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Extracellular pH variations are seen as the principal endogenous signal that triggers activation of Acid-Sensing Ion Channels (ASICs), which are basically considered as proton sensors, and are involved in various processes associated with tissue acidification. Here, we show that human painful inflammatory exudates, displaying non-acidic pH, induce a slow constitutive activation of human ASIC3 channels. This effect is largely driven by lipids, and we identify lysophosphatidylcholine (LPC) and arachidonic acid (AA) as endogenous activators of ASIC3 in the absence of any extracellular acidification. The combination of LPC and AA evokes robust depolarizing current in DRG neurons at physiological pH 7.4, increases nociceptive C-fiber firing, and induces pain behavior in rats, effects that are all prevented by ASIC3 blockers. Lipid-induced pain is also significantly reduced in ASIC3 knockout mice. These findings open new perspectives on the roles of ASIC3 in the absence of tissue pH variation, as well as on the contribution of those channels to lipid-mediated signaling.
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Canais Iônicos Sensíveis a Ácido/biossíntese , Ácido Araquidônico/metabolismo , Lisofosfatidilcolinas/metabolismo , Nociceptores/fisiologia , Animais , Linhagem Celular , Gânglios Espinais/citologia , Humanos , Camundongos Knockout , Dor , RatosRESUMO
The aim of the study was to investigate similarities and differences in health beliefs, experiences and educational needs by type of osteoporosis (OP), particularly in people with glucocorticoid-induced OP (GIOP) and men. A qualitative study was conducted via focus groups involving post-menopausal women with or without osteoporotic fractures, osteoporotic men and people with GIOP. Fifty-three participants were included in eight groups. A wide range of health beliefs was found for all types of OP. Osteoporosis was considered a natural consequence of ageing except in men or conversely a serious disease associated with risk of new fractures and disability. GIOP patients had heterogeneous knowledge of OP and reported fewer prevention behaviours, and their quality of life was affected by the causal illness. Men had difficulties coping with the loss of their functional abilities and felt that OP was a "women's" disease. Beliefs about treatments ranged from confidence to fear of adverse effects or doubt about efficacy in all types of OP. Participants were interested in physical activity, fall prevention and diet, and preferred group sessions. GIOP patients and men had an interest in face-to-face education. Men were also interested in brief information including via the Internet. Patients' beliefs about OP differed by type of OP. Specific populations such as men or people with GIOP need particular care owing to experiences and needs. Offering group sessions in educational interventions is of interest to allow for sharing experiences and also face-to-face education for men and GIOP patients or the Internet for men.
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Gerenciamento Clínico , Glucocorticoides/efeitos adversos , Osteoporose/prevenção & controle , Fraturas por Osteoporose/induzido quimicamente , Conservadores da Densidade Óssea/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , Fraturas por Osteoporose/prevenção & controle , Educação de Pacientes como Assunto , Qualidade de Vida , Fatores de Risco , Fatores SexuaisRESUMO
IMPORTANCE: One-third of patients with rheumatoid arthritis show inadequate response to tumor necrosis factor α (TNF-α) inhibitors; little guidance on choosing the next treatment exists. OBJECTIVE: To compare the efficacy of a non-TNF-targeted biologic (non-TNF) vs a second anti-TNF drug for patients with insufficient response to a TNF inhibitor. DESIGN, SETTING, AND PARTICIPANTS: A total of 300 patients (conducted between 2009-2012) with rheumatoid arthritis, with persistent disease activity (disease activity score in 28 joints-erythrocyte sedimentation rate [DAS28-ESR] ≥ 3.2 [range, 0-9.3]) and an insufficient response to anti-TNF therapy were included in a 52-week multicenter, pragmatic, open-label randomized clinical trial. The final follow-up date was in August 2013. INTERVENTIONS: Patients were randomly assigned (1:1) to receive a non-TNF-targeted biologic agent or an anti-TNF that differed from their previous treatment. The choice of the biologic prescribed within each randomized group was left to the treating clinician. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with good or moderate response according to the European League Against Rheumatism (EULAR) scale at week 24. Secondary outcomes included the EULAR response at weeks 12 and 52; at weeks 12, 24, and 52; DAS28ESR, low disease activity (DAS28 ≤3.2), remission (DAS28 ≤2.6); serious adverse events; and serious infections. RESULTS: Of the 300 randomized patients (243 [83.2%] women; mean [SD] age, 57.1 [12.2] years; baseline DAS28-ESR, 5.1 [1.1]), 269 (89.7%) completed the study. At week 24, 101 of 146 patients (69%) in the non-TNF group and 76 (52%) in the second anti-TNF group achieved a good or moderate EULAR response (OR, 2.06; 95% CI, 1.27-3.37; P = .004, with imputation of missing data; absolute difference, 17.2%; 95% CI, 6.2% to 28.2%). The DAS28-ESR was lower in the non-TNF group than in the second anti-TNF group (mean difference adjusted for baseline differences, -0.43; 95% CI, -0.72 to -0.14; P = .004). At weeks 24 and 52, more patients in the non-TNF group vs the second anti-TNF group showed low disease activity (45% vs 28% at week 24; OR, 2.09; 95% CI, 1.27 to 3.43; P = .004 and 41% vs 23% at week 52; OR, 2.26; 95% CI, 1.33 to 3.86; P = .003). CONCLUSIONS AND RELEVANCE: Among patients with rheumatoid arthritis previously treated with anti-TNF drugs but with inadequate primary response, a non-TNF biologic agent was more effective in achieving a good or moderate disease activity response at 24 weeks than was the second anti-TNF medication. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01000441.
