2008 Activity Report - UHN Research

Arthritis & Autoimmunity Research Centre

2008 Activity Report

From the Director

Arthritis & Autoimmunity Research Centre 2008 Activity Report 2

Dear Colleagues,

This 2008 AARC Activity Report provides a summary of the research activities and accomplishments of the 38 AARC scientists. A major strength of the AARC is the scope of scienti�ic investigations, from basic science experiments at the molecular level, to genomic medicine interrogating the DNA of individuals with different autoimmune diseases, to clinical research in rheumatoid arthritis, osteoarthritis, lupus, ankylosing spondylitis, psoriatic arthritis and scleroderma, to population health studies and surgical innovations. This interdisciplinary team within the AARC is building a network of excellence through collaborative studies that are focused on understanding the biology of these diseases, their course over time and how different individuals respond to different therapies. Research is

focused on identifying the earliest predictors of disease—to develop rapid and accurate diagnostic tests. Understanding the biological mechanisms that trigger a speci�ic autoimmune disease and the factors that result in the persistent in�lammation that lead to, for example, joint or organ damage, is essential for developing therapeutic interventions—new drugs. Early and aggressive intervention may prevent disease progression. By identifying those at risk of developing a particular autoimmune disease, the potential to prevent onset becomes a reality. Understanding how environmental factors, life-styles and access to health care contribute to disease outcomes helps shape patient management and in�luences health care policies. AARC scientists have the expertise to address each of these issues. AARC scientists are recognized as international leaders in their respective areas of pro�iciency. Bringing this wealth of expertise to bear on these debilitating diseases positions the AARC as a major centre for arthritis and autoimmune disease research, ful�illing the mandate to ‘beat arthritis, beat them all.’

Let me also take this opportunity to formally thank the many dedicated individuals who un�laggingly support the AARC. The AARC Foundation Board, recon�igured with additional new members, for their commitment and efforts. On behalf of all the scientists in the AARC I would like to express a special thank you to the former Board Chair, John Teolis. It has been a pleasure and a privilege working closely alongside John and we are all most appreciative of all that he accomplished for the AARC during his tenure as AARC Foundation Chair. We welcome with enthusiasm, Trudy Eagan as incoming Chair. Gerri Grant, Executive Director of the AARC Foundation and her supporting staff: Erin Moraghan, Lisa Ripper, Jess McIntyre and Althea Evans, for their tireless dedication to the AARC. The growing success of Power of Movement, our �lagship national event, is raising awareness across the country, to enable the AARC to build on our strengths and research excellence. And �inally, a thank you to my colleagues in the AARC, for your ongoing commitment and research accomplishments.

Sincerely,

Eleanor Fish


Programs & Centres

• The Musculoskeletal Health and Arthritis Program (MHA) www.uhn.ca/programs/mha

• The Arthritis Centre of Excellence (ACE)

• Arthritis Community Research and Evaluation Unit (ACREU) www.acreu.ca • Canadian Network for Improved Outcomes in Systemic Lupus Erythematosus (CaNIOS) www.canios.ca

• The Rebecca MacDonald Centre for Arthritis & Autoimmune Disease (RMCAD) www.mtsinai.on.ca/rmcad

• The Centre for Prognosis Studies in Rheumatic Diseases www.uhnres.utoronto.ca/studies/cpsrd/

AARC can be found online at: www.uhnres.utoronto.ca/programs/aarc/

Since its inception in 1998, the Arthritis & Autoimmunity Research Centre at the University Health Network has combined clinical and applied studies with basic

science research to become one of the most comprehensive centres of its kind. Our research team of 38 scientists includes leaders in genomic medicine, immunology, health services research, medical imaging, rheumatology, and orthopaedics. AARC scientists are the principals associated with a number of programs and centres:

TABLE OF CONTENTS

From the Director •••••••••••• 2Programs and Centres •••••• 3The AARC Foundation •••••• 4Physicians & Scientists •••••• 5Research Developments ••••• 9Research Activity ••••••••• 272008 Publications ••••••••• 32

The AARC Foundation

The Arthritis & Autoimmunity Research Centre Foundation is pleased to be able to provide �inancial support and raise awareness for the exceptional research carried out by the scientists associated with the AARC.

Again this year, the Foundation’s �inancial support included a core research grant of $1million toward arthritis programs in cellular and molecular biology, clinical therapeutics and population health. In addition it provided funds for disease-speci�ic research programs in areas such as lupus, scleroderma, rheumatoid arthritis and vasculitis, and out�itted laboratories for an additional $2 million in grants. Of note were the establishment of a new biobanking facility for arthritis samples at Toronto Western Hospital, and the seed funding through the Dunlop Research Challenge which was the basis for a major grant application to the Canadian Institutes of Health Research (CIHR).

The AARC has earned its reputation as the global preeminent arthritis research collaborative. Through the unparalleled relationships amongst and between its basic, translational, clinical, surgical and population health scientists the AARC is not only a national resource but an important partner in international arthritis collaborations.

This is an enviable position and one with which the Foundation is honoured to be associated.

In the area of its continued commitment to heightening awareness for the need to fund arthritis research, the Foundation with the assistance of Abbott Laboratories, staged its 3rd

Power of Movement Yoga Challenge across Canada this past year. The message that these conditions are not limited to the elderly or to “wear and tear” was expanded to a broader audience and empowered thousands of young people coast to coast to experience the power of movement while raising funds to bene�it the many whose movement may be limited by these debilitating conditions.

Our donors represent patients and their families, visionary philanthropists and corporate partners. While different in many respects, they share a common goal—to beat arthritis in its numerous forms and help improve the lives of the 4.5 million Canadians who struggle each day to live a normal life.

On behalf of those affected we applaud the AARC scientists for their excellence and we thank our donors for sharing the vision.


R. Fraser Elliott Building, 5th Floor, 190 Elizabeth Street, Toronto, On Telephone: 416-340-4975

E-mail: [email protected] Website: www.beatarthritis.ca

Physicians and Scientists

Dimitri Anastakis, MD, MEd, FRCSC, FACS, FICS Chair, Division of Plastic Surgery, UofTMember, Clinical Studies Resource Centre, Associate Professor, Divisions of Plastic and Orthopaedic Surgery, Department of Surgery, UofT

Major clinical focus: hand and peripheral nerve reconstruction and functional microsurgery

Elizabeth Badley, PhD Head, Division of Health Care & Outcomes Research, TWRI Director, Arthritis Community Research and Evaluation Unit (ACREU), UHN Professor, Department of Public Health Sciences, UofT

Major research focus: epidemiology of arthritis

Stuart Berger, PhD Senior Scientist, Division of Cellular & Molecular Biology, TGRI Associate Professor,Department of Immunology, UofT Major research focus: cell and molecular biology

Claire Bombardier, MD, FRCPC Canada Research Chair in Knowledge Transfer for Musculoskeletal CareHead, Clinical Decision Making & Health Care Division, TGRI Director, Clinical Epidemiology Program, RMCAD

Director, Division of Rheumatology, UofT Clinical Research Coordinator, Institute for Work and HealthMajor research focus: outcomes & population health

Arthur Bookman, MD, FRCPC Member, Clinical Studies Resource Centre, TWRI Chair, Medical Advisory Board, Sjörgen’s Society of Canada Associate Professor, Department of Medicine, UofT

Major clinical focus: Sjögren syndrome

Cheryl Cott, PhD Division of Health Care & Outcomes Research, TWRI Deputy Director, Associate Professor and Career Scientist, Department of Physical Therapy and Graduate Department of

Rehabilitation Science, UofT Major research focus: chronic illness & rehabilitation

Vivian Bykerk, MD, FRCPC Director, The Early Arthritis Program Assistant Director, Division of Advanced Therapeutics, RMCAD Assistant Professor, Department of Medicine, UofT Major clinical focus: rheumatoid arthritis,

osteoarthritis, osteoporosis

Simon Carette, MPhil, MD, FRCPC Division of Health Care & Outcomes Research, TWRI Head, Division of Rheumatology, UHN/Mount Sinai Hospital Director, Vasculitis Clinic, RMCAD Professor, Department of Medicine,UofT

Major clinical focus: vasculitis, soft tissue disorders

J. David Cassidy, PhD, DrMedSc Senior Scientist, Division of Health Care & Outcomes Research, TWRI Director, Centre of Research Expertise in Improved Disability Outcomes (CRE-IDO)Research Director, UHN Rehabilitation Solutions, TWH

Professor of Epidemiology, Department of Public Health Sciences, UofT Major research focus: injury epidemiology

Angela Cheung, MD, PhD, FRCPC Division of Clinical Decision Making & Health Care, TGRI Director, Osteoporosis Program, UHN Associate Director, Women’s Health Program, UHN Assistant Professor,

Department of Medicine, UofT Major clinical focus: postmenopausal health


Mark Erwin, BA, DC, PhD Assistant Professor, Department of Surgery, Division of Orthopaedic Surgery, UofT and Toronto Western HospitalMajor research focus: biology of the intervertebral disc

Brent Graham, BSc, MD, PhD, FRCSC Member, Clinical Studies Resource Centre, TWRI Head, Hand Program, UHN Assistant Professor, Department of Surgery, UofT Major clinical focus: hand surgery

Major research focus: clinical epidemiology

Duncan Gordon, MD, MACR Professor, Department of Medicine,UofT Major focus: Medical literature, editor of The Journal of Rheumatology

Dafna Gladman, MD Senior Scientist, Division of Health Care & Outcomes Research, TWRI Clinical Director, Centre for Prognosis Studies in the Rheumatic Diseases,UHN President, GRAPPAProfessor, Department of Medicine,UofT

Major clinical focus: psoriatic arthritis, lupus

Monique Gignac, PhD Senior Scientist, Division of Health Care & Outcomes Research, TWRI Research Investigator, ACREUAdjunct Scientist, Institute for Work and Health Associate Professor,

Department of Public Health Sciences, UofT Major research focus: psychosocial well being, community health, employment, arthritis

Paul Fortin, MD, MPH, FRCPC Division of Health Care & Outcomes Research, TWRIMember, Centre for Prognosis Studies in the Rheumatic Diseases, UHNDirector of Clinical Research, Arthritis Centre of Excellence (ACE), UHN

Chair, CaNIOS, UHN Associate Professor, Department of Medicine, UofT Major clinical focus: osteoarthritis, lupus. Major research focus: clinical epidemiology

Eleanor Fish, PhD Division of Cellular & Molecular Biology Director, AARC Head, Division of Cellular & Molecular Biology, TGRI Professor, Department of Immunology, UofT

Major research focus: cytokine biology

J. Rod Davey, MD, FRCSC Member, Clinical Studies Resource Centre, TWRI Head, Division of Orthopaedic SurgeryAssociate Director, Surgical Services, UHN Medical Director, Operating Rooms,TWHAssociate Professor,

Department of Surgery, UofT Major clinical focus: hip and knee arthroplasty

Aileen Davis, PhD Senior Scientist, Health Care & Outcomes Research, TWRIAssociate Professor, Departments of Physical Therapy and Surgery, UofT Major focus: arthritis & musculoskeletal oncology

Linda Dvali, MD, MSc, FRCSC Hand & Plastic Surgeon, University Hand Program Assistant Professor, Department of Surgery, UofT Major clinical focus: hand surgery Major research focus: clinical outcomes



Christopher J. Paige, PhD Vice President, Research, UHN & Ontario Cancer Institute Senior Scientist, Division of Stem Cell & Developmental Biology, Ontario Cancer Institute Professor, Departments of

Medical Biophysics and Immunology, UofT Major research focus: immunology & molecular biology

Robert Inman, BA, MD Division of Genetics and Development, TWRI Member, Clinical Studies Resource Centre, TWRIDirector, Arthritis Centre of Excellence (ACE), UHN

Professor, Departments of Medicine and Immunology, UofT Major clinical focus: ankylosing spondylitis Major research focus: immunology and genetics

Jan Jongstra, PhD Senior Scientist, Division of Genetics and Development, TWRI Associate Professor, Department of Immunology, UofT Major research focus: immunology and cell signaling

Johnny Lau, MD, MSc, FRCSC Assistant Professor, Department of Surgery, UofT Major clinical focus: foot and ankle surgery Major research focus: clinical outcomes

Peter Lee, MD, FRCPC Director, Scleroderma Clinic, RMCAD Professor, Department of Medicine, UofT Consultant Rheumatologist, MSH

Major clinical focus: scleroderma

Stephen Lewis, MD Member, Clinical Studies Resource Centre, TWRI Assistant Professor, Department of Surgery, UofT Major clinical focus: spine surgery, general orthopaedics Major research focus: clinical outcomes

Nizar Mahomed, MD, ScD, MPH, FRCSC Division of Health Care and Outcomes Research, TWRI Director, Musculoskeletal Health and Arthritis Program, UHN Associate Professor, Department of Surgery, UofT

Major clinical focus: joint replacement Major research focus: patient outcomes

Wayne Marshall, MD, PhD Division of Applied and Interventional Research, TWRI Assistant Professor, Department of Surgery, UofT Major clinical focus: arthroscopy, sports injuries Major research focus: clinical outcomes


Edward Keystone, MD, FRCPC Director, RMCADDirector, Arthritis & Immune Disorder Research Centre, MSH Clinical Associate Director, Canadian Arthritis NetworkChairman, Canadian Rheumatology

Research ConsortiumProfessor, Department of Medicine, UofTMajor clinical focus: rheumatoid arthritisMajor research focus: experimental therapeutics

Raja Rampersaud, MD, FRCSC Member, Clinical Studies Resource Centre, TWRI Assistant Professor, Department of Surgery, UofT Major clinical focus: spine surgery


Murray Urowitz, FACP, FRCPC, MD Division of Health Care & Outcomes Research, TWRI Member, Clinical Studies Resource Centre, TWRIClinical Director, Centre for Prognosis Studies in the Rheumatic Diseases, UHN

Professor, Department of Medicine, UofT Major clinical focus: lupus, rheumatoid arthritis

Herb von Schroeder, BSc, MSc, MD, FRCSC, CAQSH Member, Clinical Studies Resource Centre, TWRI Associate Professor, Department of Surgery, UofT Hand Surgeon,University Hand Program

Major clinical focus: hand and wrist surgery, Major research focus: cell signaling, bone and fracture non-union biology

Jerry Tenenbaum, MD, FRCPC Consultant, Rheumatology and Internal Medicine, Mount Sinai Hospital, UHN, Baycrest Geriatric CentreProfessor, Department of Medicine, UofT Major clinical focus: osteoarthritis

Joan Wither, BSc, FRCPC, MD, PhDSenior Scientist, Division of Genetics & Development, TWRI Associate Professor, Departments of Medicine and Immunology, UofT Major clinical focus: lupus Major research focus: molecular biology

Kathy Siminovitch, MD, FRCPC, FACP Director, Immunogenomics Program, McLaughlin Center for Molecular Medicine, UofT Director, Genomic Medicine Divisions: Samuel Lunenfeld Research Institute, MSHand Toronto General Research Institute

Director, Gene Pro�iling Facility, UHNProfessor, Departments of Medicine, Immunology, Medical Genetics & Microbiology Major research focus: genomic medicine

David Salonen, BSc, MD, FRCPC Assistant Professor, Department of Medical Imaging, UofT Major clinical focus: musculoskeletal imaging Major research focus: sports medicine

Rob Rottapel, MA, MD, FRCPC Head, Division of Stem Cell and Developmental Biology, Ontario Cancer Institute Associate Professor, Department of Immunology, UofT Major clinical focus: rheumatoid arthritis,

lupus and hepatitis C associated vasculitis Major research focus: immune cell signaling

Florence Tsui, PhD Senior Scientist, Division of Genetics & Development, TWRI Associate Professor, Department of Immunology, UofT Major focus: autoimmune disorders: genetics & the role of ion channels



Research Developments


Research Developments in Ankylosing Spondylitis

Dr. Inman and colleagues reported the results of a study of the ef�icacy and safety of up to 192 weeks of etanercept therapy in patients with AS. The majority of patients with AS from a prior randomised controlled trial of etanercept enrolled in an open label extension, and were followed by researchers. Safety end points included rates of adverse events (AE), serious adverse events (SAE), infections, serious infections and death. Ef�icacy end points included ASsessment in Ankylosing Spondylitis (ASAS20) response and partial remission rates. Study results indicated that Etanercept was well tolerated for up to 192 weeks in patients with AS, with no unexpected AEs or SAEs observed, and no deaths reported. Improvements in the signs and symptoms of AS were maintained for up to 192 weeks. (Ann Rheum Dis. 2008;67:346-52.)

