Pediatric Drugs最新文献

{"title":"Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome in Children-From Pathogenesis to Treatment Strategies: A Comprehensive Review.","authors":"Federica Anselmi, Perrine Dusser, Isabelle Kone-Paut","doi":"10.1007/s40272-025-00699-1","DOIUrl":"https://doi.org/10.1007/s40272-025-00699-1","url":null,"abstract":"<p><p>Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most frequent periodic fever syndrome in non-Mediterranean children, usually manifesting before the age of 5 years. It is characterized by clockwork episodes of fever lasting 3-7 days, accompanied by aphthous stomatitis, pharyngitis, and/or cervical adenitis. Typically, patients with PFAPA are generally well between episodes and exhibit normal growth and development. Although PFAPA often resolves spontaneously, its recurrent nature can significantly impact quality of life, and symptoms may persist into adulthood. This narrative review aimed to consolidate current knowledge on PFAPA epidemiology, pathogenesis, clinical presentation, diagnostic considerations, and therapeutic options. A structured literature search was performed using PubMed, Cochrane Library, and Scopus, focusing on relevant articles specifically addressing PFAPA. Increasing evidence suggests multifactorial pathogenesis involving innate immune dysregulation, activation of the NLRP3 inflammasome, and Th1-driven inflammation. Genetic analysis studies suggest a polygenic inheritance of PFAPA, linking it to immune pathways shared with familial Mediterranean fever and Behçet's disease. Diagnosis remains clinical, though genetic testing may be warranted in specific cases. Management strategies vary owing to the absence of standardized guidelines. Oral corticosteroids are highly effective for acute episodes but may shorten the interval between flares. Among preventive therapies, colchicine appears to reduce attack frequency, although evidence of its efficacy is limited, while tonsillectomy is often considered curative but recommended for patients with refractory disease or when there is a concurrent otolaryngologic indication. Further research is needed to refine diagnostic criteria and optimize treatment strategies, ultimately improving patients' and caregivers' quality of life.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591959","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":"Levetiracetam Versus Fosphenytoin Infusions as Second-Line Treatment for Pediatric Status Epilepticus: A Multicenter Study Examining Effectiveness, Tolerability, and Ease of Use.","authors":"Armelle Hornard, François Severac, Vincent Laugel, Marie-Thérèse Abi Wardé, Claire Bansept, Yvan de Feraudy, Sandrine Haupt, Marie-Aude Spitz, Didier Eyer, Anne de Saint Martin, Sarah Baer","doi":"10.1007/s40272-025-00709-2","DOIUrl":"https://doi.org/10.1007/s40272-025-00709-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Status epilepticus is a life-threatening neurological emergency that requires rapid and effective treatment to prevent long-term complications or death. Traditionally, phenytoin and its prodrug fosphenytoin have been used as second-line therapies following benzodiazepines. However, intravenous levetiracetam has emerged as a promising alternative because of its favorable safety profile and ease of administration, particularly in pediatric populations. This study aimed to evaluate whether intravenous levetiracetam was non-inferior to intravenous fosphenytoin as a second-line treatment for managing pediatric status epilepticus.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;From November 2021 to May 2023, we implemented an updated local protocol that replaced fosphenytoin with levetiracetam as the second-line treatment for status epilepticus. Following this change, we conducted a 2-year multicenter study to evaluate its impact. For comparison, we also included patients treated under the previous protocol during the 2 years prior to the change, as a control group. An inverse probability of treatment weighting approach, based on the propensity score, was used to adjust for baseline characteristics between the two groups. Bayesian regression models were used to assess treatment effects in the weighted cohort. Treatment effectiveness was assessed using a composite measure of need for subsequent interventions, recurrence of status epilepticus within 24 h, seizure duration and length of hospital stay. We tested non-inferiority hypotheses for effectiveness criteria and if the probability of non-inferiority was greater than 95%, we also tested a superiority hypothesis. Safety was assessed by analyzing adverse events, mortality, admission to the intensive care unit, and transfer to the resuscitation unit. For safety criteria, only superiority was tested.