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J R Kirwan

Publications and source records attributed to J R Kirwan.

At least 19 recordsLinked to original sources
PubMed2000

Non-aspirin, non-steroidal anti-inflammatory drugs for osteoarthritis of the knee.

OBJECTIVES: To determine whether there is a difference in the relative efficacy of individual non-steroidal anti-inflammatory drugs (NSAIDs) when used in the management of osteoarthritis (OA) of the knee. SEARCH STRATEGY: We searched Medline (1966-1995) and Bids Embase (Jan-Dec, 1980-1995). The searches were limited to publications in the English language, and were last perfomed in November 1996. We used modified Cochrane Collaboration search strategy to identify all randomised controlled trials. The MeSH heading osteoarthritis was combined with the generic names of the 17 non-aspirin NSAIDs licensed in the UK for the management of OA in general practice. The search of Embase used the term "osteoarthritis" if present in the abstract, title or keywords, and was combined with the generic names of the 17 non-aspirin NSAIDs, only if they were mentioned in the title, abstract or keywords. SELECTION CRITERIA: All double blind, randomised controlled trials, in the English language, comparing the efficacy of two non-aspirin NSAIDs in the management of osteoarthritis of the knee, were selected. Only trials with subjects aged 16 years and over, with clinical and/or radiological confirmation of the diagnosis of OA knee were included. Studies which compared one "trial" NSAID with one "reference" NSAID were included provided they were non-aspirin NSAIDs available in the UK and were licensed for the treatment of OA by general practitioners. Trials which were placebo-controlled and which also involved the comparison of two NSAIDs were also included. DATA COLLECTION AND ANALYSIS: The methodological design of each study was scored according to a pre-determined system. The three main outcome measures of pain, physical function and patient global assessment were chosen based on the core set agreed upon by OMERACT (Outcome Measures in Rheumatology Clinical Trials). These were used to determine the power of each trial. The equivalency of NSAID doses was calculated using the percentage of the recommended maximum daily dose. Sample size estimates for the detection of clinically relevant changes in outcome measures used in the assessment of OA knee were used for power calculations. These calculations were performed to determine whether the trials were of a sufficient size to detect clinically relevant differences which were statistically significant. The calculations incorporate estimates of standard deviation, and minimum, median and maximum differences (delta) between drugs which are deemed to be clinically important. The number of "withdrawals due to lack of efficacy" was also selected as an outcome measure for this review. The Peto odds ratio and 95% confidence intervals were calculated where possible. The results of studies which compared the same trial and reference NSAIDs were combined where possible. MAIN RESULTS: Of the 1151 trials identified by the search strategy, 22 involved knee osteoarthritis only. Sixteen of these trials fulfilled the inclusion criteria and were entered in the review. Eight NSAIDs were represented in these trials. Etodolac was represented in 11 trials. The reference NSAID in these trials was piroxicam (n=3), naproxen(n=3), diclofenac (n=3), indomethacin (n=1), and, nabumetone (n=1). The reported methodological design of the trials was poor, with a median score of 3 (out of a maximum of 8). The results of the trials comparing the same trial and reference NSAIDs were pooled for the outcome "withdrawal due to lack of efficacy". For the comparison, etodolac vesus piroxicam, the odds ratio favoured etodolac i.e. patients receiving etodolac were less likely to withdraw due to lack of efficacy. The dose of etodolac used in each of these three studies, however, was greater than the corresponding dose of piroxicam (based on percentage maximum daily dose). The significance of these results is therefore questionable. For the comparisons etodolac versus diclofenac, and etodolac versus naproxen, there were no clear differences betw

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Effects of long-term glucocorticoid therapy in rheumatoid arthritis.

