Development and validation of a claims-based algorithm to identify patients with Neuromyelitis Optica Spectrum disorder.

INTRODUCTION: No validated algorithm exists to identify patients with neuromyelitis optica spectrum disorder (NMOSD) in healthcare claims data. We developed and tested the performance of a healthcare claims-based algorithm to identify patients with NMOSD. METHODS: Using medical record data of 101 adults with NMOSD, multiple sclerosis (MS), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), we tested the sensitivity and specificity of claims-based algorithms developed through interviews with neurologists. We tested the best-performing algorithm's face validity using 2016-2019 data from IBM MarketScan Commercial and Medicare Supplemental databases. Demographics and clinical characteristics were reported. RESULTS: Algorithm inclusion criteria were age ≥ 18 years and (≥1 NMO diagnosis [or ≥ 1 transverse myelitis (TM) and ≥ 1 optic neuritis (ON) diagnosis] and ≥ 1 NMOSD drug) or (≥2 NMO diagnoses ≥90 days apart). Exclusion criteria were MS diagnosis or use of MS-specific drug after last NMO diagnosis or NMOSD drug; sarcoidosis diagnosis after last NMO diagnosis; or use of ≥1 immune checkpoint inhibitor. In medical record billing data of 50 patients with NMOSD, 30 with MS, and 21 with MOGAD, the algorithm had 82.0% sensitivity and 70.6% specificity. When applied to healthcare claims data, demographic and clinical features of the identified cohort were similar to known demographics of NMOSD. CONCLUSIONS: This clinically derived algorithm performed well in medical records. When tested in healthcare claims, demographics and clinical characteristics were consistent with previous clinical findings. This algorithm will enable a more accurate estimation of NMOSD disease burden using insurance claims datasets.

Clinical and epidemiological correlates of treatment change in patients with NMOSD: insights from the CIRCLES cohort.

OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSD) represent rare autoimmune diseases of the central nervous system largely targeting optic nerve(s) and spinal cord. The present analysis used real-world data to identify clinical and epidemiological correlates of treatment change in patients with NMOSD. METHODS: CIRCLES is a longitudinal, observational study of NMOSD conducted at 15 centers across North America. Patients with ≥ 60 days of follow-up and receiving on-study maintenance treatment were evaluated. The mean annual relapse rate (ARR) was estimated using negative binomial models; the likelihood of treatment change was estimated using Cox proportional hazards models. Relapses were included as time-varying covariates to estimate the relationship to treatment change. RESULTS: Of 542 patients included, 171 (31.5%) experienced ≥ 1 relapse on the study and 133 patients (24.5%) had ≥ 1 change in the treatment regimen. Two categories of variables significantly correlated with the likelihood of treatment change: (1) relapse: any on-study relapse (hazard ratio [HR] = 2.91; p < 0.001), relapse phenotypes (HR range = 2.15-5.49; p < 0.001), and pre-study ARR > 0.75 (HR 2.28; p < 0.001); 2) disease phenotype: brain syndrome only vs transverse myelitis involvement at onset (HR 2.44; p = 0.008), disease duration < 1 vs > 5 years (HR 1.66; p = 0.028), or autoimmune comorbidity (HR 1.55; p = 0.015). A subset of these factors significantly correlated with shorter time to first rituximab discontinuation. CONCLUSIONS: In CIRCLES, relapse patterns and disease phenotype significantly correlated with changes in the maintenance treatment regimen. Such findings may facilitate the identification of patients with NMOSD who are likely to benefit from treatment change to reduce relapse risk or disease burden and enhance the quality of life.

Health care resource utilization and costs among individuals with vs without Huntington disease in a US population.

