Vol. 46 No. 1 July 2013 Journal of Pain and Symptom Management 131

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1 Vol. 46 No. 1 July 2013 Journal of Pain and Symptom Management 131 Brief Methodological Report Validity and Reliability of the Swedish Version of the Memorial Symptom Assessment Scale (MSAS): An Instrument for the Evaluation of Symptom Prevalence, Characteristics, and Distress Maria Browall, RN, PhD, Elisabeth Kenne Sarenmalm, RN, PhD, Salmir Nasic, MSc, Yvonne Wengstr om, OCN, PhD, and Fannie Gaston-Johansson, RN, PhD, FAAN Division of Nursing (M.B., Y.W.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; School of Life Sciences (M.B.), University of Sk ovde, and Research and Development Centre (E.K.S., S.N.), Skaraborg Hospital, Sk ovde, Sweden; Institute of Health and Caring Sciences (E.K.S.), Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden, and Johns Hopkins University (M.B., E.K.S.) and Johns Hopkins School of Nursing (F.G.-J.), Baltimore, Maryland, USA Abstract Context. There are few scales in Swedish that assess symptoms in the dimensions of frequency, severity, and distress. Objectives. The purpose of this study was to translate and determine the validity and reliability of the Memorial Symptom Assessment Scale (MSAS) in a Swedish population of postmenopausal women newly diagnosed with primary or recurrent breast cancer. Methods. The original 32-item MSAS, a self-report measure for assessing symptom distress and frequency in cancer patients, was translated and administered to 206 patients (primary, n ¼ 150 and recurrent, n ¼ 56). Results. The MSAS psychological symptom subscale correlated with the emotional and cognitive functioning subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and showed the highest correlation with the EORTC QLQ-C30 emotional functioning subscale (r ¼ 0.78; P < 0.01). The psychological symptom subscale also correlated with the Hospital Anxiety and Depression Scale (HADS) within values for anxiety (r ¼ 0.68; P < 0.01) and with the EORTC QLQ-C30 within cognitive functioning values (r ¼ 0.58; P < 0.01). The Global Distress Index (GDI)-MSAS showed satisfactory correlations with the EORTC QLQ-C30 emotional functioning subscale (r ¼ 0.75; P < 0.01), whereas the correlation between the GDI-MSAS and the EORTC QLQ-C30 cognitive functioning subscale was somewhat lower (r ¼ 0.54; P < 0.01). Correlations between the GDI-MSAS Address correspondence to: Maria Browall, RN, PhD, Division of Nursing, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Ó 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved , Huddinge, Stockholm, Sweden. maria.brovall@ki.se Accepted for publication: July 11, /$ - see front matter

2 132 Browall et al. Vol. 46 No. 1 July 2013 and the HADS anxiety subscale were confirmed (r ¼ 0.62; P < 0.01), and a correlation between the MSAS physical symptom items and symptom items in the EORTC-QLQ-C30 was evident (r ¼ 0.60e0.85; P < 0.01). Cronbach s alpha coefficients for the MSAS and MSAS subscales based on symptom scores ranged from 0.80 to The internal consistency at different time points was satisfactory, ranging from 0.86 (baseline) to 0.90 (follow-up). Conclusion. The Swedish version of the MSAS presents as a valid and reliable measure for assessing symptom distress, severity, and frequency in Swedish patients diagnosed with primary and recurrent breast cancer. J Pain Symptom Manage 2013;46:131e141. Ó 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Symptom, breast cancer, Memorial Symptom Assessment Scale, MSAS, validation Introduction Patients with cancer in different stages suffer from a wide variety of physical and psychological symptoms of varying frequency, severity, and distress. Some of the symptoms are directly associated with the disease or the treatment given and some remain from earlier treatment, whereas others are associated with the progression of the disease. 1e4 The significance of symptom assessment is a central issue for postmenopausal women diagnosed with breast cancer. Comprehensive assessment is necessary to promote successful symptom management in clinical practice. 5 Health care professionals should systematically assess patient-reported outcomes on how symptoms among different age groups and stages of disease are experienced because symptom assessment is important for effective and comprehensive cancer care of all women. 6 Because of the variety of questionnaires that are available to choose from, it is important to adopt one that is relevant to the study objectives and characteristics of the sample that is being investigated. 7 The frequency, severity, and distress of a symptom are all important measures of symptom burden. Symptom burden increases with cancer stage, and may subjectively reflect the tumor burden. 