No abstract

Potent combinations of antiretroviral drugs diminish the turnover of CD4؉ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of viral replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4؉ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4؉ T cell counts, the CD45RA؉ subset, and fractions of proliferating or apoptotic CD4؉ T cells. Compared with normal controls, we documented decreased numbers of CD4؉ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4؉ T and CD45RA؉ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA؉ CD4؉ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4؉ T cell populations can be partially restored by control of active replication without eradication of HIV-1.

BackgroundFatigue is a common and debilitating symptom in multiple sclerosis (MS). Best-practice guidelines suggest that health services should repeatedly assess fatigue in persons with MS. Several fatigue scales are available but concern has been expressed about their validity. The objective of this study was to examine the reliability and validity of a new scale for MS fatigue, the Neurological Fatigue Index (NFI-MS).MethodsQualitative analysis of 40 MS patient interviews had previously contributed to a coherent definition of fatigue, and a potential 52 item set representing the salient themes. A draft questionnaire was mailed out to 1223 people with MS, and the resulting data subjected to both factor and Rasch analysis.ResultsData from 635 (51.9% response) respondents were split randomly into an 'evaluation' and 'validation' sample. Exploratory factor analysis identified four potential subscales: 'physical', 'cognitive', 'relief by diurnal sleep or rest' and 'abnormal nocturnal sleep and sleepiness'. Rasch analysis led to further item reduction and the generation of a Summary scale comprising items from the Physical and Cognitive subscales. The scales were shown to fit Rasch model expectations, across both the evaluation and validation samples.ConclusionA simple 10-item Summary scale, together with scales measuring the physical and cognitive components of fatigue, were validated for MS fatigue.

A framework, not only derived from patient experience but also meaningful in a medical context, was shown to be capable of describing fatigue in a large cross-section of MS patients. The definition may facilitate inter-disease comparison of fatigue as well as physiological enquiry.

BackgroundThe Hospital Anxiety and Depression Scale (HADS) is commonly used to assess symptoms of anxiety and depression in motor neurone disease (MND). The measure has never been specifically validated for use within this population, despite questions raised about the scale's validity. This study seeks to analyse the construct validity of the HADS in MND by fitting its data to the Rasch model.MethodsThe scale was administered to 298 patients with MND. Scale assessment included model fit, differential item functioning (DIF), unidimensionality, local dependency and category threshold analysis.ResultsRasch analyses were carried out on the HADS total score as well as depression and anxiety subscales (HADS-T, D and A respectively). After removing one item from both of the seven item scales, it was possible to produce modified HADS-A and HADS-D scales which fit the Rasch model. An 11-item higher-order HADS-T total scale was found to fit the Rasch model following the removal of one further item.ConclusionOur results suggest that a modified HADS-A and HADS-D are unidimensional, free of DIF and have good fit to the Rasch model in this population. As such they are suitable for use in MND clinics or research. The use of the modified HADS-T as a higher-order measure of psychological distress was supported by our data. Revised cut-off points are given for the modified HADS-A and HADS-D subscales.

Summating the nine items of the FSS-9 is invalid. Five items (FSS-5), which seem to be measuring the social impact of fatigue, provide a strictly unidimensional Rasch scale. Studies using the FSS-9 may need to be re-evaluated using the FSS-5, preferably using the Rasch transformed scores.

Clear relationships were found between fatigue and disability, disease type and sleep. Further physiological enquiry and trials of drug treatment and sleep modulation might be guided by these clinical relationships.

The MFIS cannot be used to generate a single overall score of fatigue. The conceptual interaction between the two dimensions remains unclear, which poses problems when interpreting change scores in these individual scales. Studies in which a global MFIS score was used as either an outcome measure or selection tool may need to be re-evaluated.