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1 Arthritis Care & Research Vol. 64, 8, August 2012, pp DOI /acr , American College of Rheumatology ORIGINAL ARTICLE Influence of Symptoms on Patient Health Questionnaire-9 Depression Scores Among Patients With Systemic Sclerosis Compared to a Healthy General Population Sample ALLISON LEAVENS, 1 SCOTT B. PATTEN, 2 MARIE HUDSON, 1 MURRAY BARON, 1 AND BRETT D. THOMBS, 1 FOR THE CANADIAN SCLERODERMA RESEARCH GROUP Objective. Depression symptom measures that include symptoms may inflate severity estimates among medically ill patients, including patients with systemic sclerosis (SSc; scleroderma). The 9-item Patient Health Questionnaire (PHQ-9) is increasingly used to assess depressive symptoms in medical settings, but it is not known whether PHQ-9 scores are influenced by symptoms common in medical illness. The objective was to assess whether SSc patients had higher symptom scores on the PHQ-9 than non medically ill respondents from the general population matched on scores. Methods. SSc patients from the Canadian Scleroderma Research Group Registry were matched with respondents from a random population survey of Alberta, Canada residents who were without chronic disease on PHQ-9 scores (5 items), sex, and, as close as possible, age. PHQ-9 scores (4 items) were compared between SSc patients and healthy Alberta survey respondents using t-tests for unadjusted analyses and analysis of covariance to adjust for age differences that remained after matching. Results. symptoms accounted for 64% of the PHQ-9 scores for 762 matched SSc patients (n 837 ) compared to 56% for 762 matched Alberta population survey respondents (n 3,304 ), a mean difference of 1.0 point, or 19% of the scores for the SSc patients (Hedges s g 0.38). After adjusting for age, the mean difference increased to 1.4 points, reflecting 25% of the SSc patients scores (Hedges s g 0.55). Conclusion. PHQ-9 scores among patients with SSc may include a small to moderate amount of variance from symptoms that are not necessarily related to depression. INTRODUCTION Systemic sclerosis (SSc; scleroderma) is a multisystem, chronic autoimmune connective tissue disease characterized by vascular injury, immune dysfunction, and abnormal fibrotic processes. SSc affects the skin, as well as internal organs such as the lungs, heart, and gastrointestinal tract (1). Most people affected by SSc are female (2). The only study of major depressive disorder (MDD) in SSc found that 19 of 100 patients met the criteria for current MDD (3), although many patients have elevated symptoms of depression based on self-report questionnaires (4). A number of different questionnaires that measure depressive symptoms have been used in patients with SSc (4), including the 9-item Patient Health Questionnaire (PHQ-9) (5). The PHQ-9 is an easily administered and scored self-report measure with 9 items that cover the 9 Dr. Patten s work was supported by a Senior Health Scholar Award from Alberta Innovates, Health Solutions. Drs. Hudson and Thombs work was supported by New Investigator Awards from the Canadian Institutes of Health Research and Établissement de Jeunes Chercheurs awards from the Fonds de la Recherche en Santé du Québec. Dr. Baron is the director of the Canadian Scleroderma Research Group, which receives grant funding from the Canadian Institutes of Health Research, the Scleroderma Society of Canada and its provincial chapters, the Scleroderma Society of Ontario, Sclérodermie Québec, the Ontario Arthritis Society, and educational grants from Actelion and Pfizer. 1 Allison Leavens, BSc, Marie Hudson, MD, MPH, Murray Baron, MD, Brett D. Thombs, PhD: McGill University and Jewish General Hospital, Montreal, Quebec, Canada; 2 Scott B. Patten, MD, PhD: University of Calgary, Calgary, Alberta, Canada. Recruiting Rheumatologists of the Canadian Scleroderma Research Group are shown in Appendix A. Address correspondence to Brett D. Thombs, PhD, Jewish General Hospital, 4333 Cote Ste Catherine Road, Montreal, Quebec H3T 1E4, Canada. brett.thombs@mcgill.ca. Submitted for publication January 4, 2012; accepted in revised form March 9,

