Health care costs and utilization of progressive fibrosing lung disease by underlying interstitial lung disease type.

BACKGROUND: Fibrosing interstitial lung disease (ILD) encompasses more than 200 diverse pulmonary disorders, of which up to 40% become progressive. The 4 underlying ILD types most likely to result in progression are unclassified ILD/idiopathic interstitial pneumonia (IIP), autoimmune ILDs, exposure-related ILD/hypersensitivity pneumonitis, and sarcoidosis. OBJECTIVE: To compare health care resource utilization (HCRU) and costs among patients with fibrosing ILD that has progressed ("progressive" fibrosing cohort) vs patients whose fibrosis did not meet criteria set for progression ("not yet progressed" cohort). METHODS: This was a noninterventional study of commercial enrollees and Medicare Advantage with Part D beneficiaries, which used administrative claims data for the period from October 1, 2015, through May 31, 2021. Adult patients (aged ≥18 years) with fibrosing ILD and 12 months of continuous health plan enrollment were included. Patients with idiopathic pulmonary fibrosis, baseline ILD diagnoses, or missing demographic data were excluded. Patients were first classified according to the underlying type of fibrosing ILD. For statistical analyses of outcomes, 2 cohorts were compared within each subtype: progressive fibrosing ILD vs not yet progressed ILD. The final study population included propensity score-matched (PSM) patients (1:1) based on pre-ILD baseline demographic and clinical characteristics. HCRU categories included inpatient hospitalization counts and the number of inpatient days and total costs (in 2021 US dollars), analyzed descriptively and weighted by the per-patient-per-month cost. Lin's regression was used to predict 12-month total cost estimates for comparison by cohort. RESULTS: The distribution by underlying conditions was as follows: autoimmune ILD (n = 4,156), HP (n = 8,181), sarcoidosis (n = 775), and unclassified ILD/IIP (n = 18,635). After PSM, pre-ILD baseline variables were generally well balanced between the progressive and not yet progressed fibrosing ILD cohorts. For all underlying subtypes of ILD, patients in the progressive cohort had significantly more utilization and higher costs compared with patients in the not yet progressed cohort. Progressive cohorts had significantly higher adjusted rates of inpatient days among patients with at least 1 inpatient stay compared with the not yet progressed cohorts (all P < 0.01). In addition, the progressive cohorts had significantly higher adjusted 12-month total costs, with the differences ranging from $24,493 to $55,072 (all comparisons P < 0.001). CONCLUSIONS: Irrespective of underlying ILD type, patients with progressive fibrosing ILD had significantly increased HCRU and cost relative to those whose fibrosing ILD had not yet progressed.

Burden of illness in progressive fibrosing interstitial lung disease.

BACKGROUND: Progressive fibrosing interstitial lung disease (ILD) is a relatively new clinical concept describing a variety of ILDs characterized by progressive pulmonary fibrosis with associated lung function decline and worsening chest imaging. Little is known about health care resource utilization (HCRU) and costs associated with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF). This study analyzed the adjusted HCRU and cost burden among patients with incident non-IPF progressive fibrosing ILD vs matched patients with incident fibrosing ILD that had not yet progressed. METHODS: This was a retrospective study of insured US adults newly diagnosed with non-IPF fibrosing ILD from October 2016 to June 2019, conducted using administrative claims data from the Optum Research Database. Progressive disease was identified using claims-based proxies comprising health care utilization associated with management of progressive fibrosing ILD. Patients in the progressive population were 1:1 propensity score matched to not-yet-progressed patients on the basis of baseline demographic and clinical characteristics. All-cause HCRU and health care costs were presented as weighted per-patient-per-month (PPPM) measures to account for variable follow-up. Differences in study outcomes between matched cohorts were evaluated using Z-tests for continuous measures and Rao-Scott tests for binary measures. RESULTS: The postmatch cohorts comprised 11,025 patients with evidence of progression matched to 11,025 patients with not-yet-progressed fibrosing ILD. Mean (SD) weighted PPPM counts of follow-up health care encounters were significantly higher for the progressive vs not-yet-progressed cohort: ambulatory visits, 4.2 (3.6) vs 3.1 (3.3); emergency department visits, 0.3 (0.5) vs 0.1 (0.3); and inpatient (IP) stays, 0.1 (0.2) vs 0.0 (0.1) (P < 0.001 for all). Among patients with an IP stay, those with progressive disease had more inpatient days than those with not-yet-progressed disease (mean [SD] 1.6 [2.4] days vs 1.0 [1.3] days, P < 0.001). Mean weighted PPPM (SD) all-cause health care costs were also significantly higher for progressive vs not-yet-progressed patients, including total costs ($4,382 [$9,597] vs $2,243 [$4,162], P < 0.001), medical costs ($3,662 [$9,150] vs $1,627 [$3,524], P < 0.001), and pharmacy costs ($720 [$2,097] vs $616 [$2,070], P = 0.002). The difference in medical costs between cohorts was driven primarily by higher inpatient costs for progressive vs not-yet-progressed patients ($1,729 [$7,557] vs $523 [$2,118], P < 0.001). CONCLUSIONS: Progressive fibrosing ILD carries a substantial economic and health care burden. Among patients with incident non-IPF fibrosing ILD, all-cause HCRU and costs were significantly higher for those with a progressive phenotype than for matched patients whose disease had not yet progressed. The cost differential was driven primarily by hospitalizations, which were longer and more frequent for the progressive cohort. Disclosures: This work was funded by Boehringer Ingelheim Pharmaceuticals, Inc. Drs Conoscenti and Shetty are employees of Boehringer Ingelheim (BI). Dr Singer was an employee of BI at the time the study was conducted. Dr Brown was a paid consultant for BI for this study. Dr Bengtson, Ms Anderson, and Dr Brekke are employees of Optum, which was contracted by BI to conduct the study. Medical writing assistance was provided by Yvette Edmonds, PhD (Optum), and was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc.

