Browsing by Author "Barnhart, Huiman"
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Item Open Access Assessing Interchangeability among Raters with Continuous Outcomes in Agreement Studies(2020) Wang, TongrongIn various medical settings, new raters are available to take measurements for evaluations of medical conditions. One may want to use new and existing raters simultaneously or replace the existing raters with the new one due to low-cost or portability. For both situations, the raters should be interchangeable, such that it makes no clinical difference in which raters measure the subject in the population of interest. This is a problem of claiming sufficient agreement among the raters. Existing literature on assessing agreement is limited to two raters, and those for more than two raters have various issues of interpretability or unrealistic assumptions. This dissertation proposes new overall agreement indexes for multiple raters by extending the preferred pairwise agreement indexes, coverage probability, total deviation index, and the relative area under the coverage probability. The new indexes have intuitive interpretations regarding the clinical judgment of interchangeability. A unified generalized estimating equation (GEE) approach is developed for inference. Simulation studies are conducted to assess the performance and theoretical properties of the proposed approach. A blood pressure dataset is used for illustration. Due to limited literature on sample size calculation in the agreement study, this dissertation investigates sample size formulas with pre-specified power if one of the proposed overall agreement indices is used for claiming satisfactory interchangeability. While the sample size formulas based on the inference of the GEE framework is somewhat complicated, simplified formulas giving conservative sample size estimation is also proposed for easy implementation. Our simulation studies indicated that the sample size formulas work well if the resulting number of subjects is at least 30 where each rater takes about 3 replicates. We demonstrate how to design an agreement study based on a pilot blood pressure data set. The U.S. Food and Drug Administration recommends using a regression-based approach in case of replacing a new device with a commercially marketed device. In the third part, we discuss the potential pitfalls of this approach and compare it with the coverage probability approach, the currently preferred approach for assessing agreement. A respiratory rate dataset is used to illustrate the issues of the regression-based approach.
Item Open Access Clinical Outcomes Among High-Risk Primary Care Patients With Diabetic Kidney Disease: Methodological Challenges and Results From the STOP-DKD Study.(Medical care, 2024-07) Bosworth, Hayden B; Patel, Uptal D; Lewinski, Allison A; Davenport, Clemontina A; Pendergast, Jane; Oakes, Megan; Crowley, Matthew J; Zullig, Leah L; Patel, Sejal; Moaddeb, Jivan; Miller, Julie; Malone, Shauna; Barnhart, Huiman; Diamantidis, Clarissa JBackground/objective
Slowing the progression of diabetic kidney disease (DKD) is critical. We conducted a randomized controlled trial to target risk factors for DKD progression.Methods
We evaluated the effect of a pharmacist-led intervention focused on supporting healthy behaviors, medication management, and self-monitoring on decline in estimated glomerular filtration rate (eGFR) for 36 months compared with an educational control.Results
We randomized 138 individuals to the intervention group and 143 to control. At baseline, mean (SD) eGFR was 80.7 (21.7) mL/min/1.73m2, 56% of participants had chronic kidney disease and a history of uncontrolled hypertension with a baseline SBP of 134.3 mm Hg. The mean (SD) decline in eGFR by cystatin C from baseline to 36 months was 5.0 (19.6) and 5.9 (18.6) mL/min/1.73m2 for the control and intervention groups, respectively, with no significant between-group difference (P=0.75).Conclusions
We did not observe a significant difference in clinical outcomes by study arm. However, we showed that individuals with DKD will engage in a pharmacist-led intervention. The potential explanations for a lack of change in DKD risk factors can be attributed to 5 broad issues, challenges: (1) associated with enrolling patients with low eGFR and poor BP control; (2) implementing the intervention; (3) limited duration during which to observe any clinical benefit from the intervention; (4) potential co-intervention or contamination; and (5) low statistical power.Item Open Access Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations.(Hepatology (Baltimore, Md.), 2014-02) Kleiner, David E; Chalasani, Naga P; Lee, William M; Fontana, Robert J; Bonkovsky, Herbert L; Watkins, Paul B; Hayashi, Paul H; Davern, Timothy J; Navarro, Victor; Reddy, Rajender; Talwalkar, Jayant A; Stolz, Andrew; Gu, Jiezhun; Barnhart, Huiman; Hoofnagle, Jay H; Drug-Induced Liver Injury Network (DILIN)Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury.We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome.Item Open Access Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance.(PloS one, 2013-01) Steuerwald, Nury M; Foureau, David M; Norton, H James; Zhou, Jie; Parsons, Judith C; Chalasani, Naga; Fontana, Robert J; Watkins, Paul B; Lee, William M; Reddy, K Rajender; Stolz, Andrew; Talwalkar, Jayant; Davern, Timothy; Saha, Dhanonjoy; Bell, Lauren N; Barnhart, Huiman; Gu, Jiezhun; Serrano, Jose; Bonkovsky, Herbert LDrug-induced liver injury (DILI) is the most common cause of acute liver failure in the United-States. The aim of the study was to describe serum immune profiles associated with acute DILI, to investigate whether there are profiles associated with clinical features or types of DILI and/or with prognosis, and to assess temporal changes in levels. Twenty-seven immune analytes were measured in the sera of 78 DILI subjects in the Drug-Induced Liver Injury Network (DILIN) and compared with 40 healthy controls. Immune analytes (14 cytokines, 7 chemokines and 6 growth factors) were measured by BioPlex multiplex ELISA at DILI onset and after 6 months. A modeling process utilizing immune principles was used to select a final set of variables among 27 immune analytes and several additional clinical lab values for prediction of early death (within 6 months of DILI onset). Nineteen of the 27 immune analytes were differentially expressed among healthy control, DILI onset and 6-month cohorts. Disparate patterns of immune responses, especially innate and adaptive cellular (mostly TH17) immunity were evident. Low values of four immune analytes (IL-9, IL-17, PDGF-bb and RANTES) and serum albumin are predictive of early death [PPV = 88% (95% CI, 65%-100%), NPV = 97% (95% CI, 93%-100%), accuracy = 96% (95% CI, 92%-100%)].Acute DILI is associated with robust and varying immune responses. High levels of expression of cytokines associated with innate immunity are associated with a poor prognosis, whereas high levels of expression of adaptive cytokines are associated with good long-term prognosis and eventual recovery. Serum immune analyte profiles at DILI onset appear to be of prognostic, and perhaps, diagnostic significance.Item Open Access Racial differences in nocturnal dipping status in diabetic kidney disease: Results from the STOP-DKD (Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease) study.(Journal of clinical hypertension (Greenwich, Conn.), 2017-12) Zullig, Leah L; Diamantidis, Clarissa J; Bosworth, Hayden B; Bhapkar, Manjushri V; Barnhart, Huiman; Oakes, Megan M; Pendergast, Jane F; Miller, Julie J; Patel, Uptal DWhile racial variation in ambulatory blood pressure (BP) is known, patterns of diurnal dipping in the context of diabetic kidney disease have not been well defined. The authors sought to determine the association of race with nocturnal dipping status among participants with diabetic kidney disease enrolled in the STOP-DKD (Simultaneous Risk Factor Control Using Telehealth to Slow Progression of Diabetic Kidney Disease) trial. The primary outcome was nocturnal dipping-percent decrease in average systolic BP from wake to sleep-with categories defined as reverse dippers (decrease <0%), nondippers (0%-<10%), and dippers (≥10%). Twenty-four-hour ambulatory BP monitoring was completed by 108 participants (54% were nondippers, 24% were dippers, and 22% were reverse dippers). In adjusted models, the common odds of reverse dippers vs nondippers/dippers and reverse dippers/nondippers vs dippers was 2.6 (95% confidence interval, 1.2-5.8) times higher in blacks than in whites. Without ambulatory BP monitoring data, interventions that target BP in black patients may be unable to improve outcomes in this high-risk group.Item Open Access Short-term effects of the DASH diet in adults with moderate chronic kidney disease: a pilot feeding study.(Clinical kidney journal, 2016-08) Tyson, Crystal C; Lin, Pao-Hwa; Corsino, Leonor; Batch, Bryan C; Allen, Jenifer; Sapp, Shelly; Barnhart, Huiman; Nwankwo, Chinazo; Burroughs, Jasmine; Svetkey, Laura PAlthough the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP) for adults with normal kidney function, evidence is lacking regarding its safety and efficacy in chronic kidney disease (CKD). We aimed to test the effects of the DASH diet on serum electrolytes and BP in adults with moderate CKD.In a prospective before-after feeding study, 11 adults with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m(2) and medication-treated hypertension were provided a reduced-sodium, run-in diet for 1 week followed by a reduced-sodium, DASH diet for 2 weeks. Changes in serum electrolytes and BP were compared pre-post DASH.Eleven participants underwent feeding; 1 completed 1 week and 10 completed 2 weeks of DASH. Compared with baseline, DASH modestly increased serum potassium at 1 week (mean ± standard deviation, +0.28 ± 0.4 mg/dL; P = 0.043) but had no significant effect on potassium at 2 weeks (+0.15 ± 0.28 mg/dL; P = 0.13). Serum bicarbonate was reduced (-2.5 ± 3.0 mg/dL; P = 0.03) at 2 weeks. Neither incident hyperkalemia nor new onset metabolic acidosis was observed. Clinic BP and mean 24-h ambulatory BP was unchanged. DASH significantly reduced mean nighttime BP (-5.3 ± 5.8 mmHg; P = 0.018), and enhanced percent declines in both nocturnal systolic BP (-2.1% to -5.1%; P = 0.004) and diastolic BP (-3.7% to -10.0%; P = 0.008).These pilot data suggest that a reduced-sodium DASH dietary pattern does not cause acute metabolic events in adults with moderate CKD and may improve nocturnal BP. Definitive studies are needed to determine long-term effects of DASH in CKD.Item Open Access Statistical Issues in Testing Conformance with the Quantitative Imaging Biomarker Alliance (QIBA) Profile Claims.(Academic radiology, 2016-04) Obuchowski, Nancy A; Buckler, Andrew; Kinahan, Paul; Chen-Mayer, Heather; Petrick, Nicholas; Barboriak, Daniel P; Bullen, Jennifer; Barnhart, Huiman; Sullivan, Daniel CA major initiative of the Quantitative Imaging Biomarker Alliance is to develop standards-based documents called "Profiles," which describe one or more technical performance claims for a given imaging modality. The term "actor" denotes any entity (device, software, or person) whose performance must meet certain specifications for the claim to be met. The objective of this paper is to present the statistical issues in testing actors' conformance with the specifications. In particular, we present the general rationale and interpretation of the claims, the minimum requirements for testing whether an actor achieves the performance requirements, the study designs used for testing conformity, and the statistical analysis plan. We use three examples to illustrate the process: apparent diffusion coefficient in solid tumors measured by MRI, change in Perc 15 as a biomarker for the progression of emphysema, and percent change in solid tumor volume by computed tomography as a biomarker for lung cancer progression.