Efficacy and safety of Regan Syrup in treatment of common cold (wind-heat syndrome):a multicenter, randomized, double-blind, double-dummy, placebo and positive drug-controlled, parallel, phase Ⅱb clinical trial / 中国中药杂志

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.

Cost-effectiveness analysis of Chaiyin Granules in treatment of influenza / 中国中药杂志

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.

Características clínicas, tratamiento y evolución de una serie de niños con síndrome inflamatorio multisistémico asociado a SARS-CoV-2 hospitalizados en dos centros de salud / Clinical characteristics, treatment and evolution of a series of children with multisystemic inflammatory syndrome associated with SARS-CoV-2 hospitalized in two health centers / Características clínicas, tratamento e evolução de uma série de crianças com síndrome inflamatória multissistêmica associada ao SARS-CoV-2 internadas em dois centros de saúde

Introducción: en marzo del 2021 se registró el pico de incidencia de COVID-19 en Uruguay y un aumento de la infección en pediatría. Objetivo: describir las características clínicas, el tratamiento y la evolución de una serie de menores de 15 años con SIM-Ped S hospitalizados en dos centros de salud. Metodología: estudio descriptivo, retrospectivo, de los niños hospitalizados entre el 1/3 y el 31/6 de 2021 que cumplieron los criterios diagnósticos de SIM-Ped de la OMS. Se analizan variables clínicas, paraclínicas, tratamiento y evolución. Resultados: se incluyeron 12 niños, mediana de edad 7 años (22 meses-10 años). Se presentaron complicación posinfecciosas en 8 y en el curso de la infección en 4. Las manifestaciones fueron: fiebre (media 6 días, rango 3-10), digestivas 10 y mucocutáneas 7. Se presentaron como enfermedad Kawasaki símil 5 y como shock 2. La infección por SARS CoV-2 se confirmó por PCR en 6, serología 4 y test antigénico 2. Recibieron tratamiento en cuidados moderados 8 e intensivos 4: inmunoglobulina 9, corticoides 11, heparina 7 y ácido acetilsalicílico 7. Presentaron dilatación de arterias coronarias 2, alteraciones valvulares 2, disminución de la FEVI 2 y derrame pericárdico 2. Todos evolucionaron favorablemente. Conclusiones: en estos centros, los primeros casos de SIMS-Ped S coincidieron con el pico de incidencia de COVID-19 en el país. Predominaron las formas postinfecciosas en escolares con manifestaciones digestivas. Este estudio puede contribuir al reconocimiento de esta entidad y adecuar los algoritmos nacionales de manejo.

Introduction: in March 2021, there was a peak incidence of COVID-19 and an increase in pediatric infections in Uruguay. Objective: describe the clinical characteristics, treatment and evolution of a group of children under 15 years of age with SIM-Ped S hospitalized in two health centers. Methodology: descriptive, retrospective study of children hospitalized between 3/1 and 6/31 of 2021 who met the WHO diagnostic criteria for SIM-Ped. Clinical and paraclinical variables, as well as treatment and evolution were analyzed. Results: 12 children were included, median age 7 years (22 months-10 years). Eight of them showed post-infectious complications and 4 of them had complications during the course of the infection. The manifestations were: fever (mean 6 days, range 3-10), digestive symptoms 10 and mucocutaneous 7. Five of them presented a Kawasaki-like disease and 2 of them shock. SARS CoV-2 infection was confirmed by PCR in 6 cases, serology in 4 and antigenic test in 2. Eight of them received treatment in moderate care and 4 of them in intensive care: immunoglobulin 9, corticosteroids 11, heparin 7 and acetylsalicylic acid 7. Two of them presented dilated arteries coronary , valvular alterations 2, decreased LVEF 2 and pericardial effusion 2. All progressed favorably. Conclusions: in these centers, the first cases of SIMS-Ped S coincided with the peak incidence of COVID-19 in the country. Post-infectious forms predominated in schoolchildren who showed digestive manifestations. This study may contribute to the recognition of this entity and to the adaptation of national management algorithms.

Introdução: em março de 2021, foi registrado no Uruguai um pico de incidência da COVID-19 e um aumento dos casos da infecção pediátrica. Objetivo: descrever as características clínicas, tratamento e evolução de uma série de crianças menores de 15 anos com SIM-Ped S internadas em dois centros de saúde. Metodologia: estudo descritivo, retrospectivo, de crianças internadas entre 1/3 e 31/6 de 2021 que preencheram os critérios diagnósticos da OMS para o SIM-Ped. Foram analisadas variáveis clínicas e para-clinicas, tratamento e evolução. Resultados: foram incluídas 12 crianças, com idade média de 7 anos (22 meses-10 anos). Oito delas apresentaram complicações pós-infecciosas e 4 delas durante o curso da infecção. As manifestações foram: febre (média de 6 dias, intervalo 3-10), digestivas 10 e mucocutânea 7. Cinco delas apresentaram doença de Kawasaki-like e 2 delas sofreram Shock. A infecção por SARS CoV-2 foi confirmada por PCR em 6, sorologia em 4 e teste antigênico em 2. Oito delas receberam tratamento em cuidados moderados e 4 delas em cuidados intensivos: imunoglobulina 9, corticosteroides 11, heparina 7 e ácido acetilsalicílico 7. Duas delas apresentaram artérias coronárias dilatadas 2, alterações valvares 2, diminuição da FEVE 2 e derrame pericárdico 2. Todas evoluíram favoravelmente. Conclusões: nesses centros, os primeiros casos de SIMS-Ped S coincidiram com um pico de incidência de COVID-19 no país. As formas pós-infecciosas predominaram em escolares com manifestações digestivas. Este estudo pode contribuir para o reconhecimento desta entidade e adaptar algoritmos nacionais de gestão.