2 1196 Leavens et al Significance & Innovations Patients with systemic sclerosis scored points higher on the items of the 9-item Patient Health Questionnaire (PHQ-9) compared to healthy population respondents matched on depression symptom scores, sex, and, as close as possible, age. symptoms not necessarily related to depression may account for as much as 25% of depressive symptom scores on the PHQ-9 among patients with systemic sclerosis. The largest single-item differences between patients with systemic sclerosis and the healthy population respondents were on items that reflect sleep problems and fatigue, both of which are common and debilitating manifestations of systemic sclerosis. symptom criteria for MDD from the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM- IV) (6). The PHQ-9 is increasingly recommended for clinical use and for use in research on depression in medical settings (7 11), including rheumatologic disorders (11). In SSc, the PHQ-9 has been found to have similar measurement characteristics to the 20-item Center for Epidemiologic Studies Depression Scale (CES-D) (12). No studies in any patient group, however, have examined the degree to which symptoms of medical illness may influence depression severity ratings on the PHQ-9 due to symptoms common to both medical illnesses and depression, including fatigue, sleep problems, and poor appetite (13 17). The PHQ-9 includes 4 items that reflect symptoms (sleep difficulties, fatigue, appetite problems, and psychomotor agitation or retardation) (18). The degree to which symptoms influence overall depression scores may vary by instrument. Among patients hospitalized with acute myocardial infarction, for instance, the original Beck Depression Inventory (BDI) appears to be influenced by symptoms potentially not related to depression (19), whereas the revised BDI-II does not (14). In a study of SSc patients, 403 patients reported only minimally higher levels of symptoms compared to a matched general population sample on the CES-D (13), which only includes 2 items related to difficulties with sleeping and eating. Of the 9 PHQ-9 items, 3 reflect common and debilitating manifestations of SSc, including fatigue (20 23), sleep difficulties (21,24,25), and poor appetite, which can occur due to gastrointestinal problems (26 28). Therefore, although the CES-D and PHQ-9 appear to perform in a generally similar manner in SSc, it is important to understand the degree to which PHQ-9 scores may be influenced by symptoms related to SSc disease manifestations, rather than depression. The objective of this study was to assess whether SSc patients had higher symptom scores on the PHQ-9 compared to non medically ill respondents from the general population matched on scores, sex, and, as close as possible, age. PATIENTS AND METHODS Patients. The SSc sample consisted of patients enrolled in the Canadian Scleroderma Research Group Registry who completed the PHQ-9 as part of their annual registry visit between February 2008 and July Patients in the registry were recruited from 15 centers across Canada. Eligibility for the registry included having a diagnosis of SSc confirmed by a registry rheumatologist, age 18 years, and fluency in English or French. At each annual visit, registry patients underwent an extensive clinical history, physical evaluation, and laboratory investigation and completed a series of self-report questionnaires, including the PHQ-9. Some patients completed the PHQ-9 at more than 1 visit, but only data from the first administration were included in this study. Patients from all sites provided informed written consent and the McGill University Institutional Review Board approved the data collection protocol. The comparison sample consisted of residents of the Canadian province of Alberta ages years who completed the PHQ-9 over the telephone (29). The sample was selected from a database of residential telephone numbers maintained by a survey unit at the Calgary Health Region. Random substitution of the final digit was used to avoid bias that might result from a failure to reach unlisted residential telephone numbers. Each number was dialed up to 9 times to attempt to determine whether the number belonged to a residential household or not. Call attempts were dispersed over weekdays, evenings, and weekends ( 3 each). When a household was successfully contacted, the person answering the phone, if age years, was invited to participate in the study. If that person declined to participate, then a household member willing to participate in the study was sought. Each respondent was assessed with the PHQ-9 during the initial call and in a series of 6 followup calls, each 2 weeks apart. For the present study, only the PHQ-9 data from the initial baseline call were included and only from phone survey respondents who indicated that they were without chronic diseases. This was determined by the question, Do you have any long-term physical health conditions that have been diagnosed by a health professional? By long-term we mean conditions that have lasted, or are expected to last, longer than 6 months. Verbal consent was provided for the anonymous survey, and the study protocol was approved by the University of Calgary Conjoint Ethics Board. Measures. The data collected from both samples included self-reported sociodemographic data and symptoms of depression, as measured by the PHQ-9. Additionally, for SSc patients, a number of disease-related variables were reported, including SSc disease duration, classification as diffuse or limited SSc, and modified Rodnan skin thickness scores. The PHQ-9 is a 9-item self-report measure in which the

