Citations

Background: Patient reported measures are fundamental to patient centered research and are often collected by questionnaires. Low participation can compromise the validity of the results; transparent reporting and comparing characteristics of participants to nonparticipants is important to assess the generalizability of survey results. We analyzed participation in a survey of social determinants of health among a population-based sample of patients with heart failure (HF). Methods: A total of 7920 residents from 11 Minnesota counties were identified with a first-ever code for HF (ICD-9 428 and ICD-10 I50) between 1/1/2013 and 12/31/2016. Participants completed a battery of 12 questionnaires by mail or telephone. Characteristics and outcomes data were extracted from medical records and compared between participants and nonparticipants. Response rate (RR) was calculated using guidelines of the American Association for Public Opinion Research (AAPOR). The association between nonparticipation and outcomes was examined by Cox proportional hazards regression for death and Andersen-Gill modeling for hospitalizations. Results: Among 7920 patients, 3438 responded to the survey (AAPOR RR#2= 43%). Numerous clinical and demographic differences between participants and non-participants were noted (Table), particularly for education, marital status, and neuropsychiatric conditions. After a mean (±SD) of 1.5±1 years after survey administration, 1,577 deaths and 5,873 hospitalizations had occurred. Nonparticipation was associated with a two-fold increased risk of death (HR: 2.30; 95% CI: 2.06-2.57; p<0.001) and a 10% increased risk of hospitalizations (HR: 1.10; 95% CI: 1.01-1.21; p=0.03) after adjusting for age, sex, marital status, coronary disease, arrhythmia, hyperlipidemia, cancer, chronic kidney disease, depression and anxiety. Conclusions: In a large survey of patients with HF, participation was associated with large differences in clinical and demographic characteristics and outcomes. Examining the impact of participation is critical to draw inference from studies of patient reported measures.

Background Many adults eligible for statin therapy for cardiovascular disease prevention are untreated. Our objective was to investigate patient‐reported reasons for statin underutilization, including noninitiation, refusal, and discontinuation. Methods and Results This study included the 5693 adults recommended for statin therapy in the PALM (Patient and Provider Assessment of Lipid Management) registry. Patient surveys evaluated statin experience, reasons for declining or discontinuing statins, and beliefs about statins and cardiovascular disease risk. Overall, 1511 of 5693 adults (26.5%) were not on treatment. Of those not on a statin, 894 (59.2%) reported never being offered a statin, 153 (10.1%) declined a statin, and 464 (30.7%) had discontinued therapy. Women (relative risk: 1.22), black adults (relative risk: 1.48), and those without insurance (relative risk: 1.38) were most likely to report never being offered a statin. Fear of side effects and perceived side effects were the most common reasons cited for declining or discontinuing a statin. Compared with statin users, those who declined or discontinued statins were less likely to believe statins are safe (70.4% of current users vs. 36.9% of those who declined and 37.4% of those who discontinued) or effective (86.3%, 67.4%, and 69.1%, respectively). Willingness to take a statin was high; 67.7% of those never offered and 59.7% of patients who discontinued a statin would consider initiating or retrying a statin. Conclusions More than half of patients eligible for statin therapy but not on treatment reported never being offered one by their doctor. Concern about side effects was the leading reason for statin refusal or discontinuation. Many patients were willing to reconsider statin therapy if offered.

