Cystic fibrosis: desensitization in delayed hypersensitivity reactions to elexacaftor/tezacaftor/ivacaftor.

Background: Cystic fibrosis transmembrane conductance regulator modulators are the only available treatment for cystic fibrosis. Although elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is well-tolerated, rash has been reported as very frequent. In severe rashes, ELX/TEZ/IVA withdrawal is necessary, leading to clinical deterioration. The objective of the study is to increment the experience of ELX/TEZ/IVA desensitization. Methods: Adult patients who developed a delayed hypersensitivity rash to ELX/TEZ/IVA between December 2021 and February 2023 and required withdrawal due to ineffective rescue medication were included. Skins test for ELX/TEZ/IVA and IVA were conducted to establish hypersensitivity mechanism. Balijepally ELX/TEZ/IVA desensitization protocol was selected. In cases where desensitization had to be discontinued due to rash, an extended desensitization was proposed. Clinical and health-related quality of life parameters were collected before ELX/TEZ/IVA and after desensitization. Results: 162 patients (81 women, 31.2 [23.8-42.5] years) started ELX/TEZ/IVA, developing rash 12 of them (7.4%, six women). Six patients (five women) required stopping ELX/TEZ/IVA and were selected for desensitization. Skin tests indicated delayed type-IV hypersensitivity in one patient. Two patients presented adequate tolerance to desensitization; while, four patients developed rash. Three of these patients, successfully concluded extended desensitization (one patient declined participation). No significant clinical deterioration or quality of life worsening was observed during desensitization; in fact, there was an improvement in practically all mesured parameters. All five patients who resumed ELX/TEZ/IVA are currently receiving therapy with good tolerance. Conclusion: Desensitization to ELX/TEZ/IVA could be a successful and safe strategy for reintroducing this essential treatment in cases of a delayed hypersensitivity rash.

Clinical practice update of antifungal prophylaxis in immunocompromised children.

Due to the rise in the number and types of immunosuppressed patients, invasive fungal infections (IFI) are an increasing and major cause of morbidity and mortality in immunocompromised adults and children. There is a broad group of pediatric patients at risk for IFI in whom primary and/or secondary antifungal prophylaxis (AFP) should be considered despite scant evidence. Pediatric groups at risk for IFI includes extremely premature infants in some settings, while in high-risk children with cancer receiving chemotherapy or undergoing haematopoietic stem cell transplantation (HCT), AFP against yeast and moulds is usually recommended. For solid organ transplanted, children, prophylaxis depends on the type of transplant and associated risk factors. In children with primary or acquired immunodeficiency such as HIV or long-term immunosuppressive treatment, AFP depends on the type of immunodeficiency and the degree of immunosuppression. Chronic granulomatous disease is associated with a particular high-risk of IFI and anti-mould prophylaxis is always indicated. In contrast, AFP is not generally recommended in children with long stay in intensive care units. The choice of AFP is limited by the approval of antifungal agents in different age groups and by their pharmacokinetics characteristics. This document aims to review current available information on AFP in children and to provide a comprehensive proposal for each type of patient.

Patología infecciosa importada en hospitales terciarios / Imported infectious diseases in tertiary hospital

