Evaluation of cell adhesion molecules (LFA-1 and L-selectin) in ankylosing spondylitis patients after treatment with ?-D-mannuronic acid (M2000)

Background & objectives: To examine ?-D-mannuronic acid (M2000) effects on L-selectin shedding and leucocyte function-associated antigen-1 (LFA-1) expression as mechanisms of action of this drug in patients with ankylosing spondylitis (AS). Methods: To investigate the molecular consequences of ?-D-mannuronic acid on L-selectin shedding, flow cytometry method was used. Furthermore, the effect of it on LFA-1 gene expression was analyzed by using quantitative real time (qRT)-PCR technique. Results: The LFA-1 expression in patients with AS was higher than controls (P=0.046). The LFA-1 expression after 12 wk therapy with ?-D-mannuronic acid was meaningfully decreased (P=0.01). After 12 wk treatment with ?-D-mannuronic acid, the frequency of CD62L-expressing CD4+ T cells in patients with AS, was not considerably altered, compared to the patients before therapy (P=0.5). Furthermore, after 12 wk therapy with ?-D-mannuronic acid, L-selectin expression levels on CD4+ T-cells in patients with AS, were not remarkably changed, compared to the expression levels of these in patients before treatment (P=0.2). Interpretation & conclusions: The results of this study for the first time showed that ?-D-mannuronic acid can affect events of adhesion cascade in patients with AS. Moreover, ?-D-mannuronic acid presented as an acceptable benefit to AS patients and could aid in the process of disease management

Clinician's dilemma: Naproxen-induced liver injury

Naproxen is a widely used nonsteroidal anti-inflammatory drug (NSAID) in pediatric population, used for mild-to-moderate pains, arthritis, and other immune-mediated disorders. It rarely causes clinically apparent liver injury in the adult population taking high doses of the drug over a prolonged period and is reported even rarer in pediatric population. We present a case of drug-induced liver injury (DILI) in a 13-year-old girl taking naproxen in therapeutic doses for juvenile rheumatoid arthritis. There was a complete recovery of liver function following discontinuation of naproxen therapy.

Diagnosis of a Case of Hepatotoxicity Due to Drugs and Herbal Supplements in a Hospital in Pasto, Colombia

The liver is a crucial organ in metabolism, and some substances can induce toxic hepatitis with high morbidity and mortality. Chemical and drug-induced liver disease is a diagnostic and therapeutic challenge since it requires extension studies to rule out other entities. We present the case of a 51-year-old female patient without underlying comorbidities, admitted due to symptoms of two-day evolution consisting of progressive jaundice, diarrheal episodes without acholia, or any other additional manifestation. Her condition was caused by the intake of nimesulide, two tablets a day for two days, for pain secondary to a mandibular cyst diagnosed in previous days. During her admission to the emergency room, the patient described chronic consumption of Herbalife® products daily for four years. She presented with elevated transaminases, prolonged prothrombin time (PT), and direct hyperbilirubinemia. Infectious and immunological diseases were ruled out. We decided to start antibiotic and vitamin K coverage. Finally, and by exclusion, a liver biopsy suggested an inflammatory process compatible with drug-induced hepatitis. The woman evolved favorably when the medication and dietary supplement were discontinued. In conclusion, this case constitutes an initial point in advancing research into hepatotoxicity by shared mechanisms of various substances simultaneously, such as what happened to the patient with the parallel use of Herbalife® and nimesulide.

El hígado es un órgano crucial en el metabolismo y algunas sustancias pueden inducir hepatitis toxica con alta morbimortalidad. La enfermedad hepática inducida por sustancias químicas y medicamentos es un desafío tanto diagnostico como terapéutico, puesto que requiere la realización de estudios de extensión para descartar otras entidades. A continuación se presenta el caso de una paciente femenina de 51 años sin comorbilidades de base, ingresada por clínica de 2 días de evolución consistente en ictericia progresiva, episodios diarreicos sin acolia ni otra manifestación adicional. Aparentemente, su cuadro fue provocado por la administración de nimesulida, 2 tabletas al día por 2 días, contra el dolor secundario a un quiste mandibular diagnosticado en días anteriores. Durante su ingreso a urgencias la paciente describió consumo crónico, a diario desde hace 4 años, de productos de Herbalife®. Cursa con elevación de transaminasas, prolongación del tiempo de protrombina (TP) e hiperbilirrubinemia directa. Se descartan enfermedades infecciosas e inmunológicas. Se decidió iniciar el cubrimiento antibiótico y vitamina K. Finalmente y por exclusión, se realizó una biopsia hepática que sugirió un proceso inflamatorio compatible con hepatitis inducida por fármacos. La mujer evolucionó favorablemente al suspender la medicación y el suplemento dietético referido. En conclusión, el caso expuesto constituye un punto inicial en el avance hacia la investigación en hepatotoxicidad por mecanismos compartidos de diversas sustancias simultáneamente, como lo sucedido a la paciente con el uso paralelo de Herbalife® y de nimesulida.

Advances in research on small intestinal injuries caused by nonsteroidal anti-inflammatory drugs and its prevention and treatment / 中国药科大学学报

@#Nonsteroidal anti-inflammatory drugs (NSAIDs) are clinically used with common gastrointestinal adverse reactions, among which NSAIDs-induced small intestinal injuries (NSIs) are manifested in the appearance of jejunum and ileal mucosa erythema, erosion, ulcer, hemorrhage, intestinal wall perforation and obstruction et al..The pathological mechanisms of NSIs are complex, with a lack of effective prevention or treatment methods.This review summarizes the research progress of the pathological mechanisms of NSIs as well as the prevention and treatment of NSIs by misoprostol, mucosal protective agents, antibiotics and probiotics, traditional Chinese medicines and their active ingredients, nutritional supplements and other drugs in the past five years, in order to provide reference and basis for the research and development of new NSIs drugs.

