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P D Fowler

Publications and source records attributed to P D Fowler.

65 records · Page 4Linked to original sources
PubMedDate not supplied

Interpretation of hematological and biochemical laboratory data in large-scale, multicenter clinical trials.

The laboratory assessment of drug tolerability is central to a long-term trial. But because of its volume, its multicenter origin, and the importance of nondrug factors, the analysis of these data is complicated. Various methods, i.e., collection of investigators' opinion, comparison of before- and after-treatment means, and analysis of transitions, were found to be unsatisfactory. A fourth method, described in this paper, seems to be more promising. An initial computer screening of the laboratory data is conducted to identify all patients with the potentially clinically relevant laboratory abnormalities. Each laboratory abnormally is then examined by the pharmaceutical physician with regard to the patient's sex and age, the trial diagnosis, concomitant and intercurrent illnesses, concurrent medication, unwanted effects, and other laboratory results, and each result is assigned a probable etiology according to a pre-defined classification system. By this method it is then possible to compare the frequency and severity of possible or probable drug-related laboratory abnormalities occurring with the various trial drugs. Our opinion regarding the importance of using this method would appear justified by the fact that a possible or probable drug effect was considered to have been responsible for only 15 per cent (112/760) of the potentially clinically relevant abnormal tests reported.

Blood Cell Count↗
PubMedDate not supplied

Aspirin, paracetamol and non-steroidal anti-inflammatory drugs. A comparative review of side effects.

Non-steroidal anti-inflammatory drugs (NSAIDs) effectively control the symptoms of many of the rheumatic diseases although they have little effect on the underlying causes. Their effect is mainly on the mediators of the inflammatory process. Unfortunately, these mediators have important physiological roles in the maintenance of health, particularly in the gastrointestinal tract and the kidney, so that their inhibition results in many unwanted reactions of varying severity. The mechanisms underlying these reactions are described. Their occurrence varies, both qualitatively and quantitatively, and an attempt is made to assess these differences, although it may be that they are related directly to differences in dosage and therapeutic efficacy. In addition, immunologically mediated adverse reactions occur. These mechanisms are outlined and related to the clinical picture. There are considerable differences in frequency of reactions between the compounds: in particular there is a wide variation in the rate of dermatological reactions of this type. Agranulocytosis has been particularly associated with the pyrazolone compounds, although it has been reported with most others. Aplastic anaemia, which may not be an immune-mediated reaction, is also thought of as a pyrazolone reaction, but the incidence with indomethacin approaches a similar level. Although all drugs analysed may cause hepatic reactions, these are rare except with the now withdrawn benoxaprofen. Several types of immunologically mediated renal reactions occur and these rarities are also described. Paracetamol does not have any effect on the inflammatory mediators. Anxieties about this substance relates to the parent compound phenacetin and its necrotic effect on the renal papillae. There is extensive literature on this subject concerning not only paracetamol, but also aspirin and other NSAIDs. This is also assessed and summarised. The danger of paracetamol as a direct hepatic toxin in self-poisoning is discussed. Novel NSAIDs are introduced and others withdrawn with frequent and monotonous regularity. Sometimes the reasons have some medical or scientific plausibility, but often they are over-reactions by registration authorities or pharmaceutical companies in response to uninformed media publicity. The problems of the numerically and scientifically accurate collection and assessment of adverse reaction data are legion and as a result useful agents have been lost. Some of these difficulties are described, and some non-drug 'adverse reactions' are described.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetaminophen↗
PubMedDate not supplied

[Clinical study on a new acetylsalicylic acid/paracetamol preparation with gastric acid resistant coating (Safapryn), and on two various phenylbutazone dosages in patients with primary chronic polyarthritis as based on a new evaluation method].

