Showing papers by "Ralph B. D'Agostino published in 2015"

Association of Cardiometabolic Multimorbidity With Mortality

Abstract: IMPORTANCE: The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE: To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES: A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES: All-cause mortality and estimated reductions in life expectancy. RESULTS: In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE: Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis.

Abstract: BACKGROUND Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new lipid-lowering approach. PURPOSE To assess the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia. DATA SOURCES MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015. STUDY SELECTION Phase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia. DATA EXTRACTION Two investigators independently extracted data on study characteristics and lipid and clinical outcomes, and rated risk of bias of trials. Prespecified primary end points were all-cause and cardiovascular mortality. DATA SYNTHESIS Twenty-four RCTs comprising 10 159 patients were included. Compared with no antibody, treatment with PCSK9 antibodies led to marked reductions in low-density lipoprotein cholesterol levels (mean difference, -47.49% [95% CI, -69.64% to -25.35%]; P < 0.001] and other atherogenic lipid fractions, and it reduced all-cause mortality (odds ratio [OR], 0.45 [CI, 0.23 to 0.86]; P = 0.015; heterogeneity P = 0.63; I2 = 0%) and cardiovascular mortality (OR, 0.50 [CI, 0.23 to 1.10]; P = 0.084; heterogeneity P = 0.78; I2 = 0%). The rate of myocardial infarction was significantly reduced with use of PCSK9 antibodies (OR, 0.49 [CI, 0.26 to 0.93]; P = 0.030; heterogeneity P = 0.45; I2 = 0%), and increases in the serum creatine kinase level were reduced (OR, 0.72 [CI, 0.54 to 0.96]; P = 0.026; heterogeneity P = 0.65; I2 = 0%). Serious adverse events did not increase with administration of PCSK9 antibodies. LIMITATION Results were derived from study-level data rather than patient-level data, and clinical outcome data are rare. CONCLUSION PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia. PRIMARY FUNDING SOURCE CRC 1116 Masterswitches in Myocardial Ischemia, German Research Council DFG.

Hyperlipidemia in Early Adulthood Increases Long-Term Risk of Coronary Heart Disease

Abstract: Background—Many young adults with moderate hyperlipidemia do not meet statin treatment criteria under the new American Heart Association/American College of Cardiology cholesterol guidelines because they focus on 10-year cardiovascular risk. We evaluated the association between years of exposure to hypercholesterolemia in early adulthood and future coronary heart disease (CHD) risk. Methods and Results—We examined Framingham Offspring Cohort data to identify adults without incident cardiovascular disease to 55 years of age (n=1478), and explored the association between duration of moderate hyperlipidemia (non–high-density lipoprotein cholesterol≥160 mg/dL) in early adulthood and subsequent CHD. At median 15-year follow-up, CHD rates were significantly elevated among adults with prolonged hyperlipidemia exposure by 55 years of age: 4.4% for those with no exposure, 8.1% for those with 1 to 10 years of exposure, and 16.5% for those with 11 to 20 years of exposure (P<0.001); this association persisted after a...

Evaluating Discrimination of Risk Prediction Models: The C Statistic

Abstract: Risk prediction models help clinicians develop personalized treatments for patients. The models generally use variables measured at one time point to estimate the probability of an outcome occurring within a given time in the future. It is essential to assess the performance of a risk prediction model in the setting in which it will be used. This is done by evaluating the model’s discrimination and calibration. Discrimination refers to the ability of the model to separate individuals who develop events from those who do not. In time-toevent settings, discrimination is the ability of the model to predict who will develop an event earlier and who will develop an event later or not at all. Calibration measures how accurately the model’s predictions match overall observed event rates. In this issueof JAMA,Melgaardet al used theCstatistic, a global measure of model discrimination, to assess the ability of the CHA2DS2-VASc model to predict ischemic stroke, thromboembolism, or death in patients with heart failure and to do so separately for patients who had or did not have atrial fibrillation (AF).1

