Analyzing risk factors for post-acute recovery in older adults with Alzheimer's disease and related dementia: A new semi-parametric model for large-scale medicare claims.

Nearly 300,000 older adults experience a hip fracture every year, the majority of which occur following a fall. Unfortunately, recovery after fall-related trauma such as hip fracture is poor, where older adults diagnosed with Alzheimer's disease and related dementia (ADRD) spend a particularly long time in hospitals or rehabilitation facilities during the post-operative recuperation period. Because older adults value functional recovery and spending time at home versus facilities as key outcomes after hospitalization, identifying factors that influence days spent at home after hospitalization is imperative.

A Cartographic Tool to Predict Disease Risk-associated Pseudo-Dynamic Networks from Tissue-specific Gene Expression.

Understanding how genes are differentially expressed across tissues is key to reveal the etiology of human diseases. Genes are never expressed in isolation, but rather co-expressed in a community; thus, they co-act through intricate but well-orchestrated networks. However, existing approaches cannot coalesce the full properties of gene-gene communication and interactions into networks.

Cumulative Consumption of Sulfur Amino Acids and Risk of Diabetes: A Prospective Cohort Study.

Background: Cross-sectional studies have suggested that consumption of sulfur amino acids (SAAs), including methionine and cysteine, is associated with a higher risk of type 2 diabetes (T2D) in humans and with T2D-related biomarkers in animals. But whether higher long-term SAA intake increases the risk of T2D in humans remains unknown.

Objectives: We aimed to investigate the association between long-term dietary SAA intake and risk of T2D.

Diabetes Is Negatively Associated With Meeting Physical Activity Time-Intensity Guidelines in Patients With Claudication.

Purposes: We determined the percentage of patients with peripheral artery disease (PAD) and claudication who meet the 2018 physical activity (PA) time-intensity guidelines, and we identified the clinical characteristics associated with the status of meeting the guidelines.

Methods: Five hundred seventy-two patients were assessed on their daily ambulatory activity for 1 wk with a step activity monitor, and were evaluated on whether or not they achieved 150 min/wk of moderate-intensity PA.

Results: Thirty-one percent (n = 175) of the patients with PAD met the PA time-intensity guidelines and 69% (n = 397) did not.

Synthesizing secondary data into survival analysis to improve estimation efficiency.

The accelerated failure time (AFT) model and Cox proportional hazards (PH) model are broadly used for survival endpoints of primary interest. However, the estimation efficiency from those models can be further enhanced by incorporating the information from secondary outcomes that are increasingly available and highly correlated with primary outcomes. Those secondary outcomes could be longitudinal laboratory measures collected from doctor visits or cross-sectional disease-relevant variables, which are believed to contain extra information related to primary survival endpoints to a certain extent.

Nonadherence to Multimodality Cancer Treatment Guidelines in the United States.

Purpose: Our purpose was to identify patients with cancer who do not receive guideline-concordant multimodality treatment and to identify factors that are associated with nonreceipt of guideline-concordant multimodality treatment.

Methods And Materials: Five cancers for which the multimodal guideline-concordant treatment (with surgery, chemotherapy, and radiation therapy) is clearly defined in national guidelines were selected from the National Cancer Database: (1) nonmetastatic anal cancer, (2) locally advanced cervical cancer, (3) nonmetastatic nasopharynx cancer, (4) locally advanced rectal cancer, and (5) locally advanced non-small cell lung cancer. Multivariable logistic regression was used to determine the odds ratios (with 95% confidence intervals) of receiving the guideline-concordant treatment versus not, adjusting for common confounding variables.

Association Between Meeting Physical Activity Time-Intensity Guidelines With Ambulation, Quality of Life, and Inflammation in Claudication.

Purpose: The aim of this investigation was to determine if meeting the 2018 physical activity (PA) time-intensity guidelines was associated with better ambulatory function, health-related quality of life (HRQoL), vascular function, and inflammation than failing to meet the guidelines in patients with peripheral artery disease and claudication. Second, we determined the optimal number of total steps/d and steps taken at moderate cadence needed to meet the PA time-intensity guidelines.

Methods: Five hundred seventy-two patients were assessed on daily ambulatory activity for 1 wk with a step activity monitor, and were grouped according to whether they achieved <150 min/wk of moderate-intensity PA (group 1 = do not meet guidelines; n = 397) or whether they were above this threshold (group 2 = meet guidelines; n = 175).

Semiparametric marginal methods for clustered data adjusting for informative cluster size with nonignorable zeros.

Clustered or longitudinal data are commonly encountered in clinical trials and observational studies. This type of data could be collected through a real-time monitoring scheme associated with some specific event, such as disease recurrence, hospitalization, or emergency room visit. In these contexts, the cluster size could be informative because of its potential correlation with disease status, since more frequency of observations may indicate a worsening health condition.

A statistical framework for recovering pseudo-dynamic networks from static data.

