Regional review of patients with psoriatic arthritis in secondary care in the West Midlands: prevalence, disease activity and eligibility for anti-tumour necrosis factor therapy.

OBJECTIVES: Tumour necrosis factor alpha-blockers (TNF-alpha) are licensed for the treatment of psoriatic arthritis (PsA) and their use has been approved by the National Institute for Health and Clinical Excellence (NICE) for use in the United Kingdom under a set of defined clinical criteria. METHODS: In this out-patient study we evaluated PsA in rheumatology secondary care clinics in units across the West Midlands over a 2-week period, assessing prevalence, disease activity and eligibility for anti TNF-alpha treatment as defined by the NICE criteria. RESULTS: Of the 1718 forms returned from the 2000 sent (86% response rate), 175 patients had PsA (10.2%). Of those, 22 (12.6%) were already on anti TNF-alpha treatment. 12 patients were noted to have purely axial disease and as per the NICE guidelines should not be assessed under the PsA criteria. A further 5 patients fulfilled the criteria for treatment with anti TNF-alpha with no contraindications. In the region 22 out of 27 patients (81%) with active disease were correctly on Anti TNF therapy. In total 27 (15.4%) patients with PsA met the NICE criteria for treatment of PsA with anti TNF-alpha therapy. 3 patients had previously failed anti TNF-alpha treatment. No patient fulfilling criteria for treatment were found to have any contraindications to treatment. CONCLUSION: We note the relatively high proportion of PsA patients eligible for treatment with anti TNF-alpha blockers in the region (15.4%) compared to the NICE estimate (2.4%). This may be in part explained by a selection bias. However, the results may have significant implications for healthcare provision given the relatively high cost of anti-TNF-alpha agents. We comment on the limitations of such criteria and the effective use of regional collaboration for both training and audit purposes.

Regional survey of tuberculosis risk assessment in rheumatology outpatients commencing anti-TNF-alpha treatment in relation to British Thoracic Society guidelines.

The aim of this study was to analyse tuberculosis (TB) risk assessment for rheumatology patients commencing anti-tumour necrosis factor-alpha (anti-TNF-alpha) therapy using the British Thoracic Society (BTS) guidelines. Data were obtained retrospectively on 856 outpatients regionally receiving anti-TNF-alpha. Prior to commencing treatment, patients had the following assessments documented: respiratory examination, 47.4%; chest X-ray, 84.5%; TB history, 92.9%; and advice about TB risk, 45.8%. Of the 856 patients, 94.3% were on immunosuppressives but 27% had a tuberculin test; 12.6% had > or =1 high-risk factors for TB. In total, 3.4% were referred to a TB specialist and of these, 24.1% had no risk factors for TB. Of patients with > or =1 risk factor, 76.9% were not referred. Only 4/28 patients at high risk for TB due to ethnicity or birthplace received chemoprophylaxis. Marked inter-unit variation was demonstrated and it was evident that patients require improved screening for TB. Greater awareness is necessary of patients with risk factors, particularly ethnicity, to facilitate more appropriate targeting of chemoprophylaxis. Multi-centre audit is a valuable clinical governance tool.

Accessibility and quality of secondary care rheumatology services for people with inflammatory arthritis: a regional survey.

Secondary care rheumatology services for patients with inflammatory arthritis (IA) in the West Midlands were audited using Arthritis and Musculoskeletal Alliance (ARMA) standards of care. Questionnaires were analysed from 1,715 patients in 11 rheumatology departments. ARMA standards recommend full multidisciplinary team assessment; referral rates to nurse specialists (52.3%), physiotherapists (48.7%) and occupational therapists (36.5%) were, however, lower than expected. Attendance at existing hospital-led education groups was rare (8.9%), awareness of existing helplines was moderate (59.2%) but the proportion of patients reporting satisfaction with advice about their disease was high (80.5%). Significant variations were found between departments. For patients with IA < 2 years (n = 236), 84.5% were seen by a rheumatologist within the ARMA standard of 12 weeks of referral; diagnosis of a type of IA was made at the first rheumatology appointment in 66.4%; 82.8% of rheumatoid arthritis patients had commenced disease-modifying drugs, although time to commencement varied across departments. This study raises issues regarding provision of rheumatology services, prioritisation of patient referral and patient education.

Audits of the prevention and treatment of corticosteroid-induced osteoporosis in outpatients with rheumatic diseases in the West Midlands.

