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Gina Nicholson,1 Shravanthi R Gandra,2 Ronald J Halbert,1 Akshara Richhariya,2 Robert J Nordyke1 1ICON, El Segundo, 2Amgen Inc., Thousand Oaks, CA, USA Objective: Robust cost estimates of cardiovascular (CV) events are required for assessing health care interventions aimed at reducing the economic burden of major adverse CV events. This review synthesizes international cost estimates of CV events.Methods: MEDLINE database was searched electronically for English language studies published during 2007-2012, with cost estimates for CV events of interest – unstable angina, myocardial infarction, heart failure, stroke, and CV revascularization. Included studies provided at least one estimate of patient-level direct costs in adults for any identified country. Information on study characteristics and cost estimates were collected. All costs were adjusted for inflation to 2013 values.Results: Across the 114 studies included, the average cost was US $6,466 for unstable angina, $11,664 for acute myocardial infarction, $11,686 for acute heart failure, $11,635 for acute ischemic stroke, $37,611 for coronary artery bypass graft, and $13,501 for percutaneous coronary intervention. The ranges for cost estimates varied widely across countries with US cost estimate being at least twice as high as European Union costs for some conditions. Few studies were found on populations outside the US and European Union.Conclusion: This review showed wide variation in the cost of CV events within and across countries, while showcasing the continuing economic burden of CV disease. The variability in costs was primarily attributable to differences in study population, costing methodologies, and reporting differences. Reliable cost estimates for assessing economic value of interventions in CV disease are needed. Keywords: cardiovascular diseases, health care costs, hospitalization economics, follow-up studies

Edmund C Lau1, Fionna S Mowat1, Michael A Kelsh1,*, Jason C Legg2, Nicole M Engel-Nitz3, Heather N Watson1, Helen L Collins2, Robert J Nordyke4,5, Joanna L Whyte21Exponent, Menlo Park, CA, USA; 2Amgen, Thousand Oaks, CA, USA; 3i3 Innovus, Eden Prairie, MN, USA; 4PriceSpective LLC, El Segundo, CA, USA; 5Department of Health Services, UCLA School of Public Health, Los Angeles, CA, USA*Now at Amgen, Thousand Oaks, CA, USAAbstract: Electronic medical records (EMRs) are used increasingly for research in clinical oncology, epidemiology, and comparative effectiveness research (CER).Objective: To assess the utility of using EMR data in population-based cancer research by comparing a database of EMRs from community oncology clinics against Surveillance Epidemiology and End Results (SEER) cancer registry data and two claims databases (Medicare and commercial claims).Study design and setting: Demographic, clinical, and treatment patterns in the EMR, SEER, Medicare, and commercial claims data were compared using six tumor sites: breast, lung/bronchus, head/neck, colorectal, prostate, and non-Hodgkin's lymphoma (NHL). We identified various challenges in data standardization and selection of appropriate statistical procedures. We describe the patient and clinic inclusion criteria, treatment definitions, and consideration of the administrative and clinical purposes of the EMR, registry, and claims data to address these challenges.Results: Sex and 10-year age distributions of patient populations for each tumor site were generally similar across the data sets. We observed several differences in racial composition and treatment patterns, and modest differences in distribution of tumor site.Conclusion: Our experience with an oncology EMR database identified several factors that must be considered when using EMRs for research purposes or generalizing results to the US cancer population. These factors were related primarily to evaluation of treatment patterns, including evaluation of stage, geographic location, race, and specialization of the medical facilities. While many specialty EMRs may not provide the breadth of data on medical care, as found in comprehensive claims databases and EMR systems, they can provide detailed clinical data not found in claims that are extremely important in conducting epidemiologic and outcomes research.Keywords: electronic health records, data generalizability, oncology research, health care claims data, epidemiology

This review assessed the use of electronic medical record (EMR) systems in outcomes research. We systematically searched PubMed to identify articles published from January 2000 to January 2007 involving EMR use for outpatient-based outcomes research in the United States. EMR-based outcomes research studies (n = 126) have increased sixfold since 2000. Although chronic conditions were most common, EMRs were also used to study less common diseases, highlighting the EMRs' flexibility to examine large cohorts as well as identify patients with rare diseases. Traditional multi-variate modeling techniques were the most commonly used technique to address confounding and potential selection bias. Data validation was a component in a quarter of studies, and many evaluated the EMR's ability to achieve similar results previously achieved using other data sources. Investigators using EMR data should aim for consistent terminology, focus on adequately describing their methods, and consider appropriate statistical methods to control for confounding and treatment-selection bias. [ABSTRACT FROM AUTHOR]

Objectives: To identify the types of disease most likely to be affected by the Institute for Clinical and Economic Review's (ICER) shared savings assumptions., Methods: For diseases with treatments that were Food and Drug Administration approved between 2019 and 2023, annual direct and indirect economic burden and characteristics of each disease were extracted from peer-reviewed literature. ICER's shared savings methodology was applied 2 ways: 50/50 shared savings and $150 000 cost-offset cap. The primary outcome was the difference in eligible cost savings provided by a hypothetical disease cure under ICER's 2 shared savings methods. Characteristics of diseases most impacted by these 2 methods were evaluated descriptively., Results: Food and Drug Administration approved 260 therapies for 89 unique diseases between 2019 and 2023. Shared savings reduced value of a hypothetical cure for hemophilia A most (50/50 method: -$367 670 per year; cap method: -$585 340 per year), followed by acute hepatic porphyria (50/50 method: -$333 948; cap method: -$517 896) and paroxysmal nocturnal hemoglobinuria (50/50 method: -$291 997; cap method: -$433 993). Compared with diseases with annual burdens <$150 000, those ≥$150 000 had earlier disease onset by 22.0 years (age 12.3 vs 34.3), lower life expectancy by 10.6 years (55.8 vs 66.4 years), and lower disease prevalence (4.7 vs 1981.5 per 100 000). Shared savings' impact on health-benefit price benchmarks was projected to be larger for diseases with shorter life expectancy (ρ = -0.319; p =.005), worse quality of life (ρ = -0.263; P =.020), and lower prevalence (ρ = -0.418; P < .001)., Conclusions: ICER's shared savings assumptions would most likely have the largest negative impact on health-benefit price benchmarks for rare, severe, and pediatric diseases., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2025. Published by Elsevier Inc.)

Introduction: BT-001 (AspyreRx™) prescription digital therapy, a form of personalized cognitive behavioral therapy, has demonstrated clinically meaningful and durable hemoglobin A1c reductions in patients with type 2 diabetes (T2D). The current study examined the cost-effectiveness of BT-001 plus standard of care (SoC) versus SoC alone in T2D over a lifetime horizon from a healthcare payer perspective., Methods: We modeled the T2D pathway using an individual patient-level simulation; clinical data were sourced from the intention-to-treat subset of the BT-001 randomized clinical trial (RCT). SoC across both arms included the composition of oral and injectable treatments for T2D. Events were simulated using the United Kingdom Prospective Diabetes Study Outcomes Model 2 risk equation. A 3-month model cycle length was used in the first year, then annual model cycles were used in line with the original risk engine specifications. Patient characteristics informed event equations and Monte Carlo random sampling was used to assess the occurrence of events within each model cycle. Incidence of hypoglycemic events, drug discontinuation, costs, and health utilities and disutility values were sourced from the literature., Results: From a payer perspective, BT-001 plus SoC versus SoC alone was dominant with a gain in quality-adjusted life years (QALYs) of 0.101 and cost savings of $7343 per patient over the lifetime horizon (i.e., more effective and less costly). BT-001 plus SoC was cost-effective at a willingness-to-pay of $100,000 per QALY (incremental net monetary benefit was $17,443). Savings with BT-001 were primarily driven by a reduction in drug acquisition costs. The reduction in hemoglobin A1c with BT-001 was associated with fewer T2D complications., Conclusions: BT-001 plus SoC was estimated to dominate SoC alone over the lifetime horizon from a payer perspective, suggesting that using BT-001 can empower patients to better manage their diabetes with the potential for lifelong advantages., (© 2023. The Author(s).)