Tratamiento del paciente pediátrico con COVID-19 / Tratamiento del paciente pediátrico con COVID-19

COVID-19 afecta entre el 1.2 al 5% de niños y adolescentes en diversos países incluyendo Guatemala, la mayoría con manifestaciones clínicas leves a moderadas. La terapéutica farmacológica para enfermedad grave aún no está completamente establecida, por lo que se realizó una revisión de literatura de artículos científicos publicados en revistas indizadas para proporcionar una actualización del tratamiento de COVID-19 en niños y adolescentes, que ayude a orientar las decisiones clínicas. El tratamiento de casos leves consiste en antipiréticos, antibióticos en neumonía leve; en casos moderados, monitoreo de signos vitales, cánula binasal, manejo de líquidos, antipiréticos y analgésicos, toma de hemocultivo, inicio de antibióticos y uso de beta agonistas de acción corta o esteroides inhalados. En enfermedad grave, ventilación mecánica no invasiva o invasiva, ventilación prono temprana, soporte nutricional, hídrico y vasopresor, mantenimiento del equilibrio ácido base y de electrolitos. Se indica el uso de antibióticos y antivirales como remdesivir y el manejo inmunológico con interferón alfa, esteroides y/o inmunoglobulina. Se monitorea función hepática, renal, inmunológica, hematológica y cardíaca. No se ha encontrado evidencia de que la hidroxicloroquina, ivermectina y algunos antivirales disminuyan la mortalidad en pacientes pediátricos. Actualmente no existe ningún medicamento específico, validado científicamente para el tratamiento de COVID-19 en niños. El tratamiento para casos graves se decide a partir de las experiencias del tratamiento en adultos, por lo cual es importante continuar con investigación de fármacos específicos para la población pediátrica.

COVID-19 affects among 1.2 to 5% of children and adolescents in various countries, counting Guatemala, the most with mild to moderate clinical manifestations. Pharmacological therapy for severe disease has not yet been fully established. A literature review of scientific articles from indexed journals was conducted to provide an update on the treatment of COVID-19 in children and adolescents, to help guide clinical decisions. Treatment of mild cases consists of antipyretics and antibiotics for pneumonia. In moderate cases is recommended to monitor vital signs, to obtain blood cultures and to treat with binasal cannula, fluids, antipyretics and analgesics, short-acting beta agonists and/or inhaled steroids and antibiotics when needed. In severe illness, treatment includes non-invasive or invasive mechanical ventilation, early prone ventilation, nutritional, hydration and vasopressor support, maintenance of acid-base, and electrolyte balance. The use of antibiotics and antivirals as remdesivir is recommended, as well as the use of immunomodulators such as interferon alfa, steroids and/or immunoglobulin. To monitor patient´s evolution; liver, kidney, immunological, hematological, and cardiac function must be assessed. No evidence has been found that hydroxychloroquine, ivermectin and other antivirals decrease mortality in pediatric patients. Currently, there is no specific, scientifically validated medication for the treatment of COVID-19 in children. Treatment for severe cases is decided based on management experiences in adults, so it is important to doing research on specific drugs for the pediatric population.

Lista de medicamentos esenciales para el manejo de pacientes que ingresan a unidades de cuidados intensivos con sospecha o diagnóstico confirmado de COVID-19 / List of essential drugs for the management of patients admitted to intensive care units with suspected or confirmed diagnosis of COVID-19

En el transcurso de la pandemia de COVID-19, numerosos países, de ingresos bajos, medianos y alto, han visto agotadas sus reservas de medicamentos esenciales necesarios para el manejo de los pacientes con COVID-19 en las unidades de cuidados intensivos (UCI). El plan de preparación para emergencias sanitarias de los países requiere incluir una lista de medicamentos esenciales y otros dispositivos médicos necesarios en las UCI para afrontar emergencias sanitarias. La lista de medicamentos esenciales para el manejo de pacientes que ingresan a unidades de cuidados intensivos con sospecha o diagnóstico confirmado de COVID-19 es un documento de orientación fundamental que ayuda a los sistemas de salud de los países a priorizar los medicamentos esenciales que deben estar ampliamente disponibles y ser asequibles para manejar los pacientes en las UCI durante las situaciones de emergencia sanitaria, en este caso con sospecha o diagnóstico confirmado de COVID-19. Está dirigida a las autoridades sanitaras y a los encargados del manejo del sistema de salud de los países. Esta lista incluye fundamentalmente los medicamentos considerados esenciales para el manejo de los cuadros clínicos que con se observan con mayor frecuencia en pacientes hospitalizados en UCI a causa de una infección por SARS-CoV-2. No se incluyen la mayoría de los medicamentos que comúnmente se encuentran en las UCI para el manejo de otras patologías, comorbilidades o la estabilización del paciente (p. ej., insulina o antihipertensivos), salvo aquellos que pueden requerirse para el tratamiento o apoyo (p. ej., bloqueantes neuromusculares o anestésicos) de las dolencias generadas por la infección. Tampoco se incluyen medicamentos específicos para el tratamiento de la infección por SARS-CoV-2, puesto que no existe, por el momento, evidencia científica de alta calidad que avale su uso, salvo en el contexto de ensayos clínicos controlados. Un equipo de expertos en el tema realizó una búsqueda de información sobre la atención de pacientes en UCI durante la pandemia de COVID-19, en Medline (a través de PubMed), Cochrane, Tripdatabase, Epistemonikos y en buscadores generales de internet (Google). Se identificaron también revisiones o guías generadas por ministerios de Salud de varios países de la Región de las Américas, la Organización Mundial de la Salud (OMS), la Organización Panamericana de la Salud (OPS), el Instituto Nacional de Salud y Excelencia Clínica (NICE) de Reino Unido, los Centros para el Control y la Prevención de Enfermedades (CDC) de Estados Unidos y los Institutos Nacionales de Salud (NIH) de Estados Unidos.

