Uso de ibuprofeno en el tratamiento de pacientes pediátricos con poliuria y disnatremia. Reporte de una serie de casos / Ibuprofen use for the treatment of pediatric patients with polyuria and dysnatremia. A case series report

Los niños con lesiones selares y/o supraselares pueden presentar diabetes insípida central con posterior secreción inadecuada de hormona antidiurética. Nosotros observamos, en algunos casos, aumento de la incidencia de poliuria, natriuresis e hiponatremia, tríada diagnóstica del síndrome cerebral perdedor de sal. Aquí comunicamos la evolución de 7 pacientes con antecedentes de daño agudo del sistema nervioso central y diabetes insípida central seguida por síndrome cerebral perdedor de sal. Como tratamiento aportamos secuencialmente fluidos salinos parenterales, cloruro de sodio oral, desmopresina, mineralocorticoides e incluso tiazidas. Ante la persistencia de poliuria con hiponatremia, agregamos ibuprofeno. Como resultado de este esquema terapéutico secuencial, este grupo redujo significativamente los valores de diuresis diaria de 10 ml/kg/h a 2 ml/kg/h en un tiempo promedio de 5 días, normalizando también las natremias (de 161 mEq/L a 143 mEq/L) en un tiempo promedio de 9 días. En ningún caso observamos efectos adversos asociados al tratamiento.

Children with sellar and/or suprasellar lesions may develop central diabetes insipidus with subsequent inappropriate antidiuretic hormone secretion. An increased incidence of polyuria, natriuresis, and hyponatremia has been reported in some cases, which make up the diagnostic triad of cerebral salt wasting syndrome. Here we report the clinical course of 7 patients with a history of acute central nervous system injury and central diabetes insipidus followed by cerebral salt wasting syndrome. Treatment included the sequential use of parenteral saline solution, oral sodium chloride, desmopressin, mineralocorticoids, and even thiazides. Due to persistent polyuria and hyponatremia, ibuprofen was added. As a result of this sequential therapeutic regimen, daily urine output reduced significantly from 10 mL/ kg/h to 2 mL/kg/h over an average period of 5 days, together with a normalization of natremia (from 161 mEq/L to 143 mEq/L) over an average period of 9 days. No treatment-related adverse effects were observed in any case.

Prescripción de fármacos cardiotóxicos en pacientes con enfermedades cardiovasculares / Prescription of cardiotoxic drugs in patients with cardiovascular diseases

Introducción: El uso de fármacos con potencial cardiotóxico para tratar enfermedades no cardiovasculares coexistentes resulta un agravante evitable. Objetivo: Evaluar la prescripción de 5 fármacos cardiotóxicos en pacientes con enfermedades cardiovasculares. Métodos: Se realizó un estudio descriptivo transversal (enmarcado en los estudios de utilización de medicamentos) de marzo a diciembre de 2020 en el Policlínico Santa Cruz (Artemisa, Cuba), en una población de 234 sujetos con enfermedades cardiovasculares que habían sido tratados con domperidona, azitromicina, ciprofloxacina, ibuprofeno y diclofenaco. Las variables estudiadas fueron: sexo, edad, consumo de fármacos cardiotóxicos, motivo de indicación, enfermedades cardiovasculares, forma farmacéutica, dosis diaria, intervalo de las dosis y duración del tratamiento. Se realizó un análisis estadístico descriptivo. Resultados: Los fármacos más prescritos fueron la azitromicina (n= 63), el ibuprofeno (n= 59) y la ciprofloxacina (n= 57). Sus principales motivos de indicación fueron, respectivamente, la neumonía adquirida en la comunidad (38,1 por ciento), las infecciones de piel y tejidos blandos (28,8 por ciento), y las infecciones del tracto urinario (43,8 por ciento). La principal enfermedad cardiovascular fue la hipertensión arterial. Para los 5 fármacos seleccionados se reportó su esquema terapéutico (forma farmacéutica, dosis diaria, intervalo de dosis y duración del tratamiento). Conclusiones: Aunque en todos los casos el motivo de indicación es el adecuado, los fármacos pueden sustituirse por otros de menor riesgo cardiovascular. En su mayoría, los esquemas terapéuticos son correctos, salvo en los casos de la domperidona (duración prolongada) y el diclofenaco (altas dosis)(AU)

Introduction: The use of drugs with cardiotoxic potential to treat coexisting noncardiovascular diseases results in avoidable aggravation. Objective: To assess the prescription of 5 cardiotoxic drugs in patients with cardiovascular disease. Methods: A cross-sectional descriptive study (framed in the studies of drug utilization) was carried out from March to December 2020 in the Policlínico Santa Cruz (Artemisa, Cuba), in a population of 234 subjects with cardiovascular diseases who had been treated with domperidone, azithromycin, ciprofloxacin, ibuprofen and diclofenac. The variables studied were: sex, age, consumption of cardiotoxic drugs, reason for indication, cardiovascular disease, pharmaceutical form, daily dose, dose interval, and duration of treatment. Descriptive statistical analysis was performed. Results: The most prescribed drugs were azithromycin (n= 63), ibuprofen (n= 59) and ciprofloxacin (n= 57). Their main reasons for indication were, respectively, community-acquired pneumonia (38.1 percent), skin and soft tissue infections (28.8 percent), and urinary tract infections (43.8 percent). The main cardiovascular disease was arterial hypertension. For the 5 selected drugs, their therapeutic scheme (pharmaceutical form, daily dose, dose interval and duration of treatment) was reported. Conclusions: Although in all cases the reason for indication was adequate, the drugs can be substituted by others of lower cardiovascular risk. For the most part, the therapeutic regimens are correct, except in the cases of domperidone (prolonged duration) and diclofenac (high doses)(AU)

Efficacy of Ibuprofen after Total Hip Arthroplasty to Prevent Heterotopic Ossification: Systematic Review and Meta-Analysis / Eficácia do ibuprofeno após artroplastia total de quadril para prevenção de ossificação heterotópica: Revisão sistemática e metanálise

Abstract The objective of this study was to conduct a systematic review and meta-analysis of relevant randomized control trials (RCTs) to determine the role of ibuprofen, as well as the optimum dose and duration of therapy, in preventing the incidence of heterotopic ossification (HO) after primary total hip arthroplasty (THA). A literature search was performed using the PubMed/MEDLINE and Cochrane Library databases for RCTs that compared the use of ibuprofen versus placebo as prophylaxis for HO in patients after THA. The main outcomes for this study were overall occurrence of HO, occurrence according to the Brooker classification, and gastrointestinal complications. A total of 27 potential articles were identified from the database. Eventually, four trials with 1,153 patients were included in the final analysis. When compared with placebo, the use of ibuprofen is associated with a reduction in the incidence of HO at the 3- and 12-month follow-up appointments, as well as the incidence of Brooker II and III HO (p < 0.05). However, there was no significant difference between the ibuprofen and placebo groups in terms of treatment discontinuation due to gastrointestinal complications or the incidence of Brooker I and IV HO (p > 0.05). The existing data indicates that ibuprofen is safe and efficacious in reducing the total incidence of HO along with Brooker II and III HO at follow-up. However, due to the small number of studies, the conclusions are limited; therefore, more high-quality clinical trials are required to develop guidelines for optimal dose and duration of therapy.

