Leibson, Cynthia L.

AbstractIntroductionEfforts to model the cost‐effectiveness of managing/modifying cognitive impairment lack reliable, objective, baseline medical, and nursing‐home (NH) costs.MethodsA stratified‐random sample of Olmsted County, MN, residents ages 70–89 years (N = 3545), well‐characterized as cognitively unimpaired, mild cognitive impairment (MCI), or dementia, were followed forward ≤1 year in provider‐linked billing data and the Centers for Medicare & Medicaid Services NH assessments. Direct medical/nursing home/medical + NH costs were estimated. Costs were stratified by vital status and NH‐use intensity (NH days/follow‐up days [0%, 1% to 24%, 25% to 99%, and 100%]). Between‐category mean‐annual cost differences were adjusted for patient characteristics and follow‐up days.ResultsCosts/follow‐up day distributions differed significantly across cognitive categories. Mean costs/follow‐up days were 2.5 to 18 times higher for decedents versus survivors. Among all persons with MCI, <9% with any NH use accounted for 18% of all total annual medical + NH costs. Adjusted‐between‐category comparisons revealed significantly higher medical and medical + NH costs for MCI versus cognitively unimpaired.DiscussionCost‐effectiveness for managing/modifying both MCI and dementia should consider end‐of‐life costs and NH‐use intensity. Results can help inform cost‐effectiveness models, predict future‐care needs, and aid decision‐making by individuals/providers/payers/policymakers.

The importance of coronary artery disease (CAD) surveillance, as recently underscored by the American Heart Association, is heightened by the obesity/diabetes epidemics. The need for surveillance is especially great for subclinical CAD, as the greatest increases in obesity/diabetes are occurring among younger age groups, where clinically-recognized CAD is infrequent. Yet few methods for such population-based surveillance exist. Using one such method, unbiased heart autopsy data, we previously showed that declines in grade of CAD observed since 1981 ended in the mid-1990s and may have reversed. In order to assess and interpret the factors underlying these observations, it is necessary to first examine trends in CAD risk factors among heart autopsied decedents and investigate the extent to which they mirror trends in the general population. Rochester Epidemiology Project (REP) medical records linkage resources were used to identify 1) all Olmsted County residents age 16-64 years who died from non-natural causes and went to autopsy 1981-2009 (96% autopsy rate) and 2) all Olmsted County residents age 16-64 years 1981-2009. We randomly selected two population subjects per decedent, stratified by calendar year. All REP inpatient/ ambulatory records were reviewed for CAD risk factors. Compared to population subjects, decedents were older and more likely to be male, smokers, alcohol abusers, and treated for hypertension; however, risk factor trends for both groups were generally of similar magnitude and direction, i.e., smoking, alcohol use, and blood pressure declined and anti-hypertensive medication use, diagnosed hyperlipidemia, and body mass index increased ( Table ). These population-based longitudinal data indicate that temporal trends in risk factors among autopsied decedents parallel those for the general population, supporting the concept that data on autopsied decedents can provide insight into trends in CAD risk and the changing burden of atherosclerosis within the source population. Characteristics of all 1) non-elderly adult Olmsted County residents who died non-natural deaths and were autopsied and 2) non-elderly adult Olmsted County residents with respect to CAD risk factors and calendar year trends CAD Risk Factor Autopsied Decedents (N=315) Population Subjects (N=672) P Value Autopsied Decedents, Temporal Trend Population Subjects, Temporal Trend N Calendar Year Estimate P value N Calendar Year Estimate P Value Age at Index, Mean (SD) 37.5 (14.0) 34.1 (13.6) <0.01 1 315 0.172 0.06 1 672 −0.059 0.33 1 Sex, % Male 236 (75%) 339 (50%) <0.01 2 315 0.008 0.60 2 672 −0.008 0.39 2 Race, % Non-White 29 (9%) 85 (13%) 0.14 3 305 0.054 0.04 3 589 0.023 0.12 3 Of Ever Smokers, Current = Yes 128/184 (70%) 118/210 (56%) 0.01 3 184 −0.040 0.048 3 210 −0.052 <0.01 3 Of Ever Alcohol Use, Current = Yes 175/238 (74%) 284/364 (78%) 0.08 3 238 −0.065 <0.01 3 364 −0.027 0.09 3 Mention of Alcoholism, Yes 80 (25%) 41 (6%) <0.01 3 315 0.014 0.35 3 672 0.042 0.04 3 Closest Systolic BP, Mean (SD) 124.1 (16.6) 120.3 (15.7) 0.34 3 285 −0.179 0.09 3 600 −0.156 0.02 3 Closest Diastolic BP, Mean (SD) 76.2 (11.6) 74.0 (10.5) 0.53 3 285 −0.194 0.01 3 600 −0.112 0.02 3 Closest BP on Medication, Yes 44 (14%) 36 (5%) <0.01 3 283 0.046 0.03 3 599 0.063 <0.01 3 Hyperlipidemia Diagnosis, Yes 32 (10%) 65 (10%) 0.32 3 315 0.114 <0.01 3 672 0.078 <0.01 3 Closest Fasting Glucose, Mean (SD) 95.8 (26.0) 95.0 (27.6) 0.63 3 177 0.270 0.23 3 335 0.505 <0.01 3 Closest BMI, Mean (SD) 26.1 (5.8) 25.9 (5.4) 0.52 3 280 0.080 0.04 3 593 0.091 <0.01 3 1 Unadjusted, Chi-square; 2 Unadjusted, Wilcoxon rank sum test; 3 Adjusted for age and sex, linear or logistic regression; BP = Blood Pressure; BMI = Body Mass Index