Autonomic Imbalance as a Predictor of Metabolic Risks, Cardiovascular Disease, Diabetes, and Mortality

Abstract: Context: Identifying novel early predictors of metabolic disorders is essential to improving effective primary prevention. Objectives: The objectives were to examine the contribution of two measures of autonomic imbalance, resting heart rate (RHR) and heart rate variability (HRV), on the development of five metabolic risk outcomes, and on cardiovascular disease, diabetes, and early mortality. Design: This study was a secondary analysis of prospective data from Offspring Cohort participants (N = 1882) in the Framingham Heart Study (FHS). Participants: Participants at FHS Exam 3 (1983–1987) with 1) age years 18 or older, and 2) data on RHR, HRV, and five measures of metabolic risk (blood pressure, fasting glucose, triglycerides, high-density lipoprotein [HDL] cholesterol, and body mass index [BMI]) at three follow-up visits over 12 years. We conducted a backward elimination variable selection procedure on a logistic regression model, using baseline RHR, HRV, age, sex, and smoking status to predict the odds ...

Guideline-Based Statin Eligibility, Coronary Artery Calcification, and Cardiovascular Events

Abstract: Importance The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for cholesterol management defined new eligibility criteria for statin therapy. However, it is unclear whether this approach improves identification of adults at higher risk of cardiovascular events. Objective To determine whether the ACC/AHA guidelines improve identification of individuals who develop incident cardiovascular disease (CVD) and/or have coronary artery calcification (CAC) compared with the National Cholesterol Education Program’s 2004 Updated Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) guidelines. Design, Setting, and Participants Longitudinal community-based cohort study, with participants for this investigation drawn from the offspring and third-generation cohorts of the Framingham Heart Study. Participants underwent multidetector computed tomography for CAC between 2002 and 2005 and were followed up for a median of 9.4 years for incident CVD. Exposures Statin eligibility was determined based on Framingham risk factors and low-density lipoprotein thresholds for ATP III, whereas the pooled cohort calculator was used for ACC/AHA. Main Outcomes and Measures The primary outcome was incident CVD (myocardial infarction, death due to coronary heart disease [CHD], or ischemic stroke). Secondary outcomes were CHD and CAC (as measured by the Agatston score). Results Among 2435 statin-naive participants (mean age, 51.3 [SD, 8.6] years; 56% female), 39% (941/2435) were statin eligible by ACC/AHA compared with 14% (348/2435) by ATP III ( P P 0 (n = 1015): 63% vs 23%; CAC score >100 (n = 376): 80% vs 32%; and CAC score >300 (n = 186): 85% vs 34% (all P Conclusions and Relevance In this community-based primary prevention cohort, the ACC/AHA guidelines for determining statin eligibility, compared with the ATP III, were associated with greater accuracy and efficiency in identifying increased risk of incident CVD and subclinical coronary artery disease, particularly in intermediate-risk participants.

Apolipoprotein B improves risk assessment of future coronary heart disease in the Framingham Heart Study beyond LDL-C and non-HDL-C

Abstract: AimsAnalyses using conventional statistical methodologies have yielded conflicting results as to whether low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) is the best marker of the apoB-associated risk of coronary heart disease. The aim of this study was to determine the additional value of apoB beyond LDL-C or non-HDL-C as a predictor of coronary heart disease.Methods and resultsFor each patient from the Framingham Offspring Cohort aged 40–75 years (n = 2966), we calculated the extent to which the observed apoB differed from the expected apoB based on their LDL-C or non-HDL-C. We added this difference to a Cox model predicting new onset coronary heart disease over a maximum of 20 years adjusting for standard risk factors plus LDL-C or non-HDL. The difference between observed and expected apoB over LDL-C or non-HDL-C was highly prognostic of future coronary heart disease events: adjusted hazard ratios 1.26 (95% confidence interva...

