Long-term use of cannabidiol-enriched medical cannabis in a prospective cohort of children with drug-resistant developmental and epileptic encephalopathy.

OBJECTIVE: We report our findings regarding effectiveness, safety, and tolerability of cannabidiol (CBD)-enriched medical cannabis as add-on therapy in children with drug-resistant epileptic encephalopathies (DEEs) after a median follow-up of 20 months. METHODS: A prospective cohort study was conducted to assess effectiveness, safety, and tolerability of CBD-enriched medical cannabis oil added to standard antiseizure medications in children with drug-resistant DEE seen at a single center. RESULTS: Between October 2018 and March 2020, 59 patients were enrolled. Mean age at enrollment was 10.5 years (range, 2-17 years). Median treatment duration was 20 months (range, 12-32). Median age at first seizure was 8 months (range, 1 day - 10 years). At the end of follow-up, 78% of the children had a ≥ 50% decrease in seizure frequency and 47.5% had a > 75% decrease. Seven patients (11.9%) were seizure free. The number of seizures was reduced from a median of 305/month to 90/month, amounting to a mean reduction of 57% and a median reduction of 71% (p < 0.0001). Adverse effects were mostly mild or moderate. CBD was discontinued in 17 patients (28.8%) due to lack of response to treatment, increased seizure frequency, intolerance to the drug, or poor compliance. CONCLUSION: In children with drug-resistant DEEs, long-term treatment of CBD-enriched medical cannabis as an adjuvant therapy to antiseizure therapy was found to be safe, well tolerated, and effective. Sustained reductions in seizure frequency and improvement of aspects of daily living were observed compared to our preliminary findings.

Effectiveness of cannabidiol in a prospective cohort of children with drug-resistant epileptic encephalopathy in Argentina.

OBJECTIVE: We report our preliminary findings regarding effectiveness, safety, and tolerability of cannabidiol (CBD) added to antiepileptic therapy in a cohort of children with drug-resistant epileptic encephalopathies (EEs) with a mean follow-up of 8.5 months (range, 3-12 months). METHODS: A prospective cohort study was designed with the aim of assessing the effectiveness, safety, and tolerability of the addition of CBD to standard antiseizure medications (ASMs) in children with drug-resistant EE enrolled at a single center (Neurology Department, Hospital de Pediatría "Juan P. Garrahan", Buenos Aires, Argentina). RESULTS: Fifty patients were enrolled between October 2018 and October 2019, 49 of whom had a follow-up of at least 3 months at the time this interim analysis was performed. Mean age at enrollment was 10.5 years (range 2-16). Median age at first seizure was 7 months. Up to the last visit of each patient (follow-up 3-12 months) 39/49 children (80 %) had responded to treatment with a decrease in seizure frequency. Overall, 77.6 % of the patients had a seizure reduction of at least 25 %, 73.5 % had a ≥ 50 % reduction, and 49 % had a ≥ 75 % reduction. Mean monthly seizure frequency was reduced from 959 to 381 (median decrease from 299 to 102, range, 38-1900; median decrease 66 %, p < 0.001). All adverse effects were mild or moderate. The most common adverse effect was drowsiness (in 32 %), usually reversed by adjusting clobazam dose (in 12 children). CONCLUSION: In children with drug-resistant EEs, CBD oil as an adjuvant therapy to antiepileptic therapy seems safe, well tolerated, and effective.