Atualização em reações de hipersensibilidade aos anti-inflamatórios não esteroidais ­ Parte 2: manifestações clínicas, fenótipos, diagnóstico e manejo / Update on hypersensitivity reactions to nonsteroidal anti-inflammatory drugs ­ Part 2: clinical features, phenotypes, diagnosis, and management

Os anti-inflamatórios não esteroidais (AINE) são os fármacos mais frequentemente associados a reações de hipersensibilidade (RH) na prática clínica. Na parte 2 dessa atualização sobre as RH aos AINE, discutiremos os aspectos clínicos dessas reações, com foco nos sinais e sintomas, como diferenciar os fenótipos clínicos, fazer a orientação desses pacientes e quando indicar procedimentos complementares, como testes cutâneos, de provocação e dessensibilização.

Nonsteroidal anti-inflammatory drugs are a major cause of drug hypersensitivity reactions in clinical practice. In this "Update Part 2", we discuss the clinical picture, including the main signs and symptoms, how to distinguish clinical phenotypes, how to manage affected patients, and when to indicate additional procedures, such as skin testing, challenge, and desensitization.

Atualização em reações de hipersensibilidade aos anti-inflamatórios não esteroidais ­ Parte 1: definições, farmacologia, epidemiologia, fisiopatologia e fatores genéticos / Update on hypersensitivity reactions to nonsteroidal anti-inflammatory drugs ­ Part 1: definitions, pharmacology, epidemiology, pathophysiology, and genetics

Os anti-inflamatórios não esteroidais (AINE) estão entre os medicamentos mais utilizados no mundo e são os fármacos mais frequentemente associados à ocorrência de reações de hipersensibilidade na América Latina. As reações têm grande variabilidade de apresentações clínicas e, consequentemente, com abordagem terapêutica difícil. Nesta revisão, abordamos aspectos farmacológicos dos AINE, bem como as definições, epidemiologia e fisiopatologia das reações de hipersensibilidade aos AINE. Por fim, discutimos aspectos genéticos associados à intolerância e alergia a esses fármacos.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications worldwide and the drugs most frequently associated with the occurrence of hypersensitivity reactions in Latin America. The clinical presentation of the reactions varies widely, which makes them difficult to treat. In this review, we address pharmacological aspects of NSAIDs, as well as the definitions, epidemiology, and pathophysiology of hypersensitivity reactions to NSAIDs. Finally, we discuss genetic factors associated with intolerance and allergy to these drugs.

Effect of nonsteroidal anti-inflammatory drugs (NSAIDs) association on physicochemical and biological properties of tricalcium silicate-based cement

Abstract The aim of this study was to investigate the physicochemical and biological properties of an experimental tricalcium silicate-based repair cement containing diclofenac sodium (CERD). For the physicochemical test, MTA, Biodentine and CERD were mixed and cement disc were prepared to evaluate the setting time and radiopacity. Root-end cavity were performed in acrylic teeth and filled with cements to analyze the solubility up to 7 days. Polyethylene tubes containing cements were prepared and calcium ions and pH were measured at 3h, 24h, 72h and 15 days. For the biological test, SAOS-2 were cultivated, exposed to cements extracts and cell proliferation were investigated by MTT assay at 6h, 24h and 48h. Polyethylene tubes containing cements were implanted into Wistar rats. After 7 and 30 days, the tubes were removed and processed for histological analyses. Parametric and nonparametric data were performed. No difference was identified in relation to setting time, radiopacity and solubility. Biodentine released more calcium ion than MTA and CERD; however, no difference between MTA and CERD were detected. Alkaline pH was observed for all cements and Biodentine exhibited highest pH. All cements promoted a raise on cell proliferation at 24h and 48h, except CERD at 48h. Biodentine stimulated cell metabolism in relation to MTA and CERD while CERD was more cytotoxic than MTA at 48h. Besides, no difference on both inflammatory response and mineralization ability for all cement were found. CERD demonstrated similar proprieties to others endodontic cements available.

Resumo O objetivo deste estudo foi investigar as propriedades físico-químicas e biológicas de um cimento reparador experimental à base de silicato de tricálcio contendo diclofenaco de sódio (CERD). Para o teste físico-químico, MTA, Biodentine e CERD foram manipulados e discos de cimentos foram preparados para avaliar o tempo de presa e a radiopacidade. Retrocavidades foram feitas em dentes de acrílico e preenchidas com cimentos para análise de solubilidade por 7 dias. Tubos de polietileno contendo cimentos foram preparados e os íons cálcio e o pH foram mensurados às 3h, 24h, 72h e 15 dias. Para o teste biológico, SAOS-2 foram cultivadas, expostas aos extratos de cimentos e a proliferação celular foi investigada pelo ensaio de MTT às 6h, 24h e 48h. Tubos de polietileno contendo cimentos foram implantados em ratos Wistar. Após 7 e 30 dias, os tubos foram removidos e processados para análises histológicas. Dados paramétricos e não paramétricos foram realizados. Nenhuma diferença foi identificada em relação ao tempo de presa, radiopacidade e solubilidade. Biodentine liberou mais íons de cálcio do que MTA e CERD; no entanto, nenhuma diferença entre MTA e CERD foi detectada. O pH alcalino foi observado para todos os cimentos e o Biodentine exibiu o pH mais alto. Todos os cimentos promoveram aumento na proliferação celular às 24h e 48h, exceto o CERD às 48h. Biodentine estimulou o metabolismo celular em relação ao MTA e CERD, enquanto CERD foi mais citotóxico do que MTA em 48h. Além disso, nenhuma diferença foi encontrada na resposta inflamatória e na capacidade de mineralização para todos os cimentos. CERD demonstrou propriedades semelhantes a outros cimentos endodônticos disponíveis.