BACKGROUND Epidemiological cohorts can assist with post-marketing surveillance as they provide community-based outcomes data. Concern was raised about the adverse impact of sulfonylureas (SU) drugs on the outcome of diabetes after myocardial infarction (MI). We evaluated the outcome of MI according to treatment among diabetic persons compared to non-diabetic counterparts in a community-based cohort. METHODS All MIs that occurred in Olmsted County, MN between 1979 and 2002 were validated by standardized epidemiological including cardiac pain, biomarkers and ECG Minnesota coding. Diabetes mellitus (DM) was defined by the National Diabetes Data Group criteria. RESULTS Among 2732 persons with MI (mean age 70 ± 12 years, 44% men), 486 (18%) had DM. Subjects with DM were treated with second generation SU (SU2) (24%), insulin (47%) or diet alone (22%) Diabetic subjects were more likely to be overweight, hyperlipidemic and to receive reperfusion therapy during hospitalization than non-diabetic subjects. One year after the MI, 518 subjects died. Diabetic subjects taking SU2 experienced better survival than subjects without diabetes, while subjects treated with diet alone or insulin experienced worse survival. (Figure ). After adjusting for age, sex, reperfusion and duration of DM, an excess risk of death was detected among persons with insulin-treated DM, particularly those with long-standing DM. No association was found for DM patients treated with SU2 or diet. CONCLUSION These data do not support the concern for an adverse impact of SU2 on survival and underscore the potential role of community studies for population surveillance.

Abstract Confinement to a nursing home (NH) is an independent risk factor for VTE and accounts for 13% of all VTE occurring in the community, but the question of which NH residents are at risk is largely unanswered. Objective: To determine VTE risk factors among NH residents. Methods: Using the Minnesota State Case Mix Review Program Public Research Files, we performed a case-control study of all Olmsted County, MN NH patients with an ICD-9 code-identified diagnosis of VTE from 1988–1994. From the same source, we identified one age-, sex-matched control and used conditional logistic regression to estimate odds ratios for an association of VTE with 46 characteristics assessed in the Minnesota Case Mix data. Results: Univariate associations between characteristics and odds of VTE are described below. Significantly increased odds were observed for residents assessed following hospitalization (a nearly 4-fold increase, p=0.002, Table) and residents considered incapable of self-preservation (i.e., unable to cope with potentially harmful situations) (&gt; 2.0 fold increase, p=0.03). Non-significant 2–3 fold increased odds were observed for limitations in certain specific Activities of Daily Living (ADL) (including walking and dressing) and for limitations in more than 3 ADLs. Similar increased odds were observed for residents using a wheelchair, taking more than 3 oral medications, enrolled in professional activity programs, and needing behavior management. Conclusions: Need for assistance (especially problems with immobility), lack of self preservation, and recent hospitalization may identify a subset of NH residents that are at especially high VTE risk and who may warrant consideration of prophylaxis. Univariate VTE Risk Factors for Nursing Home Residents Characteristic Odds Ratio 95% CI P-value Oral medications &gt; 3 3.00 0.97-9.30 0.06 Activities of Daily Living High/Medium (4-8) vs. low (0-3) 2.20 0.76-6.33 0.14 Help dressing 2.75 0.88-8.64 0.08 Help walking 3.00 0.61-14.86 0.18 Wheelchair use 2.50 0.97-6.44 0.58 Needs behavior management 3.00 0.62-14.86 0.18 Help toileting 2.00 0.68-5.85 0.20 Lack of self-preservation 2.33 1.07-5.10 0.03 Transfer from hospital 3.86 1.68-8.86 0.0015 Anti-depressant drugs 0.50 0.19-1.33 0.16 Professional activity program 2.25 0.69-7.3 0.18

