You are here

  • Home
  • Archive
  • Volume 13, Issue 5
  • Association of anxiety, depression and resilience with overall health and functioning in axial spondyloarthritis (axSpA): a cross-sectional study

Article Text

Article menu
Rheumatology
Original research
Association of anxiety, depression and resilience with overall health and functioning in axial spondyloarthritis (axSpA): a cross-sectional study
  1. Deborah Xin Yi Chung1,
  2. Ying Ern Loo1,
  3. Yu Heng Kwan2,3,4,
  4. Jie Kie Phang5,
  5. Ting Hui Woon3,
  6. Wei Rui Goh6,
  7. Stanley Angkodjojo6,
  8. Warren Fong1,3,7
  1. 1Department of Medicine, National University of Singapore, Singapore
  2. 2Program in Health Services and Systems Research, Duke-NUS Medical School, Singapore
  3. 3Department of Rheumatology and Immunology, Singapore General Hospital, Singapore
  4. 4Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore
  5. 5Centre for Population Health Research and Implementation, SingHealth Regional Health System, Singapore
  6. 6Department of General Medicine (Rheumatology), Sengkang General Hospital, Singapore
  7. 7Duke-NUS Medical School, Singapore
  1. Correspondence to Associate Professor Warren Fong; gmsfwsw{at}nus.edu.sg

Abstract

Objectives To evaluate the association between anxiety, depression and resilience with overall health and functioning in axial spondyloarthritis (axSpA).

Design Cross-sectional evaluation of baseline data from a prospective cohort study, with recruitment from January 2018 to March 2021.

Setting Outpatient clinic in a tertiary hospital in Singapore.

Participants Patients aged 21 years and above who were diagnosed with axSpA.

Outcome measures The Hospital Anxiety and Depression Scale (HADS) was used for assessing anxiety and depression, 10-item Connor Davidson Resilience Scale (CD-RISC-10) for resilience, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for disease activity, Bath Ankylosing Spondylitis Functional Index (BASFI) for functional limitation and Assessment of SpondyloArthritis International Society Health Index (ASAS HI) for overall health and functioning. Univariable and multivariable linear regression analyses were performed to assess the association between anxiety, depression and resilience with health and functioning.

Results We included 296 patients in this study. The median (IQR) score for HADS-Anxiety was 5.0 (2.0–8.0), with 13.5% and 13.9% having borderline abnormal and abnormal anxiety, respectively. The median (IQR) score for HADS-Depression was 3.0 (1.0–7.0), with 12.8% and 8.4% having borderline abnormal and abnormal depression, respectively. The median (IQR) CD-RISC-10 score was 29.0 (23.0–32.0) while the median (IQR) ASAS HI score was 4.0 (2.0–7.0). Apart from BASDAI, BASFI and disease duration, anxiety and depression were associated with overall health and functioning (β: 0.12, 95% CI 0.03, 0.20; β: 0.20, 95% CI 0.09, 0.31) in the multivariable linear regression. Level of resilience was not associated with health and functioning.

Conclusion Anxiety and depression, but not resilience, were associated with poorer health and functioning. Clinicians could consider routinely screening for anxiety and depression in their patients, especially in patients with more severe symptoms.

  • RHEUMATOLOGY
  • Anxiety disorders
  • Depression & mood disorders

Data availability statement

Data are available upon reasonable request. The datasets and statistical codes used are available from the corresponding author upon reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

http://dx.doi.org/10.1136/bmjopen-2023-071944

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Strengths and limitations of this study

    • Validated self-reported questionnaires were used to assess for anxiety, depression and resilience in this study.

    • Anxiety, depression and resilience are influenced by a multitude of dynamic factors, and their relation to overall health and functioning might change over time, which deserves further investigation using a longitudinal study design instead of the cross-sectional design employed in this study.

    • Patients were recruited from a tertiary hospital where cases of axial spondyloarthritis might be more severe than those managed in the community, which might limit the generalisability of the findings.

    • The median Bath Ankylosing Spondylitis Disease Activity Index score and levels of anxiety in this study were lower than other study cohorts, which might limit the generalisability of the results.

    Introduction

    Axial spondyloarthritis (axSpA) is an inflammatory disease marked by chronic low back pain, stiffness and fatigue, which are potentially disabling and greatly affect a patient’s function and overall health.1 2 The understanding of gender disparities in axSpA is gradually shifting internationally, from being a male predominant disease to affecting both men and women equally, especially for nr-axSpA.3 Health and functioning is a novel concept in axSpA, and was included as a core domain in the 2021 Assessment of SpondyloArthritis International Society-Outcomes Measures in Rheumatology.4 ‘Functioning’ was adapted from the International Classification of Functioning, Disability and Health (ICF) framework, which was conceptualised based on the biopsychosocial model, and encompasses disease-specific constructs (eg, pain, physical function) as well as the impact on contextual factors (eg, social function, personal factors), both of which are normally inter-related.5–7 The Assessment of SpondyloArthritis International Society Health Index (ASAS HI) was developed with the aim of having a comprehensive questionnaire to assess health and functioning in axSpA.5 8

    Mental health issues such as depression and anxiety are significant in patients with axSpA, with the prevalence of depression ranging from 15% to 52%, depending on the screening tools used and demographic factors.9 Patients afflicted with mental health issues have worse disease activity, functionality and work performance.9–12 Other studies have shown that fatigue, pain and disease activity of axSpA affect patients in multiple domains including their work productivity, ability to drive and sexual function, which have also been demonstrated to be associated with depression and anxiety.10 13–16 Resilience refers to the ability to adapt in the face of adversity by adopting healthy coping mechanisms, which improves the individual’s well-being, speed of recovery,17 18 and reduces an individual’s susceptibility to mental health issues. It has been associated with psychological and physical benefits, such as better emotional regulation, pain control, health-related quality of life (HRQoL) and the perception of normal function.19–23

    Higher disease activities, functional limitation and being of female sex were factors associated with poorer health and functioning.24 25 Apart from one study which showed that depression was strongly associated with global functioning,26 few studies have explored the role of psychological factors such as anxiety, depression and resilience on patients’ health and functioning. Therefore, we aimed to evaluate the association of depression, anxiety and resilience with overall health and functioning in axSpA. We hypothesise that more severe depression and anxiety are associated with poorer health and functioning, while increased resilience is associated with better health and functioning.

