RESUMO
In this opinion article, we would like to draw attention to the fact that COVID-19 has a significant impact not only on immune-mediated arthritis but also on osteoarthritis (OA), the most common rheumatic disease. We suggest herein strategies for pain relief and symptom prevention in patients with OA during COVID-19 pandemic.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , COVID-19 , Terapia por Exercício , Glucocorticoides/uso terapêutico , Osteoartrite/terapia , Gerenciamento Clínico , Exercício Físico , Humanos , Ácido Hialurônico/uso terapêutico , Injeções Intra-Articulares , Manejo da Dor , SARS-CoV-2 , Viscossuplementos/uso terapêuticoRESUMO
BACKGROUND: Injection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants. We have previously developed a protein-free saline-soluble galactomannan derived from guar gum (GM) that displays both analgesia and chondroprotection in experimental osteoarthritis (OA). We now demonstrate that both GM and Hylan G-F20 (HY) promote mild synovitis with cytokine release after intra-articular injection. METHODS: Mice received 100 µg/25 µL GM or HY or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, interleukin (IL)-1, IL-6, and CXCL-1 (pg/mL) levels were assessed in joint lavage at 6 h. Synovia were excised for histopathology. RESULTS: Neither GM nor HY after being given into mice knee joints induced pain albeit promoting mild cell influx into joint washings as well as mild synovitis at histology, with no damage to the underlying cartilage. HY but not GM promoted IL-1 release into mice joints. Both compounds induced IL-6 and CXCL-1 release. CONCLUSION: Intra-articular injection of HY or GM promote acute transient synovitis whilst not provoking detectable significant joint damage. Local administration of these polysaccharides induces acute intra-articular release of inflammatory cytokines, which may account for joint flares following viscosupplementation.
Assuntos
Ácido Hialurônico/análogos & derivados , Mananas/efeitos adversos , Exacerbação dos Sintomas , Sinovite/etiologia , Viscossuplementos/efeitos adversos , Doença Aguda , Animais , Artralgia/diagnóstico , Movimento Celular , Quimiocina CXCL1/metabolismo , Feminino , Galactose/análogos & derivados , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Injeções Intra-Articulares , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Camundongos , Líquido Sinovial , Sinovite/metabolismo , Sinovite/patologia , Viscossuplementos/administração & dosagemRESUMO
The intra-articular use of hyaluronic acid (HA) for the treatment of synovitis and osteoarthritis is still controversial. As a consequence, corticosteroids remain the most frequently employed therapeutic agents, despite their potential systemic and local deleterious effects. This study examined the anti-inflammatory, antioxidant, and chondroprotective activities of low and high molecular weight hyaluronic acid (LMW-HA and HMW-HA) on lipopolysaccharide (LPS)-induced synovitis in horses compared to triamcinolone acetonide (TA). LPS was injected in the metacarpophalangeal joints, which were treated intra-articularly with either TA (as control) or LMW-HA or HMW-HA. Joint clinical evaluation and synovial fluid (SF) analysis were performed at 0, 8, 24, and 48 h. The white blood cell counts (WBC), prostaglandin E2 (PGE2), interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor-α, chondroitin sulfate (CS) and HA concentrations, oxidative burst, and HA molecular weights were measured. TA reduced the lameness, swelling, and PGE2 release but increased the SF CS concentrations enormously at 24h and 48h, and decreased the SF HA modal molecular weight. These results indicate the breakdown of articular cartilage aggrecan and SF HA. In contrast, LMW-HA and HMW-HA were less effective in reducing the inflammation symptoms, but preserved the joints because only a modest increase in CS occurred at 24 h, decreasing at 48 h, and the SF HA was maintained. The HA-treatment also had anti-inflammatory actions, and LMW-HA was the most effective in reducing the release of cytokine. In summary, the HA treatment inhibited efficiently the digestion of cartilage proteoglycans and SF HA breakdown.
