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Psoriasis: HELP
Articles by Vernon T. Farewell
Based on 26 articles published since 2008
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Between 2008 and 2019, V. Farewell wrote the following 26 articles about Psoriasis.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Article Patterns of peripheral joint involvement in psoriatic arthritis-Symmetric, ray and/or row? 2018

Chandran, Vinod / Stecher, Lynne / Farewell, Vern / Gladman, Dafna D. ·Departments of Medicine & Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Centre for Prognosis Studies in The Rheumatic Diseases, Krembil Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada. · Institute of Medical Statistics and Epidemiology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Strasse 22, 81675 Munich, Germany. · MRC Biostatistics Unit, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom. · Centre for Prognosis Studies in The Rheumatic Diseases, Krembil Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address: dafna.gladman@utoronto.ca. ·Semin Arthritis Rheum · Pubmed #29724452.

ABSTRACT: OBJECTIVE: We sought to examine whether joint involvement in psoriatic arthritis (PsA) follows a symmetric, ray, and/or row pattern using longitudinal data. METHODS: Data on activity and clinical damage of the joints of the hands and feet were obtained from a PsA cohort. For each analysis (symmetry, ray or row) for each outcome (joint damage and activity) expected values for table cells under the null hypothesis that joints progress independently to damage or activity were calculated based on a logistic regression model with patient level random effects for the probability of involvement developing between clinic visits. To determine the consistency of observed with expected values, goodness-of-fit tests were performed. RESULTS: Data from 704 patients were available. The 511 (552) patients with no hand (foot) damage at clinic entry were used for analyses of hand (foot) damage. When considering joint damage, there was strong evidence against independence of joint involvement based on evident symmetric patterns. There was little suggestion of ray patterns of joint damage. There was considerable evidence for row pattern of involvement of joints. When considering joint activity, symmetric patterns were also evident but, unlike joint damage, there was evidence of ray patterns, most notably in the hands. There was also evidence for row pattern involvement. CONCLUSION: Patterns of peripheral joint involvement seen over time in PsA patients, demonstrate consistency with expected ray patterns of disease activity, especially in the hands, but there is also considerable evidence for symmetric and row patterns for both joint damage and activity.

2 Article Trivariate mover-stayer counting process models for investigating joint damage in psoriatic arthritis. 2016

Yiu, Sean / Tom, Brian D M / Farewell, Vernon T. ·MRC Biostatistics Unit, Cambridge, CB2 0SR, U.K. ·Stat Med · Pubmed #27501256.

ABSTRACT: In psoriatic arthritis, many patients do not develop permanent joint damage even after a prolonged follow-up. This has led several authors to consider the possibility of a subpopulation of stayers (those who do not have the propensity to experience the event of interest), as opposed to assuming the entire population consist of movers (those who have the propensity to experience the event of interest). In addition, it is recognised that the damaged joints process may act very differently across different joint areas, particularly the hands, feet and large joints. From a clinical perspective, interest lies in identifying possible relationships between the damaged joints processes in these joint areas for the movers and estimating the proportion of stayers in these joint areas, if they exist. For this purpose, this paper proposes a novel trivariate mover-stayer model consisting of mover-stayer truncated negative binomial margins, and patient-level dynamic covariates and random effects in the models for the movers and stayers, respectively. The model is then extended to have a two-level mover-stayer structure for its margins so that the nature of the stayer property can be investigated. A particularly attractive feature of the proposed models is that only an optimisation routine is required in their model fitting procedures. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

3 Article On Modelling Minimal Disease Activity. 2016

Jackson, Christopher H / Su, Li / Gladman, Dafna D / Farewell, Vernon T. ·MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge University, Cambridge, UK. · University of Toronto and Toronto Western Hospital, Toronto, Ontario, Canada. ·Arthritis Care Res (Hoboken) · Pubmed #26315478.

ABSTRACT: OBJECTIVE: To explore methods for statistical modelling of minimal disease activity (MDA) based on data from intermittent clinic visits. METHODS: The analysis was based on a 2-state model. Comparisons were made between analyses based on "complete case" data from visits at which MDA status was known, and the use of hidden model methodology that incorporated information from visits at which only some MDA defining criteria could be established. Analyses were based on an observational psoriatic arthritis cohort. RESULTS: With data from 856 patients and 7,024 clinic visits, analysis was based on virtually all visits, although only 62.6% provided enough information to determine MDA status. Estimated mean times for an episode of MDA varied from 4.18 years to 3.10 years, with smaller estimates derived from the hidden 2-state model analysis. Over a 10-year period, the estimated expected times spent in MDA episodes of longer than 1 year was 3.90 to 4.22, and the probability of having such an MDA episode was estimated to be 0.85 to 0.91, with longer times and greater probabilities seen with the hidden 2-state model analysis. CONCLUSION: A 2-state model provides a useful framework for the analysis of MDA. Use of data from visits at which MDA status can not be determined provide more precision, and notable differences are seen in estimated quantities related to MDA episodes based on complete case and hidden 2-state model analyses. The possibility of bias, as well as loss of precision, should be recognized when complete case analyses are used.