3 Effect of Symptoms on PHQ-9 Scores in SSc 1197 respondents rated the frequency of depression symptoms over the past 2 weeks on a 0 3 Likert-type scale, with higher scores on each item reflecting a greater amount of time in which the patient was bothered by the symptom. The 9 items are designed to align with the 9 symptoms listed in the DSM-IV criteria for a major depressive episode. Based on published PHQ-9 factor models (18) and item content, items 1, 2, 6, 7, and 9 (lack of interest, depressed mood, worthlessness, concentration problems, and suicide ideation, respectively) were summed to obtain a symptom score, and items 3, 4, 5, and 8 (sleep difficulties, fatigue, appetite problems, and psychomotor agitation or retardation, respectively) were summed to derive a symptom score for each patient. Administering the PHQ-9 in person and over the telephone are both valid methods and produce similar results (30). The SSc disease characteristics were obtained via patients medical histories and examinations by study physicians. The disease duration was determined as the time from the onset of non Raynaud s phenomenon symptoms. Limited skin disease was defined as skin involvement distal to the elbows and knees with or without face involvement, and diffuse skin disease was defined as skin involvement proximal to the elbows and knees and/or involving the trunk (31). The extent of skin involvement was assessed using the modified Rodnan skin thickness score, which ranges from 0 51 (32). Patient matching. Residents of Alberta who indicated that they were without chronic disease were matched with SSc patients exactly on both sex and symptom scores and, as close as possible on age, since the SSc patient sample on average was older. A matching procedure was used rather than purely statistical procedures because of the large difference in PHQ-9 mean severity scores between the SSc patients and the overall Alberta population sample. Statistical adjustment may not be appropriate when comparing samples with dissimilar distributions. Therefore, for men and women separately, for each possible score on the PHQ-9, all SSc patients or Alberta residents were included from the group (SSc patients or healthy Alberta residents) with fewer participants at that score level (e.g., a score of 6). Then, the same number of people from the other group with the same score were chosen. Because of the prematch age differential between the samples, at each score level, if only a subset of SSc patients was chosen, we selected the youngest SSc patients at the given score level. If there were more SSc patients at a given score level, and a subset of healthy Alberta survey respondents were chosen, we selected the oldest Alberta respondents. For example, if there were 33 SSc patients and 28 healthy Alberta respondents with a symptom score of 5, then the 28 youngest of the 33 SSc patients and all 28 Alberta respondents were included. Statistical analyses. Two-tailed t-tests were used to examine whether there was a difference in the scores between the SSc patients and healthy respondents from the Alberta sample, overall and across different score levels. Because there was a significant difference in the mean ages of the matched samples, we repeated the comparison using analysis of covariance, adjusting for age. As a post hoc analysis, we also adjusted for differences in the level of education (high school or less versus more than high school). We quantified the differ- Table 1. Comparison of sociodemographic and clinical characteristics of SSc patients and Alberta survey respondents without chronic medical disease* Sociodemographic characteristics SSc patients (n 762) Alberta sample (n 762) P Age, mean SD years Female sex 661 (86.7) 661 (86.7) Education level High school or less 387 (50.8) 220 (28.9).001 More than high school 368 (48.3) 529 (69.4) Not reported 7 (0.9) 13 (1.7) Marital status Married or common law 535 (70.2) 546 (71.7) Single 56 (7.3) 68 (8.9) Separated/divorced/widowed 160 (21.0) 146 (19.1) Not reported 11 (1.5) 2 (0.3) Annual income $30, (12.3) $40, (31.4) Clinical characteristics Time since non Raynaud s phenomenon symptom onset, mean SD years Time since diagnosis of SSc, mean SD years Modified Rodnan skin thickness score, mean SD Diffuse SSc 248 (32.5) * Values are the number () unless otherwise indicated. SSc systemic sclerosis.