8 The symptom burden directly influences a patient s daily life, distress, quality of life (QoL), and survival. 1,8e11 Portenoy et al. 12 developed the Memorial Symptom Assessment Scale (MSAS) to measure the frequency, severity, and distress of 32 physical and psychological symptoms. The original development and validation of the MSAS involved item generation and scale construction, initial evaluation and re-evaluation of factors, reliability and validity, and the differentiation of various clinical populations. The overall validation results were satisfactory. Initial and subsequent factor analysis of the MSAS items resulted in a two-factor solution that supports the meaningful grouping of symptoms. 12,13 The MSAS proved to be a valid and reliable multidimensional measure of symptom experience in many different cancer populations. 10,11,14e18 In a systematic review of cancer symptom assessment questionnaires by Kirkova et al., 19 the MSAS was one of the most comprehensive questionnaires, with good psychometric properties, and appropriate for use in both initial clinical assessment and research. This is a unique feature because instruments are most often developed for either research or clinical practice. 20 The aim of the present study was to determine the validity and reliability of the MSAS in a Swedish population of postmenopausal women diagnosed with primary or recurrent breast cancer. The hypothesis was that the Swedish version of the MSAS (MSAS-Swe) would be a valid and reliable tool to describe the frequency, severity, and distress of physical and psychological symptoms in postmenopausal women diagnosed with primary or recurrent breast cancer. To address this hypothesis, the following considerations were explored: 1) convergent validity; how does MSAS correlate with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and

3 Vol. 46 No. 1 July 2013 Validation of the Swedish Version of the MSAS 133 Hospital Anxiety and Depression Scale (HADS) measures? 2) What is the reliability of the MSAS scale as measured by internal consistency? and 3) How stable is this internal consistency at different time points? Methods Sample and Setting The total sample consisted of a consecutive series of postmenopausal women (n ¼ 206) aged 55 years and older from two university hospitals and one county hospital in Sweden. Those with Stage IeIIIa (primary cancer, n ¼ 150) were scheduled for adjuvant chemotherapy (CT) or radiotherapy (RT) and those with Stage IIIbeIV (recurrent cancer, n ¼ 56) were receiving palliative treatment (RTand/or CT) and/or hormonal treatment. Several of the patients with primary cancer also received RT and/or endocrine treatment in different combinations after the CT or RT (Table 1). The inclusion criteria were postmenopausal women, aged 55 Table 1 Clinical Characteristics of the Included Participants Characteristics Primary Group n (%) Recurrent Group n (%) Age, yrs, mean (range) 65 (55e80) 65 (55e79) Single/divorced/widowed 56 (37) 21 (37.5) College/graduate degree 73 (49) 28 (64) Employed full-/part-time 53 (35) 26 (51) Elderly, retired 86 (57) 20 (39) Comorbidities Cardiovascular disease 43 (29) 19 (34) Musculoskeletal problems 46 (31) 11 (20) Respiratory problems 46 (31) 5 (9) Psychiatric disease 10 (7) 14 (25) Surgery Total mastectomy 48 (30) 25 (44.5) Sector resection 100 (67) 28 (50) Missing 2 (1) d Treatment CT a 12 (16) 10 (18) RT b 39 (52) 7 (12.5) Endocrine therapy c d 42 (75.0) CT þ RT d 26 (35) d CT þ RT þ Endocrine d 33 (44) d CT þ Endocrine d 4 (5) d RT þ Endocrine e 8 (11) d Endocrine þ RT þ Endocrine e 28 (37) d CT ¼ chemotherapy; RT ¼ radiotherapy. a Treatment for primary (chemotherapy only) and recurrent groups. b Treatment for primary (radiotherapy only) and recurrent groups. c Treatment for recurrent group. d Treatment for primary chemotherapy group over time. e Treatment for primary radiotherapy group over time. years and older, newly diagnosed with histologically confirmed Stage IeIV breast carcinomas, receiving adjuvant or palliative treatment, able to give informed consent, able to read and speak Swedish, and able to understand the purpose of the study. Exclusion criteria included serious coexisting medical conditions, end-of-life care (less than six-month life expectancy), cognitive impairment or evidence of dementia, current psychiatric disorder, and a history of any other type of cancer within the previous five years. Design Data for the present study were extracted from a larger descriptive longitudinal project involving two different studies on postmenopausal women with primary or recurrent breast cancer, with the aim of capturing the experiences of health-related QoL and symptoms in women aged 55 years and older, with data collected at different time points. Procedure All patients received oral and written information and gave informed written consent before inclusion. All eligible