BACKGROUND: Quantifying the extent of health care resource utilization (HCRU) and costs associated with Huntington disease (HD) is vital for providers, decisionmakers, and payers to understand unmet treatment needs and to ensure limited resources can be used to benefit the maximum number of people with HD. OBJECTIVE: To quantify HCRU and costs for people with HD, overall and by disease stage, and compare these with non-HD controls. METHODS: This was a retrospective cohort study using administrative claims data from the IBM MarketScan Commercial, Multi-State Medicaid, and Medicare Supplemental Databases from January 1, 2009, to December 31, 2018. People with an HD claim between January 1, 2010, and December 31, 2017, were selected for this analysis and matched with non-HD controls for comparison. The HD cohort and the non-HD controls were exact matched on their follow-up duration and propensity score matched 1:4 to create the final analytical cohort. Index date was the first HD diagnosis for the HD cohort (proxy index date assigned to controls), and all individuals were required to have continuous enrollment for 12 or more months pre-index (baseline) and 3 or more months post-index. Proportions of all-cause HCRU (ie, outpatient visits, inpatient visits, emergency department visits, pharmacy fills, radiology visits, and physical/occupational therapy visits) in the 6-months post-index and HCRU counts and costs per patient per month (PPPM) over the entire follow-up were calculated for each cohort. RESULTS: A total of 2,473 individuals with HD and 9,522 matched non-HD controls were identified. HCRU in 6 months post-index was significantly greater in people with HD compared with non-HD controls for all health care service categories; P < 0.0001. The mean number of HCRU PPPM for all measured healthcare services was significantly higher in people with HD compared with non-HD controls (P < 0.001). Mean total costs (2018 USD PPPM) for the HD cohort ($2,260 [SD = $4,682]) were twice the total costs in the non-HD cohort ($1,056 [SD = $3,078]) (P < 0.0001) and were highest across all disease stages. CONCLUSIONS: This study provides current comprehensive HCRU and cost estimates in individuals with HD relative to those without the disease, thus demonstrating the high economic burden imposed by HD. DISCLOSURES: Dr Ta: Employment with Genentech (at time of study) and stock options with Roche; Dr To: Employment and stock options/dividends with Genentech; Dr Patel: Employment and stock options with Roche/Genentech; Dr Fuller: Employment with CHDI Management/CHDI Foundation; Mr Surinach: Employment with Genesis Research (which receives consulting fees from Genentech/Roche); Dr Abbass: Employment and stock options with Genentech; Dr Exuzides: Employment and stock options with Roche/Genentech; and Ms Luo: Employment with CHDI Management/CHDI Foundation. This study was funded by Genentech Inc. The authors thank Greg Rowe of Chrysalis Medical Communications for providing medical writing support, which was funded by F. Hoffmann-La Roche Ltd, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

A retrospective longitudinal cohort study of the clinical burden in myasthenia gravis.

BACKGROUND: Patients with generalized myasthenia gravis (MG) often experience debilitating exacerbations, with the possibility of life-threatening respiratory crises requiring hospitalization. Long-term longitudinal studies are needed to understand the burden of MG, including in patients whose disease is refractory to conventional treatment. METHODS: A retrospective, longitudinal, cohort study was conducted of patients in England aged ≥ 18 years with treatment-refractory or non-refractory MG, using data recorded during 1997-2016 in the Clinical Practice Research Datalink and the Hospital Episode Statistics databases. A control cohort of patients without MG, matched to the patients in the treatment-refractory MG cohort, was also identified. Outcome measures included myasthenic crises, MG exacerbations, MG-related hospitalizations, comorbidities, and all-cause mortality. Descriptive statistics were calculated for the overall MG population. For continuous variables, between-cohort comparisons were made using t tests for normally distributed data and Mann-Whitney U tests for non-normally distributed data. For categorical data, the comparisons were made by chi-squared tests. Differences in clinical outcomes between cohorts were modeled using negative binomial regression. RESULTS: A total of 1149 patients with MG were included. Overall, 18.4% of patients experienced myasthenic crises, 24.6% experienced exacerbations, and 38.6% underwent MG-related hospitalizations. Most of these events occurred within 2-3 years of diagnosis. Patients with MG refractory to conventional treatment (n = 66) experienced more exacerbations and MG-related hospitalizations than patients with non-refractory disease (n = 1083). Patients with refractory MG experienced a higher frequency of renal disease and hypertension compared with patients with non-refractory MG, and with matched patients without MG. They were also more likely to have diabetes and congestive heart failure than the matched controls. Rates of all-cause mortality during the follow-up period did not differ between patients with refractory MG and non-refractory MG. CONCLUSIONS: These results show that conventional treatments for MG are not adequately managing patients' symptoms and that patients with refractory MG are more likely to experience certain comorbidities than those with non-refractory MG or matched controls without MG. Future research should focus on the impact of newer targeted therapies on long-term clinical outcomes and comorbid conditions.

Healthcare resource utilization and costs in individuals with Huntington's disease by disease stage in a US population.

