2% lower than the WAC. The NADAC is less than the WAC in 89.6% of drug groups. The distributions of these relationships do not show a clear mode and have wide variation. Conclusions Our study suggests that the WAC may be an overestimate for the base case because the minimum WAC is higher than the NADAC for most drugs. Our approach balances uncertainty and lack of data for the cost of pharmaceuticals with the need for a transparent and consistent approach for valid CEAs.

Background Drug costs are frequently estimated in economic analyses using wholesale acquisition cost (WAC), but what is the best approach to develop these estimates? Pharmaceutical manufacturers recently released transparency reports disclosing net price increases after accounting for rebates and other discounts. Objective Our objective was to determine whether manufacturer net prices (MNPs) could approximate the discounted prices observed by the U.S. Department of Veterans Affairs (VA). Methods We compared the annual, average price discounts voluntarily reported by three pharmaceutical manufacturers with the VA price for specific products from each company. The top 10 drugs by total sales reported from company tax filings for 2016 were included. The discount observed by the VA was determined from each drug’s list price, reported as WAC, in 2016. Descriptive statistics were calculated for the VA discount observed and a weighted price index was calculated using the lowest price to the VA (Weighted VA Index), which was compared with the manufacturer index. Results The discounted price as a percentage of the WAC ranged from 9 to 74%. All three indexes estimated by the average discount to the VA were at or below the manufacturer indexes (42 vs. 50% for Eli Lilly, 56 vs. 65% for Johnson & Johnson, and 59 vs. 59% for Merck). Conclusions Manufacturer-reported average net prices may provide a close approximation of the average discounted price granted to the VA, suggesting they may be a useful proxy for the true pharmacy benefits manager (PBM) or payer cost. However, individual discounts for products have wide variation, making a standard discount adjustment across multiple products less acceptable.

This study explores the shifts in total US sales and net prices for all 3 insulin glargine products from quarter 1 of 2010 through quarter 2 of 2020.

Trauma related death and disability is common among working-age Americans, however the impact on older adults is consequential and increasing. Fractures are the most common traumatic injury diagnosis among Medicare beneficiaries, and though fragility fractures continue to be an important health problem, recent data indicate an increase in high-energy fractures. The purpose of this study was to produce national incidence estimates among US men and women ≥ 65 years using data from the 2003-2014 National Inpatient Sample (NIS). The study cohort included hospitalizations involving upper and/or lower extremity fractures which were further classified by mechanism as high or low energy using external cause of injury codes. Incidence was computed using survey weights provided by NIS, and population estimates from the Census Bureau. The incidence of high-energy fractures increased from 744.1/100,000 persons (95%CI: 681.1–807.1) in 2003 to 821.4/100,000 (95%CI: 795.0 – 874.8) in 2014 in women, and from 359.1/100,000 (95%CI: 331.4–386.8) to 408.2/100,000 (95%CI: 394.–809.2) in men. Over 80% were motor vehicle related. The greatest increase was among those ≥ 85 (1,856.4/100,000 to 2,126.3/100,000 in women; 1,069.1/100,000 to 1,215.1/100,000 in men). Simultaneously, the incidence of low-energy fractures declined: 748.4/100,000 (95%CI: 687.5–809.2) to 443.8/100,000 (95%CI: 423.5 -464.1) in women, and 310.6/100,000 (95%CI: 285 – 336.2) to 206.3/100,000 (95%CI: 196.5 - 216) in men. Results suggest that fractures commonly seen in younger adults will be seen more frequently in older age. It is therefore essential to establish treatment pathways to optimize outcomes for the growing number of injured older adults.

