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Early urine electrolyte patterns in patients with acute heart failure.
Collins SP, Jenkins CA, Baughman A, Miller KF, Storrow AB, Han JH, Brown NJ, Liu D, Luther JM, McNaughton CD, Self WH, Peng D, Testani JM, Lindenfeld J
(2019) ESC Heart Fail 6: 80-88
MeSH Terms: Acute Disease, Aged, Biomarkers, Disease Progression, Diuretics, Female, Follow-Up Studies, Heart Failure, Humans, Male, Middle Aged, Pilot Projects, Prognosis, Prospective Studies, Sodium, Stroke Volume
Show Abstract · Added October 25, 2018
AIMS - We conducted a prospective study of emergency department (ED) patients with acute heart failure (AHF) to determine if worsening HF (WHF) could be predicted based on urinary electrolytes during the first 1-2 h of ED care. Loop diuretics are standard therapy for AHF patients. A subset of patients hospitalized for AHF will develop a blunted natriuretic response to loop diuretics, termed diuretic resistance, which often leads to WHF. Early detection of diuretic resistance could facilitate escalation of therapy and prevention of WHF.
METHODS AND RESULTS - Patients were eligible if they had an ED AHF diagnosis, had not yet received intravenous diuretics, had a systolic blood pressure > 90 mmHg, and were not on dialysis. Urine electrolytes and urine output were collected at 1, 2, 4, and 6 h after diuretic administration. Worsening HF was defined as clinically persistent or WHF requiring escalation of diuretics or administration of intravenous vasoactives after the ED stay. Of the 61 patients who qualified in this pilot study, there were 10 (16.3%) patients who fulfilled our definition of WHF. At 1 h after diuretic administration, patients who developed WHF were more likely to have low urinary sodium (9.5 vs. 43.0 mmol; P < 0.001) and decreased urine sodium concentration (48 vs. 80 mmol/L; P = 0.004) than patients without WHF. All patients with WHF had a total urine sodium of <35.4 mmol at 1 h (100% sensitivity and 60% specificity).
CONCLUSIONS - One hour after diuretic administration, a urine sodium excretion of <35.4 mmol was highly suggestive of the development of WHF. These relationships require further testing to determine if early intervention with alternative agents can prevent WHF.
© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
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16 MeSH Terms
The CeNGEN Project: The Complete Gene Expression Map of an Entire Nervous System.
Hammarlund M, Hobert O, Miller DM, Sestan N
(2018) Neuron 99: 430-433
MeSH Terms: Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Chromosome Mapping, Gene Expression Profiling, National Institute of Neurological Disorders and Stroke (U.S.), Nervous System, Nervous System Physiological Phenomena, United States
Show Abstract · Added March 26, 2019
Differential gene expression defines individual neuron types and determines how each contributes to circuit physiology and responds to injury and disease. The C. elegans Neuronal Gene Expression Map & Network (CeNGEN) will establish a comprehensive gene expression atlas of an entire nervous system at single-neuron resolution.
Copyright © 2018. Published by Elsevier Inc.
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9 MeSH Terms
An adaptive semantic matching paradigm for reliable and valid language mapping in individuals with aphasia.
