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Biomedical subjects

D G I Scott

Publications and source records attributed to D G I Scott.

At least 19 recordsLinked to original sources
PubMed2006

Low-dose infliximab treatment for ankylosing spondylitis--clinically- and cost-effective.

OBJECTIVES: Infliximab has been shown to be effective in the treatment of ankylosing spondylitis (AS) when treated in a dose of 5 mg/kg at 6 weekly intervals. This dose of infliximab has not been determined by any structured randomized trials and has significant cost implications. We describe our experience of treating AS with low-dose infliximab (3mg/kg at 8 weekly intervals). The efficacy and cost implications are discussed. METHODS: Patients who had active AS [Bath AS Disease Activity Index (BASDAI) > or = 4] were treated with infliximab 3 mg/kg at 0, 2, 6 weeks and thereafter at 8 weekly intervals. Response to treatment was defined as 50% improvement in BASDAI. Other response criteria such as ASAS 20, 40 and five of the six criteria were also assessed. Direct drug costs for infliximab were determined. RESULTS: Twenty-two consecutive AS patients received infliximab. All 22 completed treatment for 3 months, 15 patients for 6 months and 14 for 12 months. Mean age was 45 years (range 21-62) and mean disease duration 14.5 years (range 2-43). Of the patients, 54% achieved a 50% BASDAI response at 3 months and the benefit was sustained at 12 months in 63%. Similar response rate was seen with the other assessment criteria. Direct drug costs were significantly lower when low-dose infliximab regimen was used. CONCLUSIONS: Low-dose infliximab (3 mg/kg at 8 weekly infusions) is effective in the treatment of AS. Higher doses are required in a small proportion of patients when treatment is only partially effective. Titrating the dose and frequency of infusions may be required in individual patients to achieve optimal response. Using low-dose infliximab has significant economic implications.

Adult↗
PubMed2005

Coping and psychological adjustment in recent-onset inflammatory polyarthritis: the role of gender and age.

OBJECTIVES: To examine the role of gender, age and coping in psychological adjustment of patients with early inflammatory polyarthritis (IP). METHODS: One hundred and twelve patients with IP of up to 18 months' duration from the Norfolk Arthritis Register completed questionnaires measuring coping, anxiety, disability and pain. RESULTS: Thirty-six per cent of the patients were at risk of depressive symptoms. Women had significantly higher levels of depression and anxiety than men. Regression analyses showed that pain and (low) illness acceptance predicted levels of depression. Younger age, wishful thinking and covering up predicted anxiety levels. CONCLUSIONS: The study found higher levels of depression and anxiety for women than men with early IP. Psychological distress was predicted by younger age, specific coping strategies and high levels of pain.

Adaptation, Psychological↗
PubMed2005

Methotrexate-induced pancytopenia: serious and under-reported? Our experience of 25 cases in 5 years.

OBJECTIVE: To ascertain the extent of methotrexate (MTX)-related pancytopenia at the Norfolk and Norwich University Hospital (NNUH) between 1999 and 2004. METHODS: Patients were identified by a department database search, review of pharmacy records and personal communication. Pancytopenia was defined as white blood cell count (WBC) <3.5 x 10(9)/l, haemoglobin (Hb) <11 g/dl and platelet count <130 x 10(9)/l. Severe pancytopenia was defined as WBC <2.0 x 10(9)/l, Hb <10 g/dl and platelet count <50 x 10(9)/l. RESULTS: Twenty-five patients had MTX-induced pancytopenia. Eleven patients were taking folic acid and one folinic acid. The median dose of MTX was 12.5 mg weekly (interquartile range 5.625 mg) and median duration of treatment 36 months (interquartile range 40.5 months). The severity of pancytopenia correlated with the dose (P = 0.04). The numbers of patients with potential risk factors were: renal insufficiency, 8; pre-existing folate deficiency, 7; age >75 yr, 15; hypoalbuminaemia, 18; pre-existing infection with hip prosthesis, 1; possible drug interactions, 18; dosing errors, 1; and polypharmacy, 15. Pancytopenia was detected by routine blood monitoring in nine patients. There were seven deaths (28% mortality), five from sepsis and two from acute myeloid leukaemia. CONCLUSION: This is the largest reported individual case series of MTX-induced pancytopenia. With the increasing long-term use of MTX, it is important that patients be monitored for haematological side-effects as pancytopenia can be a late manifestation. Pharmacogenetics may hold the answer to predicting who is at risk of this potentially fatal complication of MTX.

Aged↗
PubMed2005

Primary systemic vasculitis: clinical features and mortality.

