An initial application of computerized adaptive testing (CAT) for measuring disability in patients with low back pain

<p>Abstract</p> <p>Background</p> <p>Recent approaches to outcome measurement involving Computerized Adaptive Testing (CAT) offer an approach for measuring disability in low back pain (LBP) in a way that can reduce the burden upon patient and professional. The aim of this study was to explore the potential of CAT in LBP for measuring disability as defined in the International Classification of Functioning, Disability and Health (ICF) which includes impairments, activity limitation, and participation restriction.</p> <p>Methods</p> <p>266 patients with low back pain answered questions from a range of widely used questionnaires. An exploratory factor analysis (EFA) was used to identify disability dimensions which were then subjected to Rasch analysis. Reliability was tested by internal consistency and person separation index (PSI). Discriminant validity of disability levels were evaluated by Spearman correlation coefficient (r), intraclass correlation coefficient [ICC(2,1)] and the Bland-Altman approach. A CAT was developed for each dimension, and the results checked against simulated and real applications from a further 133 patients.</p> <p>Results</p> <p>Factor analytic techniques identified two dimensions named "body functions" and "activity-participation". After deletion of some items for failure to fit the Rasch model, the remaining items were mostly free of Differential Item Functioning (DIF) for age and gender. Reliability exceeded 0.90 for both dimensions. The disability levels generated using all items and those obtained from the real CAT application were highly correlated (i.e. > 0.97 for both dimensions). On average, 19 and 14 items were needed to estimate the precise disability levels using the initial CAT for the first and second dimension. However, a marginal increase in the standard error of the estimate across successive iterations substantially reduced the number of items required to make an estimate.</p> <p>Conclusion</p> <p>Using a combination approach of EFA and Rasch analysis this study has shown that it is possible to calibrate items onto a single metric in a way that can be used to provide the basis of a CAT application. Thus there is an opportunity to obtain a wide variety of information to evaluate the biopsychosocial model in its more complex forms, without necessarily increasing the burden of information collection for patients.</p

Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer

The degree of damage to DNA following ifosfamide (IFO) treatment may be linked to the therapeutic efficacy. The pharmacokinetics and metabolism of IFO were studied in 19 paediatric patients, mostly with rhabdomyosarcoma or Ewings sarcoma. Ifosfamide was dosed either as a continuous infusion or as fractionated doses over 2 or 3 days. Samples of peripheral blood lymphocytes were obtained during and up to 96 h after treatment, and again prior to the next cycle of chemotherapy. DNA damage was measured using the alkaline COMET assay, and quantified as the percentage of highly damaged cells per sample. Samples were also taken for the determination of IFO and metabolites. Pharmacokinetics and metabolism of IFO were comparable with previous studies. Elevations in DNA damage could be determined in all patients after IFO administration. The degree of damage increased to a peak at 72 h, but had returned to pretreatment values prior to the next dose of chemotherapy. There was a good correlation between area under the curve of IFO and the cumulative percentage of cells with DNA damage (r2 = 0.554, P = 0.004), but only in those patients receiving fractionated dosing. The latter patients had more DNA damage (mean ± s.d., 2736 ± 597) than those patients in whom IFO was administered by continuous infusion (1453 ± 730). The COMET assay can be used to quantify DNA damage following IFO therapy. Fractionated dosing causes a greater degree of DNA damage, which may suggest a greater degree of efficacy, with a good correlation between pharmacokinetic and pharmacodynamic data