Wilson SM, Yen M, Eriksson DK
(2018) Hum Brain Mapp 39: 3285-3307
MeSH Terms: Adult, Aged, Aged, 80 and over, Aphasia, Brain, Brain Mapping, Chronic Disease, Feasibility Studies, Female, Humans, Language, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Psychometrics, Reproducibility of Results, Stroke
Show Abstract · Added March 26, 2019
Research on neuroplasticity in recovery from aphasia depends on the ability to identify language areas of the brain in individuals with aphasia. However, tasks commonly used to engage language processing in people with aphasia, such as narrative comprehension and picture naming, are limited in terms of reliability (test-retest reproducibility) and validity (identification of language regions, and not other regions). On the other hand, paradigms such as semantic decision that are effective in identifying language regions in people without aphasia can be prohibitively challenging for people with aphasia. This paper describes a new semantic matching paradigm that uses an adaptive staircase procedure to present individuals with stimuli that are challenging yet within their competence, so that language processing can be fully engaged in people with and without language impairments. The feasibility, reliability and validity of the adaptive semantic matching paradigm were investigated in sixteen individuals with chronic post-stroke aphasia and fourteen neurologically normal participants, in comparison to narrative comprehension and picture naming paradigms. All participants succeeded in learning and performing the semantic paradigm. Test-retest reproducibility of the semantic paradigm in people with aphasia was good (Dice coefficient = 0.66), and was superior to the other two paradigms. The semantic paradigm revealed known features of typical language organization (lateralization; frontal and temporal regions) more consistently in neurologically normal individuals than the other two paradigms, constituting evidence for validity. In sum, the adaptive semantic matching paradigm is a feasible, reliable and valid method for mapping language regions in people with aphasia.
© 2018 Wiley Periodicals, Inc.
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18 MeSH Terms
Clinical Features Associated With Nascent Left Ventricular Diastolic Dysfunction in a Population Aged 40 to 55 Years.
Mosley JD, Levinson RT, Brittain EL, Gupta DK, Farber-Eger E, Shaffer CM, Denny JC, Roden DM, Wells QS
(2018) Am J Cardiol 121: 1552-1557
MeSH Terms: Adult, Age Distribution, Cohort Studies, Databases, Factual, Diabetes Mellitus, Type 2, Echocardiography, Female, Heart Failure, Diastolic, Humans, Hypertension, Incidence, Kaplan-Meier Estimate, Linear Models, Male, Middle Aged, Multivariate Analysis, Prognosis, Retrospective Studies, Risk Assessment, Severity of Illness Index, Sex Distribution, Stroke Volume, Survival Analysis, United States, Ventricular Dysfunction, Left
Show Abstract · Added June 7, 2018
Diastolic dysfunction (DD), an abnormality in cardiac left ventricular (LV) chamber compliance, is associated with increased morbidity and mortality. Although DD has been extensively studied in older populations, co-morbidity patterns are less well characterized in middle-aged subjects. We screened 156,434 subjects with transthoracic echocardiogram reports available through Vanderbilt's electronic heath record and identified 6,612 subjects 40 to 55 years old with an LV ejection fraction ≥50% and diastolic function staging. We tested 452 incident and prevalent clinical diagnoses for associations with early-stage DD (n = 1,676) versus normal function. There were 44 co-morbid diagnoses associated with grade 1 DD including hypertension (odds ratio [OR] = 2.02, 95% confidence interval [CI] 1.78 to 2.28, p <5.3 × 10-29), type 2 diabetes (OR 1.96, 95% CI 1.68 to 2.29, p = 2.1 × 10-17), tachycardia (OR 1.38, 95% CI 0.53 to 2.19, p = 2.9 × 10-6), obesity (OR 1.76, 95% CI 1.51 to 2.06, p = 1.7 × 10-12), and clinical end points, including end-stage renal disease (OR 3.29, 95% CI 2.19 to 4.96, p = 1.2 × 10-8) and stroke (OR 1.5, 95% CI 1.12 to 2.02, p = 6.9 × 10-3). Among the 60 incident diagnoses associated with DD, heart failure with preserved ejection fraction (OR 4.63, 95% CI 3.39 to 6.32, p = 6.3 × 10-22) had the most significant association. Among subjects with normal diastolic function and blood pressure at baseline, a blood pressure measurement in the hypertensive range at the time of the second echocardiogram was associated with progression to stage 1 DD (p = 0.04). In conclusion, DD was common among subjects 40 to 55 years old and was associated with a heavy burden of co-morbid disease.
Copyright © 2018 Elsevier Inc. All rights reserved.
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25 MeSH Terms
A quick aphasia battery for efficient, reliable, and multidimensional assessment of language function.