The management of corticosteroid-induced osteoporosis in rheumatology outpatients in the West Midlands was audited in relation to the 2002 Royal College of Physicians (RCP) Guidelines and re-audited in relation to the 1998 National Osteoporosis Society (NOS) Guidance. Practice was assessed from prospective data on all follow-up patients over a 2-week period in 13 rheumatology units. Data were analysed on 2,609 patients. Of the 626 patients fulfilling criteria for assessment against the RCP Guidelines, 351 (56.1%) were treated appropriately. The results do not allow for availability of, or wait for, DEXA scanning. Of 197 patients fulfilling the criteria for assessment against the NOS Guidance, 137 (69.5%) were treated appropriately, compared to 63% in a similar audit undertaken in 2000. Regional audit may facilitate clinical governance. These audits will inform discussion on both improving local practice and strengthening cases for improved osteoporosis services.

Pharmacokinetics of doxorubicin in man: dose and schedule dependence.

Doxorubicin serum elimination kinetics were measured by HPLC in three different patient groups. A dose of (a) 30 mg/m2; (b) 50 mg/m2, and (c) 4 x 15 mg/m2 every 10 h was administered by bolus injection to (a) 10, (b) 6, and (c) 8 patients. The results obtained provided strong evidence for a nonlinear dependence of doxorubicin serum elimination on the dose and administration schedule used. Comparing the 15 and 30 mg/m2 dose there was no significant increase in early drug levels but a marked increase in terminal half-life. At doses higher than 30 mg/m2, however, there was a steep increase in early drug levels, too. Moreover a marked cumulation of the anthracycline in the central compartment following short-term (4 x 15 mg/m2 every 10 h) consecutive administration was found. To obtain an optimal concentration x time product by single bolus injection a dose equal or higher than 30 mg/m2 should be used. However, in this dose range a steep dose-dependent rise in early drug levels is to be expected. As early high serum levels correlate with congestive heart failure, administration schedules reaching effective concentration x time products without high peak levels such as continuous infusion or consecutive administration of low doses seem to be necessary.

A rapid chromatographic procedure for the determination of adriamycin, daunomycin and their 13-OH metabolites adriamycinol and daunomycinol.

A rapid chromatographic procedure for the quantitative determination of the anthracycline antibiotics adriamycin and daunorubicin and their chief metabolites adriamycinol and daunorubicinol in plasma and urine is described. The extraction is performed using SEP-PAK silica cartridges. After filtration the eluate is chromatographed on a reversed-phase column.

Pharmacokinetics and metabolism of thiopurines in children with acute lymphoblastic leukemia receiving 6-thioguanine versus 6-mercaptopurine.

Mercaptopurine (6MP) has been the standard drug for maintenance therapy of acute lymphoblastic leukemia. In a multicenter study we investigated whether thioguanine (6TG), which is converted more directly to the cytotoxic thioguanine nucleotides (TGN), offers a therapeutic advantage over 6MP. In this study (COALL-92), 6TG was randomized versus 6MP in maintenance therapy, whereby the doses of both drugs had to be adjusted to a white blood cell (WBC) count of between 2 and 3/nl. In 19 children the plasma levels of both drugs and/or the accumulation of their metabolites in red blood cells (RBC) were measured during intensive treatment in two consecutive chemotherapy blocks, and in 54 children the metabolites in RBC were measured every 3 months during daily treatment in maintenance therapy. There was a marked interindividual difference in the plasma kinetics of the two drugs; after identical doses of 100 mg/m2 an about 4-fold higher peak concentration of the parent drug was reached with 6MP. The main metabolites of 6TG were thioguanine nucleotides (TGN), whereas during 6MP treatment, methylated thioinosine nucleotides (TIN) predominated in erythrocytes. In patients receiving 6TG during maintenance therapy (22 patients) the concentration of methylated TGN reached about 40% of that of unmethylated TGN; after 6MP administration (32 patients) the methylated TIN were concentrated about 26-fold higher in RBC than were TGN. In contrast to 6TG, for 6MP the pattern of metabolites shifted toward the methylated ones with increasing dose. The median TGN concentration was about 7-fold higher in the TG branch, although the median dose was only about 70% of that of 6MP. The WBC values were equivalent in the two treatment groups. Our results suggest that the cytotoxic effect of 6MP is not based solely on the formation of TGN.

Multivariate analysis of urinary RNA catabolites in malignancies: cross-sectional and longitudinal studies.

Urinary RNA catabolites, especially modified nucleosides and nucleobases, have turned out to represent valuable new criteria for diagnosis and follow-up of malignancies. Here we show for the first time that multivariate analysis of urinary RNA catabolites can distinguish between tumor carriers and controls who, if examined by univariate procedures, would remain undifferentiated. Two such models have been demonstrated. We hope that a continuation of this work will support primary clinical diagnostic procedures, the control of therapy effects, and the long-term follow-up of patients, which should be regarded as special medical applications of the general principles of molecular biology.

Hypertension is not a disease of the left arm: a difficult diagnosis of hypertension in Takayasu's arteritis.