Impact of timing of nintedanib initiation among patients newly diagnosed with idiopathic pulmonary fibrosis.

AIMS: While nintedanib treatment has been shown to slow the progression of idiopathic pulmonary fibrosis (IPF) in patients across varying levels of lung function, the effect of treatment timing on outcomes has not been examined. We assessed hospitalization risk and medical costs among patients with IPF based on the timing of nintedanib initiation after IPF diagnosis. MATERIALS AND METHODS: This retrospective administrative claims study included data from 04/01/2014-09/30/2019 for patients aged ≥40 years who initiated nintedanib within 1 year of IPF diagnosis. Patients were assigned to study cohorts based on the time from IPF diagnosis to nintedanib initiation. All-cause hospitalization and all-cause medical costs were modeled using marginal structural models including inverse probability weights to adjust for both baseline and time-varying characteristics. RESULTS: Of 11,195 patients diagnosed with IPF during the identification period, 449 met the study selection criteria (mean age 72.3 years, 68% male, mean follow-up time 13.3 months). Adjusted hospitalization risk and medical costs both varied significantly by the timing of nintedanib initiation (p < .001 and p = .020, respectively). Adjusted weighted hospitalization risk was higher among untreated vs. treated patients in months 2-3, months 4-6, and months 7-12 after diagnosis (hazard ratio [95% CI] 1.97 [1.09-3.56], p = .026; 2.62 [1.22-5.63], p = .014; and 5.57 [2.31-13.45], p < .001, respectively). Medical costs were 69% higher for patients initiating treatment in months 2-3 vs. month 1 (cost ratio [95% CI] 1.69 [1.20-2.38], p = .003). LIMITATIONS: Disease severity could not be assessed because clinical data were unavailable; however, proxies such as oxygen use were included to adjust for between-cohort differences in disease severity. CONCLUSIONS: Patients who initiate nintedanib promptly after IPF diagnosis may have reduced hospitalization risk and medical costs compared with those who start treatment later. Additional studies are warranted to improve understanding of the impact of prompt antifibrotic therapy on patient outcomes.

Relative vaccine efficacy of high-dose versus standard-dose influenza vaccines in preventing probable influenza in a Medicare Fee-for-Service population.

BACKGROUND: High-dose (HD) influenza vaccine, currently the most commonly used vaccine among US seniors (aged ≥ 65 years), has been shown to be more efficacious than standard-dose (SD) vaccine in multiple randomized trials. This study evaluated the real-world relative vaccine effectiveness (rVE) of HD vs SD over four influenza seasons. METHODS: This study included Medicare Fee-for-Service enrollees who received HD or SD at an outpatient clinic or pharmacy during influenza seasons 2011-2012 through 2014-2015. Probable influenza (an inpatient stay with an influenza diagnosis on the claim, or an outpatient visit with a rapid influenza test/culture followed by an antiviral prescription) was assessed among HD recipients matched 1:1 with SD recipients by location, vaccination date, age, and sex. Fine-Gray subdistribution hazard models with competing risk of death were used to adjust for residual confounding. Analyses were stratified by outpatient vs pharmacy vaccination. RESULTS: Across the four influenza seasons, there were 535,598, 1,017,552, 1,548,164, and 2,420,450 in the pharmacy cohort; and 821,662, 1,151,080, 1,559,488, and 2,421,758 in the outpatient cohort. During peak influenza season, rVEs for 2011-12 through 2014-15 were 21.8% (95% CI: -5.9%, 42.3%), 14.8% (9.3%, 19.9%), 16.9% (9.2%, 23.9%), and 17.2% (14.5%, 19.9%), respectively, in the pharmacy cohort; and 16.5% (-5.9%, 34.2%), 15.1% (10.9%, 19.1%), 10.0% (2.9%, 16.6%), and -0.2% (-3.0%, 2.5%), respectively, in the outpatient cohort. CONCLUSION: HD was consistently associated with better protection against probable influenza. The lower treatment effect observed in the outpatient cohort could reflect provider bias due to physicians triaging HD to frailer patients.