The Role of Physicians in the Era of Predictive Analytics

Abstract: Every day, more information becomes available about factors that affect the risk of a clinical event. Predictive analytics incorporate this information into prognostic models that estimate the likelihood of this event for an individual patient. The Framingham Heart Study pioneered this approach1 and such estimates have become core elements of clinical care and guideline recommendations, such as the recent ACC/AHA guidelines for managing blood cholesterol for primary prevention of cardiovascular disease risk.2 Advances in predictive analytics and precision medicine have and will continue to change the practice of medicine. However, to apply these risk estimates wisely, a physician must understand that the concept of risk is more subtle and complex than is generally appreciated. Specifically, it is important to distinguish between 2 meanings of risk: risk in the epidemiological sense (the risk of a group of individuals) vs risk in the clinical sense (the risk for individual members of the group). But how accurately does the overall risk for the group reflect the risk of each of the individuals who make up the group? This distinction is critical to appreciate because it underlies the essential role that physicians need to play in the era of predictive analytics. In this Viewpoint, cardiovascular risk will be used as an example, but the same concepts can be applied to risk prediction in any context.

Arterial stiffness in adolescents and young adults with and without type 1 diabetes: the SEARCH CVD study.

Abstract: Background Arterial stiffness is a useful parameter to predict future cardiovascular disease

Causes of late mortality with dual antiplatelet therapy after coronary stents

Abstract: Aims In the dual antiplatelet therapy (DAPT) study, continued thienopyridine beyond 12 months after drug-eluting stent placement was associated with increased mortality compared with placebo. We sought to evaluate factors related to mortality in randomized patients receiving either drug-eluting or bare metal stents in the DAPT study. Methods and results Patients were enrolled after coronary stenting, given thienopyridine and aspirin for 12 months, randomly assigned to continued thienopyridine or placebo for an additional 18 months (while taking aspirin), and subsequently treated with aspirin alone for another 3 months. A blinded independent adjudication committee evaluated deaths. Among 11 648 randomized patients, rates of all-cause mortality rates were 1.9 vs. 1.5% (continued thienopyridine vs. placebo, P = 0.07), cardiovascular mortality, 1.0 vs. 1.0% ( P = 0.97), and non-cardiovascular mortality, 0.9 vs. 0.5% ( P = 0.01) over the randomized period (Months 12–30). Rates of fatal bleeding were 0.2 vs. 0.1% ( P = 0.81), and deaths related to any prior bleeding were 0.3 vs. 0.2% ( P = 0.36), Months 12–33). Cancer incidence did not differ (2.0 vs. 1.6%, P = 0.12). Cancer-related deaths occurred in 0.6 vs. 0.3% ( P = 0.02) and were rarely related to bleeding (0.1 vs. 0, P = 0.25). After excluding those occurring in patients with cancer diagnosed before enrolment, rates were 0.4 vs. 0.3% ( P = 0.16). Conclusion Bleeding accounted for a minority of deaths among patients treated with continued thienopyridine. Cancer-related death in association with thienopyridine therapy was mainly not related to bleeding and may be a chance finding. Caution is warranted when considering extended thienopyridine in patients with advanced cancer. Trial Registration clinicaltrials.gov Identifier: [NCT00977938][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00977938&atom=%2Fehj%2F37%2F4%2F378.atom

An analysis of the blood pressure and safety outcomes to renal denervation in African Americans and Non-African Americans in the SYMPLICITY HTN-3 trial.

Abstract: SYMPLICITY HTN-3, the first trial of renal denervation (RDN) versus sham, enrolled 26% African Americans, a prospectively stratified cohort. Although the 6-month systolic blood pressure (SBP) reduction in African Americans (AAs) was similar in the RDN group (-15.5 ± 25.4 mm Hg, n = 85 vs. -17.8 ± 29.2, n = 49, P = .641), the sham SBP response was 9.2 mm Hg greater (P = .057) in AAs than non-AAs. In multivariate analyses, sham SBP response was predicted by an interaction between AA and a complex antihypertensive regimen (at least one antihypertensive medication prescribed ≥3 times daily), while in the RDN group, SBP response was predicted by an interaction between AA race and baseline BP ≥ 180 mm Hg. AA race did not independently predict SBP response in either sham or RDN. There appears to be effect modification by race with individual-level patient characteristics in both treatment arms that affect the observed pattern of SBP responses.

Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates

Abstract: Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response following vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for this vulnerable population. To address this issue, we established a neonatal African green monkey (AGM) nonhuman primate model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a Toll-like receptor 5 (TLR5) agonist, to serve as an effective adjuvant in this at-risk population. Four- to 6-day-old AGMs were primed and boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild-type flagellin or inactive flagellin with a mutation at position 229 (m229), the latter of which is incapable of signaling through TLR5. Increased IgG responses were observed following a boost, as well as at early times after challenge, in infants vaccinated with flagellin-adjuvanted IPR8. Inclusion of flagellin during vaccination also resulted in a significantly increased number of influenza virus-specific T cells following challenge compared to the number in infants vaccinated with the m229 adjuvant. Finally, following challenge infants vaccinated with IPR8 plus flagellin exhibited a reduced pathology in the lungs compared to that in infants that received IPR8 plus m229. This study provides the first evidence of flagellin-mediated enhancement of vaccine responses in nonhuman primate neonates. IMPORTANCE Young infants are particularly susceptible to severe disease as a result of influenza virus infection. Compounding this is the lack of effective vaccines for use in this vulnerable population. Here we describe a vaccine approach that results in improved immune responses and protection in young infants. Incorporation of flagellin during vaccination resulted in increased antibody and T cell responses together with reduced disease following virus infection. These results suggest that flagellin may serve as an effective adjuvant for vaccines targeted to this vulnerable population.

Duration and Degree of Weight Gain and Incident Diabetes in Younger Versus Middle-Aged Black and White Adults: ARIC, CARDIA, and the Framingham Heart Study.

Abstract: OBJECTIVE To determine whether duration and degree of weight gain are differentially associated with diabetes risk in younger versus middle-aged black and white adults. RESEARCH DESIGN AND METHODS We combined data from three cohort studies: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and the Framingham Heart Study. A total of 17,404 participants (56% women; 21% black) were stratified by baseline age (younger: ≥30 and RESULTS Diabetes incidence per 1,000 person-years in the younger and middle-aged groups was 7.2 (95% CI 5.7, 8.7) and 24.4 (22.0, 26.8) in blacks, respectively, and 3.4 (2.8, 4.0) and 10.5 (9.9, 11.2) in whites, respectively. After adjusting for sex, baseline BMI and other cardiometabolic factors, and age and race interaction terms, gains in BMI-years were associated with higher risk of diabetes in the younger compared with middle-aged groups: hazard ratios for 1-unit increase in log BMI-years in younger versus middle-aged blacks were 1.18 ( P = 0.02) and 1.02 ( P = 0.39), respectively ( P for interaction by age-group = 0.047), and in whites were 1.35 ( P P P for interaction by age-group = 0.008). CONCLUSIONS Although middle-aged adults have higher rates of diabetes, younger adults are at greater relative risk of developing diabetes for a given level of duration and degree of weight gain.

Insulin sensitivity and arterial stiffness in youth with type 1 diabetes: the SEARCH CVD study.

Abstract: Aims Decreased insulin sensitivity is a cardiovascular risk factor (CVRF) in youth with type 1 diabetes (T1D). Whether baseline insulin sensitivity is independently associated with changes in early arterial stiffness (pulse wave velocity (PWV)) over time in youth with T1D is not known. Methods Two hundred ninety-eight youth with T1D in the SEARCH CVD study had PWV measured~five years apart. Insulin sensitivity and other CVRFs were measured at baseline. The association between baseline insulin sensitivity with PWV over time was explored using linear mixed models. Models were adjusted for baseline age, sex and race, with subsequent adjustment for CVRFs. Results There was a significant interaction (p=0.0326) between baseline insulin sensitivity and time on PWV, independent of CVRFs, indicating that higher insulin sensitivity levels were associated with lower rate of change in PWV over time. Other significant predictors of PWV change were baseline age [β=0.007 (p=0.03) increase in logPWV/year increase in age] and mean arterial blood pressure (MAP) [β=0.005 (p Conclusions Lower insulin sensitivity at baseline appears to be an important risk factor for increased arterial stiffness over time in youth with T1D. This identifies a potentially modifiable therapeutic target.

