Agents In Pediatric Patients Research Articles

The Relationship Between Early Exposure to General Anesthesia and Neurobehavioral Deficits.

In contemporary medical practice, general anesthesia plays an essential role in pediatric surgical procedures. While modern anesthetic protocols have demonstrated safety and efficacy across various pathological conditions, concerns persist regarding the potential neurotoxic effects associated with early exposure to general anesthesia. Current research primarily examines the neurocognitive developmental impacts, with limited focus on neurobehavioral developmental disorders. This review presents a comprehensive analysis of clinical trial results related to five critical neurobehavioral developmental disorders: fine motor disability, attention-deficit-hyperactivity disorder (ADHD), impulse control disorders (ICDs), autism spectrum disorder (ASD), and developmental coordination disorder (DCD). Furthermore, the review synthesizes insights from basic research on the potential toxicological mechanisms of general anesthetic agents that could influence clinical neurobehavioral changes. These findings provide valuable guidance for the prudent and safe utilization of anesthetic agents in pediatric patients.

Early Cognitive Function after Deep Sedation Using Different Anesthetic Agents in Pediatric Patients: A Prospective, Randomized Controlled Trial.

Background and Objectives: The impact of anesthetic agents on memory and cognitive function following general anesthesia is of great interest, particularly regarding their effects on the developing pediatric brain. While numerous studies have examined the relationship between anesthetic drugs and brain function, research focusing on early cognitive function following sedation remains limited. Materials and Methods: This study was a prospective, randomized controlled trial involving 148 pediatric patients scheduled for hematological procedures, specifically bone marrow aspiration (BMA) and intrathecal chemotherapy (ITC). Patients were divided into two groups based on the primary anesthetic used: the inhalational sedation group (IHG), in which sevoflurane was used, and the intravenous sedation group (IVG), which received propofol infusion. Apart from the main anesthetic agent, all sedation methods were consistent across both groups. A cognitive function test administered before sedation involved memorizing four distinct images, each associated with a different number. Then, the patients were asked to identify the omitted image upon awakening in the recovery room. Herein, this pre- vs. post-sedation test is called the early recognition assessment (ERA) tool. The primary outcome was the correct response rate after sedation for the two groups. Secondary outcomes included the sedation score, the behavior response score, and the correct response rates according to the number of sedation procedures. Results: This study included 130 patients in the final analysis, with 74 originally assigned to each group. The initial cognitive assessment revealed no significant difference in performance between the anesthetic agents. In addition, no differences were observed in the rates of correct responses or post-sedation scores after repeated procedures. However, the IVG demonstrated higher behavior response scores compared to the IHG. Conclusions: There were no significant differences in the rates of correct responses using the ERA tool between the two groups, irrespective of the number of sedation procedures performed. While some differences were noted in preoperative, intraoperative, and post-anesthesia care, these did not significantly impact the cognitive outcomes measured.

21-plex PCR and Antifungal Susceptibility Aspects of Fungemia Agents in Pediatric Patients with Hematological Malignancies: A Single-Center Experience

Background: Fungemia is a life-threatening infection which requires an early diagnosis and use of appropriate antifungal agents to be treated effectively. Objectives: Here, we describe the clinical-epidemiological characteristics as well as the antifungal susceptibility patterns of fungal agents in pediatric patients with malignancy. Methods: Two hundred and five blood samples were cultured to detect infection. The infectious agents were identified by phenotypic methods and 21-plex PCR. Antifungal susceptibility testing was performed using an E-test and disc diffusion test based on CLSI standard M27-A3 protocol. The demographic data of the studied population were extracted and analyzed. Results: In total, 36 out of 205 patients (17.6%) were positive for fungemia. 32 (88.9%) and 4 (11.1%) cases were found to be caused by Candida and Rhodotorula species, respectively. The patient's age ranged from 1 to 14 years. The majority of the patients were males (28; 77.8%) and were hospitalized for more than seven days (33; 91.7%). Non-Candida albicans species were the most common agents of fungemia (27 patients; 75%), with C. parapsilosis (77.8 %) as the dominant agent. Fever, central venous catheters, and broad-spectrum antibiotic therapy were observed in all cases. Itraconazole resistance was observed in a species of C. orthopsilosis. While the Candida isolates were susceptible to fluconazole, C. parapsilosis showed a significant rate of resistance to caspofungin, followed by itraconazole and amphotericin B. Overall, no mortality was reported among the fungemia cases. Conclusions: This study identified acute lymphoblastic leukemia (ALL) as a hematologic malignancy associated with fungemia. The increase of non-C. albicans species, including C. parapsilosis, along with reduced susceptibility to antifungal drugs, maybe a warning sign in pediatric patients with malignancies. Furthermore, fluconazole was the most effective antifungal agent against the recovered isolates. Therefore, the best strategy for the management of fungemia is to increase knowledge based on local epidemiological and mycological characteristics.

