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Biomedical subjects

P Emery

Publications and source records attributed to P Emery.

At least 199 records · Page 11Linked to original sources
PubMed1998

Choice of NSAID and management strategy in rheumatoid arthritis and osteoarthritis. The impact on costs and outcomes in the UK.

OBJECTIVE: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective therapy for rheumatoid arthritis, they are associated with significant adverse effects, the management of which imposes additional costs on the healthcare system. Prescribing NSAIDs which have a lower risk of major adverse effects as the first-line NSAID for patients with rheumatoid arthritis and osteoarthritis may be expected to lead to an improvement in clinical outcomes and reduce overall treatment costs. This analysis examines data from a published randomised controlled trial of 5 NSAIDs to explore these hypotheses. DESIGN AND SETTING: Data from a clinical trial comparing 5 NSAIDs were combined with published cost data to construct 2 clinical decision models, reflecting alternative approaches to the management of major and minor adverse effects in the UK. INTERVENTIONS: The 5 NSAIDs evaluated in the analysis were nabumetone, diclofenac, ibuprofen, piroxicam and naproxen, although only the results for ibuprofen and nabumetone are reported. MAIN OUTCOME MEASURES AND RESULTS: The total cost of care per patient receiving nabumetone was estimated to be between 25 pounds sterling (Pound) and 41 Pounds more expensive than ibuprofen. In a hypothetical cohort of 100,000 patients, there were between 690 and 821 more major adverse effects using ibuprofen than nabumetone. The cost per life-year gained (LYG) from using nabumetone rather than ibuprofen ranged between 1880 Pounds and 2517 Pounds (1995 values), depending upon the management of adverse effects. CONCLUSIONS: These results indicate that: (i) prescribing the newer, currently more expensive, NSAIDs will not necessarily lead to cost savings; (ii) the management of adverse effects can have a significant impact on costs; and (iii) the additional cost may be justifiable in terms of the mortality and morbidity gains associated with the new lower-risk NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Effect of vitamin D receptor gene alleles on bone loss in early rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a polygenic disease characterized by localized joint destruction and generalized osteoporosis resulting in increased fracture risk. The pathogenetic mechanisms that determine the severity of generalized bone loss in RA are poorly understood. Polymorphisms in the vitamin D receptor (VDR) gene have been described as a significant determinant of bone turnover and mass. In this prospective study we describe VDR gene allele effects on bone loss in patients with early RA. METHODS: We recruited 232 patients with early RA. Bone mineral density measurements were repeated in 167 patients. Serial clinical and laboratory measures were recorded during the period of followup. DNA extraction, polymerase chain reaction amplification, and restriction fragment length polymorphism analysis of VDR alleles were performed using standard techniques. Presence of the Taq restriction site for both alleles was denoted "tt", and absence "TT". RESULTS: In women with RA the tt genotype group lost bone more rapidly than subjects with TT genotype at both the lumbar spine (-0.1 vs -4.9% p.a, respectively; p < 0.05) and femoral neck (-3.9 vs -9.6%, respectively; p < 0.01). The effect was independent of other disease characteristics. CONCLUSION: The presence of the VDR gene "t" allele in female patients with RA was associated with accelerated bone loss.

Alleles↗
PubMed1998

Safety and tolerability of conversion from stable Sandimmun maintenance treatment to Sandimmun Neoral in patients with rheumatoid arthritis.

OBJECTIVE: To assess the safety and tolerability of converting patients with rheumatoid arthritis (RA) taking a stable dose of cyclosporin A (CyA) maintenance treatment (Sandimmun, SIM) to a new microemulsion capsule formulation, Sandimmun Neoral (Neoral), at an initial dose of 2.5 mg/kg/day. METHODS: In this single arm, open multicenter study, 28 patients were recruited to enter a 6 week pre-conversion period; of these, 22 patients completed 12 weeks' treatment with Neoral. RESULTS: During the 12 week post-conversion period, 11 patients experienced adverse events considered to be drug related; most were mild to moderate in severity and reflected the known safety profile for CyA. Only slight differences in efficacy variables were observed after conversion. The mean Neoral dose at Week 12 (2.84 mg/kg/day) was lower than the mean SIM pre-conversion dose (3.38 mg/kg/day). The study showed that, in patients with RA undergoing stable SIM maintenance treatment, conversion to an initial Neoral dose of 2.5 mg/kg/day did not give rise to any clinically relevant safety and tolerability concerns, and efficacy of the treatment was maintained compared with SIM. CONCLUSION: This conversion strategy constitutes a clinically acceptable alternative to a 1:1 dose conversion.

Adult↗
PubMed1998

Osteoclastic activation is the principal mechanism leading to secondary osteoporosis in rheumatoid arthritis.

