Papers by Chung-chou Chang
Sulfonylurea Receptor-1 as a Novel Biomarker for Cerebral Edema in Patients with Severe Traumatic Brain Injury (S46.001)
Neurology, Apr 4, 2016
Objective: We hypothesized that Sur1 is measurable in human CSF after TBI and is an informative b... more Objective: We hypothesized that Sur1 is measurable in human CSF after TBI and is an informative biomarker of cerebral edema and outcome. Background: Cerebral edema is a key poor prognosticator in traumatic brain injury (TBI). Although multiple pathways potentially contribute to its formation, there are no biomarkers identifying patients at-risk or guiding individualized/molecularly precise therapies for edema. Sur1 is a sulfonylurea-receptor that in pre-clinical models is upregulated only after brain injury and opens a non-selective cation channel causing cell depolarization, edema and death. Methods: 119 CSF samples were collected from 28 patients with severe TBI. Samples were retrieved at 12, 24, 48, 72h, and before EVD removal. Control CSF was obtained from 15 patients. Sur1 levels were quantified by ELISA. Outcomes included edema on CT, ICP measurements, therapies targeting cerebral edema and 3-month Glasgow Outcome Scale score. Results: Sur1 levels were increased in TBI patients (mean 3.54±3.39ng/ml, peak 7.13±6.09ng/ml) and undetectable in controls (p<0.001). Mean and peak Sur1 levels were higher in patients with edema vs. those without edema (p<0.05) on acute CT. There was a temporal delay between peak-Sur1 and peak-ICP in 91.7[percnt] of patients with intracranial hypertension. Decreasing Sur1 trajectories between 48-72h were associated with improved edema and clinical outcome (p<0.05). AUROC curve for the multivariate model was 0.869. Conclusions: This is the first report quantifying human CSF Sur1 levels. Sur1 levels were increased in patients with severe TBI, and absent in controls. Levels correlated with edema on initial CT and preceded peak intracranial pressure (ICP). Sur1 trajectories between 48-72h post-injury were associated with outcome. Our findings suggest that Sur1 is a potentially useful biomarker for cerebral edema in TBI. Given that a therapy (Glibenclamide) inhibiting Sur1 is available, assessing CSF Sur1 in a larger study is warranted to evaluate its diagnostic, monitoring and theranostic utility in TBI. Disclosure: Dr. Jha has nothing to disclose. Dr. Puccio has nothing to disclose. Dr. Chou has received personal compensation for activities with Novartis. Dr. Chang has nothing to disclose. Dr. Wallisch has nothing to disclose. Dr. Molyneaux has nothing to disclose. Dr. Zusman has nothing to disclose. Dr. Shutter has nothing to disclose. Dr. Poloyac has nothing to disclose. Dr. Keri has nothing to disclose. Dr. Okonkwo has nothing to disclose. Dr. Kochanek has received personal compensation for activities with numerous commercial entities as a speaker.
1191: Heterogeneity in Response to Early Goal-Directed Therapy in Sepsis
Critical Care Medicine
Abstract P124: Network Meta-analysis of the Effects of Breast Cancer Hormone Therapy on Changes in Lipid Profiles
Circulation, 2017
Introduction: Adjuvant hormone therapy prolongs survival of patients with early-stage hormone rec... more Introduction: Adjuvant hormone therapy prolongs survival of patients with early-stage hormone receptor-positive breast cancer (BC). For postmenopausal patients, aromatase inhibitors (AIs) have been shown to improve disease free survival compared to tamoxifen, but the impact on overall survival has been inconsistent. A meta-analysis showed higher risk of cardiovascular diseases (CVDs) for patients taking AIs. Deteriorating lipids induced by AIs may contribute to this result. This analysis aims to compare the effects of hormone therapeutic options on changes in lipids from published randomized clinical trials (RCTs). Methods: RCTs evaluating effects of adjuvant hormone therapy on lipids (total cholesterol, high-density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc), and/or triglycerides) in postmenopausal early-stage BC patients published in PubMed and Embase, prior to Jan. 31, 2016 were reviewed. Bayesian network meta-analysis was used to compare effects o...
