Translation and validation of non-English versions of the Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire

BACKGROUND: The Ankylosing Spondylitis Quality of Life (ASQOL) questionnaire is a unidimensional, disease-specific measure developed in the UK and the Netherlands. This study describes its adaptation into other languages. METHODS: The UK English ASQOL was translated into US English; Canadian French and English; French; German; Italian; Spanish; and Swedish (dual-panel methods). Cognitive debriefing interviews were conducted with AS patients. Psychometric/scaling properties were assessed using data from two Phase III studies of adalimumab. Baseline and Week-2 data were used to assess test-retest reliability. Validity was determined by correlation of ASQOL with SF-36 and BASFI and by discriminative ability of ASQOL based on disease severity. Item response theory (Rasch model) was used to test ASQOL's scaling properties. RESULTS: Cognitive debriefing showed the new ASQOL versions to be clear, relevant and comprehensive. Sample sizes varied, but were sufficient for: psychometric/scaling assessment for US English and Canadian English; psychometric but not scaling analyses for German; and preliminary evidence of these properties for the remaining languages. Test-retest reliability and Cronbach's alpha coefficients were high: US English (0.85, 0.85), Canadian English (0.87, 0.86), and German (0.77, 0.79). Correlations of ASQOL with SF-36 and BASFI for US English, Canadian English, and German measures were moderate, but ASQOL discriminated between patients based on perceived disease severities (p < 0.01). Results were comparable for the other languages. US English and Canadian English exhibited fit to the Rasch model (non-significant p-values: 0.54, 0.68), confirming unidimensionality. CONCLUSION: The ASQOL was successfully translated into all eight languages. Psychometric properties were excellent for US English, Canadian English, and German, and extremely promising for the other languages

Psychometric performance of the CAMPHOR and SF-36 in pulmonary hypertension

BACKGROUND: The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and the Medical Outcomes Study Short Form 36 (SF-36) are widely used to assess patient-reported outcome in individuals with pulmonary hypertension (PH). The aim of the study was to compare the psychometric properties of the two measures. METHODS: Participants were recruited from specialist PH centres in Australia and New Zealand. Participants completed the CAMPHOR and SF-36 at two time points two weeks apart. The SF-36 is a generic health status questionnaire consisting of 36 items split into 8 sections. The CAMPHOR is a PH-specific measure consisting of 3 scales; symptoms, activity limitations and needs-based QoL. The questionnaires were assessed for distributional properties (floor and ceiling effects), internal consistency (Cronbach's alpha), test-retest reliability and construct validity (scores by World Health Organisation functional classification). RESULTS: The sample comprised 65 participants (mean (SD) age = 57.2 (14.5) years; n(%) male = 14 (21.5%)). Most of the patients were in WHO class 2 (27.7%) and 3 (61.5%). High ceiling effects were observed for the SF-36 bodily pain, social functioning and role emotional domains. Test-retest reliability was poor for six of the eight SF-36 domains, indicating high levels of random measurement error. Three of the SF-36 domains did not distinguish between WHO classes. In contrast, all CAMPHOR scales exhibited good distributional properties, test retest reliability and distinguished between WHO functional classes. CONCLUSIONS: The CAMPHOR exhibited superior psychometric properties, compared with the SF-36, in the assessment of PH patient-reported outcome

A highly efficient method for the production and purification of recombinant human CXCL8

Chemokines play diverse and fundamental roles in the immune system and human disease, which has prompted their structural and functional characterisation. Production of recombinant chemokines that are folded and bioactive is vital to their study but is limited by the stringent requirements of a native N-terminus for receptor activation and correct disulphide bonding required to stabilise the chemokine fold. Even when expressed as fusion proteins, overexpression of chemokines in E. coli tends to result in the formation of inclusion bodies, generating the additional steps of solubilisation and refolding. Here we present a novel method for producing soluble chemokines in relatively large amounts via a simple two-step purification procedure with no requirements for refolding. CXCL8 produced by this method has the correct chemokine fold as determined by NMR spectroscopy and in chemotaxis assays was indistinguishable from commercially available chemokines. We believe that this protocol significantly streamlines the generation of recombinant chemokines

Measuring patient-reported outcomes: moving beyond misplaced common sense to hard science

Interest in the patient's views of his or her illness and treatment has increased dramatically. However, our ability to appropriately measure such issues lags far behind the level of interest and need. Too often such measurement is considered to be a simple and trivial activity that merely requires the application of common sense. However, good quality measurement of patient-reported outcomes is a complex activity requiring considerable expertise and experience. This review considers the most important issues related to such measurement in the context of chronic disease and details how instruments should be developed, validated and adapted for use in additional languages. While there is often consensus on how best to undertake these activities, there is generally little evidence to support such accord. The present article questions these orthodox views and suggests alternative approaches that have been shown to be effective

