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The article offers information on the results of a study regarding census-based and personally reported income measures as long-term risk-adjusted mortality predictors. It says that models with income variables and various risk factor adjustments were considered to examine the influence of the adjustment on the link between income measure and all-cause mortality. It states that census tract-level and family-level income were both inverse mortality predictors in risk-adjusted models when utilized as stand-alone socioeconomic position (SEP) estimators.

Abstract Background Although highly active antiretroviral therapy (HAART) has improved HIV survival, some patients receiving therapy are still dying. This analysis was conducted to identify factors associated with increased risk of post-HAART mortality. Methods We evaluated baseline (prior to HAART initiation) clinical, demographic and laboratory factors (including CD4+ count and HIV RNA level) for associations with subsequent mortality in 1,600 patients who began HAART in a prospective observational cohort of HIV-infected U.S. military personnel. Results Cumulative mortality was 5%, 10% and 18% at 4, 8 and 12 years post-HAART. Mortality was highest (6.23 deaths/100 person-years [PY]) in those with ≤ 50 CD4+ cells/mm3 before HAART initiation, and became progressively lower as CD4+ counts increased (0.70/100 PY with ≥ 500 CD4+ cells/mm3). In multivariate analysis, factors significantly (p < 0.05) associated with post-HAART mortality included: increasing age among those ≥ 40 years (Hazard ratio [HR] = 1.32 per 5 year increase), clinical AIDS events before HAART (HR = 1.93), ≤ 50 CD4+ cells/mm3 (vs. CD4+ ≥ 500, HR = 2.97), greater HIV RNA level (HR = 1.36 per one log10 increase), hepatitis C antibody or chronic hepatitis B (HR = 1.96), and HIV diagnosis before 1996 (HR = 2.44). Baseline CD4+ = 51-200 cells (HR = 1.74, p = 0.06), and hemoglobin < 12 gm/dL for women or < 13.5 for men (HR = 1.36, p = 0.07) were borderline significant. Conclusions Although treatment has improved HIV survival, defining those at greatest risk for death after HAART initiation, including demographic, clinical and laboratory correlates of poorer prognoses, can help identify a subset of patients for whom more intensive monitoring, counseling, and care interventions may improve clinical outcomes and post-HAART survival.

Abstract Background Among HIV-infected persons initiating highly active antiretroviral therapy (HAART), early CD4+ lymphocyte count increases are well described. However, whether CD4+ levels continue to increase or plateau after 4-6 years is controversial. Methods To address this question and identify other determinants of CD4+ response, we analyzed data for 1,846 persons from a prospective HIV military cohort study who initiated HAART, who had post-HAART CD4+ measurements, and for whom HIV seroconversion (SC) date was estimated. Results CD4+ count at HAART initiation was ≤ 200 cells/mm3 for 23%, 201-349 for 31%, 350-499 for 27%, and ≥500 for 19%. The first 6 months post-HAART, the greatest CD4+ increases (93-151 cells) occurred, with lesser increases (22-36 cells/year) through the first four years. Although CD4+ changes for the entire cohort were relatively flat thereafter, HIV viral load (VL) suppressors showed continued increases of 12-16 cells/year. In multivariate analysis adjusting for baseline CD4+ and post-HAART time interval, CD4+ responses were poorer in those with: longer time from HIV SC to HAART start, lower pre-HAART CD4+ nadir, higher pre-HAART VL, and clinical AIDS before HAART (P < 0.05). Conclusions Small but positive long-term increases in CD4+ count in virally suppressed patients were observed. CD4+ response to HAART is influenced by multiple factors including duration of preceding HIV infection, and optimized if treatment is started with virally suppressive therapy as early as possible.

