Pediatric Drugs最新文献

{"title":"Adverse Event Profile of First-line Drugs for Treating Patent Ductus Arteriosus in Neonates: A Disproportionality Analysis Study of USFDA Adverse Event Reporting System.","authors":"Kannan Sridharan, Gowri Sivaramakrishnan","doi":"10.1007/s40272-024-00657-3","DOIUrl":"10.1007/s40272-024-00657-3","url":null,"abstract":"<p><strong>Background: </strong>Acetaminophen, ibuprofen, and indomethacin are widely used as first-line drugs for patent ductus arteriosus (PDA) closure in preterm neonates. However, their relative safety profiles remain unclear.</p><p><strong>Methods: </strong>Adverse event reports related to the first-line drugs used in PDA and neonates in general were retrieved from the US Food and Drug Authority (FDA) Adverse Event Reporting System. Deduplicated reports were analyzed using proportional reporting ratios and reporting odds ratios to identify disproportionality safety signals between drugs.</p><p><strong>Results: </strong>A total of 969 unique reports related to the first-line drugs used in PDA and 499 reports in the neonatal period were included. Acetaminophen signals primarily involved the liver, while ibuprofen and indomethacin signals pertained to gastrointestinal, renal, vascular, and mortality outcomes. Higher occurrences of death were reported with indomethacin and ibuprofen compared with acetaminophen.</p><p><strong>Conclusion: </strong>This first comparison of PDA drug safety profiles from spontaneous reports highlights some differences, with acetaminophen potentially conferring a safer adverse effect profile overall. While limitations include missing data and reporting biases, the signals warrant further validation. Given its comparable efficacy to ibuprofen, as demonstrated in other studies, acetaminophen has the potential to be preferred as an initial medical therapy for PDA.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"767-785"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378170","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":"Clinical Evidence Supporting FDA Approval of Gene and RNA Therapies for Rare Inherited Conditions.","authors":"Ilina C Odouard, Jeromie Ballreich, Branden Lee, Mariana P Socal","doi":"10.1007/s40272-024-00645-7","DOIUrl":"10.1007/s40272-024-00645-7","url":null,"abstract":"<p><strong>Background: </strong>Gene and RNA therapies have potential to transform the treatment of rare inherited diseases, but there are concerns about the evidence supporting their use and high costs.</p><p><strong>Objective: </strong>We analyze the evidence supporting Food and Drug Administration (FDA) approval of gene and RNA therapies for rare inherited diseases and discuss implications for clinical practice and policy.</p><p><strong>Methods: </strong>We conducted a qualitative analysis of FDA documents outlining the basis of approval for gene and RNA therapies approved for rare inherited diseases between 2016 and 2023. For each drug, we gathered five characteristics of the evidence supporting FDA approval (no phase 3 trial, nonrandomized, no clinical endpoint, lack of demonstrated benefit, and significant protocol deviation) and four characteristics of the FDA approval process (prior rejection or complete response, negative committee vote, discrepancy between label and trial population, and boxed warning). The main outcome was the number of drugs with each characteristic.</p><p><strong>Results: </strong>Between 2016 and 2023, 19 gene and RNA therapies received FDA approval to treat rare inherited diseases. The most common limitations in the evidence supporting approval of these drugs were nonrandomized studies (8/19, 42%), no clinical endpoint (7/19, 37%), lack of demonstrated benefit or inconsistent results (4/19, 21%), and no phase 3 trial (4/19, 21%). Half (3/6) of accelerated approvals and 57% (5/9) of drugs with breakthrough designation had nonrandomized trials, and gene therapies with one-time dosing were overrepresented (5/7, 71%) among the drugs with nonrandomized trials. Five of six accelerated approvals (83%) and five of nine pediatric drugs (56%), most of which were indicated for Duchenne muscular dystrophy, had no clinical endpoint. Four of nine (44%) pediatric drugs and four of six (67%) accelerated approvals failed to demonstrate benefit compared with none of the nonpediatric drugs and none of the traditional approvals. Five drugs, which all had different indications and represented a mix of RNA and gene therapies, did not have any of these evidence characteristics. Among drugs that received prior rejections or negative committee opinions, all four had nonrandomized trials and lacked a clinical endpoint, and 75% (3/4) lacked demonstrated benefit. Five of nine (56%) pediatric drugs were indicated for broader age groups according to the drug label compared with the trial populations. Of the three drugs with boxed warnings, two had pediatric indications and nonrandomized studies, and one had no phase 3 trial.