The long-term effects of non-steroidal anti-inflammatory drugs in osteoarthritis of the knee: a randomized placebo-controlled trial.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat osteoarthritis (OA), though their long-term efficacy is uncertain. We report a comparison of the symptomatic responses to therapy with tiaprofenic acid, indomethacin and placebo over 5 yr. METHODS: A parallel-group, randomized, single-blind trial of patients with knee OA recruited 812 patients from 20 centres; 307 patients received tiaprofenic acid (300 mg b.d.), 202 indomethacin (25 mg t.d.s.) and 303 matching placebo for up to 5 yr. At the end of the parallel-group study, patients receiving tiaprofenic acid or placebo entered a 4-week blinded cross-over study of tiaprofenic acid or placebo, both given for 2 weeks. Assessments were at baseline, 4 weeks, then at 6-month intervals for up to 5 yr in the parallel group study and at 2-week intervals in the cross-over study. They comprised pain scores, duration of morning stiffness, patients' global assessments, paracetamol consumption, adverse reactions, withdrawals and functional outcomes. RESULTS: There were significant falls in overall pain scores in patients receiving NSAIDs compared with placebo at 4 weeks in the parallel-group phase. Thereafter there were no advantages favouring active therapy. In the cross-over phase, pain scores were significantly lower in patients receiving tiaprofenic acid than placebo. Patients who had been receiving long-term tiaprofenic acid showed significant rises in their pain scores when receiving placebo therapy and vice versa. Adverse events were reported by 61% of patients receiving tiaprofenic acid, 63% on indomethacin and 51% on placebo. Potentially severe side-effects were rare; for example, there were only three cases of gastrointestinal bleeding on NSAIDs. The pattern of withdrawal was similar in patients taking NSAIDs and placebo in the parallel-group study; at 48 weeks 53% of the patients remained on tiaprofenic acid, 50% on indomethacin and 54% on placebo. CONCLUSIONS: NSAIDs significantly reduce overall pain over 4 weeks. This short-term responsiveness is retained, and even after several years of therapy with tiaprofenic acid pain scores increased over 2 weeks when it was changed to placebo. Our results do not show long-term benefits from the use of NSAIDs in OA and the majority of patients had persisting pain and disability despite therapy.

Hand performance assessment of ten people with rheumatoid arthritis when using a range of specified saucepans.

PURPOSE: The aim of the pilot study was to provide information about the design and use of saucepan handles to enable clinicians and designers to specify and provide products that are more appropriate for use by people with Rheumatoid Arthritis (RA). The objectives were: to evaluate aspects of new handle design for saucepans in terms of their ease of use for people with RA; document hand grip strength and configuration (grip patterns); record relevant anthropometric data to aid the development of new designs and perform an assessment of lifting techniques used in conjunction with perceived optimum handle configuration. METHOD/RESULTS: Observation and video footage show that subjects continued to use familiar, but damaging, ways of lifting the saucepan even after extensive joint protection training by occupational therapists. Grip strengths recorded using a sphygmomanometer were similar to those found by other studies. The anthropometric measurements taken from the sample group were found to be within available anthropometric surveys of able-bodied people. However, hand length within the sample group with RA was longer than the equivalent in surveys of able-bodied subjects. CONCLUSIONS: Subjects preferred the narrower handles with some surface texture to the larger and more rounded tapered handles. Large handled saucepans were found not to be viable due to the constraints of UK cooking hob sizes and existing British Standards relating to saucepan specification.

Role of opticare eye drop delivery system in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the prevalence of keratoconjunctivitis sicca in 340 patients with rheumatoid arthritis undergoing outpatient followup, and to assess their ability to use artificial tears, and the role of an aid to dispensing drops, the Opticare. METHODS: Initial questionnaire given to 340 patients based on preliminary criteria for classification of Sjögren's syndrome. Thirty symptomatic patients were invited to undergo objective and subjective assessment of the ability to instill artificial tears with and without the Opticare. RESULTS: One hundred twenty-seven (37%) patients had had symptoms lasting at least 3 months at some time, and 85 (25%) were currently symptomatic. Many patients found difficulty using artificial tears due to problems aiming and squeezing the bottles as a result of impaired upper limb function. The Opticare statistically significantly improved the ability to squeeze out drops and get them in the eye. CONCLUSION: The Opticare device allows patients with functional impairment of the upper limb to instill artificial tears, resulting in less wastage of tears and increased independence and compliance.