OBJECTIVE: To use clinical measures and biochemical markers of bone turnover to investigate mechanisms of generalized bone loss in early rheumatoid arthritis (RA). METHODS: We studied 232 patients with RA of less than 2 years' duration and 72 healthy controls using serial dual x-ray absorptiometry scanning of lumbar spine and hips. Patients attended the clinic for clinical and laboratory assessment with storage of serum, urine, and plasma at each visit. Change in bone mineral density (BMD) was calculated for patients and controls and compared with baseline and mean serial values of bone markers over the same intervals. Serum was assayed for procollagen I carboxyterminal propeptide (PICP) and skeletal alkaline phosphatase (sALP); urine for pyridinoline and deoxypyridinoline corrected for creatinine; and plasma for interleukin 1 (IL-1) and IL-6. RESULTS: Patients lost bone significantly faster than controls at all sites (p < 0.01 for all). At first visit patients had significantly lower PICP levels than controls (p < 0.05) and sALP correlated with initial BMD in both patients (p < 0.01, r > 0.35, all sites) and controls (p < 0.0001, r > 0.50, all sites). We rescanned 167 patients at one year and 121 patients at 2 years. Mean urinary pyridinoline and deoxypyridinoline levels correlated strongly with BMD change at all sites, were increased in patients with active disease (p < 0.005), and correlated closely with mean C-reactive protein (CRP) (p < 0.005, r > 0.41 for both). CONCLUSION: This study suggests that osteoclastic activation, rather than suppression of bone formation, is the dominant process leading to bone loss in early RA. Although urinary pyridinoline and deoxypyridinoline were excellent markers of BMD change, CRP was found to be best overall. This provides a rational approach for selecting and treating patients with RA to reduce their established longterm risk of osteoporotic fracture.

Absorptiometry, Photon↗
PubMed1998

Patient education in psoriatic arthritis: a cross sectional study on knowledge by a validated self-administered questionnaire.

OBJECTIVE: To assess the level of knowledge in a group of patients with psoriatic arthritis (PsA) following one reading of an information leaflet [UK Arthritis Rheumatism Council (ARC) booklet] using a validated self-administered questionnaire. Comparisons with subsets of the disease and level of general education were also made. METHODS: A multiple choice self-administered questionnaire was carried out in a group of 59 patients (32 male, 27 female, mean age 47.53 +/- 12.71 yrs) with established disease (mean duration 9.6 +/- 8.5 yrs). The questionnaire covered 4 broad areas of the disease (general knowledge of skin and joint disease, etiology, symptoms, blood test; general management and drug therapy; physiotherapy treatments; joint protection and priorities) and it was written collecting the majority of the information from an ARC booklet on PsA and from advice from the rheumatology team. Detailed statistical analysis was performed to validate the questionnaire and to measure any associations with demographic data. RESULTS: The questionnaire was consistent, reliable, and easy to read. Patients showed a lack of knowledge with some erroneous beliefs about their disease (i.e., causes, blood tests, longterm drugs). No statistical associations were found between the level of knowledge achieved and demographic data and patterns of disease. A significant association was found between the median score and level of general education (Kruskal-Wallis analysis of variance 7.97, p = 0.02). CONCLUSION: The questionnaire is a good instrument to assess knowledge in PsA. The ARC booklet alone seems inadequate to provide sufficient knowledge of disease. Patients' erroneous beliefs were highlighted and these should be addressed.

Analysis of Variance↗
PubMed1997

RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency.

Major Histocompatibility Complex class II (MHC-II) deficiency is a disease of gene regulation that provides a unique opportunity for the genetic dissection of the molecular mechanisms controlling transcription of MHC-II genes. Cell lines from MHC-II deficiency patients have been assigned to three complementation groups (A, B and C) believed to reflect the existence of distinct essential MHC-II regulatory genes. Groups B and C, as well as an in vitro generated regulatory mutant representing a fourth group (D), are characterized by a specific defect in the binding activity of RFX, a multimeric DNA binding complex that is essential for activation of MHC-II promoters. RFX5, a subunit of RFX, was recently shown to be mutated in group C. We have now isolated a novel gene, RFXAP (RFX Associated Protein), that encodes a second subunit of the RFX complex. RFXAP is mutated in the 6.1.6 cell line (group D), as well as in an MHC-II deficiency patient (DA). This establishes that group D is indeed a fourth MHC-II deficiency complementation group. Complementation of the 6.1.6 and DA cell lines by transfection with RFXAP fully restores expression of all endogenous MHC-II genes in vivo, demonstrating that RFXAP is a novel essential MHC-II regulatory gene.

Amino Acid Sequence↗
PubMed1997

Inhibition of T cell apoptosis in the rheumatoid synovium.

