The Valued Life Activities Scale (VLAs): linguistic validation, cultural adaptation and psychometric testing in people with rheumatic and musculoskeletal diseases in the UK.

BACKGROUND: The Valued Life Activities Scale (VLAs) measures difficulty in daily activities and social participation. With various versions involving a different number of items, we have linguistically and culturally adopted the full VLAs (33-items) and psychometrically tested it in adults with rheumatic and musculoskeletal diseases in the United Kingdom. METHODS: Participants with Rheumatoid Arthritis, Ankylosing Spondylitis, Chronic Pain/ Fibromyalgia, Chronic Hand/ Upper Limb Conditions, Osteoarthritis, Systemic Lupus, Systemic Sclerosis and Primary Sjogren's Syndrome were recruited from out-patient clinics in National Health Service Hospitals, General Practice and patient organisations in the UK. Phase1 involved linguistic and cultural adaptation: forward translation to British English; synthesis; expert panel review and cognitive debriefing interviews. In Phase2 participants completed postal questionnaires to assess internal construct validity using (i) Confirmatory Factor Analysis (CFA) (ii) Mokken scaling and (iii) Rasch model. RESULTS: Responders (n = 1544) had mean age of 59 years (SD13.3) and 77.2% women. A CFA failed to support a total score from the 33-items (Chi Square 3552:df 464: p < 0.0001). Mokken scaling indicated a strong non-parametric association between items. Fit to the Rasch model indicated that the VLAs was characterised by multidimensionality and item misfit, which may have been influenced by clusters of residual item correlations. An item banking approach resolved a 25-item calibrated set whose application could accommodate the 'does not apply to me' response option. CONCLUSIONS: The UK version of the VLAs failed to satisfy classical and modern psychometric standards for complete item sets. However, as the scale is not usually applied in complete format, an item bank approach calibrated 25 items with fit to the Rasch model. Suitable Computer Adaptive Testing (CAT) software could implement the item set, giving patients the choice of whether an item applies to them, or not.

Revisiting the disabilities of the arm, shoulder and hand (DASH) and QuickDASH in rheumatoid arthritis.

BACKGROUND: Limitations in upper limb functioning are common in Musculoskeletal disorders and the Disabilities of the Arm, Shoulder and Hand scale (DASH) has gained widespread use in this context. However, various concerns have been raised about its construct validity and so this study seeks to examine this and other psychometric aspects of both the DASH and QuickDASH from a modern test theory perspective. METHODS: Participants in the study were eligible if they had a confirmed diagnosis of Rheumatoid Arthritis (RA). They were mailed a questionnaire booklet which included the DASH. Construct validity was examined by fit to the Rasch measurement model. The degree of precision of both the DASH and QuickDASH were considered through their Standard Error of Measurement (SEM). RESULTS: Three hundred and thirty-seven subjects with confirmed RA took part, with a mean age of 62.0 years (SD12.1); 73.6% (n = 252) were female. The median standardized score on the DASH was 33 (IQR 17.5-55.0). Significant misfit of the DASH and QuickDASH was observed but, after accommodating local dependency among items in a two-testlet solution, satisfactory fit was obtained, supporting the unidimensionality of the total sets and the sufficiency of the raw (ordinal or standardized) scores. CONCLUSION: Having accommodated local response dependency in the DASH and QuickDASH item sets, their total scores are shown to be valid, given they satisfy the Rasch model assumptions. The Rasch transformation should be used whenever all items are used to calculate a change score, or to apply parametric statistics within an RA population. SIGNIFICANCE AND INNOVATIONS: Most previous modern psychometric analyses of both the DASH and QuickDASH have failed to fully address the effect of a breach of the local independence assumption upon construct validity. Accommodating this problem by creating 'super items' or testlets, removes this effect and shows that both versions of the scale are valid and unidimensional, as applied with a bi-factor equivalent solution to an RA population. The Standard Error of Measurement of a scale can be biased by failing to take into account the local dependency in the data which inflates reliability and thus making the SEM appear better (i.e. smaller) than the true value without bias.

Chemotherapy for primary gastric lymphoma: does in-patient observation prevent complications?

AIMS: Primary gastric lymphoma (PGL) is the most common site of extra-nodal non-Hodgkin's lymphoma (NHL). In recent years there has been a move away from a surgical approach to primary chemotherapy with or without radiotherapy. Data support this approach, with overall survival rates equivalent or superior to surgery. Concerns have been raised over the incidence of acute chemotherapy complications, primarily gastrointestinal (GI) haemorrhage and perforation. As a result, several units, including our own, have routinely admitted all patients for observation during the commencement of therapy. We conducted an audit to elucidate the incidence and timing of such complications. MATERIALS AND METHODS: We used our prospectively recorded lymphoma database to identify all patients with aggressive PGL treated with primary chemotherapy. We examined individual patient notes for the incidence of gastric perforation and GI haemorrhage, defined as a fall in haemoglobin of least 2 g/dl, or the occurrence of haematemesis or malaena. RESULTS: We identified 29 patients with aggressive PGL who received primary systemic chemotherapy. Of these, only two had acute complications, one with GI bleed and the other with perforation. Both events occurred after discharge following our standard inpatient admission period of 5 days (day 13 and day 17). CONCLUSION: In this study, the rate of acute chemotherapy-related complications is low (6.9%). This is consistent with most published series, in which the incidence seems to be around 5% or less. Both acute complications in this series occurred after the patients had been discharged following a routine admission period of 5 days for observation. Although rarely documented, other series suggest that these events also occur late after the initiation of chemotherapy. This work suggests that routine admission for the initiation of chemotherapy for PGL is not necessary and should be at the discretion of the treating physician. All patients should receive comprehensive education about the risks and clinical signs of gastric perforation and bleed. This change in policy has obvious implications for healthcare resources.