4 Article A corrected formulation for marginal inference derived from two-part mixed models for longitudinal semi-continuous data. 2016

Tom, Brian Dm / Su, Li / Farewell, Vernon T. ·Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, UK brian.tom@mrc-bsu.cam.ac.uk. · Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, UK. ·Stat Methods Med Res · Pubmed #24201470.

ABSTRACT: For semi-continuous data which are a mixture of true zeros and continuously distributed positive values, the use of two-part mixed models provides a convenient modelling framework. However, deriving population-averaged (marginal) effects from such models is not always straightforward. Su et al. presented a model that provided convenient estimation of marginal effects for the logistic component of the two-part model but the specification of marginal effects for the continuous part of the model presented in that paper was based on an incorrect formulation. We present a corrected formulation and additionally explore the use of the two-part model for inferences on the overall marginal mean, which may be of more practical relevance in our application and more generally.

5 Article Validation of the Toronto Psoriatic Arthritis Screen Version 2 (ToPAS 2). 2015

Tom, Brian D M / Chandran, Vinod / Farewell, Vernon T / Rosen, Cheryl F / Gladman, Dafna D. ·From the MRC Biostatistics Unit, UK Institute of Public Health, Cambridge, UK; the Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; Division of Dermatology, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.B.D. Tom, PhD, MRC Biostatistics Unit, UK Institute of Public Health; V. Chandran, MBBS, MD, DM, PhD, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; V.T. Farewell, PhD, MRC Biostatistics Unit, UK Institute of Public Health; C.F. Rosen, MD, FRCPC, Division of Dermatology, Toronto Western Hospital, University of Toronto; D.D. Gladman, MD, FRCPC, Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital. ·J Rheumatol · Pubmed #25834198.

ABSTRACT: OBJECTIVE: We previously developed and performed an initial validation of a screening questionnaire, the Toronto Psoriatic Arthritis Screen (ToPAS), for psoriatic arthritis (PsA). In our original analysis, we found that the index constructed appeared to discriminate well between those with a confirmed diagnosis of PsA and those without PsA in various clinical settings. However, it was suggested that ToPAS would benefit from additional refinement to the questions and the scoring system, because items pertaining to axial involvement were not included in our original index. Subsequently, a second version of ToPAS was developed, ToPAS 2, which incorporated the suggested refinements. We aimed to validate ToPAS 2 as a screening instrument for PsA. METHODS: ToPAS 2 was administered to 3 "diagnostic" groups of individuals - patients with PsA, patients with psoriasis, and healthy controls, and the data collected were analyzed. RESULTS: It was found that the new version of ToPAS, ToPAS 2, again performed well, with the axial domain now featuring in the new scoring system. The constructed index, ToPAS2_cap, had an overall area under the receiver-operation curve of 0.910, with overall values of sensitivity and specificity, at a cutpoint of 8 (or 7), of 87.2% (92.0%) and 82.7% (77.2%), respectively. CONCLUSION: ToPAS 2 shows much promise as a screening instrument for identifying PsA both in people with psoriasis and in individuals from the general population. Its performance against other proposed screening instruments for PsA should be evaluated in other clinics and for other study designs.

6 Article A likelihood-based two-part marginal model for longitudinal semicontinuous data. 2015

Su, Li / Tom, Brian Dm / Farewell, Vernon T. ·Medical Research Council Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, UK. li.su@mrc-bsu.cam.ac.uk. · Medical Research Council Biostatistics Unit, Institute of Public Health, University Forvie Site, Cambridge, UK. ·Stat Methods Med Res · Pubmed #21873302.

ABSTRACT: Two-part models are an attractive approach for analysing longitudinal semicontinuous data consisting of a mixture of true zeros and continuously distributed positive values. When the population-averaged (marginal) covariate effects are of interest, two-part models that provide straightforward interpretation of the marginal effects are desirable. Presently, the only available approaches for fitting two-part marginal models to longitudinal semicontinuous data are computationally difficult to implement. Therefore, there exists a need to develop two-part marginal models that can be easily implemented in practice. We propose a fully likelihood-based two-part marginal model that satisfies this need by using the bridge distribution for the random effect in the binary part of an underlying two-part mixed model; and its maximum likelihood estimation can be routinely implemented via standard statistical software such as the SAS NLMIXED procedure. We illustrate the usage of this new model by investigating the marginal effects of pre-specified genetic markers on physical functioning, as measured by the Health Assessment Questionnaire, in a cohort of psoriatic arthritis patients from the University of Toronto Psoriatic Arthritis Clinic. An added benefit of our proposed marginal model when compared to a two-part mixed model is the robustness in regression parameter estimation when departure from the true random effects structure occurs. This is demonstrated through simulation.