Assuntos
Doenças dos Cavalos/tratamento farmacológico , Ácido Hialurônico/farmacologia , Injeções Intra-Articulares/veterinária , Líquido Sinovial/efeitos dos fármacos , Sinovite/veterinária , Viscossuplementos/farmacologia , Animais , Doenças dos Cavalos/induzido quimicamente , Cavalos , Lipopolissacarídeos/administração & dosagem , Masculino , Distribuição Aleatória , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológicoRESUMO
Knee osteoarthritis affects 3.8% of the world population and manifests as pain, edema, stiffness, and reduced joint function, impacting the patient's quality of life. Treatment consists of the pharmacological, non-pharmacological, and surgical modalities. Viscosupplementation (intraarticular hyaluronate) has been proposed to relieve symptoms and potentially postpone surgery. This study estimated the budget impact of the association of this drug and non-surgical treatment (standard treatment) from the perspective of the Brazilian Unified National Health System. Based on the assumption that 5% of patients proceed to treatment and on the direct costs of the pharmacological and non-pharmacological modalities, the authors calculated the reference and alternative scenarios that compared the different treatment options in a three-year timeline. The principal analysis estimated an incremental budget impact of approximately BRL 126 million (U$ 32 million) for one vial of hyaluronate a year and BRL 252 million (USD 64 million) for two vials a year. Diacerein, an oral chondroprotector, assessed as an alternative, showed a budget impact of BRL 334 million (USD 86 million) in relation to standard treatment, representing a 24% cost increase compared to two vials a year of hyaluronate, making it less economically advantageous. Viscosupplementation can provide better quality of life for patients, reduce costs for the health system, and optimize the flow of care in health services. The estimates presented in this study can assist administrators in the best use of resources and thus in decision-making on the technology's incorporation.
A osteoartrite de joelho afeta cerca de 3,8% da população mundial e se manifesta por dor, edema, rigidez e redução da função articular, impactando na qualidade de vida do paciente. O tratamento consiste na modalidade farmacológica, não farmacológica e cirúrgica. A viscossuplementação (ácido hialurônico intra-articular) se propõe a oferecer alívio dos sintomas e a possibilidade de adiamento da cirurgia. Este estudo estimou o impacto orçamentário entre a associação desse medicamento e o tratamento não cirúrgico (tratamento padrão), sob a perspectiva do Sistema Único de Saúde. Com base no pressuposto de que 5% dos portadores da doença seguem para tratamento e nos custos diretos das modalidades: farmacológica e não farmacológica foram calculados os cenários de referência e alternativos que compararam as diferentes opções de tratamento para um horizonte temporal de três anos. A análise principal estimou um impacto orçamentário incremental de aproximadamente R$ 126 milhões (1 ampola anual) e R$ 252 milhões (2 ampolas anuais). Já a diacereína, um condroprotetor oral, avaliada como uma opção alternativa, mostrou um impacto de R$ 334 milhões no orçamento em relação ao tratamento padrão, o que proporciona um aumento de 24% no custo em relação ao uso de 2 ampolas anuais de ácido hialurônico, tornando-a economicamente menos vantajosa. A viscossuplementação pode proporcionar maior qualidade de vida ao paciente, redução de custos para o sistema e otimização do fluxo de atendimento nas unidades de saúde. As estimativas apresentadas neste estudo podem auxiliar o gestor quanto à melhor utilização dos recursos financeiros e consequente tomada de decisão quanto à incorporação da tecnologia.