women were consecutively invited to participate in the study by the two study investigators (M. B., E. K. S.). Demographic information was self-reported, and medical data were collected from the hospital charts. Baseline data, for all of the women diagnosed with primary breast cancer, were collected during the week before the start of treatment. Those receiving CT and scheduled for treatment at the university hospitals completed the questionnaires at the hospital, whereas women treated at the county hospital had the questionnaires mailed to them together with a prepaid envelope and information explaining the procedures. At subsequent data collection points (one week after the first, third, and last [sixth] cycle of CT, and at follow-up, four months after the completion of treatment) all patients were mailed their questionnaires. All women scheduled for RT were from the same university hospital, and baseline data were collected at the hospital. Subsequent data collection points were after three weeks of treatment, two weeks after the completion of treatment, and at the follow-up at four months. Patients diagnosed with recurrent breast cancer were invited to participate after

4 134 Browall et al. Vol. 46 No. 1 July 2013 confirmation of recurrence. Baseline data were collected at the time of diagnosis of a recurrence and questionnaires were completed at the hospital. The follow-up questionnaires at one, three, and six months after diagnosis were mailed to the participants. Questionnaires The questionnaires included in this study were the MSAS, HADS, and EORTC QLQ- C30. For validation and reliability purposes in this study, the subscales of the HADS and EORTC QLQ-C30 questionnaires were used, as specified in the following sections. MSAS. Twenty-four of the symptoms included in this questionnaire are evaluated with respect to frequency, severity, and distress, and a further eight symptoms are evaluated in terms of severity and distress. 12 Each symptom is recorded as being either present or absent and, if present, is rated using a four-point rating scale (1e4) for frequency and severity, and a five-point scale (0e4) recording distress during the previous seven days, with higher scores indicating greater frequency, more severity, and higher distress. If a symptom is present, the symptom score is an average of the total of all scores within these dimensions. The scoring of the MSAS yields several subscale scores, including a physical symptom subscale score (PHYS- MSAS), a psychological symptom subscale score (PSYCH-MSAS), and a Global Distress Index (GDI-MSAS). The PHYS-MSAS includes 12 symptoms: lack of appetite, lack of energy, pain, feeling drowsy, constipation, dry mouth, nausea/vomiting, change in food taste, weight loss, feeling bloated, and dizziness. The PSYCH-MSAS includes six symptoms: worrying, feeling sad, feeling nervous, difficulty sleeping, feeling irritable, and difficulty concentrating. The GDI-MSAS includes four psychological symptoms (feeling sad, worrying, feeling irritable, and feeling nervous) and the distress associated with six physical symptoms (lack of appetite, lack of energy, pain, feeling drowsy, constipation, and dry mouth). HADS. HADS is a 14-item multiple-choice questionnaire with two subscales: depression (seven items) and anxiety (seven items). 21,22 Each item is rated on a four-point scale, reflecting a continuum of increasing levels of emotional distress. Scale scores range from 0 (no symptoms) to 21 (maximum distress) for anxiety and depression. Scores of 0e7 represent normal, 8e10 borderline, and scores of 11 or more on either subscale are considered to indicate those who are at risk of having psychological morbidity. The validity and reliability of this scale are well established. 22 Originally developed for the assessment of emotional disorders in medical and surgical patients, 21 the HADS focuses only on the psychological aspects of depression as well as anxiety and avoids items concerned with somatic manifestations of depression (e.g., fatigue, sleep disturbance, and weight loss). The scale has been validated and used in a wide range of somatic disorders. A Swedish version was developed in 1986 and was initially validated in patients with spinal cord injuries. 23 Since then, it has been used in populations with various malignant diagnoses, including lung cancer, 24 head and neck cancer, 25 breast cancer, 26 and malignant melanoma. 