Additional file 1: of Net ultrafiltration intensity and mortality in critically ill patients with fluid overload
S1. Study population. S2. Determination of cumulative fluid balance. S3. Vasopressor standardizat... more S1. Study population. S2. Determination of cumulative fluid balance. S3. Vasopressor standardization to norepinephrine equivalents. S4. Grayâ s survival model. S5. Propensity score estimation and matching. S6. Quantitative bias sensitivity analysis of potential impact of an unmeasured confounder. Figure S1. Study population and analysis cohort. Figure S2. Association between intensity of net ultrafiltration and crude hospital mortality. Figure S3. Association between net ultrafiltration intensity and time to mortality using Grayâ s model. Figure S4. Quantitative bias sensitivity analysis to assess the impact of an unmeasured confounder on mortality. Table S1. Cumulative fluid balance, mean arterial pressure and vasopressor dose for entire duration of RRT. Table S2. Association between net ultrafiltration intensity and 1-year risk-adjusted mortality. Table S3. Association between net ultrafiltration intensity and 1-year risk-adjusted mortality using net ulftrafiltration as a continuo...
MOESM1 of Murine sepsis phenotypes and differential treatment effects in a randomized trial of prompt antibiotics and fluids
Additional file 1: Murine sepsis phenotypes and differential treatment effects in a randomized tr... more Additional file 1: Murine sepsis phenotypes and differential treatment effects in a randomized trial of prompt antibiotics and fluids. Supplementary figures (Figure S1 and Figure S2) with accompanying legends.
Journal of Surgical Research, 2021
tions experienced less under-triage in the year after the trial than before (41% versus 58% [-17%... more tions experienced less under-triage in the year after the trial than before (41% versus 58% [-17%], P = 0.015); patients treated by physicians randomized to the control experienced no difference in under-triage (49% versus 56% [-7%], P = 0.35). The difference-in-the-difference was non-significant (10%, P = 0.18). Conclusions: It was feasible to track trial participants' performance in national claims. Sample size limitations constrained causal inference about the effect of the interventions.
Abstract 18446: Receipt of Implantable Cardioverter-Defibrillator Among HIV+ and HIV- Veterans With Cardiomyopathy
Circulation, 2013
Introduction: Those with HIV infection (HIV+) are at increased risk for AMI, CHF, and sudden card... more Introduction: Those with HIV infection (HIV+) are at increased risk for AMI, CHF, and sudden cardiac death compared to uninfected individuals (HIV-). HIV+ people also receive fewer cardiac procedur...
Abstract 12503: Liver Injury is Associated With Total Cardiovascular Disease, Heart Failure, Stroke, Coronary Heart Disease and Acute Myocardial Infarction Including Among Those Without Viral Hepatitis (B Or C), Hiv, Alcohol Abuse and Obesity
Circulation, 2015
Introduction: Hepatitis C and human immunodeficiency virus (HCV, HIV) are associated with cardiov... more Introduction: Hepatitis C and human immunodeficiency virus (HCV, HIV) are associated with cardiovascular disease (CVD). Liver injury is common in HIV and HCV and is associated with pro-atherosclero...
Alzheimer's & Dementia, 2018
Exercise is among the most promising modifiable behaviors associated with reduced risk for cognit... more Exercise is among the most promising modifiable behaviors associated with reduced risk for cognitive impairment.
P1‐623: Declining Dementia Incidence in the Monongahela Valley: Birth Cohort Analyses from the Movies and Myhat Studies
Alzheimer's & Dementia, 2018
symptoms. Those with probable AD had a prevalence of 60.3 percent while those with MCI had a prev... more symptoms. Those with probable AD had a prevalence of 60.3 percent while those with MCI had a prevalence of 45.9 percent. Of those with normal cognition, 21.5 percent had depressive symptoms. GDS scores were found to be significantly negatively correlated with MoCA-P scores. Higher GDS scores were correlated with lower MoCA-P scores. There was also a significant difference in age among the three groups. A higher age was associated with a higher GDS score and a lower MoCA-P score. Conclusions:A high prevalence of depressive symptoms was found among the study cohort at 36.8 percent. This was higher than the estimated global prevalence. Prevalence was higher among those with probable AD compared to those with MCI and normal cognition. The presence of depressive symptoms also strongly correlated with cognitive impairment. Further research should confirm whether depressive symptoms at baseline increase the risk of developing dementia among community-dwelling Filipino elderly and to investigate factors that contribute to a higher prevalence of depression among the study cohort compared to the global population. P1-623 DECLINING DEMENTIA INCIDENCE IN THE MONONGAHELAVALLEY: BIRTH COHORTANALYSES FROM THE MOVIES AND MYHAT STUDIES Kevin J. Sullivan, Hiroko H. Dodge, Tiffany F. Hughes, ChungChou Chang, Mary Ganguli, University of Pittsburgh, Pittsburgh, PA, USA; Michigan Alzheimer’s Disease Center, Ann Arbor, MI, USA; Youngstown State University, Youngstown, OH, USA; University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Contact e-mail: [email protected]
JAMA Surgery, 2019