AIMS: To quantify healthcare resource utilization (HRU) and costs by disease stage in individuals with Huntington's disease (HD) in a US population. MATERIALS AND METHODS: This retrospective cohort study used administrative claims data from the IBM MarketScan Commercial, Multi-State Medicaid, and Medicare Supplemental Databases between 1 January 2009 and 31 December 2018. Individuals with an HD claim between 1 January 2010 and 31 December 2017 were selected. Index date was the date of first HD diagnosis. Individuals were required to have continuous enrollment for ≥ 12 months pre-index, 3 months post-index, and have no pre-index HD claims. All-cause HRU and costs per patient per month (PPPM) (overall and stratified by disease stage) were assessed for individuals with HD. RESULTS: A total of 2,669 individuals with HD were identified. Of these, 1,432 (53.7%), 689 (25.8%), and 548 (20.5%) had early-, middle-, and late-stage HD at baseline, respectively. Mean HRU PPPM by post-index HD stage increased with disease stage for outpatient visits, pharmacy claims, and HD-related pharmacy claims (p < 0.05 for all). Mean inpatient visits and emergency room visits PPPM were highest in individuals with middle-stage HD (p <0.05 for all). Mean total all-cause healthcare cost PPPM for individuals with HD was $2,889, and it was significantly higher in middle-stage individuals, at $7,988, compared with early- and late-stage individuals, at $3,726 and $5,125, respectively; p <0.0001. LIMITATIONS: In the absence of disease staging information in administrative claims data, staging was based on the presence of clinical markers in claims. Our evaluations didn't include the indirect costs of HD, which may be substantial as HD typically affects people at their peak earning potential. CONCLUSIONS: HRU and costs of care are high among individuals with HD, particularly among those with middle- and late-stage disease. This indicates that the disease burden in HD increases with disease stage, highlighting the need for interventions that can slow or prevent disease progression.

Epidemiology of Huntington's Disease in the United States Medicare and Medicaid Populations.

INTRODUCTION: Huntington's disease (HD) is a rare, genetic, and ultimately fatal neurodegenerative disease, with a devastating impact on individuals and families across generations. Few estimates of HD epidemiology in the United States (US) exist. METHODS: This study employed a retrospective cross-sectional design to examine the epidemiology of HD in the US Medicare and Medicaid beneficiary populations using 2016-2017 claims data from the Medicare 100% Research Identifiable Files (RIFs) and 2014 claims data from the Medicaid Analytic eXtract (MAX) files for 17 states. Medicare beneficiaries ≥65 years with a diagnosis of HD (≥1 claim with ICD-10-CM code G10) in 2017 and Medicaid beneficiaries <65 years with a diagnosis of HD (≥1 claim with ICD-9-CM code 333.4) in 2014 were identified. The study outcomes included the 2017 prevalence proportion and incidence rate of HD in the Medicare population and the 2014 prevalence proportion of HD in the Medicaid population. RESULTS: In the Medicare population, 1,941 prevalent and 819 incident cases of HD were identified in 2017, corresponding to a prevalence proportion of 13.1 per 100,000 persons and incidence rate of 6.1 per 100,000 person-years. In the Medicaid population, 353 prevalent cases of HD were identified in 2014, corresponding to a prevalence proportion of 15.2 per 100,000 persons. CONCLUSION: This study suggests that prevalence and incidence of HD in the US may be higher than previously estimated. This has important implications in raising awareness of HD among providers and payers and ensuring availability of and access to services for HD patients and care partners in the Medicare and Medicaid populations.

Understanding the Burdens Associated with Huntington's Disease in Manifest Patients and Care Partners-Comparing to Parkinson's Disease and the General Population.

BACKGROUND: The study provides real-world data on the impact of Huntington's disease (HD) from the perspective of individuals with HD (IHD) and care partners (HD-CP) and contextualizes these results relative to Parkinson's disease (PD) and the general population (GP). METHODS: Cross-sectional survey of IHD and HD-CP in the US (July 2019-August 2019) conducted using the Rare Patient Voice panel. Data for individuals with Parkinson's Disease (IPD), the general population (GP), and respective care partners (PD-CP; GP-CP) came from the 2018 US National Health and Wellness Survey. Outcomes included demographics, mental health, clinical characteristics, and health-related quality of life (HRQoL). RESULTS: IHD had greater comorbid anxiety (IHD = 51.2%, IPD = 28.8%, GP = 2.0%), and HD-CP had greater comorbid anxiety (HD-CP = 52.5%, PD-CP = 28.6%, GP-CP = 19.6%) and depression (HD-CP = 65.0%, PD-CP = 29.9%, GP-CP = 19.6%), relative to other cohorts (p < 0.05). Respective of their GP cohorts, IHD exhibited lower HRQoL (EQ-5D: 0.66 ± 0.21 vs. 0.81 ± 0.17) and greater depression (PHQ-9: 11.59 ± 7.20 vs. 5.85 ± 6.71), whereas HD-CP exhibited greater depression only (PHQ-9: 6.84 ± 6.38 vs. 4.15 ± 5.58) (p < 0.001). No differences were observed between HD/HD-CP and PD/PD-CP cohorts on PHQ-9 or HRQoL. CONCLUSIONS: HD has a significant burden on patients and care partners, which is higher than GP. Notably, anxiety and depression were greater among HD vs. PD, despite similar HRQoL.