Objective: The Institute for Clinical and Economic Review (ICER) publishes annual Unsupported Price Increase (UPI) reports on prescription drugs, which have gained attention from policymakers and healthcare stakeholders. These reports do not adjust for inflation in their analyses of net price changes. This study aimed to evaluate the economic context of reported drug price increases in ICER's UPI reports by applying inflation adjustments to the estimated impact on healthcare spending., Methods: Separate inflation adjustments using the Medical Consumer Price Index (Medical CPI) and the Consumer Price Index for All Urban Consumers (CPI-U) were applied to unadjusted UPI findings. The study analyzed data from four most recent UPI reports spanning pricing data from 2018 to 2019 (report year 2020) to 2021 to 2022 (report year 2023), focusing on drugs classified as having "unsupported" price increases., Results: Inflation-adjusted analyses showed lower estimates of real changes in spending compared to ICER's unadjusted figures across all drugs analyzed. Across the four UPI reports, the average report-year difference in Medical CPI inflation adjustment spending versus unadjusted findings was 53%, whereas the average report-year difference in CPI-U inflation adjustment spending versus unadjusted findings was 80%. In the most recent report year of 2023, ICER's unadjusted estimate of a $1.3 billion increase in healthcare spending transformed to a $134 million decrease when adjusted by Medical CPI and a $1.51 billion decrease when adjusted by CPI-U., Conclusion: This study demonstrates that inflation adjustment can alter not only the findings but also the interpretation of drug spending changes in UPI reports. The findings highlight the importance of considering economic context in evaluating drug pricing trends and suggest that unadjusted figures may overstate the impact of real price changes. Given the influence of these reports on policy discussions, incorporating inflation adjustments into analyses is one of many steps toward informing evidence-based policy decisions.

While access-related dysfunction is a clear driver of clinical outcomes and costs, the full impact of vascular access dysfunction on patient experience and quality of life is not fully characterized in the literature. One way to more comprehensively characterize the patient experience from the patient perspective is through patient reported outcomes (PROs). However, the limited implementation of PROs in clinical trials, patient registries, quality measurement, and other research settings has significantly constrained the patient voice in evaluation of vascular access outcomes and vascular access decision-making. To address these issues, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the U.S. Food and Drug Administration, assembled an interdisciplinary workgroup to enhance uptake of access-related PROs with the aims of: (1) reviewing the domains of HRQOL that are affected by vascular access, collect information on existing instruments that measure access-specific HRQOL in hemodialysis, and identify gaps in existing measures; (2) identifying and critically assessing barriers to widespread use of access-specific PRO measures; and (3) defining initiatives to overcome barriers and make recommendations for strategies to improve the use and utility of access-specific PRO measures. A consensus group process identified potential barriers to use of PRO measures in six categories: (1) PRO misperceptions, (2) patient factors, (3) regulators and payers, (4) instrument factors, (5) study design, and (6) physicians. The workgroup provided recommendations for actions to promote the widespread utilization of vascular access-related PRO measures in five categories: (1) development of vascular access-specific PRO measures, (2) ensuring comprehensive assessment when using vascular access PRO measures, (3) ensuring accessibility and applicability of vascular access PRO measures to all end stage kidney disease populations, (4) establishing universal guidelines and accepted vascular access PRO measures, and (5) engaging stakeholders across all facets.

Relationships between renal function and medical costs for deceased donor kidney transplant recipients are not fully quantified post-transplant. We describe these relationships with renal function measured by estimated glomerular filtration rate (eGFR) and graft failure. The United States Renal Data System identified adults receiving single-organ deceased donor kidneys 2012-2015. Inpatient, outpatient, other facility costs and eGFRs at discharge, 6 and 12 months were included. A time-history of costs was constructed for graft failures and monthly costs in the first year post-transplant were compared to those without failure. The cohort of 24,021 deceased donor recipients had a 2.4% graft failure rate in the first year. Total medical costs exhibit strong trends with eGFR. Recipients with 6-month eGFRs of 30-59 ml/min/1.73m 2 have total costs 48% lower than those <30 ml/min/1.73m 2 . For recipients with graft failure monthly costs begin to rise 3-4 months prior to failure, with incremental costs of over $38,000 during the month of failure. Mean annual total incremental costs of graft failure are over $150,000. Total costs post-transplant are strongly correlated with eGFR. Graft failure in the first year is an expensive, months-long process. Further reductions in early graft failures could yield significant human and economic benefits., Competing Interests: Authors ZW and WW are employed by company Genesis Research LLC; RJN is employed by Beta6 Consulting Group, LLC. MC received research funding and/or consultancy fees unrelated to this study from Angion Biomedica. RJN was an employee of Angion Biomedica at the time of writing. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that Angion Biomedica provided funding for the analysis supporting this research. Genesis Research performed the data analysis under contract to Angion Biomedica. Funding for open access fees has not been provided., (Copyright © 2022 Cooper, Schnitzler, Nilubol, Wang, Wu and Nordyke.)

Background: Estimated glomerular filtration rate (eGFR) at 1 year post transplantation has been shown to be a strong predictor of long-term graft survival. However, intercurrent events (ICEs) may affect the relationship between eGFR and failure risk., Methods: The OPTN and USRDS databases on single-organ kidney transplant recipients from 2012 to 2016 were linked. Competing risk regressions estimated adjusted subhazard ratios (SHRs) of 12-month eGFR on long-term graft failure, considering all-cause mortality as the competing risk, for deceased donor (DD) and living donor (LD) recipients. Additional predictors included recipient, donor, and transplant characteristics. ICEs examined were acute rejection, cardiovascular events, and infections., Results: Cohorts comprised 25,131 DD recipients and 7471 LD recipients. SHRs for graft failure increased rapidly as 12-month eGFR values decreased from the reference 60 ml/min per 1.73 m 2 . At an eGFR of 20 ml/min per 1.73 m 2 , SHRs were 13-15 for DD recipients and 12-13 for LD recipients; at an eGFR of 30 ml/min per 1.73 m 2 , SHRs were 5.0-5.7 and 5.0-5.5, respectively. Among first-year ICEs, acute rejection was a significant predictor of long-term graft failure in both DD (SHR=1.63, P <0.001) and LD (SHR=1.51, P =0.006) recipients; cardiovascular events were significant in DD (SHR=1.24, P <0.001), whereas non-CMV infections were significant in the LD cohort (SHR=1.32, P =0.03). Adjustment for ICEs did not significantly reduce the association of eGFR with graft failure., Conclusions: Twelve-month eGFR is a strong predictor of long-term graft failure after accounting for clinical events occurring from discharge to 1 year. These findings may improve patient management and clinical evaluation of novel interventions., Competing Interests: F. Corvino reports being an employee of Genesis Research and having ownership interest in Genesis Research. S. Mohan reports consultancy for Angion Biomedica; research funding from Angion Biomedica and the NIH (NIDDK, NIHMD, and NIBIB); being deputy editor of Kidney International Reports (ISN); being vice chair of UNOS; and being a member of the SRTR Visiting Committee and the Angion Pharma scientific advisory board. B. Nordyke reports being an employee of Angion Biomedica at the time of writing. J. Schold reports consultancy agreements with Guidry and East, Novartis, Sanofi, and the Transplant Management Group; honoraria from Novartis and Sanofi; being a Data Safety Monitoring Board Member—Bristol Myers Squibb and Nephrosant; and participating in a speaker’s bureau for Sanofi. W. Wang reports being an employee of Genesis Research; consultancy for Genesis Research; and ownership interest in Apple, BMS, and Snapchat. Z. Wu reports being an employee of Genesis Research., (Copyright © 2022 by the American Society of Nephrology.)