INTRODUCCIÓN: En el ańo 2009 se crea en nuestro centro una Consulta de Patología Importada. El objetivo de este trabajo es conocer su aportación en cuanto a capacidad, calidad asistencial y docencia ofrecida. PACIENTES Y MÉTODOS: Estudio retrospectivo entre 2009 y 2011 donde se analizan: a) desarrollo del conocimiento mediante la valoración de protocolos y publicaciones realizadas, así como la docencia impartida; y b) capacidad y calidad asistencial ofrecida mediante el análisis de los pacientes atendidos, la adecuación a los protocolos y la accesibilidad a la consulta. Se clasifican los pacientes atendidos en 3 grupos: grupo 1 cribado del paciente inmigrante; grupo 2 consulta tras viaje a zona tropical o subtropical; grupo 3 cribado de enfermedad importada de transmisión vertical. RESULTADOS: Se han desarrollado y difundido en la web de la unidad 6 protocolos y 5 publicaciones científicas. Se han atendido 316 pacientes: 191 incluidos en el grupo 1 (29 adoptados y 162 inmigrantes); 57 en el grupo 2 (94,7% Visiting Friends and Relatives y 81,5% sin consulta previaje), que acudieron principalmente por clínica gastrointestinal (52,6%) y fiebre (43,8%); y 68 en el grupo 3 con riesgo de infección importada de transmisión vertical (62 Trypanosoma cruzi, 1 virus linfotrópico T humano y 5 Plasmodium spp.). La adecuación global a los protocolos disponibles fue del 77,1%. DISCUSIÓN: Las unidades de patología infecciosa deben adaptarse a la realidad de la población que atienden, siendo flexibles en su estructura. Es imprescindible la valoración periódica de la calidad asistencial ofrecida, así como la valoración en la rentabilidad de los estudios complementarios a realizar (AU) - es INTRODUCTION: An Imported Diseases Clinic was created in the hospital in 2009. The aim of this study was to asses its contribution in terms of capacity, quality of care and teaching offered. PATIENTS AND METHODS: A retrospective study was conducted from 2009 to 2011, analyzing: A) development of knowledge by means of protocols and publications created, and subject taught; B) capacity and quality of care offered by the analysis of patients seen, the adequacy of the protocols and accessibility.The patients were classified into 3 groups. Group 1: immigrant patient screening, group 2: patient consultation after tropical or sub-tropical travel, group 3: screening of vertical transmission of imported disease. RESULTS: Six protocols have been developed and disseminated on the unit website, as well as 5 scientific publications. A total of 316 patients were evaluated: 191 included in group 1 (29 Adopted and 162 Immigrants), 57 in group 2 (94.7% Visiting Friends and Relatives and 81.5% without a pre-travel consultation). They consulted due to, gastrointestinal symptoms (52.6%) and fever (43.8%), with 68 included in group 3 at risk of imported disease by vertical transmission (62 Trypanosoma cruzi, 1 Human T Lymphotropic Virus and 5 Plasmodium spp.). The overall adherence to the protocols was about 77.1%. DISCUSSION: Infectious Diseases Units must adapt to the reality of the population and be flexible in its structure. Periodic assessment of the quality of care offered is essential, as well as an evaluation on the need for additional studies

INTRODUCTION: An Imported Diseases Clinic was created in the hospital in 2009. The aim of this study was to asses its contribution in terms of capacity, quality of care and teaching offered. PATIENTS AND METHODS: A retrospective study was conducted from 2009 to 2011, analyzing: A) development of knowledge by means of protocols and publications created, and subject taught; B) capacity and quality of care offered by the analysis of patients seen, the adequacy of the protocols and accessibility.The patients were classified into 3 groups. Group 1: immigrant patient screening, group 2: patient consultation after tropical or sub-tropical travel, group 3: screening of vertical transmission of imported disease. RESULTS: Six protocols have been developed and disseminated on the unit website, as well as 5 scientific publications. A total of 316 patients were evaluated: 191 included in group 1 (29 Adopted and 162 Immigrants), 57 in group 2 (94.7% Visiting Friends and Relatives and 81.5% without a pre-travel consultation). They consulted due to, gastrointestinal symptoms (52.6%) and fever (43.8%), with 68 included in group 3 at risk of imported disease by vertical transmission (62 Trypanosoma cruzi, 1 Human T Lymphotropic Virus and 5 Plasmodium spp.). The overall adherence to the protocols was about 77.1%. DISCUSSION: Infectious Diseases Units must adapt to the reality of the population and be flexible in its structure. Periodic assessment of the quality of care offered is essential, as well as an evaluation on the need for additional studieS

[Imported infectious diseases in tertiary hospital]. / Patología infecciosa importada en hospitales terciarios.

INTRODUCTION: An Imported Diseases Clinic was created in the hospital in 2009. The aim of this study was to asses its contribution in terms of capacity, quality of care and teaching offered. PATIENTS AND METHODS: A retrospective study was conducted from 2009 to 2011, analyzing: A) development of knowledge by means of protocols and publications created, and subject taught; B) capacity and quality of care offered by the analysis of patients seen, the adequacy of the protocols and accessibility. The patients were classified into 3 groups. Group 1: immigrant patient screening, group 2: patient consultation after tropical or sub-tropical travel, group 3: screening of vertical transmission of imported disease. RESULTS: Six protocols have been developed and disseminated on the unit website, as well as 5 scientific publications. A total of 316 patients were evaluated: 191 included in group 1 (29 Adopted and 162 Immigrants), 57 in group 2 (94.7% Visiting Friends and Relatives and 81.5% without a pre-travel consultation). They consulted due to, gastrointestinal symptoms (52.6%) and fever (43.8%), with 68 included in group 3 at risk of imported disease by vertical transmission (62 Trypanosoma cruzi, 1 Human T Lymphotropic Virus and 5 Plasmodium spp.). The overall adherence to the protocols was about 77.1%. DISCUSSION: Infectious Diseases Units must adapt to the reality of the population and be flexible in its structure. Periodic assessment of the quality of care offered is essential, as well as an evaluation on the need for additional studies.

Uso de derivados intravenosos de artemisinina en la malaria grave / Use of intravenous artemisinin derivatives in severe malaria

No disponible

[Osmolality of oral liquid dosage forms to be administered to newborns in a hospital]. / Osmolalidad de las formas farmacéuticas orales líquidas en un hospital para su aplicación en neonatos.