Dr. Inman et al also reported on a study that sought to determine whether macrophages, a type of cell implicated in the pathogenesis of AS, exhibit a characteristic gene expression pattern. After deriving macrophages from the peripheral blood of AS patients and controls, scientists either stimulated cells with interferon-gamma (IFN gamma), left them untreated, or treated them with lipopolysaccharide (LPS). RNA was then isolated and examined. Study �indings revealed consistent differences in gene expression in macrophages from AS patients, with evidence of a striking “reverse” IFN signature, where IFN gamma-up-regulated genes were underexpressed and down-regulated genes were overexpressed. Together with poor expression and responsiveness of the IFN gamma gene, these results suggest that there may be a relative defect in IFN gamma gene regulation in AS, with autocrine consequences and implications for disease pathogenesis. (Arthritis Rheum. 2008;58:1640-9.)

In an international study of the genetics of AS, Drs. Gladman and Inman and colleagues sought to determine the contribution of interleukin (IL)1 gene

cluster polymorphisms previously implicated in susceptibility for AS to AS susceptibility in different populations worldwide. Scientists genotyped nine polymorphisms in the IL-1 gene cluster in AS cases and controls from 10 countries, and then tested association of variants with AS. Results con�irmed that IL1A is associated with susceptibility to AS. Association of the other IL-1 gene complex members could not be excluded in speci�ic populations. Scientists concluded that prospective meta-analysis is a useful tool in con�irmation studies of genes associated with complex genetic disorders such as AS, providing suf�iciently large sample sizes to produce robust �indings often not achieved in smaller individual cohorts. (Ann Rheum Dis. 2008;67:1305-9. )

Recent studies have shown that a nonsynonymous single-nucleotide polymorphism (SNP) in the interleukin-23 receptor (IL-23R) gene on chromosome 1p31 is associated with Crohn’s disease and psoriasis. Due to the clinical and immunologic overlap between AS and these diseases, Drs. Inman Gladman and colleagues undertook a study to examine the association of IL-23R variants with AS in multiple Canadian populations. Investigators examined 3 cohorts of AS patients from established rheumatic disease centers in Canada. Ten IL-23R SNPs were genotyped, 9 of which were incorporated in the haplotype analysis, and allele and haplotype associations were then calculated. Results demonstrated an AS association with the IL-23R locus and implicate the same polymorphisms associated with IBD and psoriasis. (Arthritis Rheum. 2008;58:1020-5.)

In a recent study, Drs. Tsui, Inman and colleagues assessed the gene expression changes following in�liximab infusion for AS patients. Researchers conducted microarray analysis on peripheral blood RNA at baseline and post-in�liximab to screen for changes in gene expression. Soluble LIGHT (sLIGHT) in corresponding serum samples was estimated and compared to clinical data. From their results, researchers concluded that the gene expression of


LIGHT was signi�icantly downregulated by in�liximab and the changes in sLIGHT correlated well with changes in other markers of in�lammation. (Ann Rheum Dis. 2008; Dec 22. [Epub])

An important unresolved issue in pathogenesis and clinical course of AS has been whether juvenile-onset AS (JoAS) is a clinical entity in its own right, or just an earlier onset variant of its adult-onset AS (AoAS) counterpart. Dr. Inman and colleagues addressed this issue in a recent study. Subjects extracted from the database of a large Spondylitis Clinic with symptoms onset of </= 16 years were compared to those with symptom onset >/= 17 years. Investigators concluded from their comparison that JoAS follows a distinctive clinical course from its AoAS counterpart. Furthermore, these clinical features are dictated by factors other than male gender and HLA-B27 and warrant further investigation. (Ann Rheum Dis. 2008; Sep 9. [Epub])

The role of microbial triggers in the pathogenesis of AS has remained an active area of clinical and basic research but remains unresolved. Based on recent evidence of an important role for TLR4 in experimental reactive arthritis, Dr. Inman and colleagues conducted research on whether genetic polymorphisms in TLR4 affects susceptibility to AS. A cohort of relatively genetically homogeneous Korean AS patients and ethnically matched controls were studied. Subjects were genotyped for two functional SNPs in the TLR4 gene: Asp299Gly and TLR-4 (Thr399Ile), which have been shown to be associated with increased risk of Gram-negative bacteremia in sepsis patients and with susceptibility to in�lammatory bowel disease. Results showed that all cases and controls were homozygous for the (A) allele for 299 variant and similarly for the 399 variant all cases and controls were homozygous for the (C) allele. Genetic-environmental interactions �igure prominently in current concepts of the pathogenesis of AS. These �indings indicate that the polymorphisms in the TLR4 gene cannot be regarded as major contributors to AS susceptibility in the Korean population. (Rheumatol Int. 2008;28:627-30.)

Dr. Inman collaborated on the GO-RAISE study, which evaluated the ef�icacy and safety of golimumab in patients with AS. Patients with active AS, a Bath AS Disease Activity Index (BASDAI) score > or =4, and a back pain score of > or =4 were randomly assigned to receive subcutaneous injections of golimumab or placebo every 4 weeks. The primary end point was the proportion of patients with at least 20% improvement in the ASsessment in AS (ASAS20) criteria at week 14. After 14 weeks, more than half of patients receiving golimumab were ASAS20 responders. Patients receiving golimumab also showed signi�icant improvement in the physical and mental component summary scores of the Short Form 36 Health Survey, the Jenkins Sleep Evaluation Questionnaire score, the BASDAI score, and the Bath AS Functional Index score, but not the Bath AS Metrology Index score. From these results, researchers concluded that golimumab was effective and well tolerated in a large cohort of patients with AS during a 24-week study period. (Arthritis Rheum. 2008;58:3402-12.)

The M03-606 Study Group, including Dr. Inman, conducted a randomized controlled trial to analyze the effects of adalimumab on biomarkers predictive of structural damage in in�lammatory arthritis. Patients with active AS received adalimumab every other week. Ef�icacy measures included ASsessment in Ankylosing Spondylitis International Working Group response, Bath AS Disease Activity Index (BASDAI), Total Back Pain, Bath AS Functional Index, C-reactive protein (CRP), and patient’s global assessment of disease activity. Urinary type II collagen C-telopeptides (CTX-II), serum type I collagen N-telopeptides (NTX), and serum metalloproteinase-3 (MMP-3) were assessed, and researchers determined correlations between changes in biomarkers and AS ef�icacy outcomes. From their results, the M03-606 Study Group was able to conclude that adalimumab suppresses biomarkers that re�lect matrix turnover in patients with AS. (J Rheumatol. 2008;35:2030-7.)



Research Developments in Lupus

The Canadian Scleroderma Research Group (CSRG) and the Canadian Network for Improved Outcomes in Systemic Lupus Erythematosus (CaNIOS) collaborated on a study seeking to assess the construct validity of the Self-Administered Comorbidity Questionnaire (SCQ) in patients with systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). Drs. Fortin, Wither et al published the results of this study, in which the SCQ was administered to SSc and SLE patients. Construct validity of the SCQ was evaluated separately in the SSc and SLE cohorts by testing the hypotheses that a valid comorbidity index should correlate with age and health-related quality of life (Medical Outcomes Trust Short Form 36 [SF 36]) but not with disease-speci�ic variables. The assessment showed that the SCQ score correlated with age in the SSc patients only and not in the SLE patients. It correlated with the SF 36 in both SSc and SLE. However, it also correlated with several disease-related variables. There was signi�icant overlap between reports of comorbidities and disease-related problems in the SSc cohort. Investigators therefore concluded that patients with systemic autoimmune diseases cannot distinguish true comorbidities from conditions related to their index disease and, as such, a self-administered comorbidity questionnaire does not appear useful in these diseases.( J Clin Epidemiol. 2008;61:654-62.)

Drs. Urowitz, Gladman and colleagues conducted a study examining changes in mortality and other outcomes over time in a large SLE cohort. Scientists followed patients from the University of Toronto Lupus Clinic through four 9-year calendar periods de�ined over the same intervals. Both cohort and calendar effects were assessed for the following outcomes: mortality (standardized mortality ratio; SMR), disease activity over time (adjusted mean SLEDAI; AMS), cumulative damage (Systemic Lupus International Collaborating Clinics Damage Index; SDI), coronary artery disease (CAD), and osteonecrosis (ON). Scientists also investigated mortality and the in�luence on it of the disease-

related factors. Study results demonstrated improved survival in patients with SLE over a 36-year period. Disease-related variables included in the model are important factors for mortality in this SLE cohort, but could not completely explain the trend of improved survival over calendar period observed. (J Rheumatol. 2008;35:2152-8.)

In a collaborative case-cohort study of the relationship between cancer and medication exposures in SLE, Drs. Urowitz, Gladman and Fortin examined if, in SLE, exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk. Studying subjects within a multi-site international SLE cohort, investigators calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug. In the SLE sample, age > or = 65, damage, and tobacco exposure were associated with cancer risk. Investigators therefore concluded that, though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent in�luence of medication exposures and disease activity on risk of malignancy. (Ann Rheum Dis. 2008;67:74-9.)

In an analytical study of the genetic complexities of SLE, Drs. Wither, Gladman, Fortin and colleagues used �low cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their �irst-degree relatives. Through their analysis of peripheral blood mononuclear cells isolated from the subjects, investigators found evidence of increased chronic low-grade activation of the immune system in �irst-degree relatives of lupus patients. They noted a de�iciency of natural killer (NK)T cells among �irst-degree relatives that was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. As well, there was a signi�icant association between mean parental, sibling, and proband values for the proportion of natural killer (NK)T cells, suggesting



that this is a heritable trait. The �indings indicate that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by natural killer (NK)T cells predisposes �irst-degree relatives of lupus patients to the development of autoimmunity. (Arthritis Res Ther. 2008;10:R108.)

In order to investigate potential differences between childhood-onset and adult-onset SLE, Drs. Gladman and Urowitz collaborated on a comparative study. Researchers collected and analyzed data from two inception cohorts: one with childhood-onset SLE and one with adult-onset SLE. From their data assessment, researchers concluded that children with childhood-onset SLE have more active disease at presentation and over time than do adults with SLE, especially active renal disease. Compared with adults with SLE, children receive more intensive drug therapy and accrue more damage, often related to steroid toxicity. (Arthritis Rheum. 2008;58:556-62.)

Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) is a group of rheumatologists and methodologists from 27 international centers who have a particular interest and expertise in SLE. As members of the SLICC, Drs. Urowitz and Gladman reported that in 2000, the SLICC Registry for Atherosclerosis was established to determine the incidence, prevalence, nature, and risk factors of atherosclerotic coronary artery disease in SLE. Risk factors for coronary artery disease at presentation to the cohort were reported, as well as their accumulation over the �irst few years. Development of the metabolic syndrome was also described. Among the �irst 1078 patients who entered the cohort, 61 vascular events have occurred in 47 patients who were older at diagnosis and more likely male and hypertensive than were the patients without vascular events. (Curr Rheumatol Rep. 2008;10:281-5.)

Drs. Urowitz, Gladman, Fortin et al published the results of a separate SLICC study that examined the accumulation of coronary artery disease risk factors

over 3 years in a cohort of patients from the SLICC Registry for Atherosclerosis. Both classic and other coronary artery disease (CAD) risk factors were collected at entry and through 3 years of followup. Therapy was documented over the 3 years. Results showed that at enrollment a substantial number of patients already demonstrated several risk factors for CAD, both classic and other. All risk factors increased from enrollment over the 3 years of followup. Researchers concluded that patients with SLE should be monitored for CAD risk factors from the time of diagnosis and appropriate treatment should be instituted early. (Arthritis Rheum. 2008;59:176-80.)

The SLICC also undertook a study of the short-term outcome of neuropsychiatric (NP) events upon enrollment into an international inception cohort of patients with SLE. Drs. Urowitz, Fortin, Gladman and colleagues conducted research on patients that were enrolled within 15 months of SLE diagnosis, and investigators characterized NP events using the American College of Rheumatology case de�initions. Decision rules were derived to identify NP events attributable to SLE. Physician outcome scores of NP events and patient-derived mental component summary (MCS) and physical component summary (PCS) scores of the Short Form 36 were recorded. Results showed that outcome scores for NP events attributed to SLE were signi�icantly better than for NP events due to non-SLE causes. Higher global disease activity was associated with worse outcomes. MCS scores were lower in patients with NP events and there was a signi�icant association between physician outcome scores and patient MCS scores only for NP events attributed to SLE. Researchers therefore concluded that in SLE patients, the short-term outcome of NP events is determined by both the characteristics and attribution of the events. (Arthritis Rheum. 2008;59:721-9.)

In another SLICC investigation, Drs. Urowitz, Gladman and Fortin co-authored a report on the association between NP events and anti-ribosomal P (anti-P), antiphospholipid (lupus anticoagulant [LAC],



anticardiolipin), anti-beta2-glycoprotein I, and anti-NR2 glutamate receptor antibodies in an inception cohort of SLE patients. Scientists identi�ied and clustered NP events, and determined the attribution of NP events to SLE using decision rules of differing stringency. From their results, scientists were able to conclude that clinically distinct NP events attributed to SLE and occurring around the time of diagnosis were associated with anti-P antibodies and LAC. This suggests that there are different autoimmune pathogenetic mechanisms, although low sensitivity limits the clinical application of testing for these antibodies. (Arthritis Rheum. 2008;58:843-53.)

In an unrelated SLICC study, Drs. Gladman, Urowitz and colleagues aimed to develop a measure of renal activity in SLE and use it to develop a renal response index. Abstracted data from the medical records of patients with lupus nephritis were sent to nephrologists and rheumatologists for rating. Each physician rated each patient visit with respect to renal disease activity. Using the most commonly selected rating for each patient as the gold standard, researchers identi�ied the variables most related to renal disease activity, and these variables were then used to create an activity score. This activity score could then be applied to 2 consecutive visits to de�ine a renal response index. Ratings derived from this index for rating of renal response showed reasonable agreement with physician ratings in a pilot study. Scientists concluded that a data-driven approach to create renal activity and renal response indices will be useful in both clinical care and research settings. (Arthritis Rheum. 2008;58:1784-8.)

Drs. Urowitz, Gladman et al published the results of a study that aimed to determine whether peripheral blood gene expression of patients with SLE correlates with disease activity measured using the SLE Disease Activity Index 2000 (SLEDAI-2K). Patient RNA was isolated from peripheral blood and pro�iled, and samples were then categorised into major clusters based on gene expression pattern. Correlates, including demographic and disease-related characteristics

such as SLEDAI-2K score, of the major sample clusters were compared. Investigators observed that a set of 31 interferon (IFN)-regulated genes were driving the separations of samples into two clusters, one characterised by a relatively high IFN-regulated gene signature and the other by a relatively low IFN-regulated gene signature. Disease activity measured using the SLEDAI-2K was signi�icantly correlated with the high IFN gene signature. These results led investigators to conclude that peripheral blood gene expression pro�iling (GEP) may be a useful biomarker of disease activity in SLE. (Ann Rheum Dis. 2008;67:1069-75. )

To gain insight into the immune mechanisms leading to Polyclonal B cell activation in SLE, researchers Drs. Fortin, Gladman, Urowitz, Wither and colleagues extensively characterized the activated peripheral blood B cell populations in SLE. PBMC from lupus patients and healthy controls were stained with various combinations of conjugated Ab to identify distinct peripheral B cell subsets, and activation was assessed. SLE patients had altered proportions of several B cell subsets, many of which demonstrated increased activation. This activation occurred at an early developmental stage, as B cells in the transitional (T2) stage were already signi�icantly larger than those seen in controls. Researchers ultimately found an expanded population of activated antigen-engaged cells within the naive B cell compartment of patients with SLE. (J Immunol. 2008;180:1276-84.)