27 For validation of the MSAS-Swe, the anxiety subscale of that questionnaire was used. EORTC QLQ-C30. The EORTC developed a modular system for QoL assessment in cancer patients participating in clinical trials. The system consists of a central questionnaire, the EORTC QLQ-C30, 28 and includes the tumorspecific breast cancer module EORTC QLQ- BR The QLQ-C30 comprises 30 items grouped into subscales that evaluate physical, emotional, social, cognitive, as well as role functioning, and three symptom scales (fatigue, pain, and nausea/vomiting), five single symptom items (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and financial difficulties. Included in the questionnaire is a scale measuring the overall QoL. In the present study, all scales in the questionnaire were transformed to a percentile scale ranging from 1 to 100. High scores in the functioning scales and overall QoL indicate high levels of functioning and overall QoL, whereas high scores in the symptom/problem scales indicate high levels of symptoms/problems. The reliability of the Swedish version has been assessed in both healthy individuals and different groups of cancer patients, with an internal consistency (Cronbach s alpha) ranging from 0.55 to For validation of the MSAS-Swe, single items of separate symptoms that were found

5 Vol. 46 No. 1 July 2013 Validation of the Swedish Version of the MSAS 135 in both instruments were tested, and the questions about emotional functioning (Did you feel tense, worried, irritable, and depressed?) and cognitive function (Have you had difficulty in concentrating on things, such as reading a newspaper or watching television? Have you had difficulty remembering things?) were tested from the EORTC QLQ-C30. Validation Procedures Two phases were included in the validation procedure Phase I. The published English version of the MSAS was translated into Swedish using a standard forward-backward translation procedure. 31 Two of the authors (M.B. and E.K.S.) independently translated the MSAS from English to Swedish. These two versions were discussed and discrepancies were solved by mutual consensus. The Swedish items were then submitted to two independent bilingual translators for back translation into English. The original English version and the back translated version of the questionnaire were further analyzed for discrepancies by a physician and a nurse, both bilingual and experts in the oncology-surgery field. When consensus was established, a pilot study with 20 participants tested the feasibility (i.e., how easy it was to understand the questions and the length of time it took to fill out the survey) of the translated version. The feasibility was found to be good and the questionnaire was perceived as easy to understand; completion took, on average, 10 minutes. Phase II. To determine its psychometric properties, the participating patients (N ¼ 206) were asked to complete the MSAS-Swe to test its validity and reliability. The statistical analysis started with an assessment of the pattern of missing values among the responses to the MSAS items. The number of missing values was quite low for different MSAS items and did not exceed 2% of all observations for any item. In comparison, for those items within the Swedish version of the EORTC QLQ-C30 that were used in the correlation analyses, the proportion of missing values varied between 3% and 6%, and the subscales of anxiety and depression within the HADS had missing values in approximately 12% of all observations. The MSAS has previously demonstrated good construct validity in both inpatient and outpatient cancer populations. 12,14,17,18 The initial psychometric evaluation by Portenoy et al. 12 used factor analysis to define the two subscales: psychological symptoms and physical symptoms. Using Cronbach s a coefficient, their results show estimates of internal consistency reliability and appropriate reliability at 0.88 and 0.83, respectively. To assess validity, additional correlational analysis between MSAS- Swe and corresponding EORTC and HADS subscales was conducted to explore the convergent validity of the instrument. The subscales used to explore convergent validity were based on the same subscales that were established in the English version of the MSAS. 32 We hypothesized that the PSYCH-MSAS in the subscale of the Swedish version would correlate with the emotional and cognitive functioning scale in the EORTC QLQ-C30 and the HADS anxiety subscale. We further hypothesized that the GDI-MSAS subscale would also correlate with the EORTC QLQ-C30 emotional functioning and HADS anxiety subscales (Table 2). Because physical subscales in the MSAS, EORTC, and HADS were not comparable with respect to number and type of included items in the subscale, we evaluated all the items and explored those in the PHYS-MSAS that were hypothesized to correlate with the symptom items in the EORTC QLQ-C30 (Table 3). Reliability Cronbach s alpha coefficient was used to assess the internal consistency reliability of the MSAS and to explore if it was stable at different time points. An alpha within the range of 0.70e0.95 was accepted as satisfactory for internal consistency. 33,34 Statistical Analyses To investigate the convergent validity correlations between the MSAS-Swe subscales and corresponding HADS subscales, EORTC QLQ-C30 subscales also were included in the analysis. For physical subscales, only correlations on factor (item) level were conducted because there were no equivalent predefined subscales. Spearman s correlation coefficient was used because data were on the ordinal level. A factor analysis of the MSAS-Swe data was conducted to check whether subscales

