True Rate of Allergy among Pediatric Inpatients with Penicillin Allergy Labels (TRIAL).

Background: Penicillin allergy is a common drug allergy diagnosis in pediatric patients; however, upon appropriate allergy testing, many of these patients are found not to have a true allergy. For patients with a reported allergy, alternative antibiotics are prescribed, which are less effective, more toxic, or more expensive. There is a lack of data evaluating allergies in hospitalized children and comparing allergy assessments conducted by pediatric allergists and pharmacists. Objective: To estimate the percentage of pediatric patients admitted with reported penicillin allergy who did not have a true penicillin allergy. Methods: This single-centre prospective cohort study included inpatients between 6 months and 17 years of age, with a documented penicillin allergy, who were admitted to the general pediatric and oncology units of a tertiary care children's hospital between November 2019 and March 2023. The allergy history, evaluation, and risk categorization were performed by pharmacists. The history was reviewed with the allergist, and the patient was then referred, underwent skin testing, or received oral amoxicillin challenge with monitoring for 1 hour. Results: Thirty patients were included, of whom 29 (97%) had delabelling of their penicillin allergy. Four patients (13%) had delabelling on the basis of history alone, without risk assessment. Twenty-five (83%) of the patients were assessed as having low risk; 24 of these had delabelling following oral challenge, and 1 did not complete the oral challenge because of transfer to another hospital. One patient (3%) was assessed as having moderate risk, with delabelling on the basis of results of skin testing and oral challenge. The pharmacist's and allergist's risk assessments were in agreement in 29 (97%) of the 30 cases. Conclusions: Pediatric patients, including those with oncologic malignancies, are often mislabelled as having a penicillin allergy. Pharmacists are able to accurately determine true allergy risk and delabel penicillin allergies for pediatric patients in the hospital setting.

Contexte: L'allergie à la pénicilline est un diagnostic d'allergie médicamenteuse courant chez les patients pédiatriques; cependant, après des tests d'allergie appropriés, bon nombre de ces patients ne présentent pas de véritable allergie. Pour ceux présentant une allergie signalée, des antibiotiques alternatifs sont prescrits, moins efficaces, plus toxiques ou plus coûteux. Peu de données permettent d'évaluer les allergies chez les enfants hospitalisés et de comparer les évaluations des allergies réalisées par les allergologues pédiatriques et les pharmaciens. Objectif: Estimer le pourcentage de patients pédiatriques admis avec une allergie à la pénicilline signalée, mais qui n'avaient pas de véritable allergie à la pénicilline. Méthodologie: Cette étude de cohorte prospective monocentrique comprenait des patients hospitalisés âgés de 6 mois à 17 ans, présentant une allergie documentée à la pénicilline, qui ont été admis dans les unités de pédiatrie générale et d'oncologie d'un hôpital pour enfants de soins tertiaires entre novembre 2019 et mars 2023. Les antécédents, l'évaluation et la catégorisation des risques de l'allergie ont été renseignés par les pharmaciens. L'anamnèse a été revue avec l'allergologue, et le patient a ensuite été référé, a subi un test cutané ou a reçu une provocation orale à l'amoxicilline avec surveillance pendant 1 heure. Résultats: Sur 30 patients inclus, 29 (97 %) ont vu un désétiquetage de leur allergie à la pénicilline. Quatre patients (13 %) ont bénéficié d'un désétiquetage sur la seule base de leurs antécédents, sans évaluation des risques. Vingt-cinq (83 %) patients ont été évalués comme présentant un faible risque; 24 d'entre eux ont bénéficié d'un désétiquetage à la suite d'une provocation orale, et 1 n'a pas terminé la provocation orale en raison d'un transfert vers un autre hôpital. Un patient (3 %) a été évalué comme présentant un risque modéré, avec un désétiquetage basé sur les résultats des tests cutanés et de la provocation orale. Les évaluations des risques par le pharmacien et l'allergologue concordaient dans 29 (97 %) des 30 cas. Conclusions: Les patients pédiatriques, y compris ceux atteints de cancers malins, sont souvent étiquetés à tort comme ayant une allergie à la pénicilline. Les pharmaciens sont en mesure de déterminer avec précision le risque réel d'allergie et de désétiqueter les allergies à la pénicilline chez les patients pédiatriques en milieu hospitalier.

Clinical pathway development to standardize pharmacological medication management of agitation in pediatric inpatient settings.

Objective: Acute agitation in pediatrics is commonly encountered in hospital settings, can contribute to significant physical and psychological distress, and management is highly varied in practice. As such, the development of a standardized pharmacologic guideline is paramount. We aimed to develop a novel clinical pathway (CP) for management of acute agitation for all hospitalized pediatric patients in Canada. Methods: Healthcare professionals in Canada with expertise in treating and managing pediatric agitation formed a working group and developed a CP through conducting a literature review, engaging key partners, and obtaining interdisciplinary consensus (iterative real-time discussions with content experts). Once developed, the preliminary CP was presented to additional internal and external partners via multiple grand rounds and a webinar; feedback from participants guided final CP revisions. Results: The working group created a pediatric inpatient CP to guide pharmacologic management of agitation and serve as an easy-to-use clinical and educational resource with three complementary sections including: 1) a treatment algorithm, 2) a quick reference medication chart, and 3) two supporting documents, which provide a general overview of non-pharmacologic strategies prior to CP implementation and an illustrative scenario to accompany the medication chart to ensure effective utilization. Conclusions: This is the first CP to standardize pharmacological treatment and management of acute agitation in children in inpatient settings in Canada. Although further research is warranted to assess implementation and support process improvement, the CP can be adapted by individual institutions to assist in prompt pharmacological management of pediatric agitation to potentially improve outcomes for patients, families, and healthcare professionals.