Radiographic erosions develop in about two thirds of patients with rheumatoid arthritis (RA). Glucocorticoids offer rapid and substantial control of the symptoms of inflammation in the short and medium term. Data are reviewed which suggest that this benefit may not last into the longer term (more than 1 year). However, recent studies provide unequivocal evidence that joint destruction can be halted in this disease. Also, by separating the short-term anti-inflammatory effect from a more prolonged suppression of joint destruction, these studies have shed light on the underlying pathological processes. The evidence from these therapeutic clinical trials strengthens the view that inflammation and joint destruction are parallel processes, loosely linked by the underlying cause of RA, but progressing to some extent independently. It is intriguing to speculate that different effects of glucocorticoids might relate to their different modes of action outlined elsewhere in this symposium.

Arthritis, Rheumatoid↗
PubMed2000

Relationship between disease severity and responses by blood mononuclear cells from patients with rheumatoid arthritis to human heat-shock protein 60.

The hypothesis that T-cell responses to the 60 000 MW family of heat-shock proteins (hsp) may be related to the severity of rheumatoid arthritis (RA) was examined. Peripheral blood mononuclear cells (PBMC) from most normal individuals and both early and established RA patients proliferated in vitro in response to human hsp 60 and mycobacterial hsp 65 as well as tetanus toxoid (TT) and mycobacterial purified protein derivative (PPD). PBMC from some patients with established RA gave responses to hsp 60 that were above the normal range and/or peaked earlier than PBMC from normal individuals. The responses of PBMC from established RA to hsp 65, but not PPD or TT, were also higher than those from normal individuals, but the peak responses to all three antigens appeared delayed. Thus a selective increase in responsiveness to hsp 60 develops with disease duration in many RA patients. Six assessments of disease activity and severity were made but apart from rheumatoid factor titre, they were unrelated to the proliferative response. Similarly, disease activity and severity did not differ between those RA patients whose hsp 60 stimulated cells produced interferon-gamma and those who did not, although patients whose hsp 60-stimulated T cells produced interleukin-4 (IL-4) and/or IL-10, appeared to have less disease activity and severity than those who did not. Significant negative correlations were found between IL-10 production by hsp 60-stimulated cells and disease assessments. It is considered that RA is less severe in those patients whose hsp 60-stimulated cells produce T-helper 2 type cytokines.

Adult↗
PubMed2000

Focal myositis - a new presentation.

This article is a case report and review of literature of a very rare condition, not previously written in general surgical literature, including a new presentation

Adult↗
PubMed2000

Patient-initiated hospital follow-up for rheumatoid arthritis.

OBJECTIVES: To evaluate the clinical efficacy, cost and acceptability of a shared care system of patient- or general practitioner (GP)-initiated hospital review in rheumatoid arthritis (RA). METHODS: A 2-yr randomized controlled trial of routine rheumatologist-initiated review was compared with a shared care system. Shared care patients had no routine follow-up but patients or GPs initiated access to rapid review by the multidisciplinary team via a nurse-run helpline. Control patients had a rheumatologist-initiated medical review at intervals of 3-6 months. Clinical and psychological status, resource use, and patient and GP satisfaction and confidence were assessed. Three-monthly clinical data were assessed (blind) for safety monitoring, with failure set at a 20% increase in pain, disability or disease activity. RESULTS: Two hundred and nine established RA patients participated, of whom 182 were evaluable. Safety-net failures were not different between groups. Shared care patients had less pain (24 months, 3.9 cm on a 10-cm visual analogue scale vs 4.8 cm for controls; P: < 0.05), a smaller increase in pain over 2 yr (+ 0.4 cm vs +1.6 cm for controls; P: < 0.01), greater self-efficacy (6, 15, 18, 21 months, P: < 0.05), used 33.5% less resources (208 ponds sterling per patient per year vs 313 pound sterling for controls; P: < 0.001) and were more confident in the system (6, 9, 12, 18, 21, 24 months, P: < 0.01 to P: < 0.001). CONCLUSIONS: A patient-initiated system for hospital review over 2 yr offers some clinical benefit compared with the traditional system, using fewer resources and attracting greater patient confidence. Longer-term assessment of the system would be appropriate.