PURPOSE: We have previously reported results of a pilot study in patients with locally advanced breast cancer receiving primary systemic chemotherapy (PST) showing that a decrease in tumor choline concentration ([tCho]) measured one day after starting treatment was associated with clinical response based on MRI. In this follow-up study with a larger cohort, we assessed whether early changes in [tCho] were associated with clinical response, based on both MRI and pathology, and survival. METHODS AND MATERIALS: Women with locally advanced breast cancer scheduled for PST were scanned using a high-field MRI/MRS protocol prior to treatment, day 1 after treatment, and at the end of the first course of chemotherapy. MRI/MRS was performed on a 4 T Varian system with unilateral transmit/receive breast coils. MRI consisted of contrast-enhanced T1-weighted 3D gradient echo scans with one-minute temporal resolution. A single-voxel MR spectrum was acquired from the index lesion after MRI, and the concentration of total choline compounds ([tCho]) was quantified using water as an internal reference. Clinical response was assessed using RECIST criteria for measuring the longest diameter (LD) of the index lesion, and by pathologic complete response (pCR) at definitive surgery. Overall survival (OS) and invasive disease free survival (IDFS) were assessed by retrospective review of clinical records and the social security death index. The associations of change in [tCho] with pCR/LD response and with IDFS/OS were assessed using logistic/Cox regression, respectively, adjusted for node positivity and pCR status. RESULTS: Of the 74 women enrolled in the trial, 51 women (ages 28-71, median 47 years) were scanned at all time points and included in the final analysis. Of these, 17 subjects had a partial or complete imaging RECIST response based on a ≥30% decrease of the LD of the index lesion. Pathologic complete response, defined as no detectable invasive disease in the breast, was observed in 13/51 overall subjects and in 6/35 hormone receptor positive (ER+ or PR+) subjects. Median follow-up time for survival analysis was 64 months (range 11-102 months). Linear models showed no significant association between change in [tCho] and either pCR or RECIST response. An increase in [tCho] between the pretreatment scan and day 1 after treatment was found to be associated with reduced likelihood of both OS and IDFS. We found no association between pCR status and either OS or IDFS when considering all subjects and in the HR+ cohort (see Table 1). No results could be reported for the HR- group (14 subjects) due to an insufficient number of events. CONCLUSION: Compared to our previous study, we did not confirm that changes in [tCho] were associated with RECIST responses. However, increased MRS-measured [tCho] after 1 day of treatment was associated with reduced OS and IDFS independent of pCR. We conclude that increases in [tCho] might be a negative predictor of chemotherapy benefit. [ABSTRACT FROM AUTHOR]

Epidemiologic and genetic studies in many complex diseases suggest subgroup disparities (e.g. by sex, race) in disease course and patient outcomes. We consider this from the standpoint of integrative analysis where we combine information from different views (e.g. genomics, proteomics, clinical data). Existing integrative analysis methods ignore the heterogeneity in subgroups, and stacking the views and accounting for subgroup heterogeneity does not model the association among the views. We propose Heterogeneity in Integration and Prediction (HIP), a statistical approach for joint association and prediction that leverages the strengths in each view to identify molecular signatures that are shared by and specific to a subgroup. We apply HIP to proteomics and gene expression data pertaining to chronic obstructive pulmonary disease (COPD) to identify proteins and genes shared by, and unique to, males and females, contributing to the variation in COPD, measured by airway wall thickness. Our COPD findings have identified proteins, genes, and pathways that are common across and specific to males and females, some implicated in COPD, while others could lead to new insights into sex differences in COPD mechanisms. HIP accounts for subgroup heterogeneity in multi-view data, ranks variables based on importance, is applicable to univariate or multivariate continuous outcomes, and incorporates covariate adjustment. With the efficient algorithms implemented using PyTorch, this method has many potential scientific applications and could enhance multiomics research in health disparities. HIP is available at https://github.com/lasandrall/HIP, a video tutorial at https://youtu.be/O6E2OLmeMDo and a Shiny Application at https://multi-viewlearn.shinyapps.io/HIP&#95;ShinyApp/ for users with limited programming experience., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: Tuberculosis (TB) is the second most deadly infectious disease globally, posing a significant burden in Brazil and its Amazonian region. This study focused on the "riverine municipalities" and hypothesizes the presence of TB clusters in the area. We also aimed to train a machine learning model to differentiate municipalities classified as hot spots vs. non-hot spots using disease surveillance variables as predictors., Methods: Data regarding the incidence of TB from 2019 to 2022 in the riverine town was collected from the Brazilian Health Ministry Informatics Department. Moran's I was used to assess global spatial autocorrelation, while the Getis-Ord GI* method was employed to detect high and low-incidence clusters. A Random Forest machine-learning model was trained using surveillance variables related to TB cases to predict hot spots among non-hot spot municipalities., Results: Our analysis revealed distinct geographical clusters with high and low TB incidence following a west-to-east distribution pattern. The Random Forest Classification model utilizes six surveillance variables to predict hot vs. non-hot spots. The machine learning model achieved an Area Under the Receiver Operator Curve (AUC-ROC) of 0.81., Conclusion: Municipalities with higher percentages of recurrent cases, deaths due to TB, antibiotic regimen changes, percentage of new cases, and cases with smoking history were the best predictors of hot spots. This prediction method can be leveraged to identify the municipalities at the highest risk of being hot spots for the disease, aiding policymakers with an evidenced-based tool to direct resource allocation for disease control in the riverine municipalities.

