David M Meads

The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension

Objective: No outcome measures specific to pulmonary hypertension (PH) currently exist. The aim of the study was to develop health-related quality of life (symptoms and functioning) scales and a quality of life scale that would allow comprehensive, accurate and valid patient-reported outcome assessment in clinical studies. Methods: The content of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) was derived from qualitative interviews conducted with 35 patients. Item reduction was based on the analysis of responses to a postal survey (n=75) and patient interviews (n=15) designed to determine face and content validity. A final postal validation study (n=91) was performed to determine reproducibility and construct validity. Results: The questionnaire was well received by participants who found it to be relevant, comprehensible and quick and easy to complete. Rasch and factor analyses were conducted to ensure unidimensionality of the final CAMPHOR scales; Overall symptoms (made up of Energy, Breathlessness and Mood subscales), Functioning and Quality of life. The CAMPHOR scales had good internal consistency (α=0.90–0.92) and reproducibility (test–retest correlations=0.86–0.92). They also exhibited convergent, divergent and known groups validity. Conclusions: The CAMPHOR is a valuable new instrument for assessing patient-reported outcome in PH clinical trials and routine practice.

Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial

BACKGROUND Early intervention and tight control of inflammation optimise outcomes in rheumatoid arthritis but these approaches have not yet been studied in psoriatic arthritis. We aimed to assess the effect of tight control on early psoriatic arthritis using a treat-to-target approach. METHODS For this open-label multicentre randomised controlled trial, adult patients (aged ≥18 years) with early psoriatic arthritis (<24 months symptom duration), who had not previously received treatment with any disease-modifying anti-rheumatic drugs, were enrolled from eight secondary care rheumatology centres in the UK. Enrolled patients were randomly assigned in a 1:1 ratio to receive either tight control (with review every 4 weeks and with escalation of treatment if minimal disease activity criteria not met) or standard care (standard therapy according to the treating clinician, with review every 12 weeks) for 48 weeks. Randomisation was done by minimisation incorporating a random element, to ensure treatment groups were balanced for randomising centre and pattern of arthritis (oligoarticular vs polyarticular). The randomisation procedure was done through a central 24-h automated telephone system based at the Leeds Institute of Clinical Trials Research (Leeds, UK). This was an open-label study in which patients and clinicians were aware of treatment group assignment. Clinical outcomes were recorded by a masked assessor every 12 weeks. The primary outcome was the proportion of patients achieving an American College of Rheumatology (ACR) 20% (ACR20) response at 48 weeks, analysed by intention to treat with multiple imputation for missing ACR components. Cost-effectiveness was also assessed. This trial is registered with ClinicalTrials.gov, number NCT01106079, and the ISCRCTN registry, number ISCRCTN30147736. FINDINGS Between May 28, 2008, and March 21, 2012, 206 eligible patients were enrolled and randomly assigned to receive tight control (n=101) or standard care (n=105). In the intention-to-treat patient population, the odds of achieving an ACR20 response at 48 weeks were higher in the tight control group than in the standard care group (odds ratio 1·91, 95% CI 1·03-3·55; p=0·0392). Serious adverse events were reported by 20 (10%) patients (25 events in 14 [14%] patients in the tight control group and eight events in six [6%] patients in the standard care group) during the course of the study. No unexpected serious adverse events or deaths occurred. INTERPRETATION Tight control of psoriatic arthritis disease activity through a treat-to-target approach significantly improves joint outcomes for newly diagnosed patients, with no unexpected serious adverse events reported. FUNDING Arthritis Research UK and Pfizer.

United States Validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR)

BACKGROUND The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first pulmonary hypertension-specific instrument for assessing patient-reported symptoms, functioning, and quality of life. To enable use in the United States, this study adapted, field-tested, and evaluated its reliability and validity at a single center in Chicago. METHODS A lay panel confirmed appropriate wording of CAMPHOR for United States patients, and 15 patients with pulmonary hypertension field-tested the CAMPHOR for face and content validity. A postal validation study, with the Medical Outcomes Study Short Form 36 (SF-36) Health Survey as a comparator, was sent to patients on 2 occasions, 2 weeks apart. World Health Organization (WHO) functional class and 6-minute walk test data were obtained. RESULTS Field-test interviews found the CAMPHOR relevant and comprehensible. A total of 147 patients (84.0% women) with a mean of 50 +/- 14.6 years participated in the validation study. The new scales had good test-retest reliability (range, 0.80-0.95) and internal consistency (range, 0.78-0.95). The CAMPHOR scales correlated with the SF-36 and 6-minute walk test. Patients in WHO functional class III had worse scores than those in class II (p = 0.02), as did patients who rated their health worse (p < 0.001). CONCLUSIONS The US CAMPHOR is a reliable and valid measure of quality of life and health status in pulmonary hypertension and can be recommended for use in clinical practice and trials in the United States.