The CaNIOS GenES Investigators, including AARC members Dr. Wither and Dr. Fortin, published study results indicating that methods to improve the reliability of self-reported autoimmune disease history could enhance population and clinic-based research. Investigators reached this conclusion after analyzing self-reported medical histories of �irst-degree relatives of lupus patients and controls. Results showed that of 178 reports of an autoimmune disease, 44% were con�irmed by medical records; excluding those whose medical records were unavailable, the con�irmation rate was 76%. The prevalence of at



least one con�irmed autoimmune disease was 12% in lupus relatives and 2% in controls.(J Rheumatol. 2008;35:2001-4.) In a separate article by CaNIOS GenES Investigators, Drs Fortin and Wither discuss a genomic association study in UK and Canadian SLE families. Previous genome-wide linkage studies in human SLE identi�ied several linkage regions, including one at 1q23, which contains multiple susceptibility genes, including the members of the signalling lymphocyte activation molecule (SLAM) locus. The SLAM genes are functionally related cell-surface receptors, which regulate signal transduction of cells in the immune system. Drs. Fortin and Wither report that the CaNIOS GenES Investigators identi�ied variants in the promoter and coding region of SLAMF7 and LY9 contributing to SLE disease susceptibility. (Genes Immun. 2008;9:93-102.)

Drs. Urowitz, Gladman and colleagues studied patients at the University of Toronto Lupus Clinic in order to determine whether killer cell immunologlobulin-like receptor (KIR) genotypes are associated with vasculitis, vascular arterial events or anticardiolipin (aCL) antibodies in patients with lupus. Investigators assessed subjects for the occurrence of vasculitis and vascular arterial events, performed Molecular HLA-C and KIR (presence or absence of KIR2DL1, 2DL2, 2DL3, 2DS1 and 2DS2) genotyping, and analysed the association between KIR genes and vascular arterial events and aCL antibodies. Results showed that in patients with vascular arterial events, there was a signi�icant increase in KIR2DS2 and KIR2DL2 compared with patients without events. In patients with vasculitis, there was no increase in activating KIR genotypes. In patients with aCL antibodies, signi�icant increases were seen in KIR2DS2 and KIR2DL2, but KIR2DL3 was decreased. (Lupus. 2008;17:793-8.)

Dr. Fortin et al published the CaNIOS study on the steroid-sparing effects of methotrexate in SLE. In order to assess the potential bene�its of methotrexate

in patients with SLE, investigators conducted a double-blind, placebo-controlled trial of methotrexate with folic acid. Researchers analysed data to assess the treatment effects on lupus disease activity and daily steroid dose, and to test if the treatment effects depended on selected participant characteristics. Study results indicated that methotrexate conferred a signi�icant advantage in participants with moderately active lupus by lowering daily prednisone dose and slightly decreasing lupus disease activity. Therefore, as a therapeutic option in moderate SLE, methotrexate can be considered to be steroid sparing. (Arthritis Rheum. 2008;59:1796-804.)

Coronary artery disease (CAD) is a complication of SLE which is often crucial for the patient’s prognosis. Drs. Gladman, Urowitz and colleagues hypothesized that apolipoprotein E (Apo E), which is involved in cholesterol metabolism, might play a role in this process. In order to investigate this hypothesis, researchers conducted a study in which patients with SLE registered at the University of Toronto Lupus Clinic who had DNA available for study had their Apo E genotype determined. Each case was assessed for the presence of CAD, and Apo E allele frequencies in patients with SLE were compared with data from the general population. Age at onset and disease duration of CAD were also recorded and compared between groups. Results indicated that the distribution of Apo E genotypes in SLE is not signi�icantly different from that of the North American population. In SLE, Apo E2 was associated with a more rapid development of CAD. Therefore, Apo E2 might interact with other disease-related factors to accelerate the onset of CAD in some patients with SLE and as such might be an additional marker of risk in this population. (Med Sci Monit. 2008;14:CR233-237.)

In another collaborative study, Drs. Gladman and Urowitz sought to determine whether quality of life in patients with SLE measured by the Short Form 36 (SF-36) changes over time and which patient- and disease-related factors in�luence such change. Investigators identi�ied SLE patients from a database who had > or =6 SF-36 evaluations


during followup. Outcomes were slopes of scores of the 8 SF-36 domains as well as the physical and mental component scores. Based on the direction of the slope, patients were designated as unchanged, improved, or worsened. Investigators then tested the contribution of risk factors to slopes, and evaluated risk factors between patterns of clinical change. During the study interval, investigators observed that the majority of patients showed no change in the SF-36 domains and only a small minority demonstrated improvement. According to slopes of the domains and summary scores, only physical functioning showed a signi�icant decrease over time. There were no lupus disease features associated with decline in physical functioning except for the presence of �ibromyalgia. These results lead to the conclusion that the SF-36 in SLE patients with established disease changed little over an 8-year period. Changes in the SF-36 were not affected by disease activity, steroids, or damage accumulation during the interval, but were affected by the presence of �ibromyalgia. (Arthritis Rheum. 2008;59:181-5.)

Drs. Gladman, Urowitz , Fortin, Wither et al published the results of a study investigating the longitudinal expression of interferon (IFN)-inducible genes in SLE, and their suitability as disease biomarkers. Researchers isolated RNA from the peripheral blood of SLE patients and reverse transcribed it into cDNA. The expression levels of �ive IFN-responsive genes were determined, and summed to generate a global IFN score. Patients were followed longitudinally and the association between disease activity, as measured by the SLEDAI-2K and other variables, was examined. Results indicated that expression of all �ive IFN-responsive genes was signi�icantly elevated in SLE patients versus controls. Expression of three of the genes and the global IFN score were associated with high disease activity. However, there was a poor correlation between changes in this score and changes in disease activity, C3, or anti-dsDNA antibody levels in patients followed longitudinally. In most patients, the levels of IFN-induced gene expression remained relatively stable over 3-12 months despite marked changes in disease activity. Nevertheless, in patients

with low/moderate disease activity, those with high IFN scores had a more recent history of sustained high disease activity. The �indings indicate that IFN-induced gene expression has limited clinical utility as a biomarker of acute changes in disease activity. (Ann Rheum Dis. 2008 Sep 4. [Epub])

SLE is characterized by a markedly elevated risk for coronary heart disease (CHD), the exact pathogenesis of which is unknown. In particular, the causal roles of corticosteroid therapy and SLE disease activity, and whether their putative effects are mediated through conventional risk factors, remain unclear. Dr. Fortin and colleagues sought to investigate these questions in a retrospective study of patient data abstracted from Montreal General Hospital clinic charts. Researchers studied the associations of recent corticosteroid dose and recent Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score with 8 CHD risk factors and the aggregate estimate of 2-year CHD risk. Researchers then estimated the mutually-adjusted effects of average daily corticosteroid dose and average SLEDAI score within the past year on the current level of each risk factor. Data analysis indicated that higher past-year corticosteroid dose was independently associated with signi�icantly higher overall 2-year CHD risk and with higher levels of all 8 individual risk factors. Higher past-year lupus disease activity was independently associated with higher overall 2-year CHD risk, and higher values of several CHD risk factors. Researchers therefore concluded that in SLE, both recent use of corticosteroids and recent lupus activity are independently associated with higher values of several well-recognized CHD risk factors and overall 2-year CHD risk. (Arthritis Rheum. 2008;59:169-75.)

Research Developments in Osteoarthritis

Dr. Tenenbaum et al published the results of an investigation that sought an approach to the clinical, radiographic, and molecular diagnosis of an underlying skeletal dysplasia in adults presenting with early-onset polyarticular osteoarthritis (OA). After identifying a family with 2 adults with



polyarticular OA and a child with generalized arthralgia, researchers conducted general, musculoskeletal, ocular, and auditory evaluations. While radiographs of the affected adults showed severe polyarticular OA but did not reveal diagnostic evidence of an underlying skeletal dysplasia, the child’s radiographs showed enlarged epiphyses with an advanced bone age. Based on their observations, researchers were able to diagnose the adults with otospondylomegaepiphyseal dysplasia, also known as Stickler syndrome type III. They con�irmed this diagnosis by identifying a mutation in the COL11A2 gene that encodes the pre-pro-alpha2(XI) chain of type XI collagen. Their research demonstrates that early-onset polyarticular OA may occur in adults without a known or obvious underlying skeletal dysplasia, and provides an approach to the diagnosis of an underlying skeletal dysplasia in such individuals. (J Rheumatol. 2008;35:920-6.)

Drs. Gignac, Badley and colleagues conducted a longitudinal study to examine the roles of symptoms, activity limitations, and depression in the relationship between OA and social participation. The study tested a model that hypothesizes that the relationship between physical symptoms and later participation restrictions among older adults with OA is mediated by activity limitations and depressive symptoms. Study participants were community-dwelling senior adults with a physician diagnosis of OA, who were interviewed at two time points. Measures included demographic variables; a derived physical symptoms measure based on severity of pain, stiffness, and fatigue in the previous week; and depressive symptoms measured by the Center for Epidemiologic Studies Depression Scale. Researchers derived measures of activity limitations and participation restrictions and then tested for mediation. Results indicated that severity of time 1 physical symptoms was associated with dif�iculties in participation 18 months later. This relationship was partially mediated by time 1 activity limitations and time 1 depressive symptoms. When both of these variables were included in the model, the effect of symptoms severity was completely mediated. This study demonstrates the

importance of taking into account both the physical and psychological consequences of OA symptoms and suggests that these factors act as a pathway to subsequent participation restrictions. (Arthritis Rheum. 2008;59:129-35.)

Fatigue in OA is not routinely evaluated and has only been considered in a very limited number of studies. To date, these studies have focused primarily on patients with OA under rheumatological care, which represent the minority of people living with OA. Dr. Badley and colleagues therefore conducted a qualitative study aiming to increase our understanding of the fatigue experience in community dwelling people with OA. Study participants completed self-administered questionnaire, which included demographics, measures of OA severity, depression and fatigue. Participants with OA described experiencing notable amounts of fatigue and indicated that it had a substantial impact on their lives. Factors believed to increase fatigue included OA pain and pain medications, aging, various types of weather and poor sleep. Mental health was identi�ied as both affecting fatigue and being affected by fatigue. Participants described fatigue as impacting physical function, and their ability to participate in social activities and to do household chores. Researchers concluded that further research is required to better understand the role of fatigue in OA in order to identify strategies to reduce its impact. (BMC Musculoskelet Disord. 2008;9:63.)

OARSI/OMERACT developed a new OA pain measure, comprised of 12 questions on constant vs intermittent pain. In order to evaluate the measurement properties of the new tool, Dr. Davis collaborated on a study in which the new pain measure was administered to 100 subjects with hip or knee OA. A number of other tests and pain-measurement questionnaires were then administered to the subjects, after which researchers assessed item response distributions, inter-item correlations, item total correlations and Cronbach’s alpha. Results indicated that there was a good distribution of responses across all items, no item redundancy, and factorial complexity. Preliminary



psychometric testing therefore suggests this OA pain measure is reliable and valid. (Osteoarthritis Cartilage. 2008;16:409-14.)

Prevalence of OA is expected to increase due to population aging. However, there is little information on the trends in the incidence of OA over time. Dr. Badley and colleagues therefore conducted a study to describe changes in physician-diagnosed OA incidence rates between 1996-1997 and 2003-2004 in British Columbia (BC), Canada. Scientists used data on all visits to health professionals and hospital admissions covered by the Medical Services Plan of BC for the �iscal years 1991-1992 through 2003-2004. Rates were standardized to the BC population in 2000. Scientists used two de�initions of OA: 1) at least 1 visit or hospitalization with a diagnostic code for OA, and 2) at least 2 visits or 1 hospitalization with a code for OA. Scientists calculated incidence rates, and observed an increase in the incidence of OA in both men and women due to population aging and an additional increase in women beyond the effect of aging. They concluded that these trends have important implications for public health and provision of health services to this very large group of patients. (Arthritis Rheum. 2008;59:929-34.)

Research Developments in Outcomes and Population Health

Drs. Gignac and Badley collaborated on a study that sheds light on a process of diverse employment changes that may occur in the lives of many individuals with arthritis. The study aimed to prospectively examine arthritis-related productivity losses, work changes, and leaving employment, the relationships among these work transitions, and the factors associated with them. Participants with in�lammatory arthritis or osteoarthritis were interviewed using a structured questionnaire. Work transitions considered were productivity losses, work changes, and leaving employment. Also measured were demographic, illness, work context, and psychological variables. Investigators found that work transitions

were common, and were related to subsequently making other work transitions, including leaving employment. Age, sex, education, activity limitations, control, depression, and arthritis-work spillover were also associated with work transitions. These results emphasize the interrelationships among work transitions, as well as other factors in predicting work transitions, and it provides insight into work changes that may signal impending dif�iculties with remaining employed. (Arthritis Rheum. 2008;59:1805-13.)

In order to examine the extent to which differences in individual- and regional-level socioeconomic status and racial/cultural origin account for geographic variations in the prevalence of self-reported arthritis, Dr. Badley and colleagues performed a multilevel analysis based on the 2000-2001 Canadian Community Health Survey. Investigators also sought to determine whether regional characteristics modify the effect of individual characteristics associated with reporting arthritis. Individual-level variables examined included age, sex, income, education, immigration status, racial/cultural origin, smoking, physical activity, and body mass index. Regional-level variables included the proportion of low-income families, low education, unemployment, recent immigrants, Aboriginals, and Asians. Study results showed that both individual and regional factors contribute to variations in the prevalence of arthritis, although signi�icant unexplained variation remained. Further research is required to better understand the mechanisms that underlie these regional effects and to identify other contributing factors to the remaining variation. (Arthritis Rheum. 2008;59:399-407.)

Dr. Fish published a review highlighting the need to address sex-based differences in autoimmune disease pathogenesis and in the pharmacokinetics and pharmacodynamics of therapeutic medications to provide optimal disease management for both sexes. While there is much evidence to support sex-based differences in innate and adaptive immune responses, in the susceptibility to infectious diseases



and in the prevalence of autoimmune diseases, health research and clinical practice do not address these distinctions, and most research studies of immune responses do not stratify by sex. (Nat Rev Immunol. 2008;8:737-44. )

The burden of arthritis is increasing in the face of diminishing health human resources to deliver care. In response, innovative models of care delivery are developing to facilitate access to quality care. Since most models have developed in response to local needs with limited evaluation, Dr. Badley collaborated on a study to a) examine the range of models of care that deliver specialist services using a medical/surgical specialist and at least one other health care provider and b) document the strengths and challenges of the identi�ied models. A secondary objective was to identify key elements of best practice models of care for arthritis. Investigators conducted semi-structured interviews with experts in arthritis from jurisdictions with primarily publicly-funded health care systems. Qualitative data were analyzed using a constant comparative approach to identify common types of models of care, strengths and challenges of models, and key components of arthritis care. Five main types of models of care emerged. 1) Specialized arthritis programs deliver comprehensive, multidisciplinary team care for arthritis. Two models were identi�ied using health care providers in expanded clinical roles: 2) triage of patients with musculoskeletal conditions to the appropriate services including specialists; and 3) ongoing management in collaboration with a specialist. Two models promoting rural access were 4) rural consultation support and 5) telemedicine. Key informants described important components of models of care including knowledgeable health professionals and patients. These results lead investigators to conclude that a range of models of care for arthritis have been developed. This classi�ication can be used as a framework for discussing care delivery. (BMC Health Serv Res. 2008;8:147.)

