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1.
RMD Open ; 6(3)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33188136

RESUMO

OBJECTIVES: Review of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs). METHODS: A systematic literature research (SLR) of all publications on JAK inhibitors (JAKi) treatment published until March 2019 using MEDLINE, EMBASE and the Cochrane Library. Efficacy and safety were assessed in randomised controlled trials (RCTs), integrating long-term extension periods additionally for safety evaluation. RESULTS: 3454 abstracts were screened with 85 included in the final analysis (efficacy and RCT safety: n=72; safety only: n=13). Efficacy of RCTs investigating tofacitinib (TOFA, n=27), baricitinib (BARI, n=9), upadacitinib (UPA, n=14), filgotinib (FILGO, n=7), decernotinib (DEC, n=3) and peficitinib (PEF, n=7) was evaluated. Six head-to-head trials comparing JAKi with tumour necrosis factor inhibitors (TNFi) were included. Efficacy of JAKi was shown in rheumatoid arthritis (RA) for all agents, psoriatic arthritis (TOFA, FILGO), ankylosing spondylitis (TOFA, FILGO), systemic lupus erythematosus (BARI), chronic plaque psoriasis (TOFA, BARI, PEF), ulcerative colitis (TOFA, UPA), Crohn's disease (UPA, FILGO) and atopic dermatitis (TOFA, BARI, UPA). Safety analysis of 72 RCTs, one cohort study and 12 articles on long-term extension studies showed increased risks for infections, especially herpes zoster, serious infections and numerically higher rates of venous thromboembolic events. No increased malignancy rates or major adverse cardiac events were observed. CONCLUSION: JAKi provide good efficacy compared to placebo (and to TNFi in RA and Pso) across various IMIDs with an acceptable safety profile. This SLR informed the task force on points to consider for the treatment of IMIDs with JAKi with the available evidence.

2.
Ann Rheum Dis ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158881

RESUMO

OBJECTIVES: Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use based on a systematic literature review (SLR) on efficacy and safety. METHODS: Existing data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration. RESULTS: The Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale. CONCLUSION: The consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management.

5.
Ther Adv Musculoskelet Dis ; 12: 1759720X20934934, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655702

RESUMO

Aims: Radiographic imaging is essential in the diagnosis of hand osteoarthritis (HOA); however, it is unknown whether a multiplanar examination would add essential information to dorso-palmar (dp) views alone. This study evaluated whether an additional radiographic view would aid clinicians in the diagnostic process of HOA. Methods: The dp radiographs of both hands from 159 HOA patients were assessed according to the scores described by Kellgren and Lawrence (K/L). In oblique view images, structures similar to classic ostophytes (OPs) were found, namely bony proliferations on the dorsal and/or ventral margins of joints, and were documented as dorsal/ventral OPs (dvOPs). Function and pain were assessed by applying standardised read-out systems. Logistic regression analysis and Mann-Whitney tests were implemented. Results: The presence of dvOPs was associated with the degree of joint damage; however, dp views were sufficient to estimate radiographic changes. Only a few joints showed dvOPs as the only structural alteration; nevertheless, in almost all cases, classical radiographic OA changes were found in dp views of other joints of the same or the contralateral hand. The presence of dvOPs did not affect joint function or pain according to established scores, but was associated with radiographic progression in distal interphalangeal joints. Conclusion: This is the first study to confirm that additional radiographic planes, oblique/lateral views, are not necessary in the diagnostic process in HOA in daily clinical practice. Nevertheless, the presence of dvOPs reflect more severe joint damage and is associated with radiographic progression in HOA; hence, oblique/lateral views could be a useful tool for academic purposes.