BACKGROUND: Wegener's granulomatosis (WG), Churg Strauss syndrome (CSS) and microscopic polyangiitis (MPA) are primary systemic vasculitides (PSV), the clinical features of which have been described from tertiary centres. AIM: To provide the first clinical description of MPA from a general hospital and compare clinical features with WG and CSS. DESIGN: Retrospective analysis of patient records. METHODS: Records of 99 PSV patients attending a single hospital, from 1988 to 2000, were reviewed for: clinical features, date/age at diagnosis, sex, duration of illness, anti-neutrophil cytoplasmic antibodies (ANCA), treatment, comorbidity and deaths. Cases were classified using ACR, CHCC and Lanham criteria/definitions. Birmingham vasculitis activity scores (BVAS) and damage index (VDI) were calculated. Survival was assessed using Cox proportional hazards model and standardized mortality ratios (SMRs). RESULTS: Compared to previous reports there was more ENT (29%) and respiratory (29%) but less renal (92%) involvement in MPA, and less ENT involvement in WG (81%). CSS showed high neurological (72%), cardiovascular (28%) and gastrointestinal (17%) involvement and the highest median (range) VDI (p = 0.01 vs. WG; p = 0.001 vs. MPA). BVAS1 was significantly lower in MPA than in WG [median (range) 15 (4-29) vs. 21 (6-39), (p = 0.001)] but not in CSS [20 (7-28), p = 0.08]. SMR (95%CI) for PSV was 4.8 (3.0-6.6); 5-year survival was 45.1% for MPA, 75.9% for WG and 68.1% for CSS. Age was a significant risk, but only to the same extent as in the reference population. When age was adjusted for, no other significant factor was found. DISCUSSION: The clinical characteristics seen here are similar to those in previous series. There are difficulties in using the MPA CHCC definitions in classification. There is a high proportion of neurological involvement in CSS, causing permanent damage. MPA may have a poorer prognosis than WG or CSS.

Aged↗
PubMed2004

Chronic periaortitis.

Chronic periaortitis commonly involves the infrarenal portion of the abdominal aorta. Idiopathic retroperitoneal fibrosis, inflammatory abdominal aortic aneurysm and perianeurysmal retroperitoneal fibrosis are its various clinical presentations. They present as a non-specific systemic inflammatory disorder and may lead to ureteric obstruction and consequent renal failure. An exaggerated inflammatory response to advanced atherosclerosis has been thought to be the main pathogenetic process. Autoimmunity has also been proposed as a contributing factor. Contrast-enhanced CT scanning is the diagnostic test of choice. Steroids and immunosuppressive agents are successfully used in the treatment of idiopathic retroperitoneal fibrosis and selected cases of inflammatory abdominal aortic aneurysm, and surgery is used in others. Early diagnosis is important in order to reduce morbidity from complications such as renal failure and mortality from aortic rupture.

Aged↗
PubMed2004

Rheumatoid vasculitis: becoming extinct?

BACKGROUND: Systemic rheumatoid vasculitis (SRV) is a relatively rare complication of RA. The incidence of SRV appeared to increase during the 1970s and 1980s from 6.0 to 12.5/million. During the 1990s there have been major changes in the treatment of RA, with more aggressive control of inflammation. Our aim was to study the epidemiology of SRV in a stable, well-defined population over a 15-yr period. METHODS: Since 1988 we have maintained a prospective register of all patients with systemic vasculitis attending the Norfolk and Norwich University Hospital. Patients presenting with new-onset SRV, as defined by the criteria of Scott and Bacon, and registered with general practitioners in the former Norwich Health Authority area between 1988 and 2002 were identified. The population in 2002 was estimated to be 445 000 (215 000 males). RESULTS: Fifty-one patients (24 male) with SRV were identified, with median age 61 yr and disease duration 16.8 yr. The overall annual incidence was 7.9/million (95% CI 5.9-10.4) (males, 7.7/million; females, 8.1/million). During the first quinquennium (1988-92) the incidence was 11.6/million (95% CI 7.4-17.0) and during the third (1998-2002) it was 3.6/million (95% CI 1.6-7.1). A rolling 3-yr average showed that the peak incidence was in 1992-94, at 15.2/million (95% CI 9.1-23.8), and the nadir was in 1998-2000, at 3.0/million (95% CI 0.8-7.8). A similar pattern was seen for males and females. There was no difference in age or disease duration at onset of SRV between the three quinquennia. CONCLUSIONS: The incidence of SRV has declined dramatically since the 1980s. This could be due to better control of inflammatory disease or changes in smoking habits.

Aged↗
PubMed2003

Influence of disease-modifying therapy on radiographic outcome in inflammatory polyarthritis at five years: results from a large observational inception study.