IMPORTANCE Despite evidence that treatment of severely injured patients at trauma centers is asso... more IMPORTANCE Despite evidence that treatment of severely injured patients at trauma centers is associated with reduced mortality, nearly half of all such patients are treated at nontrauma centers (undertriaged). Little is known about whether interfacility undertriage occurs because of practitioner decision-making or institutional and regional factors. OBJECTIVES To assess the associations between variation in triage practitioners at nontrauma centers and between practitioner-level variation and patient outcomes after injury. This retrospective cohort study used Medicare claims data from severely injured patients presenting to nontrauma centers and the practitioners who evaluated them in the emergency department from
BMC Health Services Research, 2019
Background In the United States, there is well-documented regional variation in prescription drug... more Background In the United States, there is well-documented regional variation in prescription drug spending. However, the specific role of physician adoption of brand name drugs on the variation in patient-level prescription drug spending is still being investigated across a multitude of drug classes. Our study aims to add to the literature by determining the association between physician adoption of a first-in-class anti-diabetic (AD) drug, sitagliptin, and AD drug spending in the Medicare and Medicaid populations in Pennsylvania. Methods We obtained physician-level data from QuintilesIMS Xponent™ database for Pennsylvania and constructed county-level measures of time to adoption and share of physicians adopting sitagliptin in its first year post-introduction. We additionally measured total AD drug spending for all Medicare fee-for-service and Part D enrollees (N = 125,264) and all Medicaid (N = 50,836) enrollees with type II diabetes in Pennsylvania for 2011. Finite mixture model r...
Variation in SPINK-1 N34S Effect Size Is Population-Dependant
American Journal of Gastroenterology, 2006
71st Annual Scientific Meeting of the American-College-of-Gasroenterology -- OCT 20-25, 2006 -- L... more 71st Annual Scientific Meeting of the American-College-of-Gasroenterology -- OCT 20-25, 2006 -- Las Vegas, NVWOS: 000240656100210Amer Coll Gastroentero
Meta-analysis of effect of hormone therapies on lipid levels in breast cancer patients
Journal of Clinical Oncology, 2019
e18243 Background: Breast cancer (BC) patients with hormone-sensitive tumors often receive adjuva... more e18243 Background: Breast cancer (BC) patients with hormone-sensitive tumors often receive adjuvant hormone therapy for an extended period. How this affects lipid levels is not known. This study evaluated the relationship between dyslipidemia, a cardiovascular disease risk factor, and use of adjuvant hormone therapy among breast cancer patients. Methods: Randomized clinical trials for adjuvant hormone treatment in post-menopausal BC patients without residual cancer after primary treatment that reported lipid levels were identified in PubMed and EMBASE (N = 13). Bayesian network meta-analysis for longitudinal data was used to evaluate each drug’s effect on the mean changes in lipid levels from baseline. Key covariates were examined to determine heterogeneity of treatment effects; consistency of estimates was assessed using the arm-based method. Results: Toremifene improved all lipids more than any other hormone drug studied (see Table). Most aromatase inhibitors (AIs) did not signifi...
The American Journal of Geriatric Psychiatry, 2019
Observational studies report that people with psychotic major depressive disorder (PMD) have poor... more Observational studies report that people with psychotic major depressive disorder (PMD) have poorer functional outcome than those with non-psychotic major depression (NPMD), but this finding could be explained by less robust recovery and residual symptoms in PMD. In addition, neuropsychological performance is worse in those with PMD than NPMD, both acutely and in remission. The aim of this study was to examine the relative contributions of a history of psychosis and neuropsychological performance to impaired everyday function in patients with remitted later-life major depressive disorder (MDD). We hypothesized that, in later-life patients with MDD, a history of psychotic features and poorer neuropsychological function would be independently associated with poorer everyday functioning, but that poorer neuropsychological performance would be more strongly associated with poorer functioning compared to history of psychosis. In order to place the results in a broader context, we examined everyday functioning in an age-and gender-matched non-psychiatric comparison group. Methods: This cross-sectional design study included 73 patients aged 50 years and older with a history of MDD (n = 51 with NPMD and n = 22 with PMD) in sustained remission and 42 non-psychiatric comparison subjects. Sociodemographic, clinical, neuropsychological, and functional data were collected by an investigator blind to the history of psychotic features. Everyday functioning, the dependent variable, was divided into general functioning (measured by participant-report) and IADL performance (measured by observer-rated assessment). The independent variables were i) history of psychosis and ii) neuropsychological performance in the domains of processing