    Methods

    Study design

    This study was a cross-sectional evaluation of baseline data from a prospective cohort study. Consecutive patients were recruited from an outpatient clinic in Singapore General Hospital, a tertiary hospital in Singapore, from January 2018 to March 2021. Informed consent was obtained from all participants. Inclusion criteria included being 21 years and above and being diagnosed with axSpA by a rheumatologist. All patients fulfilled the 2009 Assessment of SpondyloArthritis International Society criteria.27 28 None of the patients were clinically diagnosed with fibromyalgia, anxiety or depression prior to diagnosis of axSpA. Three hundred and twenty-two patients were assessed for enrolment and eight patients who did not provide consent were not enrolled. Out of the 314 patients enrolled, 18 patients were not included in the analysis as 13 did not complete the questionnaires at baseline and 5 had incomplete data for Hospital Anxiety and Depression Scale (HADS) and/or 10-item Connor Davidson Resilience Scale (CD-RISC-10) (figure 1). This study was reported in line with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.29

    Figure 1
    Figure 1

    Flowchart for patient recruitment. CD-RISC-10, 10-item Connor Davidson Resilience Scale; HADS, Hospital Anxiety and Depression Scale.

    Measurements

    Sociodemographic and clinical variables

    Sociodemographic and clinical variables collected include: age, sex, ethnicity, level of education, body mass index, human leukocyte antigen (HLA-B27) results, disease duration, history of peripheral arthritis and extramusculoskeletal symptoms such as psoriasis, uveitis and inflammatory bowel disease, current medication use and comorbid conditions.

    Assessment of anxiety, depression and resilience

    Anxiety and depression were measured using the HADS, which was developed to assess states of anxiety and depression in non-psychiatric patients.30 31 It contains two subscales (HADS-A and HADS-D) that measure anxiety and depression, respectively.31 Each subscale contains seven questions, with each question having a score from 0 to 3, and total scores ranging from 0 to 21. A normal level of anxiety or depression was defined as having scores <8, a borderline level of anxiety or depression as having scores ≥8 and <11 and an abnormal level of anxiety or depression as having scores ≥11 and <21.32 These cut-offs have been used in Singaporeans previously.33–40 Resilience was measured using the CD-RISC-10. Each question is scored from 0 to 4, with higher scores indicating greater resilience.41 CD-RISC-10 has been validated in Singapore and is reliable in the measure of resilience in axSpA.42

    Assessment of health and functioning

    Health and functioning was assessed using the ASAS HI, which has been validated in patients with axSpA.5 43 It was conceptualised based on the ICF framework and contains 17 questions related to the biopsychosocial model of health, which range from disease-specific aspects such as physical mobility, to other aspects such as self-care and community life.8 Questions use dichotomous response options, where agreeing with the statement will equate to a score of 1, and disagreeing with the statement will equate to a score of 0. Scores range from 0 to 17 and higher scores indicate poorer health and functioning. Scores ≤5 were considered as having good health and functioning, scores >5 and <12 were considered as moderate health and functioning and scores ≥12 were considered as poor health and functioning.

    Assessment of disease activity and functional limitation

    Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a 6-item validated patient-reported outcome, which contains questions related to fatigue, spinal pain, joint pain, enthesitis, duration and severity of morning stiffness.44 45 Each question is scored on a numerical rating scale from 0 (no symptoms) to 10 (very severe symptoms or having morning stiffness lasting for ≥2 hours). The BASDAI sum score ranges between 0 and 10, with higher scores indicating higher disease activities, and a score of 4 or more suggesting suboptimal disease control.44 Functional limitation was assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI), which contains 10 questions—eight that assess the amount of functional limitation for activities such as bending and reaching, as well as two that assess how well patients’ cope with everyday life.46 Each question is scored on a numerical rating scale from 0 (easy to perform the activity) to 10 (impossible to perform the activity). Total scores range from 0 to 10 and higher scores indicate greater functional impairment.

    Statistical analysis

    Continuous variables were reported in mean and SD if normally distributed, or median and IQR if otherwise. Categorical variables were expressed as frequencies and percentages. Univariable linear regression analyses were used to determine the association between each variable and the ASAS HI score. Variables were selected based on previous literature.24 26 47 48 Variables with p<0.1 in the univariable analyses were then included in a multivariable analysis, and was considered to be significant if p<0.05. As some variables might be correlated, we used the variance inflation factor to determine if multicollinearity was present, with a value of 5 as the threshold.49 The potential of resilience modifying the association between anxiety, depression and ASAS HI scores was tested, where effect modification was considered to be significant if the p value of the interaction term was <0.05.50 A post-hoc non-parametric equality-of-medians test was conducted to determine if there were differences in the BASDAI, BASFI, HADS-Anxiety, HADS-Depression scores between patients with longer as compared with shorter disease durations. Disease duration was categorised as long if it was 10 years and above.51 Data analyses were conducted using Stata SE V.15 (StataCorp).

    Patient and public involvement

    None.

    Results

    Patient demographics and characteristics

    A total of 296 patients were included in the study. Patient demographics and characteristics are shown in table 1. Patients had a median (IQR) age of 41.0 (29.5–53.0) years. Majority of the patients were men (n=225, 76.0%), Chinese (n=274, 92.6%), diagnosed with radiographic axSpA (n=224, 75.7%) and positive for HLA-B27 (n=246, 85.4%). The median (IQR) disease duration was 9.0 (4.0–14.5) years. The median BASDAI and BASFI scores were 2.2 (1.3–3.9) and 1.1 (0.2–3.0), respectively. The proportion of patients who used non-steroidal anti-inflammatory drugs (NSAIDs) was the highest (n=174, 58.8%), followed by biological disease-modifying antirheumatic drugs and targeted synthetic disease-modifying antirheumatic drugs at 19.6%, and conventional synthetic disease-modifying antirheumatic drugs and immunosuppressants at 15.2%.

