Ricardo Fuller

Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases

Background Despite the WHO recommendation that the 2010–2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behçets disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjögrens syndrome, Takayasus arteritis, polymyositis and Granulomatosis with polyangiitis (Wegeners) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p<0.0001), seroconversion rates (63.4% vs 76.9%, p<0.001) and the factor increase in GMT (8.9 vs 13.2 p<0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p<0.0001), RA (p<0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p<0.0001), RA (p<0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p<0.0001), RA (p<0.0001) and PsA (p<0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644)

Osteoarthritis: can anti-cytokine therapy play a role in treatment?

Osteoarthritis (OA) is the most common joint disorder worldwide, and it has an enormous socioeconomic impact both in the United States and throughout the world. The degree of articular inflammation is usually associated with the disease’s progression, indicating that this process could contribute to articular damage. IL-1 beta and anti-TNF alpha are the two major cytokines players in the physiopathology of OA. Hence, we aimed to review the current literature on the effects of IL-1 and TNF-alpha neutralization as a new OA therapy. In vitro and experimental models showed a reduction in cartilage destruction with IL-1 inhibition therapy by IL-1 receptor antagonists (IL-1Ra). Despite this favorable evidence in animal models, studies on the inhibition of IL-1R in humans are still scarce. Although there is clear evidence that TNF-alpha plays a role in the pathophysiology of OA, only a few experimental trials have investigated the efficacy of blocking this pro-inflammatory cytokine in the treatment of OA. So far, the few studies available in humans using anti-TNF-alpha and IL-1 receptor antagonist are not remarkable, suggesting that further investigation and new therapeutic approaches are needed.

Effectiveness of medial-wedge insole treatment for valgus knee osteoarthritis.

OBJECTIVE To assess the efficacy of medial-wedge insoles in valgus knee osteoarthritis (OA). METHODS Thirty consecutive women with valgus-deformity knee OA > or = 8 degrees were randomized into 2 groups: medial insole (insoles with 8-mm medial elevation at the rearfoot [n = 16]) and neutral insole (similar insole without elevation [n = 14]). Both groups also wore ankle supports. A blinded examiner assessed pain on movement, at rest, and at night with a visual analog scale (VAS), the Lequesne index, and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. Femorotibial, talocalcaneal, and talar tilt angles were evaluated at baseline and after 8 weeks of insole use. RESULTS Significant reductions in the medial insole group were observed for pain on movement (mean +/- SD VAS pre- and postintervention 8.1 +/- 1.5 versus 4.2 +/- 2.4; P = 0.001), at rest (5.1 +/- 2.3 versus 2.7 +/- 2.4; P = 0.002), and at night (6.1 +/- 2.7 versus 3.1 +/- 2.1; P = 0.001). In addition, a decrease in Lequesne (14.7 +/- 3.4 versus 9.6 +/- 3.8; P = 0.001) and WOMAC scores (74.1 +/- 14.2 versus 56.1 +/- 14.9; P = 0.001) was observed for the medial insole group. In the neutral insole group, a significant reduction was observed only for night pain (mean +/- SD VAS pre- and postintervention 5.8 +/- 2.4 versus 4.6 +/- 2.4; P = 0.019). An increase in femorotibial angle (169.0 +/- 3.4 versus 170.8 +/- 3.7; P = 0.001) occurred only in the medial insole group. Moreover, the difference in measured femorotibial angles pre- and postintervention was 1.84 +/- 1.42 versus -0.18 +/- 0.67 (P < 0.001) for the medial and neutral insole groups. CONCLUSION The use of medial-wedge insoles was highly effective in reducing pain at rest and on movement and promoted a functional improvement of valgus knee OA.