Work disability is a common outcome of in�lammatory arthritis (IA), yet few services address

employment. Dr. Gignac collaborated on a proof-of-concept study of the “Employment and Arthritis: Making It Work” self-management program aimed at preventing work disability and maintaining at-work productivity in employed people with IA. The program was developed using the precede-proceed model and self-management concepts. Program goals included modifying risk factors for work disability and enhancing self-management of work problems due to IA, as identi�ied in initial focus groups. Researchers pilot tested the program in 2 groups and evaluated over 12 months of followup. Participants consisted of 19 employed women with IA. Process evaluation demonstrated feasibility and excellent attendance and use of the self-learning manual. Improvements were observed in self-con�idence in managing problems at work, fatigue interference with work, measures of limitations, and at-work productivity. From these results, researchers concluded that “Employment and Arthritis: Making It Work” is a novel intervention to prevent work disability in patients with IA, combining self-management group sessions and professional assessments aimed at job retention, which resulted in people making changes to adapt their work to their arthritis, and improved fatigue, self-ef�icacy, and at-work productivity. (Arthritis Rheum. 2008;59:1647-55.)

In an editorial commentary, Dr. Badley discusses the magnitude of the impact of musculoskeletal (MSK) disorders on the population, and the lack of attention paid to these disorders by policy makers, politicians, and the general public. As Dr. Badley explains, a recent article by Loza et al aims to describe the extent to which rheumatic diseases affect health-related quality of life and functional ability and to compare their in�luence with that of other chronic diseases. The Loza report uses a number of different approaches to illustrate the high impact of MSK disorders, including counting the number of affected people, looking at the contribution of chronic diseases to disability and physical and mental functioning, and offering a visual representation of population effect as compared with other chronic conditions. The Loza study �indings con�irm the overall high impact of rheumatic diseases



on quality of life. This is consistent with evidence from other studies and countries, which show that individuals with MSK disorders have poorer levels of physical functioning and worse quality of life compared to those with most other chronic conditions. Dr. Badley therefore questions the public’s continued lack of recognition of the severity of MSK disorders. (J Rheumatol. 2008;35:6-7.)

Research Developments in Psoriatic Arthritis

Drs. Keystone, Gladman et al reported on the �indings of the In�liximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT), which sought to investigate longterm ef�icacy/safety of in�liximab over 2 years in patients with active psoriatic arthritis (PsA). In their study, scientists used the American College of Rheumatology response criteria to assess patient improvement, and assessed radiographic progression by the PsA-modi�ied van der Heijde-Sharp score. The �indings of the IMPACT study indicated led scientists to conclude that therapy with in�liximab 5 mg/kg through Week 94 produced sustained improvement in joint and skin symptoms, inhibited radiographic progression, and continued to exhibit a favorable bene�it-risk ratio in this population with treatment-refractory PsA. (J Rheumatol. 2008;35:869-76.)

While in a previous clinic study, methotrexate conferred no advantage with respect to clinical response or progression of damage after 24 months in patients with PsA, Dr. Gladman collaborated on a new study to reappraise the effectiveness of methotrexate in PsA. Investigators sought to determine whether methotrexate is being used earlier in the course of PsA and in a higher dose, and whether that has led to improved outcomes. Using the clinic’s longitudinal observational cohort, investigators compared new data to those obtained from their previous study. Results of data analysis and comparison showed that there was a trend for methotrexate to be used earlier, at a higher dose, with greater clinical improvement and less progression of damage. Investigators therefore concluded that treatment with methotrexate has

changed in the past decade to include patients with shorter disease duration and less damage, at increased dose, and that there may be better response with less progression of damage. (J Rheumatol. 2008;35:469-71.)

At the 2007 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members of the GRAPPA genetics committee, including Dr. Gladman, presented a discussion of the genetics of psoriasis and PsA, including future trends. Psoriasis and psoriatic arthritis (PsA) both have substantive genetic determinants. Numerous candidate regions and genes have now been replicated in disease susceptibility, and to a lesser extent in disease expression, in both disease entities. Intensive efforts are now under way or are being planned to perform genome-wide association scans (GWAS) in psoriasis and PsA. A major determinant of success for GWAS is likely to be accumulation of multiple large well-phenotyped cohorts, sophisticated data management, and veri�ication of the �indings. (J Rheumatol. 2008;35:1449-53.)

Dr. Gladman et al also summarized the proceedings of GRAPPA meetings where members of the clinical registries and genetics committees described several ongoing registries, including their construction, protocols, and some results from their analyses. In breakout groups, members discussed data issues, including identi�ication of core datasets, ownership, and how to share data; and ethical issues and possible sources of funding for registries. Clinical and genetic registries are an important tool in studying psoriasis and PsA. They assist in delineating disease features and are crucial in de�ining phenotype and identifying genetic and other markers of disease expression. (J Rheumatol. 2008;35:1458-63.)

In a study aiming to describe cardiovascular morbidity in PsA, determine its prevalence, and identify risk factors for its development Dr. Gladman and colleagues prospectively followed a cohort of PsA patients according to a standard protocol including




disease-related features as well as co-morbidities. Patients with cardiovascular disease (CVD) including myocardial infarction (MI), angina, hypertension (HTN), and cerebrovascular accident (CVA) were identi�ied. The prevalences of CVD morbidities in these patients were compared to data from the Canadian Community Health Survey (CCHS) through Standardized Prevalence Ratios (SPRs). Results indicated that patients with PsA are at increased risk of cardiovascular morbidities compared to the general population. In addition to known risk factor for CVD, severe psoriasis is an important predictor in patients with PsA. (Ann Rheum Dis. 2008 Aug 12. [Epub])

Dr. Gladman collaborated on a study aiming to determine the prevalence and types of malignancy in a large cohort of patients with PsA, and to compare this rate with that in the general population. Researchers performed a cohort analysis of patients at the University of Toronto Psoriatic Arthritis Clinic who were followed prospectively. Rates of �irst malignancy in the cohort were compared with rates in the population to derive standardized incidence ratios (SIRs). Overall, 10.2% of patients in the Toronto PsA cohort developed cancer. The most frequent cancers were breast, lung, and prostate cancer. The incidence of malignancy in the large PsA cohort did not differ from that in the general population. (Arthritis Rheum. 2008;58:82-7.)

Research Developments in Rheumatoid Arthritis

Drs. Bombardier and Keystone collaborated on the �irst joint European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) publication on recommendations of how to report disease activity in clinical trials of rheumatoid arthritis (RA). Researchers conducted a literature review that followed the EULAR standardised operating procedures, and an ACR panel then approved the recommendations elaborated by the expert group. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease

activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. The higher level of homogeneity in disease activity reporting may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses. (Arthritis Rheum. 2008;59:1371-7.)

In order to elaborate EULAR/ACR recommendations on how to report disease activity in clinical trials of patients with RA, Dr. Keystone and colleagues conducted a literature review and sought expert consensus. After an initial expert meeting, during which relevant research questions were identi�ied, a systematic literature search was performed. The results of the literature search were discussed by the expert panel, modi�ied and expanded, and were used as the basis for the elaboration of the recommendation in the consensus process. Researchers obtained �ive pieces of evidence from the literature search: (1) timing and the sustaining of a response is relevant to achieve better outcomes; (2) composite disease activity indices have been used to de�ine low disease activity and remission and these de�initions have been validated as has the American Rheumatism Association (ARA) remission criteria. The “patient-reported symptom state” (PASS) is not yet well validated; (3) evidence was obtained to identify those measures, scales and patient-reported instruments, for which there is a documented association with relevant outcomes; (4) baseline disease activity is associated with disease activity levels at the end of follow-up; and (5) there was not suf�icient evidence relating the added bene�it of MRI or ultrasound over clinical assessments. The literature review was supplemented by input from experts, who then used the results as the basis for the elaboration of seven


recommendations. Endorsed by both EULAR and ACR, this approach based on scienti�ic evidence from the literature as well as on expert input provided suf�icient information to derive recommendations on reporting disease activity in RA clinical trials. (Ann Rheum Dis. 2008;67:1365-73.)

Dr. Bombardier was one of 751 rheumatologists from 17 countries who participated in the 3E (Evidence Expertise Exchange) Initiative of 2007-2008 consisting of 3 separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-2007 ACR/EULAR meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford Levels of Evidence. Ten multinational recommendations for the use of methotrexate in daily clinical practice focused on RA were developed, which are evidence-based and supported by a large panel of rheumatologists, enhancing their validity and practical use. (Ann Rheum Dis. 2008; Nov 25. [Epub])

In order to investigate whether the Canadian healthcare system is neglecting patients with “smoldering” RA disease activity, Dr. Bykerk and colleagues collected data from an audit entitled the Assessment in Rheumatology (AIR) program. Rheumatologists from across Canada were invited by the Canadian Rheumatology Association to participate in the AIR program. Researchers used program data to investigate rheumatology practice in Canada with regard to evaluating disease activity status and treatment regimens in patients with RA. One thousand �ive hundred ninety-six consecutive patients with RA seen in regular clinics were classi�ied according to 4 states of disease activity: remission, controlled adequately, smoldering, and uncontrolled. The majority of patients had “smoldering” or “uncontrolled” disease, with the remainder in “remission” or “controlled adequately” at the time of their visit. Following the appointment, the uncontrolled group had a 100% increase in the

addition of biological agents; however, there was no signi�icant increase in the rates for those with smoldering disease. Researchers therefore concluded that despite Canada’s universal healthcare system, current treatment regimens may not be optimized on the basis of disease activity. A large proportion of patients with RA seen in Canadian rheumatology practices may be experiencing unnecessary disease for a variety of reasons. (J Rheumatol. 2008;35:1506-12.)

Dr. Inman et al authored a review examining bacterial triggers of autoimmune rheumatic diseases. Reactive arthritis (ReA), rheumatic fever (RF) and Lyme disease are among the rheumatic diseases where bacterial agents are more clearly involved as triggers. The role of bacterial infections in inducing other seronegative spondyloarthritis and antiphospholipid antibody syndrome has been hypothesized but is still not proven. The classic form of ReA is associated with the presence of HLA-B27 and is triggered by the urethritis or enteritis causing pathogens Chlamydia trachomatis and the enterobacteria Salmonella, Shigella, and Yersinia, respectively. But several other pathogens have also been reported to cause ReA. RF is due to an autoimmune reaction triggered by an untreated throat infection by Streptococcus pyogenes in susceptible individuals. Carditis is the most serious manifestation of RF and HLA-DR7 is predominantly observed in the development of valvular lesions. Lyme disease is a tick-transmitted disease caused by the spirochete Borrelia burgdorferi. Knowledge is limited about how this spirochete interacts with human tissues and cells. Some data report that Borrelia burgdorferi can manipulate resident cells towards a pro- but also anti-in�lammatory reaction and persist over a long period of time inside the human body or even inside human cells. (Clin Exp Rheumatol. 2008;26:S12-7.)

Immunotherapy offers the promise of antigen-speci�ic suppression of pathological immune responses in conditions such as autoimmunity. Substantial advances have been made in recent years in terms of understanding basic immunological mechanisms



of autoreactivity, as well as clinically implementing immune-based therapies that are antigen nonspeci�ic. In a published review, Dr. Inman and colleagues sought to provide an integrated overview of the current state of the art in terms of antigen-speci�ic tolerance induction, as well as to predict future directions for the �ield. Investigators reviewed examples of successes and failures of antigen-speci�ic immunotherapy, paying particular attention to the well-established collagen II-induced model of arthritis. It was found that previous failures of antigen-speci�ic immunotherapy were associated with lack of identi�ication of clinically relevant antigens, as well as inappropriate tolerogenic methodologies. Investigators concluded that the advances in proteomics combined with novel gene-speci�ic immune modulatory techniques place today’s translational researchers in a unique position to tackle the problem of antigen-speci�ic immunotherapeutic protocols. (Expert Opin Biol Ther. 2008;8:191-9.)

Dr. Keystone et al published the results of a literature study that aimed to evaluate the safety of biologic treatments for RA using results from randomized controlled trials (RCTs). Scientists searched the literature for RCTs evaluating inhibitors of tumour necrosis factor alpha (anti-TNFs) for RA. Safety data was abstracted and risk estimates were calculated using three approaches, meta-analysis with and without adjustment for exposure and simple exposure adjusted pooling. Scientists found that meta-analytic and exposure adjusted pooled analyses on over 8,800 RA subjects in RCTs treated over an average of 0.8 years did not identify an increased risk of serious adverse events with recommended doses. High dose anti-TNF therapy was associated with a twofold increase in the risk of serious infections. (Ann Rheum Dis. 2008; Aug 27. [Epub])

Researchers recently created a model to predict progression from undifferentiated arthritis (UA) to RA, and Dr. Bykerk collaborated on a study aiming to validate the model in a Canadian UA cohort. The prediction rule consists of variables, which are scored (range 0-13), with higher scores re�lecting

an increased risk of RA. The model was applied to baseline characteristics of all UA patients, and progression to RA was determined at 6 months. After analyzing the results, investigators found that high scores in the study cohort predicted those who progressed to RA by 6 months. Baseline scores >/= 8 corresponded with higher rates of progression, validating the original prediction model. The study suggests that future research focus on how to predict disease outcome and response to therapy among patients with intermediary scores. (Ann Rheum Dis. 2008; Nov 17. [Epub])

Dr. Keystone collaborated on a study that sought to evaluate the ef�icacy and safety of 2 dosage regimens of lyophilized certolizumab pegol (a novel PEGylated anti-tumor necrosis factor agent) as adjunctive therapy to methotrexate in patients with active RA with an inadequate response to methotrexate therapy alone. In the 52-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, patients were randomized to receive treatment with certolizumab pegol plus methotrexate or placebo plus methotrexate. Co-primary end points were the response rate according to ACR20 and the mean change from baseline in the modi�ied total Sharp score. Researchers observed that treatment with both dosages of certolizumab pegol plus methotrexate resulted in a rapid and sustained reduction in RA signs and symptoms, inhibited the progression of structural joint damage, and improved physical function as compared with placebo plus methotrexate treatment in RA patients with an incomplete response to methotrexate. (Arthritis Rheum. 2008;58:3319-29.)

Dr. Keystone also collaborated on the phase III RADIATE study, which examined the ef�icacy and safety of tocilizumab, an anti-IL-6 receptor monoclonal antibody in patients with RA refractory to tumour necrosis factor (TNF) antagonist therapy. Patients with inadequate response to one or more TNF antagonists were randomly assigned to receive tocilizumab or placebo (control) intravenously every 4 weeks with stable methotrexate for 24 weeks.




American College of Rheumatology 20% criteria for improvement (ACR20) responses, secondary ef�icacy and safety endpoints were assessed. Results led researchers to conclude that Tocilizumab plus methotrexate is effective in achieving rapid and sustained improvements in signs and symptoms of RA in patients with inadequate response to TNF antagonists and has a manageable safety pro�ile. (Ann Rheum Dis. 2008;67:1516-23.)

In another recent study, Dr. Keystone and colleagues assessed the effects of treatment with rituximab plus methotrexate on patient-reported outcomes in patients with active RA who experienced inadequate response to anti-tumor necrosis factor therapy. Patients with active RA were randomly assigned to rituximab or placebo. The primary end point was the proportion of patients with an ACR20 response. Additional goals were to assess treatment effects on pain, fatigue, functional disability, health-related quality of life, and disease activity by comparing mean changes between groups. Investigators determined the proportion of patients who achieved the minimum clinically important difference on the Health Assessment Questionnaire (HAQ) disability index (DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Short Form 36 (SF-36). From their analysis, investigators concluded that rituximab produced rapid, clinically meaningful, and statistically signi�icant improvements in patient-reported pain, fatigue, functional disability, health-related quality of life, and disease activity. These effects were sustained throughout the study. (Arthritis Rheum. 2008;59:785-93.)