Resumo O objetivo deste estudo foi realizar uma revisão sistemática e metanálise de estudos clínicos randomizados (ECRs) relevantes para determinar o papel do ibuprofeno, sua dose ideal, e a duração do tratamento na prevenção de ossificação heterotópica (OH) após a artroplastia total primária do quadril (ATQ). Uma pesquisa bibliográfica foi feita nos bancos de dados PubMed/MEDLINE e Cochrane Library para a obtenção de ECRs quecomparassem ouso de ibuprofeno edeplacebo como profilaxiaparaOHem pacientes submetidos à ATQ. Os principais desfechos deste estudo foram ocorrência geral de OH, classificação de Brooker da OH, e complicações gastrintestinais. No total, 27 artigos foram identificados nos bancos de dados e 4 estudos, com 1.153 pacientes, foram incluídos na análise final. Em comparação ao placebo, o uso de ibuprofeno reduziu a incidência de OH aos 3 e 12 meses de acompanhamento e a incidência de OH Brooker II e III (p < 0,05). No entanto, não houve diferença significativa entre os grupos que receberam ibuprofeno e placebo em termos de interrupção do tratamento devido a complicações gastrintestinais ou da incidência de OH Brooker I e IV (p > 0,05). Os dados existentes indicam que o ibuprofeno é seguro e eficaz na redução da incidência total de OH e de OH Brooker II e III durante o acompanhamento. No entanto, as conclusões são limitadas devido ao pequeno número de estudos; logo, mais estudos clínicos de alta qualidade são necessários para o desenvolvimento de diretrizes em relação à dose e duração ideal da terapia.

Comparación: acetaminofén vs ibuprofeno para el tratamiento de los síntomas en pacientes con infección por SARS-CoV-2 / Comparação: paracetamol vs ibuprofeno para o tratamento de sintomas em pacientes com infecção por SARS-CoV-2 / Comparison: acetaminophen vs ibuprofen for the treatment of symptoms in patients with SARS-CoV-2 infection

La propagación del COVID-19 fue expedita y tras varios informes la eficacia de algunos medicamentos antiinflamatorios no esteroideos, como el ibuprofeno, estuvo bajo sospecha. Mientas que el paracetamol (acetaminofén) se sugirió como una alternativa segura y recomendable para el manejo temprano y domiciliario del dolor y fiebre en pacientes. Objetivo. Comparar el uso del acetaminofén vs ibuprofeno para tratamiento de los síntomas en pacientes con infección por SARS-COV-2". Metodología. La investigación es una revisión sistemática, donde, se analizaron artículos científicos publicados en revistas vinculadas a áreas de salud, disponibles en buscadores y plataformas digitales tales, como Scienedirect, Pubmed, Elsevier y Springer Link. Las búsquedas se realizaron utilizando las palabras claves previamente definidas. Conclusión. El uso del ibuprofeno ha estado en duda desde sus inicios, en pacientes con COVID-19. Sin embargo, ningún estudio afirma asociar el uso del mismo con aumentos importantes en estadía hospitalaria, ingresos en UCI, necesidad de ventilación mecánica, ni mortalidad. Sin embargo, el acetaminofén ha sido utilizado desde un principio, su uso no estuvo en duda, pero los hallazgos recientes parecen indicar que no es tan eficaz como se pensaba en un principio. Siendo bastante inferior en la comparación directa con el ibuprofeno.

The spread of COVID-19 was expeditious and after several reports the efficacy of some non-steroidal anti-inflammatory drugs, such as ibuprofen, was under suspicion. While paracetamol (acetaminophen) was suggested as a safe and recommended alternative for early and home management of pain and fever in patients. Objective. To compare the use of acetaminophen vs ibuprofen for symptom management in patients with SARS-COV-2 infection". Methodology. The research is a systematic review, where scientific articles published in journals related to health areas, available in search engines and digital platforms such as Scienedirect, Pubmed, Elsevier and Springer Link, were analyzed. Searches were performed using previously defined keywords. Conclusion. The use of ibuprofen has been in question since its inception in patients with COVID-19. However, no study claims to associate its use with significant increases in hospital stay, ICU admissions, need for mechanical ventilation, or mortality. However, acetaminophen has been used from the beginning, its use was not in doubt, but recent findings seem to indicate that it is not as effective as originally thought. It is quite inferior in direct comparison with ibuprofen.

A disseminação da COVID-19 foi rápida e, após vários relatos, a eficácia de alguns anti-inflamatórios não esteroides, como o ibuprofeno, ficou sob suspeita. Já o paracetamol (acetaminofeno) foi sugerido como uma alternativa segura e recomendada para o tratamento precoce e domiciliar da dor e da febre nos pacientes. Objetivo. Comparar o uso de acetaminofeno versus ibuprofeno para o controle dos sintomas em pacientes com infecção por SARS-COV-2". Metodologia. A pesquisa é uma revisão sistemática, onde foram analisados artigos científicos publicados em periódicos relacionados às áreas de saúde, disponíveis em sites de busca e plataformas digitais como Scienedirect, Pubmed, Elsevier, e Springer Link. As buscas foram realizadas por meio de palavras-chave previamente definidas. Conclusões. O uso do ibuprofeno tem sido questionado desde sua criação em pacientes com COVID-19. No entanto, nenhum estudo afirma associar seu uso a aumentos significativos na permanência hospitalar, internações em UTI, necessidade de ventilação mecânica ou mortalidade. No entanto, o acetaminofeno tem sido usado desde o início, seu uso não foi questionado, mas descobertas recentes parecem indicar que ele não é tão eficaz quanto se pensava originalmente. Ele é muito inferior em comparação direta com o ibuprofeno.

Conducto arterioso permeable: mecanismos moleculares del cierre y su relacion con el tratamiento / Patent ductus arteriosus: molecular mechanisms of closure and their relationship with the treatment

El conducto arterioso establece una conexión esencial entre la arteria aorta descendente proximal y la arteria pulmonar principal cerca del origen de la rama pulmonar izquierda, siendo vital durante la vida fetal y generalmente cerrándose poco después del nacimiento en la mayoría de los recién nacidos a término; no obstante, en recien nacidos pretermino, es común la persistencia del conducto arterioso debido a estímulos vasodilatadores que mantienen su permeabilidad y flujo sanguíneo constante, requiriendo enfoques de tratamiento que involucran la inhibición de la prostaglandina E2 y antiinflamatorios no esteroides, aunque la comparación de su eficacia con métodos conservadores sigue siendo poco clara, especialmente en recién nacidos prematuros extremos. La presente revisión tiene como objetivo proporcionar una comprensión de los mecanismos moleculares clave detrás de la fisiopatología del conducto arterioso persistente y su abordaje terapéutico.

