N. Bellamy

Pain assessment in osteoarthritis: Experience with the WOMAC osteoarthritis index

P AIN IS AN ENTIRELY personal experience, and by necessity the methods used to measure pain are difficult to validate. However, this does not mean that measurement is impossible, but rather that the methods used must be of acceptable reliability, validity (face, content, and construct), and responsiveness. In the last 50 years,’ musculoskeletal clinical metrology has undergone a progressive evolution, although much more attention has been given to measurement issues in inflammatory forms of arthritis (particularly rheumatoid arthritis) than to the more common degenerative forms of arthritis. Indeed, the clinical metrology of osteoarthritis (OA) has been relatively neglected until recent years. Thus, Doyle et al’ have modified the Ritchie Index to develop a joint count applicable to OA subjects, while Lequesne has developed two scales, for the assessment of gonarthrosis3 and coxarthrosis,4 respectively. The McGill pain questionnaire has been applied to mixed arthritis populations, and in one study was found to identify qualitative differences between patients with RA and patients with localized OA,’ although in another study no significant differences were detected between patients with inflammatory and degenerative forms of arthritis.6 Several functional status instruments have appeared in the last 10 years, and a number have recently been compared to explore their relative efficiency.’ Our own interest has been in developing WOMAC, a purposebuilt multidimensional instrument capable of measuring clinically important, patient-relevant symptoms in OA of the hip and/or knee.’

Topical diclofenac and its role in pain and inflammation: An evidence-based review

ABSTRACT Objective: Topical diclofenac is widely used in the treatment of pain and inflammation. This comprehensive review assesses the safety and efficacy of topical diclofenac in a range of painful and inflammatory disorders. Methods: Double-blind, randomized, placebo- or active-controlled trials (RCT) evaluating topical diclofenac in soft-tissue injuries, soft-tissue rheumatic disorders and osteoarthritis were identified through detailed literature searches. In addition, non-RCT evidence from publications evaluating the pharmacologic characteristics of topical diclofenac were also included in this review to obtain a more complete picture of the drugs profile, its efficacy and safety. Results: Studies demonstrate that the drug preferentially distributes to the target tissues in sufficient concentrations to produce a therapeutic effect. A total of 19 double-blind RCTs in more than 3000 patients, supported by single-blind or open trials, consistently show that topical diclofenac significantly reduces pain and inflammation in acute and chronic conditions compared with placebo and is comparable to other topical non-steroidal anti-inflammatory drugs (NSAIDs) and some oral NSAIDs (diclofenac, ibuprofen, naproxen). Improvements have also been observed in patients’ functional capacity and mobility. Topical diclofenac is well tolerated, resulting mostly in mild, easily resolved local skin irritation, and is associated with fewer side-effects than other topical NSAIDs and a lower rate of gastrointestinal complications than oral NSAIDs (diclofenac, ibuprofen, naproxen). Conclusion: This evidence-based review shows topical diclofenac to be an effective and well tolerated treatment in painful and inflammatory conditions, at least in the short-term. However, only published RCT studies have been included in this analysis, which may exclude some interesting data from non-RCT studies. Future trials of topical diclofenac need to be of longer duration, be better reported and consider a broader spectrum of acute and chronic pain indications.

Circadian rhythm in pain, stiffness, and manual dexterity in rheumatoid arthritis: relation between discomfort and disability.

Fourteen patients with rheumatoid arthritis (RA) self rated their pain and stiffness on separate 10 cm visual analogue scales and performed bead intubation coordinometry (BIC) on six occasions each day for seven consecutive days. In addition, 14 healthy controls matched for age and sex also performed BIC measurements according to the same schedule. Data were analysed using least squares and cosine vector techniques. Significant circadian rhythms in patients with RA were detected in pain, stiffness, and BIC, and in controls in BIC. Pain was least in patients with RA at 1700 and stiffness at 1724. Peak BIC performance occurred almost simultaneously in RA (1544) and control (1528) subjects and for subjects with RA occurred within the 95% confidence interval of least pain and stiffness. These data suggest that the inferior performance of subjects with RA may be an accentuation of the normal physiological variation seen in healthy controls, but may be modulated by the patients level of pain or stiffness, or both.

