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

Single-center, retrospective study on changes in pain-relieving therapy after bone metastasis detection by bone scintigraphy in prostate cancer patients

Abstract Whole-body bone scintigraphy (WB-BS) is used for detecting and monitoring metastatic spread of prostate cancer (PCa) and to investigate bone pain episodes. To investigate the impact of a positive WB-BS on pain-relieving medicine prescription in PCa patients, a single-center, retrospective cohort study with PCa patients classified as positive for bone metastases (BM) by WB-BS was conducted. Demographic, clinical, and ambulatory pain-relieving medicine prescription data were evaluated. Pain-relieving medicines were categorized according to the WHO 'Analgesic Ladder'. Regimens adopted before and after WB-BS were compared. Differences were considered significant at p<0.05. A total of 180 PCa patients were diagnosed with BM, 64.4% of whom were ≥65 years of age. Thirty-three patients were prescribed analgesics only after WB-BS, mostly including NSAIDs and weak opioids. Pain-relieving prescription changed after WB-BS in patients with prescriptions before and after WB-BS, with a reduction in NSAIDs and adjuvants and an increase in weak and strong opioids. In addition, 40% of patients with WHO analgesic step 1 drugs and 21.7% of patients with WHO step 2 drugs before WB-BS changed to other WHO steps after WB-BS. Pain-relieving prescriptions changed after a positive WB-BS, providing evidence that it could contribute to clinical management of painful metastatic PCa patients.

Proteinuria en habitantes de una aldea costera de Santa Rosa, Guatemala / Proteinuria in inhabitants of a coastal village of Santa Rosa, Guatemala

Objetivo: determinar la presencia de proteinuria en habitantes de una aldea de la región costera de Santa Rosa, Guatemala, julio del año 2019. Material y métodos: estudio descriptivo y transversal, en una muestra de 575 habitantes de la aldea Casas Viejas, captada por durante cuatro jornadas médicas. Las muestras de orina fueron analizadas con tiras reactivas. Resultados: de los habitantes que participaron, 55.48 % (319) fueron de sexo femenino, la mediana de edad fue de 24 años, el 39.820% (229) estudiante y el 85.2 % (490) sin antecedentes patológicos. De los factores predisponentes de enfermedad renal, el 56.170% (323) consume antiinflamatorios no esteroideo -AINES-, el 82.26 % (473) bebidas carbonatadas, el 13.570% (78) bebidas alcohólicas; la mediana de consumo de agua fue de 6 vasos diarios y 13.22 % (76) han estado expuestos a agroquímicos. Proteinuria se documentó en 8.87 % (51) de los habitantes. Conclusiones: más de la mitad de los sujeto de estudio son de sexo femenino y sin antecedentes patológicos; de los factores predisponentes a enfermedad renal los más frecuentes son el consumo de -AINES-, bebidas carbonatadas y la hidratación inadecuada. Nueve de cada cien sujetos de estudio presentan proteinuria.

Objetive: to establish urine protein presence in inhabitants of a small village of the coastal region in Santa Rosa, Guatemala. July 2019. Material y methods: Descriptive and transversal study performed on 575 persons from Casas Viejas village, using a nonprobabilistic sampling. Proteinuria was determined by urine test strips. Results: Of the persons studied, 55.48% (319) were female, mean age was 24 years old, 39.82% (229) were students and 85.25% had no pathological background. Predisposing factors of kidney disease were noted, 56.17% (323) consumed Non-steroidal Anti-inflammatory Drugs (NSAIDs), 82.26% (473) consumed carbonated drinks, 13.57% (78) alcoholic beverages, the mean water consumption was 6 glasses per day, and 13.22% (76), were exposed to agrochemical pesticides. Proteinuria was found in 8.87% (51) of the sample. Conclutions: more than half of population were female and didn´t showed pathological signs. Predisposing factors to kidney disease were, frequent NSAIDs use, carbonated drinks consumption a no adequate hydration. Nine of each one hundred people studied presented urine protein.

Development of controlled release dexketoprofen tablets and prediction of drug release using Artificial Neural Network (ANN) modelling

Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.

