Pediatric Drugs最新文献

{"title":"Dexmedetomidine for Less Invasive Surfactant Administration: A Pilot Study.","authors":"Sagee Nissimov, Amitai Kohn, Rimona Keidar, Ayelet Livne, Mazal Shemer, Ayala Gover, Calanit Hershkovich-Shporen, Matitiahu Berkovitch, Iris Morag","doi":"10.1007/s40272-024-00667-1","DOIUrl":"10.1007/s40272-024-00667-1","url":null,"abstract":"<p><strong>Introduction: </strong>Less invasive surfactant administration (LISA) involves delivering surfactant to a spontaneously breathing infant by passing a thin catheter through the vocal cords and has become the preferred method for surfactant delivery. However, the role of pre-LISA sedation remains unclear.</p><p><strong>Objective: </strong>The aim of this study was to describe the use of dexmedetomidine for LISA in preterm and early-term infants.</p><p><strong>Methods: </strong>This retrospective study evaluated preterm and early-term infants who received intravenous dexmedetomidine for LISA between December 2022 and March 2024. Primary outcomes included safety parameters such as the absence of bradycardia, hypotension, hypothermia, or respiratory depression, and the success rate of LISA, determined by the lack of endotracheal intubation within 72 h. Intergroup comparison based on a cutoff of 32 weeks post-menstrual age (PMA) was performed.</p><p><strong>Results: </strong>Thirty-seven infants were included. The mean ± SD PMA at birth, birth weight, and age at LISA were 32.2 ± 2.7 weeks, 1879 ± 698 g, and 13.9 ± 12.4 h, respectively. Mean dexmedetomidine dosage was 0.66 ± 0.26 μg/kg. Six patients (16.2%) developed mild hypothermia, and 10 (27%) experienced apnea/bradycardia within 24 h. The success rate of the procedure was 89.2%. Infants born before 32 weeks received lower doses of dexmedetomidine than those born at 32 weeks and above (0.54 ± 0.24 versus 0.76 ± 0.24 μg/kg, p < 0.01). Safety and success rates of LISA were similar across groups.</p><p><strong>Conclusion: </strong>This is the first report on dexmedetomidine as pre-LISA sedation, demonstrating its feasibility with comparable success rates regardless of PMA. These findings may inform future studies on sedation strategies for LISA.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"247-255"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgement to Referees.","authors":"Rod McNab","doi":"10.1007/s40272-024-00677-z","DOIUrl":"https://doi.org/10.1007/s40272-024-00677-z","url":null,"abstract":"","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Narrative Review of Pain in Pediatric Oncology: The Opioid Option for Procedural and Surgical Pain.","authors":"Elizabeth A Hall, Chasity M Shelton, Tracy M Hagemann, Hilary M Jasmin, Karissa Grey, Doralina L Anghelescu","doi":"10.1007/s40272-024-00654-6","DOIUrl":"10.1007/s40272-024-00654-6","url":null,"abstract":"<p><p>This narrative review examines the evolving role of opioids in managing procedural and surgical pain in pediatric oncology patients. The review evaluates studies on opioid use across various oncological surgeries including thoracic, abdominal, orthopedic, and neurosurgical procedures, as well as for common painful procedures such as bone marrow aspirations and lumbar punctures. While opioids remain important for acute procedural and postoperative pain management in pediatric oncology patients, there is an increasing emphasis on multimodal, opioid-sparing approaches. The evidence presented within this review highlights the growing focus on judicious postoperative opioid prescribing to mitigate risks of adverse effects and persistent use or potential misuse. The review synthesizes findings from studies investigating various analgesic regimens, including the use of regional anesthesia techniques like epidural analgesia and peripheral nerve blocks, which have shown promise in reducing opioid requirements. For procedural pain, the review explores the efficacy of combining opioids with sedatives like midazolam or propofol, as well as the potential of ketamine as an opioid-sparing alternative. Key findings indicate that opioid-sparing techniques can effectively reduce overall opioid consumption without compromising pain control or patient satisfaction. Several studies demonstrated that regional anesthesia techniques and non-opioid adjuncts can significantly lower postoperative opioid requirements across various surgical procedures. For procedural pain, ketamine-based regimens often showed comparable or superior pain control to opioid-based approaches, with some studies reporting better patient satisfaction. This review also addresses the importance of tailored postoperative opioid prescribing, with some studies presenting algorithms to predict outpatient opioid needs more accurately. These approaches aim to ensure adequate pain control while minimizing excess opioid dispensing.