Tight control is a strategy of aggressive management with close monitoring and appropriate adjustments in treatment using a prespeci�ied outcome measure for decision-making. Dr. Keystone published an editorial discussing the use of this strategy to optimize therapy for patients with RA. While several studies have used this concept, few have evaluated the tight control strategy in comparison with routine care, results obtained to date have been contradictory, and protocol violations have occurred. Dr. Keystone

therefore addressed issues that need to be resolved before the rheumatology community accepts tight control, including whether the same target outcome should be used for all DMARDs, the optimum time interval needed for decision making, and the collection of information necessary to generate composite outcomes for decision making. (Nat Clin Pract Rheumatol. 2008;4:57.)

Through a systematic review of randomized trials comparing methotrexate alone and in combination with other non-biologic disease-modifying anti-rheumatic drugs (DMARDs), Dr. Bombardier and colleagues sought to evaluate the ef�icacy and toxicity of the two treatments in adults with RA. Trials were identi�ied, and primary outcomes were withdrawals for adverse events or lack of ef�icacy. Data analysis revealed that trials in DMARD naive patients showed no signi�icant advantage of the methotrexate combination versus monotherapy; withdrawals for lack of ef�icacy or toxicity were similar in both groups. Trials in methotrexate or non methotrexate DMARDs inadequate responder patients also showed no difference in withdrawal rates between the methotrexate combo vs mono groups. Researchers concluded that in DMARD naive patients the balance of ef�icacy/toxicity favours methotrexate monotherapy. In DMARD inadequate responders the evidence is inconclusive. Trials are needed that compare currently used methotrexate doses and combination therapies. (Ann Rheum Dis. 2008; Dec 3. [Epub])

Other research developments

In 2005, 592 individuals in Ontario developed acute gastroenteritis, predominantly after consuming bean sprouts contaminated with Salmonella enteritidis. Salmonella is a known trigger of ReA. Drs. Tsui, Inman et al published a report describing the population affected by the Salmonella outbreak in terms of clinical presentation of self-reported arthritic symptoms and HLA-B27 genotyping. In the study, one of the largest for a dysenteric outbreak, subjects completed a questionnaire that assessed symptoms consistent


with ReA, and submitted saliva samples, which were analyzed for HLA-B27. Upon analyzing study results, investigators found high event rate of self-reported symptoms consistent with ReA in those infected with Salmonella. Results showed that HLA-B27 may have rendered individuals more susceptible to Salmonella infection, but did not contribute to the development of symptoms consistent with ReA after infection. Given the rarity of large outbreaks of Salmonella, the study adds valuable knowledge about the course of ReA. (J Rheumatol. 2008;35:1599-602.)

Drs. Tsui, Inman et al published a follow-up report to their earlier investigation of a recent salmonellosis outbreak in which some individuals developed complications of the enteric infection. This study aimed to identify genetic variants that might predispose infected individuals to develop articular and/or extraarticular sequelae after Salmonella enteritidis infection. Scientists genotyped Salmonella-infected patients as well as a cohort of uninfected subjects, and conducted statistical analyses. Study results led researchers to conclude in this outbreak genetic variants of Toll-like receptor 2 (TLR-2) but not TLR-4 were associated with acute reactive arthritis following infection with S enteritidis. (Arthritis Rheum. 2008;58:3436-8.)

Dr. Gladman et al published the results of an investigation into the relationship between fatigue and disease-related and psychosocial variables in PsA. Scientists administered the modi�ied Fatigue Severity Scale (mFSS) to patients attending the University of Toronto PsA Clinic, and recorded clinical and laboratory measures of disease activity and damage. Scientists then examined the cross-sectional relationship between disease-related and psychosocial variables and mFSS scores. Results led scientists to conclude that 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. (Ann Rheum Dis. 2008; Oct 17. [Epub])

In a study seeking to evaluate the wait times and impact of waiting for revision total joint arthroplasty (TJA), Drs. Davis, Badley, Davey, Mahomed and colleagues followed 127 revision hip arthroplasty patients prospectively while they waited for surgery. After collecting and analyzing data, researchers were able to conclude that waiting > 6 months for revision hip arthroplasy resulted in the signi�icant increases in pain and physical disability. (Can J Surg. 2008;51:92-6.)

Proponents of navigated hip arthroplasty have suggested that it may increase the precision of acetabular component placement. Dr. Mahomed collaborated on a systematic review and meta-analysis to evaluate the validity of this theory. Scientists searched, in duplicate, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials for randomised trials comparing the use of computer navigation with the freehand technique for acetabular cup placement within the desired alignment. They then assessed the methodological quality of the studies and abstracted the relevant data. Tests of heterogeneity and publication bias were performed. From the three studies included, there was no evidence of heterogeneity between studies. From their results, they were able to conclude that navigation in hip arthroplasty improves the precision of acetabular cup placement by decreasing the number of outliers from the desired alignment. (Int Orthop. 2008; Apr 3. [Epub])

A genome-wide association scan and replication study conducted by Drs. Wither, Fortin and colleagues revealed an association between SLE and a variant in TNFAIP3. Scientists also found evidence of two independent signals near TNFAIP3 associated with SLE, including one previously associated with RA. These results establish that variants near TNFAIP3 contribute to differential risk of SLE and RA. (Nat Genet. 2008;40:1059-61.)

In a double-blind, placebo-controlled, phase 1 dose escalation study, Drs. Bookman, Keystone and colleagues examined the safety and tolerability





of a single intraarticular injection of rAAV2-TNFR:Fc, an adeno-associated virus serotype 2 vector containing the cDNA for the human tumor necrosis factor-immunoglobulin Fc fusion gene (tgAAC94), in subjects with in�lammatory arthritis. 15 subjects with in�lammatory arthritis not receiving tumor necrosis factor-alpha (TNF-alpha) inhibitors received a single intraarticular injection of rAAV2-TNFR:Fc into a knee or ankle. Safety was assessed through adverse event monitoring. As a secondary objective, changes in injected joint tenderness and swelling scores, each measured on a 4-point scale, were evaluated. Researchers found that the injections were well-tolerated with no major safety issues, and twelve weeks after injection, a 2-point decrease in swelling was noted in 2/11 subjects injected with rAAV2-TNFR:Fc. From their results, researchers were able to conclude that a single dose of intraarticular rAAV2-TNFR:Fc appears to be safe and well-tolerated in subjects without concurrent systemic TNF-alpha antagonist use. It is therefore feasible to proceed with larger trials to further test the safety and ef�icacy of local TNFR:Fc gene transfer as a therapeutic modality for patients with in�lammatory arthritis. (Ann Rheum Dis. 2008; Aug 4. [Epub])

Members of the consensus group to consider the use of biological agents in the treatment of rheumatic diseases met during the 10th Annual Workshop on Advances in Targeted Therapies. The group, which included Dr. Keystone, consisted of rheumatologists from a number of universities among the continents of Europe, North America, South America, Australia and Asia. This update of the previous consensus statement takes into account the new data for tumour necrosis factor a (TNFa) blocking agents, B-cell-speci�ic agents and interleukin 1 receptor antagonists (IL1ra). Expert participants at the consensus conference reviewed a draft document developed by the coauthors, based on a review of all relevant clinical published articles relating to TNF and IL-1 blocking agents, as well as abatacept and rituximab. After working-group discussions and an open session, the �inal updated consensus statement was produced. The aim of the group statement is to provide guidance to the

clinician in his/her efforts to improve the quality of life of patients with conditions treatable with biologic agents. In addition, this consensus statement should provide evidence-based support for the selection of agents and justi�ication for their use. (Ann Rheum Dis. 2008;67 2-25.)

In a recent case report, Dr. Lee and a colleague provided indirect evidence for the ef�icacy of methotrexate in 3 patients with diffuse systemic sclerosis (SSc) who had good response of skin scores to methotrexate, signi�icant worsening after stopping methotrexate, and subsequent improvement with reinstitution of methotrexate. The patients studied by Dr. Lee were 39 to 51 years old at reported onset of skin thickening, and initial modi�ied Rodnan skin scores (mRSS) were all ≥ 20. All patients had Raynaud’s phenomenon and joint and gastrointestinal (GI) manifestations. Researchers compared mRSS over 3 time periods: (1) �irst methotrexate treatment; (2) methotrexate discontinuation; (3) second methotrexate treatment. They observed that skin scores in all patients responded to methotrexate with > 30% improvement in the 2 treatment periods and that mRSS worsened signi�icantly with methotrexate cessation. This suggests that the treatment may have played a role in suppressing skin progression. This case report serves as an impetus for prospective randomized controlled trials involving larger numbers of patients and higher doses of methotrexate to evaluate its ef�icacy in early diffuse SSc. (J Rheumatol. 2008;35:2286.)

In a published commentary about fractures and osteoporosis, Dr. Cheung and a colleague discuss the measure of bone mineral density (BMD) as a risk factor for osteoporotic fractures. In her article, Dr. Cheung applies principles from engineering to highlight that bone strength depends on a combination of its structural and material properties, both of which are modulated by bone turnover. Experts in osteoporosis are highly cognizant of the limitations of using BMD for the prediction of fracture risk. In response to these limitations, WHO and other organizations recently have recommended using an individual’s 10-year


fracture risk to guide therapy decisions. Although this long-awaited WHO instrument is a substantial improvement over using BMD as the sole criterion for initiating therapy, it still has limitations. Few large prospective cohort studies which identi�ied risk factors for osteoporosis and fractures examined muscle strength, sarcopenia, gait, balance, history of falls, and other risk factors for falls in methodologically rigorous ways. As a result, these important factors are not included in the WHO model. The commentary concludes that, in the effort to prevent fractures, attention focuses too heavily on BMD to the exclusion of other vital factors. Low BMD is one of a number of risk factors for osteoporotic fractures. The current paradigm must be broadened to include the study of how muscle, nerves, and bone work together as a unit for coordination, mobility, balance, and strength. Dr. Cheung and colleague recommend that assessing the risk of falls using orthostatic blood pressure measurements and validated tools, such as the timed up-and-go, functional reach, and physiological pro�ile assessment tests, should be a routine component of assessing fracture risk, and more research is needed in this area. (JAMA. 2008;299:1468-70.)


AARC Protocols: 2005-2008*

•� The number of active AARC protocols has been increasing with approximately 47 new

studies being initiated per year. New AARC protocols increased 41% from 2007 to 2008

* NOTE: Reflects UHN REB-approved protocols where an investigator was listed as PI


Research Activity

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Research Activity

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UHN-U of T Administered Funding: 2005-2008

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Research Activity


Comparative Bibliometric Analysis

•� AARC investigators’ publications and those with similar research

foci from Johns Hopkins Arthritis Center, the University of Alabama

(U Alabama) and The Rosalind Russell Medical Research Center for

Arthritis at the University of California in San Francisco (UCSF)

were compared to view AARC’s impact relative to leading

institutions.

•� Publication, journal impact and citation data were derived from

Thomson Scientific databases.

•� Analysis was conducted on a per-publication basis using 2005-2008

publications.

•� Citation data reflects the number of cites to 2005-2008 papers as of

April 2009.

Metrics

•� Per investigator or per paper rates are reported to control for differences in the size of

the groups compared or numbers of publications.

•� “High-Impact” journals are those with a Journal Impact Factor (JIF) score > 10

(indicating a journal has 10 cites for each paper published in a two year period).

Metrics controlling for subject area bias:

•� A median journal impact factor score by subject area (e.g. surgery, immunology, haematology) is

now available for 2005 to 2007. The difference between this subject-area median impact (SAMI) and

the JIF of each publication has been used to calculate a group’s average deviation from the SAMI.

This can demonstrate the degree to which papers are being published in journals considered higher-

impact for that subject area.

•� ISI uses citation data to identify highly cited (top 10%) papers across 22 broad subject areas (e.g.

Clinical Medicine). Top papers from 2005-2008 have been identified using current subject-area

specific citation thresholds. Differences in the proportions of Top Papers is reported.

Research Activity


Comparative Publications and Citations

•� AARC investigators continue to publish significantly more papers than AARC’s comparators.

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��

��

Research Activity


Research Activity Data Source: AARC Research Activity (2005-2008), April 2009.Contact: [email protected]

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All groups have seen an established pattern in their proportions of highly cited papers over the

years. Further analysis revealed a significant rise of AARC’s proportion of highly cited papers in

2008 from the previous two years.

2008 Publications


Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O’Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D; EULAR; ACR. Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. Arthritis Rheum. 2008;59:1371-7.

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O’Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D. Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. Ann Rheum Dis. 2008;67:1360-4.

Ammendolia C, Taylor JA, Pennick V, Côté P, Hogg-Johnson S, Bombardier C. Adherence to radiography guidelines for low back pain: a survey of chiropractic schools worldwide. J Manipulative Physiol Ther. 2008;31:412-8.

Anastakis DJ, Malessy MJ, Chen R, Davis KD, Mikulis D. Hand Clin. Cortical plasticity following nerve transfer in the upper extremity. 2008;24:425-44, vi-vii.

Antoni CE, Kavanaugh A, van der Heijde D, Beutler A, Keenan G, Zhou B, Kirkham B, Tutuncu Z, Burmester GR, Schneider U, Furst DE, Molitor J, Keystone E, Gladman DD, Manger B, Wassenberg S, Weier R, Wallace DJ, Weisman MH, Kalden JR, Smolen JS. Two-year ef�icacy and safety of in�liximab treatment in patients with active psoriatic arthritis: �indings of the In�liximab Multinational Psoriatic Arthritis Controlled Trial. J Rheumatol. 2008;35:869-76.

Avcin T, Makitie O, Susic M, Miller S, Thorne C, Tenenbaum J, Laxer RM, Cole WG. Early-onset osteoarthritis due to otospondylomegaepiphyseal dysplasia in a family with a novel splicing mutation of the COL11A2 gene. J Rheumatol. 2008;35:920-6.

Badley EM. Enhancing the conceptual clarity of the activity and participation components of the International Classi�ication of Functioning, Disability, and Health. Soc Sci Med. 2008;66:2335-45.

Badley EM. Rheumatic diseases: the unnoticed elephant in the room. J Rheumatol. 2008;35:6-7.

Baig E, Fish EN. Distinct signature type I interferon responses are determined by the infecting virus and the target cell. Antivir Ther. 2008;13:409-22.

Bello AM, Bende T, Wei L, Wang X, Majchrzak-Kita B, Fish EN, Kotra LP. De novo design of nonpeptidic compounds targeting the interactions between interferon-alpha and its cognate cell surface receptor. J Med Chem. 2008;51:2734-43.

Bernatsky S, Joseph L, Boivin JF, Gordon C, Urowitz M, Gladman D, Fortin PR, Ginzler E, Bae SC, Barr S, Edworthy S, Isenberg D, Rahman A, Petri M, Alarcón GS, Aranow C, Dooley MA, Rajan R, Sénécal JL, Zummer M, Manzi S, Ramsey-Goldman R, Clarke AE. The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case-cohort study. Ann Rheum Dis. 2008;67:74-9.

Bhargava S, Patterson JM, Inman RD, MacNeil S, Chapple CR. Tissue-engineered buccal mucosa urethroplasty-clinical outcomes. Eur Urol. 2008;53:1263-9.

Bingener J, Boyd T, Van Sickle K, Jung I, Saha A, Winston J, Lopez P, Ojeda H, Schwesinger W, Anastakis D. Randomized double-blinded trial investigating the impact of a curriculum focused on error recognition on laparoscopic suturing training. Am J Surg. 2008;195:179-82.

2008 Publications


Borkhoff CM, Hawker GA, Kreder HJ, Glazier RH, Mahomed NN, Wright JG. The effect of patients’ sex on physicians’ recommendations for total knee arthroplasty. CMAJ. 2008;178:681-7.

Boyle E, Côté P, Grier AR, Cassidy JD. Examining vertebrobasilar artery stroke in two Canadian provinces. Spine. 2008;33:S170-5.

Brunner HI, Gladman DD, Ibañez D, Urowitz MD, Silverman ED. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008;58:556-62.