Ibuprofen-induced aseptic meningitis: a case report / Meningite asséptica induzida por ibuprofeno: um caso clínico

ABSTRACT Objective: To report a case of a male adolescent with the diagnosis of ibuprofen-induced meningitis. We discuss themain causes of drug-induced aseptic meningitis (DIAM) and highlight the importance of early recognition of DIAM, sothat the offending drug can be withdrawn, and recurrences prevented. Only few DIAM cases have been reported in pediatric age. Case description: A healthy 15-year-old boy presented to the emergency department with headache, nausea, dizziness, fever, conjunctival hyperemia and blurred vision 30 minutes after ibuprofen-intake. During his stay, he developed emesis and neck stiffness. Cerebrospinal fluid analysis excluded infectious causes, and DIAM was considered. He totally recovered after drug withdrawal. Comments: DIAM is a rare entity, that should be considered in the differential diagnosis of an aseptic meningitis. The major causative agents are nonsteroidal anti-inflammatory drugs, particularly ibuprofen. Suspicion is made by the chronologic link between drug intake and the beginning of symptoms, but infectious causes should always be ruled out.

RESUMO Objetivo: Descreve-se o caso de um adolescente do sexo masculino com diagnóstico de meningite asséptica por ibuprofeno. Discutem-se as causas de meningite asséptica induzida por medicamentos (MAIM) e a importância do reconhecimento precoce dessa situação, para que a medicação envolvida seja suspensa e as recorrências prevenidas. Poucos casos foram descritos em idade pediátrica. Descrição do caso: Adolescente de 15 anos, gênero masculino, saudável, procurou o serviço de urgência por cefaleia, náuseas, tonturas, febre, hiperemia conjuntival e visão desfocada 30 minutos após o uso de ibuprofeno. Durante a internação, iniciou vômitos e rigidez na nuca. A análise do líquido cefalorraquidiano excluiu causas infeciosas, e considerou-se como diagnóstico mais provável a MAIM. A recuperação foi total após a suspensão do medicamento. Comentários: A MAIM é rara, mas deve ser considerada no diagnóstico diferencial de meningite asséptica. A principal causa são os anti-inflamatórios não esteroides, principalmente o ibuprofeno. A suspeita clínica é evocada pela relação temporal entre o uso do medicamento e o início dos sintomas, mas as causas infeciosas devem ser sempre excluídas.

Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs / Aspectos fisiopatológicos da nefropatia por anti-inflamatórios não esteroidais

Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used medications associated with nephrotoxicity, especially when used chronically. Factors such as advanced age and comorbidities, which in themselves already lead to a decrease in glomerular filtration rate, increase the risk of NSAID-related nephrotoxicity. The main mechanism of NSAID action is cyclooxygenase (COX) enzyme inhibition, interfering on arachidonic acid conversion into E2 prostaglandins E2, prostacyclins and thromboxanes. Within the kidneys, prostaglandins act as vasodilators, increasing renal perfusion. This vasodilatation is a counter regulation of mechanisms, such as the renin-angiotensin-aldosterone system works and that of the sympathetic nervous system, culminating with compensation to ensure adequate flow to the organ. NSAIDs inhibit this mechanism and can lead to acute kidney injury (AKI). High doses of NSAIDs have been implicated as causes of AKI, especially in the elderly. The main form of AKI by NSAIDs is hemodynamically mediated. The second form of NSAID-induced AKI is acute interstitial nephritis, which may manifest as nephrotic proteinuria. Long-term NSAID use can lead to chronic kidney disease (CKD). In patients without renal diseases, young and without comorbidities, NSAIDs are not greatly harmful. However, because of its dose-dependent effect, caution should be exercised in chronic use, since it increases the risk of developing nephrotoxicity.