6 136 Browall et al. Vol. 46 No. 1 July 2013 Table 2 Correlations Among the MSAS Subscales and Corresponding Subscales Within the EORTC QLQ-C30 and HADS HADS EORTC QOL-C30 Instruments Anxiety a Depression b Emotional Functioning c Cognitive Functioning d MSAS Subscale PSYCH-MSAS e GDI-MSAS f MSAS ¼ Memorial Symptom Assessment Scale; EORTC QLQ-C30 ¼ European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; HADS ¼ Hospital Anxiety and Depression Scale; PSYCH-MSAS ¼ Psychological Symptom Subscale; GDI-MSAS ¼ Global Distress Index-Memorial Symptom Assessment Scale. All correlations were significant at the 0.01 level or higher. a I feel tense or wound up ; I get a sort of frightened feeling as if something awful is about to happen; worrying thoughts go through my mind; I can sit at ease and feel relaxed; I get a sort of frightened feeling like butterflies in the stomach; I feel restless as I have to be on the move; I get sudden feelings of panic. b I still enjoy the things I used to enjoy; I can laugh and see the funny side of things; I feel cheerful; I feel as if I am slowed down; I have lost interest in my appearance; I look forward with enjoyment to things; I can enjoy a good book or TV program. c Did you feel tense; worried; irritable; and depressed? d Have you had difficulty in concentrating on things, like reading a newspaper or watching television? Have you had difficulty remembering things? e Worrying, feeling sad, feeling nervous, difficulty sleeping, feeling irritable, and difficulty concentrating. f Psychological symptoms (feeling sad, worrying, feeling irritable, and feeling nervous) and the distress associated with physical symptoms (lack of appetite, lack of energy, pain, feeling drowsy, constipation, and dry mouth). could be recovered from the original items. The unrotated solution based on the principal component analysis is presented here. To explore the internal consistency of the MSAS- Swe instrument as a whole and for the primary and recurrent groups, Cronbach s alpha was calculated. Ethical Approval The study was performed in accordance with the ethical standards of the Helsinki Declaration and Good Clinical Practice guidelines. The Ethics Committees at Gothenburg University and Stockholm University approved the study (No. O049-02,03-441). Table 3 Correlations Between Items According to the PHYS-MSAS and EORTC QLQ-C30 MSAS Item a EORTC QLQ-C30 Questions from EORTC QLQ-C30 Correlation Coefficient b,c Q1. Difficulty concentrating Cognitive functioning d Q20. Have you had difficulty in concentrating 0.60 on things, like reading a newspaper or watching television? Q2. Pain Pain Q9. Have you had pain? 0.81 Q19. Did pain interfere with your daily activities? 0.70 Q3. Lack of energy Fatigue Q10. Did you need to rest? 0.60 Q12. Have you felt weak? 0.65 Q18. Were you tired? 0.69 Q5. Feeling nervous Emotional functioning Q21. Did you feel tense? 0.64 Q7. Nausea Nausea Q14. Have you felt nauseated? 0.85 Q10. Difficulty sleeping Insomnia Q11. Have you had trouble sleeping? 0.85 Q13. Vomiting Vomiting Q15. Have you vomited? 0.73 Q14. Shortness of breath Dyspnea Q8. Were you short of breath? 0.78 Q15. Diarrhea Diarrhea Q17. Have you had diarrhea? 0.79 Q16. Sad Emotional functioning Q24. Did you feel depressed? 0.69 Q18. Worrying Emotional functioning Q22. Did you worry? 0.68 Q21. Lack of appetite Appetite loss Q13. Have you lacked appetite? 0.73 Q24. Irritation Emotional functioning Q23. Did you feel irritable? 0.73 Q29. Constipation Constipation Q16. Have you been constipated? 0.83 PHYS-MSAS ¼ Physical Symptom Subscale; EORTC QLQ-C30 ¼ European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; MSAS ¼ Memorial Symptom Assessment Scale. The questions about cough, feeling drowsy, numbness/tingling in hands/feet, feeling bloated, problems with urination, itching, dizziness, sexual interest, difficulty swallowing, mouth sores, weight loss, changes in skin, dry mouth, food and drinks taste different than usual, lost any hair, hot flushes, swollen arm or hand, and do not look like self from the MSAS were not correlated with the EORTC QLQ-C30 because these symptoms were not measured with this instrument. a MSAS scores that include all three dimensions, frequency, severity, and distress, were used here. b Spearman s coefficient. c All correlations were statistically significant at the 1% level (P-value < 0.01). d Questions from the EORTC QLQ-C30.