7 Article The versatility of multi-state models for the analysis of longitudinal data with unobservable features. 2014

Farewell, Vernon T / Tom, Brian D M. ·MRC Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge, CB2 0SR, UK, vern.farewell@mrc-bsu.cam.ac.uk. ·Lifetime Data Anal · Pubmed #23225140.

ABSTRACT: Multi-state models provide a convenient statistical framework for a wide variety of medical applications characterized by multiple events and longitudinal data. We illustrate this through four examples. The potential value of the incorporation of unobserved or partially observed states is highlighted. In addition, joint modelling of multiple processes is illustrated with application to potentially informative loss to follow-up, mis-measured or missclassified data and causal inference.

8 Article The functional MICA-129 polymorphism is associated with skin but not joint manifestations of psoriatic disease independently of HLA-B and HLA-C. 2013

Pollock, R A / Chandran, V / Pellett, F J / Thavaneswaran, A / Eder, L / Barrett, J / Rahman, P / Farewell, V / Gladman, D D. ·University of Toronto Psoriatic Arthritis Program, Toronto Western Research Institute, Toronto, Ontario, Canada. ·Tissue Antigens · Pubmed #23611695.

ABSTRACT: A methionine/valine polymorphism at amino acid 129 of the major histocompatibility complex class I chain-related gene A (MICA-129) categorizes alleles into strong and weak binders of the natural killer (NK) and T-cell receptor NKG2D. We investigated whether MICA-129 is differentially associated with skin and joint manifestations of psoriatic disease (PsD) independently of human leukocyte antigen (HLA)-C and HLA-B in patients and controls from Toronto and St. John's. The MICA-129 methionine (Met) allele, particularly Met/Met homozygosity, was strongly associated with both cutaneous psoriasis (PsC) and psoriatic arthritis (PsA) independently of HLA-B and HLA-C in Toronto patients, and was also associated with PsA in St. John's patients, but with no additional effect of Met/Met homozygosity. No association remained after adjustment for HLA alleles in St. John's patients. MICA-129 was not associated with PsA when compared with PsC. We conclude that MICA-129 is a marker of skin manifestations of PsD that is independent of HLA class I in Toronto patients.

9 Article Mixture distributions in multi-state modelling: some considerations in a study of psoriatic arthritis. 2013

O'Keeffe, Aidan G / Tom, Brian D M / Farewell, Vernon T. ·MRC Biostatistics Unit, Cambridge, U.K. aidan.okeeffe@mrc-bsu.cam.ac.uk ·Stat Med · Pubmed #22833400.

ABSTRACT: In many studies, interest lies in determining whether members of the study population will undergo a particular event of interest. Such scenarios are often termed 'mover-stayer' scenarios, and interest lies in modelling two sub-populations of 'movers' (those who have a propensity to undergo the event of interest) and 'stayers' (those who do not). In general, mover-stayer scenarios within data sets are accounted for through the use of mixture distributions, and in this paper, we investigate the use of various random effects distributions for this purpose. Using data from the University of Toronto psoriatic arthritis clinic, we present a multi-state model to describe the progression of clinical damage in hand joints of patients with psoriatic arthritis. We consider the use of mover-stayer gamma, inverse Gaussian and compound Poisson distributions to account for both the correlation amongst joint locations and the possible mover-stayer situation with regard to clinical hand joint damage. We compare the fits obtained from these models and discuss the extent to which a mover-stayer scenario exists in these data. Furthermore, we fit a mover-stayer model that allows a dependence of the probability of a patient being a stayer on a patient-level explanatory variable.

10 Article Longitudinal study of the bidirectional association between pain and depressive symptoms in patients with psoriatic arthritis. 2012

Husted, Janice A / Tom, Brian D / Farewell, Vernon T / Gladman, Dafna D. ·University of Waterloo, Waterloo, Ontario, Canada. ·Arthritis Care Res (Hoboken) · Pubmed #22231988.