Interferon Beta and Interferon Alpha 2a Differentially Protect Head and Neck Cancer Cells from Vesicular Stomatitis Virus-Induced Oncolysis

Abstract: Oncolytic viruses (OV) preferentially kill cancer cells due in part to defects in their antiviral responses upon exposure to type I interferons (IFNs). However, IFN responsiveness of some tumor cells confers resistance to OV treatment. The human type I IFNs include one IFN-β and multiple IFN-α subtypes that share the same receptor but are capable of differentially inducing biological responses. The role of individual IFN subtypes in promoting tumor cell resistance to OV is addressed here. Two human IFNs which have been produced for clinical use, IFN-α2a and IFN-β, were compared for activity in protecting human head and neck squamous cell carcinoma (HNSCC) lines from oncolysis by vesicular stomatitis virus (VSV). Susceptibility of HNSCC lines to killing by VSV varied. VSV infection induced increased production of IFN-β in resistant HNSCC cells. When added exogenously, IFN-β was significantly more effective at protecting HNSCC cells from VSV oncolysis than was IFN-α2a. In contrast, normal keratinocytes and endothelial cells were protected equivalently by both IFN subtypes. Differential responsiveness of tumor cells to IFN-α and -β was further supported by the finding that autocrine IFN-β but not IFN-α promoted survival of HNSCC cells during persistent VSV infection. Therefore, IFN-α and -β differentially affect VSV oncolysis, justifying the evaluation and comparison of IFN subtypes for use in combination with VSV therapy. Pairing VSV with IFN-α2a may enhance selectivity of oncolytic VSV therapy for HNSCC by inhibiting VSV replication in normal cells without a corresponding inhibition in cancer cells. IMPORTANCE There has been a great deal of progress in the development of oncolytic viruses. However, a major problem is that individual cancers vary in their sensitivity to oncolytic viruses. In many cases this is due to differences in their production and response to interferons (IFNs). The experiments described here compared the responses of head and neck squamous cell carcinoma cell lines to two IFN subtypes, IFN-α2a and IFN-β, in protection from oncolytic vesicular stomatitis virus. We found that IFN-α2a was significantly less protective for cancer cells than was IFN-β, whereas normal cells were equivalently protected by both IFNs. These results suggest that from a therapeutic standpoint, selectivity for cancer versus normal cells may be enhanced by pairing VSV with IFN-α2a.

High plasma folate is negatively associated with leukocyte telomere length in Framingham Offspring cohort

Abstract: Purpose Shortening of telomeres, the protective structures at the ends of eukaryotic chromosomes, is associated with age-related pathologies. Telomere length is influenced by DNA integrity and DNA and histone methylation. Folate plays a role in providing precursors for nucleotides and methyl groups for methylation reactions and has the potential to influence telomere length.

Graphical assessment of incremental value of novel markers in prediction models : From statistical to decision analytical perspectives