Capacitación hospitalaria de profesionales pediátricos en investigación y gestión / In-hospital capacity-building in research and management for pediatric professionals

Se describe una estrategia de capacitación en investigación y gestión para profesionales hospitalarios iniciada en 2006 en un hospital pediátrico y sus resultados a ocho años de su implementación. Gestión e Investigación en Pediatría es un curso anual de 250 horas, teórico-práctico, semipresencial con soporte en campus virtual. Proporciona herramientas de investigación (epidemiología, metodología, búsqueda bibliográfica, medicina basada en evidencias, bioestadistica) y gestión (planificación estratégica, programas de gestión, investigación en servicios de salud, calidad, economía de la salud). Se evalúa mediante ejercicios de integración, un examen final y un proyecto grupal de investigación o gestión. Los resultados obtenidos entre 2006 y 2013 fueron altamente satisfactorios. La implementación en el ámbito hospitalario de un programa de capacitación intensivo en gestión e investigación para profesionales de la salud es una estrategia útil para facilitar la incorporación y aplicación de herramientas prácticas para investigación, interpretación crítica de la bibliografía biomédica y gestión racional de servicios pediátricos.

We describe an educational strategy aimed at capacity-building of hospital health care professionals in research and management initiated at a pediatric hospital in 2006, and the results obtained eight years after its implementation. Research and Management in Pediatrics (GIP) is an annual 250-hour course combining meetings and off-site assignments delivered through the Hospital's on-line campus. It provides students with practical tools for research (epidemiology, methodology, bibliographic search, evidence-based medicine, biostatistics) and management (strategic planning, management programs, health services research, quality improvement, health economics). Assessment methods included integrative exercises, a final evaluation, and a group research or management project. Results obtained over the 2006-2013 period were highly satisfactory. An intensive training program on research and management is a useful strategy for in-hospital capacity-building of pediatric health care professionals in basic tools for research activities, critical reading of biomedical literature and rational management ofpediatric health services.

In-hospital capacity-building in research and management for pediatric professionals. / Capacitación hospitalaria de profesionales pediátricos en investigación y gestión.

We describe an educational strategy aimed at capacity-building of hospital health care professionals in research and management initiated at a pediatric hospital in 2006, and the results obtained eight years after its implementation. Research and Management in Pediatrics (GIP) is an annual 250-hour course combining meetings and off-site assignments delivered through the Hospital's on-line campus. It provides students with practical tools for research (epidemiology, methodology, bibliographic search, evidencebased medicine, biostatistics) and management (strategic planning, management programs, health services research, quality improvement, health economics). Assessment methods included integrative exercises, a final evaluation, and a group research or management project. Results obtained over the 2006-2013 period were highly satisfactory. An intensive training program on research and management is a useful strategy for in-hospital capacity-building of pediatric health care professionals in basic tools for research activities, critical reading of biomedical literature and rational management of pediatric health services.

Se describe una estrategia de capacitación en investigación y gestión para profesionales hospitalarios iniciada en 2006 en un hospital pediátrico y sus resultados a ocho años de su implementación. Gestión e Investigación en Pediatría es un curso anual de 250 horas, teórico-práctico, semipresencial con soporte en campus virtual. Proporciona herramientas de investigación (epidemiología, metodología, búsqueda bibliográfica, medicina basada en evidencias, bioestadística) y gestión (planificación estratégica, programas de gestión, investigación en servicios de salud, calidad, economía de la salud). Se evalúa mediante ejercicios de integración, un examen final y un proyecto grupal de investigación o gestión. Los resultados obtenidos entre 2006 y 2013 fueron altamente satisfactorios. La implementación en el ámbito hospitalario de un programa de capacitación intensivo en gestión e investigación para profesionales de la salud es una estrategia útil para facilitar la incorporación y aplicación de herramientas prácticas para investigación, interpretación crítica de la bibliografía biomédica y gestión racional de servicios pediátricos

A 10-YEAR HOSPITAL-BASED HEALTH TECHNOLOGY ASSESSMENT PROGRAM IN A PUBLIC HOSPITAL IN ARGENTINA.