The ductus arteriosus establishes an essential connection between the proximal descending aorta and the main pulmonary artery near the origin of he left pulmonary branch, being vital during fetal life and generally closing shortly after birth in most term newborns; However, in preterm infants, persistence of the ductus arteriosus is common due to vasodilator stimuli that maintain its patency and constant blood flow, requiring treatment approaches involving prostaglandin E2 inhibition and nonsteroidal anti-inflammatory drugs, although the comparison of their efficacy with conservative methods remains unclear, especially in extremely preterm infants. The present review aims to provide an understanding of the key molecular mechanisms behind the pathophysiology of patent ductus arteriosus and its therapeutic approach.

Reversal of itraconazole resistance in Sporothrix brasiliensis and Sporothrix schenckii by nonsteroidal anti-inflammatory drugs.

BACKGROUND: The emergence of resistant isolates has brought challenges to the treatment of sporotrichosis, prompting the search for new therapeutic strategies. Previous studies reported that nonsteroidal anti-inflammatory drugs (NSAIDs) show in vitro activity against several pathogenic fungi, including species of Candida, Cryptococcus, and Trichosporon. AIMS: This study aimed to investigate the in vitro efficacy of three NSAIDs (acetylsalicylic acid, diclofenac sodium, and ibuprofen), alone and in combination with itraconazole, against eleven clinical isolates of Sporothrix brasiliensis and Sporothrix schenckii. METHODS: Minimal inhibitory concentrations were determined by the broth microdilution method. Drug interactions and the fractional inhibitory concentration index of NSAIDs and itraconazole were assessed by the checkerboard method. RESULTS: When used alone, ibuprofen was the most active NSAID, followed by acetylsalicylic acid. Combinations of NSAIDs with itraconazole showed synergistic antifungal activity against nine isolates. It was also found that itraconazole combined with acetylsalicylic acid, diclofenac sodium, or ibuprofen, led to resistance reversal in two, three, and five of the six drug-resistant isolates, respectively. CONCLUSIONS: The results indicate that the combination of itraconazole and the evaluated NSAIDs are a promising strategy for the treatment of sporotrichosis.

Comparison of intravenous ibuprofen versus ketorolac for postoperative analgesia in children undergoing lower abdominal surgery: A randomized, controlled, non-inferiority study.

BACKGROUND: Non-steroidal anti-inflammatory drugs are often used as part of multimodal analgesia to control postoperative pain. This randomized, controlled, double-blinded, non-inferiority study aimed to compare the postoperative analgesic effects of intravenous ibuprofen versus ketorolac in children undergoing open unilateral lower abdominal surgery. The authors hypothesized that postoperative analgesia produced by intravenous ibuprofen would be non-inferior to that of intravenous ketorolac. METHODS: Sixty-six children aged 2 to 8 years who were scheduled to undergo unilateral lower abdominal surgery, were recruited. Patients in the ibuprofen group received 10mg/kg/6h intravenous ibuprofen. Patients in the ketorolac group were given 0.5mg/kg/6h intravenous ketorolac. The primary outcome measure was 24-h postoperative morphine consumption. The secondary outcome measures were postoperative pain score, the incidence of early postoperative fever and the incidence of ibuprofen and ketorolac adverse effects including pain during drug infusion, vomiting, epigastric pain and allergic reaction. RESULTS: Fifty-nine patients completed the study (30 ibuprofen, 29 ketorolac). There was no significant difference (P=0.305) in the mean (SD) 24-h postoperative morphine consumption (µ/kg) between intravenous ibuprofen, 16.00 (5.31), and ketorolac, 14.65 (4.61). The reported pain scores were similar in both groups. The incidence of postoperative fever was significantly lower (p=0.039) in the ibuprofen group (3%) than the ketorolac group (20%). The incidence of adverse effects was similar in both ibuprofen and ketorolac groups. CONCLUSIONS: Intravenous ibuprofen can be used as an alternative to ketorolac for postoperative analgesia in children undergoing unilateral lower abdominal surgery because both drugs similarly provide safe and effective postoperative analgesia.

Effect of ibuprofen and low-intensity pulsed ultrasound on the reduction of pain after initial archwire placement: a double-blind randomized clinical trial / Efecto del ibuprofeno y el ultrasonido pulsado de baja intensidad en la reducción del dolor después de la colocación inicial del arco de ortodoncia: un ensayo clínico aleatorizado doble ciego

Objective: This study aimed to compare the effect of ibuprofen and low intensity pulsed ultrasound (LIPUS) on the reduction of pain after the placement of initial archwire in orthodontic patients. Material and Methods: This double-blind clinical trial study was carried out on 60 female candidates for fixed orthodontic treatment referring to the Orthodontic Department of School of Dentistry in Mashhad University of Medical Sciences, Mashhad, Iran, during 2015-2016. The subjects were divided into four groups of ibuprofen, LIPUS, placebo, and mock LIPUS. A questionnaire and a rectangular and flexible cubic silicone were given to each patient to record the severity of pain based on the visual analog scale at specified time points (i.e., 2 h, 6 h, at bedtime, 2nd, 3rd, and 7th days after archwire placement) when biting the silicone block with the anterior and posterior teeth and without biting at all. Repeated measures analysis of variance was used in order to compare the pain severity at different time points. Results: The comparison of pain severity at various time points showed that the highest and lowest mean scores of pain were reported at bedtime and seven days after the intervention (p<0.001). In each of the three conditions (i.e., biting the silicone block with the anterior and posterior teeth and without biting the teeth) at six time points (i.e., 2 h, 6 h, at bedtime, 2nd, 3rd, and 7th days following archwire placement), no significant difference was observed in the severity of pain (p>0.05). Conclusion: In conclusion, LIPUS (with a frequency of 1 MHz and an intensity of 100 mW) and ibuprofen have no significant effects on reduction of the pain severity at different time points and various conditions in orthodontic patients.