7 Vol. 46 No. 1 July 2013 Validation of the Swedish Version of the MSAS 137 Results Of 233 eligible newly diagnosed patients (primary patients, n ¼ 168 and recurrent, n ¼ 65), 206 patients agreed to participate (primary, n ¼ 150 and recurrent, n ¼ 56) and completed the questionnaires. Participant ages ranged from 55 to 80 years, with a mean SD of years. Most of the women were married (primary, 63% vs. recurrent, 62.5%). In the primary group, 57% were retired, compared with 39% in the recurrent group. Most of the women had a higher level of education (primary, 64% and recurrent, 49%). Musculoskeletal and respiratory problems were the most common comorbidities in the primary group (31%), and cardiovascular disease in the recurrent group (34%). Sector resection was the most common surgical procedure (primary, 67% vs. recurrent, 50%), and the most common treatment for the first recurrence was endocrine treatment (75%). For women in the primary group, RT alone (52%) or a combination of CT þ RT þ endocrine (44%) was the most common treatment. Validity Convergent Validity. Correlations between the MSAS subscales and subscales from other questionnaires used in the validation analysis are shown in Table 2. The results show that the PSYCH-MSAS subscale correlates with the emotional and cognitive functioning scales in the EORTC QLQ-C30, and had the highest correlation with the EORTC QLQ-C30 emotional functioning subscale (r ¼ 0.78; P < 0.01). The PSYCH-MSAS also correlated with HADS anxiety values (r ¼ 0.68; P < 0.01) and with the EORTC QLQ-C30 cognitive functioning values (r ¼ 0.58; P < 0.01). In addition, the GDI- MSAS correlates with the EORTC QLQ-C30 subscale of emotional functioning and showed satisfactory correlations (r ¼ 0.75; P < 0.01), whereas the correlation between the GDI- MSAS and EORTC QLC-C30 cognitive functioning subscale was lower (r ¼ 0.54; P < 0.01). Correlations between GDI-MSAS and HADS anxiety subscales also were confirmed (r ¼ 0.62; P < 0.01) (Table 2). Furthermore, we found correlations between symptom items in the PHYS-MSAS and symptom items in the EORTC-QLQ-C30 (r ¼ 0.60e0.85; P < 0.01), as shown in Table 3. Initial psychometric evaluation following the methods outlined by Portenoy et al. 12 was computed for the principal components by completing factor analysis on the Swedish data using the symptom burden score, that is, the average of the total severity, frequency, and distress scores for each of the 32 symptoms. The two components resulting from the factor analysis accounted together for 32% of the total variance, whereas the first factor accounted for 25%, correlating highly with most symptoms. By means of the factor analysis, we could recover meaningful clusters of symptoms (Fig. 1). The group labeled GASTR contained eight symptoms that mainly related to gastrointestinal distress. A second cluster labeled PHYS contained 17 physical symptoms. A third cluster labeled PSYCH comprised six symptoms related to psychological distress. Urination problems (M12_S) and constipation (M29_S) were borderline cases as they could belong either to cluster GASTR or to cluster PHYS. The three clusters based on the MSAS-Swe data corresponded with the subscales established by the MSAS English version. Reliability Internal Consistency. Cronbach s alpha coefficients for the MSAS and MSAS subscales, based on symptom scores, ranged from 0.80 to Both in the primary and the recurrent group, the alpha coefficient was 0.89, and, accordingly, 0.89 for the total sample (Table 4). The internal consistency at different time points was satisfactory, ranging from 0.86 from the baseline measurement, to 0.90 at the last four-month follow-up, with a total of 0.90 for all measurements (Table 5). Discussion Despite an instrument having been developed in a different language and culture, comprehensive instruments with good psychometric properties are appropriate for translation and cultural adaptation for use in clinical practice as well as research. The present study demonstrated that the MSAS-Swe has adequate psychometric properties of convergent validity and internal consistency. A factor analysis showed that MSAS-Swe data corresponded with the subscales established by the original MSAS English version.

