Publications by authors named "Murray Baron"

229 Publications

A randomised, double-blind, placebo-controlled phase 3 study of lenabasum in diffuse cutaneous systemic sclerosis: RESOLVE-1 design and rationale.

Clin Exp Rheumatol 2021 Jul-Aug;39 Suppl 131(4):124-133. Epub 2021 Jul 21.

UCL Centre for Rheumatology and Connective Tissue Diseases, Royal Free Campus, University College London, UK.

Objectives: The multi-systemic, heterogenous nature of diffuse cutaneous systemic sclerosis (dcSSc) presents challenges in designing clinical studies that can demonstrate a treatment effect on overall disease burden. We describe the design of the first Phase 3 study in dcSSc patients where the American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score was chosen prospectively as the primary outcome. The CRISS measures key clinical disease parameters and patient-reported outcomes (PROs).

Methods: RESOLVE-1 is a Phase 3, randomised, double-blind, placebo-controlled trial of dcSSc patients evaluating the efficacy and safety of lenabasum. Patients ≥18 years of age with dc-SSc and disease duration ≤6 years were eligible. Patients could continue stable background therapy for dcSSc, including stable immunosuppressive therapies. They were randomised to lenabasum 5 or 20 mg twice daily or placebo. The primary efficacy outcome was the mean change from baseline to 52 weeks in the ACR CRISS score.

Results: The study enrolled 365 patients over 1.5 years at 77 sites in 13 countries in North America, Europe, Israel, and Asia-Pacific, with the last patient first visit on May 1, 2019.

Conclusions: RESOLVE-1 is the first Phase 3 interventional study to date in dcSSc to prospectively use the ACR CRISS as the primary efficacy outcome. Eligibility criteria allowed background therapy as might occur in clinical practice. This approach also facilitated timely patient enrolment. RESOLVE-1 provides a novel study design that may be used for future Phase 3 dcSSc studies to assess the holistic efficacy of therapy.
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August 2021

ASSOCIATION BETWEEN IMMUNOSUPPRESSIVE THERAPY AND INCIDENT RISK OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS.

Chest 2021 Jun 18. Epub 2021 Jun 18.

Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada; Division of Rheumatology, Jewish General Hospital, Montreal, Quebec, Canada.

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http://dx.doi.org/10.1016/j.chest.2021.06.014DOI Listing
June 2021

Immunosuppression does not prevent severe gastrointestinal tract involvement in systemic sclerosis.

Clin Exp Rheumatol 2021 Jul-Aug;39 Suppl 131(4):142-148. Epub 2021 Jun 9.

Department of Medicine, McGill University, Montreal, Quebec; Division of Rheumatology, Jewish General Hospital, Montreal, Quebec, and Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.

Objectives: We aimed to test the hypothesis that exposure to immunosuppression in early systemic sclerosis (SSc) could modify the risk of developing new onset severe gastrointestinal (GIT) involvement.

Methods: A total of 762 subjects with <3 years of disease duration and without severe GIT disease at baseline study visit were identified from combined longitudinal cohort data from the Canadian Scleroderma Research Group (CSRG) and Australian Scleroderma Interest Group (ASIG). The primary exposure was ever use of methotrexate, cyclophosphamide, mycophenolate mofetil and/or azathioprine during the study period. Severe GIT disease was defined as: 1-malabsorption, 2-hyperalimentation, 3-pseudo-obstruction, and/or 4-≥10% weight loss in association with the use of antibiotics for bacterial overgrowth or oesophageal stricture. The change in the hazard of severe GIT disease due to exposure was estimated using a marginal structural Cox proportional hazards model fit by inverse probability of treatment weights (IPTW) to address potential confounding.

Results: Study subjects were 81.5% female, had a mean age of 53.7±13.0 years and mean disease duration at baseline of 1.4±0.8 years. During a mean follow-up of 4.0±2.6 years, severe GIT involvement developed in 11.6% of the 319 subjects exposed to immunosuppression and in 6.8% of the 443 unexposed subjects. In an IPTW-adjusted analysis, exposure to immunosuppression was not associated with severe GIT disease (weighted hazard ratio 0.91, 95% confidence interval 0.52-1.58).

Conclusions: In this large inception SSc cohort, the risk of severe GIT involvement was not modified by exposure to immunosuppression.
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August 2021

Oxidative stress-induced senescence mediates inflammatory and fibrotic phenotypes in fibroblasts from systemic sclerosis patients.

Rheumatology (Oxford) 2021 Jun 11. Epub 2021 Jun 11.

Faculty of Pharmacy, Université de Montréal, Québec, Canada.

Objective: Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by inflammation and fibrosis. Although constitutive activation of fibroblasts is proposed to be responsible for the fibrotic and inflammatory features of the disease, the underlying mechanism remains elusive and, effective therapeutic targets are still lacking. The aim of this study was to evaluate the role of oxidative stress-induced senescence and its contribution to the pro-fibrotic and pro-inflammatory phenotypes of fibroblasts from SSc patients.

Methods: Dermal fibroblasts were isolated from SSc (n = 13) and healthy (n = 10) donors. Fibroblast's intracellular and mitochondrial reactive oxygen species were determined by flow cytometry. Mitochondrial function measured by Seahorse XF24 analyzer. Fibrotic and inflammatory gene expressions were assessed by qPCR and key pro-inflammatory components of the fibroblasts' secretome (interleukin (IL) 6 and IL8) were quantified by ELISA.

Results: Compared to healthy fibroblasts, SSc fibroblasts displayed higher levels of both intracellular and mitochondrial ROS. Oxidative stress in SSc fibroblasts induced the expression of fibrotic genes and activated the transforming growth factor-β-activated kinase 1 (TAK1) -IκB kinase β (IKKβ)- interferon regulatory factor 5 (IRF5) inflammatory signaling cascade. These cellular responses paralleled the presence of a DNA damage response, a senescence-associated secretory phenotype and a fibrotic response. Treatment of SSc fibroblasts with ROS scavengers reduced their pro-inflammatory secretome production and fibrotic gene expression.