From the kitchen to the medicine cabinet: Examples of functional herbs and spices.

In many cultures, "food as medicine" has existed for centuries as the foundation of health. It is a practice built on the knowledge that food and diet play important roles in disease prevention and management. Foods possessing therapeutic properties are often referred to as functional foods. Many herbs and spices contain numerous nutritional and non-nutritional components that can interact with pharmacologically relevant receptors, either directly or indirectly via their metabolites, to regulate cellular biochemical processes. Although opinions are changing, the concept of food as a therapeutic intervention goes against conventional Western medicine. To provide guidance to clinicians interested in using these products, members of the Food as Medicine working group of the Nutrition Committee NASPGHAN, as part of a two-part review series, have identified frequently used foods, supplements, herbs, and spices that are utilized for therapeutic intent and have created summaries of commonly used indications, doses, and caveats. In this review, the focus is the use of select herbs and spices for medicinal purposes. Gaps in our knowledge in how to effectively use these agents in pediatric patients are discussed. Evidence supporting their use for management of gastrointestinal conditions, especially in the pediatric population, is provided when available. Circumstances in clinical settings and patient indications may require actions different from those recommended in this review and professional judgment should prevail.

Anticoagulation in Pediatric Patients

The use of antithrombotic agents is increasing in infants, children and adolescents. The more recent routine inclusion of children in FDA-monitored clinical trials has propelled the rapid accumulation of safety and efficacy data on these agents in pediatric patients. Antithrombotic agents in current use include indirect or antithrombin-dependent anticoagulants, intravenous direct thrombin inhibitors, direct oral anticoagulants (DOACs) targeting thrombin or factor Xa, antiplatelet agents and thrombolytic therapies. Each class of antithrombotic agent has distinct mechanisms of action, clearance routes, half-lives, safety and dosing. Anticoagulant efficacy is dependent upon the specific clinical indication and stability of the pediatric patient. Duration of anticoagulant course is also dependent upon the clinical indication as well as rate of thrombus resolution. This manuscript reviews the mechanism of action, route of administration, route of clearance and plasma half-life for the antithrombotic agents in current use in children. Use of anticoagulation in the context of thrombolytic therapy is discussed.

Long-term, Low-Dose Oral Azithromycin Treatment for Chronic Severe Bilateral Blepharokeratoconjunctivitis in Pediatric Patients.

To evaluate the efficacy and safety of oral azithromycin treatment combined with topical antibiotic and anti-inflammatory agents in pediatric patients with chronic severe bilateral blepharokeratoconjunctivitis. Patients younger than 14 years with chronic and severe bilateral blepharokeratoconjunctivitis were reviewed retrospectively. Consecutive patients receiving oral azithromycin treatment were included. All patients received oral azithromycin (5 mg/kg/single dose daily) for at least 4 weeks combined with topical antibiotic and anti-inflammatory agents. Before and after the treatment, clinical symptoms were noted, and corneal and conjunctival fluorescein staining and corneal neovascularization were graded. Meibomian gland secretion and meibomian gland plugging were also assessed. All patients completed at least 3 months of follow-up after completion of the oral azithromycin treatment. Patients' clinical data at the time of diagnosis and last follow-up visit were statistically compared. Twenty-nine children (58 eyes, mean age of 6.51 years) were included. The mean time of oral azithromycin use was 5.87 weeks (range: 4 to 10 weeks). Clinical symptoms and signs and visual acuity were significantly improved after treatment. The mean fluorescein staining and corneal neovascularization grades and meibomian gland secretion and meibomian gland plugging scores also improved after treatment (P < .001). Eyelid distortion or fornix shortening was not observed. At the last follow-up visit, all patients were stable with treatment only with daily eyelid hygiene, topical cyclosporine, and artificial tears. Long-term, low-dose oral azithromycin combined with topical antibiotic and anti-inflammatory agents is an effective treatment option for pediatric patients with chronic severe bilateral blepharokeratoconjunctivitis. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Oral Dexmedetomidine Achieves Superior Effects in Mitigating Emergence Agitation and Demonstrates Comparable Sedative Effects to Oral Midazolam for Pediatric Premedication: A Systematic Review and Meta-Analysis of Randomized Controlled Studies.