8 138 Browall et al. Vol. 46 No. 1 July 2013 Fig. 1. Results of principal components factor analysis using the symptom scores, that is, the average of the intensity, frequency, and distress for 32 symptoms. Factor loadings are presented in the table on the left and patterns of groupings are illustrated in the plot on the right. There are two main factors that distinguish three major clusters of symptoms: GASTR (gastrointestinal symptoms), PHYS (physical symptoms), and PSYCH (psychological symptoms).

9 Vol. 46 No. 1 July 2013 Validation of the Swedish Version of the MSAS 139 Table 4 Internal Consistency of the MSAS Based on Symptom Scores for Items Included in Each Subscale Both Groups Subscale Primary Recurrent Combined PHYS PSYCH GDI Entire MSAS (32 items) MSAS ¼ Memorial Symptom Assessment Scale; PHYS ¼ physical symptoms; PSYCH ¼ psychological symptoms; GDI ¼ Global Distress Index. All scores are based on all dimensions of symptoms (frequency, severity, and distress). This finding was shown both for the two diagnoses separately (primary and recurrent) as well as for the total sample. In the present study, one of the hypotheses was that the PSYCH- MSAS subscale and GDI-MSAS would correlate with the emotional and cognitive functioning scales in the EORTC QLQ-C30 and the HADS anxiety subscale. The strong correlations between the PSYCH-MSAS, GDI-MSAS, and EORTC-QLQ-C30 are congruent with the study by Lam et al. 35 in which the MSAS-Short Form PSYCH subscale correlated strongly with the EORTC QLQ-C30 emotional functioning scale. In contrast to the study by Lam et al., 35 our findings showed a stronger correlation between the PSYCH-MSAS, the GDI-MSAS, and the cognitive functioning symptoms of the EORTC-QLQ-C30. This difference in findings is probably because they used the short and condensed version of the MSAS. Interestingly, the correlations within the subscale at times comprised different items because the subscales differed between questionnaires; however, despite these differences, the correlations were quite high at a 0.60e0.70 level. The PSYCH-MSAS correlated more strongly with the HADS anxiety subscale and with the EORTC QLQ-C30 emotional functioning scale. This result also has been shown by Lam et al. 35 and Webber et al. 36 Results from the study by Webber et al. 36 also imply that the MSAS is more strongly correlated with anxiety than depression. This means that the psychological distress assessed by the MSAS is a separate construct from depression, and the symptoms included in the subscale are more representative of an anxiety disorder. Our hypothesis that there would be a correlation between symptom items in the PHYS-MSAS and symptom items in the EORTC QLQ-C30 was confirmed and, where possible, the symptoms were compared on a subscale level, but for most of the physical symptoms there were no subscales in the MSAS and, therefore, we made the comparison at the item level. In an earlier study, both the MSAS-Short Form and the condensed MSAS showed positive convergent validity as seen from inverse correlations with EORTC QLQ-C30 symptom scales. 35 Reliability Study results showed high internal consistency with Cronbach s alpha for the instrument of 0.80e0.89. These findings are in line with results published by Cheng et al. 18 At different time points, results reached satisfactory internal consistency that increased and reached 0.90 at the four-month follow-up. The values for PSYCH in the study by Cheng et al. 18 were 0.81 compared with our 0.84, and PHYS was 0.79 compared with our Comparing the results of Portenoy et al. 12 in the original validation of PHYS 0.88 and PSYCH 0.83, with the results from the Swedish validation, supports the reliability of the questionnaire in Swedish. Limitations There are some limitations to this study; first, the population was limited to Swedish Measurement Points Table 5 Internal Consistency of the MSAS at Different Time Points Symptom Occurrence and Level of Bother 1. Baseline: both primary and recurrent groups One week after the first treatment (CT/RT): primary group Third cycle of CT/three weeks of RT: primary group Last cycle of CT/after finished RT: primary group Follow-up four months after the completion of treatment CT/RT: primary group 0.90 Total: all measurement points 0.90 MSAS ¼ Memorial Symptom Assessment Scale; CT ¼ chemotherapy; RT ¼ radiotherapy.

