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Putting translational science on to a global stage.Gilliland CT, Zuk D, Kocis P, Johnson M, Hay S, Hajduch M, Bietrix F, Aversa G, Austin C, Ussi AENat Rev Drug Discov , (15), 217-8, 2016. Article Pubmed Global collaboration in translational science promises to accelerate the discovery, development and dissemination of new medical interventions. Here, we introduce a new international collaboration of translational science organizations and highlight our initial strategy to reduce or remove bottlenecks in translation.
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Gene Therapy: The View from NCATS.Brooks P, Yang NN, Austin CHum. Gene Ther. , (27), 7-13, 2016. Article Pubmed |
Hospital variation in admission to intensive care units for patients with acute myocardial infarction.Chen R, Strait KM, Dharmarajan K, Li SX, Ranasinghe I, Martin J, Fazel R, Masoudi FA, Cooke CR, Nallamothu BK, Krumholz HMAm. Heart J. , (170), 1161-9, 2015. Article Pubmed BACKGROUND: The treatment for patients with acute myocardial infarction (AMI) was transformed by the introduction of intensive care units (ICUs), yet we know little about how contemporary hospitals use this resource-intensive setting and whether higher use is associated with better outcomes.
METHODS: We identified 114,136 adult hospitalizations for AMI from 307 hospitals in the 2009 to 2010 Premier database using codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. Hospitals were stratified into quartiles by rates of ICU admission for AMI patients. Across quartiles, we examined in-hospital risk-standardized mortality rates and usage rates of critical care therapies for these patients.
RESULTS: Rates of ICU admission for AMI patients varied markedly among hospitals (median 48%, Q1-Q4 20%-71%, range 0%-98%), and there was no association with in-hospital risk-standardized mortality rates (6% all quartiles, P = .7). However, hospitals admitting more AMI patients to the ICU were more likely to use critical care therapies overall (mechanical ventilation [from Q1 with lowest rate of ICU use to Q4 with highest rate 13%-16%], vasopressors/inotropes [17%-21%], intra-aortic balloon pumps [4%-7%], and pulmonary artery catheters [4%-5%]; P for trend < .05 in all comparisons).
CONCLUSIONS: Rates of ICU admission for patients with AMI vary substantially across hospitals and were not associated with differences in mortality, but were associated with greater use of critical care therapies. These findings suggest uncertainty about the appropriate use of this resource-intensive setting and a need to optimize ICU triage for patients who will truly benefit.
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Circulating Sex Hormones and Risk of Uterine Fibroids: Study of Women's Health Across the Nation (SWAN).Wong JY, Gold EB, Johnson WO, Lee JSJ. Clin. Endocrinol. Metab. , (101), 123-30, 2016. Article Pubmed CONTEXT: Estrogen has been implicated in the development of uterine fibroids. However, the contribution of androgen in women is unknown.
OBJECTIVE: Our objective was to assess the longitudinal relations of circulating androgens and estradiol (E2) and their joint effects to the risk of developing fibroids.
DESIGN: This is a 13-year longitudinal study in the Study of Women's Health Across the Nation.
SETTING: This study was conducted in seven sites across the United States (1997-2013).
PARTICIPANTS: At baseline, 3240 pre- or early peri-menopausal women with an intact uterus, ages 45-52 years were included; 43.6% completed the follow-up. There were 512 incident and 478 recurrent fibroid cases.
EXPOSURES: We measured near-annual time-varying serum levels of bioavailable E2 and bioavailable T, dichotomized at the median (high vs low).
MAIN OUTCOMES AND MEASURES: We estimated the conditional odds ratio (OR) of fibroids in the ensuing year using discrete-time proportional odds models adjusted for race/ethnicity/site, age, body mass index, menopausal stage, reproductive factors, smoking, timing of blood draw, and FSH.
RESULTS: Women with high T had a statistically significant increased risk of incident fibroids (OR, 1.33; 95% confidence interval [CI], 1.01-1.76; P = .04), but not recurrent fibroids. This risk was further elevated in those with high T and E2 (OR, 1.52; 95% CI, 1.07-2.17; P = .02). High E2 and T was associated with lower risk of recurrent fibroids (OR, 0.50; 95% CI, 0.26-0.96; P = .04).