Anti-inflamatórios não esteroides tópicos para o alívio da dor artritica, beneficios para idosos / Non-steroid anti-inflammatory topics for arthritic pain relief, benefits for elderly / Temas antiinflamatorios no esteroides para el alívio del dolor artritico, beneficios para personas mayores

Objetivo: Identificar e analisar os anti-inflamatórios não esteroides tópicos para o alívio da dor artrítica, benefícios para idosos. Métodos: Trata-se de uma revisão integrativa realizada nas bases de dados no mês de maio de 2020, mediante consulta às bases de dados MEDLINE/PubMed, CINAHL, EMBASE, Web of Science, SCOPUS e índice bibliométrico LILACS, acessados por meio do Portal Periódicos da Comissão de Aperfeiçoamento de Pessoal de Ensino Superior, utilizando os descritores: idoso (Aged/elderly), anti-inflamatório não esteroide (Anti-Inflammatory Agents, Non-Steroidal) artrite (Arthritides/Polyarthritis). No qual foram selecionados 13 artigos sem limitador para tempo e idioma. Resultados: Detectou se que as variáveis mais evidenciadas foram: inglês (100%); artigos indexados na MEDLINE/PubMed (69,2%); pais com mais publicações Inglaterra (46%). Destaca-se que 69,3% dos artigos foram ensaios clínicos randomizados controlados; anti-inflamatório tópico mais usado diclofenaco sódico (61,5% seguido do cetoprofeno (38,7%). Conclusão: Concluiu se o diclofenaco e o cetoprofeno apresentam eficácia e segurança no alívio da dor artrítica, e baixa toxicidade cutânea local. (AU)

Objective To identify and analyze topical non-steroidal anti-inflammatory drugs for the relief of arthritic pain, benefits for the elderly. Methods: This is an integrative review carried out on the databases in May 2020, by consulting the MEDLINE / PubMed, CINAHL, EMBASE, Web of Science, SCOPUS and LILACS bibliometric index databases, accessed through the Portal Journals of the Higher Education Personnel Improvement Commission, using the descriptors: elderly (Aged / elderly), non-steroidal anti-inflammatory (Anti-Inflammatory Agents, Non Steroidal) arthritis (Arthritides / Polyarthritis). In which 13 articles were selected without time and language limitations. Results: It was found that the most evident variables were: English (100%); articles indexed in MEDLINE / PubMed (69.2%); parents with the most publications in England (46%). It is noteworthy that 69.3% of the articles were randomized controlled clinical trials; most commonly used topical anti-inflammatory diclofenac sodium (61.5% followed by ketoprofen (38.7%). Conclusion: Diclofenac and ketoprofen were concluded to be effective and safe in relieving arthritic pain and low local skin toxicity. (AU)

Objetivo: Identificar y analizar medicamentos antiinflamatorios no esteroideos tópicos para el alivio del dolor artrítico, beneficios para los ancianos. Métodos: Esta es una revisión integradora realizada en las bases de datos en mayo de 2020, consultando las bases de datos del índice bibliométrico MEDLINE / PubMed, CINAHL, EMBASE, Web of Science, SCOPUS y LILACS, a las que se accede a través del Portal Revistas de la Comisión de Mejoramiento del Personal de Educación Superior, utilizando los descriptores: artritis de edad avanzada (Ancianos / ancianos), antiinflamatorios no esteroideos (agentes antiinflamatorios, no esteroideos) (artritis / poliartritis). En el que se seleccionaron 13 artículos sin limitaciones de tiempo e idioma. Resultados: se encontró que las variables más evidentes fueron: inglés (100%); artículos indexados en MEDLINE / PubMed (69,2%); padres con más publicaciones en Inglaterra (46%). Es de destacar que el 69,3% de los artículos fueron ensayos clínicos controlados aleatorios; diclofenaco sódico antiinflamatorio tópico más utilizado (61.5% seguido de ketoprofeno (38.7%). Conclusión: Se concluyó que el diclofenaco y el ketoprofeno son efectivos y seguros para aliviar el dolor artrítico y la baja toxicidad local de la piel. (AU)

Prescripción de protectores gástricos en pacientes reumatológicos: análisis desde Consulta Externa de Gastroenterología / Prescription of gastric protectors in rheumatological patients: Analysis from a gastroenterology outpatient clinic

Introducción: Los antinflamatorios no esteroideos son los medicamentos más recetados por reumatólogos y traumatólogos. Pero a pesar de tener una eficacia similar para controlar la inflamación y el dolor, los diferentes antinflamatorios no esteroideos disponibles presentan variabilidad en su perfil de seguridad. Objetivo: Brindar una panorámica sobre la prescripción de protectores gástricos en pacientes reumatológicos, en dos centros hospitalarios, desde una perspectiva gastroenterológica. Métodos: La investigación se inscribe en el paradigma cuantitativo con un estudio observacional. Se conformaron dos grupos de pacientes, uno de ellos provenientes del hospital A y el segundo grupo pertenecía al hospital B. Discusión: Los gastroprotectores se han convertido en los fármacos de mayor demanda en las farmacias comunitarias de Ecuador, y los más prescritos son los inhibidores de la bomba de protones y en menor frecuencia los antihistamínicos H2. Respecto a los gastroprotectores más frecuentemente prescritos, según nuestro estudio, estos valores podrían obedecer a la disponibilidad y los costos de la famotidina y el omeprazol con respecto a otros medicamentos de probada eficacia (ansoprazol, pantoprazol, rabeprazol y ranitidina). Conclusiones: Durante los últimos años, el uso de los fármacos gastroprotectores en América Latina ha experimentado un importante desarrollo, con la observancia de normas y guías clínicas de manejo de casos que ofrecen recomendaciones importantes al respecto. Por tanto, desde una perspectiva gastroenterológica, para tener éxito, es indispensable procurar un conocimiento de estos aportes y evidencias científicas(AU)