Objectif: L'agitation aiguë en pédiatrie survient couramment en milieu hospitalier, elle peut contribuer à une détresse physique et psychologique significative, et la prise en charge en est très variée dans la pratique. Ainsi, l'élaboration de lignes directrices pharmacologiques standardisées est essentielle. Nous cherchions à développer un nouveau parcours clinique (PC) de la prise en charge de l'agitation aiguë pour tous les patients pédiatriques hospitalisés au Canada. Méthodes: Les professionnels de la santé au Canada qui ont l'expertise du traitement et de la prise en charge de l'agitation pédiatrique ont formé un groupe de travail et développé un PC en menant une revue littéraire, en embauchant des partenaires cibles, et en obtenant un consensus interdisciplinaire (discussions itératives en temps réel avec des experts en contenu). Une fois développé, le PC préliminaire a été présenté à des partenaires internes et externes additionnels lors de multiples grandes rondes et à un webinaire; les commentaires des participants ont guidé les révisions finales du PC. Résultats: Le groupe de travail a créé un PC pour patient psychiatrique hospitalisé afin de guider la prise en charge pharmacologique de l'agitation et de servir de ressource clinique et éducative facile à utiliser munie de trois sections complémentaires notamment : 1) un algorithme de traitement, 2) un tableau des médicaments de référence, et 3) deux documents de soutien, qui offrent un aperçu général de stratégies non-pharmacologiques avant la mise en œuvre du PC et un scénario illustré pour accompagner le tableau des médicaments afin d'assurer une utilisation efficace. Conclusions: C'est le premier PC qui normalise le traitement pharmacologique et la prise en charge de l'agitation aiguë chez les enfants en milieu hospitalier au Canada. Bien que plus de recherche soit justifiée afin d'évaluer la mise en œuvre et de soutenir l'amélioration du processus, le PC peut être adapté par les institutions individuelles afin d'aider à une gestion pharmacologique rapide de l'agitation pédiatrique et de potentiellement aider à la gestion pharmacologique de l'agitation pédiatrique pour les patients, les familles et les professionnels de la santé.

Describing Intravenous Extravasation Injuries in Children (DIVE2 Study).

Background: Extravasation is the erroneous delivery of IV medication or fluid into the extravascular space. Complications ranging from mild injury to amputation can result, depending on the physical and pharmacologic properties of the infusate. Children are at increased risk for extravasation injuries. There is a paucity of data on the treatment and outcomes of extravasation injuries, particularly in terms of the role of pharmacologic antidotes. Objectives: To describe the incidence of extravasation at a tertiary pediatric care centre (as an update to a previous study), to identify the agents most commonly involved in extravasation injuries, to describe the antidotes used for management of injuries and their related adverse drug effects, and to describe complications related to injuries. Methods: The medical records of pediatric patients who experienced an extravasation injury at the BC Children's and BC Women's Hospitals, between September 1, 2008, and September 30, 2020, were reviewed. Data regarding management (adherence with institutional protocol) and outcomes of injuries were collected. Results: The 242 charts included in the analysis noted a total of 245 extravasation injuries, for an extravasation incidence of 0.04% per patient-day. Of the 242 patients, 110 were excluded from secondary outcome analysis due to lack of data detailing the extravasation event. Of the remaining 132 patients, the majority were neonates (n = 54, 40.9%), infants (n = 33, 25.0%), and children (n = 34, 25.8%), and more than a third were treated on general pediatric wards (n = 50, 37.9%). The medications most frequently involved were total parenteral nutrition with lipids (36/132, 27.3%), vancomycin (36/132, 27.3%), and IV fluids (35/132, 26.5%). Most of the patients had mild outcomes and recovered without complications. No adverse drug events from antidotes were reported. Conclusions: The incidence of extravasation at the study institution remained low, with the medications involved being similar to those reported in the literature and the majority of patients having mild outcomes. Additional prospective studies are needed to assess the efficacy and safety of antidotes administered for extravasation injuries.

Contexte: L'extravasation est l'administration erronée de médicaments ou de liquides IV dans l'espace extravasculaire. Des complications allant d'une blessure légère à l'amputation peuvent en résulter, en fonction des propriétés physiques et pharmacologiques de la perfusion. Les enfants courent un risque accru de blessures par extravasation. Il existe peu de données sur le traitement et les conséquences des blessures par extravasation, notamment en ce qui concerne le rôle des antidotes pharmacologiques. Objectifs: Décrire l'incidence des extravasations dans un centre de soins pédiatriques tertiaires (en tant que mise à jour d'une étude précédente), recenser les agents les plus couramment impliqués dans les blessures par extravasation, décrire les antidotes utilisés pour la gestion des blessures et leurs effets indésirables liés aux médicaments et décrire les complications liées aux blessures. Méthodologie: Les dossiers médicaux des patients pédiatriques ayant subi une blessure par extravasation entre le 1er septembre 2008 et le 30 septembre 2020 aux hôpitaux BC Children's Hospital et BC Women's Hospital ont été examinés. Des données concernant la prise en charge (c'est-à-dire le respect du protocole de l'établissement) et les conséquences des blessures ont été recueillies. Résultats: Les 242 dossiers inclus dans l'analyse indiquaient un total de 245 blessures par extravasation, pour une incidence d'extravasation de 0,04 % par jour-patient. Parmi les 242 patients, 110 ont été exclus de l'analyse secondaire des conséquences en raison d'un manque de données concernant les détails de l'extravasation. Sur les 132 patients restants, la majorité était des nouveau-nés (n = 54, 40,9 %), des nourrissons (n = 33, 25,0 %) et des enfants (n = 34, 25,8 %) et plus du tiers ont reçu des soins dans un service de pédiatrie générale (n = 50, 37,9 %). Les médicaments les plus fréquemment impliqués étaient la nutrition parentérale totale avec des lipides (36/132, 27,3 %), la vancomycine (36/132, 27,3 %) et des liquides IV (35/132, 26,5 %). Les conséquences sur la plupart des patients étaient bénignes et ils se sont rétablis sans complications. Aucun effet indésirable lié aux antidotes n'a été signalé. Conclusions: L'incidence des extravasations dans l'établissement à l'étude est restée faible, les médicaments impliqués étant similaires à ceux rapportés dans la littérature et les conséquences pour la majorité des patients étaient bénignes. Des études prospectives supplémentaires sont nécessaires pour évaluer l'efficacité et la sécurité des antidotes administrés pour les blessures par extravasation.

