Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins.

Immobilized rabbit and rat C-reactive protein (CRP) were found to selectively bind apolipoprotein B (apoB)-containing lipoproteins (low density lipoprotein, LDL and very low density lipoprotein, VLDL) from whole serum in a manner similar to that previously reported with human CRP. In acute phase human serum the CRP is in a free form, not complexed with lipoprotein or any other macromolecular ligand, and in acute phase serum from most rabbits fed on a normal diet the rabbit CRP was also free. However, in acute phase serum or heparinized plasma from hypercholesterolemic rabbits part or all of the CRP was found by gel filtration and immunoelectrophoretic techniques to be complexed with beta-VLDL, an abnormal apoB-containing plasma lipoprotein present in these animals. The presence of extent in different serum samples of CRP complexed with lipoprotein correlated closely with the serum apoB concentration. The formation of complexes between native, unaggregated rabbit CRP in solution and apoB-containing lipoproteins was readily demonstrable experimentally both with the isolated proteins and in whole serum. In all cases these interactions were calcium-dependent and inhibitable by free phosphoryl choline. The present findings extend earlier work in man and the rabbit and indicate that among the C-reactive proteins from different species, which are structurally highly conserved, the capacity for selective binding to apoB-containing plasma lipoproteins is also a constant feature. These interactions may therefore be related to the in vivo function of CRP in all species and this function may in turn be relevant to pathological conditions, such as atherosclerosis, in which lipoproteins are important.

Eight years' experience of regional audit: an assessment of its value as a clinical governance tool.

Strengthening clinical audit is crucial for improving the quality of healthcare provision. The West Midlands Rheumatology Service and Training Committee coordinates an innovative programme of regional audits and the experience of rheumatology healthcare professionals involved was surveyed. This was a questionnaire-based study in which respondents rated statements relating to regional audit on Likert scales. Out of 105 staff, 70 replied. There was consensus that results of regional audit have been robust, valid and reliable; regional audits benefit patients and units; provide educational opportunities for specialist registrars (SpRs); and are more efficient than local audit by allowing comparison between units. Opinion was divided about how well informed respondents were and how effective they are at closing the audit loop. Many units reported changes in practice. Regional audit is widely perceived to be a valuable clinical governance tool supporting significant changes to clinical practice, and an excellent training opportunity for SpRs. Recommendations for a successful regional audit scheme are described in this article.

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.

Continuous subcutaneous insulin infusion does not provoke significant acute-phase response.

C-reactive protein (CRP), the classical acute-phase reactant, and serum amyloid A protein (SAA), the putative precursor of AA-type amyloid fibrils, were measured in 62 diabetic patients. They were all attending their regular clinic appointments and had been asymptomatic during the 2 wk preceding sampling. CRP and SAA levels were similar in 18 patients on continuous subcutaneous insulin infusion (CSII), 27 patients treated by conventional insulin therapy (CIT), nine treated by diet only, and eight treated by diet and oral hypoglycemic agents, and were almost entirely within the normal range. It is concluded that CSII does not provoke an acute-phase reaction in diabetic patients and, while caution should always be exercised with a new form of treatment, it does not seem likely that CSII will predispose to the development of reactive systemic amyloidosis.

Measurement of serum C reactive protein concentration after bone marrow transplantation for leukaemia.

C reactive protein concentration was measured serially in 19 patients with leukaemia after bone marrow transplantation. Six episodes of graft versus host disease occurred in the presence of fever but with no evidence of infection, and these were associated with C reactive protein concentrations as high as 200 mg/l. C reactive protein values were also increased in 12 febrile episodes associated with infection, in seven of which graft versus host disease was also present. C reactive protein concentrations are of no value in differentiating infection from graft versus host disease, but in both cases they may be useful as an objective index of response to appropriate treatment.

Candidal infection of bone. Assessment of serologic tests in diagnosis and management.