Motivation: The collection of temporal or perturbed data is often a prerequisite for reconstructing dynamic networks in most cases. However, these types of data are seldom available for genomic studies in medicine, thus significantly limiting the use of dynamic networks to characterize the biological principles underlying human health and diseases.

Results: We proposed a statistical framework to recover disease risk-associated pseudo-dynamic networks (DRDNet) from steady-state data.

Minimal clinically important differences in daily physical activity outcomes following supervised and home-based exercise in peripheral artery disease.

We estimated minimal clinically important differences (MCID) for small, moderate, and large changes in daily step counts and time spent in moderate-to-vigorous physical activity (MVPA) following both supervised and home-based exercise programs in symptomatic patients with peripheral artery disease (PAD). Patients were randomized to either 12 weeks of a supervised exercise program ( = 60), a home-based exercise program ( = 60), or an attention-control group ( = 60). Using the anchor-based method to determine MCID, the MCID value for a large change in health-related quality of life (HRQoL) was an increase of 1211 total daily steps and an increase in 11 minutes in the time spent in MVPA following 12 weeks of exercise intervention.

Light and moderate intensity physical activity are associated with better ambulation, quality of life, and vascular measurements in patients with claudication.

Objective: We sought to determine whether patients with claudication who reported performing either light intensity physical activity (LPA) or moderate-to-vigorous intensity physical activity (MVPA) would have higher levels of objectively determined physical activity and better physical function, health-related quality of life (HRQoL), and vascular measures, consisting of exercise time to minimum calf muscle oxygen saturation (StO) and high-sensitivity C-reactive protein, than patients who reported being physically sedentary.

Methods: A total of 269 patients were assessed using the Johnson Space Center physical activity scale. The patients were grouped according to whether they performed no physical activities (n = 75), LPAs (n = 140), or MVPAs (n = 54).

Association Between Daily Steps at Moderate Cadence and Vascular Outcomes in Patients With Claudication.

Purpose: We determined whether patients with peripheral artery disease (PAD) and claudication grouped according to tertiles of community-based daily steps taken at a moderate cadence had differences in vascular function and biomarkers and whether group differences in vascular function and biomarkers persisted after adjusting for demographic variables, comorbid conditions, and severity of PAD.

Methods: Two hundred sixty-three patients were evaluated for 1 wk on steps taken at a moderate cadence (exceeding 60 steps/min), and patients were placed into low (group 1), intermediate (group 2), and high (group 3) tertiles.

Results: Ankle/brachial index (ABI) at 1 min after exercise (mean ± SD) was significantly higher in groups 2 and 3 than in group 1 in unadjusted (P < .

Cognitive decrement in older adults with symptomatic peripheral artery disease.

Peripheral artery disease (PAD) is highly prevalent, affecting up to 20% of people over 70 years of age. To test the hypothesis that PAD promotes the pathogenesis of vascular cognitive impairment (VCI), we compared cognitive function in older adults with symptomatic PAD and in participants without PAD who had a burden of comorbid conditions. Furthermore, we compared the cognitive function of these groups after adjusting for demographic and clinical characteristics, comorbid conditions, and cardiovascular risk factors.

Impact of radiation therapy facility volume on survival in patients with cancer.

Background: This study examined whether radiation therapy facility volumes correlate with survival after curative intent treatment of solid tumors.

Methods: The National Cancer Database was queried for patients with solid tumors treated with curative-intent radiation therapy from 2004-2013. Facilities were stratified into 4 volume categories: low, intermediate, high, and very high.

Joint modeling of longitudinal data with informative cluster size adjusted for zero-inflation and a dependent terminal event.

Repeated measures are often collected in longitudinal follow-up from clinical trials and observational studies. In many situations, these measures are adherent to some specific event and are only available when it occurs; an example is serum creatinine from laboratory tests for hospitalized acute kidney injuries. The frequency of event recurrences is potentially correlated with overall health condition and hence may influence the distribution of the outcome measure of interest, leading to informative cluster size.

Impact of Facility Surgical Volume on Survival in Patients With Cancer.

Background: Increased facility surgical treatment volume is sometimes associated with improved survival in patients with cancer; however, published studies evaluating volume are heterogeneous and disparate in their patient inclusion and definition of volume. The purpose of this work was to evaluate uniformly the impact of surgical facility volume on survival in patients with cancer.

Methods: The National Cancer Database was searched for patients diagnosed in 2004 through 2013 with the 12 cancers most commonly treated surgically.

Association between meeting daily step count goals with ambulatory function and quality of life in patients with claudication.

Objective: To determine (a) whether patients with peripheral artery disease (PAD) who walked at least 7000 and 10,000 steps/day had better ambulatory function and health-related quality of life (HRQoL) than patients who walked less than 7000 steps/day, and (b) whether differences in ambulatory function and HRQoL in patients grouped according to these daily step count criteria persisted after adjusting for covariates.