Validation and Assessment of the COPD Treatment Ratio as a Predictor of Severe Exacerbations.

BACKGROUND: Population-based risk assessments are needed to identify individuals who may benefit from chronic obstructive pulmonary disease (COPD) management programs for preventing exacerbations. This study compared the validated COPD treatment ratio (CTR) versus other COPD exacerbation predictors: prior exacerbation and rescue and maintenance medication use. METHODS: A retrospective observational study using medical and pharmacy claims data among Medicare Advantage with Part D beneficiaries with COPD (January 2011-August 2016). Unadjusted and adjusted logistic regression models tested the predictive performance (C-statistic) of potential exacerbation predictors for future severe exacerbations. RESULTS: The unadjusted association between exacerbation predictors and severe exacerbation was examined in 60,776 patients: baseline severe exacerbation had the highest C-statistic (0.668), then number of rescue units dispensed (0.651), CTR (0.619), and number of controller units dispensed (0.562). During the at-risk period, baseline CTR was inversely associated with severe exacerbation (odds ratio, <1.0); other predictors were positively associated with a severe exacerbation (odds ratio, >1.0). Adjusting for age, geographic region, chronic oxygen, and nebulizer use, the severe exacerbation odds were 0.90 (95% confidence interval [CI], 0.89-0.91) lower per 0.10 change in CTR (C-statistic, 0.710). The C-statistic was 0.734 when baseline exacerbation was added to the model. CONCLUSIONS: The CTR is an effective tool for identifying patients diagnosed with COPD who are at increased risk of severe exacerbation. Although CTR does not predict future exacerbation as well as prior severe exacerbation history, it has the advantage of being applicable in predicting future exacerbations in patients without an exacerbation history, or in databases limited to pharmacy claims only. In addition, the significant reduction in risk has been observed with incremental increases in the ratio: the ratio can be monitored to assess COPD health improvements over time.

The effect of delaying initiation with umeclidinium/vilanterol in patients with COPD: an observational administrative claims database analysis using marginal structural models.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high clinical and economic burden. Optimal pharmacological therapy for COPD aims to reduce symptoms and the frequency and severity of exacerbations. Umeclidinium/vilanterol (UMEC/VI) is an approved combination therapy for once-daily maintenance treatment of patients with COPD. This study evaluated the impact of delaying UMEC/VI initiation on medical costs and exacerbation risk. METHODS: A retrospective analysis of patients with COPD who initiated UMEC/VI between 4/28/2014 and 7/31/2016 was conducted using the Optum Research Database. The index date was the first COPD visit after UMEC/VI available on US formulary (Commercial 4/28/2014; Medicare Advantage 1/1/2015). Patients were followed for 12 months post-index, and categorized into 12 cohorts corresponding to month (30-day period) of UMEC/VI initiation (i.e. Months 1-12) post-index. The outcomes studied during the follow up period included COPD-related and all-cause medical costs, and risk of COPD exacerbations. Marginal structural models (MSM) were used to control for time-varying confounding due to changes in treatment and severity during follow up. RESULTS: 2,200 patients initiating UMEC/VI were included in the study sample. Patients' average age was 69.3 years, 49.9% were female and 69.7% were Medicare insured. Following MSM analysis, 12-month adjusted COPD-related medical costs increased by 2.9% (95% confidence interval [CI]: 0.1-5.9%; p = 0.044) for each monthly delay in UMEC/VI initiation, with a 37.4% higher adjusted cost for patients initiating UMEC/VI in Month 12 versus Month 1 ($13,087 vs. $9524). The 12-month adjusted all-cause medical costs increased by 2.8% (95% CI: 0.6-5.2%; p = 0.013) for each monthly delay, with a 36.1% higher adjusted cost for patients initiating UMEC/VI at Month 12 versus Month 1 ($22,766 vs. $16,727). The monthly risk of severe exacerbation was significantly higher in patients who had not yet initiated UMEC/VI than those who had (hazard ratio: 1.74; 95% CI: 1.35-2.23; p < 0.001). CONCLUSIONS: Prompt use of UMEC/VI following a physician visit for COPD appears to result in economic and clinical benefits, with reductions in medical costs and exacerbation risk. Additional research is warranted to assess the benefits of initiating UMEC/VI as a first-line therapy compared with escalation to UMEC/VI from monotherapies.

Incidence of febrile neutropenia during chemotherapy among patients with nonmyeloid cancer receiving filgrastim vs a filgrastim biosimilar.