Effectiveness of Alprostadil for Ductal Patency.

OBJECTIVES: This study aims to describe the effectiveness of low initial alprostadil dosages to maintain a patent ductus arteriosus (PDA) in infants with ductal-dependent congenital heart disease (DDCHD). Secondary objectives were to describe any adverse drug events, describe prescribing trends, describe ductus arteriosus diameter changes, and compare the safety and efficacy of very low and low initial alprostadil dosage regimens. METHODS: This retrospective observational cohort study at the British Columbia's Women's and Children's Hospital neonatal intensive care unit and pediatric intensive care unit examined neonates admitted with DDCHD who received alprostadil to maintain ductal patency. Very low-dose alprostadil (less than 0.01 mcg/kg/min) versus low-dose alprostadil (equal to or greater than 0.01 mcg/kg/min) was examined. Effectiveness was defined as survival and infants not requiring a resuscitation event (cardiac arrest, cardiogenic shock, code blue, extracorporeal life support, requirement for emergent cardiac surgery, and respiratory acidosis). Adverse drug events with a Naranjo score of 3 or more were included. RESULTS: Alprostadil was effective for 88% of patients, with no difference between the very low-dose and low-dose groups. Of the 75 patients included, 25 received very low-dose alprostadil. Adverse drug events were common (51%) with neonates in the low-dose group experiencing more apnea and pyrexia than neonates in the very low-dose group. CONCLUSIONS: Alprostadil therapy was effective in maintaining the PDA in neonates with DDCHD with low-dosage regimens. Adverse drug events were common with both dosage regimens; however, the very low dosage appeared to have less apnea and pyrexia.

A Review of Histamine-2 Receptor Antagonist and Proton Pump Inhibitor Therapy for Gastroesophageal Reflux Disease in Neonates and Infants.

Proton pump inhibitors (PPI) and histamine-2 receptor antagonists (H2RA) are commonly used medications in neonates and infants for the treatment of gastroesophageal reflux disease (GERD), especially in neonatal intensive care units (NICUs). A literature review was conducted to evaluate the efficacy and safety of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) in preterm neonates, term neonates, and infants. A total of 27 studies were included in this review. Antacid medications in studies have consistently shown positive pharmacodynamic effects, including increasing gastric pH, reducing the reflux index, and reducing the number of acidic reflux events. The benefit found in placebo-controlled trials are limited exclusively to these surrogate outcomes. The actual clinically salient outcomes which H2RAs and PPIs are used for, such as reduction in GERD symptoms, especially irritability and improved feed tolerance and weight gain, have consistently shown no clinical benefit. H2RAs and PPIs appear to be extremely well tolerated by the neonatal and infant populations, which would mimic our experience with these medications in our unit. The available data from large, retrospective cohort and case-control studies paint a much more concerning picture regarding the potential for an increased risk in the development of allergies, anaphylactic reactions, necrotizing enterocolitis (NEC), other nosocomial infections, and lower respiratory tract infections. Given the risks associated with and lack of clinical effectiveness of both H2RAs and PPIs, use of these medications should be limited to specific clinical situations. Further studies are required to determine whether antacid pharmacologic therapy might benefit certain neonates and infants, such as those with complex medical issues.

Characterizing the Use of Nabiximols (Δ9-Tetrahydrocannabinol-Cannabidiol) Buccal Spray in Pediatric Patients.

Background: Nabiximols is a commercially available cannabinoid buccal spray containing 2.7 mg Δ9-tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD) per spray. It is approved by Health Canada for adults with cancer pain or spasticity/neuropathic pain related to multiple sclerosis. Despite a lack of published studies regarding the use of nabiximols in children, it is being used in clinical practice for indications of pain, nausea/vomiting, and spasticity. Objective: To describe the use of nabiximols in children. Methods: This retrospective single-cohort study involved hospitalized pediatric patients who received at least 1 dose of nabiximols between January 2005 and August 2018. Descriptive statistical analyses were performed. Results: A total of 34 patients were included. The median age was 14 (range 0.6-18) years, and 11 patients (32%) were admitted under the oncology service. The median dose of nabiximols was 1.9 (range 0.3-10.8) sprays per day, and the median duration was 3.8 (range 1-213) days. Nabiximols was most commonly used to treat pain and nausea/vomiting and was most frequently prescribed by pain specialists. Perceived effectiveness was documented in 17 (50%) of the cases, with variable results being reported. The most commonly reported adverse effects were drowsiness and tachycardia (3/34, 9%, for each). Conclusion: In this study, nabiximols was prescribed for children in all age groups, for a variety of conditions, but most commonly for pain and nausea/vomiting. Further study, in the form of a large, prospective randomized controlled trial with clearly defined efficacy and safety end points for nausea/vomiting and/or pain, is needed to determine whether nabiximols is effective and safe in children.

Contexte: Le nabiximols est un vaporisateur buccal cannabinoïde disponible dans le commerce qui contient 2,7 mg de Δ9-tetrahydrocannabinol [THC] et 2,5 mg de cannabidiol [CBD] par vaporisation. Il est approuvé par Santé Canada pour les adultes souffrant de douleur cancéreuse ou de spasticité/douleur neuropathique liée à la sclérose en plaques. Malgré le manque d'études publiées concernant l'utilisation du nabiximols chez les enfants, il est utilisé en pratique clinique pour des indications de douleur, de nausées/vomissements et de spasticité. Objectif: Décrire l'utilisation du nabiximols chez les enfants. Méthodes: Cette étude rétrospective à cohorte unique comprenait des patients pédiatriques hospitalisés ayant reçu au moins 1 dose de nabiximols entre janvier 2005 et août 2018. Des analyses statistiques descriptives ont été réalisées. Résultats: Au total, 34 patients ont été inclus. L'âge médian était de 14 ans [intervalle de 0,6 à 18 ans] et 11 enfants (32 %) étaient des patients en oncologie. La dose médiane de nabiximols était de 1,9 [intervalle de 0,3 à 10,8] vaporisation par jour et la durée médiane était de 3,8 [intervalle de 1 à 213] jours. Le nabiximols était le plus couramment utilisé pour traiter la douleur et les nausées/vomissements et était le plus souvent prescrit par des spécialistes de la douleur. L'efficacité perçue a été documentée dans 17 (50 %) des cas, avec des résultats variables rapportés. Les effets indésirables le plus fréquemment rapportés étaient la somnolence et la tachycardie (3/34, 9 % chacun). Conclusion: Dans cette étude, le nabiximols a été prescrit à des enfants de toutes les tranches d'âge, pour diverses pathologies, mais le plus souvent pour des douleurs et des nausées/vomissements. Une étude plus approfondie, sous la forme d'un vaste essai contrôlé randomisé prospectif avec des paramètres d'efficacité et d'innocuité clairement définis pour les nausées/vomissements et/ou la douleur, est nécessaire pour déterminer si le nabiximols est efficace et sûr chez les enfants.