Resumo Os anti-inflamatórios não esteroidais (AINEs) são medicamentos comumente utilizados, associados à nefrotoxicidade, sobretudo quando utilizados cronicamente. Fatores como idade avançada e comorbidades, que por si só já levam à diminuição da taxa de filtração glomerular, aumentam o risco de nefrotoxicidade dos AINEs. O principal mecanismo de ação dos AINEs é a inibição da enzima ciclooxigenase (COX), interferindo na conversão do ácido araquidônico em prostaglandinas E2, prostaciclinas e tromboxanos. Nos rins, as prostaglandinas atuam como vasodilatadoras, aumentando a perfusão renal. Essa vasodilatação atua como uma contrarregulação de mecanismos, como a atuação do sistema renina-angiotensina-aldosterona e do sistema nervoso simpático, culminando com uma compensação para assegurar o fluxo adequado ao órgão. O uso de AINEs inibe esse mecanismo, podendo causar lesão renal aguda (LRA). Altas doses de AINEs têm sido implicadas como causas de LRA, especialmente em idosos. A principal forma de LRA por AINEs é a hemodinamicamente mediada. A segunda forma de apresentação da LRA induzida por AINES é a nefrite intersticial aguda, que pode se manifestar com proteinúria nefrótica. O uso de AINEs em longo prazo pode ocasionar doença renal crônica (DRC). Nos pacientes sem doenças renais, jovens e sem comorbidades, os AINEs não apresentam grandes malefícios. Entretanto, por seu efeito dose-dependente, deve-se ter grande cautela no uso crônico, por aumentar risco de desenvolver nefrotoxicidade.

New metallophamaceutic reduced renal injury induced by non-steroidal anti-inflammatory

Abstract Purpose To evaluate the effect of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor, able to modulate the histological changes caused by the NASID (meloxicam). Methods Wistar rats were assigned into three groups (n=6 rats/group): Sham group (saline solution), NSAID group (meloxicam - 15 mg/kg) and Rut-bpy group (100 mg/kg of Rut-bpy associated with 15mg/kg of meloxicam). At the end of experiments, kidneys were removed for histological study, fractal dimension and lacunarity in all animals. Results At the histological examination, all animals (six animals - 100 %) in the NSAID group had membrane thickening and other changes (necrosis, acute tubular congestion and vascular congestion); on the other hand, only one animal (16.6 %) of the Rut-bpy group had congestion. The fractal dimension and lacunarity were greater in the control and Rut-bpy group than in NSAIDs group (p<0.05). Conclusion Rut-bpy may prevent renal histological changes in rats caused by meloxicam.

Riesgo cardiovascular de los antiinflamatorios no esteroideos / Cardiovascular risk of non-steroidal anti-inflammatory drug

Los antiinflamatorios no esteroideos (AINEs) se encuentran entre los fármacos más utilizados en la práctica clínica. Actúan mediante el bloqueo de las enzimas ciclooxigenasas (COX), pero el grado de inhibición de COX-1 y COX-2 varía entre ellos. Se ha generalizado la clasificación entre COX-2 selectivos o coxibs, y los no selectivos o AINEs tradicionales. Tanto los efectos analgésico y antiinflamatorio como los efectos adversos cardiovasculares dependen de la inhibición de COX-2. Este trabajo revisa las evidencias disponibles del aumento del riesgo de eventos trombóticos tanto para los coxibs como para los AINEs tradicionales. El efecto protrombótico podría deberse a la inhibición de la COX-2 endotelial, con disminución de la prostaciclina y un incremento relativo de los niveles del tromboxano plaquetario. Los coxibs y el diclofenac, 150 mg/día, aumentarían el riesgo de eventos vasculares mayores en más de un tercio. El ibuprofeno 2400 mg/día aumentaría levemente el riesgo de eventos coronarios. El naproxeno 1000 mg/día no incrementaría el riesgo de eventos vasculares. Además, el ibuprofeno y el naproxeno tienen el potencial del disminuir el efecto cardioprotector de bajas dosis de aspirina. El naproxeno (≤ 1000 mg/día) y el ibuprofeno a bajas dosis (≤ 1200 mg/día) deberían considerarse los AINEs con el mejor perfil de seguridad cardiovascular. Las decisiones terapéuticas deben basarse en una adecuada evaluación del riesgo del paciente, utilizando los AINEs más seguros, a las menores dosis efectivas, por el menor tiempo posible que permita el control de los síntomas, restringiendo su utilización en enfermos con aumento del riesgo cardiovascular.