La osteoartritis de rodilla afecta a cerca de un 3,8% de la población mundial y se manifiesta por dolor, edema, rigidez y reducción de la función articular, impactando en la calidad de vida del paciente. El tratamiento consiste en la modalidad farmacológica, no farmacológica y quirúrgica. La viscosuplementación (ácido hialurónico intraarticular) se propone ofrecer un alivio de los síntomas y la posibilidad de un aplazamiento de la cirugía. Este estudio estimó el impacto presupuestario entre la asociación de este medicamento y el tratamiento no quirúrgico (tratamiento estándar), desde la perspectiva del Sistema Único de Salud. Basándonos en el supuesto de que un 5% de los portadores de la enfermedad siguen el tratamiento y en los costos directos de las modalidades tanto farmacológica, como no farmacológica, se calcularon los escenarios de referencia y alternativos que compararon las diferentes opciones de tratamiento para un horizonte temporal de tres años. El análisis principal estimó un impacto presupuestario incremental de aproximadamente BRL 126 millones (1 ampolla anual) y BRL 252 millones (2 ampollas anuales). En el caso de la diacereína, un condroprotector oral, evaluado como una opción alternativa, mostró un impacto de BRL 334 millones en el presupuesto, respecto al tratamiento estándar, lo que proporciona un aumento de un 24% en el costo, en relación con el uso de 2 ampollas anuales de ácido hialurónico, haciéndola económicamente menos ventajosa. La viscosuplementación puede proporcionar mayor calidad de vida al paciente, reducción de costes para el sistema y la optimización del flujo de atención en las unidades de salud. Las estimaciones presentadas en este estudio pueden ayudar al gestor en lo referente a una mejor utilización de los recursos financieros y, consecuentemente, en la toma de decisiones respecto a la incorporación de tecnología.
Assuntos
Ácido Hialurônico/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Viscossuplementação/economia , Viscossuplementos/uso terapêutico , Brasil/epidemiologia , Orçamentos , Humanos , Programas Nacionais de Saúde , Osteoartrite do Joelho/epidemiologia , PrevalênciaRESUMO
BACKGROUND: To evaluate the efficacy and safety of prolotherapy with hypertonic dextrose in patients with knee osteoarthritis. A systematic search was performed in electronic databases including PUBMED, SCIELO, DIALNET and Google Scholar. MAIN BODY: We searched for randomized clinical trials that evaluated therapeutic interventions in patients with knee osteoarthritis. These trials compared the effect of intra-articular and / or extra-articular infiltrations of hypertonic dextrose vs the effect of intra-articular and / or extra-articular infiltrations of other substances or some interventional procedure application, via assessing pain, physical function and secondary effects and / or adverse reactions. Ten randomized clinical trials were included in this systematic review, the total sample size comprised 328 patients treated with hypertonic dextrose (prolotherapy) vs 348 controls treated with other infiltrations such as local anesthetics, hyaluronic acid, ozone, platelet-rich plasma or interventional procedures like radiofrequency. CONCLUSIONS: In terms of pain reduction and function improvement, prolotherapy with hypertonic dextrose was more effective than infiltrations with local anesthetics, as effective as infiltrations with hyaluronic acid, ozone or radiofrequency and less effective than PRP and erythropoietin, with beneficial effect in the short, medium and long term. In addition, no side effects or serious adverse reactions were reported in patients treated with hypertonic dextrose. Although HDP seems to be a promising interventional treatment for knee OA, more studies with better methodological quality and low risk of bias are needed to confirm the efficacy and safety of this intervention.
Assuntos
Glucose/administração & dosagem , Osteoartrite do Joelho/terapia , Proloterapia/métodos , Anestésicos Locais/administração & dosagem , Eritropoetina/administração & dosagem , Humanos , Ácido Hialurônico/administração & dosagem , Soluções Hipertônicas , Ozônio/administração & dosagem , Plasma Rico em Plaquetas , Terapia por Radiofrequência , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Viscossuplementos/administração & dosagemRESUMO
PURPOSE: To evaluate the hyaluronic acid (HA) inflammatory reaction, fibroblasts, fibrosis and duration of effect in the dorsal region of tobacco-exposed rats. METHODS: Ten Wistar rats were divided into two groups: tobacco-exposed-group (TEG;n=5) and air-control-group (CG;n=5). The TEG animals were tobacco-exposed twice a day, 30-minutes/session, during 60 days. After this period, all animals received 0.1 mL HA subcutaneous injection in the dorsal area. The volume of HA was measured immediately after HA injection and weekly using a hand-caliper in nine weeks. After this period, all the animals were euthanized, and a specimen of was collected to evaluate inflammatory cells, fibroblasts, and fibrosis by HE. RESULTS: This study showed a higher inflammatory reaction in TEG than CG: inflammatory cell-count (CG: 1.07±0.9; TEG: 8.61±0.36, p<0.001); fibroblast count (CG: 2.92±0.17; TEG: 19.14±0.62, p<0.001), and fibrosis quantification (CG: 2.0; TEG: 3.75, p<0.001). The analysis of the HA volume in nine weeks in the dorsal region did not show a difference between groups (p=0.39). CONCLUSIONS: This study suggested that the HA injection in the TEG caused an increase in inflammatory cell count, fibroblast, and fibrosis quantification when compared to the CG. There was no difference in the duration of effect of HA between the groups.