Abstract: New markers may improve prediction of diagnostic and prognostic outcomes. We aimed to review options for graphical display and summary measures to assess the predictive value of markers over standard, readily available predictors. We illustrated various approaches using previously published data on 3264 participants from the Framingham Heart Study, where 183 developed coronary heart disease (10-year risk 5.6%). We considered performance measures for the incremental value of adding HDL cholesterol to a prediction model. An initial assessment may consider statistical significance (HR = 0.65, 95% confidence interval 0.53 to 0.80; likelihood ratio p < 0.001), and distributions of predicted risks (densities or box plots) with various summary measures. A range of decision thresholds is considered in predictiveness and receiver operating characteristic curves, where the area under the curve (AUC) increased from 0.762 to 0.774 by adding HDL. We can furthermore focus on reclassification of participants with and without an event in a reclassification graph, with the continuous net reclassification improvement (NRI) as a summary measure. When we focus on one particular decision threshold, the changes in sensitivity and specificity are central. We propose a net reclassification risk graph, which allows us to focus on the number of reclassified persons and their event rates. Summary measures include the binary AUC, the two-category NRI, and decision analytic variants such as the net benefit (NB). Various graphs and summary measures can be used to assess the incremental predictive value of a marker. Important insights for impact on decision making are provided by a simple graph for the net reclassification risk.

Longitudinal association between television watching and computer use and risk markers in diabetes in the SEARCH for Diabetes in Youth Study

Abstract: Background The study provides evidence of the longitudinal association between screen time with hemoglobin A1c (HbA1c) and cardiovascular risk markers among youth with type 1 diabetes (T1D) and type 2 diabetes (T2D). Objective To examine the longitudinal relationship of screen time with HbA1c and serum lipids among youth with diabetes. Subjects Youth with T1D and T2D. Methods We followed up 1049 youth (≥10 yr old) with recently diagnosed T1D and T2D participating in the SEARCH for Diabetes in Youth Study. Results Increased television watching on weekdays and during the week over time was associated with larger increases in HbA1c among youth with T1D and T2D (p-value <0.05). Among youth with T1D, significant longitudinal associations were observed between television watching and TG (p-value <0.05) (week days and whole week), and low-density lipoprotein cholesterol (LDL-c, p-value <0.05) (whole week). For example, for youth who watched 1 h of television per weekday at the outset and 3 h per weekday 5 yr later, the longitudinal model predicted greater absolute increases in HbA1c (2.19% for T1D and 2.16% for T2D); whereas for youth who watched television 3 h per weekday at the outset and 1 h per weekday 5 yr later, the model predicted lesser absolute increases in HbA1c (2.08% for T1D and 1.06% for T2D). Conclusions Youth with T2D who increased their television watching over time vs. those who decreased it had larger increases in HbA1c over 5 yr. Youth with T1D who increased their television watching over time had increases in LDL-c, TG, and to a lesser extent HbA1c.

Assessing endothelial dysfunction in adolescents and young adults with type 1 diabetes mellitus using a non-invasive heat stimulus.

Abstract: Background Microvascular dysfunction is a key event in the development of atherosclerosis, which predates the clinical manifestations of vascular disease including stroke and myocardial infarction. Dysfunction of the microvasculature can be measured as a decreased microperfusion in response to heat.

Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma

Abstract: Inflammatory cytokines in the colonic microenvironment have been shown to increase with advance colorectal cancer disease state. However, the contribution of inflammatory cytokines to pre-malignant disease, such as the formation of adenomas, is unclear. Using the Milliplex® MAP Human Cytokine/ Chemokine Magnetic Bead Panel Immunoassay, serum cytokine and chemokine profiles were assayed among participants without an adenoma (n = 97) and those with an adenoma (n = 97) enrolled in the NCI-funded Insulin Resistance Atherosclerosis Colon Study. The concentrations of interleukin-10 (IL-10), IL-1β, IL-6, IL-17A, IL-2, IL-4, IL-7, IL-12(p70), interferon-γ (IFN-γ), macrophage chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), granulocyte macrophage colony-stimulating factor (GM-CSF), and macrophage inflammatory protein-1β (MIP-1β) were determined. Multiple logistic regression analyses were used to evaluate the association between adenoma prevalence and cytokine levels. The presence of colorectal adenomas was not associated with significant increases in the systemic levels of proinflammatory (TNF-α, IL-6, IL-1β) or T-cell polarizing (IL-12, IL-2, IL-10, IL-4, IL-17, IFN-γ) cytokines. Furthermore, MCP-1 and RANTES levels were equivalent in the serum of study participants with and without adenomas. These findings suggest colorectal adenoma prevalence may not be associated with significant alterations in systemic inflammation.