Conocimientos y manejo de la fiebre en padres de niños menores de 5 años en un hospital pediátrico / Knowledge and management of fever in parents of children under 5 years of age at a children's hospital

Introducción. La fiebre en pediatría es motivo de consulta frecuente. El objetivo fue evaluar los conocimientos, actitudes y temores de los padres ante la fiebre de sus hijos.Material y métodos. Estudio observacional, analítico, transversal. En 2018, se realizó una encuesta a padres de niños de entre 6 meses y 5 años que asistieron al Hospital de Niños Ricardo Gutiérrez de la Ciudad de Buenos Aires.Se analizó la asociación entre las variables sociodemográficas y los conocimientos, actitudes y temores frente al cuadro febril.Resultados. Se realizaron 201 encuestas. El 56,7 % de los padres consideró que la fiebre era mala para la salud. El 37 % definió fiebre entre 37 °C y 37,5 °C, y el 59 %, 38-38,5 ºC. La media de temperatura considerada grave fue 39,2 °C (desvío estándar 0,69). El 93 % de los cuidadores utilizaba medidas físicas; el 97 % administraba antitérmicos y el 14,5 % los alternaba. Los temores a las consecuencias fueron, en el 82 %, convulsiones; en el 41 %, deshidratación; en el 18 %, daño cerebral y, en el 12 %, muerte. El 86,5 % despertaba a sus hijos para administrarles antitérmico. En el estrato de mayor instrucción materna, fue menor el temor a la fiebre (odds ratio0,5; intervalo de confianza del 95 %: 0,28-0,91).Conclusiones. Un tercio de los encuestados consideró fiebre valores bajos de temperatura. El temor a la fiebre fue elevado y el nivel de instrucción materna podría mitigarlo.

Introduction. In pediatrics, fever is a common reason for consultation. The objective was to assess parental knowledge, behaviors, and fears in the management of fever in their children.Materials and methods. Observational, analytical, cross-sectional study. In 2018, a survey was administered to the parents of children aged 6 months to 5 years who attended Hospital de Niños Ricardo Gutiérrez, in the Autonomous City of Buenos Aires. The association between sociodemographic outcome measures and knowledge, behaviors, and fears in cases of fever was analyzed.Results. A total of 201 surveys were completed: 56.7 % of parents considered that fever was bad for health; 37 % defined fever between 37 °C and 37.5 °C, and 59 %, between 38 °C and 38.5 °C. The mean temperature considered severe was 39.2 °C (standard deviation: 0.69). Physical methods were used by 93 % of caregivers; 97 % administered antipyretic agents, and 14.5 % used alternating agents. Fears of consequences included seizures in 82 %, dehydration in 41 %, brain damage in 18 %, and death in 12 %. Also, 86.5 % woke up their children to give them an antipyretic agent. Among the higher maternal education level, fear of fever was lower (odds ratio: 0.5; 95 % confidence interval: 0.28-0.91).Conclusions. One-third of survey respondents considered low body temperature values as fever. Fear of fever was high, and the level of maternal education may mitigate it.

Antipyretic effect of active components of Mahuang Decoction and its correlation with pharmacokinetics in febrile rats / 中国中药杂志

To investigate the antipyretic effect of active components of Mahuang Decoction in febrile rats, and explore its correlation with pharmacokinetics at different time points. The feverished rat models were induced by dry yeast, and intragastrically administered with the effective components of Mahuang Decoction with different orthogonal compatibility ratios. At different time points after administration, body temperature was measured; blood was taken from orbital vena plexus, and the contents of interleukin-6(IL-6), interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α) in rat serum were determined with the kits. Combined with the pharmacokinetic data of the seven effective components in Mahuang Decoction, PK-PD(pharmacokinetics-pharmacodynamics) data fitting was conducted by using the analysis method of non-atrioventricular model, and then the pharmacodynamic parameters were calculated to determine the optimal binding model. The results showed that the effective components of Mahuang Decoction inhibited the release of heat-causing factors IL-6, IL-1β and TNF-α, and reduced the increase of body temperature. There was a significant lag between drug effect and blood drug concentration, which was consistent with Sigmoid-E_(max) model. The model fitting value showed a good correlation with mea-sured data, which could be used to evaluate and predict the correlation between PK and PD in Mahuang Decoction, and further applied to the multiple-indicator and multiple-effect study of PK-PD in other compound traditional Chinese medicines.

Síndrome de Klippel-Feil: a propósito de un caso en Ecuador / Klippel-Feil syndrome: about a case in Ecuador

El síndrome de Klippel-Feil (KFS) es un grupo heterogéneo de malformaciones a nivel vertebral que presentan un componente genético monogénico; se caracteriza por presentar un defecto en la formación o segmentación de las vértebras cervicales, que da como resultado una apariencia fusionada. La tríada clínica consiste en un cuello corto, una línea de implantación baja del cabello y un movimiento limitado del cuello. Presentamos el caso de un paciente masculino de 17 años que manifiesta los hallazgos clínicos y radiológicos de esta anomalía. (AU)

Klippel-Feil syndrome (KFS) is a heterogeneous group of vertebral malformations that presents a monogenic genetic component, characterized by a defect in the formation or segmentation of the cervical vertebrae, which results in a fused appearance. The clinical triad consists of a short neck, a low hairline and a limited movement of the neck. We present the case of a 17 year-old male patient who presented the clinical and radiological findings of this anomaly. (AU)

Fiebre y terapia antipirética en el paciente con sepsis en la unidad de cuidados intensivos: actualización / Fever and antipyretic therapy in the septic patient in the intensive care unit: an update