Comparison of Sodium Bicarbonate and Lactated Ringers Hydration for High-dose Methotrexate Chemotherapy in Children.

BACKGROUND: High-dose methotrexate is part of the treatment of pediatric cancers. To reduce the risk of toxicity, supportive measures, including hydration and alkalinization, are recommended. At our institution, we switched from intravenous sodium bicarbonate to Lactated Ringers during a worldwide shortage. PROCEDURE: This was a retrospective cohort of children who received high-dose methotrexate from January 1, 2016 to August 31, 2018. The primary outcome was the prevalence of delayed methotrexate clearance. Secondary outcomes were proportion of cycles with delayed methotrexate clearance, time to methotrexate clearance, adverse events, risk factors for delayed clearance, and association between hydration type and delayed clearance. RESULTS: Eighty-two patients, with a total of 325 methotrexate cycles, were included. Forty-four patients received sodium bicarbonate, 31 received Lactated Ringers, and 7 received both. There was no difference in the prevalence of delayed methotrexate clearance between those who received sodium bicarbonate and Lactated Ringers (64% vs. 68%). The proportion of cycles with delayed methotrexate clearance, time to methotrexate clearance, and adverse events were similar between groups. Cancer type, methotrexate dose, and vomiting were associated with delayed clearance. CONCLUSIONS: Our study suggests that Lactated Ringers may be used in place of sodium bicarbonate for intravenous hydration during high-dose methotrexate.

Development and validation of the Pediatric Asthma kNowleDge and mAnagement (P.A.N.D.A) questionnaires.

OBJECTIVE: The objective of this study was to assess the validity, feasibility and reliability of the Pediatric Asthma kNowleDge and mAnagement (PANDA) questionnaires that we developed. METHODS: We developed 3 questionnaires aimed for Children, Teenagers and Parents of children living with asthma. Experts in childhood asthma reviewed the questionnaires to evaluate face and content validity with a measure of the Scale-Content Validity Index (S-CVI). Children age 7 and up and their parents participated in the feasibility and reliability assessment. Reliability was assessed by doing a test re-test, using the Intraclass Correlation Coefficient (ICC), for each questionnaire topic. RESULTS: Face validity was validated for the three PANDA questionnaires with a satisfactory length and comprehension level. Content validity, with a total S-CVI of 0.91, was found for the Children and Parents questionnaires. With 84 participants, the ICC were found to be higher than 0.7 with a 95%CI [0.5-0.9] for the total scores and higher than 0.5 for each topic for each questionnaire, indicating reliability. CONCLUSION: Face and content validity and reliability of the PANDA questionnaires was established, with an appropriate comprehension level and length. Other types of validation like construct validity and responsiveness would need to be assessed to complete the validation of the questionnaires. The PANDA questionnaires could be used for research and in everyday practice.

Navigating the complex realm of drug access in paediatric care.

A Drug Access Navigator (DAN) is a role that has been established in patient care settings with the goal of expediting the process by which patients obtain drugs through the Health Canada Special Access Program (SAP), individual drug companies' patient access programs (PAP), and public and private drug plans. In the paediatric setting, the process of accessing many drugs has grown increasingly complex. The majority of paediatric prescriptions involve 'off-label' drug use. This leads to an increased need for drug access through the SAP and/or PAPs and demonstrates that the need for a DAN may be particularly prominent in the paediatric population. To our knowledge, there is no evidence in the literature of a DAN functioning in a paediatric setting, though there is a demonstrable need. We plan to address this need by introducing a DAN for shared use at BC Children's Hospital, a paediatric tertiary care centre.

Conflict between Pharmacy Preceptors and Pharmacy Learners in Experiential Education.

BACKGROUND: The relationship between a preceptor and a learner is complex and can be prone to conflict. The issue of conflict in experiential education has been studied in medicine, nursing, social work, and education; however, conflict between pharmacy preceptors and learners has not been described. OBJECTIVE: To describe types of conflict between pharmacy preceptors and learners, the outcomes of such conflict, the impacts on the preceptor-learner relationship, and conflict-resolution strategies. METHODS: An anonymous electronic survey of pharmacist preceptors and pharmacy residents in British Columbia was conducted. The survey included various types of questions to enrich the quality of responses (e.g., Likert scale, ranking, and requests for comments). Descriptive statistics were used. RESULTS: Forty-nine participants completed the survey from the preceptor's perspective, 12 from the learner's perspective, and 4 from both perspectives. Sixty percent of preceptors (32/53) and 75% of learners (12/16) admitted experiencing conflict. Preceptors (n = 27) cited the learner's professionalism (74%), knowledge/skills (59%), communication issues (59%), personal issues (56%), and punctuality/attendance (52%) as causes of conflict. Learners, however (n = 12), cited differing expectations (67%), teaching versus learning style preferences (50%), and communication issues (67%) as causes of conflict. The majority of preceptors and learners indicated that conflict had negatively affected the relationship; however, most preceptors (69% [18/26]) and learners (50% [6/12]) agreed or strongly agreed with the statement, "I have generally felt comfortable working with preceptors/learners after a conflict." More learners than preceptors felt that the learner's ability to perform was negatively affected by the conflict (92% [11/12] versus 52% [13/25]). Preceptors were more likely to take initiative to resolve conflict. Verbal communication was the method of conflict resolution preferred by both preceptors and learners. Most preceptors and learners indicated that they felt that conflicts were generally resolved. CONCLUSIONS: Conflict was common in the pharmacy preceptor-learner relationship. Pharmacy preceptors and learners had different perspectives about the causes and outcomes of conflict.