Synovial T cells in rheumatoid arthritis are highly differentiated and express a phenotype suggesting susceptibility to apoptosis (CD45RB dull, CD45RO bright, Bcl-2 low, Bax high, Fas high). However, no evidence of T cell apoptosis was found in synovial fluid from any of 28 patients studied. In contrast, synovial fluid from 10 patients with crystal arthritis showed substantial levels of T cell apoptosis. The failre of apoptosis was not an intrinsic property of rheumatoid synovial T cells, as they showed rapid spontaneous apoptosis on removal from the joint. Synovial T cells from rheumatoid arthritis and gout patients could be rescued from spontaneous apoptosis in vitro either by IL-2R gamma chain signaling cytokines (which upregulate Bcl-2 and Bcl-XL) or by interaction with synovial fibroblasts (which upregulates Bcl-xL but not Bcl-2). The phenotype of rheumatoid synovial T cells ex vivo (Bcl-2 low, Bcl-xL high) suggested a fibroblast-mediated mechanism in vivo. This was confirmed by in vitro culture of synovial T cells with fibroblasts which maintained the Bcl-xL high Bcl-2 low phenotype. Synovial T cells from gout patients were Bcl-2 low Bcl-xL low and showed clear evidence of apoptosis in vivo. Inhibition experiments suggested that an integrin-ligand interaction incorporating the Arg-Gly-Asp motif is involved in fibroblast-mediated synovial T cell survival. We propose that environmental blockade of cell death resulting from interaction with stromal cells is a major factor in the persistent T cell infiltration of chronically inflamed rheumatoid synovium.

Apoptosis↗
PubMed1997

A randomized, double-blind study comparing twenty-four-week treatment with recombinant interferon-gamma versus placebo in the treatment of rheumatoid arthritis.

OBJECTIVE: To evaluate the safety and efficacy of recombinant interferon-gamma (rIFN gamma) in patients with active rheumatoid arthritis (RA), using an induction and maintenance regimen. METHODS: A multicenter, randomized, double-blind trial of 197 patients with RA was conducted to compare the effects in a group receiving 50 micrograms of rIFN gamma, given subcutaneously in a decreasing regimen over 24 weeks, with those in a placebo group receiving injections of placebo at the same time frequency. Standard clinical assessments were performed. RESULTS: Both rIFN gamma and placebo produced a significant improvement from baseline to end point visit for most measurements (except erythrocyte sedimentation rate, duration of morning stiffness, and grip strength), but no significant intergroup differences were seen. Regarding adverse effects, mild local skin reactions at the site of injection were observed, and among the cardiovascular events, mild edema and vasodilatation were reported. CONCLUSION: IFN gamma proved no more effective than placebo in this group of patients with RA. IFN gamma was well tolerated in this group of patients, without increased toxicity compared with placebo.

Adolescent↗
PubMed1997

A phase 1 study to address the safety and efficacy of granulocyte colony-stimulating factor for the mobilization of hematopoietic progenitor cells in active rheumatoid arthritis.

OBJECTIVE: To examine the safety and efficacy of granulocyte colony-stimulating factor (G-CSF) alone for the mobilization of peripheral blood progenitor cells in patients with resistant active rheumatoid arthritis (RA). METHODS: Five patients with resistant active RA were studied. A dose of 5 microg/kg of G-CSF (Filgrastim) was given subcutaneously each day for 5 days, and the number of stem cells mobilized into the peripheral blood was assessed by daily CD34 counts. RA disease activity was assessed by standard clinical methods. RESULTS: The absolute numbers of peripheral blood CD34+ cells peaked on day 4, with a mean value of 0.025 x 10(9)/liter (range 0.013-0.048 x 10(9)/liter). There was no significant change in disease activity during the study or in the month following therapy. CONCLUSION: Using G-CSF alone, CD34+ progenitor peripheral blood cells were mobilized in numbers suitable for leukopheresis. G-CSF therapy was well-tolerated in patients with active RA, and was not associated with a flare during treatment or in the month following treatment.

Adult↗
PubMed1997

What is early rheumatoid arthritis?: definition and diagnosis.

The diagnosis of early rheumatoid arthritis (RA) has inherent difficulties. It requires assessment, not only of the current clinical picture, but of the potential for change. As the pathognomonic feature of RA, is persistence it is not surprising that the American College of Rheumatologists criteria perform better in predicting persistence than severity. An adequate histological/imaging method of diagnosing RA is awaited. In the interim, a pragmatic approach to defining disease has been suggested, which takes a homogeneous group of patients with persistent inflammatory small joint synovitis and secondarily stages them for severity. This proposal is currently being assessed for clinical usefulness.