Rheumatic and congenital heart disease, cardiomyopathies, and hypertensive heart disease are major causes of suffering and death in low- and lower middle-income countries (LLMICs), where the world's poorest billion people reside. Advanced cardiac care in these counties is still predominantly provided by specialists at urban tertiary centers, and is largely inaccessible to the rural poor. This situation is due to critical shortages in diagnostics, medications, and trained healthcare workers. The Package of Essential NCD Interventions - Plus (PEN-Plus) is an integrated care model for severe chronic noncommunicable diseases (NCDs) that aims to decentralize services and increase access. PEN-Plus strategies are being initiated by a growing number of LLMICs. We describe how PEN-Plus addresses the need for advanced cardiac care and discuss how a global group of cardiac organizations are working through the PEN-Plus Cardiac expert group to promote a shared operational strategy for management of severe cardiac disease in high-poverty settings., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: The burden of informal caregiving represents a chronic stressor for the informal caregivers (ICs). The study investigates differences in the physical and mental health of ICs and that of non-informal caregivers before and during COVID-19., Methods: We used data from the 2019/2020 Behavioral Risk Factor Surveillance System (BRFSS) to investigate differences in the rates of days of poor physical and mental health among ICs compared to non-informal caregivers before and after the COVID-19 National Emergency Declaration (NED). A propensity score model simulated a pseudo experimental design, comparing ICs ("treated") with non-informal caregivers ("control"). A difference-in-difference regression model estimated the incidence rate ratios for days of poor physical and mental health as a function of IC status and time of care provision., Results: A total of 44,583 respondents were identified with valid responses on informal caregiving status and key sociodemographic characteristics. Of those, 6.24% (n = 3073) were ICs, matched against 15,365 non-informal caregivers. In the matched sample (n = 18,848), the incidence rate for days of poor physical health among ICs was 17% (p = 0.003) higher compared to non-informal caregivers. The incidence rate for days of poor physical health was 23% (p < 0.001) lower in the post-NED compared to the pre-NED periods. The incidence rate for days of poor mental health was 44% (p < 0.001) higher among ICs compared to non-informal caregivers and 22% higher among respondents who took the survey post-NED compared to those who answered during the pre-NED period. No statistically significant differences were found between the two groups in their incidence rates for days of poor physical and mental health from the pre-to the post-NED period., Conclusion: These findings suggest a need to balance between the benefits conferred by public health restrictions versus the mental health burden that may result among certain groups, including ICs, who experience higher negative mental health outcomes., Competing Interests: The authors declare no conflict of interests., (© 2024 The University of North Carolina at Charlotte. Published by Elsevier Ltd.)