Assuntos
Fibroblastos/efeitos dos fármacos , Ácido Hialurônico/efeitos adversos , Inflamação/patologia , Exposição por Inalação/efeitos adversos , Nicotiana/efeitos adversos , Viscossuplementos/efeitos adversos , Animais , Modelos Animais de Doenças , Espaço Epidural/efeitos dos fármacos , Espaço Epidural/patologia , Fibroblastos/patologia , Fibrose , Inflamação/induzido quimicamente , Masculino , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Resumo: A osteoartrite de joelho afeta cerca de 3,8% da população mundial e se manifesta por dor, edema, rigidez e redução da função articular, impactando na qualidade de vida do paciente. O tratamento consiste na modalidade farmacológica, não farmacológica e cirúrgica. A viscossuplementação (ácido hialurônico intra-articular) se propõe a oferecer alívio dos sintomas e a possibilidade de adiamento da cirurgia. Este estudo estimou o impacto orçamentário entre a associação desse medicamento e o tratamento não cirúrgico (tratamento padrão), sob a perspectiva do Sistema Único de Saúde. Com base no pressuposto de que 5% dos portadores da doença seguem para tratamento e nos custos diretos das modalidades: farmacológica e não farmacológica foram calculados os cenários de referência e alternativos que compararam as diferentes opções de tratamento para um horizonte temporal de três anos. A análise principal estimou um impacto orçamentário incremental de aproximadamente R$ 126 milhões (1 ampola anual) e R$ 252 milhões (2 ampolas anuais). Já a diacereína, um condroprotetor oral, avaliada como uma opção alternativa, mostrou um impacto de R$ 334 milhões no orçamento em relação ao tratamento padrão, o que proporciona um aumento de 24% no custo em relação ao uso de 2 ampolas anuais de ácido hialurônico, tornando-a economicamente menos vantajosa. A viscossuplementação pode proporcionar maior qualidade de vida ao paciente, redução de custos para o sistema e otimização do fluxo de atendimento nas unidades de saúde. As estimativas apresentadas neste estudo podem auxiliar o gestor quanto à melhor utilização dos recursos financeiros e consequente tomada de decisão quanto à incorporação da tecnologia.
Abstract: Knee osteoarthritis affects 3.8% of the world population and manifests as pain, edema, stiffness, and reduced joint function, impacting the patient's quality of life. Treatment consists of the pharmacological, non-pharmacological, and surgical modalities. Viscosupplementation (intraarticular hyaluronate) has been proposed to relieve symptoms and potentially postpone surgery. This study estimated the budget impact of the association of this drug and non-surgical treatment (standard treatment) from the perspective of the Brazilian Unified National Health System. Based on the assumption that 5% of patients proceed to treatment and on the direct costs of the pharmacological and non-pharmacological modalities, the authors calculated the reference and alternative scenarios that compared the different treatment options in a three-year timeline. The principal analysis estimated an incremental budget impact of approximately BRL 126 million (U$ 32 million) for one vial of hyaluronate a year and BRL 252 million (USD 64 million) for two vials a year. Diacerein, an oral chondroprotector, assessed as an alternative, showed a budget impact of BRL 334 million (USD 86 million) in relation to standard treatment, representing a 24% cost increase compared to two vials a year of hyaluronate, making it less economically advantageous. Viscosupplementation can provide better quality of life for patients, reduce costs for the health system, and optimize the flow of care in health services. The estimates presented in this study can assist administrators in the best use of resources and thus in decision-making on the technology's incorporation.