Methods: Two hundred forty-eight patients were assessed on their daily ambulatory activity for 1 week with a step activity monitor, and were grouped according to daily step count targets. Patients who took fewer than 7000 steps/day were included in group 1 (n = 153), those who took 7000 to 9999 steps/day were included in group 2 (n = 57), and patients who took at least 10,000 steps/day were included in group 3 (n = 38).

Daily Step Counts in Participants With and Without Peripheral Artery Disease.

Purpose: We compared the prevalence of participants with and without symptomatic peripheral artery disease (PAD) who met the goals of attaining >7000 and 10 000 steps/d, and we determined whether PAD status was significantly associated with meeting the daily step count goals before and after adjusting for demographic variables, comorbid conditions, and cardiovascular risk factors.

Methods: Participants with PAD (n = 396) and without PAD (n = 396) were assessed on their walking for 7 consecutive days with a step activity monitor.

Results: The PAD group took significantly fewer steps/d than the non-PAD control group (6722 ± 3393 vs.

A multiple robust propensity score method for longitudinal analysis with intermittent missing data.

Longitudinal data are very popular in practice, but they are often missing in either outcomes or time-dependent risk factors, making them highly unbalanced and complex. Missing data may contain various missing patterns or mechanisms, and how to properly handle it for unbiased and valid inference still presents a significant challenge. Here, we propose a novel semiparametric framework for analyzing longitudinal data with both missing responses and covariates that are missing at random and intermittent, a general and widely encountered situation in observational studies.

Patients With Peripheral Arterial Disease With Exaggerated Pressor Response Have Greater Ambulatory Dysfunction Than Patients With Lower Pressor Response.

We determined whether patients with peripheral arterial disease (PAD) who have either an exaggerated or a negative pressor response during treadmill walking have shorter peak walking time (PWT) and claudication onset time (COT) than patients with a normal pressor response, independent of comorbid conditions. A total of 249 patients were categorized to 1 of 3 groups based on systolic blood pressure (SBP) responses at 2 minutes of treadmill walking (speed = 2 mph, grade = 0%): group 1 (negative pressor response, SBP < 0 mm Hg), group 2 (normal pressor response, SBP 18 mm Hg), and group 3 (exaggerated pressor response, SBP > 18 mm Hg). After adjusting for comorbid conditions, group 3 (exaggerated) had significantly reduced COT ( = .

Diet is associated with ankle-brachial index, inflammation, and ambulation in patients with intermittent claudication.

Objective: The aims of this investigation were to determine whether the daily dietary intake of nutrients by patients with peripheral artery disease (PAD) and intermittent claudication (IC) met recommended levels for adults older than 50 years and to determine whether meeting recommended levels of nutrients was associated with ankle-brachial index (ABI), inflammation, and ambulation of patients with PAD and IC.

Methods: A total of 48 patients were assessed on their dietary intake of 20 nutrients during a 3-day period. Patients were further characterized on demographic variables, comorbid conditions, cardiovascular risk factors, ABI, 6-minute walk distance (6MWD), and high-sensitivity C-reactive protein (hsCRP) concentration.

Association between calf muscle oxygen saturation with ambulatory function and quality of life in symptomatic patients with peripheral artery disease.

Objective: The objective of this study was to determine whether calf muscle hemoglobin oxygen saturation (Sto) obtained during a standardized treadmill test is associated with ambulatory function and health-related quality of life (HRQoL) in patients with symptomatic peripheral artery disease (PAD). We hypothesized that a rapid decline in calf muscle Sto during walking is associated with impaired ambulatory function and HRQoL and that these associations are independent of ankle-brachial index (ABI).

Methods: Calf muscle Sto, peak walking time, and claudication onset time were obtained during a treadmill test in 151 symptomatic men and women with PAD.

An omnidirectional visualization model of personalized gene regulatory networks.

Gene regulatory networks (GRNs) have been widely used as a fundamental tool to reveal the genomic mechanisms that underlie the individual's response to environmental and developmental cues. Standard approaches infer GRNs as holistic graphs of gene co-expression, but such graphs cannot quantify how gene-gene interactions vary among individuals and how they alter structurally across spatiotemporal gradients. Here, we develop a general framework for inferring informative, dynamic, omnidirectional, and personalized networks (idopNetworks) from routine transcriptional experiments.

Sex differences in metabolic effects of angiotensin-(1-7) treatment in obese mice.

Background: Angiotensin-(1-7) is a beneficial hormone of the renin-angiotensin system known to play a positive role in regulation of blood pressure and glucose homeostasis. Previous studies have shown that in high-fat diet (HFD)-induced obese male mice, circulating angiotensin-(1-7) levels are reduced and chronic restoration of this hormone reverses diet-induced insulin resistance; however, this has yet to be examined in female mice. We hypothesized angiotensin-(1-7) would improve insulin sensitivity and glucose tolerance in obese female mice, to a similar extent as previously observed in male mice.