Objetivo: Este estudio tuvo como objetivo comparar el efecto del ibuprofeno y el ultrasonido pulsado de baja intensidad (LIPUS) en la reducción del dolor después de la colocación del arco inicial en pacientes de ortodoncia. Material y Métodos: Este estudio de ensayo clínico doble ciego se llevó a cabo en 60 candidatas a tratamiento de ortodoncia fija referidas al Departamento de Ortodoncia de la Facultad de Odontología de la Universidad de Ciencias Médicas de Mashhad, Mashhad, Irán, durante 2015-2016. Los sujetos se dividieron en cuatro grupos: ibuprofeno, LIPUS, placebo y LIPUS simulado. Se entregó un cuestionario y un bloque de silicona cúbica rectangular y flexible a cada paciente para registrar la intensidad del dolor según la escala analógica visual en puntos de tiempo específicos (es decir, 2 h, 6 h, hora de acostarse, 2do, 3er y 7mo día después de la colocación del arco) al morder el bloque de silicona con los dientes anteriores y posteriores, y sin morder en absoluto. Se utilizó el análisis de varianza de medidas repetidas para comparar la intensidad del dolor en diferentes momentos.Resultados: La comparación de la intensidad del dolor en varios puntos de tiempo mostró que las puntuaciones medias de dolor más altas y más bajas se informaron a la hora de acostarse y siete días después de la intervención (p<0,001). En cada una de las tres condiciones (es decir, al morder el bloque de silicona con los dientes anteriores y posteriores, y sin morder) en seis momentos (2 h, 6 h, antes de acostarse 2do, 3er y 7mo día después de la colocación del arco), no se observó diferencia significativa en la severidad del dolor (p>0.05).Conclusión: En conclusión, LIPUS (con una frecuencia de 1 MHz y una intensidad de 100 mW) y el ibuprofeno no tienen efectos significativos en la reducción de la severidad del dolor en diferentes puntos de tiempo y diversas condiciones en pacientes de ortodoncia.

Qual Deve Ser o Tratamento de Primeira Linha para o Fechamento de Persistência de Canal Arterial Hemodinamicamente Significativo em Bebês Prematuros? / What Should be the First-line Treatment for the Closure of Hemodynamically Significant Patent Ductus Arteriosus in Premature Infants?

Resumo Fundamento É importante saber qual medicamento usar como tratamento de primeira linha para fechar o duto. Objetivos O objetivo deste estudo é comparar a eficácia e os efeitos colaterais das formas intravenosas (IV) de ibuprofeno e paracetamol e contribuir para a literatura investigando o primeiro medicamento selecionado no tratamento clínico da persistência do canal arterial (PCA). Métodos Nosso estudo foi realizado entre janeiro de 2017 e dezembro de 2019. Foram incluídos no estudo bebês prematuros com peso ao nascer (PN) ≤1500 g e idade gestacional (IG) ≤32 semanas. No período do estudo, todos os bebês com persistência do canal arterial hemodinamicamente significativa (hsPCA) receberam ibuprofeno intravenoso (IV) como resgate como tratamento clínico primário ou tratamento com paracetamol IV se houvesse contraindicações para o ibuprofeno. Os pacientes foram divididos em dois grupos: pacientes que receberam ibuprofeno IV e pacientes que receberam paracetamol IV. Resultados Desses pacientes, 101 receberam paracetamol IV e 169 receberam ibuprofeno IV. A taxa de sucesso do fechamento da PCA com o primeiro curso do tratamento foi de 74,3% no grupo de paracetamol IV e 72,8% no grupo de ibuprofeno IV (p=0,212). Conclusões Nossos resultados mostram que o paracetamol IV é tão eficaz quanto o ibuprofeno IV no tratamento de primeira linha de hsPCA, podendo se tornar o tratamento preferencial para o controle de hsPCA.

Abstract Background It is important which medicine to use as a first-line treatment to close the duct. Objectives The aim of this study is to compare the effectiveness and side effects of intravenous (IV) forms of ibuprofen and paracetamol and to contribute to the literature investigating the first drug selected in the medical treatment of patent ductus arteriosus (PDA). Methods Our study was conducted between January 2017 and December 2019. Premature infants with birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks were included in the study. In the study period, all infants with hemodynamically significant patent ductus arteriosus (hsPDA) were given rescue intravenous (IV) ibuprofen as a primary medical treatment or IV paracetamol treatment if there were contraindications for ibuprofen. The patients were divided into two groups: patients receiving IV ibuprofen and patients receiving IV paracetamol. Results Of these patients, 101 were given IV paracetamol and 169 were given IV ibuprofen. The success rate of PDA closure with first-course treatment was 74.3% in the IV paracetamol group and 72.8% in the IV ibuprofen group (p=0.212). Conclusions Our results show that IV paracetamol is as effective as IV ibuprofen in the first-line treatment of hsPDA, and can become the preferred treatment for the management of hsPDA.

Patent ductus arteriosus in preterm newborns: A tertiary hospital experience.

INTRODUCTION: Patent ductus arteriosus (PDA) in preterm infants has been associated with increased mortality and comorbidities. This study aimed to characterize the population of preterm infants diagnosed with PDA and to identify predictive factors of response to medical treatment of PDA. METHODS: An eight-year retrospective observational study was carried out, which included all preterm infants with a gestational age (GA) between 23 and 32 weeks diagnosed with PDA, admitted to the Neonatal Unit of the CHUSJ. Univariate comparative analysis was performed, and models for predicting the effectiveness of PDA treatment with ibuprofen were explored by multivariate logistic regression analysis. RESULTS: 115 cases were included and 34 were excluded, with a final sample of 81 preterm infants with PDA. The univariate analysis revealed significant differences in the closure efficacy via medical treatment with ibuprofen in several variables, and a multivariate logistic regression model was obtained (discriminative capacity 72.2%, sensitivity 98.1%, specificity 57.1%), taking into account the effect of GA, type of delivery, need for diuretics treatment and platelet transfusion. CONCLUSION: This study enabled the population of preterm infants diagnosed with PDA to be characterized and the identification of a predictive model that can help predict the efficacy of medical treatment and thus contribute to optimizing the medical approach to the non-responders.

Patent ductus arteriosus closure: experience from a tertiary referral center / Experiência de uma maternidade terciária no fechamento do canal arterial patente

ABSTRACT Objective: To characterize the number and methods of closure of Persistent Ductus Arteriosus (PDA) over a span of 16 years in a third level maternity hospital. Methods: Retrospective study of neonates born between January 2003 and Deccember 2018, who underwent ductus arteriosus closure by pharmacological, surgical and/or transcatheter methods. Gestational age, birth weight, number and methods of closures per year were evaluated. The success rate of the pharmacologic method was calculated, as well as the mortality rate. The association between mortality and birthweight, treatment used and treatment failure was explored. Results: There were 47,198 births, 5,156 were preterm, 325 presented PDA and 106 were eligible for closure (median gestational age - 27 weeks, birthweight <1000 g - 61%). Frequency of PDA closure decreased during the study period, especially starting in 2010. Success rate with pharmacologic treatment was 62% after the first cycle and 74% after the second. After drug failure, 12 underwent surgical ligation and two underwent transcatheter closure. Exclusive surgical ligation was indicated in four infants. Ibuprofen replaced indomethacin in 2010, and acetaminophen was used in three infants. Among the 106 infants, hospital mortality was 12% and it was associated with birthweight <1000 g (13/65 <1000 vs. 0/41 >1000 g; p=0.002) and with failure in the first pharmacologic treatment cycle (13/27 with failure, vs. 0/75 without failure; p<0.001). Conclusions: The national consensus published in 2010 for the diagnosis and treatment of PDA in preterm infants led to a decrease in the indication for closure. Pharmacological closure was the method of choice, followed by surgical ligation. Birthweight <1000 g and first cycle of pharmacologic treatment failure were associated with higher mortality.