Cameron JI, Cheung AM, Streiner DL, Coyte PC, Singh MD, Stewart DE. Factor structure and reliability of the brain impairment behavior scale. J Neurosci Nurs. 2008;40:40-7.

Cameron JI, Gignac MA. “Timing It Right”: a conceptual framework for addressing the support needs of family caregivers to stroke survivors from the hospital to the home. Patient Educ Couns. 2008;70:305-14.

Cañizares M, Power JD, Perruccio AV, Badley EM. Association of regional racial/cultural context and socioeconomic status with arthritis in the population: a multilevel analysis. Arthritis Rheum. 2008;59:399-407.

Carragee EJ, Hurwitz EL, Cheng I, Carroll LJ, Nordin M, Guzman J, Peloso P, Holm LW, Côté P, Hogg-Johnson S, van der Velde G, Cassidy JD, Haldeman S; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Treatment of neck pain: injections and surgical interventions: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S153-69.

Carroll LJ, Cassidy JD, Peloso PM, Giles-Smith L, Cheng CS, Greenhalgh SW, Haldeman S, van der Velde G, Hurwitz EL, Côté P, Nordin M, Hogg-Johnson S, Holm LW, Guzman J, Carragee EJ; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Methods for the best evidence synthesis on neck pain and its associated disorders: the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S33-8.

Carroll LJ, Hogg-Johnson S, Côté P, van der Velde G, Holm LW, Carragee EJ, Hurwitz EL, Peloso PM, Cassidy JD, Guzman J, Nordin M, Haldeman S; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Course and prognostic factors for neck pain in workers: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S93-100.

Carroll LJ, Hogg-Johnson S, van der Velde G, Haldeman S, Holm LW, Carragee EJ, Hurwitz EL, Côté P, Nordin M, Peloso PM, Guzman J, Cassidy JD; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Course and prognostic factors for neck pain in the general population: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S75-82.

Carroll LJ, Holm LW, Hogg-Johnson S, Côté P, Cassidy JD, Haldeman S, Nordin M, Hurwitz EL, Carragee EJ, van der Velde G, Peloso PM, Guzman J; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Course and prognostic factors for neck pain in whiplash-associated disorders (WAD): results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S83-92.

Carroll LJ, Hurwitz EL, Côté P, Hogg-Johnson S, Carragee EJ, Nordin M, Holm LW, van der Velde G, Cassidy JD, Guzman J, Peloso PM, Haldeman S; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Research priorities and methodological implications: the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S214-20. s

Cassidy JD, Boyle E, Côté P, He Y, Hogg-Johnson S, Silver FL, Bondy SJ. Risk of vertebrobasilar stroke and chiropractic care: results of a population-based case-control and case-crossover study. Spine. 2008;33:S176-83.

Cassidy JD, Côté P. Is it time for a population health approach to neck pain? J Manipulative Physiol Ther. 2008;31:442-6. s

Chandran V, Schentag CT, Gladman DD. Reappraisal of the effectiveness of methotrexate in psoriatic arthritis: results from a longitudinal observational cohort. J Rheumatol. 2008;35:469-71.

Chandran V, Schentag CT, Gladman DD. Sensitivity and speci�icity of the CASPAR criteria for psoriatic arthritis in a family medicine clinic setting. J Rheumatol. 2008;35:2069-70.

Chang NH, McKenzie T, Bonventi G, Landolt-Marticorena C, Fortin PR, Gladman D, Urowitz M, Wither JE. Expanded population of activated antigen-engaged cells within the naive B cell compartment of patients with systemic lupus erythematosus. J Immunol. 2008;180:1276-84.

Chesworth BM, Mahomed NN, Bourne RB, Davis AM; OJRR Study Group. Willingness to go through surgery again validated the WOMAC clinically important difference from THR/TKR surgery. J Clin Epidemiol. 2008;6:907-18. Cheung AM, Detsky AS. Osteoporosis and fractures: missing the bridge? JAMA. 2008;299:1468-70.

Cheung AM, Lee Y, Kapral M, Scher J, Ho I, Lui-Yee D, Stewart DE. Barriers and motivations for women to participate in cardiovascular trials. J Obstet Gynaecol Can. 2008;30:332-7.

Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson L, Jamal S, Josse R. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008;5:e196.

Cheung AM. Combined HRT increased CV events more than placebo but did not differ from oestrogen HRT after menopause. Evid Based Med. 2008;13:52.

Cheung AM. Risk of cancer was still increased over 2 years after stopping hormone therapy. Evid Based Med. 2008;13:142.

Cibere J, Thorne A, Bellamy N, Greidanus N, Chalmers A, Mahomed N, Shojania K, Kopec J, Esdaile JM. Reliability of the hip examination in osteoarthritis: effect of standardization. Arthritis Rheum. 2008;59:373-81.

Cooper GS, Wither J, McKenzie T, Claudio JO, Bernatsky S, Fortin PR; CaNIOS GenES Investigators. The prevalence and accuracy of self-reported history of 11 autoimmune diseases. J Rheumatol. 2008;35:2001-4.

Correa DD, Shi W, Thaler HT, Cheung AM, DeAngelis LM, Abrey LE. Longitudinal cognitive follow-up in low grade gliomas. J Neurooncol. 2008;86:321-7.

Côté P, Cassidy JD, Carette S, Boyle E, Shearer HM, Stupar M, Ammendolia C, van der Velde G, Hayden JA, Yang X, van Tulder M, Frank JW. Protocol of a randomized controlled trial of the effectiveness of physician education and activation versus two rehabilitation programs for the treatment of Whiplash-associated Disorders: The University Health Network Whiplash Intervention Trial. Trials. 2008;9:75.

2008 Publications


Côté P, van der Velde G, Cassidy JD, Carroll LJ, Hogg-Johnson S, Holm LW, Carragee EJ, Haldeman S, Nordin M, Hurwitz EL, Guzman J, Peloso PM; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. The burden and determinants of neck pain in workers: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S60-74.

Cott CA, Falter LB, Gignac M, Badley E. Helping networks in community home care for the elderly: types of team. Can J Nurs Res. 2008;40:19-37.

Cunninghame Graham DS, Vyse TJ, Fortin PR, Montpetit A, Cai YC, Lim S, McKenzie T, Farwell L, Rhodes B, Chad L, Hudson TJ, Sharpe A, Terhorst C, Greenwood CM, Wither J, Rioux JD; CaNIOS GenES Investigators. Association of LY9 in UK and Canadian SLE families. Genes Immun. 2008;9:93-102.

Davis AM, Agnidis Z, Badley E, Davey JR, Gafni A, Gollish J, Mahomed NN, Saleh KJ, Schemitsch EH, Szalai JP, Waddell JP, Gross AE. Waiting for hip revision surgery: the impact on patient disability. Can J Surg. 2008;51:92-6.

Davis AM, Perruccio AV, Canizares M, Tennant A, Hawker GA, Conaghan PG, Roos EM, Jordan JM, Maillefert JF, Dougados M, Lohmander LS. The development of a short measure of physical function for hip OA HOOS-Physical Function Shortform (HOOS-PS): an OARSI/OMERACT initiative. Osteoarthritis Cartilage. 2008;16:551-9.

Davis JC Jr, van der Heijde DM, Braun J, Dougados M, Clegg DO, Kivitz AJ, Fleischmann RM, Inman RD, Ni L, Lin SL, Tsuji WH. Ef�icacy and safety of up to 192 weeks of etanercept therapy in patients with ankylosing spondylitis. Ann Rheum Dis. 2008;67:346-52.

Dimitriou ID, Clemenza L, Scotter AJ, Chen G, Guerra FM, Rottapel R. Putting out the �ire: coordinated suppression of the innate and adaptive immune systems by SOCS1 and SOCS3 proteins. Immunol Rev. 2008;224:265-83.

Dionne CE, Dunn KM, Croft PR, Nachemson AL, Buchbinder R, Walker BF, Wyatt M, Cassidy JD, Rossignol M, Leboeuf-Yde C, Hartvigsen J, Leino-Arjas P, Latza U, Reis S, Gil Del Real MT, Kovacs FM, Oberg B, Cedraschi C, Bouter LM, Koes BW, Picavet HS, van Tulder MW, Burton K, Foster NE, Macfarlane GJ, Thomas E, Underwood M, Waddell G, Shekelle P, Volinn E, Von Korff M. A consensus approach toward the standardization of back pain de�initions for use in prevalence studies. Spine. 2008;33:95-103.

Duf�in KC, Chandran V, Gladman DD, Krueger GG, Elder JT, Rahman P. Genetics of psoriasis and psoriatic arthritis: update and future direction. J Rheumatol. 2008;35:1449-53.

Dvali LT, Myckatyn TM. End-to-side nerve repair: review of the literature and clinical indications. Hand Clin. 2008;24:455-60.

Edworthy S, Zummer M, Garner S, Boire G, Leclercq S, Bykerk V, Kraag G, Markland J, Thomas D, Thomson J, Henderson J. Smoldering rheumatoid arthritis: is the Canadian healthcare system neglecting a signi�icant disease population? J Rheumatol. 2008;35:1506-12.

Emery P, Keystone E, Tony HP, Cantagrel A, van Vollenhoven R, Sanchez A, Alecock E, Lee J, Kremer J. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis. 2008;67:1516-23.

Fish EN. The X-�iles in immunity: sex-based differences predispose immune responses. Nat Rev Immunol. 2008;8:737-44.

2008 Publications


Fortin PR, Abrahamowicz M, Ferland D, Lacaille D, Smith CD, Zummer M; Canadian Network For Improved Outcomes in Systemic Lupus. Steroid-sparing effects of methotrexate in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2008;59:1796-804.

Fortin PR. How to put wellness on the prescription pad: recommendations. Curr Oncol. 2008;15 Suppl 2:s109.es79-80.

Friedman TM, Goldgirsh K, Berger SA, Zilberberg J, Filicko-O’Hara J, Flomenberg N, Donato M, Rowley SD, Korngold R. Overlap between in vitro donor antihost and in vivo posttransplantation TCR Vbeta use: a new paradigm for designer allogeneic blood and marrow transplantation. Blood. 2008;112:3517-25.

Furlan AD, Tomlinson G, Jadad AA, Bombardier C. Examining heterogeneity in meta-analysis: comparing results of randomized trials and nonrandomized studies of interventions for low back pain. Spine. 2008;33:339-48.

Furlan JC, Fehlings MG, Tator CH, Davis AM. Motor and sensory assessment of patients in clinical trials for pharmacological therapy of acute spinal cord injury: psychometric properties of the ASIA Standards. J Neurotrauma. 2008;25:1273-301.

Furst DE, Keystone EC, Kirkham B, Kavanaugh A, Fleischmann R, Mease P, Breedveld FC, Smolen JS, Kalden JR, Burmester GR, Braun J, Emery P, Winthrop K, Bresnihan B, De Benedetti F, Dörner T, Gibofsky A, Schiff MH, Sieper J, Singer N, Van Riel PL, Weinblatt ME, Weisman MH. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2008. Ann Rheum Dis. 2008 Dec;67 Suppl 3:iii2-25.

Gandhi R, Alomran A, Mahomed N. Bilateral non-union of high tibial osteotomies treated by total knee arthroplasty: a case report. Knee. 2008;15:242-5.

Gandhi R, Davey JR, Mahomed N. Patient Expectations Predict Greater Pain Relief with Joint Arthroplasty. J Arthroplasty. 2008 Aug 11.

Gandhi R, Davey JR, Mahomed NN. Predicting patient dissatisfaction following joint replacement surgery. J Rheumatol. 2008;35:2415-8.

Gandhi R, Marchie A, Farrokhyar F, Mahomed N. Computer navigation in total hip replacement: a meta-analysis. Int Orthop. 2008 Apr 3 [Epub].

Gandhi R, Razak F, Davey JR, Mahomed NN. Ethnicity and patient’s perception of risk in joint replacement surgery. J Rheumatol. 2008;35:1664-7.

Gandhi R, Razak F, Mahomed NN. Ethnic differences in the relationship between obesity and joint pain and function in a joint arthroplasty population. J Rheumatol. 2008;35:1874-7.

Gandhi R, Razak F, Pathy R, Davey JR, Syed K, Mahomed NN. Antibiotic Bone Cement and the Incidence of Deep Infection after Total Knee Arthroplasty. J Arthroplasty. 2008 Sep 25 [Epub].

Gignac MA, Backman CL, Davis AM, Lacaille D, Mattison CA, Montie P, Badley EM. Understanding social role participation: what matters to people with arthritis? J Rheumatol. 2008;35:1655-36.

Gignac MA, Cao X, Lacaille D, Anis AH, Badley EM. Arthritis-related work transitions: a prospective analysis of reported productivity losses, work changes, and leaving the labor force. Arthritis Rheum. 2008 Dec 15;59:1805-13.

Girschick HJ, Guilherme L, Inman RD, Latsch K, Rihl M, Sherer Y, Shoenfeld Y, Zeidler H, Arienti S, Doria A. Bacterial triggers and autoimmune rheumatic diseases. Clin Exp Rheumatol. 2008;26:S12-7.

Gladman DD, Ang M, Su L, Tom BD, Schentag CT Phd, Farewell VT. Cardiovascular morbidity in psoriatic arthritis (PsA). Ann Rheum Dis. 2008 Aug 12 [Epub].

2008 Publications


Gladman DD, Rahman P, Krueger GG, Mease PJ, Qureshi AA, Dutz JP, Lindqvist U, Carneiro S, Helliwell PS, Ujfalussy I, Gottlieb AB, Behrens F, Ståhle M. Clinical and genetic registries in psoriatic disease. J Rheumatol. 2008;35:1458-63.

Gladman DD. Adalimumab, etanercept and in�liximab are equally effective treatments for patients with psoriatic arthritis. Nat Clin Pract Rheumatol. 2008;4:510-1.

Gladman DD. Can we identify psoriatic arthritis early? Curr Rheumatol Rep. 2008;10:419-21.

Gladman DD. GRAPPA 2007: Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. J Rheumatol. 2008;35:1420-2.

Gladman DD. Mortality in psoriatic arthritis. Clin Exp Rheumatol. 2008;26:S62-5.

Goldenberg NA, Bombardier C, Hathaway WE, McFarland K, Jacobson L, Manco-Johnson MJ. In�luence of factor IX on overall plasma coagulability and �ibrinolytic potential as measured by global assay: monitoring in haemophilia B. Haemophilia. 2008;14:68-77.

Graham B, Scho�ield M. Self-reported symptoms of cold intolerance in workers with injuries of the hand. Hand (N Y). 2008;3:203-9.

Graham B. The value added by electrodiagnostic testing in the diagnosis of carpal tunnel syndrome. J Bone Joint Surg Am. 2008;90:2587-93.

Graham RR, Cotsapas C, Davies L, Hackett R, Lessard CJ, Leon JM, Burtt NP, Guiducci C, Parkin M, Gates C, Plenge RM, Behrens TW, Wither JE, Rioux JD, Fortin PR, Graham DC, Wong AK, Vyse TJ, Daly MJ, Altshuler D, Moser KL, Gaffney PM. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet. 2008;40.

Guzman J, Haldeman S, Carroll LJ, Carragee EJ, Hurwitz EL, Peloso P, Nordin M, Cassidy JD, Holm LW, Côté P, van der Velde G, Hogg-Johnson S; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Clinical practice implications of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders: from concepts and �indings to recommendations. Spine. 2008;33:S199-213.

Guzman J, Hurwitz EL, Carroll LJ, Haldeman S, Côté P, Carragee EJ, Peloso PM, van der Velde G, Holm LW, Hogg-Johnson S, Nordin M, Cassidy JD; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. A new conceptual model of neck pain: linking onset, course, and care: the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S14-23.

Haldeman S, Carroll L, Cassidy JD, Schubert J, Nygren A; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. The Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders: executive summary. Spine. 2008;33:S5-7.

Haldeman S, Carroll LJ, Cassidy JD; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. The empowerment of people with neck pain: introduction: the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S8-S13.

