Pediatric Drugs最新文献

{"title":"Neonatal Necrotizing Enterocolitis: An Update on Pathophysiology, Treatment, and Prevention.","authors":"Annette Gawron Roberts, Noelle Younge, Rachel Gottron Greenberg","doi":"10.1007/s40272-024-00626-w","DOIUrl":"10.1007/s40272-024-00626-w","url":null,"abstract":"<p><p>Necrotizing enterocolitis (NEC) is a life-threatening disease predominantly affecting premature and very low birth weight infants resulting in inflammation and necrosis of the small bowel and colon and potentially leading to sepsis, peritonitis, perforation, and death. Numerous research efforts have been made to better understand, treat, and prevent NEC. This review explores a variety of factors involved in the pathogenesis of NEC (prematurity, low birth weight, lack of human breast milk exposure, alterations to the microbiota, maternal and environmental factors, and intestinal ischemia) and reports treatment modalities surrounding NEC, including pain medications and common antibiotic combinations, the rationale for these combinations, and recent antibiotic stewardship approaches surrounding NEC treatment. This review also highlights the effect of early antibiotic exposure, infections, proton pump inhibitors (PPIs), and H₂ receptor antagonists on the microbiota and how these risk factors can increase the chances of NEC. Finally, modern prevention strategies including the use of human breast milk and standardized feeding regimens are discussed, as well as promising new preventative and treatment options for NEC including probiotics and stem cell therapy.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"259-275"},"PeriodicalIF":3.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336502","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":"Comparison of Deep and Moderate Neuromuscular Blockade for Major Laparoscopic Surgery in Children: A Randomized Controlled Trial.","authors":"Guo Wei, Yong-Xin Li, Ying Chen, Mei Diao, John Wei Zhong, Shou-Dong Pan","doi":"10.1007/s40272-024-00622-0","DOIUrl":"10.1007/s40272-024-00622-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Neuromuscular blocking agents are routinely used in laparoscopic surgery to optimize operative conditions. We compared the effect of a deep and moderate neuromuscular blockade (NMB) on surgical conditions and postoperative outcomes in children undergoing major laparoscopic surgery.</p><p><strong>Methods: </strong>Sixty children aged 2-14 years scheduled to undergo major laparoscopic surgery were randomly allocated to deep (post-tetanic count 1-2 twitches) or moderate (train-of-four 1-2 twitches) NMB groups. The anesthesia was maintained with propofol and remifentanil, and the NMB was maintained with a rocuronium continuous infusion. At the end of the operation, the NMB were antagonized with sugammadex. The intra-abdominal pressure, airway pressure, Leiden Surgical Rating Scale, intraoperative hemodynamics, drug usages, duration of surgery, postoperative recovery time, pain, and complications were compared between the groups.</p><p><strong>Results: </strong>The maximum and mean intra-abdominal pressure, the peak inspiratory pressure, and mean airway pressure were significantly lower in the deep NMB group than in the moderate NMB group (p < 0.001). The Leiden Surgical Rating Scale and the dosage of rocuronium were significantly higher in the deep NMB group than the moderate NMB group (p < 0.001). The intraoperative hemodynamics, duration of surgery, post-operative recovery time, pain, and the incidence rate of complications were not significantly different between the groups (p > 0.05).</p><p><strong>Conclusions: </strong>A deep NMB provided better operative conditions and similar recovery profiles compared with a moderate NMB as reversed with sugammadex in children undergoing major laparoscopic surgery.</p><p><strong>Clinical trial registration: </strong>Chinese Clinical Trial Registry, No. ChiCTR2100053821.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"347-353"},"PeriodicalIF":3.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185093","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":"Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review","authors":"Sebastiano A. G. Lava, Craig Laurence, Alessandro Di Deo, Nicole Sekarski, Michael Burch, Oscar Della Pasqua","doi":"10.1007/s40272-024-00623-z","DOIUrl":"https://doi.org/10.1007/s40272-024-00623-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>We aimed to review information on compassionate use, clinical pharmacology, efficacy, and safety of dapagliflozin and empagliflozin in children.