RESUMO Objetivo: Caraterizar o número e métodos de fechamento de canal arterial durante 16 anos numa maternidade de nível terciário. Métodos: Estudo retrospetivo de nascidos entre 01 de janeiro de 2003 a 31 de dezembro de 2018 submetidos a fechamento do canal arterial por métodos farmacológico, cirúrgico e/ou percutâneo. Avaliaram-se idade gestacional, sexo, peso ao nascimento, número de fechamentos por ano e método utilizado. Aferiram-se as taxas de sucesso de método farmacológico e de mortalidade e sua associação com peso ao nascer, fármaco utilizado e insucesso do fechamento. Resultados: Verificaram-se 47.198 recém-nascidos, 5.156 prematuros, dos quais 325 com canal arterial patente, sendo 106 com indicação para fechamento (idade gestacional mediana 27 semanas, peso <1000 g em 61%). Verificou-se diminuição do número de fechamentos ao longo dos anos, sobretudo a partir de 2010. O fechamento ocorreu em 62% após primeiro ciclo de tratamento farmacológico e em 74% após segundo. Após insucesso farmacológico, 12 realizaram ligadura cirúrgica e dois, fechamento percutâneo. Houve indicação de ligadura cirúrgica exclusiva em quatro. O ibuprofeno substituiu a indometacina em 2010. O acetaminofen foi usado em três doentes. A mortalidade nos 106 pacientes foi de 12%, associando-se ao peso ao nascer (13/65 <1000 vs. 0/41 >1000 g; p=0,002) e à falha do primeiro ciclo de tratamento farmacológico (13/27 com falha vs. 0/75 com sucesso; p<0,001). Conclusões: Consenso nacional de 2010 para diagnóstico e tratamento do canal arterial nos prematuros levou à diminuição do número de fechamentos desse canal. O fechamento farmacológico foi o método mais utilizado, seguido da ligadura cirúrgica. Peso <1000 g e falha no primeiro ciclo de fechamento farmacológico se associaram à maior mortalidade.

Standard headache and neuralgia treatments and SARS-CoV-2: opinion of the Spanish Society of Neurology's Headache Study Group. / Tratamientos habituales utilizados en cefaleas, neuralgias y SARS-CoV-2. Posicionamiento del grupo de estudio de cefaleas de la Sociedad Española de Neurología.

INTRODUCTION: In recent months, doubts have arisen among patients, general practitioners, and neurologists as to whether some drugs commonly used in patients with headaches and neuralgia may favour or complicate the disease caused by SARS-CoV-2. MATERIAL AND METHODS: We collected information on the opinions of scientific societies and medicines agencies (American, European, and Spanish) to clarify doubts regarding the use of drugs such as lisinopril, candesartan, ibuprofen, corticosteroids, carbamazepine, and monoclonal antibodies targeting the calcitonin gene-related peptide in the context of the COVID-19 pandemic. RESULTS: We make recommendations about the use of standard headache treatments in the context of the COVID-19 pandemic, based on the current scientific evidence. CONCLUSIONS: At present, there is no robust scientific argument to formally contraindicate any of the standard treatments employed for headaches and neuralgias.

Study of the antifungal activity of ibuprofen and its association with amphotericin B or ketoconazole against Candida spp / Estudio de la actividad antifúngica del ibuprofeno y su asociación con anfotericina B o ketoconazol contra Candida spp / Estudo da atividade antifúngica do ibuprofeno e sua associação com anfotericina B ou cetoconazol contra Candida spp

SUMMARY The objective was evaluating the antifungal activity of ibuprofen alone and when associated with amphotericin B or ketoconazole against Candida species. Strains of C. albicans, C. tropicalis, C. guilliermondii, C. krusei and C. parapsilosis were used. The minimum inhibitory concentration (MIC) was determined by the microdilution method and the association study performed through the checkerboard assay. The concentration of 512 μg/mL inhibited approximately 65% of the tested strains, while against 35% of the strains presented MIC values above 2048 μg/mL. Associations of ibuprofen with amphotericin B against C. tropicalis and ibuprofen with ketoconazole against C. krusei showed synergistic effect. Antagonistic effects were evidenced in the combination of ibuprofen with amphotericin B against C. guilliermondii and C. albicans, as well as in the association of ibuprofen with ketoconazole against C. albicans and C. tropicalis. Through the experiments, it was found that ibuprofen showed antifungal activity against most of the Candida species tested. The combinations of ibuprofen and antifungals had synergistic effects. However, antagonistic results were evidenced in the association with ibuprofen, which would make clinical applicability difficult. Therefore, studies of this combined activity should be investigated, considering that this association may be positive for anti-fungal therapy.

RESUMEN El objetivo fue evaluar la actividad antifúngica del ibuprofeno solo y asociado con anfotericina B o ketoconazol contra especies de Candida. Se utilizaron cepas de C. albicans, C. tropicalis, C. guilliermondii, C. krusei y C. parapsilosis. La concentración inhibitoria mínima (MIC) se determinó mediante el método de microdilución y el estudio de asociación fue realizado a través del ensayo de checkboard. La concentración de 512 μg/mL inhibió aproximadamente el 65% de las cepas analizadas, mientras 35% de las cepas presentaron valores de MIC superiores a 2048 μg/mL. Las asociaciones de ibuprofeno con anfotericina B contra C. tropicalis e ibuprofeno con ketoconazol contra C. krusei mostraron un efecto sinérgico. Se evidenciaron efectos antagonistas en la combinación de ibuprofeno con anfotericina B contra C. guilliermondii y C. albicans, así como en la asociación de ibuprofeno con ketoconazol contra C. albicans y C. tropicalis. Se descubrió, a través de los experimentos, que el ibuprofeno mostró actividad antifúngica contra la mayoría de las especies de Candida probadas. Las combinaciones de ibuprofeno y antifúngicos tuvieron efectos sinérgicos. Sin embargo, se evidenciaron resultados antagónicos en la asociación con ibuprofeno, lo que dificultaría la aplicabilidad clínica. Por lo tanto, los estudios de esta actividad combinada deben investigarse, considerando que esta asociación puede ser positiva para la terapia antimicótica.