Background: A Minimal Clinically Meaningful Difference (MCMD) has not been defined for Estimated glomerular filtration rate (eGFR). Our goal was to define the MCMD for eGFR anchored to kidney graft failure., Methods: A systematic review of studies with 12-month eGFR and subsequent renal graft failure was conducted. For observational studies, we calculated hazard ratio (HR) differences between adjacent eGFR intervals weighted by population distribution. Interventional trials yielded therapeutically induced changes in eGFR and failure risk. OPTN data analysis divided 12-month eGFR into bands for Cox regressions comparing adjacent eGFR bands with a death-censored graft survival outcome., Results: Observational studies indicated that lower eGFR was associated with increased death-censored graft failure risk; each 5 ml/min/1.73 m 2 12-month eGFR band associated with a weighted incremental HR = 1.12 to 1.23. Clinical trial data found a 5 ml/min/1.73 m 2 difference was associated with incremental HR = 1.16 to 1.35. OPTN analyses showed weighted mean HRs across 10, 7, and 5 ml/min/1.73 m 2 bands of 1.47, 1.30, and 1.19., Conclusions: A 5 ml/min/1.73 m 2 difference in 12-month eGFR was consistently associated with ~20% increase in death-censored graft failure risk. The magnitude of effect has been interpreted as clinically meaningful in other disease states and should be considered the MCMD in renal transplantation clinical trials., (© 2021 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Arteriovenous grafts (AVGs) are an appropriate option for vascular access in certain hemodialysis patients. Expanded polytetrafluoroethylene (ePTFE) has become the dominant material for such grafts, due in part to innovations in graft design and surgical interventions to reduce complications and improve patency rates. Comprehensive evidence syntheses have not been conducted to update AVG performance in an era in which both access choice and ePTFE graft functioning may have changed. We conducted a systematic review and meta-analysis summarizing outcomes from recent studies of ePTFE AVGs in hemodialysis, following PRISMA standards. Literature searches were conducted in multiple databases to identify observational and interventional studies of AVG patency and infection risk. Primary, primary-assisted, and secondary patency rates were analyzed at 6, 12, 18, and 24 months postplacement. Kaplan-Meier graft survival plots were digitized to recreate individual patient-level data. Patency rates were pooled using a random effects model. We identified 32 studies meeting our selection criteria that were published from 2004 through 2019. A total of 38 study arms of ePTFE grafts were included, representing 3381 AVG accesses placed. The mean primary, primary-assisted, and secondary patency rates at 1 year were 41% (95% CI, 35% to 47%), 46% (95% CI, 41% to 51%), and 70% (95% CI, 64% to 75%), respectively. Mean 24-month patency rates were 28% (95% CI, 22% to 33%), 34% (95% CI, 27% to 41%), and 54% (95% CI, 47% to 61%), respectively. A high degree of heterogeneity across studies was observed. Overall risk of infection was not consistently reported, but among available studies the pooled estimate was 9% per patient-year (95% CI, 6% to 12%). This meta-analysis provides an up-to-date estimate of the performance of ePTFE AVGs, within the context of improved graft designs and improved interventional techniques., Competing Interests: R.J. Halbert, G. Nicholson, and R.J. Nordyke were employees of Beta6 Consulting Group at the time of this study, which received a grant from Humacyte. L.E. Niklason is a founder and shareholder in Humacyte, Inc., which is a regenerative medicine company. Humacyte, Inc. produces engineered blood vessels from allogeneic smooth muscle cells for vascular surgery. L.E. Niklason’s spouse has equity in Humacyte, Inc., and L.E. Niklason serves on Humacyte, Inc.’s Board of Directors. L.E. Niklason is an inventor on patents that are licensed to Humacyte, Inc. and that produce royalties for L.E. Niklason. L.E. Niklason has received an unrestricted research gift to support research in her laboratory at Yale. A. Pilgrim is a former employee and a stockholder of Humacyte, Inc., (Copyright © 2020 by the American Society of Nephrology.)

Individuals with dialysis-dependent kidney failure experience considerable disease- and treatment-related decline in functional status and overall well-being. Despite these experiences, there have been few substantive technological advances in KRT in decades. As such, new federal initiatives seek to accelerate innovation. Historically, integration of patient perspectives into KRT product development has been limited. However, the US Food and Drug Administration recognizes the importance of incorporating patient perspectives into the total product life cycle ( i.e. , from product conception to postmarket surveillance) and encourages the consideration of patient-reported outcomes in regulatory-focused clinical trials when appropriate. Recognizing the significance of identifying patient-reported outcome measures (PROMs) that capture contemporary patient priorities, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to ( 1 ) develop a conceptual framework for a health-related quality of life PROM; ( 2 ) identify and map existing PROMs to the conceptual framework, prioritizing them on the basis of their supporting evidence for use in the regulatory environment; and ( 3 ) describe next steps for identifying PROMs for use in regulatory clinical trials of transformative KRT devices. This paper summarizes the proposed health-related quality-of-life PROM conceptual framework, maps and prioritizes PROMs, and identifies gaps and future needs to advance the development of rigorous, meaningful PROMS for use in clinical trials of transformative KRT devices., (Copyright © 2020 by the American Society of Nephrology.)

Aims: Cold agglutinin disease (CAD) is a rare subtype of autoimmune hemolytic anemia associated with increased thromboembolism risk and early mortality. Healthcare resource utilization (HRU) in CAD has not been reported. We aimed to compare HRU of patients with CAD with a matched non-CAD cohort in the United States. Materials and methods: Patients with CAD were identified from 2006 to 2016 in the Optum-Humedica database using CAD terms in clinical notes and hematologist review. Patients were required to have Integrated Delivery Network records and ≥6 months' follow-up before and after the first CAD mention date (index date). Patients with CAD were matched to a non-CAD cohort based on demographics. Multivariate analyses assessed inpatient hospitalizations, outpatient visits, emergency room visits, and transfusion use between cohorts 6 months before and 12 months after the index date. Results: Of 814 patients with CAD, 410 met inclusion criteria and were matched to 3,390 patients without CAD. Mean age of patients with CAD was 68.0 years; approximately 62% were female. In the 12 months after the index date, mean inpatient hospitalizations (0.83 vs. 0.25), outpatient visits (17.26 vs. 6.77), emergency room visits (0.55 vs. 0.32), and transfusion days (1.05 vs. 0.05) were higher for patients with CAD than the matched non-CAD cohort (all p  < .0001). Similarly, in the 6 months before the index date, patients with CAD had higher HRU than matched patients without CAD for all measures evaluated. Limitations: Results of this study are based on patient information from the Optum-Humedica database, which is limited to commercially insured patients and may not represent the overall CAD population. Conclusions: CAD places a substantial burden on patients and healthcare systems. In addition, the high HRU for patients with CAD observed in the 6 months before diagnosis indicates that disease awareness and better diagnostic practices may be needed.

Background: Patients with distributive shock who are unresponsive to traditional vasopressors are commonly considered to have severe distributive shock and are at high mortality risk. Here, we assess the cost-effectiveness of adding angiotensin II to the standard of care (SOC) for severe distributive shock in the US critical care setting from a US payer perspective., Methods: Short-term mortality outcomes were based on 28-day survival rates from the ATHOS-3 study. Long-term outcomes were extrapolated to lifetime survival using individually estimated life expectancies for survivors. Resource use and adverse event costs were drawn from the published literature. Health outcomes evaluated were lives saved, life-years gained, and quality-adjusted life-years (QALYs) gained using utility estimates for the US adult population weighted for sepsis mortality. Deterministic and probabilistic sensitivity analyses assessed uncertainty around results. We analyzed patients with severe distributive shock from the ATHOS-3 clinical trial., Results: The addition of angiotensin II to the SOC saved .08 lives at Day 28 compared to SOC alone. The cost per life saved was estimated to be $108,884. The addition of angiotensin II to the SOC was projected to result in a gain of .96 life-years and .66 QALYs. This resulted in an incremental cost-effectiveness ratio of $12,843 per QALY. The probability of angiotensin II being cost-effective at a threshold of $50,000 per QALY was 86 percent., Conclusions: For treatment of severe distributive shock, angiotensin II is cost-effective at acceptable thresholds.

Background: End stage kidney disease and hemodialysis dependence are associated with impairments in health-related quality of life (HRQOL), which may be related to vascular access (VA). Few HRQOL measures are VA-specific and none differentiate HRQOL impact by VA type. We developed a VA-targeted HRQOL measure to distinguish the impact of fistulas, grafts and catheters., Methods: We created an initial item pool based on literature review and then conducted focus groups at 4 US sites with 37 adults and interviews with nine dialysis clinicians about VA's impact on HRQOL. We then drafted the Hemodialysis Access-Related Quality of Life (HARQ) measure and cognitively tested it with 17 hemodialysis patients. Focus group and cognitive interview participants were diverse in age, gender, years on dialysis, and VA., Results: We identified six domains for the HARQ: symptoms, physical functioning, emotional impacts, social and role functioning, sleep, and care-related burdens. Cognitive interviews indicated that items were easily understood and supported content validity. Attributing HRQOL impact to VA as opposed to other hemodialysis burden was challenging for some items. Some items were dropped that were considered redundant by patients, limitations while dressing was added, and reference to VA-specific impact was included for each item. The average Flesch-Kincaid reading grade level for the revised 47-item HARQ was 5.3., Conclusions: The HARQ features VA-specific content not addressed in other HRQOL measures, making it ideal for comparisons of different VA types and new VA technologies. The psychometric properties of the HARQ will be evaluated in future research.