Wilson SM, Eriksson DK, Schneck SM, Lucanie JM
(2018) PLoS One 13: e0192773
MeSH Terms: Aphasia, Case-Control Studies, Humans, Language, Stroke
Show Abstract · Added March 26, 2019
This paper describes a quick aphasia battery (QAB) that aims to provide a reliable and multidimensional assessment of language function in about a quarter of an hour, bridging the gap between comprehensive batteries that are time-consuming to administer, and rapid screening instruments that provide limited detail regarding individual profiles of deficits. The QAB is made up of eight subtests, each comprising sets of items that probe different language domains, vary in difficulty, and are scored with a graded system to maximize the informativeness of each item. From the eight subtests, eight summary measures are derived, which constitute a multidimensional profile of language function, quantifying strengths and weaknesses across core language domains. The QAB was administered to 28 individuals with acute stroke and aphasia, 25 individuals with acute stroke but no aphasia, 16 individuals with chronic post-stroke aphasia, and 14 healthy controls. The patients with chronic post-stroke aphasia were tested 3 times each and scored independently by 2 raters to establish test-retest and inter-rater reliability. The Western Aphasia Battery (WAB) was also administered to these patients to assess concurrent validity. We found that all QAB summary measures were sensitive to aphasic deficits in the two groups with aphasia. All measures showed good or excellent test-retest reliability (overall summary measure: intraclass correlation coefficient (ICC) = 0.98), and excellent inter-rater reliability (overall summary measure: ICC = 0.99). Sensitivity and specificity for diagnosis of aphasia (relative to clinical impression) were 0.91 and 0.95 respectively. All QAB measures were highly correlated with corresponding WAB measures where available. Individual patients showed distinct profiles of spared and impaired function across different language domains. In sum, the QAB efficiently and reliably characterized individual profiles of language deficits.
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MeSH Terms
Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.
Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O'Flaherty M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, Ritchey MD, Rodriguez CJ, Roth GA, Rosamond WD, Sampson UKA, Satou GM, Shah SH, Spartano NL, Tirschwell DL, Tsao CW, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
(2018) Circulation 137: e67-e492
MeSH Terms: American Heart Association, Comorbidity, Data Interpretation, Statistical, Health Status, Heart Diseases, Humans, Life Style, Prognosis, Risk Assessment, Risk Factors, Stroke, United States
Added April 2, 2019
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12 MeSH Terms
Nephrolithiasis Among Middle Aged and Elderly Urban Chinese: A Report from Prospective Cohort Studies in Shanghai.
Shu X, Cai H, Xiang YB, Li H, Lipworth L, Miller NL, Zheng W, Shu XO, Hsi RS
(2017) J Endourol 31: 1327-1334
MeSH Terms: Adult, Aged, Body Mass Index, Cardiovascular Diseases, China, Cohort Studies, Coronary Disease, Female, Humans, Hypertension, Incidence, Male, Middle Aged, Nephrolithiasis, Obesity, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Distribution, Sex Factors, Stroke, Urban Population, Waist-Hip Ratio
Show Abstract · Added January 16, 2018
INTRODUCTION - Kidney stone risk factors are understudied among Asians. Our study objective was to investigate associations of obesity and other chronic diseases with incident kidney stones among the urban Chinese.
PATIENTS AND METHODS - Included in this study are two prospective cohorts: the Shanghai Women's Health Study (N = 69,166) and Shanghai Men's Health Study (N = 58,054). Incident kidney stones were determined by self-report in 2004 and 2008. Cox regression models were used to evaluate the associations of study variables with stone risk with adjustment of demographics, medical history, and dietary intakes.
RESULTS - There were 2653 incident stones over 1,007,958 person-years of follow-up. Overall incidence rates (per 1000 person-years, 95% confidence interval [CI]) were 2.10 (1.99, 2.21) among women and 3.80 (3.59, 4.02) among men. Higher body mass index (BMI) was associated with risk (BMI ≥25 vs 18.5-24.9 kg/m, women: hazard ratio [HR] = 1.14 [95% CI 1.01, 1.28]; men: HR = 1.17 [1.03, 1.32]). High waist-hip ratio (≥0.80 and ≥0.90 for women and men, respectively) was associated with risk (HR 1.13, 95% CI 1.01, 1.27 for women; HR 1.19, 95% CI 1.05, 1.35 for men). Coronary heart disease or stroke history was associated with risk in women only (HR 1.31, 95% CI 1.10, 1.56). Hypertension history was associated with risk in men only (HR 1.27, 95% CI 1.11, 1.45). No significant association with diabetes mellitus was observed.