10 140 Browall et al. Vol. 46 No. 1 July 2013 postmenopausal outpatients, aged 55 years and older, with breast cancer. However, the MSAS instrument has been successfully studied and applied in a variety of settings and in patients with different cancers. 37 Future studies should examine this instrument s validity for use among Swedish patients with other types of cancer, in other age groups, and in other settings. Second, including an additional questionnaire in the study could have strengthened our results; however, the EORTC QLQ-C30 has numerous symptom items, and we wished to minimize respondent burden for the participants in this study. Third, it also would have been desirable to test the repeatability (as a part of reliability) over time with a test-retest method but that was not possible in this study. Therefore, further prospective studies will need to be carried out to evaluate the testretest reliability and the responsiveness over time of the MSAS-Swe; studies with other symptom instruments, applying a test-retest to the questionnaire, also should be conducted. The importance of cancer-related symptoms, their high prevalence, and the impact these have on patient QoL is well known. 38 Symptoms need to be considered as an important patient-reported outcome in clinical practice and research. Despite this knowledge, there are still concerns about the effective and appropriate assessment and measurement of symptom experiences. Therefore, it is of vital importance that psychometrically sound instruments are available for use in a variety of different settings and cultures. Conclusion The MSAS-Swe presents as a valid and reliable measure for assessing symptom distress, severity, and frequency in Swedish patients diagnosed with primary and recurrent breast cancer. The instrument shows good potential for being useful for clinicians to assess physical and psychological symptoms during cancer therapy and at follow-up in Swedish-speaking patients. Disclosures and Acknowledgments This study was funded and supported by the King Gustav V Jubilee Clinic Cancer Research Foundation, Gothenburg, Sweden. The authors declare no conflicts of interest. The authors acknowledge all the women taking part in this study, and thank Aileen Ireland for English-language editing. References 1. Browall M, Ahlberg K, Karlsson P, et al. Healthrelated quality of life during adjuvant treatment for breast cancer among postmenopausal women. Eur J Oncol Nurs 2008;12:180e Kenne Sarenmalm E, Ohlen J, Jonsson T, Gaston-Johansson F. Coping with recurrent breast cancer: predictors of distressing symptoms and health-related quality of life. J Pain Symptom Manage 2007;34:24e Wood LJ, Nail M, Gilster A, Winters KA, Elsea CR. Cancer chemotherapy-related symptoms: evidence to suggest a role for proinflammatory cytokines. Oncol Nurs Forum 2006;33:535e Miaskowski C, Cooper BA, Paul SM, et al. Subgroups of patients with cancer with different symptom experiences and quality-of-life outcomes: a cluster analysis. Oncol Nurs Forum 2006;33:E79eE Kirkova J, Davis MP, Walsh D, et al. Cancer symptom assessment instruments: a systematic review. J Clin Oncol 2006;24:1459e Hughes EF, Wu AW, Carducci MA, Snyder CF. What can I do? Recommendations for responding to issues identified by patient-reported outcomes assessments used in clinical practice. J Support Oncol 2012;10:143e Tishelman C, L ovgren M, Broberger E, Hamberg K, Sprangers M. Are the most distressing concerns of patients with inoperable lung cancer adequately assessed? A mixed-methods analysis. J Clin Oncol 2010;28:1942e Cleeland CS, Reyes-Gibby CC. When is it justified to treat symptoms? Measuring symptom burden. Oncology 2002;16:64e Tishelman C, Degner LF, Rudman A, et al. Symptoms in patients with lung carcinoma distinguishing distress from intensity. Cancer 2005;104: 2013e Portenoy RK, Thaler HT, Kornblith AB, et al. Symptom prevalence, characteristics and distress in a cancer population. Qual Life Res 1994;3: 183e Hwang SS, Scott CB, Chang VT, et al. Prediction of survival for advanced cancer patients by recursive partitioning analysis: role of Karnofsky performance status, quality of life, and symptom distress. Cancer Invest 2004;22:678e Portenoy RK, Thaler HT, Kornblith AB, et al. The Memorial Symptom Assessment Scale: an

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