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| 4. |
- Ip, H. F., et al.
(author)
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Genetic association study of childhood aggression across raters, instruments, and age
- 2021
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Journal article (peer-reviewed)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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| 5. |
- Jami, E. S., et al.
(author)
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Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
- 2022
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In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 61:7, s. 934-945
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Journal article (peer-reviewed)abstract
- Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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| 6. |
- Parr, E., et al.
(author)
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Single-particle states and parity doublets in odd- Z Ac 221 and Pa 225 from α -decay spectroscopy
- 2022
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In: Physical Review C. - 2469-9985. ; 105:3
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Journal article (peer-reviewed)abstract
- Low-lying states in the odd-Z isotopes Ac13289221 and Pa13491225 have been studied using α-particle and αγ-coincidence spectroscopy in the Pa225→Ac221→Fr217 decay chain. Ground-state spin and parity assignments of Iπ = 5/2- are proposed for both Ac221 and Pa225, with the odd proton occupying the ω = 5/2 orbital of the quadrupole-octupole deformed shell model in both nuclei. In Ac221, excited states in the bands based on the ω = 5/2 and ω = 3/2 orbitals have been identified, including proposed parity-doublet states. The results suggest that reflection-asymmetric deformation of the ground state persists in the odd-A members of the isotope chains down to N = 132 for Ac and N = 134 for Pa, before reaching the transitional region at N = 130.
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| 8. |
- Smolen, JS, et al.
(author)
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EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update
- 2017
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:6, s. 960-977
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Journal article (peer-reviewed)abstract
- Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
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| 9. |
- van Vollenhoven, R, et al.
(author)
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A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS)
- 2017
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:3, s. 554-561
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Journal article (peer-reviewed)abstract
- Treat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE.MethodsAn international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%.ResultsThe task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life.ConclusionsThe work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.
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| 10. |
- Smolen, JS, et al.
(author)
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EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update
- 2020
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 79:6, s. 685-699
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Journal article (peer-reviewed)abstract
- To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.
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| 11. |
- Fanouriakis, A, et al.
(author)
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2019 update of the EULAR recommendations for the management of systemic lupus erythematosus
- 2019
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:6, s. 736-745
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Journal article (peer-reviewed)abstract
- Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007–12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.
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| 12. |
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| 13. |
- Fanouriakis, A, et al.
(author)
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2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis
- 2020
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 79:6, s. 713-723
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Journal article (peer-reviewed)abstract
- To update the 2012 EULAR/ERA–EDTA recommendations for the management of lupus nephritis (LN).MethodsFollowing the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements.ResultsThe changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5–0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2–3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3–0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin–angiotensin–aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease.ConclusionsWe have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.
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| 14. |
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| 15. |
- Lewis, M. C., et al.
(author)
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Decay of a 19(-) isomeric state in Lu-156
- 2018
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In: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 98:2
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Journal article (peer-reviewed)abstract
- A multiparticle spin-trap isomeric state having a half-life of 179(4) ns and lying 2601 keV above the yrast 10(+) state in Lu-156 has been discovered. The Lu-156 nuclei were produced by bombarding isotopically enriched Cd-106 targets with beams of Ni-58 ions, separated in flight using the gas-filled separator RITU and their decays were measured using the GREAT spectrometer. Analysis of the main decay path that populates yrast states observed previously suggests a spin-parity assignment of 19(-) for the isomeric state, which is consistent with isomeric states identified in the N = 85 isotones. Comparison with other decay paths in Lu-156 indicates that the [pi h(11/)(2)(-1) circle times nu h(9/2)]10(+) state at the bottom of the yrast sequence is likely to be the a-decaying isomeric state, with the [pi h(11/)(2)(-1) circle times nu f(7/2)]9(+) state lying 62 keV above it. The relative ordering of the lowest-lying 9(+) and 10(+) states is inverted in Lu-156 compared with its odd-odd isotones.
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| 16. |
- Parr, E., et al.