Rhythmic variations in pain, stiffness, and manual dexterity in hand osteoarthritis

Objective: To explore circadian variation in pain, stiffness, and manual dexterity in patients with hand osteoarthritis (OA). Methods: Twenty one patients with hand OA, as defined by ACR criteria (17 women, four men, mean age 62.2 years, range 52–74 years) self rated pain and stiffness on separate 10 cm horizontal visual analogue scales and performed bead intubation coordinometry (BIC) six times each day (on waking up, at bedtime, and every four hours in between) for 10 consecutive days. Each series (using data with the trend removed if there was a significant trend) was analysed for circadian rhythmicity by a cosine vector technique (single cosinor). With individual data expressed as the percentage of the mean, group rhythm characteristics at period 24 hours were summarised for each variable by population mean cosinor analysis. Results: Individual analyses identified significant circadian rhythms at p≤0.05 for pain (n=15/21), stiffness (n=16/20), and dexterity (n=18/21), and a significant circadian rhythm on a group basis was identified for pain (p=0.013), stiffness (p<0.001), and dexterity (p<0.001). Pain was least at 1610 and stiffness at 1618. Peak dexterity occurred in mid-afternoon at 1548 and occurred within the 95% confidence interval of least pain (1312–1800) and stiffness (1520–1732). Conclusions: Dexterity was influenced by the patients level of pain or stiffness, which changed systematically throughout the day. Similar results have been previously reported in 14 patients with rheumatoid arthritis where peak dexterity occurred at 1544 and at 1528 in 14 age and sex matched healthy controls. The predictability of rhythmic variation in pain, stiffness, and dexterity has implications for scheduling activities of daily living and for timing antirheumatic drug treatment.

Rheumatoid arthritis in twins: a study of aetiopathogenesis based on the Australian Twin Registry.

The 1980 cohort of the Australian Twin Registry contains 3808 pairs of twins, 258 of whom self reported a diagnosis of rheumatoid arthritis (RA) in one or both subjects. Seventy two pairs were lost to follow up by 1990. The remaining 186 pairs received a self administered questionnaire, followed, if necessary, by telephone interviews to them, their general practitioners, and their specialists. Twenty discordant and three concordant pairs of twins were verified as having RA. The prevalence of RA in this sample was 0.40%. There was an 89% false positive rate for the self reported diagnosis of RA. Pairwise concordance percentages for RA were as follows: monozygotic 21% (95% confidence interval (CI) = 6 to 44), dizygotic 0% (95% CI = 0 to 25). It was concluded that: (a) there is a high false positive rate in self reporting RA; (b) the prevalence of RA in Australia may be less than the 0.8-1.0% often quoted; and (c) genetic factors play some part in the aetiopathogenesis of RA but do not account entirely for its determination.

A comparative study of the relative efficiency of the WOMAC, AIMS and HAQ instruments in evaluating the outcome of total knee arthroplasty

The relative efficiency of the WOMAC, AIMS, and HAQ instruments was compared in 21 patients with osteoarthritis who received total knee replacement surgery. Assessments of pain and physical function were made pre-operatively and 6 months post-operatively and the relative efficiency of the three instruments in detecting change was determined. Overall, the WOMAC Osteoarthritis Index was greater in relative efficiency than the HAQ and AIMS instruments, particularly in the detection of change in functional status. We conclude that the WOMAC Index can be used as an alternative to the HAQ or AIMS instruments in outcome assessment in osteoarthritis clinical trials.