CONTEXTE: La relation entre le précepteur et l'apprenant est complexe et peut entraîner des conflits. Le problème du conflit dans le domaine de l'éducation expérientielle a été étudié en médecine, en infirmerie, en travail social et en éducation; cependant, il n'existe aucune description des conflits entre les précepteurs et les apprenants en pharmacie. OBJECTIF: Décrire les types de conflits entre les précepteurs en pharmacie et les apprenants, les conséquences de tels conflits ainsi que les impacts sur la relation précepteur-apprenant et les stratégies de résolution de conflit. MÉTHODES: Une enquête électronique anonyme a été menée auprès de précepteurs et de résidents en pharmacie en Colombie-Britannique. L'enquête comprenait diverses questions visant à enrichir la qualité des réponses (p. ex., échelle de Likert, classement et demandes de commentaires). L'étude s'appuie sur des statistiques descriptives. RÉSULTATS: Quarante-neuf participants ont répondu à l'enquête en adoptant le point de vue du précepteur, 12 en adoptant celui de l'apprenant et 4 ont adopté le point de vue de l'apprenant et du précepteur. Soixante pour cent des précepteurs (32/53) et 75 % des apprenants (12/16) ont admis traverser des conflits. Les sources de conflits citées par les précepteurs (n = 27) sont le professionnalisme de l'apprenant (74 %), les connaissances et compétences (59 %), les problèmes de communication (59 %), les problèmes personnels (56 %) ainsi que la ponctualité et la présence (52 %). Quant aux apprenants (n = 12), ils ont cité des attentes divergentes (67 %), des préférences de style d'enseignement ou d'apprentissage (50 %) et des problèmes de communication (67 %) comme causes de conflit. La majorité des précepteurs et des apprenants ont indiqué que ces conflits avaient affecté la relation; cependant, la plupart des précepteurs (69 % [18/26]) et des apprenants (50 % [6/12]) étaient d'accord ou fortement d'accord avec l'énoncé suivant : « En général, je me suis senti à l'aise de travailler avec des précepteurs ou des apprenants après un conflit. ¼ Un plus grand nombre d'apprenants que de précepteurs ont perçu que le conflit avait perturbé la capacité de l'apprenant (92 % [11/12] par rapport à 52 % [13/25]). Les précepteurs étaient plus enclins à faire preuve d'initiative pour résoudre le conflit. La communication verbale était la méthode de résolution de conflit préférée des précepteurs et des apprenants. La plupart des précepteurs et des apprenants ont indiqué ressentir que les conflits étaient généralement résolus. CONCLUSIONS: Le conflit était répandu dans la relation précepteur et apprenant en pharmacie. Les précepteurs en pharmacie et les apprenants avaient différents points de vue sur les causes et les conséquences de ces conflits.

Survey of Therapeutic Drug Monitoring Practices in Pediatric Health Care Programs across Canada.

BACKGROUND: Therapeutic drug monitoring (TDM) is helpful in situations where a drug has a narrow therapeutic index, a drug dosage does not reliably predict serum concentration, or a serum drug concentration has surrogate value (i.e., is reflective of clinical outcomes). TDM is especially important for the pediatric population, where wide variability in pharmacokinetics and differences in body composition and drug disposition exist. Unfortunately, very little is known about pediatric TDM patterns and the factors that affect the ordering of serum drug measurements. OBJECTIVES: To describe TDM practice for pediatric patients in Canada, to report on the drugs that are monitored and how they are monitored, and to discern factors that influence pediatric TDM patterns. METHODS: An electronic survey was developed with online survey software and was disseminated to 42 pediatric health care centres in Canada over the period January to March 2016. RESULTS: Of the 42 sites invited to participate in the survey, 20 (48%) responded. All sites reported performing TDM for pediatric patients, and the median number of drugs monitored was 18.5 (range 9-28) per site. The sites differed in terms of TDM practice (e.g., indications for TDM, types of serum drug measurements). Pharmacogenetic testing currently does not play a major role in TDM. Reported barriers to TDM practice include perceived lack of clinical value for certain drugs, limited access to analytical testing, and delayed return of test results. CONCLUSIONS: TDM practice is widespread in Canada. To better utilize TDM for clinical practice, future efforts can be aimed toward increasing awareness of the clinical value of TDM and improving the timeliness of access to TDM results.

CONTEXTE: Le suivi thérapeutique pharmacologique est utile dans les cas où un médicament possède un indice thérapeutique étroit, si une posologie ne permet pas d'établir de façon fiable les concentrations sériques ou si les concentrations sériques d'un médicament ont une valeur de substitution (c'est-à-dire qu'elles reflètent les résultats cliniques). Le suivi thérapeutique pharmacologique est particulièrement important pour la population pédiatrique, où il existe une grande variabilité pharmacocinétique et des différences quant à la composition corporelle et au devenir des médicaments dans l'organisme. Malheureusement, on ne connaît que peu de choses à propos des habitudes de suivi thérapeutique pharmacologique de l'enfant et des facteurs qui influencent la prescription d'examens mesurant les concentrations sériques des médicaments. OBJECTIFS: Offrir un portrait des habitudes de suivi thérapeutique pharmacologique de la population pédiatrique au Canada, faire un compte rendu des médicaments qui nécessitent un suivi et la manière dont se déroule cette surveillance et déceler les facteurs qui influencent les habitudes de suivi thérapeutique pharmacologique de l'enfant. MÉTHODES: Un sondage électronique a été mis au point à l'aide d'un logiciel de sondage en ligne puis envoyé à 42 centres de soins pédiatriques au Canada de janvier à mars 2016. RÉSULTATS: Vingt (48 %) des 42 établissements interrogés ont répondu au sondage. Tous les établissements ont indiqué réaliser des suivis thérapeutiques pharmacologiques auprès de la population pédiatrique et le nombre médian de médicaments nécessitant une surveillance était de 18,5 (écart de 9 à 28) par établissement. Les établissements présentaient des différences en ce qui a trait aux habitudes de suivi thérapeutique pharmacologique (comme les indications pour les suivis thérapeutiques pharmacologiques et les types de mesures sériques de médicaments). À ce jour, les examens pharmacogénétiques ne jouent pas un rôle important dans le suivi thérapeutique pharmacologique. Selon les répondants, des éléments faisaient obstacle à la réalisation du suivi thérapeutique pharmacologique, notamment la croyance que certains médicaments n'ont pas de valeur clinique, l'accès limité à des tests diagnostiques et les retards dans l'obtention des résultats d'examen. CONCLUSIONS: La réalisation du suivi thérapeutique pharmacologique est répandue au Canada. Afin de l'exercer de façon plus optimale dans le cadre de la pratique clinique, le personnel de la santé doit être davantage sensibilisé à la valeur clinique du suivi thérapeutique pharmacologique et il est nécessaire d'améliorer la rapidité d'accès aux résultats de ce suivi.

