Abstract
Background
Hidradenitis suppurativa (HS) is a chronic inflammatory disease that is not well understood. The HS core outcome set calls for a patient global assessment (PtGA), for which measures are limited.
Objectives
Our aim is to assess the validity, reliability, and responsiveness of a candidate single-item PtGA for HS-specific health-related quality of life (HRQOL).
Methods
Cognitive debriefing interviews were conducted with HS patients in Denmark (DK) and the United States (US). Field testing was conducted via a cross-sectional observational study with adults with HS in the US and DK. The candidate PtGA item, demographic items, and multiple patient-reported scales including the Hidradenitis Suppurativa Quality of Life (HiSQOL), Dermatology Life Quality Index (DLQI), numerical rating scale (NRS) for pain were concurrently administered to evaluate convergent and known-groups validity. The scales with a single-item assessment of change were administered again 24-72 hours later to evaluate reliability and responsiveness.
Results
After cognitive debriefing, the candidate PtGA for HS-specific HRQOL was finalized with five response levels. Convergent validity of the PtGA was supported with significant correlations with the HiSQOL score r = 0.79 [95CI: 0.75-0.82] and DLQI (r = 0.78, [95CI: 0.74-0.82]). The PtGA displayed known-groups validity with the DLQI score bands based on significance of an analysis of variance (p<.0001). Good test-retest reliability was supported by the intraclass correlation coefficient (ICC value = 0.82, [95CI: 0.78-0.85]) for those who reported stable HS. Responsiveness was assessed by differences in PtGA score against a patient-reported assessment of change, which showed significant differences towards improvement.
Conclusions
The single-item PtGA exhibits reliability, validity, and responsiveness in assessing HS-specific HRQOL in HS, making it a good provisional tool for HS clinical research.
Introduction
Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic, recurrent inflammatory disease known to cause painful nodules in the axillae, groin, breast, and buttocks regions. There is a frequent delay in diagnosing patients with HS, as it is commonly mistaken for a skin infection.1 HS has an estimated prevalence of 0.1-4% worldwide.2 Those ranging from puberty to age 50 are often affected and there is a predilection for women.1 Treatments such as topical antibiotics, biologics, and systemic antibiotics are routinely prescribed, however, there is a need to develop and investigate additional treatments to reduce the negative impact of this condition.2
The HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) was formed to construct a Core Outcome set (COS) to guide assessments in future clinical trials.2-4 Six domains were recommended in the core domain set including global assessment, both patient- and physician-rated. Single-item assessments such as a physician global assessment in clinical trials has been effective in assessing and tracking dermatologic disease severity over time. Simplicity in its use in a clinical setting can result in a high physician compliance rate5, thus allowing for the physician global assessment to dually serve as a measurement of physician performance as well as a tool for justifying changes in care, both clinically and for cost. Similarly, a patient global assessment (PtGA) assess a construct comprehensively, such as disease impact on health-related quality of life (HRQOL), and allows the patient to consider all contributory factors (such as multiple symptoms, treatments, risks, and benefits) related to the condition or disease. While a single item PtGA is needed for clinical trials, this type of broadly encompassing item will likely provide an effective and agile method for assessment in the clinical setting. To our knowledge, there have not been any studies describing the development or measurement properties of a PtGA specifically for HS. Thus, the objective of this study was to develop and investigate the measurement properties of a single-item PtGA, to serve as a valid, reliable, and responsive measure of HS-specific HRQOL.