PurposeThe goal of this work is to demonstrate 1 mm through‐plane resolution in multislice T2SE MRI using k‐space processing of overlapping slices and show applicability in prostate MRI.MethodsMultiple overlapped slices are acquired and Fourier transformed in the slice‐select direction. The slice profile is incorporated into a Tikhonov‐regularized reconstruction. Through‐plane resolution is tested in a resolution phantom. An anthropomorphic prostate phantom is used to study the SNR, and results are compared with theoretical prediction. The proposed method is tested in 16 patients indicated for clinical prostate MRI who gave written informed consent as overseen by our IRB. The “proposed” vs. “reference” multislice images are compared using multiple evaluation criteria for through‐plane resolution.ResultsThe modulation transfer function (MTF) plots of the resolution phantom show good modulation at frequency 0.5 lp/mm, demonstrating 1 mm through‐plane resolution restoration. The SNR measurements experimentally match the theoretically predicted values. The radiological evaluation shows that the proposed method is superior to the reference method for five criteria of sharpness but inferior with respect to artifacts.ConclusionsIn conjunction with overlapped slices a k‐space‐based reconstruction approach can be used to improve through‐plane resolution in multislice T2SE MRI. 1 mm resolution is demonstrated from 3.2 mm thick slices. The in vivo results from prostate MRI show improved sharpness when compared to the standard multislice method.

Background: The decline in cardiovascular disease (CVD) mortality in the United States noted since the mid 1970s has recently leveled off. This has generated concern and a need for further analyses to understand geographic variation, cause-specific deaths, location of death, and age-specific trends. Methods: Death certificate data obtained from the Minnesota Department of Health were used for analysis. The American Heart Association (AHA) classification was applied to the underlying cause of death to generate the following CVD categories: coronary heart disease (CHD), non-CHD diseases of the heart, and non-cardiac circulatory diseases. Temporal trends in death rates were explored by negative binomial regression, which enables estimates of age- and sex-adjusted average annual percentage changes (AAPCs). Differences in AAPCs between 2000-2009 and 2010-2017 were tested overall and across demographic, CVD, and location of death categories. Results: CVD mortality rates, which were declining in 2000-2009, have leveled off in 2010-2017 (Table). These trends were observed across all subgroups. After adjusting for sex, the age group that drove the decline in rates from 2000-2009 was the 65-84 year old group, which experienced no change in rates from 2010-2017. Across CVD categories, after adjusting for age and sex, the decline in rates from 2000-2009 was largely attributable to steep reductions in CHD and non-cardiac circulatory diseases, with lesser reduction in non-CHD diseases of the heart. In 2010-2017, CHD and non-cardiac circulatory diseases rates showed no change, whereas the rate of non-CHD diseases of the heart increased. The rates for in- and out-of-hospital deaths improved in 2000-2009 with no further improvement observed in 2010-2017. Conclusions: CVD mortality rates are no longer declining in Minnesota, paralleling national trends. These trends are particularly concerning for non-CHD diseases of the heart.

Background: Previous studies have indicated that living in a rural or non-urban area may be associated with poor health outcomes. However, data on rurality and death in heart failure (HF) are scarce. Methods: Residents from 11 southeast MN counties with a first-ever code for HF (including codes ICD-9 428 and ICD-10 I50) between 1/1/2013 and 12/31/2016 were identified. Resident address was geo-coded and classified according to the Rural-Urban Commuting Area (RUCA) codes, which classifies US census tracts to measure population density, urbanization and daily commuting. Rurality was defined as living in a non-metropolitan area. Cox proportional hazards regression was used to determine the association between living in a rural vs. urban area and death. Results: Among 6,996 patients (mean age 73 years, 52% male), 54% of patients lived in a rural area. These patients were older and had a lower level of educational attainment and comorbidity burden (p<0.001). After a mean (SD) follow-up of 2.9 (1.3) years, 1,856 deaths occurred. Living in a rural area was univariately associated with a higher risk of death (HR 1.20, 95% CI: 1.09-1.31; Table). After adjustment for age, sex, education status and comorbidity burden, rurality remained associated with an increased risk of death (HR 1.15; 95% CI: 1.04-1.27). Conclusions: Among patients with HF, living in a rural area is associated with an increased risk of death. Further study to identify and address the mechanisms through which rural residence influences mortality in patients with HF is needed.