6.
Ann Rheum Dis ; 79(6): 778-786, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32381564

RESUMO

OBJECTIVE: To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA). METHODS: This is a systematic literature research of 2015-2018 publications on all DMARDs in patients with PsA, searching Medline, Embase and the Cochrane Library. Efficacy was assessed in randomised controlled trials. For safety, cohort studies, case-control studies and long-term extensions (LTEs) were analysed. RESULTS: 56 publications (efficacy: n=33; safety n=23) were analysed. The articles were on tumour necrosis factor (TNF) inhibitors (n=6; golimumab, etanercept and biosimilars), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), IL-23-p19 inhibitors (n=2; guselkumab, risankizumab), clazakizumab (IL-6 inhibitor), abatacept (CD80/86 inhibitor) and ABT-122 (anti-TNF/IL-17A), respectively. One study compared ustekinumab (IL-12/23i) with TNF inhibitor therapy in patients with entheseal disease. Three articles investigated DMARD tapering. Trials on targeted synthetic DMARDs investigated apremilast (phosphodiesterase-4 inhibitor) and Janus kinase inhibitors (JAKi; tofacitinib, filgotinib). Biosimilar comparison with bio-originator showed non-inferiority. Safety was evaluated in 13 LTEs, 9 cohort studies and 1 case-control study investigating malignancies, infections, infusion reactions, multiple sclerosis and major cardiovascular events, as well as efficacy and safety of vaccination. No new safety signals were identified; however, warnings on the risk of venous thromboembolic events including pulmonary embolism when using JAKi were issued by regulators based on other studies. CONCLUSION: Many drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Humanos , Interleucina-17/antagonistas & inibidores , Subunidade p19 da Interleucina-23/antagonistas & inibidores , Terapia de Alvo Molecular , Medicamentos Sintéticos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
7.
Ann Rheum Dis ; 79(6): 700-712, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32434812

RESUMO

OBJECTIVE: To update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA). METHODS: According to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined. RESULTS: The updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed. CONCLUSION: These recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Glucocorticoides/uso terapêutico , Sociedades Médicas , Consenso , Conferências de Consenso como Assunto , Tomada de Decisão Compartilhada , Europa (Continente) , Humanos , Interleucina-12/antagonistas & inibidores , Interleucina-17/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Medicamentos Sintéticos/uso terapêutico , Revisões Sistemáticas como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
9.
Nat Med ; 26(6): 974-980, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32313250

RESUMO

Phase 3 trials are the mainstay of drug development across medicine but have often not met expectations set by preceding phase 2 studies. A systematic meta-analysis evaluated all randomized controlled, double-blind trials investigating targeted disease-modifying anti-rheumatic drugs in rheumatoid and psoriatic arthritis. Primary outcomes of American College of Rheumatology (ACR) 20 responses were compared by mixed-model logistic regression, including exploration of potential determinants of efficacy overestimation. In rheumatoid arthritis, phase 2 trial outcomes systematically overestimated subsequent phase 3 results (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.39, 95% confidence interval: 1.25-1.57, P < 0.001). Data for psoriatic arthritis trials were similar, but not statistically significant (odds ratio comparing ACR20 in phase 2 versus phase 3: 1.35, 95% confidence interval: 0.94-1.94, P = 0.09). Differences in inclusion criteria largely explained the observed differences in efficacy findings. Our findings have implications for all stakeholders in new therapeutic development and testing, as well as potential ethical implications.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Desenvolvimento de Medicamentos , Humanos , Modelos Logísticos , Avaliação de Resultados em Cuidados de Saúde , Resultado do Tratamento
11.
Ann Rheum Dis ; 79(6): 744-759, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32033937