OBJECTIVE: Oral administration of hypertonic solutions can contribute to intestinal damage in the initial stages of neonatal necrotizing enterocolitis. The purpose of this study is to determine the osmolality of oral liquid dosage forms used in a division of neonatology and to establish some recommendations for their dilution. METHOD: The osmolality of 26 oral liquid dosage forms has been measured using the freezing-point depression method. RESULTS: Oral liquid dosage forms used in the division of neonatology present an osmolality greater than 350 mOsm/kg H2O. 19.2% of all the analysed forms presented an osmolality lower than 1500 mOsm/kg H2O, 80.7% were over that figure, while 23% presented an extremely high osmolality (> 5,000 mOsm/kg H2O). CONCLUSIONS: Knowledge of osmolality of oral liquid dosage forms in the division of neonatology enables the risk of intestinal aggression caused by enteral administration of the medication to be assessed.

Osmolalidad de las formas farmacéuticas orales líquidas en un hospital para su aplicación en neonatos / No disponible

Objetivo: La administración oral de soluciones hipertónicaspuede participar en la lesión intestinal en la fase inicial de la enterocolitisnecrotizante neonatal. El objetivo del estudio es determinarla osmolalidad de las fórmulas farmacéuticas orales líquidasutilizadas en una unidad de neonatología y establecer recomendacionesde dilución.Método: Se ha medido la osmolalidad de 26 fórmulas farmacéuticasorales líquidas por el método de descenso crioscópico.Resultados: Las fórmulas farmacéuticas orales líquidas utilizadasen la unidad de neonatología presentan una osmolalidad superiora 350 mOsm/kg H2O. Del total analizado, el 19,2% de las fórmulaspresentaban una osmolalidad inferior a 1.500 mOsm/kgH2O, el 80,7% superior y el 23% presentaban una osmolalidadextremadamente alta (> 5.000 mOsm/kg H2O).Conclusiones: El conocimiento de la osmolalidad de las fórmulasfarmacéuticas orales líquidas administradas en la unidad deneonatología permite valorar el riesgo de agresividad intestinalque produce la administración enteral de la medicación

Objective: Oral administration of hypertonic solutions can contributeto intestinal damage in the initial stages of neonatal necrotizingenterocolitis. The purpose of this study is to determine the osmolalityof oral liquid dosage forms used in a division of neonatologyand to establish some recommendations for their dilution.Method: The osmolality of 26 oral liquid dosage forms hasbeen measured using the freezing-point depression method.Results: Oral liquid dosage forms used in the division ofneonatology present an osmolality greater than 350 mOsm/kgH2O. 19.2% of all the analysed forms presented an osmolalitylower than 1500 mOsm/kg H2O, 80.7% were over that figure,while 23% presented an extremely high osmolality (> 5,000mOsm/kg H2O).Conclusions: Knowledge of osmolality of oral liquid dosageforms in the division of neonatology enables the risk of intestinalaggression caused by enteral administration of the medication tobe assessed

[Administration of anti-infective agents through the inhaled route]. / Administración de antiinfecciosos por vía inhalatoria.

OBJECTIVE: To report the doses of inhaled anti-infective agents described in the literature for both the adult and paediatric population. In the case of anti-infective agents which were not approved for inhaled administration, to propose the optimum manner in which these should be prepared in order to achieve osmolality and pH values as similar as possible to physiological values. METHOD: A search was carried out of Pubmed (between 1960 and 2005) for each of the anti-infective agents using the words "inhalation OR inhaled OR aerosol OR aerosolized OR nebulized". We also consulted text books, Micromedex and the technical specifications of the pharmaceutical products. Nebulised solutions were prepared using the drugs for which information was found. The drugs approved for inhaled administration were prepared according to the manufacturers recommendations. For anti-infective agents which were not approved for inhaled administration, the raw materials and the branded drug products for intravenous administration available at our hospital were diluted using physiological saline solution and/or water for injection up to a final volume of 4-5 ml. The osmolality and pH values of all the solutions were measured. The optimum form of preparation was considered to be one with values as close as possible to between 150 and 550 mOsm/kg for osmolatity osmolality and 7 +/- 0.5 for pH. RESULTS: Information about doses of 18 inhaled anti-infective agents was found (12 antibiotics, 5 antifungals and 1 antiviral); paediatric doses were described in 9 of these. Three of the anti-infective agents reviewed were approved for inhaled use in adult patients and four in paediatric patients. Of the 48 recommendations for dilution suggested for administration, two had an osmolality > 1,100 mOsm/kg and 5 an osmolality of < 100 mOsm/kg. Two dilutions had a pH > 8 and 14 a pH < 5. CONCLUSIONS: There is limited literature regarding the doses of anti-infective agents for inhaled administration. The majority of anti-infective agents are not approved for inhaled administration. The dilution of the raw material or proprietary drugs with water or physiological saline solution for intravenous administration achieved solutions with appropriate osmolality in the majority of cases. Some of the solutions have extreme osmolality and/or pH levels, implying that it is reasonable to expect a greater risk of bronchospasm.

