Length of stay (LOS), 30-day mortality, and 30-day readmission rates have not been compared between Medicare beneficiaries with heart failure (HF) with reduced ejection fraction (HFrEF) and ...beneficiaries with heart failure with preserved ejection fraction (HFpEF), although HFpEF is common in patients with HF. To determine whether type of HF (HFrEF or HFpEF) was associated with LOS, 30-day mortality, and 30-day readmission, we used a cohort of 19,477 Medicare beneficiaries admitted to the hospital and discharged alive with a primary discharge diagnosis of HF between 2007 and 2011. Gamma regression, Poisson regression, and Cox proportional hazards with a competing risk for death were used to model LOS, 30-day mortality, and 30-day readmission rate, respectively. All models were adjusted for HF severity, co-morbidities, demographics, nursing home residence, and calendar year of admission. Beneficiaries with HFpEF had an LOS 0.02 days shorter than beneficiaries with HFrEF and a nearly identical 30-day readmission rate. Thirty-day mortality was 10% lower in beneficiaries with HFpEF versus HFrEF. In conclusion, readmission rates were as high in those with HFpEF as they are in those with HFrEF, with comparable LOS in the hospital.
Studies of the effect of air pollution on cognitive health are often limited to populations living near cities that have air monitoring stations. Little is known about whether the estimates from such ...studies can be generalized to the U.S. population, or whether the relationship differs between urban and rural areas. To address these questions, we used a satellite-derived estimate of fine particulate matter (PM2.5) concentration to determine whether PM2.5 was associated with incident cognitive impairment in a geographically diverse, biracial US cohort of men and women (n = 20,150). A 1-year mean baseline PM2.5 concentration was estimated for each participant, and cognitive status at the most recent follow-up was assessed over the telephone using the Six-Item Screener (SIS) in a subsample that was cognitively intact at baseline. Logistic regression was used to determine whether PM2.5 was related to the odds of incident cognitive impairment. A 10 µg/m(3) increase in PM2.5 concentration was not reliably associated with an increased odds of incident impairment, after adjusting for temperature, season, incident stroke, and length of follow-up OR (95% CI): 1.26 (0.97, 1.64). The odds ratio was attenuated towards 1 after adding demographic covariates, behavioral factors, and known comorbidities of cognitive impairment. A 10 µg/m(3) increase in PM2.5 concentration was slightly associated with incident impairment in urban areas (1.40 1.06-1.85), but this relationship was also attenuated after including additional covariates in the model. Evidence is lacking that the effect of PM2.5 on incident cognitive impairment is robust in a heterogeneous US cohort, even in urban areas.
The beta blockers carvedilol, bisoprolol, and sustained-release metoprolol succinate reduce readmissions and mortality among patients with heart failure with reduced ejection fraction (HFrEF), based ...upon clinical trial and registry studies. Results from these studies may not generalize to the typical patient with HFrEF. We conducted a retrospective cohort study of beneficiaries in the Medicare 5% sample hospitalized for HFrEF between 2007 and 2013 and were discharged alive. We compared the 30-day and 365-day heart failure (HF) readmission, all-cause readmission, and mortality rates between beneficiaries who filled a prescription for an evidence-based beta blocker and those who did not after being hospitalized for HFrEF. Out of 12,127 beneficiaries hospitalized for HFrEF, 20% were readmitted for HF, 62% were readmitted for any cause, and 27% died within 365 days. In competing risk models adjusted for demographics, healthcare utilization, and comorbidities, beta blocker use was associated with a lower risk of HF readmission between 8-365 days post discharge (hazard ratio 0.79 95% confidence interval 0.76, 0.82), but was not significantly associated with all-cause readmission (1.02 0.97-1.07). In Cox models adjusted for the same covariates, beta blocker use was associated with lower mortality 8-365 days post discharge (0.65 0.60-0.71). Results were similar when follow up was truncated at 30 days post discharge. Increasing the use of beta blockers following HFrEF hospitalization may not decrease all-cause readmissions among Medicare beneficiaries, but may reduce HF-specific readmissions and mortality.
Electronic health record (EHR) data are underutilized for abstracting classification criteria for heart disease. We compared extraction of EHR data on troponin I and T levels with human abstraction.