Introduction: As healthcare costs continue to increase in the United States, it is important to understand the trends in the allocation of healthcare spending for common orthopaedic surgical procedures. We investigated the recent trends in (1) total net payments (for episode of care), (2) payments to hospitals, (3) payments to physicians, (4) payments to physicians as a percentage of total net payments, and (5) regional variation in hospital and physician payments for four common orthopaedic procedures. Methods: Using a private insurance claims database, we analyzed the payments to US hospitals and physicians from 2010 to 2016 for primary total hip arthroplasty (THA) (n = 128,269), total knee arthroplasty (TKA) (n = 223,319), 1-level anterior cervical diskectomy and fusion (ACDF) (n = 51,477), and 1-level lumbar-instrumented posterior spinal fusion (PSF) (n = 45,680). Regional variations in payments were also assessed. Trends were analyzed using linear regression models adjusting for age, sex, comorbidities, duration of hospital stay, and inflation (alpha = 0.05). Results: Inflation-adjusted total net payments for the episode of care increased by the following percentages per year: 5.2% for ACDF, 3.2% for PSF, 2.9% for TKA, and 2.6% for THA. Annual inflation-adjusted hospital payments increased significantly for all 4 procedures, whereas annual inflation-adjusted physician payments decreased by −2.2%/year for PSF, −1.5%/year for TKA, −1.1%/year for THA, and −0.4%/year for ACDF (all, P < 0.001). As a percentage of total net payments, physician payments decreased markedly for ACDF (−4.6%), PSF (−3.1%), TKA (−2.1%), and THA (−1.8%). Hospital and physician payments varied significantly by region and were both highest in the West (P < 0.001). Conclusions: From 2010 to 2016, inflation-adjusted total net payments for 4 common orthopaedic surgical procedures increased markedly, as did payments to the US hospitals for these procedures. Payments to orthopaedic surgeons for these procedures decreased markedly during the same period.

Objectives To determine the recovery priorities of extremity fracture patients during the subacute phase and the patient factors associated with variation in recovery priorities. Design Discrete choice experiment. Setting Academic trauma center. Patients One hundred ninety-eight patients with a fracture to the appendicular skeleton. Patients with severe traumatic brain injuries, spinal cord injuries, and non-English-speaking patients were excluded. Main outcome measurement The relative importance of clinical recovery, work-related recovery, and obtaining disability benefits after injury. Results In the subacute period, clinical recovery was the main priority for fracture patients (mean: 62%, SD: 5.3). Work-related recovery (mean: 27%, SD: 3.9) and the receipt of other disability benefits (mean: 11%, SD: 6.4) were each of significantly less importance. Heterogeneity was observed across these estimates based on the physical demands of preinjury employment, preinjury physical health, preinjury work status, health insurance type, and the severity of the fracture. Conclusion Clinical recovery was of paramount importance for fracture patients during the subacute recovery phase. However, patients also valued resuming work and access to disability benefits. Understanding a patient's recovery priorities early in the clinical care pathway will enable the development of multidisciplinary care plans that are responsive to these priorities and, hence, deliver value-based health care. Level of evidence Level V. See Instructions for Authors for a complete description of levels of evidence.

Introduction. Estimating costs of medical care attributable to treatments over time is difficult due to costs that cannot be explained solely by observed risk factors. Unobserved risk factors cannot be accounted for using standard econometric techniques, potentially leading to imprecise prediction. The goal of this work is to describe methodology to account for latent variables in the prediction of longitudinal costs. Methods. Latent class growth mixture models (LCGMMs) predict class membership using observed risk factors and class-specific distributions of costs over time. Our motivating example models cost of care for children with cystic fibrosis from birth to age 17. We compare a generalized linear mixed model (GLMM) with LCGMMs. Both models use the same covariates and distribution to predict average costs by combinations of observed risk factors. We adopt a Bayesian estimation approach to both models and compare results using the deviance information criterion (DIC). Results. The 3-class LCGMM model has a lower DIC than the GLMM. The LCGMM latent classes include a low-cost group where costs increase slowly over time, a medium-cost group with initial higher costs than the low-cost group and with more rapidly increasing costs at older ages, and a high-cost group with a U-shaped trajectory. The risk profile-specific mixtures of classes are used to predict costs over time. The LCGMM model shows more delineation of costs by age by risk profile and with less uncertainty than the GLMM model. Conclusions. The LCGMM approach creates flexible prediction models when using longitudinal cost data. The Bayesian estimation approach to LCGMM presented fits well into cost-effectiveness modeling where the estimated trajectories and class membership can be used for prediction.

