Is it necessary to adjust current creatine kinase reference ranges to reflect levels found in professional footballers?

OBJECTIVE: We aimed to explore the validity of applying current reference ranges of the enzyme creatine kinase (CK) when analysing the medical status of professional footballers and to offer a more functional CK reference range for professional footballers. METHODS: A sample of 27 professional male footballers competing in The Football League Championship was analysed. The single sample Wilcoxon signed-rank test was used to compare the CK distribution of the study group with that of a control group of military personnel reported in the literature. RESULTS: The median values for study group and the published control group were 284 U/L and 124 U/L, respectively (P<0.001) suggesting that the average CK activity of professional footballers is higher than that of the normal healthy military population. CONCLUSION: Ethnicity, sex, age and physical exercise are factors that likely influence CK levels among various populations. From our analysis, we recommend a new 95% reference interval of 64.9 U/L to 1971.7 U/L for professional footballers.

FDG Uptake by Prosthetic Arterial Grafts in Large Vessel Vasculitis Is Not Specific for Active Disease.

OBJECTIVES: This study investigated the incidence and clinical significance of arterial graft-associated uptake of fluorodeoxyglucose in large-vessel vasculitis (LVV). BACKGROUND: The role of 18F-labeled fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) in the management of LVV remains to be defined. Although [18F]FDG uptake at arterial graft sites raises concerns regarding active arteritis or infection, its clinical significance in LVV has never been formally studied. METHODS: An observational prospective study sought to identify patients with Takayasu arteritis (TA) undergoing [18F]FDG-PET/CT more than 6 months after graft surgery from a large cohort of patients from 2 tertiary referral centers. [18F]FDG uptake by the graft and native arteries was scored on a scale of 0 to 3 relative to hepatic uptake, and periprosthetic maximum standardized uptake value (SUVmax) was calculated. Periprosthetic [18F]FDG uptake in active disease was compared with that in inactive disease, and arterial progression was assessed by prospective magnetic resonance angiography (MRA). RESULTS: Twenty-six subjects with TA were enrolled. All were afebrile with negative blood culture. Periprosthetic uptake was significant in 23 of 26 patients, and the mean SUVmax was 4.21 ± 1.46. Median periprosthetic [18F]FDG uptake score (3; interquartile range [IQR]: 3 to 3) was higher than in native aorta (1; IQR: 0 to 1; p < 0.001). Graft-specific [18F]FDG uptake was unrelated to disease activity. Despite the high frequency of graft-associated [18F]FDG uptake, sequential MRAs did not reveal arterial progression in 25 of 26 patients; the 1 remaining case showed minor progression limited to native arteries. Nine patients underwent repeated PET/CT scanning without showing changes in graft-specific uptake, despite increased treatment. CONCLUSIONS: Significant [18F]FDG uptake that is confined to arterial graft sites in patients with LVV does not reflect clinically relevant disease activity or progression. To minimize exposure to immunosuppression and in the face of negative blood culture, clinically quiescent arteritis, normal or stably raised C-reactive protein levels, we elected not to escalate treatment and monitor progression with MRA.

A rheumatology perspective on cutaneous vasculitis: assessment and investigation for the non-rheumatologist.

Vasculitis, by definition, is inflammation of the vasculature. This inflammation can result in either vessel wall destruction causing aneurysm or rupture, or stenosis causing ischaemia or necrosis. This autoimmune response does not always have a clear cause. Vasculitis is a heterogeneous group of disorders that has been categorised not only by primary and secondary causes, but also by the size of the affected vessel. The secondary causes that can trigger vasculitis include infection (particularly hepatitis B and C and haemorrhagic fever);cancer, autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjogren's; drugs or allergic reactions. As vasculitis can affect any part of the vasculature, it can result in a wide range of signs and symptoms. However, one of the most common presentations of vasculitis is a rash, due to small vessel vasculitis, which is most common. A vasculitic rash has certain characteristics that are easily identifiable and differentiate it from other rashes. This is a review from a rheumatologist's perspective of how to identify vasculitis skin changes. If cutaneous vasculitis is suspected, this article identifies other areas of skin that can be affected that need identification, in addition to what to screen for in the history and other differential diagnoses to consider. Subsequently, the article addresses the key investigations to request and a brief overview of the treatment principles for primary vasculitis.

Unusual presentation of Sjögren's syndrome.

We present a case of a 67-year-old woman admitted from the neurology clinic for further investigations of progressive ataxia and sensory symptoms. Neurological examination showed reduced pinprick and absent vibration sensations in the lower limbs. Motor system examination was normal. Her antinuclear antibodies titre was 1:100 with positive Ro antibodies. Her initial nerve conduction studies were normal. However, the lower limb somatosensory-evoked potentials (SSEP) demonstrated impairment of central sensory conduction pathway. Rheumatology review revealed a history of fatigue and Sicca symptoms and her Schirmer's test was strongly positive. This lead to the diagnosis of ganglionopathy associated to Sjögren's syndrome. She had an excellent response to intravenous methylprednisolone followed by oral prednisolone and intravenous cyclophosphamide infusions. This case highlights that dorsal column involvement can precede the diagnosis of primary Sjögren's syndrome.

Cost effectiveness of etoricoxib versus celecoxib and non-selective NSAIDS in the treatment of ankylosing spondylitis.