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We conducted a systematic review of published clinical trials, case reports, and observational studies in Medline, Excerpta Medica, and Web of Science databases from inception to September 2023. For the two randomised controlled trials on type 2 diabetes mellitus (T2DM), we implemented a meta-analysis on the primary outcome (mean difference in glycosylated haemoglobin [HbA1c] between intervention and placebo groups). Review Manager (RevMan), version 5.4.1, was used for this purpose.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Thirty-five articles (nine case reports, ten case series, one prospective non-controlled trial, four controlled randomised trials, two surveys, six pharmacokinetic studies, and three pharmacovigilance studies) were selected, in which 415 children were exposed to either dapagliflozin or empagliflozin: 189 diabetic patients (mean age 14.7 ± 2.9 years), 32 children with glycogen storage disease type Ib (GSD Ib), glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency, or severe congenital neutropenia type 4 (8.5 ± 5.1 years), 47 children with kidney disease or heart failure (11.2 ± 6.1 years), 84 patients in pharmacokinetic studies (15.1 ± 2.3 years), and 63 patients in toxicological series. The effect of dapagliflozin and empagliflozin in T2DM was demonstrated by HbA1c reduction in two randomised trials among a total of 177 adolescents, with a mean HbA1c difference of -0.82% (95% confidence interval -1.34 to -0.29) as compared to placebo (no heterogeneity, <i>I</i>² = 0%). Dosage ranged between 5 and 20 mg (mean 11.4 ± 3.7) once daily for dapagliflozin and between 5 and 25 mg (mean 15.4 ± 7.4) once daily for empagliflozin. Among the paediatric cases of GSD Ib, empagliflozin 0.1–1.3 mg/kg/day improved neutropenia, infections, and gastrointestinal health. Dapagliflozin (mean dosage 6.9 ± 5.2 mg once daily) was well-tolerated in children with chronic kidney disease and heart failure. Side effects were generally mild, the most frequent being hypoglycaemia in children with GSD Ib (33% of patients) or T2DM (14% of patients) on concomitant hypoglycaemic drugs. Diabetic ketoacidosis is rare in children.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Early evidence suggests that dapagliflozin and empagliflozin are well tolerated in children. A clinical pharmacology rationale currently exists only for adolescents with diabetes mellitus.</p><h3 data-test=\"abstract-sub-heading\">Prospero Registration Number</h3><p>CRD42023438162.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":"122 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624768","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 of Adalimumab in Juvenile Idiopathic Arthritis Patients: A Retrospective Cohort Study Using Clinical Care Data","authors":"Amara Nassar-Sheikh Rashid, Femke Hooijberg, Sandy C. Bergkamp, Mariken P. Gruppen, Taco W. Kuijpers, Mike Nurmohamed, Theo Rispens, Gertjan Wolbink, J. Merlijn van den Berg, Dieneke Schonenberg-Meinema, Ron A. A. Mathôt","doi":"10.1007/s40272-024-00629-7","DOIUrl":"https://doi.org/10.1007/s40272-024-00629-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background and Objective</h3><p>Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disorder that primarily affects the joints in children. Notably, it is known to co-occur with uveitis. Adalimumab, a monoclonal anti-TNF antibody, is effective in treating both conditions. A deeper understanding of the pharmacokinetics (PK) of adalimumab in JIA is crucial to advance in more personalized treatment approaches. The objective of this study is to evaluate the population PK profile of adalimumab in JIA and to explain causes for its variability.</p><h3 data-test=\"abstract-sub-heading\">Materials and Methods</h3><p>Adalimumab and antidrug antibody concentrations were retrospectively retrieved from the charts of patients with JIA. Initially, five literature-based population PK models of adalimumab were evaluated to assess their ability to describe the observed concentration–time profiles in the JIA cohort. These models included one specifically for the pediatric Crohn’s disease population and four derived from studies in adult populations in healthy subjects and rheumatoid arthritis patients. Subsequently, a novel population PK model tailored to the JIA population was developed using NONMEM software. Monte Carlo simulations were then conducted utilizing the final PK model to visualize the concentration–time profile of adalimumab in patients with JIA and the impact of covariates.