In this case report, 30 sera from a 25-year-old heroin abuser with intervertebral candidosis were treated for the presence of anti-Candida albicans antibodies by agglutination, counterimmunoelectrophoresis, and indirect immunofluorescent assay. Sera were also adsorbed with heat-killed blastospores to remove antibodies against yeast-phase cells and tested by indirect immunofluorescent assay for anti-C. albicans germ tube antibodies (CAGTAs). Humoral responses to candidal 47-kD antigen were studied by immunoblotting in 23 unadsorbed sera. Anti-C. albicans antibodies were found in high titers by the three procedures but correlated poorly with the clinical evolution of the disease. CAGTAs were present from the beginning of the infection: Titers decreased in association with antifungal treatment and the patient's improvement, eventually becoming negative. Only class IgG antibodies to the 47-kD antigen were detected. These were present during the full course of the infection, failing to disappear at the end of the study. In this case, detection of CAGTAs appeared to be an important aid to diagnosis of the bony candidal infection, as they are detected early during the illness and seemed to have a prognostic significance.

Comparison of knowledge and psychological well-being between patients with a short disease duration (< or = 1 year) and patients with more established rheumatoid arthritis (> or = 10 years duration).

Patients with rheumatoid arthritis (RA) of short disease duration (i.e. < or = 1 year) compared with patients of longer disease duration (i.e. > or = 10 years) in terms of RA knowledge, symptoms of anxiety, symptoms of depression and disease acceptance. In addition, the predictors of psychological distress (i.e. symptoms of anxiety and depression) were examined. Data were collected by self-administered questionnaires. As expected, patients with more established disease were significantly older and had more physical dysfunction. However, there were no statistically significant differences on anxiety, depression, acceptance of illness, pain or knowledge about RA. The need for education regarding RA and its implications was expressed by all participants regardless of disease duration. Illness acceptance beliefs were identified as significant predictors of both anxiety and depression.

Educational preferences, psychological well-being and self-efficacy among people with rheumatoid arthritis.

As a basis for developing interventions to meet the psycho-educational needs of rheumatoid arthritis (RA) outpatients attending a regional hospital have been investigated. Specifically, patients' preferences for interventions addressing education (e.g. the disease and its treatment), self-management (e.g. pain-management, exercise) and the consequences (e.g. emotions, impact on work, family relationships) of RA were examined. In addition, psychological well-being and self-efficacy were examined. Results showed that patients preferred education about the disease and its treatment to be delivered on a one-to-one basis by health professionals. Similarly, emotional issues were believed to be best dealt with one-to-one although this could be with a similar other (i.e. a patient). Group interventions were the preferred format for self-management, exercise and relationship issues, whereas videos were thought to be useful for demonstrating use of aids and how other families cope. None of the participants would welcome computer-based interventions. Psychological well-being (e.g. depression, anxiety) remained stable over a 12-month period. Both physical and psychological health status were correlated with arthritis self-efficacy. The implications of these findings are discussed in relation to development of interventions to better meet the psycho-educational needs of outpatients with RA.

Piloting education days for patients with early rheumatoid arthritis and their partners: a multidisciplinary approach.

OBJECTIVES: To develop, pilot, refine and reassess an education day presented by a rheumatology multidisciplinary team (MDT) for recently diagnosed (less than six months) rheumatoid arthritis (RA) patients and their partners/carers. METHODS: A patient education day was developed drawing on an assessment of local patient educational needs and preferences and input from a rheumatology MDT. Feedback from the first education day (2004) (Day 1; 12 patients; age range 19-63 years (median 46); 10 of whom were accompanied by a partner) informed the development of a second education day (2005) (Day 2; 19 patients; age range 36-75 years (median 57.5); 13 of whom were accompanied by a partner). Participants completed evaluation forms on both days and at follow-up between six and seven weeks later, rating each session on a 5-point scale on dimensions of 'informative', 'useful', 'interesting' and 'enjoyable'. A global rating of the day's 'usefulness' was completed at the end of each day on a 10-point scale. Participants were asked to write comments on each session and on aspects of the entire day. RA knowledge, and general and RA-specific self-efficacy were also measured on day 2 (and at follow-up) using the 12-item Patient Knowledge Questionnaire, the 10-item generalized self-efficacy scale and a four-item RA-specific self-efficacy scale. Both qualitative and quantitative methodologies were used in the analysis. RESULTS: Ratings for individual sessions were all high, with no session being rated below 4 out of 5 (1 = 'totally disagree' to 5 = 'totally agree') on both days. The majority of patients (84%) and their partners (57%) responded to the follow-up. Many had used the information package distributed on the day. Some patients and their partners reported positive changes in RA management. Although patient knowledge did not increase significantly (medians 11 at both time points, p = 0.054) (Day 2), RA self-efficacy improved (baseline 11 and 14, respectively), suggesting that patients were more confident in managing their condition (p = 0.010). CONCLUSIONS: The development of this 'local' education and information intervention was carried out in line with Medical Research Council guidelines, and the lessons learned from Day 1 informed further development for Day 2. A one-day format for education of early RA involving the rheumatology MDT was rated highly by participants and warrants further examination. Although this study was a small 'local' intervention, its strengths are that it informs the possibility of wider developments of this kind using a MDT.