4 1198 Leavens et al Table 2. Comparison of cognitive and PHQ-9 scores between SSc patients and Alberta survey respondents without chronic medical disease* SSc Alberta score comparison Cognitive/ scores of of Difference %ofssc patient P Total * PHQ-9 9-item Patient Health Questionnaire; SSc systemic sclerosis. ence in scores with the Hedges s g statistic, which represents a standardized mean difference (33). In addition, we compared scores on each of the 4 PHQ-9 items between SSc patients and healthy respondents from the Alberta population sample using the Mann-Whitney U test with Hochberg s sequential method to maintain a family-wise type I error rate of 0.05 for multiple item comparisons. All analyses were conducted using SPSS, version RESULTS Sample characteristics. Before matching, the mean SD PHQ-9 score was for 837 SSc patients versus for 2,034 Alberta residents without chronic medical disease (of 3,304 respondents sampled). The mean SD age for the SSc patients was years, and 732 (87.5%) were women. For the healthy comparison sample, the mean SD age was years, and 1,343 (66.0%) were women. There were 762 exact matches on sex and scores, with 101 men (13.3%) and 661 women (86.7%) included in each of the matched samples. The mean SD PHQ-9 score for the matched SSc patients was , compared to for the healthy respondents from Alberta. The mean SD age was years for the SSc group versus years for the Alberta comparison sample. Sociodemographic characteristics of the 2 samples and disease characteristics of the SSc sample are shown in Table 1. The samples were closely matched on marital status, with 535 (70.2%) of the SSc patients and 546 (71.7%) of the general population sample being married. The general population group had an overall higher education level, with 529 (69.4%) having some form of postsecondary education compared to 368 SSc patients (48.3%). Cognitive/ and symptoms. Overall, the mean symptom score was 1.8 for both the matched SSc patients and healthy Alberta survey respondents. The mean SD PHQ-9 score was for the SSc patients and for the healthy Alberta survey respondents. symptom scores accounted for 64.4% of the PHQ-9 scores for the 762 SSc patients versus 56.2% of the scores for the matched healthy population sample. As shown in Table 2, the SSc patients had statistically significantly higher scores than the general population sample across all symptom score ranges. Overall, the SSc patients scored 1 point higher on the symptom items compared to the population sample, corresponding to 18.9% of the of mean PHQ-9 score for SSc patients (Table 2).The Hedges s g for the difference in overall symptoms between matched SSc patients and the survey respondents was The SSc patients had significantly higher scores on all 4 items (Table 3). The largest differences were for the items that reflected sleep problems and fatigue. After adjusting for age, the difference in the scores between the 2 groups increased to 1.37 points, Table 3. Comparison of PHQ-9 symptom item scores between SSc patients and Alberta population survey respondents without chronic medical disease* PHQ-9 item SSc Alberta Difference P 3. Sleep Fatigue Appetite Psychomotor agitation or retardation * Values are the mean SD unless otherwise indicated. PHQ-9 9-item Patient Health Questionnaire; SSc systemic sclerosis. Difference in item scores. The definition of scores is in the Patients and Methods section. All P values are significant based on Mann-Whitney U test with Hochberg s sequential method to maintain a family-wise type I error rate of 0.05 for multiple-item comparisons.

