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Biomedical subjects

P G Conaghan

Publications and source records attributed to P G Conaghan.

47 records · Page 3Linked to original sources

Disease-modifying antirheumatic drugs, including methotrexate, gold, sulfasalazine, antimalarials, and D-penicillamine.

The class of agents known as disease-modifying antirheumatic drugs remains the predominant treatment for rheumatoid arthritis. Methotrexate has again demonstrated efficacy in long-term studies, and more reports on its pharmacokinetics and possible mechanism of action have been published. Renal impairment has been highlighted again as a major risk factor for methotrexate toxicity, and studies have supported the American College of Rheumatology guidelines concerning elevated transaminases as a warning sign for liver toxicity. Although questions about the long-term efficacy of gold have again been raised, some interesting reports have focused on its mechanism of action. The sulfasalazine literature includes reports on possible immunomodulatory roles for the drug in the gastrointestinal tract. The usefulness of hydroxychloroquine has been confirmed in a large study of early rheumatoid arthritis. The minimal effective dose of D-penicillamine has been questioned in a clinical study. Combination therapy using existing disease-modifying antirheumatic drugs has not demonstrated major benefits over single-drug therapy.

Antimalarials↗

Disease-modifying antirheumatic drugs, including methotrexate, gold, antimalarials, and D-penicillamine.

Recent literature continues to promote the early use of disease-modifying antirheumatic drugs (DMARDs), especially the less toxic agents such as hydroxychloroquine. Reports of combination DMARD treatments have been disappointing, and careful attention must be paid to clinical trial design if the efficacy of combination therapies is to be established. Methotrexate retains its prominent role, and its mechanism of action has been the subject of many reports; its toxicity remains the most common reason for treatment termination. Guidelines for monitoring hepatic toxicity of methotrexate have been published and may help reduce the need for invasive biopsy procedures. Significant risk factors for methotrexate pulmonary toxicity remain difficult to identify. Large placebo-controlled studies of both sulfasalazine and hydroxychloroquine have been reported and have demonstrated the efficacy of these agents in the treatment of early rheumatoid arthritis. Awareness of drug-toxicity profiles is important for physicians who prescribe these agents.

Anti-Inflammatory Agents, Non-Steroidal↗

Adverse drug reactions and their measurement in the rheumatic diseases.

Drugs administered as therapy for rheumatological disorders are a relatively common cause of adverse events. Important data regarding the effects of drugs on patients with rheumatological conditions is being lost or rendered inaccessible because of deficiencies in classification, measurement, and collection methods for adverse drug reactions. A significant number of adverse reactions to drugs will not be known before marketing, and hence vigilance on the part of clinicians and patients in observing and documenting these reactions is paramount in building our knowledge and modifying our practice accordingly. A variety of systems and methods for detecting adverse drug reactions are described, critically evaluated, and compared for cost, potential bias, ethical concerns, and subject recruitment required for necessary statistical power. Systems need to be developed to give access to the wealth of clinical experimental data available in the individual practices of a broad spectrum of clinicians. To facilitate this, representative organizations need to make adverse drug reactions a high priority as well as contributing expertise and finance to database formulation and accessibility.

Antirheumatic Agents↗

Rheumatic manifestations of malignancy.

The rheumatic associations of cancer therapy are highlighted in this review. Interleukin-2, interferon alfa, and Calmette-Guérin bacillus immunotherapies are related to an inflammatory arthritis, and septic arthritis can complicate breast-cancer therapy. In a large retrospective study, an increased incidence of cancer in systemic sclerosis was confirmed, especially lung and breast cancers. Lymphoproliferative associations of Sjögren's syndrome were explored in a study of non-Hodgkin's lymphoma patients in which clinical and histologic criteria were used to diagnose Sjögren's syndrome. B- and T-cell lymphomas continue to be reported with rheumatologic manifestations such as seronegative polyarthritis and sacroiliitis. Malignant angioendotheliomatosis, which mimics central nervous system vasculitis diseases, has been reported. Paraneoplastic associations of lung, ovarian, and renal-cell carcinomas are discussed.

Arthritis↗

Disease-modifying antirheumatic drugs, including methotrexate, sulfasalazine, gold, antimalarials, and penicillamine.

