Osteoarthritis antirheumatic drug trials: effects of a standardized instructional videotape on the reliability of observer-dependent dependent outcome measures.

AIMS: A study was designed to assess the effects of a standardized instructional videotape on reducing interobserver variability for several commonly used observer dependent outcome measures. METHODS: During a single day, six rheumatologists independently examined six patients with osteoarthritis (OA) in a predetermined order using a Latin square design, before and after viewing a standardized videotape demonstrating 13 examination techniques. Reliability coefficients were calculated based on variance components of the analysis of variance (ANOVA) table. RESULTS: Prestandardization reliability coefficients were >0.80 for all measures and remained above 0.80 following the intervention. CONCLUSIONS: It is usually assumed that serial measurement in clinical trials should be performed by the same assessor because of concern regarding interobserver variability. However, the high levels of prestandardization interobserver reliability observed in this study indicate that, for these variables, serial measurements in a clinical trial could be made by different assessors, assuming they were equally skilled. This observation has important implications for outcome measurement in OA clinical trials. Although high levels of prestandardization reliability precluded the demonstration of any significant improvement, we speculate that the videotape might be effective in training less-experienced assessors. Reductions in observer variability have the potential to diminish sample size requirements for OA antirheumatic drug studies. The use of a videotape to achieve this goal offers cost and convenience advantages over one-on-one training procedures, and this method should be further assessed in less-experienced assessors.

Digging in the desert.

Palaeopathology is the study of disease in antiquity. Doctor Christopher Browne has spent several years studying skeletal material recovered from an archaeological site in Jordan to gain insight into the evolution of rheumatic and bone diseases.

In search of the pathogenesis of refractory cervicobrachial pain syndrome. A deconstruction of the RSI phenomenon.

OBJECTIVE: To discuss the clinical and social phenomenon of refractory cervicobrachial pain, more popularly known as repetitive strain injury (RSI), from the standpoint of medical knowledge and to present the phenomenon as a problem of chronic musculoskeletal pain in which clinical clues suggest a neuropathic pathogenesis. DATA SOURCES: Published articles from both medical and non-medical literature, primarily since 1980, were integrated with our clinical experience and observations. DATA SYNTHESIS: Three sets of formal responses to the issue--medical, psychiatric and sociological--were identified and analysed with respect to the validity of their conclusions, which formed the conventional wisdom. Clinical observation revealed clues to disturbed nociception in a carefully defined set of subjects with chronic cervicobrachial pain. Theoretical pathophysiological correlations of these led to the formulation of an hypothesis. CONCLUSIONS: We doubt that clinical method and diagnostic logic were rigorously applied to the RSI phenomenon, which helped to produce an unresolved controversy with widespread ramifications. Our hypothesis is that there is a central disturbance of nociception in this syndrome, induced by continual afferent barrage from nociceptors in anatomically relevant sites in the neck and upper limbs. Initial and proposed testing of this hypothesis are discussed.

Corticosteroid injection for osteoarthritis of the knee: peripatellar compared to intra-articular route.

Intra-articular injection of micro-crystalline corticosteroid is used to treat symptomatic osteoarthritis (OA) of the knee, but its duration of effect and efficacy are uncertain. From the observation that pain in OA of the knee can often be blocked by infiltration of the soft tissues at the patella margin with local anaesthetic, this study investigated an injection technique in which corticosteroid was infiltrated around the patella. Thirty-eight patients with radiologically demonstrable and painful OA of the knee were treated either with peripatellar or intra-articular methylprednisolone in a randomised double blind study. Assessments of response to either injection were made at one week, one month and three months. Eleven of 15 measures improved significantly over time in both groups, but the differences between groups were not statistically significant. Analysis of individual responses showed that the majority of good outcomes were in the peripatellar group. Five patients receiving intra-articular injections but only one receiving a peripatellar injection withdrew because of treatment failure. Peripatellar injection is an alternative method of local administration of corticosteroid which is highly effective in a proportion of patients and merits further evaluation.

The oncogenicity of chlorambucil in rheumatoid arthritis.

Chlorambucil is useful in patients with rheumatoid arthritis (RA) refractory to other agents but there is concern about the risk of haematological malignancy with this agent. A retrospective survey was performed to assess the incidence of all types of malignancy in 39 patients treated with chlorambucil (mean daily dose 4.25 mg, mean duration of treatment 25 months). These patients were compared with 30 patients with RA who received contemporaneously, the purine analogues azathioprine or 6-mercaptopurine (mean dose 100 mg, mean duration of treatment 24 months). Eight patients treated with chlorambucil and one patient receiving purine analogues developed cutaneous malignancy (p = 0.03). In the chlorambucil-treated patients these were mostly multiple and recurrent. Three patients treated with chlorambucil developed myeloid leukaemia or a preleukaemic state, whilst no patient treated with purine analogues developed this complication. The use of chlorambucil in RA is associated with an increased risk of cutaneous as well as haematological oncogenesis.

Dose response studies and longterm evaluation of auranofin in rheumatoid arthritis.

