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Ulf Müller-Ladner,1 Christopher J Edwards,2 Andreas Erkens3 1Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Giessen, Campus Kerckhoff, Bad Nauheim, Germany; 2Musculoskeletal Research Unit, NIHR Southampton Clinical Research Facility, University Hospital Southampton, Southampton, UK; 3Aurum Research GmbH, Lauf a.d., Pegnitz, GermanyCorrespondence: Ulf Müller-Ladner, Department of Rheumatology and Clinical Immunology, Justus-Liebig-University Giessen, Benekestrasse 2-8, D-61231 Bad Nauheim, Germany, Fax +49 6032-996 2104, Email u.mueller-ladner@kerckhoff-klinik.dePurpose: Prefilled syringes (PFS) and various types of pens are available for subcutaneous injection of methotrexate (MTX) in patients with rheumatoid arthritis or moderate to severe psoriasis. A new MTX pen with modernized button-free autoinjection technology was developed as a successor to a button-activated pen (metoject®/metex® PEN). To assess the needs of users and the relevance of features of the new MTX autoinjector an international online survey was performed.Methods: A structured questionnaire was distributed to physicians, nurses and patients in Germany, France, and the United Kingdom. Participants received illustrations and information about features of the new MTX autoinjector.Results: In total, 189 rheumatologists, 111 dermatologists, 90 nurses, and 180 patients answered the questions. Specific reasons for a preference for the use of MTX pens over PFS could predominantly be assigned to the categories “dosing/administration” and “ease of use”. The first impression of the new MTX autoinjector was positive in 82% of physicians, 87% of nurses, and 76% of patients, respectively. The four most important features of the new MTX autoinjector were 2-step autoinjector mechanism (receiving a mean 14.1 to 18.1 chips of a total of 100 chips), small injection volume (9.7 to 11.7 chips), 10 different doses for dose flexibility (8.0 to 13.2 chips), and short injection time below 5 seconds (8.5 to 11.1 chips).Conclusion: Arguments for the use of MTX pens as opposed to PFS predominantly refer to dosing/administration and ease of use. The new button-free MTX autoinjector combines a number of advantageous features identified by the international survey.Plain Language Summary: Subcutaneous injection of methotrexate (MTX) is an option to treat patients with specific inflammatory diseases. A new MTX autoinjector with button-free activation of the injection and no need to build a skin fold was developed to address some of the reasons for non-adherence. The importance of specific needs of users as well as the relevance of features of the new MTX autoinjector are unknown. Therefore, a structured questionnaire was distributed to physicians, nurses and patients in Germany, France, and the United Kingdom. Illustrations and information about features of the new MTX autoinjector were distributed to the participants. The results of the study show that arguments for the use of MTX pens as opposed to prefilled syringes predominantly affect the categories dosing/administration and ease of use followed by safety/side effects. In addition, the study identified four main advantageous features of the new MTX autoinjector, ie simplicity due to the 2-step button-free autoinjector mechanism, the small injection volume, 10 different doses for dose flexibility, and the short injection time below 5 seconds.Keywords: autoinjector, methotrexate, pen, psoriasis, rheumatoid arthritis, syringe

Edward Burn,1 Christopher J Edwards,2 David W Murray,1 Alan Silman,1 Cyrus Cooper,1,3 Nigel K Arden,1,3 Daniel Prieto-Alhambra,1,4 Rafael Pinedo-Villanueva1,3 1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; 2NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton, Southampton, UK; 3MRC Lifecourse Epidemiology Unit, Southampton University, Southampton, UK; 4GREMPAL Research Group, Idiap Jordi Gol and CIBERFes, Universitat Autonoma de Barcelona and Instituto de Salud Carlos III, Barcelona, Spain Purpose: To assess whether rheumatoid arthritis (RA) is associated with a greater risk of adverse events following total knee replacement (TKR) and total hip replacement (THR) than osteoarthritis (OA).Patients and methods: Individuals with a diagnosis of RA or OA were identified using primary care records. TKR and THR following diagnosis were identified using linked hospital records. Myocardial infarction (MI), prosthetic joint infection (PJI), venous thromboembolism (VTE), and death were identified within 90 days following surgery, and revision procedures over 10 years following surgery. The impact of RA compared to OA on the risk for these adverse events was assessed using Cox proportional hazard models. Univariable models, with diagnosis as the only explanatory variable, and multivariable models, with age, gender, and year of surgery first added and then a measure of other comorbidities also included, were estimated.Results: In all 20,763 individuals, with 10,260 TKR and 10,961 THR, were included in the analysis. Compared to those with OA, individuals with a diagnosis of RA had a greater incidence of MI over 90 days following TKR (OA: 0.28%, RA: 0.75%) and revision over 10 years following THR (OA: 5.55%, RA: 8.68%). Both of these differences were statistically significant with, for example, hazard ratios of 3.54 (1.44 to 8.73) for MI and 1.61 (1.06 to 2.46) for revision after controlling for age, gender, year of surgery, and other comorbidities.Conclusion: These findings suggest that, compared to individuals with OA, those with RA have an increased short-term risk of MI following TKR. While risk of MI remains below 1%, this does underline the importance of the management of cardiovascular risk factors for those with RA. RA was also associated with an increased long-term risk of revision following THR, which strengthens the argument for investing in therapies which may prevent the need for joint replacement. Keywords: hip, knee, arthroplasty, osteoarthritis, surgery