Resumen La fiebre es un signo frecuente en el niño críticamente enfermo durante su estadía en la unidad de cuidados intensivos, y debe ser entendida como una respuesta biológica evolutiva, de carácter adaptativo normal del huésped al estrés fisiológico. Es el resultado de una compleja respuesta a estímulos pirogénicos, resultando en la generación de citocinas y prostaglandinas. Los mecanismos moleculares implicados en el inicio de la fiebre aún no están totalmente precisados, originando dificultades en el conocimiento de los procesos fisiopatológicos exactos involucrados y, por ende, necesarios para elaborar una adecuada y específica estrategia terapéutica. Estudios experimentales concluyen que la fiebre y la inflamación son benéficas para el huésped; no obstante, la terapia antipirética es comúnmente empleada y estudios en humanos sobre la presencia de fiebre y su tratamiento para el pronóstico del paciente crítico con sepsis no son concluyentes. Para el médico intensivista es esencial disponer de información actualizada referente a la fisiología de la termorregulación humana, el efecto de la temperatura en rango febril sobre múltiples procesos biológicos involucrados en la defensa del huésped y las intervenciones termorreguladoras en el paciente con sepsis.

Abstract Fever is a very common sign to observe in critically ill children during their intensive care unit stay. This should be understood as an evolutionary biological response, of normal adaptive character, from the host to the physiological stress. It is the result of a complex response to pyrogenic stimuli, resulting in the generation of cytokines and prostaglandins. The molecular mechanisms involved in the onset of fever are not yet fully specified, thus creating difficulties in the knowledge of the exact pathophysiological processes involved and, therefore, necessary to elaborate an adequate and specific therapeutic strategy. Experimental studies conclude that fever and inflammation are beneficial to the host. However, antipyretic therapy is commonly employed and human studies on the presence of fever and its treatment for the prognosis of critically ill septic patients are inconclusive. Up-to-date information on the physiology of human thermoregulation, the effect of temperature on febrile range over multiple biological processes involved in host defense, and thermoregulatory interventions in the septic patient are essential to know by the critical care physician.

Analysis of analgesic, antipyretic, and nonsteroidal anti-inflammatory drug use in pediatric prescriptions / Análise do uso de analgésicos, antipiréticos e anti-inflamatórios não esteroides em prescrição pediátrica

ABSTRACT OBJECTIVE: Data on clinical practice in pediatrics on the use of analgesic, antipyretic, and nonsteroidal anti-inflammatory drugs considering the best available evidence and regulatory-agency approved use are uncertain. This study aimed to determine the frequency of prescription of these drugs according to the best scientific evidence and use approved by regulatory agencies. METHODS: This was a cross-sectional study of 150 pediatric prescriptions containing analgesic, antipyretic, and nonsteroidal anti-inflammatory drugs, followed by interview with caregivers at 18 locations (nine private drugstores and nine Basic Health Units of the Brazilian Unified Health System). The assessed outcomes included recommended use or use with no contraindication, indications with benefit evidence, and health surveillance agency-approved use. Data were analyzed in electronic databases and the variables were summarized by simple frequency. RESULTS: A total of 164 analgesic, antipyretic, and nonsteroidal anti-inflammatory drugs were prescribed to 150 children aged 1-4 years (38.6%). Dipyrone was included in 82 (54.6%) and ibuprofen in 40 (26.6%) prescriptions. Non-recommended uses were identified in 15% of prescriptions and contraindicated uses were observed in 13.3%. Nimesulide (1.5%) is still prescribed to children younger than 12 years. The dose was incorrect in 74.3% of prescriptions containing dipyrone. Of the 211 reported clinical indications, 56 (26.5%) had no evidence of benefit according to the best available scientific evidence and 66 (31.3%) had indications not approved by the regulatory agencies. CONCLUSION: There are significant discrepancies between clinical practice and recommended use of analgesic, antipyretic, and nonsteroidal anti-inflammatory drugs in pediatrics.

RESUMO OBJETIVO: Dados sobre a prática clínica em pediatria no uso de analgésicos, antipiréticos e anti-inflamatórios não esteroides considerando a melhor evidência disponível e o uso aprovado por agências reguladoras são incertos. Este estudo tem como objetivo verificar a frequência de prescrição de tais medicamentos segundo a melhor evidência científica e o uso aprovado por agências reguladoras. MÉTODO: Estudo transversal de 150 prescrições pediátricas, contendo analgésicos, antipiréticos e anti-inflamatórios não esteroides, seguido de entrevista aos cuidadores, em 18 locais (nove drogarias privadas e nove unidades de saúde do SUS). Os desfechos avaliados incluíram uso recomendado ou sem contraindicação, indicações com evidência de benefício e o uso autorizado por agências de vigilância sanitária. Os dados foram analisados em banco eletrônico e as variáveis sumarizadas por frequência simples. RESULTADOS: Foram prescritos 164 analgésicos, antipiréticos e anti-inflamatórios não esteroides para as 150 crianças entre um e quatro anos (38,6%). Dipirona constou em 82 (54,6%) e ibuprofeno em 40 (26,6%). Usos não recomendados foram encontrados em 15% das receitas e usos contraindicados em 13,3%. Nimesulida (1,5%) ainda é usada em crianças com menos de 12 anos. Em 74,3% das prescrições contendo dipirona a dose estava incorreta. Das 211 indicações clínicas referidas, 56 (26,5%) não tinham evidências de benefício segundo a melhor prova científica disponível e 66 (31,3%) eram indicações não aprovadas em agências de vigilância sanitária. CONCLUSÃO: Existem importantes discrepâncias entre prática clínica e recomendações de uso de analgésicos, antipiréticos e anti-inflamatórios não esteroides em pediatria.

