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Biomedical subjects

V M Chinchilli

Publications and source records attributed to V M Chinchilli.

At least 19 recordsLinked to original sources
PubMed2004

Acute effects of moderate intensity resistance exercise on bone cell activity.

Resistance exercise has positive effects on bone mass, but little is known about the mechanisms by which this occurs. The purpose of this study was to determine if a single bout of moderate intensity resistance exercise alters biochemical markers of bone cell activity. Indices of bone turnover were measured in nine healthy, untrained men (21.9 +/- 1.2 yrs old), before and following a single 45 minute session of resistance exercise, and during a control trial. A cross-over design was used so that all participants performed both trials in random order. Blood samples were collected immediately before, immediately after, and at 1, 8, 24, and 48 hours post exercise and analyzed for bone-specific alkaline phosphatase (BAP), type I collagen propeptide (PICP), and type I collagen N-telopeptide (sNTX). Urine from the second morning void was collected over four days (day before, day of, and two days following exercise) and analyzed for type I collagen N-telopeptide (uNTX). Exercise resulted in a significant increase (p < 0.05) in the ratio of biochemical markers of bone formation to bone resorption eight hours post exercise, largely due to a decrease in sNTX. Markers return to baseline within 24 hrs. These data suggest that moderate intensity resistance training acutely reduces bone resorption, leading to a favorable change in overall bone turnover, for at least 8 hours post exercise in untrained young men. Further work is needed to determine if long-term benefits to bone strength follow with persistent training.

Adult↗
PubMed2004

Empirical bayes gene screening tool for time-course or dose-response microarray data.

An efficient method to reduce the dimensionality of microarray gene expression data from thousands or tens of thousands of cDNA clones down to a subset of the most differentially expressed cDNA clones is essential in order to simplify the massive amount of data generated from microarray experiments. An extension to the methods of Efron et al. [Efron, B., Tibshirani, R., Storey, J., Tusher, V. (2001). Empirical Bayes analysis of a microarray experiment. J. Am. Statist. Assoc. 96:1151-1160] is applied to a differential time-course experiment to determine a subset of cDNAs that have the largest probability of being differentially expressed with respect to treatment conditions across a set of unequally spaced time points. The proposed extension, which is advocated to be a screening tool, allows for inference across a continuous variable in addition to incorporating a more complex experimental design and allowing for multiple design replications. With the current data the focus is on a time-course experiment; however, the proposed methods can easily be implemented on a dose-response experiment, or any other microarray experiment that contains a continuous variable of interest. The proposed empirical Bayes gene-screening tool is compared with the Efron et al. (2001) method in addition to an adjusted model-based t-value using a time-course data set where the toxicological effect of a specific mixture of chemicals is being studied.

1-Methyl-3-isobutylxanthine↗
PubMed2001

A generalized concordance correlation coefficient for continuous and categorical data.

This paper discusses a generalized version of the concordance correlation coefficient for agreement data. The concordance correlation coefficient evaluates the accuracy and precision between two measures, and is based on the expected value of the squared function of distance. We have generalized this coefficient by applying alternative functions of distance to produce more robust versions of the concordance correlation coefficient. In this paper we extend the application of this class of estimators to categorical data as well, and demonstrate similarities to the kappa and weighted kappa statistics. We also introduce a stratified concordance correlation coefficient which adjusts for explanatory factors, and an extended concordance correlation coefficient which measures agreement among more than two responses. With these extensions, the generalized concordance correlation coefficient provides a unifying approach to assessing agreement among two or more measures that are either continuous or categorical in scale.

Computer Simulation↗
PubMed2001

Summarizing methacholine challenges in clinical research.

In clinical trials in asthma, airway reactivity is commonly assessed by performing a methacholine challenge. Airway reactivity is thought to vary in proportion to asthma severity, and methacholine causes the airways of asthma subjects to constrict, thus lowering forced expiratory volume in 1 second (FEV(1)). A dose-response curve is obtained for each subject who meets standardized eligibility requirements to proceed with a methacholine challenge. When data from a methacholine challenge are used as an outcome variable in analysis, a univariate measure called the PC(20), the concentration of methacholine needed to produce a 20% fall in FEV(1) from baseline, is typically used to summarize the dose-response curve. Questions that arise regarding data generated from the methacholine challenge include: how to express data that do not yield a PC(20) value; whether PC(20) actually represents the best way to capture airway activity as expressed in a methacholine challenge; and whether the baseline FEV(1) is defined appropriately in calculation of PC(20). The impact of these issues on the statistical analysis of methacholine challenge data is described in this article. Some adjustments to the usual estimates of PC(20) and parametric modeling of the entire dose-response curve are proposed as alternatives that address some of the shortcomings of PC(20).

Asthma↗
PubMed2001

The organization of the Asthma Clinical Research Network: a multicenter, multiprotocol clinical trials team.