Background: Oral midazolam is the most commonly used sedative premedication agent in pediatric patients. While effective, oral midazolam cannot reduce the incidence of emergence agitation. Oral dexmedetomidine may be effective in providing satisfactory sedation and reduce the incidence of emergence agitation, although the results of different randomized controlled trials are conflicting. Methods: This study enrolled randomized controlled trials (RCTs) examining premedication with oral dexmedetomidine versus oral midazolam in pediatric patients undergoing general anesthesia. PubMed, the Cochrane Library, Embase, and the Web of Science database were searched from their inception until June 2023. The outcomes were the incidence of satisfactory preoperative sedation, satisfactory sedation during separation from parents, satisfactory sedation during anesthesia induction using an anesthesia mask, and the incidence of emergence agitation. Results: A total of 9 RCTs comprising 885 patients were analyzed. Our data revealed comparable effects of dexmedetomidine and midazolam with respect to satisfactory preoperative sedation and a satisfactory incidence of sedation during parental separation and mask acceptance before anesthesia induction. Notably, our data revealed that the rate of emergence agitation was significantly lower in pediatric patients receiving dexmedetomidine (n = 162) than in those receiving midazolam (n = 159) (odds ratio = 0.16; 95% confidence interval: 0.06 to 0.44; p < 0.001; I2 = 35%). Conclusions: Data from this meta-analysis revealed comparable effects for premedication with oral dexmedetomidine or oral midazolam with respect to satisfactory sedation; furthermore, premedication with oral dexmedetomidine more effectively mitigated emergence agitation in pediatric patients receiving general anesthesia compared with oral midazolam.

Oral analgesic for musculoskeletal injuries in children: A systematic review and network meta-analysis.

Pain in pediatric musculoskeletal (MSK) injuries can lead to increased anxiety, fear, and avoidance of medical care, making analgesic management critical. Therefore, we evaluated analgesic efficacy and adverse effects to select the optimal analgesic agent in pediatric patients with MSK injuries. Four databases were searched from inception to March 2023 for peer-reviewed, open randomized controlled trials (RCTs). Inclusion criteria were: (1) trials with RCT design, (2) children aged 1 month-18 years with MSK injury, (3) outpatient setting, (4) interventions and control, (5) primary outcome of pain score at 60 and 120 min and secondary outcome of adverse effects, and (6) full-text and peer-reviewed articles. Two reviewers screened, extracted data, and assessed the risk of bias. A frequentist random-effects network meta-analysis (NMA) was performed. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation working group approach. We included eight trials comprising 1645 children. Ibuprofen was significantly associated with pain reduction at 120 min, compared with acetaminophen (SMD 0.31 [95% CI 0.11-0.51]; moderate certainty) and opioids (SMD 0.34 [95% CI 0.20-0.48]; moderate certainty). Compared with opioids alone, ibuprofen-opioid combination was significantly associated with pain reduction at 120 min (SMD 0.19 [95% CI 0.03-0.35]). No significant differences were found in pain interventions at 60 min. Ibuprofen had statistically fewer adverse events than opioids (RR, 0.54 [95% CI 0.33-0.90]; moderate certainty) and ibuprofen with opioids (RR 0.47 [95% CI 0.25-0.89]; moderate certainty). In terms of limitations, the eight RCTs included had relatively small sample sizes; only two were high-quality RCTs. Our NMA found ibuprofen to be the most effective and least adverse analgesic in pediatric patients with MSK injuries.

Pharmacological Targeting of Interferon-Related DNA Damage Resistant Signature (IRDS) and XRCC4-Mediated DNA Repair Pathways ss a Novel Therapeutic Approach to DIPG Radio-Sensitization