Conclusions: Oxidative stress-induced cellular senescence in SSc fibroblasts underlies their pro-inflammatory and pro-fibrotic phenotypes. Targeting redox imbalance of SSc fibroblasts enhances their in vitro functions and could be of relevance for SSc therapy.
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http://dx.doi.org/10.1093/rheumatology/keab477DOI Listing
June 2021

Association between gastroprotective agents and risk of incident interstitial lung disease in systemic sclerosis.

Respir Med 2021 May 27;185:106482. Epub 2021 May 27.

Department of Medicine, Université de Montréal, Montreal, Quebec, Canada; Division of Rheumatology, Centre hospitalier de l'Université de Montréal, Montreal, Quebec, Canada. Electronic address:

Objectives: Although interstitial lung disease (ILD) occurs in over half of systemic sclerosis (SSc) patients and represents a leading cause of mortality, there are currently no preventative strategies. We evaluated if gastroprotective agents were associated with a lower incident risk of SSc-ILD.

Methods: An SSc cohort without clinically apparent ILD at baseline was constructed from the Canadian Scleroderma Research Group registry. The primary exposure was any use of gastroprotective agents. Treatment with promotility agents was assessed as a secondary exposure. Time to development of clinically apparent ILD was compared between exposed and unexposed person-time, using a multivariable marginal structural Cox model incorporating inverse probability of treatment weights to address time-varying confounding.

Results: In total, 798 subjects met inclusion criteria. At cohort entry, median disease duration was 7.6 (IQR 3.9-15.6) years. During a median 4.4 (IQR 2.6-7.2) years of follow-up, 158 new ILD cases were diagnosed, for a crude incidence of 4.4 (95% CI 3.8-5.1) events per 100 person-years. Most (2085, 73.4%) person-visits were exposed to gastroprotective agents, 579 (20.4%) were exposed to promotility agents, and 554 (19.5%) were exposed to both agents. The marginal structural weighted hazard ratio (HR) for incident ILD related to gastroprotective agents was 0.86 (95% CI 0.52-1.41). When exposure was defined as treatment with promotility agents, the weighted adjusted HR was 0.79 (95% CI: 0.35-1.77).

Conclusion: In this large retrospective cohort study, we were unable to demonstrate a protective role for gastroprotective and promotility agents in preventing clinically apparent SSc-ILD.
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http://dx.doi.org/10.1016/j.rmed.2021.106482DOI Listing
May 2021

Systematic analysis of the literature in search of defining systemic sclerosis subsets.

J Rheumatol 2021 May 15. Epub 2021 May 15.

Schulich School of Medicine & Dentistry, Western University, London, ON, Canada; University of Michigan, Ann Arbor, MI, USA; St. Maartenskliniek and Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; University of Michigan, Ann Arbor, MI, USA; Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; Department of Experimental and Clinical Medicine & Division of Rheumatology AOUC, Florence Italy University of Florence, Florence, Italy; McGill University, Division Head Rheumatology Jewish General Hospital, Montreal, Quebec, Canada; University College London Division of Medicine, London, UK; Toronto Scleroderma Program, Toronto Western and Mount Sinai Hospitals, Department of Medicine; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada. Acknowledgements. This work was supported by a grant from the Scleroderma Foundation and the World Scleroderma Foundation. Dr. Johnson is supported by a Canadian Institutes of Health Research New Investigator Award and the Gurmej Kaur Dhanda Scleroderma Research Award. Dr Khanna was funded by the NIH /NIAMS 5K24AR063120-07. Address correspondence and requests for reprints to: Dr. Sindhu Johnson, Toronto Scleroderma Program, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario, Canada, M5T 2S8. Phone 1-416-603-6417.

Objective: Systemic sclerosis (SSc) is a multisystem disease with heterogeneity in presentation and prognosis. An international collaboration to develop new SSc subset criteria is underway. Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria.

Methods: Medline, Cochrane MEDLINE, CINAHL, EMBASE and Web of Science were searched from their inceptions to December 2019 for studies related to SSc sub-classification, limited to humans without language or sample size restrictions.

Results: Of 5686 citations, 102 articles reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and/or scleroderma-specific autoantibodies (n=61), nailfold capillary patterns (n=29), molecular, genomic and cellular patterns (n=12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality; only subsetting by gene expression signatures in tissue samples has been associated with response to therapy.

Conclusion: Subsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns and tissue gene expression signatures have been proposed as innovative means of SSc subsetting.
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http://dx.doi.org/10.3899/jrheum.201594DOI Listing
May 2021

Trigeminal neuralgia in systemic sclerosis.

Semin Arthritis Rheum 2021 02 7;51(1):318-323. Epub 2021 Jan 7.

Lady Davis Institute for Medical Research, Montreal, QC, Canada; Division of Rheumatology, Jewish General Hospital, Montreal, QC, Canada; Department of Medicine, McGill University, Montreal, QC, Canada.

Objectives: Although trigeminal neuralgia (TN) has been associated with systemic sclerosis (SSc), there is a paucity of evidence and pathophysiological processes remain unknown. We undertook a nested case-control study to identify associations between TN and SSc in a large multi-centered cohort and identify possible pathophysiological links.

Methods: Data were derived from a longitudinal cohort of 1652 SSc subjects. Cases with a physician-reported diagnosis of TN were identified at baseline visit (prevalent) and during follow-up (incident). Each case was matched on study visit to four SSc patients without TN. Sociodemographic, clinical and serological characteristics of cases and controls were compared.