RELATE: Relationship of limited sampling strategy and adverse effects of mycophenolate mofetil in pediatric renal transplant patients.

MMF, a prodrug converted to the active form MPA, is an immunosuppressant used to prevent rejection in solid organ transplant recipients. MPA exposure, defined by AUC, can be estimated using limited sampling strategies (LSS). The relationship between MPA AUC and clinical outcomes has not been studied in pediatrics. The objectives were to describe the relationship of MPA AUC (estimated via LSS) with adverse effects and rates of rejection, and to compare clinical outcomes between different MPA monitoring practices. Descriptive statistics were used to summarize demographics, adverse effects, and rejection. Thirty-three patients (91 trough concentrations and 12 LSS sets) aged 2-20 years old were included. The estimated median MPA AUCs (David-Neto and Filler) were higher for those who did not have any adverse effects reported (65.85 and 85.05 mg*h/L, respectively) compared to those who had an adverse effect (60.75 and 54.2 mg*h/L, respectively). The median trough concentration when no adverse effects occurred was comparable to when adverse effects occurred. The median MPA AUC at which rejection occurred was lower than in those without rejection. The median trough concentration at which rejection occurred was higher than those without rejection (3.1 mg/L compared to 1.9 mg/L). The occurrence of adverse effects or rejection was not shown to be related to measured MPA trough or AUC outside of the target therapeutic range. The value of MPA concentration monitoring remains unclear; therefore, the practice of monitoring MPA AUC by LSS or trough concentrations should be reconsidered.

Pharmacologic Management of Agitation and Aggression in a Pediatric Emergency Department - A Retrospective Cohort Study.

BACKGROUND: Benzodiazepine and antipsychotic use for acute management of agitation and aggression in the pediatric emergency department (ED) setting has not been well described. OBJECTIVES: To describe medication utilization in the management of agitation and aggression in a pediatric ED and to assess the safety of their use. METHODS: This was a retrospective observational study. Patients less than 20 years of age who presented to our pediatric ED and had agitation or aggression as part of their chief complaint were included if they received at least 1 dose of benzodiazepine or antipsychotic. Outcomes included frequency of benzodiazepine and antipsychotic use, dosing of medications, and reported adverse events. RESULTS: During the 5-year study period, there were 128 visits of 120 patients who met the inclusion criteria. Lorazepam was most commonly given (70%), followed by chlorpromazine (20%). Most patients (82%) required a single dose of medication. Intoxication was associated with needing more than 1 dose of medication. Patients with autism or Asperger syndrome were more likely to receive an antipsychotic medication compared to not having these conditions (75% vs. 28%, respectively). Adverse events were documented in 6 visits: oxygen desaturation (n = 1), dizziness and nausea (n = 2), dizziness (n = 1), and paradoxical excitation (n = 2). The Naranjo Score indicated a probable adverse drug reaction for the cases of paradoxical excitation. CONCLUSIONS: Benzodiazepine and antipsychotic drug therapy for acute agitation and aggression in children appears to be safe and well tolerated when used as a single agent and at the recommended doses in this setting.

Pediatric Obesity: Pharmacokinetics and Implications for Drug Dosing.

PURPOSE: Clinicians are increasingly likely to have under their care obese children with diseases requiring pharmacotherapy. Optimal drug dosing for this population is unclear. Excess weight likely leads to alterations in pharmacokinetics. The purpose of this article was to describe the pharmacokinetics and pharmacodynamics in overweight and obese children and, where possible, provide recommendations for drug dosing. METHODS: EMBASE (1980-May 2015), MEDLINE (1950-May 2015), and International Pharmaceutical Abstracts (1970-May 2015) databases were searched by using the following terms: obesity, morbid obesity, overweight, pharmacokinetics, pharmacodynamics, drug, dose, drug levels, pediatric, and child. The search was limited to English-language articles. References of relevant articles were searched to identify additional studies. FINDINGS: Total body weight (TBW) is an appropriate size descriptor for dosing antineoplastic agents, succinylcholine, and cefazolin. Obese children seem to require less heparin, enoxaparin, and warfarin per kilogram TBW than normal-weight children; providing standard adult doses may be insufficient, however. Obese children may also require less vancomycin and aminoglycosides per kilogram TBW than normal-weight children. For these medications, an alternate size descriptor in children has not been described, and initial dosing based on TBW and monitoring serum concentrations (vancomycin and aminoglycosides) or coagulation parameters (heparin, enoxaparin, and warfarin) is warranted. Obese children require less propofol than normal-weight children; however, there is limited information about the dosing of other anesthetics or opioids. IMPLICATIONS: Limitations to the available data include the inherent design constraints to case reports and retrospective cohort studies, as well as the small numbers of children in some of the studies. Use of normal-weight historical control subjects for obese children in the context of a pharmacokinetic study is not ideal. Although more information is becoming available, our understanding of the pharmacokinetics in obese children is still limited. When dosing information is not available for obese children, it may be necessary to extrapolate from available data in obese adults, but one should consider the effects of the child's age on pharmacokinetics.