Introduction: Nonsteroidal anti-inflammatory drugs are the most prescribed medications by rheumatologists and traumatologists. However, despite having similar efficacy in controlling inflammation and pain, the different available nonsteroidal anti-inflammatory drugs show variability in their safety profile. Objective: To provide an overview of the prescription of gastric protectors in rheumatological patients, in two hospital centers, from a gastroenterological perspective. Methods: The research is part of the quantitative paradigm with an observational study. Two groups of patients were formed, one of them from hospital A and the second group belonged to hospital B. Discussion: Gastroprotectors have become the drugs in greatest demand in community pharmacies in Ecuador, the most prescribed being Proton Pump Inhibitors (IBPS) and, to a lesser extent, H2 antihistamines (anti-H2). Regarding the most frequently prescribed gastroprotectors, according to our study, these values ​​could be due to the availability and costs of famotidine and omeprazole compared to other drugs with proven effectiveness, such as ansoprazol, pantoprazole, rabeprazole and ranitidine. Conclusions: In recent years, the use of gastroprotective drugs in Latin America has undergone significant development, with the observance of clinical case management norms and guidelines that offer important recommendations in this regard. Therefore, from a gastroenterological perspective, to be successful, it is essential to seek knowledge of these contributions and scientific evidence(AU)

Efectos de los antiinflamatorios no esteroideos en las tendinopatías / Effects of Non-Steroidal Anti-Inflammatory Drugs in Tendinopathies

Introducción: Los antiinflamatorios no esteroideos son comúnmente usados para el tratamiento de las tendinopatías, pero la evidencia sobre este tratamiento es escasa. Objetivo: Realizar una revisión sistemática acerca de los efectos de los en las tendinopatías. Métodos: Se desarrolló una búsqueda bibliográfica en PubMed, WOS, PEDro, Medline, Cinahl y SPORTDiscus. Se incluyeron un total de 13 ensayos clínicos con una calidad metodológica media de 7,15/10 en la escala PEDro. Conclusiones: En la mayoría de los artículos se observó una mejoría corto plazo en el dolor y la funcionalidad con el uso de AINEs. Los ensayos clínicos incluidos no analizaron la presencia de inflamación en esta patología. Se necesitan más estudios que determinen la función de la inflamación en la tendinopatía que justifique el uso de los antiinflamatorios no esteroideos(AU)

Introduction: Non-steroidal anti-inflammatory drugs are commonly used for the treatment of tendinopathies, but the evidence on this treatment is scarce. Objective: To carry out a systematic review about the effects of non-steroidal anti-inflammatory drugs in tendinopathies. Methods: A bibliographic search was carried out in PubMed, WOS, PEDro, Medline, Cinahl and SPORTDiscus. A total of 13 clinical trials with a mean methodological quality of 7.15/10 on the PEDro scale were included. Conclusions: In most of the articles, a short-term improvement in pain and functionality was observed with the use of non-steroidal anti-inflammatory drugs. The clinical trials included did not analyze the presence of inflammation in this pathology. More studies are needed to determine the role of inflammation in tendinopathy that justifies the use of nonsteroidal anti-inflammatory drugs(AU)

A prospective, multicentric study to determine the safety and effectiveness of fixed-dose combination of camylofin dihydrochloride and nimesulide in patients presenting with acute colicky abdominal pain in India

Background:Spasmolytics and NSAIDs are a therapy of choice in colic pain. However, the tolerability and effectiveness of this combination remains unexplored. The aim of this prospective, single-arm, open label, multicenter study was to evaluate the safety and effectiveness of Anafortan-N�(fixed-dose combination of camylofin dihydrochloride 50 mg + nimesulide 100 mg) in patients with acute colicky abdominal pain.Methods: In all, 295 patients with acute colicky abdominal pain and at least one episode of colicky pain in the last 24 hours were enrolled in this study. None of the patients were hospitalized. All patients were advised Anafortan-N畉ablets twice daily orally for 5 days. The safety of Anafortan-N畐as assessed by number and percentage of patients with adverse events (AEs) and change in the severity and frequency of AEs by the end of treatment. The tolerability was determined by number and percentage of patients who hadto discontinue the treatment due to AEs. The effectiveness was evaluated as percentage change in the mean intensity of pain score (based on a 100-mm visual analog scale) from baseline to end of treatment.Results: Overall, 14 (4.7%) patients reported 14 AEs, all of which were treatment-emergent and non-serious. Of the 14 AEs, 7 AEs were mild, 6 AEs were moderate, and 1 AE was severe. No serious adverse events (SAEs) were reported. No adjustment of the study medication was required in response to any of the AEs, and none of the AEs led to discontinuation of the study treatment. At end of treatment(EOT), the pain intensity significantly (p<0.0001) reduced to 1.7�49 with a mean change of -69.9�.42 from baseline, and the daily pain intensity significantly (p<0.0001) reduced to 0.1�38 with a mean change of -3.5�77 from baseline.Conclusions: Among Indian patients presenting with acute abdominal colicky pain, twice daily treatment with a FDC of camylofin dihydrochloride 50 mg and nimesulide 100 mg (Anafortan-N�) showed significant reduction in pain intensity with very few side effects, thereby confirming its safety, tolerability, and effectiveness in acute colicky abdominal pain.

Impact of nonsteroidal anti-inflammatory drugs on efficacy of anti-PD-1 therapy for primary liver cancer / 南方医科大学学报

OBJECTIVE@#To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma.@*METHODS@#We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups.@*RESULTS@#There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729).@*CONCLUSION@#Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.