Results: At enrolment, 43/1652 (2.6%) subjects had a history of TN. During follow-up, an additional 36 subjects developed TN over 6193 person-years of observation (incidence rate 5.8 per 1000 person-years). Cases were identified and matched to 172 and 144 controls, respectively. Compared to controls, prevalent cases had more inflammatory myositis (24.4% versus 5.2%, p<0.001) and inflammatory arthritis (46.5% versus 30.2%, p = 0.043). Incident cases also had more inflammatory myositis (19.4% versus. 6.3%, p = 0.033) and inflammatory arthritis (50.0% versus. 16.2%, p<0.001) compared to controls. There was a trend towards more interstitial lung disease in prevalent (32.6% versus 23.8%, p = 0.241) and incident (55.6% versus 40.6%, p = 0.105) cases compared to controls.

Conclusion: This study provides novel evidence for a clinical association linking TN, inflammatory myositis, inflammatory arthritis and possibly interstitial lung disease. In addition to ischemia, we propose that TN in SSc could also be a consequence of inflammatory and possibly fibrotic processes.
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http://dx.doi.org/10.1016/j.semarthrit.2021.01.001DOI Listing
February 2021

Toward Understanding of Environmental Risk Factors in Systemic Sclerosis [Formula: see text].

J Cutan Med Surg 2021 Mar-Apr;25(2):188-204. Epub 2020 Sep 28.

54473 Division of Dermatology, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada.

Importance: Systemic sclerosis (SSc) is a severe, chronic, and incurable autoimmune fibrotic skin disease with significant extracutaneous involvement. Low concordance rate in twin studies and unequal geographic distribution of SSc argues for importance of environment in disease initiation and progression.

Objective: In this manuscript we provide a summary of all investigated potential external risk factors for SSc.

Data Sources: A literature search in PubMed and EMBASE database was performed for studies published until January 1, 2020 by 2 reviewers (EN and LO) independently.

Findings: Occupational and/or environmental exposures to silica and organic solvents are associated with increased incidence and severity of SSc. Exposure to epoxy resins, asbestos, and particulate air pollution favors increased risk of SSc, but data are based on limited number of observational studies. There is insufficient evidence to conclude an association between SSc development and other occupational (eg, welding fumes) or personal exposures (eg, smoking, vitamin D deficiency). Association of SSc with silicone breast implants has been disproven. Infectious pathogens (eg, and angiotropic viruses) and dysbiosis seem to play a role in SSc development and severity, but their role remains to be clarified.

Conclusions And Relevance: It may be prudent to counsel our patients with SSc (or those at risk of SSc) to avoid occupations with exposure to silica, organic solvents, asbestos and epoxy resins; restraint from smoking, using cocaine or drugs with pro-fibrotic potential. While the association between low vitamin D and SSc remains to be confirmed, we believe that SSc patients should be encouraged to maintain healthy vitamin D levels as benefits outweigh the risks.
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http://dx.doi.org/10.1177/1203475420957950DOI Listing
September 2020

Association of Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis With Marked Improvement in Health-Related Quality of Life.

Arthritis Rheumatol 2021 02 29;73(2):305-314. Epub 2020 Dec 29.

Centre de Référence des Maladies Auto-Immunes Systémiques Rares d'Ile-de-France, AP-HP, Hôpital St. Louis, Université de Paris, Institut de Recherche St. Louis, EA 3518, Hôpital St. Antoine, Paris, France, and McGill University, Montreal, Quebec, Canada.

Objective: To quantify the magnitude, domains, and duration of change in health-related quality of life (HRQoL) in patients with systemic sclerosis (SSc) who underwent autologous hematopoietic stem cell transplantation (HSCT) as compared to SSc patients with similar characteristics who did not undergo autologous HSCT.

Methods: The study was designed as a retrospective study comparing SSc patients who underwent autologous HSCT and SSc patients who met the criteria for transplantation but were treated with conventional care. Outcomes included scores on the 36-item Short Form (SF-36) health survey and the Health Assessment Questionnaire (HAQ) and its disease-specific symptom scales. Differences in scores between the groups were compared using linear models, adjusting for baseline scores and inverse probability of treatment and censoring weights.

Results: In total, 41 SSc patients who underwent autologous HSCT and 65 SSc patients treated with conventional care were compared. In marginal linear weighted models, the SF-36 physical component summary score was a mean ± SEM 7.02 ± 1.94 points higher at the first annual visit (P = 0.001) and 14.40 ± 6.16 points higher at the seventh annual visit (P = 0.03) in patients treated with autologous HSCT compared to the conventional care group. HAQ scores were significantly better in the autologous HSCT group compared to the conventional care group during follow-up (mean ± SEM difference from baseline -0.57 ± 0.13 [P < 0.001] at the first annual visit and -0.94 ± 0.49 [P = 0.07] at the seventh annual visit). There were no differences in the SF-36 mental component summary scores between the 2 groups either at baseline or during follow-up.

Conclusion: This study provides robust complementary HRQoL data, including overall and event-free survival data, to expand on the standard repertoire of biomedical variables, thus potentially supporting the physical benefits of autologous HSCT in patients with SSc.
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http://dx.doi.org/10.1002/art.41519DOI Listing
February 2021

Calcinosis is associated with ischemic manifestations and increased disability in patients with systemic sclerosis.

Semin Arthritis Rheum 2020 10 17;50(5):891-896. Epub 2020 Jun 17.

Stanford University School of Medicine and Palo Alto VA Health Care System, Department of Immunology and Rheumatology and Dermatology (by courtesy), USA. Electronic address:

Objective: Calcinosis is a debilitating complication of systemic sclerosis (SSc) with no effective treatments. We sought to identify clinical correlations and to characterize complications and disability associated with calcinosis in a multi-center, international cohort of SSc patients.

Methods: We established a cohort of 568 consecutive SSc patients who fulfill 2013 revised ACR/EULAR criteria at 10 centers within North America, Australia, and Mexico. Calcinosis was defined as subcutaneous calcium deposition by imaging and/or physical examination, or a clear history of extruded calcium. All patients completed the Scleroderma Health Assessment Questionnaire Disability Index and Cochin Hand Functional Scale.