OBJECTIVE: To determine the effect of early treatment with disease-modifying antirheumatic drugs (DMARDs) in reducing radiographic progression over a 5-year period in patients with new-onset inflammatory polyarthritis. METHODS: Three hundred thirty-five consecutive patients with paired radiographs obtained 1 year and 5 years after enrollment in a population-based arthritis register were studied. Logistic regression was used to model differences in baseline factors associated with the start of DMARDs. The time from symptom onset to first use of DMARDs was stratified to represent 4 groups: no DMARD use, <6 months, 6-12 months, and >12 months. Radiographs of the hands and feet were scored using the Larsen method. Progression in the Larsen score was evaluated as a 5-year score adjusted for the first film score. Negative binomial regression was used to compare Larsen score progression for each of the 3 treatment groups with that for patients not receiving DMARDs. Results were then adjusted for severity, based on propensity modeling. RESULTS: Patients who received treatment had more radiographic progression than did patients who were untreated. Coefficients (95% confidence intervals), expressed as a multiple of the Larsen score in DMARD-treated patients compared with untreated patients, were as follows: 1.6 (1.1-2.3) for <6 months, 2.4 (1.5-3.6) for 6-12 months, and 2.0 (1.4-2.8) for >12 months. As expected, patients receiving treatment had more severe disease at baseline. Using the propensity score as a method of adjusting for disease severity, the influence of treatment on outcome became attenuated as follows: 1.1 (0.8-1.7) for <6 months, 1.6 (1.0-2.6) for 6-12 months, and 1.5 (1.0-2.2) for >12 months. This effect was also seen in the crude Larsen score at year 5. CONCLUSION: In this observational study, DMARD treatment was a marker not only of worse disease at presentation but also of the radiographic state and radiographic progression at 5 years. After adjustments were made for baseline disease severity, earlier therapy was shown to have a beneficial effect on outcome.

Adult↗
PubMed2003

British Society for Rheumatology Biologics Register.

The British Society for Rheumatology (BSR) established a register of patients newly treated with biological agents, the BSR Biologics Register (BSRBR), which became active in January 2002. The goal is to register all patients in the United Kingdom with rheumatic diseases, newly starting treatment with these agents and to follow them up to determine the incidence of any short and long term hazards to health. The Register is also recruiting a comparison cohort of patients with rheumatoid arthritis treated with standard disease modifying antirheumatic drugs to determine the relative contributions of disease factors and other treatments apart from biological agents on any risks observed.

Antirheumatic Agents↗
PubMed2002

Rheumatoid factor is the major predictor of increasing severity of radiographic erosions in rheumatoid arthritis: results from the Norfolk Arthritis Register Study, a large inception cohort.

OBJECTIVE: To identify the relative contributions of clinical and laboratory variables, determined at baseline, in predicting the deterioration of radiographic damage 5 years after presentation in patients with inflammatory polyarthritis. METHODS: Data from 439 subjects who sought primary care for inflammatory polyarthritis were analyzed. All subjects had paired radiographs, of which the first was obtained within 24 months of presentation and the second at 5 years after presentation. The contribution of baseline clinical and laboratory variables in predicting the degree of radiologic severity as judged by the Larsen score was assessed at both time points. Additionally, the role of these factors in predicting change after adjustment for baseline severity was also measured. RESULTS: By 5 years, 49% of subjects had evidence of erosions. The median Larsen score on the first film was 2 (interquartile range [IQR] 0-10) and the median score on the followup film was 7 (IQR 1-25). These corresponded to a median deterioration of 3 (IQR 0-14) in all subjects, whereas those subjects with evidence of erosions at first film showed a median deterioration of 15 (IQR 6-29) on followup. The rheumatoid factor (RF) status, C-reactive protein levels, the presence of nodules, and number of swollen joints at baseline were all predictive of radiographic severity at first film. Not surprisingly, the baseline radiographic score was a predictor of severity of deterioration. However, after adjusting for baseline severity, a high titer of RF (>1:160) was also an independent predictor of deterioration over 5 years: individuals with an initial RF at that level had a progression in their Larsen score that was 2.3 times (95% confidence interval 1.7-3.2) higher than that in the RF-negative individuals. Apart from this, only age had an independent effect, after adjusting for baseline severity, in predicting increasing radiographic joint damage. CONCLUSION: High-titer RF is an important variable in predicting continuing severity of radiographic damage during the first 5 years after presentation with inflammatory polyarthritis.

Adult↗
PubMed2002

Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial.