Actividad antipirética del producto natural Noni-C en un modelo experimental en conejos / Antipyretic activity of the natural product called Noni C in an experimental rabbit model

INTRODUCCIÓN: en la medicina tradicional de Cuba se usa el fruto de la planta conocida como Noni por su efecto beneficioso sobre la salud. A esta se le atribuyen innumerables propiedades curativas. Sin embargo, no existen estudios preclínicos que demuestren el efecto antipirético y validen su uso. OBJETIVO: evaluar la actividad antipirética del producto natural Noni-C (Morinda Citrifolia Linn) en un modelo experimental en conejos. MÉTODOS: se realizó un ensayo preclínico en el Departamento de Investigaciones Médico Militares del Hospital militar "Dr. Luis Díaz Soto". Se utilizaron 30 conejos de la línea nueva Zelanda, sexo masculino y peso corporal entre 2,2 ­ 2,5 kg, distribuidos al azar en 5 grupos. Al grupo I se le inoculó Cloruro de Sodio 0,9 %, mientras que el grupo II fue tratado con ibuprofeno (100 mg/Kg). A los grupos III, IV y V se les administró Noni-C en dosis de 200, 400 y 800 mg/Kg respectivamente. Se midió temperatura basal rectal y los tiempos de una, dos, cuatro y seis horas postratamiento. Como inductor de la fiebre se utilizó una solución al 20 % de levadura desecada en cloruro de sodio al 0,9 %. El nivel de significación se fijó en p<0,05. RESULTADOS: se observó una disminución significativa de la temperatura corporal (p=0,00) a las dosis de 400 y 800 mg/Kgde N oni-C (38,5 ºC y 38,2 ºC) respectivamente, similar al del fármaco de referencia ibuprofeno, 38,5 ºC posterior a las 2 horas de haber suministrado la sustancia en estudio. Se pudo concluir que el producto natural Noni-C mostró actividad antipirética a las dosis de 400 y 800 mg/Kg administrado por vía oral.

INTRODUCTION: in the Cuban traditional folk medicine, the fruit of a plant called Noni is used because of its beneficial effects on health and attributable curative qualities. However, there are no preclinical research studies that prove the antipyretic effect of Noni and validate its use in this field. OBJECTIVE: to evaluate the antipyretic activity of the natural product Noni C (Morinda Citrifolia Linn) in an experimental rabbit model. METHODS: a preclinical assay was performed in the military medical research department of ¨Dr Luis Diaz Soto¨ military hospital. Thirty male New Zealand-line rabbits, weighed 2.2-2.5 kg and randomly distributed into 5 groups were used in the study. The first group was inoculated 0.9% sodium chloride; Group II was treated with Ibuprofen (100 mg/kg) whereas groups III, IV and V received Noni C at a dose of 200, 400 and 800 mg/kg, respectively. The basal rectal temperatures were measured at one, two, four and six hours after the treatment. The fever inducer was 0.9% sodium chloride-dried 20% yeast solution. The level of significance was set at p<0.05. RESULTS: body temperature significantly lowered with the 400 and 800 mg doses (38.5 and 38.2) respectively, similar to the figure of the reference drug Ibuprofen after two hours of administration of the substance under study. CONCLUSIONS: it was concluded that the natural product Noni-C showed its antipyretic action with the 400 and 800 mg/kg orally administered doses.

Devemos tratar febre em doentes graves? Resumo da evidência atual de três ensaios clínicos randomizados / Should we treat fever in critically ill patients? A summary of the current evidence from three randomized controlled trials

A febre é uma resposta não específica a vários tipos de insultos, de origem infecciosa ou não, e sua importância em doenças continua a ser um enigma. Nosso objetivo foi resumir a evidência atual para o uso de antipiréticos em pacientes graves. Foram realizadas revisão sistemática e meta-análise de publicações entre 1966 e 2013. As bases de dados MEDLINE e CENTRAL foram pesquisadas para estudos sobre antipirese em pacientes graves. A meta-análise restringiu-se a ensaios clínicos randomizados em humanos adultos; pacientes graves; tratamento com antipiréticos em um braço contra placebo ou não tratamento no outro; e dados sobre mortalidade. Os desfechos avaliados foram: mortalidade geral na unidade de terapia intensiva, mudança de temperatura e tempo de internação na unidade de terapia intensiva e no hospital. Três ensaios clínicos randomizados com 320 participantes foram incluídos. Os pacientes tratados com antipiréticos tiveram mortalidade na unidade de terapia intensiva semelhante aos controles (razão de risco de 0,91, com intervalo de confiança de 95% de 0,65-1,28). A única diferença observada foi uma diminuição na temperatura após 24 horas em pacientes tratados com antipiréticos (-1,70±0,40 x - 0,56±0,25ºC; p=0,014). Não houve diferença entre tratar ou não a febre em pacientes graves.

Fever is a nonspecific response to various types of infectious or non-infectious insult and its significance in disease remains an enigma. Our aim was to summarize the current evidence for the use of antipyretic therapy in critically ill patients. We performed systematic review and meta-analysis of publications from 1966 to 2013. The MEDLINE and CENTRAL databases were searched for studies on antipyresis in critically ill patients. The meta-analysis was limited to: randomized controlled trials; adult human critically ill patients; treatment with antipyretics in one arm versus placebo or non-treatment in another arm; and report of mortality data. The outcomes assessed were overall intensive care unit mortality, changes in temperature, intensive care unit length of stay, and hospital length of stay. Three randomized controlled trials, covering 320 participants, were included. Patients treated with antipyretic agents showed similar intensive care unit mortality (risk ratio 0.91, with 95% confidence interval 0.65-1.28) when compared with controls. The only difference observed was a greater decrease in temperature after 24 hours in patients treated with antipyretics (-1.70±0.40 versus - 0.56±0.25ºC; p=0.014). There is no difference in treating or not the fever in critically ill patients.