ABSTRACT: OBJECTIVE: To test the bidirectional hypothesis that depressive symptoms influence changes in pain over time, and pain influences changes in depressive symptoms. METHODS: A total of 394 patients attending the University of Toronto Psoriatic Arthritis clinic were followed over a mean period of 7.5 years with annual assessments, including number of swollen joints (SJC), Health Assessment Questionnaire (HAQ), and the Medical Outcomes Survey Short Form 36 (SF-36). Linear mixed-effects models were used to examine the cross- and lagged associations between the changes in HAQ pain and in the SF-36 mental component summary (MCS) score, adjusting for SJC and other covariates. RESULTS: The strongest predictors of changes in pain, SJC, and depressive symptoms between visits were scores of the corresponding variables at the previous visit, with standardized regression coefficients exceeding 0.75 in absolute value. There was, however, evidence of a small, but consequential, bidirectional relationship (i.e., standardized regression coefficients <0.3) between depressive symptoms and pain. Both previous MCS scores and change in MCS scores were associated with change in pain between visits; conversely, previous pain scores and change in pain scores were associated with change in depressive symptoms between visits. CONCLUSION: Even though cross-variable associations between pain and depressive symptoms exist, changes in pain and depressive symptoms appear to be strongly driven by their measurements at the previous visit. To optimize patient outcomes, a clinical approach that assesses and treats clinically significant depressive symptoms, as well as pain, is required.

11 Article Intermittent observation of time-dependent explanatory variables: a multistate modelling approach. 2011

Tom, Brian D M / Farewell, Vernon T. ·MRC Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge CB2 0SR, UK. brian.tom@mrc-bsu.cam.ac.uk ·Stat Med · Pubmed #22139873.

ABSTRACT: Motivated by investigations of factors related to various patient-reported outcome measures in psoriatic arthritis patients, after controlling for the effect of disease activity on these outcomes, we outline an approach for dealing with a rapidly fluctuating explanatory variable in a multistate model. On the basis of a representation of this variable as an ordinal classification, we suggest the use of an expanded multistate model. We examine the bias in estimating effects associated with other variables via simulation for different modelling choices. We present an analysis of a motivating data set on physical functional disability in psoriatic arthritis patients.

12 Article Differential major histocompatibility complex class I chain-related A allele associations with skin and joint manifestations of psoriatic disease. 2011

Pollock, R / Chandran, V / Barrett, J / Eder, L / Pellett, F / Yao, C / Lino, M / Shanmugarajah, S / Farewell, V T / Gladman, D D. ·Psoriatic Arthritis Program, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Research Institute, University of Toronto, Toronto, Ontario, Canada. ·Tissue Antigens · Pubmed #21457151.

ABSTRACT: About 30% of patients with psoriasis have psoriatic arthritis (PsA), an inflammatory arthritis that can affect both axial and peripheral joints. Major histocompatibility complex class I chain-related A (MICA) alleles have previously been shown to be associated with PsA; however it is unclear whether there is a differential association of MICA alleles with skin and joint manifestations of PsA. Here, we describe a case-control study that aims to validate previously reported MICA allele associations with PsA and determine whether MICA alleles differentiate patients with PsA from those with psoriasis without PsA. Two hundred forty-nine unrelated Caucasian PsA patients, 243 psoriasis patients without arthritis, and 248 healthy controls were genotyped for 55 MICA alleles using PCR-SSP, and for human leucocyte antigen (HLA)-B and HLA-C alleles by PCR-SSO reverse line blot. Allele frequencies were calculated and logistic regressions were performed, adjusting for HLA-B and HLA-C alleles previously shown to be associated with psoriasis and/or PsA. Several MICA alleles were associated with psoriatic disease, PsA, and psoriasis compared with controls, and PsA compared with psoriasis in univariate analyses. Haplotype analysis showed evidence of strong linkage disequilibrium (LD) between PsA and psoriasis risk alleles of HLA-C, HLA-B, and MICA. After adjusting for significant HLA-B and HLA-C alleles in multivariate analyses, MICA*016 remained significantly associated with psoriasis [odds ratio (OR) = 5.5, P = 0.008]. MICA*00801 homozygosity was associated with susceptibility to PsA when compared with patients with psoriasis alone (OR = 2.26, P = 0.009). We conclude that most MICA allele associations with psoriasis and PsA are dependent on LD with HLA-B and HLA-C risk alleles. Independent of HLA, only MICA*016 influences the risk of developing psoriasis without arthritis, and homozygosity for MICA*00801 increases the risk of developing PsA in patients with psoriasis.

13 Article Assessment of joint symmetry in arthritis. 2011

Cresswell, Lynne / Farewell, Vern. ·Department of Biostatistics, University of Liverpool, Shelley's Cottage, Brownlow Street, Liverpool L693GS, UK. ·Stat Med · Pubmed #21284011.

ABSTRACT: We evaluate three methods for the assessment of symmetry in the joints affected by an arthritic disease. The first two methods, based on published methodology, are limited by their assumptions. We introduce a third method that enables a more comprehensive investigation. In common with previous methods, this method examines tabulations of observed data for evidence of symmetry. Expected values for the table cells are simulated under an assumption of independent joint disease, whilst allowing for differences between patients, and joint locations, in terms of their susceptibility to disease symptoms. Departures of observed from expected values are assessed via a Pearson-type goodness-of-fit test and are examined for consistency with symmetry. We illustrate the three methods using data on the damage accrued in the hand joints of patients registered at the University of Toronto Psoriatic Arthritis clinic.