</p><p><strong>Conclusions: </strong>Issues related to trial design, outcome, and data integrity in the evidence supporting FDA approval of rare inherited disease gene and RNA therapies raise questions about whether this evidence is adequate to inform prescribing decisions. Gene and RNA therapies with accelerated approval an","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"741-752"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889930","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":"Role of mTOR Inhibitors in Pediatric Liver Transplant Recipients: A Systematic Review","authors":"Marjan Moghadamnia, Simin Dashti-Khavidaki, Hosein Alimadadi","doi":"10.1007/s40272-024-00648-4","DOIUrl":"https://doi.org/10.1007/s40272-024-00648-4","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Background&lt;/h3&gt;&lt;p&gt;Immunosuppressive medications play a crucial role in determining both organ and patient survival following liver transplantation (LT). Typically, immunosuppressive protocols for pediatric LT patients rely on calcineurin inhibitors (CNIs). While inhibitors of mammalian target of rapamycin (mTOR) have demonstrated beneficial outcomes in adult recipients of liver allografts, such as improved renal function post-LT, their application in pediatric liver transplant recipients is a subject of debate due to uncertain efficacy and potential adverse effects.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Objectives&lt;/h3&gt;&lt;p&gt;This review evaluates the potential roles of mTOR inhibitors in the context of pediatric LT patients.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Methods&lt;/h3&gt;&lt;p&gt;This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for conduct and reporting. Databases until 31 August 2023 were searched using specific terms and keywords. All clinical studies focusing on mTOR inhibitors in pediatric LT were included.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;Out of 888 identified articles, 30 studies, involving 386 children who had undergone liver transplantation and received mTOR-inhibitor-based immunosuppressive regimens, met the inclusion criteria. The beneficial impacts of switching from a CNI to an mTOR inhibitor or adding an mTOR inhibitor to CNI-reduced immunosuppression in LT pediatric patients with impaired kidney function are controversial, and high-powered clinical studies are need. It appears that enhancing immunosuppression by adding an mTOR inhibitor to CNI is helpful for pediatric LT recipients who are experiencing refractory acute rejection or chronic rejection. mTOR-inhibitor-containing regimens failed to reduce the occurrence of post-transplant lymphoproliferative disorders (PTLD) among children with LT that may be due to concomitant high CNI concentration among studied patients. The effectiveness of mTOR inhibitors in treating PTLD remains uncertain; however, in patients with PTLD who are at high risk of rejection, mTOR inhibitors may be administered. Conversion to or the addition of mTOR inhibitors to maintenance immunosuppression seems to be suitable for pediatric patients who received a transplant due to hepatic malignancies such as hepatoblastoma or hepatocellular carcinoma or for those with post-transplant primary or recurrent malignancies. Switching to an mTOR inhibitor may improve some CNI-related adverse effects such as gingival hyperplasia, neurotoxicity, nephropathy, hypertrophic cardiomyopathy, or thrombotic microangiopathy.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Conclusion&lt;/h3&gt;&lt;p&gt;Although the exact role of mTOR inhibitors among pediatric patients who have received a liver transplant needs further study, two algorithms are presented in this review to guide conversion from CNIs to mTOR inhibitors or the ad","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":"69 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221035","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":"Methotrexate Intolerance in Juvenile Idiopathic Arthritis: Definition, Risks, and Management.","authors":"Camilla Wibrand, Nini Kyvsgaard, Troels Herlin, Mia