Rosuvastatin might have an effect on C-reactive protein but not on rheumatoid disease activity: Tayside randomized controlled study.

The aim of this study was to study the effects of rosuvastatin in patients with rheumatoid arthritis (RA) looking at the C-reactive protein (CRP), interleukin-6 (IL-6) and joint disease activity. Fifty RA patients were randomized in a double-blind placebo-controlled trial to receive either 10 mg of rosuvastatin or placebo as an adjunct to existing disease-modifying antirheumatic therapy. Patients were followed up for a six-month period. Measurements were done at baseline and six months. CRP and IL-6 were measured in the blood. RA disease activity was measured using disease activity score based on 28 joint counts (DAS 28). When analysing from baseline to six months there was no difference between the rosuvastatin and placebo groups in rheumatoid disease activity (-0.01; standard deviation [SD], 1.08; and +0.18; SD, 0.95; respectively; P value 0.509). There was a trend towards improvement in CRP in the rosuvastatin group (-3.23; SD, 18.18) compared with the placebo group (+17.43; SD, 38.03); P value, 0.161. IL-6 showed a trend towards worsening in the rosuvastatin group (+0.15; SD, 1.09) compared with placebo (-0.73; SD, 1.4); P value, 0.054. These data show that rosuvastatin with might decrease the CRP independent to IL-6 in patients with RA but does not improve the overall rheumatoid disease activity.

C-reactive protein: the underlying cause of microvascular dysfunction in rheumatoid arthritis.

OBJECTIVE: RA is a chronic autoimmune inflammatory condition associated with increased cardiovascular morbidity and mortality. Endothelial dysfunction, a marker of early atherosclerotic disease, occurs in some inflammatory diseases but this relationship has not been previously explored within the microvasculature of patients with RA. We therefore assessed forearm microvascular endothelial function in patients with RA and determined its relationship to RA disease activity and inflammation. METHODS: A total of 128 RA patients with no previous history of cardiovascular disease were evaluated. Endothelium-dependent and -independent forearm skin microvascular function was measured using laser Doppler imaging after iontophoretic delivery of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. Parameters of RA disease activity and inflammation were also checked. RESULTS: There was a significant negative correlation between the level of inflammation measured by log(10)CRP and maximum vasodilatation measured by peak ACh response (r(2) = -0.209, P = 0.018, Pearson correlation test). In a multiple regression model, age (beta = -0.449, P < 0.0001) and log(10)CRP (beta = -0.193, P = 0.026) were independently negatively associated with ACh responses. When RA patients were sub-divided according to their systemic inflammatory status (CRP > 10 mg/l vs CRP

Time to stop counting the tablets?

We attempted to assess compliance using both a pharmacologic indicator (low-dose phenobarbital) and a return tablet count in 225 patients who were taking part in three separate studies. There were 216 patients (96%) who kept a follow-up appointment after 28 days; 161 patients appeared to have good compliance (90% to 109%) by return tablet count. Of these 161 patients, 51 (32%) had plasma phenobarbital concentrations (corrected for dose and weight) that were less than 90% of the lowest value previously found in normal volunteers, which suggested poorer compliance. When compared with the age-related volunteer values, 77 (48%) had values that were less than 90% of the lowest volunteer value. There were 6 of 10 patients with apparently excessive (greater than or equal to 110%) compliance by return tablet count and 4 of 12 who failed to return their container who also had phenobarbital concentrations that were less than 90% of the lowest volunteer value. We concluded that return tablet count grossly overestimates compliance.

Use of a pharmacologic indicator to compare compliance with tablets prescribed to be taken once, twice, or three times daily.

By use of an interview, return tablet count, and a pharmacologic indicator (low-dose phenobarbital), we compared compliance with tablets prescribed to be taken once, twice, or three times daily. One hundred seventy-nine patients with type II diabetes were randomly allocated to take one 2 mg phenobarbital tablet once, twice, or three times daily for 28 days. Phenobarbital level/dose ratios indicated that compliance was similar with once- and twice-daily regimens, and both were better than thrice-daily dosing. Mean return tablet counts suggested that compliance was best with the once-daily regimen; both twice- and thrice-daily regimens were similarly inferior. This difference between the techniques may be explained by the inadequacies of the residual tablet count, which identified only 13% of cases identified by phenobarbital. We conclude that compliance with the once-daily regimen was best, but that compliance with a twice-daily regimen was very similar, and both were superior to dosing three times a day.