(author)
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Identification of the J(pi)=1(-) state in Ra-218 populated via alpha decay of Th-222
- 2016
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In: PHYSICAL REVIEW C. - 2469-9985. ; 94:1
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Journal article (peer-reviewed)abstract
- The alpha decay of Th-222 populating the low-lying J(pi) = 3(-) state, and also a proposed 1(-) state, in Ra-218 has been observed. The observations suggest an excitation energy of 853 keV for the 1(-) state, which is 60 keV above the 3(-) state. The hindrance factors of these alpha decays give a possible boundary to the region of ground-state octupole deformation in the light-actinide nuclei. The relative positions of the J(pi) = 1(-) and 3(-) states suggest they are produced by an octupole-vibrational mechanism, as opposed to alpha clustering or rotations of a reflection-asymmetric octupole-deformed shape.
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| 17. |
- Smolen, JS, et al.
(author)
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EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs
- 2010
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:6, s. 964-975
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Journal article (peer-reviewed)abstract
- 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.
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| 19. |
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| 20. |
- Bertsias, GK, et al.
(author)
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EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs
- 2010
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:12, s. 2074-2082
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Journal article (peer-reviewed)abstract
- To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.MethodsThe authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.ResultsSystemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence >5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1–5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.ConclusionsNeuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.
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| 21. |
- Gessl, I, et al.
(author)
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Role of joint damage, malalignment and inflammation in articular tenderness in rheumatoid arthritis, psoriatic arthritis and osteoarthritis
- 2021
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 80:7, s. 884-890
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Journal article (peer-reviewed)abstract
- To determine whether clinical tenderness can be considered a sign of inflammatory joint activity in patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PsA) and to assess other possible factors associated with tenderness.MethodsPatients diagnosed with RA, PsA and OA underwent clinical and ultrasound examination of wrists and finger joints. Radiographs of the hands were scored for erosions, joint space narrowing (JSN), osteophytes and malalignment. A binary damage score (positive if ≥1 erosion, JSN and/or presence of malalignment) was calculated. Differences in grey scale signs of synovitis and power Doppler (PD) between tender non-swollen (TNS) versus non-tender non-swollen (NTNS) joints were calculated. Disease duration was assessed,<2 years was regarded as early and >5 years as long-standing arthritis.ResultsIn total, 34 patients (9 early and 14 long-standing) from patients with RA, 31 patients (7 early and 15 long-standing) with PsA and 30 with OA were included. We found equal frequencies of PD signal between TNS and NTNS joints in RA (p=0.18), PsA (p=0.59) or OA (p=0.96). However, PD had a significant association with tenderness in early arthritis both in RA (p=0.02) and in PsA (p=0.02). The radiographic damage score showed significant association with tenderness in RA (p<0.01), PsA (p<0.01) and OA (p=0.04).ConclusionTenderness might not always be a sign of active inflammation in RA, PsA and OA. While tenderness in early arthritis may be more related to inflammation, established disease is better explained by joint damage and malalignment.
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| 22. |
- Bertsias, G., et al.
(author)
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EULAR recommendations for the management of systemic lupus erythematosus. Report of a task force of the EULAR standing committee for international clinical studies including therapeutics
- 2008
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 67:2, s. 195-205
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Research review (peer-reviewed)abstract
- Objective: Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. We sought to develop evidence-based recommendations addressing the major issues in the management of SLE. Methods: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Key questions for the management of SLE were compiled using the Delphi technique. A systematic search of PubMed and Cochrane Library Reports was performed using McMaster/Hedges clinical queries' strategies for questions related to the diagnosis, prognosis, monitoring and treatment of SLE. For neuropsychiatric, pregnancy and antiphospholipid syndrome questions, the search was conducted using an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence, and agreement on the statements was measured across the 19 specialists. Results: Twelve questions were generated regarding the prognosis, diagnosis, monitoring and treatment of SLE, including neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome and lupus nephritis. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements. The average agreement among experts was 8.8 out of 10. Conclusion: Recommendations for the management of SLE were developed using an evidence-based approach followed by expert consensus with high level of agreement among the experts.
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| 23. |
- Bertsias, G. K., et al.
(author)
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EULAR points to consider for conducting clinical trials in systemic lupus erythematosus: literature based evidence for the selection of endpoints
- 2009
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:4, s. 477-483
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Research review (peer-reviewed)abstract
- Objective: To assess available evidence on the use of end-points ( outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE. Methods: The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists. Results: Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken. Conclusion: This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.