2008 Publications


Hanly JG, Urowitz MB, Siannis F, Farewell V, Gordon C, Bae SC, Isenberg D, Dooley MA, Clarke A, Bernatsky S, Gladman D, Fortin PR, Manzi S, Steinsson K, Bruce IN, Ginzler E, Aranow C, Wallace DJ, Ramsey-Goldman R, van Vollenhoven R, Sturfelt G, Nived O, Sanchez-Guerrero J, Alarcón GS, Petri M, Khamashta M, Zoma A, Font J, Kalunian K, Douglas J, Qi Q, Thompson K, Merrill JT; Systemic Lupus International Collaborating Clinics. Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: results from an international inception cohort study. Arthritis Rheum. 2008;58:843-53.

Hanly JG, Urowitz MB, Su L, Sanchez-Guerrero J, Bae SC, Gordon C, Wallace DJ, Isenberg D, Alarcón GS, Merrill JT, Clarke A, Bernatsky S, Dooley MA, Fortin PR, Gladman D, Steinsson K, Petri M, Bruce IN, Manzi S, Khamashta M, Zoma A, Font J, Van Vollenhoven R, Aranow C, Ginzler E, Nived O, Sturfelt G, Ramsey-Goldman R, Kalunian K, Douglas J, Qiufen Qi K, Thompson K, Farewell V; Systemic Lupus International Collaborating Clinics. Short-term outcome of neuropsychiatric events in systemic lupus erythematosus upon enrollment into an international inception cohort study. Arthritis Rheum. 2008;59:721-9.

Harley I, Rosen B, Risch HA, Siminovitch K, Beiner ME, McLaughlin J, Sun P, Narod SA. Ovarian cancer risk is associated with a common variant in the promoter sequence of the mismatch repair gene MLH1. Gynecol Oncol. 2008;109:384-7.

Haroon N, Tsui FW, O’Shea FD, Chiu B, Tsui HW, Zhang H, Marshall WK, Inman RD. From gene expression to serum proteins: biomarker discovery in Ankylosing Spondylitis. Ann Rheum Dis. 2008 Dec 22 [Epub].

Hassett AL, Li T, Buyske S, Savage SV, Gignac MA. The multi-faceted assessment of independence in patients with rheumatoid arthritis: preliminary validation from the ATTAIN study. Curr Med Res Opin. 2008;24:1443-53.

Hawker GA, Davis AM, French MR, Cibere J, Jordan JM, March L, Suarez-Almazor M, Katz JN, Dieppe P. Development and preliminary psychometric testing of a new OA pain measure--an OARSI/OMERACT initiative. Osteoarthritis Cartilage. 2008;16:409-14.

Hayden JA, Côté P, Steenstra IA, Bombardier C; QUIPS-LBP Working Group. Identifying phases of investigation helps planning, appraising, and applying the results of explanatory prognosis studies. J Clin Epidemiol. 2008;61:552-60.

Hincapié CA, Cassidy JD, Côté P. Is a history of work-related low back injury associated with prevalent low back pain and depression in the general population? BMC Musculoskelet Disord. 2008;9:22.

Hincapié CA, Morton EJ, Cassidy JD. Musculoskeletal injuries and pain in dancers: a systematic review. Arch Phys Med Rehabil. 2008;89:1819-29.

Hogg-Johnson S, van der Velde G, Carroll LJ, Holm LW, Cassidy JD, Guzman J, Côté P, Haldeman S, Ammendolia C, Carragee E, Hurwitz E, Nordin M, Peloso P; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. The burden and determinants of neck pain in the general population: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S39-51.

Holm LW, Carroll LJ, Cassidy JD, Hogg-Johnson S, Côté P, Guzman J, Peloso P, Nordin M, Hurwitz E, van der Velde G, Carragee E, Haldeman S; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. The burden and determinants of neck pain in whiplash-associated disorders after traf�ic collisions: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S52-9.

Holm LW, Carroll LJ, Cassidy JD, Skillgate E, Ahlbom A. Expectations for recovery important in the prognosis of whiplash injuries. PLoS Med. 2008;5:e105.

2008 Publications


Hudak PL, Grassau P, Glazier RH, Hawker G, Kreder H, Coyte P, Mahomed N, Wright JG. “Not everyone who needs one is going to get one’’: the in�luence of medical brokering on patient candidacy for total joint arthroplasty. Med Decis Making. 2008;28:773-80.

Hudson M, Bernatsky S, Taillefer S, Fortin PR, Wither J, Baron M; Canadian Scleroderma Research Group (CSRG); Canadian Network for Improved Outcomes in Systemic Lupus Erythematosus (CaNIOS). Patients with systemic autoimmune diseases could not distinguish comorbidities from their index disease. J Clin Epidemiol. 2008;61:654-62.

Hurwitz EL, Carragee EJ, van der Velde G, Carroll LJ, Nordin M, Guzman J, Peloso PM, Holm LW, Côté P, Hogg-Johnson S, Cassidy JD, Haldeman S; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Treatment of neck pain: noninvasive interventions: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S123-52.

Husted JE, Tom BD, Schentag CT, Farewell VT, Gladman DD. Occurrence and correlates of fatigue in psoriatic arthritis (PsA). Ann Rheum Dis. 2008 Oct 17 [Epub].

Ichim TE, Zheng X, Suzuki M, Kubo N, Zhang X, Min LR, Beduhn ME, Riordan NH, Inman RD, Min WP. Antigen-speci�ic therapy of rheumatoid arthritis. Expert Opin Biol Ther. 2008;8:191-9.

Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, Mack M, Han J, Visvanathan S, Xu Z, Hsu B, Beutler A, Braun J. Ef�icacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008;58:3402-12.

Janzen V, Fleming HE, Riedt T, Karlsson G, Riese MJ, Lo Celso C, Reynolds G, Milne CD, Paige CJ, Karlsson S, Woo M, Scadden DT. Hematopoietic stem cell responsiveness to exogenous signals is limited by caspase-3. Cell Stem Cell. 2008;2:584-94.

Jensen AR, Wright AS, Lance AR, O’Brien KC, Pratt CD, Anastakis DJ, Pellegrini CA, Horvath KD.The emotional intelligence of surgical residents: a descriptive study. Am J Surg. 2008;195:5-10.

Jensen AR, Wright AS, McIntyre LK, Levy AE, Foy HM, Anastakis DJ, Pellegrini CA, Horvath KD. Laboratory-based instruction for skin closure and bowel anastomosis for surgical residents. Arch Surg. 2008;143:852-8.

Joseph V, Al Jahwari AS, Rampersaud YR. Mediastinal migration of distal occipito-thoracic instrumentation. Eur Spine J. 2008;17.

Karonitsch T, Aletaha D, Boers M, Bombardieri S, Combe B, Dougados M, Emery P, Felson D, Gomez-Reino J, Keystone E, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Richards P, van Riel P, Siegel J, Smolen JS, Sokka T, van der Heijde D, van Vollenhoven R, Ward M, Wells G, Zink A, Landewe R. Methods of deriving EULAR/ACR recommendations on reporting disease activity in clinical trials of patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67:1365-73.

Karp I, Abrahamowicz M, Fortin PR, Pilote L, Neville C, Pineau CA, Esdaile JM. Recent corticosteroid use and recent disease activity: independent determinants of coronary heart disease risk factors in systemic lupus erythematosus? Arthritis Rheum. 2008;59:169-75.

2008 Publications


Katchamart W, Trudeau J, Phumethum V, Bombardier C. The ef�icacy and toxicity of MTX (methotrexate) monotherapy vs. methotrexate combination therapy with non-biologic disease-modifying anti-rheumatic drugs in rheumatoid arthritis: A systematic review and metaanalysis. Ann Rheum Dis. 2008 Dec 3 [Epub].

Katsoulidis E, Sassano A, Majchrzak-Kita B, Carayol N, Yoon P, Jordan A, Druker BJ, Fish EN, Platanias LC. Suppression of interferon (IFN)-inducible genes and IFN-mediated functional responses in BCR-ABL-expressing cells. J Biol Chem. 2008;283:10793-803.

Kaur S, Sassano A, Dolniak B, Joshi S, Majchrzak-Kita B, Baker DP, Hay N, Fish EN, Platanias LC. Role of the Akt pathway in mRNA translation of interferon-stimulated genes. Proc Natl Acad Sci U S A. 2008;105:4808-13.

Kaur S, Sassano A, Joseph AM, Majchrzak-Kita B, Eklund EA, Verma A, Brachmann SM, Fish EN, Platanias LC. Dual regulatory roles of phosphatidylinositol 3-kinase in IFN signaling. J Immunol. 2008;181:7316-23.

Keystone E, Burmester GR, Furie R, Loveless JE, Emery P, Kremer J, Tak PP, Broder MS, Yu E, Cravets M, Magrini F, Jost F. Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy. Arthritis Rheum. 2008;59:785-93.

Keystone E, Heijde D, Mason D Jr, Landewé R, Vollenhoven RV, Combe B, Emery P, Strand V, Mease P, Desai C, Pavelka K. Certolizumab pegol plus methotrexate is signi�icantly more effective than placebo plus methotrexate in active rheumatoid arthritis: �indings of a �ifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 2008;58:3319-29.

Keystone EC, Genovese MC, Klareskog L, Hsia EC, Hall ST, Miranda PC, Pazdur J, Bae SC, Palmer W, Zrubek J, Wiekowski M, Visvanathan S, Wu Z, Rahman MU. Golimumab, a human antibody to TNF-{alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate: The GO-FORWARD Study. Ann Rheum Dis. 2008 Dec 11 [Epub].

Keystone EC. Is a step-down regimen more effective than a step-up regimen in the treatment of early rheumatoid arthritis? Nat Clin Pract Rheumatol. 2008;4:396-7.

Keystone EC. Tight control for the management of RA--a therapeutic approach worth pursuing. Nat Clin Pract Rheumatol. 2008;4:57.

Kim TJ, Kim TH, Lee HJ, Peddle L, Rahman P, Hu P, Greenwood CM, Inman RD. Interleukin 1 polymorphisms in patients with ankylosing spondylitis in Korea. J Rheumatol. 2008;35:1603-8.

Konforte D, Simard N, Paige CJ. Interleukin-21 regulates expression of key Epstein-Barr virus oncoproteins, EBNA2 and LMP1, in infected human B cells. Virology. 2008;374:100-13.

Kopec JA, Rahman MM, Sayre EC, Cibere J, Flanagan WM, Aghajanian J, Anis AH, Jordan JM, Badley EM. Trends in physician-diagnosed osteoarthritis incidence in an administrative database in British Columbia, Canada, 1996-1997 through 2003-2004. Arthritis Rheum. 2008;59:929-34.

Kraft GH, Johnson KL, Yorkston K, Amtmann D, Bamer A, Bombardier C, Ehde D, Fraser R, Starks H. Setting the agenda for multiple sclerosis rehabilitation research. Mult Scler. 2008;14:1292-7.

2008 Publications


Kristman VL, Côté P, Van Eerd D, Vidmar M, Rezai M, Hogg-Johnson S, Wennberg RA, Cassidy JD. Prevalence of lost-time claims for mild traumatic brain injury in the working population: improving estimates using workers compensation databases. Brain Inj. 2008;22:51-9.

Kuriya B, Cheng CK, Chen HM, Bykerk VP. Validation of a prediction rule for development of rheumatoid arthritis in patients with early undifferentiated arthritis. Ann Rheum Dis. 2008 Nov 17 [Epub].

Kuriya B, Gladman DD, Ibañez D, Urowitz MB. Quality of life over time in patients with systemic lupus erythematosus. Arthritis Rheum. 2008;59:181-5.

Labbe A, Nelles M, Walia J, Jia L, Furlonger C, Nonaka T, Medin JA, Paige CJ. IL-12 Immunotherapy of Murine Leukemia: Comparison of Systemic Versus Gene Modi�ied Cell Therapy. J Cell Mol Med. 2008 Jun 28 [Epub].

Lacaille D, White MA, Rogers PA, Backman CL, Gignac MA, Esdaile JM. A proof-of-concept study of the “Employment and Arthritis: Making It Work” program. Arthritis Rheum. 2008;59:1647-55.

Landolt-Marticorena C, Bonventi G, Lubovich A, Ferguson C, Unnitahn T, Su J, Gladman DD, Urowitz M, Fortin PR, Wither J. Lack of association between the interferon-alpha signature and longitudinal changes in disease activity in Systemic Lupus Erythematosus. Ann Rheum Dis. 2008 Sep 4 [Epub].

Landry MD, Jaglal S, Wodchis WP, Raman J, Cott CA. Analysis of factors affecting demand for rehabilitation services in Ontario, Canada: a health-policy perspective. Disabil Rehabil. 2008;30:1837-47.

Lee J, Viakhireva N, Cesca C, Lee P, Kohler S, Hoppe RT, Kim YH. Clinicopathologic features and treatment outcomes in Woringer-Kolopp disease. J Am Acad Dermatol. 2008;59:706-12.

Leombruno JP, Einarson TR, Keystone EC. The safety of anti-Tumor Necrosis Factor treatments in rheumatoid arthritis: meta and exposure adjusted pooled analyses of serious adverse events. Ann Rheum Dis. 2008 Aug 27 [Epub].

Li LC, Badley EM, MacKay C, Mosher D, Jamal SW, Jones A, Bombardier C. An evidence-informed, integrated framework for rheumatoid arthritis care. Arthritis Rheum. 2008;59:1171-83.

Li SK, Smith DK, Leung WY, Cheung AM, Lam EW, Dimri GP, Yao KM. FoxM1c counteracts oxidative stress-induced senescence and stimulates Bmi-1 expression. J Biol Chem. 2008;283:16545-53.

Lineker SC, Bell MJ, Boyle J, Badley EM, Flakstad L, Fleming J, Lyddiatt A, Macdonald J, McCarthy J, Zummer M. Implementing arthritis clinical practice guidelines in primary care. Med Teach. 2008:1-8.

Low AH, Lee P. Indirect evidence for the ef�icacy of methotrexate in diffuse systemic sclerosis. J Rheumatol. 2008;35:2286.

Machado GP, Gignac MA, Badley EM. Participation restrictions among older adults with osteoarthritis: a mediated model of physical symptoms, activity limitations, and depression. Arthritis Rheum. 2008;59:129-35.

MacKay C, Veinot P, Badley EM. Characteristics of evolving models of care for arthritis: a key informant study. BMC Health Serv Res. 2008;8:147.

Mahomed NN, Davis AM, Hawker G, Badley E, Davey JR, Syed KA, Coyte PC, Gandhi R, Wright JG. Inpatient compared with home-based rehabilitation following primary unilateral total hip or knee replacement: a randomized controlled trial. J Bone Joint Surg Am. 2008;90:1673-80.

2008 Publications


Mahomed NN, Syed K, Sledge CB, Brennan TA, Liang MH. Improving the Postmarket Surveillance of Total Joint Arthroplasty Devices. Open Rheumatol J. 2008;2:7-12.

Maksymowych WP, Rahman P, Shojania K, Olszynski WP, Thomson GT, Ballal S, Wong RL, Inman RD; M03-606 Study Group. Bene�icial effects of adalimumab on biomarkers re�lecting structural damage in patients with ankylosing spondylitis. J Rheumatol. 2008;35:2030-7.

Marshman LA, Friesem T, Rampersaud YR, Le Huec JC, Krishna M. Subsidence and malplacement with the Oblique Maverick Lumbar Disc Arthroplasty: technical note. Spine J. 2008;8:650-5.

McGilton KS, Mahomed N, Davis AM, Flannery J, Calabrese S. Outcomes for older adults in an inpatient rehabilitation facility following hip fracture (HF) surgery. Arch Gerontol Geriatr. 2008 Oct 7 [Epub].

