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Dalbeth N.,University of Auckland | Schauer C.,University of Auckland | MacDonald P.,Takeda Global Research and Development | Perez-Ruiz F.,Hospital de Cruces | And 6 more authors.
Annals of the Rheumatic Diseases | Year: 2011

Objective: To identify methods of tophus measurement for gout studies, summarise the properties of these methods and compile a detailed pictorial reference guide to demonstrate the methods. Methods: A systematic search strategy for methods of tophus measurement was formulated. For each method, papers were assessed by two reviewers to summarise information according to the specific components of the Outcomes Measures in Rheumatology (OMERACT) filter: feasibility, truth and discrimination. Detailed images were obtained to construct the reference guide. Results: Eight methods of tophus measurement were identified: counting the total number of tophi, physical measurement using tape measure, physical measurement using Vernier callipers, digital photography, ultrasonography (US), MRI, CT and dual energy CT. Feasibility aspects of the methods are well documented. Physical measurement techniques are more feasible than advanced imaging methods, but do not allow for assessment of intra-articular tophi or for data storage and central reading. The truth aspect of the filter has been documented for many methods, particularly Vernier callipers, US, MRI and CT. Reliability of most methods has been reported as very good or excellent. Sensitivity to change has been reported for all methods except MRI and CT. Conclusion: A variety of methods of tophus assessment have been described for use in clinical trials of chronic gout. Physical measurement techniques (particularly the Vernier calliper method) and US measurement of tophus size appear to meet most aspects of the OMERACT filter.

Dalbeth N.,University of Auckland | McQueen F.M.,University of Auckland | Singh J.A.,University of Alabama at Birmingham | MacDonald P.A.,Takeda Global Research and Development | And 9 more authors.
Journal of Rheumatology | Year: 2011

Despite the recognition that tophus regression is an important outcome measure in clinical trials of chronic gout, there is no agreed upon method of tophus measurement. A number of methods have been used in clinical trials of chronic gout, from simple physical measurement techniques to more complex advanced imaging methods. This article summarizes methods of tophus measurement and discusses their properties. Physical measurement using Vernier calipers meets most aspects of the Outcome Measures in Rheumatology (OMERACT) filter. Rigorous testing of the complex methods, particularly with respect to reliability and sensitivity to change, is needed to determine the appropriate use of these methods. Further information is also required regarding which method of physical measurement is best for use in future clinical trials. The need to develop and test a patient-reported outcome measure of tophus burden is also highlighted. The Journal of Rheumatology Copyright © 2011. All rights reserved.

Murthy N.V.,Glaxosmithkline | Murthy N.V.,Takeda Global Research and Development | Mahncke H.,PositScience | Wexler B.E.,Yale University | And 12 more authors.
Schizophrenia Research | Year: 2012

A recent single-site study (Fisher et al., 2009. Am J Psychiatry. 166 (7) 805-11) showed that repeated training with the Brain Fitness Program (BFP) improved performance on a battery of neuropsychological tasks. If replicated these data suggest an important non-pharmacological method for ameliorating cognitive impairment in schizophrenia. Our study evaluated the BFP training effects in an open-label, multi-site, multinational clinical trial. Fifty-five stable adult patients with schizophrenia on regular antipsychotic medication completed ≥ 32 BFP training sessions over 8-10. weeks. Training effects on cognitive performance and functional capacity outcome measures were measured using CogState® schizophrenia battery, UCSD Performance based Skills Assessment (UPSA-2) and Cognitive Assessment Interview (CAI). BFP training showed a large and significant treatment effect on a training exercise task (auditory processing speed), however this effect did not generalize to improved performance on independent CogState® assessment. There were no significant effects on UPSA-2 or CAI scores. Our study demonstrated the feasibility of implementing BFP training in a multi-site study. However, BFP training did not show significant treatment effects on cognitive performance or functional capacity outcome measures despite showing large and significant effects on a training exercise. © 2012 Elsevier B.V.