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| 24. |
- Gessl, I, et al.
(author)
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Tenderness and radiographic progression in rheumatoid arthritis and psoriatic arthritis
- 2023
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 82:3, s. 344-350
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Journal article (peer-reviewed)abstract
- The aim of this study was to assess the predictive value of tenderness in the absence of swelling with consideration of other potential risk factors for subsequent radiographic progression in rheumatoid arthritis (RA) and psoriatic arthritis (PsA).MethodsClinical and sonographic (grey scale and power Doppler (PD)) examination of 22 joints of the hand were performed in patients with RA and PsA. The impact of tenderness on progression after 2 years was analysed in non-swollen joints for RA and PsA separately with multilevel mixed logistic regression analysis.ResultsWe included 1207 joints in 55 patients with RA and 352 joints in 18 patients with PsA. In RA, tenderness was associated with radiographic progression after 2 years (model 2: OR 1.85 (95% CI 1.01 to 3.27), p=0.047), although the association of PD (OR 2.92 (95% CI 1.71 to 5.00), p<0.001) and erosions (OR 4.74 (95% CI 2.44 to 9.23), p<0.001) with subsequent structural damage was stronger. In PsA, we found a positive but not significant association between tenderness and radiographic progression (OR 1.72 (95% CI 0.71 to 4.17), p=0.23). In contrast, similarly to RA, erosions (OR 4.62 (95% CI 1.29 to 16.54), p=0.019) and PD (OR 3.30 (95% CI 1.13 to 9.53), p=0.029) had a marked effect on subsequent structural damage.ConclusionOur findings imply that tenderness in non-swollen joints in RA is associated with subsequent damage. In both diseases, additional risk factors, such as sonographic signs for synovitis and baseline radiographic damage are associated with radiographic progression.
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| 25. |
- Gordon, C., et al.
(author)
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EULAR points to consider for conducting clinical trials in systemic lupus erythematosus
- 2009
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:4, s. 470-476
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Journal article (peer-reviewed)abstract
- Objective: Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions. Designing a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE. Methods: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Initially, the evidence for clinical trial end-points in SLE was evaluated and this has been reported separately. A consensus approach was developed by the SLE Task Force in formulating recommendations for points to consider when conducting clinical trials in SLE. Results: The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not actually been validated in clinical trials, although other forms of validation have been undertaken. The final recommendations for points to consider for conducting clinical trials in SLE address the following areas: study design, eligibility criteria, outcome measures including adverse events, concomitant therapies for SLE and its complications. Conclusions: Recommendations for points to consider when conducting clinical trials in SLE were developed using an evidence-based approach followed by expert consensus. The recommendations should be disseminated, implemented and then reviewed in detail and revised using an evidence-based approach in about 5 years, by which time there will be further evidence to consider from current clinical trials.
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| 26. |
- Gossec, L., et al.
(author)
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European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies : 2015 update
- 2016
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In: Annals of the Rheumatic Diseases. - London : BMJ Books. - 0003-4967 .- 1468-2060. ; 75:3, s. 499-510
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Journal article (peer-reviewed)abstract
- BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations.METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated.RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used.CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion. © 2015 BMJ Publishing Group Ltd & European League Against Rheumatism.
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| 27. |
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| 29. |
- Parr, E., et al.
(author)
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Fine structure in the alpha decay of high-spin isomers in Lu-155 and Hf-156
- 2018
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In: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 98:2
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Journal article (peer-reviewed)abstract
- Fine structure in the a decay of high-spin isomers in Lu-155( 25/2(-)) and Hf-156(8(+))has been studied for the first time using alpha gamma- coincidence analysis. Three new a decays from Lu-155(25/2(-)) and two from Hf-156(8(+)) have been identified, populating seniority s > 1 states in the N = 82 nuclei Tm-151 and Yb-152, respectively. The reduced hindrance factors of the a decays support the previous configuration assignments of the populated states. This is the first observation of states with excitation energy greater than 1.5 MeV being populated following a decay in nuclei outside of the Pb-208 region.