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"19-39"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and Safety of Endotracheal Lidocaine for Endotracheal Intubation in Critically Ill Children.","authors":"Jordan Anderson, Erin B Owen, Shannon Mayes, Janice E Sullivan, Mark J McDonald","doi":"10.1007/s40272-024-00662-6","DOIUrl":"10.1007/s40272-024-00662-6","url":null,"abstract":"<p><strong>Introduction: </strong>Critically ill pediatric patients are endotracheally intubated in pediatric intensive care units for a variety of illnesses and indications. Management of an endotracheal tube (ETT) requires suctioning to remove patient secretions and prevent occlusion, but this practice can be associated with adverse events, such as hemodynamic deterioration or increases in intracranial pressure. Instillation of lidocaine into the ETT before suctioning may be beneficial in preventing these events. The purpose of this phase I, fixed-dose, open-label pharmacokinetic and safety study, conducted in endotracheally intubated and mechanically ventilated infants and children requiring ETT suctioning, was to determine the serum concentrations and safety of lidocaine after ETT administration.</p><p><strong>Methods: </strong>A total of 21 infants and children meeting inclusion criteria received a single dose of ETT lidocaine per institutional protocol. Blood samples were obtained pre-dose and at 5, 10, 30, and 120 minutes after administration for serum concentration analysis. Lidocaine dosing was driven by weight and age, with infants and children aged >  38 weeks' estimated gestational age and < 3 years receiving 0.5 mg/kg/dose (maximum: 20 mg/dose) and children aged 3-18 years receiving 1 mg/kg/dose (maximum: 100 mg/dose).</p><p><strong>Results: </strong>No subjects aged < 3 years had detectable serum lidocaine concentrations. Four subjects in the group aged ≥  3 years had detectable serum lidocaine concentrations at 5, 10, and/or 30 minutes, but no serum concentrations were within the toxic range. No adverse effects, such as cough, bronchospasm, seizure activity, or clinically significant depression of cardiac or respiratory function, were noted in any subjects.</p><p><strong>Conclusions: </strong>Pharmacokinetic sampling showed that only 4 of 21 subjects had detectable serum lidocaine concentrations and none were within the toxic range. The safety of ETT administration of lidocaine in endotracheally intubated infants and children requiring ETT suctioning was demonstrated at the doses used in this study. The study was conducted at Norton Children's Hospital. The research team confirmed that this study was not registered with clinicaltrials.gov.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"103-109"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apremilast: First Pediatric Approval.","authors":"Hannah A Blair","doi":"10.1007/s40272-024-00668-0","DOIUrl":"10.1007/s40272-024-00668-0","url":null,"abstract":"<p><p>Apremilast (Otezla^®) is an inhibitor of phosphodiesterase-4 (PDE-4) being developed by Amgen. It is approved in multiple countries worldwide, including the USA and those of the EU, for the treatment of adults with psoriatic arthritis, plaque psoriasis, or oral ulcers associated with Behçet's disease. In April 2024, based on clinical data in patients aged 6-17 years, apremilast received its first pediatric approval in the USA for the treatment of pediatric patients aged ≥ 6 years and weighing ≥ 20 kg with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. Apremilast was also approved in the EU in October 2024 for the treatment of moderate to severe plaque psoriasis in children and adolescents from the age of 6 years and weighing ≥ 20 kg who are candidates for systemic therapy. This article summarizes the milestones in the development of apremilast leading to the first pediatric approval for plaque psoriasis.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"119-124"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Fidelity Clinical Simulation to Improve a Pediatric Clinical Trial Design: Lessons Learned and Conceptualization of the Return on Investment (ROI) and Return on Engagement (ROE) Analysis.","authors":"Jose Maria Quintillá, Carmen de la Gala, Ruben Berrueco, Joana Claverol, Bibiana Figueres, Anna Bergós, Lourdes Rodríguez, Anna Mora, Victoria DiBiaso, Cristina Llanos, Begonya Nafria","doi":"10.1007/s40272-024-00660-8","DOIUrl":"10.1007/s40272-024-00660-8","url":null,"abstract":"<p><strong>Introduction: </strong>Clinical trials entail complex processes that are more challenging when they are addressed to pediatric patients and include a decentralized design. High-realistic simulation allows for the testing and refining of procedures, organizational systems, and interactions between professionals and patients/families, narrowing the gap between work-as-imagined and work-as-done.