Glerup","doi":"10.1007/s40272-024-00643-9","DOIUrl":"10.1007/s40272-024-00643-9","url":null,"abstract":"<p><p>Juvenile idiopathic arthritis is the most common rheumatic disorder in childhood and adolescence posing a significant threat of short-term and long-term disability if left untreated. Methotrexate is a folic acid analog with various immunomodulatory properties. It has demonstrated significant efficacy for the treatment of juvenile idiopathic arthritis, often considered the preferred first-line disease-modifying anti-rheumatic drug given as monotherapy or in combination with biological drugs. Despite this, there is a considerable risk for treatment disruptions owing to the high prevalence of methotrexate intolerance, with symptoms such as nausea, stomach ache, vomiting, and behavioral symptoms. Many different risk factors for the intolerance have been proposed including gender, age, disease activity, treatment duration, dosing and administration, and genetic and psychological factors. As the studies have shown contradictory results, many questions are left unanswered. Therefore, a consensus regarding outcome measures and reporting is crucial. In this review, we describe the identification and assessment of methotrexate intolerance and evaluate potential risk factors, genetic associations as well as management strategies.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"479-498"},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752359","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":"Effectiveness and Safety of Ustekinumab in Pediatric Ulcerative Colitis: A Multi-center Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN.","authors":"Shlomi Cohen, Helena Rolandsdotter, Kaija-Leena Kolho, Dan Turner, Christos Tzivinikos, Matteo Bramuzzo, Gemma Pujol-Muncunill, Luca Scarallo, Darja Urlep, Firas Rinawi, Maya Granot, Ben Kang, Ylva Longueville, Marta Velasco Rodríguez-Belvís, Yael Weintraub, Víctor Manuel Navas-López, Anat Yerushalmy-Feler","doi":"10.1007/s40272-024-00631-z","DOIUrl":"10.1007/s40272-024-00631-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>Current data on ustekinumab therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBDU) are limited. We aimed to evaluate the effectiveness and safety of ustekinumab in pediatric UC and IBDU.</p><p><strong>Methods: </strong>This multicenter retrospective study included 16 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. Children with UC or IBDU treated with ustekinumab were enrolled. Demographic, clinical, laboratory, endoscopic, and imaging data as well as adverse events were recorded. Analyses were all based on the intention-to-treat principle.</p><p><strong>Results: </strong>Fifty-eight children (39 UC and 19 IBDU, median age 14.5 [IQR 11.5-16.5] years) were included. All had failed biologic therapies, and 38 (66%) had failed two or more biologics. Corticosteroid-free clinical remission (CFR) was observed in 27 (47%), 33 (57%), and 37 (64%) children at 16, 26, and 52 weeks, respectively. Normalization of C-reactive protein and calprotectin < 150 μg/g were achieved in 60% and 52%, respectively, by 52 weeks. Endoscopic and radiologic remissions were reached in 8% and 23%, respectively. The main predictors of CFR were diagnosis of UC compared with IBDU (hazard ratio [HR] 2.2, 95% CI 1.03-4.85; p = 0.041) and no prior vedolizumab therapy (HR 2.1, 95% CI 1.11-4.27; p = 0.023). Ustekinumab serum levels were not associated with disease activity. Adverse events were recorded in six (10%) children, leading to discontinuation of the drug in three.</p><p><strong>Conclusion: </strong>Based on these findings, ustekinumab appears as an effective therapy for pediatric refractory UC and IBDU. The potential efficacy should be weighed against the risks of serious adverse events.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"609-617"},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081744","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":"Comparison of Different Doses of Oral and Ocular Propranolol for Retinopathy of Prematurity: A Network Meta-Analysis.","authors":"Amparo Ortiz-Seller, Pablo Martorell, Patricia Roselló, Esteban Morcillo, José L Ortiz","doi":"10.1007/s40272-024-00647-5","DOIUrl":"10.1007/s40272-024-00647-5","url":null,"abstract":"<p><strong>Objective: </strong>The efficacy and safety of propranolol for retinopathy of prematurity (ROP) remain under debate. This network meta-analysis (NMA) focuses on whether a ranking may be established for different dose levels of propranolol as treatment of ROP in terms of stage progression as the primary outcome, with appearance of plus disease and need for anti-vascular endothelial growth factors (anti-VEGFs) or laser therapy as secondary endpoints.