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 127 patients with status epilepticus were evaluated during the study period; 84 patients in the fosphenytoin group (66%) and 43 patients in the levetiracetam group (34%). Of these, 52 patients had febrile status epilepticus (40.9%), 27 patients were treated with oral levetiracetam as part of their daily treatment regimen at the time of status epilepticus (21.3%), and 12 (9.4%) patients had been treated with levetiracetam during their lifetime but stopped at the time of status epilepticus. With intravenous levetiracetam, 62.8% of children were seizure free, compared with 37.2% of children taking fosphenytoin. The length of hospital stay was significantly shorter with levetiracetam than with fosphenytoin (reduction of 1.9 days with levetiracetam) and children were less likely to be admitted to the intensive care unit (reduction of 18.1% with levetiracetam). The need for third-line treatment or seizure recurrence was significantly lower in the levetiracetam group (16.3% reduction compared with fosphenytoin). Adverse effects and seizure du","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584537","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":"Effective Sirolimus Use in Prenatal and Postnatal Management of Symptomatic Extensive Congenital Capillary-Lymphatic-Venous Malformations (CLVMs): A Report of Two Cases.","authors":"Anna Klosowska, Malgorzata Styczewska, Malgorzata A Krawczyk, Lena Gluszkiewicz, Przemyslaw Adamski, Katarzyna Wartecka-Zielinska, Lukasz Matwiejczyk, Magda Rybak-Krzyszkowska, Daria Dziechcinska-Poletek, Anna Jankowska, Katarzyna Sinacka, Dariusz Wyrzykowski, Anna Taczanowska-Niemczuk, Anna Gabrych, Paulina Kielpinska, Natalia K Mazur-Ejankowska, Iwona Domzalska-Popadiuk, Magdalena Emilia Grzybowska, Dariusz G Wydra, Wojciech Gorecki, Ninela Irga-Jaworska, Ewa Bien","doi":"10.1007/s40272-025-00708-3","DOIUrl":"https://doi.org/10.1007/s40272-025-00708-3","url":null,"abstract":"<p><strong>Introduction: </strong>Congenital capillary-lymphatic-venous malformations (CLVMs) often result in life-threatening complications, which may begin in utero. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been successfully used in children and adults with CLVMs due to its antiproliferative and antiangiogenic properties. However, only two cases of prenatal sirolimus treatment of fetal CLVMs have been published to date, with very limited data on optimal therapeutic scheme and drug dosing.</p><p><strong>Case reports: </strong>Here we report two cases of effective prenatal and postnatal sirolimus treatment of extensive, complicated fetal CLVMs. The CLVMs were diagnosed prenatally by ultrasound and confirmed by magnetic resonance. The pregnancies were complicated with intralesional bleeding in both cases and polyhydramnios in one. The pregnant women received oral sirolimus from the 32nd and 33rd weeks of gestation to delivery (for 11 and 31 days, respectively). The dose of oral sirolimus for the pregnant women ranged from 2 to 6 mg/day, with a target trough whole-blood level of 7-12 ng/mL, which resulted in the umbilical cord arterial blood levels of 3.8 and 6.4 ng/mL, respectively. Therapeutic effects of prenatal sirolimus were observed in both fetuses: one experienced reduced intralesional bleeding, while the other had a significant decrease in CLVM size. The sirolimus treatment has been continued postnatally in both children, currently aged 20 and 9 months. The mothers and children experienced no adverse events from the treatment.</p><p><strong>Conclusions: </strong>Administration of sirolimus during pregnancy with maternal blood drug-level monitoring seems to be an efficient and safe treatment option that should be considered in high-risk fetal CLVMs.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567730","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":"Physiologically Based Pharmacokinetic Modeling-Based Evaluation of Current Carbamazepine and Valproic Acid Dosing Guidelines for Pediatric Epilepsy Treatment.","authors":"Joyce E M van der Heijden, Violette Gijsen, Anne M van Uden, Marika de Hoop-Sommen, Jolien J M Freriksen, Elke Jacobs, Rick Greupink, Saskia N de Wildt","doi":"10.1007/s40272-025-00707-4","DOIUrl":"https://doi.org/10.1007/s40272-025-00707-4","url":null,"abstract":"<p><strong>Background: </strong>Carbamazepine and valproic acid (VPA) are long-standing treatments for epilepsy in children. Interestingly, they display unique drug disposition characteristics, and maturation of drug metabolizing enzymes further complicates personalized dosing. Physiologically based pharmacokinetic (PBPK) modeling includes these mechanisms so is a promising tool to optimize dosing. Our aim was to better support pediatric drug dosing of carbamazepine and VPA.</p><p><strong>Methods: </strong>All carbamazepine and VPA dosing simulations were conducted with Simcyp, using available carbamazepine and VPA compound models linked with adult and pediatric population models. To verify model adequacy, adult and pediatric pharmacokinetic data were retrieved from the literature to compare predicted carbamazepine and VPA concentrations with observed data. Current Dutch national dosing strategies were then simulated to evaluate their appropriateness to achieve therapeutic levels. Where doses could be optimized, alternative dosing strategies were proposed based on simulations. In addition, the effect of altered albumin levels in children on VPA was explored through simulations under conditions of +20%, average, - 20%, and - 35% age normalized reference albumin levels.