5 Effect of Symptoms on PHQ-9 Scores in SSc 1199 Table 4. Comparison of cognitive and PHQ-9 scores between SSc patients and Alberta survey respondents without chronic medical disease adjusted for age* SSc Alberta score comparison Cognitive/ scores of of Difference %ofssc patient P Total * PHQ-9 9-item Patient Health Questionnaire; SSc systemic sclerosis. reflecting 24.5% of the scores for the SSc patients (Table 4). Again, the score differential held across the range of score levels, and the overall Hedges s g was Additionally adjusting for education level did not change this result ( score difference 1.34). DISCUSSION The main finding of this study was that SSc patients scored 1 point higher on the 4 items of the PHQ-9 compared to the randomly selected respondents who were without chronic disease. This difference was equivalent to almost 20% of the PHQ-9 scores of patients with SSc (standardized mean difference 0.38). After adjusting for age differences that remained after matching, the score difference was 1.4 points, or 25% of the PHQ-9 scores among SSc patients (standardized mean difference 0.55). SSc patients were significantly more likely to endorse all 4 PHQ-9 items (sleep difficulties, fatigue, appetite problems, and psychomotor agitation or retardation) compared to population controls matched on symptoms, sex, and, as close as possible, age. The largest differences were for items that reflected sleep problems and fatigue, both of which are common problems with important ramifications for quality of life among people living with SSc (20,21 25). The results of this study differed from those of a previous report that examined the influence of symptoms on CES-D scores among SSc patients (13). That study found that SSc patients were more likely to endorse items related to sleep and appetite, but that the overall effect on CES-D scores was minimal (13). This finding is likely because the CES-D has only 2 symptom items of a of 20 items, equivalent to 10% of the possible score. The PHQ-9, on the other hand, has 4 symptom items, which account for 44% of possible scores. Another study involving SSc patients directly compared measurement properties of the CES-D and PHQ-9 and found that they generally performed similarly, although there was some evidence that the CES-D may be more closely associated with sociodemographic variables than medical variables compared to the PHQ-9 (12). Overall, evidence from this study and previous studies suggests that, compared to non medically ill respondents, symptoms from SSc play a larger role in PHQ-9 scores than CES-D scores. On the other hand, in analyses that only include patients with SSc, most or all of whom experience some level of physical impact, differences between the 2 instruments may not be great. One important ramification of the results of this study is that PHQ-9 cutoff scores to identify respondents with possible depression, which have been calibrated in general or primary care populations, may not work well among SSc patients whose symptom burden is likely greater. Consistent with this, the limited number of studies that have assessed the diagnostic accuracy of the PHQ-9 among patients from primary care settings and patients with chronic medical disease suggest that disease-specific cutoffs may improve upon general guidelines for some patient groups (8,9). To date, no studies have evaluated the diagnostic accuracy of the PHQ-9, or any other depression questionnaire, against a gold standard diagnosis of depression in SSc. This will be an important step to take, both to better understand the burden of depression and care needs in SSc and in order to set cutoff levels for identifying possible cases of depression using the PHQ-9. Researchers who use the PHQ-9 as a continuous measure should be aware of the possibility that the PHQ-9 could exaggerate the link between depressive symptoms and aspects of SSc, although in studies that include only SSc patients, this effect may be minimal. There are several limitations that should be considered in interpreting results from this study. First, the sample of SSc patients may not reflect the full spectrum of SSc patients because it was a subsample of SSc patients who were enrolled in the Canadian Scleroderma Research Group Registry. The patients enrolled in the Canadian Scleroderma Research Group Registry may overrepresent SSc patients who are being treated by a rheumatologist (versus primary care) and typically include patients who are more severely affected. Second, the SSc patients were sampled from across Canada, whereas the healthy comparisons were sampled from only 1 province, although there is no reason to believe that this would influence the results. Third, the matching procedure eradicated most, but not all, of the age difference between the SSc patients and healthy Alberta respondents. The samples were, nonethe-

