In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at

/pdf/eular-recommendations-for-the-management-of-rheumatoid-4fujp4paik.pdf

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-à-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes for textbooks, and their legal implications have been discussed previously. Guidelines and recommendations should help physicians to make decisions in their daily practice. However, the ultimate judgement regarding the care of an individual patient must be made by his/her responsible physician(s).

A large number of Guidelines have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC Web Site (http://www.escardio.org/guidelines/rules).

Members of this Task Force were selected by the ESC to represent all physicians involved with the medical care of patients in this pathology. In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger populations are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to pre-defined scales, as outlined in Tables 1 and 2 .

View this table:

Table 1 
Classes of recommendations



View this table:

Table 2 
Levels of evidence



The experts of the writing and reviewing panels have provided disclosure statements of all relationships they may have which …

/pdf/esc-guidelines-for-the-management-of-grown-up-congenital-542gk4n515.pdf

ESC Guidelines for the management of grown-up congenital heart disease (new version 2010).

Background Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). Objective To develop recommendations for achieving optimal therapeutic outcomes in RA. Methods A task force of rheumatologists and a patient developed a set of recommendations on the basis of evidence derived from a systematic literature review and expert opinion; these were subsequently discussed, amended and voted upon by >60 experts from various regions of the world in a Delphi-like procedure. Levels of evidence, strength of recommendations and levels of agreement were derived. Results The treat-to-target activity resulted in 10 recommendations. The treatment aim was defined as remission with low disease activity being an alternative goal in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with appropriate therapeutic adaptation to reach the desired state within 3 to a maximum of 6 months was recommended. Follow-up examinations ought to employ composite measures of disease activity which include joint counts. Additional items provide further details for particular aspects of the disease. Levels of agreement were very high for many of these recommendations (≥9/10). Conclusion The 10 recommendations are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA based on evidence and expert opinion.

Treating rheumatoid arthritis to target: recommendations of an international task force (vol 69, pg 631, 2010)

Table 1. Classes of recommendation

Table 2. Levels of evidence

Table 3. Estimated fetal and maternal effective doses for various diagnostic and interventional radiology procedures

Table 4. Predictors of maternal cardiovascular events and risk score from the CARPREG study

Table 5. Predictors of maternal cardiovascular events identified in congential heart diseases in the ZAHARA and Khairy study

Table 6. Modified WHO classification of maternal cardiovascular risk: principles

Table 7. Modified WHO classification of maternal cardiovascular risk: application

Table 8. Maternal predictors of neonatal events in women with heart disease

Table 9. General recommendations

Table 10. Recommendations for the management of congenital heart disease

Table 11. Recommendations for the management of aortic disease

Table 12. Recommendations for the management of valvular heart disease

Table 13. Recommendations for the management of coronary artery disease

Table 14. Recommendations for the management of cardiomyopathies and heart failure

Table 15. Recommendations for the management of arrhythmias

Table 16. Recommendations for the management of hypertension

Table 17. Check list for risk factors for venous thrombo-embolism

Table 18. Prevalence of congenital thrombophilia and the associated risk of venous thrombo-embolism during pregnancy

Table 19. Risk groups according to risk factors: definition and preventive measures

Table 20. Recommendations for the prevention and management of venous thrombo-embolism in pregnancy and puerperium

Table 21. Recommendations for drug use

ABPM
: ambulatory blood pressure monitoring
ACC
: American College of Cardiology
ACE
: angiotensin-converting enzyme
ACS
: acute coronary syndrome
AF
: atrial fibrillation
AHA
: American Heart Association
aPTT
: activated partial thromboplastin time
ARB
: angiotensin receptor blocker
AS
: aortic stenosis
ASD
: atrial septal defect
AV
: atrioventricular
AVSD
: atrioventricular septal defect
BMI
: body mass index
BNP
: B-type natriuretic peptide
BP
: blood pressure
CDC
: Centers for Disease Control
CHADS
: congestive heart failure, hypertension, age (>75 years), diabetes, stroke
CI
: confidence interval
CO
: cardiac output
CoA
: coarction of the aorta
CT
: computed tomography
CVD
: cardiovascular disease
DBP
: diastolic blood pressure
DCM
: dilated cardiomyopathy
DVT
: deep venous thrombosis
ECG
: electrocardiogram
EF
: ejection fraction
ESC
: European Society of Cardiology
ESH
: European Society of Hypertension
ESICM
: European Society of Intensive Care Medicine
FDA
: Food and Drug Administration
HCM
: hypertrophic cardiomyopathy
ICD
: implantable cardioverter-defibrillator
INR
: international normalized ratio
i.v.
: intravenous
LMWH
: low molecular weight heparin
LV
: left ventricular
LVEF
: left ventricular ejection fraction
LVOTO
: left ventricular outflow tract obstruction
MRI
: magnetic resonance imaging
MS
: mitral stenosis
NT-proBNP
: N-terminal pro B-type natriuretic peptide
NYHA
: New York Heart Association
OAC
: oral anticoagulant
PAH
: pulmonary arterial hypertension
PAP
: pulmonary artery pressure
PCI
: percutaneous coronary intervention
PPCM
: peripartum cardiomyopathy
PS
: pulmonary valve stenosis
RV
: right ventricular
SBP
: systolic blood pressure
SVT
: supraventricular tachycardia
TGA
: complete transposition of the great arteries
TR
: tricuspid regurgitation
UFH
: unfractionated heparin
VSD
: ventricular septal defect
VT
: ventricular tachycardia
VTE
: venous thrombo-embolism
WHO
: World Health Organization

Guidelines summarize and evaluate all available evidence, at the time of the writing process, on a particular issue with the aim of assisting physicians in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are no substitutes but are complements for textbooks and cover the European Society of Cardiology (ESC) Core Curriculum topics. Guidelines and recommendations should help the …

/pdf/esc-guidelines-on-the-management-of-cardiovascular-diseases-3xh319x7m6.pdf

ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC).