RESUMO O objetivo do estudo foi avaliar a atividade antifúngica do ibuprofeno sozinho e quando associado com anfotericina B ou cetoconazol contra espécies de Candida. Foram utilizadas cepas fúngicas de C. albicans, C. tropicalis, C. guilliermondii, C. krusei e C. parapsilosis, entre isolados clínicos e cepas padrão. A concentração inibitória mínima (CIM) foi determinada pela técnica de microdiluição e o estudo de associação realizado através do ensaio checkerboard. A concentração de 512 μg/mL foi capaz de inibir, aproximadamente, 65% das cepas ensaiadas, enquanto que 35% das estirpes apresentaram valores da CIM acima de 2048 μg/mL. Associações do ibuprofeno com anfotericina B contra C. tropicalis e ibuprofeno mais cetoconazol contra C. krusei mostraram efeito sinérgico. Efeitos antagônicos foram evidenciados na combinação do ibuprofeno com anfotericina B contra C. guilliermondii e C. albicans, como também na associação do ibuprofeno com cetoconazol contra C. albicans e C. tropicalis. Por meio dos experimentos, pôde-se afirmar que o ibuprofeno exerceu atividade antifúngica contra a maioria das espécies de Candida ensaiadas. Os efeitos das combinações entre o ibuprofeno e os antifúngicos promoveram efeitos sinérgicos. No entanto, resultados antagônicos foram evidenciados na associação com o ibuprofeno, o que dificultaria aplicabilidade clínica. Logo, estudos dessa atividade combinada devem ser investigados, pois esta associação pode traçar pontos positivos na terapia antifúngica.

Evaluation of ibuprofen prescriptions into a Psychiatric Hospital: regarding safety, indication, and dose / Avaliação das prescrições de ibuprofeno em um hospital psiquiátrico: aspectos de segurança, indicação e dose

Introduction: non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are widely used throughout the world. In the psychiatric hospital, where this study was conducted, drugs such as selective serotonin reuptake inhibitors (SSRI) and lithium are widely used and may interact with ibuprofen (IBU). The literature also shows that ibuprofen may lead to changes in the central nervous system, which may trigger the imbalance of psychiatric disorders. Objective: to evaluate whether both the frequency of use and the prescriptions of ibuprofen are in agreement with the information contained in the literature regarding safety, indication, and dose. Methodology: retrospective observational cross-sectional study to evaluate the use of ibuprofen on patients from a psychiatric hospital. The prescriptions were evaluated for a 10-month period. Results: of the total number of prescriptions, 43 contained ibuprofen 600 mg. Note that in most cases, the drug was being prescribed according to the literature. However, in some cases there were divergences in the literature regarding: i) safety ­ information about the absence or presence of ulcers (1; 2.3%), gastrointestinal events (0; 0%) and absence of dyspepsia, abdominal pain and discomfort gastrointestinal (11; 25.5%) ­ ii) and the dose, in which in 19 cases (44%) it was higher than recommended by the literature. In addition, in 2 prescriptions (4.7%), the concomitant use of IBU and SSRI was observed and in 5 (11.6%) of IBU and lithium. Conclusion: the use of this drug often escaped safety and dosage criteria concerning scientific literature.

Introdução: os anti-inflamatórios não esteróides (AINEs), como o ibuprofeno, são amplamente utilizados no mundo todo. No hospital psiquiátrico em que este estudo foi realizado, medicamentos como inibidores seletivos da recaptação de serotonina e lítio são amplamente utilizados e sabe-se que podem interagir com o ibuprofeno. A literatura também mostra que o ibuprofeno pode levar a alterações no sistema nervoso central, o que pode desencadear o desequilíbrio dos distúrbios psiquiátricos. Objetivo: avaliar a frequência da utilização do ibuprofeno e se suas prescrições estão de acordo com as informações contidas na literatura com relação à segurança, indicação e dose. Metodologia: realizou-se um estudo transversal observacional retrospectivo para avaliar o uso de ibuprofeno em pacientes de um hospital psiquiátrico. As prescrições foram avaliadas por um período de 10 meses. Resultados: entre as 43 prescrições avaliadas, recomendou-se a dose de 600 mg. Foi observado que, na maioria dos casos, o medicamento estava sendo usado conforme prescrito na literatura. No entanto, em alguns casos houve divergências da literatura em relação a i) segurança ­ informações sobre a ausência ou presença de úlceras (1; 2,3%), de eventos gastrointestinais (0; 0%) e ausência de dispepsia, dor abdominal e desconforto gastrointestinal (11; 25,5%) ­ ii) dose, em que em 19 casos (44%) foi maior do que o preconizado pela literatura. Além disso, em duas (4,7%) prescrições, foi observado o uso concomitante de IBU e ISRS) e em cinco (11,6%) de IBU e lítio. Conclusão: o uso desse medicamento frequentemente de modo geral não obedeceu aos critérios de segurança e dosagem referentes à literatura científica.

Clinical outcomes after more conservative management of patent ductus arteriosus in preterm infants / Desfechos clínicos após tratamento mais conservador da persistência do canal arterial em prematuros

Abstract Objective: Management of patent ductus arteriosus is still controversial. This study aimed to describe the impact of a more conservative approach on treatment rates and on main outcomes of prematurity, especially in preterm infants with <26 weeks of gestation. Method: Clinical charts review of infants ≤30 weeks with patent ductus arteriosus between 2009 and 2016 at two centers. In 2011, the authors changed patent ductus arteriosus management: in first period (2009-2011), patients who failed medical treatment underwent surgical closure; in second period (2012-2016), only those with cardiopulmonary compromise underwent surgical ligation. Medical treatment, surgical closure, mortality, and survival-without-morbidity were compared. Results: This study included 188 patients (27 ± 2 weeks, 973 ± 272 grams); 63 in P1 and 125 in P2. In P2, significantly lower rates of medical treatment (85.7% P1 versus 56% P2, p < 0.001) and surgical closure (34.5% P1 versus 16.1% P2, p < 0.001) were observed. No differences were found in chronic lung disease (28.8% versus 13.9%, p = 0.056), severe retinopathy of prematurity (7.5% versus 11.8%, p = 0.403), necrotizing enterocolitis (15.5% versus 6.9%, p = 0.071), severe intraventricular hemorrhage (25.4% versus 18.4%, p = 0.264), mortality (17.5% versus 15.2%, p = 0.690) or survival-without-morbidity adjusted OR = 1.10 (95% CI: 0.55-2.22); p = 0.783. In P2, 24.5% patients were discharged with patent ductus arteriosus. The subgroup born between 23 and 26 weeks (n = 82) showed significant differences: lower incidence of chronic lung disease (50% versus 19.6%, p = 0.019) and more survival-without-morbidity (20% versus 45.6%, p = 0.028) were found. Conclusion: A conservative approach in preterm infants with patent ductus arteriosus can avoid medical and surgical treatments, without a significant impact in survival-without-morbidity. However, two-thirds of preterm infants under 26 weeks are still treated.