Can We Rely on the Dermatology Life Quality Index as a Measure of the Impact of Psoriasis or Atopic Dermatitis

The Dermatology Life Quality Index (DLQI) is a widely used health-related quality of life measure. However, little research has been conducted on its dimensionality. The objectives of the current study were to apply Rasch analysis to DLQI data to determine whether the scale is unidimensional, to assess its measurement properties, test the response format, and determine whether the measure exhibits differential item functioning (DIF) by disease (atopic dermatitis versus psoriasis), gender, or age group. The results show that there were several problems with the scale, including misfitting items, DIF by disease, age, and gender, disordered response thresholds, and inadequate measurement of patients with mild illness. As the DLQI did not benefit from the application of Rasch analysis in its development, it is argued that a new measure of disability related to dermatological disease is required. Such a measure should use a coherent measurement model and ensure that items are relevant to all potential respondents. The current use of the DLQI as a guide to treatment selection is of concern, given its inadequate measurement properties.

Serial Change in Health-Related Quality of Life Over 1 Year After Transcatheter Aortic Valve Implantation: Predictors of Health Outcomes

OBJECTIVES The goal of this study was to assess serial changes in patient health-related quality of life (HRQOL) over time and identify predictors of patient benefit. BACKGROUND Severe aortic stenosis reduces the length and quality of a patients life. Transcatheter aortic valve implantation (TAVI) is superior to standard medical therapy and noninferior to surgical aortic valve replacement for 1-year mortality. HRQOL is an important outcome measure for which there is limited evidence in TAVI populations. METHODS A total of 102 patients (mean age 80 ± 0.6 years; 49% male) undergoing TAVI consented to participate. Two HRQOL questionnaires-the social functioning (SF)-12v2 with physical component summaries (PCS) and mental component summaries (MCS) and the EQ-5D (with a visual analog scale [VAS])-were completed at baseline, 30 days, 6 months, and 1 year according to the recommendations of the Valve Academic Research Consortium. A SF-6D utility measure was calculated from the SF-12 survey. RESULTS HRQOL significantly improved over 1 year (PCS p = 0.02; EQ-5D p = 0.02; VAS p = 0.01; SF-6D p = 0.03), becoming similar to age-adjusted U.S. population norms. The greatest change occurred from baseline to 30 days (p < 0.001), with further significant improvements to 6 months (p < 0.01). An insignificant decline occurred between 6 months and 1 year (p > 0.05), but a linear pattern of change remained for PCS, EQ-5D, and VAS (p < 0.05). Male sex (SF-6D p = 0.01) and increased operator experience (PCS, EQ-5D, and VAS p < 0.05) were independent predictors of a greater improvement in HRQOL. CONCLUSIONS HRQOL significantly improved early after TAVI and was maintained out to 1 year. Patient factors, procedural complications, and operator experience are predictors of health benefit at 1 year.

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

BackgroundThe 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.MethodsThe 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 ASQOLs scaling properties.ResultsCognitive 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 Cronbachs 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.ConclusionThe 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.

Development and psychometric assessment of the COPD and Asthma Sleep Impact Scale (CASIS)

BackgroundPatients with respiratory disease experience disturbed sleep, but there is no widely accepted measure of sleep impairment due to respiratory disease. We developed and evaluated the psychometric performance of a patient-reported measure to assess the impact on sleep due to respiratory disease, the COPD and Asthma Sleep Impact Scale (CASIS).MethodsIdentification of the items forming the CASIS was guided by patient interviews and focus groups. An observational study involving patients from the US and UK was then conducted to assess the psychometric characteristics of the measure.ResultsQualitative data from 162 patients were used to develop the CASIS (n = 78 COPD; n = 84 asthma). The observational study included 311 patients with COPD and 324 patients with asthma. The final seven items used in the CASIS were identified based on factor and item response theory analyses. Internal consistency was 0.90 (COPD) and 0.92 (asthma), and test-retest reliability was 0.84 (both groups). In the COPD sample, CASIS scores were significantly correlated with the Saint Georges Respiratory Questionnaire scores (all p < 0.0001) and differed significantly by patient-reported disease severity, exacerbation status, and overall health status (all p ≤ 0.005). In the asthma sample, CASIS scores were significantly correlated with the Asthma Quality of Life Questionnaire scores (all p < 0.0001) and differed significantly by clinician and patient-reported disease severity, exacerbation status, and overall health status (all p ≤ 0.0005).ConclusionThe CASIS shows good internal consistency, test-retest reliability, and construct validity and may be useful in helping to understand the impact that COPD and asthma have on sleep outcomes.