6 1200 Leavens et al less, close in age after matching, and we were able to reasonably assess the differential influence of symptoms on the PHQ-9 items. Fourth, there were also differences in education level between the groups, although adjusting for education level did not change results. Finally, the healthy respondent comparison sample was based on the self-report of not having chronic diseases. This may have resulted in some people with a chronic disease being included in the comparison sample. In conclusion, this study found that SSc patients reported more symptoms than healthy respondents without any chronic illness matched on symptoms, sex, and, as close as possible, age. This may exaggerate depression scores on the PHQ-9 to some degree among patients with SSc. Future research that compares PHQ-9 scores to depression diagnoses among patients with SSc needs to be done. AUTHOR CONTRIBUTIONS All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Thombs had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design. Leavens, Patten, Thombs. Acquisition of data. Patten, Hudson, Baron, Thombs. Analysis and interpretation of data. Leavens, Hudson, Thombs. ROLE OF THE STUDY SPONSOR Actelion and Pfizer had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by Actelion and Pfizer. REFERENCES 1. Seibold J. Scleroderma. In: Harris ED, Budd RC, Firestein GS, Genovese MC, Sergent JS, Ruddy S, et al, editors. Kelley s textbook of rheumatology. 7th ed. Philadelphia: Elsevier; p Mayes MD, Lacey JV Jr, Beebe-Dimmer J, Gillespie BW, Cooper B, Laing TJ, et al. Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population. Arthritis Rheum 2003;48: Baubet T, Ranque B, Taieb O, Berezne A, Bricou O, Mehallel S, et al. Mood and anxiety disorders in systemic sclerosis patients. Presse Med 2011;40:e Thombs BD, Taillefer SS, Hudson M, Baron M. Depression in patients with systemic sclerosis: a systematic review of the evidence. Arthritis Rheum 2007;57: Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001;16: American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; Wittkampf KA, Naeije L, Schene AH, Huyser J, van Weert HC. Diagnostic accuracy of the mood module of the Patient Health Questionnaire: a systematic review. Gen Hosp Psychiatry 2007;29: Gilbody S, Richards D, Brealey S, Hewitt C. Screening for depression in medical settings with the Patient Health Questionnaire (PHQ): a diagnostic meta-analysis. J Gen Intern Med 2007;22: Davidson KW, Kupfer DJ, Bigger JT, Califf RM, Carney RM, Coyne JC, et al. Assessment and treatment of depression in patients with cardiovascular disease: National Heart, Lung, and Blood Institute Working Group report. Psychosom Med 2006;68: Lichtman JH, Bigger JT Jr, Blumenthal JA, Frasure-Smith N, Kaufmann PG, Lesperance F, et al. Depression and coronary heart disease: recommendations for screening, referral, and treatment. A science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation 2008; 118: Hyphantis T, Kotsis K, Voulgari PV, Tsifetaki N, Creed F, Drosos AA. Diagnostic accuracy, internal consistency, and convergent validity of the Greek version of the Patient Health Questionnaire 9 in diagnosing depression in rheumatologic disorders. Arthritis Care Res (Hoboken) 2011;63: Milette K, Hudson M, Baron M, Thombs BD, and the Canadian Scleroderma Research Group. Comparison of the PHQ-9 and CES-D depression scales in systemic sclerosis: internal consistency reliability, convergent validity and clinical correlates. Rheumatology (Oxford) 2010;49: Thombs BD, Fuss S, Hudson M, Schieir O, Taillefer SS, Fogel J, et al. High rates of depressive symptoms among patients with systemic sclerosis are not explained by differential reporting of symptoms. Arthritis Rheum 2008;59: Thombs BD, Ziegelstein RC, Pilote L, Dozois DJ, Beck AT, Dobson KS, et