Resumo Objetivo O tratamento da persistência do canal arterial ainda é controverso. Nosso objetivo foi descrever o impacto de uma abordagem mais conservadora em nossas taxas de tratamento e nos principais desfechos da prematuridade, especialmente em prematuros com < 26 semanas de gestação. Método Revisão de prontuários de lactentes com ≤ 30 semanas e persistência do canal arterial entre 2009-2016 em dois centros. Em 2011, mudamos o manejo da persistência do canal arterial: no primeiro período (2009-2011), os pacientes que não apresentaram sucesso com o tratamento clínico foram submetidos a fechamento cirúrgico; no segundo período (2012-2016), apenas aqueles com comprometimento cardiopulmonar foram submetidos ao fechamento cirúrgico. Comparamos o tratamento clínico, fechamento cirúrgico, mortalidade e sobrevida sem morbidade. Resultados Foram incluídos 188 pacientes (27 ± 2 semanas, 973 ± 272 gramas); 63 em P1 e 125 em P2. Em P2, foram observadas taxas significativamente mais baixas de tratamento clínico (85,7% no P1 versus 56% no P2, p < 0,001) e fechamento cirúrgico (34,5% no P1 versus 16,1% no P2, p < 0,001). Não foram encontradas diferenças em relação à doença pulmonar crônica (28,8% versus 13,9%, p = 0,056), retinopatia grave da prematuridade (7,5% versus 11,8%, p = 0,403), enterocolite necrosante (15,5% versus 6,9%, p = 0,071), hemorragia intraventricular grave (25,4% versus 18,4%, p = 0,264), mortalidade (17,5% versus 15,2%, p = 0,690) ou OR ajustado pela sobrevida sem morbidade = 1,10 (IC95%: 0,55-2,22); p = 0,783. Em P2, 24,5% dos pacientes receberam alta com persistência do canal arterial. O subgrupo nascido entre 23 a 26 semanas (n = 82) apresentou diferenças significativas, foram encontradas menor incidência de doença pulmonar crônica (50% versus 19,6%, p = 0,019) e maior sobrevida sem morbidade (20% versus 45,6%, p = 0,028). Conclusão Uma abordagem conservadora em prematuros com persistência do canal arterial pode evitar tratamentos clínicos e cirúrgicos, sem um impacto significativo na sobrevida sem morbidade. No entanto, dois terços dos prematuros com menos de 26 semanas ainda são tratados.

Clinical outcomes after more conservative management of patent ductus arteriosus in preterm infants.

OBJECTIVE: Management of patent ductus arteriosus is still controversial. This study aimed to describe the impact of a more conservative approach on treatment rates and on main outcomes of prematurity, especially in preterm infants with <26 weeks of gestation. METHOD: Clinical charts review of infants ≤30 weeks with patent ductus arteriosus between 2009 and 2016 at two centers. In 2011, the authors changed patent ductus arteriosus management: in first period (2009-2011), patients who failed medical treatment underwent surgical closure; in second period (2012-2016), only those with cardiopulmonary compromise underwent surgical ligation. Medical treatment, surgical closure, mortality, and survival-without-morbidity were compared. RESULTS: This study included 188 patients (27±2 weeks, 973±272 grams); 63 in P1 and 125 in P2. In P2, significantly lower rates of medical treatment (85.7% P1 versus 56% P2, p<0.001) and surgical closure (34.5% P1 versus 16.1% P2, p<0.001) were observed. No differences were found in chronic lung disease (28.8% versus 13.9%, p=0.056), severe retinopathy of prematurity (7.5% versus 11.8%, p=0.403), necrotizing enterocolitis (15.5% versus 6.9%, p=0.071), severe intraventricular hemorrhage (25.4% versus 18.4%, p=0.264), mortality (17.5% versus 15.2%, p=0.690) or survival-without-morbidity adjusted OR=1.10 (95% CI: 0.55-2.22); p=0.783. In P2, 24.5% patients were discharged with patent ductus arteriosus. The subgroup born between 23 and 26 weeks (n=82) showed significant differences: lower incidence of chronic lung disease (50% versus 19.6%, p=0.019) and more survival-without-morbidity (20% versus 45.6%, p=0.028) were found. CONCLUSION: A conservative approach in preterm infants with patent ductus arteriosus can avoid medical and surgical treatments, without a significant impact in survival-without-morbidity. However, two-thirds of preterm infants under 26 weeks are still treated.

Ibuprofen increases the serum Omentin levels in rats after abdominal surgery

SUMMARY AIMS Omentin is an adipokine primarily produced by visceral adipose tissue and its reduced levels have been shown to be associate with worse metabolic outcomes. We aimed to study the effects of preoperative ibuprofen on postoperative omentin levels in rats after surgery. METHODS Forty-eight albino Wistar rats, 6 in each of 8 groups according to the surgical procedure (laparotomy, laparotomy plus ibuprofen (IBU), nephrectomy, nephrectomy plus IBU, hepatectomy, hepatectomy plus IBU, splenectomy and splenectomy plus IBU). The Omentin levels of the groups were postoperatively analyzed. RESULTS The mean omentin was significantly higher in the laparotomy plus IBU group compared to the laparotomy group (p<0.001). Mean Omentin was significantly higher in the hepatectomy plus IBU group compared to the hepatectomy group (p=0.01). Mean Omentin was significantly higher in the nephrectomy plus IBU group compared to the nephrectomy group (p=0.001). CONCLUSION We suggest that preoperative ibuprofen may enhance circulating levels of Omentin, which has beneficial effects in trauma and inflammation settings in subjects that undergo minor or major abdominal surgery.

RESUMO OBJETIVOS A omentina é uma adipocina produzida principalmente pelo tecido adiposo visceral e níveis reduzidos dela foram associados a piores desfechos metabólicos. Nosso objetivo foi estudar os efeitos do uso pré-operatório do ibuprofeno nos níveis pós-operatórios da omentina em ratos. METODOLOGIA Quarenta e oito ratos Wistar albinos foram divididos em 8 grupos (6 em cada), de acordo com o procedimento cirúrgico: laparotomia, laparotomia e ibuprofeno (IBU), nefrectomia, nefrectomia e IBU, hepatectomia, hepatectomia e IBU, esplenectomia, e esplenectomia e IBU. Os níveis de omentina dos grupos foram analisados após a cirurgia. RESULTADOS A omentina média foi significativamente maior no grupo de laparotomia e IBU do que no grupo de laparotomia (p<0,001). A omentina média foi significativamente maior no grupo de hepatectomia e IBU do que no grupo de hepatectomia (p = 0,01). A omentina média foi significativamente maior no grupo de nefrectomia e IBU do que no grupo de nefrectomia (p = 0,001). CONCLUSÃO Sugerimos que o uso pré-operatório de ibuprofeno pode aumentar os níveis circulantes de omentina, que têm efeitos benéficos em um contexto de trauma e inflamação em indivíduos submetidos cirurgia abdominal.