A homeopatia na prevenção e tratamento da dengue: uma revisão / Homeopathic medicines in the treatment and prevention of dengue: a review

A dengue é uma importante doença tropical, com um número estimado de 50 a 100 milhões de casos a cada ano. Atualmente, não se dispõe de tratamentos específicos nem de uma vacina para a prevenção da doença, mas os praticantes da medicina homeopática sugerem que formulações homeopáticas sejam úteis como medidas profiláticas e terapêuticas para a dengue. Trata-se de uma revisão da literatura que busca identificar e sumarizar os estudos que investigaram medicamentos homeopáticos para o tratamento e a prevenção da dengue. Realizou-se busca sistemática de publicações científicas nas seguintes bases de dados: PubMed, LILACS, Scopus, ISI Web of Science, The Cochrane Library, PsycInfo e SciELO, utilizando os termos "dengue" e "homeopatia" em inglês, português e espanhol. Foi identificado um único ensaio clínico aleatorizado controlado duplo-cego, além de dois ensaios de comunidade. Entretanto, tais estudos não evidenciaram a eficácia terapêutica ou profilática das formulações homeopáticas. Conclusões: Até o momento, pela falta de ensaios clínicos randomizados, duplo-cegos e controlados bem conduzidos e em número suficiente não há evidências claras da utilidade dos medicamentos homeopáticos para o tratamento e a prevenção da dengue. Assim, as medidas usuais e já bem conhecidas empregadas na prevenção primária da doença não devem ser substituídas por formulações homeopáticas.

Dengue is an important tropical disease with an estimated number of 50 to 100 million cases per year. Currently, there are no specific treatments or a vaccine available for the control of dengue disease, but homeopathic practitioners suggest that homeopathic formulations are useful to prevent and treat symptoms of dengue. To present a review of literature that seeks to identify and summarize all studies that had investigated the utility of the homeopathic medicines in the treatment and prevention of dengue. We conducted a systematic search of published scientific articles in the following databases: PubMed, LILACS, Scopus, ISI Web of Science, The Cochrane Library, PsycInfo and SciELO, employing English, Portuguese and Spanish language. The search terms used were "dengue" and "homeopathy". It was found only one randomized controlled double-blind clinical trial and two trials of community. However, these studies do not provided reliable evidences of therapeutic or prophylactic efficacy of homeopathic formulations. To date, due to the lack of randomized, double-blind controlled and well conducted studies in sufficient numbers, there are no clear evidences of the usefulness of homeopathic medicines for the treatment and prevention of dengue. Thus, the usual measures and well known employed in the primary prevention of disease should not be replaced by homeopathic formulations. .

Preclinical validation of antinociceptive, antiinflammatory, and antipyretic activities of Cordia martinicensis leave decoction / Validación preclínica de las actividades antinociceptiva, antiinflamatoria y antipirética de decocción de hojas de Cordia martinicensis

INTRODUCTION: leave decoction of Cordia martinicensis (Jacq.) Roem. & Schult. is commonly used in Dominica, Martinique and St. Lucia to relieve thoracic pain and fever. OBJECTIVES: to validate the antiinflammatory, antinociceptive (analgesic), and antipyretic ethnobotanical uses of Cordia martinicensis in experimental animal models. METHODS: 30 % aqueous extract of Cordia martinicensis dry leaves was prepared just before use. Analgesic activity was assayed by writhing and tail flick, and antiinflammatory activity by the ear oedema test, both in mice. Finally, antipyretic activity was tested by inducing pyrexia with brewer's yeast in rats. RESULTS: decoction of Cordia martinicensis significantly decreased the number of abdominal stretchings by 44.4 %, but it didn't produce a significant antinociceptive response to thermal stimuli. It also displayed strong antiinflammatory activity, the percentage of inhibition was near 60 %, and a dose of 5 mg/kg showed significant antipyretic activity. Cordia martinicensis reacted positively to alkaloids, flavonoids, tannins, and anthocyanidines, and did not show any signs of toxicity. CONCLUSIONS: this is the first report on the activity of Cordia martinicensis directly related to its popular use, and it provides pharmacological validation for the relief of fever, inflammation and pain. Further studies should be done to identify the active principles responsible for the biological activity of the plant.

INTRODUCCIÓN: la decocción de hojas de Cordia martinicensis (Jacq.) Roem. & Schult. muestra un uso tradicional significativo para el alivio del dolor torácico y la fiebre, por parte de la población de Dominica, Martinica y Santa Lucía. OBJETIVOS: validar el uso etnobotánico de Cordia martinicensis en esta región, como antiinflamatorio, antinociceptivo (analgésico) y antipirético, en modelos experimentales en animales. MÉTODOS: el extracto acuoso al 30 % de hojas secas de Cordia martinicensis se preparó justo antes de ser usado. La actividad analgésica fue estudiada mediante el modelo de contorciones abdominales y retirada de la cola en ratones. El efecto antiinflamatorio se evaluó sobre el edema en la oreja del ratón inducido por aceite de Croton.Finalmente, la actividad antipirética del extracto se evaluó mediante la inducción de fiebre en ratas por levadura de cerveza. RESULTADOS: la decocción de Cordia martinicensis disminuyó significativamente el número de contorciones abdominales en 44.4 %, pero no la respuesta al estímulo térmico; en edema en la oreja inhibió la inflamación 60 %, tanto tópico como oral. Resultó capaz de disminuir la fiebre a dosis de 5 mg/kg. Cordia martinicensis contiene alcaloides, flavonoides, taninos, y antocyanidinas y no mostró señales de toxicidad. CONCLUSIONES: constituye el primer estudio de validación del uso tradicional de Cordia martinicensis, avalando el uso farmacológico en procesos de fiebre, dolor e inflamación. Es necesario continuar los estudios fitoquímicos para determinar los principios activos responsables de su actividad biológica.