Despite significant efforts to improve the outcomes of pediatric diffuse midline gliomas, such as diffuse intrinsic pontine glioma (DIPG), prognosis remains dismal with a 5-year survival of <1%. The standard of care treatment for DIPG is fractionated radiation, but the disease inevitably progresses in 6 months or less. There is a significant unmet need to improve the clinical outcomes for pediatric DIPG patients. Approximately 70-80% of DIPG tumors contain mutations in TP53 tumor suppressor protein. These TP53 mutations are associated with resistance to radiation treatments in DIPG patients. The mechanisms of increased radio-resistance of p53-mutant DIPG are poorly understood. The objective of this study was to identify novel pharmacological agents that would augment radiation sensitivity of p53 mutant DIPG cell lines, and to establish their molecular mechanism of action. SF8628 pediatric DIPG cell line harboring p53 mutation was obtained from MilliporeSigma. CellRad benchtop X-ray irradiator (Precision X-Ray) was used for radiation sensitization experiments. Vi-CELL BLU cell viability analyzer was used for high-throughput screening of small molecule compound libraries with and without radiation treatments. Proteomics Core facility was utilized for mass spec analysis of protein targets of Compound-X. To identify novel drug candidates that would sensitize DIPG to therapeutic radiation, we carried out an unbiased screen of curated libraries of small molecules with diverse scaffolds in p53 mutant DIPG cells. This radio-sensitization screen yielded a single molecule, Compound-X, that was found to have profound growth-inhibitory and radiation-sensitizing effects in DIPG cells. Compound-X was found to induce a robust cell cycle arrest of DIPG cells in G2/M, the most radio-sensitive phase of the cell cycle. Furthermore, Compound-X elicited a massive apoptotic cell death of DIPG cells. An unbiased RNA sequencing approach revealed that Compound-X inhibits expression of the Interferon-related DNA damage Resistant Signature (IRDS), a sub-group of interferon-stimulated genes (ISGs) known to promote radiation and chemotherapy resistance in high-grade gliomas. To identify the target of Compound-X, we carried out affinity purification of Compound-X associated complexes from p53 mutant DIPG cell lysates. Mass spectrometry analysis of Compound-X-purified protein complexes identified XRCC4 as a protein that uniquely associated with Compound-X. RNAi knock-down experiments revealed that XRCC4 is required for cytotoxic effects of Compound-X. Importantly, Compound-X-mediated XRCC4 targeting caused a delay in DNA DSBs repair after radiation treatment. An unbiased screen of small molecule drug candidates identified a novel XRCC4-targeting agent, Compound-X, as potent radiation sensitizer in p53 mutant DIPG cells. This work may lead to clinical trials investigating novel XRCC4-targeting agent in pediatric patients with DIPG.

Utilization of volumetric absorptive microsampling and dried plasma spot for quantification of anti-fungal triazole agents in pediatric patients by using liquid chromatography-tandem mass spectrometry

BackgroundRecently, increasing attention has been paid to the use of microsampling techniques for therapeutic drug monitoring (TDM) in neonatal and pediatric populations. Volumetric Absorptive Microsampling (VAMS) has been introduced in the market under the name Mitra® (Neoteryx). These devices consist of porous absorbent tips that allow collection of fixed blood volumes (10–30 µL) to overcome the DBS-related hematocrit effect. Here, the authors analyzed the concentrations of triazole agents (voriconazole, posaconazole, and isavuconazole) in VAMS and dried plasma spot (DPS) samples. MethodsFifty whole blood samples were obtained from pediatric patients subjected to systemic anti-fungal therapy. VAMS were collected by dipping the tip into whole blood before centrifugation for plasma recovery. Then, 30 µL of plasma was carefully spotted on filter paper to obtain DPS. Anti-fungal concentrations were measured using a validated LC-MS/MS kit (MassTox® Antimycotic Drugs/EXTENDED) provided by Chromsystems (Chromsystems Instruments & Chemicals). Drug concentrations in VAMS and DPS samples were compared to those in fresh plasma using Passing-Bablok and Bland-Altman tests. ResultsPlasma concentrations of voriconazole, posaconazole, and isavuconazole were positively and significantly correlated with those obtained in VAMS and DPS samples (Spearman r range, 0.82–0.94, p < 0.001). Data were further analyzed using the Bland-Altman test, which showed a % mean difference compared to fresh plasma of −15.06–10.98 (range). The stability of both VAMS and DPS was ensured for at least 14 d at room temperature. ConclusionsThese results demonstrate that VAMS and DPS can be used for the TDM of anti-fungal agents. Owing to their stability, both sampling devices can be easily stored and shipped, without the need for refrigeration, to TDM laboratories that facilitate remote TDM applications. Finally, VAMS could be particularly suitable for pediatric and neonatal patients because they allow the collection of a few microliters of blood, thus improving ethical and compliance limitations.