Administración de antiinfecciosos por vía inhalatoria / No disponible

Objetivo: Describir las dosis de los antiinfecciosos inhalados descritas en la literatura tanto en la población adulta como en la pediátrica. Para aquellos antiinfecciosos que no tienen la vía inhalatoria aprobada, proponer la forma óptima de preparación para conseguir una osmolaridad y un pH lo más cercano posible a los valores fisiológicos. Método: Se realizó una búsqueda en PubMed (entre 1960 y 2005) con cada uno de los antiinfecciosos y las palabras "inhalation OR inhaled OR aerosol OR aerosolized OR nebulized". También se consultaron libros de texto, Micromedex y las fichas técnicas de las especialidades farmacéuticas. De los fármacos que se encontró información se prepararon las soluciones para nebulizar. Los fármacos con vía inhalada aprobada se prepararon según las recomendaciones del laboratorio fabricante. Para los antiinfecciosos que no tienen la vía inhalatoria aprobada se prepararon diluciones de la materia prima o de las presentaciones comerciales por vía intravenosa disponibles en nuestro hospital con solución salina fisiológica y/o agua para inyección hasta un volumen final de 4-5 ml. Se midió la osmolaridad y pH de todas las soluciones. Se consideró como forma óptima de preparación, la más próxima posible a una solución de una osmolaridad entre 150 y 550 mOsm/kg y a un pH de 7 ± 0,5. Resultados: Se encontró información sobre dosificación por vía inhalatoria de 18 antiinfecciosos (12 antibióticos, 5 antifúngicos y 1 antivírico), de los cuales en 9 se describe la dosis pediátrica. Tres de los antiinfecciosos revisados tienen la vía inhalatoria aprobada en adultos y 4 en pediatría. De las 48 recomendaciones de dilución propuestas para la administración, dos tienen una osmolaridad > 1.100 mOsm/kg y 5 una osmolaridad 8 y 14 un pH < 5. Conclusiones: La información bibliográfica sobre las dosificaciones de los antiinfecciosos por vía inhalatoria es escasa. La mayoría de antiinfecciosos no tienen aprobada la administración por vía inhalatoria. La dilución de la materia prima o de las especialidades por vía intravenosa con agua o solución salina fisiológica consigue soluciones con osmolaridad adecuada en la mayoría de los casos. Algunas de las soluciones tienen valores extremos de osmolaridad y/o pH con lo que cabe esperar un riesgo mayor de broncoespasmo

Objective: To report the doses of inhaled anti-infective agents described in the literature for both the adult and paediatric population. In the case of anti-infective agents which were not approved for inhaled administration, to propose the optimum manner in which these should be prepared in order to achieve osmolality and pH values as similar as possible to physiological values. Method: A search was carried out of Pubmed (between 1960 and 2005) for each of the anti-infective agents using the words “inhalation OR inhaled OR aerosol OR aerosolized OR nebulized”. We also consulted text books, Micromedex and the technical specifications of the pharmaceutical products. Nebulised solutions were prepared using the drugs for which information was found. The drugs approved for inhaled administration were prepared according to the manufacturers’ recommendations. For anti-infective agents which were not approved for inhaled administration, the raw materials and the branded drug products for intravenous administration available at our hospital were diluted using physiological saline solution and/or water for injection up to a final volume of 4-5 ml. The osmolality and pH values of all the solutions were measured. The optimum form of preparation was considered to be one with values as close as possible to between 150 and 550 mOsm/kg for osmolatity osmolality and 7 ± 0.5 for pH. Results: Information about doses of 18 inhaled anti-infective agents was found (12 antibiotics, 5 antifungals and 1 antiviral); paediatric doses were described in 9 of these. Three of the antiinfective agents reviewed were approved for inhaled use in adult patients and four in paediatric patients. Of the 48 recommendations for dilution suggested for administration, two had an osmolality > 1,100 mOsm/kg and 5 an osmolality of 8 and 14 a pH < 5. Conclusions: There is limited literature regarding the doses of anti-infective agents for inhaled administration. The majority of anti-infective agents are not approved for inhaled administration. The dilution of the raw material or proprietary drugs with water or physiological saline solution for intravenous administration achieved solutions with appropriate osmolality in the majority of cases. Some of the solutions have extreme osmolality and/or pH levels, implying that it is reasonable to expect a greater risk of bronchospasm