E. C. Huskisson

Graphic representation of pain.

&NA; Of the different types of visual analogue and graphic rating scales tested in a series of experiments, only two were satisfactory: these were the visual analogue scale and the graphic rating scales used horizontally with the words spread out along the whole length of the line. Other types of scale used gave distributions of results which were not uniform. Unusual distribution of results occurred when patients selected a position adjacent either to descriptive terms or preferred numbers. In some experiments, the distribution of results was determined by the nature of the experiment. Alternation of the ends of a scale did not affect the results. The behaviour of the graphic rating scale was different in patients accustomed to completing it and in those not so accustomed. The results of pain severity measured by these methods showed a very good correlation with pain severity measured by the simple descriptive pain scale. Changes in visual analogue scores also correlated well with changes in simple descriptive pain scores. The visual analogue and graphic rating scales were more sensitive than the traditional simple descriptive pain scale. Most patients could readily use visual analogue and graphic rating scales despite having no previous experience. The failure rate was slightly lower with the graphic rating method. Use of these scales is the best available method for measuring pain or pain relief.

Radiological progression of osteoarthritis: an 11 year follow up study of the knee.

A follow up study was carried out in 1990 on 169 well documented patients initially presenting with osteoarthritis of the hands or knees between 1975 and 1977. Radiographic change in the knee was used as the outcome measure. Sixty three subjects had paired knee radiographs a mean of 11 years apart and were 69 (range 52-87) years old at follow up. Thirty subjects were known to have died, 28 were untraceable, and 48 were traced but did not have paired films available. The films were read independently and blind to time sequence by two observers using five different radiological scoring methods. Most of the knees did not increase in Kellgren and Lawrence grade, with only 33% deteriorating over the time period. The results were similar when a subject was categorised by their worst knee. When a more sensitive global score on paired films was used 50% of knees showed a slight deterioration and 10% improved. Visual analogue pain scores remained unchanged. Those with knee pain at baseline had a greater chance of progressing, as did those with existing osteoarthritis in the contralateral knee. These results suggest that most patients with osteoarthritis attending rheumatology clinics do not deteriorate radiographically or symptomatically over an 11 year period. More work is needed in the selection and early detection of subjects with a poor prognosis and in focusing early intervention on this high risk group.

Four new anti-inflammatory drugs: responses and variations.

Ninety patients with rheumatoid arthritis completed a double-blind crossover trial comparing fenoprofen, ibuprofen, ketoprofen, and naproxen. Fenoprofen and naproxen were slightly more effective than the other two drugs but there were striking individual variations in response. Groups of patients could be identified who preferred each of the four drugs. The commonest side effects were those related to the upper gastrointestinal tract; these showed individual variation and seldom occurred with more than one or two of the drugs. Side effects were least common with ibuprofen and naproxen.Since naproxen combined greater effectiveness with a lower incidence of side effects it must be regarded as the first choice among these drugs. It may be necessary to try several drugs before finding the right one for a particular patient.

An articular index for the assessment of osteoarthritis.

An articular index was devised for the sequential assessment of patients with osteoarthritis (OA). Forty-eight joint units, chosen to reflect the characteristic pattern of the disease, were scored for tenderness on pressure or movement on a 4-point scale. Four observers examined patients to assess inter- and intraobserver error. The index was highly reproducible both within and between observers; intraobserver error was, however, significantly smaller. In a double-blind, cross-over trial the index was sufficiently sensitive to detect a statistically significant difference between the responses of patients with OA to an anti-inflammatory agent and to a simple analgesic. It is likely to be a useful addition to current methods of measurement in osteoarthritis.

Non-steroidal anti-inflammatory drugs current status and rational therapeutic use