Infliximab vs adalimumab: Points to consider when selecting anti-tumor necrosis factor agents in pediatric patients with Crohn's disease.

Biologic agents with various mechanisms against Crohn's disease (CD) have been released and are widely used in clinical practice. However, two anti-tumor necrosis factor (TNF) agents, infliximab (IFX) and adalimumab (ADL), are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently. Therefore, in pediatric CD, the choice of biologic agents should be made more carefully to achieve the therapeutic goal. There are currently no head-to-head trials of biologic agents in pediatric or adult CD. There is a lack of accumulated data for pediatric CD, which requires the extrapolation of adult data for the positioning of biologics in pediatric CD. From a pharmacokinetic point of view, IFX is more advantageous than ADL when the inflammatory burden is high, and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase. Additionally, we reviewed the safety profile, immunogenicity, preference, and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD. Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents. In addition, factors such as the efficacy of induction and maintenance of remission, safety profile, immunogenicity, patient preference, and compliance play an important role in evaluating and selecting treatment options.

The Effect of Leflunomide as Adjunctive Therapy With a TNF Inhibitor in Pediatric Patients With Uveitis.

To describe the effectiveness of leflunomide as adjunctive therapy with anti-tumor necrosis factor (anti-TNF) agents in pediatric patients with uveitis who are not able to tolerate methotrexate. A retrospective case series was performed of pediatric patients who were receiving leflunomide in conjunction with anti-TNF agent therapy after intolerance to a combination of methotrexate with anti-TNF therapy. Dose and duration of methotrexate, leflunomide, and anti-TNF therapy were recorded. Extensive history, demographics, laboratory data, and uveitis flare rate were obtained. A total of five children were included in the study. Most patients were initially receiving methotrexate and an anti-TNF agent was added subsequently due to inadequate response to monotherapy. After discontinuation of methotrexate, leflunomide was initiated with anti-TNF therapy. The replacement of methotrexate with leflunomide showed decreased side effects and was associated with lower flare rates and steroid-free remission. Leflunomide was found to be well tolerated and effective at maintaining uveitis quiescence in conjunction with anti-TNF agents in pediatric patients who do not tolerate methotrexate. [J Pediatr Ophthalmol Strabismus. 2023;60(6):417-420.].

Salmonella gastroenteritis in children: six-year experience in İstanbul, Turkey.

The aim of this study was to evaluate the demographic and clinical characteristics and treatment outcomes of children with Salmonella gastroenteritis. We retrospectively reviewed the medical records of pediatric patients aged between 1 month and 18 years with the diagnosis of Salmonella gastroenteritis between May 2015 and December 2021. A total of 172 children diagnosed with Salmonella gastroenteritis, including 113 outpatients and 59 hospitalized children, were included in this study. There were 95 (55.2%) males and 77 (44.8%) females with a median age of 59.5 months (interquartile range [IQR]: 33.5-96 months, min-max: 1-205 months). The most common clinical symptoms were diarrhea (n = 166, 96.5%), fever (n = 113, 65.7%) and abdominal pain (n = 73, 42.4%). Bloody diarrhea was seen in 19.2% of patients. Fifty (29.1%) of the Salmonella species could not be typed. Serogroup D (n = 106, 61.6%) was the predominant serogroup isolated from stool cultures, followed by serogroup B (n = 16, 9.3%). 62.2% of the isolates were susceptible to ampicillin, 97.7% to ciprofloxacin, 98.8% to trimethoprim-sulfamethoxazole, and 98.8% to ceftriaxone. Fever, vomiting, and underlying disease occurred more frequently in hospitalized patients than in outpatients (p: 0.005, p: 0.000, p: 0.000, respectively). C-reactive protein value was found to be higher in hospitalized patients (p: 0.000). Salmonella should be considered as a causative agent in pediatric patients with abdominal pain, fever, and bloody-mucous diarrhea, and patients with severe clinical conditions should be hospitalized and antibiotic therapy initiated if indicated.