Non-steroidal anti-inflammatories (NSAIDs) are among the most commonly used drugs in clinical practice. They block cyclooxygenases (COX) enzymes, but the degree of inhibition of COX-1 and COX-2 varies between them. In general, NSAIDs are classified in selective COX-2 or coxibs and non-selective or traditional NSAIDs. Both the analgesic and anti-inflammatory effects, as well as the cardiovascular adverse effects, depend on the COX-2 inhibition. This paper reviews the available evidence of the increased risk of thrombotic events for both coxibs and traditional NSAID. The prothrombotic effect could be due to the inhibition of endothelial COX-2, with a decrease in production of prostacyclin and a relative increase in platelet thromboxane levels. Coxibs and diclofenac 150 mg/day seem to increase the risk of major vascular events by more than a third. Ibuprofen 2400 mg/day could slightly increase the risk of coronary events. Naproxen 1000 mg/day apparently does not increase the risk of vascular events. Besides ibuprofen and naproxen have the potential to decrease the cardioprotective effect of low doses of aspirin. Naproxen (≤ 1000 mg/day) and low doses of ibuprofen (≤ 1200 mg/day) are considered to have the most favorable thrombotic cardiovascular safety profiles of all NSAIDs. Therapeutic decisions should be based on an assessment of a person´s individual risk factors, using the safest NSAIDs, at the lowest effective doses, for the shortest duration necessary to control symptoms, restricting their use in patients with increased cardiovascular risk.

Daño renal agudo secundario a nefritis tubulointersticial aguda por uso de medicamentos. Caso clínico / Acute renal damage secondary to acute tubulointerstitial nephritis drug use. Case report

Resumen Introducción: La nefritis tubulointersticial aguda (NTIA) es infrecuente en la edad pediátrica. Se caracteriza por la infiltración del parénquima renal por células mononucleares y/o polinucleares con afectación secundaria de los túbulos sin lesión glomerular, y puede ser producida por infecciones, enfermedades inmunológicas, fármacos, o ser de origen idiopático. Objetivo: Describir un caso de NTIA secundario a antiinflamatorios no esteroidales (AINE) en un lactante, con énfasis en esta aso ciación para ser considerada por los pediatras. Caso clínico: Lactante de 10 meses, sin antecedentes previos, trasladada a nuestro hospital por daño renal agudo estadio 3, clasificación KDIGO 2012. Los tres días previos recibió tratamiento con amoxicilina e ibuprofeno por otitis media aguda. En la exploración física destacaba leve edema palpebral con presión arterial normal. En la orina presentaba proteinuria no nefrótica con componente tubular, microhematuria y leucocituria. La ecografía renal no mostraba alteraciones. Ante la sospecha de NTIA se cambió el antibiótico a cefotaxima intrave nosa y se suspendió el ibuprofeno realizándose manejo conservador del daño renal agudo. Presentó aumento de la creatinina (4.14 mg/dL) y eosinofilia, siendo el estudio inmunológico negativo. Se trató con metilprednisolona, con normalización de la función renal. Conclusión: La NTIA se puede producir por cualquier medicamento mediante una reacción inmunológica idiosincrásica. Entre los medicamentos responsables se identifican fármacos de uso frecuente en la edad pediátrica, como los AINEs, por lo que se necesita una alta sospecha diagnóstica por parte de los pediatras.

Abstract Introduction: Acute tubulointerstitial nephritis (ATIN) is a rare entity in the pediatric age. It is de fined by the infiltration of the renal parenchyma by mononuclear and/or polynuclear cells with se condary involvement of the tubules, without glomerular injury. It can be triggered by infections or immunological diseases, drugs like NSAIDs or be of idiopathic origin. Objective: To raise awareness among pediatricians about the prescription of NSAIDs, especially to patients of less than a year old, since they can provoke renal damage. Case report: A ten month old child, with no nephrological an tecedents of interest, was transferred to our hospital due to acute renal failure stage 3 KDIGO 2012. The three previous days received treatment with amoxicillin and ibuprofen for acute otitis media. Physical examination revealed mild eyelid edema with normal blood pressure. In the urine analysis, there were non-nephrotic proteinuria with tubular component, microhematuria and leukocyturia. Renal ultrasound showed no abnormalities. ATIN was suspected and so the antibiotic was changed to intravenous cefotaxime and ibuprofen was discontinued, opting for conservative management of acute renal damage. There was an increase in the number of creatinine up to 4.14 mg/dL and eosinophilia, with the immunological study being negative. Treatment with methylprednisolone was initiated, achieving normalization of renal function. Discussion: NTIA can be produced by any me dication through an idiosyncratic immune reaction. Among the responsible drugs, there are ones commonly used in the pediatric age, such as NSAIDs. Therefore, the pediatricians should pay special attention during prescriptions and have a high diagnostic suspicion of this disease.