Methods
The single item PtGA item was concurrently developed along with the HiSQOL, a multi-item HS-specific HRQOL measure.6 In short, a mixed methods study design was utilized and included four phases aligned with guidance from the US Food and Drug Administration.7 Conduct of the study was overseen by the international group of investigators, which included patient research partners, clinicians with expertise in HS, and researchers with expertise in instrument development. People with HS who were 18 years or older were identified based on diagnostic code for HS (International Classification of Diseases (ICD) −9 and −10 codes 705.83 and L73.2, respectively) in the medical record at academic institutions in the United States and Demark. People who gave informed consent, had a confirmed diagnosis of HS, and were fluent in English or Danish were recruited by phone and in clinic. The PtGA item was developed using the expertise of the investigators and four patient research partners. The item was developed with a 7-day recall period since longer recall periods can be limited by recall bias.8 The initial item was translated into Danish based on recognized methods for cross-cultural adaptation.9 Cognitive debriefing interviews and focus groups were conducted with people with HS to evaluate the item. Participants were asked to complete the instrument using the “think-aloud” technique, which facilitates feedback on the instrument. The interviewers (JSK, ES) also asked probing questions to elicit suggestions. All sessions were audio recorded, transcribed, and the qualitative data was analyzed with Nvivo 11 software (QSR International, Burlington, MA). Analysis was conducted independently by two researchers in the original language by a native speaker. Using grounded theory methods10 and qualitative analysis software, quotations were assigned a code determined by the underlying concept and grouped into higher level concepts.
Field testing and psychometric assessment of the item was conducted with an observational non-interventional study conducted in the US and DK. The candidate PtGA item, Hidradenitis Suppurativa Quality of Life (HiSQOL) measure6, Dermatology Life Quality Index (DLQI)11,12 , the Hospital Anxiety and Depression Scale (HADS)13 and numerical rating scale (NRS) for pain14 were administered concurrently. A web version of all instruments and items was developed in REDCap (Research Electronic Data Capture), a secure, web-based application designed to support data capture for research studies.15 All measures and a patient-rated impression of change item (7-point Likert scale from very much worse to very much improved) were administered a second time (24-72 hours later). This timeframe was chosen due to the unpredictable, intermittent, and rapid onset of HS worsening. This study was approved by the ethics committee of each institution and the Danish Data Protection Agency. All participants gave informed consent prior to participation in the study.
Analysis
Patient demographics and characteristics were reported as means with standard deviations and sum totals with percentages. Psychometric properties of the PtGA item including convergent validity, test-retest reliability, known-groups validity, and responsiveness were assessed. Convergent validity was assessed with the Spearman correlation using Fisher’s z Transformation of the PtGA and other measures using baseline responses (Day 0). Correlations were interpreted as 0.00-0.19 poor, 0.20-0.39 average, 0.40-0.59 moderate, 0.60-0.79 significant, and 0.80-1.0 strong.16 It was hypothesized the item would have at least strong correlation with the DLQI and HiSQOL. It was hypothesized the PtGA item would have at least moderate correlation with the NRS for pain and each of the HADS sub-scales. Known-groups validity was based on an analysis of covariance (ANCOVA) for DLQI score bands17 with the PtGA responses as the dependent variable and adjusted for country, age, or sex. It was hypothesized there would be significant differences of the PtGA item scores for the DLQI groups.
Test-retest reliability was used to evaluate score reproducibility over time when the condition was stable, taken as ‘no change’ on the patient-reported assessment of change item at the second administration (24-72 hours later). It was hypothesized that the group that reported stable disease would have two PtGA scores with strong correlation, supporting test-retest reliability.
It was also hypothesized that the groups that reported improvement or worsening HS on the patient-reported assessment of change, administered 24-72 hours later) would have PtGA scores that were significantly different in a positive and negative direction, respectively, compared to the first administration. Intraclass correlation coefficients (ICCs) were used to appraise test-retest reliability, where an ICC > 0.9 is an indication of excellent reliability, 0.75 to 0.9 is good reliability, 0.5 to 0.75 is moderate reliability, and ICC < 0.5 is poor reliability.18 Responsiveness was assessed using ANCOVA for the mean differences in the PtGA score as described above. Linear regression was used to evaluate responsiveness of the PtGA. The PtGA was the dependent variable, while the patient impression of change was an independent variable along with adjustment for age, sex, and country. All data analysis and statistical tests were computed using SAS software, version 9.4 (SAS Institute, Inc., Cary NC, US).
Results
Development of the Patient Global Assessment Item (PtGA)
After cognitive debriefing, the candidate PtGA for HS-specific HRQOL was finalized as: “In the past 7 days, how much has HS influenced your quality of life?” Five response levels were provided and included: not at all, slightly, moderately, very much, and extremely. The score applied to each response was 0, 1, 2, 3, and 4 respectively.