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| 30. |
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| 31. |
- Gerlag, Danielle M., et al.
(author)
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EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis : report from the Study Group for Risk Factors for Rheumatoid Arthritis
- 2012
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 71:5, s. 638-641
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Journal article (peer-reviewed)abstract
- The Study Group for Risk Factors for Rheumatoid Arthritis was established by the EULAR Standing Committee on Investigative Rheumatology to facilitate research into the preclinical and earliest clinically apparent phases of rheumatoid arthritis (RA). This report describes the recommendation for terminology to be used to define specific subgroups during different phases of disease, and defines the priorities for research in this area. Terminology was discussed by way of a three-stage structured process: A provisional list of descriptors for each of the possible phases preceding the diagnosis of RA were circulated to members of the study group for review and feedback. Anonymised comments from the members on this list were fed back to participants before a 2-day meeting. 18 participants met to discuss these data, agree terminologies and prioritise important research questions. The study group recommended that, in prospective studies, individuals without RA are described as having: genetic risk factors for RA; environmental risk factors for RA; systemic autoimmunity associated with RA; symptoms without clinical arthritis; unclassified arthritis; which may be used in a combinatorial manner. It was recommended that the prefix 'pre-RA with:' could be used before any/any combination of the five points above but only to describe retrospectively a phase that an individual had progressed through once it was known that they have developed RA. An approach to dating disease onset was recommended. In addition, important areas for research were proposed, including research of other tissues in which an adaptive immune response may be initiated, and the identification of additional risk factors and biomarkers for the development of RA, its progression and the development of extra-articular features. These recommendations provide guidance on approaches to describe phases before the development of RA that will facilitate communication between researchers and comparisons between studies. A number of research questions have been defined, requiring new cohorts to be established and new techniques to be developed to image and collect material from different sites.
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| 32. |
- Gessl, I, et al.
(author)
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TENDERNESS AND RADIOGRAPHIC PROGRESSION IN RHEUMATOID ARTHRITIS AND PSORIATIC ARTHRITIS
- 2022
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1231-1231
-
Conference paper (other academic/artistic)abstract
- In inflammatory arthritis swelling is regarded as a sign of synovitis and is associated with radiographic progression. However, the association of tenderness with radiographic progression is not clear.ObjectivesTo assess the predictive value of tenderness alone and with consideration of sonographic signs for synovitis, disease duration and baseline radiographic damage for subsequent radiographic progression in rheumatoid arthritis (RA) and psoriatic arthritis (PsA).MethodsClinical and sonographic (grey scale (GS) and power Doppler (PD)) examination of 22 joints of the hand were performed cross-sectionally in consecutive patients with RA and PsA with at least one tender joint. Radiographs were scored for erosions and joint space narrowing (JSN) at inclusion and radiographic progression of each joint was assessed after 2 years. The impact of tenderness on progression was analyzed in non-swollen joints for RA and PsA separately with logistic regression analyses. As a second step, the association of PD, GS, disease duration, C-reactive protein, baseline erosions and JSN and global joint counts with subsequent structural damage was assessed using univariate logistic regression in tender non-swollen joints again on the joint level.ResultsWe included 1207 joints in 54 RA patients and 396 joints in 18 PsA patients. Tenderness was associated with subsequent radiographic progression in non-swollen joints in PsA (OR 3.44, 95%CI 1.78-6.62, p<0.01) but not in RA (OR 1.60, 95% CI 0.99-2.48, p=0.55) (Figure 1). In tender non-swollen joints in RA patients, PD (OR 3.74, 95% CI 1.10-13.30, p=0.04) and baseline erosions (OR 4.42, 95% CI 1.22-15.95, p=0.02) had a significant impact on radiographic progression. In PsA patients, PD (OR 8.46, 95% CI 1.72-41.72, p<0.01), baseline erosions (OR 6.71, 95% CI 1.43-31.39, p=0.02), baseline JSN (OR 7.27, 95% CI 1.47-35.89, p=0.02) and SJC (OR 1.26, 95%CI 1.07-1.48, p<0.01) were associated with radiographic progression.Figure 1.The proportion of joints with progression in tender non-swollen and non-tender non-swollen joints in patients with rheumatoid and psoriatic arthritis; NTNS: non-tender non-swollen; TNS: tender non-swollenConclusionOur findings indicate that tenderness in non-swollen joints is associated with subsequent radiographic progression in PsA, while in RA it is a risk factor for radiographic progression only in the presence of additional factors, such as sonographic signs for synovitis.Disclosure of InterestsIrina Gessl: None declared, Mihaela Popescu: None declared, Gabriela Supp: None declared, Thomas Deimel: None declared, Paul Studenic: None declared, Martina Durechova: None declared, Michael Zauner: None declared, Josef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, Merck Sharp & Dohme, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB, Grant/research support from: Abbvie, AstraZeneca, Lilly and Roche, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Peter Mandl Speakers bureau: from AbbVie, Janssen and Novartis, Grant/research support from: from AbbVie, BMS, Novartis, Janssen, MSD and UCB;
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| 33. |
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| 34. |
- Mattsson, M., et al.