RESUMO

OBJECTIVES: To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA). METHODS: A systematic literature research (SLR) to investigate the efficacy of any disease-modifying antirheumatic drug (DMARD) (conventional synthetic (cs)DMARD, biological (b) and biosimilar DMARD, targeted synthetic (ts)DMARD) or glucocorticoid (GC) therapy in patients with RA was done by searching MEDLINE, Embase and the Cochrane Library for articles published between 2016 and 8 March 2019. RESULTS: 234 abstracts were selected for detailed assessment, with 136 finally included. They comprised the efficacy of bDMARDs versus placebo or other bDMARDs, efficacy of Janus kinase (JAK) inhibitors (JAKi) across different patient populations and head-to-head of different bDMARDs versus JAKi or other bDMARDs. Switching of bDMARDs to other bDMARDs or tsDMARDs, strategic trials and tapering studies of bDMARDs, csDMARDs and JAKi were assessed. The drugs evaluated included abatacept, adalimumab, ABT-122, baricitinib, certolizumab pegol, SBI-087, CNTO6785, decernotinib, etanercept, filgotinib, golimumab, GCs, GS-9876, guselkumab, hydroxychloroquine, infliximab, leflunomide, mavrilimumab, methotrexate, olokizumab, otilimab, peficitinib, rituximab, sarilumab, salazopyrine, secukinumab, sirukumab, tacrolimus, tocilizumab, tofacitinib, tregalizumab, upadacitinib, ustekinumab and vobarilizumab. The efficacy of many bDMARDs and tsDMARDs was shown. Switching to another tumour necrosis factor inhibitor (TNFi) or non-TNFi bDMARDs after TNFi treatment failure is efficacious. Tapering of DMARDs is possible in patients achieving long-standing stringent clinical remission; in patients with residual disease activity (including patients in LDA) the risk of flares is increased during the tapering. Biosimilars are non-inferior to their reference products. CONCLUSION: This SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR's RA management recommendation.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Substituição de Medicamentos , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Humanos , Inibidores de Janus Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicamentos Sintéticos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
12.
Ann Rheum Dis ; 79(6): 760-770, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32033941

RESUMO

OBJECTIVES: To perform a systematic literature review (SLR) concerning the safety of synthetic (s) and biological (b) disease-modifying anti rheumatic dugs (DMARDs) to inform the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis (RA). METHODS: An SLR of observational studies comparing safety outcomes of any DMARD with another intervention for the management of RA. A comparator group was required for inclusion. For treatments still without registry data (eg, sarilumab and the Janus kinase (JAK) inhibitors baricitinib, upadacitinib), randomised controlled trials (RCTs) and long-term extensions (LTEs) were used. Risk of bias (RoB) was assessed according to standard procedures. RESULTS: Forty-two observational studies fulfilled the inclusion criteria, addressing safety outcomes with bDMARDs and sDMARDs. Nine studies showed no difference in the risk of serious infections across bDMARDs and two studies (high RoB) showed an increased risk with bDMARDs compared with conventional synthetic (cs) DMARDs (adjusted incidence rate ratio 3.1-3.9). The risk of Herpes zoster infection was similar across bDMARDs, but one study showed an increased risk with tofacitinib compared with abatacept (adjusted HR (aHR) 2.0). Five studies showed no increased risk of cancer for bDMARDs compared with csDMARDs. An increased risk of lower intestinal perforation was found for tocilizumab compared with csDMARDs (aHR 4.5) and tumour necrosis factor inhibitor (TNFi) (aHR 2.6-4.0). Sixty manuscripts reported safety data from RCTs/LTEs. Overall, no unexpected safety outcomes were found, except for the possibly increased risk of venous thromboembolism (VTE) with JAK inhibitors. CONCLUSION: Data obtained by this SLR confirm the known safety profile of bDMARDs. The risk of VTE in RA, especially in patients on JAK inhibitors, needs further evaluation.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Infecções/induzido quimicamente , Perfuração Intestinal/induzido quimicamente , Produtos Biológicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Herpes Zoster/induzido quimicamente , Humanos , Neoplasias/induzido quimicamente , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicamentos Sintéticos/efeitos adversos , Tromboembolia Venosa/induzido quimicamente
13.
Ann Rheum Dis ; 79(6): 685-699, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31969328

RESUMO

OBJECTIVES: 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. METHODS: An 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. RESULTS: The 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. CONCLUSIONS: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Sociedades Médicas , Medicamentos Sintéticos/uso terapêutico , Antirreumáticos/economia , Produtos Biológicos/economia , Consenso , Quimioterapia Combinada , Europa (Continente) , Humanos , Inibidores de Janus Quinases/uso terapêutico , Medicamentos Sintéticos/economia , Revisões Sistemáticas como Assunto , Fator de Necrose Tumoral alfa/antagonistas & inibidores
14.
Semin Arthritis Rheum ; 49(2): 211-217, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30799033