Results: 215 (38%) patients had calcinosis. In multivariable analysis, disease duration (OR=1.24, p = 0.029), digital ischemia (OR=1.8, p = 0.002) and Acro-osteolysis (OR=2.97, p = 0.008) were significantly associated with calcinosis. In the subset of patients with bone densitometry (n = 68), patients with calcinosis had significantly lower median T-scores than patients without (-2.2 vs. -1.7, p = 0.004). The most common location of calcinosis lesions was the hands (70%), particularly the thumbs (19%) with decreasing frequency moving to the fifth fingers (8%). The most common complications were tenderness (29% of patients) and spontaneous extrusion of calcinosis through the skin (20%), while infection was rare (2%). Disability and hand function were worse in patients with calcinosis, particularly if locations in addition to the fingers/thumbs were involved.

Conclusions: We confirmed a strong association between calcinosis and digital ischemia. Calcinosis in SSc patients most commonly affects the hands and is associated with a high burden of disability and hand dysfunction.
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http://dx.doi.org/10.1016/j.semarthrit.2020.06.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205269PMC
October 2020

Immunosuppressive treatment in diffuse cutaneous systemic sclerosis is associated with an improved composite response index (CRISS).

Arthritis Res Ther 2020 06 5;22(1):132. Epub 2020 Jun 5.

Division of Rheumatology, Jewish General Hospital, McGill University, Montreal, QC, Canada.

Background: Outcomes of therapeutic studies in diffuse cutaneous systemic sclerosis (dcSSc) have mainly been measured for specific organs, particularly the skin and lungs. A new composite response index in dcSSc (CRISS) has been developed for clinical trials. The goal of this study was to determine whether, in an observational dcSSc cohort, immunosuppression was associated with global disease improvement measured with the CRISS.

Methods: We conducted a retrospective cohort study in a multi-centered SSc registry comparing 47 patients newly exposed to immunosuppression for ≥ 1 year to 254 unexposed patients. Inverse probability of treatment weighting (IPTW) was performed to create comparable exposed and unexposed groups by balancing for age, sex, disease duration, modified Rodnan skin score (mRSS), forced vital capacity, patient and physician global assessments, and Health Assessment Questionnaire score. A CRISS score ≥ 0.6 at 1 year was defined as improvement.

Results: Exposed patients had shorter disease duration (5.5 versus 11.7 years, p < 0.01), more interstitial lung disease (67.4% versus 40.3%, p < 0.01), and worse physician global severity scores (4.2 versus 2.5 points, p < 0.01) compared to unexposed patients. Improvement in CRISS scores was more common in exposed patients after IPTW (odds ratio 1.85, 95% confidence interval 1.11, 3.09). Of the individual CRISS variables, only mean patient global assessment scores were significantly better among exposed than unexposed patients (- 0.4 versus 0 points, p = 0.03) while other variables including mRSS were similar.

Conclusion: Using a composite response measure, immunosuppression was associated with better outcomes at 1 year in a dcSSc cohort. These results provide real-world data that align with clinical trials to support our current use of immunosuppression.
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http://dx.doi.org/10.1186/s13075-020-02220-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275378PMC
June 2020

Skin improvement is a surrogate for favourable changes in other organ systems in early diffuse cutaneous systemic sclerosis.

Rheumatology (Oxford) 2020 Jul;59(7):1715-1724

Division of Rheumatology, McGill University, Montreal, QC, Canada.

Objectives: Skin improvement in diffuse cutaneous SSc (dcSSc), measured with modified Rodnan skin score (mRSS), is frequently used as a primary outcome in clinical trials, but it is uncertain whether mRSS changes reflect changes in other organ systems. This aim of this study was to explore if skin changes in early dcSSc over 1 and 2 years are associated with changes in severity of other organ involvement.

Methods: Canadian Scleroderma Research Group database patients with dcSSc, disease duration of ≤5 years, no evidence of initial end-stage organ damage and/or significant comorbidity who had 1 year (n = 154) and 2 years (n = 128) of follow-up data were included. mRSS changes of 25% and/or ≥5 points were considered significant. Organ involvement was assessed by Medsger Disease Severity Score and Canadian Scleroderma Research Group definitions using bivariate, chi-square, ANOVA, adjusted regression and longitudinal mixed effect model analyses.

Results: Improvement in mRSS was found in 41% of patients at 1 year and in 50% at 2 years. Improved patients showed less forced vital capacity decline (P = 0.012) and less frequent new cardiac involvement (P = 0.02) over 1 year, as well as better lung (by both Disease Severity Score, P = 0.006, and Δforced vital capacity%, P = 0.026), peripheral vascular (P = 0.006) and joint/tendon (P = 0.002) involvement over 2 years. mRSS worsening was consistently linked to less favourable lung outcomes at both 1- and 2-year follow-up visits, and more severe gastrointestinal disease at 2 years.

Conclusion: Changes in lung function in early dcSSc closely parallel skin changes. mRSS improvement reflects better prognosis for visceral disease and may be a reliable outcome measure in clinical trials.
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http://dx.doi.org/10.1093/rheumatology/kez529DOI Listing
July 2020

The Accuracy of the Patient Health Questionnaire-9 Algorithm for Screening to Detect Major Depression: An Individual Participant Data Meta-Analysis.

Psychother Psychosom 2020 8;89(1):25-37. Epub 2019 Oct 8.

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China.

Background: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results.

Objective: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10.

Methods: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview.

Results: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88).

Conclusions: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.
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http://dx.doi.org/10.1159/000502294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960351PMC
November 2020

Association between immunosuppressive therapy and course of mild interstitial lung disease in systemic sclerosis.

Rheumatology (Oxford) 2020 05;59(5):1108-1117

Lady Davis Institute, Jewish General Hospital.