(author)
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Personal factors in systemic sclerosis and their coverage by patient-reported outcome measures
- 2015
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In: European Journal of Physical and Rehabilitation Medicine. - 1827-1804. ; 51:4, s. 405-421
-
Journal article (peer-reviewed)abstract
- Background. Systemic sclerosis (SSc) is an autoimmune disease where thickening of the skin can lead to reduced body function and limitations in activities. Severe forms can also affect and seriously damage inner organs. Patient-centred rehabilitation emphasises considerations of patients' background, experience and behavior which highlights the need to know if patient-reported outcome measures (PROMs) include such personal factors. Aim. To identify and describe personal factors in the experiences of functioning and health of persons with SSc and to examine if and to what extent PROMs in SSc research cover these factors. Design. Data from a qualitative study with focus group interviews were analysed. PROMs in SSc research were identified in a literature review between 2008-2013. Setting. Participants were recruited from outpatient clinics at rheumatology department. Population. Sixty-three patients with SSc from four European countries participated. Methods. Data from interviews were analysed using a structure of personal factors developed by Geyh et al. Identified PROMs were analysed and linked to main concepts, related to the personal factors, found in the interview data. Results. Nineteen main concepts were related to the area "patterns of experience and behaviour" in the personal factor structure, 16 to "thoughts and beliefs", nine to "feelings", one to "motives" and one to "personal history and biography", respectively. Among the 35 PROMs identified, 15 did not cover any of the identified concepts. Concepts within the area "feelings" were mostly covered by the PROMs. Five of the PROMs covered "patterns of experience and behaviour", while "motives" and "personal history and biography" were not covered at all. Four of the identified PROMs covered concepts within the areas "feelings", "thoughts and beliefs" and "patterns of experience and behaviour" in the same instrument. The Illness Cognition Questionnaire and Illness Behaviour Questionnaire were such PROMs. Conclusion. Patterns of experience and behaviour had the highest number of concepts related to personal factors, but few of the PROMs in SSc research covered these factors. Only a few PROMs covered several personal factors areas in the same instrument. Clinical Rehabilitation Impact. The results would be of value when developing core sets for outcome measurements in SSc.
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| 35. |
- Woolf, K, et al.
(author)
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Management of osteoporosis
- 2004
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In: Practical Rheumatology. - 0323029396 - 9780323029391 ; , s. 561-561
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Book chapter (other academic/artistic)
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| 36. |
- Åkesson, Kristina, et al.
(author)
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Management of osteoporosis
- 2003
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In: Rheumatology. - 0323024041 ; , s. 2093-2093, s. 77-77
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Book chapter (other academic/artistic)
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| 37. |
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| 38. |
- Chatzidionysiou, K, et al.