Recently, there has been an interest in rethinking the classification of antirheumatic drugs. Emphasis continues to be on aggressive control of inflammation in the early phase of rheumatoid arthritis. The mistake of extrapolating short-term clinical trial results to long-term outcomes has been appreciated, pointing to the need for long-term studies. Interest in the role of cytokines and their receptors in the inflammatory process continues, as well as in the cellular mechanisms of action of the various disease-modifying antirheumatic drugs (DMARDs). Troublesome toxicity profiles continue to be reported, and a consideration of efficacy-toxicity trade-offs are important. Methotrexate still shows long-term efficacy, and low-dose folinic acid has been shown to reduce toxicity but not efficacy. New information on other DMARDs is presented, ie, sulfasalazine inhibition of signal transduction, the effects of hydroxychloroquine on cytokines and lipid metabolism, and the immunosuppressive effects of bucillamine, a penicillamine-related compound.

Age Factors↗

Risks and benefits of drugs used in the management and prevention of gout.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are now commonly used for the treatment of acute gout, but caution is required in view of their adverse effects, especially in the elderly. Colchicine is still an effective acute agent, but care must be taken to monitor toxicity. Intra-articular glucocorticosteroid therapy is useful and very safe; oral steroids and corticotrophin (adrenocorticotrophic hormone) may have a small role in acute therapy and seem safe when used over short time spans. Low dose colchicine may have a cost and toxicity advantage over NSAIDs in the prophylaxis of gout when commencing therapy aimed at reducing elevated plasma urate concentrations. Allopurinol is more frequently used than uricosuric agents such as probenecid, and toxicity may be largely avoided by tailoring dosage schedules according to renal function.

Adrenocorticotropic Hormone↗

Disease-modifying antirheumatic drugs, including methotrexate, sulfasalazine, gold, antimalarials, and D-penicillamine.

Rheumatoid arthritis is a progressive inflammatory disease with evidence of early cartilage damage. Consequently, there is a trend toward earlier use of disease-modifying antirheumatic drugs. This review focuses on recent data on methotrexate, sulfasalazine, gold, hydroxychloroquine, D-penicillamine, and combination therapy. Methotrexate is focused on most, reflecting the increasing popularity of this agent; studies continue to show its good clinical efficacy. Combination therapy studies have been disappointing and are still marred by short duration and low power. Sulfasalazine has a fairly rapid onset of clinical effects and modulates immune function. Gold is still the subject of new studies, with evidence that clinical experience leads to improved patient efficacy. The beneficial effect of hydroxychloroquine in mild rheumatoid arthritis has been confirmed, and information on D-penicillamine suggests an effect on oxygen radical scavenging. Clinical studies are still required to ascertain the relative efficacy of these drugs, and potential long-term adverse effects remain a source of concern.

Anti-Inflammatory Agents↗

New approaches to imaging of early rheumatoid arthritis.

Conventional radiology (CR) is a major tool for the diagnosis and assessment of early arthritis. However, CR does not image the primary pathology of rheumatoid arthritis (RA), i.e. the synovium, and is insensitive for radiological erosions. New techniques, particularly magnetic resonance imaging (MRI) and ultrasonography (US) have shown their potential to improve on the sensitivity of CR. This article reviews the current status of this approach in early disease.

Arthritis, Rheumatoid↗

The role of ultrasonography and magnetic resonance imaging in early rheumatoid arthritis.

Advances in ultrasound (US) and magnetic resonance imaging (MRI) techniques have provided new methods for evaluating early rheumatoid arthritis (RA). Their diagnostic properties in terms of detecting primary pathology of RA (i.e., erosions, bone changes, synovitis, tenosynovitis, and effusion) are reviewed. High-resolution US plays a significant role in therapeutic and diagnostic procedures. MRI also assists in the understanding of RA pathogenesis and joint mechanics.

Adult↗

New approaches to imaging early inflammatory arthritis.

Imaging techniques such as musculoskeletal ultrasonography (MUS) and magnetic resonance imaging (MRI) are playing an increasingly important role in the assessment of patients with inflammatory arthritis. Such modalities are now used routinely in the evaluation of joint, tendon and soft tissue inflammation and bone damage in many early arthritis clinics. They have the ability to directly visualise, characterise and quantify the earliest inflammatory changes and have proved not only to be useful additional complimentary clinical tools to improve the speed and accuracy of diagnosis, direct appropriate treatment, monitor response to therapy, measure disease progression and outcome but also continue to contribute to our understanding of disease pathogenesis. These imaging methods may therefore offer a significant advantage as they endorse the principles of early diagnosis and optimal targeted therapy essential to providing the most favourable long term outcome for patients with inflammatory arthritis. This article reviews the current evidence supporting the role of MUS and MRI in the assessment of patients with inflammatory arthritis.

Arthritis, Rheumatoid↗