BACKGROUND: Filgrastim and other granulocyte colony-stimulating factors are recommended to decrease febrile neutropenia (FN) incidence among patients with nonmyeloid cancers undergoing chemotherapy. Data comparing biosimilar filgrastim-sndz with reference filgrastim (filgrastim-ref) are limited outside of clinical trials in the US. OBJECTIVE: To compare the incidence of FN across chemotherapy cycles 1-6 between patients treated with filgrastim-sndz vs filgrastim-ref. MATERIALS AND METHODS: This was a retrospective claims analysis of patients with nonmyeloid cancer enrolled in commercial or Medicare Advantage plans from March 2015 to June 2016 and receiving filgrastim-sndz or filgrastim-ref during ≥1 completed chemotherapy cycle. Patients undergoing hematopoietic stem cell transplantation, pregnant patients, and those with missing data were excluded. FN was identified using the diagnosis codes for neutropenia + fever, neutropenia + bacterial/fungal infection, and neutropenia + infection + fever. Equivalence testing for FN incidence at the cycle level across chemotherapy cycles 1-6 was conducted for filgrastim-sndz vs filgrastim-ref after adjusting for baseline characteristics using inverse probability of treatment weighting. Results were considered equivalent if the 90% CIs for between-cohort differences were within ±6.0%. RESULTS: The analysis included 3,459 patients (162 filgrastim-sndz and 3,297 filgrastim-ref). Before weighting, the filgrastim-sndz cohort was younger than filgrastim-ref and had a higher proportion of men, a higher proportion with commercial insurance, and lower proportions with granulocyte colony-stimulating factor prophylaxis or metastatic cancer. After weighting, baseline characteristics were similar between cohorts. Adjusted FN incidence was equivalent for filgrastim-sndz vs filgrastim-ref, respectively: neutropenia + fever, 0.81% vs 0.61% (difference [90% CI]=0.20 [-0.57 to 1.56]); neutropenia + infection, 1.21% vs 1.33% (difference [90% CI]=-0.12 [-1.17 to 2.28]); neutropenia + infection + fever, 0.0% vs 0.14% (difference=-0.14; CI not calculated because filgrastim-sndz had 0 events). CONCLUSION: Filgrastim-sndz and filgrastim-ref are statistically equivalent for preventing FN across chemotherapy cycles 1-6 among patients with nonmyeloid cancer.

Clinical Outcomes of Treatment with Filgrastim Versus a Filgrastim Biosimilar and Febrile Neutropenia-Associated Costs Among Patients with Nonmyeloid Cancer Undergoing Chemotherapy.

BACKGROUND: Granulocyte colony-stimulating factors such as filgrastim are used to decrease the incidence of febrile neutropenia (FN) among patients with nonmyeloid cancers undergoing chemotherapy treatment. Although the biosimilar filgrastim-sndz has been approved in the United States since 2015, limited real-world comparisons of filgrastim-sndz versus reference filgrastim (filgrastim-ref) have been conducted. OBJECTIVE: To compare FN incidence and assess overall FN-related health care resource utilization and medical costs among U.S. patients with non-myeloid cancer who received filgrastim-sndz or filgrastim-ref during their first chemotherapy cycle. METHODS: This was a retrospective claims analysis of patients with non-myeloid cancer who were enrolled in commercial or Medicare Advantage insurance plans from March 2015 through June 2016 and received filgrastim-sndz or filgrastim-ref during their first observed chemotherapy cycle. Patients with evidence of hematopoietic stem cell transplantation or pregnancy and those with missing demographic information were excluded. FN was defined on the basis of diagnosis codes for neutropenia and fever (N/F); neutropenia and infection (N/I); and neutropenia, infection, and fever (N/I/F). Cohorts were adjusted for differences in baseline patient characteristics using the inverse probability of treatment weighting (IPTW) method, and equivalence testing was used to compare the proportion of patients who developed FN between weighted cohorts. On the basis of the range of neutropenic fever incidence found in the PIONEER clinical trial, FN incidence was considered equivalent if 90% CIs for between-cohort differences were within ± 6%. Mean FN-related health care resource utilization and total FN-related medical costs were calculated for the overall study population. RESULTS: A total of 3,542 patients were included in the study (172 filgrastim-sndz; 3,370 filgrastim-ref; mean ages 62.1 years and 64.7 years, respectively). After IPTW, there were 162 patients in the filgrastim-sndz cohort and 3,297 in the filgrastim-ref cohort (mean age 64.5 years for both). FN incidence in the weighted filgrastim-sndz versus filgrastim-ref cohorts, respectively, was 1.4% versus 0.9% for N/F, 2.3% versus 1.7% for N/I, and 0.0% versus 0.3% for N/I/F; FN incidence was statistically equivalent between treatment cohorts. Among patients in either treatment cohort who developed FN, the proportion with FN-related inpatient stays during the first chemotherapy cycle ranged from 35.0% for N/I to 70.0% for N/I/F. Mean (SD) FN-related total medical costs across all patients who developed FN were $11,977 ($18,383) for N/F, $8,040 ($14,809) for N/I, and $21,733 ($30,003) for N/I/F, in 2015 U.S. dollars. For all 3 definitions of FN, the largest proportions (73.5%-93.4%) of medical costs were inpatient related. CONCLUSIONS: In this real-world study of patients with nonmyeloid cancers undergoing chemotherapy, the incidence of FN was statistically equivalent between individuals treated with filgrastim-sndz versus filgrastim-ref during their first chemotherapy cycle. FN-related health care resource utilization and medical costs among patients who developed FN were substantial. DISCLOSURES: This work was funded by Sandoz, which participated in the study design, data interpretation, writing and revision of the manuscript, and decision to submit the manuscript for publication. Balu and Campbell are employees of Sandoz, which is the manufacturer of the filgrastim biosimilars Zarzio and Zarxio. DeLeon was an employee of Sandoz at the time this study was conducted. Lal, Brekke, Elliott, and Korrer are employees of Optum, which was contracted by Sandoz to conduct this study.