...Using EHR for hospitalizations identified through the Atherosclerosis Risk in Communities (ARIC) Study in four US hospitals, we compared blood levels of troponins I and T extracted from EHR structured data elements with levels obtained through data abstraction by human abstractors to 3 decimal places. Observations were divided randomly 50/50 into training and validation sets. Bayesian multilevel logistic regression models were used to estimate agreement by hospital in first and maximum troponin levels, troponin assessment date, troponin upper limit of normal (ULN), and classification of troponin levels as normal (< ULN), equivocal (1-2× ULN), abnormal (>2× ULN), or missing.
Estimated overall agreement in first measured troponin level in the validation data was 88.2% (95% credible interval: 65.0%-97.5%) and 95.5% (91.2-98.2%) for the maximum troponin level observed during hospitalization. The largest variation in probability of agreement was for first troponin measured, which ranged from 66.4% to 95.8% among hospitals.
Extraction of maximum troponin values during a hospitalization from EHR structured data is feasible and accurate.
•Algorithmic extraction of troponin values from EHR is accurate.•Algorithmic protocols can accommodate serial troponin assessments.•Such information can be easily applied in diagnostic classification.
Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids, and genetic material, playing important roles in intracellular communication. They have ...remarkable potential as non-toxic and non-immunogenic nanocarriers for drug delivery to unreachable organs and tissues, in particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage-derived EVs to treat Parkinson disease (PD). Specifically, we evaluated the therapeutic potential of EVs secreted by autologous macrophages that were transfected ex vivo to express glial-cell-line-derived neurotrophic factor (GDNF). EV-GDNF were collected from conditioned media of GDNF-transfected macrophages and characterized for GDNF content, size, charge, and expression of EV-specific proteins. The data revealed that, along with the encoded neurotrophic factor, EVs released by pre-transfected macrophages carry GDNF-encoding DNA. Four-month-old transgenic Parkin Q311(X)A mice were treated with EV-GDNF via intranasal administration, and the effect of this therapeutic intervention on locomotor functions was assessed over a year. Significant improvements in mobility, increases in neuronal survival, and decreases in neuroinflammation were found in PD mice treated with EV-GDNF. No offsite toxicity caused by EV-GDNF administration was detected. Overall, an EV-based approach can provide a versatile and potent therapeutic intervention for PD.
NAFLD is highly prevalent with limited treatment options. Bile acids (BAs) increase in the systemic circulation and liver during NAFLD progression. Changes in plasma membrane localization and zonal ...distribution of BA transporters can influence transport function and BA homeostasis. However, a thorough characterization of how NAFLD influences these factors is currently lacking. This study aimed to evaluate the impact of NAFLD and the accompanying histologic features on the functional capacity of key hepatocyte BA transporters across zonal regions in human liver biopsies.
A novel machine learning image classification approach was used to quantify relative zonal abundance and plasma membrane localization of BA transporters (bile salt export pump BSEP, sodium-taurocholate cotransporting polypeptide, organic anion transporting polypeptide OATP 1B1 and OATP1B3) in non-diseased (n = 10), NAFL (n = 9), and NASH (n = 11) liver biopsies. Based on these data, membrane-localized zonal abundance (MZA) measures were developed to estimate transporter functional capacity.
NAFLD diagnosis and histologic scoring were associated with changes in transporter membrane localization and zonation. Increased periportal BSEPMZA (mean proportional difference compared to non-diseased liver of 0.090) and decreased pericentral BSEPMZA (-0.065) were observed with NASH and also in biopsies with higher histologic scores. Compared to Non-diseased Liver, periportal OATP1B3MZA was increased in NAFL (0.041) and NASH (0.047). Grade 2 steatosis (mean proportional difference of 0.043 when compared to grade 0) and grade 1 lobular inflammation (0.043) were associated with increased periportal OATP1B3MZA.
These findings provide novel mechanistic insight into specific transporter alterations that impact BA homeostasis in NAFLD. Changes in BSEPMZA likely contribute to altered BA disposition and pericentral microcholestasis previously reported in some patients with NAFLD. BSEPMZA assessment could inform future development and optimization of NASH-related pharmacotherapies.