OBJECTIVES: To describe the first hospital-based health technology assessment (HTA) program in a public hospital in Argentina, and report some clinical, educational, economic and organizational results after 10 years of its implementation. METHODS: A hospital-based HTA program was created in March 2001 at Hospital Garrahan (Buenos Aires, Argentina), a national pediatric facility with a self-managed budget. Its main goal is to promote a rational and evidence-based technologic development. The program consists of HTA reports for technology acquisition, clinical practice guidelines (CPG), capacity building in research and management, and technical support for health services research (HSR). The evaluation cycle comprises: prioritization, evidence synthesis, dissemination and monitoring. We report program performance, comment educational and organizational effects, and discuss unresolved issues and future challenges. RESULTS: During the first 10 years the program produced 18 HTA reports on drugs (6 = 33 percent), therapeutic (6 = 33 percent), preventive (2 = 11 percent) or diagnostic (2 = 11 percent) procedures and institutional programs (3 = 17 percent). The scope covered effectiveness (12 = 67 percent), safety (10 = 56 percent), budget impact (6 = 33 percent), cost-effectiveness (2 = 11 percent) and organizational impact (3 = 17 percent). Mean time from request to report was 10 months. Eleven pediatric CPGs were submitted to expert consensus and disseminated for full-text Web access. A 1-year course on research and management was completed by 225 professionals in 6 years, and twenty-two projects for HSR were coached. CONCLUSIONS: Our experience shows that an HTA program is both feasible and useful in a public hospital of a developing country. Promotion of hospital-based HTA, professional integration in HTA activities and network collaboration to discuss unresolved issues with colleagues can multiply the benefits and optimize the use of hospital budgets.

Anterior segment invasion in retinoblastoma: is it a risk factor for extraocular relapse?

We report a retrospective review of patients with retinoblastoma and anterior segment invasion (ASI) as risk factors for extraocular relapse. Only those with ASI combined with postlaminar optic nerve invasion and/or scleral invasion received adjuvant chemotherapy and those with tumor at the resection margin received orbital radiotherapy. Those with only uveal invasion did not receive adjuvant therapy. Of 479 evaluable patients, 67 patients had pathologically confirmed ASI, including 52 with anterior chamber invasion and 47 with iris or ciliary body invasion. ASI occurred with other pathology risk factors (25 had concomitant posterior uveal invasion, 36 had postlaminar optic nerve invasion, 11 with cut-end invasion, and 25 with scleral invasion). The 5-year disease-free survival (pDFS) was 0.9 (95% CI, 0.8-0.95) for children with ASI with no significant differences among children with other pathology risk factors with and without ASI. ASI was not significantly associated with extraocular relapse in multivariate analysis. There were no significant differences in pDFS for patients with anterior chamber invasion and those with iris-ciliary body invasion (pDFS 0.89 [95% CI, 0.65-0.96] vs. 0.93 [95% CI, 0.61-0.98]). To conclude, ASI was seen with other pathology risk factors and it did not add a significant risk for extraocular relapse.

Clinical presentation of retinoblastoma in a middle-income country.

The presenting features of retinoblastoma in developing countries and their correlation with disease stage and patient survival are poorly known and they may be useful as background information for planning early diagnosis initiatives. Therefore, we undertook a retrospective review of 508 patients (467 evaluable, 296 unilateral) treated in Argentina from 1988 to 2008. Patients presented at an older age than reported from high-income countries [mean age 24 mo (range, 0 to 165 mo), 31 mo for unilateral (range, 0 to 165 mo), and 13.3 mo (range, 0 to 62 mo) for bilateral disease]. Leukocoria was the most common presenting sign (n=402, 86%). Strabismus was the only complaint in 25 (5.3%) patients. Forty-two patients (9%) presented with an enlarged eyeball and 37 (7.9%) with a red eye. Retinoblastoma was diagnosed in 22 (4.7%) asymptomatic children. These patients and those with strabismus alone were significantly younger and had a significantly better survival. Children presenting with enlarged eyeballs were significantly older and had significantly lower survival. In multivariable analysis older age and presentation with enlarged eyeballs were independently associated to advanced stage and mortality (P<0.001). Retinoblastoma is diagnosed in later stages in our setting and presentation with eye enlargement and increasing age at diagnosis correlate with worse outcome.