The use of rheumatoid factors in clinical practice.

Rheumatoid factor is a commonly requested test in the investigation of joint problems. Although the test has been found to be both sensitive and specific for rheumatoid arthritis in patients attending Rheumatology Clinics, when the test is applied to general hospital or community populations it performs poorly. Thus the setting in which rheumatoid factor tests are requested and awareness of the test's limitations are critical for appropriate use and interpretation of results. We studied 295 consecutive requests for testing at four centres. The majority were performed for the investigation of joint problems but only 6% of these were positive, suggesting unselective requesting. Half of the results were used to make diagnoses and influence management. However, significant numbers of clinicians felt that the test result had either excluded or confirmed a diagnosis of rheumatoid arthritis suggesting that results were being over-interpreted and that clinical decisions made on this basis may have been inappropriate. We conclude that in this setting rheumatoid factor testing is of limited value and generates misleading information.

Dermatomyositis presenting in pregnancy.

We report the onset of dermatomyositis in a woman pregnant 38-weeks who subsequently delivered a healthy infant. The disease improved rapidly following delivery. The association of dermatomyositis with pregnancy is unusual, and fetal outcome may be adversely affected.

The effects of joint washout and steroid injection compared with either joint washout or steroid injection alone in rheumatoid knee effusion.

Patients with rheumatoid arthritis attending rheumatology out-patients who had a symptomatic knee effusion were randomly allocated to receive one of three treatments: group I, a steroid injection without washout; group II, a joint washout with normal saline; group III, a joint washout with normal saline and steroid injection. Sixty knees in all were studied. Laboratory parameters for disease activity (erythrocyte sedimentation rate, C-reactive protein) were monitored in all patients prior to the study and at 3 months. Clinical assessment of disease activity (pain, morning stiffness involving the knee, circumference of the knee, walking distance and range of movement) were recorded prior to the study, at 1 month and at 3 months. All three treatments, resulted in a reduction of pain and increased movement. However, patients who had a joint washout alone showed significantly less improvement as compared with the other two groups. Symptomatic improvement was marginally greater in patients following joint washout and injection than in those who had had joint injection alone. The results of the study indicate that the simple procedure of joint aspiration and steroid injection, which can be carried out in the out-patient clinic, provides satisfactory relief of symptoms in rheumatoid patients with knee effusions. Joint washout alone was less beneficial.

Myositis and eosinophilia in a patient with sarcoidosis.

We present a patient with muscle manifestations of sarcoidosis associated with raised creatine kinase levels, eosinophilia and interstitial lung disease. She had significant improvement on prednisolone 30 mg per day.

A clinical, serological and neurophysiological study of restless legs syndrome in rheumatoid arthritis.

The restless legs syndrome (RLS), defined by Gibb and Lees criteria, was investigated in patients with RA. RLS symptoms were more frequent in RA patients (25%) than in non-RA controls with OA or seronegative arthropathy (4%). RLS was significantly more common in females. Judged by a variety of clinical and laboratory indices, RA disease severity and current disease activity were greater in patients with RLS than in RA patients unaffected by RLS. In five out of 14 RLS patients undergoing neurophysiological study, delays in the P40 component of posterior tibial somatosensory evoked potentials (SSEPs) were observed suggesting the existence of myelopathy, whilst in another four RLS patients evidence of peripheral neuropathy was found. Though the higher frequency of neurophysiological abnormalities in RA patients with RLS was not statistically significant, possibly because of the small numbers of patients studied, these data suggest that RLS symptoms in RA may reflect the presence of neurological disorder.

The incidence of acute arthritis in stroke patients, and its impact on rehabilitation.