Background Our objective was to determine associations of occupational exposures with cardiac structure and function in Hispanic/Latino adults. Methods and Results Employed participants were included ...(n=782; 52% women, mean age 52.9 years). Occupational exposures to burning wood, vehicle exhaust, solvents, pesticides, and metals at the current and longest-held job were assessed by questionnaire. Survey multivariable linear regression analyses were used to model the relationship of each self-reported exposure with echocardiographic measures of cardiac structure and function. Exposure to burning wood at the current job was associated with decreased left ventricular (LV) ejection fraction (-3.1%; standard error SE, 1.0
=0.002). When the analysis was restricted to exposure at the longest-held job, occupational exposure to burning wood was associated with increased LV diastolic volume (6.7 mL; SE, 1.6
<0.0001), decreased LV ejection fraction (-2.7%; SE, 0.6
<0.0001), worse LV global longitudinal strain (1.0%; SE, 0.3
=0.0009), and decreased right ventricular fractional area change (-0.02; SE, 0.004
<0.001). Exposure to pesticides was associated with worse average global longitudinal strain (0.8%; SE, 0.2
<0.0001). Exposure to metals was associated with worse global longitudinal strain in the 2-chamber view (1.0%; SE, 0.5
=0.04), increased stroke volume (3.6 mL; SE, 1.6
=0.03), and increased LV mass indexed to BSA (9.2 g/m
; SE, 3.8
=0.01) or height (4.4 g/m
; SE, 1.9
=0.02). Conclusions Occupational exposures to burning wood, vehicle exhaust, pesticides, and metals were associated with abnormal parameters of LV and right ventricular systolic function. Reducing exposures to toxic chemicals and particulates in the workplace is a potential opportunity to prevent cardiovascular disease in populations at risk.
Perinatal health outcomes are influenced by a variety of socioeconomic, behavioral, and economic factors that reduce access to health services. Despite these observations, rural communities continue ...to face barriers, including a lack of resources and the fragmentation of health services.
To evaluate patterns in health outcomes, health behaviors, socioeconomic vulnerability, and sociodemographic characteristics across rural and nonrural counties within a single health system catchment area.
Socioeconomic vulnerability metrics, health care access as determined by licensed provider metrics, and behavioral data were obtained from FlHealthCHARTS.gov and the County Health Rankings. County-level birth and health data were obtained from the Florida Department of Health. The University of Florida Health Perinatal Catchment Area (UFHPCA) was defined as all Florida counties where ≥5% of all infants were delivered at Shands Hospital between June 2011 and April 2017.
The UFHPCA included 3 nonrural and 10 rural counties that represented more than 64,000 deliveries. Nearly 1 in 3 infants resided in a rural county, and 7 out of 13 counties did not have a licensed obstetrician gynecologist. Maternal smoking rates (range 6.8%-24.8%) were above the statewide rate (6.2%). Except for Alachua County, breastfeeding initiation rates (range 54.9%-81.4%) and access to household computing devices (range 72.8%-86.4%) were below the statewide rate (82.9% and 87.9%, respectively). Finally, we found that childhood poverty rates (range 16.3%-36.9%) were above the statewide rate (18.5%). Furthermore, risk ratios suggested negative health outcomes for residents of counties within the UFHPCA for each measure, except for infant mortality and maternal deaths, which lacked sample sizes to adequately test.
The health burden of the UFHPCA is characterized by rural counties with increased maternal death, neonatal death, and preterm birth, as well as adverse health behaviors that included increased smoking during pregnancy and lower levels of breastfeeding relative to nonrural counties. Understanding perinatal health outcomes across a single health system has potential to not only estimate community needs but also facilitate planning of health care initiatives and interventions in rural and low-resource communities.
Abstract In longitudinal studies, the devices used to measure exposures can change from visit to visit. Calibration studies, wherein a subset of participants is measured using both devices at ...follow-up, may be used to assess between-device differences (i.e., errors). Then, statistical methods are needed to adjust for between-device differences and the missing measurement data that often appear in calibration studies. Regression calibration and multiple imputation are two possible methods. We compared both methods in linear regression with a simulation study, considering various real-world scenarios for a longitudinal study of pulse wave velocity. Regression calibration and multiple imputation were both essentially unbiased, but correctly estimating the standard errors posed challenges. Multiple imputation with predicted mean matching produced close agreement with the empirical standard error. Fully stochastic multiple imputation underestimated the standard error by up to 50%, and regression calibration with bootstrapped standard errors performed slightly better than fully stochastic multiple imputation. Regression calibration was slightly more efficient than either multiple imputation method. The results suggest use of multiple imputation with predictive mean matching over fully stochastic imputation or regression calibration in longitudinal studies where a new device at follow-up might be error-prone compared to the device used at baseline.
The trailing 1-year mean (°C) of the NLDAS daily mean temperatures for the grid cell containing the geographic location of the participants’ residence was used to define the temperature exposure for ...each participant. 1. (2013) Fine Particulate Matter and Incident Cognitive Impairment in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort.
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