Fifty-eight patients with rheumatoid arthritis (RA) entered a double blind trial of auranofin (AF) designed to assess dose response relationships and longterm outcome. Multivariate analysis of repeated measures with trend analysis and discriminant function analysis of standard measures of RA activity were applied to a randomized double blind trial of AF at daily doses of 4, 6 and 8 mg over 6 months. Improvement occurred in each group. There was a highly significant (p less than 0.001) linear trend in the 6 mg group, 73% of whom showed linear improvement. A significant correlation (p less than 0.05) was found between response of individual patients and AF dose (mg/kg/day), but there was no significant correlation between dosage and mean steady state serum gold concentration. No significant correlation was seen between outcome and pretreatment demographic and disease variables. In a subsequent 6 month phase of dosage adjustment, aiming for optimal dosage, no advantage resulted from increasing the dose above 6 mg/day. Patients apparently benefiting from treatment continued an open long-term trial of AF. By 45 months, 33.5% had stopped treatment due to lack of efficacy and 14.5% due to toxicity, mainly rash and diarrhea.

Comparison of methotrexate with azathioprine or 6-mercaptopurine in refractory rheumatoid arthritis: a life-table analysis.

Methotrexate (MTX) appears to be useful in patients with rheumatoid arthritis (RA) refractory to other drugs but its long-term toxicity and efficacy are uncertain. A retrospective study of MTX in such patients in comparison with the purine analogues, azathioprine and 6-mercaptopurine was made using life-table analysis. Eighty-four patients took MTX in a median dose of 7.5 mg/week whilst 55 received purine analogues, 100 mg/day (median). By 12 months, 19.3% of patients had ceased MTX due to toxicity, compared with 29.3% for purine analogues. Toxicity severe enough to warrant stopping therapy was uncommon after 8 months with either drug. At 12 months 61.5% of the MTX patients had achieved defined criteria of improvement compared with 25.6% for the purine analogues (p less than 0.05). The number of patients improving on purine analogues did not increase substantially after 6 months, whereas the number improving with MTX continued to 12 months. MTX in a low-dose regimen is useful in refractory RA and superior to low-dose purine analogues.

Aurothioglucose in rheumatoid arthritis. Outcome of treatment in patients intolerant of sodium aurothiomalate.

Forty-three patients in whom treatment with sodium aurothiomalate was discontinued because of adverse reactions that either were relatively severe or recurred on rechallenge received treatment with aurothioglucose in oily base. Thirty-six of them had rheumatoid arthritis, four had psoriatic arthritis and three had juvenile chronic arthritis. Aurothioglucose therapy was introduced cautiously and increased gradually to a maintenance regimen, usually 5-20 mg/week, administered by intramuscular injection. The clinical response was good in 25 patients (60%), 14 of whom continued to receive aurothioglucose therapy on a long-term basis. Adverse reactions to aurothioglucose developed in 17 patients (40%); these were generally mild, and, in all but four patients, were of the same type as those induced by sodium aurothiomalate therapy. Results show that aurothioglucose in oily base may be successfully administered in a low-dose regimen to selected patients who are intolerant of sodium aurothiomalate.

Occupational repetition strain injuries. Guidelines for diagnosis and management.

Occupational repetition strain injuries (RSI) are a major, unchecked source of disability in industry and commerce, and have considerable social and economic consequences. The long-term morbidity associated with these injuries is preventable, but a coordinated approach to awareness, diagnosis, management, and prevention has been lacking. Confusing diagnostic terminology on medical certificates makes it difficult to obtain accurate data on the incidence and prevalence of different types of repetition injury. The terminology in use at present includes RSI, "tenosynovitis" and "overuse injury". Uniformity of diagnosis on an anatomical basis in relation to repetition or static load would greatly assist in epidemiological study, and improve notification and the impact of prevention programmes. Therefore, the Occupational Repetition Strain Injuries Advisory Committee, which was convened by the Division of Occupational Health, New South Wales Government Department of Industrial Relations, has prepared a set of guidelines for the diagnosis and management of these injuries.

Terminations of treatment with gold sodium thiomalate in rheumatoid arthritis.

Treatment terminations with gold sodium thiomalate (GST) in 200 patients with rheumatoid arthritis (RA) were analyzed using the life table method. The termination rate was 27% at 6 months, 48% at 12 months and 84% at 48 months. The major reason for termination was mucocutaneous reaction. Pretreatment clinical and laboratory status of the RA did not influence terminations significantly. Concurrent administration of oral corticosteroids had no significant effect on gold terminations. Complete control of synovitis was achieved in 38% of patients by a median time of 6 months but sustained for greater than 12 months in only 19%.

The effect of smoking on the distribution of gold in blood.

The uptake of gold by the red blood cells (RBC) of patients treated with aurothiomalate (GSTM) was greatly potentiated by smoking. The ratios of gold concentrations in RBC to the concentrations in plasma were 0.35 +/- 0.07 (mean +/- SE, n = 14) in smokers and 0.028 +/- 0.003 (n = 23) in non-smokers. Gold uptake by RBC in vitro was also greater in smokers than in blood from non-smokers. Thiocyanate appears to be a major factor which enhances the uptake of gold by RBC. The toxicity of GSTM was not altered by smoking but side effects occurred earlier in smokers.