CONCLUSIONS: High T with high E2 was associated with an elevated risk of incident fibroids in midlife women who never reported fibroids before baseline. Conversely, the risk of recurrent fibroids was mitigated in women with high E2 and high T.
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Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker.Ju W, et al.Sci Transl Med , (7), 316ra193, 2015. Article Pubmed Chronic kidney disease (CKD) affects 8 to 16% people worldwide, with an increasing incidence and prevalence of end-stage kidney disease (ESKD). The effective management of CKD is confounded by the inability to identify patients at high risk of progression while in early stages of CKD. To address this challenge, a renal biopsy transcriptome-driven approach was applied to develop noninvasive prognostic biomarkers for CKD progression. Expression of intrarenal transcripts was correlated with the baseline estimated glomerular filtration rate (eGFR) in 261 patients. Proteins encoded by eGFR-associated transcripts were tested in urine for association with renal tissue injury and baseline eGFR. The ability to predict CKD progression, defined as the composite of ESKD or 40% reduction of baseline eGFR, was then determined in three independent CKD cohorts. A panel of intrarenal transcripts, including epidermal growth factor (EGF), a tubule-specific protein critical for cell differentiation and regeneration, predicted eGFR. The amount of EGF protein in urine (uEGF) showed significant correlation (P < 0.001) with intrarenal EGF mRNA, interstitial fibrosis/tubular atrophy, eGFR, and rate of eGFR loss. Prediction of the composite renal end point by age, gender, eGFR, and albuminuria was significantly (P < 0.001) improved by addition of uEGF, with an increase of the C-statistic from 0.75 to 0.87. Outcome predictions were replicated in two independent CKD cohorts. Our approach identified uEGF as an independent risk predictor of CKD progression. Addition of uEGF to standard clinical parameters improved the prediction of disease events in diverse CKD populations with a wide spectrum of causes and stages.
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Diet quality of cancer survivors and noncancer individuals: Results from a national survey.Zhang FF, Liu S, John EM, Must A, Demark-Wahnefried WCancer , (121), 4212-21, 2015. Article Pubmed BACKGROUND: Patterns of poor nutritional intake may exacerbate the elevated morbidity experienced by cancer survivors. It remains unclear whether cancer survivors adhere to existing dietary guidelines and whether survivors' diets differ from those of individuals without cancer over the long term.
METHODS: The authors evaluated dietary intake and quality in 1533 adult cancer survivors who participated in the National Health and Nutrition Examination Survey from 1999 to 2010 compared with dietary intake and quality in 3075 individuals who had no history of cancer and were matched to the cancer survivors by age, sex, and race/ethnicity. Dietary intake was assessed using 24-hour dietary recalls. The 2010 Healthy Eating Index (HEI-2010) was used to evaluate diet quality.
RESULTS: The mean ± standard deviation HEI-2010 total score was 47.2 ± 0.5 in the cancer survivors and 48.3 ± 0.4 in the noncancer group (P = .03). Compared with the noncancer group, cancer survivors had a significantly lower score for empty calories (13.6 vs 14.4; P = .001), which corresponded to worse adherence to dietary intake of calories from solid fats, alcohol, and added sugars. Cancer survivors also had significantly lower dietary intake of fiber than the noncancer group (15.0 vs 15.9 g per day; P = .02). In relation to recommended intake, survivors' mean dietary intake of vitamin D, vitamin E, potassium, fiber, and calcium was 31%, 47%, 55%, 60%, and 73%, respectively; whereas their mean dietary intake of saturated fat and sodium was 112% and 133%, respectively, of the recommended intake.
CONCLUSIONS: Cancer survivors had poor adherence to the US Department of Agriculture 2010 Dietary Guidelines for Americans, and their intake patterns were worse than those in the general population for empty calories and fiber.
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HPV vaccine completion and dose adherence among commercially insured females aged 9 through 26 years in the US.Liu G, Kong L, Du PPapillomavirus Res , (2), 1-8, 2016. Article Pubmed BACKGROUND: Although HPV vaccination has been recommended for use in girls and young women since 2007, HPV vaccine uptake is low in the US.
METHODS: We conducted a retrospective cohort study using the 2008-2011 MarketScan data to examine HPV vaccine completion and dose adherence among commercially insured females aged 9-26 years. We performed multivariable logistic regression models to examine factors related to HPV vaccine completion and HPV vaccine dose adherence.