Field Testing and Psychometric Assessment
Overall, 441 patients with a diagnosis of HS participated in this study; most were female and the majority reported a moderate or very large impact on HRQOL based on DLQI score (Table 1). The novel PtGA item responses included the full range of responses (Figure 1) and the most frequent response categories were ‘slightly’ or ‘moderately’.
Table 1:
Demographic characteristics and baseline assessments of the field testing participants
| Characteristics | US | DK | ||
|---|---|---|---|---|
| Total participants, n | 224 | 217 | ||
| Age in years, mean (range) | 39.6 (19-77) | 42.9 (19-72) | ||
| Sex, n (%) | ||||
| Female | 195 (87%) | 194 (91%) | ||
| Male | 29 (13%) | 20 (9%) 3 missing | ||
| Race, n (%) | ||||
| White | 159 (71%) | |||
| Asian | 3 (1%) | |||
| Black | 49 (22%) | NC | ||
| North American Indian | 0 (0%) | |||
| Hispanic/Latino | 6 (3%) | |||
| Mixed | 1 (0%) | |||
| Other | 6 (3%) | |||
| Education | ||||
| <12 years of school | 6 (3%) | 28 (13%) | ||
| High School/GED | 45 (20%) | 11 (5%) | ||
| Occupational, technical, or vocational | 20 (9%) | 50 (23%) | ||
| Some College/No Degree | 58 (26%) | 0 (0%) | ||
| Associate’s Degree | 25 (11%) | 46 (21%) | ||
| Bachelor’s Degree | 49 (22%) | 70 (33%) | ||
| Master’s Degree | 19 (8%) | 10 (5%) | ||
| Doctoral Degree | 2 (1%) | 0 (0%) 2 missing | ||
| Instrument | Mean (SD) |
Median | Mean (SD) |
Median |
| PtGA | 2.09 (1.34) |
2 | 1.96 (1.26) |
2 |
| HiSQOL, total | 28.98 (17.53) |
27 | 26.92 (17.86) |
27 |
| DLQI | 12.97 (8.33) |
12 | 11.17 (8.02) |
9 |
| NRS for pain | 3.29 (2.83) |
3 | 3.15 (2.61) |
3 |
| HADS, Anxiety subscale | 8.14 (4.91) |
8 | 7.05 (5.09) |
7 |
| HADS, Depression subscale | 6.43 (4.67) |
6 | 5.13 (2.96) |
4 |
US: United States sample, DK: Denmark sample, NC: not collected
HiSQOL: The Hidradenitis suppurativa quality of life (HiSQOL) instrument is a recently developed HS-specific health-related quality of life instrument. A higher score (maximum of 68) indicates a higher negative impact of HS. The three sub-scale are Symptoms, Psychosocial Effects, and Activities & Adaptations.
DLQI: The Dermatology Life Quality Index (DLQI) is a skin-specific health-related quality of life index. This 10-item scale has a score range from 0 (better) to 30 (worse) indicating more negative impact on quality of life.
NRS for pain: Numerical rating scale is a single item 11-point scale was used to assess severity of HS-related pain.
HADS: The Hospital Anxiety and Depression Scale is used to measure symptoms of anxiety and depression. The scale was administered to the patients in the form of 14 questions, 7 questions were dedicated to depression and anxiety respectively with scoring ranges from 0 (better) to 21 (worse) for each sub-scale.
Figure 1.
Participant responses for the patient global assessment (PtGA). DK, Denmark.
The PtGA item demonstrated convergent validity through correlation with existing measures (Table 2). The strongest overall correlation of the PtGA, a significant-to-strong correlation of 0.79 (95% confidence interval 0.75-0.82), was with the HiSQOL total score. The PtGA item had overall correlations of 0.78 (0.74-0.82) with the DLQI and 0.65 (0.60-0.71) with the NRS for pain. The PtGA item had lower correlations of 0.53 (0.46-0.59) and 0.55 (0.48-0.61) with the HADS depression and anxiety subscale scores, respectively. Correlations for the US sample were lower than the Danish sample, but as described here, the HiSQOL had the highest correlation for both groups, followed by the DLQI, and NRS for pain.