Exploring differential item functioning in the SF-36 by demographic, clinical, psychological and social factors in an osteoarthritis population

The SF-36 is a very commonly used generic measure of health outcome in osteoarthritis (OA). An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items work in the same way across subgroup of a population. That is, if respondents have the same 'true' level of outcome, does the item give the same score in different subgroups or is it biased towards one subgroup or another. Differential item functioning (DIF) can identify items that may be biased for one group or another and has been applied to measuring patient reported outcomes. Items may show DIF for different conditions and between cultures, however the SF-36 has not been specifically examined in an osteoarthritis population nor in a UK population. Hence, the aim of the study was to apply the DIF method to the SF-36 for a UK OA population. The sample comprised a community sample of 763 people with OA who participated in the Somerset and Avon Survey of Health. The SF-36 was explored for DIF with respect to demographic, social, clinical and psychological factors. Well developed ordinal regression models were used to identify DIF items. Results: DIF items were found by age (6 items), employment status (6 items), social class (2 items), mood (2 items), hip v knee (2 items), social deprivation (1 item) and body mass index (1 item). Although the impact of the DIF items rarely had a significant effect on the conclusions of group comparisons, in most cases there was a significant change in effect size. Overall, the SF-36 performed well with only a small number of DIF items identified, a reassuring finding in view of the frequent use of the SF-36 in OA. Nevertheless, where DIF items were identified it would be advisable to analyse data taking account of DIF items, especially when age effects are the focus of interest

Synchrony of change in depressive symptoms, health status, and quality of life in persons with clinical depression

BACKGROUND: Little is known about longitudinal associations among measures of depression, mental and physical health, and quality of life (QOL). We followed 982 clinically depressed persons to determine which measures changed and whether the change was synchronous with change in depressive symptoms. METHODS: Data were from the Longitudinal Investigation of Depression Outcomes (LIDO). Depressive symptoms, physical and mental health, and quality of life were measured at baseline, 6 weeks, 3 months, and 9 months. Change in the measures was examined over time and for persons with different levels of change in depressive symptoms. RESULTS: On average, all of the measures improved significantly over time, and most were synchronous with change in depressive symptoms. Measures of mental health changed the most, and physical health the least. The measures of change in QOL were intermediate. The 6-week change in QOL could be explained completely by change in depressive symptoms. The instruments varied in sensitivity to changes in depressive symptoms. CONCLUSION: In clinically depressed persons, measures of physical health, mental health, and quality of life showed consistent longitudinal associations with measures of depressive symptoms

The protease associated (PA) domain in ScpA from Streptococcus pyogenes plays a role in substrate recruitment

Annually, over 18 million disease cases and half a million deaths worldwide are estimated to be caused by Group A Streptococcus. ScpA (or C5a peptidase) is a well characterised member of the cell enveleope protease family, which possess a S8 subtilisin-like catalytic domain and a shared multi-domain architecture. ScpA cleaves complement factors C5a and C3a, impairing the function of these critical anaphylatoxins and disrupts complement-mediated innate immunity. Although the high resolution structure of ScpA is known, the details of how it recognises its substrate are only just emerging. Previous studies have identified a distant exosite on the 2nd fibronectin domain that plays an important role in recruitment via an interaction with the substrate core. Here, using a combination of solution NMR spectroscopy, mutagenesis with functional assays and computational approaches we identify a second exosite within the protease-associated (PA) domain. We propose a model in which the PA domain assists optimal delivery of the substrate's C terminus to the active site for cleavage

An educational leaflet improves response to invitation for screening for arthritis in patients with psoriasis in primary care, but only in practices in the most deprived areas

This study hypothesises that an educational leaflet about psoriatic arthritis (PsA) will improve psoriasis patients’ attendance for screening for PsA. A random sample of patients ≥18 years old with a coded diagnosis of psoriasis and no diagnosis of PsA, rheumatoid arthritis or ankylosing spondylitis were identified from five GP surgeries in Yorkshire, UK. Patients were randomised 1:1 to receive study information alone or with the educational leaflet, with an invitation to attend for a screening examination by a dermatologist and rheumatologist. Nine hundred thirty-two invitation packs were sent to recruit 191 (20.5%) participants. One hundred sixty-nine (88.5%) had current or previous psoriasis and 17 (10.1%) had previously undiagnosed PsA. The estimated prevalence of PsA was 18.1% (95% CI: 16.2, 20.1%). The response rate was lower than expected and was not significantly higher when patients received the educational leaflet (22.8 vs 18.3%, p = 0.08). Response rates varied by practice (14.7 to 30.6%). However, deprivation scores for each practice revealed a significant increase in response with the leaflet for deprivation decile of 3 (p < 0.001) but no significant differences in the other practices. An educational leaflet about PsA improves attendance for screening in primary care, but only in those practices with higher levels of socioeconomic deprivation