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Biomedical subjects

R Madhok

Publications and source records attributed to R Madhok.

At least 73 records · Page 4Linked to original sources

Oral iloprost in Raynaud's phenomenon secondary to systemic sclerosis: a multicentre, placebo-controlled, dose-comparison study.

OBJECTIVE: To identify the optimal dose of oral iloprost on the basis of efficacy and tolerability in patients with Raynaud's phenomenon secondary to systemic sclerosis. DESIGN: Multicentre, randomized, parallel-group comparison of two different doses of oral iloprost and placebo. SETTING: European university hospitals. PATIENTS: A total of 103 patients with Raynaud's phenomenon secondary to systemic sclerosis. INTERVENTION: Patients received one of three treatments for 6 weeks: placebo, oral iloprost 50 microg or oral iloprost 100 microg. Each treatment was taken twice daily, giving total daily doses of iloprost of 100 and 200 microg. MEASUREMENTS: The frequency, total daily duration and severity of Raynaud's attacks were recorded in a specially designed patient diary; physician's global assessment and adverse events were recorded at visits to the clinic. Analysis was performed on an intention-to-treat population. RESULTS: A total of 103 patients were recruited, 89 completed the assessments throughout the treatment period and 82 completed an additional 6 weeks of follow-up after treatment. Thirty-five patients received placebo, 33 received iloprost 50 microg and 35 received iloprost 100 microg. The mean percentage reductions in the frequency, total daily duration and severity of Raynaud's attacks were numerically greater in the iloprost groups at the end of treatment and at the end of follow-up. At the end of treatment (6 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.03), but not in the severity (P = 0.07) or the frequency of attacks (P = 0.37). At the end of follow-up (12 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.001) and in the severity of attacks (P = 0.007), but not in the frequency of attacks (P = 0.07). Percentages of patients improved at the end of treatment as assessed by the physician were 44% placebo, 57% iloprost 50 microg and 64% iloprost 100 microg (not significant). Side-effects were reported by 80% of patients on placebo, 85% on oral iloprost 50 microg and 97% on oral iloprost 100 microg. Premature discontinuations of treatment in each group were 9, 30 and 51%, respectively, with 6, 27 and 51% being due to adverse events. CONCLUSION: The results on the daily duration of Raynaud's attacks suggest that both 50 and 100 microg oral iloprost twice daily may be effective in the treatment of Raynaud's phenomenon secondary to systemic sclerosis. The 50 microg iloprost dose was better tolerated in this patient group.

Administration, Oral↗

Improved functional outcome in patients with early rheumatoid arthritis treated with intramuscular gold: results of a five year prospective study.

OBJECTIVE: To determine whether there is a relation between disease duration and functional outcome in patients with rheumatoid arthritis (RA) treated with intramuscular sodium aurothiomolate (gold) for five years. METHODS: 440 patients with RA were enrolled in a prospective trial of gold treatment. Initial demographic details were recorded. Disease activity was assessed at yearly intervals using a combination of clinical (pain score, Ritchie articular index, duration of morning stiffness) and laboratory (erythrocyte sedimentation rate, C reactive protein) parameters. Change in functional status was assessed using the health status questionnaire (HAQ). Patients were stratified according to disease duration at outset (group 1 = 0-2 years n = 106, group 2 = > 2-5 years n = 93, and group 3 = > 5 years n = 235). RESULTS: There were no significant differences between the groups at outset. A total of 160 patients completed five years of treatment (group 1 n = 44 (42%), group 2 n = 37 (40%), and group 3 n = 79 (34%)). Patients in group 1 had a significantly lower HAQ from year 1 to year 5 with a mean improvement of 30% at the end of the study (p < 0.001). Neither group 2 nor group 3 had a significant change in their HAQ at study end. There were significant improvements in all other variables (p < 0.05) in each group apart from pain in group 2. CONCLUSION: Patients with early RA have a larger reversible component to their HAQ. Only patients with disease duration of up to two years have a longlasting improvement in their functional ability after starting intramuscular gold treatment.

Adult↗

Pulmonary artery pressure variation in patients with connective tissue disease: 24 hour ambulatory pulmonary artery pressure monitoring.