The diagnosis of Marfan syndrome (MFS) relies on defined clinical criteria (Ghent nosology), outlined by international expert opinion to facilitate accurate recognition of this genetic aneurysm syndrome and to improve patient management and counselling. These Ghent criteria, comprising a set of major and minor manifestations in different body systems, have proven to work well since with improving molecular techniques, confirmation of the diagnosis is possible in over 95% of patients. However, concerns with the current nosology are that some of the diagnostic criteria have not been sufficiently validated, are not applicable in children or necessitate expensive and specialised investigations. The recognition of variable clinical expression and the recently extended differential diagnosis further confound accurate diagnostic decision making. Moreover, the diagnosis of MFS—whether or not established correctly—can be stigmatising, hamper career aspirations, restrict life insurance opportunities, and cause psychosocial burden. An international expert panel has established a revised Ghent nosology, which puts more weight on the cardiovascular manifestations and in which aortic root aneurysm and ectopia lentis are the cardinal clinical features. In the absence of any family history, the presence of these two manifestations is sufficient for the unequivocal diagnosis of MFS. In absence of either of these two, the presence of a bonafide FBN1 mutation or a combination of systemic manifestations is required. For the latter a new scoring system has been designed. In this revised nosology, FBN1 testing, although not mandatory, has greater weight in the diagnostic assessment. Special considerations are given to the diagnosis of MFS in children and alternative diagnoses in adults. We anticipate that these new guidelines may delay a definitive diagnosis of MFS but will decrease the risk of premature or misdiagnosis and facilitate worldwide discussion of risk and follow-up/management guidelines.

/pdf/the-revised-ghent-nosology-for-the-marfan-syndrome-9nxw47tanr.pdf

The revised Ghent nosology for the Marfan syndrome

Objective To evaluate the effect of adalimumab on pain, fatigue, and stiffness in patients with active ankylosing spondylitis (AS). Methods The Adalimumab Trial Evaluating Long-Term Safety and Efficacy for Ankylosing Spondylitis (ATLAS) was an ongoing 5-year study that included an initial 24-week, randomized, placebo-controlled, double-blind period. Patients were randomized to adalimumab 40 mg or placebo by subcutaneous injection every other week. Pain was assessed by the bodily pain domain scores of the Medical Outcomes Study Short Form-36 Health Survey (SF-36) and also by total back pain and nocturnal pain using visual analog scales. Fatigue was measured by the SF-36 vitality domain and question 1 of the Bath AS Disease Activity Index (BASDAI). Morning stiffness was measured by the mean of BASDAI questions 5 and 6. Results Of 315 patients enrolled, 208 received adalimumab 40 mg and 107 received placebo. At Week 12, adalimumab-treated patients experienced significant improvement compared with placebo-treated patients in the SF-36 bodily pain score (p Conclusion Adalimumab significantly improved symptoms of pain, fatigue, and stiffness in patients with AS. Improved symptoms were associated with improved physical function and HRQOL.

https://www.jrheum.org/content/jrheum/35/7/1346.full.pdf

Adalimumab reduces pain, fatigue, and stiffness in patients with ankylosing spondylitis: results from the adalimumab trial evaluating long-term safety and efficacy for ankylosing spondylitis (ATLAS).

Genome-wide association studies (GWAS) have heralded a major breakthrough in the search for genes underlying rheumatoid arthritis (RA). Indeed, GWAS in UK, US and Swedish populations have identified a number of confirmed RA loci.1 Recently, a modestly-sized GWAS was undertaken in a Spanish population comprising 400 patients with RA and 400 controls.2 Association with the KLF12 gene was detected (p=6.5×10−6) and subsequently replicated in an independent cohort of 410 Spanish patients with RA and 394 controls (p=0.01). The most strongly associated single nucleotide polymorphism (SNP) was rs1324913 mapping to intron 1 of the KLF12 gene. The KLF12 protein is a repressor for a transcriptional regulatory factor, AP-2α, which has been implicated in the control of inflammation. Other SNPs at this locus also showed weak evidence for association with RA in UK …

https://ard.bmj.com/content/annrheumdis/69/7/1407.full.pdf

Paul Wordsworth

Papers

The revised Ghent nosology for the Marfan syndrome

Adalimumab reduces pain, fatigue, and stiffness in patients with ankylosing spondylitis: results from the adalimumab trial evaluating long-term safety and efficacy for ankylosing spondylitis (ATLAS).

No evidence for association of the KLF12 gene with rheumatoid arthritis in a large UK cohort

Il-23r is a major determinant of ankylosing spondylitis risk - The tasc study