Background: Multimorbidity is common in atrial fibrillation (AF); however, the impact of the number and type of comorbid conditions on death and hospitalizations is uncertain. Methods: The prevalence of 17 chronic conditions was obtained in 1430 patients with incident AF from 2000-2010 from Olmsted County, MN. Chronic conditions were ascertained electronically prior to AF and were classified into 3 groups: cardiovascular (CV), other physical, and mental. All hospitalizations and deaths were obtained through 12/31/2014. Associations of the number and type of condition and each individual condition with hospitalizations and death were determined using Andersen-Gill and Cox regression, respectively. Results: Among the 1430 patients with AF (median age 76 years, 48.6% men), the mean (SD) number of chronic conditions was 4.7 (2.7). A total of 4496 hospitalizations and 812 deaths occurred over a mean (SD) follow-up of 5.4 (4.1) years. An increase in the number of conditions of each type was associated with increased risks of death and hospitalizations (Table). Mental conditions (which included depression, anxiety, dementia, schizophrenia, and substance abuse) exhibited the strongest association with death, whereas other physical conditions exhibited the strongest association with hospitalizations. Individual predictors of death included heart failure (HF), hypertension, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), depression, dementia, and substance abuse. Predictors of hospitalizations included HF, coronary artery disease, diabetes, COPD, CKD, arthritis, osteoporosis, and substance abuse. Conclusions: Patients with AF have many comorbid conditions which are associated with death and hospitalizations. Although conditions of each type were associated with outcomes, mental conditions exhibited strongest association with death. These data highlight the importance of management of not only CV comorbidities but other physical and mental comorbidities in patients with AF.

Background: Accurate identification of stroke cases from electronic health record (EHR) is needed for efficient and valid clinical and epidemiology research. A number of studies have evaluated the validity of using ICD-9 and ICD-10 codes for stroke identification. Previous research results show that sensitivity and positive predictive value (PPV) for stroke identification is the lowest among all other cerebrovascular diseases, with notable differences observed by stroke pathological subtypes. While most prevalent cerebrovascular disease cases can be detected using 430-438/I60-I69 collectively, more accurate and comprehensive stroke phenotyping algorithm is needed to identify incident stroke cases from EHR. In our work, we compared case identification results using ICD-codes exclusively with ICD plus a natural language processing (NLP) algorithm. Methods: We developed the NLP part of our stroke algorithm using a list of expert provided stroke-related keywords, which covers transient ischemic attack (TIA), ischemic stroke, and hemorrhagic stroke. We validated the hybrid (ICD+NLP) algorithm and compared it with ICD-exclusive algorithm in a previously established atrial fibrillation cohort (n=5,062). Clinical notes and ICD codes of all patients after the incident AF event were reviewed by two nurse abstracters to confirm new stroke incidences. All past clinical notes and ICD codes of a subset of patients (n=402) were reviewed to confirm lifetime (prior and current) stroke cases. Manual abstraction results were considered the gold standard for evaluation of ICD only and ICD+NLP automatic extraction. Sensitivity and positive predictive values (PPV) of both algorithms were calculated. Results: Among 5,062 patients, 593 patients were confirmed to have suffered a stroke after atrial fibrillation while 4,469 patients were confirmed with no EHR evidence of stroke after AF. The ICD-exclusive algorithm had a sensitivity of 47.2% and a PPV of 47.8% for detecting new stroke incidences. The hybrid stroke algorithm achieved a sensitivity of 92.4% and a PPV of 60.6% for extraction of incident stroke. For extraction of lifetime stroke cases, the hybrid approach achieved a sensitivity of 93.9% and a PPV of 88.7%. Performance of new stroke incidence extraction is limited because past/current stroke mentions in clinical notes are difficult to distinguish by our NLP algorithm (may be a future direction). Conclusions: We developed and validated a stroke algorithm that performed well for identifying incident and lifetime stroke cases. The addition of NLP into the stroke algorithm improved the sensitivity and PPV of compared to an ICD-exclusive algorithm.