14 Article Inflammation in an individual joint predicts damage to that joint in psoriatic arthritis. 2011

Cresswell, Lynne / Chandran, Vinod / Farewell, Vernon T / Gladman, Dafna D. ·MRC Biostatistics Unit, Cambridge, UK. ·Ann Rheum Dis · Pubmed #20980703.

ABSTRACT: OBJECTIVE: The authors have previously reported on the relationship between activity and subsequent damage at the patient level for patients with psoriatic arthritis (PsA). The aim of this study was to identify key predictors of damage to individual joints in the hands and feet of patients with PsA, in particular those that capture previous activity. METHODS: Data from patients followed prospectively at the University of Toronto PsA clinic between 1978 and 2006 were available for analysis. Logistic regression was used to relate the probability of a joint developing damage, within a specified time interval after the most recent clinic visit, to potential predictor variables. The predictor variables considered encompassed the history of disease activity of the joint and elsewhere, previous damage and the timing of clinical assessments. RESULTS: 511 patients with no hand damage at clinic entry and 552 patients with no foot damage at clinic entry were included in the analysis of the hand and foot joints, respectively. The analysis of the hand and foot joints demonstrated that the activity (tenderness and/or swelling) history of the specific joint is associated with subsequent damage. For the joints of the feet, activity observations elsewhere in the same foot, and in particular the same toe, were also shown to be associated with subsequent damage. CONCLUSIONS: Both joint tenderness and swelling are important predictors of joint damage in PsA.

15 Article A multistate model for events defined by prolonged observation. 2011

Farewell, Vernon T / Su, Li. ·MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge CB2 0SR, UK. vern.farewell@mrc-bsu.cam.ac.uk ·Biostatistics · Pubmed #20581216.

ABSTRACT: Time-to-event and similar analyses can be problematic if the event of interest is operationally defined by some condition being true for a prolonged period of time. A particular example of this, remission in psoriatic arthritis, is considered in detail for illustration. A 3-state model is proposed for characterizing the transition rates into and out of remission. Remission is linked to an initial and subsequent state for the purpose of introducing the condition that remission must be of some duration to be clinically meaningful. The model is compared with alternative approaches that have been used in such situations. These involve 2-state models where the duration of remission is allowed for through different definitions for the time of entry into remission. Both definitions are linked to prolonged observation of a particular clinical state.

16 Article Informing response criteria for psoriatic arthritis (PsA). II: Further considerations and a proposal--the PsA joint activity index. 2010

Gladman, Dafna D / Tom, Brian D M / Mease, Philip J / Farewell, Vernon T. ·University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada. dafna.gladman@utoronto.ca ·J Rheumatol · Pubmed #20952468.

ABSTRACT: OBJECTIVE: To develop a recommended measure of response for use in psoriatic arthritis (PsA) clinical trials and observational cohort studies reflecting joint involvement. METHODS: Previously, we used data from phase III randomized placebo-controlled trials of anti-tumor necrosis factor (TNF) agents to determine models, based primarily on statistical considerations but with some clinical input when necessary, that best distinguish drug-treated from placebo-treated patients. For the same data, we examine response criteria currently used for PsA and logistic regression models based on the individual components of these response criteria. Comparison with our previously developed models, based primarily on statistical consideration, is made. RESULTS: A simplified score, the PsA Joint Activity Index (PsAJAI), based on components of the ACR30, performed better than the ACR20 and PsARC, and comparable to our previously developed models. The PsAJAI is a weighted sum of 30% improvement in core measures with weights of 2 given to the joint count measure, the C-reactive protein laboratory measure, and the physician global assessment of disease activity measure. Weights of 1 should be given to the remaining 30% improvement measures including pain, patient global assessment of disease activity, and the Health Assessment Questionnaire. CONCLUSION: We recommend the PsAJAI be used as an outcome measure for assessing joint disease response in PsA clinical trials.

17 Article Longitudinal analysis of fatigue in psoriatic arthritis. 2010

Husted, Janice A / Tom, Brian D M / Farewell, Vernon T / Gladman, Dafna D. ·Department of Health Studies and Gerontology, University of Waterloo, Waterloo, Canada. ·J Rheumatol · Pubmed #20595286.