New topical microemulsions of etofenamate as sufficient management of osteoarthritis

Abstract In this study, microemulsions containing etofenamate were prepared and evaluated as dermal delivery carriers. The developed microemulsions consist of oleic acid, Span 80, Tween 20, Cremophor EL, Transcutol and ethanol. The percentage of etofenamate loading in the microemulsions was 5% (w/w). The characterization of formulations included droplet size, zeta potential, pH, conductivity, PDI, refractive index and viscosity. Moreover, ex vivo penetration study was carried out using mice abdominal skin. The developed formulations were analyzed for their cytotoxicity via MTT assay and tested for their anti-inflammatory properties opposed to LPS-stimulated nitrite prοduction in RAW 264.7 cells. As ideal formulation, M2ETF, was chosen due to its greater permeation, lower penetration as well as higher anti-inflammatory

Maintained activity in ankylosing spondylitis patients treated with TNFi and/or NSAID for at least 12 weeks: a cross-sectional study in Brazil

Abstract Background The aim of this study was to evaluate disease activity among patients with axial spondyloarthritis (AS) treated with tumor necrosis factor inhibitors (TNFi) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) for at least 12 weeks in private outpatient settings in Brazil. Methods This was a cross-sectional, real-world study conducted in 17 Brazilian private health care institutes. Patients were selected if diagnosed with AS or axial radiographic spondyloarthritis (AxSpA) and treated with NSAIDs or TNFi for at least 12 weeks within the last 26 weeks prior to enrollment. The data were collected from interviewed-based and self-administered questionnaires from patients and physicians. Disease activity was defined as active (≥ 4), low /suboptimal (≥ 2 and < 4) and inactive (< 4) by Bath AS Disease Activity Index (BASDAI) and/or very high (≥ 3.5), high (≥ 2.1 to < 3.5), low (≥ 1.3 to < 2.1), and inactive (< 1.3) by AS Disease Activity Score (ASDAS-CRP). Both patients and physicians' perceptions of disease control were assessed using a numeric rating scale (NRS; 0—inactive to 10—very active disease). Results The cohort included 378 patients with a mean age of 46 years, and the median time since diagnosis until enrollment was 5.4 years (interquartile range 2.7-10.5). Most patients were treated with TNFi alone (74%), followed by TNFi in combination with NSAID (15%), and NSAID alone (11%). About half AS patients showed active disease and 24% of patients showed low activity/suboptimal disease control despite having been treated for at least 12 weeks. Although TNFi showed better disease control than NSAID, inactive disease was experienced by few patients. The NRS (mean [standard deviation]) score for disease perception was 4.24 (3.3) and 2.85 (2.6) for patients and physicians, respectively. Conclusion This real-world study showed that most AS patients on TNFi and/or NSAID had not achieved an adequate disease control, as almost 75% of them exhibited active disease or low activity/suboptimal disease control. There remains a need for improved disease management among patients with AS.

Anti-inflammatories for delayed onset muscle soreness: systematic review and meta-analysis / Antiinflamatorios para el dolor muscular de inicio tardío: revisión sistemática y metanálisis / Anti-inflamatórios para dor muscular de início tardio: revisão sistemática e metanálise

ABSTRACT Objective: To investigate the effectiveness of pharmacological interventions in the treatment of delayed onset muscle soreness (DOMS). Design: A systematic review and meta-analysis of randomized controlled clinical trials (RCTs). Data sources: The PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for RCTs published prior to August 3, 2020. Eligibility criteria for selecting studies: Studies that 1) used an RCT design; 2) evaluated the effectiveness of steroidal or nonsteroidal anti-inflammatory drugs (NSAIDs) in treating DOMS; and 3) therapeutically used drugs after exercise were included. Results: In total, 26 studies (patients = 934) were eligible for inclusion in the qualitative analysis on the treatment of DOMS. The results of the meta-analysis showed no superiority between the use and non-use of NSAIDs in the improvement of late muscle pain, as no statistically significant differences were verified (21 studies, n= 955; standard mean difference (SMD)= 0.02; 95% confidence interval (CI) −0.58, 0.63; p=0.94; I2=93%). The quality of the synthesized evidence was very low according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, and there was significant heterogeneity among the included studies. Conclusion: The results demonstrate that NSAIDs are not superior to controls/placebos in treating DOMS. The inclusion of both studies with dose-response protocols and those with exercise protocols may have influenced the results. In addition, the high risk of bias identified reveals that limitations need to be considered when interpreting the results. Level of evidence I; ystematic review of RCT (Randomized and Controlled Clinical Trials).

RESUMEN Objetivo: Investigar la efectividad de las intervenciones farmacológicas en el tratamiento del dolor muscular de aparición tardía (DOMS). Metodología: Revisión sistemática y metanálisis de ensayos clínicos controlados aleatorios (RCT). Fuentes de datos: Se realizaron búsquedas en las bases de datos de PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo y Cochrane Central Register of Controlled Trials (CENTRAL) para ECA publicados antes del 3 de agosto de 2020. Criterios de elegibilidad para la selección de estudios: Estudios en los que 1) se utilizó un diseño de RCT; 2) se evaluó la eficacia de los fármacos antiinflamatorios no esteroideos (AINE) y esteroideos en el tratamiento de DOMS; y 3) se incluyó el uso terapéutico de medicamentos para dolor después del ejercicio. Resultados: En total, 26 estudios (pacientes = 934) fueron elegibles para su inclusión en el análisis cualitativo sobre el tratamiento de DOMS. Los resultados encontrados en el metanálisis no demostraron superioridad entre el uso y no uso de AINE para mejorar el dolor muscular tardío cuando se comparó con una condición de control, ya que no hubo diferencias estadísticamente significativas (21 estudios, n = 955; media estándar diferencia = 0,02; intervalo de confianza (IC) del 95% −0,58, 0,63; p = 0,94; I2 = 93%). La calidad de la evidencia encontrada se clasificó como muy baja según los criterios del "Grading of Recommendations Assessment, Development and Evaluation" (GRADE), principalmente porque existe una heterogeneidad significativa entre los estudios incluidos. Conclusión: Los resultados demuestran que los AINE no son superiores a los controles o placebos en el tratamiento de DOMS. La inclusión de ambos modelos de estudio con protocolos de dosis-respuesta y protocolos de ejercicio puede haber influido en los resultados. Además, el alto riesgo de sesgo identificado revela que la interpretación de los resultados debe verse con limitaciones. Nivel de evidencia: I; Revisión sistemática de ECRC (Ensayos clínicos aleatorizados y controlados).