In the past few years, there have been rapid advances in technology and the use of digital tools in health care and clinical research. Although these innovations have immense potential to improve health care delivery and outcomes, there are genuine concerns related to inadvertent widening of the digital gap consequentially exacerbating health disparities. As such, it is important that we critically evaluate the impact of expansive digital transformation in medicine and clinical research on health equity. For digital solutions to truly improve the landscape of health care and clinical trial participation for all persons in an equitable way, targeted interventions to address historic injustices, structural racism, and social and digital determinants of health are essential. The urgent need to focus on interventions to promote health equity was made abundantly clear with the coronavirus disease 2019 pandemic, which magnified long-standing social and racial health disparities. Novel digital technologies present a unique opportunity to embed equity ideals into the ecosystem of health care and clinical research. In this review, we examine racial and ethnic diversity in clinical trials, historic instances of unethical research practices in biomedical research and its impact on clinical trial participation, and the digital divide in health care and clinical research, and we propose suggestions to achieve digital health equity in clinical trials. We also highlight key digital health opportunities in cardiovascular medicine and dermatology as exemplars, and we offer future directions for development and adoption of patient-centric interventions aimed at narrowing the digital divide and mitigating health inequities., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Sudden cardiac arrest is associated with high morbidity and mortality. Despite having a disproportionate burden of sudden cardiac death (SCD), rates of primary and secondary prevention of SCD with implantable cardioverter-defibrillator (ICD) therapy are lower among eligible racially minoritized patients. This review highlights the racial and ethnic disparities in ICD utilization, associated barriers to ICD care, and proposed interventions to improve equitable ICD uptake., Recent Findings: Racially minoritized populations are disproportionately eligible for ICD therapy but are less likely to see cardiac specialists, be counseled on ICD therapy, and ultimately undergo ICD implantation, fueling disparate outcomes. Racial disparities in ICD utilization are multifactorial, with contributions at the patient, provider, health system, and structural/societal level., Summary: Racial and ethnic disparities have been demonstrated in preventing SCD with ICD use. Proposed strategies to mitigate these disparities must prioritize care delivery and access to care for racially minoritized patients, increase the diversification of clinical and implementation trial participants and the healthcare workforce, and center reparative justice frameworks to rectify a long history of racial injustice., Competing Interests: Conflict of Interest Larry R. Jackson II reports consulting fees from Sanofi, Johnson and Johnson, Inc., Pfizer, Bristol-Myers Squibb, and Biosense Webster, Inc. Dr. Jackson also reports payment or honoraria from Zoll Life Vest, CME Outfitters, Prime Education, Health Monitor, and WebMD/Medscape. Lauren Eberly reports speaking fees from Pfizer, and Virtual Advisory Board: Understanding Native American/Alaskan Native Population and Cardiac Amyloidosis (Pfizer). The other authors have nothing to disclose.

Recurrent hypoglycemia leads to impaired awareness of hypoglycemia where the blood glucose threshold that elicits the counterregulatory response is lowered. Hypoglycemia-induced oxidative stress is hypothesized to contribute to impaired awareness of hypoglycemia development and hypoglycemia-associated autonomic failure. Our group conducted a randomized, double-blinded, placebo-controlled, crossover study in healthy individuals undergoing experimentally induced recurrent hypoglycemia to evaluate the impact of intravenous N-acetylcysteine (NAC) during experimental hypoglycemia to preserve the counterregulatory response to subsequent hypoglycemia. The work presented herein aimed to characterize the NAC pharmacokinetics and its effects on oxidative stress. Whole blood and plasma samples were collected at specified time points during separate NAC and placebo infusions from 10 healthy volunteers. Samples were analyzed for NAC, cysteine, and glutathione (GSH) concentrations. A 2-compartment population NAC pharmacokinetic model was developed. Estimates for central compartment clearance and volume of distribution were 19.8 L/h, and 12.2 L, respectively, for a 70-kg person. Peripheral compartment clearance and volume of distribution estimates were 34.9 L/h and 13.1 L, respectively, for a 70-kg person. The PK parameters estimated here were different from those reported in the literature, suggesting a higher NAC clearance during hypoglycemic episodes. NAC leads to a significant increase in circulating cysteine concentration in a NAC concentration-dependent manner, suggesting rapid biotransformation. A transient decrease in plasma GSH was observed, supporting the hypothesis that NAC can act as a reducing agent displacing glutathione from the disulfide bond allowing for increased clearance and/or distribution of GSH., (© 2023 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Objective: To understand how differences in primary care appointment completion rates between Black and non-Black patients changed in 2020 within the context of the COVID-19 pandemic and when telemedicine utilization peaked. Materials and Methods: We conducted a retrospective cohort study using the electronic health record from January 1 to December 31, 2020, among all adults scheduled for a primary care appointment within a large academic medical center. We used mixed-effects logistic regression to estimate adjusted appointment completion rates for Black patients compared with those for non-Black patients in 2020 as compared with those in 2019 within four time periods: (1) prepandemic (January 1, 2020, to March 12, 2020), (2) shutdown (March 13, 2020, to June 3, 2020), (3) reopening (June 4, 2020, to September 30, 2020), and (4) second wave (October 1, 2020, to December 31, 2020). Results: Across 1,947,399 appointments, differences in appointment completion rates between Black and non-Black patients improved in all time periods: +1.4 percentage points prepandemic (95% confidence interval [CI]: +0.8 to +2.0), +11.7 percentage points during shutdown (95% CI: +11.0 to +12.3), +8.2 percentage points during reopening (95% CI: +7.8 to +8.7), and +7.1 percentage points during second wave (95% CI: +6.4 to +7.8) (all p -values <0.001). The types of conditions managed by primary care shifted during the shutdown period, but the remainder of 2020 mirrored those from 2019. Discussion: Racial differences in appointment completion rates narrowed significantly in 2020 even as the mix of disease conditions began to mirror patterns observed in 2019. Conclusions and Relevance: Telemedicine may be an important tool for improving access to primary care for Black patients. These findings should be key considerations as regulators and payors determine telemedicine's future.