Healthcare utilization and cost burden of Huntington's disease among Medicare beneficiaries in the United States.

AIMS: To examine healthcare utilization and costs in a US Medicare population diagnosed with Huntington's disease (HD). METHODS: This was a retrospective matched cohort study using Medicare fee-for-service (FFS) claims data using 2013-2017 Research Identifiable Files. Medicare beneficiaries diagnosed with HD based on the presence of at least one medical claim with an International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification (ICD-9/10-CM) diagnosis code for HD (ICD-9-CM: 333.4; ICD-10-CM: G10) during the identification period (2014-2016). Beneficiaries without HD were drawn from a 5% random sample of Medicare beneficiaries and 1:1 matched to those with HD for comparison. All-cause and HD-related (any utilization related to HD diagnosis or symptoms associated with HD) healthcare utilization and costs were reported. RESULTS: We identified 3,688 matched pairs of beneficiaries with and without HD. Of those with HD, 1,922 (52.1%) were late-stage, 916 (24.8%) were middle-stage, and 850 (23.1%) were early-stage. Mean [SD] annual total healthcare costs were higher for HD beneficiaries than beneficiaries without HD ($41,631 [57,393] vs. $17,222 [31,218], p < .001) and were primarily driven by outpatient pharmacy costs ($19,182 [45,469] vs. $4,318 [11,553], p < .001). In the stratified analysis, total healthcare costs were highest among beneficiaries with late-stage HD (mean [SD] cost: $20,475 [$41,122] for early-stage vs. $29,733 [$44,977] for middle-stage vs. $56,657 [$64,185] for late-stage; p < .001). LIMITATIONS: Results are not generalizable to beneficiaries enrolled in other non-FFS Medicare plans. Administrative claims are intended for billing purposes, not research, and may not capture all symptoms, comorbidities, and other adverse events. CONCLUSIONS: This original, comprehensive analysis of healthcare utilization and economic burden among Medicare beneficiaries with HD found that healthcare needs and associated costs are substantially higher among Medicare beneficiaries who are diagnosed with HD compared to beneficiaries without HD.

The costs of care from a US claims database in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system that often leads to severe disability. Patients with highly active NMOSD have approximately a 10-times higher hospital inpatient admission rate compared with patients without NMOSD. Accurate assessments of the impact of NMOSD treatments on the burdens of illness require quantitative metrics of these burdens, including costs of care. METHODS: This study evaluated claims data from the IBM MarketScan Commercial and Medicare Supplemental Databases between 2014 and 2018. Patients were included based on inpatient or outpatient claims meeting criteria defined for NMOSD. Non-NMOSD controls were matched 5:1 to patients with NMOSD. Total costs of healthcare services in consumer price index-adjusted 2019 US dollars during the 1-year postindex follow-up period were calculated for patients and controls. RESULTS: Patients with NMOSD required more healthcare services and incurred significantly greater costs for inpatient hospitalizations (annual mean [SD] cost: $29,054 [$144,872] vs controls $1521 [$10,759]), outpatient services ($24,881 [$35,463] vs $4761 [$26,447]), and emergency department (ED) visits ($2400 [$7771] vs $408 [$2579]). Almost 12% of patients with NMOSD were further burdened with plasma exchange or intravenous immunoglobulin G treatments, costing an annual median (interquartile range) of $1684 ($566-$3817) and $24,353 ($5425-$42,975), respectively. CONCLUSIONS: Compared with controls, patients with NMOSD had significantly higher costs associated with hospitalizations, ED visits, and prescriptions. These results highlight the considerable economic burden of NMOSD, which may be favorably impacted by disease-modifying therapies that are regulatory-approved to be safe and effective.