ABSTRACT: OBJECTIVE: To describe the longitudinal course of fatigue in psoriatic arthritis (PsA). METHODS: Our study included 390 patients who attended the University of Toronto Psoriatic Arthritis Clinic between 1998 and 2006 and who completed 2 or more administrations of the modified Fatigue Severity Scale (mFSS) at yearly intervals. Clinical data were used that corresponded to visits in which mFSS was administered. We used linear mixed effects models to examine the relationships of disease-related and nondisease-related variables with mFSS scores across multiple clinic visits, and linear regression models to investigate the association between change in mFSS scores (DeltamFSS) and changes in covariates between visits. RESULTS: Clinical measures of disease activity were related to fatigue over time; however, these relationships disappeared in the context of patient-reported physical disability and pain. Patient-reported measures of physical disability, pain, and psychological distress were most closely related to higher mFSS scores (greater fatigue) across clinic assessments. Fatigue was found to vary over time, at least when assessed at yearly intervals. In general, measures of clinical and functional status at the current visit were more predictive of DeltamFSS in between previous and current visits than change scores in these measures between visits. Comorbid fibromyalgia or hypertension were also associated with greater fatigue across multiple visits and with change in fatigue between visits. CONCLUSION: A combination of factors is associated with fatigue in PsA. The full effect of comorbidities on fatigue warrants further study to better understand the effective management of fatigue in PsA.

18 Article Informing response criteria for psoriatic arthritis. I: discrimination models based on data from 3 anti-tumor necrosis factor randomized studies. 2010

Gladman, Dafna D / Tom, Brian D M / Mease, Philip J / Farewell, Vernon T. ·Toronto Western Hospital, 399 Bathurst Street, 1E410B, Toronto, Ontario M5T 2S8, Canada. dafna.gladman@utoronto.ca ·J Rheumatol · Pubmed #20595285.

ABSTRACT: OBJECTIVE: To develop statistical models, based on the analysis of data from phase III randomized placebo-controlled trials of tumor necrosis factor-alpha (TNF-alpha) inhibitors over a 24-week period, that may inform the definition of response measures for clinical trials in psoriatic arthritis (PsA). METHODS: Data from phase III randomized controlled trials with anti-TNF agents were used. A training set using baseline and 24-week data from 2 trials was used to derive the models, which were then tested on a dataset using baseline and interim data from the third trial, and baseline and interim data from the first 2 trials. Logistic regression, tree analysis, and factor analysis were considered in the development of the models. Receiver-operating characteristic curves were constructed and area under the curve (AUC) calculated to assess performance of the models. RESULTS: Two models were derived. One was based on differences between baseline and last-visit values, which identified the current 68 tender joint count (TJC68), baseline and change in C-reactive protein (CRP), and the measure with the highest difference among the patient and physician global assessment of disease activity (GDA), patient assessment of pain and the Health Assessment Questionnaire (HAQ). The second model was based on percentage change from baseline and included TJC68, CRP, physician GDA, patient global assessment of arthritis pain, and HAQ. Both models provided high AUC of at least 0.8 for both the training and testing sets. CONCLUSION: Models for discriminating joint disease response patterns in PsA were derived from data from randomized controlled trials. These models can now be used to inform further consideration of response measures for trials.

19 Article Folate pathway enzyme gene polymorphisms and the efficacy and toxicity of methotrexate in psoriatic arthritis. 2010

Chandran, Vinod / Siannis, Fotios / Rahman, Proton / Pellett, Fawnda J / Farewell, Vernon T / Gladman, Dafna D. ·University of Toronto,Toronto, Canada. ·J Rheumatol · Pubmed #20472929.

ABSTRACT: OBJECTIVE: To determine the association between folate pathway gene polymorphisms and the effectiveness, toxicity, and drug survival of methotrexate (MTX) in psoriatic arthritis (PsA). METHODS: Data were obtained from a longitudinal cohort of PsA patients evaluated according to a standard protocol. Data on duration of drug therapy, dose, side effects, and reasons for discontinuation are systematically recorded. Patients treated with MTX after clinic admission who had > or = 3 swollen joints prior to initiating MTX therapy were selected for evaluation of effectiveness. Response to MTX treatment was assessed at 6 months. Data from all patients treated in the clinic with MTX were used in evaluation of toxicity and drug survival. The following single-nucleotide polymorphisms (SNP) were measured using the Sequenom platform: MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), DHFR -473T>C (rs1650697), DHFR 35289A>G (rs1232027), and RFC 80G>A (rs1051266). Fisher's exact test, logistic regression, and Cox proportional hazard analyses were used to determine association. RESULTS: Two hundred eighty-one patients were identified from the database. All patients were included in the analysis for side effects and drug survival, and 119 patients were included in the effectiveness analysis. The minor A allele of DHFR gene at +35289 was the only SNP demonstrating association with response to MTX therapy (OR 2.99, p = 0.02). Patients homozygous for the minor allele of MTHFR 677C/T (677TT) had more liver toxicity (Fisher exact test, p = 0.04). CONCLUSION: Polymorphisms of the DHFR gene may be associated with MTX efficacy. MTHFR 677TT may have a relationship with MTX-induced liver toxicity in PsA.

