M. F. Prummel

On assessing responsiveness of health-related quality of life instruments: Guidelines for instrument evaluation

A lack of clarity exists about the definition and adequate approach for evaluating responsiveness. An overview is presented of different categories of definitions and methods used for calculating responsiveness identified through a literature search. Twenty-five definitions and 31 measures were found. When applied to a general and a disease-specific quality of life questionnaire large variation in results was observed, partly explained by different goals of existing methods. Four major issues are considered to claim the usefulness of an evaluative health-related quality of life (HRQL) instrument. Their relation with responsiveness is discussed. The confusion about responsiveness arises mostly from a lack of distinction between cross-sectional and longitudinal validity and from a lack of distinction between responsiveness defined as the effect of treatment and responsiveness defined as the correlation of changes in the instrument with changes in other measures. All measures of what is currently called responsiveness can be looked at as measures of longitudinal validity or as measures of treatment effect. The latter ones tell us little about how well the instrument serves its purpose and are only of use in interpreting score changes. We therefore argue that the concept of responsiveness can be rejected as a separate measurement property of an evaluative instrument.

TSH-R expression and cytokine profile in orbital tissue of active vs. inactive Graves' ophthalmopathy patients

objective From in vitro studies using cultures of orbital fibroblasts, it has become clear that cytokines play an important role in the orbital inflammation in Graves’ ophthalmopathy (GO). Orbital fibroblasts seem to be the key target cells of the autoimmune attack, and they are able to express the TSH receptor (TSH‐R). In vivo data on the presence of cytokines in orbital tissues are sparse, and mostly limited to samples obtained from patients with endstage, inactive GO; the same holds true for the presence of the TSH‐R. The aim of the present study was to determine whether the cytokine profile and TSH‐R expression differ in the active vs. the inactive stage of GO.

Surgical or medical decompression as a first-line treatment of optic neuropathy in Graves’ ophthalmopathy? A randomized controlled trial

Objective  Only a small percentage of Graves’ ophthalmopathy (GO) patients develop optic neuropathy with impending loss of visual acuity. Therapy with methylprednisolone pulses is the treatment of first choice in severe and active GO patients. When the effect is insufficient, patients are usually treated with surgical decompression. We investigated whether surgery could become the first‐line treatment, thus preventing treatment with steroids.

Measuring disease activity to predict therapeutic outcome in Graves' ophthalmopathy.

Objective  The concept of disease activity in Graves’ ophthalmopathy (GO) might explain why as many as one‐third of patients do not respond to immunosuppressive treatment, because only patients in the active stage of disease are expected to respond. The hypothesis was adopted that a parameter used to measure disease activity should be able to predict a response to immunosuppressive treatment. The aim of this study was to develop a multivariate prediction model in which all previous tested activity parameters are integrated.

Smoking and disease severity are independent determinants of serum adhesion molecule levels in Graves’ ophthalmopathy

Adhesion molecules play a key role in autoimmune disorders, and serum concentrations of soluble adhesion molecules are increased in Graves’ ophthalmopathy (GO). Whether this is due to the strong association with smoking is unknown. It is also not known if the severity or activity of GO determine the serum levels of adhesion molecules. We measured serum concentrations of sICAM‐1, sVCAM‐1 and sELAM‐1 in 62 euthyroid Graves’ patients with untreated GO, in 62 healthy controls matched for sex, age and smoking habits, and in 26 euthyroid Graves’ patients without GO. GO severity was assessed by the Total Eye Score and the activity by the Clinical Activity Score. Adhesion molecules were measured by highly sensitive ELISAs. GO patients had higher levels than controls (median values in ng/ml with range): sICAM‐1 300 [171–575] versus 244 [119–674], P < 0·001; sVCAM‐1 457 [317–1060] versus 410 [238–562], P < 0·001; and sELAM‐1 61 [19–174] versus 53 [23–118], P = 0·021. Euthyroid Graves’ disease patients without GO had levels similar to controls: sICAM‐1 273 138–453), sVCAM‐1 386 [260–1041] and sELAM‐1 46 [22–118]. Smoking had an independent effect and was associated with higher levels of sICAM‐1 and lower levels of sVCAM‐1 in both GO patients and controls; sELAM‐1 levels were comparable. In the 62 GO patients, sICAM‐1 correlated significantly with severity of eye disease (r = 0·40, P = 0·002). No correlation was found with the duration of GO, the Clinical Activity Score or TBII levels. Multivariate analysis of all 150 subjects showed that the presence of GO and smoking are independent determinants of sICAM‐1 and sVCAM‐1 concentrations. In GO patients, the Total Eye Score was a stronger determinant than smoking. It is concluded that (i) smoking is associated with increased sICAM‐1 and decreased sVCAM‐1 levels; (ii) independent from smoking, euthyroid GO patients have higher levels of sICAM‐1, sVCAM‐1 and sELAM‐1 than patients with euthyroid Graves’ disease or healthy controls; (iii) the major determinant of sICAM‐1 in GO patients is the severity of their eye disease.