ABSTRACT Objectives Albumin messenger RNA (mRNA) expression is a marker of hepatocellular differentiation. Most published data are from review of tissue microarrays, and albumin in situ hybridization (ISH) expression across several tumor types is incompletely characterized. Methods Sections from 221 tumors were evaluated for albumin mRNA. Immunohistochemistry was used to confirm diagnoses. Albumin ISH was performed according to manufacturer-provided instructions. Fifty-nine cases were evaluated with both commercial ISH assays. Results Albumin mRNA was detected in all hepatocellular carcinomas (HCCs) and 81% of intrahepatic cholangiocarcinomas. Lung (20%), gallbladder (39%), hepatoid pancreatic (n = 1 of 1) adenocarcinoma, breast invasive ductal carcinoma (18%), yolk sac tumor (25%), and acinar cell carcinoma (29%) showed expression. Both assays were concordant in 93% of cases. Conclusions Albumin ISH was expressed in all HCCs studied. It was also positive in intrahepatic cholangiocarcinoma and patchy positive in gallbladder adenocarcinoma and a subset of other neoplasms, which can be a potential pitfall.

Abstract Introduction Quantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B–based and florbetapir‐based amyloid imaging in the same participants from two independent cohorts using a crossover design. Methods Pittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter‐individual variability of the two tracers were compared using multivariate linear models both cross‐sectionally and longitudinally. Results Global amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers. Discussion Although the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers.

Background: The FOXO3a (forkhead box O3a)-BNIP3 (B-cell lymphoma 2/adenovirus E1B 19kDa interacting protein 3) pathway modulates mitochondrial dynamics and function and contributes to myocardial remodeling in rodent models of heart failure. We sought to investigate the expression of this pathway along with the expression of mitochondrial biogenesis (PGC-1α [peroxisome proliferator-activated receptor-γ coactivator-1α]), dynamics (DRP-1 [dynamin-related protein 1], OPA-1 [optic atrophy 1], and MFN 2 [mitofusin 2]), and oxidative phosphorylation (citrate synthase and electron transport chain complexes) markers and COX IV (cytochrome C oxidase) activity in myocardium from patients with valvular or ischemic heart disease and heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF). Methods and Results: Subepicardial left ventricular biopsies (10×1×1 mm 3 ) were obtained at aortic valve replacement (HFpEF AVR , n=5; and HFrEF AVR , n=4), coronary artery bypass grafting (HFpEF CABG , n=5; and HFrEF CABG , n=5), or left ventricular assist device implantation (HFrEF LVAD , n=4). Subepicardial biopsies from patients with normal left ventricular function (n=2) and from donor hearts (n=3) served as controls (normal). Relative to normal, mitochondrial fragmentation and cristae destruction were evident, and mitochondrial area was decreased in HFpEF; 1.00±0.09 versus 0.71±0.08; P =0.016. These mitochondrial morphological changes were more pronounced in HFrEF (0.54±0.06); P =0.002 HFpEF versus HFrEF. BNIP3 (monomer+dimer) expression was increased in HFpEF (3.99±2.44) and in HFrEF (5.19±1.70) relative to normal; P =0.004 and P <0.001, respectively. However, BNIP3 monomer was increased in HFrEF (4.32±1.43) compared with normal (0.99±0.06) and HFpEF (1.97±0.90); P =0.001 and 0.004, respectively. The HFrEF group uniquely showed increase in DRP-1 expression (1.94±0.38) and decreases in PGC-1α expression (0.61±0.07) and COX IV activity (0.70±0.10) relative to normal; P =0.013, P <0.001, and P <0.001, respectively, with no significant change in electron transport chain complexes expression. Conclusions: These findings in human myocardium confirm studies in rodents where contractile dysfunction is associated with activation of the FOXO3a-BNIP3 pathway and altered mitochondrial dynamics, biogenesis, and function.