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Panagiota Anyfanti,1 Athanasia Dara,2 Elena Angeloudi,1 Eleni Bekiari,1 Theodoros Dimitroulas,2 George D Kitas3,4 1Second Medical Department, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 2Fourth Department of Internal Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Rheumatology, Russells Hall Hospital, Dudley Group NHS Foundation Trust, Dudley, UK; 4School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UKCorrespondence: Panagiota AnyfantiHippokration General Hospital, 49, Konstantinoupoleos str, 54642, Thessaloniki, GreeceTel +30 2310 892 244Fax +30 2310 512 378Email panyfan@hotmail.comGeorge D KitasDudley Group NHS Foundation Trust, Russells Hall Hospital, Clinical Research Unit, Dudley, DY1 2HQ, UKEmail george.kitas@nhs.netAbstract: Cardiovascular disease (CVD) is common in immune-mediated inflammatory diseases (IMIDs) and it is predominately attributed to the interplay between chronic inflammation and traditional CVD risk factors. CVD has significant impact on the survival of patients with IMIDs as it is associated with increased morbidity and mortality. Despite recommendations for monitoring and managing CVD in patients with IMIDs, the individual CVD risk assessment remains problematic as CVD risk calculators for the general population consistently underestimate the risk in patients with IMIDs. Application of new technologies utilizing artificial intelligence techniques have shown promising potential for tailoring predictive medicine to the individual patient, but further validation of their role in clinical decision-making is warranted. In the meantime, individuals with IMIDs should be encouraged to adopt behavioral interventions targeting at modifiable lifestyle CVD risk factors, whereas rheumatologists need to be well aware of the unfavorable effects of antirheumatic medication on various CVD risk factors and outcomes. In the current paper, we aim to provide an overview of current and emerging strategies for mitigating CVD risk in patients with IMIDs, based on a practical approach.Keywords: chronic inflammatory diseases, cardiovascular risk assessment, lifestyle modifications, pharmacological management

George E Fragoulis,1,* Stergios Soulaidopoulos,2,* Petros P Sfikakis,1 Theodoros Dimitroulas,3 George D Kitas4,5 1Rheumatology Unit, Joint Rheumatology Program, Medical School, First Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, “Laiko” General Hospital, Athens, 115 27, Greece; 2First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, 115 27, Greece; 3Fourth Department of Internal Medicine, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, 546 41, Greece; 4Department of Rheumatology, Russells Hall Hospital, Dudley Group NHS FT, Dudley, DY1 2HQ, UK; 5Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, M13 9PT, UK*These authors contributed equally to this workCorrespondence: Stergios SoulaidopoulosFirst Department of Cardiology, National and Kapodistrian University of Athens, 114 Vasilissis Sofias av., Athens, 11527, GreeceTel +306932528561Fax +302132088676Email soulaidopoulos@hotmail.comAbstract: It is increasingly recognized that atherosclerosis and consequently cardiovascular disease (CVD) are closely linked with inflammatory processes. The latter is in the center of the pathogenic mechanism underlying autoimmune rheumatic diseases (ARD). It follows then, that optimal control of inflammation in ARDs may lead to a decrease of the accompanied CVD risk. Major trials (eg, CANTOS, CIRT), aimed at examining the possible benefits of immunomodulatory treatments in CVD, demonstrated conflicting results. On the other hand, substantial evidence is accumulating about the possible beneficial effects of biologic disease modifying antirheumatic drugs (bDMARDs) in patients with ARDs, particularly those with rheumatoid arthritis (RA). It seems that bDMARDs (some more than others) alter the lipid profile in RA patients but do not adversely affect, in most cases, the TC/HDL ratio. Favorable effects are noted for arterial stiffness and endothelial function. This is reflected in the lower risk for CVD events, seen in observational studies of RA patients treated with bDMARDs. It should be stressed that more data exist for the TNF-inhibitors than for other bDMARDs, such as tocilizumab, abatacept and rituximab. As regards the spondyloarthropathies (SpA), data are less robust. For TNF-inhibitors, effects appear to be on par with those seen in RA but no conclusions can be drawn for newer biologic drugs used in SpA (eg, IL-17 blockers). Finally, there is accumulating evidence for a beneficial effect of immunosuppressive treatment in cardiac inflammation and function in several ARDs. Introduction of newer therapeutic options in clinical practice seem to have a positive impact on CVD in the setting of ARD. This is probably due to better control of inflammation, but direct improvement in vascular pathology is also a valid hypothesis. Most data are derived from observational studies and, therefore, randomized controlled trials are needed to assess the possible favorable effect of bDMARDs on CVD outcomes.Keywords: atherosclerosis, cardiovascular disease, biologic agents, interleukins, inflammatory disorders