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OBJECTIVES: Rheumatoid arthritis (RA) patients are at an increased risk of developing comorbid conditions. A close monitoring of the disease targeting a status of low disease activity is associated with a better outcome. The aim of this trial was to evaluate the impact of a nurse-led programme on comorbidities and the impact of patient self-assessment of disease activity on the management of RA. METHODS: We enrolled 970 patients (mean age 58â years, 79% women) in a prospective, randomised, controlled, open-label, 6-month trial. In the comorbidity group (n=482), the nurse checked comorbidities and sent the programme results to the attending physicians. In the self-assessment group (n=488), the nurse taught the patient how to calculate his/her Disease Activity Score which had to be reported on a booklet to be shared with the treating rheumatologist. The number of measures taken for comorbidities and the percentage of patients recording a change (initiation, switch or increased dose) in disease-modifying antirheumatic drugs (DMARDs) in the 6â months follow-up period of the study defined the outcomes of the trial. RESULTS: The number of measures taken per patient was statistically higher in the comorbidity group: 4.54±2.08 versus 2.65±1.57 (p<0.001); incidence rate ratio: 1.78 (1.61-1.96) and DMARD therapy was changed more frequently in the self-assessment group: 17.2% versus 10.9% (OR=1.70 (1.17; 2.49), p=0.006). CONCLUSIONS: This study demonstrates the short-term benefit of a nurse-led programme on RA comorbidity management and the impact of patient self-assessment of disease activity on RA treatment intensification. TRIAL REGISTRATION NUMBER: NCT #01315652.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/terapia , Autocuidado/métodos , Idoso , Artrite Reumatoide/epidemiologia , Comorbidade , Diabetes Mellitus/epidemiologia , Gerenciamento Clínico , Dislipidemias/epidemiologia , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Padrões de Prática em Enfermagem , Autoexame/métodos , Fumar/epidemiologiaAssuntos
Assistência ao Convalescente/métodos , Artrite Reumatoide/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Autoavaliação (Psicologia) , Fatores de Tempo , Adulto , Assistência ao Convalescente/psicologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
Chondrogenesis has been widely investigated in vitro using bone marrow-derived mesenchymal stromal cells (BM-MSCs) or primary chondrocytes. However, their use raises some issues partially circumvented by the availability of Adipose tissue-derived MSCs. Herein; we characterized the chondrogenic potential of human Multipotent Adipose-Derived Stem (hMADS) cells, and their potential use as pharmacological tool. hMADS cells are able to synthesize matrix proteins including COMP, Aggrecan and type II Collagen. Furthermore, hMADS cells express BMP receptors in a similar manner to BM-MSC, and BMP6 treatment of differentiated cells prevents expression of the hypertrophic marker type X Collagen. We tested whether IL-1ß and nicotine could impact chondrocyte differentiation. As expected, IL-1ß induced ADAMTS-4 gene expression and modulated negatively chondrogenesis while these effects were reverted in the presence of the IL-1 receptor antagonist. Nicotine, at concentrations similar to those observed in blood of smokers, exhibited a dose dependent increase of Aggrecan expression, suggesting an unexpected protective effect of the drug under these conditions. Therefore, hMADS cells represent a valuable tool for the analysis of in vitro chondrocyte differentiation and to screen for potentially interesting pharmacological drugs.