This cohort study examines whether certain patient-cost characteristics, drug characteristics, and drug-class characteristics are associated with manufacturer drug coupon use., Key Points Question Why do manufacturers choose to offer coupons for some prescription drugs and not for others? Findings In this cohort analysis of 2501 unique brand-name prescription drug products, drug companies offered a coupon for approximately half of the drugs; coupons were likely to be used for later-in-class-entrant products with high total costs in settings where direct competitors also offered coupons. Coupon use was not associated with a given product’s mean out-of-pocket cost. Meaning Manufacturer-sponsored coupons were more likely to be used for high-cost later-in-class-entrant products facing within-class competition where coupon use is prevalent., Importance Drug companies offer coupons to lower the out-of-pocket costs for prescription drugs, yet little is known about why they do so for some drugs but not for others. Objective To examine whether the following factors are associated with manufacturer drug coupon use: (1) patient-cost characteristics (mean per-patient cost per drug, mean patient copay); (2) drug characteristics (generics availability or “later-in-class-entrant” drugs); (3) drug-class characteristics (in-class coupon use among competitors; in-class generic competition; in-class mean cost and copay). Design, Setting, and Participants This was a retrospective cohort analysis of anonymized transactional pharmacy claims sourced from retail US pharmacies from October 2017 to September 2019, supplemented with information derived from Medi-Span, Red Book, and FDA.gov. Data were analyzed from September 2020 to February 2021. Main Outcomes and Measures The primary outcome was availability of a manufacturer’s coupon. The secondary outcome was the mean proportion of transactions in which a coupon was used for each product. Results The sample of 2501 unique brand-name prescription drugs accounted for a total of 8 995 141 claims. Manufacturers offered a coupon for 1267 (50.7%) of these drugs. When the manufacturer offered a coupon, it was used in a mean (SD) 16.3% (20.3%) of the transactions. Within a drug class, higher mean total cost per patient was positively associated with the likelihood of coupon use (odds ratio [OR], 1.03 per 10% increase; 95% CI, 1.01-1.04), but higher mean patient copay was inversely associated (OR, 0.98; 95% CI, 0.97-0.99). For drug characteristics, single-source later-in-class-entrant products were associated with a greater likelihood of coupon use compared with first entrants and multisource brands (OR, 1.44; 95% CI, 1.09-1.89). The intensity of coupon use was associated with later-in-class-entrant products and the class mean per-patient cost (4.16-percentage-point increase; 95% CI, 1.20-7.13; 0.27 per 10% increase; 95% CI, 0.09-0.44). Drugs with a new in-class brand-name competitor had greater mean coupon use compared with drugs without a new competitor (10.2% of claims with a coupon vs 5.9%). Conclusions and Relevance In this cohort study of transactional pharmacy claims, higher mean per-patient total cost within a class was significantly associated with the likelihood of coupon use, but not patient out-of-pocket cost. Manufacturers’ coupons were more likely to be used for expensive later-in-class-entrant products facing within-class competition where coupon use was prevalent.

Background: This study is the first to utilize a large claims database to estimate medical costs of patients with alpha-1 antitrypsin deficiency (AATD) in the United States. Methods: Adult AATD patients were identified from the OptumLabs™ Data Warehouse. Insurer and patient out-of-pocket costs were categorized into the following cost buckets, stratified by augmentation therapy use: physician visits (PV), emergency department visits (ED), inpatient stays (IP), augmentation therapy (AUG), other prescription drug costs (RX), and other costs (OTH). Costs were weighted and adjusted to 2017 U.S. dollars using the medical care component of the consumer price index. Results: The study cohort consisted of9117 AATD patients followed for 53,872 person years observed between 1993 and 2015. The annual costs among AATD patients totaled $127,537 among augmentation therapy users and $15,874 among non-users. The major drivers of annual costs to the insurer among the 7975 patients not on augmentation therapy were: PV: $5352 (37.7%) and IP: $4506 (31.8%). Among the 1142 augmentation users, major annual cost drivers to the insurer were PV: $15,064 (12.3%) and AUG: $82,002 (66.7%). Annual patient out-of-pocket costs were $4601 (AUG: $2084 [45.3%]; RX: $940 [20.4%]) and $1689 (PV: $727 [43.0%]; RX: $589 [34.9%]) among augmentation therapy users and non-users, respectively. Averaged across the entire cohort, the average annual costs per AATD patient were $22,975, paid by insurers ($21,100) and patients ($1875). Conclusions: Annual medical costs among patients with AATD are $127,537 and $15,874 among augmentation therapy users and non-users, respectively, with 75.3% of the cost difference attributable to AUG.