SummaryAspirin (acetylsalicylic acid), the first of the NSAIDs (introduced in 1899), was initially never referred to as an anti-inflammatory agent. It was the advent of cortisone in 1949 that demonstrated dramatically that corticosteroids had anti-inflammatory properties and the term ‘non-steroidal anti-inflammatory drug’ was first used when phenylbutazone was introduced 3 years later. Since then, the NSAIDs have proliferated. There is to date no good evidence that they halt progression of rheumatoid disease, but by easing pain and diminishing swelling they make life much easier in osteoarthrosis, rheumatoid arthritis and many other types of arthritis, and are the drugs of first choice in acute gout. Their mode (or modes) of action are obscure and though inhibition of cyclo-oxygenase (prostaglandin synthetase) is clearly important, other mechanisms are also involved.The assessment of the anti-inflammatory action of these agents has received considerable attention in clinical trials because, whatever their action may be in experimental animal models, their action in inflamed joints in human patients must be ascertained, since there may be little parallel between the two. Different experimental animal models give different results with various agents and often bear little relation to their therapeutic action in man. No attempt has been made here to review in depth all the NSAIDs that have appeared since 1952. All have anti-inflammatory and analgesic activity and all can cause gastrointestinal side effects, though effectiveness and toxicity vary from drug to drug and patient to patient, there being very great interpatient variability. Non-reactors, patients who apparently fail to respond to certain agents, need further study, for it seems that these subjects may metabolise these agents differently from others.Considerable ingenuity has been shown not only in evolving new NSAIDs but in finding new ways of administering them. The number and variety of NSAIDs in their various forms varies greatly from country to country, depending largely on the regulatory bodies of those countries. In the meantime, the search for a better, less toxic compound continues with the hope that one may be found which has a deeper and more basic action on the underlying disease process.

Treatment of rheumatoid arthritis with fenoprofen: comparison with aspirin.

Fenoprofen, a compound with analgesic, anti-inflammatory, and antipyretic properties in animals, has been compared with placebo in a double-blind cross-over trial in 60 patients with rheumatoid arthritis. There was a statistically highly significant reduction in pain, duration of morning stiffness, analgesic requirements, and articular index, with increase in grip strength. There was no significant reduction in joint size or temperature. In a subsequent double-blind group-comparative study fenoprofen proved to be as effective as aspirin in relieving the symptoms of rheumatoid arthritis, with strikingly fewer side effects. Almost half of the patients taking aspirin were unable to tolerate the drug in adequate dosage for six months. The remainder were able to take on average only 4 g daily, and at this dose almost half still complained of tinnitus and deafness. Fenoprofen is likely to be useful for patients who cannot tolerate aspirin and other more toxic anti-inflammatory drugs or whose disease is not of sufficient severity to justify their use.

Mixed crystal deposition disease and osteoarthritis.

tumour with metastatic deposits in the liver and mesenteric lymph nodes. Preoperative alphaand beta-adrenoreceptor blockade was not used, and biopsy of both primary and secondary tumour tissue produced short bursts of hypertension and extrasystoles. On her return to the intensive care unit her blood pressure rose to 240/140 mm Hg. Labetalol (50 mg), a drug with both alphaand beta-blocking activity, was given intravenously, and continuous monitoring showed a fall in blood pressure to 75/50 mm Hg over three to four minutes. There was an increase in finger pulse volume (as detected by a Philips infrared sensor) but no change in heart rate. Pethidine 50 mg, given intravenously at this time and during two other short periods of labetalol infusion in the first 24 hours after operation, caused no change in blood pressure. It was noticed, however, on subsequent examination of the trace, that in the absence of labetalol, pethidine had produced a rise in systolic pressure of 30-80 mm Hg and in diastolic pressure of 10-30 mm Hg (see figure). The maximum pressures developed over four minutes and lasted about 10 minutes. Five episodes were recorded and in three a slight drop in blood pressure lasting 10 seconds preceded the rise. The hypertension was accompanied by a simultaneous decrease in finger pulse volume.

Measurement in rheumatoid arthritis.

Abstract The proper use of drugs in clinical practice is based on accurate assessment in carefully designed trials using validated methods of measurement. Such trials are becoming increasingly important in the current pharmaceutical scene.

Pertussis vaccine oedema: an experimental model for the action of penicillamine-like drugs.

A delayed hypersensitivity response was induced in the rat paw using pertussis vaccine. Oedema was measured after the challenging injection.d-Penicillamine and levamisole enhanced the response, while indomethacin suppressed it. This model is useful to distinguish the effects of antiinflammatory drugs from those liked-penicillamine which have a specific activity in rheumatoid arthritis.

D-penicillamine and immune complex deposition.

Dense, granular immunoglobulin deposits have been identified at the epidermo-dermal junction in 4 out of 10 patients who developed toxic reactions to D-penicillamine therapy for rheumatoid arthritis. Three of 4 patients developing a lupus-like syndrome while on penicillamine had similar findings on skin biopsy. Serum immunoglobulin and complement levels decreased significantly in patients treated with penicillamine. It is suggested that, in addition to penicillamine nephropathy, other side effects of this drug may be related to widespread deposition of immune complexes.