    View this table:
    Table 1

    Patient demographics and characteristics (N=296)

    The median (IQR) score for HADS anxiety was 5.0 (2.0–8.0), with 40 (13.5%) and 41 (13.9%) patients having borderline abnormal and abnormal scores for anxiety, respectively. The median (IQR) score for HADS depression was 3.0 (1.0–70), with 38 (12.8%) and 25 (8.4%) patients having borderline abnormal and abnormal scores for depression, respectively. The median (IQR) score for CD-RISC-10 and ASAS HI were 29.0 (23.0–32.0) and 4.0 (2.0–7.0), respectively. Most of the patients in this study had good functioning (n=176, 59.5%), while only 18 (6.1%) had poor functioning.

    When stratified by the level of overall health and functioning, patients with poor functioning had the highest median (IQR) BASDAI scores of 6.0 (4.5–6.7), while those with good functioning had the lowest scores of 1.8 (1.0–2.6) (p<0.01). Similarly, median (IQR) BASFI scores were the highest in patients with poor functioning and lowest in those with good functioning (6.4 (4.9–6.8), 0.5 (0.0–1.4) p<0.01). For psychological factors, patients with poor functioning had the highest anxiety and depression scores. As reflected by the median (IQR) CD-RISC-10 scores, patients with poor functioning had the lowest resilience (19.5 (16.0–28.0)) compared with those of moderate functioning (26.0 (20.0–30.0)) and good functioning (30.0 (27.0–35.0)) (p<0.01) (table 2).

    View this table:
    Table 2

    Patient-reported outcomes categorised by level of overall health and functioning* (N=296)

    Factors associated with health and functioning

    The univariable analysis showed that being women, having higher BASDAI, BASFI, HADS-Anxiety and HADS-Depression scores were associated with higher ASAS HI scores. Higher CD-RISC-10 scores and longer disease duration were associated with lower ASAS HI scores (table 3). In the multivariable analysis, higher anxiety and depression scores were associated with higher ASAS HI scores, as shown by HADS-Anxiety (β: 0.12, 95% CI 0.03, 0.20) and HADS-Depression (β: 0.20, 95% CI 0.09, 0.31). The level of resilience as measured by CD-RISC-10 was not associated with ASAS HI scores (β: −0.02, 95% CI −0.06, 0.03) (table 3). Interaction terms between resilience and anxiety, and resilience and depression were non-significant (p=0.796 and p=0.934, respectively, data not shown).

    View this table:
    Table 3

    Univariable and multivariable linear regression analyses to identify factors associated with Assessment of Spondyloarthritis International Society Health Index score

    Higher disease activities and functional limitation were also associated with higher ASAS HI scores, as reflected by BASDAI (β: 0.41, 95% CI 0.22, 0.60) and BASFI (β: 0.71, 95% CI 0.54, 0.88). Having a longer disease duration was associated with having lower ASAS HI scores (β: −0.04, 95% CI −0.07 to –0.01). The post-hoc analysis showed that patients with a longer disease duration (≥10 years) had lower median (IQR) BASDAI scores of 1.9 (1.1–3.3) than patients with a shorter disease duration, whose median (IQR) BASDAI scores were 2.6 (1.5–4.4) (p<0.01). Differences for BASFI, HADS-Anxiety and HADS-Depression scores were non-significant (online supplemental file 1).

    Discussion

    This study aimed to determine the association between anxiety, depression and resilience with health and functioning in patients with axSpA. To our knowledge, few studies have assessed the role of psychological factors and this is the first study assessing the association between anxiety and resilience with overall health and functioning. Validated scales were also used for the rating of anxiety, depression and resilience. Psychological symptoms are often under-recognised and the use of self-reported outcomes instead of formal diagnoses might be more relevant.52

    As expected, higher disease activities and functional limitation as reflected by the BASDAI and BASFI scores were positively associated with poorer overall health and functioning, similar to prior studies.24 43 The ASAS HI was developed with the aim of having an all-encompassing tool for assessing the disease impact of axSpA, by mapping items from existing tools (including BASDAI and BASFI) to the ICF categories.2 8 Apart from disease activities and functional limitation, we found that anxiety and depression were associated with poorer overall health and functioning in our population, while the level of resilience was not. Previous studies have reported that patients with axSpA had higher levels of depression and anxiety as compared with the general population.53 In our study, 27.4% had possible anxiety (HADS-A≥8), which was lower than previous studies (32%–63%),52 54 55 while 21.2% had possible depression (HADS-D≥8), which was consistent with previous reports (14%–56%).9 54 Though often comorbid, anxiety often develops prior to depression, and symptoms could have been more reflective of depression at the point of data collection, hence causing the lower prevalence of anxiety.56 57 Apart from disease activity and functional limitation, levels of anxiety and depression were associated with poorer health and functioning in our study population. This could be explained by the fact that factors such as pain, fatigue and functional impairment were also identified as major drivers and correlated to psychological issues including anxiety and depression.53 58 59 Anxiety and depression were also found to impair treatment responses,52 which might imply reciprocal effects between anxiety and depression with disease activity. Given the association between anxiety and depression with poorer overall health and functioning, it further emphasises that clinicians should be aware of and screen for anxiety and depression in their patients with axSpA,60 61 especially in patients with more severe symptoms. Clinicians should also factor in possible anxiety and depression when interpreting disease activities.

    Our study did not find a significant association between resilience and higher overall health and functioning in axSpA. This is similar to a previous study which showed that levels of resilience did not contribute to patients’ perception of their disease activities for axSpA, though direct comparisons cannot be drawn as different resilience scales were used.62 Our observation could possibly be explained by various reasons. Resilience is a multi-dimensional concept, which not only depends on an individual’s disposition during adversities, but also the strength of interpersonal ties, the resources available in an individual’s community and family that can be used to facilitate resilience, biological factors, stressors, as well as an individual’s level of self-awareness.63–65 Having experienced past traumas as well as higher levels of education and income were also related to the level of resilience.66 67 Although the CD-RISC-10 is one of the most widely used and reliable scales,68 it mainly focuses on resilience at the level of the individual and does not account for other aspects.41 63 There is currently no gold standard for the measurement of resilience and out of the available scales, only the Resilience Scale for Adults covered both intrapersonal and interpersonal aspects of resilience,63 69 but this scale has neither been validated in the axSpA cohort nor in Singapore. Limited studies related to resilience have been conducted in patients with axSpA, and future research could focus on validating alternative resilience scales in axSpA. Despite resilience not being associated with higher overall health and functioning in our study, previous studies have shown that higher levels of resilience were associated with positive outcomes, such as experiencing less fatigue, better medication adherence and a better quality of life in patients with primary Sjögren’s syndrome, systemic lupus erythematosus and chronic kidney disease, respectively.70–72 Resilience was found to moderate the effect of disease activity on mental HRQoL (assessed by the 36-item Short-Form Health Survey Mental Component Summary) in patients with rheumatoid arthritis.73 In patients with fibromyalgia, apart from pain intensity, having a higher resilience was associated with lower pain catastrophisation and disease burden.74 75 When examined in geriatric populations, greater resilience was associated with more successful ageing, fewer depressive symptoms as well as lower mortality.76 77 Contextual factors such as helplessness have been shown to be associated with a poorer quality of life in axSpA and improving resilience might contribute to better health and functioning in these patients.78