The Use of Decomposition Methods in Real-World Treatment Benefits Evaluation for Patients with Type 2 Diabetes Initiating Different Injectable Therapies: Findings from the INITIATOR Study.

BACKGROUND: Determining characteristics of patients likely to benefit from a particular treatment could help physicians set personalized targets. OBJECTIVES: To use decomposition methodology on real-world data to identify the relative contributions of treatment effects and patients' baseline characteristics. METHODS: Decomposition analyses were performed on data from the Initiation of New Injectable Treatment Introduced after Antidiabetic Therapy with Oral-only Regimens (INITIATOR) study, a real-world study of patients with type 2 diabetes started on insulin glargine (GLA) or liraglutide (LIRA). These analyses investigated relative contributions of differences in baseline characteristics and treatment effects to observed differences in 1-year outcomes for reduction in glycated hemoglobin A1c (HbA1c) and treatment persistence. RESULTS: The greater HbA1c reduction seen with GLA compared with LIRA (-1.39% vs. -0.74%) was primarily due to differences in baseline characteristics (HbA1c and endocrinologist as prescribing physician; P < 0.050). Patients with baseline HbA1c of 9.0% or more or evidence of diagnosis codes related to mental illness achieved greater HbA1c reductions with GLA, whereas patients with baseline polypharmacy (6-10 classes) or hypogylcemia achieved greater reductions with LIRA. Decomposition analyses also showed that the higher persistence seen with GLA (65% vs. 49%) was mainly caused by differences in treatment effects (P < 0.001). Patients 65 years and older, those with HbA1c of 9.0% or more, those taking three oral antidiabetes drugs, and those with polypharmacy of more than 10 classes had higher persistence with GLA; patients 18 to 39 years and those with HbA1c of 7.0% to less than 8.0% had higher persistence with LIRA. CONCLUSIONS: Although decomposition does not demonstrate causal relationships, this method could be useful for examining the source of differences in outcomes between treatments in a real-world setting and could help physicians identify patients likely to respond to a particular treatment.

A real-world study of treatment patterns and outcomes in US managed-care patients with type 2 Diabetes initiating injectable therapies.

AIMS: Examine real-world outcomes in patients with type 2 diabetes mellitus (T2DM) initiating injectable therapy as part of the Initiation of New Injectable Treatment Introduced after Antidiabetic Therapy with Oral-only Regimens (INITIATOR) study. MATERIALS AND METHODS: Linked insurance claims and medical record data were collected from 2 large US health insurers (April 1, 2010 to March 31, 2012) of T2DM adults initiating treatment with glargine (GLA) or liraglutide (LIRA). Baseline characteristics were examined and changes in 12-month follow-up outcomes were described for both treatment groups: HbA1c, weight change, hypoglycaemia, persistence, healthcare utilisation and costs. RESULTS: A total of 4490 patients were included (GLA, 2116; LIRA, 2374). At baseline, GLA patients had significantly higher HbA1c vs LIRA patients (9.72% vs 8.19%; P < .001), lower likelihood of having HbA1c < 7% (7.1% vs 23.8%; P < .001), lower bodyweight (100.9 kg vs 110.9 kg, P < .001), higher Charlson Comorbidity Index score (0.88 vs 0.63; P < .001), and higher diabetes-related costs ($3492 vs $2089; P < .001), respectively. During 12-months of follow-up, treatment persistence was 64%, mean HbA1c reduction was -1.24% and weight change was + 1.17 among GLA patients, and was 49%, -0.51% and -2.74 kg, respectively, among LIRA patients. Diabetes-related costs increased significantly from baseline to follow-up for LIRA patients ($2089 vs $3258, P < .001) but not for GLA patients ($3492 vs $3550, P = .890). CONCLUSIONS: There were clinically relevant baseline differences in both groups, suggesting that GLA and LIRA are prescribed for different patient groups, and highlighting that efficacy results from clinical trials do not always translate into real-world practice. Significant increases in healthcare costs were observed in the LIRA group, warranting further cost-effectiveness analysis.