To evaluate the cost effectiveness of etoricoxib (90 mg/day) relative to celecoxib (200 or 400 mg/day), and the non-selective NSAIDs naproxen (1000 mg/day) and diclofenac (150 mg/day) in the initial treatment of ankylosing spondylitis (AS) from the UK NHS perspective. A Bayesian cost-effectiveness model was developed to estimate the costs and benefits associated with initiating AS treatment with etoricoxib, celecoxib, diclofenac or naproxen. Efficacy, safety and medical resource and cost data were obtained from the literature. The obtained efficacy estimates were synthesized with a mixed treatment comparison meta-analysis. Treatment benefit and degree of disease activity, as reflected with Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, were related to QALYs and AS-specific costs (related to BASDAI). Other cost outcomes related to drug acquisition, and gastrointestinal and cardiovascular safety. Uncertainty in the source data was translated into uncertainty in cost-effectiveness estimates and therefore decision uncertainty. Costs and outcomes were discounted at 3.5% per annum. There was a >98% probability that treatment with etoricoxib results in greater QALYs than the other interventions. Over a 30-year time horizon, starting AS treatment with etoricoxib was associated with about 0.4 more QALYs than the other interventions. At 2 years there was a 77% probability that etoricoxib had the lowest cost. This increased to >99% at 30 years. Etoricoxib is expected to save 13 620 UK pounds (year 2007 values) relative to celecoxib (200/400 mg), 9957 UK pounds relative to diclofenac and 9863 UK pounds relative to naproxen. For a willingness-to-pay ceiling ratio of 20 000 UK pounds per QALY, there was a >97% probability that etoricoxib was the most cost-effective treatment. Additional analysis with different assumptions, including celecoxib 200 mg, and ignoring cost-offsets associated with improvements in disease activity, supported these findings. This economic evaluation suggests that, from the UK NHS perspective, etoricoxib is the most cost-effective initial NSAID treatment for AS patients.

Economic evaluation of etoricoxib versus non-selective NSAIDs in the treatment of ankylosing spondylitis in the UK.

OBJECTIVES: To evaluate the cost-effectiveness of etoricoxib, a cyclooxygenase (COX)-2 selective inhibitor, versus non-selective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in the treatment of ankylosing spondylitis (AS). METHODS: The cost-effectiveness of etoricoxib versus nsNSAIDs was evaluated from the UK National Health Service (NHS) and society perspective with a decision-analytic model. Patients stayed on initial therapy throughout 52 weeks unless they experienced an adverse event (AE) or lacked efficacy, in which case they switched to another nsNSAID or a tumor necrosis factor alpha antagonist. Efficacy data were obtained from a 1-year etoricoxib clinical trial in AS. Bath AS Functional Index (BASFI) data were translated into Quality Adjusted Life Year (QALY) weights using a published data on the relation between BASFI and Short-form (SF) 36 Quality of life scores, as well as the relation between SF-36 and utility. Safety data were based on meta-analyses of etoricoxib trials. Information on treatment pathways, resource consumption, and absenteeism from work was obtained from literature and experts. Model outcomes included QALYs, perforations, ulcers, or bleeds, cardiovascular events, and costs. RESULTS: Etoricoxib was cost-effective compared to nsNSAIDs in terms of cost per QALY saved ( pound5611). Probabilistic sensitivity analysis found a 77% probability of the incremental cost per QALY saved being within a threshold for cost-effectiveness of pound20 000. The expected direct costs over the 52-week period were pound1.23 (95% uncertainty distribution pound1.10; pound1.39) and pound1.13 per day ( pound0.78; pound1.55) for patients starting with etoricoxib and nsNSAIDs, respectively. When costs related to absenteeism were taken into account, the cost per QALY saved was pound281. CONCLUSIONS: Given the underlying assumptions and data used, this economic evaluation demonstrated that, compared to nsNSAIDs, etoricoxib is a cost-effective therapy for AS patients in the UK.

Defective Fc-dependent processing of immune complexes in patients with systemic lupus erythematosus.

OBJECTIVE: To explore the Fc receptor-dependent handling of immune complexes (ICs) by the fixed mononuclear phagocytic systems (MPS) in patients with systemic lupus erythematosus (SLE). METHODS: The processing in vivo of soluble model (123)I-hepatitis B/ anti-hepatitis B ICs was studied in 12 healthy subjects and 10 patients with active SLE. ICs that fixed complement poorly were prepared specifically in order to explore Fc receptor-dependent clearance mechanisms. Clearance kinetics and organ uptake were assessed by computer-aided gamma scintigraphy and serial blood sampling. RESULTS: In both patients and controls, the main site of IC clearance was the liver; only 2-6% of injected ICs were taken up in the spleen. The kinetics of initial IC clearance were similar in both groups, but defective hepatic retention of ICs was demonstrated in patients with SLE. At 1 hour, hepatic activity in patients had fallen to 56% of maximum, compared with 74% in controls (P = 0.0002). Precipitation studies performed on serum samples using staphylococcal protein A-Sepharose indicated that antibody-complexed tracer was released from the liver 20-50 minutes after injection. CONCLUSION: These results indicate that Fc-mediated clearance of ICs is defective in patients with SLE and suggest that ligation of ICs by Fc receptors is critical for their efficient binding and retention by the fixed MPS in the liver.