    In addition, we also found longer disease duration to be associated with better health and functioning, which was unexpected as previous studies showed that having a longer symptom duration was associated with lower pain tolerance, more functional disabilities and poorer health and functioning.26 79 On further subgroup analysis, patients with a longer disease duration (≥10 years) had significantly better BASDAI scores, which could possibly explain the higher overall health and functioning.

    One limitation of our study was the cross-sectional design. Thus, a causal relationship could not be established. As anxiety, depression and resilience are dynamic and influenced by a multitude of factors, it might be more beneficial to observe changes over time and how this relates to overall health and functioning. Patients were recruited from a tertiary hospital where cases of axSpA might be more severe than those managed in the community. The median BASDAI score for our cohort was 2.2, which was slightly lower than that of other cohort studies and might limit the generalisability of the results, though other characteristics such as the proportion of males and HLA-B27 positivity were largely similar.80 81 Differences in the disease activity could be a reflection of country-level variation.82 83 Similarly, fewer patients in this study had possible anxiety as compared with other axSpA populations, which should be taken into consideration when interpreting results in other cohorts. Majority of the patients in this study were Chinese, and findings might not be similar in other ethnic populations. However, the racial proportion in this study is similar to other local studies, where majority of the patients are of Chinese ethnicity.51 84 Age and gender profiles were also similar to prior studies.26 85 Patient’s pain score could be a possible confounding factor for this study, but we had sought to mitigate this by including the BASDAI into the multivariate analysis, which includes a pain score for both the axial skeleton and peripheral joints, which are important manifestations of pain in patients with axSpA.

    Conclusion

    In summary, our study demonstrated that depression and anxiety were associated with poorer health and functioning in patients with axSpA, while resilience was not. Abnormal levels of anxiety and depression were found in 13.9% and 8.4% of patients, respectively. Hence, it would be beneficial for clinicians to screen for depression and anxiety in patients with axSpA, especially since mental health conditions are often under-detected.

    Data availability statement

    Data are available upon reasonable request. The datasets and statistical codes used are available from the corresponding author upon reasonable request.

    Ethics statements

    Patient consent for publication

    Ethics approval

    This study involves human participants and was approved by SingHealth Centralized Institutional Review Board (reference: 2017/2626). Participants gave informed consent to participate in the study before taking part.