Abstract Introduction: Diabetes mellitus is often cited as a VTE risk factor. However, persons with diabetes are frequently hospitalized for medical illness or undergo surgery, both major VTE risk factors. Thus, the association of VTE with diabetes independent of surgery or hospitalization is uncertain. Methods: Using longitudinal, population-based Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents who met objective criteria for incident VTE over the 25-year period, 1976–2000 (n=1922), and one to two controls per case, matched on age, gender, Olmsted County residency, and length of medical history (n=2115). For cases and controls, we reviewed their complete medical history in the community for baseline characteristics previously identified as independent VTE risk factors, including clinically-diagnosed diabetes mellitus. We tested diabetes as a potential VTE risk factor both alone and after adjusting for other baseline characteristics, and in the subset of cases with idiopathic VTE, using conditional logistic regression. Results: Among all cases and controls, 231 (12%) and 199 (9.4%) had diabetes, respectively. Univariately, diabetes was associated with overall VTE (odds ratio [OR]=1.32; 95% CI: 1.07, 1.62; p=0.009). However, after controlling for body mass index (OR=1.04, p<0.001), hospitalization with major surgery (OR=25.2, p<0.001) or hospitalization for medical illness (OR=7.3, p<0.001), active cancer (OR=8.3, p<0.001) and varicose veins (OR=1.3, p=0.003), diabetes was no longer associated with VTE (OR=1.09; 95% CI: 0.85, 1.41; p=0.49). Among 458 idiopathic VTE cases and 518 matched controls, 43 (9.4%) and 46 (8.9%) had diabetes, respectively. Diabetes was not associated with idiopathic VTE (OR=1.07, 95% CI: 0.69, 1.67; p=0.76). Conclusions: Diabetes mellitus is not an independent risk factor for overall or idiopathic incident VTE.

Abstract Abstract 1241 Background: Hospitalization (with or without surgery) is a major risk factor for incident venous thromboembolism (VTE); however, the contribution of interim hospitalization to risk of recurrent VTE is unknown. Objective: To estimate risk of recurrent VTE related to interim hospitalization by conducting a population-based longitudinal review of provider-linked detailed medical records. Methods: We performed a nested case-cohort study. The cohort consisted of all Olmsted County residents with incident VTE 1988–2000 and ≥1 day follow-up. Cases were cohort members with recurrent VTE. Subjects were followed for all interim hospitalizations and warfarin use from incident VTE until earliest of emigration, death, recurrent VTE, or 12/31/2005. Data were analyzed using Cox proportional hazards and time dependent covariates to test for the effects of interim hospitalization and prophylaxis on VTE recurrence, adjusting for gender and age at incident VTE. Analyses were limited to subjects who survived free of death and recurrent VTE for ≥ 6 months. Results: Of 1262 incident VTE events (cohort), there were 309 VTE recurrences (cases). We randomly sampled 272 subjects from the cohort and 163 cases. Of the random samples, 210 incident events and 83 cases survived ≥ 6 months free of death and recurrent VTE and form our analysis population. The rate of secondary (interim) prophylaxis was approximately 50% for both incident events and cases, and was not predictive of recurrence (p=0.73). Male gender and interim hospitalization were associated with increased VTE recurrence even after adjusting for age at incident VTE and use of secondary warfarin prophylaxis. The hazard of recurrent VTE was nearly 10-fold higher for subjects with interim hospitalization versus those with none (HR: 9.6; 95% CI: 6.6, 13.8); men had a 1.5-fold increased recurrence rate compared with women (HR: 1.5; 95% CI: 1.1, 2.1). Conclusions: Our results, for the first time, show the importance of interim hospitalization as a predictor of VTE recurrence. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 476 Background: The burden of VTE among nursing home (NH) residents is known to be high. Yet very little data exist to help determine which NH residents to target for VTE prophylaxis. The need to characterize VTE risk in this population is especially great because the advanced age and high comorbidity that typify NH residents contribute to increased likelihood of adverse consequences from VTE prophylaxis. To compound the problem, results of our prior univariate analyses of certain factors known to contribute substantially to VTE risk in the general population (e.g., major surgery, medical hospitalization, trauma) suggest that impact of these factors on VTE may be less substantial among NH residents. Objective: To use the longitudinal population-based resources of the Rochester Epidemiology Project (REP) to investigate the contribution of multiple clinical characteristics to risk of VTE among NH residents. Methods: We took advantage of the previous identification of all Olmsted County, MN residents who met research