Objective: Interstitial lung disease (ILD) is a leading cause of mortality in SSc. Little is known about the benefits of immunosuppressive drugs in mild ILD. Our aim was to determine whether use of CYC or MMF was associated with an improved ILD course in patients with normal or mildly impaired lung function.

Methods: A retrospective cohort of SSc subjects with ILD, disease duration below seven years and no exposure to CYC or MMF prior to the baseline visit was constructed from the Canadian Scleroderma Research Group registry. Subjects were categorized as having mild ILD if baseline forced vital capacity (FVC % predicted) was >85%. The primary exposure was any use of CYC or MMF at the baseline visit. FVC at one year was compared between exposed and unexposed subjects, using multivariate linear regression.

Results: Out of 294 eligible SSc-ILD subjects, 116 met criteria for mild ILD. In this subgroup, mean (s.d.) disease duration was 3.7 (2.0) years. Thirteen (11.2%) subjects were exposed to CYC or MMF at baseline. The one-year FVC was higher in exposed subjects compared with unexposed subjects, by a difference of 8.49% (95% CI: 0.01-16.98%). None of the exposed subjects experienced clinically meaningful progression over two years, whereas 24.6% of unexposed subjects did.

Conclusion: In this real-world setting, CYC/MMF exposure at baseline was associated with higher FVC values and a lower risk of progression among subjects with mild ILD. These data suggest a window of opportunity to preserve lung function in SSc-ILD.
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http://dx.doi.org/10.1093/rheumatology/kez407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850061PMC
May 2020

Can Patient-Reported Symptoms Be Used to Measure Disease Activity in Systemic Sclerosis?

Arthritis Care Res (Hoboken) 2020 10;72(10):1459-1465

St. Vincent's Hospital Melbourne and the University of Melbourne, Fitzroy, Victoria, Australia.

Objective: To evaluate the association between patient-reported symptoms and changes in disease activity over time in systemic sclerosis (SSc).

Methods: Using data from 1,636 patients enrolled in the Australian Scleroderma Cohort Study, we used generalized estimating equations to determine the relationship between patient-reported worsening of Raynaud's phenomenon (RP), skin involvement, and breathlessness in the month preceding each study visit and features of disease activity in the corresponding organ systems. The associations between the following parameters were analyzed: patient-reported worsening RP and the presence of new-onset digital pitting and digital ulcers; patient-reported worsening skin involvement and increasing modified Rodnan skin thickness score (MRSS); new areas of skin involvement and new-onset joint contractures; patient-reported worsening breathlessness and deteriorating respiratory functions test (RFT) results, indicated by a 10% decrease in forced vital capacity (FVC) and a 15% decrease in diffusing capacity for carbon monoxide (DLco), new-onset interstitial lung disease (ILD), and new-onset pulmonary arterial hypertension (PAH).

Results: We found a significant association between patient-reported worsening RP and the presence of digital ulcers (odds ratio [OR] 1.53 [95% confidence interval (95% CI) 0.60-0.93]), patient-reported worsening skin involvement and increasing MRSS (OR 2.10 [95% CI 1.54-2.86]), and worsening patient breathlessness and deteriorating RFTs (FVC OR 2.12 [95% CI 1.70-2.65]; DLco OR 1.97 [95% CI 1.34-2.02]), new-onset ILD (OR 1.91 [95% CI 1.40-2.61]), and new-onset PAH (OR 5.08 [95% CI 3.59-7.19]).

Conclusion: These results demonstrate that patient-reported symptoms are associated with clinically meaningful changes in disease activity in patients with SSc. This suggests that when objective measures of change in disease status are unavailable, patient-reported symptoms could be used to indicate a change in SSc disease activity.
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http://dx.doi.org/10.1002/acr.24053DOI Listing
October 2020

Changes in skin score in early diffuse cutaneous systemic sclerosis are associated with changes in global disease severity.

Rheumatology (Oxford) 2020 02;59(2):398-406

Division of Rheumatology, McGill University, Montreal, QC, Canada.

Objective: To determine whether skin score changes are associated with changes in overall disease severity, function and quality of life in early dcSSc patients.

Methods: A total of 154 and 128 dcSSc patients from the Canadian Scleroderma Research Group database with 1 and 2 year follow-up and a disease duration ⩽5 years without end-stage organ damage and/or significant comorbidity at the initial visit were included. Skin was assessed using the modified Rodnan skin score (mRSS) and disease severity by the summed Medsger disease severity score (DSS) (without skin domain), physician and patient global assessments, function [HAQ disability index (HAQ-DI)] and quality of life [36-item Short Form Health Survey (SF-36) physical component summary (PCS)]. Analyses were repeated in patients with a disease duration ⩽3 years.

Results: At 2 years, 64 (50%) patients had improved skin (mRSS decrease of ⩾5 points and/or ⩾25%). Skin improvers had improved summed DSS (P = 0.002); better physician global assessments of disease activity, severity and damage (all P ⩽ 0.003); better HAQ-DI (P = 0.001) and SF-36 PCS (P = 0.005). Changes in the mRSS were positively correlated with changes in summed DSS (P = 0.006) and other disease outcomes. In the 26 (20.3%) patients with worsened skin (mRSS increase of ⩾5 points and/or ⩾25%), the summed DSS and physician global assessments were worse (P = 0.01 and P ⩽ 0.009, respectively). In the subgroup with a disease duration ⩽3 years, similar associations were found.

Conclusion: At 1 and 2 years, overall disease improvement parallels skin improvement in early dcSSc. This is important for prognosis and reflects the value of mRSS as an outcome measure in trials with these patients.
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http://dx.doi.org/10.1093/rheumatology/kez299DOI Listing
February 2020

Changes in skin score in early diffuse cutaneous systemic sclerosis are associated with changes in global disease severity.

Rheumatology (Oxford) 2020 02;59(2):398-406

Division of Rheumatology, McGill University, Montreal, QC, Canada.