RESUMO

BACKGROUND: Despite modern therapeutics and treatment strategies, a subset of rheumatoid arthritis (RA) patients remains insufficiently responsive to multiple therapies. Here, we identify predictors of such refractory RA ("reRA"). METHODS: Patients from a longitudinal academic clinical database with reRA (defined as failing to reach the treatment target of at least low disease activity with ≥3 DMARD courses, including ≥1 biological, over a total of ≥18 months) were compared to patients who did respond within the first two treatments (treatment amenable RA, "taRA"). We performed logistic regression analysis to identify risk factors for refractory disease, and several sensitivity analyses concerning different potential definitions for reRA to confirm the robustness of the results; key findings were also validated in an independent community cohort. RESULTS: We enrolled 412 patients, of whom 70 were reRA and 102 taRA; 240 patients fulfilled neither definition. ReRA patients were more frequently female (92.9 vs. 70.6%, p < 0.001), younger (44.37 vs. 51.14 years, p = 0.002), and had higher CDAI levels at first presentation (26.06 vs. 15.39, p < 0.001). Treatment delay was significantly longer for reRA than for taRA (3.17 vs. 1.45 years, p = 0.001). In multivariable analyses, treatment delay, female gender and higher disease activity remained as independent predictors of refractory disease. Based on the identified predictors, we developed a matrix model for risk of future reRA. CONCLUSIONS: Our data identified delay to initial treatment, female gender and higher disease activity as important predictors of a later refractory course of RA. Delay of treatment initiation is the single most important modifiable risk factor of refractory disease.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Tempo para o Tratamento
15.
16.
Best Pract Res Clin Rheumatol ; 32(3): 401-414, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171311

RESUMO

Psoriatic arthritis (PsA) is an inflammatory disease in patients with a personal or family history of psoriasis. While synovitis is the major hallmark, enthesitis, dactylitis, axial inflammation, and skin and nail involvement are variable in prevalence and severity. The assessment of disease activity is important to determine the treatment target ("Treat-to-Target") as well as early response to therapy, because a prolonged ineffective medication may not only be associated with an adverse disease outcome but constitutes a waste of individual and/or societal expenses. Various measures of disease activity have been established for all manifestations individually ('uni-dimensional approach') or by combining such measures into a single umbrella score ('multi-dimensional approach'). Because pathogeneses and therapeutic responsiveness differ among individual domains, a uni-dimensional approach is preferred. The major uni-dimensional index is the Disease Activity index for PSoriatic Arthritis, which provides a continuous scale and allows calculating disease activity at any point in time, determining response to therapy and defining disease activity states, such as remission, as a treatment target. The assessment of the various domains by individual and combined indices is discussed.


Assuntos
Artrite Psoriásica/diagnóstico , Artrite Psoriásica/patologia , Humanos , Indução de Remissão , Índice de Gravidade de Doença
17.
Ann Rheum Dis ; 76(12): 2038-2045, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28835465

RESUMO

BACKGROUND: Functional outcomes are central in patients with chronic inflammatory musculoskeletal diseases. In a secondary data analysis of the GO-REVEAL trial (NCT00265096), we investigated wether structural damage is linked to functional impairment in patients with psoriatic arthritis (PsA), a link that is still elusive in this disease. METHODS: We analysed 363 patients enrolled in the GO-REVEAL study and obtained modified Sharp/van der Heijde Scores (mSvdHS) from X-rays performed at baseline, after 24, 52 and 104 weeks. Using longitudinal analyses, we assessed the effect of total mSvdHS (and its subscores, joint space narrowing (JSN) and erosions (ERO)) on functional status (measured by the Health Assessment Questionnaire) in all patients and in those attaining remission (n=117). Furthermore, we analysed wether structural damage reduces the responsiveness of functional limitations to treatment in a subgroup of responders who had functional impairment at baseline (n=67). Additionally, internal and external validation analyses were performed. RESULTS: The effect of damage on function was seen in the disease activity-adjusted models using total mSvdHS (p=0.005), JSN (p=0.019) and ERO (p=0.001) as well as in the remission analyses for mSvdHS (p=0.029) and JSN (p=0.010), respectively. Functional responsiveness was limited by increasing total mSvdHS (p=0.010), JSN (p=0.002) and ERO (p=0.040). The results were validated using other functional outcomes and in an independent clinical cohort. CONCLUSIONS: In PsA, structural damage, particularly JSN, has implications for physical function. Functional outcomes have an irreversible component that is strongly related to the extent of joint destruction. This needs to be considered when targeting functional outcomes in clinical practice.