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A cohort of 50 patients with JIA with 78 available adalimumab samples was assessed. The mean age was 11.8 ± 3.9 years, with a median body weight of 49 kg (interquartile range 29.4–59.8 kg). All literature models adequately described the concentration–time profiles in JIA. The best model, which was developed in patients with rheumatoid arthritis during the maintenance phase of treatment, served as a basis for estimating clearance in JIA, resulting in a value of 0.37 L per day per 70 kg. Patient body weight, antidrug antibodies, methotrexate use, CRP level, and comorbidity of uveitis were found to have a significant impact on adalimumab clearance, and these reduced the inter-patient variability from 58.6 to 28.0%. On steady state in the simulated patient population, the mean trough level was 7.4 ± 5.5 mg/L. The two dosing regimens of 20 and 40 mg every other week, based on patients’ body weight, resulted in comparable simulated overall drug exposure.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Five literature models effectively described adalimumab PK in this pediatric cohort, highlighting the potential for extrapolating existing models to the pediatric population. The new JIA model confirmed the effect of several known covariates and found a novel association for drug clearance with methotrexate use (lower) and uveitis (higher), which might have clinical relevance for personalized dosing in JIA.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":"49 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140616291","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":"Distribution of Bevacizumab into the Cerebrospinal Fluid of Children and Adolescents with Recurrent Brain Tumors","authors":"Iris K. Minichmayr, Ursula Knaack, Johannes Gojo, Daniel Senfter, Christine Haberler, Amedeo A. Azizi, Lisa Mayr, Markus Zeitlinger, Andreas Peyrl","doi":"10.1007/s40272-024-00624-y","DOIUrl":"https://doi.org/10.1007/s40272-024-00624-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>To date, evidence has been lacking regarding bevacizumab pharmacokinetics in the cerebrospinal fluid (CSF).</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study assessed the penetration of bevacizumab, as part of a metronomic antiangiogenic treatment regimen, into the CSF of children, adolescents, and young adults with recurrent brain tumors.</p><h3 data-test=\"abstract-sub-heading\">Patients and Methods</h3><p>Serum and CSF concentrations, malignant cells, and vascular endothelial growth factor A (VEGF-A) were analyzed in 12 patients (5–27 years) following 10 mg/kg bevacizumab intravenous biweekly administration (EudraCT number 2009-013024-23). A population pharmacokinetic model including body weight, albumin, and tumor type as influential factors was extended to quantify the CSF penetration of bevacizumab.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Apart from in serum (minimum concentration/maximum concentration [<i>C</i>_min/<i>C</i>_max] 77.0–305/267–612 mg/L, median 144/417 mg/L), bevacizumab could be quantified in the CSF (0.01–2.26 mg/L, median 0.35 mg/L). The CSF/serum ratio was 0.16 and highly variable between patients. Malignant cells could be detected in CSF before initiation of treatment in five of 12 patients; after treatment, the CSF was cleared in all patients. VEGF-A was detected in three patients before treatment (mean ± SD: 20 ± 11 pg/mL), and was still measurable in one of these patients despite treatment (16 pg/mL).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This pharmacokinetic pilot study indicated penetration of bevacizumab into the CSF in a population of children, adolescents, and young adults with recurrent brain tumors.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":"13 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140572377","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":"The Effect of Polymorphisms and Other Biomarkers on Infliximab Exposure in Paediatric Inflammatory Bowel Disease: Development of a Population Pharmacokinetic Model","authors":"Susana Clemente-Bautista, Iñaki F. Trocóniz, Óscar Segarra-Cantón, Sara Salvador-Marín, Carlos J. Parramón-Teixidó, Marina Álvarez-Beltrán, Luís A. López-Fernández, Helena Colom, Maria J. Cabañas-Poy, Maria Q. Gorgas-Torner, Marta Miarons","doi":"10.1007/s40272-024-00621-1","DOIUrl":"https://doi.org/10.1007/s40272-024-00621-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Therapeutic drug monitoring (TDM) of infliximab has been shown to be a effective strategy for inflammatory bowel disease (IBD). Population pharmacokinetic (PopPK) modeling can predict trough concentrations for individualized dosing.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The aim of this study was to develop a PopPK model of infliximab in a paediatric population with IBD, assessing the effect of single nucleotide polymorphisms (SNPs) and other biomarkers on infliximab clearance.