Resumen: La osteoartritis de rodilla afecta a cerca de un 3,8% de la población mundial y se manifiesta por dolor, edema, rigidez y reducción de la función articular, impactando en la calidad de vida del paciente. El tratamiento consiste en la modalidad farmacológica, no farmacológica y quirúrgica. La viscosuplementación (ácido hialurónico intraarticular) se propone ofrecer un alivio de los síntomas y la posibilidad de un aplazamiento de la cirugía. Este estudio estimó el impacto presupuestario entre la asociación de este medicamento y el tratamiento no quirúrgico (tratamiento estándar), desde la perspectiva del Sistema Único de Salud. Basándonos en el supuesto de que un 5% de los portadores de la enfermedad siguen el tratamiento y en los costos directos de las modalidades tanto farmacológica, como no farmacológica, se calcularon los escenarios de referencia y alternativos que compararon las diferentes opciones de tratamiento para un horizonte temporal de tres años. El análisis principal estimó un impacto presupuestario incremental de aproximadamente BRL 126 millones (1 ampolla anual) y BRL 252 millones (2 ampollas anuales). En el caso de la diacereína, un condroprotector oral, evaluado como una opción alternativa, mostró un impacto de BRL 334 millones en el presupuesto, respecto al tratamiento estándar, lo que proporciona un aumento de un 24% en el costo, en relación con el uso de 2 ampollas anuales de ácido hialurónico, haciéndola económicamente menos ventajosa. La viscosuplementación puede proporcionar mayor calidad de vida al paciente, reducción de costes para el sistema y la optimización del flujo de atención en las unidades de salud. Las estimaciones presentadas en este estudio pueden ayudar al gestor en lo referente a una mejor utilización de los recursos financieros y, consecuentemente, en la toma de decisiones respecto a la incorporación de tecnología.
Assuntos
Humanos , Osteoartrite do Joelho/tratamento farmacológico , Viscossuplementos/uso terapêutico , Viscossuplementação/economia , Ácido Hialurônico/uso terapêutico , Brasil/epidemiologia , Orçamentos , Prevalência , Osteoartrite do Joelho/epidemiologia , Programas Nacionais de SaúdeRESUMO
Abstract Purpose: To evaluate the hyaluronic acid (HA) inflammatory reaction, fibroblasts, fibrosis and duration of effect in the dorsal region of tobacco-exposed rats. Methods: Ten Wistar rats were divided into two groups: tobacco-exposed-group (TEG;n=5) and air-control-group (CG;n=5). The TEG animals were tobacco-exposed twice a day, 30-minutes/session, during 60 days. After this period, all animals received 0.1 mL HA subcutaneous injection in the dorsal area. The volume of HA was measured immediately after HA injection and weekly using a hand-caliper in nine weeks. After this period, all the animals were euthanized, and a specimen of was collected to evaluate inflammatory cells, fibroblasts, and fibrosis by HE. Results: This study showed a higher inflammatory reaction in TEG than CG: inflammatory cell-count (CG: 1.07±0.9; TEG: 8.61±0.36, p<0.001); fibroblast count (CG: 2.92±0.17; TEG: 19.14±0.62, p<0.001), and fibrosis quantification (CG: 2.0; TEG: 3.75, p<0.001). The analysis of the HA volume in nine weeks in the dorsal region did not show a difference between groups (p=0.39). Conclusions: This study suggested that the HA injection in the TEG caused an increase in inflammatory cell count, fibroblast, and fibrosis quantification when compared to the CG. There was no difference in the duration of effect of HA between the groups.