[Evidence-based pediatrics: diagnostic tests (2nd part)]. / Pediatría basada en la evidencia: Estudios de diagnóstico (2ª parte).

Diagnosis is a complex process, demanding experience and proper instruments. Technology has advanced rapidly, increasing the number of available diagnostic tests. However, few well designed and validated useful clinical tools exist. This article summarizes the development process for clinical prediction rules and the use of ROC curves to select the best cutoff point for tests with continuous results.

Pediatría basada en la evidencia: estudios de diagnóstico (2ª parte) / Evidence-based pediatrics: diagnostic tests (2nd part)

El proceso diagnóstico es complejo y ejercitarlo exige experiencia e instrumentos adecuados. Elavance tecnológico ha multiplicado el número de pruebas diagnósticas disponibles, aunque son pocas las herramientas clínicas bien diseñadas,validadas y útiles. En este artículo describimos el proceso de construcción de reglas de predicción clínica y el uso de curvas ROC para la seleccióndel valor límite óptimo para una pruebacon resultado numérico.

Diagnosis is a complex process, demanding experience and proper instruments. Technology has advanced rapidly, increasing the number of available diagnostic tests. However, fewwell designed and validated useful clinical tools exist. This article summarizes the development process for clinical prediction rules and the use of ROC curves to select the best cutoff point for tests with continuous results.

[Transfusional requirements for escharectomy in burned children]. / Requerimientos transfusionales para escarectomía en niños quemados.

INTRODUCTION: Early excision has considerably improved outcome in extensive burns, but massive resections usually mean copious bleeding that must be conveniently corrected. The purpose of this study was to measure blood component use during escharectomies in children. MATERIAL AND METHODS: All pediatric patients with acute burns excised at the Burn Unit of the Hospital Garrahan during one year were included. Volume of blood component used during and immediately after surgery was analyzed and related to percent excised, time post-burn, and the coexistence of infection and autograft at the time of excision. RESULTS: Ninety-four surgeries in 51 children aged 0-14 years with total burned body surface areas of 5-80% who underwent resections of 3-70% were studied. Total blood use (intra + post-operatively) was 2.07 ml/kg/%excised for red blood cells (60% during surgery) and 0.7 ml/kg/% excised for plasma. Only 12% of patients required platelet transfusion. There was no significant requirement variation with the existence of infection, grafting or time post-burn. CONCLUSIONS: Approximately 2 ml/kg/% excised of red blood cells (2/3 for surgery) and 1 ml/kg/% excised of plasma are needed for escharectomies in children. The need for platelets must be judged considering the individual patient.

Requerimientos transfusionales para escarectomía en niños quemados / Transfusional requirements for escharectomy in burned children

La escarectomía masiva temprana ha mejorado los resultados en grandes quemados, pero las grandes resecciones se asocian a sangrados considerables que obligan a una reposición de sangre en forma oportuna. El presente estudio se diseño con el objetivo de cuantificar el consumo de hemocomponentes durante escarectomías de niños quemados. Material y métodos. Se incluyeron todos los pacientes pediátricos con quemaduras agudas escarectomizados en la Unidad de Quemados del Hospital Nacional de Pediatría Prof. Dr. Juan P. Garrahan en un año. Se analizó el volumen de hemocomponetes (glóbulos rojos, plasma y plaquetas) utilizados en el intraoperatorio y posoperatorio inmediato, y se relacionó con el porcentaje de superficie corporal resecada (por ciento SCR), tiempo de evolución, presencia de infección y autoinjerto en el mismo acto quirúrgico. Resultados. Se estudiaron 94 resecciones 51 pacientes de 0 - 14 años de edad con superficies corporales quemadas (por ciento SCQ) de 5 - 80 por ciento sometidos a escarectomías de 3-70 por ciento por sesión. El consumo total (intraoperatorio más posoperatorio) promedio de hemocomponentes fue de 2,07 ml/kg/ por ciento SCR para los glóbulos rojos (el 60 por ciento del cual fue durante la cirugía) y de 0,7 ml/Kg/ por ciento SCR para el plasma. Sólo un 12 por ciento requirió transfusión de plaquetas. Los requerimientos no variaron significativamente con la coexistencia de infección, autoinjerto o el tiempo de evolución. Conclusiones. Se estima que, para una escarectomía, se requerirán alrededor de 2 ml/Kg/por ciento resecado de concentrados de glóbulos rojos (2/3 para la cirugía) y 1 ml/Kg/por ciento resecado de plasma. La necesidad de plaquetas debe preverse según cada paciente.

