Pediatric Drugs最新文献

{"title":"Optimizing Drug Selection in Children with Multiple Sclerosis: What Do We Know and What Remains Unanswered?","authors":"Rabporn Suntornlohanakul, E Ann Yeh","doi":"10.1007/s40272-024-00675-1","DOIUrl":"10.1007/s40272-024-00675-1","url":null,"abstract":"<p><p>Pediatric-onset multiple sclerosis (POMS) refers to multiple sclerosis with onset before 18 years of age. It is characterized by a more inflammatory course, more frequent clinical relapses, and a greater number of magnetic resonance imaging (MRI) lesions compared with adult-onset MS (AOMS), leading to significant impacts on both disability progression and cognitive outcomes in affected individuals. Managing POMS presents distinct challenges due to the unique needs of pediatric patients and the limited number of disease-modifying therapies (DMTs) approved for pediatric use. Notably, only one therapy (fingolimod) is approved by the United States (US) Food and Drug Administration (FDA) and three (fingolimod, teriflunomide, and dimethyl fumarate) by the European Medicines Agency (EMA) for use in youth with MS. However, observational evidence identifies use of almost all agents off-label in this population. This review provides a comprehensive overview of literature supporting the use of DMTs for POMS, including evidence from observational studies. In this paper, we highlight the shift in clinical practice, which has led to increased use of high-efficacy therapies (HETs) at or near disease onset. We review emerging evidence indicating better cognitive and motor outcomes in this population with early initiation of therapy. Finally, in this paper, we provide a suggested treatment algorithm for managing POMS. We underscore the need for personalized approaches in POMS management. We identify special considerations unique to pediatric care, including attention to family dynamics, and strategies to improve medication adherence and a smooth transition to adult care. Further research on DMTs in POMS is essential to optimize outcomes and improve long-term prognosis.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"161-179"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896379","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":"Optimizing Pediatric Sedation: Evaluating Remimazolam and Dexmedetomidine for Safety and Efficacy in Clinical Practice.","authors":"Vera Scheckenbach, Frank Fideler","doi":"10.1007/s40272-024-00659-1","DOIUrl":"10.1007/s40272-024-00659-1","url":null,"abstract":"<p><p>Daily, children undergo countless investigations and interventions, which require sedation and immobilization to ensure safety and accuracy. This remains associated with a persistent risk of sedation-induced life-threatening events as children are particularly vulnerable to adverse medical events and complications. Consequently, there is an urgent need to increase the safety of pediatric sedation and anesthesia. An ideal approach involves the use of drugs with fewer intrinsic side effects. In this context, on the basis of their pharmacokinetic properties, remimazolam (RMZ) and dexmedetomidine (DEX) were evaluated for their suitability as ideal sedatives. RMZ and DEX, both of which are currently available in pediatric medicine, have shown great promise in initial publications. To date, only very limited data concerning RMZ in small children are available. RMZ is a novel, ultrashort-acting benzodiazepine that is metabolized by tissue esterase, largely independent of organ function. It has a context-sensitive half-life of approximately 10 min, with minimal accumulation even with prolonged use. Its effects can be completely reversed with flumazenil. DEX, an isomer of medetomidine, is a potent α2-receptor-agonist with multiple indications in anesthesia and intensive care medicine. It has coanalgesic potential, allows for 'arousal sedations' and has a low profile for cardiorespiratory side effects. DEX is metabolized in the liver and is predominantly excreted renally. Both drugs show potential in the prevention and treatment of delirium, with DEX having additional neuroprotective effects. DEX and RMZ possess several properties of an optimal sedative, including clinically insignificant main metabolites and a broad dosage range, indicating their potential to reduce the incidence of sedation-related life-threatening events in children. However, further clinical research is necessary to better evaluate their potential risks.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"181-189"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562425","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":"How Consistent are Anti-Infective Drug Dosing Recommendations Across Three European Paediatric Formularies?","authors":"Lukas Higi, Elisabeth Carydias, Andrea M Burden, Priska Vonbach","doi":"10.1007/s40272-024-00674-2","DOIUrl":"10.1007/s40272-024-00674-2","url":null,"abstract":"<p><strong>Background: </strong>Drug dosing recommendations in paediatrics are mainly based on the age and bodyweight of the child. Because of the limited amount of label information, several paediatric drug formularies have been developed. This study compares anti-infective drug dosing recommendations across three European formularies.</p><p><strong>Methods: </strong>Recommendations from three paediatric formularies (German Pediatric Formulary [GPF], SwissPedDose [SPD] and the British National Formulary for Children [BNF]) were collected. Using population growth curves, we simulated one child for each month from 1 month up to 18 years of age. The recommendations from each formulary were used to calculate doses for each simulated child. Equivalence and difference in calculated doses were analysed.</p><p><strong>Results: </strong>In total, dosing recommendations for 34 anti-infective substances were collected with 74 corresponding indications, which resulted in 47,154 calculated doses. The mean (± standard deviation) proportion of equivalent doses (difference ≤10%) across all three formularies was 40% (±16), while for pairwise comparisons it was 53% (±19) for GPF versus BNF, 67% (±14) for GPF versus SPD and 52% (±19) for SPD versus BNF. The median [25th quantile, 75th quantile] differences in daily doses across all three formularies were 0%, [0, 26] while for pairwise comparisons it was 4% [0, 32] for GPF versus BNF, 0% [0, 17] for GPF versus SPD and 7% [0, 33] for SPD versus BNF.</p><p><strong>Conclusions: </strong>The majority of recommended anti-infective drug doses were consistent, with the highest equivalence found between GPF and SPD. Maintaining formularies is resource intensive; therefore, a common standard in Europe could prove beneficial when moving towards digitalisation of the healthcare systems.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"221-232"},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824419","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":"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}