Persistence with denosumab therapy among osteoporotic women in the Canadian patient-support program.

OBJECTIVE: The objective of this study was to evaluate persistence with denosumab among postmenopausal women with osteoporosis participating in the Canadian patient-support program (ProVital * ). Denosumab is an injectable therapeutic option for osteoporosis that is administered subcutaneously every 6 months. METHODS: ProVital, a support program in which patients voluntarily enroll, provides next injection reminder calls and educational material. A retrospective database analysis of patient self-reported data was conducted among osteoporotic women aged ≥50 who enrolled in the ProVital program and received their first denosumab injection between August 2010 and June 2011. To achieve 12 month persistence patients had to receive at least two denosumab injections, and to achieve 24 month persistence patients had to receive at least four denosumab injections, with consecutive injections no more than 6 months + 8 weeks apart. Logistic regression analysis was used to identify predictors of persistence. RESULTS: A total of 1676 patients (mean age 74 years) were included. The 12 month persistence with denosumab was 81.6% (1367/1676 patients), and the 24 month persistence was 59.1% (991/1676 patients). Characteristics associated with both 12 and 24 month persistence were possession of private medication insurance and residence in Quebec. Additionally, age greater than 75, previous postmenopausal osteoporosis medication use, and fracture were associated with 24 month persistence. LIMITATIONS: Patient enrollment in the program was voluntary, so there may be selection bias for the patient population included in this study. Also, this study did not have a control group of patients who were not enrolled in a patient support program. CONCLUSIONS: The persistence with denosumab among patients enrolled in the program was higher than historical persistence with oral bisphosphonates, and similar to persistence of patients in an education program taking teriparatide, patients taking bisphosphonates in a pharmaceutical care program, and two observational studies of denosumab.

Field testing the ENSEMBLE Minimum Dataset: performance of an instrument to address heterogeneity of treatment effects.

AIM: To assess the ability of ENterprising SElective Multi-instrument BLend for hEterogeneity analysis (ENSEMBLE) Minimum Dataset instrument dimensions to discriminate among subgroups of patients expected to have differential outcomes. MATERIALS & METHODS: Patients with Type 2 diabetes, knee osteoarthritis, ischemic heart disease or heart failure completed a survey designed to represent three dimensions (health, personality and behavior). Health-related outcomes and utilization were investigated using claims data. Discriminant validity and associations between the dimensions and outcomes were assessed. RESULTS: A total of 2625 patients completed the survey. The dimensions discriminated 50-100% of the outcome levels across disease cohorts; behavior dimension scores did not differ significantly among the healthcare utilization level subgroups in any disease cohort. CONCLUSION: ENSEMBLE Minimum Dataset dimensions discriminated health-related outcome levels among patients with varied diseases.

The INITIATOR study: pilot data on real-world clinical and economic outcomes in US patients with type 2 diabetes initiating injectable therapy.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) progression often results in treatment intensification with injectable therapy to maintain glycemic control. Using pilot data from the Initiation of New Injectable Treatment Introduced after Anti-diabetic Therapy with Oral-only Regimens study, real-world treatment patterns among T2DM patients initiating injectable therapy with insulin glargine or liraglutide were assessed. METHODS: This was a retrospective analysis of claims from the OptumInsight™ (OI; January 1, 2010 to July 30, 2010) and HealthCore(®) (HC; January 1, 2010 to June 1, 2010) health insurance databases. Baseline characteristics, health care resource utilization, and costs were compared between adults with T2DM initiating injectable therapy with insulin glargine pen versus liraglutide. Follow-up outcomes, including glycated hemoglobin A1c (A1C), hypoglycemia, health care utilization, and costs, were assessed. RESULTS: At baseline, almost one in three liraglutide patients (OI, n = 363; HC, n = 521) had A1C <7.0%, while insulin glargine patients (OI, n = 498; HC, n = 1,188) had poorer health status, higher A1C (insulin glargine: 9.8% and 9.1% versus liraglutide: 7.9% and 7.7%, OI and HC, respectively, both P < 0.001), and were less likely to be obese (insulin glargine: 10.8% and 9.2% versus liraglutide: 17.4% and 18.8%, OI and HC, respectively, both P < 0.01). The percentage of patients experiencing a hypoglycemic event was numerically higher for insulin pen use for both cohorts (OI 4.4% versus 3.0%; HC 6.2% versus 2.3%). During follow-up, in the insulin glargine cohort, annualized diabetes-related costs remained unchanged ($8,344 versus $7,749 OI, and $7,094 versus $7,731 HC), despite a significant increase in pharmacy costs, due to non-significant decreases in medical costs, while the liraglutide cohort had a significant increase in annualized diabetes-related costs ($4,510 versus $7,731 OI, and $4,136 versus $7,111 HC; both P < 0.001) due to a non-significant increase in medical costs coupled with a significant increase in pharmacy costs. CONCLUSION: These descriptive data identified differences in demographic and baseline clinical characteristics among patients initiating injectable therapies. The different health care utilization and cost patterns warrant further cost-effectiveness analysis.