Aamer Sandoo,1,2 George D Kitas,2 Amtul R Carmichael2 1School of Sport, Health and Exercise Sciences, Bangor University, Bangor, Wales, 2Dudley Group of Hospitals NHS Trust, Russells Hall Hospital, Dudley, UK Abstract: Breast cancer is the most common cancer in the UK. Advances in the methods of early diagnosis as well as newer and more effective treatments have led to improvements of disease-free and overall survival over the last decade. Almost one-third of breast cancers present with an aggressive form characterized by increased expression of human epidermal growth receptor 2 (HER2) proteins. A targeted treatment using monoclonal antibodies against HER2 expression such as trastuzumab has been shown to improve survival. Unfortunately, there is a degree of cardiotoxicity associated with these agents, as inhibition of HER2 pathways can also impair cardioprotective pathways. In the present review, we discuss the mechanisms by which trastuzumab might affect vascular homeostasis leading to endothelial dysfunction. We also provide suggestions for future research examining the effects of trastuzumab on the vasculature in breast cancer. Keywords: endothelial dysfunction, microvasculature, macrovasculature, congestive heart failure

Abstract Background To investigate the effects of intravenous lignocaine infusions (IV lignocaine) in fibromyalgia. Methods Prospective study of the adverse effects of IV lignocaine in 106 patients with fibromyalgia; retrospective questionnaire study of the efficacy of IV lignocaine in 50 patients with fibromyalgia. Results Prospective study: Two major (pulmonary oedema and supraventricular tachycardia) and 42 minor side-effects were reported. None had long-term sequelae. The commonest was hypotension (17 cases). Retrospective study: Pain and a range of psychosocial measures (on single 11-point scales) improved significantly after treatment. There was no effect of the treatment on work status. The average duration of pain relief after the 6-day course of treatment was 11.5 ± 6.5 weeks. Conclusions Intravenous lignocaine appears to be both safe and of benefit in improving pain and quality of life for patients with fibromyalgia. This needs to be confirmed in prospective randomised controlled trials.

Abstract Background Continuous intrathecal drug delivery has been shown in open studies to improve pain and quality of life in those with intractable back pain who have had spinal surgery. There is limited data on long term effects and and even less for patients with mechanical back pain without prior spinal surgery. Methods We have investigated spinal drug administration systems for patients with failed back syndrome and chronic mechanical low back pain by patient questionnaire study of the efficacy of this therapy and a case notes review. Results 36 patients (97% of 37 approached) completed questionnaires, 24 with failed back syndrome and 12 with chronic mechanical low back pain. Recalled pre-treatment levels with current post-treatment levels of pain and a range of quality of life measures (recorded on 11-point numerical rating scales) were compared. Pain improved significantly in both groups (Wilcoxan signed ranks test, p < 0.005). The majority of quality of life measures improved significantly in the failed back syndrome group (Wilcoxan signed ranks test, p < 0.005) although work interruption and the effect of pain on sex life did not change. There was a trend towards improvement in the majority of quality of life measures in the mechanical back pain group but this did not reach statistical significance due to the smaller numbers in this cohort (p > 0.005, Wilcoxan signed ranks test with Bonferroni correction). Diamorphine was used in all 37 patients, bupivacaine in 32, clonidine in 27 and baclofen in 3. The mean dose of diamorphine increased for the first 2 years but did not change 2–6 years post implant, averaging 4.5 mg/day. Revision surgery was required in 24% of cases, but reduced to 12% in the later years of our experience. Conclusions We conclude that spinal drug administration systems appear to be of benefit in alleviating pain in the failed back syndrome and chronic mechanical low back pain but need to be examined prospectively.

Objectives: The aim of our study was to determine whether asymmetric dimethylarginine (ADMA) levels are associated with homocysteine (Hcy) and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) gene variants in patients with rheumatoid arthritis (RA).Method: Serum ADMA and Hcy levels were measured in 201 RA individuals [155 (77.1%) females, median age 67 years (interquartile range 59-73)]. The MTHFR C677T polymorphism was assessed by using the LightCyclerTM System. Initially, ADMA was compared across the categories of MTHFR using a one-way analysis of variance (ANOVA), followed by a multivariate model, which accounted for Hcy, age, erythrocyte sedimentation rate (ESR), and homeostatic model assessment (HOMA).Results: In univariable analysis, ADMA differed significantly across the categories of MTHFR (p = 0.037). Patients with the MTHFR 677TT genotype had the highest ADMA levels, with a mean of 0.62 (SE = 0.03), significantly higher than either those patients carrying the MTHFR 677CT (0.55, SE = 0.01) or the MTHFR 677CC (0.55, SE = 0.01) genotype (p = 0.042) in both cases. In the multivariable model, Hcy (p = 0.022) and ESR (p < 0.001) were found to have significant positive associations with ADMA but the relationship between MTHFR gene variants and ADMA was found to be non-significant (p = 0.102).Conclusions: Hcy and ADMA are significantly associated in RA. It is plausible that abnormal Hcy metabolism plays an important role in premature atherosclerosis in RA by promoting ADMA accumulation and leading to the derangement of vascular haemostasis. [ABSTRACT FROM AUTHOR]