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Tecido Adiposo/citologia , Condrócitos/citologia , Condrogênese/fisiologia , Células-Tronco Multipotentes/citologia , Proteínas ADAM/genética , Proteína ADAMTS4 , Agrecanas/biossíntese , Proteína Morfogenética Óssea 6/farmacologia , Receptores de Proteínas Morfogenéticas Ósseas/metabolismo , Separação Celular , Condrogênese/genética , Colágeno Tipo X/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1beta/farmacologia , Células-Tronco Multipotentes/efeitos dos fármacos , Células-Tronco Multipotentes/metabolismo , Nicotina/farmacologia , Pró-Colágeno N-Endopeptidase/genéticaRESUMO
OBJECTIVES: To assess the efficacy and safety of rituximab (RTX) in patients with refractory idiopathic inflammatory myopathies (IIMs). METHODS: RTX efficacy was based on improvement in three criteria: creatine phosphokinase (CPK) level, daily CS dose and physicians' opinion. A decrease in CPK level or CS dose was significant if it was >25%. RESULTS: Thirty patients were studied (21 women; age 52.5 years, disease duration 6.1 years). All had previously received immunosuppressors (ISs). Twenty-five patients received 1 g of RTX twice 2 weeks apart and five received 4 weekly RTX infusions (375 mg/m(2)). RTX was given in association with IS in 21 patients. Twenty-eight patients received CS (mean dose 21.2 mg/day). Mean follow-up was 17.2 months. Thirteen adverse events were reported, including seven infections and one serious infection (pyelonephritis). RTX was effective in 16 patients. Duration of efficacy was 15.5 months. Of the 20 patients with baseline CPK level ≥2 × upper limit of normal (ULN), 11 (55%) improved. The main level fell from 20.7 to 11 × ULN. CS decreased in 15 patients, stopped in 4, remained stable in 8 and increased in the remaining 3. The CS dose decreased from 21.2 to 9.9 mg/day. The physicians' opinion was favourable in 21 patients. Manual muscle testing was performed in only five patients: it increased from 87 to 91/100 at 6 months. CONCLUSIONS: RTX was well tolerated and had some beneficial effects on patients with IIM, the main limitation of this study resulted in a lack of manual muscle testing.
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Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais Murinos/administração & dosagem , Miosite/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Murinos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Rituximab , Resultado do TratamentoRESUMO
Osteoporosis constitutes a major worldwide public health burden characterized by enhanced skeletal fragility. Bone metabolism is the combination of bone resorption by osteoclasts and bone formation by osteoblasts. Whereas increase in bone resorption is considered as the main contributor of bone loss that may lead to osteoporosis, this loss is accompanied by increased bone marrow adiposity. Osteoblasts and adipocytes share the same precursor cell and an inverse relationship exists between the two lineages. Therefore, identifying signaling pathways that stimulate mesenchymal stem cells osteogenesis at the expense of adipogenesis is of major importance for developing new therapeutic treatments. For this purpose, we identified by transcriptomic analysis the oxytocin receptor pathway as a potential regulator of the osteoblast/adipocyte balance of human multipotent adipose-derived stem (hMADS) cells. Both oxytocin (OT) and carbetocin (a stable OT analogue) negatively modulate adipogenesis while promoting osteogenesis in both hMADS cells and human bone marrow mesenchymal stromal cells. Consistent with these observations, ovariectomized (OVX) mice and rats, which become osteoporotic and exhibit disequilibrium of this balance, have significant decreased OT levels compared to sham-operated controls. Subcutaneous OT injection reverses bone loss in OVX mice and reduces marrow adiposity. Clinically, plasma OT levels are significantly lower in postmenopausal women developing osteoporosis than in their healthy counterparts. Taken together, these results suggest that plasma OT levels represent a novel diagnostic marker for osteoporosis and that OT administration holds promise as a potential therapy for this disease.