Asthma is an increasingly serious cause of morbidity and mortality in the United States, affecting approximately 12 million people, including men and women, children and adults, and all racial and ethnic groups. It is now recognized that asthma is a complex disease of varied etiology triggered by a number of factors such as allergens, drugs, chemicals, exercise, cold dry air, infections, and emotions. Asthma is a chronic disease requiring multiple medications to treat and control symptoms as well as medications thought to control the underlying inflammation. Despite major advances in understanding the etiology and pathophysiology of asthma and the development of new therapeutic modalities, the prevalence, severity, and mortality from asthma have all increased over the past decades in all age groups. Hospitalizations for asthma have doubled in adults and increased fivefold for children over the past 20 years. Mortality appears to be particularly high in urban and rural minority populations. Asthma continues to place a heavy burden on patients and their families as well as the health-care system. In an attempt to respond to the need for well-designed clinical trials to allow rapid evaluation of new and existing therapeutic approaches for asthma and for dissemination of laboratory and clinical findings to the health-care community, the Division of Lung Diseases, National Heart, Lung, and Blood Institute, established the Asthma Clinical Research Network.

Adult↗
PubMed2001

Modem remote support of pulmonary-function testing and quality control systems.

The data coordinating center (DCC) of the Asthma Clinical Research Network (ACRN) is responsible for the support of 11 pulmonary-function testing systems and two quality control systems. Pulmonary-function data from these systems are used as outcome indicators in studies conducted by the ACRN. Each of these systems is composed of a spirometer, a personal computer for data acquisition from the spirometer, a modem, and a printer. These systems are located at six clinical centers nationwide. An analysis conducted at the beginning of the first ACRN protocol identified the following requirements: (1) standard pulmonary-function testing, (2) standard methacholine-challenge testing, (3) the ability to handle simultaneous multiple protocols as well as have data from non-ACRN subjects, (4) the ability to separate data from different protocols as well as separate ACRN and non-ACRN data, (5) the ability to transmit data from the remote clinical centers to the DCC, (6) the ability to ensure quality data and to report on those results, and (7) the ability to provide remote support.

Asthma↗
PubMed2001

Development and deployment of an internet-based data management system for use by the Asthma Clinical Research Network.

Data management system development for the first Asthma Clinical Research Network (ACRN) study began at the data coordinating center (DCC) in May 1995 with the requirement for delivery of a production system by November 1995. Special methods had to be used to establish an internet local area network (LAN), place clinical client systems, and achieve an accelerated software development cycle. The development of a fully integrated data management system prior to the start of the study was not possible. Therefore an early analysis focused on identifying discrete groupings of data management functions that would allow development of distinct database modules to provide specific functionality such as subject randomization, subject registration, and data entry. The modules were categorized as either being associated with clinical centers or the DCC so that the clinical center modules could be developed and delivered to meet the start date of the study. In the second phase of development during the relatively slow patient-enrollment period, the DCC functional modules were delivered discretely over time. While at the time this development model was a necessity due to limited DCC resources, it continues to be used today as it permits the DCC to implement studies more rapidly and efficiently for the ACRN. This paper describes the methodologies used to develop an internet-based LAN, establish clinical center client systems, establish DCC client and server operations, and develop a data management system. It describes the circumstances that contributed to the development of these systems and the special methodologies developed. The technical aspects of the data management system and LAN are presented as well as a description of the requirements and constraints analysis used to develop the hardware and software systems.

Asthma↗
PubMed2001

Robust estimators of the concordance correlation coefficient.

This paper proposes a generalized version of Lin' s concordance correlation coefficient for the agreement assessment of continuous data. Lin's coefficient evaluates the accuracy and precision between two measures, and is based on the expected value of the squared distance function. We generalize Lin's coefficient, apply alternative distance functions, and produce more robust versions of the concordance correlation coefficient. In this paper, we develop the asymptotic theory for this class of estimators, investigate small-sample properties via computer simulation, and demonstrate their use with two real data examples.

Algorithms↗
PubMed2001

A measure of association between two sets of multivariate responses.

Let X and Y denote two distinct sets of multivariate responses, each of which can be a mix of continuous and ordinal data. Suppose that it is of interest to quantify the overall strength of association between X and Y. Our two approaches to this problem are to construct correlation coefficients similar to Kendall's tau in the bivariate case. The first approach uses the average concordance of each pair of individuals, where the average concordance is obtained across all possible pairings of variables between the two sets, as the kernel of the U-statistic. Then the overall correlation between the two sets of multivariate data is expressed in terms of the expected value of the kernel. The second approach estimates pairwise Kendall's taus between the two sets, then uses a summary measure to quantify the overall association. One option for the summary measure is to take the average of taus, and another option is to take the distance of taus. The two approaches yield the same results when the summary measure of the latter is the average. However, using the distance of taus can sometimes detect relationships not seen in the average. We illustrate the proposed methods using data from a national asthma clinical trial in which the first set of variables comprises 12 binary responses of skin allergen tests and the second set of variables comprises three continuous outcomes of pulmonary function and one clinical outcome.

Adrenergic beta-Agonists↗
PubMed2001

Is nausea associated with chronic hepatitis C infection?