The rheumatoid arthritis quality of life (RAQoL) for Sweden : adaptation and validation

Objective: To produce and evaluate the official Swedish language version of the Rheumatoid Arthritis Quality of Life instrument (RAQoL). Methods: The UK RAQoL was translated into Swedish by a bilingual translation panel. A separate lay panel was conducted to consider the appropriateness and comprehensibility of the items in Swedish. Interviews were conducted with 15 Swedish RA patients to assess face and content validity. Responses to a postal survey were used to calculate reproducibility and construct validity. Results: Few difficulties arose in the translation process and the new language version was well received by the lay panel and field‐test participants. One hundred and sixty‐five RA patients participated in the postal survey (69% female; mean age 62.7 years, SD 11.3, RA duration range 1–62 years). Cronbach’s α for the Swedish RAQoL was 0.91 and test–retest reliability was 0.95, indicating that the instrument has adequate inter‐relatedness of items and very low inherent random measurement error. A high correlation with the Health Assessment Questionnaire (HAQ) was observed; this was expected because RA has significant physical manifestations that are in turn a significant determinant of QoL. The Swedish RAQoL was able to distinguish between patients who differed according to their self‐perceived RA severity, general health, and rating of their RA today, in addition to whether or not the patient was experiencing a flare of RA. Conclusions: The official Swedish RAQoL was well received by RA patients. The psychometric quality of the adapted questionnaire means that it is suitable for inclusion in clinical trials involving patients with RA.

International Development of the Patient-Reported Outcome Indices for Multiple Sclerosis (PRIMUS)

BACKGROUND The Patient-Reported Indices for Multiple Sclerosis (PRIMUS) comprises a suite of three scales for assessing symptoms, activity limitations, and quality of life in multiple sclerosis (MS). It was developed in the UK and has been shown to have excellent psychometric properties. This study describes the adaptation of eight language versions for Canadian English, Canadian French, French, German, Italian, Spanish, Swedish, and US English. METHODS The PRIMUS was translated using the dual-panel process. Cognitive debriefing interviews conducted with MS patients assessed face and content validity. Psychometric and scaling properties were assessed via a two-administration postal survey conducted in each country involving the PRIMUS, the Nottingham Health Profile (NHP), the Unidimensional Fatigue Impact Scale (U-FIS), and demographic questions. RESULTS Cognitive debriefing interviews demonstrated the acceptability of the new language versions. Analysis of survey data showed that the new language versions of the three PRIMUS scales were unidimensional (as indicated by fit to the Rasch model) and that they had good internal consistency and reproducibility. PRIMUS scale scores correlated as expected with those on the NHP and the U-FIS. The scales in all countries were able to discriminate between groups of patients on the basis of their self-reported MS severity, general health, and employment status. CONCLUSIONS The PRIMUS was successfully adapted into eight new languages. Most of the tests showed the PRIMUS to have good unidimensionality and to have good internal consistency, reproducibility, and construct validity. The measure is now available for use in clinical studies and trials involving these countries and the UK. Further work is required to assess the measures responsiveness.

Do electronic cigarettes increase cigarette smoking in UK adolescents? Evidence from a 12-month prospective study.

Background In cross-sectional surveys, increasing numbers of adolescents report using both electronic cigarettes (e-cigarettes) and cigarettes. This study assessed whether adolescent e-cigarette use was associated prospectively with initiation or escalation of cigarette use. Methods Data were from 2836 adolescents (aged 13–14 years at baseline) in 20 schools in England. At baseline, breath carbon monoxide levels, self-reported e-cigarette and cigarette use, sex, age, friends and family smoking, beliefs about cigarette use and percentage receiving free school meals (measure of socioeconomic status) were assessed. At 12-month follow-up, self-reported cigarette use was assessed and validated by breath carbon monoxide levels. Results At baseline, 34.2% of adolescents reported ever using e-cigarettes (16.0% used only e-cigarettes). Baseline ever use of e-cigarettes was strongly associated with subsequent initiation (n=1726; OR 5.38, 95% CI 4.02 to 7.22; controlling for covariates, OR 4.06, 95% CI 2.94 to 5.60) and escalation (n=318; OR 1.91, 95% CI 1.14 to 3.21; controlling for covariates, this effect became non-significant, OR 1.39, 95% CI 0.97 to 1.82) of cigarette use. Conclusions This is the first study to report prospective relationships between ever use of e-cigarettes and initiation and escalation of cigarette use among UK adolescents. Ever use of e-cigarettes was robustly associated with initiation but more modestly related to escalation of cigarette use. Further research with longer follow-up in a broader age range of adolescents is required.