A randomised study of protracted venous infusion of 5-fluorouracil (5-FU) with or without bolus mitomycin C (MMC) in patients with carcinoma of unknown primary.

No standard regimen has been identified for patients with a carcinoma of unknown primary (CUP). This study compared protracted venous infusion 5-fluorouracil (PVI 5-FU) with or without mitomycin C (MMC) in patients with CUP in a multicentre, prospectively randomised study. 88 patients were randomised to PVI 5-FU (300 mg/m(2)/day for a maximum of 24 weeks) +/-MMC (7 mg/m(2) 6 weekly for four courses). The overall response rate was 11.6% for PVI 5-FU alone compared with 20.0% for PVI 5-FU plus MMC (P=0.29). Median failure-free survival (FFS) was 4.1 months for PVI 5-FU and 3.6 months for PVI 5-FU plus MMC (P=0.78) with an equivalent overall survival (OS) (6.6 versus 4.7 months, P=0.60). Symptomatic benefit was observed in most patients in each arm. PVI 5-FU is a well tolerated outpatient treatment regimen for patients with CUP, although the addition of MMC provides little extra benefit. PVI 5-FU may be a potential reference regimen in randomised trials with newer chemotherapy agents in patients with CUP.

Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer.

This study was designed to evaluate the benefits of neoadjuvant chemotherapy prior to chemoradiation and surgery in patients with locally advanced rectal cancer. Patients with previously untreated primary rectal cancer, reviewed in a multidisciplinary meeting and considered to have locally advanced disease on the basis of physical examination and imaging (MRI+CT n=30, CT alone n=6), were recruited. Patients received protracted venous infusion 5-FU (300 mg m(-2) day(-1) for 12 weeks) with mitomycin C (MMC) (7 mg m(-2) i.v. bolus every 6 weeks). Starting on week 13, 5-FU was reduced to 200 mg m(-2) day(-1) and concomitant pelvic radiotherapy 45 Gy in 25 fractions was commenced followed by 5.4-9 Gy boost to tumour bed. Surgery was planned 6 weeks after chemoradiation. Postoperatively, patients received 12 weeks of MMC and 5-FU at the same preoperative doses. Between January 99 and August 01, 36 eligible patients were recruited. Median age was 63 years (range=40-85). Following neoadjuvant chemotherapy, radiological tumour response was 27.8% (one CR and nine PRs) and no patient had progressive disease. In addition, 65% of patients had a symptomatic response including improvement in diarrhoea/constipation (59%), reduced rectal bleeding (60%) and diminished pelvic pain/tenesmus (78%). Following chemoradiation, tumour regression occurred in 80.6% (six CRs and 23 PRs; 95% CI=64-91.8%) and only one patient still had an inoperable tumour. R0 resection was achieved in 28 patients (82%). When compared with initial clinical staging, the pathological downstaging rate in T and/or N stage was 73.5% and pathological CR was found in one patient. Neoadjuvant systemic chemotherapy as a prelude to synchronous chemoradiation can be administered with negligible risk of disease progression and produces considerable symptomatic response with associated tumour regression.

A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer.

BACKGROUND: This randomised study compared protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin C (MMC) in patients with advanced oesophago-gastric cancer. PATIENTS AND METHODS: Two hundred and fifty-four patients with adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma involving the oesophagus, oesophago-gastric junction or the stomach were randomised. The major end points were tumour response, survival, toxicity and quality of life. RESULTS: The median age of patients treated was 72 years and the two arms were well-balanced for baseline demographic factors. The overall response rate was 16.1% [95% confidence interval (CI) 9.5% to 22.7%] in patients treated with PVI 5-FU alone compared with 19.1% (95% CI 12.0% to 26.0%) for those treated with PVI 5-FU plus MMC (P = 0.555). Median time to treatment failure was 3.9 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC (P = 0.195). Median survival was 6.3 months for PVI 5-FU and 5.3 months for PVI 5-FU plus MMC (P = 1.0). Toxicity was mild for both treatments. Symptomatic benefit measured by improvement in pain control, weight loss, dysphagia and oesophageal reflux was observed in over 64% of patients in each arm. Quality of life scores were comparable in each arm. CONCLUSIONS: PVI 5-FU is a safe, effective form of palliation for patients with advanced oesophago-gastric cancer although the addition of MMC adds little extra benefit.