Mease PJ, Hobbs K, Chalmers A, El-Gabalawy H, Bookman A, Keystone E, Furst DE, Anklesaria P, Heald AE. Local delivery of a recombinant adeno-associated vector containing a tumor necrosis factor-{alpha} antagonist gene in in�lammatory arthritis: a phase 1 dose-escalation safety and tolerability study. Ann Rheum Dis. 2008 Aug 4 [Epub].

Milne CD, Corfe SA, Paige CJ. Heparan sulfate and heparin enhance ERK phosphorylation and mediate preBCR-dependent events during B lymphopoiesis. J Immunol. 2008;180:2839-47.

Murooka TT, Rahbar R, Platanias LC, Fish EN. CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1. Blood. 2008;111:4892-901.

Na KS, Kim TH, Rahman P, Peddle L, Choi CB, Inman RD. Analysis of single nucleotide polymorphisms in Toll-like receptor 4 shows no association with ankylosing spondylitis in a Korean population. Rheumatol Int. 2008;28:627-30.

Nam RK, Zhang WW, Loblaw DA, Klotz LH, Trachtenberg J, Jewett MA, Stanimirovic A, Davies TO, Toi A, Venkateswaran V, Sugar L, Siminovitch KA, Narod SA. A genome-wide association screen identi�ies regions on chromosomes 1q25 and 7p21 as risk loci for sporadic prostate cancer. Prostate Cancer Prostatic Dis. 2008;11:241-6.

Nepal RM, Zaheen A, Basit W, Li L, Berger SA, Martin A. AID and RAG1 do not contribute to lymphomagenesis in Emu c-myc transgenic mice. Oncogene. 2008;27:4752-6.

Niapour M, Yu Y, Berger SA. Regulation of calpain activity by c-Myc through calpastatin and promotion of transformation in c-Myc-negative cells by calpastatin suppression. J Biol Chem. 2008;283:21371-81.

Nikpour M, Dempsey AA, Urowitz MB, Gladman DD, Barnes DA. Association of a gene expression pro�ile from whole blood with disease activity in systemic lupus erythaematosus. Ann Rheum Dis. 2008;67:1069-75.

Nordin M, Carragee EJ, Hogg-Johnson S, Weiner SS, Hurwitz EL, Peloso PM, Guzman J, van der Velde G, Carroll LJ, Holm LW, Côté P, Cassidy JD, Haldeman S; Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Assessment of neck pain and its associated disorders: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008;33:S101-22.


2008 Publications


2008 Publications

O’Brien KK, Bayoumi AM, Strike C, Young NL, Davis AM. Exploring disability from the perspective of adults living with HIV/AIDS: development of a conceptual framework. Health Qual Life Outcomes. 2008;6:76.

O’Shea FD, Boyle E, Riarh R, Tse SM, Laxer RM, Inman RD. Comparison of clinical and radiographic severity of juvenile-onset versus adult-onset ankylosing spondylitis. Ann Rheum Dis. 2008 Sep 9 [Epub].

Orlacchio A, Bruce IN, Rahman P, Kawarai T, Bernardi G, St George-Hyslop PH, Gladman DD, Urowitz MB. The apolipoprotein E2 isoform is associated with accelerated onset of coronary artery disease in systemic lupus erythematosus. Med Sci Monit. 2008;14:CR233-237.

Parsons JA, Eakin JM, Bell RS, Franche RL, Davis AM. “So, are you back to work yet?” Re-conceptualizing ‘work’ and ‘return to work’ in the context of primary bone cancer. Soc Sci Med. 2008;67:1826-36.

Paul J, Park L, Ryter E, Miller W, Ahmed S, Cott CA, Landry MD. Delisting publicly funded community-based physical therapy services in Ontario, Canada: a 12-month follow-up study of the perceptions of clients and providers. Physiother Theory Pract. 2008;24:329-43.

Perruccio AV, Stefan Lohmander L, Canizares M, Tennant A, Hawker GA, Conaghan PG, Roos EM, Jordan JM, Maillefert JF, Dougados M, Davis AM. The development of a short measure of physical function for knee OA KOOS-Physical Function Shortform (KOOS-PS) - an OARSI/OMERACT initiative. Osteoarthritis Cartilage. 2008;16:542-50.

Petri M, Kasitanon N, Lee SS, Link K, Magder L, Bae SC, Hanly JG, Isenberg DA, Nived O, Sturfelt G, van Vollenhoven R, Wallace DJ, Alarcón GS, Adu D, Avila-Casado C, Bernatsky SR, Bruce IN, Clarke AE, Contreras G, Fine DM, Gladman DD, Gordon C, Kalunian KC, Madaio MP, Rovin BH, Sanchez-Guerrero J, Steinsson K, Aranow C, Balow JE, Buyon JP, Ginzler EM, Khamashta MA, Urowitz MB, Dooley MA, Merrill JT, Ramsey-Goldman R, Font J, Tumlin J, Stoll T, Zoma A; Systemic Lupus International Collaborating Clinics. Systemic lupus international collaborating clinics renal activity/response exercise: development of a renal activity score and renal response index. Arthritis Rheum. 2008;58:1784-8.

Petri M, Kasitanon N, Singh S, Link K, Magder L, Bae SC, Hanly JG, Nived O, Sturfelt G, van Vollenhoven R, Wallace DJ, Alarcón GS, Adu D, Avila-Casado C, Bernatsky SR, Bruce IN, Clarke AE, Contreras G, Fine DM, Gladman DD, Gordon C, Kalunian KC, Madaio MP, Rovin BH, Sanchez-Guerrero J, Steinsson K, Aranow C, Balow JE, Buyon JP, Ginzler EM, Khamashta MA, Urowitz MB, Dooley MA, Merrill JT, Ramsey-Goldman R, Font J, Tumlin J, Stoll T, Zoma A; Systemic Lupus International Collaborating Clinics. Systemic lupus international collaborating clinics renal activity/response exercise: comparison of agreement in rating renal response. Arthritis Rheum. 2008;58:1789-95.

Power JD, Badley EM, French MR, Wall AJ, Hawker GA. Fatigue in osteoarthritis: a qualitative study. BMC Musculoskelet Disord. 2008;9:63.

Qu G, von Schroeder HP. The osteogenic potential of pseudoarthrosis tissue and bone from human scaphoid non-unions. J Hand Surg Eur 2008;33:449-56.

Qu G, von Schroeder HP. Trabecular microstructure at the human scaphoid nonunion. J Hand Surg [Am]. 2008;33:650-5.

2008 Publications


Qureshi AA, Dominguez P, Duf�in KC, Gladman DD, Helliwell P, Mease PJ, Husni ME. Psoriatic arthritis screening tools. J Rheumatol. 2008;35:1423-5.

Rahman P, Inman RD, Gladman DD, Reeve JP, Peddle L, Maksymowych WP. Association of interleukin-23 receptor variants with ankylosing spondylitis. Arthritis Rheum. 2008;58:1020-5.

Rampersaud YR, Ravi B, Lewis SJ, Stas V, Barron R, Davey R, Mahomed N. Assessment of health-related quality of life after surgical treatment of focal symptomatic spinal stenosis compared with osteoarthritis of the hip or knee. Spine J. 2008;8:296-304.

Rastogi R, Chesworth BM, Davis AM. Change in patient concerns following total knee arthroplasty described with the International Classi�ication of Functioning, Disability and Health: a repeated measures design. Health Qual Life Outcomes. 2008;6:112.

Ritchlin CT, Kavanaugh A, Gladman DD, Mease PJ, Helliwell P, Boehncke WH, de Vlam K, Fiorentino D, Fitzgerald O, Gottlieb AB, McHugh N, Nash PT, Qureshi A, Soriano ER, Taylor WJ. Treatment recommendations for psoriatic arthritis. Ann Rheum Dis. 2008 Oct 24 [Epub].

Rohekar S, Tom BD, Hassa A, Schentag CT, Farewell VT, Gladman DD. Prevalence of malignancy in psoriatic arthritis. Arthritis Rheum. 2008;58:82-7.

Rohekar S, Tsui FW, Tsui HW, Xi N, Riarh R, Bilotta R, Inman RD. Symptomatic acute reactive arthritis after an outbreak of salmonella. J Rheumatol. 2008;35:1599-602.

Santaguida PL, Hawker GA, Hudak PL, Glazier R, Mahomed NN, Kreder HJ, Coyte PC, Wright JG. Patient characteristics affecting the prognosis of total hip and knee joint arthroplasty: a systematic review. Can J Surg. 2008;51:428-36.

Saraiva D, de Camargo B, Davis AM. Cultural adaptation, translation and validation of a functional outcome questionnaire (TESS) to Portuguese with application to patients with lower extremity osteosarcoma. Pediatr Blood Cancer. 2008;50:1039-42.

Saryeddine T, Levy C, Davis A, Flannery J, Jaglal S, Hurley L, McGlasson R, Mahomed N. Patient education as a strategy for provider education and engagement: a case study using myJointReplacement.ca. Healthc Q. 2008;11:84-90.

Sims AM, Timms AE, Bruges-Armas J, Burgos-Vargas R, Chou CT, Doan T, Dowling A, Fialho RN, Gergely P, Gladman DD, Inman R, Kauppi M, Kaarela K, Laiho K, Maksymowych W, Pointon JJ, Rahman P, Reveille JD, Sorrentino R, Tuomilehto J, Vargas-Alarcon G, Wordsworth BP, Xu H, Brown MA; International Genetics of Ankylosing Spondylitis. Prospective meta-analysis of interleukin 1 gene complex polymorphisms con�irms associations with ankylosing spondylitis. Ann Rheum Dis. 2008;67:1305-9.

Smith JA, Barnes MD, Hong D, DeLay ML, Inman RD, Colbert RA. Gene expression analysis of macrophages derived from ankylosing spondylitis patients reveals interferon-gamma dysregulation. Arthritis Rheum. 2008;58:1640-9.

Smith SD, Gignac MA, Richardson D, Cameron JI. Differences in the experiences and support needs of family caregivers to stroke survivors: does age matter? Top Stroke Rehabil. 2008;15:593-601.

Stein JD, Lee P, Kuriya B, Tenenbaum J, Daniel LB, Butany J, Provost YL, David TE. Critical coronary artery stenosis and aortitis in a patient with relapsing polychondritis. J Rheumatol. 2008;35:1898-900.


2008 Publications

Stöckli J, Davey JR, Hohnen-Behrens C, Xu A, James DE, Ramm G. Regulation of glucose transporter 4 translocation by the Rab guanosine triphosphatase-activating protein AS160/TBC1D4: role of phosphorylation and membrane association. Mol Endocrinol. 2008;22:2703-15.

Stone MA, Pomeroy E, Keat A, Sengupta R, Hickey S, Dieppe P, Gooberman-Hill R, Mogg R, Richardson J, Inman RD. Assessment of the impact of �lares in ankylosing spondylitis disease activity using the Flare Illustration. Rheumatology (Oxford). 2008;47:1213-8.

Thompson MD, Siminovitch KA, Cole DE. G protein-coupled receptor pharmacogenetics. Methods Mol Biol. 2008;448:139-85.

Toloza S, Pellett F, Chandran V, Ibanez D, Urowitz M, Gladman D. Association of killer cell immunoglobulin-like receptor genotypes with vascular arterial events and anticardiolipin antibodies in patients with lupus. Lupus. 2008;17:793-8.

Tsui FW, Xi N, Rohekar S, Riarh R, Bilotta R, Tsui HW, Inman RD. Toll-like receptor 2 variants are associated with acute reactive arthritis. Arthritis Rheum. 2008;58:3436-8.

Urowitz MB, Gladman D, Ibañez D, Fortin P, Sanchez-Guerrero J, Bae S, Clarke A, Bernatsky S, Gordon C, Hanly J, Wallace D, Isenberg D, Ginzler E, Merrill J, Alarcón GS, Steinsson K, Petri M, Dooley MA, Bruce I, Manzi S, Khamashta M, Ramsey-Goldman R, Zoma A, Sturfelt G, Nived O, Maddison P, Font J, van Vollenhoven R, Aranow C, Kalunian K, Stoll T; Systemic Lupus International Collaborating Clinics. Accumulation of coronary artery disease risk factors over three years: data from an international inception cohort. Arthritis Rheum. 2008;59:176-80.

Urowitz MB, Gladman DD, MacKinnon A, Ibañez D, Bruto V, Rovet J, Silverman E. Neurocognitive abnormalities in offspring of mothers with systemic lupus erythematosus. Lupus. 2008;17:555-60.

Urowitz MB, Gladman DD, Tom BD, Ibañez D, Farewell VT. Changing patterns in mortality and disease outcomes for patients with systemic lupus erythematosus. J Rheumatol. 2008;35:2152-8.

Urowitz MB, Gladman DD. The SLICC inception cohort for atherosclerosis. Curr Rheumatol Rep. 2008;10:281-5.

van der Velde G, Hogg-Johnson S, Bayoumi AM, Cassidy JD, Côté P, Boyle E, Llewellyn-Thomas H, Chan S, Subrata P, Hoving JL, Hurwitz E, Bombardier C, Krahn M. Identifying the best treatment among common nonsurgical neck pain treatments: a decision analysis. Spine. 2008;33:S184-91.

Verma A, Cheung AM, Burns DL. Stabilization of the pertussis toxin secretion apparatus by the C terminus of PtlD. J Bacteriol. 2008;190:7285-90.

Visser K, Katchamart W, Loza E, Martinez-Lopez JA, Salliot C, Trudeau J, Bombardier C, Carmona L, van der Heijde D, Bijlsma JW, Boumpas DT, Canhao H, Edwards CJ, Hamuryudan V, Kvien TK, Leeb BF, Martín-Mola EM, Mielants H, Müller-Ladner U, Murphy G, Ostergaard M, Pereira IA, Ramos-Remus C, Valentini G, Zochling J, Dougados M. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis. 2008 Nov 25 [Epub].

Walmsley S, Cheung AM, Fantus G, Gough K, Smaill F, Azad, Diong C, Raboud J. A prospective study of body fat redistribution, lipid, and glucose parameters in HIV-infected patients initiating combination antiretroviral therapy. HIV Clin Trials. 2008;9:314-23.


Wang J, Tsui HW, Beier F, Pritzker KP, Inman RD, Tsui FW. The ANKH DeltaE490Mutation in Calcium Pyrophosphate Dihydrate Crystal Deposition Disease (CPPDD) Affects Tissue Non-speci�ic Alkaline Phosphatase (TNAP) Activities. Open Rheumatol J. 2008;2:23-30.

Weyand B, Israelowitz M, von Schroeder HP, Vogt PM. Fluid Dynamics in Bioreactor Design: Considerations for the Theoretical and Practical Approach. Adv Biochem Eng Biotechnol. 2008 Oct 1 [Epub].

Wither J, Cai YC, Lim S, McKenzie T, Roslin N, Claudio JO, Cooper GS, Hudson TJ, Paterson AD, Greenwood CM, Gladman D, Pope J, Pineau CA, Smith CD, Hanly JG, Peschken C, Boire G; CaNIOS Investigators, Fortin PR. Reduced proportions of natural killer T cells are present in the relatives of lupus patients and are associated with autoimmunity. Arthritis Res Ther. 2008;10:R108.

Wong J, El Beheiry H, Rampersaud YR, Lewis S, Ahn H, De Silva Y, Abrishami A, Baig N, McBroom RJ, Chung F. Tranexamic Acid reduces perioperative blood loss in adult patients having spinal fusion surgery. Anesth Analg. 2008;107:1479-86.

Yee G, Lau J. Current concepts review: hallux rigidus. Foot Ankle Int. 2008;29:637-46.

Yu Y, Niapour M, Zhang Y, Berger SA. Mitochondrial regulation by c-Myc and hypoxia-inducible factor-1 alpha controls sensitivity to econazole. Mol Cancer Ther. 2008;7:483-91.

Zwillinger N, Carette S, Lorenceau B. [Salvage of a leg avulsion injury by vacuum negative pressure therapy: a case report] Ann Chir Plast Esthet. 2008;53:74-8.

2008 Publications

Documents

2008 Activity Report - UHN Research