Assuntos
Animais , Masculino , Ratos , Nicotiana/efeitos adversos , Exposição por Inalação/efeitos adversos , Viscossuplementos/efeitos adversos , Fibroblastos/efeitos dos fármacos , Ácido Hialurônico/efeitos adversos , Inflamação/patologia , Fatores de Tempo , Fibrose , Ratos Wistar , Modelos Animais de Doenças , Espaço Epidural/efeitos dos fármacos , Espaço Epidural/patologia , Fibroblastos/patologia , Inflamação/induzido quimicamenteRESUMO
OBJECTIVE: Our purpose was to assess the effectiveness of hyaluronic acid infiltrations for chronic shoulder pain as an alternative to the non-surgical and surgical treatments that are currently available. MATERIAL AND METHODS: This is a prospective study of 80 consecutive patients suffering from chronic shoulder pain followed for twelve months. Five subacromial hyaluronic acid injections on five consecutive weeks were administrated to all patients. RESULTS: A significant improvement within the whole group after six months was observed. Constant score improved by 7.7 points, DASH questionnaire decreased by 5 points and Visual Analog Scale for pain decreased by 1.6 points. Patients with history of less than 24 months of pain responded better to treatment. Females responded better. Patients with decreased subacromial space or cuff tear in the MRI improved but patients diagnosed by the MRI of acromioclavicular osteoarthritis worsened in all scales assessed. DISCUSSION: Subacromial hyaluronic acid injections are specially effective in patients with history of less than 24 months of pain, a decreased subacromial space or partial or total cuff tear but, in our experience, its result is not good in patients with acromioclavicular osteoarthritis.
OBJETIVO: Nuestro objetivo fue evaluar la efectividad de las infiltraciones subacromiales de ácido hialurónico en el tratamiento del dolor crónico de hombro como alternativa a los tratamientos quirúrgicos y no quirúrgicos actualmente disponibles. MATERIAL Y MÉTODOS: Estudio prospectivo de 80 pacientes consecutivos con dolor crónico de hombro seguidos durante 12 meses. Se realizaron cinco infiltraciones subacromiales con ácido hialurónico durante cinco semanas consecutivas y se analizaron los resultados clínicos obtenidos. RESULTADOS: La puntuación en la escala de Constant mejoró en 7.7 puntos, el cuestionario DASH disminuyó en cinco puntos y la puntuación en la escala visual analógica para el dolor disminuyó 1.6 puntos por término medio. Los pacientes que presentaban dolor de menos de 24 meses de evolución respondieron mejor al tratamiento. Las mujeres respondieron mejor. Los pacientes con disminución del espacio subacromial o lesión del manguito rotador según la resonancia magnética mejoraron, pero los pacientes que mostraron signos de artrosis acromioclavicular en la resonancia empeoraron en todas las escalas evaluadas. DISCUSIÓN: Las infiltraciones subacromiales de ácido hialurónico son especialmente efectivas en el tratamiento del dolor crónico de hombro de menos de 24 meses de evolución, con disminución del espacio subacromial o lesión parcial o total del manguito rotador, pero en nuestra experiencia, su resultado no es bueno en pacientes con artrosis acromioclavicular.
Assuntos
Ácido Hialurônico , Dor de Ombro , Viscossuplementos , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Injeções , Masculino , Estudos Prospectivos , Dor de Ombro/tratamento farmacológico , Resultado do Tratamento , Viscossuplementos/administração & dosagemRESUMO
Viscosupplementation is a minimally invasive technique that replaces synovial fluid by intra-articular injection of hyaluronic acid (HA). Although effective in some joints, there is not conclusive evidence regarding temporomandibular disorders. This case series described the efficacy of a viscosupplementation protocol in intra-articular temporomandibular disorders. Ten patients with a diagnosis of disc displacement and/or osteoarthritis by Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) were submitted to four monthly injections of low or medium molecular weight HA. Pain, mandibular function, image analysis by tomography and magnetic resonance, and quality of life were assessed at baseline and follow-ups (1 and 6 months). Pain, jaw range-of-motion, mandibular function, and quality of life improved at follow-up evaluations. Osteoarthritis changes decreased, and 20% of patients improved mandibular head excursion after treatment. Resolution of effusion and improvement in disc morphology were observed for most patients. This viscosupplementation protocol reduced pain and symptoms associated with internal derangement of temporomandibular joint, improved quality of life, and showed benefits from both low and medium molecular weight HA in alternate cycles.