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Células-Tronco Mesenquimais/patologia , Osteoporose/patologia , Ocitocina/fisiologia , Adipogenia , Idoso , Idoso de 80 Anos ou mais , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Células Cultivadas , Pré-Escolar , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Pessoa de Meia-Idade , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteoclastos/patologia , Osteogênese , Osteoporose/metabolismo , Osteoporose/terapia , Osteoporose Pós-Menopausa/sangue , Ovariectomia , Ocitocina/análogos & derivados , Ocitocina/sangue , Ocitocina/farmacologia , Ratos , Receptores de Ocitocina/metabolismoRESUMO
OBJECTIVE: To evaluate the performance of combined (computed tomography (CT) and fluoroscopic) guidance of balloon kyphoplasty in comparison to fluoroscopic guidance alone. MATERIALS AND METHODS: Forty-one kyphoplasties were performed between January 2005 and March 2006 according to two different protocols. Study group 1 consisted of 20 consecutive patients with 20 balloon kyphoplasty procedures under dual guidance (CT scan and fluoroscopy) for osteoporotic or traumatic vertebral fractures. Study group 2 consisted of 21 consecutive patients in whom kyphoplasty was performed with fluoroscopy alone. Visualization of the pedicles, the final of the balloon position, and cement distribution were evaluated(1-poor, 2-intermediate, 3-good). RESULTS: Combined use of CT and fluoroscopy (group 1) was superior in identifying the pedicles (100% versus 66.7%, p = 0.009) and balloon placement (100% versus 71.4%, p = 0.02) but not in monitoring of cement distribution within the vertebral body (100% versus 90.5%, p = 0.49). The difference between the two groups was more pronounced in the thoracic spine than in the lumbar spine. CONCLUSION: CT/fluoroscopic guidance of kyphoplasty combines safe CT-guided insertion of the osteointroducers and balloons as well as fluoroscopic real-time monitoring of polymethylmethacrylate injection.
Assuntos
Tomografia Computadorizada por Raios X , Vertebroplastia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vertebroplastia/classificaçãoRESUMO
The WHO definition of osteoporosis excludes cervical fractures. Recent studies suggest that atraumatic odontoid fractures (OF) may be favored by osteoporosis but global bone status for osteoporosis diagnosis has not been described. We present a case series of patients >65 years old hospitalized for low-energy OF who had an evaluation of their bone status within 3 months after fracture, including clinical risk factors of osteoporosis, bone mineral density (BMD), vertebral fracture assessment (VFA) by dual X-ray absorptiometry, and laboratory tests. Osteoporosis was defined as a T-score ≤ -2.5 on at least one site, or a bone fragility fracture associated with a T-score ≤ -1 at one site. Thirty-three patients were hospitalized for OF, 30 of them as a consequence of a low-energy impact: 20 women and 10 men (mean age: 85 years). Eight patients died before bone evaluation, four refused, and six were lost to follow-up. Twelve patients were included: 11 women and one man (mean age: 83.8 years). Ten out of twelve patients fulfilled diagnostic criteria of osteoporosis, including eight with previous osteoporotic fractures (six severe fractures). Eight fulfilled specific treatment of osteoporosis criteria, but only two were treated. The mean follow-up period was 12.2 ± 4.1 months. Prior to OF occurrence, all lived at home and were independent; at the time of discharge, six went to a nursing home. At 3 months of follow-up (n = 10), one was dead and nine lived at home. At 12 months (n = 9), two were dead and seven lived at home. This study provides for the first time a classical evaluation of osteoporotic status for low-energy OF in the elderly and shows that it occurs in osteoporotic subjects. These preliminary results require larger-scale studies to determine whether OF could be considered as a severe osteoporotic fracture. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
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Background/purpose: Cardiovascular (CV) risk, cancer, infections and osteoporosis should be screened for in rheumatoid arthritis (RA). The objective was to assess 3-year effects of a nurse visit for comorbidity counselling. Methods: This was an open long-term (3 years) extension of the Comorbidities and Education in Rheumatoid Arthritis 6-month randomised controlled trial in which patients with definite, stable RA were visiting a nurse for comorbidity counselling. Comorbidity status was assessed and nurses provided advice on screening and management, at baseline and 3 years later. A score was developed to quantify comorbidity screening and management: 0-100, where lower scores indicate better screening and management. The score was compared between baseline and 3-year assessment using a Wilcoxon test for paired data. Results: Of the 970 recruited patients, 776 (80%) were followed-up at 2-4 years and 769 (79%) had available data for comorbidities at both time points: mean (±SD) age 58 (±11) years and mean disease duration 14 (±10) years; 614 (80%) were women, the mean Disease Activity Score 28 was 3.0±1.3, and 538 (70%) were receiving a biologic. At baseline, the mean comorbidity screening score was 36.6 (±19.9) and it improved at 3 years to 24.3 (±17.8) (p<0.0001), thus with a relative improvement of 33% (improvement of 12 points). CV risk screening, vaccination status and bone densitometry performance improved the most. Conclusions: Comorbidity screening was suboptimal but improved notably over 3 years, after a nurse-led programme aiming at checking systematically for comorbidity screening and giving patient advice. This long-term efficacy pleads in favour of nurse-led interventions to better address comorbidities in RA. Trial registration number: NCT01315652.