Burden and cost of comorbidities in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is associated with various comorbidities, including non-autoimmune and autoimmune conditions. The burden and cost of illness for NMOSD are unclear, particularly in the context of comorbidities. METHODS: Claims data from IBM MarketScan Commercial and Medicare Supplemental Databases between 2014 and 2018 were analyzed. Patients with NMOSD were specified as having inpatient or outpatient claims for NMOSD diagnosis or specific NMOSD symptoms claims and no subsequent claims for multiple sclerosis (MS) or use of MS disease-modifying therapy (DMT). Continuous enrollment ≥ 6 months before and ≥ 1 year after the first claim (index date) was required for study inclusion. Total costs stratified by comorbidities within 12 months post-index date were calculated per patient and compared 1:5 with matched non-NMOSD controls. RESULTS: A total of 162 patients with NMOSD and 810 non-NMOSD controls were evaluated. A significantly higher proportion of NMOSD patients had comorbidities than non-NMOSD controls (66.7% vs 41.5%; P < 0.001). Concomitant autoimmune disease occurred in 19.1% vs 4.9% (P < 0.001) of patients with NMOSD vs non-NMOSD controls. NMOSD patients incurred significantly higher total median (interquartile range) healthcare costs per patient ($68,386.48 [$23,373.54-$160,862.70]) than matched non-NMOSD controls with autoimmune disease ($17,215.13 [$6715.48-$31,441.93]; P < 0.001) or patients with NMOSD without autoimmune comorbidity ($23,905.42 [$8632.82-$67,251.54]; P = 0.022). Similarly, patients with NMOSD and non-autoimmune comorbidities incurred higher median healthcare costs than matched controls. CONCLUSIONS: Patients with NMOSD experience significant disease burden and cost that are amplified by comorbidities. Effective therapies are needed, particularly for patients with concomitant autoimmune disease.

Identification and temporal trends of patients with neuromyelitis optica spectrum disorder in a US insurance claims database.

BACKGROUND: This US claims-based study aimed to identify and characterize temporal trends in diagnostic pathways for patients likely to have neuromyelitis optica spectrum disorder (NMOSD). METHODS: Patients were identified from IBM MarketScan Commercial Databases if, within 1 year, they had two NMOSD claims separated by ≥ 60 days; two transverse myelitis (TM) or optic neuritis (ON) claims separated by ≥ 60 days, and one additional symptom (TM, ON, or area postrema syndrome); or one NMOSD claim and one additional symptom. The first NMOSD or TM/ON claim was the index date, and the second claim was the diagnosis date. Similar methodology was used in temporal trend and incidence and prevalence analyses. RESULTS: Among 1,901 patients with NMOSD, 34.2% were identified by two NMO claims, 53.2% by ON or TM +1 symptom, and 12.6% by one NMOSD claim +1 symptom. Anti-aquaporin-4 immunoglobin G (AQP4-IgG) autoantibody tests and magnetic resonance imaging was used for 23.0% and 71.9% of cases, respectively. Across cohorts, 21.4-49.1% had multiple sclerosis (MS) diagnosis claims prior to index date, and 37.3-60.6% had an MS diagnosis, 14.9-31.0% had MS disease-modifying therapy (DMT) claims and 6.3-44.8% had immunosuppressive therapy (IST) claims <1 year after diagnosis. Over time, there were slight changes in MS diagnosis claims, AQP4-IgG autoantibody testing, and DMT and IST use before and after NMOSD diagnosis. LIMITATIONS: This study is limited by the information available in US claims databases, which included the potential for misclassification of NMOSD based solely on claims codes and lack of reimbursement for AQP4-IgG testing by insurance companies. CONCLUSIONS: Among patients likely to have NMOSD, low AQP4-IgG testing rates, IST use, frequent MS diagnosis claims, and DMT use highlight the need for a diagnostic algorithm and timely treatment of NMOSD.

Healthcare resource utilization by patients with treatment-refractory myasthenia gravis in England.