CONCLUSIONS - Among the Chinese, kidney stone incidence in men is almost twice that of women. Obesity is a shared risk factor. Hypertension history is associated with risk in men, whereas history of coronary heart disease or stroke is associated with risk in women.
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23 MeSH Terms
Blood Pressure and Risk of Cardiovascular Events in Patients on Chronic Hemodialysis: The CRIC Study (Chronic Renal Insufficiency Cohort).
Bansal N, McCulloch CE, Lin F, Alper A, Anderson AH, Cuevas M, Go AS, Kallem R, Kusek JW, Lora CM, Lustigova E, Ojo A, Rahman M, Robinson-Cohen C, Townsend RR, Wright J, Xie D, Hsu CY, CRIC Study Investigators*
(2017) Hypertension 70: 435-443
MeSH Terms: Aged, Blood Pressure Determination, Cohort Studies, Female, Humans, Hypertension, Kidney Failure, Chronic, Male, Middle Aged, Myocardial Infarction, Prognosis, Proportional Hazards Models, Prospective Studies, Renal Dialysis, Risk Assessment, Risk Factors, Stroke, United States
Show Abstract · Added September 19, 2017
We recently reported a linear association between higher systolic blood pressure (SBP) and risk of mortality in hemodialysis patients when SBP is measured outside of the dialysis unit (out-of-dialysis-unit-SBP), despite there being a U-shaped association between SBP measured at the dialysis unit (dialysis-unit-SBP) with risk of mortality. Here, we explored the relationship between SBP with cardiovascular events, which has important treatment implications but has not been well elucidated. Among 383 hemodialysis participants enrolled in the prospective CRIC study (Chronic Renal Insufficiency Cohort), multivariable splines and Cox models were used to study the association between SBP and adjudicated cardiovascular events (heart failure, myocardial infarction, ischemic stroke, and peripheral artery disease), controlling for differences in demographics, cardiovascular disease risk factors, and dialysis parameters. Dialysis-unit-SBP and out-of-dialysis-unit-SBP were modestly correlated (=0.34; <0.001). We noted a U-shaped association of dialysis-unit-SBP and risk of cardiovascular events, with the nadir risk between 140 and 170 mm Hg. In contrast, there was a linear stepwise association between out-of-dialysis-unit-SBP with risk of cardiovascular events. Participants with out-of-dialysis-unit-SBP ≥128 mm Hg (top 2 quartiles) had >2-fold increased risk of cardiovascular events compared with those with out-of-dialysis-unit-SBP ≤112 mm Hg (3rd SBP quartile: adjusted hazard ratio, 2.08 [95% confidence interval, 1.12-3.87] and fourth SBP quartile: adjusted hazard ratio, 2.76 [95% confidence interval, 1.42-5.33]). In conclusion, among hemodialysis patients, although there is a U-shaped (paradoxical) association of dialysis-unit-SBP and risk of cardiovascular disease, there is a linear association of out-of-dialysis-unit-SBP with risk of cardiovascular disease. Out-of-dialysis-unit blood pressure provides key information and may be an important therapeutic target.
© 2017 American Heart Association, Inc.
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18 MeSH Terms
Genome-wide association and pathway analysis of left ventricular function after anthracycline exposure in adults.