    References

    1. ↵
      1. Strand V,
      2. Singh JA
      . Patient burden of axial spondyloarthritis. J Clin Rheumatol 2017;23:383–91. doi:10.1097/RHU.0000000000000589
      OpenUrlPubMed
    2. ↵
      1. Kiltz U,
      2. van der Heijde D,
      3. Boonen A, et al
      . Development of a health index in patients with ankylosing spondylitis (ASAS HI): final result of a global initiative based on the ICF guided by ASAS. Ann Rheum Dis 2015;74:830–5. doi:10.1136/annrheumdis-2013-203967
      OpenUrlAbstract/FREE Full Text
    3. ↵
      1. Chimenti M-S,
      2. Alten R,
      3. D’Agostino M-A, et al
      . Sex-associated and gender-associated differences in the diagnosis and management of axial spondyloarthritis: addressing the unmet needs of female patients. RMD Open 2021;7:e001681. doi:10.1136/rmdopen-2021-001681
    4. ↵
      1. Navarro-Compán V,
      2. Boel A,
      3. Boonen A, et al
      . The ASAS-OMERACT core domain set for axial spondyloarthritis. Semin Arthritis Rheum 2021;51:1342–9.:S0049-0172(21)00152-9. doi:10.1016/j.semarthrit.2021.07.021
      OpenUrlPubMed
    5. ↵
      1. Kiltz U,
      2. van der Heijde D,
      3. Boonen A, et al
      . The asas health index (asas HI)-a new tool to assess the health status of patients with spondyloarthritis. Clin Exp Rheumatol 2014;32(5 Suppl 85):S105–S108.
      OpenUrl
    6. ↵
      1. Boonen A,
      2. Braun J,
      3. van der Horst Bruinsma IE, et al
      . ASAS/WHO ICF core sets for ankylosing spondylitis (as): how to classify the impact of as on functioning and health. Ann Rheum Dis 2010;69:102–7. doi:10.1136/ard.2008.104117
      OpenUrlAbstract/FREE Full Text
    7. ↵
      International classification of functioning, disability and health (ICF). Available: https://www.who.int/standards/classifications/international-classification-of-functioning-disability-and-health [Accessed 18 Dec 2022].
    8. ↵
      1. Kiltz U,
      2. Wendling D,
      3. Braun J
      . ASAS health index: the "all in one" for spondyloarthritis evaluation? J Rheumatol 2020;47:1457–60. doi:10.3899/jrheum.200708
      OpenUrlFREE Full Text
    9. ↵
      1. Zhao S,
      2. Thong D,
      3. Miller N, et al
      . The prevalence of depression in axial spondyloarthritis and its association with disease activity: a systematic review and meta-analysis. Arthritis Res Ther 2018;20:140. doi:10.1186/s13075-018-1644-6
    10. ↵
      1. Morton L,
      2. Macfarlane GJ,
      3. Jones G, et al
      . Driving difficulties in patients with axial spondyloarthritis: results from the Scotland Registry for ankylosing spondylitis. Arthritis Care & Research 2022;74:1541–9. doi:10.1002/acr.24595 Available: https://onlinelibrary.wiley.com/toc/21514658/74/9
      OpenUrl
    11. ↵
      1. Healey EL,
      2. Haywood KL,
      3. Jordan KP, et al
      . Impact of ankylosing spondylitis on work in patients across the UK. Scand J Rheumatol 2011;40:34–40. doi:10.3109/03009742.2010.487838
      OpenUrlCrossRefPubMed
    12. ↵
      1. Ulus Y,
      2. Akyol Y,
      3. Bilgici A, et al
      . Association of work instability with fatigue and emotional status in patients with ankylosing spondylitis: comparison with healthy controls. Clin Rheumatol 2019;38:1017–24. doi:10.1007/s10067-018-4366-x
      OpenUrl
    13. ↵
      1. Parkinson JT,
      2. Foley ÉM,
      3. Jadon DR, et al
      . Depression in patients with spondyloarthritis: prevalence, incidence, risk factors, mechanisms and management. Therapeutic Advances in Musculoskeletal 2020;12:1759720X2097002. doi:10.1177/1759720X20970028
      OpenUrl
    14. ↵
      1. Fang ML,
      2. Wu CS,
      3. Weng LC, et al
      . Factors associated with depressive symptoms in patients with ankylosing spondylitis in Northern Taiwan. PLoS One 2019;14:e0224298. doi:10.1371/journal.pone.0224298
    15. ↵
      1. Sağ S,
      2. Nas K,
      3. Sağ MS, et al
      . Relationship of work disability between the disease activity, depression and quality of life in patients with ankylosing spondylitis. J Back Musculoskelet Rehabil 2018;31:499–505. doi:10.3233/BMR-169657
      OpenUrl
    16. ↵
      1. Cakar E,
      2. Dincer U,
      3. Kiralp MZ, et al
      . Sexual problems in male ankylosing spondylitis patients: relationship with functionality, disease activity, quality of life, and emotional status. Clin Rheumatol 2007;26:1607–13. doi:10.1007/s10067-007-0545-x
      OpenUrlCrossRefPubMedWeb of Science
    17. ↵
      1. Tay PKC,
      2. Lim KK
      . Psychological resilience as an emergent characteristic for well-being: a pragmatic view. Gerontology 2020;66:476–83. doi:10.1159/000509210
      OpenUrl
    18. ↵
      1. Macía P,
      2. Barranco M,
      3. Gorbeña S, et al
      . Resilience and coping strategies in relation to mental health outcomes in people with cancer. PLoS One 2021;16:e0252075. doi:10.1371/journal.pone.0252075
    19. ↵
      1. Hemington KS,
      2. Rogachov A,
      3. Cheng JC, et al
      . Patients with chronic pain exhibit a complex relationship triad between pain, resilience, and within- and cross-network functional connectivity of the default mode network. Pain 2018;159:1621–30. doi:10.1097/j.pain.0000000000001252
      OpenUrlPubMed
    20. ↵
      1. Tugade MM,
      2. Fredrickson BL
      . Resilient individuals use positive emotions to bounce back from negative emotional experiences. J Pers Soc Psychol 2004;86:320–33. doi:10.1037/0022-3514.86.2.320
      OpenUrlCrossRefPubMedWeb of Science
    21. ↵
      1. Kirchberger I,
      2. Burkhardt K,
      3. Heier M, et al
      . Resilience is strongly associated with health-related quality of life but does not buffer work-related stress in employed persons 1 year after acute myocardial infarction. Qual Life Res 2020;29:391–401. doi:10.1007/s11136-019-02306-6
      OpenUrl
    22. ↵
      1. Shin YC,
      2. Kim SM,
      3. Kim H, et al
      . Resilience as a protective factor for depressive mood and anxiety among Korean employees. J Korean Med Sci 2019;34:e188. doi:10.3346/jkms.2019.34.e188
    23. ↵
      1. Dombrowsky AR,
      2. Kirchner G,
      3. Isbell J, et al