Purpose To perform a systematic review and meta-analysis of all published studies since 2005 that evaluate the accuracy of magnetic resonance imaging (MRI) for the diagnosis of acute appendicitis in the general population presenting to emergency departments. Materials and Methods All retrospective and prospective studies evaluating the accuracy of MRI to diagnose appendicitis published in English and listed in PubMed, Web of Science, Cinahl Plus, and the Cochrane Library since 2005 were included. Excluded studies were those without an explicitly stated reference standard, with insufficient data to calculate the study outcomes, or if the population enrolled was limited to pregnant women or children. Data were abstracted by one investigator and confirmed by another. Data included the number of true positives, true negatives, false positives, false negatives, number of equivocal cases, type of MRI scanner, type of MRI sequence, and demographic data including study setting and gender distribution. Summary test characteristics were calculated. Forest plots and a summary receiver operator characteristic plot were generated. Results Ten studies met eligibility criteria, representing patients from seven countries. Nine were prospective and two were multicenter studies. A total of 838 subjects were enrolled; 406 (48%) were women. All studies routinely used unenhanced MR images, although two used intravenous contrast-enhancement and three used diffusion-weighted imaging. Using a bivariate random-effects model the summary sensitivity was 96.6% (95% confidence interval [CI]: 92.3%–98.5%) and summary specificity was 95.9% (95% CI: 89.4%–98.4%). Conclusion MRI has a high sensitivity and specificity for the diagnosis of appendicitis, similar to that reported previously for computed tomography. J. Magn. Reson. Imaging 2016;43:1346–1354.

INTRODUCTION: More than 60,000 women are diagnosed with ductal carcinoma in situ (DCIS) annually and offered the option of breast conserving surgery (BCS), often including radiation (RT) to reduce local recurrence. Although the incidence of radiation-associated sarcoma (RAS) is low (0.05-0.25% at 10 years), the low mortality associated with DCIS and large number of DCIS diagnoses means that an increasingly large number of women are at risk of RAS. This study sought to weigh the risk of RAS with the benefits of BCS+RT for DCIS. METHODS: A second-order Monte Carlo micro-simulation model of women ages 35 and older with DCIS was constructed. The decision analysis compared harm-benefit ratios of sarcoma-related deaths per breast cancer deaths averted within 20 years of treatment with BCS+RT versus BCS alone. Stratified analyses were performed by age group to account for differential life expectancy. To generate parameter estimates for model inputs, Bayesian network meta-analysis was used to synthesize rates of DCIS and invasive recurrence from clinical trials of BCS+RT and BCS alone using a Weibull specification. Sarcoma incidence was estimated non-parametrically using SEER. Constant hazard rates for breast cancer mortality after invasive recurrence and RAS mortality were estimated from clinical trials. To account for uncertainty, probabilistic sensitivity analysis was conducted using 10,000 Monte Carlo samples and 95% credible intervals (CrI) were constructed for event rates and harm-benefit ratios. RESULTS: The micro-simulation model of an age-distributed cohort demonstrated that 1 in 840 women with DCIS (95%CrI 1:648 to 1:3522) would develop RAS within 20 years after treatment with BCS+RT. Overall, there would be 1 RAS-related death for every 12 breast cancer deaths averted (95%CrI 1:7 to 1:19) by the addition of RT to BCS. Stratified analysis demonstrated that the harm-benefit ratio was higher in women CONCLUSIONS: The risk of developing a RAS following BCS+RT for DCIS should not be overlooked. This may be especially true for women at low risk of recurrence and younger women ( Age-Stratified Incremental Harm-Benefit Ratios for BCS+RT versus BCS AloneAge GroupRAS Deaths: Breast Cancer Deaths Averted* Posterior Median Ratio (95% CrI)Overall1:12 (1:7 to 1:19)35 to 541:10 (1:6 to 1:14 )55 to 741:11 (1:7 to 1:15)75+1:17 (1:9 to 1:24)*Probabilistic sensitivity analysis using 10,000 second-order parameter samples with a 20 year time horizon Citation Format: Marquita R Decker, Joseph F Levy, Lee G Wilke, David J Vanness, Heather B Neuman. Balancing the harms and benefits of radiation therapy for DCIS: A decision analysis examining the risk of radiation-associated sarcoma [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-09-06.