</p><p><strong>Results: </strong>Therapeutic levels of carbamazepine and VPA will be reached after 1 or 2 weeks of treatment with the current dosing strategies. Simulations suggest a carbamazepine starting dose of 10 mg/kg/day for neonates rather than 7 mg/kg/day. In addition, children aged 12-18 years may receive a higher starting dose (e.g., 400 mg/day instead of 200 mg/day) to reach therapeutic levels more quickly. For VPA, mean total VPA concentrations dropped below the therapeutic target with reduced albumin levels (i.e., - 20% and - 35%), whereas unbound levels remained within the therapeutic window.</p><p><strong>Conclusion: </strong>Our PBPK simulations support the current pediatric drug dosing recommendations of carbamazepine and VPA. In patients with hypoalbuminemia and when higher VPA doses are needed (i.e., ≥ 30 mg/kg/day), routine determination of unbound VPA concentrations is advised to monitor free VPA concentrations. We demonstrate that PBPK modeling is a valuable tool to confirm and further optimize dosing recommendations in children. PBPK modeling provides valuable comprehensive evidence for guiding clinical practice and potentially informing pediatric drug labeling.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554103","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":"Learning-Based Models for Predicting IVIG Resistance and Coronary Artery Lesions in Kawasaki Disease: A Review of Technical Aspects and Study Features.","authors":"Danilo Mirata, Anna Chiara Tiezzi, Lorenzo Buffoni, Ilaria Pagnini, Ilaria Maccora, Edoardo Marrani, Maria Vincenza Mastrolia, Gabriele Simonini, Teresa Giani","doi":"10.1007/s40272-025-00693-7","DOIUrl":"10.1007/s40272-025-00693-7","url":null,"abstract":"<p><p>Kawasaki disease (KD) is a common pediatric vasculitis, with coronary artery lesions (CALs) representing its most severe complication. Early identification of high-risk patients, including those with disease resistant to first-line treatments, is essential to guide personalized therapeutic approaches. Given the limited reliability of current scoring systems, there has been growing interest in the development of new prognostic models based on machine learning algorithms and artificial intelligence (AI). AI has the potential to revolutionize the management of KD by improving patient stratification and supporting more targeted treatment strategies. This narrative review examines recent applications of AI in stratifying patients with KD, with a particular focus on the ability of models to predict intravenous immunoglobulin resistance and the risk of CALs. We analyzed studies published between January 2019 and April 2024 that incorporated AI-based predictive models. In total, 21 papers met the inclusion criteria and were subject to technical and statistical review; 90% of these were conducted in patients from Asian hospitals. Most of the studies (18/21; 85.7%) were retrospective, and two-thirds included fewer than 1000 patients. Significant heterogeneity in study design and parameter selection was observed across the studies. Resistance to intravenous immunoglobulin emerged as a key factor in AI-based models for predicting CALs. Only five models demonstrated a sensitivity > 80%, and four studies provided access to the underlying algorithms and datasets. Challenges such as small sample sizes, class imbalance, and the need for multicenter validation currently limit the clinical applicability of machine-learning-based predictive models. The effectiveness of AI models is heavily influenced by the quantity and quality of data, labeling accuracy, and the completeness of the training datasets. Additionally, issues such as noise and missing data can negatively affect model performance and generalizability. These limitations highlight the need for rigorous validation and open access to model code to ensure transparency and reproducibility. Collaboration and data sharing will be essential for refining AI algorithms, improving patient stratification, and optimizing treatment strategies.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"465-479"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780868","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":"Diagnosis and Oral Sirolimus Treatment of Fibro-Adipose Vascular Anomaly in Pediatric Patients: A Case Series and Comprehensive Review.","authors":"Rui He, Jie Yin, Nan Zhang, Yanni Wang, Yun Peng, Bin Zhang","doi":"10.1007/s40272-025-00686-6","DOIUrl":"10.1007/s40272-025-00686-6","url":null,"abstract":"<p><strong>Background: </strong>Fibro-adipose vascular anomaly (FAVA) is a rare and complex vascular malformation that, to date, has hardly been studied, especially in children. The diagnosis and management of FAVA is complicated, and no treatment guidelines have yet been published.</p><p><strong>Objectives: </strong>This study aimed to analyze the clinical manifestations and diagnostic and genetic evidence of FAVA and to explore safe and effective treatment with sirolimus in pediatric patients.