Aims: To examine healthcare resource utilization associated with refractory myasthenia gravis (MG) in England. Materials and methods: This was a retrospective cohort study of linked data from the Clinical Practice Research Datalink and the Hospital Episode Statistics database collected between 1997 and 2016. Included patients were ≥18 years of age at the index MG diagnosis. Patients with refractory MG were identified using an algorithm based on treatments received. Healthcare resource utilization since the index date was compared between refractory and non-refractory cohorts. Results: The study included 1149 patients with MG, of whom 66 (5.7%) were refractory. Sex and age at diagnosis did not significantly differ between the refractory and non-refractory cohorts. Rates of healthcare resource utilization per person-year were significantly higher (p < .05) for patients with refractory compared to non-refractory MG for GP visits, visits to other healthcare professionals, outpatient visits and inpatient hospitalization. Patients in the refractory cohort spent more total days hospitalized since the index visit than patients in the non-refractory cohort (median, 33 vs. 16 days [p < .0001]). Limitations: The algorithm for identifying refractory patients did not include clinical criteria. Also, treatments administered in hospitals or by specialists were not available in the databases. Conclusions: Patients in England with refractory MG more often visit healthcare providers, are hospitalized and visit an emergency room than patients with non-refractory MG.

Statistical Modeling of Disease Progression for Chronic Obstructive Pulmonary Disease Using Data from the ECLIPSE Study.

BACKGROUND: To develop statistical models predicting disease progression and outcomes in chronic obstructive pulmonary disease (COPD), using data from ECLIPSE, a large, observational study of current and former smokers with COPD. METHODS: Based on a conceptual model of COPD disease progression and data from 2164 patients, associations were made between baseline characteristics, COPD disease progression attributes (exacerbations, lung function, exercise capacity, and symptoms), health-related quality of life (HRQoL), and survival. Linear and nonlinear functional forms of random intercept models were used to characterize these relationships. Endogeneity was addressed by time-lagging variables in the regression models. RESULTS: At the 5% significance level, an exacerbation history in the year before baseline was associated with increased risk of future exacerbations (moderate: +125.8%; severe: +89.2%) and decline in lung function (forced expiratory volume in 1 second [FEV1]) (-94.20 mL per year). Each 1% increase in FEV1 % predicted was associated with decreased risk of exacerbations (moderate: -1.1%; severe: -3.0%) and increased 6-minute walk test distance (6MWD) (+1.5 m). Increases in baseline exercise capacity (6MWD, per meter) were associated with slightly increased risk of moderate exacerbations (+0.04%) and increased FEV1 (+0.62 mL). Symptoms (dyspnea, cough, and/or sputum) were associated with an increased risk of moderate exacerbations (+13.4% to +31.1%), and baseline dyspnea (modified Medical Research Council score ≥2 v. <2) was associated with lower FEV1 (-112.3 mL). CONCLUSIONS: A series of linked statistical regression equations have been developed to express associations between indicators of COPD disease severity and HRQoL and survival. These can be used to represent disease progression, for example, in new economic models of COPD.

Development of the Galaxy Chronic Obstructive Pulmonary Disease (COPD) Model Using Data from ECLIPSE: Internal Validation of a Linked-Equations Cohort Model.

BACKGROUND: The recent joint International Society for Pharmacoeconomics and Outcomes Research / Society for Medical Decision Making Modeling Good Research Practices Task Force emphasized the importance of conceptualizing and validating models. We report a new model of chronic obstructive pulmonary disease (COPD) (part of the Galaxy project) founded on a conceptual model, implemented using a novel linked-equation approach, and internally validated. METHODS: An expert panel developed a conceptual model including causal relationships between disease attributes, progression, and final outcomes. Risk equations describing these relationships were estimated using data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study, with costs estimated from the TOwards a Revolution in COPD Health (TORCH) study. Implementation as a linked-equation model enabled direct estimation of health service costs and quality-adjusted life years (QALYs) for COPD patients over their lifetimes. Internal validation compared 3 years of predicted cohort experience with ECLIPSE results. RESULTS: At 3 years, the Galaxy COPD model predictions of annual exacerbation rate and annual decline in forced expiratory volume in 1 second fell within the ECLIPSE data confidence limits, although 3-year overall survival was outside the observed confidence limits. Projections of the risk equations over time permitted extrapolation to patient lifetimes. Averaging the predicted cost/QALY outcomes for the different patients within the ECLIPSE cohort gives an estimated lifetime cost of £25,214 (undiscounted)/£20,318 (discounted) and lifetime QALYs of 6.45 (undiscounted/5.24 [discounted]) per ECLIPSE patient. CONCLUSIONS: A new form of model for COPD was conceptualized, implemented, and internally validated, based on a series of linked equations using epidemiological data (ECLIPSE) and cost data (TORCH). This Galaxy model predicts COPD outcomes from treatment effects on disease attributes such as lung function, exacerbations, symptoms, or exercise capacity; further external validation is required.

Burden of illness for osteoporotic fractures compared with other serious diseases among postmenopausal women in the United States.