A naloxone admixture to prevent opioid-induced pruritus in children: a randomized controlled trial.

PURPOSE: Morphine administered by continuous opioid infusion (COI) or by patient-controlled analgesia (PCA) is associated with opioid-induced pruritus (OIP). Intravenous naloxone administered separately to the morphine infusion at a dose of 0.25-1.65 µg·kg(-1)·hr(-1) can provide effective prevention from OIP. Nevertheless, this strategy requires a dedicated intravenous line and an additional infusion pump. The purpose of this study was to determine whether an admixture of naloxone with morphine in normal saline administered via COI or PCA would also prevent OIP in children without attenuation of analgesia or increased opioid utilization. METHODS: In this randomized controlled trial, children meeting the inclusion criteria (aged 8-18 yr, American Society of Anesthesiologists physical status I-III, normal developmental profile and prescribed COI/PCA morphine for postoperative analgesia) were randomized to receive an infusion containing a naloxone, opioid, and saline admixture (NOSA) of 12 µg naloxone per 1 mg morphine per 1 mL normal saline or morphine only (control). The severity of opioid-induced pruritus was assessed by self-report using a modified colour analogue scale (mCAS; score 0-10). The groups were also compared for opioid utilization, pain scores, and administration of antipruritic medications, which were recorded for up to 48 hr or until the COI/PCA was discontinued. RESULTS: Ninety-two participants were enrolled in the study. The median [interquartile range] dose of naloxone administered to the NOSA participants was 0.37 [0.30-0.48] µg·kg(-1)·hr(-1). The incidence of OIP, determined by self-report and treatment, was not different between groups: 22% in the NOSA group vs 36% in the control group (mean difference, -15%; 95% confidence interval [CI], -33 to 4; P = 0.164). The severity of opioid-induced pruritus was similar in the two groups, with a median difference in the participants' mean mCAS score of -0.29 (95% CI, -0.75 to 0.26; P = 0.509). Opioid utilization did not differ between groups, with a median difference of -1.35 µg·kg(-1)·hr(-1) (95% CI, -5.85 to 7.55; P = 0.518), and pain scores did not differ, with a median difference of 0.0 (95% CI, -1.0 to 1.5; P = 0.659). CONCLUSION: This admixture of naloxone and morphine in normal saline did not decrease the incidence or severity of OIP in this sample. Separate administration of naloxone may be the more effective strategy for prevention of OIP. This trial was registered at ClinicalTrials.gov (NCT01071057).

Pediatric Assessment of Vancomycin Empiric Dosing (PAVED): a Retrospective Review.

BACKGROUND: Pediatric studies and anecdotal experience suggest that current empiric vancomycin dosing does not reach serum trough concentration targets of at least 10 mg/L for uncomplicated infections or 15-20 mg/L for serious or complicated infections. OBJECTIVES: This study reviewed vancomycin dosing and serum concentrations to (i) determine the proportion of patients who reached initial target concentrations; (ii) describe pharmacokinetic parameters; and (iii) compare patient-specific area-under-the-curve (AUC) values to population estimates using the Rodvold equation. METHODS: Following ethics approval, data were extracted from medical records of 200 patients aged 1 month-18 years, who received intravenous (IV) vancomycin and had at least two pharmacokinetically evaluable serum concentrations. RESULTS: Trough vancomycin concentrations of 10-15 and 15-20 mg/L were achieved in 25 (29%) and 2 (2%) patients receiving vancomycin 15 mg/kg IV every 6 h (q6 h) and 22 (20%) and 9 (8%) patients receiving vancomycin 20 mg/kg IV every 8 h (q8 h), respectively. Patients were stratified into four age groups (1 month-1 year, 1-6 years, 6-13 years and 13-18 years). Median (IQR) pharmacokinetic parameters were elimination rate constant 0.25 (0.09), 0.29 (0.07), 0.24 (0.10) and 0.22 (0.07) h(-1); volume of distribution 0.56 (0.20), 0.61 (0.21), 0.47 (0.26) and 0.49 (0.22) L/kg; and half-life 2.8 (1.1), 2.4 (0.5), 2.9 (1.1) and 3.2 (1.0) h, respectively. Median (IQR) AUCs were 458 (170), 338 (132), 478 (215) and 513 (179) mg h/L and population-estimated AUCs were 67 (44), 108 (70), 299 (102) and 454 (103) mg h/L (p < 0.05 for all groups). CONCLUSIONS: Based on these findings, we recommend vancomycin 70 and 90 mg/kg/day divided q6 h for troughs of 10-15 and 15-20 mg/L, respectively (patients 1 month-6 years) and 60 mg/kg/day divided q8 h and 70 mg/kg/day divided q6 h, respectively (patients >6 years) to undergo further testing as initial dosing regimens. Furthermore, population estimates grossly underestimate vancomycin AUC in patients 1-18 years old and thus patient-specific parameters are required.

Stability of epinephrine at standard concentrations.

BACKGROUND: To minimize medication errors, standard concentrations are recommended for medications intended for continuous infusion in pediatric patients. Premixing of epinephrine (commonly used to manage septic shock in children) would improve timeliness, safety, and cost-effectiveness. However, information about the stability of epinephrine at standard concentrations is limited. OBJECTIVES: To evaluate the stability of epinephrine in 5% dextrose in water at standard concentrations and to extend its expiration date after storage in infusion bags at 4°C and 25°C for up to 30 days. METHODS: A total of 6 infusion bags were prepared with 200 mL of epinephrine solution, 2 bags for each of 3 standard concentrations (25, 50, and 100 µg/mL). Three bags (one for each concentration) were stored under refrigeration (4°C), and the remaining 3 bags were stored at room temperature (25°C). Physical characteristics (including pH, colour, and presence of precipitate) were evaluated daily for the first 14 days and every 1 to 5 days thereafter until day 30. Three 1.5-mL samples were collected from each bag immediately after preparation (time 0), every 24 h (at 24 h, 48 h, 72 h, 96 h, etc.) for the first 14 days, and every 1 to 5 days thereafter until day 30. Each sample was analyzed by stability-indicating high-performance liquid chromatography. A solution was considered stable if it maintained at least 90% of its initial concentration. RESULTS: No notable changes in pH, colour, or precipitation were observed in any of the solutions after storage at 4°C or 25°C for up to 30 days. All formulations maintained more than 95% of the initial epinephrine concentration on day 30. In addition, the calculated lower limit of the 95% confidence interval indicated that 93% or more of the initial concentration remained on day 30. CONCLUSIONS: Preparations of epinephrine were stable for up to 30 days, with or without refrigeration. Because stability alone does not guarantee bioavailability or efficacy of a drug, future clinical studies are recommended to evaluate the pharmacokinetics and pharmacodynamics of these formulations.