RESUMO Objetivo: Investigar a eficácia das intervenções farmacológicas no tratamento da dor muscular de início tardio (DOMS). Desenho: Revisão sistemática e metanálise de estudos clínicos randomizados e controlados (RCTs). Fontes de dados: Os bancos de dados PubMed/MEDLINE, EMBASE, SPORTDiscus, Scielo e Cochrane Central Register of Controlled Trials (CENTRAL) foram pesquisados em busca de RCTs publicados antes de 3 de agosto de 2020. Critérios de elegibilidade para selecionar estudos: Estudos que 1) usaram um desenho de RCT; 2) avaliaram a eficácia de anti-inflamatórios esteroides ou não esteroides (AINEs) no tratamento de DOMS e 3) incluíram tratamento medicamentoso depois de exercício. Resultados: No total, 26 estudos (pacientes = 934) foram elegíveis para inclusão na análise qualitativa do tratamento de DOMS. Os resultados da metanálise não mostraram superioridade entre o uso e não uso de AINEs na melhora da dor muscular tardia, pois não foram verificadas diferenças estatisticamente significativas (21 estudos, n = 955; diferença média padronizada (SMD) = 0,02; Intervalo de confiança (IC) de 95% −0,58, 0,63; p = 0,94; I2 = 93%). A qualidade da evidência encontrada foi muito baixa de acordo com os critérios da Grading of Recommendations Assessment, Development and Evaluation (GRADE), e verificou-se heterogeneidade significante entre os estudos incluídos. Conclusão: Os resultados demonstram que os AINEs não são superiores aos controles ou placebos no tratamento de DOMS. A inclusão de estudos com protocolos de dose-resposta e com protocolos de exercícios podem ter influenciado os resultados. Além disso, o alto risco de viés identificado revela que as limitações devem ser consideradas na interpretação dos resultados. Nível de evidência I; Revisão sistemática de ECRC (Estudos clínicos randomizados e controlados).

Risk factors for radiological hip involvement in patients with ankylosing spondylitis

SUMMARY OBJECTIVE: Our study aimed to explore the potential risk factors for radiological hip joint involvement in patients with ankylosing spondylitis (AS). METHODS: This cross-sectional convey collected the clinical data, laboratory indicators, and radiographic data of patients with AS. Radiographic hip joint involvement was defined as a Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-hip) score ≥2. Multivariate logistic regression analyses were conducted to explore the potential risk factors for radiological hip involvement in patients with AS. RESULTS: Based on BASRI-hip score, all enrolled 386 patients with AS were classified as patients involving with radiological hip joint involvement (BASRI-hip ≥2; n=203) and those without it (BASRI-hip ≤1; n=183). Mean age of enrolled patients with AS were 36.7±11.9 years, and 320 (82.9%) patients were male. Mean course of disease was 10.7±8.3 years, and 349 (90.4%) patients were with a positive HLAB27. Multivariate analyses indicated that Juvenile onset (onset age ≤16 years) (odds ratio [OR]=4.159, 95% confidence interval [CI], 1.779-9.721, p<0.001), body mass index (BMI) <18.5 kg/m2 (OR=1.986, 95%CI 1.187-3.323, p=0.009), continuous nonsteroidal anti-inflammatory drug (NSAID) use (OR=0.351, 95%CI 0.155-0.794, p=0.012), and bone mass below the expected range for age (Z score ≤-2) (OR=2.791, 95%CI 1.456-5.352, p=0.002) were independently associated with radiological hip joint involvement in patients with AS. CONCLUSIONS: The potential risk factors for radiological hip joint involvement were juvenile onset, lower BMI, and bone mass below the expected range for age. Furthermore, continuous NSAID use was the protective factor for radiological hip joint involvement in these population.

Bioequivalence Study Comparing Meloxicam 15mg Tablet of Pascual Laboratories, Inc. with Meloxicam (Mobic®) 15mg Tablet of Boehringer Ingelheim in Healthy Male Filipino Subjects under Fasting Conditions

@#<p style="text-align: justify;"><strong>Objective.</strong> Proof of bioequivalence is important for the interchangeability of pharmaceutically equivalent drug products. This study aimed to compare the rate and extent of absorption of meloxicam 15 mg tablet of Pascual Laboratories, Inc. (Test) with meloxicam 15 mg tablet (Mobic) of Boehringer Ingelheim (Reference) in healthy Filipino men. In addition, the study also determined the safety and tolerability of single doses of the said medications, under the same conditions.</p><p style="text-align: justify;"><strong>Methods.</strong> This was a randomized, open label, blind-endpoint analysis, truncated, crossover study with single drug doses administered in the fasting condition in each of the two treatment periods, separated by a two-week washout period. Pharmacokinetic blood sampling was performed up to 72 h post-dose. Plasma samples were analyzed using a validated liquid chromatography with tandem mass spectrometry technology. The primary endpoints were: area under plasma-concentration-time curve from time zero to the last observed concentration at time 72 h (AUC0-72) and maximum plasma concentration (Cmax) for meloxicam.</p><p style="text-align: justify;"><strong>Results.</strong> Eighteen men (mean age 21.5 years; mean body mass index 22.9 kg/m2) completed the study. When administered one meloxicam 15 mg tablet, the ratios of the geometric means of the primary endpoints AUC0-72 and Cmax, were within the established bioequivalence limits of 80% to 125% compared with Mobic 15 mg tablet: 104.07% (90% Confidence Interval [CI]: 100.26, 108.03), and 103.34% (90% CI: 96.22, 110.97), respectively. No adverse event was reported.</p><p style="text-align: justify;"><strong>Conclusion.</strong> Meloxicam 15 mg tablet of Pascual Laboratories, Inc. and the innovator Mobic 15 mg tablet are bioequivalent. Single doses of both products were safe and well tolerated.</p>