Requerimientos transfusionales para escarectomía en niños quemados / Transfusional requirements for escharectomy in burned children

La escarectomía masiva temprana ha mejorado los resultados en grandes quemados, pero las grandes resecciones se asocian a sangrados considerables que obligan a una reposición de sangre en forma oportuna. El presente estudio se diseño con el objetivo de cuantificar el consumo de hemocomponentes durante escarectomías de niños quemados. Material y métodos. Se incluyeron todos los pacientes pediátricos con quemaduras agudas escarectomizados en la Unidad de Quemados del Hospital Nacional de Pediatría Prof. Dr. Juan P. Garrahan en un año. Se analizó el volumen de hemocomponetes (glóbulos rojos, plasma y plaquetas) utilizados en el intraoperatorio y posoperatorio inmediato, y se relacionó con el porcentaje de superficie corporal resecada (por ciento SCR), tiempo de evolución, presencia de infección y autoinjerto en el mismo acto quirúrgico. Resultados. Se estudiaron 94 resecciones 51 pacientes de 0 - 14 años de edad con superficies corporales quemadas (por ciento SCQ) de 5 - 80 por ciento sometidos a escarectomías de 3-70 por ciento por sesión. El consumo total (intraoperatorio más posoperatorio) promedio de hemocomponentes fue de 2,07 ml/kg/ por ciento SCR para los glóbulos rojos (el 60 por ciento del cual fue durante la cirugía) y de 0,7 ml/Kg/ por ciento SCR para el plasma. Sólo un 12 por ciento requirió transfusión de plaquetas. Los requerimientos no variaron significativamente con la coexistencia de infección, autoinjerto o el tiempo de evolución. Conclusiones. Se estima que, para una escarectomía, se requerirán alrededor de 2 ml/Kg/por ciento resecado de concentrados de glóbulos rojos (2/3 para la cirugía) y 1 ml/Kg/por ciento resecado de plasma. La necesidad de plaquetas debe preverse según cada paciente.(AU)

Pediatría basada en la evidencia. Estudios de diagnóstico (1a parte) / Evidence-based pediatrics. Diagnostic tests (1st part)

Arribar a un diagnóstico correcto es un gran desafío que enfrenta el médico diariamente. A través de la anamnesis y del examen físico se llega a la sospecha clínica y con frecuencia se requiereun estudio auxiliar para confirmarla o descartarla.El avance de la tecnología ha hecho que el número de estudios disponibles para una misma enfermedad sea cada vez mayor. El médico debe elegir cuál es el adecuado, según el desempeñode la prueba, características del paciente, riesgos y costos. En este artículo analizaremos la confiabilidad, interpretación y aplicación de losresultados de una prueba diagnóstica.

Pediatría basada en la evidencia. Estudios de diagnóstico (1a parte) / Evidence-based pediatrics. Diagnostic tests (1st part)

Arribar a un diagnóstico correcto es un gran desafío que enfrenta el médico diariamente. A través de la anamnesis y del examen físico se llega a la sospecha clínica y con frecuencia se requiereun estudio auxiliar para confirmarla o descartarla.El avance de la tecnología ha hecho que el número de estudios disponibles para una misma enfermedad sea cada vez mayor. El médico debe elegir cuál es el adecuado, según el desempeñode la prueba, características del paciente, riesgos y costos. En este artículo analizaremos la confiabilidad, interpretación y aplicación de losresultados de una prueba diagnóstica.(AU)

Some clinical findings at presentation can predict high-risk pathology features in unilateral retinoblastoma.