OBJECTIVES: To provide a national estimate of the incidence of hospitalizations due to osteoporotic fractures (OFs) in women; compare this with the incidence of myocardial infarction (MI), stroke, and breast cancer; and assess temporal trends in the incidence and length of hospitalizations. PATIENTS AND METHODS: The study included all women 55 years and older at the time of admission, admitted to a hospital participating in the US Nationwide Inpatient Sample for an outcome of interest. We performed a retrospective analysis of hospitalizations for OFs (hip, forearm, spine, pelvis, distal femur, wrist, and humerus), MI, stroke, or breast cancer, using the US Nationwide Inpatient Sample, 2000-2011. RESULTS: From 2000 to 2011, there were 4.9 million hospitalizations for OF, 2.9 million for MI, 3.0 million for stroke, and 0.7 million for breast cancer. Osteoporotic fractures accounted for more than 40% of the hospitalizations in these 4 outcomes, with an age-adjusted rate of 1124 admissions per 100,000 person-years. In comparison, MI, stroke, and breast cancer had age-adjusted incidence rates of 668, 687, and 151 admissions per 100,000 person-years, respectively. The annual total population facility-related hospital cost was highest for hospitalizations due to OFs ($5.1 billion), followed by MI ($4.3 billion), stroke ($3.0 billion), and breast cancer ($0.5 billion). CONCLUSION: These data provide evidence that in US women 55 years and older, the hospitalization burden of OFs and population facility-related hospital cost is greater than that of MI, stroke, or breast cancer. Prioritization of bone health and supporting programs such as fracture liaison services is needed to reduce this substantial burden.

The COSEHC™ Global Vascular Risk Management quality improvement program: first follow-up report.

The Global Vascular Risk Management (GVRM) Study is a 5-year prospective observational study of 87,863 patients (61% females) with hypertension and associated cardiovascular risk factors began January 1, 2010. Data are gathered electronically and cardiovascular risk is evaluated using the Consortium for Southeastern Hypertension Control™ (COSEHC™)-11 risk score. Here, we report the results obtained at the completion of 33 months since study initiation. De-identified electronic medical records of enrolled patients were used to compare clinical indicators, antihypertensive medication usage, and COSEHC™ risk scores across sex and diabetic status subgroups. The results from each subgroup, assessed at baseline and at regular follow-up periods, are reported since the project initiation. Inference testing was performed to look for statistically significant differences between goal attainments rates between sexes. At-goal rates for systolic blood pressure (SBP) were improved during the 33 months of the study, with females achieving higher goal rates when compared to males. On the other hand, at-goal control rates for total and low-density lipoprotein (LDL) cholesterol (chol) were better in males compared to females. Diabetic patients had lower at-goal rates for SBP and triglycerides but higher rates for LDL-chol. The LDL-chol at-goal rates were higher for males, while high-density lipoprotein (HDL)-chol rates were higher for females. Utilization of antihypertensive medications was similar during and after the baseline period for both men and women. Patients taking two or more antihypertensive medications had higher mean COSEHC™-11 scores compared to those on monotherapy. With treatment, hypertensive patients can reach SBP and cholesterol goals; however, population-wide improvement in treatment goal adherence continues to be a challenge for physicians. The COSEHC™ GVRM Study shows, however, that continuous monitoring and feedback to physicians of accurate longitudinal data is an effective tool in achieving better control rates of cardiovascular risk factors.

A retrospective comparison of mortality in critically ill hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent.

OBJECTIVES: To compare acute mortality in critically ill hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent (UCA). BACKGROUND: Because of serious cardiopulmonary reactions reported immediately after administration of perflutren-containing UCAs, the FDA required a black box safety warning for this class of agents, including perflutren protein-type A microspheres injectable suspension. METHODS: This study used the largest hospital service-level database in the U.S. All adult patients undergoing in-patient echocardiography between January 2003 and October 2005 were identified (n = 2,588,722, of which 22,499 received perflutren protein-type A microspheres injectable suspension). Of the 22,499 contrast echocardiography patients, 2,900 had diagnoses meeting criteria for critical illness (heart failure, acute myocardial infarction, arrhythmia, respiratory failure, pulmonary embolism, emphysema, and pulmonary hypertension). To control for the differences between the contrast and noncontrast patients, we used propensity score matching. Variables used in the construction of the propensity score included comorbidities, demographic factors, hospital-specific factors, level of care, and mechanical ventilation status. Patients receiving contrast echocardiography were matched to 4 control patients who received noncontrast echocardiography. Conditional logistic regression was used to estimate mortality effects. RESULTS: There were 167 deaths in the study among critically ill patients, 38 of 2,900 from the contrast group and 129 of 11,600 from the control group. The contrast agent was not associated with an increase in same-day mortality (odds ratio: 1.18; 95% confidence interval: 0.82 to 1.71; p = 0.37). Before matching, contrast patients showed greater morbidity than noncontrast patients (Deyo-Charlson comorbidity score 2.45 vs. 2.25, p < 0.0001). After propensity score matching, these differences were significantly reduced, showing that both groups were well balanced. CONCLUSIONS: There is no increase in mortality in critically ill patients undergoing echocardiography with the UCA compared with case-matched control patients.