Beneficial Effect of Creatine Supplementation in Knee Osteoarthritis

INTRODUCTION The aim of this study was to investigate the efficacy of creatine (CR) supplementation combined with strengthening exercises in knee osteoarthritis (OA). METHODS A randomized, double-blind, placebo-controlled trial was performed. Postmenopausal women with knee OA were allocated to receive either CR (20 g·d(-1) for 1 wk and 5 g·d(-1) thereafter) or placebo (PL) and were enrolled in a lower limb resistance training program. They were assessed at baseline (PRE) and after 12 wk (POST). The primary outcome was the physical function as measured by the timed-stands test. Secondary outcomes included lean mass, quality of life, pain, stiffness, and muscle strength. RESULTS Physical function was significantly improved only in the CR group (P = 0.006). In addition, a significant between-group difference was observed (CR: PRE = 15.7 ± 1.4, POST = 18.1 ± 1.8; PL: PRE = 15.0 ± 1.8, POST = 15.2 ± 1.2; P = 0.004). The CR group also presented improvements in physical function and stiffness subscales as evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (P = 0.005 and P = 0.024, respectively), whereas the PL group did not show any significant changes in these parameters (P > 0.05). In addition, only the CR group presented a significant improvement in lower limb lean mass (P = 0.04) as well as in quality of life (P = 0.01). Both CR and PL groups demonstrated significant reductions in pain (P < 0.05). Similarly, a main effect for time revealed an increase in leg-press one-repetition maximum (P = 0.005) with no significant differences between groups (P = 0.81). CONCLUSIONS CR supplementation improves physical function, lower limb lean mass, and quality of life in postmenopausal women with knee OA undergoing strengthening exercises.

Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy?

OBJECTIVE To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. METHODS A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) ≥20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. RESULTS The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED ≥20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED ≥20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED ≥20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED ≥20 mg + IS + CQ (57.4%; P = 0.09). CONCLUSION Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity. Trial registration. www.clinicaltrials.gov, NCT01151644.

Joint loading decreased by inexpensive and minimalist footwear in elderly women with knee osteoarthritis during stair descent

Previous studies indicate that flexible footwear, which mimics the biomechanics of walking barefoot, results in decreased knee loads in patients with knee osteoarthritis (OA) during walking. However, the effect of flexible footwear on other activities of daily living, such as descending stairs, remains unclear. Our objective was to evaluate the influence of inexpensive and minimalist footwear (Moleca) on knee adduction moment (KAM) during stair descent of elderly women with and without knee OA.

Osteoartrite (artrose): tratamento

DESCRICAO DO METODO DE COLETA DE EVIDENCIAS: Foram utilizados os estudos disponiveis na literatura medica presentes nas seguintes bases de dados, acessiveis atraves da internet: OVID (EBM-Reviews, incluindo-se as bases de dados da Cochrane) e o Medline, de 1966 ate o presente, atraves do Pubmed. Foram selecionados trabalhos de meta-analise e estudos duplo-cegos randomizados, quando presentes. Relatos ou serie de casos foram utilizados quando publicados em jornaisde reconhecida idoneidade. As opinioes dos especialistas presentes foram utilizadas em relacao a terapias nao disponiveis na literatura e que fossem consideradas pela unanimidade dos presentes como importante para o manejo dos pacientes com osteoartrite. Envio previo da bibliografia principal aos participantes. Reuniao para elaboracao do documento. Colocacao do rascunho na internet por dez dias para mudancas. Elaboracao final do documento. GRAU DE RECOMENDACAO E FORCA DE EVIDENCIA: A: Estudos experimentais e observacionais de melhor consistencia. B: Estudos experimentais e observacionais de menor consistencia. C: Relatos de casos (estudos nao controlados). D: Opiniao desprovida de avaliacao critica, baseada em consensos, estudos fisiologicos ou modelos animais. OBJETIVOS: Conciliar informacoes e condutas referentes ao tratamento da osteoartrite pelas tres principais especialidades envolvidas, reumatologia, fisiatria e ortopedia. As condutas consensuais para a maioria dos participantes foram entao agrupadas e constam nas recomendacoes deste documento. CONFLITO DE INTERESSE: Os autores Coimbra IB, Pucinelli MLC, Cavalcanti FS e Maciel FMB, declararam vinculo com a Industria Farmaceutica.