The authors describe a simple non-crossover-blind test for the evaluation of subjective indices. A table for recording pains during the 14 days' study is described. The patient's satisfaction with the treatment and the number of days until withdrawal from the trial are recorded. The statistical procedure takes into consideration differences between the treatment groups and makes possible a valuable comparison with drugs tested in other clinical trials. The three dose schedules of antirheumatic treatment were tested on 122 patients and the results compared with those of 342 patients treated with the 6 other antirheumatic drugs (enteric-coated aspirin, paracetamol, indomethacin, flurbiprofen, mefenamic acid, and prednisolone) and those of 41 patients who received placebos. The results show that Safapryn (3,6 g aspirin + 3.0 g paracetamol daily) compared with 3.9 g enteric coated aspirin does not offer any advantage in its analgesic effect, although it gives rise to fewer side effects. Phenylbutazone (3000 mg) was almost as effective as 15 mg prednisolone daily. Between the effects of this dosage of phenylbutazone and other non-steroidal antirheumatic drugs, however, no significant difference could be detected. 50 mg phenylbutazone daily and placebo treatment could not be distinguished. The authors thank the Arthritis and Rheumatism Council for Research in Great Britain for its financial support. One of the authors (PL) was a Merck, Sharp, and Dohme Research Fellow and another one (PMB) received a Robins research scholarship.

Acetaminophen↗
PubMedDate not supplied

Improving the response to gold or D-penicillamine by addition of sulphasalazine. A pilot study in 25 patients with rheumatoid arthritis.

In a 6-month open pilot study 25 patients with Rheumatoid Arthritis (RA) whose disease was refractory to Gold or D-Penicillamine (DPA) were given Sulphasalazine (SAS) in addition. Three patients withdrew because of nausea. Twenty-two patients who completed therapy showed significant improvement in clinical and laboratory measures of disease activity.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Treatment of early rheumatoid arthritis: a review of current and future concepts and therapy.

This review contrasts the difficulty of differentiating early rheumatoid arthritis (RA) from the many other causes of inflammatory polyarthritis and emphasizes the need for early treatment of RA with drugs that are present considered inappropriate for a mild, self-limiting disease. Pointers to help establish a definitive diagnosis of RA include the use of the American College of Rheumatology (ACR; formerly the American Rheumatism Association) diagnostic criteria, the presence of rheumatoid factor (RF), a raised erythrocyte sedimentation rate (ESR), raised serum levels of C-reactive protein (CRP) and low concentrations of serum sulphydryl (SH) groups. More sophisticated tests that are helpful and indicative of erosive-type disease are genetic markers such as the human leukocyte antigen HLA DR4 (especially the third allelic variable of DR beta 1) as well as an impaired sulphoxidation status. Similarly, the presence of the shared epitope alleles 0401 and 0404 quantitatively increases disease susceptibility and severity as their penetration increases. Experience with treatment indicates that control of the inflammatory process of RA reduces the progression of radiological damage. It is concluded that antimalarials are effective in mild disease, as is auranofin, whilst sulphasalazine is more effective than hydroxychloroquine in patients with disease diagnosed as definitive or classical RA. Intramuscular gold also lessens the development of erosions. The role of corticosteroids has not been defined. A number of combinations of drugs have been used, although they are probably not indicated as the first choice treatment for very early disease. Attitudes towards early treatment are changing; these are briefly reviewed and the authors' opinions on the management of early disease are outlined. Finally some new ideas, both theoretical and practical, on future development are summarized.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Use of the Stoke Index to differentiate between disease-modifying agents and non-steroidal anti-inflammatory drugs in rheumatoid arthritis.

The Stoke Index is a validated composite algorithm that has been designed to give a global measure of disease activity in rheumatoid arthritis (RA). The use of this single measure of disease activity in RA simplifies the critical evaluation of drug therapy. 368 patients with RA of varying duration and severity, entered into comparative drug trials between 1980 and 1987, had the algorithm calculated four weeks prior to therapy, at the start of treatment, and bi-monthly to six months. The index score was significantly improved by drugs with known slow acting anti-rheumatic drug (SAARD) activity and improvement could be seen as early as two months after the beginning of treatment. Non-steroidal anti-inflammatory drugs (NSAIDs) did not improve the score. The index differentiates between treatments in patients with minor or major disease activity. We conclude that this composite index of disease activity provides a sensitive, meaningful measure for the evaluation of therapy in RA.

Adult↗