To investigate the occurrence of acute arthritis after stroke, we prospectively studied 111 patients presenting with their first stroke and no history of previous arthritis. Clinical, biochemical and serological assessment was complemented by brain CT scan; appropriate X-rays were taken of any inflamed joints and synovial fluid was collected and analysed. Those with aseptic arthritis were randomly chosen to receive either intra-articular steroids or non-steroidal anti-inflammatory drugs (NSAIDs). Patients with significant renal impairment were excluded. Acute arthritis was observed within 8.34 (median) days, on the paretic side in 19 patients (10 crystal, 4 inflammatory osteoarthritis, 1 septic, 4 unexplained) and on the non-paretic side in 4 patients (1 inflammatory osteoarthritis, 1 septic, 2 unexplained). One patient had pseudogout affecting both sides. Thiazide therapy prior to the stroke was associated with gout in 3 patients. Hospital patients with arthritis had a longer median length of stay than those without (41 vs. 21 days: p = 0.01). Patients receiving intra-articular steroids recovered more rapidly than those treated with NSAIDs (p < 0.05). This prospective study demonstrates the occurrence of acute arthritis in paretic limbs after stroke. Physicians should be aware of this complication, and that administration of intra-articular steroids in aseptic cases speeds rehabilitation and recovery.

Pharmacokinetics of single oral doses of feprazone in patients with rheumatoid arthritis or with impaired renal clearance.

1. The pharmacokinetics of feprazone have been studied in 10 patients with rheumatoid arthritis (RA), and in a further six patients with renal impairment (RI) who were not suffering from rheumatoid disease. 2. For RA patients, the mean elimination half-life (t1/2) of feprazone after a single oral dose was 21 +/- 5 h (SD), the mean apparent clearance (Cl) was 0.012 +/- 0.009 l/h per kg, and the mean apparent volume of distribution (Vd) was 0.33 +/- 0.17 l/kg. Corresponding values for RI patients were 25 +/- 13 h, 0.016 +/- 0.011 l/h per kg, and 0.46 +/- 0.24 l/kg, respectively. 3. These results show no impairment of the elimination of feprazone in RA or RI patients; Vd and Cl are greater than in healthy young volunteers or elderly subjects, the AUC values are lower, but t1/2 values are similar in all groups. 4. It is suggested that the greater Cl and Vd, and lower AUC, in RA and RI patients may be due to renal insufficiency and decreased plasma protein binding of feprazone and its metabolite, or to induction of glucuronyl transferase activity by the prior medication, thus enhancing the formation of the major metabolite, the C(4)-glucuronide, and increasing drug elimination.

Shoulder joint movement and its relationship to disability in the elderly.

One hundred healthy subjects over the age of 65 years were interviewed and examined. The range of movement of their shoulder joints was recorded. Assessment of the prevalence of symptomatic shoulder joint disorders and their nature was also made. The impact of the presence and severity of such disorders on their functional independence was evaluated by means of the Katz Scale of Index of Independence in the Activities of Daily Living. Ranges of all movements were considerably reduced in this age group compared to figures for a younger population. The prevalence of symptomatic shoulder disorders was 34% of which a rotator cuff lesion was the most common. Disability related to these disorders was found in 30% of the study population and was significantly associated with reduced movement. It is suggested that treatment of these disorders might improve quality of life and that routine examination of the shoulder in the aging population would identify those at risk of losing their independence.

A longitudinal study of pulmonary function in patients with rheumatoid arthritis treated with gold and D-penicillamine.

Sixty-two patients with classical or definite RA who were considered suitable for disease-modifying drug therapy were entered into a prospective longitudinal study to determine the long-term effects of commonly used drugs such as gold, D-penicillamine and azathioprine on pulmonary function. Each patient had an assessment of pulmonary function, including spirometry, static lung volumes and diffusion tests, before starting drug therapy and at 6-monthly intervals during treatment. In those patients where drug therapy was discontinued, pulmonary functions were performed at withdrawal and 1 year later. Forty-six per cent of the patients in the 'gold group' and 21% in the 'penicillamine group' had developed a restrictive defect after 2 years. There was a significant reduction in vital capacity and transfer factor for carbon monoxide (P < 0.001) in both groups. A significant improvement in pulmonary function was found in the gold-treated patients (P < 0.05) a year after treatment was discontinued. This study shows that a significant proportion of rheumatoid patients on second-line drugs such as gold and penicillamine develop chronic progressive pulmonary damage indistinguishable from fibrosing alveolitis or 'rheumatoid lung'. Its recognition is important as the condition is asymptomatic, slowly progressive and appears to be reversible on withdrawal of the drug therapy in the majority of the patients.