Arthritis, Rheumatoid↗
PubMed1997

Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis.

Although cyclophosphamide and prednisolone are effective in treating systemic vasculitis, the optimum treatment regimes and duration of treatment are unknown. We randomized 54 patients aged 15-70 years (median 57.5 years) with systemic vasculitis (classical polyarteritis n = 8, microscopic polyarteritis n = 17, Wegener's granulomatosis n = 29) to treatment with either pulse cyclophosphamide and prednisolone (PCYP) (n = 24) or continuous oral and prednisolone and cyclophosphamide, with the latter followed after a median of 3 months (range 1.5-10 months) by azathioprine (CCAZP) (n = 30). Patients on CCAZP were more likely to develop leucopenia (13/30) than patients on PCYP, (7/24) although the difference was not significant. The numbers of infective episodes during follow up were comparable in the two groups at 1.7/patient for PCYP and 1.66/patient for CCAZP. Overall, 26/30 patients (87%) treated with CCAZP developed treatment-related toxicity, as did 17/24 patients (71%) treated with PCYP. After a median follow-up of 40.4 months (range 0.7-64.8), there was no difference in the frequency of deaths (PCYP 5, CCAZP 4), relapses (PCCYP 7, CCAZP 8), treatment failures (PCYP 4, CCAZP 4), improvement in disease activity scores or renal function. Survival at three years was 77% in patients treated with PCYP, and 90% in patients on CCAZP (p = 0.38). There was a tendency towards increased toxicity in patients treated with the continuous regimen.

Adolescent↗
PubMed1997

The acute phase and function in early rheumatoid arthritis. C-reactive protein levels correlate with functional outcome.

OBJECTIVE: To discover whether normalization of C-reactive protein (CRP) in patients with rheumatoid arthritis (RA) results in stabilization of their functional state, and whether a measure of disease activity can be used as a predictor of functional outcome. To examine the relationship between change of CRP and Health Assessment Questionnaire (HAQ) over a 24 mo period to define the sensitivity of HAQ to change. METHODS: A prospective study of 109 consecutive patients who fulfilled the American College of Rheumatology criteria for RA and had elevated CRP before steroid or 2nd line therapy. A full clinical assessment including HAQ was performed at presentation and at 3, 6, 12, and 24 mo. On the basis of the change in CRP at 6 mo, patients were divided into 3 groups: (1) CRP suppression to normal, (2) 50% reduction in CRP, and (3) less than 50% CRP change. RESULTS: The 3 groups were clinically and immunologically similar at onset. At 6 mo the median HAQ fell to 5 (lower to upper quartiles 7.5 to 19) in Group 1 (CRP normalized, n = 34), 6 (3.75 to 10) in Group 2 (CRP reduced by 50%, n = 30), and 12 (6 to 18) in Group 3 (less than 50% CRP change, n = 44), p < 0.005 for Groups 1 and 2 versus Group 3. At 12 and 24 mo HAQ remained significantly lower in Groups 1 and 2 compared with Group 3. In Group 1, patients either maintained a normal CRP (n = 28) or their CRP became elevated (n = 6). Only in those patients in whom a re-elevation of the CRP occurred was deterioration in HAQ subsequently seen. CONCLUSION: Suppression of elevated CRP in patients with active RA is associated with improvement in functional score, whereas persistent elevation of CRP is associated with functional deterioration. Once abnormal CRP is suppressed, no functional deterioration is likely to occur without re-elevation in CRP. Therefore, elevated CRP provides a convenient short term correlation with functional outcome and can be used as a guide for therapy. A HAQ score is a sensitive indicator of change in early disease.

Analysis of Variance↗
PubMed1997

von Willebrand factor: increased levels are related to poor prognosis in systemic sclerosis and not to tissue autoantibodies.

von Willebrand factor, C-reactive protein, rheumatoid factor, major organ involvement, antibodies to extractable nuclear antigen, anti-cardiolipin antibodies, anti-centromere antibodies and anti-nuclear antibodies were measured in 33 patients with systemic sclerosis. After five years, the nine patients who had died had initial levels of von Willebrand factor significantly higher (median 288 IU/dL, range 150-1170) than levels in the 24 who were still alive (median 148 IU/dL, range 65-262, Mann Whitney P = 0.0002). Increased levels of von Willebrand factor correlated with the time interval from blood sampling until the patient's death (Spearman's r = 0.73, P = 0.02). Levels of C-reactive protein, rheumatoid factor, and tissue autoantibodies, and age or the number of organs involved were unable to predict this outcome. We suggest that endothelial perturbation, as indicated by increased levels of von Willebrand factor, is a strong indicator of a poor prognosis in systemic sclerosis.

Adult↗