</p><p><strong>Methods: </strong>Fourteen studies (10 randomised controlled trials, three single-arm trials and one retrospective observational study) of 474 patients treated with oral or ocular propranolol were retrieved from databases up to April 2024. Meta-insight and model-based NMA were undertaken to evaluate the propranolol dose-response relationship. Studies were evaluated for model fit, risk of bias and Confidence of evidence In Network Meta-Analysis (CINeMA). Effect sizes were determined as odds ratio (OR) with 95% credible interval (CrI).</p><p><strong>Results: </strong>Bayesian analysis showed a trend towards improved effects for propranolol given at late stages (stages 2-3; S23) of ROP progression compared with its administration at earlier stages (stages 0-1; S01). OR values for oral propranolol 1.5 and 2 mg/kg/day given at S23 were 0.13 (95% CrI 0.04-0.37) and 0.16 (95% CrI 0.04-0.61), respectively, while given at S01 were 0.28 (95% CrI 0.02-2.96) and 0.78 (95% CrI 0.14-4.43), respectively. Similarly, OR of eye propranolol 0.2% at S23 was 0.37 (95% CrI 0.09-1.00) versus an S01 OR of 0.64 (95% CrI 0.21-2.04). Surface under the cumulative ranking curve (SUCRA) analyses confirmed best probability values for oral propranolol 1.5-2 mg/kg followed by eye propranolol 0.2%, all at S23. Model-based NMA showed nonlinearity in the dose-response for oral propranolol with a trend to greater maximal effect for its administration at late versus early stages. For secondary endpoints, lower risk values were found with oral propranolol 1.5 mg/kg/day at S23 for progression to plus disease (OR 0.14; 95% CrI 0.02-0.84) and need for anti-VEGFs (OR 0.23; 95% CrI 0.05-0.93) and laser (OR 0.16; 95% CrI 0.02-1.10) therapies also followed by eye propranolol 0.2%, and a similar profile was obtained with SUCRA analysis. Lower doses (0.5-1.0 mg/kg/day) of oral propranolol retained efficacy. Threat of adverse events was estimated as risk difference versus control with no difference for eye propranolol 0.2% and oral propranolol 0.5 mg/kg/day, modest increases of risk for oral propranolol 1.0 and 1.5 mg/kg/day and the highest risk difference for oral propranolol 2.0 mg/kg/day (0.06; 95% CI -0.01 to 0.13).</p><p><strong>Conclusion: </strong>A diminished risk of disease progression and need for additional treatment was obtained with propranolol in ROP, but safety is a potential concern. Propranolol eye micro-drops (0.2%) can be as efficacious as oral propranolol. Nonetheless, the evidence is limited due to the pa","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"499-518"},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902595","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":"Paediatric Drug Development in China: Current Status and Future Prospects.","authors":"Lin Song, Ni Zhang, Ting-Ting Jiang, Yuntao Jia, Yao Liu","doi":"10.1007/s40272-024-00636-8","DOIUrl":"10.1007/s40272-024-00636-8","url":null,"abstract":"<p><p>For more than two decades, regulatory agencies throughout the world released guidelines, rules and laws to stimulate and assist in paediatric drug development. In 2014, the National Health and Family Planning Commission (now known as the National Health Commission, NHC) and five other departments in China jointly issued 'Several Opinions on Safeguarding Medication for Children', after which several policies and regulations were issued to implement the priority review and approval of paediatric medicinal products and support the development of new drugs, including new dosage forms and strengths, for children. A total of 172 special medicinal products for children were approved from 2018 to 2022. Since 2016, the NHC, together with relevant administrative departments, has formulated and issued four paediatric drug lists containing 129 medicinal products to encourage research and development. At present, approximately 25 of these drugs (at exactly the same dosage forms and strengths as on the lists) have been approved for marketing, including antitumour drugs and immunomodulators, nervous system drugs, drugs for mental disorders and drugs for rare diseases. In this review, we analysed the regulations issued for promoting paediatric drug development in China, including the priority review and approval system, technical guidelines, data protection and financial support policies and general profiles of paediatric drug approval, clinical trials and the addition of information for children in the labels of marketed medicinal products. Finally, we discussed the challenges and possible strategies in the research and development of paediatric drugs in China.