</p><p><strong>Objectives: </strong>The aim of this research was to analyze the impact of simulation in three key moments of a clinical trial: the baseline visit, home administration of the investigational drug by parents, and the drawing and processing of pharmacokinetics samples by a home nurse.</p><p><strong>Methods: </strong>Multidisciplinary meetings were held between the team of Barcelona Children's Hospital and the sponsor to define the simulation objectives. Three simulation scenarios were executed in 2 days. Subsequently, a post-process analysis was performed, including the assessment of the patient/family experience.</p><p><strong>Results: </strong>In the baseline visit scenario, minimum duration was calculated, and main aspects related to task dynamics, materials, and training were identified. In the drug administration scenario, the family was able to carry out the infusion within the time established in the protocol, but with some difficulties. In the home nursing scenario, some recommendations for improving safety and patient experience were suggested.</p><p><strong>Conclusions: </strong>High-realistic clinical simulation can contribute to anticipate risks, refine the design of activities, and to identify specific needs prior to the protocol finalization, a timepoint in the process when modifications can still be made that constitutes a significant return on investment and return on the engagement, in the experience of the patients that will participate in the study.</p><p><strong>Clinicaltrial: </strong></p><p><strong>Gov identifier number: </strong>NCT04644575.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"73-84"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing CAR T-Cell Therapies for Pediatric Solid Tumors.","authors":"Gabriele Canciani, Francesco Fabozzi, Claudia Pinacchio, Manuela Ceccarelli, Francesca Del Bufalo","doi":"10.1007/s40272-024-00653-7","DOIUrl":"10.1007/s40272-024-00653-7","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematological malignancies, inducing notable and durable clinical responses. However, for solid tumors, including but not limited to pediatric tumors, several peculiar biological features posed substantial challenges for achieving comparable results. Despite sound pre-clinical evidence of the ability of CAR T cells to eradicate solid malignancies, their activity remains suboptimal when facing the in vivo complexity of solid tumors, characterized by antigen heterogeneity, scarce T-cell infiltration, and an immunosuppressive microenvironment. Neuroblastoma was amongst the first tumors to be evaluated as a potential candidate for GD2-targeting CAR T cells, which recently documented promising results in high-risk, heavily pre-treated patients. Moreover, innovative engineering strategies for generating more potent and persistent CAR T cells suggest the possibility to reproduce, and potentially improve, these promising results on a larger scale. In the next years, harnessing the full therapeutic potential of CAR T cells and other immunotherapeutic strategies may open new possibilities for effectively treating the most aggressive forms of pediatric tumors.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"5-18"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics and Dose Optimization of Piperacillin in Infants and Children with Pneumonia.","authors":"Totsapol Jirasomprasert, Li-Yuan Tian, Dian-Ping You, Ya-Kun Wang, Lei Dong, Ya-Hui Zhang, Guo-Xiang Hao, John van den Anker, Yue-E Wu, Bo-Hao Tang, Wei Zhao, Yi Zheng","doi":"10.1007/s40272-024-00664-4","DOIUrl":"10.1007/s40272-024-00664-4","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to determine the piperacillin disposition and optimize the dosing regimens for infants and children with pneumonia.</p><p><strong>Methods: </strong>An opportunistic sampling strategy was used in this pharmacokinetic study. High-performance liquid chromatography was used to measure the concentrations of piperacillin in plasma samples. A population pharmacokinetic model was conducted using NONMEM.