Patterns of Direct Oral Anticoagulant Use in Pediatric Patients: Results from a Multicenter National Database

Introduction: The first direct oral anticoagulant (DOAC) agents were approved for pediatric use in 2021. These have quickly gained favor over traditional anticoagulants among many hematologists and patients due to oral availability, favorable risk profile, and elimination of the need for frequent lab monitoring. This study aims to evaluate trends in DOAC use among pediatric patients with new venous thrombotic events (VTE) and patient-level and hospital-level factors associated with their selection. Methods: This retrospective study used data from the Pediatric Health Information System (PHIS), an administrative database of >50 US children's hospitals. We included initial inpatient encounters from 2014-2021 for pediatric patients (age <18). The visit required an ICD9 or ICD10 code for an acute thrombotic event and medication charge for one of the following anticoagulation agents: dabigatran, edoxaban, rivaroxaban, apixaban, betrixaban, low molecular weight heparin (LMWH), or warfarin. We included only the first encounter for each patient which met these criteria. We compared characteristics of patients who received DOACs to those who did not through descriptive and statistical analysis, and utilized multivariate regression to evaluate factors associated with DOAC selection. Results: In 20,432 cases of new VTE, DOACs were administered in 733 encounters (3.59%). Rivaroxaban was the most administered (71.9% of DOAC use), followed by apixaban. DOAC use increased over time, it was prescribed in 0.24% of the encounters in 2014 up to 11.4% of the encounters in 2021. DOACs were first only administered to grade school age children (5-12 years) in 2016 and then moved to younger groups in 2019. Patients who received DOAC agents had a greater median age (16 vs 4 years, p<0.001), were more commonly female (51.7% vs 46.7%, p=0.008), had greater median income ($60,428 vs $55,089, p<0.001), and were more likely to carry private insurance (47.1% vs 40.6%, p=0.002). Geographic variation was also observed, with midwest hospitals prescribing DOACs more often than in the south and west (5.5% vs 2.8%). Patients who received DOACs during their admission had a shorter median duration of hospitalization, lower hospitalization costs, and were less likely to have a complex chronic condition (all comparisons were statistically significant). DOACs were most prescribed in cases of pulmonary embolism (8.2% of encounters carrying ICD code for pulmonary embolism). On multivariate regression analysis including age, gender, race, ethnicity, insurance payor, income, and geographic region, only age, income and geographic region remained statistically significant predictors of DOAC use (p<0.05). Conclusion: This abstract describes the increase in DOAC usage over time. The decision to prescribe a DOAC agent appears to be affected by patient age, medical co-morbidities and income. The data presented suggests the presence of prescription trends that may not be based on clinical evidence. A better understanding of the safety and efficacy of DOAC agents in pediatric patients and education of pediatric hematology providers is necessary. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Systematic review and meta-analysis comparing the efficacy of dexmedetomidine to midazolam as premedication and a sedative agent in pediatric patients undergoing dental procedures.

Pediatric dental surgeries are associated with the emotions of fear, anxiety, and other behavioral disturbances of children that need to be managed. Sedation using drugs like dexmedetomidine (DEX) and midazolam (MID) is a common pharmacological behavior managing technique. We conducted this meta-analysis to evaluate the efficacy of both these drugs in current literature. A thorough literature search was conducted on PubMed, MEDLINE, Google Scholar, and Cochrane's database for randomized studies that compared sedative efficacy of dexmedetomidine with midazolam in children of 0-15 years of age undergoing dental surgeries. Sedation in children during dental procedure, when used as a premedication, at the time of separation from parents and at the time of mask induction, onset time, duration of anesthesia, and surgery were evaluated. The mean differences (MDs), odds ratio (OR), and their 95% confidence intervals (CIs) were calculated both for continuous and dichotomous outcome data using random-effects model. Seven studies met out inclusion criteria and were analyzed. Results of premedication with DEX was associated with more anxiolysis (OR=0.29, 95% CI: 0.17-0.52, p=0.0001; I2=0%) and at the time of separation from parents (OR=0.36, 95% CI: 0.19-0.69, p=0.002; I2=52%) in comparison to MID. No significant differences in results were seen at mask induction (OR=0.63, 95% CI: 0.34-1.18, p=0.15; I2=47%) and for sedation in children during dental procedures (OR=0.52, 95% CI: 0.07-3.70, p=0.51; I2=72%). Also, there were no significant differences in onset time, duration of anesthesia, and surgery between the two agents. DEX proved to be a better premedicant than MID for pediatric patients. No significant difference in efficacy of both sedative agents was observed in children undergoing dental treatment. More clinical trials need to be conducted to see its efficacy in dental surgeries in children of standardized ages and with standard doses.

Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis

BackgroundA recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions.MethodsPubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences.ResultsData from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups.ConclusionConsidering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.