</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical manifestations and examination data of 18 pediatric patients with FAVA who presented at the Vascular Anomaly Center from September 2019 to February 2023 and summarized the basis on which a diagnosis of FAVA was made. A genetic examination was completed in five cases. A total of 12 cases were treated with oral sirolimus. We analyzed changes in skin lesions before and after treatment and recorded the occurrence of adverse reactions.</p><p><strong>Results: </strong>Of the 18 patients, 15 were girls and 3 were boys. Most lesions (15 cases) were in the lower extremities, accompanied by varying degrees of chronic pain, functional impairment, contractures, and other functional disorders. Imaging findings can be divided into three categories: focal, focal infiltrative, and diffuse. Histopathological manifestations were malformed vascular fibro-adipose tissue. A genetic examination of five cases identified a PIK3CA somatic mutation. After oral sirolimus treatment, pain and dysfunction associated with the lesions were significantly improved, the lesion volume dramatically diminished, and no obvious adverse reactions occurred.</p><p><strong>Conclusions: </strong>With the help of imaging, and histopathological and somatic genetic examinations, FAVA can be promptly diagnosed and treated to avoid serious dysfunction. The efficacy and safety of oral sirolimus in the treatment of FAVA deserves further study.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"417-426"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582346","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":"Ceftazidime/Avibactam for the Treatment of Infections in Children: A Case Series of Real-World Use.","authors":"Almudena Castro-Frontiñán, Luis Manuel Prieto-Tato, Jose Manuel Caro-Teller, Cristina Epalza, Álvaro González-Gómez, Serena Villaverde, Adriana Shan-Núñez, Esther Viedma, Jose Miguel Ferrari-Piquero","doi":"10.1007/s40272-025-00685-7","DOIUrl":"10.1007/s40272-025-00685-7","url":null,"abstract":"<p><p>Ceftazidime/avibactam (CAZ/AVI) is effective against a wide range of carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas. The European Medicines Agency (EMA) approved its use in children from 3 months of age for urinary tract (UTI) and intra-abdominal infections (IAI). Published data in children are limited. We performed a review of existing literature on the use of CAZ/AVI in children. Our search identified a phase I dose-exploratory trial, two registrational phase II clinical trials and nine real-world case series. The efficacy, adverse effects and pharmacokinetics of CAZ/AVI in children were summarized. We also describe the experience of the use of CAZ/AVI in a tertiary hospital in Madrid, Spain. Up to March 2023, 22 episodes of treatment with CAZ/AVI were recorded in 14 patients (50% female, with a median age of 4 years [interquartile range (IQR) 3.5-9]). UTI, bacteraemia or sepsis were the most common clinical conditions for which CAZ/AVI was prescribed. CAZ/AVI was started as targeted therapy in 10 paediatric patients and as empirical therapy in 12 (54.5%) children. The treatment indication was reviewed and adapted according to microbiological results by a paediatric infectious diseases team. Effectiveness of CAZ/AVI was adequate, and there were no discontinuations in any case because of adverse effects.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"427-438"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524114","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":"Cardioprotective Effect of Nigella sativa in Pediatric Patients with Type 1 Diabetes Mellitus: A Randomized Controlled Study.","authors":"Dalia El-Afify, Doaa El Amrousy","doi":"10.1007/s40272-025-00687-5","DOIUrl":"10.1007/s40272-025-00687-5","url":null,"abstract":"<p><strong>Background and objective: </strong>Nigella sativa is a widely used medicinal plant with several potential therapeutic uses. This study aimed to investigate the possible beneficial cardioprotective effect of Nigella sativa in pediatric patients with type 1 diabetes mellitus.</p><p><strong>Methods: </strong>Sixty children and adolescents with type 1 diabetes were randomized into two groups: group I (n = 30) who received Nigella sativa seed oil 450 mg twice daily after meals for 3 months in addition to insulin, and group II (n = 30) who received insulin alone. Echocardiographic examinations were performed before and after the treatment. The lipid profile, malondialdehyde, nitric oxide, tumor necrosis factor-α, transforming growth factor-β, and troponin I were also measured before and after Nigella sativa treatment.</p><p><strong>Results: </strong>After 3 months of Nigella sativa administration, group I had significantly lower cholesterol and low-density lipoprotein-cholesterol, malondialdehyde, nitric oxide, tumor necrosis factor-α, transforming growth factor-β, and troponin I levels compared with their pretreatment levels and compared with group II. In addition, group I had a significantly higher left ventricular E'/A' ratio and two-dimensional left ventricular global longitudinal strain (2D-LV GLS) compared with baseline values and compared with group II after treatment.