Experience of six years of a regional peer review scheme in rheumatology.

OBJECTIVE: Following discussions on peer review by the British Society for Rheumatology, the West Midlands Rheumatology Service and Training Committee established a peer review scheme for the West Midlands in 1998. We report our initial 6 yr of experience, during which all 14 units have been visited. METHODS: A rotating programme of visits was organized. Following this first cycle of peer review, questionnaires were sent to all consultants and senior allied health professionals in each visited unit and to all members of each visiting team to evaluate the process. RESULTS: There was clear consensus amongst staff from both visited units and visiting teams that a peer review visit is worthwhile and constructive. It is a good opportunity for education and exchange of ideas between staff and to promote the multidisciplinary team in rheumatology. Most recommendations from the reports were considered necessary. The most frequent recommendations were for an increase in consultants and therapy staff. Appointing further consultants has been successful. Opinion was only divided on whether the reports were viewed seriously by Trusts, whether peer review should be regional or national, and how to accurately assess the quality, as well as the quantity, of care provided. Staff would support further cycles of peer review visits. CONCLUSIONS: This has been a successful initiative and a positive learning experience for all staff involved. Specifically, it helped to obtain more staff and secure facilities. We recommend developing this scheme and promoting it to other regions.

A regional audit of the use of COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) in rheumatology clinics in the West Midlands, in relation to NICE guidelines.

OBJECTIVES: Whilst all non-steroidal anti-inflammatory drugs (NSAIDs) can cause adverse gastrointestinal events, COX-2-selective inhibitors (COX-2) may have improved gastrointestinal safety compared with non-selective NSAIDs (NSNSAIDs). In 2001, the National Institute for Clinical Excellence (NICE) published guidance on the use of the COX-2 agents celecoxib, rofecoxib, meloxicam and etodolac for rheumatoid arthritis (RA) and osteoarthritis (OA). This study aimed to audit the appropriateness of NSAID use in relation to NICE guidance in rheumatology out-patients. METHODS: Questionnaires were completed for all patients attending clinics in 18 rheumatology units in the West Midlands over a 2-week period. Data collected included patient demographics, NSAID type, indications, duration of use (> or =3 months was considered prolonged), and concomitant prescription of corticosteroids, warfarin and gastroprotective agents. RESULTS: Data were collected on 2846 patients; 1164 (41%) were taking NSAIDs (791 NSNSAIDs, 373 COX-2). Of the 1164 NSAID users, 753 (65%) had a diagnosis of RA or OA (483 NSNSAIDs, 270 COX-2). Overall, 37% of NSAID prescriptions were appropriate. Of the NSNSAID users, 92% had at least one risk factor for adverse gastrointestinal events and were therefore inappropriately treated. Prolonged use (in 89%) and age > or =65 yr (in 23%) were the most frequent risk factors identified. Of the COX-2 users, 97% had one or more risk factors and were appropriately treated. Analysis of the RA/OA subgroup revealed similar findings. Thirty-six per cent were taking NSAIDs appropriately; 97% of NSNSAID use was inappropriate and 97% of COX-2 use was appropriate treatment. In the whole cohort, gastroprotective agents were used in 26% of NSNSAID users, 56% of gastroprotective agents being proton pump inhibitors. CONCLUSIONS: Ninety-two per cent of patients attending rheumatology clinics who were taking NSNSAIDs should have been prescribed a COX-2-selective agent in relation to NICE guidance. Duration of use and age > or =65 yr emerged numerically as the most important risk factors. Significant numbers of patients taking NSNSAIDs may be at risk from adverse gastrointestinal events and clinicians may wish to review their prescribing patterns. Conversely, 97% of patients taking COX-2 agents were treated appropriately. Although practice overall conformed poorly with NICE guidance, NSAID prescribing also needs to be considered in the context of recent concerns regarding the cardiovascular risks of COX-2 agents.