Context: Impaired awareness of hypoglycemia (IAH) is characterized by the diminished ability to perceive symptoms of hypoglycemia. Gold and Clark questionnaires are commonly used to identify patients with IAH. The relationship between IAH status on questionnaires and a person's symptom and epinephrine responses to hypoglycemia are not well understood., Objective: We aimed to examine the relationship between hypoglycemia awareness status on Clarke and Gold questionnaires with both hormonal and symptomatic responses to experimental hypoglycemia., Methods: In this university medical center study, we examined data from 78 subjects with type 1 diabetes (T1D) who completed both questionnaires and underwent a hyperinsulinemic hypoglycemic clamp (target glucose 50 mg/dL)., Results: Clarke and Gold scores were highly correlated with one another (r = 0.82) and each had a moderate negative relationship with epinephrine (Clarke: r = -0.51, Gold: r = -0.50) and total symptom response (Clarke: r = -0.59, Gold: r = -0.57). However, 32% of the subjects were classified inconsistently by Clark vs Gold. A clustering analysis was done to examine how disagreement between the 2 questionnaires on IAH classification relates to epinephrine and symptoms responses during hypoglycemia. Subjects who had partial loss of symptoms or of epinephrine response were more likely to be classified inconsistently., Conclusion: Our results show that IAH classification may be discordant between Clark and Gold questionnaires and that hypoglycemia awareness status on Clarke and Gold questionnaires poorly predicts hormonal and symptomatic responses to hypoglycemia in subjects with T1D and moderate blunting of symptoms or epinephrine., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: The epinephrine response (Epi) to a first episode of hypoglycemia (HG) has been proposed to be predictive of Epi in subsequent HG and to provide insight into the risk for developing HG-associated autonomic failure (HAAF) in healthy controls (HCs)., Objective: To determine if Epi and symptom response (SR) to the first episode of HG predicts who will develop HAAF after exposure to recurrent HG in volunteers with type 1 diabetes (T1D) and in HCs., Design: Review of data collected between 2013 and 2019., Setting: Academic clinical research unit., Patients or Participants: Volunteers with T1D and HCs., Interventions: Subjects participated in a preinduction protocol where they were exposed to three 2-hour episodes of clamped HG over 2 days. Data collected during clamp 1 were compared with data collected during clamp 3., Main Outcome Measure: Difference in Epi and SR., Results: Using the standard definition of HAAF in which HG-induced Epi during clamp 3 is at least 20% lower than during clamp 1, 21/28 HCs and 13/19 volunteers with T1D developed HAAF. Epi during clamp 1 was significantly higher in those subjects who developed HAAF than in those who did not in both groups ( P  = 0.02). If HAAF is defined as achieving a 20% reduction in HG-induced SR measured during clamp 3 compared with clamp 1, 10/27 HCs and 10/19 volunteers with T1D developed SR-based HAAF., Conclusion: There was heterogeneity in the response to the preinduction protocol. Epi during clamp 1 was higher than in clamp 3 in HCs and in those with T1D who developed HAAF., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose of Review: The purpose of this review is to summarize what is known about the relationship between exercise and arrhythmogenic right ventricular cardiomyopathy (ARVC) with regard to disease onset, diagnosis, progression, and clinical severity. This relationship forms the basis of the management recommendations for restricting physical activity in individuals with and at risk for ARVC., Recent Findings: While ARVC can be challenging to diagnose, there are several diagnostic testing and imaging modalities that may help distinguish athletic heart remodeling from ARVC. There is an increased risk of adverse clinical outcomes in ARVC from endurance and competitive sports participation, including a dose-dependent relationship between exercise intensity and risk of disease penetrance and progression., Summary: High-intensity exercise can lead to earlier disease onset, increased penetrance, and clinical progression among individuals with and at risk for ARVC. Both amount and intensity of exercise are correlated with adverse outcomes, including ventricular arrhythmias and worsening biventricular function. All individuals with and at risk for ARVC should undergo detailed clinical phenotyping and risk stratification to reduce the risk of such outcomes, including sudden cardiac death. Consensus guidelines recommend against participation in competitive or high-intensity and endurance exercise for individuals with and at risk for ARVC., Competing Interests: Conflict of Interest Lauren Eberly declares that she has no conflict of interest. Lohit Garg declares that he has no conflict of interest. Mahesh Vidula declares that he has no conflict of interest. Nosheen Reza declares that she has no conflict of interest. Sheela Krishnan declares that she has no conflict of interest.

