University of Colorado Denver

About: University of Colorado Denver is a education organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Population & Health care. The organization has 27444 authors who have published 57213 publications receiving 2539937 citations. The organization is also known as: CU Denver & UCD.

Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study.

Abstract: Treatment for Hodgkin's disease (HD) is associated with a variety of thyroid abnormalities, including hypothyroidism, hyperthyroidism, and thyroid neoplasms. Due to the small sample size and short follow-up time of most published studies, it has been difficult to appreciate the full extent of the problem and to characterize the interaction between various patient and treatment variables. To overcome these limitations we have assessed thyroid status in 1,791 (959 males) HD survivors from among 13,674 participants in the Childhood Cancer Survivor Study, a cohort of 5-yr survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. Thyroid abnormalities were ascertained as part of a 22-page questionnaire sent to participants. Survivors were a median of 14 yr (range, 2-20 yr) at diagnosis of HD and a median of 30 yr (range, 12-47 yr) at follow-up. Seventy-nine percent of subjects were treated with radiation (median dose of radiation to the thyroid, 3,500 cGy; range, 0.37-5,500 cGy). Control data were available from 2,808 (1,346 males) sibling controls. Thirty-four percent of the entire cohort has been diagnosed with at least one thyroid abnormality. Hypothyroidism was the most common disturbance, with a relative risk of 17.1 (P < 0.0001) compared to sibling controls. Increasing dose of radiation, older age at diagnosis of HD, and female sex were all independently associated with an increased risk of hypothyroidism. Actuarial risk of hypothyroidism for subjects treated with 4,500 cGy or more is 50% at 20 yr from diagnosis. Hyperthyroidism was reported by 5% of survivors, which was 8-fold greater (P < 0.0001) than the incidence reported by the controls. Thyroid dose of 3,500 cGy or more was the only risk factor identified for hyperthyroidism. The risk of thyroid nodules was 27 times (P < 0.0001) that in sibling controls. Female sex and radiation dose to the thyroid of 2,500 cGy or more were independent risk factors for thyroid nodules. The actuarial risk of a female survivor developing a thyroid nodule is 20% at 20 yr from diagnosis. Thyroid cancer was diagnosed in 20 survivors, which is 18 times the expected rate for the general population. After taking into account the possibility that some of the relative risk estimates may be exaggerated due to ascertainment bias, abnormalities of the thyroid are still extremely common in young adult survivors of childhood HD, particularly among females treated with high doses of radiation to the neck.

Step-up Therapy for Children with Uncontrolled Asthma Receiving Inhaled Corticosteroids

Abstract: Background For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking. Methods We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 μg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 μg of fluticasone twice daily (ICS step-up), 100 μg of fluticasone plus 50 μg of a long-acting beta-agonist twice daily (LABA step-up), or 100 μg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%. Results A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up thera...

Inflammatory markers and the risk of Alzheimer disease: The Framingham Study

Abstract: Objective: To examine whether serum cytokines and spontaneous production of peripheral blood mononuclear cell (PBMC) cytokines are associated with the risk of incident Alzheimer disease (AD). Methods: We followed 691 cognitively intact community-dwelling participants (mean age 79 years, 62% women) and related PBMC cytokine production (tertiles of spontaneous production of interleukin 1 [IL-1], IL-1 receptor antagonist, and tumor necrosis factor α [TNF-α]) and serum C-reactive protein and interleukin 6 (IL-6) to the risk of incident AD. Results: Adjusting for clinical covariates, individuals in the top two tertiles (T2 and T3) of PBMC production of IL-1 or the top tertile (T3) of PBMC production of TNF-α were at increased risk of developing AD (multivariable-adjusted hazard ratio [HR] for IL-1 T2 = 2.84, 95% CI 1.09 to 7.43; p = 0.03 and T3 = 2.61, 95% CI 0.96 to 7.07; p = 0.06; for TNF-α, adjusted HR for T2 = 1.30, 95% CI 0.53 to 3.17; p = 0.57 and T3 = 2.59, 95% CI 1.09 to 6.12; p = 0.031]) compared with those in the lowest tertile (T1). Interpretation: Higher spontaneous production of interleukin 1 or tumor necrosis factor α by peripheral blood mononuclear cells may be a marker of future risk of Alzheimer disease (AD) in older individuals. These data strengthen the evidence for a pathophysiologic role of inflammation in the development of clinical AD.

Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia.

Abstract: Context Exploration of the genetic architecture of specific endophenotypes may be a powerful strategy for understanding the genetic basis of schizophrenia. Objective To characterize the genetic architecture of some key endophenotypic measures selected for their reported heritabilities in schizophrenia. Design Family-based heritability study. Setting Seven sites across the United States. Participants At the time of these initial data analyses, the members of 183 nuclear families ascertained through probands with schizophrenia had been assessed for these endophenotypes. Main Outcome Measures Variance component models were used to assess the heritability of and the environmental and genetic correlations among the endophenotypes. The Consortium on the Genetics of Schizophrenia assesses the neurophysiologic measures of prepulse inhibition of acoustic startle, P50 event-related potential suppression, and the antisaccade task for eye movements and the neurocognitive measures of the Continuous Performance Test (Degraded Stimulus version), the California Verbal Learning Test, the Letter-Number Sequencing test, and 6 measures from the University of Pennsylvania Computerized Neurocognitive Battery. The heritabilities of these 12 measures are the focus of this article. Results All of the endophenotypes and the University of Pennsylvania Computerized Neurocognitive Battery measures were found to be significantly heritable ( P ≤ .005), with heritabilities ranging from 24% to 55%. Significant environmental and genetic correlations were also observed between many of the endophenotypic measures. Conclusion This is the first large-scale, multisite, family-based heritability study of a collection of endophenotypes for schizophrenia and suggests that endophenotypes are important measures to consider in characterizing the genetic basis of schizophrenia.

Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus.

Abstract: Background: In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the compo...