      . Resilience correlates with patient reported outcomes after reverse total shoulder arthroplasty. Orthop Traumatol Surg Res 2021;107:102777. doi:10.1016/j.otsr.2020.102777
      OpenUrl
    24. ↵
      1. Chen H-H,
      2. Chen Y-M,
      3. Lai K-L, et al
      . Gender difference in ASAS HI among patients with ankylosing spondylitis. PLoS ONE 2020;15:e0235678. doi:10.1371/journal.pone.0235678
    25. ↵
      1. Min HK,
      2. Lee J,
      3. Ju JH, et al
      . Predictors of assessment of spondyloarthritis International Society (ASAS) health index in axial spondyloarthritis and comparison of ASAS health index between ankylosing spondylitis and nonradiographic axial spondyloarthritis: data from the Catholic axial spondyloarthritis cohort (casco). JCM 2019;8:467. doi:10.3390/jcm8040467
      OpenUrl
    26. ↵
      1. Kiltz U,
      2. Wiatr T,
      3. Redeker I, et al
      . Effects of patient and disease characteristics on global functioning in patients with axial spondyloarthritis in routine care. Seminars in Arthritis and Rheumatism 2022;55:152006. doi:10.1016/j.semarthrit.2022.152006
      OpenUrl
    27. ↵
      1. Rudwaleit M,
      2. Landewe R,
      3. van der Heijde D, et al
      . The development of assessment of spondyloarthritis International Society classification criteria for axial spondyloarthritis (Part I): classification of paper patients by expert opinion including uncertainty appraisal. Annals of the Rheumatic Diseases 2009;68:770–6. doi:10.1136/ard.2009.108217
      OpenUrlAbstract/FREE Full Text
    28. ↵
      1. Rudwaleit M,
      2. van der Heijde D,
      3. Landewe R, et al
      . The development of assessment of spondyloarthritis International Society classification criteria for axial spondyloarthritis (Part II): validation and final selection. Annals of the Rheumatic Diseases 2009;68:777–83. doi:10.1136/ard.2009.108233
      OpenUrlAbstract/FREE Full Text
    29. ↵
      1. von Elm E,
      2. Altman DG,
      3. Egger M, et al
      . The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med 2007;4:e296. doi:10.1371/journal.pmed.0040296
    30. ↵
      1. Djukanovic I,
      2. Carlsson J,
      3. Årestedt K
      . Is the hospital anxiety and depression scale (HADS) a valid measure in a general population 65-80 years old? A psychometric evaluation study. Health Qual Life Outcomes 2017;15:193. doi:10.1186/s12955-017-0759-9
      OpenUrlPubMed
    31. ↵
      1. Zigmond AS,
      2. Snaith RP
      . The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70. doi:10.1111/j.1600-0447.1983.tb09716.x
      OpenUrlCrossRefPubMedWeb of Science
    32. ↵
      1. Bjelland I,
      2. Dahl AA,
      3. Haug TT, et al
      . The validity of the hospital anxiety and depression scale. An updated literature review. J Psychosom Res 2002;52:69–77. doi:10.1016/s0022-3999(01)00296-3
      OpenUrlCrossRefPubMedWeb of Science
    33. ↵
      1. Chan JJI,
      2. Yeam CT,
      3. Kee HM, et al
      . The use of pre-operative virtual reality to reduce anxiety in women undergoing gynecological surgeries: a prospective cohort study. BMC Anesthesiol 2020;20:261. doi:10.1186/s12871-020-01177-6
    34. ↵
      1. Abhiram K,
      2. Tan BYQ,
      3. Tan M, et al
      . The effect of COVID-19 endemicity on the mental health of health workers. J Am Med Dir Assoc 2022;23:405–413.S1525-8610(22)00099-8. doi:10.1016/j.jamda.2022.01.059
      OpenUrlPubMed
    35. ↵
      1. Tan BYQ,
      2. Kanneganti A,
      3. Lim LJH, et al
      . Burnout and associated factors among health care workers in Singapore during the covid-19 pandemic. J Am Med Dir Assoc 2020;21:1751–8. doi:10.1016/j.jamda.2020.09.035
      OpenUrlCrossRefPubMed
    36. ↵
      1. Tee SI,
      2. Lim ZV,
      3. Theng CT, et al
      . A prospective cross‐sectional study of anxiety and depression in patients with psoriasis in Singapore. J Eur Acad Dermatol Venereol 2016;30:1159–64. doi:10.1111/jdv.13615 Available: https://onlinelibrary.wiley.com/toc/14683083/30/7
      OpenUrl
    37. ↵
      1. Wang W,
      2. Chow A,
      3. Thompson DR, et al
      . Predictors of health-related quality of life among patients with myocardial infarction. West J Nurs Res 2016;38:43–56. doi:10.1177/0193945914546201
      OpenUrlCrossRefPubMed
    38. ↵
      1. Muhammad IM,
      2. He HG,
      3. Koh K, et al
      . Health-Related quality of life and its predictors among outpatients with coronary heart disease in Singapore. Appl Nurs Res 2014;27:175–80.:S0897-1897(13)00129-8. doi:10.1016/j.apnr.2013.11.008
      OpenUrlCrossRefPubMed
    39. ↵
      1. Chua CY,
      2. Koh MRE,
      3. Chia NS-Y, et al
      . Subjective cognitive complaints in early Parkinson’s disease patients with normal cognition are associated with affective symptoms. Parkinsonism & Related Disorders 2021;82:24–8. doi:10.1016/j.parkreldis.2020.11.013
      OpenUrl
    40. ↵
      1. Yim PWC,
      2. Wang W,
      3. Jiang Y, et al
      . Health-Related quality of life, psychological well-being, and sexual function in patients with benign prostatic hyperplasia after prostatic surgery. Appl Nurs Res 2015;28:274–80.:S0897-1897(15)00057-9. doi:10.1016/j.apnr.2015.02.007
      OpenUrl
    41. ↵
      1. Connor KM,
      2. Davidson JRT
      . Development of a new resilience scale: the connor-davidson resilience scale (CD-RISC). Depress Anxiety 2003;18:76–82. doi:10.1002/da.10113
      OpenUrlCrossRefPubMedWeb of Science
    42. ↵
      1. Kwan YH,
      2. Ng A,
      3. Lim KK, et al
      . Validity and reliability of the ten-item connor-davidson resilience scale (CD-RISC10) instrument in patients with axial spondyloarthritis (axspa) in Singapore. Rheumatol Int 2019;39:105–10. doi:10.1007/s00296-018-4217-8
      OpenUrlPubMed
    43. ↵
      1. Kiltz U,
      2. van der Heijde D,
      3. Boonen A, et al
      . Measurement properties of the ASAS health index: results of a global study in patients with axial and peripheral spondyloarthritis. Ann Rheum Dis 2018;77:1311–7. doi:10.1136/annrheumdis-2017-212076
      OpenUrlAbstract/FREE Full Text
    44. ↵
      1. Garrett S,