Trends in 10-year predicted risk of cardiovascular disease in the United States, 1976 to 2004.

BACKGROUND: There have been significant bidirectional changes in the prevalence of cardiovascular (CV) risk factors over time in the United States, making the net trend in risk for incident CV disease unknown. We assessed these trends by applying the Framingham Heart Study prediction model to national data. METHODS AND RESULTS: The National Health and Nutrition Examination Survey (NHANES) II (1976-1980), NHANES III (1988-1994), and NHANES 1999-2004 are cross-sectional representative samples of the noninstitutionalized population of the United States. We excluded people with a history of CV disease, pregnant women, participants with missing CV risk factors data, and individuals outside the Framingham age range of 30 to 74 years. The Framingham risk function was used to estimate the 10-year risk for incident symptomatic CV disease. We calculated the slope of change or rate of change per year between NHANES II and III, and between NHANES III and 1999-2004. The difference between slopes was calculated and compared to zero. The average age-adjusted 10-year CV risk between NHANES II and III decreased from 10.0% to 7.9% between NHANES II and III, with a statistically significant slope (P<0.001). However, the average age-adjusted CV risk decreased at a lesser magnitude between NHANES III and NHANES 1999-2004 from 7.9% to 7.4% (P<0.001). These slopes were significantly different (P<0.0001). In women and middle-aged participants, CV risk did not change between NHANES III and NHANES 1999-2004 (P=0.40). CONCLUSIONS: The estimated net risk for CV disease in the US population decreased from 1976-1980 to 1988-1994 but has changed minimally from 1988-1994 to 1999-2004, particularly in women and middle-aged people.

Effect of weight loss on predicted cardiovascular risk: change in cardiac risk after bariatric surgery.

OBJECTIVE: Our goal was to assess the effect of bariatric surgery on cardiovascular risk estimations of preventable, long-term adverse outcomes. RESEARCH METHODS AND PROCEDURES: We performed a population-based, historical cohort study between 1990 and 2003 of 197 consecutive patients from Olmsted County, MN, with Class II to III obesity (defined as BMI > or = 35 kg/m2) treated with Roux-en-Y gastric bypass and 163 non-operative patients assessed in a weight-reduction program. We used the observed change in cardiovascular risk factors and risk models derived from data from the National Health and Nutrition Examination Survey (NHANES) I and the NHANES I Epidemiological Follow-up Study (NHEFS) to calculate the predicted impact on cardiovascular events and mortality for the operative and non-operative groups. RESULTS: Mean follow-up was 3.3 years. Hypertension, diabetes, and dyslipidemia all improved after bariatric surgery. The estimated 10-year risk for cardiovascular events for the operative group decreased from 37% at baseline to 18% at follow-up, while the estimated risk for the non-operative group did not change from 30% at baseline to 30% at follow-up. Risk modeling to predict 10-year outcomes estimated 4 overall deaths and 16 cardiovascular events prevented by bariatric surgery per 100 patients compared with the non-operative group. CONCLUSIONS: Bariatric surgery induces an improvement in cardiovascular risk factors in patients with Class II to III obesity. Weight loss predicts a major, 10-year reduction in cardiovascular events and deaths. Bariatric surgery should be considered as an alternative approach to reduce cardiovascular risk in patients with Class II to III obesity.

Preventing sudden death with n-3 (omega-3) fatty acids and defibrillators.

BACKGROUND: Because interventions that prevent and treat events due to cardiovascular disease are applied to different, but overlapping, segments of the population, it can be difficult to estimate their effectiveness if formal calculations are not available. METHODS: Markov chain analysis, including sensitivity analysis, was used with a hypothetical population resembling that of Olmsted County, MN, aged 30 to 84 in the year 2000 to compare the estimated impact of three interventions to prevent sudden death: (1) raising blood levels of n-3 (omega-3) fatty acids, (2) distributing automated external defibrillators (AEDs), and (3) implanting cardioverter defibrillators (ICDs) in appropriate candidates. The analysis was performed in 2004, 2005, and 2006. RESULTS: Raising median n-3 fatty acid levels would be expected to lower total mortality by 6.4% (range from sensitivity analysis = 1.6% to 10.3%). Distributing AEDs would be expected to lower total mortality by 0.8% (0.2% to 1.3%), and implanting ICDs would be expected to lower total mortality by 3.3% (0.6% to 8.7%). Three fourths of the reduction in total mortality due to n-3 fatty acid augmentation would accrue from raising n-3 fatty acid levels in the healthy population. CONCLUSIONS: Based on central values of candidacy and efficacy, raising n-3 fatty acid levels would have about eight times the impact of distributing AEDs and two times the impact of implanting ICDs. Raising n-3 fatty acid levels would also reduce rates of sudden death among the subpopulation that does not qualify for ICDs.