criteria for incident VTE 1988 through 2005 (N=2,332). We then determined which individuals were resident of a local NH at time of VTE symptom onset, regardless of location of symptom onset (i.e., individuals whose VTE occurred in-hospital having been admitted from a NH were considered NH residents). For each such NH VTE case (N=269), we identified 2 same sex Olmsted County residents of similar age and duration of medical history who were also resident of a local NH at the time of the case's VTE event (i.e., index date) (N=538). We reviewed the detailed provider-linked medical records of NH VTE cases and NH non-VTE controls for 3 months before index for information on multiple characteristics identified or hypothesized as contributing to VTE risk in studies of the general population and other at-risk subgroups by our group and others (e.g., patient demographics, body mass index, major surgery, hospitalization for acute medical illness, outpatient surgical procedures, trauma/fracture, leg paresis, active cancer, superficial vein thrombosis, varicose veins, infections, diabetes mellitus, coronary artery disease, congestive heart failure, and multiple medications, including anticoagulants, statins, beta-blockers, ACE inhibitors and angiotensin II receptor antagonists). We tested and estimated the odds ratio associated with each factor using step-wise conditional logistic regression. Variables for which <10 cases or <10 controls exhibited the characteristic were excluded from analysis. Results: The first five variables to enter the model were urinary tract infection, active cancer, superficial vein thrombosis, pneumonia, and leg paresis. The respective odds ratios (95% confidence intervals) with all five in the model were 1.7 (1.2, 2.4); 2.1 (1.3, 3.5); 2.1 (1.3, 3.4); 1.9 (1.3, 2.8); 2.3 (1.3, 4.2); each p value was <0.01. Variables associated with high VTE risk in the general population (i.e., surgery, hospitalization for medical illness, trauma/fracture) were not included in the top five risk factors for NH residents. Conclusions: Infection is a potent VTE risk factor among NH residents. Our study results will help inform development of practice guidelines in the NH and stimulate future research on putative VTE mechanisms. REP data afford limited information on cognitive and physical disability, immobility, and need for NH care. Additional investigations are needed that combine information from clinical and NH assessments. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 5118 Background: Increased factor VIII:C (FVIII:C) and hypofibrinolysis are VTE risk factors, and beta-blockers and angiotensin converting enzyme (ACE) inhibitors reduce FVIII:C and enhance fibrinolysis, respectively. Objective: To test the hypotheses that beta-blockers and ACE inhibitors reduce VTE risk. Methods: Using longitudinal, population-based Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents with objectively-diagnosed incident VTE over the 13-year period, 1988–2000 (n=1306), and one to two Olmsted County residents per case matched on age, event year and duration of prior medical history (n=1500). For cases and controls, we reviewed their complete medical history in the community for previously-identified VTE risk factors (e.g., hospitalization with or without surgery, nursing home confinement, trauma/fracture, leg paresis, active cancer, superficial vein thrombosis and varicose veins), as well as body mass index (BMI), coronary artery disease (CAD), congestive heart failure (CHF), and the use of statins, beta-blockers, ACE inhibitors and angiotensin II receptor antagonist drugs. Using conditional logistic regression, we tested beta-blockers and ACE inhibitors/angiotensin II receptor antagonists for an association with VTE, both individually and after adjusting for age, BMI, previously-identified VTE risk factors, CAD, CHF and the use of statins. Results: Among cases and controls respectively, 191 and 173 received beta-blockers, and 171 and 154 received ACE inhibitors/angiotensin II receptor antagonists. Univariately, both beta-blockers (unadjusted OR=1.31; p=0.02) and ACE inhibitors/angiotensin II receptor antagonists (unadjusted OR=1.32; p=0.02) were modestly associated with increased VTE risk. However, after controlling for age, BMI, previously-identified VTE risk factors, CAD, CHF and the use of statins, beta-blockers (OR=1.06; 95% CI: 0.74, 1.51; p=0.75) and ACE inhibitors/angiotensin II receptor antagonists (OR=0.94; 95% CI: 0.65, 1.37; p=0.75) were no longer associated with VTE. Conclusions: Beta-blockers and ACE inhibitors/angiotensin II receptor antagonists do not appear to be protective against VTE. Disclosures: No relevant conflicts of interest to declare.