Objective: To determine whether skin score changes are associated with changes in overall disease severity, function and quality of life in early dcSSc patients.

Methods: A total of 154 and 128 dcSSc patients from the Canadian Scleroderma Research Group database with 1 and 2 year follow-up and a disease duration ⩽5 years without end-stage organ damage and/or significant comorbidity at the initial visit were included. Skin was assessed using the modified Rodnan skin score (mRSS) and disease severity by the summed Medsger disease severity score (DSS) (without skin domain), physician and patient global assessments, function [HAQ disability index (HAQ-DI)] and quality of life [36-item Short Form Health Survey (SF-36) physical component summary (PCS)]. Analyses were repeated in patients with a disease duration ⩽3 years.

Results: At 2 years, 64 (50%) patients had improved skin (mRSS decrease of ⩾5 points and/or ⩾25%). Skin improvers had improved summed DSS (P = 0.002); better physician global assessments of disease activity, severity and damage (all P ⩽ 0.003); better HAQ-DI (P = 0.001) and SF-36 PCS (P = 0.005). Changes in the mRSS were positively correlated with changes in summed DSS (P = 0.006) and other disease outcomes. In the 26 (20.3%) patients with worsened skin (mRSS increase of ⩾5 points and/or ⩾25%), the summed DSS and physician global assessments were worse (P = 0.01 and P ⩽ 0.009, respectively). In the subgroup with a disease duration ⩽3 years, similar associations were found.

Conclusion: At 1 and 2 years, overall disease improvement parallels skin improvement in early dcSSc. This is important for prognosis and reflects the value of mRSS as an outcome measure in trials with these patients.
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http://dx.doi.org/10.1093/rheumatology/kez299DOI Listing
February 2020

Setting the international standard for longitudinal follow-up of patients with systemic sclerosis: a Delphi-based expert consensus on core clinical features.

RMD Open 2019 4;5(1):e000826. Epub 2019 Mar 4.

Rheumatology A Department, Universite Paris Descartes, Paris, France.

Background: Systemic sclerosis (SSc) is a severe, progressive multiorgan disease but to date, there are no established standardised international guidelines for follow-up of patients with SSc. The goal of this project was to develop an expert consensus for annual systematic investigations in patients with SSc to enhance their standard-of-care.

Material And Methods: The Delphi method was applied. All SSc experts from the European Scleroderma Trials and Research group network and the Scleroderma Clinical Trial Consortium were invited to participate. All experts were asked to answer questionnaires in five Delphi steps to determine the domains of interest and tools for each domain for an annual systematic assessment of patients with SSc. Each item was rated on a scale between 0% and 100% (not and very important), and parameters rated >80% by more than 75% of the experts were regarded as acceptable.

Results: In total, 157 experts worldwide participated with 71.3% experts seeing >50 patients with SSc annually. In the first round, 23 domains and 204 tools were suggested. After five Delphi steps, experts agreed on 10 domains including (1) Raynaud's phenomenon; (2) Digital ulcers; (3) Skin and mucosa; (4) Lung; (5); Heart; (6) GI domain, (7) Renal; (8) Musculoskeletal; (9) Laboratory and (10) Treatment. Overall, 55 tools were identified including clinical assessments, laboratory measurements and imaging or functional investigations.

Conclusion: Through five Delphi steps with world leading experts, a consensus was established on strongly suggested tools for a minimum annual systemic assessment of organ involvement in SSc. This work should enhance the standardisation and homogenisation of the practices.
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http://dx.doi.org/10.1136/rmdopen-2018-000826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446182PMC
April 2020

Development and validation of the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis.

Ann Rheum Dis 2019 06 30;78(6):807-816. Epub 2019 Mar 30.

Department of Medicine, University of Melbourne at St. Vincent Hospital, Melbourne, Fitzroy, Victoria, Australia

Objective: We sought to develop the first Damage Index (DI) in systemic sclerosis (SSc).

Methods: The conceptual definition of 'damage' in SSc was determined through consensus by a working group of the Scleroderma Clinical Trials Consortium (SCTC). Systematic literature review and consultation with patient partners and non-rheumatologist experts produced a list of potential items for inclusion in the DI. These steps were used to reduce the items: (1) Expert members of the SCTC (n=331) were invited to rate the appropriateness of each item for inclusion, using a web-based survey. Items with >60% consensus were retained; (2) Using a prospectively acquired Australian cohort data set of 1568 patients, the univariable relationships between the remaining items and the endpoints of mortality and morbidity (Physical Component Summary score of the Short Form 36) were analysed, and items with p<0.10 were retained; (3) using multivariable regression analysis, coefficients were used to determine a weighted score for each item. The DI was externally validated in a Canadian cohort.

Results: Ninety-three (28.1%) complete survey responses were analysed; 58 of 83 items were retained. The univariable relationships with death and/or morbidity endpoints were statistically significant for 22 items, with one additional item forced into the multivariable model by experts due to clinical importance, to create a 23-item weighted SCTC DI (SCTC-DI). The SCTC-DI was predictive of morbidity and mortality in the external cohort.

Conclusions: Through the combined use of consensus and data-driven methods, a 23-item SCTC-DI was developed and retrospectively validated.
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http://dx.doi.org/10.1136/annrheumdis-2018-214764DOI Listing
June 2019

An Interim Report of the Scleroderma Clinical Trials Consortium Working Groups.

J Scleroderma Relat Disord 2019 Feb 18;4(1):17-27. Epub 2018 Jul 18.

Rheumatology Unit, University Hospital of Cagliari.