BACKGROUND: The specific contribution of secondary pulmonary hypertension to the morbidity and mortality of patients with underlying lung disease can be difficult to assess from single measurements of pulmonary artery pressure. We have studied patients with secondary pulmonary hypertension using an ambulatory system for measuring continuous pulmonary artery pressure (PAP). We chose to study patients with connective tissue disease because they represent a group at high risk of pulmonary vascular disease, but with little disturbance of lung function. METHODS: Six patients (five with progressive systemic sclerosis and one with systemic lupus erythematosis) were studied. They underwent preliminary cardiopulmonary investigations followed by Doppler echocardiography, right heart catheterisation, and ambulatory pulmonary artery pressure monitoring to measure changes in pressure over a 24 hour period including during a formal exercise test. RESULTS: All patients had pulmonary hypertension as measured by Doppler echocardiography with estimated pulmonary artery systolic pressures of 40-100 mm Hg. Pulmonary function testing revealed virtually normal spirometric values (mean FEV1 86.9% predicted) but marked reduction in CO gas transfer factor (KCO 57.8% predicted). Exercise responses were impaired with mean VO2max 50.6% predicted. Ambulatory PAP monitoring indicated significant changes in pressures with variation in posture and activity throughout 24 hours. Resting PAP did not predict the change in PAP seen on exercise. CONCLUSION: Conventional methods of assessment of the pulmonary circulation based on single measurements in the supine position may underestimate the stresses faced by the right side of the circulation. This ambulatory system allows monitoring of pulmonary haemodynamics continuously over 24 hours during normal activities of daily living. These measurements may increase our understanding of the contribution made by secondary pulmonary hypertension to the morbidity and mortality of the underlying lung disease.

Adult↗

Intention-to-treat analysis of 200 patients with rheumatoid arthritis 12 years after random allocation to either sulfasalazine or penicillamine.

OBJECTIVE: To assess existing disease modifying antirheumatic drugs (DMARD) using a strategy aiming for sustained suppression of inflammation. METHODS: We conducted intention-to-treat analysis of open randomized study [sulfasalazine (SASP) or penicillamine (PEN)], followup 12 years, conducted at specialist rheumatology clinics in Glasgow, Scotland. Subjects were 200 patients with rheumatoid arthritis (RA) with established disease. In this "true to life" approach, comorbidity was not an exclusion criterion unless it prejudiced assessment of drug toxicity. The main outcome measure was the Health Assessment Questionnaire (HAQ) functional score. RESULTS: Over 12 year followup 95 (47.5%) patients died; this was the commonest reason for study groups being unfulfilled. There was one drug related death (methotrexate). Patients who were socially disadvantaged were more likely to die prematurely. HAQ did not deteriorate significantly in those who continued taking their original DMARD, or in the SASP intention-to-treat group over 12 years. Sustained suppression of disease activity was possible in the entire group available for followup at 12 years. Most toxicity occurred early and no unexpected side effects were observed. CONCLUSION: High premature mortality in RA was confirmed and an association between mortality and deprivation was demonstrated. Sustained reduction in acute phase response was possible using sequential single DMARD. This study provides useful baseline and longterm information against which to evaluate combination therapy or new agents.

Adult↗

Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis.

OBJECTIVE: To determine the effect of intramuscular gold and oral hydroxychloroquine (HCQ) on the lipid profile of patients with rheumatoid arthritis (RA). METHOD: A prospective randomised clinical trial of 12 months' duration was performed in 100 RA patients. Data on clinical and laboratory parameters of disease activity, and fasting serum lipid samples was collected at baseline and at three monthly intervals over one year. RESULTS: The expected second line response was seen with no significant difference in efficacy between the groups at 12 months. The HCQ group had a significant overall improvement in their lipid profile while there was a trend for lipid profiles in the gold group to worsen. CONCLUSIONS: HCQ is an effective second line agent that has beneficial effects on serum lipids. This should be taken into account when choosing a disease modifying anti-rheumatic drug in patients who suffer from RA and who have significant cardiovascular risk factors.

Adult↗

Effect of social deprivation on disease severity and outcome in patients with rheumatoid arthritis.

OBJECTIVE: Social deprivation is now recognised to have an important impact on morbidity and mortality. This study sought to ascertain the effect of deprivation, if any, on disease severity, functional disability, and outcome in rheumatoid patients in Glasgow. METHODS: 814 patients with rheumatoid arthritis (RA) were assessed for clinical, functional, and laboratory indices of disease activity. Deprivation categories for individual patients were determined using the Carstairs index. Five year follow up is available for 440 patients. RESULTS: The study population of RA patients live largely in the most deprived areas. Patients from deprived areas have significantly poorer function at outset and at five years as defined by the Health Assessment Questionnaire (HAQ) score. This is not attributable to differences in disease duration in patients from the most deprived regions or compliance with treatment. Furthermore, these patients do not achieve over five years the initial functional level of those living in the most advantaged localities. CONCLUSION: RA patients from deprived areas have poorer function, which is associated with greater need--medical, social, and paramedical. Strategies and resources for healthcare need to be adjusted according to this variation.

Adult↗

Non-Hodgkin's lymphomas complicating Sjögren's syndrome: can Epstein Barr virus be implicated?