Objective: Cardiovascular disease (CVD) is the leading cause of death in Britain, and its prevention is a priority. Rheumatoid arthritis (RA) patients have an increased risk of CVD, and management of modifiable classical risk factors requires a programme with patient education at its heart. Before a programme for RA patients is implemented, it is important to explore the perceptions of patients and relevant healthcare professionals and consider how these could influence the subsequent content, timing and delivery of such education. Here, we assess healthcare professionals' perceptions.Methods: Qualitative focus group methodology was adopted. Four group meetings of healthcare professionals were held using a semi-structured interview schedule. The focus group transcripts were analysed using interpretative phenomenological analysis.Results: Three superordinate themes emerged: professional determinations about people with RA, including their perceptions about patients' priorities and motivations; communication about CVD risk, including what should be communicated, how, to whom and when; and responsibility for CVD management, referring to patients and the healthcare community.Conclusions: Although healthcare professionals agree that it is important to convey the increased CVD risk to patients with RA, there is concern they may be less proactive in promoting risk management strategies. There was uncertainty about the best time to discuss CVD with RA patients. Maintaining a close relationship between primary and secondary care was thought to be important, with all healthcare professionals 'singing from the same hymn sheet'. These findings can inform the development of novel education material to fulfil a currently unmet clinical need. Copyright (c) 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: There are no patient education programmes addressing the increased risk of cardiovascular disease (CVD) associated with rheumatoid arthritis (RA). This is the second in a pair of studies exploring stakeholder perceptions of developing such educational material. Healthcare professionals' perceptions were explored in the first study; here, we explore the perceptions of people with RA.Methods: Semi-structured interviews were held individually with 18 people with RA, purposively sampled to include participants with no co-morbid history of CVD, those with CVD risk factors and those who had experienced a CVD event. The interview transcripts were analysed using interpretative phenomenological analysis.Results: Four superordinate themes were identified: experiences of living with RA; reactions to learning about co-morbid CVD; implementing lifestyle changes; and expectations of education. Participants found being diagnosed with RA a devastating experience and were mostly unaware of their increased risk of CVD co-morbidity. They explained how information about CVD would be overwhelming and irrelevant at diagnosis, but they would have coped with 'extra information a bit further down the line'.Conclusion: There is a need to develop educational material or programmes. Their design must consider factors which facilitate lifestyle change, such as motivation or receiving personalized advice, and factors that inhibit change, such as depression or fatalism. Emphasizing the positive effects that some CVD lifestyle changes may have on RA symptom control may be particularly persuasive. Group education would be a popular format. These findings can be directly translated into clinical practice. Copyright (c) 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Fatigue is common in both Sjögren's syndrome (SS) and rheumatoid arthritis (RA) and can restrict functioning.Aims: We tested the convergent validity of the Profile of Fatigue (ProF) using the Multidimensional Fatigue Inventory (MFI) in SS and RA.Methods: The 16-item ProF and the 20-item MFI were completed by 82 White-British women aged 35-79 years (mean 60.4 years). Thirty-four had been diagnosed with SS for a mean of 7.0 years and 48 had been diagnosed with RA for a mean of 14.5 years. The ProF measures four somatic facets of fatigue and two mental facets; the MFI contains one mental and four somatic facets. The structures of the items from both measures were tested by principal component factor analysis using varimax rotation.Results: No significant differences in fatigue were found between the women with SS or RA. Five factors explained a total of 76% of the variance of the MFI; six factors explained 94% of the variance of the ProF. Mental fatigue items from both questionnaires loaded onto separate factors from somatic fatigue items; the two original facets of mental fatigue in the ProF were replicated. The four somatic fatigue facets of the ProF were generally replicated but the somatic facets of the MFI did not replicate as clearly. Equivalent facets correlated well between the two questionnaires (r >/= 0.65).Conclusions: Both the ProF and the MFI distinguish between somatic and mental fatigue in SS and RA but the ProF appears better at resolving somatic facets of fatigue. Copyright (c) 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Cogan's syndrome may be associated with large-vessel arteritis. We describe a patient with ocular inflammation, sensorineural hearing loss and arm claudication in whom a diagnosis of 'atypical' Cogan's syndrome and Takayasu's arteritis was made. All symptoms resolved with treatment. [ABSTRACT FROM PUBLISHER]