al. symptom overlap in Beck Depression Inventory-II scores following myocardial infarction. Br J Psychiatry 2010;197: Koenig HG, George LK, Peterson BL, Pieper CF. Depression in medically ill hospitalized older adults: prevalence, characteristics, and course of symptoms according to six diagnostic schemes. Am J Psychiatry 1997;154: Von Ammon Cavanaugh S. Depression in the medically ill: critical issues in diagnostic assessment. Psychos 1995;36: Cavanaugh S, Clark DC, Gibbons RD. Diagnosing depression in the hospitalized medically ill. Psychos 1983;24: De Jonge P, Mangano D, Whooley MA. Differential association of cognitive and depressive symptoms with heart rate variability in patients with stable coronary heart disease: findings from the Heart and Soul Study. Psychosom Med 2007; 69: Delisle V, Abbey S, Beck A, Dobson K, Dozois D, Grace S, et al. The influence of symptoms on BDI versus BDI-II scores in patients hospitalized following myocardial infarction. Can J Psychiatry. In press. 20. Thombs BD, Hudson M, Bassel M, Taillefer SS, Baron M, and the Canadian Scleroderma Research Group. Sociodemographic, disease, and symptom correlates of fatigue in systemic sclerosis: evidence from a sample of 659 Canadian Scleroderma Research Group Registry patients. Arthritis Rheum 2009;61: Bassel M, Hudson M, Taillefer SS, Schieir O, Baron M, Thombs BD. Frequency and impact of symptoms experienced by patients with systemic sclerosis: results from a Canadian national survey. Rheumatology (Oxford) 2011;50: Assassi S, Leyva AL, Mayes MD, Sharif R, Nair DK, Fischbach M, et al. Predictors of fatigue severity in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort. PLoS One 2011;6:e Sandusky SB, McGuire L, Smith MT, Wigley FM, Haythornthwaite JA. Fatigue: an overlooked determinant of physical function in scleroderma. Rheumatology (Oxford) 2009;48: Milette K, Razykov I, Pope J, Hudson M, Motivala SJ, Baron M, et al. Clinical correlates of sleep problems in systemic sclerosis: the prominent role of pain. Rheumatology (Oxford) 2011;50: Frech T, Hays RD, Maranian P, Clements PJ, Furst DE, Khanna

7 Effect of Symptoms on PHQ-9 Scores in SSc 1201 D. Prevalence and correlates of sleep disturbance in systemic sclerosis: results from the UCLA Scleroderma Quality of Life Study. Rheumatology (Oxford) 2011;50: Gyger G, Baron M. Gastrointestinal manifestations of scleroderma: recent progress in evaluation, pathogenesis, and management. Curr Rheumatol Rep 2012;14: Baron M, Bernier P, Cote LF, Delegge MH, Falovitch G, Friedman G, et al. Screening and therapy for malnutrition and related gastro-intestinal disorders in systemic sclerosis: recommendations of a North American expert panel. Clin Exp Rheumatol 2010;28:S Khanna D, Hays RD, Maranian P, Seibold JR, Impens A, Mayes MD, et al. Reliability and validity of the University of California, Los Angeles scleroderma clinical trial consortium gastrointestinal tract instrument. Arthritis Rheum 2009;61: Patten SB, Schopflocher D. Longitudinal epidemiology of major depression as assessed by the brief Patient Health Questionnaire (PHQ-9). Compr Psychiatry 2009;50: Pinto-Meza A, Serrano-Blanco A, Penarrubia MT, Blanco E, Haro JM. Assessing depression in primary care with the PHQ-9: can it be carried out over the telephone? J Gen Intern Med 2005;20: LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988;15: Clements P, Lachenbruch P, Siebold J, White B, Weiner S, Martin R, et al. Inter and intraobserver variability of skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol 1995;22: Hedges LV. Estimation of effect size from a series of independent experiments. Psychol Bull 1982;92: APPENDIX A: RECRUITING RHEUMATOLOGISTS OF THE CANADIAN SCLERODERMA RESEARCH GROUP Recruiting rheumatologists of The Canadian Scleroderma Research Group Recruiting Rheumatologists are as follows: M. Baron, J. P. Mathieu, M. Hudson, S. Ligier, T. Grodzicky: Montreal, Quebec, Canada; J. Pope: London, Ontario, Canada; J. Markland: Saskatoon, Saskatchewan, Canada; D. A. Masetto: Sherbrooke, Quebec, Canada; E. Sutton: Halifax, Nova Scotia, Canada; N. A. Khalidi, E. Kaminska: Hamilton, Ontario, Canada; D. Robinson, S. Mittoo: Winnipeg, Manitoba, Canada; N. Jones: Edmonton, Alberta, Canada; P. Docherty: Moncton, New Brunswick, Canada; C. D. Smith: Ottawa, Ontario, Canada; M. Fritzler: Calgary, Alberta, Canada.