RESULTS: Among 378,484 females aged 9-26 years who initiated HPV vaccination, only 29.4% completed HPV vaccination. Compared with females receiving vaccines from primary care providers, those receiving vaccines from OB/GYN providers were more likely to complete the vaccine series. Age at HPV vaccine initiation, health insurance plan, seasonal pattern, and flu vaccination were also significantly associated with vaccine completion. Among 111,286 females who completed HPV vaccination, 62.4% received all doses within 30 days of the recommended schedules. Similar factors relating to HPV vaccine completion were consistently associated with HPV vaccine dose adherence. However, younger age (<22 years) and receipt of flu vaccine were negatively related to HPV vaccine dose adherence.
CONCLUSIONS: Intervention programs to improve HPV vaccine reminding system and reduce logistic barriers for both physicians and patients are warranted.
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Geospatial Resolution of Human and Bacterial Diversity with City-Scale Metagenomics.Afshinnekoo E, et al.Cell Syst , (1), 72-87, 2015. Article Pubmed The panoply of microorganisms and other species present in our environment influence human health and disease, especially in cities, but have not been profiled with metagenomics at a city-wide scale. We sequenced DNA from surfaces across the entire New York City (NYC) subway system, the Gowanus Canal, and public parks. Nearly half of the DNA (48%) does not match any known organism; identified organisms spanned 1,688 bacterial, viral, archaeal, and eukaryotic taxa, which were enriched for harmless genera associated with skin (e.g., Acinetobacter). Predicted ancestry of human DNA left on subway surfaces can recapitulate U.S. Census demographic data, and bacterial signatures can reveal a station's history, such as marine-associated bacteria in a hurricane-flooded station. Some evidence of pathogens was found (Bacillus anthracis), but a lack of reported cases in NYC suggests that the pathogens represent a normal, urban microbiome. This baseline metagenomic map of NYC could help long-term disease surveillance, bioterrorism threat mitigation, and health management in the built environment of cities.
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Randomized controlled pilot trial of mindfulness-based stress reduction for breast and colorectal cancer survivors: effects on cancer-related cognitive impairment.Johns SA, Von Ah D, Brown LF, Beck-Coon K, Talib TL, Alyea JM, Monahan PO, Tong Y, Wilhelm L, Giesler RBJ Cancer Surviv , (10), 437-48, 2016. Article Pubmed PURPOSE: Cancer-related cognitive impairment (CRCI) is a common, fatigue-related symptom that disrupts cancer survivors' quality of life. Few interventions for CRCI exist. As part of a randomized pilot study targeting cancer-related fatigue, the effects of mindfulness-based stress reduction (MBSR) on survivors' cognitive outcomes were investigated.
METHODS: Breast and colorectal cancer survivors (n = 71) with moderate-to-severe fatigue were randomized to MBSR (n = 35) or a fatigue education and support (ES; n = 36) condition. The Attentional Function Index (AFI) and the Stroop test were used to assess survivors' cognitive function at baseline (T1), after the 8-week intervention period (T2), and 6 months later (T3) using intent-to-treat analysis. Mediation analyses were performed to explore mechanisms of intervention effects on cognitive functioning.
RESULTS: MBSR participants reported significantly greater improvement on the AFI total score compared to ES participants at T2 (d = 0.83, p = 0.001) and T3 (d = 0.55, p = 0.021). MBSR also significantly outperformed ES on most AFI subscales, although both groups improved over time. MBSR produced greater Stroop accuracy rates relative to ES at T2 (r = 0.340, p = 0.005) and T3 (r = 0.280, p = 0.030), with improved accuracy over time only for the MBSR group. There were no significant differences in Stroop reaction time between groups. Improvements in mindfulness mediated the effect of group (e.g., MBSR vs. ES) on AFI total score at T2 and T3.
CONCLUSIONS: Additional randomized trials with more comprehensive cognitive measures are warranted to definitively assess the efficacy of MBSR for CRCI.
IMPLICATIONS FOR CANCER SURVIVORS: This pilot study has important implications for all cancer survivors as it is the first published trial to show that MBSR offers robust and durable improvements in CRCI.
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