Previous estimates of the cost of care for pediatric Cystic fibrosis (CF) showed wide variation, without specific summary of pulmonary drug costs.Enrolled CF children from the Wisconsin newborn screening trial were evaluated quarterly per protocol. Assessments systematically included all treatments, hospitalizations, and nutritional and pulmonary outcomes. Direct medical costs from hospital billing and medical records from 1989 to 2010 were used to describe costs by age-ranges and subgroups throughout follow-up. Outpatient drugs were separated by category (pulmonary/otherwise). Inpatient and drug costs were examined by clinical risk factors (presence of meconium ileus, pancreatic insufficiency, and expected severity of genetic mutations).Seventy-three children were followed for an average of 12.9 years with an average annual total cost of care of $24,768. Outpatient drug costs (53%) and hospitalizations (32%) represented the majority of costs. Drug costs were 48% for pulmonary indications and 52% for non-pulmonary. Pulmonary drug costs for children taking dornase were 54% of their drug costs while pulmonary drug costs were only 31% for children not taking dornase. Significant differences in frequency of inpatient stays existed for children with pancreatic insufficiency. Substantial differences in treatment costs exist as children age and by clinical risk factor.This study provides more accurate longitudinal estimates of CF care costs throughout childhood and shows that increasing age, pancreatic insufficiency, use of dornase, and hospitalizations are key determinants of cost. These estimates can be included in evaluations of the cost-effectiveness of new, highly expensive treatments being introduced for any CF population. Pediatr Pulmonol. 2016;51:1295-1303. © 2016 Wiley Periodicals, Inc.

To understand the association of race/ethnicity with engagement in pediatric primary care and examine how any racial/ethnic disparities are influenced by socioeconomic status.Visit videos and parent surveys were obtained for 405 children who visited for respiratory infections. Family and physician engagement in key visit tasks (relationship building, information exchange, and decision making) were coded. Two parallel regression models adjusting for covariates and clustering by physician were constructed: (1) race/ethnicity only and (2) race/ethnicity with SES (education and income).With and without adjustment for SES, physicians seeing Asian families spoke 24% fewer relationship building utterances, compared to physicians seeing White, non-Latino families (p0.05). Latino families gathered 24% less information than White, non-Latino families (p0.05), but accounting for SES mitigates this association. Similarly, African American families were significantly less likely to be actively engaged in decision making (OR=0.32; p0.05), compared to White, non-Latino families, but adjusting for SES mitigated this association.While engagement during pediatric visits differed by the family's race/ethnicity, many of these differences were eliminated by accounting for socioeconomic status.Effective targeting and evaluation of interventions to reduce health disparities through improving engagement must extend beyond race/ethnicity to consider socioeconomic status more broadly.

The relationship between DNA methylation and the expression of the gamma- and beta-casein genes was investigated in both expressing and nonexpressing tissues and in isolated tumor cell subpopulations displaying differential casein gene expression. MspI/HpaII digestions of DNA isolated from liver, a totally nonexpressing tissue, indicated that specific sites of hypermethylation existed in these genes as compared to the DNA isolated from casein-producing lactating mammary gland. The positions of these sites were mapped in the gamma-casein gene by comparing total genomic DNA Southern blots to the restriction digests of several overlapping phage clones constituting the gamma-casein gene. In contrast, the methylation status of the HhaI sites in the gamma-casein gene was found to be invariant regardless of the expression status of the gene. The inverse correlation between the hypermethylation of certain MspI/HpaII restriction sites in the casein genes and their potential expressibility was further substantiated by studies in 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced mammary carcinomas, which have an attenuated casein gene expression, and in cell subpopulations isolated from the 7,12-dimethylbenz(a)-anthracene tumor which were either depleted or enriched in casein-producing cells. Analysis of total tumor DNAs indicated that the casein genes were hypermethylated at the same sites observed in liver. However, a very faint hybridization signal was observed in the HpaII digests, suggesting cell-specific methylation differences. We have confirmed the hypomethylation of at least two of these MspI/HpaII sites within the subpopulation containing the casein-producing cells at a level consistent with the relative enrichment in that fraction. These results demonstrate differential site-specific casein gene methylation not only between tissues but also between cell subpopulations within a single tissue.