Background: Behavioral interventions can meaningfully improve cardiometabolic conditions. Digital therapeutics (DTxs) delivering these interventions may provide benefits comparable to pharmacologic therapies, displacing medications for some patients., Objective: Our objective was to estimate the economic impact of a digital behavioral intervention in type 2 diabetes mellitus (T2DM) and hypertension (HTN) and estimate the impact of clinical inertia on deprescribing medications., Methods: Decision analytic models estimated health resource savings and cost effectiveness from a US commercial payer perspective. A 3-year time horizon was most relevant to the intervention and payer. Effectiveness of the DTx in improving clinical outcomes was based on cohort studies and published literature. Health resource utilization (HRU), health state utilities, and costs were drawn from the literature with costs adjusted to 2018 dollars. Future costs and quality-adjusted life years (QALYs) were discounted at 3%. Sensitivity analyses assessed uncertainty., Results: Average HRU savings ranged from $97 to $145 per patient per month, with higher potential benefits in T2DM. Cost-effectiveness acceptability analyses using a willingness-to-pay of $50,000/QALY indicated that the intervention would be cost effective at total 3-year program costs of $6468 and $6620 for T2DM and HTN, respectively. Sensitivity analyses showed that reduced medication costs are a primary driver of potential HRU savings, and the results were robust within values tested. A resistance to deprescribe medications when a patient's clinical outcomes improve can substantially reduce the estimated economic benefits. Our models rely on estimates of clinical effectiveness drawn from limited cohort studies with DTxs and cannot account for other disease management programs that may be implemented. Performance of DTxs in real-world settings is required to further validate their economic benefits., Conclusions: The DTxs studied may provide substantial cost savings, in part by reducing the use of conventional medications. Clinical inertia may limit the full cost savings of DTxs., (©Robert J Nordyke, Kevin Appelbaum, Mark A Berman. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 09.10.2019.)

Introduction: Hemodialysis (HD) in end-stage renal disease (ESRD) patients requires vascular access (VA) through an arteriovenous fistula (AVF), a prosthetic arteriovenous graft (AVG), or a central venous catheter. While AVF or AVG is commonly used for HD, the economic implications of AVF versus AVG use have not been fully established. We describe the healthcare resource utilization and costs of AVF and AVG use for incident ESRD patients in the United States., Methods: This observational cohort study of AVF and AVG placements used data from the United States Renal Data System to identify and follow access placements. AVF and AVG placements after ESRD onset for incident patients from 2012 to 2014 with continuous Medicare primary coverage were included. All-cause and access-related Medicare costs were averaged over the placement lifetime and expressed as per dialysis-month costs., Results: The analysis included 38,035 AVF placements and 12,789 AVG placements. Total all-cause monthly costs for AVF averaged USD 8,508; mean monthly costs were USD 3,027 for inpatient (IP), USD 3,139 for outpatient (OP), USD 1,572 for physician services, and USD 770 for other care settings. Access-related monthly costs averaged USD 1,699 and represented 20% of all-cause charges for AVFs. Mean all-cause monthly costs for AVG were USD 9,605; by setting monthly costs were USD 3,811 for IP, USD 3,034 for OP, USD 1,881 for physician services and USD 879 for other care settings. Access-related monthly costs averaged USD 2,656 and represented 28% of all-cause charges for AVGs., Discussion/conclusions: This study indicates that costs due to VA are a significant burden on Medicare budgets and on patients. The factors driving access-related utilization and costs merit attention in future research. Both optimizing process of care and discovery innovation may significantly accelerate better stewardship of available healthcare resources., (© 2019 S. Karger AG, Basel.)

Background: Chronic hemodialysis requires a mode of vascular access through an arteriovenous fistula (AVF), a prosthetic arteriovenous graft (AVG), or a central venous catheter (CVC). AVF is recommended over AVG or CVC due to increased patency and decreased intervention rates for those that mature. AVG are preferred over CVC due to decreased infection and mortality risk. The aims of this study were to evaluate the lifespan of AVF and AVG in maturation, sustained access use, and abandonment., Methods: The United States Renal Data System (USRDS), Medicare claims, and CROWNWeb were used to identify access placements. Patients with a first end-stage renal disease (ESRD) service from January 1, 2012 to June 30, 2014 with continuous coverage with Medicare as primary payer and ≥1 AVF or AVG placed after ESRD onset were included. Maturation was defined as the first use of the access for hemodialysis recorded in CROWNWeb. Sustained access use was defined as 3 consecutive months of use without catheter placement or replacement. Accesses that were never used at any time post-placement were considered abandoned., Results: The cohort included 38,035 AVF placements and 12,789 AVG placements. Sixty-nine percent of AVF and 72% of AVG matured. Fifty-two percent of AVF and 51% of AVG achieved sustained access use. One quarter of AVF and 14% of AVG were abandoned without use as recorded in CROWNWeb., Conclusion: Although considered the gold standard for vascular access, only half of AVF and AVG placements achieved sustained access use. The USRDS database has inherent limitations but provides useful clinical insight into maturation, sustained use, and abandonment., (© 2019 S. Karger AG, Basel.)

Background: Apheresis is an important treatment for reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). We systematically reviewed the current literature surrounding LDL-C apheresis for FH., Methods and Results: Electronic databases were searched for publications of LDL-C apheresis in patients with FH. Inclusion criteria include articles in English published in 2000-2013 that provide descriptions of practice patterns, efficacy/effectiveness, and costs related to LDL-C apheresis in patients with FH. Data were stratified by country and FH genotype where possible. Thirty-eight studies met the inclusion criteria: 8 open-label clinical trials, 11 observational studies, 17 reviews/guidelines, and 2 health technology assessments. The prevalence of FH was not well characterized by country, and underdiagnosis was a barrier to FH treatment. Treatment guidelines varied by country, with some guidelines recommending LDL-C apheresis as first-line treatment in patients with homozygous FH and after drug therapy failure in patients with heterozygous FH. Additionally, guidelines typically recommended weekly or biweekly LDL-C apheresis treatments conducted at apheresis centers that may last 2 to >3 hours per session. Studies reported a range for mean LDL-C reduction after apheresis: 57-75% for patients with homozygous FH and 58-63% for patients with heterozygous FH. Calculated annual costs (in US$2015) may reach US$66 374 to US$228 956 per patient for weekly treatment., Conclusions: LDL-C apheresis treatment may be necessary for patients with FH when drug therapy is inadequate in reducing LDL-C to target levels. While apheresis reduces LDL-C, high per-session costs and the frequency of guideline-recommended treatment result in substantial annual costs, which are barriers to the optimal treatment of FH., (© 2016 The Authors and Amgen Inc. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Purpose: The perspective of commercial payers on comparative effectiveness research (CER) has not been well researched. This study aims to describe how US commercial payers use and value CER for formulary decision making in different disease states., Methods: We recruited 20 medical and pharmaceutical directors from national and regional plans who are involved in pharmaceutical and therapeutics committees to participate in the study. We conducted in-depth qualitative interviews with the payers and asked them to rate the usefulness of CER study types across various disease states and market conditions. The results were analyzed for thematic content., Results: Our findings indicate that payers are interested in a broad range of CER study types, are unsatisfied with the current state of CER, and would like to partner with research groups to develop research and treatment guidelines to better leverage CER. Payers value CER less in oncology than in other disease states because of limitations in their ability to manage oncology therapies., Conclusion: To improve formulary design processes and support payers in providing more effective healthcare, policy makers should consider involving commercial payers in the development of CER as well as in the creation of research and treatment guidelines.

Cancer patients frequently develop chemotherapy-induced anemia, which can be treated with erythropoiesis-stimulating agents. These agents have shifted the standard of chemotherapy-induced anemia treatment away from the previous mainstay of red blood cell transfusions. In July 2007, the Centers for Medicare and Medicaid Services issued a National Coverage Decision restricting reimbursement for erythropoiesis-stimulating agents to those chemotherapy patients who have hemoglobin levels <10 g/dL at initiation of therapy. This decision was hypothesized to place a greater reliance on transfusions for chemotherapy-induced anemia treatment. This observational study examined transfusions and erythropoiesis-stimulating agent utilization rates within defined episodes of chemotherapy care using electronic medical records from seven practices consisting of 39 sites of care across seven states. We compared the frequency of myelosuppressive chemotherapy treatment, erythropoiesis-stimulating agent administrations, and red blood cell transfusions before and after the National Coverage Decision in oncology patients with chemotherapy-induced anemia. Although exposure to myelosuppressive chemotherapy was not different, erythropoiesis-stimulating agent administrations significantly decreased and blood transfusions significantly increased after implementation of the National Coverage Decision. The 31% increase in transfusions for patients aged 65 years and older was significant (P = 0.007) and higher than the 8% increase for patients younger than 65 years (P = 0.358). Changes in practice patterns for chemotherapy-induced anemia treatment that followed the Centers for Medicare and Medicaid Services reimbursement decision for erythropoiesis-stimulating agents seem to be impacting practice patterns. Further research is necessary to determine whether these changes represent a widespread and durable shift in patient treatment., (© 2010 Wiley-Liss, Inc.)