Objective: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA).Methods: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate rounds of discussions and modified Delphi votes. In the first round 10 clinical questions were selected. A bibliographic team systematically searched Medline, Embase, the Cochrane Library and ACR/EULAR 2007-2008 meeting abstracts. Relevant articles were reviewed for quality assessment, data extraction and synthesis. In the second round each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed.Results: A total of 39,756 references were identified, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related to the diagnostic and prognostic value of clinical and laboratory assessments in established UPIA (history and physical examination, acute phase reactants, autoantibodies, radiographs, MRI and ultrasound, genetic markers and synovial biopsy), one recommendation highlighted predictors of persistence (chronicity) and the final recommendation addressed monitoring of clinical disease activity in UPIA.Conclusions: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity and practical use. [ABSTRACT FROM AUTHOR]

The emergency department (ED) is a fast-paced, but error-prone work environment. Clinical pharmacists based in the ED can assist with the selection, acquisition, preparation, administration, and monitoring of appropriate evidence-based therapeutic drug regimens. These services may be particularly useful during emergent and code situations. Emergency pharmacists can also provide drug information to the department. Clinical pharmacists in the ED serve as a liaison between the departments of pharmacy and emergency medicine, and can help develop policies and procedures that are beneficial and amenable to both departments. Having the right pharmacist in the ED may improve nursing and physician satisfaction with pharmacy services, reduce costs, and improve patient safety. [ABSTRACT FROM AUTHOR]

Objectives: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders.Methods: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed.Results: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases.Conclusions: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use. [ABSTRACT FROM AUTHOR]

Patients with systemic lupus erythematosus (SLE) frequently have gastrointestinal (GI) symptoms. These are usually self-limiting and related to treatment side-effects or concurrent illness. However, abdominal pain may be due to bowel ischaemia which can lead to infarction and perforation. The likelihood of these serious events is increased in individuals with pain severe enough to require assessment in hospital or a SLEDAI score > 5. This paper describes a group of patients with active SLE and GI symptoms severe enough to require admission to hospital using a retrospectivereview of 52 SLE patients admitted to hospital with acute abdominal symptoms. The results showed that abdominal pain (87%), vomiting (82%) and diarrhoea (67%) had been present for a mean of 4.4 ± 6.5 days and SLEDAI score was ≥4 in 83% of patients. CT scanning showed evidence of serositis and bowel involvementin 63% of patients who underwent this investigation. Intravenous(iv) &fluids were used in 87%, parenteral steroids in 90% and iv cyclophosphamidein 31%. Most (n = 51) were discharged well. Recurrence of GI symptoms occurred in 12 patients. The conclusions are that active SLE may manifest as an acute gastrointestinal syndrome. Early diagnosis, bowel rest, supportive medical therapy and treatment with corticosteroids and/or immunosupressives can result in a good outcome. [ABSTRACT FROM AUTHOR]

We sought to test our clinical impression that using a low dose methylprednisolone pulse (MEP; ≤1500mg over 3 days) in treating flares of systemic lupus erythematosus (SLE) was effective and associated with fewer serious infections. We retrospectively studied SLE patients who received MEP between 1989 and 2000. A 'low dose' group of 26 patients who had received 1-1.5g and a 'high dose' group of 29 patients who received 3-5g of MEP were identified. SLEDAI scores and prednisolone doses were recorded at the time of MEP pulses and 6 months later. All serious infections (requiring admission and i.v. antibiotics) occurring during this 6 month period and their outcomes were recorded. Both groups had similar demographic data, initial SLEDAI scores, i.v. cyclophosphamide use, and SLE organ involvement. Despite high- and low-dose MEP being efficacious in controlling disease activity (lowering of SLEDAI scores and subsequent prednisolone dose) there were only nine episodes of serious infection in seven patients in the low-dose group compared with 20 episodes in 17 patients from the high-dose group (P=0.04). In both groups a majority of infections (75 and 77% in the high- and low-dose groups) occurred in the first month after MEP. Those with a low serum albumin (<20g/l) had an increased risk of mortality (OR 44, 90% CI 6.19-312.98) and a trend towards greater numbers of infections. Low-dose MEP was effective in controlling SLE flares and associated with fewer serious infections than traditional high-dose MEP. [ABSTRACT FROM AUTHOR]

The article presents the author's views on the cause of systemic lupus erythematosus (SLE). According to the author, like other autoimmune rheumatic diseases there is evidence of polygenic inheritance influenced by environmental factors. A huge effort has been directed towards identifying the genes of importance including the major histocompatability complex (MHC) and susceptibility loci within a number of chromosomal areas. However, with heritability of SLE estimated to be around 60% environmental factors must also play a key role in the pathogenesis of lupus. To date, a number of chemical exposures have been associated with lupus or related autoimmune phenomena. These include aromatic amines and hydrazines, silica, silicone, vinyl chloride, organic solvents and heavy metals.

An introduction is presented in which the editor discusses various reports within the issue on topics including epigenetics, the aetiology of lupus, and microbiome.