In vivo analgesic, antipyretic, and anti-inflammatory potential in Swiss albino mice and in vitro thrombolytic activity of hydroalcoholic extract from Litsea glutinosaleaves

BACKGROUND: The study was conducted to evaluate the in vitro thrombolytic activity, and in vivo analgesic, anti-inflammatory and antipyretic potentials of different hydrocarbon soluble extracts of Litsea glutinosaleaves for the first time widely used in the folkloric treatments in Bangladesh. This work aimed to create new insights on the fundamental mechanisms of the plant extracts involved in these activities. RESULTS: In thrombolytic activity assay, a significant clot disruption was observed at dose of 1 mg/mL for each of the extracts (volume 100 µL) when compared to the standard drug streptokinase. The n-hexane, ethyl acetate, chloroform, and crude methanolic extracts showed 32.23 ± 0.26, 37.67 ± 1.31, 43.13 ± 0.85, and 46.78 ± 0.9% clot lysis, respectively, whereas the positive control streptokinase showed 93.35 ± 0.35% disruption at the dose of 30,000 I.U. In hot plate method, the highest pain inhibitory activity was found at a dose of 500 mg/kg of crude extract (15.54 ± 0.37 sec) which differed significantly (P <0.01 and P <0.001) with that of the standard drug ketorolac (16.38 ± 0.27 sec). In acetic acid induced writhing test, the crude methanolic extract showed significant (P <0.01 and P <0.001) analgesic potential at doses 250 and 500 mg/kg body weight (45.98 and 56.32% inhibition, respectively), where ketorolac showed 64.36% inhibition. In anti-inflammatory activity test, the crude methanolic extract showed significant (P <0.001) potential at doses 250 and 500 mg/kg body weight (1.51 ± 0.04 and 1.47 ± 0.03 mm paw edema, respectively), where ketorolac showed 1.64 ± 0.05 mm edema after 3 h of carrageenan injection. In antipyretic activity assay, the crude extract showed notable reduction in body temperature (32.78 ± 0.46°C) at dose of 500 mg/kg-body weight, when the standard (at dose 150 mg/kg-body weight) exerted 33.32 ± 0.67°C temperature after 3 h of administration. CONCLUSIONS: Our results yield that the crude hydroalcoholic extract has better effects than the other in all trials. In the context, it can be said that the leaves of L. glutinosa possess remarkable pharmacological effects, and justify its traditional use as analgesic, antipyretic, anti-inflammatory, and thrombolytic agent.

Assessment of pharmacological activities of two medicinal plant of Bangladesh: Launaea sarmentosa and Aegialitis rotundifolia roxb in the management of pain, pyrexia and inflammation

BACKGROUND: The current study aims at evaluating the analgesic, anti-pyretic and anti-inflammatory properties of methanolic extract of the stem, bark and leaves of Launaea sarmentosa and Aegialitis rotundifolia roxb. RESULTS: The AELS and AEAR extract presented a significant (***p < 0.001) dose dependent increase in reaction time in writhing method and showed inhibition of 63.1% and 57.1% respectively at the doses of 400 mg/kg body weight while standard drug showed (P < 0.001) inhibition of 69.23%. In tail immersion method, AELS and AEAR showed maximum time of tail retention at 30 min in hot water i.e. 6.93 sec and 6.54 sec respectively at highest doses of 400 mg/kg body weight than lower dose while standard pentazocine showed reaction time of 7.62 sec. The AELS and AEAR extract also exhibited promising anti-inflammatory effect as demonstrated by statistically significant inhibition of paw volume by 32.48% and 26.75% respectively at the dose of 400 mg/kg body weight while the value at the dose of 200 mg/kg body weight were linear to higher dose at the 3rd hour of study. On the other hand, Standard indomethacin inhibited 40.13% of inflammation (***P < 0.001). In Cotton-pellet granuloma method, AELS and AEAR extract at the dose of 400 mg/kg body weight exhibited inhibition of inflammation of 34.7% and 29.1% respectively while standard drug showed (P < 0.001) inhibition of 63.22%. Intraperitoneal administration of AELS and AEAR showed dose dependent decrease in body temperature in brewer's yeast induced hyperthermia in rats at both doses. However, AELS significantly decreased body temperature (***p < 0.001) at 400 mg/kg compared to control. CONCLUSIONS: Present work propose that the methanolic extract of Launaea sarmentosa and Aegialitis rotundifolia roxb possesses dose dependent pharmacological action which supports its therapeutic use in folk medicine possibly mediated through the inhibition or blocking of release of prostaglandin and/or actions of vasoactive substances such as histamine, serotonin and kinins.

Analgésicos, antipiréticos e anti-inflamatórios não esteroides em prescrições pediátricas / Analgesics, antipyretics and non-steroidal anti-inflammatory drugs in pediatric prescriptions

O uso de analgésicos, antipiréticos e anti-inflamatórios não esteroides por crianças muitas vezes não tem aprovação das agências reguladoras, nem respaldo das evidências científicas. Prescrições pediátricas podem ser influenciadas por fatores que não favorecem o uso racional dos medicamentos desta classe. O objetivo deste trabalho foi avaliar a utilização de analgésicos, antipiréticos e anti-inflamatórios não esteroides em crianças, considerando os setores público (SUS) e privado (N-SUS). A amostra foi composta por 150 prescrições (101 SUS e 49 N-SUS) seguidas de entrevista aos cuidadores, em dezoito locais (nove drogarias privadas e nove Unidades de Saúde do SUS). Os medicamentos foram prescritos de forma apropriada, segundo faixa etária, somente em 21,8% (SUS) e 29,6% (N-SUS) das prescrições. Mais de 95% das receitas, independente da origem, não atenderam aos critérios estabelecidos para avaliação do uso racional, com erros de dose, frequência e duração do tratamento. A análise das prescrições de analgésicos, antipiréticos e anti-inflamatórios não esteroides para crianças não apresentou diferenças significantes nos setores público e privado.