Objective: Forecast the return on investment (ROI) for advances in biologic therapies in years 2015 and 2030, based upon impact on disease prevalence, morbidity, and mortality for asthma, diabetes, and colorectal cancer., Methods: A deterministic, spreadsheet-based, forecasting model was developed based on trends in demographics and disease epidemiology. 'Return' was defined as reductions in disease burden (prevalence, morbidity, mortality) translated into monetary terms; 'investment' was defined as the incremental costs of biologic therapy advances. Data on disease prevalence, morbidity, mortality, and associated costs were obtained from government survey statistics or published literature. Expected impact of advances in biologic therapies was based on expert opinion. Gains in quality-adjusted life years (QALYs) were valued at $100,000 per QALY., Results: The base case analysis, in which reductions in disease prevalence and mortality predicted by the expert panel are not considered, shows the resulting ROIs remain positive for asthma and diabetes but fall below $1 for colorectal cancer. Analysis involving expert panel predictions indicated positive ROI results for all three diseases at both time points, ranging from $207 for each incremental dollar spent on biologic therapies to treat asthma in 2030, to $4 for each incremental dollar spent on biologic therapies to treat colorectal cancer in 2015. If QALYs are not considered, the resulting ROIs remain positive for all three diseases at both time points., Conclusions: Society may expect substantial returns from investments in innovative biologic therapies. These benefits are most likely to be realized in an environment of appropriate use of new molecules., Limitations: The potential variance between forecasted (from expert opinion) and actual future health outcomes could be significant. Similarly, the forecasted growth in use of biologic therapies relied upon unvalidated market forecasts.

Background: Prior to 2007, the erythropoiesis-stimulating agents (ESAs) epoetin alfa and darbepoetin alfa were indicated for use in chemotherapyinduced anemia to achieve target hemoglobin (Hb) levels of approximately 12 grams per deciliter (gm per dL), and treatment was to be withheld if Hb exceeded 13 gm per dL. In March 2007, the FDA changed the labeling of the ESAs to add boxed warnings, updated in November 2007, to include the following key points: (a) ESAs should be used only to treat anemia that occurs in patients with cancer while they are undergoing chemotherapy; (b) treatment with ESAs should be stopped when chemotherapy ends; and (c) dosing ESAs to an Hb target of 12 gm per dL or greater has resulted in more rapid cancer progression or shortened overall survival in patients with breast, head and neck, lymphoid, cervical, and non-small cell lung malignancies. In January 2008, the FDA specified that the increased risk of more rapid tumor growth or shortened survival was associated with ESAs when "administered in an attempt to achieve a Hb level of 12 gm per dL or greater, although many patients did not reach that level." A new black-box warning regarding this association was added to the labels of the ESAs in March 2008, and the FDA mandated further label changes on July 30, 2008, that ESA therapy should not be initiated in patients receiving chemotherapy at Hb levels of 10 gm per dL or higher., Objective: To (a) assess the prevalence and predictors of ESA administrations at Hb levels above 12 gm per dL among patients with a diagnosis of solid or hematologic cancer or myelodysplastic syndrome who began their first regimen of conventional myelosuppressive chemotherapy between 2002 and 2006, and (b) describe patterns of ESA treatment subsequent to the first ESA administration at Hb above 12 gm per dL., Methods: Using the Health Insurance Portability and Accountability Act (HIPAA)-compliant Varian Medical Oncology database of de-identified electronic medical records from 17 U.S. outpatient oncology practices, adults (aged 18 years or older) with any cancer diagnosis who began chemotherapy between January 1, 2002, and September 30, 2006, were identified. The Hb value associated with each ESA administration was defined as the closest Hb measurement within 7 days prior to the ESA administration. A first ESAHb > 12 was defined as the first time an ESA, either epoetin or darbepoetin, was given with an associated Hb greater than 12 gm per dL during the first chemotherapy regimen recorded in the database for each patient. Hb levels and ESA administrations after the first ESAHb > 12 were determined. Logistic regression models identified predictors of initial receipt of an ESAHb > 12, and of receiving further ESA treatment following the first such administration., Results: Between January 1, 2002, and September 30, 2006, there were 17,731 patients on chemotherapy, the mean (SD) age was 60 (13.2) years; 58.9% were female; 24.6% had breast cancer, 22.2% had lung cancer, 15.8% had colorectal cancer, 11.8% had hematologic cancer, and 25.6% had other or multiple cancers. Of these, 8,086 (45.6%) received an ESA at any time during the regimen, and 7,606 (42.9%) received an ESA at a known Hb level (i.e., Hb measurement within 7 days prior to ESA administration). During the first recorded chemotherapy regimen, 1,844 patients (10.4% of the chemotherapy cohort, 24.2% of ESA users with a known Hb; n = 1,226 epoetin, n = 618 darbepoetin) received an ESAHb > 12. Among patients receiving ESA treatment at a known Hb level, significant predictors of receiving an ESAHb > 12 included treatment in a community-based clinic rather than a hospital-affiliated clinic (odds ratio [OR] = 2.96, 95% confidence interval [CI] = 2.40-3.65), location of practice in the eastern United States (OR for Midwest = 0.67, 95% CI = 0.57- 0.78; OR for West = 0.27, 95% CI = 0.22-0.34), hematologic cancer rather than solid tumor (OR = 1.44, 95% CI = 1.21-1.71), private health insurance (OR for public health insurance = 0.80, 95% CI = 0.70-0.93; OR for other/ unknown insurance = 0.54, 95% CI = 0.47-0.62), and year of regimen 2002- 2003 (ORs = 0.75, 0.74, and 0.71 for 2004, 2005, and 2006, respectively). Following the first ESAHb > 12, 276 (22.5%) of the patients on epoetin and 276 (44.7%) on darbepoetin received no further ESA treatment during the next 6 weeks (Pearson chi-square = 96.1, P < 0.001)., Conclusions: This analysis of outpatient oncology practices between 2002 and 2006 revealed that 24% of ESA users with a known Hb level received ESAHb > 12. Dose withholding subsequently occurred in 23%- 45% of those patients. A higher proportion of patients on epoetin than darbepoetin continued ESA treatment after the first administration of ESAHb > 12.

Objective: Previous labeling and guidelines recommended initiating erythropoiesis agents (ESAs) for chemotherapy-induced anemia (CIA) at hemoglobin (Hb) levels < 11 g/dL, maintaining near 12 g/dL, and withholding at > or = 13 g/dL. This study analyzed adherence with recommendations in administration of darbepoetin (DA) to cancer patients., Design, Setting, and Participants: Retrospective analysis of Hb levels at which DA was administered using Varian electronic medical records (EMRs). The dataset comprises 141 694 cancer patients from 82 sites across 13 states. The study evaluated DA administrations with respect to recorded Hb for 8988 patients from 1/1/05 to 5/31/07., Main Outcome Measures: Proportion of DA administrations at Hb > or = 12 and Hb > or = 13 g/dL. Hb level was analyzed for all administrations, stratified by year and anemia type (CIA, anemia-of-cancer, and myelodysplastic syndrome)., Results: There were 51 111 DA administrations with Hb results. The proportion of administrations at Hb > or = 12 g/dL was 7.2% and at Hb > or = 13 g/dL was 0.6%, and for CIA 6.9%/0.6%, anemia of cancer (AOC) 8.8%/0.8%, and myelodysplastic syndrome (MDS) 6.5%/0.6%. The proportion of all DA administrations at Hb > or = 12 g/dL and > or = 13 g/dL declined from 8.6% to 5.3% (p < 0.0001) and from 0.7% to 0.4% (p < 0.0007), respectively during 1/1/05-5/31/07., Conclusions: In this population, DA administration at Hb > or = 12 g/dL and Hb > or = 13 g/dL occurred in 7.2% and 0.6% of administrations, respectively, a approximately 93% adherence rate with recommendations. Further research is required to understand dose titrations at Hb 12-13 g/dL, and whether similar patterns are observed for other ESAs, and in other practice settings. This study provides context for the debate regarding the utilization, benefits and risks of ESAs in cancer patients.