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Artrite Reumatoide/diagnóstico , Comorbidade/tendências , Programas de Rastreamento/métodos , Enfermeiros de Saúde Comunitária/estatística & dados numéricos , Idoso , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Atenção à Saúde/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Educação de Pacientes como Assunto/métodos , Estudos ProspectivosRESUMO
BACKGROUND: Two-phase surveys often are used to estimate prevalence, in particular when the disease is rare or the case ascertainment procedure difficult and/or costly. However, few authors of such surveys take into account the sensitivity error associated with the use of a screening procedure in the first phase and its imprecision in correcting the prevalence estimate and confidence interval. METHODS: Two examples of two-phase surveys of rheumatic diseases (hip and knee osteoarthritis, rheumatoid arthritis and spondyloarthropathies) are used to present methodological approaches to obtain corrected prevalence estimates. Two methods for assessing the accuracy of the screening procedure are described--two-phase pilot and case-control designs--that are best suited for frequent and rare diseases, respectively, and naive and corrected estimates of prevalence compared. RESULTS: When the sensitivity error is not taken into account, prevalence is underestimated, as is, especially, the width of its confidence interval. In our examples, the corrected confidence interval width increased up to 50% as compared with naïve one. CONCLUSIONS: The screening procedure accuracy should be thoroughly assessed in two-phase prevalence surveys and prevalence estimates and their confidence intervals corrected accordingly.
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Projetos de Pesquisa Epidemiológica , Inquéritos Epidemiológicos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Reprodutibilidade dos Testes , Intervalos de Confiança , França/epidemiologia , Humanos , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/epidemiologia , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/fisiopatologia , PrevalênciaAssuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Nódulo Reumatoide/tratamento farmacológico , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Autoanticorpos/sangue , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Pneumopatias/sangue , Pneumopatias/complicações , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Peptídeos Cíclicos/imunologia , Sistema de Registros , Fator Reumatoide/análise , Nódulo Reumatoide/sangue , Nódulo Reumatoide/complicações , Nódulo Reumatoide/etiologia , Rituximab , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Focal bone damage and generalized bone loss are features of rheumatoid arthritis (RA). The introduction of TNFalpha antagonists has radically improved the management of RA by providing a means of slowing or preventing the occurrence of focal bone damage. However, some patients with severe RA have contraindications to TNFalpha antagonist therapy and others either fail to respond or fail to tolerate TNFalpha antagonists. In addition, whether TNFalpha antagonists effectively combat generalized bone loss remains unknown. Bisphosphonates can prevent generalized bone loss. Their main target is the osteoclast, which has been identified as the culprit in focal bone damage caused by inflammatory diseases. As a result, the potential effects of bisphosphonates on focal bone damage related to RA are generating strong interest. Although results from the few studies in humans have been disappointing, new insights into the mechanisms of action of amino-bisphosphonates and recent data obtained in animals, most notably with new-generation bisphosphonates, have rekindled the hope that bisphosphonates may be beneficial in RA. We review herein the main studies of the effects of bisphosphonate therapy on focal bone damage and generalized bone loss in patients with RA.
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Artrite Reumatoide/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Artrite Reumatoide/complicações , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/etiologia , Humanos , Resultado do TratamentoRESUMO
Intraarticular sodium hyaluronate injection to treat osteoarthritis is associated with minor side effects. Infections seem uncommon. We report two cases of septic knee arthritis. One patient was an 80-year-old woman who was admitted for Staphylococcus aureus knee arthritis after several intraarticular injections of sodium hyaluronate and corticosteroids. In the other patient, a 78-year-old woman, Neisseria mucosa knee arthritis occurred after a single sodium hyaluronate injection. Faultless aseptic technique is essential when administering hyaluronate viscosupplementation. Patients should be informed of the risk of septic arthritis.