This project investigated whether structural changes are present in the subthalamic nucleus (STN) of people with mild-to-moderate severity of Parkinson's disease (PD). Within-subject measures of STN volume and fractional anisotropy (FA) were derived from high-resolution 7Tesla magnetic resonance imaging (MRI) for 29 subjects with mild-to-moderate PD (median disease duration = 2.3±1.9 years) and 18 healthy matched controls. Manual segmentation of the STN was performed on 0.4 mm in-plane resolution images. FA maps were generated and FA values were averaged over the left and right STN separately for each subject. Motor sign severity was assessed using the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Linear effects models showed that STN volume was significantly smaller in the PD subjects compared to controls (p = 0.01). Further, after controlling for differences in STN volumes within or between groups, the PD group had lower FA values in the STN compared to controls (corrected p ≤ 0.008). These findings demonstrate that morphological changes occur in the STN, which likely impact the function of the hyperdirect and indirect pathways of the basal ganglia and movement control.

Aim: Administration of N-acetyl cysteine (NAC) during hypoglycaemia will preserve the counterregulatory response to subsequent hypoglycaemia in healthy humans., Methods: This was a randomized double-blind cross over study where humans were given either a 60-minute infusion of NAC (150 mg/kg) followed by a 4-hour infusion of NAC (50 mg/kg) or saline starting 30 minutes before the initiation of a 2-hour hypoglycaemic (HG) clamp at 8 am. After rest at euglycaemia for ~2 hours, subjects were exposed to a 2nd HG clamp at 2 pm and discharged home in euglycaemia. They returned the following day for a 3rd HG clamp at 8 am., Results: Twenty-two subjects were enrolled. Eighteen subjects completed the entire protocol. The epinephrine response during clamp 3 (171 ± 247 pg/mL) following clamp 1 NAC infusion was lower than the response during the clamp 1 NAC infusion (538 ± 392 pg/mL) (clamp 3 to clamp 1 NAC: P  = .0013). The symptom response during clamp 3 (7 ± 5) following clamp 1 NAC infusion was lower than the response during the clamp 1 NAC infusion (16 ± 10) (clamp 3 to clamp 1 NAC: P  = .0003). Nine subjects experienced rash, pruritus or nausea during NAC infusion., Conclusion: We found no difference in the hormone and symptom response to experimental hypoglycaemia measured in subjects who were administered NAC as opposed to saline the day before. This observation suggests that further development of NAC as a therapy for impaired awareness of hypoglycaemia in patients with diabetes may be unwarranted., Competing Interests: ERS has served as a consultant to Lilly, Sanofi, MannKind and Zucara., (© 2020 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Purpose of Review: To describe the role of big data in cardio-oncology., Recent Findings: There is a trend towards developing cloud-based, integrated registries to improve data collection, access, and analysis. Using a template from pediatric oncology, a cardio-oncology data commons is a novel opportunity to integrate data elements into a cloud-based platform. A cloud-based registry provides advantages of multi-institutional collaboration, rapid data access, a virtual visualization, and analytic tools to reduce infrastructure redundancy. The data commons would include integrated clinical data, blood samples, and genomic data to streamline discovery and analysis for researchers. A cardio-oncology data commons would be a large step forward in bringing cardio-oncology to the forefront of big data.