Perioperative management of drugs commonly used in patients with rheumatic diseases: a review

Rheumatic diseases are very prevalent, affecting about 7 million people in North America; they affect the musculoskeletal system, often with systemic involvement and potential for serious consequences and limitation on quality of life. Clinical treatment is usually long-term and includes drugs that are considered either simple or complex and are occasionally unknown to many health professionals who do not know how to manage these patients in emergency units and surgical wards. Thus, it is important for clinicians, surgeons and anesthesiologists who are involved with rheumatic patients undergoing surgery to know the basic principles of therapy and perioperative management. This study aims to do a review of the perioperative management of the most commonly used drugs in rheumatologic patients. Manuscripts used in this review were identified by surveying MEDLINE, LILACS, EMBASE, and COCHRANE databases and included studies containing i) the perioperative management of commonly used drugs in patients with rheumatic diseases: and ii) rheumatic diseases. They are didactically discussed according to the mechanism of action and pharmacokinetics; and perioperative management. In total, 259 articles related to the topic were identified. Every medical professional should be aware of the types of drugs that are appropriate for continuous use and should know the various effects of these drugs before indicating surgery or assisting a rheumatic patient postoperatively. This information could prevent possible complications that could affect a wide range of patients.

Complicaciones digestivas y renales por indometacina e ibuprofeno en prematuros extremos con ductus arterioso permeable / Digestive and Kidney Complications by indomethacin and ibuprofen in extreme preterm infants with patent ductus arteriosus

El ductus arterioso permeable sintomático (DAPs) es frecuente en prematuros extremos (PE), siendo importante su cierre para disminuir la repercusión hemodinámica. Para ello se usa indometacina o ibuprofeno con los riesgos subyacentes. OBJETIVO: Caracterizar las complicaciones digestivas y renales en PE tratados por DAPs. PACIENTES Y MÉTODO: Estudio retrospectivo en PE nacidos entre enero de 2004 y diciembre de 2013. Según diagnóstico se distribuyeron en 3 grupos: sin DAPs, con DAPs tratados con indometacina y con ibuprofeno. Se excluyeron PE con otras complicaciones graves. Se evaluaron complicaciones digestivas y renales graves. Se usó significación estadistica con p ≤ 0,05. RESULTADOS: Se enrolaron 599 PE; 33,1% recibió tratamiento por DAPs, 66,9% no lo requirió. Hubo asociación estadística entre DAPs y menor edad gestacional, depresión neonatal y distrés respiratorio. Del grupo no tratado, el 5% presentó enterocolitis y el 0,25% falla renal; entre los tratados el 2,5% presentó enterocolitis y el 1,0% falla renal. No hubo diferencias estadísticas significativas considerando ambas complicaciones (p = 0,17), sólo enterocolitis (p = 0,11) o sólo falla renal (p = 0,33) entre tratados y no tratados; tampoco las hubo al comparar complicaciones entre tratados con indometacina o ibuprofeno. CONCLUSIONES: Los resultados en nuestra población demuestran que el tratamiento médico del DAPs, en ausencia de otras complicaciones clínicas, no representa un mayor riesgo de complicaciones graves digestivas o renales. No se demostraron ventajas entre la indometacina e ibuprofeno.