</p><p><strong>Results: </strong>The pharmacokinetic data of 90 samples from 64 infants and children with pneumonia (age range: 0.09-1.72 years for infants and 2.12-11.10 years for children) were available. A two-compartment model with first-order elimination was the most suitable model to describe the population pharmacokinetics of piperacillin. A covariate analysis indicated that body weight and age were significant factors affecting clearance. Monte Carlo simulations showed that a 50-mg/kg every 8 h or every 12 h dosing regimen results in underdosing. Results both in infants and children showed that an extended infusion (3 h) of various dosing regimens (80, 100, or 130 mg/kg) three times daily or a 300-mg/kg continuous infusion can reach a therapeutic level based on the chosen target for the probability of target attainment threshold of 70%, 80%, and 90% at minimum inhibitory concentration breakpoints of 8 mg/L and 16 mg/L.</p><p><strong>Conclusions: </strong>A population pharmacokinetic model was obtained to evaluate the disposition of piperacillin, and the optimal dosing regimens were provided for use in infants and children with pneumonia.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"91-102"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gentamicin Pharmacokinetics in Neonates Undergoing Therapeutic Hypothermia for Hypoxic Ischemic Encephalopathy.","authors":"Mamta Naik, Emily Warden, Rick Pittman, Lakshmi Katakam","doi":"10.1007/s40272-024-00661-7","DOIUrl":"10.1007/s40272-024-00661-7","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to review the pharmacokinetic profile of gentamicin among neonates with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) treatment.</p><p><strong>Methods: </strong>This was a retrospective study of neonates with HIE undergoing TH in the neonatal intensive care unit who received gentamicin between 2009 and 2014. Demographic information, diagnoses, laboratory test results, and medication administration and monitoring information were collected, and data were analyzed using SciPy.</p><p><strong>Results: </strong>A total of 57 neonates were analyzed. The median birth weight was 3.25 kg (interquartile range [IQR] 2.8-3.68), and median gestational age was 39 weeks (IQR 38-40). An elevated gentamicin trough level (defined as > 2 mg/L) was observed in 61% (35/57) of neonates. Half of the neonates (49%) had multiple gentamicin trough levels obtained, and 4% of the neonates were switched to an alternate agent. There was a significant difference in the number of dosing interval changes in neonates with elevated gentamicin trough levels compared with those with therapeutic gentamicin trough levels (P < 0.001). Of the neonates with elevated gentamicin trough levels, 14% (5/35) failed their hearing screen (P = 0.389).</p><p><strong>Conclusions: </strong>Neonates with HIE undergoing TH may have an altered pharmacokinetic profile, requiring multiple blood draws so medication levels can be monitored and doses adjusted. Traditional gentamicin dosing regimens may not be ideal for this patient population, and further guidance is required for alternative treatment regimens.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"85-90"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Drug Monitoring of Antimicrobial Drugs in Children with Cancer: A New Tool for Personalized Medicine.","authors":"Riccardo Masetti, Gianluca Bossù, Edoardo Muratore, Davide Leardini, Milo Gatti, Riccardo Di Sario, Federico Pea, Susanna Esposito","doi":"10.1007/s40272-024-00663-5","DOIUrl":"10.1007/s40272-024-00663-5","url":null,"abstract":"<p><p>The risk of fungal, bacterial, and viral infections is higher in children with hematological and solid malignancies, particularly during periods of profound neutropenia. Although early administration of antimicrobial agents is common, optimizing pharmacological therapy in pediatric patients with cancer is challenging because of their variable pharmacokinetics compared with adults, including differences in body mass and augmented renal clearance, as well as chemotherapy-induced organ toxicity. Therapeutic drug monitoring, which involves measuring drug concentrations in serum or plasma at specific timepoints and adjusting doses accordingly, can be applied to various medications. While standardized targets for all antimicrobial agents in children are lacking, therapeutic drug monitoring appears to be beneficial in preventing serious toxicity and addressing treatment failure or non-compliance. This narrative review aims to analyze current perspectives on therapeutic drug monitoring for antimicrobial drugs in the special population of children with hematological or oncological diseases, including those undergoing hematopoietic cell transplantation. The review provides evidence on the clinical benefits of this method and explores potential future developments in this area.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"41-56"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}