Background: Cholera has caused 7 global pandemics, including the current one which has been ongoing since 1961. A systematic review of risk factors for symptomatic cholera infection has not been previously published., Methods: In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we performed a systematic review and meta-analysis of individual and household risk factors for symptomatic cholera infection., Results: We identified 110 studies eligible for inclusion in qualitative synthesis. Factors associated with symptomatic cholera that were eligible for meta-analysis included education less than secondary level (summary odds ratio [SOR], 2.64; 95% confidence interval [CI], 1.41-4.92; I2 = 8%), unimproved water source (SOR, 3.48; 95% CI, 2.18-5.54; I2 = 77%), open container water storage (SOR, 2.03; 95% CI, 1.09-3.76; I2 = 62%), consumption of food outside the home (SOR, 2.76; 95% CI, 1.62-4.69; I2 = 64%), household contact with cholera (SOR, 2.91; 95% CI, 1.62-5.25; I2 = 89%), water treatment (SOR, 0.37; 95% CI, .21-.63; I2 = 74%), and handwashing (SOR, 0.29; 95% CI, .20-.43; I2 = 37%). Other notable associations with symptomatic infection included income/wealth, blood group, gastric acidity, infant breastfeeding status, and human immunodeficiency virus infection., Conclusions: We identified potential risk factors for symptomatic cholera infection including environmental characteristics, socioeconomic factors, and intrinsic patient factors. Ultimately, a combination of interventional approaches targeting various groups with risk-adapted intensities may prove to be the optimal strategy for cholera control.

Background: Pain levels in patients with osteoarthritis (OA) of the knee are commonly assessed by using a numeric scoring system, but results may be influenced by factors other than the patient's actual physical discomfort or disease severity, including psychosocial and demographic variables. We examined the possible relation between knee-pain scores and several psychosocial, sociodemographic, disease, and treatment variables in 355 patients with knee OA., Methods: The pain-evaluation instrument was a 0- to 10-point rating scale. Data obtained retrospectively from the patients' medical records were demographic characteristics, body mass index (BMI), concomitant disorders, illicit and prescription drug use, alcohol use, smoking, knee OA treatment, and severity of knee OA indicated by Kellgren-Lawrence (KL) radiographic grade. Univariate and multivariate analyses were performed to determine whether these variables correlated with reported pain scores., Results: On univariate analysis, higher pain scores were significantly associated with Native American or Hispanic ethnicity; a higher BMI; current prescription for an opioid, antidepressant, or gabapentinoid medication; depression; diabetes mellitus; fibromyalgia; illicit drug use; lack of health insurance; smoking; previous knee injection; and recommendation by the clinician that the patient undergo knee surgery. Neither the patient's sex nor the KL grade showed a correlation. On multivariate analysis, depression, current opioid prescription, and Native American or Hispanic ethnicity retained a significant association with higher pain scores., Conclusions and Implications: Our results in a large, ethnically diverse group of patients with knee OA suggest that psychosocial and sociodemographic factors may be important determinants of pain levels reported by patients with knee OA.

A computational approach for estimating several indices of performance on the animal category verbal fluency task was validated, and examined in a large longitudinal study of aging. The performance indices included the traditional verbal fluency score, size of semantic clusters, density of repeated words, as well as measures of semantic and lexical diversity. Change over time in these measures was modeled using mixed effects regression in several groups of participants, including those that remained cognitively normal throughout the study (CN) and those that were diagnosed with mild cognitive impairment (MCI) or Alzheimer's disease (AD) dementia at some point subsequent to the baseline visit. The results of the study show that, with the exception of mean cluster size, the indices showed significantly greater declines in the MCI and AD dementia groups as compared to CN participants. Examination of associations between the indices and cognitive domains of memory, attention and visuospatial functioning showed that the traditional verbal fluency scores were associated with declines in all three domains, whereas semantic and lexical diversity measures were associated with declines only in the visuospatial domain. Baseline repetition density was associated with declines in memory and visuospatial domains. Examination of lexical and semantic diversity measures in subgroups with high vs. low attention scores (but normal functioning in other domains) showed that the performance of individuals with low attention was influenced more by word frequency rather than strength of semantic relatedness between words. These findings suggest that various automatically semantic indices may be used to examine various aspects of cognitive performance affected by dementia., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Little is known about the prevalence of pressure ulcers (PUs) among racial and ethnic groups of older individuals admitted to nursing homes (NHs). NHs admitting higher percentages of minority individuals may face resource challenges for groups with more PUs or ones of greater severity. This study examined the prevalence of PUs (Stages 2 to 4) among older adults admitted to NHs by race and ethnicity at the individual, NH, and regional levels. Results show that the prevalence of PUs in Black older adults admitted to NHs was greater than that in Hispanic older adults, which were both greater than in White older adults. The PU rate among admissions of Black individuals was 1.7 times higher than White individuals. A higher prevalence of PUs was observed among NHs with a lower percentage of admissions of White individuals. [Journal of Gerontological Nursing, 40(3), 20-26.]., (Copyright 2014, SLACK Incorporated.)

Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for Parkinson disease. However, DBS is not responsive to an individual's disease state, and programming parameters, once established, do not change to reflect disease state. Local field potentials (LFPs) recorded from DBS electrodes are being investigated as potential biomarkers for the Parkinson disease state. However, no patient data exist about what happens to LFPs over the lifetime of the implant., Objective: We investigated whether LFP amplitude and response to limb movement differed between patients implanted acutely with subthalamic nucleus DBS electrodes and patients implanted 2 to 7 years previously., Methods: We recorded LFPs at DBS surgery time (9 subjects), 3 weeks after initial placement (9 subjects), and 2 to 7 years (median: 3.5) later during implanted programmable generator replacement (11 sides). LFP power-frequency spectra for each of 3 bipolar electrode derivations of adjacent contacts were calculated over 5-minute resting and 30-second movement epochs. Monopolar impedance data were used to evaluate trends over time., Results: There was no significant difference in β-band LFP amplitude between initial electrode implantation (OR) and 3-week post-OR times (P=.94). However, β-band amplitude was lower at implanted programmable generator replacement times than in OR (P=.008) and post-OR recordings (P=.039). Impedance measurements declined over time (P<.001)., Conclusion: Postoperative LFP activity can be recorded years after DBS implantation and demonstrates a similar profile in response to movement as during acute recordings, although amplitude may decrease. These results support the feasibility of constructing a closed-loop, patient-responsive DBS device based on LFP activity.

Background: The Multiple Risk Factor Intervention Trial evaluated a multifactor intervention on coronary heart disease (CHD) in 12 866 men. A priori defined endpoints (CHD death, CHD death or nonfatal myocardial infarction, cardiovascular disease [CVD] death, and all-cause death) did not differ significantly between the special intervention (SI) and usual care (UC) groups over an average follow-up period of 7 years. Event rates were lower than anticipated, reducing power. Other nonfatal CVD outcomes were prespecified but not considered in composite outcomes comparing SI with UC., Methods and Results: Post-trial CVD mortality risks associated with nonfatal CVD events occurring during the trial were determined with Cox regression. Nonfatal outcomes associated with >2-fold risk of CVD death over the subsequent 20 years were combined with during-trial deaths to create 2 new composite outcomes. SI/UC hazard ratios and 95% confidence intervals were estimated for each composite outcome. Of 10 during-trial nonfatal events, 6 were associated (P<0.001) with >2-fold risk of CVD death. A CHD composite outcome (CHD death, myocardial infarction [clinical or serial ECG change], CHF, or coronary artery surgery) was experienced by 520 SI and 602 UC men (SI/UC hazard ratio = 0.86; 95% confidence interval, 0.76-0.97; P=0.01). A CVD composite outcome (CHD [as above], other CVD deaths, stroke, or renal impairment) was experienced by 581 SI and 652 UC men (hazard ratio = 0.89; 95% confidence interval, 0.79-0.99; P=0.04)., Conclusions: In post hoc analyses, composite fatal/nonfatal CHD and CVD rates over 7 years were significantly lower for SI than for UC. These findings reinforce recommendations for improved dietary/lifestyle practices, with pharmacological therapy as needed, to prevent and control major CVD risk factors.

This is the first study of the effect of topiramate on linguistic behavior and verbal recall using a computational linguistics system for automated language and speech analysis to detect and quantify drug-induced changes in speech recorded during discourse-level tasks. Healthy volunteers were administered a single, 100-mg oral dose of topiramate in two double-blind, randomized, placebo-controlled, crossover studies. Subjects' topiramate plasma levels ranged from 0.23 to 2.81 μg/mL. We found a significant association between topiramate levels and impairment on measures of verbal fluency elicited during a picture description task, correct number of words recalled on a paragraph recall test, and reaction time recorded during a working memory task. Using the tools of clinical pharmacology and computational linguistics, we elucidated the relationship between the determinants of a drug's disposition as reflected in plasma concentrations and their impact on cognitive functioning as reflected in spoken language discourse., (Copyright © 2012 Elsevier Inc. All rights reserved.)