Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence

Background: A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice.Method: A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses' experiences and views.Results: The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance.Conclusion: Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children

A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice

This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug

MODRIC - manipulation of drugs in children

Background: Lack of age-appropriate drugs for children and newborns makes neonatal nursing care a high-risk task preparing and administering medication. Aim: To propose a manual with recommendations about preparation and medication administration of high-risk drugs at NICU. Method: A cross-sectional descriptive study was carried out at two neonatal care units to identify frequently used drugs. Then, a qualitative descriptive study using semi-structured interviews was conducted to identify critical aspects for preparing and administering medicines. Finally, a narrative literature review was made to contrast evidence with lack of identified information. Results: The most common used medications were Ampicillin, gentamicin, dextrose and electrolytes. Medication(s), to preparing/preparation and administrating/administration were the most used words, and were used 567, 383 and 349 times, respectively. Dilution, process and correct(s) were used among 100 and 200 times. Doubt, neonatal/neonate(s) and patient among 80 and 90 times. Several publications reviewed have demonstrated that do not include information about 32 critical aspects identified for preparing and administering drugs by nurses. Conclusion: Preparation and administration of drugs are complex processes. To improve patient care and minimize medication errors at NICU, it is necessary to provide knowledge of the physicochemical properties of drugs to determine their stability, effectiveness and safety of use. This knowledge should be available in easily accessible documents so nurses can perform these processes safely.La baja disponibilidad de medicamentos en presentaciones pediátricas para neonatos convierte la profesión de enfermería neonatal en una actividad de alto riesgo a la hora de preparar y administrar medicamentos. Con el fin de realizar un aporte a dicho problema, se pretende elaborar una propuesta de manual con recomendaciones para la preparación y administración de medicamentos de alto riesgo en unidades de cuidado neonatal. Para lograrlo, se llevó a cabo un estudio descriptivo de corte transversal en dos servicios de neonatología que permitieron identificar los medicamentos más utilizados. A continuación, con un estudio cualitativo descriptivo y utilizando entrevistas semiestructuradas, se identificaron aspectos críticos a tener en cuenta en la preparación y administración de medicamentos. Finalmente, una búsqueda exhaustiva de la literatura permitió contrastar la evidencia con las necesidades de información identificadas en el estudio. Los resultados encontrados señalan que electrolitos, ampicilina, gentamicina, dextrosas y otros azúcares fueron los medicamentos más utilizados. Señalan también que las palabras medicamento(s), preparar/preparación y administrar/administración fueron empleadas 567, 383 y 349 veces, respectivamente. Dilución, proceso y correcto(s) fueron usadas entre 100 y 200 veces. Duda, neonatal/neonato(s) y paciente, entre 80 y 90 veces. También se pudo evidenciar que ninguna fuente incluye información completa, dirigida a profesionales de enfermería, de los 32 aspectos críticos para la preparación y administración de medicamentos. Este conocimiento debería encontrarse disponible y fácilmente accesible para llevar a cabo los procesos en forma segura.Magister en Ciencias - Farmacología. Línea de Investigación: Uso racional de medicamentos: pediatría y neonatologíaMaestrí

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field