20 Article Axial psoriatic arthritis: update on a longterm prospective study. 2009

Chandran, Vinod / Barrett, Jessica / Schentag, Catherine T / Farewell, Vernon T / Gladman, Dafna D. ·Division of Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada. ·J Rheumatol · Pubmed #19884276.

ABSTRACT: OBJECTIVE: To evaluate changes in symptoms, spinal mobility, and radiographic features in patients with axial psoriatic arthritis (AxPsA). METHODS: Patients with AxPsA were identified from the University of Toronto Psoriatic Arthritis clinic database. Axial symptoms, metrology, and radiographic features at study entry were compared to 5-year and 10-year followup assessments. Data were analyzed using continuity adjusted McNemar's test, an exact binomial test, or logistic regression. RESULTS: Of 297 patients (mean age 42.5 yrs, PsA duration 8 yrs) in the study, 56% had axial symptoms, 43% had radiographic evidence of sacroiliitis, and 13% had syndesmophytes at entry. The number of patients with neck/back pain, neck/back stiffness, and clinical sacroiliitis declined significantly at both 5- and 10-year followup periods. There was a significant increase in the number of patients with restricted cervical spinal mobility at both 5- and 10-year visits and significant reduction in lateral flexion at both timepoints. At 5 (10) years, of those without sacroiliitis at baseline, 36.6% (51.7%) developed at least grade 2 sacroiliitis; 46.5% (52.0%) of those who presented with grade 2 progressed to a higher grade; and 15.6% (25.0%) with grade 3 progressed to grade 4 sacroiliitis. Of the patients without cervical/thoracic/lumbar syndesmophytes at study entry, 11%/16%/14% (14%/21%/20%) developed syndesmophytes in these regions at 5 (10) year followup. Similar results were obtained when analyses were restricted to patients satisfying radiographic criteria alone. CONCLUSION: Over a 10-year period, patients with AxPsA had improvement in neck and back pain, but lateral spinal flexion and cervical mobility deteriorated.

21 Article Bias in 2-part mixed models for longitudinal semicontinuous data. 2009

Su, Li / Tom, Brian D M / Farewell, Vernon T. ·Medical Research Council, Biostatistics Unit, Robinson Way, Cambridge CB2 0SR, UK. li.su@mrc-bsu.cam.ac.uk ·Biostatistics · Pubmed #19136448.

ABSTRACT: Semicontinuous data in the form of a mixture of zeros and continuously distributed positive values frequently arise in biomedical research. Two-part mixed models with correlated random effects are an attractive approach to characterize the complex structure of longitudinal semicontinuous data. In practice, however, an independence assumption about random effects in these models may often be made for convenience and computational feasibility. In this article, we show that bias can be induced for regression coefficients when random effects are truly correlated but misspecified as independent in a 2-part mixed model. Paralleling work on bias under nonignorable missingness within a shared parameter model, we derive and investigate the asymptotic bias in selected settings for misspecified 2-part mixed models. The performance of these models in practice is further evaluated using Monte Carlo simulations. Additionally, the potential bias is investigated when artificial zeros, due to left censoring from some detection or measuring limit, are incorporated. To illustrate, we fit different 2-part mixed models to the data from the University of Toronto Psoriatic Arthritis Clinic, the aim being to examine whether there are differential effects of disease activity and damage on physical functioning as measured by the health assessment questionnaire scores over the course of psoriatic arthritis. Some practical issues on variance component estimation revealed through this data analysis are considered.

22 Article Occurrence and correlates of fatigue in psoriatic arthritis. 2009

Husted, J A / Tom, B D / Schentag, C T / Farewell, V T / Gladman, D D. ·Department of Health Studies and Gerontology, University of Waterloo, Waterloo, Ontario, Canada. ·Ann Rheum Dis · Pubmed #18930991.

ABSTRACT: OBJECTIVE: To determine the relationship between fatigue and disease-related and psychosocial variables in psoriatic arthritis (PsA). METHOD: 499 patients attending the University of Toronto PsA Clinic were administered the modified fatigue severity scale (mFSS). At the time of mFSS administration, clinical and laboratory measures of disease activity and damage were recorded. Linear regression models were used to examine the cross-sectional relationship between disease-related and psychosocial variables and mFSS scores. RESULTS: At least moderate fatigue occurred in 49.5% of patients and severe fatigue in 28.7%. Univariately the vast majority of variables were significantly associated with mFSS scores. The final multivariate model was composed of female sex, the medical outcome survey short form 36 (SF-36) pain and mental health scales, the number of fibromyalgia tender points, the health assessment questionnaire (HAQ) and "ever used" methotrexate, and explained 54.5% of the variation in mFSS scores. The SF-36 mental health scale played the largest role in the multivariate model, uniquely accounting for 6.6% of the variation in the fatigue severity scale. The disease-related factors significant at the univariate level did not achieve statistical significance in the context of HAQ and pain measures. CONCLUSION: Fatigue is a common symptom in PsA, and is associated, in a multivariate model, with pain, female sex, physical functional disability, medication status and psychological distress. Fatigue appears to provide some information that does not overlap with the core set of outcome domains in PsA.