      2. Jenkinson T,
      3. Kennedy LG, et al
      . A new approach to defining disease status in ankylosing spondylitis: the Bath ankylosing spondylitis disease activity index. J Rheumatol 1994;21:2286–91. Available: https://pubmed.ncbi.nlm.nih.gov/7699630/
      OpenUrlPubMedWeb of Science
    45. ↵
      1. Kwan YH,
      2. Tan JJ,
      3. Phang JK, et al
      . Validity and reliability of the ankylosing spondylitis disease activity score with C‐reactive protein (ASDAS‐CRP) and Bath ankylosing spondylitis disease activity index (BASDAI) in patients with axial spondyloarthritis (axspa) in Singapore. Int J Rheum Dis 2019;22:2206–12. doi:10.1111/1756-185X.13735 Available: https://onlinelibrary.wiley.com/toc/1756185x/22/12
      OpenUrl
    46. ↵
      1. Zochling J
      . Measures of symptoms and disease status in ankylosing spondylitis: ankylosing spondylitis disease activity score (ASDAS), ankylosing spondylitis quality of life scale (asqol), Bath ankylosing spondylitis disease activity index (basdai), Bath ankylosing sp. Arthritis Care Res 2011;63:S47–58. doi:10.1002/acr.20575 Available: http://doi.wiley.com/10.1002/acr.v63.11s
      OpenUrlCrossRefWeb of Science
    47. ↵
      1. Liew JW,
      2. Huang IJ,
      3. Louden DN, et al
      . Association of body mass index on disease activity in axial spondyloarthritis: systematic review and meta-analysis. RMD Open 2020;6:e001225. doi:10.1136/rmdopen-2020-001225
    48. ↵
      1. Puche Larrubia MÁ,
      2. Castro Villegas MC,
      3. Ortega Castro R, et al
      . ASAS health index in patients with spondyloarthritis and its association with disease activity and disease burden including fibromyalgia. Clin Exp Rheumatol 2021;39 Suppl 130:82–8. doi:10.55563/clinexprheumatol/zr61xv
      OpenUrl
    49. ↵
      1. Petter S,
      2. Straub D,
      3. Rai A
      . Specifying formative constructs in information systems research. MIS Quarterly 2007;31:623. doi:10.2307/25148814
      OpenUrl
    50. ↵
      1. Delgado C,
      2. Roche M,
      3. Fethney J, et al
      . Mental health nurses’ psychological well-being, mental distress, and workplace resilience: a cross-sectional survey. Int J Ment Health Nurs 2021;30:1234–47. doi:10.1111/inm.12874
      OpenUrl
    51. ↵
      1. Lee YX,
      2. Kwan YH,
      3. Png WY, et al
      . Association of obesity with patient-reported outcomes in patients with axial spondyloarthritis: a cross-sectional study in an urban Asian population. Clin Rheumatol 2017;36:2365–70. doi:10.1007/s10067-017-3585-x
      OpenUrl
    52. ↵
      1. Zhao SS,
      2. Jones GT,
      3. Hughes DM, et al
      . Depression and anxiety symptoms at TNF inhibitor initiation are associated with impaired treatment response in axial spondyloarthritis. Rheumatology (Oxford) 2021;60:5734–42. doi:10.1093/rheumatology/keab242
      OpenUrlPubMed
    53. ↵
      1. Xu X,
      2. Shen B,
      3. Zhang A, et al
      . Anxiety and depression correlate with disease and quality-of-life parameters in Chinese patients with ankylosing spondylitis. Patient Prefer Adherence 2016;10:879–85. doi:10.2147/PPA.S86612
      OpenUrlPubMed
    54. ↵
      1. Meesters JJL,
      2. Petersson IF,
      3. Bergman S, et al
      . Sociodemographic and disease-related factors are associated with patient-reported anxiety and depression in spondyloarthritis patients in the Swedish spascania cohort. Clin Rheumatol 2014;33:1649–56. doi:10.1007/s10067-014-2699-7
      OpenUrlPubMed
    55. ↵
      1. Reddy KN,
      2. Sabu N,
      3. Pandey N, et al
      . Anxiety and depression among patients with axial spondyloarthritis. Eur J Rheumatol 2022;9:8–13. doi:10.5152/eurjrheum.2021.21022
      OpenUrl
    56. ↵
      1. Stern AF
      . The hospital anxiety and depression scale. Occupational Medicine 2014;64:393–4. doi:10.1093/occmed/kqu024
      OpenUrlCrossRefPubMed
    57. ↵
      1. Kalin NH
      . The critical relationship between anxiety and depression. AJP 2020;177:365–7. doi:10.1176/appi.ajp.2020.20030305
      OpenUrl
    58. ↵
      1. Jiang Y,
      2. Yang M,
      3. Lv Q, et al
      . Prevalence of psychological disorders, sleep disturbance and stressful life events and their relationships with disease parameters in Chinese patients with ankylosing spondylitis. Clin Rheumatol 2018;37:407–14. doi:10.1007/s10067-017-3907-z
      OpenUrl
    59. ↵
      1. Godfrin-Valnet M,
      2. Prati C,
      3. Puyraveau M, et al
      . Evaluation of spondylarthritis activity by patients and physicians: ASDAS, BASDAI, pass, and flares in 200 patients. Joint Bone Spine 2013;80:393–8. doi:10.1016/j.jbspin.2013.01.003
      OpenUrlCrossRefPubMed
    60. ↵
      1. Kroenke K,
      2. Spitzer RL,
      3. Williams JBW, et al
      . Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med 2007;146:317–25. doi:10.7326/0003-4819-146-5-200703060-00004
      OpenUrlCrossRefPubMedWeb of Science
    61. ↵
      1. Gilbody S,
      2. Whitty P,
      3. Grimshaw J, et al
      . Educational and organizational interventions to improve the management of depression in primary care: a systematic review. JAMA 2003;289:3145–51. doi:10.1001/jama.289.23.3145
      OpenUrlCrossRefPubMedWeb of Science
    62. ↵
      1. Brionez TF,
      2. Assassi S,
      3. Reveille JD, et al
      . Psychological correlates of self-reported disease activity in ankylosing spondylitis. J Rheumatol 2010;37:829–34. doi:10.3899/jrheum.090476
      OpenUrlAbstract/FREE Full Text
    63. ↵
      1. Windle G,
      2. Bennett KM,
      3. Noyes J
      . A methodological review of resilience measurement scales. Health Qual Life Outcomes 2011;9:8. doi:10.1186/1477-7525-9-8
    64. ↵
      1. Donoghue EM,
      2. Sturtevant VE
      . Social science constructs in ecosystem assessments: revisiting community capacity and community resiliency. Society & Natural Resources 2007;20:899–912. doi:10.1080/08941920701561114
      OpenUrl
    65. ↵
      1. Sisto A,
      2. Vicinanza F,
      3. Campanozzi LL, et al
      . Towards a transversal definition of psychological resilience: a literature review. Medicina 2019;55:745. doi:10.3390/medicina55110745