(author)
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Efficacy of glucocorticoids, conventional and targeted synthetic disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis
- 2017
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:6, s. 1102-1107
-
Journal article (peer-reviewed)abstract
- To perform a systematic literature review (SLR) informing the 2016 update of the recommendations for the management of rheumatoid arthritis (RA).MethodsAn SLR for the period between 2013 and 2016 was undertaken to assess the efficacy of glucocorticoids (GCs), conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and targeted synthetic DMARDs (tsDMARDs) (tofacitinib and baricitinib) in randomised clinical trials.ResultsFor GCs, four studies were included in the SLR. Patients without poor prognostic factors experienced benefit when GCs were added to methotrexate (MTX). Lower doses of GCs were similar to higher doses. For csDMARDs, two new studies comparing MTX monotherapy with combination csDMARD were included in the SLR. In the tREACH trial at the end of 12 months no difference between the groups in disease activity, functional ability and radiographic progression was seen, using principles of tight control (treat-to-target). In the CareRA trial, combination therapy with csDMARDs was not superior to MTX monotherapy and monotherapy was better tolerated.For tsDMARDs, tofacitinib and baricitinib were shown to be more effective than placebo (MTX) in different patient populations.ConclusionsAddition of GCs to csDMARD therapy may be beneficial but the benefits should be balanced against the risk of toxicity. Under tight control conditions MTX monotherapy is not less effective than combination csDMARDs, but better tolerated. Tofacitinib and baricitinib are efficacious in patients with RA, including those with refractory disease.
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| 39. |
- Combe, B, et al.
(author)
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2016 update of the EULAR recommendations for the management of early arthritis
- 2017
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:6, s. 948-959
-
Journal article (peer-reviewed)abstract
- Since the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis.MethodsIn accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of ‘management’ and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process.ResultsThe updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research.ConclusionsThese recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.
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| 40. |
- Fanouriakis, Antonis, et al.
(author)
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EULAR recommendations for the management of systemic lupus erythematosus : 2023 update
- 2024
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In: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 83:1, s. 15-29
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
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| 41. |
- Gandhi, Sanya K., et al.
(author)
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Cost-effectiveness of resuvastatin in comparison with generic atorvastatin and simvastatin in a Swedish population at high risk of cardiovascular events
- 2012
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In: ClinicoEconomics and Outcomes Research. - : Dove Medical Press. - 1178-6981. ; 4, s. 1-11
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Journal article (peer-reviewed)abstract
- Background: To assess the long-term cost-effectiveness of rosuvastatin therapy compared with generic simvastatin and generic atorvastatin in reducing the incidence of cardiovascular events and mortality in a Swedish population with Framingham risk ≥20%.Methods: A probabilistic Monte Carlo simulation model based on data from JUPITER (the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) was used to estimate the long-term cost-effectiveness of rosuvastatin 20 mg daily versus simvastatin or atorvastatin 40 mg for the prevention of cardiovascular death and morbidity. The three-stage model included cardiovascular event prevention simulating the 4 years of JUPITER, initial prevention beyond the trial, and subsequent cardiovascular event prevention. A Swedish health care payer perspective (direct costs only) was modeled for a lifetime horizon, with 2008/2009 as the costing period. Univariate and probabilistic sensitivity analyses were performed.Results: The incremental cost per quality-adjusted life-year (QALY) gained with rosuvastatin 20 mg over simvastatin or atorvastatin 40 mg ranged from SEK88,113 (rosuvastatin 20 mg versus simvastatin 40 mg; Framingham risk ≥30%; net avoidance of 34 events/1000 patients) to SEK497,542 (versus atorvastatin 40 mg: Framingham risk ≥20%; net avoidance of 11 events/1000 patients) over a lifetime horizon. Probabilistic sensitivity analyses indicated that at a willingness-to-pay threshold of SEK500,000/QALY, rosuvastatin 20 mg would be cost-effective for approximately 75%–85% of simulations relative to atorvastatin or simvastatin 40 mg. Sensitivity analyses indicated the findings to be robust.Conclusion: Rosuvastatin 20 mg is cost-effective over a lifetime horizon compared with generic simvastatin or atorvastatin 40 mg in patients at high cardiovascular risk in Sweden.
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| 42. |
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| 43. |
- Meisters, Rachelle, et al.