23 Article Cardiovascular morbidity in psoriatic arthritis. 2009

Gladman, D D / Ang, M / Su, L / Tom, B D M / Schentag, C T / Farewell, V T. ·Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada. dafna.gladman@utoronto.ca ·Ann Rheum Dis · Pubmed #18697777.

ABSTRACT: BACKGROUND: Increasing evidence for cardiovascular mortality among patients with psoriasis and psoriatic arthritis (PsA) has accumulated, together with evidence for increased prevalence of risk factors for cardiovascular disease (CVD). OBJECTIVES: To describe cardiovascular morbidity in PsA, determine its prevalence and identify risk factors for its development. METHODS: At the University of Toronto, patients were followed up prospectively according to a standard protocol, including disease-related features and comorbidities. Patients with CVD, including myocardial infarction (MI), angina, hypertension and cerebrovascular accident (CVA), were identified. The prevalence of CVD morbidities in these patients was compared with data from the Canadian Community Health Survey through standardised prevalence ratios (SPRs). Cox relative risk regression analysis was used to analyse risk factors. RESULTS: At the time of analysis, 648 patients were registered in the database. After clinic entry, 122 developed hypertension, 38 had an MI and 5, 21 and 11 had CVA, angina and congestive heart failure (CHF), respectively. 155 patients had at least one of these conditions. The SPRs for MI (2.57; 95% CI 1.73 to 3.80), angina (1.97; 95% CI 1.24 to 3.12) and hypertension (1.90; 95% CI 1.59 to 2.27) were statistically significant, whereas the SPRs for CHF (1.19; 95% CI 0.50 to 2.86) and CVA (0.91; 95% CI 0.34 to 2.43) were not. Factors associated with CVD included diabetes, hyperlipidaemia and high Psoriasis Area and Severity Index scores. CONCLUSION: Patients with PsA are at increased risk of cardiovascular morbidities compared with the general population. In addition to known risk factors for CVD, severe psoriasis is an important predictor in patients with PsA.

24 Article Development and initial validation of a screening questionnaire for psoriatic arthritis: the Toronto Psoriatic Arthritis Screen (ToPAS). 2009

Gladman, D D / Schentag, C T / Tom, B D M / Chandran, V / Brockbank, J / Rosen, C / Farewell, V T. ·Toronto Western Research Institute, Psoriatic Arthritis Program, Centre for Prognosis Studies in The Rheumatic Diseases, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada. dafna.gladman@utoronto.ca ·Ann Rheum Dis · Pubmed #18445625.

ABSTRACT: OBJECTIVE: To develop and validate a psoriatic arthritis (PsA) screening questionnaire: the Toronto Psoriatic Arthritis Screen (ToPAS). METHODS: The ToPAS was developed through review of items seen in patients with PsA and evaluation by patients with PsA and patients with other rheumatological conditions, and was administered to consecutive consenting patients attending five clinics: PsA, psoriasis, general dermatology, general rheumatology (excluding PsA patients) and family medicine. All patients were assessed by a rheumatologist according to a standard protocol. A three-step analysis strategy was adopted: a stepwise logistic regression to identify the questions most important in discriminating between those with and without PsA; a logistic model was fitted to three clinically relevant domains for PsA: skin, joints and nails; and a simpler weighting of each of the domains used in step 2. Receiver operating characteristic (ROC) curves were obtained based on these various models. RESULTS: In all, there were 134 patients from the PsA clinic, 123 with psoriasis, 118 from dermatology, 135 from rheumatology and 178 from family medicine. A simplified discriminatory score based on the skin, joint and nail domains gave results comparable to other methods with an observed overall sensitivity and specificity, based on a single cut point, of 86.8% and 93.1%. When the patients with PsA were compared with each of the other four patient groups individually, the sensitivity and specificity of the ToPAS were: psoriasis 89.1%, 86.3%; dermatology 91.9%, 95.2%; rheumatology 92.6%, 85.7%; and family medicine 90.4%, 100%. CONCLUSION: Our simplified index is very good at classifying those who are not diagnosed with PsA and those who are diagnosed with PsA.

25 Article A variant of the IL4 I50V single-nucleotide polymorphism is associated with erosive joint disease in psoriatic arthritis. 2008

Rahman, Proton / Snelgrove, Tara / Peddle, Lynette / Siannis, Fiotos / Farewell, Vernon / Schentag, Cathy / Gladman, Dafna. ·Memorial University of Newfoundland, St. John's, Newfoundland. ·Arthritis Rheum · Pubmed #18576348.

ABSTRACT: -- No abstract --

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