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Adjuvantes Imunológicos/efeitos adversos , Artrite Infecciosa/etiologia , Ácido Hialurônico/efeitos adversos , Infecções por Neisseriaceae/etiologia , Osteoartrite do Joelho/tratamento farmacológico , Infecções Estafilocócicas/etiologia , Adjuvantes Imunológicos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/patologia , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intra-Articulares , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Neisseria mucosa/isolamento & purificação , Neisseria mucosa/fisiologia , Infecções por Neisseriaceae/patologia , Osteoartrite do Joelho/complicações , Oxacilina/uso terapêutico , Infecções Estafilocócicas/patologia , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/fisiologiaRESUMO
OBJECTIVE: Our objective was to compare the use of both anteroposterior (AP) extended-knee X-ray and semi-flexed X-ray (current gold standard) versus the use of semi-flexed X-ray alone to detect femoro-tibial osteoarthritis (OA). METHODS: Individuals 40 to 75 years of age with symptomatic hip and/or knee OA (Kellgren/Lawrence [KL] score≥2) were recruited using a multiregional prevalence survey in France. Both AP and schuss X-rays were performed and read; two years later, the same examiner, blinded to the results of the first reading, performed a second reading of the schuss X-ray. We compared the KL stages of each knee and analyzed osteophyte detection and localization, joint space narrowing (JSN), and the relationship to obesity. RESULTS: The analysis included 350 participants with OA of various stages. Comparing the two readings showed that a higher proportion of patients had KL≥2 when the two X-ray views were combined (right knee: P<0.0001; left knee: P<0.001). There were no differences when using the schuss X-ray alone versus in combination with an AP X-ray in terms of detecting JSN, osteophytes. A comparison of schuss X-ray alone versus AP X-ray alone demonstrated the superiority of the schuss view for evaluating JSN (P=0.0001 and P=0.0001) and no difference in osteophyte detection. CONCLUSION: Our study shows that the schuss view alone was sufficient for detecting knee osteophytes and JSN. Using one X-ray rather than two will reduce medical costs and irradiation burden. Using two views seems preferable for epidemiological studies.
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Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Joelho/diagnóstico por imagem , Adulto , Idoso , Feminino , Fêmur/diagnóstico por imagem , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , Tíbia/diagnóstico por imagemRESUMO
OBJECTIVES: To evaluate influenza and pneumococcal vaccine coverage in patients taking biological therapy for chronic inflammatory joint disease and to identify factors associated with the decision to administer these two vaccines. METHODS: Retrospective cross-sectional questionnaire study of a cohort of 584 patients taking biological therapy for chronic inflammatory joint disease (rheumatoid arthritis or spondyloarthritis). We studied the influenza and pneumococcal vaccine coverage rates, information about these vaccines given to patients by the primary-care physician and rheumatologist, and reasons for not administering the vaccines. RESULTS: Overall vaccine coverage rates were 44% for influenza and 62% for pneumococcus. Factors associated with being vaccinated were patient age, previous influenza vaccination, and patient information. Concern about adverse effects and absence of patient information by the primary-care physician and rheumatologist were associated with very low coverage rates. CONCLUSION: This study showed insufficient vaccine coverage rates, particularly against influenza, in a population at high risk because of exposure to biological therapy. Patient information by healthcare professionals about influenza and pneumococcal vaccination has a major impact and should be renewed as often as possible.