</p><p><strong>Conclusions: </strong>Nigella sativa can improve subclinical left ventricular dysfunction in pediatric patients with type 1 diabetes mellitus.</p><p><strong>Clinical trial registration: </strong>this clinical trial was registered at www.pactr.org with ID: PACTR202302478939306.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"481-489"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567885","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":"Risks and Benefits of Pharmacological Treatment for Pediatric Chronic Non-cancer Pain: When Safety Evidence Lags Behind Prescription Pads.","authors":"Dominique Dundaru-Bandi, Kacper Niburski, Rebecca Pitt, Nada Mohamed, Victor Hugo Gonzalez Cardenas, Lisa M Einhorn, Pablo Ingelmo","doi":"10.1007/s40272-025-00698-2","DOIUrl":"10.1007/s40272-025-00698-2","url":null,"abstract":"<p><p>The evidence to support the efficacy and safety of pharmacological treatments for chronic non-cancer pain in children is limited. In practice, clinicians are often required to establish therapeutic plans using data extrapolated from adult studies, which may not apply to younger patients. Recent systematic reviews and meta-analyses indicate minimal evidence of benefit for these treatments in children; however, the low quality of studies included in these reviews complicates the conclusions that can be derived from them. In this article, we focus on safety, an outcome as critical as efficacy in clinical trial design but often designated as secondary or even exploratory. Specifically, we examine methods for assessing adverse events in clinical research and propose a practical approach for evaluating these events in everyday practice. Additionally, we outline our strategy to conduct a risk-benefit analysis at the individual patient level, highlighting the importance of using a composite risk-benefit metric rather than assessing these outcomes separately. This approach enables real-time monitoring of both drug-related symptom relief and adverse effects, facilitating clinically meaningful risk-benefit discussions with patients and their families. Finally, we advocate for improvements in clinical trial design for pediatric chronic pain treatments, particularly around adverse events. Future trials should incorporate standardized definitions, comprehensive risk-benefit evaluations, and transparent outcome reporting. Implementing these changes may enhance decision-making by balancing the safety and the effectiveness of pharmacological treatments for children and adolescents with chronic pain.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"405-415"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017133","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":"Risk Factors for Nephrotoxicity Among Neonates Receiving Vancomycin: A Systematic Review and Meta-analysis.","authors":"Yuan Gao, Tong Wu, Libin Pu, Mengjie Wang, Chang Wang, Yinyin Guo, Wen Qiu","doi":"10.1007/s40272-025-00690-w","DOIUrl":"10.1007/s40272-025-00690-w","url":null,"abstract":"<p><strong>Background: </strong>Nephrotoxicity may increase the risk of neonatal mortality. Early identification of risk factors for nephrotoxicity is essential to improve clinical outcomes. This study aimed to determine the risk factors for nephrotoxicity in neonates receiving vancomycin to promote the safe use of vancomycin.</p><p><strong>Methods: </strong>We searched international and Chinese databases from 1990 to 24 March 2024 for studies involving neonates receiving vancomycin and reporting their nephrotoxic outcomes. Effects were estimated with 95% confidence intervals (CIs), odds ratios (ORs), and standardized mean differences. We evaluated the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.</p><p><strong>Results: </strong>In total, the study included 12 retrospective cohort studies involving 2079 neonates. In neonates receiving vancomycin, the incidence of nephrotoxicity varied from 2.7 to 20.0%. Moderate-quality evidence indicated that furosemide (OR 5.80; 95% CI 2.98-11.28), amphotericin B (OR 2.75; 95% CI 1.23-6.12), patent ductus arteriosus (OR 5.93; 95% CI 2.80-12.55), and necrotizing enterocolitis (OR 4.49; 95% CI 2.12-9.49) were risk factors for nephrotoxicity in neonates receiving vancomycin. Low-quality evidence suggested that vasoactive agents (OR 9.23; 95% CI 1.06-80.62) were risk factors. Subgroup analysis with moderate-quality evidence identified a steady-state vancomycin trough concentration > 20 mg·L^-1 (OR 6.87; 95% CI 3.81-12.39) as a risk factor. Very low-quality evidence indicated that aminoglycosides (OR 0.29; 95% CI 0.13-0.62) were not risk factors.</p><p><strong>Conclusions: </strong>This study reveals the nephrotoxic risk factors for neonates receiving vancomycin, which could help in the implementation of measures to prevent further renal impairment.</p><p><strong>Prospero registration number: </strong>CRD42024564584.</p>","PeriodicalId":19955,"journal":{"name":"Pediatric Drugs","volume":" ","pages":"439-448"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042001","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}