speed, memory, and executive function. Relationships between each independent variable and functioning were analyzed using multiple linear regression models. The relative contribution of history of psychosis and neuropsychological performance to functioning was analyzed using multiple regression models with history of psychosis entered in the first step and the neuropsychological variable in the second step. All models included covariates that were potential confounders. We also calculated effect sizes for the difference in functioning between MDD and non-psychiatric comparison participants. Results: Patients with PMD exhibited substantial deficits in measures of processing speed and, to a lesser extent, executive function, compared to NPMD patients and to population norms. History of psychosis was independently related to poorer IADL performance (b = 0.262, t = 3.03, p = 0.004) and general functioning (b = -0.29, t = -2.46, p = 0.017). Poorer performance on measures of processing speed (b = -0.468, t = -4.99, p <0.0001), executive function-inhibition (b =-0.458, t = -5.04, p <0.0001), and verbal learning (b = -3.05, t = -3.25, p = 0.002) were associated with poorer IADL performance and poorer general functioning (processing speed b = 0.454, t = 4.31, p <0.0001; executive function-inhibition b = 0.334, t = 2.93, p = 0.005; verbal learning b = 0.307, t = 2.78, p = 0.007). When history of psychosis and each neuropsychological measure were entered together into models for IADL and general functioning, psychosis was no longer associated with function. In comparison to non-psychiatric subjects, the effect size of functional impairment in patients with remitted PMD was large (Cohen's d for IADL function = 0.80; Cohen's d for general functioning = 0.97), whereas the impairment was small to moderate in remitted NPMD (Cohen's d for IADL function = 0.10; Cohen's d for general functioning = 0.64). Conclusions: Later-life remitted PMD is associated with poorer everyday functioning compared to NPMD, with clinicallysignificant deficits. However, this relationship is no longer significant when neuropsychological function, especially processing speed, is accounted for. This study advances previous literature by including only patients with rigorously-defined sustained remission and measuring functioning comprehensively using both participant-report and performance-based measures. We will discuss future directions of these research findings, including examining neurobiological correlates of processing speed deficits in remitted PMD.
The Journal of Urology, 2018
time, even in the case of bladder neck suspensions. Among those undergoing a sling for the first ... more time, even in the case of bladder neck suspensions. Among those undergoing a sling for the first procedure, 0.22% underwent a urethrolysis, 1.2% underwent a sling revision or takedown, and 3.4% underwent a repeat sling operation. There was no correlation between provider volume and reoperation rates (r¼0.0058, p¼0.96). There was a wide range of reoperation rates between practices (0-77%). CONCLUSIONS: The sling, even after the mesh controversy with its negative press, dominates as the most common anti-incontinence procedure. Overall, sling failure rates, revisions, and takedowns were acceptably low across various practice settings. These low reoperation rates indicate that both low and high-volume providers can attain good outcomes with the sling.
Critical care (London, England), Jan 24, 2018
Although net ultrafiltration (UF) is frequently used for treatment of fluid overload in criticall... more Although net ultrafiltration (UF) is frequently used for treatment of fluid overload in critically ill patients with acute kidney injury, the optimal intensity of UF is unclear. Among critically ill patients with fluid overload receiving renal replacement therapy (RRT), we examined the association between UF intensity and risk-adjusted 1-year mortality. We selected patients with fluid overload ≥ 5% of body weight prior to initiation of RRT from a large academic medical center ICU dataset. UF intensity was calculated as the net volume of fluid ultrafiltered per day from initiation of either continuous or intermittent RRT until the end of ICU stay adjusted for patient hospital admission body weight. We stratified UF as low (≤ 20 ml/kg/day), moderate (> 20 to ≤ 25 ml/kg/day) or high (> 25 ml/kg/day) intensity. We adjusted for age, sex, body mass index, race, surgery, baseline estimated glomerular filtration rate, oliguria, first RRT modality, pre-RRT fluid balance, duration of RR...
Journal of Cardiovascular Magnetic Resonance, 2015
The Longitudinal Trajectories of Depressive Symptoms and Cognitive Function
The American Journal of Geriatric Psychiatry, 2015
BioMed Research International, 2015
Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial inf... more Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8+T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baseline CD8+T-cell counts (>1065 cells/mm3) had increased AMI risk (adjustedHR=1.82, P<0.001, 95% CI: 1.46 to 2.28). There was evidence that the effect of CD8+T-cell tertiles on AMI risk differed by CD4+T-cell level: compared to uninfected people, HIV-infected people with CD4+T-cell counts ≥200 cells/mm3had increased AMI risk with high CD8+T-cell count, while those with ...
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Papers by Chung-chou Chang