Inotuzumab ozogamicin as single agent in pediatric patients with relapsed and refractory acute lymphoblastic leukemia: results from a phase II trial

Inotuzumab Ozogamicin is a CD22-directed antibody conjugated to calicheamicin, approved in adults with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (BCP-ALL). Patients aged 1–18 years, with R/R CD22 + BCP-ALL were treated at the RP2D of 1.8 mg/m2. Using a single-stage design, with an overall response rate (ORR) ≤ 30% defined as not promissing and ORR > 55% as expected, 25 patients needed to be recruited to achieve 80% power at 0.05 significance level. Thirty-two patients were enrolled, 28 were treated, 27 were evaluable for response. The estimated ORR was 81.5% (95%CI: 61.9–93.7%), and 81.8% (18/22) of the responding subjects were minimal residual disease (MRD) negative. The study met its primary endpoint. Median follow up of survivors was 16 months (IQR: 14.49–20.07). One year Event Free Survival was 36.7% (95% CI: 22.2–60.4%), and Overall Survival was 55.1% (95% CI: 39.1−77.7%). Eighteen patients received consolidation (with HSCT and/or CAR T-cells therapy). Sinusoidal obstructive syndrome (SOS) occurred in seven patients. MRD negativity seemed correlated to calicheamicin sensitivity in vitro, but not to CD22 surface expression, saturation, or internalization. InO was effective in this population. The most relevant risk was the occurrence of SOS, particularly when InO treatment was followed by HSCT.

Remifentanil requirement for acceptable intubation conditions with two different doses of ketamine without a neuromuscular blocking agent in pediatric patients.

The optimal remifentanil concentration for improving intubation conditions when intubation is performed without neuromuscular blocking agents (NMBAs) but with ketamine as an induction agent remains unknown. Here, we aimed to identify the effective bolus doses of remifentanil required to achieve acceptable intubation conditions upon anesthesia induction with 1 or 2 mg/kg ketamine without NMBAs. In this prospective, double-blinded, randomized up-down sequential allocation study, we enrolled pediatric patients aged 3-12 years undergoing general anesthesia for inguinal hernia surgery. The patients were randomly allocated to one of two groups to receive either ketamine 1.0 mg/kg (K1 group) or 2.0 mg/kg (K2 group) intravenously until seven success-failure pairs were achieved. The remifentanil dose for each patient was determined using the modified Dixon's up-and-down method with an initial dose of 2.5 μg/kg and a step size of 0.5 μg/kg. In total, 51 patients (22 in the K1 group and 29 in the K2 group) were enrolled. The effective dose (ED)50s of remifentanil for obtaining clinically acceptable intubation conditions under anesthesia induction with ketamine but without NMBAs was 3.2 μg/kg in the K1 group and 1.6 μg/kg in the K2 group. High-dose remifentanil with 1 mg/kg ketamine was associated with more severe chest wall rigidity and lower mean blood pressure and heart rate than was low-dose remifentanil with 2 mg/kg ketamine. The ED50 of remifentanil required for clinically acceptable intubation conditions with anesthesia induction using 1 mg/kg ketamine without NMBAs in pediatric patients was twice that when using 2 mg/kg ketamine. The combination of 2 mg/kg ketamine and remifentanil was better at preventing chest wall rigidity.

Application of Biological Agents in Pediatric Patients with Inflammatory Bowel Disease – Data From a Large Multicenter Registry Study

Application of Biological Agents in Pediatric Patients with Inflammatory Bowel Disease – Data From a Large Multicenter Registry Study

Efficacy of nitrous oxide-oxygen inhalation versus oral midazolam-promethazine as sedative agents in pediatric patients: a comparative study

Background Managing difficult and uncooperative pediatric dental patients is a challenging task. Conscious sedation has been propagated as a pharmacological means for handling such situations.Objective To evaluate the effects of sedation using nitrous oxide-oxygen inhalation versus oral midazolam-promethazine in pediatric patients.Patients and methods A total of 100 pediatric patients were selected and divided into two equal categories: group 1 (midazolam-promethazine) and group 2 (N2O-O2). Ethical committee approval was obtained, and patients were assessed. Data collected were analyzed using an unpaired t test.Results Duration of sedation was found to be statistically significant, and a higher duration was found for group 1. No significant differences were noted in the behavior rating scale with either of the combinations and in pulse oximeter readings.Conclusion Midazolam/promethazine is better in inducing longer sedation than N2O/O2.