OBJECTIVE: Biological products that neutralize tumour necrosis factor alpha (TNF-alpha) are beneficial in rheumatoid arthritis (RA). We studied the effects of CDP870, a novel anti-TNF-alpha antibody fragment modified to obtain a prolonged plasma half-life ( approximately 14 days). METHODS: Thirty-six patients were randomized in a double-blind, ascending-dose group study to a single intravenous infusion of placebo (n = 12) or 1, 5 or 20 mg/kg CDP870 (each n = 8). The patients were predominantly female (30/36), had a mean age of 56 yr and a mean duration of RA of 13 years. They had received a mean of five DMARDs or experimental therapies (with 1 month washout before the study started) and had active disease. Continuation of NSAIDs and up to 7.5 mg prednisolone daily was allowed. Following the blinded dosing period, 32 patients received a single open-label infusion of either 5 or 20 mg/kg CDP870. RESULTS: In the blinded dosing period, 6/12 placebo patients withdrew from the study (for deteriorating RA < or =4 weeks after dosing). Two of 24 CDP870-treated patients withdrew, both in the 1 mg/kg group (for deteriorating RA or lost to follow up >4 weeks after dosing). The proportion of patients with ACR20 improvement for the per-protocol population with the last observation carried forward was 16.7, 50, 87.5 and 62.5% after 0, 1, 5 and 20 mg/kg CDP870 respectively (combined treatment effect, P = 0.012, primary analysis) at 4 weeks and 16.7, 25, 75 and 75% (P = 0.032) at 8 weeks. The proportion of patients with ACR50 improvement for the per-protocol population with the last observation carried forward was 0, 12.5, 12.5 and 50% after 0, 1, 5 and 20 mg/kg CDP870 respectively (combined treatment effect, P = 0.079) at 4 weeks and 0, 12.5, 12.5 and 50% (P = 0.079) at 8 weeks. Following the open-label dose of CDP870, similar beneficial effects were achieved. CONCLUSION: CDP870 is effective, was very well tolerated in this small study, and has an extended duration of action following one or more intravenous doses.

Adolescent↗
PubMed2002

Evaluation of the Sørensen diagnostic criteria in the classification of systemic vasculitis.

OBJECTIVES: To evaluate the use of the diagnostic criteria for Wegener's granulomatosis (WG) and microscopic polyangiitis (mPA) proposed by Sørensen et al. in the classification of primary systemic vasculitis (PSV). METHODS: We applied to our cohort of PSV patients the American College of Rheumatology (ACR) criteria for WG, Churg-Strauss syndrome (CSS) and polyarteritis nodosa (PAN), the Chapel Hill Consensus Conference (CHCC) definitions for WG, mPA and CSS, the Hammersmith criteria for CSS and the Sørensen criteria for WG and mPA. RESULTS: Ninety-nine PSV cases were identified. Fifty-six fulfilled criteria for WG (ACR), 60 for PAN (ACR) and 15 for CSS (ACR). Four fulfilled the Hammersmith criteria for CSS. Thirty-nine were defined as mPA (CHCC). Fifty-three patients fulfilled the Sørensen criteria for WG and three for mPA. Five of six patients classified as WG (ACR) who did not meet the Sørensen criteria were excluded by eosinophilia. Six patients who did not fulfil WG (ACR) met the Sørensen criteria for WG. CONCLUSION: The classification of systemic vasculitis is complicated and many cases fulfil more than one set of criteria. The Sørensen criteria for WG is limited by its exclusion of eosinophilia despite reports of an association. We recommend that tissue eosinophilia or peripheral eosinophilia of <1.5x10(9)/l should not exclude a diagnosis of WG. With this modification, the Sørensen criteria for WG may be a useful method of classification, especially in confirming the classification of WG in patients who fulfil both WG (ACR) and mPA (CHCC). Few patients fulfilled the Sørensen criteria for mPA which suggests that they are not of value in classification.

Churg-Strauss Syndrome↗
PubMed2002

HFE mutations in an inflammatory arthritis population.

OBJECTIVES: To determine the value of screening patients with inflammatory arthritis for haemochromatosis-associated mutations in the HFE gene. METHODS: We screened 1000 patients with inflammatory arthritis and 1000 controls for the HFE gene mutations that are associated with haemochromatosis. The arthritis patients were diagnosed between 1989 and 1995 and their blood DNA was archived as part of the Norfolk Arthritis Register project. RESULTS: Five out of 1000 (0.005) patients in the arthritis group were homozygous for the HFE C282Y mutation. This frequency is the same as the frequency of 5/1000 (0.005) for C282Y homozygosity observed in the normal population. It is slightly above the predicted frequency of homozygosity of 0.0044 derived from the gene frequency in the normal population. CONCLUSIONS: These data suggest that most of the C282Y homozygotes occurred in this arthritis group by chance and that their arthritis was incidental to their HFE genotype. This implies that screening for HFE mutations among patients with inflammatory arthritis would infrequently identify patients whose arthritis might benefit from additional treatment.

Adult↗