Table 2.
Reliability and convergent validity of the PtGA item
| Test-retest reliability |
ICC (95%CI) | ||
|---|---|---|---|
| Overall | 0.84 (0.80, 0.87) | ||
| Country | |||
| Denmark | 0.88 (0.83, 0.91) | ||
| US | 0.81 (0.79, 0.87) | ||
| Sex | |||
| Female | 0.84 (0.79, 0.87) | ||
| Male | 0.84 (0.73, 0.92) | ||
| Age Group | |||
| ≤20 | 1.00 (1.00, 1.00) | ||
| 21-30 | 0.81 (0.71, 0.88) | ||
| 31-40 | 0.87 (0.80, 0.92) | ||
| 41-50 | 0.85 (0.77, 0.90) | ||
| 51-60 | 0.82 (0.70, 0.89) | ||
| 61-70 | 0.84 (0.64 0.94) | ||
| 71-80 | 0.93 (0.68, 0.99) | ||
| Race | |||
| White | 0.82 (0.76, 0.87) | ||
| Asian | NC | ||
| Black | 0.77 (0.61, 0.88) | ||
| North American | NC | ||
| Indian | NC | ||
| Hispanic/Latino | NC | ||
| Mixed | NC | ||
| Other | |||
| Convergent validity | Spearman correlation (95%CI) | ||
| Overall | US | DK | |
| DLQI | 0.78 (0.74, 0.82) | 0.72 (0.64,0.77) | 0.85 (0.81,0.89) |
| HiSQOL | 0.82 (0.78,0.85) | 0.76 (0.69,0.81) | 0.88 (0.84,0.90) |
| HADS | |||
| Anxiety | 0.55 (0.48, 0.61) | 0.52 (0.41,0.68) | 0.58 (0.48,0.66) |
| Depression | 0.53 (0.48, 0.59) | 0.57 (0.48,0.66) | 0.48 (0.37,0.58) |
| NRS for pain | 0.66 (0.60, 0.71) | 0.60 (0.51,0.68) | 0.72 (0.65,0.78) |
The PtGA demonstrated known groups validity in a comparison of its scores across DLQI score bands (Figure 2), showing an increase in the mean PtGA score of participants with more severe DLQI scores. Adjustment for age, sex, or country did not significantly impact these analyses.
Figure 2.
Known-groups validity of patient global assessment (PtGA) item for established Dermatology Life Quality Index (DLQI) score groups.
The PtGA demonstrated good test-retest reliability (ICC 0.84 (0.80, 0.87)) among patients with stable HS (Table 2). The test-retest reliability was similar for respondents from DK and the US, as well as across age groups and race.
Responsiveness of the PtGA item was measured by assessing the mean score change for respondents that reported HS worsening or improvement. For those reporting improved HS, the mean PtGA score was significantly lower, with mean (95%CI) decrease of −0.54 points (p<.0001) indicating decreased impact on HRQOL. For those with worsening of HS, there was no significant mean change (0.03 point, p=.78). With adjustment for country, sex and age, those reporting worsening had a non-significant change in score PtGA score (0.03 (−0.16, 0.22)). Those reporting stable disease had a significant small decrease in score (−0.28 (−0.37, −0.19)) and those with improved disease had a significant decrease in score indicating lower impact (−0.53 (−0.76, −0.29)).
Discussion
The results of this study suggest that the PtGA mainly measures and reflects the patient’s HRQOL, as it correlates well with the HiSQOL, a patient-reported outcome measure with HS-specific items that address HRQOL as well as the DLQI, a skin-related HRQOL instrument. This was expected given that the PtGA specifically asks about the impact of HS on quality of life. As also expected, the degree of association to specific scales that assesses pain or emotion domain only were lower. The directions of the correlations were as postulated and support the convergent validity of the PtGA item. The PtGA demonstrated significant correlation with the NRS for pain scale, which illustrates the importance of pain as a determinant of HRQOL in individuals with HS. The PtGA further appears to be an appropriate discriminator of HRQOL since there were significant differences across the known score bands of the DLQI. Importantly, age, sex, or country did not significantly influence these results.