We examined eight (6 parotid, 1 caecum, 1 lymph node) non Hodgkin's Lymphomas (NHL) complicating primary Sjögren's syndrome (SS), four parotid NHL, in patients without SS, and three salivary gland biopsies from SS patients and no NHL, for Epstein Barr virus (EBV), using immunohistochemistry for late membrane protein, in situ hybridisation (ISH) for EBER, and PCR for EBV DNA. Late membrane protein was not detected. In NHL's complicating SS, EBERs were detected in two parotid lymphomas by ISH. EBV DNA was detected in three SS parotid NHL. Cecal and lymph node SS NHL were negative for EBER and EBV DNA. EBV DNA was detected in two non SS NHLs, one expressed EBER. Despite positive EBV DNA results by PCR in three samples expression of EBER was noted in only one by ISH. This was a high grade NHL complicating SS. There was no evidence of EBV in low grade NHLs complicating SS.

DNA Primers↗

Is rheumatoid arthritis becoming a milder disease? Or are we starting second-line therapy in patients with milder disease?

The aim of the study was to see whether rheumatoid arthritis (RA) is becoming a milder disease. Information on the initial disease activity and patient function (modified Health Assessment Questionnaire-HAQ) was collected in all RA patients enrolled into studies of sulphasalazine since 1980 in two Glasgow teaching hospitals. Patients (352) were enrolled in trials in the decade 1980-1989, and were compared to 374 patients enrolled in 1990-1994. Patients recruited in the 1980s were significantly younger, but had a similar disease duration to the 1990s patients. The 1980s patients had more active disease as measured by erythrocyte sedimentation rate (61 vs 44, P < 0.0001) and C-reactive protein (40 vs 26, P < 0.0001), and significantly worse function (HAQ 2.3 vs 1.9, P < 0.001). The response to sulphasalazine was very similar in the two cohorts, in terms of the percentage of patients remaining on therapy for 6 months, and the percentage improvement in measures of disease activity. Patients with milder disease were enrolled into the more recent trials of sulphasalazine. This may be because RA is becoming a milder disease, but other possible explanations are discussed.

Adult↗

Low dose desensitisation does not reduce the toxicity of sulphasalazine in rheumatoid arthritis.

OBJECTIVE: To examine the proposal that pretreatment low dose desensitisation may reduce the incidence of toxicity of sulphasalazine in the treatment of rheumatoid arthritis (RA). METHODS: A double blind, placebo controlled trial was performed with 422 patients satisfying the American College of Rheumatology criteria for RA who required sulphasalazine treatment because of increased disease activity. Patients received either sulphasalazine desensitisation, or placebo, for three weeks before commencement of sulphasalazine treatment. The frequency and nature of adverse effects and changes in clinical and laboratory parameters of disease activity were measured after three and six months. RESULTS: Improvement in the efficacy of sulphalasazine (measured by clinical and laboratory parameters) was significant and similar in magnitude in both groups. There was no significant difference between actively and placebo desensitised patients as regards the incidence or profile of adverse effects (toxicity). CONCLUSION: Pretreatment low dose desensitisation is unhelpful in reducing the toxicity associated with sulphasalazine treatment of RA.

Anorexia↗

Bone densitometry at a district general hospital: evaluation of service by doctors and patients.

OBJECTIVE: To assess doctors' and patients' views about a district general hospital bone densitometry service and to examine existing practice to influence future provision. DESIGN: Three postal surveys: (a) of doctors potentially using the service, (b) of patients undergoing a bone densitometry test during a six month period, and (c) of the referring doctors of the patients undergoing the test. SETTING: Bone densitometry service at South Cleveland Hospital, Middlesbrough and two district health authorities: South Tees and Northallerton. SUBJECTS: All general practitioners (n=201) and hospital consultants in general medicine, rheumatology, obstetrics and gynaecology, orthopaedics, radio therapy and oncology, haematology, and radiology (n=61); all patients undergoing an initial bone densitometry test (n=309) during a six month period; and their referring doctors. MAIN MEASURES: Service awareness and use, knowledge of clinical indications, test results, influence of test results on patient management, satisfaction with the service and its future provision. RESULTS: The overall response rates for the three surveys were 87%, 70%, and 61%. There was a high awareness of the service among doctors and patients; 219(84%) doctors were aware and 155 of them (71%) had used it, and patients often (40%) suggested the test to their doctor. The test was used for a range of reasons including screening although the general use was consistent with current guidelines. Two hundred (65%) bone densitometry measurements were normal, 71(23%) were low normal, and 38(12%) were low. Although doctors reported that management of patients had been influenced by the test results, the algorithm for decision making was unclear. Patients and doctors were satisfied with the service and most (n=146, 68%) doctors wanted referral guidelines for the service. CONCLUSIONS: There was a high awareness of, use of, and satisfaction with the service. Patients were being referred for a range of reasons and a few of these could not be justified, many tests were normal, and clinical decision making was not always influenced by the test result. It is concluded that bone densitometry services should be provided but only for patients whose management will be influenced by test results and subject to guidelines to ensure appropriate use of the technology.

Absorptiometry, Photon↗