Wells QS, Veatch OJ, Fessel JP, Joon AY, Levinson RT, Mosley JD, Held EP, Lindsay CS, Shaffer CM, Weeke PE, Glazer AM, Bersell KR, Van Driest SL, Karnes JH, Blair MA, Lagrone LW, Su YR, Bowton EA, Feng Z, Ky B, Lenihan DJ, Fisch MJ, Denny JC, Roden DM
(2017) Pharmacogenet Genomics 27: 247-254
MeSH Terms: Adult, Anthracyclines, Cohort Studies, Demography, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Reproducibility of Results, Signal Transduction, Stroke Volume, Ventricular Function, Left
Show Abstract · Added March 14, 2018
BACKGROUND - Anthracyclines are important chemotherapeutic agents, but their use is limited by cardiotoxicity. Candidate gene and genome-wide studies have identified putative risk loci for overt cardiotoxicity and heart failure, but there has been no comprehensive assessment of genomic variation influencing the intermediate phenotype of anthracycline-related changes in left ventricular (LV) function. The purpose of this study was to identify genetic factors influencing changes in LV function after anthracycline chemotherapy.
METHODS - We conducted a genome-wide association study (GWAS) of change in LV function after anthracycline exposure in 385 patients identified from BioVU, a resource linking DNA samples to de-identified electronic medical record data. Variants with P values less than 1×10 were independently tested for replication in a cohort of 181 anthracycline-exposed patients from a prospective clinical trial. Pathway analysis was performed to assess combined effects of multiple genetic variants.
RESULTS - Both cohorts were middle-aged adults of predominantly European descent. Among 11 candidate loci identified in discovery GWAS, one single nucleotide polymorphism near PR domain containing 2, with ZNF domain (PRDM2), rs7542939, had a combined P value of 6.5×10 in meta-analysis. Eighteen Kyoto Encyclopedia of Gene and Genomes pathways showed strong enrichment for variants associated with the primary outcome. Identified pathways related to DNA repair, cellular metabolism, and cardiac remodeling.
CONCLUSION - Using genome-wide association we identified a novel candidate susceptibility locus near PRDM2. Variation in genes belonging to pathways related to DNA repair, metabolism, and cardiac remodeling may influence changes in LV function after anthracycline exposure.
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13 MeSH Terms
Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial).
Galadanci NA, Umar Abdullahi S, Vance LD, Musa Tabari A, Ali S, Belonwu R, Salihu A, Amal Galadanci A, Wudil Jibir B, Bello-Manga H, Neville K, Kirkham FJ, Shyr Y, Phillips S, Covert BV, Kassim AA, Jordan LC, Aliyu MH, DeBaun MR
(2017) Am J Hematol 92: 780-788
MeSH Terms: Anemia, Sickle Cell, Antisickling Agents, Child, Child, Preschool, Female, Follow-Up Studies, Hospitalization, Humans, Hydroxyurea, Incidence, Male, Medication Adherence, Nigeria, Reproducibility of Results, Sensitivity and Specificity, Stroke, Treatment Outcome, Ultrasonography, Doppler, Transcranial
Show Abstract · Added April 27, 2017
The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non-imaging TCD measurements (≥200 cm/s) received moderate fixed-dose hydroxyurea therapy (∼20 mg/kg/day). A comparison group of children with TCD measurements <200 cm/s was followed prospectively. Approximately 88% (330 of 375) of families agreed to be screened, while 87% (29 of 33) of those with abnormal TCD measurements, enrolled in the trial. No participant elected to withdraw from the trial. The average mean corpuscular volume increased from 85.7 fl at baseline to 95.5 fl at 24 months (not all of the children who crossed over had a 24 month visit), demonstrating adherence to hydroxyurea. The comparison group consisted of initially 210 children, of which four developed abnormal TCD measurements, and were started on hydroxyurea. None of the monthly research visits were missed (n = total 603 visits). Two and 10 deaths occurred in the treatment and comparison groups, with mortality rates of 2.69 and 1.81 per 100 patient-years, respectively (P = .67). Our results provide strong evidence, for high family recruitment, retention, and adherence rates, to undertake the first randomized controlled trial with hydroxyurea therapy for primary stroke prevention in children with SCA living in Africa.
© 2017 Wiley Periodicals, Inc.
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18 MeSH Terms