Variables affecting efficacy and toxicity of sulphasalazine in rheumatoid arthritis. A review.

Studies of sulphasalazine in rheumatoid arthritis have used largely empirical doses. The available literature suggests that the optimum dose appears to be greater than 40 mg/kg/day. Despite the relationship between dose and efficacy and a good correlation between dose and serum concentrations of sulphasalazine and its metabolites, no relationship has been demonstrated between efficacy and serum concentrations of sulphasalazine or its metabolites, although there is some suggestion that higher concentrations on single dosing are achieved in patients who develop upper gastrointestinal symptoms. Furthermore, acetylator phenotype does not affect efficacy, although upper gastrointestinal symptoms are more common in slow acetylators.

Comparison of white blood cell dyscrasias during sulphasalazine therapy of rheumatoid arthritis and inflammatory bowel disease.

A total of 7 out of 158 rheumatoid arthritis patients followed for 6 months have developed leucopenia during sulphasalazine therapy at our centre. Two of these patients developed profound leucopenia which necessitated admission to a laminar flow unit, and case reports of these are documented in detail. These results are compared with those from other centres in the United Kingdom where patients with rheumatoid arthritis have been treated, and also with experience gained from patients with inflammatory bowel disease who have been treated with sulphasalazine.

Chest wall tenderness is unhelpful in the diagnosis of recurrent chest pain.

We investigated whether the presence of chest wall tenderness or fibromyalgia helped to distinguish between ischaemic and non-ischaemic chest pain. Seventy-one patients with recurrent chest pain, 36 with normal (group A) and 35 with abnormal coronary angiograms (group B), were assessed by investigator-administered questionnaires, and were examined for chest wall tenderness and fibromyalgia by a single blinded observer. Chest wall tenderness was greater in group A. However, it was much greater in women, who predominated in group A, than in men, who predominated in group B, and this explained the intergroup difference. Seven patients (25%) (six female, one male) in the group A and one patient (3%) (male) in group B (chi(2) p=0.027) fulfilled criteria for fibromyalgia. Patients with recurrent chest pain are more likely to have a ischaemic cause if they are male. Although our study suggests that chest wall tenderness alone in patients with recurrent chest pain has no value in excluding myocardial ischaemia as a cause, the confounding factor of gender prevents our study design from answering this question conclusively. Fibromyalgia is commoner in patients with chest pain and normal coronary angiograms, but may be related to the excess of females in this group. Its presence does not preclude the co-existence of ischaemic heart disease.

The prevalence and significance of positive antinuclear antibodies in patients with fibromyalgia syndrome: 2-4 years' follow-up.

The aim of this study was to ascertain whether fibromyalgia patients with positive ANA develop other features of connective tissue disease over 2-4 years' follow-up. Patients attending our clinic with a diagnosis of fibromyalgia were identified. All ANA-positive patients (n = 12) were recruited and matched for age and sex with 12 ANA-negative FMS patients. As further control groups, patients with a diagnosis of osteoarthritis (OA) were included. A screening questionnaire for possible features of connective tissue disease was sent to all participants. Patients who had three or more positive criteria were invited for further assessment. The ANA-positive rate was 12/137 (8.8%) in FMS and 20/225 (8.9%) in OA patients. All ANA positivity was at a low titre. Fourteen out of 20 (70%) FMS patients and 17/30 (56.7%) OA patients had three or more criteria (P = 0.34). No significant differences in the number of the positive criteria were found between those who were ANA positive or negative in both groups. On full assessment we found one patient who fulfilled the criteria for SLE from the ANA-positive FMS group and one in the ANA-negative group who fulfilled the criteria for primary Sjögren's syndrome. Of the patients with OA, one who was ANA positive was diagnosed as having rheumatoid arthritis. The results from our study show that ANA (at least in low titre) is not a good predictor of the future development of connective tissue.

Second line therapy in rheumatoid arthritis--a four year prospective study.