Introduction: Underdiagnosis of COPD appears to be common, although the degree of underdiagnosis is rarely measured. To document the extent of underdiagnosis in a high risk group of ambulatory patients, we performed spirometry in smokers aged 40 years and over drawn from general practices in two countries., Methods: Subjects were recruited from primary care practices in Aberdeen, Scotland, and Denver, Colorado, via random mailing. Current and former smokers aged 40 or older with no prior diagnosis of chronic obstructive respiratory disease (and no respiratory medications within the past year) were enrolled. Participants underwent pre- and post-bronchodilator spirometry. A study diagnosis of COPD was defined as post-bronchodilator FEV1/FVC < 0.70. RESULTS Spirometric examination was complete in 818 patients, of whom 155 (18.9%) had a study diagnosis of COPD. Using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity criteria, the COPD was mild in 57.4%, moderate in 36.8%, and severe in 5.8%. No patients had very severe disease according to GOLD criteria., Discussion: Screening of smokers over 40 in general practice may yield 10 - 20% undiagnosed COPD cases, with a substantial proportion of these having moderate to severe disease. Earlier diagnosis through targeted case-finding will allow early, aggressive smoking cessation efforts and may lead to a reduction in the burden of COPD symptoms and a reduced impact of the disease on health-related quality of life in these patients.

Objectives: In most primary care settings, spirometric screening of all patients at risk is not practical. In prior work, we developed questionnaires to help identify COPD in two risk groups: (1) persons with a positive smoking history but no history of obstructive lung disease (case finding), and (2) patients with prior evidence of obstructive lung disease (differential diagnosis). For these questionnaires, we now present a scoring system for use in primary care., Methods: Scores for individual questions were based on the regression coefficients from logistic regression models using a spirometry-based diagnosis of obstruction as the reference outcome. Receiver operator characteristic analysis was used to determine performance characteristics for each questionnaire. Several simplified scoring systems were developed and tested., Results: For both scenarios, we created a scoring system with two cut points intended to place subjects within one of three zones: persons with a high likelihood of having obstruction (high predictive value of a positive test result); persons with a low likelihood of obstruction (high predictive value of a negative test result); and an intermediate zone. Using these scoring systems, we achieved sensitivities of 54 to 82%, specificities of 58 to 88%, positive predictive values of 30 to 78%, and negative predictive values of 71 to 93%., Conclusions: These questionnaires can be used to help identify persons likely to have COPD among specific risk groups. The use of a simplified scoring system makes these tools beneficial in the primary care setting. Used in conjunction with spirometry, these tools can help improve the efficiency and accuracy of COPD diagnosis in primary care.

Background: Treating anemia associated with chemotherapy and many cancers is often necessary. However, patient satisfaction with anemia treatment is limited by the lack of validated instruments. We developed and validated a new treatment-specific patient satisfaction instrument: the Patient Satisfaction Questionnaire for Anemia Treatment (PSQ-An). Treatment burden and overall satisfaction scales were designed for ease of use in clinical practice., Methods: 312 cancer patients (141 breast, 69 gynecological, and 102 non-small cell lung) were targeted to complete the PSQ-An at 4 week intervals. Data from weeks 5 and 9 were analyzed. Patients also completed the MOS SF-36 Global Health assessment and questions concerning resources devoted to anemia treatment. Item reduction used endorsement rates, floor/ceiling effects, and item-item correlations. Factor analysis identified meaningful subscales. Test-retest reliability was assessed. Construct validity was tested, using Pearson's correlations, by comparing subscale scores to Global Health, hemoglobin levels, and resources devoted to anemia treatment., Results: The overall response rate was 92.9% (264/284) at week 5. Most (84.2%) of the patients were female, and the mean (SD) age was 60.2 (+/- 11.8) years. Two distinct subscales were identified measuring treatment burden (7 items) and overall satisfaction (2 items). Test-retest reliability was examined (ICC: 0.45-0.67); both were internally consistent (alpha = 0.83). Both subscales exhibited convergent and divergent validity with independent measures of health. ANOVA results indicated that the PSQ-An Satisfaction subscale discriminated between 5 levels of MOS SF-36 Global Health (P = 0.006)., Conclusion: The PSQ-An is a validated, treatment-specific instrument for measuring satisfaction with anemia treatment for cancer patients. PSQ-An subscales reflect the burden of injection anemia treatment on cancer patients and their assessment of the overall treatment value.

Research has revealed significant variation in both the quality of clinical care and the health status of populations. We conducted a study to determine if variations in the quality of clinical care can be quantitatively linked to variations in health status, at the patient and the population level. This study, conducted at health facilities in four municipalities in Macedonia, collected cross-sectional data on (1) structural measures (such as infrastructure, facilities, equipment and costs) and the quality of clinical care provided by physicians (as measured by clinical vignettes); (2) detailed health and socioeconomic status information on patients using the facilities; and (3) nearly the same information on a random sample of adults in each municipality. Data were collected from a total of 57 facilities, 273 physicians, 1451 patients, and 1627 adults from the general population. The main outcome measure was health status, based on self-reported health surveys. Objective health measures were obtained to control for preexisting conditions. The main explanatory variable was quality of clinical care, based on physicians' clinical vignette scores. Structural measures were included in our model but had a more distal relationship to health status. We found that quality of care strongly predicted self-reported health status of patients using the facilities even after controlling for other factors (p < .05). Quality of care was also associated with higher health status for the population living in the surrounding community, regardless of utilization (p < .05). This linkage between quality of clinical care and health suggests that policies that improve clinical practice have the potential to improve population health more rapidly than other interventions.

Background: Many patients with obstructive lung disease (OLD) carry an inaccurate diagnostic label. Symptom-based questionnaires could identify persons likely to need spirometry., Objectives: We prospectively tested questions derived from a comprehensive literature review and an international Delphi panel to help identify chronic OLD (COPD) in persons with prior evidence of OLD., Methods: Subjects were recruited via random mailing to primary-care practices in Aberdeen, Scotland, and Denver, Colorado. Persons aged 40 and older reporting any prior diagnosis of OLD or any respiratory medications in the past year were enrolled. Participants answered 54 questions covering demographics and symptoms and underwent spirometry with reversibility testing. A study diagnosis of COPD was defined by fixed airway obstruction as measured by post-bronchodilator FEV(1)/FVC <0.70. We examined ability of individual questions in a multivariate framework to discriminate between persons with and without the study diagnosis of COPD., Results: 597 persons completed all investigations and proceeded to analysis. The list of 54 questions yielded 52 items for analyses, which was reduced to 19 items for entry into a multivariate regression model. Nine items had significant relationships with the study diagnosis of COPD, including increased age, pack-years, worsening cough, breathing-related disability or hospitalization, worsening dyspnea, phlegm quantity, cold going to the chest, and receipt of treatment for breathing. Individual items yielded odds ratios ranging from 0.33 to 20.7. This questionnaire demonstrated a sensitivity of 72.0 and a specificity of 82.7., Conclusions: A short, symptom-based questionnaire identifies persons more likely to have COPD among persons with prior evidence of OLD., (Copyright (c) 2006 S. Karger AG, Basel.)

Background: Symptom-based questionnaires may enhance chronic obstructive pulmonary disease (COPD) screening in primary care., Objectives: We prospectively tested questions to help identify COPD among smokers without prior history of lung disease., Methods: Subjects were recruited via random mailing to primary care practices in Aberdeen, UK, and Denver, Colo., USA. Current and former smokers aged 40 or older with no prior respiratory diagnosis and no respiratory medications in the past year were enrolled. Participants answered questions covering demographics and symptoms and then underwent spirometry with reversibility testing. A study diagnosis of COPD was defined as fixed airway obstruction as measured by post-bronchodilator FEV(1)/FVC <0.70. We examined the ability of individual questions in a multivariate framework to correctly discriminate between persons with and without COPD., Results: 818 subjects completed all investigations and proceeded to analysis. The list of 54 questions yielded 52 items for analysis, which was reduced to 17 items for entry into multivariate regression. Eight items had significant relationships with the study diagnosis of COPD, including age, pack-years, body mass index, weather-affected cough, phlegm without a cold, morning phlegm, wheeze frequency, and history of any allergies. Individual items yielded odds ratios ranging from 0.23 to 12. This questionnaire demonstrated a sensitivity of 80.4 and specificity of 72.0., Conclusions: A simple patient self-administered questionnaire can be used to identify patients with a high likelihood of having COPD, for whom spirometric testing is particularly important. Implementation of this questionnaire could enhance the efficiency and diagnostic accuracy of current screening efforts., (Copyright (c) 2006 S. Karger AG, Basel.)