The Scleroderma Clinical Trials Consortium (SCTC) represents many of the clinical researchers in the world who are interested in improving the efficiency of clinical trials in Systemic Sclerosis (SSc). The SCTC has established 11 working groups (WGs) to develop and validate better ways of measuring and recording multiple aspects of this heterogeneous disease. These include groups working on arthritis, disease damage, disease activity, cardiac disease, juvenile SSc, the gastrointestinal tract, vascular component, calcinosis, scleroderma renal crisis, interstitial lung disease, and skin measurement. Members of the SCTC may join any one or more of these groups. Some of the WGs have only recently started their work, some are nearing completion of their mandated tasks and others are in the midst of their projects. All these projects, which are described in this paper, will help to improve clinical trials and observational studies by improving or developing better, more sensitive ways of measuring various aspects of the disease. As Lord Kelvin stated, "To measure is to know. If you cannot measure it you cannot improve it." The SCTC is dedicated to improving the lives of patients with SSc and it is our hope that the contributions of the WGs will be one important step in this process.
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http://dx.doi.org/10.1177/2397198318783926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428445PMC
February 2019

Generation of a Core Set of Items to Develop Classification Criteria for Scleroderma Renal Crisis Using Consensus Methodology.

Arthritis Rheumatol 2019 06 12;71(6):964-971. Epub 2019 Apr 12.

Jewish General Hospital, McGill University and Lady Davis Institute, Montreal, Quebec, Canada.

Objective: To generate a core set of items to develop classification criteria for scleroderma renal crisis (SRC) using consensus methodology.

Methods: An international, multidisciplinary panel of experts was invited to participate in a 3-round Delphi exercise developed using a survey based on items identified by a scoping review. In round 1, participants were asked to identify omissions and clarify ambiguities regarding the items in the survey. In round 2, participants were asked to rate the validity and feasibility of the items using Likert-type scales ranging from 1 to 9 (where 1 = very invalid/unfeasible, 5 = uncertain, and 9 = very valid/feasible). In round 3, participants reviewed the results and comments from round 2 and were asked to provide final ratings. Items rated as highly valid and feasible (median scores ≥7 for each) in round 3 were selected as the provisional core set of items. A consensus meeting using a nominal group technique was conducted to further reduce the core set of items.

Results: Ninety-nine experts from 16 countries participated in the Delphi exercise. Of the 31 items in the survey, consensus was achieved on 13, in the categories hypertension, renal insufficiency, proteinuria, and hemolysis. Eleven experts took part in the nominal group technique discussion, where consensus was achieved in 5 domains: blood pressure, acute kidney injury, microangiopathic hemolytic anemia, target organ dysfunction, and renal histopathology.

Conclusion: A core set of items that characterize SRC was identified using consensus methodology. This core set will be used in future data-driven phases of this project to develop classification criteria for SRC.
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http://dx.doi.org/10.1002/art.40809DOI Listing
June 2019

Severe gastrointestinal disease in very early systemic sclerosis is associated with early mortality.

Rheumatology (Oxford) 2019 04;58(4):636-644

Department of Medicine, McGill University, Montreal, Quebec, Canada.

Objectives: To examine the incidence, predictors and outcomes associated with severe gastrointestinal (GI) disease in a large inception SSc cohort.

Methods: SSc subjects with <2 years of disease duration were identified from two multicentre cohorts. Severe GI disease was defined as: malabsorption, hyperalimentation, pseudo-obstruction and/or ⩾10% weight loss in association with the use of antibiotics for bacterial overgrowth or oesophageal stricture. Kaplan-Meier, multivariate logistic regression and Cox proportional hazard analyses were performed to determine the cumulative incidence rate, independent clinical correlates and mortality rate associated with severe GI disease. A longitudinal mixed model was used to assess the impact of severe GI disease on the Short Form Health Survey.

Results: In this inception SSc cohort, the probability of developing severe GI disease was estimated at 9.1% at 2 years and 16.0% at 4 years. In multivariate analysis, severe GI disease was associated with inflammatory myositis (odds ratio 4.68, 95% CI 1.65, 13.24), telangiectasias (odds ratio 2.45, 95% CI 1.19, 5.04) and modified Rodnan skin score (odds ratio 1.03, 95% CI 1.01, 1.07). Severe GI disease was associated with a >2-fold increase in the risk of death (hazard ratio 2.27, 95% CI 1.27, 4.09) and worse health-related quality of life [Short Form Health Survey physical (β = -2.37, P = 0.02) and mental (β = -2.86, P = 0.01) component summary scores].

Conclusion: Severe GI disease is common in early SSc and is associated with significant morbidity and increased mortality. More research is needed to understand, prevent and mitigate severe GI disease in SSc.
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http://dx.doi.org/10.1093/rheumatology/key350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434374PMC
April 2019

Determinants of health-related quality of life in a multinational systemic sclerosis inception cohort.

Clin Exp Rheumatol 2018 Jul-Aug;36 Suppl 113(4):53-60. Epub 2018 Aug 31.

Rheumatology Unit, Royal Adelaide Hospital, North Terrace, Australia; and Discipline of Medicine, University of Adelaide, Australia.

Objectives: To evaluate health-related quality of life (HRQoL) and its determinants in a systemic sclerosis (SSc) multinational inception cohort. We performed a meta-analysis of data from individual countries, and compared the meta-analysis to individual country results by pooling data from each of the countries.

Methods: SSc patients within 2 years of disease onset were recruited from 5 countries participating in the International Systemic Sclerosis Inception Cohort (INSYNC). Data from each country's database were exported for analysis using a harmonised platform. HRQoL was assessed using the Medical Outcomes Short Form-36 (SF-36). Multivariate linear regression assessed associations between HRQoL and predictors in cohorts separately and meta-analyzed to generate pooled estimates. The analyses were repeated using individual patient data.

Results: Of the 637 SSc patients recruited, the majority was female (80.2%-83.3%), aged between 52.4-56.7 years with limited cutaneous disease subtype (48.6%-66.7%). HRQoL scores were lower for SSc patients than the general population (SF-36 physical component summary (PCS) score (36.4-39.6), mental component summary (MCS) score (41.0-46.4)). Determinants of SF-36 PCS by meta-analysis included increasing age (β=-0.1, 95%CI -0.2, -0.01), diffuse cutaneous disease subtype (β=-8.4, 95%CI -10.6, -6.3), and pulmonary arterial hypertension (β=-10.9, 95%CI -16.6, -5.3). Increasing age (β=0.09, 95%CI 0.0, 0.18) was the only variable associated with SF-36 MCS. Analyses using individual patient data revealed similar results to those of the meta-analysis of cohort data.