      OpenUrl
    66. ↵
      1. Scali J,
      2. Gandubert C,
      3. Ritchie K, et al
      . Measuring resilience in adult women using the 10-items connor-davidson resilience scale (CD-RISC). Role of trauma exposure and anxiety disorders. PLoS ONE 2012;7:e39879. doi:10.1371/journal.pone.0039879
    67. ↵
      1. Campbell-Sills L,
      2. Forde DR,
      3. Stein MB
      . Demographic and childhood environmental predictors of resilience in a community sample. J Psychiatr Res 2009;43:1007–12. doi:10.1016/j.jpsychires.2009.01.013
      OpenUrlCrossRefPubMed
    68. ↵
      1. Velickovic K,
      2. Rahm Hallberg I,
      3. Axelsson U, et al
      . Psychometric properties of the connor-davidson resilience scale (CD-RISC) in a non-clinical population in Sweden. Health Qual Life Outcomes 2020;18:132. doi:10.1186/s12955-020-01383-3
    69. ↵
      1. Friborg O,
      2. Hjemdal O,
      3. Rosenvinge JH, et al
      . A new rating scale for adult resilience: what are the central protective resources behind healthy adjustment? Int J Methods Psychiatr Res 2003;12:65–76. doi:10.1002/mpr.143
      OpenUrlCrossRefPubMedWeb of Science
    70. ↵
      1. Priori R,
      2. Giardina F,
      3. Izzo R, et al
      . Resilience in women with primary Sjögren’s syndrome. Rheumatol Int 2021;41:1987–94. doi:10.1007/s00296-021-04899-z
      OpenUrl
    71. ↵
      1. Mendoza-Pinto C,
      2. García-Carrasco M,
      3. Campos-Rivera S, et al
      . Medication adherence is influenced by resilience in patients with systemic lupus erythematosus. Lupus 2021;30:1051–7. doi:10.1177/09612033211004722
      OpenUrl
    72. ↵
      1. García-Martínez P,
      2. Temprado-Albalat MD,
      3. Ballester-Arnal R, et al
      . Predictive model of variables associated with health-related quality of life in patients with advanced chronic kidney disease receiving hemodialysis. Qual Life Res 2020;29:1817–27. doi:10.1007/s11136-020-02454-0
      OpenUrl
    73. ↵
      1. Liu L,
      2. Xu X,
      3. Xu N, et al
      . Disease activity, resilience and health-related quality of life in Chinese patients with rheumatoid arthritis: a multi-center, cross-sectional study. Health Qual Life Outcomes 2017;15:149. doi:10.1186/s12955-017-0725-6
    74. ↵
      1. Notario-Pacheco B,
      2. Martínez-Vizcaíno V,
      3. Trillo-Calvo E, et al
      . Validity and reliability of the Spanish version of the 10-item CD-RISC in patients with fibromyalgia. Health Qual Life Outcomes 2014;12:14. doi:10.1186/1477-7525-12-14
    75. ↵
      1. Angarita-Osorio N,
      2. Pérez-Aranda A,
      3. Feliu-Soler A, et al
      . Patients with fibromyalgia reporting severe pain but low impact of the syndrome: clinical and pain-related cognitive features. Pain Pract 2020;20:255–61. doi:10.1111/papr.12847
      OpenUrl
    76. ↵
      1. Wermelinger Ávila MP,
      2. Lucchetti ALG,
      3. Lucchetti G
      . Association between depression and resilience in older adults: a systematic review and meta‐analysis. Int J Geriatr Psychiatry 2017;32:237–46. doi:10.1002/gps.4619 Available: https://onlinelibrary.wiley.com/toc/10991166/32/3
      OpenUrl
    77. ↵
      1. MacLeod S,
      2. Musich S,
      3. Hawkins K, et al
      . The impact of resilience among older adults. Geriatric Nursing 2016;37:266–72. doi:10.1016/j.gerinurse.2016.02.014
      OpenUrlCrossRef
    78. ↵
      1. Gordeev VS,
      2. Maksymowych WP,
      3. Evers S, et al
      . Role of contextual factors in health-related quality of life in ankylosing spondylitis. Ann Rheum Dis 2010;69:108–12. doi:10.1136/ard.2008.100164
      OpenUrlAbstract/FREE Full Text
    79. ↵
      1. Mogard E,
      2. Olofsson T,
      3. Bergman S, et al
      . Chronic pain and assessment of pain sensitivity in patients with axial spondyloarthritis: results from the SPARTAKUS cohort. J Rheumatol 2021;48:1672–9. doi:10.3899/jrheum.200872
      OpenUrlAbstract/FREE Full Text
    80. ↵
      1. Chen Y-H,
      2. Huang W-N,
      3. Chen Y-M, et al
      . The BASDAI cut-off for disease activity corresponding to the ASDAS scores in a Taiwanese cohort of ankylosing spondylitis. Front Med 2022;9:856654. doi:10.3389/fmed.2022.856654
      OpenUrl
    81. ↵
      1. Kwon OC,
      2. Park MC
      . BASDAI cut-off values corresponding to ASDAS cut-off values. Rheumatology (Oxford) 2022;61:2369–74. doi:10.1093/rheumatology/keab494
      OpenUrl
    82. ↵
      1. Poddubnyy D,
      2. Sieper J,
      3. Akar S, et al
      . Characteristics of patients with axial spondyloarthritis by geographic regions: proof multicountry observational study baseline results. Rheumatology (Oxford) 2022;61:3299–308. doi:10.1093/rheumatology/keab901
      OpenUrl
    83. ↵
      1. Capelusnik D,
      2. Zhao SS,
      3. Boonen A, et al
      . Individual-Level and country-level socio-economic factors and health outcomes in spondyloarthritis: analysis of the ASAS-perspa study. Rheumatology (Oxford) 2022;61:2043–53. doi:10.1093/rheumatology/keab638
      OpenUrl
    84. ↵
      1. Png WY,
      2. Kwan YH,
      3. Lee YX, et al
      . Factors associated with initiation of biologics in patients with axial spondyloarthritis in an urban Asian City: a PRESPOND study. J Clin Rheumatol 2019;25:59–64. doi:10.1097/RHU.0000000000000762
      OpenUrl
    85. ↵
      1. Mease PJ,
      2. McLean RR,
      3. Dube B, et al
      . Comparison of men and women with axial spondyloarthritis in the US-based corrona psoriatic arthritis/spondyloarthritis registry. J Rheumatol 2021;48:1528–36. doi:10.3899/jrheum.201549
      OpenUrlAbstract/FREE Full Text

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • DXYC and YEL are joint first authors.

    • Contributors YHK, SA, WF conceptualised the study design. YHK, JKP, THW, WRG, SA, WF executed the study and acquired the data. JKP and THW analysed the data. DXYC and YEL wrote the first manuscript draft. WF is the content guarantor. All authors critically revised the article for important intellectual content and approved of the final manuscript.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.