Sjogren's syndrome: An underdiagnosed condition in mixed connective tissue disease

OBJECTIVE: To determine the prevalence of sicca symptoms, dry eye, and secondary Sjögrens syndrome and to evaluate the severity of dry eye in patients with mixed connective tissue disease. METHODS: In total, 44 consecutive patients with mixed connective tissue disease (Kasukawas criteria) and 41 healthy controls underwent Schirmers test, a tear film breakup time test, and ocular surface staining to investigate dry eye. In addition, the dry eye severity was graded. Ocular and oral symptoms were assessed using a structured questionnaire. Salivary gland scintigraphy was performed in all patients. Classification of secondary Sjögrens syndrome was assessed according to the American-European Consensus Group criteria. RESULTS: The patients and controls had comparable ages (44.7±12.4 vs. 47.2±12.2 years) and frequencies of female gender (93 vs. 95%) and Caucasian ethnicity (71.4 vs. 85%). Ocular symptoms (47.7 vs. 24.4%) and oral symptoms (52.3 vs. 9.7%) were significantly more frequent in patients than in controls. Fourteen (31.8%) patients fulfilled Sjögrens syndrome criteria, seven of whom (50%) did not have this diagnosis prior to study inclusion. A further comparison of patients with mixed connective tissue disease with or without Sjögrens syndrome revealed that the former presented significantly lower frequencies of polyarthritis and cutaneous involvement than did the patients without Sjögrens syndrome. Moderate to severe dry eye was found in 13 of 14 patients with mixed connective tissue disease and Sjögrens syndrome (92.8%). CONCLUSIONS: Sjögrens syndrome, particularly with moderate to severe dry eye, is frequent in patients with mixed connective tissue disease. These findings alert the physician regarding the importance of the appropriate diagnosis of this syndrome in such patients.

Tomografia computadorizada quantitativa periférica de alta resolução para avaliação de parâmetros morfológicos e funcionais ósseos

High resolution peripheral quantitative computed tomography (HR-pQCT) is a new technology commercially available for less than 10 years that allows performing in vivo assessment of bone parameters. HR-pQCT assesses the trabecular thickness, trabecular separation, trabecular number and connectivity density and, in addition, cortical bone density and thickness and total bone volume and density in high-definition mode, which additionally allows obtaining digital constructs of bone microarchitecture. The application of mathematics to captured data, a method called finite element analysis (FEA), allows the estimation of the physical properties of the tissue, simulating supported loads in a non-invasive way. Thus, HR-pQCT simultaneously acquires data previously provided separately by dual energy x-ray absorptiometry (DXA), magnetic resonance imaging and histomorphometry, aggregating biomechanical estimates previously only possible in extracted tissues. This method has a satisfactory reproducibility, with coefficients of variation rarely exceeding 3%. Regarding accuracy, the method shows a fair to good agreement (r(2) = 0.37-0.97). The main clinical application of this method is in the quantification and monitoring of metabolic bone disorders, more fully evaluating bone strength and fracture risk. In rheumatoid arthritis patients, this allows gauging the number and size of erosions and cysts, in addition to joint space. In osteoarthritis, it is possible to characterize the bone marrow edema-like areas that show a correlation with cartilage breakdown. Given its high cost, HR-pQCT is still a research tool, but the high resolution and efficiency of this method reveal advantages over the methods currently used for bone assessment, with a potential to become an important tool in clinical practice.

The frequency of anti-β2-glycoprotein I antibodies is low and these antibodies are associated with pulmonary hypertension in mixed connective tissue disease:

The objective of this study is to evaluate the prevalence of antiphospholipid antibodies, mainly anti-β2-glycoprotein I (anti-β2-GPI), and their possible clinical and laboratory relevance in mixed connective tissue disease (MCTD). This study included 39 consecutive patients with MCTD (Kasukawa’s criteria) from January, 2005, to March, 2007, and compared them with 21 age- and sex-matched healthy controls. IgG and IgM anticardiolipin (aCL) and anti-β2-GPI were measured by ELISA. Lupus anticoagulant (LA) was detected by functional coagulation tests. Medium to high titres of aCL and anti-β2-GPI antibodies were found in sera from four (10.2%) MCTD patients. One of these patients was found to be positive for IgM aCL, IgM anti-β2-GPI and LA antibodies simultaneously. Additionally, this patient had a previous history of foetal loss in the second trimester and new-onset pulmonary arterial hypertension (PAH). The other three patients had none of the manifestations of antiphospholipid syndrome (APS) or PAH. The mean value of IgG anti-β2-GPI was higher among those MCTD patients with PAH than in the group without PAH (34.2 ± 46.8 vs 12.3 ± 9.1, P = 0.018). None of the controls were positive for antiphospholipid antibodies. High to moderate titres of anti-β2-GPI as well as APS were rare in MCTD, and these antibodies may be correlated with the development of PAH in these patients.