OBJECTIVES: Hepatitis C virus is a common chronic infection that is widely associated with symptoms of fatigue and pain in the right upper quadrant. Nausea may be an underrecognized symptom. This study was designed to study the frequency of nausea in patients with hepatitis C virus infection compared to controls. METHODS: A cross-sectional study design with consecutive outpatients was used. Three groups were administered a dyspepsia and a previously validated Nausea Profile questionnaire. Univariate and multivariate analysis was performed. RESULTS: A total of 64 hepatitis C virus (HCV) patients, 53 liver disease controls (LC), and 64 normal controls (NC) were studied. An increased period prevalence of nausea was found in HCV patients 43% versus 29.7% in NC and 18.9% in LC (p = 0.009). There was an increased frequency of fatigue and abdominal pain in HCV patients over 1 month compared to LC and NC combined (p = 0.0001 and 0.0065 respectively). The Nausea Profile score revealed statistically higher total scores and higher subscale scores in the HCV group compared to controls. The total NP score expressed as a percentage of the maximum was 27% in HCV versus 12.7% for LC and 9.2% for NC (p = 0.0005). The odds of nausea using logistic regression were 2.1 CI (1.0-4.5) in HCV patients compared to controls (p = 0.05). Using linear regression, higher Nausea Profile scores were found to be independently associated with the diagnosis of HCV (.0005), fatigue (p = 0.0003), and abdominal pain (p = 0.0001). CONCLUSIONS: HCV infection is associated with an increased risk for nausea. The strong association between abdominal pain and nausea may be a clue to the etiology of nausea in these patients. Further etiological studies are needed.

Abdominal Pain↗
PubMed2001

Safety and reproducibility of sputum induction in asthmatic subjects in a multicenter study.

The safety of sputum induction and the reproducibility of measurements in induced sputum in multicenter studies is unknown. We examined the safety of sputum induction in a two-visit, six-center study in 79 subjects with moderate to severe asthma (mean +/- SD FEV(1) 71 +/- 12% predicted, 67% taking inhaled corticosteroids). In addition, we compared the reproducibility of markers of inflammation in induced sputum with the reproducibility of the FEV(1) and the methacholine PC(20). The FEV(1) decreased > or = 20% from the postbronchodilator baseline in 14% of all subjects and in 25% of subjects whose initial prebronchodilator baseline was 40 to 60% of predicted. All subjects responded promptly to additional albuterol treatment, and no subject developed refractory bronchoconstriction requiring treatment other than reversal of bronchospasm in the study laboratory. The reproducibility of measurements of the eosinophil percentage, eosinophil cationic protein, tryptase, and methacholine PC(20) were similar (concordance correlation coefficients of 0.74, 0.81, 0.79, and 0.74, respectively), without any significant among-center effect. We conclude that sputum induction can be performed safely in subjects with moderate to severe asthma in multicenter clinical trials when carried out under carefully monitored conditions. Importantly, we demonstrate that measurement of markers of inflammation in induced sputum is as reproducible as methacholine PC(20) and should prove useful in the assessment of airway inflammation in multicenter clinical trials.

Aged↗
PubMed2001

The utility of peak flow, symptom scores, and beta-agonist use as outcome measures in asthma clinical research.

STUDY OBJECTIVES: Several methods of utilizing peak expiratory flow (PEF) and other markers of disease activity have been suggested as useful in the management of asthma. It remains unclear, however, as to which surrogate markers of disease status are discriminative indicators of treatment failure, suitable for use in clinical trials. DESIGN: We analyzed the operating characteristics of 66 surrogate markers of treatment failure using a receiver operating characteristic (ROC) curve analysis. PARTICIPANTS: Information regarding FEV(1), symptoms, beta(2)-agonist use, and PEF was available from 313 subjects previously enrolled in two Asthma Clinical Research Network trials, in which 71 treatment failures occurred (defined by a 20% fall in FEV(1) from baseline). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: None of the measures had an acceptable ability to discriminate subjects with a > or % fall in FEV(1) from those without, regardless of the duration of the period of analysis or the criteria for test positivity employed. Areas under the ROC curves generated ranged from 0.51 to 0.79, but none were statistically superior. Sensitivity and specificity combinations were generally poor at all cutoff values; true-positive rates could not be raised without unacceptably elevating false-positive rates concurrently. CONCLUSIONS: Studies that seek to detect treatment failure defined by a significant fall in FEV(1) should not use such individual surrogate measures to estimate disease severity.

Adolescent↗
PubMed2000

An alternative index for assessing profile similarity in bioequivalence trials.

In a typical bioequivalence trial, summary measures of the plasma concentration versus time profile are used to compare two formulations of a drug product. Commonly used measures include area under the curve (AUC), maximum plasma concentration (C(max)) and time to maximum concentration (T(max)). Equivalence of these summary measures, in general, does not guarantee equivalence of the entire profile. Rescigno and Chinchilli and Elswick propose indices which measure profile similarity, but can be overly sensitive to unimportant differences and are not easily interpreted pharmacologically. We propose an alternative index based on smoothing the relative difference between bioavailability profiles. This provides a method for assessing bioequivalence over the entire profile which has a familiar interpretation and can be tuned to provide a compromise between the insensitivity to pattern differences of summary measures and the oversensitivity of pointwise comparisons.

Area Under Curve↗