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Artrite Reumatoide/complicações , Terapia Biológica/efeitos adversos , Vacinas contra Influenza/administração & dosagem , Vacinas Pneumocócicas/administração & dosagem , Espondilartrite/complicações , Adulto , Idoso , Artrite Reumatoide/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Influenza Humana/etiologia , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/etiologia , Infecções Pneumocócicas/prevenção & controle , Estudos Retrospectivos , Espondilartrite/tratamento farmacológico , Inquéritos e QuestionáriosRESUMO
PURPOSE: Bisphosphonates have been found to reduce the incidence of skeletal-related events (SREs) in patients with multiple myeloma. This is the first double-blind, randomized, placebo-controlled study to assess the efficacy of ibandronate, a third-generation amino-bisphosphonate, in preventing SREs in advanced-stage multiple myeloma patients. PATIENTS AND METHODS: Patients with multiple myeloma stage II or III were randomly assigned to receive either ibandronate 2 mg or placebo as a monthly intravenous (IV) bolus injection for 12 to 24 months in addition to conventional chemotherapy. SREs such as peripheral pathologic or vertebral fractures, hypercalcemia, severe bone pain, and bone radiotherapy or surgery were analyzed. Bone-turnover markers were also studied. Finally, post hoc analyses of bone morbidity and survival were performed. RESULTS: Ninety-nine patients per treatment group were assessable for efficacy analysis. The occurrence of SRE per patient year and the time to first SRE were not significantly different between the two treatment groups. In overall evaluation, no differences were found between the treatment groups regarding bone pain, analgesic drug use, quality of life, and median survival (33.1 v 28.2 months, respectively). Explorative post hoc analyses revealed that ibandronate patients with strongly suppressed bone-turnover markers (> or = 30% and > or = 50% mean reduction of serum osteocalcin and urinary C-terminal telopeptides) developed significantly less bone morbidity. Ibandronate was tolerated well during as many as 25 therapy cycles. CONCLUSION: Monthly injections of ibandronate 2 mg IV neither reduced bone morbidity nor prolonged survival in the overall population of stage II/III multiple myeloma patients.
Assuntos
Difosfonatos/uso terapêutico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Reabsorção Óssea/etiologia , Reabsorção Óssea/prevenção & controle , Distribuição de Qui-Quadrado , Método Duplo-Cego , Feminino , Fraturas Ósseas/etiologia , Fraturas Ósseas/prevenção & controle , Humanos , Hipercalcemia/etiologia , Hipercalcemia/prevenção & controle , Ácido Ibandrônico , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Dor/etiologia , Dor/prevenção & controle , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/prevenção & controle , Análise de Sobrevida , Resultado do TratamentoRESUMO
Bone resorption is regulated by the immune system, where receptor activator of nuclear factor (NF)kappaB ligand (RANKL), a new member of the tumor-necrosis factor family, may contribute to pathological conditions. Due to the role of RANKL in the maturation of monocyte-derived osteoclasts, we hypothesized that RANKL could exert chemotactic properties toward monocytic cells. Our results demonstrate that RANKL induces the migration of MonoMac-6 monocytic cells as well as human freshly isolated total peripheral blood mononuclear cells (PBMC) and CD14+ purified PBMC. RANKL induces the migration of MonoMac-6 cells in a dose-dependent manner and with an efficacy similar to MCP-1. After an 8-h incubation, the soluble form of RANKL (sRANKL) started to exhibit a chemoattractive effect on MonoMac-6 cells, with an increased effect observed up to 24 h. RANKL elicits an additive chemotactic effect to MCP-1. Furthermore, addition of the RANKL decoy receptor osteoprotegerin in the lower well or RANKL in the upper well abrogates the RANKL-induced migration of MonoMac-6 cells, hallmarking a true specific activity. RNase protection assay experiments indicate that exposure of MonoMac-6 cells to RANKL had no significant effect on the expression of a variety of chemokines, known to attract monocytes. This study provides evidence that RANKL behaves as a chemotactic factor for monocytic cells, emphazing the cross-talk between bone and immune systems.
Assuntos
Proteínas de Transporte/farmacologia , Fatores Quimiotáticos/farmacologia , Glicoproteínas de Membrana/farmacologia , Monócitos/imunologia , Linhagem Celular , Quimiocina CCL2/farmacologia , Quimiotaxia/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Modelos Imunológicos , Monócitos/efeitos dos fármacos , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-BRESUMO
OBJECTIVES: Severe hidradenitis suppurativa (HS), under infliximab, can be associated with different forms of arthritis whose mechanism is unclear. Our objective is to establish the frequency and clinical presentation of new-onset arthritis in HS under infliximab. METHODS: Severe HS patients under infliximab were followed up between 2007-2012. New articular inflammatory manifestations were investigated by rheumatologist. RESULTS: Three patients over eleven developed a polyarthritis. Mean duration of arthritis was 3 months. At treatment's stop: 2 patients improved and 1 relieved with adalimumab. CONCLUSION: The inflammatory rheumatism's frequency in HS under infliximab seems underestimated.