Double-blind randomized controlled trial and six-year open follow-up of yttrium-90 radiosynovectomy versus triamcinolone hexacetonide in persistent rheumatoid knee synovitis

Knee joints (n=30) from 22 adult rheumatoid arthritis (RA) patients who were previously randomized and subjected to a six-month double-blind controlled trial of yttrium-90 vs. triamcinolone hexacetonide with a six-year follow-up. In contrast to most previous studies, there was no co-administration of a steroid agent at the time the radiopharmaceutical was injected. One month after treatment the triamcinolone group had less pain (p<0.05), fewer effusions (p<0.001) and a better range of movement (p<0.01) than the yttrium group. Six months after treatment, the response in the triamcinolone group had partially regressed but was still superior to that of the yttrium group (p<0.05). At the six-year follow-up, half the yttrium-treated knees were found to have required treatment by intra-articular steroid, surgical synovectomy or total knee arthroplasty. The rates for therapeutic success were no different for yttrium-90 or triamcinolone. These results bring into question the reported efficacy of yttrium-90 and suggest that the benefit observed in clinical practice may be dependent upon the co-administration of a corticosteroid agent, and that the long-term benefits of yttrium may be relatively small.

Etodolac in the management of pain: A clinical review of a multipurpose analgesic

Etodolac is a non-steroidal anti-inflammatory drug with analgesic properties. Its primary anti-inflammatory mechanism of action is through a selective effect on cyclo-oxygenase-2 (COX-2). It is rapidly absorbed after oral administration, and maximum plasma concentration (Cmax) is reached in 1-2 h, with an elimination half-life (t1/2 ) of 6-8 h.Etodolac has been widely applied in the treatment of inflammatory arthritides such as rheumatoid arthritis, ankylosing spondylitis and gout and in osteoarthritis and has been shown to be efficacious and well tolerated.However, etodolac has other applications which rely primarily on its efficacy as an analgesic. In particular, etodolac has been evaluated in the treatment of a variety of different pain states. Etodolac has been observed to be efficacious in the treatment of acute pain following dental extraction, orthopaedic and urological surgery, and episiotomy, as well as in the treatment of pain due to acute sports injuries, primary dysmenorrhoea, tendonitis, bursitis, periarthritis, radiculalgia and low back pain.These studies indicate that etodolac is a multipurpose analgesic with many clinical applications in addition to its use in the treatment of inflammatory and degenerative forms of arthritis.

Estimation of observer reliability and sample size calculation parameters for outcome measures in fibromyalgia clinical trials

AbstractBellamy N, Bell MJ, Carette S, Fam AG, Haraoui BW, McCain GA, Reynolds WJ, Wells GA, Campbell J. Estimation of observer reliability and sample size calculation parameters for outcome measures in fibromyalgia clinical trials. Inflammopharmacology. 1994;2:345-360.n Aims: To estimate the reliability of observer-dependent outcome measures and the variance and minimum clinically important difference parameters of observer-dependent and observer-independent outcome measures used in fibromyalgia clinical trials.n Methods: Three separate, but related, studies were conducted. In Study 1, the inter- and intra-observer reliability of 4 observer-dependent outcome measures (average [total] myalgic score, physician global assessment, skinfold tenderness, reactive hyperaemia) was determined. In Study 2, the variance of the 4 observer-dependent and 8 observer-independent outcome measures was estimated. In Study 3, the minimum clinically important difference (delta) for all outcome measures was estimated.n Results: Most inter- and intra-observer reliability coefficients were adequate for observer-dependent measures. The variance tables will be useful to clinical researchers in selecting which outcome measures to employ. When used in combination with the delta tables, sample size can be calculated for future fibromyalgia trials.n Conclusions: The data suggest that sample size requirements differ substantially for different outcome measures.

Statistical reappraisal of the clinical significance of nail beading in rheumatoid arthritis

Nail beading has previously been reported as an accompaniment of rheumatoid arthritis. In order to assess the clinical significance of this form of nychodystrophy the fingernails and toenails of 119 patients with rheumatoid arthritis and an equal number of control subjects were studied. Analysis of data based on 4642 nails indicates that the presence of a global pattern of beading (i.e. greater than or equal to 50% involvement of the nail area) on the surface of at least six fingernails or four toenails is highly suggestive of underlying rheumatoid disease. The positive predictive value of these configurations is in the order of 95%. Nail beading, however, is infrequent in early disease and therefore its diagnostic value is limited. Although there is a strong association between nail beading and rheumatoid arthritis, the aetiology and prognostic implications of this clinical sign remain obscure.