The use of analgesic, antipyretic and non-steroidal anti-inflammatory drugs by children more often than not neither have the approval of regulatory agencies nor the endorsement of scientific evidence. Pediatric prescriptions can be influenced by factors that do not promote the rational use of drugs by this category. The objective of this study was to evaluate the use of analgesic, antipyretic and non-steroidal anti-inflammatory drugs in children, considering the public (SUS) and private (N-SUS) sectors. The sample comprised 150 prescriptions (101 SUS and 49 Non-SUS) followed by interviews with the caregivers in eighteen locations (nine private drugstores and nine units of the Unified Health System (SUS). The drugs were prescribed appropriately, by age group, only in 21.8% (SUS) and 29.6% (Non-SUS) prescriptions. Over 95% of prescription, regardless of source, did not meet the established criteria for evaluation of their rational use, with dosage, frequency and duration of treatment errors. The analysis of prescriptions for analgesic, antipyretic and non-steroidal anti-inflammatory drugs for children revealed no significant differences between the public and private sectors.

Fever Phobia in Korean Caregivers and Its Clinical Implications

Fever is the most common complaint among children brought into the emergency department (ED). 'Fever phobia' is a descriptive term for an unrealistic concern about the consequences of fever. 'Fever phobia' is prevalent among parents and even healthcare providers, worldwide. The aim of this study was to determine the implications of fever-phobic ideas in Korean caregivers. A prospective, multi-center survey was conducted on Korean caregivers who visited the EDs with febrile children. In total, 746 caregivers were enrolled. The mean age of the subjects was 34.7 yr (SD+/-5.0). Three hundred sixty respondents (48.3%) believed that the body temperature of febrile children can reach higher than 42.0degrees C. Unrealistic concerns about the improbable complications of fever, such as brain damage, unconsciousness, and loss of hearing/vision were believed by 295 (39.5%), 66 (8.8%), and 58 (7.8%) caregivers, respectively. Four hundred ninety-four (66.2%) guardians woke children to give antipyretics. These findings suggest that fever phobia is a substantial burden for Korean caregivers.

Efectividad de métodos físicos y antipiréticos versus sólo antipiréticos en el manejo de fiebre en niños de 3 meses a 5 años. Instituto Nacional de Salud del Niño. Ensayo clínico aleatorizado / Effectiveness of antipyretic and physical methods versus only antipyretics in the management of fever in children 3 months to 5 years. National Institute of Child Health. Randomized clinical trial

Antecedentes: La fiebre es uno de los principales motivos de consulta pediátrica. El rol de los métodos físicos en el manejo de la fiebre es controversial. Objetivo: Comparar la efectividad de métodos físicos y antipiréticos versus sólo antipiréticos en el manejo de la fiebre en niños. Método: Ensayo clínico aleatorizado donde participaron niños desde los 3 meses hasta los 5 años que acudieron a emergencia del Instituto Nacional de Salud del Niño con fiebre. 80 pacientes fueron aleatorizados en cada grupo de comparación (paracetamol, ibuprofeno, paracetamol y métodos físicos, ibuprofeno y métodos físicos). El objetivo primario fue determinar la disminución de la temperatura luego de los minutos 15, 30, 45, 60, 90 y 120 de aplicado el tratamiento. Se evaluó también los efectos secundarios. Resultados: En los primeros 30 y 45 minutos, la disminución de la temperatura fue significativamente mayor en el grupo manejado con antipiréticos y métodos físicos (p<0.001). Entre los minutos 60 y 120 no hubo diferencia significativa entre los grupos de tratamiento. Se encontró llanto y escalofríos en el 12.5 por ciento de los pacientes manejados con antipiréticos y métodos físicos y en el 2.5 por ciento de los pacientes manejados sólo con antipiréticos, esta diferencia es estadísticamente significativa (p<0.001). Conclusiones: La efectividad del uso de antipiréticos y métodos físicos es mayor para disminuir la tempera a los minutos 30 y 45, luego la temperatura disminuye con la misma velocidad que al usar sólo antipiréticos. La presencia de efectos secundarios es mayor al usar antipiréticos y métodos físicos.

Anti-inflammatory and antipyretic activities of the ethanolic extract of Shorea robusta Gaertn. f. resin.

Shorea robusta Gaertn. f. (Sal) is one of the most important traditional Indian medicinal plants. The resin of the plant has been used in the treatment of inflammation in folklore medicine. In the present study, ethanolic extract (70%) of S. robusta resin (SRE) was investigated for its anti-inflammatory and antipyretic activities. Acute inflammation was produced by carrageenan-induced hind paw edema and sub-acute by cotton pellet-induced granuloma in male Wistar rats. The antipyretic activity of SRE was studied using Brewer’s yeast-induced pyrexia in rats. The rats were divided into five groups with five animals in each group. Group I was treated with vehicle i.e. 1% v/v Tween-80 and served as control. Groups II to IV were treated with three different doses of SRE (30, 100 and 300 mg/kg orally). Group V was treated with standard drug etoricoxib (10 mg/kg orally). The anti-inflammatory activity of SRE was assessed by per cent reduction in edema volume of carrageenan-induced hind paw edema and by per cent decrease in granuloma formation in cotton pellet-induced granuloma test. SRE (100 and 300 mg/kg) produced a significant reduction in edema volume and decrease in granulation tissue formation in rats. Significant reduction in pyrexia was observed at all the dose levels of SRE i.e. 30, 100 and 300 mg/kg. The results of the present study demonstrated anti-inflammatory and antipyretic activities of S. robusta resin and supported its traditional therapeutic use in painful inflammatory conditions and fever.