Bleeding after tooth extraction in patients receiving anticoagulation/antiplatelet therapy / 口腔疾病防治

@#Tooth extraction in patients receiving anticoagulation/antiplatelet therapy is often considered contraindicated by many oral and maxillofacial surgeons because of a higher risk of postoperative bleeding. Multiple factors contribute to postoperative bleeding, but there is no consensus. Based on recent literature, this article reviews factors related to bleeding after tooth extraction in patients receiving anticoagulation/antiplatelet therapy. The literature review indicates that patients taking antiplatelet drugs have a lower postoperative bleeding risk than patients taking anticoagulant drugs. Prescription of anticoagulants together with non-steroidal anti-inflammatory drugs, selective serotonin inhibitors or serotonin-norepinephrine inhibitors increases the risk of bleeding, so does preoperative antibiotic use increase. In addition, systemic diseases such as diabetes, history of infection at the extraction site, and greater surgical trauma are associated with a higher risk of postoperative bleeding. At present, it is generally believed that it is safe and feasible to use different hemostatic measures after tooth extraction and to rationally apply different hemostatic measures after surgery. More prospective controlled trials are needed in the future to establish an assessment system for patients undergoing anticoagulation/antiplatelet therapy under different conditions during tooth extraction.

Effects of flunixin meglumine, meloxicam, and firocoxib on the acute-phase proteins in horses following standing castration

ABSTRACT: Excessive infection and inflammation are the most common complications associated with castration. The objective of this study was to compare the efficacy of flunixin meglumine (FM), meloxicam (MX), or firocoxib (FX) for inflammation control after castration in horses using acute-phase proteins (APP) as markers of inflammation. Thirty healthy, unbroken, mixed-breed horses (body weight 358.62±45.57kg and age 4.99±2.63 years) were randomly (n=10 animals/group) allocated to receive one of three different post-castration anti-inflammatory medicines: Group 1 (FM 1.1mg/kg bwt, IV, s.i.d for 5 days); Group 2 (MX 0.6mg/kg bwt, IV, s.i.d for 5 days); and Group 3 (FX 0.1mg/kg bwt, IV, s.i.d for 5 days). All horses were castrated in standing position, using the open technique. Serum and peritoneal APP concentrations were measured by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and determined before castration (0), and 3, 5, 24, 48, 72, 120 and 168 hours after castration. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (p 0.05). Three animals from the MX group developed hyperthermia (with rectal temperatures of 39.8, 39.3 and 38.9°C on day 4, 5 and 6, respectively) and showed local clinical signs of inflammation (inguinal and excessive scrotal edema) and reluctance to walk, as well as a rigid gait of the hind limbs. The same complications were observed in one FX horse. No complications were observed among the FM animals. The castration resulted in significant changes in serum and peritoneal values of total proteins, ceruloplasmin (Cp), transferrin (Tf), albumin (Alb), haptoglobin (Hp) and 1-acid glycoprotein (Gp) in animals of all experimental groups. However, the animals of the MX and FX groups presented more intense acute phase response compared to the animals of the FM group. Changes in the APP were associated with the surgical trauma of castration, but the differences between groups were associated with the ability of the nonsteroidal anti-inflammatory drug to control the inflammation. In conclusion, and based on the findings of acute phase proteins, flunixin is more efficient to control the magnitude of inflammation following castration as compared to meloxicam and firocoxib.

RESUMO: Infecção e inflamação excessivas são as complicações mais comuns associadas à castração. O objetivo deste estudo foi comparar a eficácia do flunixin meglumine (FM), meloxicam (MX) ou firocoxib (FX) no controle da inflamação após a castração em cavalos usando proteínas da fase aguda (APP) como marcadores de inflamação. Trinta equinos saudáveis (358,62±45,57kg; 4,99±2,63 anos) foram em função dos anti-inflamatórios utilizados após as castrações aleatoriamente (n= 10 animais/grupo) alocados em três diferentes grupos: Grupo 1 (FM 1,1mg/kg de peso, IV, sid por 5 dias); Grupo 2 (MX 0,6mg/kg de peso, IV, s.i.d por 5 dias); e Grupo 3 (FX 0,1mg/kg de peso, IV, s.i.d por 5 dias). Todos os cavalos foram castrados em posição quadrupedal, utilizando a técnica aberta. As concentrações de APP sérica e peritoneal foram separadas por eletroforese em gel de poliacrilamida (PAGE) com dodecil-sulfato de sódio (SDS) e determinadas no momento 0 (antes da castração) e com 3, 5, 24, 48, 72, 120 e 168 horas após a castração. Os resultados foram submetidos à análise de variância pelo programa estatístico SAS e as médias foram comparadas pelo teste de Student-Newman-Keuls (p 0,05). Três animais do grupo MX desenvolveram hipertermia (com temperatura retal de 39,8, 39,3 e 38,9° C nos dias 4, 5 e 6, respectivamente) e mostraram sinais clínicos locais de inflamação (edema inguinal e escrotal excessivo) e relutância em andar, bem como marcha rígida dos membros posteriores. As mesmas complicações foram observadas em um cavalo do FX. Não foram observadas complicações entre os animais do FM. Independente do grupo, a castração resultou em alterações significativas nos valores séricos e peritoneais de proteínas totais, ceruloplasmina (Cp), transferrina (Tf), albumina (Alb), haptoglobina (Hp) e glicoproteína ácida 1 (Gp). No entanto, os animais dos grupos MX e FX apresentaram resposta de fase aguda mais intensa quando comparados aos animais do FM. Alterações na resposta de fase aguda deveram-se ao trauma cirúrgico da castração, mas as diferenças entre os grupos foram associadas à capacidade do anti-inflamatório em controlar a inflamação. Em conclusão, baseado da resposta de fase aguda, o flunixin em comparação com o meloxicam e o firocoxib é mais eficiente no controle da inflamação após a castração em equinos.