CardioVision 2020: program acceptance and progress after 4 years.

OBJECTIVE: To report program acceptance and progress after 4 years of a heart disease prevention program. SUBJECTS: All Olmsted County, Minnesota residents aged >/=20 years. METHODS: The analysis is based on independent population-based interview samples from 1999, 2000, 2001, and 2003; a dietary questionnaire mailed to interviewees; and blood pressure and cholesterol data from medical records of consenting Olmsted County residents. National, Minnesota, and Olmsted County Behavioral Risk Factor Surveillance System trends for fruit and vegetable consumption, body mass index, participation in physical activity, and smoking are compared. The data were analyzed in 2005. RESULTS: More than 90% of the population considers CardioVision 2020 to be a good, very good, or excellent idea. The program is associated with a 25% reduction in the number of people exposed to environmental tobacco smoke and small but significant increases in consumption of fruits and daily physical activity. The population meeting the serum cholesterol goal increased from 52.0% in 1999 to 57.5% in 2003, and the population meeting the blood pressure goal increased from 53.7% in 1999 to 59.9% in 2003. However, attempts to quit smoking and the amount of time spent in physical activity did not increase. By 2003, nearly 9% of the population reported making a behavior change because of CardioVision 2020. Compared to Minnesota and national trends, fruit and vegetable consumption increased significantly in Olmsted County. CONCLUSIONS: The population of Olmsted County views CardioVision 2020 in a positive light. Positive changes in several personal behaviors and risk factor levels have occurred.

Design and development of a coronary heart disease decision support tool.

We are developing a decision support tool to help clinicians and policy makers estimate the impact of various coronary heart disease (CHD) treatments on disease outcomes for populations. We have created seven modules that correspond to states commonly encountered with CHD, that is, congestive heart failure, tachyarrhythmia, stable angina pectoris, acute coronary syndrome, bradycardia, postmyocardial infarction, and postcoronary artery bypass grafting, and a healthy individual module. Within each module, we created event-decision- intervention-outcome flow pathways to simulate risk of a clinical event and the expected outcome as the result of a particular intervention. We will combine disease state probability estimates based on the experience of the Olmsted County, Minnesota, population and estimates of intervention efficacy based on clinical trial data to estimate the impact of interventions on a population. We plan to make this tool available to the public through the internet.

Dietary intake of fruits, vegetables, and fat in Olmsted County, Minnesota.

OBJECTIVE: To assess self-reported dietary intake in the adult population of Olmsted County, Minnesota. SUBJECTS AND METHODS: We conducted a random-digit-dial telephone survey between March 1 and April 21, 1999, of 1232 adults residing in Olmsted County, Minnesota. We then mailed a structured questionnaire to the survey respondents and achieved a response rate of 732 individuals. Percentages of individuals and predictors of those who meet recommendations for intake of fruits and vegetables and for dietary fats were determined by using chi2 tests of general association and multivariate logistic regression. RESULTS: Only 16% of the population of Olmsted County reported meeting standard dietary recommendations for consuming both 5 or more servings of fruits and/or vegetables per day and no more than 30% of calories from fat. Fifty-one percent of the population was meeting neither recommendation. Women were more likely than men to report meeting both goals (22% vs 8%, P<.001), but still more women were meeting neither goal than were meeting both goals (40% vs 22%, P<.001). Multivariate logistic regression revealed the following factors to predict adherence to both goals: female sex, lower body mass index, nonsmoker, history of high cholesterol, and daily physical activity. CONCLUSION: Few individuals in Olmsted County are meeting national recommendations for intake of fruits, vegetables, and dietary fat. More effective interventions are needed to improve dietary habits in all subgroups of this community.

Opportunities to prevent sudden out-of-hospital death due to coronary heart disease in a community.

BACKGROUND: Intervening successfully to reduce the burden of sudden out-of-hospital death due to coronary heart disease (OHCD) requires knowledge of where these deaths occur and whether they are observed by bystanders. METHODS: To establish the proportion of OHCDs that were witnessed and where they occurred, we reviewed the coroner's notes and medical records of a previously-described sample of OHCD cases among residents of Olmsted County, Minnesota. This cohort (n=113) consisted of a 10% random sample of all Olmsted County residents who died out-of-hospital between 1981 and 1994 and whose deaths were attributed to coronary heart disease. RESULTS: Excluding deaths in nursing homes (n=27), 71 (83%) of the deaths occurred in private homes and 15 (17%) occurred in public places. The event was not witnessed in 59% of deaths occurring in private homes and in 20% of deaths occurring in public places. The presence or absence of a bystander could not be established for 10% of deaths in private homes and 7% of deaths in public areas. CONCLUSIONS: A significant proportion of OHCDs occur in private homes and are not witnessed. Prevention of unwitnessed deaths will require programs that result in primary prevention and/or calls to first responders at the time of impending cardiac arrest.