Chronic obstructive pulmonary disease (COPD) is often misdiagnosed as asthma, leading to inappropriate treatment and suboptimal patient outcomes. As part of a prospective study of patients with a history consistent with obstructive lung disease, we compared prior diagnostic labels with a study diagnosis based on spirometric results. We enrolled persons 40 years of age or older with prior diagnoses or medications consistent with obstructive lung disease. Patients were recruited via random mailing to primary care practices in Aberdeen, Scotland, and Denver, Colorado. Prior diagnoses of chronic bronchitis or emphysema (CBE) and asthma were reported by the subjects. Participants underwent pre- and post-bronchodilator spirometry. A study diagnosis of COPD was defined using post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) < 0.70. Spirometric examination was complete in 597 patients, of whom 235 (39.4%) had a study diagnosis of COPD. Among subjects with a spirometry-based study diagnosis of COPD, 121 (51.5%) reported a prior diagnosis of asthma without concurrent CBE diagnosis, 89 (37.9%) reported a prior diagnosis of CBE, and 25 (10.6%) reported no prior diagnosis of obstructive lung disease. Despite the availability of consensus guideline diagnostic recommendations, diagnostic confusion between COPD and asthma appears common. Increased awareness of the differences between the two conditions is needed to promote optimal patient management and treatment.

Purpose: Chronic obstructive pulmonary disease (COPD) is usually described as a disease of cigarette smoking. COPD is rarely considered in persons with no smoking history except in the context of another exposure. Accordingly, the disease has not been well characterized in these "never smokers.", Methods: We evaluated airway obstruction (defined as forced expiratory volume in 1 second/forced vital capacity <0.70) in US adults aged 30 to 80 years interviewed in the Third National Health and Nutrition Examination Survey with valid spirometry who had never smoked. Previously described risk factors were examined for their association with obstruction in bivariate and multivariate analyses., Results: Never smokers represented 42% of the Third National Health and Nutrition Examination Survey population aged 30 to 80 years, with obstruction prevalence of 91 per 1000. Never smokers accounted for 4.56 million cases of obstruction, or 23% of the total burden. Among these obstructed never smokers, 19% reported a prior diagnosis of asthma alone, and 12.5% reported COPD (alone or with asthma), leaving 68.5% with no prior respiratory diagnosis. After adjustment for other factors, higher rates of obstruction were significantly associated with increasing age, male sex, lower body mass index, and a history of allergies., Conclusions: Never smokers represent a significant proportion of airway obstruction in US adults. Only one fifth of obstruction in this group is explained by asthma. COPD may explain much of the remainder, although known risk factors were not explanatory in this dataset. Recommendations that lung health screening programs be limited to smokers should be reconsidered.

Objectives: To test questions usable in an ambulatory clinic to identify persons likely to have chronic obstructive pulmonary disease (COPD)., Methods: Analyses were performed as part of a study to identify patients with likely COPD in the Glenfield UK primary care clinic. Patients age 40 and older were recruited based on one of the following criteria: (1) respiratory medications in previous 2 years; (2) history of smoking or (3) history of asthma with no current medications based on case notes. Consenting patients reported smoking history, symptoms, and personal and family history of respiratory conditions. Spirometry with reversibility was conducted to ATS standards. Analyses were performed on this database to test questions for identifying patients with COPD from a sample of patients with a positive smoking history. Multivariate logistic regression identified the question set that best discriminated COPD from other conditions using receiver operating characteristic curves. The usefulness of a simple scoring system was assessed., Results: The study sample included 369 current and former smokers. Patients were diagnosed as: COPD=62 (16.8%); asthma=30 (8.1%); or no obstructive lung disease=277 (75.1%). The best questions for discriminating between persons with and without COPD included items on age, dyspnoea on exertion, and wheeze. This set of questions identified COPD patients with a sensitivity of 77.4--87.1% and specificity of 71.3--76.2%., Conclusions: A simple questionnaire can facilitate the diagnosis of COPD in a primary care setting.

Objective: Underdiagnosis of COPD is widespread, at least in part due to underuse of spirometry. Symptom-based questionnaires may be helpful as an adjunct to spirometry. The aim of this study was to determine which types of questions might aid in identifying COPD., Methodology: Questionnaires were identified by literature review and input from a multinational advisory board of primary care providers. Questions were placed into groups and evaluated with respect to their ability to perform in two scenarios: (i) to identify persons with COPD from a general population (Case-finding scenario); and (ii) to distinguish persons with COPD from those with asthma (Differential Diagnosis scenario). Questions were retrospectively validated using the Third National Health and Nutrition Examination Survey data. Potential predictive ability was examined in bivariate and multivariate frameworks., Results: Four published question sets and six additional documents were included. There was agreement in the use of smoking and symptom-based questions, but important differences in the use of demographic, personal history and other information. Most question types had significant bivariate relationships with airway obstruction. In multivariate analysis, age, BMI, smoking status and pack-years, symptoms (cough, phlegm, dyspnoea, wheeze), and prior diagnosis consistent with asthma or COPD all showed significant ability to discriminate between persons with and without obstruction in a general population., Conclusion: Simple self-administered questionnaires can be used to identify persons for whom spirometric testing may be especially appropriate. Development of such questionnaires will require additional study, including prospective validation of items in an appropriate clinical setting and policy recommendations on the use of these tools.

Objective: COPD treatment guidelines are available worldwide, yet it is not known how widely they are followed. This study evaluated the clinical care of COPD patients in Japan as compared to guideline recommendations., Methods: A sample of general and specialist physicians was selected from private outpatient clinics and public hospitals in Japan. Physicians were provided two clinical vignettes (COPD and asthma) and asked to make a diagnosis. They were next asked to define diagnostic tests and treatment recommendations specifically for a COPD patient. Responses were compared to recommendations from current COPD guidelines., Results: For the COPD unknown vignette, 6.2% of physicians diagnosed COPD while 54% diagnosed chronic bronchitis or emphysema. For COPD diagnosis, 81.9% of physicians recommended a CXR, 49.1% spirometry, and 17.7% a computed tomography scan. The most frequently recommended medication for a newly diagnosed COPD patient was theophylline (37.2%) followed by expectorants (32.1%) and inhaled anticholinergics (25.9%). Inhaled beta-agonists were recommended by fewer than 20% of all physicians., Conclusion: Care for COPD patients by selected Japanese physicians diverges from published practice guidelines. COPD is an infrequently used diagnostic label; diagnostic evaluation is characterized by a high use of computed tomography scans, particularly by specialists; and bronchodilator use was low.

COPD is commonly under-diagnosed, in part because people at risk are unaware of the relevant risk factors and do not recognize related symptoms. Providing this information might permit earlier disease identification but the questions chosen should identify those with spirometrically defined airflow obstruction. Using a population-based data set, we have determined which questions identify persons most likely to have airflow obstruction. Potential questions were selected by review of COPD risk factors and clinical features. Validation was by retrospective analysis of the NHANES III data set, a population-based U.S. household survey that included spirometry. We examined the predictive ability of individual questions in a multi-variate framework to correctly discriminate between persons with and without spirometric airway obstruction (defined as FEV1/FVC < 0.70). We then tested the discriminatory ability of the questions in combination. The following items showed significant predictive ability: increased age, smoking status, pack-years, cough, wheeze, and prior diagnosis of asthma or COPD. The best performing combination was age, smoking status, pack-years smoked, wheeze, phlegm, body mass index, and prior diagnosis of obstructive lung disease. Using this combination in a population of current and former smokers aged 40 and over, we achieved a sensitivity of 85% and specificity of 45%, with a positive predictive value of 38% and a negative predictive value of 88%. Performance of this tool is comparable to other screening methods designed for use in a general population. Symptom-based questionnaires can be a viable method to identify persons likely to have COPD in the general population. Dissemination of such tools should raise awareness among at-risk persons and help identify COPD patients in the primary care setting.