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"555-563"},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248336","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":"Commercial Versus Compounded Preparations in Pediatric Ophthalmology.","authors":"Annegret Dahlmann-Noor, Jill Bloom, Saw Keng Lee, Samiya Chowdhury, Kanwal Nischal, Dominique Bremond-Gignac","doi":"10.1007/s40272-024-00642-w","DOIUrl":"10.1007/s40272-024-00642-w","url":null,"abstract":"<p><p>Many conditions managed by pediatric ophthalmologists are rare diseases, and even if pharmacological treatments are available, these have often not been evaluated in children. Off-label prescribing is a common practice in pediatric ophthalmology. In addition, there is often no commercial case for the production of a medicine that may only be used for a small number of patients worldwide. Compounded preparations prepared locally are therefore still in frequent use, although it is known that production may not meet stringent quality assurance standards. For several indications, commercial preparations, evaluated in rigorous clinical trials with children, are now available. Myopia management is joining the list of these indications, with low-concentration atropine formulations derived from recent clinical trials in Australia, USA, and Europe now entering the market. This short article gives an overview of the background and recent developments of compounded and commercial preparations for use in pediatric ophthalmology.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"475-477"},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470018","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":"Impact of Prolonged Continuous Ketamine Infusions in Critically Ill Children: A Prospective Cohort Study.","authors":"Paulo Sérgio Lucas da Silva, Emerson Yukio Kubo, Rafael da Motta Ramos Siqueira, Marcelo Cunio Machado Fonseca","doi":"10.1007/s40272-024-00635-9","DOIUrl":"10.1007/s40272-024-00635-9","url":null,"abstract":"<p><strong>Background: </strong>Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24 hours) in the pediatric intensive care unit (PICU).</p><p><strong>Objective: </strong>We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24 hours in mechanically ventilated children.</p><p><strong>Methods: </strong>We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium.</p><p><strong>Results: </strong>A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4 mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p = 0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n = 4), hypersecretion (n = 14), tachycardia (n = 6), and nystagmus (n = 2). There were no significant changes in hemodynamic variables 24 h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68-80.5%) of the time in the 24 hours before ketamine initiation, compared with 84% (range 74.5-90%) of the time during the 24 h after ketamine initiation (p < 0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group.</p><p><strong>Conclusion: </strong>The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"597-607"},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958751","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.","authors":"Elizabeth A Hall, Tracy M Hagemann, Chasity M Shelton, Hilary M Jasmin, Alexis N Calvasina, Doralina L Anghelescu","doi":"10.1007/s40272-024-00640-y","DOIUrl":"10.1007/s40272-024-00640-y","url":null,"abstract":"<p><p>Opioid therapy is the mainstay for managing pain in pediatric oncology. This narrative review describes the current literature regarding opioids for pediatric cancer pain. The review explores the multifaceted landscape of opioid utilization in this population, including the role of opioids in certain clinical circumstances, modalities of opioid delivery, unique opioids, outpatient and at-home pain management strategies, and other key concepts such as breakthrough pain. This review highlights the importance of individualized dosing and multimodal approaches to enhance efficacy and minimize adverse effects. Drawing from a wide range of evidence, this review offers insights to optimize pediatric oncology pain management.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"565-596"},"PeriodicalIF":3.4,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492980","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}