Conclusions: Our study provides estimates of HRQoL in a large inception SSc cohort and provides evidence that individual patient data analysis is valid in the INSYNC dataset.
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January 2019

Defining primary systemic sclerosis heart involvement: A scoping literature review.

Semin Arthritis Rheum 2019 04 31;48(5):874-887. Epub 2018 Jul 31.

Department of Medicine at St Vincent's Hospital, University of Melbourne, 41 Victoria Parade, Fitzroy, VIC 3065, Australia; Department of Rheumatology, St Vincent's Hospital, 41 Victoria Parade, Fitzroy, VIC 3065, Australia. Electronic address:

Background: Clinically evident primary heart involvement due to systemic sclerosis (SHI) is considered a poor prognostic factor and is a leading cause of systemic sclerosis (SSc) related death. Yet, there remains no consensus definition of SHI and poor understanding of the natural history and risk factors for the development of SHI.

Methods: We performed a scoping literature review of published articles with a primary focus of SHI to capture previously used definitions of SHI and items used to measure SHI. Any factors reported to be associated with an increased risk of SHI were recorded.

Results: Of the 2436 records identified in a search of MEDLINE, EMBASE and PubMed databases, 295 were included in the final scoping review. Analysis of the literature revealed studies of variable quality, generally low patient numbers and highly heterogeneous definitions of SHI within studies. There is no clear consensus from the literature as to the scope of SHI and the prognostic significance of sub-clinical investigation abnormalities commonly detected.

Conclusion: The lack of a standardised definition of SHI remains a significant unmet need in SSc. The results of this review will assist in the development of consensus classification criteria to enable more accurate quantification of the burden of SHI, identification of factors associated with increased risk of developing SHI, and evaluation of the efficacy of any novel therapeutic strategies.
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http://dx.doi.org/10.1016/j.semarthrit.2018.07.008DOI Listing
April 2019

Methods for shortening patient-reported outcome measures.

Stat Methods Med Res 2019 Oct-Nov;28(10-11):2992-3011. Epub 2018 Aug 20.

Division of Rheumatology, Sir Mortimer B, Davis Jewish General Hospital, Montreal, Canada.

Patient-reported outcome measures are widely used to assess patient experiences, well-being, and treatment response in clinical trials and cohort-based observational studies. However, patients may be asked to respond to many different measures in order to provide researchers and clinicians with a wide array of information regarding their experiences. Collecting such long and cumbersome patient-reported outcome measures may burden patients, increase research costs, and potentially reduce the quality of the data collected. Nonetheless, little research has been conducted on replicable, and reproducible methods to shorten these instruments that result in shortened forms of minimal length. This manuscript proposes the use of mixed integer programming through Optimal Test Assembly as a method to shorten patient-reported outcome measures. This method is compared to the existing standard in the field, which is selecting items based on having high discrimination parameters from an item response theory model. The method is then illustrated in an application to a fatigue scale for patients with Systemic Sclerosis.
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http://dx.doi.org/10.1177/0962280218795187DOI Listing
December 2020

The Scleroderma Patient-Centered Intervention Network Cohort: baseline clinical features and comparison with other large scleroderma cohorts.

Rheumatology (Oxford) 2018 09;57(9):1623-1631

Division of Rheumatology, Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

Objectives: The Scleroderma Patient-centered Intervention Network (SPIN) Cohort is a web-based cohort designed to collect patient-reported outcomes at regular intervals as a framework for conducting trials of psychosocial, educational, self-management and rehabilitation interventions for patients with SSc. The aim of this study was to present baseline demographic, medical and patient-reported outcome data of the SPIN Cohort and to compare it with other large SSc cohorts.

Methods: Descriptive statistics were used to summarize SPIN Cohort characteristics; these were compared with published data of the European Scleroderma Trials and Research (EUSTAR) and Canadian Scleroderma Research Group (CSRG) cohorts.

Results: Demographic, organ involvement and antibody profile data for SPIN (N = 1125) were generally comparable with that of the EUSTAR (N = 7319) and CSRG (N = 1390) cohorts. There was a high proportion of women and White patients in all cohorts, though relative proportions differed. Scl70 antibody frequency was highest in EUSTAR, somewhat lower in SPIN, and lowest in CSRG, consistent with the higher proportion of interstitial lung disease among dcSSc patients in SPIN compared with in CSRG (48.5 vs 40.3%). RNA polymerase III antibody frequency was highest in SPIN and remarkably lower in EUSTAR (21.1 vs 2.4%), in line with the higher prevalence of SSc renal crisis (4.5 vs 2.1%) in SPIN.

Conclusion: Although there are some differences, the SPIN Cohort is broadly comparable with other large prevalent SSc cohorts, increasing confidence that insights gained from the SPIN Cohort should be generalizable, although it should be noted that all three cohorts include primarily White participants.
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http://dx.doi.org/10.1093/rheumatology/key139DOI Listing
September 2018

Probability of major depression diagnostic classification using semi-structured versus fully structured diagnostic interviews.

Br J Psychiatry 2018 06 2;212(6):377-385. Epub 2018 May 2.

Department of Pediatrics,University of North Carolina at Chapel Hill School of Medicine,Chapel Hill,North Carolina,USA.

Background: Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.AimsTo evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.

Method: Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.

Results: A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15-3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98-10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7-15) (OR = 0.96; 95% CI = 0.56-1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26-0.97).

Conclusions: The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.Declaration of interestDrs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
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http://dx.doi.org/10.1192/bjp.2018.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415695PMC
June 2018
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