Sun S.S.,Virginia Commonwealth University | Sabo R.,Virginia Commonwealth University | Arslanian S.,University of Pittsburgh | Wu R.,Takeda Global Research and Development | Sabo C.,Virginia Commonwealth University
Journal of Public Health (Germany) | Year: 2012

Objective To document age- and sex-related differences in the 16 phenotypes of risk factors for the metabolic syndrome (MS) among adults in the Fels Longitudinal Study (FLS). Methods Data on risk factors for the MS were analyzed in 471 white men and 503 white women in the FLS. We used the Cochran-Armitage test to compare age- and sex-related differences in the prevalence of the 16 diagnostic clusters of positive risk factors. Results Of the 974 subjects, 238 were found to meet diagnostic criteria for 15 of a possible 16 phenotypes of the MS. The prevalence of the MS was four times greater in subjects older than 40 years than in subjects 20-40 years old. Older subjects had more risk factors exceeding criterion values than younger subjects. Among those who met three-to-five criteria for the MS, younger subjects were more likely to have dyslipidemia, less likely to have high blood pressure (HBP), and two times less likely to have impaired fasting plasma glucose (IFG) than subjects 40+ years old. Older men were more likely than older women to have HBP and IFG. . We found that if one of the five risk factors reaches a criterion value, the values for the other four risk factors move closer to their own diagnostic criterion values in apparent synchrony. Conclusions Subjects 40+ years old are four times likelier to have the MS than younger subjects, and older men are at higher risk than older women. The mean values for each of the five risk factors get progressively worse as the number of risk factors meeting diagnostic criteria increases. Therefore, when one factor is found to meet its diagnostic criterion, levels of the other four risk factors should be measured. The different phenotypic patterns that comprise the MS should prompt clinicians to target specific risk factors for prevention or treatment. Certain phenotypes were found more commonly in women and certain others more commonly in men. Similarly, certain phenotypes were found more commonly in older than in younger age groups. These age- and sex-specific phenotypes should help clinicians to identify subjects at highest risk for certain risk factors and to initiate specifically tailored preventive and therapeutic interventions. Our observations should also stimulate clinical investigators and epidemiologists to ascertain what factors determine the sex and age specificity of certain phenotypes of the MS. © The Author(s) 2012.

Balakrishnan K.,University of Texas M. D. Anderson Cancer Center | Verma D.,University of Texas M. D. Anderson Cancer Center | O'Brien S.,University of Texas M. D. Anderson Cancer Center | Kilpatrick J.M.,BioCryst Pharmaceuticals | And 9 more authors.
Blood | Year: 2010

Forodesine is a new and potent purine nucleoside phosphorylase (PNP) inhibitor. Patients with chronic lymphocytic leukemia (CLL) with primary resistance to fludarabine-based therapy or with progressive disease were eligible for oral forodesine (200 mg/d) for up to 24 weeks. Eight patients with median lymphocyte count of 35.9 × 109/L and median serum β2 microglobulin level of 6.45 mg/L were treated. Six had Rai stage III to IV and were previously heavily treated (median prior therapy = 5). Two had transient decrease in lymphocyte count to normal, whereas in 5, disease progressed. Adverse events were mild. Steady-state level of forodesine ranged from 200 to 1300nM and did not reach desired 2μM level. PNP inhibition ranged from 57% to 89% and steady-state 2′-deoxyguanosine (dGuo) concentration median was 1.8μM. Intracellular deoxyguanosine triphosphate (dGTP) increase was very modest, from median of 6μM to 10μM. Compared with in vivo, in vitro incubations of CLL lymphocytes with 10 or 20μM dGuo and forodesine (2μM) resulted in accumulation of higher levels of dGTP (40-250μM) which resulted in increase in apoptosis. Forodesine has biologic activity in CLL; pharmacodynamic parameters suggest that an alternate dosing schedule and/or higher doses to achieve greater intracellular dGTP may be beneficial in this patient population. This study is registered at www.clinicaltrials.gov as #NCT00289549. © 2010 by The American Society of Hematology.

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