Hypertension and its cause may be missed by failure to measure blood pressure in both arms. We report a case of Takayasu's arteritis where diagnostic confusion arose because there was a failure to detect a difference in blood pressure between the arms.

Polypharmacy among people with rheumatoid arthritis: the role of age, disease duration and comorbidity.

BACKGROUND: People with rheumatoid arthritis (RA) often have comorbidities with associated disability and complex medication regimens. Little published evidence exists about why people with RA require so many medications, although it is logical to hypothesize that this may relate to older age, longer duration of RA, more active RA, worse functional disability and a greater number of comorbidities. OBJECTIVES: We set out to quantify polypharmacy in RA and identify its predictors in an observational cohort. METHODS: The case notes of 348 people receiving secondary care for RA were reviewed to record polypharmacy. The 28-joint Disease Activity Score (DAS28) was calculated and the Health Assessment Questionnaire (HAQ) and the Self-administered Comorbidity Questionnaire (SCQ) were completed. RESULTS: The mean total number of medications was 5.39, with a maximum of 16; of these, a mean of 2.41 medications were directly for RA. A mediational relationship was identified: older age and longer RA duration were significant predictors of a greater total number of medications, but these relationships were explained by the greater number of comorbidities in older participants and those with longer RA duration. Polypharmacy was not related to RA activity or functional disability. CONCLUSIONS: Polypharmacy is common among people with RA and associates with older age and longer RA duration through a greater number of comorbidities. Regular review of the full treatment plan of individuals with RA by pharmacists and other health professionals specializing in rheumatology, to weigh the benefits and risks of each medication and their interactions in light of RA activity and comorbidities, is advocated.

'Concealing the evidence': the importance of appearance concerns for patients with systemic lupus erythematosus.

Outwardly visible signs associated with systemic lupus erythematosus (SLE) can include facial rashes, alopecia and weight gain. We sought to understand the concerns of SLE patients about their appearance and the recognition of this by healthcare professionals. Semi-structured interviews were carried out with 10 women aged 26-68 years diagnosed with SLE for one to 12 years. Data were analysed with Interpretative Phenomenological Analysis (IPA); this seeks to describe and provide understanding of people's experience of a phenomenon by studying in-depth a small number from a relatively homogeneous group (women with SLE in the present study). Analysis revealed three themes concerning appearance issues. Participants described public self-consciousness after the onset of SLE. Cosmetics and clothing were used skilfully to appear 'normal', hide the 'self' and assert control but could increase feelings of difference and isolation. Self-imposed isolation was also described and may relate to depression. The understanding of family, friends, colleagues and healthcare providers was also important. Awareness of the psychosocial concerns of SLE patients with life-changing skin disease may enable multidisciplinary healthcare teams to offer a more sensitive, practical service. The physical and emotional needs of SLE patients need to be ascertained and appropriate educational and psychological services are required.

Cutaneous abnormalities in rheumatoid arthritis compared with non-inflammatory rheumatic conditions.

BACKGROUND: Cutaneous abnormalities are common in rheumatoid arthritis, but exact prevalence estimates are yet to be established. Some abnormalities may be independent and coincidental, whereas others may relate to rheumatoid arthritis or its treatment. OBJECTIVES: To determine the exact nature and point prevalence of cutaneous abnormalities in patients with rheumatoid arthritis compared with those in patients with non-inflammatory rheumatic disease. METHODS: 349 consecutive outpatients for rheumatology (205 with rheumatoid arthritis and 144 with non-inflammatory rheumatic conditions) were examined for skin and nail signs by a dermatologist. Histories of rheumatology, dermatology, drugs and allergy were noted in detail. RESULTS: Skin abnormalities were reported by more patients with rheumatoid arthritis (61%) than non-inflammatory controls (47%). More patients with rheumatoid arthritis (39%) than controls (10%) attributed their skin abnormality to drugs. Cutaneous abnormalities observed by the dermatologist were also more common in patients with rheumatoid arthritis (76%) than in the group with non-inflammatory disease (60%). Specifically, bruising, athlete's foot, scars, rheumatoid nodules and vasculitic lesions were more common in patients with rheumatoid arthritis than in controls. The presence of bruising was predicted only by current steroid use. The presence of any other specific cutaneous abnormalities was not predicted by any of the variables assessed. In the whole group, current steroid use and having rheumatoid arthritis were the only important predictors of having any cutaneous abnormality. CONCLUSIONS: Self-reported and observed cutaneous abnormalities are more common in patients with rheumatoid arthritis than in controls with non-inflammatory disease. These include cutaneous abnormalities related to side effects of drugs or to rheumatoid arthritis itself and other abnormalities previously believed to be independent but which may be of clinical importance.

Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome.