Aged↗
PubMed2000

Increased serum C reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee.

OBJECTIVE: Raised serum C reactive protein (CRP) and hyaluronate (HA) concentrations predict the progression of knee osteoarthritis (OA) in the long term but the consistency of these relations with time is unknown. The purpose of this work was therefore to determine if raised CRP and HA at entry and three years before entry (-3 years) predict radiological progression of knee OA in a group of patients between entry and five years. METHODS: Knee radiographs from 90 patients with knee OA at entry and five years follow up were assessed for progression of disease over five years. The concentrations of serum CRP and HA were measured at entry (n=90) and also in 40 serum samples available from -3 years. Odds ratios (OR) for predicting progression were calculated by logistic regression. RESULTS: Serum CRP at entry was not predictive of progression between entry and five years (OR 1.12, 95% CI 0.81, 1.55) but serum CRP at -3 years was predictive of progression (OR 1.90, 95% CI 1.01, 3.28). Serum HA concentration at entry predicted progression between entry and five years (OR 2.32, 95% CI 1.16, 4.66). CONCLUSION: These results are consistent with previous reports relating to HA, and suggest that raised serum CRP reflects events that precede a period of later radiographic progression in knee OA. However, because of the large overlap between groups, the serum CRP or HA concentration are not good predictors of individual patient progression and have a poor sensitivity and specificity.

Aged↗
PubMed2000

Using the Larsen index to assess radiographic progression in rheumatoid arthritis.

To describe the Larsen index and its strengths and weaknesses. I reviewed the original publication, a number of published modifications, tests of reproducibility, and some clinical studies that have used the index. The Larsen index is essentially a grading of erosion severity that has satisfactory reproducibility for use in groups of patients. The Larsen index can clearly distinguish different rates of erosive progression in groups of patients with different characteristics or treatments. Recent studies using the Larsen index have identified clear treatment effects. Difficulty in measuring the success of previous treatments designed to hold back the progression of erosions relates to the inefficacy of those treatments, not insensitivity of the Larsen index.

Arthritis, Rheumatoid↗
PubMed2000

General practitioners miss disability and anxiety as well as depression in their patients with osteoarthritis.

BACKGROUND: General practitioners (GPs) integrate physical, psychological, and social factors when assessing patients, particularly those with chronic diseases. Recently, the emphasis has been on assessment of depression but not of other factors. AIM: To determine functional disability, psychological morbidity, social situation, and use of health and social services in patients with osteoarthritis and examine GP knowledge of these factors. METHOD: Two hundred patients completed a validated postal questionnaire about functional disability (Health Assessment Questionnaire [HAQ]), mood (Hospital Anxiety and Depression Scale [HAD]), employment status, who they lived with, welfare benefits received, and use of health and social services. A similar questionnaire was completed by the patient's GP, including a HAQ. However, a three-point scale was used to assess depression and anxiety. RESULTS: Forty-seven per cent of patients were moderately or severely disabled (HAQ > 1). GPs underestimated functional disability: mean patient HAQ = 1.04 (95% confidence interval [CI] = 0.92-1.16), mean GP HAQ = 0.74 (95% CI = 0.65-0.83), and there was low correlation between patient and GP scores (kappa = 0.24). There was moderate prevalence of depression and high prevalence of anxiety, which the GP often did not recognise: patient depression = 8.3% (95% CI = 4.1%-12.8%), GP depression = 6.0% (95% CI = 2.4%-9.6%), kappa = 0.11; patient anxiety = 24.4% (95% CI = 17.8%-31.0%), GP anxiety = 11.9% (95% CI = 6.9%-16.9%), kappa = 0.19. Only 46% of severely disabled patients (HAQ > 2) were receiving disability welfare benefits. GPs were often unaware of welfare benefits received or the involvement of other professionals. CONCLUSION: GPs frequently lack knowledge about functional disability, social factors, and anxiety as well as depression in their patients with osteoarthritis.