Monarthritis: an unusual presentation of renal cell carcinoma.

Two cases of acute monarthritis secondary to asymptomatic renal cell carcinoma are described. This association has not previously been reported. The patients were initially thought to have a septic arthritis, but hot spots were seen on isotope bone scans and biopsy samples showed secondary neoplasms, which were later confirmed to be a result of renal cell carcinomas. The value of cytological examination of synovial fluid when there is clinical doubt as to the cause of a joint effusion is shown.

Antibodies to cardiolipin in stroke: association with mortality and functional recovery in patients without systemic lupus erythematosus.

Antibodies to cardiolipin were measured in 100 consecutive patients with first ever stroke, on admission and at three and six months after the acute event. One hundred healthy, age- and sex-matched, British elderly individuals were also screened for antibodies to cardiolipin as a control group. Elevated levels of anticardiolipin antibody (i.e. 5 SD above the laboratory control mean) were present in none of the control group, but in 21 per cent of the patients with stroke. Thirteen of these 21 patients (62 per cent) died within three months, compared to 17 (21.5 per cent) of the seventy-nine patients without elevated levels of anticardiolipin antibodies (p less than 0.001). Six of the eight survivors with persistently elevated anticardiolipin antibodies had significant residual disability following stroke (Barthel score 0-9) compared to 11 of the 62 without (p less than 0.001). Two patients with initially raised anticardiolipin antibodies who became independent at six months showed a progressive decline in the level of these antibodies to normal. The presence of high levels of anticardiolipin antibody did not correlate with other recognized prognostic indices of stroke, except for incontinence. No correlation was noted between levels of antibody to cardiolipin, antinuclear factor, antibody to double-stranded DNA and C-reactive protein, either in the stroke patients or in the elderly control population. Hypertension was significantly more common in the patients with high anticardiolipin antibodies than in the rest of the patients in the stroke population (p = 0.33). There was no correlation between levels of anticardiolipin antibody and age. Anticardiolipin antibody may be considered as an independent prognostic marker for both mortality and clinical outcome after acute stroke.

Prevalence of anticardiolipin antibodies in the elderly British population.

In a cross-sectional study of 100 healthy elderly individuals, anticardiolipin antibodies (aCL) were measured using an ELISA technique. aCL were not detected in the majority of subjects (63%), and in the remaining 37% titres were within the laboratory reference range (mean +5 standard deviations) previously determined for adults of all ages. In contrast, significant titres of IgM rheumatoid factor were found in 10%, antimitochondrial antibody in 13%, antinuclear factor in 5%, anti-smooth muscle antibody in 18%, antiparietal cell antibody in 10%, and antireticulin antibody in 1%. Antibodies to single or double-stranded DNA were not detected in any subject. We conclude that, although other auto-antibodies may be present in the healthy aging population in Britain, abnormally elevated levels of aCL antibody do not occur, and when present may be an indicator of autoimmune-mediated pathology.

A comparative study of nabumetone and indomethacin in ankylosing spondylitis.

Forty-two patients with ankylosing spondylitis were entered into a double-blind study to compare treatment with indomethacin and a new non-steroidal anti-inflammatory drug, nabumetone. Clinical, laboratory and side-effect profiles were measured over a three month period. Both drugs were effective in relieving pain and morning stiffness, indomethacin was better in alleviating general stiffness, nabumetone resulted in less side-effects. Objective measurements of spinal movements revealed no difference between the two drugs. Nabumetone, available as Relifex, appears as effective as indomethacin in relieving the symptoms of ankylosing spondylitis and is possibly better tolerated.

Elbow synovectomy and excision of the radial head in rheumatoid arthritis: a short term palliative procedure.

We present the results of synovectomy and excision of the radial head in 65 elbows affected by rheumatoid arthritis. Eighty-four percent of elbows had good pain relief 6 months after operation but after an average of 5 years only 54% remained relatively pain-free. Range of motion remained the same or improved in the majority of patients. Synovitis occurred in 39% of elbows during the followup period and intraarticular steroid injections were frequently given. This undoubtedly modified results of pain relief that might have been attributed to the operation. Destructive changes in the humeroulnar joint were considered the main cause of elbow pain at the time of review.