CONTEXTE: Afin de réduire au maximum les erreurs de médication, il est recommandé d'utiliser des concentrations standards pour les médicaments administrés par perfusion continue aux enfants. La préparation préalable des solutions d'épinéphrine (couramment utilisée pour traiter le choc septique chez l'enfant) permettrait d'améliorer la rapidité d'action, la sécurité et le rapport coût-efficacité. Il existe malheureusement peu de données portant sur la stabilité de solutions d'épinéphrine de concentrations standards. OBJECTIFS: Évaluer la stabilité de l'épinéphrine de concentrations standards dans du dextrose à 5 % dans l'eau et augmenter la durée de conservation des solutions entreposées dans des sacs pour perfusion à 4 °C et à 25 °C jusqu'à 30 jours. MÉTHODES: Six sacs pour perfusion contenant 200 mL d'une solution d'épinéphrine ont été préparés, soit une paire de chacune des trois concentrations standards (25, 50 et 100 µg/mL). Trois sacs ont été conservés au réfrigérateur (4 °C) et les trois autres ont été entreposés à la température ambiante (25 °C). Les propriétés physiques (notamment le pH, la couleur et la présence de précipité) ont été évaluées quotidiennement les 14 premiers jours, puis à des intervalles de 1 à 5 jours jusqu'au jour 30. Trois échantillons de 1,5 mL ont été recueillis de chaque sac immédiatement après la préparation de la solution (temps 0), puis toutes les 24 heures (24 h, 48 h, 72 h, 96 h, etc.) pendant les 14 premiers jours et ensuite à des intervalles de 1 à 5 jours jusqu'à la fin de la période de 30 jours. Chaque échantillon a été analysé à l'aide d'une épreuve mesurant la stabilité par chromatographie liquide haute performance. Une solution était considérée comme stable si elle conservait au moins 90 % de sa concentration initiale. RÉSULTATS: Aucun précipité et aucun changement notable du pH ou de la couleur n'ont été observés dans l'ensemble des solutions après un entreposage à 4 °C ou à 25 °C d'une période de 30 jours. Toutes les préparations avaient conservé plus de 95 % des concentrations initiales d'épinéphrine au jour 30. De plus, la limite inférieure de l'intervalle de confiance à 95 % indiquait que les préparations avaient conservé 93 % ou plus de leurs concentrations initiales au jour 30. CONCLUSIONS: Les préparations d'épinéphrine sont demeurées stables pendant les 30 jours, qu'elles aient été réfrigérées ou non. Comme la stabilité seule ne garantit pas la biodisponibilité ou l'efficacité d'un médicament, d'autres études cliniques sont recommandées afin d'évaluer le comportement pharmacocinétique et pharmacodynamique de ces préparations. [Traduction par l'éditeur].

Standard-dose versus high-dose acyclovir in children treated empirically for encephalitis: a retrospective cohort study of its use and safety.

BACKGROUND: Intravenous acyclovir is the treatment of choice for herpes simplex virus encephalitis. In 2006, the American Academy of Pediatrics updated its dosing recommendations for children aged 3 months to 12 years to receive high-dose acyclovir (60 mg/kg/day). The association between acyclovir dose and toxicity is unclear. OBJECTIVE: The purpose of our study was to review our institution's experience with standard- and high-dose acyclovir for the empiric treatment of encephalitis. STUDY DESIGN, SETTING AND PATIENTS: This retrospective cohort study included patients aged 1 month to 18 years who received acyclovir as empiric treatment for encephalitis between 2005 and 2009 at a tertiary care children's hospital. We excluded patients with baseline renal impairment and those without serum creatinine measurements prior to and during treatment. MAIN OUTCOME MEASURE: The main outcome measure of this study was to compare the occurrence of renal injury or failure between children who received the standard- versus high-dose regimen. RESULTS: Sixty-one patients were included (n = 32 standard-dose; n = 29 high-dose). There was no statistical difference in change in serum creatinine from baseline between children who received standard- versus high-dose acyclovir (0 vs. 5.1 %; p = 0.79). One child in the standard-dose group and three children in the high-dose group developed renal injury or failure during treatment (3.1 vs. 10.3 %; p = 0.34). Children with renal injury or failure were older, had a longer length of stay, and longer duration of therapy than children without. CONCLUSIONS: The incidence of renal injury or failure was similar between children who received standard-dose and high-dose acyclovir.

A pharmacokinetics module taught within a pediatrics pharmacotherapy course.

OBJECTIVE: To review the effectiveness of a pedagogical approach and methods used to teach pediatric pharmacokinetics to a large class of pharmacy students in a required course in the third-year of a bachelor of science in pharmacy program. DESIGN: The pharmacokinetic sessions emphasized facilitating student understanding of the basic pharmacokinetic principles learned in earlier courses and applying that knowledge to pediatric case scenarios. This was accomplished using lectures with PowerPoint slides followed by small-group, context-focused discussions that required students to apply the principles outlined in the lecture. EVALUATION: Student understanding of the pharmacokinetics concepts discussed within the course was assessed via a written examination. CONCLUSION: The small-group context-focused approach to teaching pediatric pharmacokinetics in a large class size with minimal resources allowed opportunities for students to apply their foundational knowledge in an interactive and engaging atmosphere.