BACKGROUND: Cardiovascular mortality is increased in rheumatoid arthritis. Possible reasons include an increased incidence of ischaemic heart disease or worse outcome after acute coronary syndrome (ACS). OBJECTIVES: To assess the outcome of ACS in rheumatoid arthritis compared with case matched controls in the context of underlying cardiac risk factors, clinical presentation, and subsequent management. METHODS: 40 patients with rheumatoid arthritis and ACS identified from coronary care admission registers between 1990 and 2000 were case matched as closely as possible for age, sex, classical cardiovascular risk factors, type and severity of ACS, and admission date (+/-3 months) with 40 controls. A standardised proforma was used for detailed case note review. RESULTS: Age, sex, other cardiovascular risk factors, and type and severity of presenting ACS were not significantly different between cases and controls. Recurrent cardiac events were commoner in rheumatoid arthritis (23/40, 57.5%) than controls (12/40, 30%) (p = 0.013); there were 16/40 deaths in rheumatoid arthritis (40%) v 6/40 (15%) in controls (p = 0.012). Recurrent events occurred earlier in rheumatoid arthritis (log rank survival, p = 0.05). Presentation with chest pain occurred in all controls compared with 33/40 rheumatoid patients (82%) (p = 0.006); collapse occurred in one control (2.5%) v 7/40 rheumatoid patients (17.5%) (p = 0.025). Treatment during the ACS was not significantly different in the two groups. CONCLUSIONS: Recurrent ischaemic events and death occur more often after ACS in rheumatoid arthritis. Atypical presentation is commoner in rheumatoid arthritis. There is an urgent need to develop identification and intervention strategies for ACS specific to this high risk group.

"Joining the dots" for patients with systemic lupus erythematosus: personal perspectives of health care from a qualitative study.

OBJECTIVES: To examine the perceptions of patients with systemic lupus erythematosus (SLE) about their health care provision in the United Kingdom. METHODS: Semistructured interviews were conducted with 10 women aged 26 to 68 years who were diagnosed with SLE one to 12 years earlier. Interviews were audio recorded, transcribed verbatim, and analysed using interpretative phenomenological analysis to organise the themes of importance to participants. RESULTS: Four themes emerged: diagnostic difficulties; understanding; communication; and integrated health care. Before diagnosis there was concern to appear legitimately ill and to have a label for the condition. After diagnosis participants still encountered health care professionals who were poorly informed about SLE. Family, friends, and employers did not understand the fluctuating nature of SLE, which often led to isolation. Participants felt that even health care professionals who specialised in SLE could not fully understand the psychosocial impact of the condition, and therefore did not provide information to meet those needs. Participants did not know which of the many health care professionals they had contact with to approach about their concerns. Lack of communication at an interdisciplinary level left them feeling that nobody was "joining the dots" for their health care. CONCLUSIONS: Patients with SLE do not feel understood by health care providers or people close to them. Support from trained volunteers with SLE, as available at the open access lupus clinic in Dudley (West Midlands, UK), would ensure more adequate information from someone with personal experience. Such services may improve communication and help minimise SLE patients' isolation.

The impact of anti-tumour necrosis factor therapy for rheumatoid arthritis on the use of other drugs and hospital resources in a pragmatic setting.

BACKGROUND: Anti-tumour necrosis factor (anti-TNF) therapy has been an important development for the treatment of rheumatoid arthritis (RA) but the impact of its delivery on hospital resources in still emerging. AIMS: We audited the effect of starting anti-TNF on the use of other anti-rheumatic therapies and hospital resources in a routine secondary care setting. METHODS: A retrospective study of resource use before and after anti-TNF was conducted. Hospital records of 54 RA patients were studied and data taken from the time of commencing anti-TNF to 1 October 2004 and an equal time period prior to commencing anti-TNF. Identical data were collected for 54 controls not on anti-TNF. Relevant figures were extrapolated to per annum rates. Results were analysed using two-factor ANOVAs comparing the pre- versus post-anti-TNF period. Cases on intravenous (IV) versus subcutaneous (SC) anti-TNF were also compared in separate ANOVAs. RESULTS: Mean duration of anti-TNF therapy was 17.04 months (range 3.60-42.36). Mean pre- and 3-months post-anti-TNF Disease Activity Scores (DAS28) were 6.93 and 3.88, respectively. Cases were more likely than controls to be on oral prednisolone pre- and post-anti-TNF. Methylprednisolone requirement, number of disease-modifying anti-rheumatic drugs (DMARDs), telephone helpline contacts and duration as an inpatient reduced significantly post-anti-TNF. Day case admissions increased but outpatient appointments decreased only in cases on IV anti-TNF. CONCLUSIONS: In a pragmatic setting, anti-TNF therapy led to reduced need for steroid injections and other DMARDs, as well as reductions in use of several hospital resources. Wider replication of these findings will be important for planning delivery.