(author)
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EULAR/eumusc.net standards of care for rheumatoid arthritis : cross-sectional analyses of importance, level of implementation and care gaps experienced by patients and rheumatologists across 35 European countries
- 2020
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:11, s. 1423-1431
-
Journal article (peer-reviewed)abstract
- Objective As part of European League against Rheumatism (EULAR)/European Musculoskeletal Conditions Surveillance and Information Network, 20 user-focused standards of care (SoCs) for rheumatoid arthritis (RA) addressing 16 domains of care were developed. This study aimed to explore gaps in implementation of these SoCs across Europe. Methods Two cross-sectional surveys on the importance, level of and barriers (patients only) to implementation of each SoC (0-10, 10 highest) were designed to be conducted among patients and rheumatologists in 50 European countries. Care gaps were calculated as the difference between the actual and maximum possible score for implementation (ie, 10) multiplied by the care importance score, resulting in care gaps (0-100, maximal gap). Factors associated with the problematic care gaps (ie, gap≥30 and importance≥6 and implementation<6) and strong barriers (≥6) were further analysed in multilevel logistic regression models. Results Overall, 26 and 31 countries provided data from 1873 patients and 1131 rheumatologists, respectively. 19 out of 20 SoCs were problematic from the perspectives of more than 20% of patients, while this was true for only 10 SoCs for rheumatologists. Rheumatologists in countries with lower gross domestic product and non-European Union countries were more likely to report problematic gaps in 15 of 20 SoCs, while virtually no differences were observed among patients. Lack of relevance of some SoCs (71%) and limited time of professionals (66%) were the most frequent implementation barriers identified by patients. Conclusions Many problematic gaps were reported across several essential aspects of RA care. More efforts need to be devoted to implementation of EULAR SoCs.
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| 44. |
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| 45. |
- Nam, JL, et al.
(author)
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Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis
- 2017
-
In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:6, s. 1108-1113
-
Journal article (peer-reviewed)abstract
- To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform European League Against Rheumatism (EULAR) Task Force treatment recommendations.MethodsMEDLINE, EMBASE and Cochrane databases were searched for phase III or IV (or phase II, if these studies were lacking) randomised controlled trials (RCTs) published between January 2013 and February 2016. Abstracts from the American College of Rheumatology and EULAR conferences were obtained.ResultsThe RCTs confirmed greater efficacy with a bDMARD+conventional synthetic DMARD (csDMARD) versus a csDMARDs alone (level 1A evidence). Using a treat-to-target strategy approach, commencing and escalating csDMARD therapy and adding a bDMARD in cases of non-response, is an effective approach (1B). If a bDMARD had failed, improvements in clinical response were seen on switching to another bDMARD (1A), but no clear advantage was seen for switching to an agent with another mode of action. Maintenance of clinical response in patients in remission or low disease activity was best when continuing rather than stopping a bDMARD, but bDMARD dose reduction or ‘spacing’ was possible, with a substantial proportion of patients achieving bDMARD-free remission (2B). RCTs have also demonstrated efficacy of several new bDMARDs and biosimilar DMARDs (1B).ConclusionsThis systematic literature review consistently confirmed the previously reported efficacy of bDMARDs in RA and provided additional information on bDMARD switching and dose reduction.
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| 46. |
- Ramiro, S, et al.
(author)
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Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis
- 2017
-
In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:6, s. 1093-1101
-
Journal article (peer-reviewed)abstract
- To assess the safety of synthetic (s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) for the management of rheumatoid arthritis (RA) to inform the European League Against Rheumatism recommendations for the management of RA.MethodsSystematic literature review (SLR) of observational studies comparing any DMARD with another intervention for the management of patients with RA. All safety outcomes were included. A comparator group was required for the study to be included. Risk of bias was assessed with the Hayden's tool.ResultsTwenty-six observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria (15 on serious infections, 4 on malignancies). Substantial heterogeneity precluded meta-analysis. Together with the evidence from the 2013 SLR, based on 15 studies, 7 at low risk of bias, patients on bDMARDs compared with patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1 to 1.8)—without differences across bDMARDs—a higher risk of tuberculosis (aHR 2.7 to 12.5), but no increased risk of infection by herpes zoster. Patients on bDMARDs did not have an increased risk of malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5).ConclusionsThese findings confirm the known safety pattern of bDMARDs, including both tumour necrosis factor-α inhibitor (TNFi) and non-TNFi, for the treatment of RA.
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