Objectives: Chronic obstructive pulmonary disease (COPD) as a cause of disability with subsequent costs remains poorly recognized. The small, growing body of literature on COPD shows that it is one of the leading causes of missed work.greater than asthma or diabetes. However, much less is known about the impact of COPD on long-term disability (LTD). Because the health care burden for disabled, working-age patients will fall heavily on managed care organizations, better estimates of the economic and pharmacoeconomic costs of COPD are required. We seek to improve understanding of the burden of COPD on several national LTD programs., Methods: We reviewed occupational health and disability literature and government statistics to determine how long-term, respiratory-related disability is addressed by disability pension programs in 8 developed countries (Canada, France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States). We then applied respiratory-specific disability definitions to country-specific population and pension information to estimate the potential burden of COPD on LTD insurance programs in each country., Results: Comprehensive, relevant data to evaluate respiratory-related disability are lacking. Of the study countries, only the United States has explicit respiratory specific criteria for disability eligibility, which are based solely on spirometry. We estimate that the total burden of COPD in the study countries may range from 5 billion dollars to as high as 25 billion dollars per year if all persons who met U.S. eligibility criteria for respiratory-related disability were granted compensation., Conclusion: The potential burden of COPD on LTD programs may be large. The lack of standard criteria for respiratory-related disability may lead to underrecognition of COPD's true potential impact. Further work is needed to develop consistent and cost-effective ways to measure the impact of COPD and to assist in disability determination for COPD patients.

We inform a county's efforts to provide health insurance to uninsured working immigrants-a group left out of national and state strategies that aim to expand coverage. We analyzed a population-based survey data administered in English, Spanish, Cantonese, Mandarin, Korean, Vietnamese, and Dari on 5,540 nonelderly adult workers in Alameda County, California. The study models the likelihood of employment-based coverage, estimates the eligibility for public programs, and evaluates the affordability of average employee share of premiums by citizenship status and years lived in the United States (tenure). Immigrant workers in Alameda County are disproportionately uninsured. They constitute 29% of the employee labor force but 54% of uninsured employees. Employment-based coverage increased with citizenship and length of stay (tenure) in the United States. Noncitizens with less than 5 years residency in the United States faced the greatest disadvantage in securing employment-based coverage, an effect that is greater than disadvantages associated with race/ethnicity. A citizenship-tenure divide existed in obtaining employment-based coverage, suggesting that policies focusing on noncitizen and new immigrant workers would greatly relieve the disparate uninsured rates among workers. The expansion of nonemployment-based coverage programs would cover more than 30% of Alameda County's uninsured immigrant workers; but subsidies will also be needed for the lowest-income workers who are not eligible for these programs.

Objective: To determine whether clinical vignettes can measure variations in the quality of clinical care in two economically divergent countries., Data Source/study Setting: Primary data collected between February 1997 and February 1998 at two Veterans Affairs facilities in the United States and four government-run outpatient facilities in Macedonia., Study Design: Randomly selected, eligible Macedonian and U.S. physicians (>97 percent participation rate) completed vignettes for four common outpatient conditions. Responses were judged against a master list of explicit quality criteria and scored as percent correct. DATA COLLECTION/ EXTRACTION: An ANOVA model and two-tailed t-tests were used to compare overall scores by case, study site, and country. Principal Findings. The mean score for U.S. physicians was 67 percent (+/-11 percent) compared to 48 percent (+/-11 percent) for Macedonian physicians. The quality of clinical practice, which emphasizes basic skills, varied greatly in both sites, but more so in Macedonia. However, the top Macedonian physicians in all sites approached or-in one case-exceeded the median score in the U.S. sites., Conclusions: Vignettes are a useful method for making cross-national comparisons of the quality of care provided in very different settings. The vignette measurements revealed that some physicians in Macedonia performed at a standard comparable to that of their counterparts in the United States, despite the disparity of the two health systems. We infer that in poorer countries, policy that promotes improvements in the quality of clinical practice-not just structural inputs-could lead to rapid improvements in health.

Objectives: Although anemia is known to influence clinical outcomes in heart failure (HF) patients, little is known about its impact on economic outcomes. A retrospective analysis was performed to determine the impact of hemoglobin (Hb) level on hospital length of stay (LOS), total charges, and hospital mortality in HF patients., Methods: Claims data were drawn from 21 teaching and nonteaching hospitals for patients hospitalized between October 1, 2000 and September 30, 2001. The impact of Hb on LOS, charges, and hospital mortality was determined using multivariate analyses. Two-stage least squares regression methods were used to assess the potential endogeneity of the economic outcomes (LOS and total charges) and Hb level., Results: Of the 8569 patients in the analysis, 40.2% had Hb < 12 g/dl and 73.8% were > or = 70 years of age. Hemoglobin had significant independent effects on all three outcomes. A 1 g/dl increase in Hb was associated with a 5.1% reduction in LOS (P < 0.001), a 4.3% decrease in charges (P < 0.001), and an 8.7% reduction in mortality risk (P < 0.001). The impact of Hb on all outcomes was greatest in younger HF patients., Conclusions: This analysis demonstrates that higher Hb is associated with reductions in LOS, charges, and mortality in hospitalized HF patients. Further clinical studies are necessary to validate the cost effectiveness of pharmacologic intervention in anemic HF patients and its impact on patient care.

Background: Cross-sectional analyses have identified significant associations between quality of life (QOL), and comorbidities and adverse effects in cardiac transplant recipients. However, little is known about factors that influence changes in QOL over time. This study examines both cross-sectional and longitudinal data from long-term survivors to identify factors that affect differences in QOL among recipients and individual changes in QOL during a 1-year period., Methods: Self-selected enrollees completed questionnaires, including QOL scales, at 3-month intervals. Repeated measures multiple regression analysis was used to examine the association between the QOL scales and comorbidities, adverse effects, and compliance measures, controlling for other factors., Results: We included 569 participants in the analysis, with a mean time since transplantation of 8.6 years. Cross-sectional results showed that the number of comorbidities, treatment non-compliance, and several adverse effects were associated with low QOL. In longitudinal results, waiting to take medications and taking less medication because of lifestyle restrictions were associated with decreases in QOL over time. Hair loss, changes in face shape, and decreased sexual interest or ability also had the largest adverse effects on changes in QOL., Conclusions: These findings provide new opportunities for interventions to address factors related to decreases in QOL. Clinicians should actively solicit information about compliance with medication regimens. In addition, information about the adverse effects of medications should be considered when making therapeutic decisions.

The dominant reform paradigm for developing countries introduces market forces into health care provision to improve quality and efficiency. Yet, there is very little empirical evidence as to how individual physicians respond to such incentives. Using a survey of primary health care providers in the Republic of Macedonia, the effect of privatization on physician workload and resource utilization is examined. The survey of physicians in public and private clinics provides extensive data on physician demographics, practice patterns and capital inputs, with an innovation being a measure of physician skill based on responses to several clinical vignettes. Physician production of patient visits is modeled as a jointly determined process of workload and input utilization. Such a formulation acknowledges the endogeneity of input and output and, more importantly, allows the straightforward estimation of the demand equations for labor and capital inputs. Controlling for physician and practice characteristics, private physicians do exhibit higher productivity and greater capital resource use per patient. Major factors influencing workload and resource use are skill and referral rates, both of which have important implications for designing comprehensive and effective physician incentive systems.

The Republic of Macedonia is undertaking sweeping reforms of its health sector. Funded by a World Bank credit, the reforms seek to improve the efficiency and quality of primary health care (PHC) by significantly strengthening the role of the market in health care provision. On the supply-side, one of the key reform proposals is to implement a capitation payment system for PHC physicians. By placing individual physicians on productivity-based contracts, these reforms will effectively marketize all PHC provision. In addition, the Ministry of Health is considering the sale or concessions of public PHC clinics to private groups, indicating the government's commitment to marketization of health care provision. Macedonia is in a unique position to develop a new role for the private sector in PHC provision. The private provision of outpatient care was legalized soon after independence in 1991; private physicians now account for nearly 10% of all physicians and 22% of PHC physicians. If the reforms are fully realized, all PHC physicians-over 40% of all physicians-will be financially responsible for their clinical practices. This study draws on Macedonia's experience with limited development of private outpatient care starting in 1991 and the reform proposals for PHC, finding a network of policies and procedures throughout the health sector that negatively impact private and public sector provision. An assessment of the effects that this greater policy environment has on private sector provision identifies opportunities to strategically enhance the reforms. With respect to established market economies, the study finds justification for a greater role for government intervention in private health markets in transition economies. In addition to micro-level payment incentives and administrative controls, marketization in Central and Eastern Europe requires an examination of insurance contracting procedures, quality assurance practices, public clinic ownership, referral practices, hospital privileges, and capital investment policies.