COSEHC global vascular risk management quality improvement program: rationale and design.

BACKGROUND: The Consortium for Southeastern Hypertension Control (COSEHC) promotes global risk factor management in patients with metabolic syndrome. The COSEHC Global Vascular Risk Management Study (GVRM) intends to quantify these efforts on long-term patient outcomes. The objectives of this study were to present baseline demographics of patients enrolled in the GVRM, calculate a modified COSEHC risk score using 11 variables (COSEHC-11), and compare it with the original COSEHC-17 and Framingham, Prospective Cardiovascular Münster (PROCAM), and Systemic Coronary Risk Evaluation (SCORE) risk scores. METHODS: Deidentified electronic medical records of enrolled patients were used to calculate the risk scores. The ability of the COSEHC-11 score to predict the COSEHC-17 score was assessed by regression analysis. Raw risk scores were converted to probability estimates of fatal coronary heart disease (CHD) and compared with predicted risks from other algorithms. RESULTS: Of the 177,404 patients enrolled, 43,676 had data for all 11 variables. The COSEHC-11 score (mean ± standard deviation) of these 43,676 patients was 31.75 ± 11.66, implying a five-year fatal CHD risk of 1.4%. The COSEHC-11 score was highly predictive of the COSEHC-17 score (R(2) = 0.93; P < 0.0001) and correlated well with the SCORE algorithm. CONCLUSION: The COSEHC-11 risk score is statistically similar to the COSEHC-17 risk score and should be a viable tool for evaluating its ability to predict five-year cardiovascular mortality in the coming years.

Hyponatremia and hospital outcomes among patients with pneumonia: a retrospective cohort study.

BACKGROUND: Community-acquired (CAP) and nosocomial pneumonias contribute substantially to morbidity and hospital resource utilization. Hyponatremia, occurring in >1/4 of patients with CAP, is associated with greater disease severity and worsened outcomes. METHODS: To explore how hyponatremia is associated with outcomes in hospitalized patients with pneumonia, we analyzed a large administrative database with laboratory component from January 2004 to December 2005. Hyponatremia was defined as at least two [Na+] < 135 mEq/L within 24 hours of admission value. RESULTS: Of 7,965 patients with pneumonia, 649 (8.1%) with hyponatremia were older (72.4 +/- 15.7 vs. 68.0 +/- 22.0, p < 0.01), had a higher mean Deyo-Charlson Comorbidity Index Score (1.7 +/- 1.7 vs. 1.6 +/- 1.6, p = 0.02), and higher rates of ICU (10.0% vs. 6.3%, p < 0.001) and MV (3.9% vs. 2.3%, p = 0.01) in the first 48 hours of hospitalization than patients with normal sodium. Hyponatremia was associated with an increased ICU (6.3 +/- 5.6 vs. 5.3 +/- 5.1 days, p = 0.07) and hospital lengths of stay (LOS, 7.6 +/- 5.3 vs. 7.0 +/- 5.2 days, p < 0.001) and a trend toward increased hospital mortality (5.4% vs. 4.0%, p = 0.1). After adjusting for confounders, hyponatremia was associated with an increased risk of ICU (OR 1.58, 95% CI 1.20-2.08), MV (OR 1.75 95% CI 1.13-2.69), and hospital death (OR 1.3, 95% CI 0.90-1.87) and with increases of 0.8 day to ICU and 0.3 day to hospital LOS, and over $1,300 to total hospital costs. CONCLUSION: Hyponatremia is common among hospitalized patients with pneumonia and is associated with worsened clinical and economic outcomes. Studies in this large population are needed to explore whether prompt correction of [Na+] may impact these outcomes.