Effects of flunixin meglumine, meloxicam, and firocoxib on the acute-phase proteins in horses following standing castration / Efeitos do flunixin meglumine, meloxicam e firocoxib na concentração de proteínas da fase aguda após em equinos após castração

Excessive infection and inflammation are the most common complications associated with castration. The objective of this study was to compare the efficacy of flunixin meglumine (FM), meloxicam (MX), or firocoxib (FX) for inflammation control after castration in horses using acute-phase proteins (APP) as markers of inflammation. Thirty healthy, unbroken, mixed-breed horses (body weight 358.62±45.57kg and age 4.99±2.63 years) were randomly (n=10 animals/group) allocated to receive one of three different post-castration anti-inflammatory medicines: Group 1 (FM 1.1mg/kg bwt, IV, s.i.d for 5 days); Group 2 (MX 0.6mg/kg bwt, IV, s.i.d for 5 days); and Group 3 (FX 0.1mg/kg bwt, IV, s.i.d for 5 days). All horses were castrated in standing position, using the open technique. Serum and peritoneal APP concentrations were measured by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and determined before castration (0), and 3, 5, 24, 48, 72, 120 and 168 hours after castration. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (p<0.05). Three animals from the MX group developed hyperthermia (with rectal temperatures of 39.8, 39.3 and 38.9°C on day 4, 5 and 6, respectively) and showed local clinical signs of inflammation (inguinal and excessive scrotal edema) and reluctance to walk, as well as a rigid gait of the hind limbs. The same complications were observed in one FX horse. No complications were observed among the FM animals. The castration resulted in significant changes in serum and peritoneal values of total proteins, ceruloplasmin (Cp), transferrin (Tf), albumin (Alb), haptoglobin (Hp) and α1-acid glycoprotein (Gp) in animals of all experimental groups. However, the animals of the MX and FX groups presented more intense acute phase response compared to the animals of the FM group. Changes in the APP were associated with the surgical trauma of castration, but the differences between groups were associated with the ability of the nonsteroidal anti-inflammatory drug to control the inflammation. In conclusion, and based on the findings of acute phase proteins, flunixin is more efficient to control the magnitude of inflammation following castration as compared to meloxicam and firocoxib.(AU)

Infecção e inflamação excessivas são as complicações mais comuns associadas à castração. O objetivo deste estudo foi comparar a eficácia do flunixin meglumine (FM), meloxicam (MX) ou firocoxib (FX) no controle da inflamação após a castração em cavalos usando proteínas da fase aguda (APP) como marcadores de inflamação. Trinta equinos saudáveis (358,62±45,57kg; 4,99±2,63 anos) foram em função dos anti-inflamatórios utilizados após as castrações aleatoriamente (n= 10 animais/grupo) alocados em três diferentes grupos: Grupo 1 (FM 1,1mg/kg de peso, IV, sid por 5 dias); Grupo 2 (MX 0,6mg/kg de peso, IV, s.i.d por 5 dias); e Grupo 3 (FX 0,1mg/kg de peso, IV, s.i.d por 5 dias). Todos os cavalos foram castrados em posição quadrupedal, utilizando a técnica aberta. As concentrações de APP sérica e peritoneal foram separadas por eletroforese em gel de poliacrilamida (PAGE) com dodecil-sulfato de sódio (SDS) e determinadas no momento 0 (antes da castração) e com 3, 5, 24, 48, 72, 120 e 168 horas após a castração. Os resultados foram submetidos à análise de variância pelo programa estatístico SAS e as médias foram comparadas pelo teste de Student-Newman-Keuls (p<0,05). Três animais do grupo MX desenvolveram hipertermia (com temperatura retal de 39,8, 39,3 e 38,9° C nos dias 4, 5 e 6, respectivamente) e mostraram sinais clínicos locais de inflamação (edema inguinal e escrotal excessivo) e relutância em andar, bem como marcha rígida dos membros posteriores. As mesmas complicações foram observadas em um cavalo do FX. Não foram observadas complicações entre os animais do FM. Independente do grupo, a castração resultou em alterações significativas nos valores séricos e peritoneais de proteínas totais, ceruloplasmina (Cp), transferrina (Tf), albumina (Alb), haptoglobina (Hp) e glicoproteína ácida α1 (Gp). No entanto, os animais dos grupos MX e FX apresentaram resposta de fase aguda mais intensa quando comparados aos animais do FM. Alterações na resposta de fase aguda deveram-se ao trauma cirúrgico da castração, mas as diferenças entre os grupos foram associadas à capacidade do anti-inflamatório em controlar a inflamação. Em conclusão, baseado da resposta de fase aguda, o flunixin em comparação com o meloxicam e o firocoxib é mais eficiente no controle da inflamação após a castração em equinos.(AU)