Arthritis in the acquired immunodeficiency syndrome and other viral infections.

Musculoskeletal conditions occurring in individuals with human immunodeficiency virus infection are becoming increasingly well documented. Arthritis with features of Reiter's syndrome or psoriatic arthritis has been further studied; an association with HLA-B27 but not with HLA antigens chemically associated with psoriasis or psoriatic arthritis has been demonstrated. Human immunodeficiency virus has been identified in synovial fluid dendritic cells and in the synovium; immunohistochemical analysis is revealing the nature of the lymphocyte infiltrate in the synovium of affected individuals. Postmortem studies suggest that there may be histologic evidence of premature aging in clinically unaffected joints from patients with acquired immunodeficiency syndrome. Epidemiologic studies are needed to elucidate which rheumatic lesions occur as a direct consequence of human immunodeficiency infection and which may be chance associations.

Serum C-reactive protein measurement in pyoderma gangrenosum.

A case of pyoderma gangrenosum is reported in a patient with a past history of ulcerative colitis. Serial C-reactive protein (CRP) concentrations were measured and were found to be markedly elevated at presentation. Levels were also raised during two subsequent relapses. CRP levels proved to be a useful objective indicator of disease activity and response to therapy, and reflected changes in disease activity before the erythrocyte sedimentation rate.

Pyogenic infection and rheumatoid arthritis.

Ten episodes of severe pyogenic infection occurring in nine patients with rheumatoid arthritis are reported. There was a wide range of presenting features including pyoarthrosis in 7 episodes. Three cases presented with meningitis, bacterial endocarditis and probable multiple abscesses respectively. Infection was caused by Staphylococcus aureus in 7 episodes and by Staphylococcus epidermidis, Streptococcus pneumoniae and beta-haemolytic Streptococcus in each of one episode. Three infective episodes were fatal. Pyogenic, especially staphylococcal, infection should be considered in patients with rheumatoid arthritis with unexplained illness with or without sudden deterioration in joint symptoms. It is important to recognize and treat infection rapidly.

In vivo turnover studies of C-reactive protein.

The in vivo plasma clearance rate of the acute phase reactant C-reactive protein (CRP) was studied in mice and rats. The clearance rate of 125I-human CRP in mice and 125I-rat CRP in rats showed a T1/2 of approximately 4 h. The T1/2 was independent of circulating levels of CRP and was not affected by the presence of C-polysaccharide (CPS), a ligand to which CRP binds. However, in mice receiving sufficient CPS, more radioactivity localized to the spleen compared to mice receiving 125I-CRP only. 125I-CPS was rapidly cleared at the same rate by normal mice and by mice undergoing an acute phase response while rats cleared 125I-CPS more slowly despite having high circulating CRP concentrations. These findings suggest that CRP does not provide a mechanism for extremely rapid clearance of its ligands from the circulation, although the handling and subsequent fate of these ligands may be affected.

Acute-phase high-density lipoprotein in the rat does not contain serum amyloid A protein.

Serum amyloid A protein (SAA) is an acute-phase apolipoprotein of high-density lipoprotein (HDL). Its N-terminal sequence is identical with that of amyloid A protein (AA), the subunit of AA amyloid fibrils. However, rats do not develop AA amyloidosis, and we report here that neither normal nor acute-phase rat HDL contains a protein corresponding to SAA of other species. mRNA coding for a sequence homologous with the C-terminal but not with the N-terminal part of human SAA is synthesized in greatly increased amounts in acute-phase rat liver. These observations indicate that the failure of rats to develop AA amyloid results from the absence of most of the AA-like part of their SAA-like protein, and that the N-terminal portion of SAA probably contains the lipid-binding sequences.