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This observational and ambispective single-centre study was conducted in paediatric patients with IBD treated with infliximab between July 2016 and July 2022 in the Paediatric Gastroenterology Service of the Hospital Universitari Vall d’Hebron (HUVH) (Spain). Demographic, clinical, and analytical variables were collected. Twenty SNPs potentially associated with variations in the response to infliximab plasma concentrations were analysed. infliximab serum concentrations and antibodies to infliximab (ATI) were determined by ELISA. PopPK modelling was performed using nonlinear mixed-effects analysis (NONMEM).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Thirty patients (21 males) were included. The median age (range) at the start of infliximab treatment was 13 years (16 months to 16 years). A total of 190 samples were obtained for model development (49 [25.8%] during the induction phase). The pharmacokinetics (PK) of infliximab were described using a two-compartment model. Weight, erythrocyte sedimentation rate (ESR), faecal calprotectin (FC), and the SNP rs1048610 (<i>ADAM17</i>) showed statistical significance for clearance (CL), and albumin for inter-compartmental clearance (Q). Estimates of CL1 (genotype 1-AA), CL2 (genotype 2-AG), CL3 (genotype 3-GG), Q, <i>V</i>_c, and <i>V</i>_p (central and peripheral distribution volumes) were 0.0066 L/h/46.4 kg, 0.0055 L/h/46.4 kg, 0.0081 L/h/46.4 kg, 0.0029 L/h/46.4 kg, 0.6750 L/46.4 kg, and 1.19 L/46.4 kg, respectively. The interindividual variability (IIV) estimates for clearance, <i>V</i>_c, and <i>V</i>_p were 19.33, 16.42, and 36.02%, respectively.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>A popPK model utilising weight, albumin, FC, ESR, and the SNP rs1048610 accurately predicted infliximab trough concentrations in children with IBD.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":"3 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140172734","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":"Treatment Options for Alopecia Areata in Children and Adolescents","authors":"","doi":"10.1007/s40272-024-00620-2","DOIUrl":"https://doi.org/10.1007/s40272-024-00620-2","url":null,"abstract":"<h3>Abstract</h3> <p>Alopecia areata (AA) lifetime incidence is around 2%, with many patients first experiencing symptoms during childhood. However, ritlecitinib is the only FDA-approved treatment for pediatric patients 12 years and older. This review outlines reported topical, injectable, and oral treatment options for pediatric patients with AA. Clinical studies were obtained via a PubMed search using the following search terms: alopecia areata, areata, universalis, or totalis and medication, therapy, treatment, drug, or management. Only studies with pediatric patients were included in this review. Commonly used therapies, including corticosteroids, methotrexate, and minoxidil, newer promising medications, such as Janus kinase inhibitors, and less frequently used topical and systemic treatments are included. A summary of the drug development pipeline and ongoing interventional clinical trials with pediatric patients is provided. Treatments demonstrate variable efficacy, and many patients require combination therapy for maximal response. More robust clinical data is needed for many of the medications reviewed in order to provide better care for these patients.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":"96 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140097310","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":"Oral Ibuprofen for the Treatment of PDA in Preterm Neonates: Urgent Need for a Safer Alternative to Hyperosmolar Formulations.","authors":"Jaemaela Del Rosario, Gerhard Fusch, Ali McBryde, Katelyn Sushko, John van den Anker, Samira Samiee-Zafarghandy","doi":"10.1007/s40272-023-00617-3","DOIUrl":"10.1007/s40272-023-00617-3","url":null,"abstract":"","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"205-207"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570554","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 Voriconazole in Critically Ill Pediatric Patients: A Single-Center Retrospective Study.","authors":"Khalid W Taher, Razan Almofada, Sufyan Alomair, Ahmed A Albassam, Abdullah Alsultan","doi":"10.1007/s40272-023-00616-4","DOIUrl":"10.1007/s40272-023-00616-4","url":null,"abstract":"<p><strong>Background and objective: </strong>Voriconazole pharmacokinetics are highly variable in pediatric patients, and the optimal dosage has yet to be determined. The purpose of this study was to describe voriconazole pharmacokinetic and pharmacodynamic targets achieved and evaluate the efficacy and safety of voriconazole for critically ill pediatrics.