Adult↗
PubMed1999

The analysis of a bivariate multi-state Markov transition model for rheumatoid arthritis with an incomplete disease history.

In many long-term chronic diseases, patients pass through an observable sequence of ordered clinical states as their condition progressively worsens. Often the information on which disease state the patient is in is incompletely recorded, usually with information only available on the occasion of a clinic visit. This article describes a novel analysis of data from a clinical trial, in which several such outcome measures of disease state have been recorded simultaneously. The article is motivated by the analysis of a multi-centre double-blind placebo-controlled clinical study into the effect of continual low dose corticosteroid treatment on the progression of X-ray scores for patients with rheumatoid arthritis. Previous methods of analysis of such data have been based on an independence analysis, thus ignoring any correlation that may exist between the outcomes. This article shows that such an approach can lead to biased underestimates of the covariate effects if an independence model is used. Biased estimates of the covariate effects were found when the model was fitted to the trial data. The bivariate model was also shown to provide a significantly better fit to the data. However, the bivariate model did prove more difficult to fit, and both models demonstrated a highly significant treatment effect with comparable clinical effect.

Adolescent↗
PubMed1999

Ability of T cells from patients with rheumatoid arthritis to respond to immunoglobulin G.

The ability of T cells from rheumatoid factor (RF)-positive patients with rheumatoid arthritis (RA) to respond to immunoglobulin G (IgG) was assessed. Peripheral blood mononuclear cells (PBMC) from RA patients and normal individuals were cultured with and without human IgG or Mycobacterium tuberculosis-purified protein derivative (PPD) for 7 days and their proliferative response measured at intervals by their ability to take up tritiated thymidine. PBMC from 14/26 RA patients proliferated in response to IgG (taking a stimulation index of 3 or above as positive). The peak response varied between individuals but usually occurred on day 5, the same day, or 1 day later than the peak response to PPD. By contrast, PBMC from a significantly lower proportion (1/9) of normal individuals and patients with other arthritides (0/6) responded to IgG, although all responded to PPD. PBMC from 9/14 RA patients responded to Fab fragments of IgG but only 3/9 to the Fc fragment. Higher proliferative responses from RA PBMC were elicited by IgG aggregates than the original IgG preparation, but PMBC from 5/5 normal individuals and 5/6 patients with other arthritides failed to respond to the aggregates. The response to IgG was human leucocyte antigen (HLA)-DR restricted and mediated by CD4+ T cells. It is considered that these results advance the hypothesis that IgG-reactive T cells contribute to the initiation or perpetuation of RA.

Adult↗
PubMed1999

Conceptual issues in scoring radiographic progression in rheumatoid arthritis.

Radiographic scoring systems for rheumatoid arthritis (RA) should be based on current understanding of disease pathology. Evidence suggests that there may be at least two intraarticular pathologies that may result in change in different radiographic features. There is therefore a strong argument for devising a radiographic score based on the observation of features rather than broad categorizations of the total radiographic change. Features may subsequently be amalgamated in relation to other criteria such as sensitivity, specificity, and responsiveness to change, and may be related to subsequent developments in understanding the biology of RA. A second challenge is in elucidating the relationship between radiographic change and the longterm consequences of RA for the patient. Current practice is predicated on the assumption that in the longterm radiographic change correlates well with functional loss and possibly noninflammatory, endstage joint pain. Although hand and feet radiographs broadly represent destructive change in all joints, in cross sectional studies they correlate only moderately with late stage functional loss. The issue may be resolved by longterm observational studies of radiographic change and functional loss. It is recommended that specific radiographic features relevant to joint pathophysiology be used to create a radiographic damage index for comparison with current scoring systems and that longterm observational studies specifically address the relationship between radiographic joint damage and functional outcome.

Animals↗