One hundred and twenty-three rheumatoid patients were commenced on one of the three second-line agents: sodium aurothiomalate (GST), penicillamine (P), or levamisole (L). After four years, 39% of the GST group, 20% of the penicillamine group, and 8% of the levamisole group remained on the original agent. Fifty five % of patients, however, were receiving some second-line agent at four years, and patients showed an improvement in inflammatory indices irrespective of whether or not they were still receiving second-line therapy. It is unclear whether this improvement reflects the natural history of the disease, or the fact that regular clinic attendance identifies patients who require further second-line therapy following cessation of the initial agent.

Spontaneous fractured neck of femur in rheumatoid arthritis: absence of radiographic changes on initial X-ray.

Spontaneous fractures have been documented in patients with osteoporosis and have been described in patients with rheumatoid arthritis. Two patients with rheumatoid arthritis who sustained femoral neck fractures in the absence of trauma are documented. Despite severe pain initial radiograph failed to demonstrate evidence of fracture, but subsequent radiographs later showed fractures in both cases. It is important in rheumatoid patients with continuing severe hip pain of sudden onset to suspect a stress fracture even if initial radiographs are normal.

Assessment and referral patterns of patients admitted after deliberate self-poisoning.

The assessment and referral patterns of adult patients after deliberate self-poisoning in Dundee were examined. Questionnaires were completed by the admitting physicians and assessing psychiatrists over a 3 month period. Demographic data concerning the patients and the nature of self-harm were similar to previous studies. Initial referral rate was 95% but dropped to between 70% and 81% after the post receiving round. Up to 2 hours/day could be required for assessment and 75% of the cases required some form of psychiatric follow-up. Although both groups of doctors considered that the majority of patients required or would benefit from psychiatric referral, there was poor agreement when patients were independently categorised into high or low suicide risk (kappa = 0.04). Agreement was also low regarding whether referral was essential or not (kappa = 0.06). Although junior medical staff can play an important role in screening of patients, the psychiatric service, including trained nurses, may be best placed to provide a full assessment, where required.

General practitioner assistance with gold and penicillamine therapy of rheumatoid arthritis--a four year prospective study.

One hundred patients with active rheumatoid arthritis, uncontrolled by symptom relieving agents, were allocated randomly to intramuscular gold or oral penicillamine therapy. Their general practitioners (97 in all) were requested to assist with blood, urine, skin and mucous membrane monitoring. After four years, 16 patients in each treatment group remained on their original therapy, and three-quarters of these continued attending their family doctor for toxicity monitoring. Most GP monitoring problems occurred in the first six months of treatment. Sustained improvement in haemoglobin and ESR was seen in both treatment groups. Second-line drug toxicity monitoring by general practitioners allows specialist time to be diverted to rheumatological problem solving but may make it more difficult to relate rare but serious adverse adverse events to drug therapy.

Have the newer NSAIDS contributed to the management of rheumatoid arthritis?

Approximately 30 non-steroidal anti-inflammatory agents are available for the treatment of rheumatoid arthritis. In this study patient acceptability of five such agents (benoxaprofen, fenbufen, feprazone, flurbiprofen, ketoprofen) is compared in groups of 50 patients with rheumatoid arthritis. Less than 40 per cent of patients continued on the prescribed drug for six months. Significantly more patients stopped fenbufen than stopped feprazone, otherwise dropout rates between the groups were similar. The overall efficacy and toxicity of most currently prescribed NSAIDs appear to be similar, and the availability of a surfeit of such agents dilutes clinical experience with any one drug. Despite subsequent events this method failed to differentiate benoxaprofen from the other agents. It would seem likely that this surfeit of similar drugs hinders detection of unusual complications, and impedes satisfactory management of inflammatory rheumatic disorders.

Compliance with drug therapy.

Although no single method is ideal for measuring compliance the methods now available allow accurate assessment of compliance in most settings. Studies using new and more accurate methods of measuring compliance have shown poor compliance to be an even greater problem than was previously thought. Using these methods, efforts in the future should be directed at relating compliance to treatment outcome, and investigating whether manoeuvres aimed at improving compliance actually improve patient outcome.