AIMS: To identify clinical features at presentation to help in detecting patients with retinoblastoma and pathology risk factors (PRFs) preoperatively, and therefore selecting a high-risk population that could benefit from preoperative treatment. METHODS: A retrospective analysis of a prospectively filled form of 182 consecutive patients with unilateral retinoblastoma treated with initial enucleation from 1988 to 2006. Univariate and multivariate analyses were carried out. Major choroidal invasion and postlaminar optic nerve and scleral extension were considered PRFs. Within this subgroup, a higher-risk cohort (microscopical residual disease caused by trans-scleral invasion or invasion to the resection margin of the optic nerve) was analyzed separately. RESULTS: One hundred sixty-four patients had completely resected and 18 had microscopical residual disease. Seventy three had at least 1 PRF (massive invasion to the choroid in 25, to the postlaminar optic nerve in 41, intrascleral in 10, to the resection margin of the optic nerve in 12, and trans-scleral in 6). Seventy-one patients had glaucoma and 19 had buphthalmia. Intraocular pressure, glaucoma, and buphthalmia correlated significantly with the occurrence of both PRF and microscopical residual disease in multivariate analysis. Buphthalmia was the most specific factor but the sensitivity was lower. Glaucoma and buphthalmia had a high negative predictive value. CONCLUSIONS: Patients presenting with glaucoma and/or buphthalmia have a significantly higher risk for the occurrence of PRF, including those resulting in microscopically residual disease.

[Evidence-based pediatrics: diagnostic tests (1st part)]. / Pediatría basada en la evidencia: estudios de diagnóstico (1a parte).

To arrive to an accurate diagnosis is a great challenge in medical daily practice. Through anamnesis and physical examination, it is possible to have a clinical suspicion but it is often required a diagnosis test to confirm or rule out it. For the same condition, technological advances have multiplied the available tests. From them, doctors have to choose the most suitable test, according to its performance, patient characteristics, harms and costs. We will analyze the reliability, interpretation and application for one diagnosis test results.

Carga de enfermedad y costos asociados a las internaciones porinfección respiratoria aguda en niños / Disease burden and associated costs for hospitalitations due to acute respiratory infections in children

Introducción. El 1 por ciento de los lactantes necesitan serinternados por infecciones respiratorias agudas bajas, entre las que predomina netamente el síndrome de obstrucción bronquial y la neumonía. Es frecuente que la población consulte a centros dealta complejidad para resolver problemas de escasa relevancia, lo que provoca empleo inadecuado delos recursos hospitalarios y aumento de la carga de enfermedad asociada.Objetivos. 1) Estimar el costo para las familias de una internación por infección respiratoria aguda baja. 2) Realizar una evaluación económica comparativade los costos asociados a la internación de un episodio de infección respiratoria aguda baja entre un centro de tercer nivel de atención y los centros demenor complejidad próximos al domicilio. 3) Explorar los motivos que llevan a la población a consultarfuera de su área programática.Población. Pacientes de 0 a 10 años internados en tres hospitales del conurbano bonaerense pertenecientesa las regiones sanitarias V, VI y VIIª y elHospital de Pediatría Prof. Dr. Juan P. Garrahan.Material y métodos. Se trató de un estudio observacional,descriptivo analítico, prospectivo y transversal.El estudio se llevó a cabo durante el brote epidémico estacional, entre los meses de junio, julio y agosto de 2004. Se diseñó una encuesta de tipo semiestructurada y se realizaron entrevistas con las familias en los cuatro hospitales incluidos en el proyecto