</p><p><strong>Methods: </strong>This is a single-center retrospective study conducted at a pediatric intensive care unit at a tertiary/quaternary hospital. Pediatrics admitted to the pediatric intensive care unit and who received voriconazole for a proven or suspected fungal infection with at least one measured trough concentration were included. The primary outcomes included the percentage of pediatric patients who achieved the pharmacokinetic and pharmacodynamic targets. Secondary outcomes included assessing the correlation between voriconazole trough concentrations and clinical/microbiological outcomes. All statistical analyses were performed using the R statistical software and Microsoft Excel. Multiple logistic regression was used to assess the predictors of both clinical and microbiologic cures. Multiple linear regression was used to determine significant factors associated with trough concentrations.</p><p><strong>Results: </strong>A total of 129 voriconazole trough concentrations were measured from 71 participants at steady state after at least three doses of voriconazole. The mean (± standard deviation) of the first and second trough concentrations were 2.9 (4.2) and 2.3 (3.3) mg/L, respectively. Among the first trough concentrations, only 33.8% were within the therapeutic range (1-5 mg/L), 46.5% were below the therapeutic range, and 19.7% were above the therapeutic range. A clinical cure occurred in 78% of patients, while a microbiologic cure occurred in 80% of patients.</p><p><strong>Conclusions: </strong>Voriconazole trough concentrations vary widely in critically ill pediatric patients and only a third of the patients achieved therapeutic concentrations with initial doses.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"197-203"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478669","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":"Infections in Children Aged 6 Months to 5 Years Treated with Dupilumab in a Placebo-Controlled Clinical Trial of Moderate-to-Severe Atopic Dermatitis.","authors":"Amy S Paller, Elaine C Siegfried, Michael J Cork, Peter D Arkwright, Lawrence F Eichenfield, Michele Ramien, Faisal A Khokhar, Zhen Chen, Annie Zhang, Sonya L Cyr","doi":"10.1007/s40272-023-00611-9","DOIUrl":"10.1007/s40272-023-00611-9","url":null,"abstract":"<p><strong>Background: </strong>Patients with atopic dermatitis (AD), particularly infants and young children, are at greater risk of developing skin infections. In this study, we assessed infection rates in AD patients aged 6 months to 5 years treated with dupilumab.</p><p><strong>Methods: </strong>In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo, with concomitant low-potency topical corticosteroids, every 4 weeks for 16 weeks. Exposure-adjusted infection rates were used to compare treatment groups.</p><p><strong>Results: </strong>The analysis included 162 patients, of whom 83 received dupilumab and 79 received placebo. Total infection rates were not significantly different between the dupilumab and placebo groups (rate ratio [RR] 0.75, 95% CI 0.48-1.19; p = 0.223). Non-herpetic adjudicated skin infections and bacterial infections were significantly less frequent with dupilumab versus placebo (non-herpetic skin infections: RR 0.46, 95% CI 0.21-0.99; p = 0.047; bacterial infections: RR 0.09, 95% CI 0.01-0.67; p = 0.019), and the number of patients using systemic anti-infective medication was significantly lower in the dupilumab group (RR 0.52, 95% CI 0.30-0.89; p = 0.019). There were no significant differences in the number of herpetic infections between the dupilumab and placebo groups (RR 1.17, 95% CI 0.31-4.35; p = 0.817). The number of patients with two or more infection events was significantly higher in the placebo group (RR 0.29, 95% CI 0.12-0.68; p = 0.004), and no severe or serious infections (including eczema herpeticum) were observed among patients receiving dupilumab.</p><p><strong>Conclusions: </strong>These data suggest that dupilumab treatment in infants and children younger than 6 years with AD does not increase overall risk of infections and is associated with a reduced risk of bacterial and non-herpetic skin infections compared with placebo, resulting in a reduced need for anti-infective medication.</p><p><strong>Trial registration: </strong>The trial was registered with ClinicalTrials.gov with ID number NCT03346434 on November 17, 2017. INFOGRAPHIC.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"163-173"},"PeriodicalIF":3.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10890978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139547110","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}