The symptomatic patent ductus arteriosus (sPDA) is common in extremely premature infants (EPI). In order to decrease the hemodynamic repercussion and avoid complications it is necessary to close it. Indomethacin or ibuprofen are used for this purpose with its associated risks. OBJECTIVE: Characterize digestive and renal complications in EPI who received indomethacin or ibuprofen as sPDA treatment. PATIENTS AND METHOD: Retrospective study on EPI between January-2004 and December-2013. Three groups were compared: treated with indomethacin or ibuprofen and a non-treated group. EPI with other serious complications were excluded. The primary outcomes on each group were digestive and/or renal complications. Statistical significance was p < 0.05. RESULTS: 599 EPI were included, 33.1% with PDA received treatment and 66.9% did not need it. A statistical association was found between sPDA and lower gestational ages, neonatal depression and respiratory distress. In the non-treated group, 5% presented enterocolitis and 0.25% renal failure; on the treated group, 2.5% presented enterocolitis and 1.0% renal failure. No significant differences were found between the treated and non-treated groups in relation to complications considering enterocolitis (p = 0.11) or renal failure (p = 0.33) alone, or combined (p = 0.17). No difference were detected either between those treated with indomethacin or ibuprofen. CONCLUSIONS: The results show that in absence of other clinical complication, medical treatment of sPDA with indomethacin or ibuprofen, do not increase the risk of serious digestive or renal disorders. There were no advantages of using indomethacin or ibuprofen over the other.

Eficacia y seguridad del uso de tocilizumab para el tratamiento de artritis idiopatica juvenil en pacientes con falla alt ratamiento con aines, glucocorticoides y farmes / Efficacy and safety of the use of tocilizumab for the treatment of juvenile idiopathic arthritis in patients with failure to treat with aines, glucocorticoids and pharmacies

INTRODUCCIÓN: Antecedentes: El presente dictamen responde a la solicitud de evaluación del uso fuera del petitorio de tocilizumab para el tratamiento de pacientes con Artritis Idiopática Juvenil refractarios a tratamiento con FARMES. La Artritis Idiopática Juvenil (AIJ) engloba varios tipos de artritis crónica cuyo inicio se da antes de los 16 años, y está dada de manera general por un mal funcionamiento del sistema inmune que resulta en producción excesiva de moléculas pro-inflamatorias dirigidas principalmente a la membrana (revestimiento de las articulaciones). Tecnologia Sanitaria de Interés: Tocilizumab, con nombre comercial Actemra, es un anticuerpo monoclonal recombinante humanizado contra el receptor de interleucina-6 (IL-6). Este anticuerpo se une a los receptores de IL-6 que se encuentran en las membranas celulares o disueltos en el plasma, interrupiendo la unión de la IL-6 con su receptor en los tejidos. La IL-6 es una citoquina pro-inflamatoria secretada por células del sistema inmune, y que participa en diversas patologias asociadas a procesos inflamatorios. Tocilizumab ejerce su acción bloqueando los receptos de IL-6 de tal manera que no pued ser activada la cascada de señalización intracelular que lleva a la inflamación de los tejidos. METODOLOGÍA: Estrategia de Busqueda: Se utilizó el motor de búsqueda Pubmed empleando el algoritmo mostrado en la subsección B y los filtros correspondientes a meta-análisis, revisiones sistemáticas y ensayos clínicos, en línea con los criterios de elegibilidad. Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de tocilizumab para el tratamiento de Artritis Idiopática Juvenil de varidad sistémica. La búsqueda se inició revisando la información sobre el uso del medicamento de acuerdo con entidades reguladoras como la Food And Drug Administration (FDA), la European Medicines Agency (EMA) y la Dirección General de Medicamentos y Drogas (DIGEMID). Posteriormente, se revisaron las bases de datos de PubMed, TRIPDATABASE y www.clinicaltrials.gov. Adicionalmente, se realizó una búsqueda de evaluaciones de tecnologías y guías de práctica clínica en las páginas wev de grupos dedicados a la invstigación y educación en salud en general como The National Institute for Health and Care Excellence (NICE); y especializados en Enfermedades Reumatoides como el American College or Rheumatology (ACR). RESULTADOS: Sinopsos de la Evidencia: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda de evidencia científica relacionada al uso de tocilizumab como tratamiento de pacientes con Artritis Idiopática Juvenil varidad sistémica refractaria a tratamiento convencional con AINEs, corticoides y FARMEs. En la presente sinopsis se describe la evidencia disponible según el tipo de publicación, siguiendo lo indicado en los criterios de elegibilidad (GPC, ETS, RS, MA y ECA fase III). CONCLUSIONES: La GPC y la ETS recomiendan el uso de tocilizumab como una alternativa de tratamiento de AIJ sistémica en niños mayores de 2 años quienes han presentado una respuesta inadecuada a AINEs, corticosteroides sistémicos y metotrexato (FARME). Tocilizumab presenta una mayor frecuencia de eventos adversos moderados y severos en comparación con placebo. Sin embargo, estos son controlables. Tocilizumab no está recomendado para el tratamiento de pacientes mayores de 2 años con AIJ que responden al tratamiento con metotrexato o no han sido tratados con metotrexato previamente. El Instituto de Evaluaciones de Tecnologías en Salud e Investigación-IETSI, aprueba el uso de tocilizumab para el manejo de los pacientes con diagnóstico de AIJ variedad sistémica refractaria a AINEs corticosteroides y FARMEs.