Assuntos
Artrite Psoriásica/diagnóstico por imagem , Avaliação da Deficiência , Articulações/diagnóstico por imagem , Índice de Gravidade de Doença , Adulto , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/fisiopatologia , Progressão da Doença , Feminino , Humanos , Articulações/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Radiografia/métodos , Radiografia/estatística & dados numéricos , Indução de Remissão , Inquéritos e Questionários , Resultado do Tratamento
19.
Environ Monit Assess ; 189(3): 134, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28247286

RESUMO

A dense monitoring network is vital for the reliable assessment of PM10 in different parts of an urban area. In this study, a new idea is employed for the re-construction of the 20 shut-down PM10 monitoring stations of Berlin. It endeavours to find the non-linear relationship between the hourly PM10 concentration of both the still operating and the shut-down PM10 monitoring stations by using a fuzzy modelling technique, called modified active learning method (MALM). In addition, the simulations were performed by using not only raw PM10 databases but also log-transformed PM10 databases for skewness reduction. According to the results of hourly PM10 simulation (root mean square error about 13.0 µg/m3, correlation coefficient 0.88), the shut-down stations have been appropriately simulated and the idea of dense monitoring network development by the re-construction of the shut-down stations was realised. The results of simulations using raw and log-transformed databases showed that data transformation has no significant effect on the performance of MALM in the simulation of shut-down PM10 stations. By the combination of the 11 still operating stations and the 20 re-constructed stations, a dense monitoring network was generated for Berlin and was utilised for the calculation of the reliable monthly and mean annual PM10 concentration for five different PM10 zones in Berlin (the suburban-background, urban-background, urban-traffic, rural-background and suburban-traffic areas). The results showed that the mean annual concentration of PM10 at the five zones increased by about 13.0% in 2014 (26.3 µg/m3) in comparison with 2013 (23.3 µg/m3). Furthermore, the mean annual concentration of PM10 in the traffic lanes of the suburban (2013 25.0 µg/m3, 2014 26.9 µg/m3) and urban (2013 27.7 µg/m3, 2014 31.3 µg/m3) areas is about 14 and 20% higher than the PM10 concentration of suburban-background (2013 21.3 µg/m3, 2014 24.5 µg/m3) and urban-background (2013 23.0 µg/m3, 2014 26.1 µg/m3) areas, respectively.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Berlim , Cidades , Simulação por Computador , Interpretação Estatística de Dados , Lógica Fuzzy , Geografia , Aprendizagem , Material Particulado/análise , Probabilidade
20.
Wien Klin Wochenschr ; 128(21-22): 791-795, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27822746

RESUMO

Psoriatic arthritis is a chronic inflammatory joint disease occurring in a subgroup of patients suffering from psoriasis. This article gives an overview of the complexity of psoriatic arthritis, looking at several aspects of this heterogeneous disease, such as epidemiology, important clinical features and comorbidities as well as current concepts of the pathophysiology and subsequent insights in novel treatment targets.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/terapia , Inflamação/diagnóstico , Inflamação/terapia , Avaliação de Sintomas/métodos , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Psoriásica/epidemiologia , Comorbidade , Diagnóstico Diferencial , Medicina Baseada em Evidências , Humanos , Incidência , Inflamação/epidemiologia , Terapia de Alvo Molecular/métodos , Fatores de Risco , Resultado do Tratamento
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