Influence of ibuprofen-arginine on the concentration of amoxicillin in the plasma and tissues of rats with induced periapical lesion / Influência do ibuprofeno arginina sobre a concentração plasmática e tecidual da amoxicilina em ratos com lesão periapical induzida

ABSTRACT Objective The aim of this study was to evaluate the influence of ibuprofen-arginine on the concentration of amoxycillin in the plasma and periapical tissues of rats with induced apical periodontitis. Methods Twenty-eight Wistar rats were divided into the following four groups: PL: placebo (saline); AM: amoxycillin (100 mg/kg); IB: ibuprofen-arginine (100 mg/kg); and AM+IB: amoxycillin (100 mg/kg) + ibuprofen-arginine (100 mg/kg). The animals were submitted to pulp exposure in the first lower left molar, which remained open for fifteen days; this was then closed with composite resin and remained for a further seven days. The treatments were performed using a single dose of the medication (gavage) one hour before taking the samples. Two mL of blood was collected from the aorta to obtain the blood plasma and the periapical tissue samples, which were homogenized to obtain the supernatant. The samples (plasma and the supernatant periapical tissue) were used to obtain the antibiogram for the analysis of the levels of amoxycillin in the plasma and periapical tissues. Results The amoxycillin concentration was higher in the AM group compared to the other groups (p < 0.05, ANOVA with Tukey's test). Ibuprofen-arginine interfered with plasma concentration of amoxycillin; however, the AM+IB group had a higher concentration of amoxycillin than the PL and IB groups (p < 0.05, ANOVA with Tukey's test). The analysis of the supernatant from the periapical tissues showed no significant difference between the groups (p > 0.05, Kruskal-Wallis test). Conclusion Ibuprofenarginine can interfere with the plasma concentration of amoxycillin but this study failed to show the effect of ibuprofen-arginine on the concentration of amoxycillin in the periapical tissues .

RESUMO Objetivo A proposta desta pesquisa foi avaliar a influência do ibuprofeno arginina, sobre a concentração de amoxicilina no plasma e no tecido periapical de ratos com periodontite apical induzida. Métodos Foram utilizados 28 ratos Wistar, divididos em 4 grupos:PL: placebo (salina); AM: amoxicilina (100mg/kg); IB: ibuprofeno arginina (100mg/kg); e AM+IB: amoxicilina (100mg/kg) + ibuprofeno arginina (100mg/kg). Os animais foram submetidos à exposição pulpar do primeiro molar inferior esquerdo que permaneceu aberto por 15 dias e, então, fechado com resina composta, permanecendo por mais 07 dias. Os tratamentos foram realizados com dose única dos medicamentos (gavagem), uma hora antes da obtenção das amostras. Foram coletados 2mL de sangue da artéria aorta para a obtenção do plasma sanguíneo e amostras do tecido periapical que foram homogeneizadas para a obtenção do sobrenadante. A partir das amostras (plasma e sobrenadante do tecido periapical) realizou-se o antibiograma para análise da concentração plasmática e tecidual de amoxicilina. Resultados A concentração de antibiótico foi maior no grupo AM em comparação aos demais grupos (p<0,05, ANOVA com Tukey). O ibuprofeno arginina interferiu na concentração plasmática de amoxicilina, no entanto, a concentração de amoxicilina no grupo AM+IB foi maior que nos grupos PL e IB (p<0,05, ANOVA com Tukey). A análise do sobrenadante do tecido periapical não mostrou diferença significativa entre os grupos (p>0,05, Kruskal-Wallis). Conclusão O ibuprofeno arginina podeinterferir com a concentração plasmática de amoxicilina, porém o estudo não foi capaz de mostrar o efeito do anti-inflamatório na concentração de amoxicilina no tecido periapical.

Diseño y desarrollo de un sistema de entrega de fármaco autoemulsificable líquido de ibuprofeno incorporado por el método de adsorción por portador en una forma farmacéutica sólida (comprimidos) / Design and development of a liquids self emulsyfing drug delivery system of ibuprofen incorporated by the method adsorption by carriers in solids dosage forms

RESUMEN El ibuprofeno es uno de los fármacos más utilizados e indicado para terapias antiinflamatorias, dolor, entre otras patologías. Sin embargo, este fármaco presenta una baja y errática biodisponibilidad, debido a la pobre solubilidad acuosa intrínseca del mismo, por lo cual esta categorizado como clase II en el sistema de clasificación biofarmacéutica. El objetivo de este trabajo fue desarrollar, diseñar y evaluar un sistema de entrega de fármaco autoemulsificable (SEDDS) para mejorar la solubilidad y velocidad de disolución de ibuprofeno. Aceites, cosolventes, tensioactivos y portadores porosos fueron evaluados por su capacidad de mejorar la solubilidad del ibuprofeno, habilidad de autoemulsificación, robustez en diferentes pH y capacidad de adsorción. El aceite de coco, Tween 80 y propilenglicol lograron un aumento significativo de la solubilidad acuosa del ibuprofeno en un tiempo de autoemulsificación menor a 2 minutos. Neusilin US2® fue seleccionado como portador, dando como resultado un pequeño granulo de excelente fluidez, que permitió obtener comprimidos que cumplieron satisfactoriamente las pruebas de control de acuerdo con las especificaciones establecidas. Los SEDDS líquidos y sólidos son una alternativa de formulación ventajosa y prometedora para mejorar la solubilidad de fármacos pobremente solubles de acuerdo al sistema de clasificación biofarmacéutica, a través de sus propiedades de solubilización.

SUMMARY Ibuprofen is one of the most used drugs and it's indicated for anti-inflammatory therapies and pain, among other pathologies. However, this drug has a low and erratic bioavailability, due to its poor aqueous intrinsic solubility, which is categorized as class II in the Biopharmaceutical Classification System. The objective of this work was to develop, design and evaluate a self-emulsifying drug delivery system (SEDDS) to improve the solubility and dissolution rate of ibuprofen. Oils, co-solvents, surfactants and carriers were evaluated for their ability to improve the solubility of ibuprofen, self-emulsification ability, robustness at different pH levels and adsorption capacity. Coconut oil, Tween 80 and propylene glycol achieved a significant increase in the aqueous solubility of ibuprofen in a self-emulsification time of less than 2 minutes. Neusilin US2® was selected as carrier, resulting in a small granule of excellent fluidity, which allowed to obtain tablets that satisfactorily fulfilled the control tests according to the established specifications. The liquid and solid SEDDS are an advantageous and promising formulation alternative to improve the solubility of poorly soluble drugs according to the biopharmaceutical classification system, through their solubilization properties.

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.