The role of aspirin desensitization in patients with aspirin-exacerbated respiratory disease (AERD) / O papel da dessensibilização à aspirina em pacientes portadores de doença respiratória exacerbada por aspirina (DREA)

ABSTRACT INTRODUCTION: Aspirin-exacerbated respiratory disease (AERD) consists of a classic tetrad: moderate/severe asthma, chronic rhinosinusitis, nasal polyps, and intolerance to aspirin or other nonsteroidal anti-inflammatory drugs. Clinical control with drugs, surgery, and desensitization are treatment options. OBJECTIVE: To evaluate the efficacy and tolerability of aspirin desensitization in patients with AERD. METHODS: Periodic symptom assessment and endoscopy in patients with AERD undergoing surgery who were desensitized. RESULTS: Seventeen patients were desensitized. Eight patients completed the desensitization and were followed for a minimum of a one-year period (mean 3.1 years). These patients showed improvement in all symptoms. Moreover, surgical reassessment was not indicated in any of these patients and there was a decrease in costs with medication and procedures. Eight patients did not complete desensitization, mainly due to procedure intolerance and uncontrolled asthma, whereas another patient was lost to follow-up. CONCLUSION: Aspirin desensitization, when tolerated, was effective in patients with AERD and with poor clinical/surgical response.

Resumo Introdução: A doença respiratória exacerbada por aspirina é composta pela tétrade clássica: asma moderada/grave, rinossinusite crônica, pólipos nasais e intolerância à aspirina ou outro anti-inflamatório não esteroide. Controle clínico com medicamentos, cirurgias e dessensibilização são opções de tratamento. Objetivo: Avaliar a eficácia e tolerabilidade da dessensibilização à aspirina em pacientes com doença exacerbada por aspirina. Método: Avaliação periódica dos sintomas e exame endoscópico em pacientes com doença respiratória exacerbada por aspirina submetidos à cirurgia e dessensibilizados. Resultados: Dezessete pacientes foram dessensibilizados, dos quais oito pacientes completaram a dessensibilização e foram acompanhados pelo tempo mínimo de 1 ano (média de 3,1 anos). Todos referiram melhora de todos os sintomas; não houve nenhuma indicação de reabordagem cirúrgica, e houve redução de gastos com medicações e procedimentos. Outros oito pacientes não completaram a dessensibilização, principalmente por intolerância ao procedimento e descontrole da asma, enquanto outro paciente perdeu o seguimento. Conclusão: A dessensibilização à aspirina, quando tolerada, mostrou-se eficaz nos pacientes com doença respiratória exacerbada por aspirina com resposta clínica/cirúrgica insatisfatória.

Cardiac complications in a metamizole-induced type I Kounis syndrome / Complicações cardíacas em síndrome de Kounis tipo I induzida por metamizol

ABSTRACT Kounis syndrome is defined as the coincidental occurrence of allergic reaction and acute coronary syndrome secondary to vasospasm. Anti-inflammatory drugs are included as one of the multiple causes. Current data available about this syndrome come from case reports. We present the case of a patient who suffered Kounis syndrome with cardiogenic shock and asystole after intravenous infusion of Metamizole, and in which no lesions were observed in coronariography.

RESUMO A síndrome de Kounis é definida como a ocorrência concomitante de reação alérgica e síndrome coronariana aguda secundária ao vasoespasmo. Os medicamentos anti-inflamatórios estão incluídos como uma das múltiplas causas. Os dados atuais disponíveis sobre essa síndrome são provenientes de relatos de caso. Relatamos o caso de um paciente que apresentou síndrome de Kounis com choque cardiogênico e assistolia após infusão intravenosa de metamizol e no qual não foram observadas lesões na coronariografia.