The PtGA demonstrated good reliability among patients that reported stable HS in the 24 to 72 hours between the administrations of the scales. Since power calculations are highly dependent on sample size and reliability in validating clinical hypotheses19, a measure like the PtGA with good test-retest reliability allows a more efficient sample size. Item responsiveness showed a significant and appropriate decrease in score associated with improved disease, however, further work is needed since the item showed a small significant difference in those with reportedly stable disease and no significant difference in those with worsened disease. The five-item response options may constrain the ability of the item to discriminate between changes in disease impact. Work to investigate the psychometric properties of a revised version of the PtGA with a revised response option and more sensitive external criterion, may demonstrate improved responsiveness.
The results of this study should be taken in the context of its limitations. There were instances of missing data which can limit the robustness of the results. Participants of this study were selected from academic institutions, where the population tends to have more severe disease. This study describes the initial evaluation of a valid and reliable PtGA measure for clinical trials. The PtGA is one of the most frequently used in other inflammatory disease, such as rheumatoid arthritis.20 However, it is important to note that this work focused on the construct of HRQOL. The PtGA could also be used as a global assessment of disease activity. The wording determines this construct, but if altered from one version or study to another may result in a varied response.21
Overall, the results on one hand support the PtGA as a simple single-item patient-reported outcome measure for HS-specific HRQOL, while on the other hand demonstrate its limitations as a measure of change. The findings in this study are exploratory and need to be confirmed in additional studies. It has also not been explored how the PtGA works longitudinally in a treated population and this would further elucidate the responsiveness, minimally important change, and score bands. Once established, the single-item PtGA could be used quickly in a clinic visit, allowing for the provider to review the patient’s response and discuss the management plan.
What’s already known about this topic?
HS can have a large negative impact on health-related quality of life.
Patient global assessments are useful in eliciting the important aspects of the patient’s perspective on an individual basis.
There are few studies that developed and investigated the measurement properties of a patient global assessment item for HS.
What does this study add?
This study describes the development, validation, and psychometric properties of a patient global assessment item for HS.
This patient global assessment item for health-related quality of life shows promise with its validity and reliability, allowing for its further development as a clinical research tool.
Acknowledgments
Funding Sources: Dr Kirby received funding from the Agency for Healthcare Research and Quality for this research (K08HS024585).
Use of REDCap through Penn State is supported by NIH/NCATS Grant Number UL1 TR000127 and UL1 TR002014 through The Penn State Clinical & Translational Research Institute, Pennsylvania State University CTSA
Dr Ingram received funding from Health and Care Research Wales (Health Fellowship 14-08).
Footnotes
IRB approval status: IRB approved
Conflicts of Interest:
Kirby: AbbVie: Speaker, Advisory Board (Honoraria), Investigator; Incyte, ChemoCentryx: Consultant (Fees), Investigator; UCB: Investigator; InflaRx: Investigator
Thorlacius: Abbvie, Janssen: travel expenses. Regeneron: Investigator
Garg: Advisor for AbbVie, Pfizer, Janssen, Asana Biosciences, and UCB (honoraria)
Ingram: UCB Pharma, Novartis: Consultant; Abbvie: travel expenses.
Tan: UCB Advisory Board (Honoraria); Incyte: Investigator
Jemec: Advisory Board (honoraria): AbbVie, Chemocentryx, Coloplast, Incyte, Inflarx, Novartis, Pierre Fabre and UCB; Abbvie, Leo Pharma, Janssen-Cilag, Regeneron, Sanofi, Astra-Zeneca and Novartis: Investigator; AbbVie, Boehringer-Ingelheim, Galderma and MSD: speaker (honoraria); Abbvie, Leo Pharma and Novartis: unrestricted grants.
Hereford, Villumsen, Butt, Esmann, King: None
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