Let's Not Put All Our Eggs in One Basket

Abstract: A “basket study” testing a drug in patients whose tumor, in any tissue, has a specific mutation is a useful first research step. Next steps could be anatomic-site–specific trials comparing drug–mutation combinations with standard care and registries of off-label use.

Autonomic Imbalance as a Predictor of Metabolic Risks, Cardiovascular Disease, Diabetes, and Mortality Autonomic Imbalance Predicts CVD, DM, Mortality

Abstract: Cincinnati VA Medical Center and University of Cincinnati College of Medicine, Department of Psychiatry; Cincinnati VA Medical Center and University of Cincinnati, Department of Mathematics; Cincinnati VA Medical Center and University of Cincinnati College of Medicine, Department of Psychiatry; Boston University School of Public Health, Department of Biostatistics; Boston University, Department of Mathematics and Statistics Draft date: 2.16.15

The association between gastrostomy tube placement, poor post-operative outcomes, and hospital re-admissions in head and neck cancer patients.

Abstract: Objectives Investigate the relationship of G-tube placement timing on post-operative outcomes. Participants 908 patients underwent resection of head and neck upper aerodigestive tract tumors between 2007 and 2013. Patient charts were retrospectively screened for patient demographics, pre-operative nutrition variables, co-morbid conditions, Tumor-Node-Metastasis staging, surgical treatment type, and timing of G-tube placement. Exclusionary criteria included death within the first three months of the resection and resections performed solely for nodal disease. Main Outcomes Post-surgical outcomes, including wound and medical complications, hospital re-admissions, length of inpatient hospital stay (LOS), intensive care unit (ICU) time. Results 793 surgeries were included: 8% of patients had G-tubes pre-operatively and 25% had G-tubes placed post-operatively. Patients with G-tubes (pre-operative or post-operative) were more likely to have complications and prolonged hospital care as compared to those without G-tubes (p Conclusions Though having enteral access in the form of a G-tube at any point suggests a more high risk patient, having a G-tube placed in the pre-operative period may protect against poor post-operative outcomes. Post-operative outcomes can be predicted based on patient characteristics available to the physician in the pre-operative period.

Urinary F2-isoprostanes and metabolic markers of fat oxidation.

Abstract: Metabolomic studies of increased fat oxidation showed increase in circulating acylcarnitines C2, C8, C10, and C12 and decrease in C3, C4, and C5. We hypothesize that urinary F2-isoprostanes reflect intensity of fatty acid oxidation and are associated with circulating C2, C8, C10, and C12 directly and with C3, C4, and C5 inversely. Four urinary F2-isoprostane isomers and serum acylcarnitines are quantified using LC-MS/MS within the Insulin Resistance Atherosclerosis Study nondiabetic cohort (n = 682). Cross-sectional associations between fasting urinary F2-isoprostanes (summarized as a composite index) and the selected acylcarnitines are examined using generalized linear models. F2-isoprostane index is associated with C2 and C12 directly and with C5 inversely: the adjusted beta coefficients are 0.109, 0.072, and −0.094, respectively (P < 0.05). For these acylcarnitines and for F2-isoprostanes, the adjusted odds ratios (ORs) of incident diabetes are calculated from logistic regression models: the ORs (95% CI) are 0.77 (0.60–0.97), 0.79 (0.62–1.01), 1.18 (0.92–1.53), and 0.51 (0.35–0.76) for C2, C12, C5, and F2-isoprostanes, respectively. The direction of the associations between urinary F2-isoprostanes and three acylcarnitines (C2, C5, and C12) supports our hypothesis. The inverse associations of C2 and C12 and with incident diabetes are consistent with the suggested protective role of efficient fat oxidation.