Pediatric Patient Safety Research Articles

Thrombopoietin Receptor Agonists for Thrombocytopenia in Pediatric Hematologic Malignancies.

Thrombopoietin receptor agonists (TPO-RAs) have demonstrated efficacy in treating clinically significant thrombocytopenia, including chemotherapy-induced thrombocytopenia in adults. However, data regarding their safety and efficacy in pediatric, adolescents, and young adult (AYA) patients with hematologic malignancies are limited. We retrospectively identified 15 pediatric and AYA patients aged 25 years or younger with hematologic malignancies treated with a TPO-RA at UCSF Benioff Children's Hospitals between 2015 and 2023. Platelet counts and transfusion requirements were compared before and after TPO-RA therapy. The median age at TPO-RA initiation was 16 years (range: 7-25 years). Nine patients (60%) had a history of bleeding or comorbidity that predisposed to severe bleeding risk. Eleven patients received romiplostim and four patients received eltrombopag. The median platelet count significantly increased from 24×109/L at baseline to 54×109/L after 3 weeks of any TPO-RA therapy (p = 0.029). Monthly platelet transfusion requirements significantly decreased from a median of 15 to two units after TPO-RA therapy (p = 0.007). Fourteen of the 15 patients (93%) achieved a sustained platelet count >50,000/µL within 8 weeks, with a median time to response of 3 weeks. No TPO-RA-related adverse events were observed. TPO-RAs were effective in managing refractory thrombocytopenia in pediatric and young adult patients being treated for hematologic malignancies, with a favorable safety profile, even among patients with multiple comorbidities. These findings warrant further investigation through prospective clinical trials to confirm efficacy and establish clinical guidelines for this population.

Impact of Intravenous Busulfan Pharmacokinetics on Safety in Pediatric Patients who have undergone Hematopoietic Stem Cell Transplant

Impact of Intravenous Busulfan Pharmacokinetics on Safety in Pediatric Patients who have undergone Hematopoietic Stem Cell Transplant

Inequities in Inpatient Pediatric Patient Safety Events by Category.

Few studies have analyzed potential inequities in both pediatric patient safety events (PSEs) and adverse events (AEs) - PSEs leading to harm - nor in PSEs by event type. We sought to examine potential inequities in rates of pediatric PSEs overall, by severity, and by category based on race and ethnicity, insurance payor, and language as measured using voluntary incident reports (IRs). We conducted a retrospective cohort study of pediatric hospitalizations between January 19, 2012 through December 31, 2019 at a US urban, tertiary care children's hospital. Analyzing 85 458 hospitalizations, we compared PSEs overall, by severity, and by event category by race and ethnicity, insurance payor, and language using incident rate ratios (IRRs). In models controlling for covariates, we found that hospitalizations of Latinx (IRR 1.17, 95% confidence interval [CI] 1.07-1.29), non-Latinx Black/African American (IRR 1.17, 95% CI 1.01-1.34), publicly insured (IRR 1.10, 95% CI 1.02-1.20), and nonprivately/nonpublicly insured (IRR 1.12, 95% CI 1.02-1.23) children had higher rates of PSEs compared with reference groups, but the association between language and PSEs was not significant. There were similar patterns among AEs, although only the association between hospitalizations of Latinx patients and AEs was significant. Medication, fluid, or blood and lines or tubes PSEs drove many inequities. We found inequities in PSEs as recorded by IRs, suggesting differences in care related to race, ethnicity, and payor. Limitations include analysis of a single center, that event categories are unique to the institution analyzed, and the voluntary nature of IRs.

Belimumab safety in adult and paediatric Chinese patients with systemic lupus erythematosus: A Phase 4, multicentre, observational study.

Although belimumab has been widely used in patients with systemic lupus erythematosus (SLE) globally, real-world safety data among Chinese patients are limited, particularly for children. This study assessed the safety and tolerability of belimumab in adult and paediatric patients with SLE in China in real-world clinical practice. This Phase 4, multicentre, prospective, observational study enrolled patients prescribed intravenous belimumab by their physicians in tertiary hospitals, independent of a clinical study, during routine clinical visits between May 2021 and May 2022. Patients could have been receiving belimumab prior to enrolment. The primary objective was to describe the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs) and AEs of special interest (AESIs) over the 24-week follow-up period. Data were collected at enrolment and approximately 4, 12 and 24weeks post-enrolment, during routine clinical visits. AEs, ADRs and SAEs were collected as independent events. The safety population comprised patients who received ≥1 dose of belimumab and completed ≥1 follow-up visit. Overall, 417 patients were included in the analysis (safety population); 89.2% were female and mean (standard deviation) age was 35.5 (11.9) years. AEs were reported in 158 patients (37.9%) and were mostly mild (79.1%). The most common AEs were upper respiratory tract infections (n = 19, 4.6%) and hypokalaemia (n = 18, 4.3%; all mild). Among 22 patients (5.3%) with SAEs, four patients (1.0%) had drug-related SAEs (pneumonia, respiratory tract infection, gingivitis and decreased white blood cell and neutrophil count). ADRs were experienced by 25 patients (6.0%), most commonly urinary tract infections (n = 5, 1.2%). There were no fatal SAEs. AESIs occurred in 14 patients (3.4%), including infections of interest (n = 5, 1.2% all herpes zoster), serious selected psychiatric events (n = 3, 0.7%) and infusion-related systemic and anaphylactic reactions (n = 7, 1.7%). Of 14 paediatric patients enrolled, six experienced AEs, zero ADRs, two SAEs and one AESI. Belimumab was generally well tolerated in adult and paediatric patients with SLE in this real-world setting in China, with no new safety signals identified. Future assessment of long-term belimumab safety in China beyond 24weeks will extend this current body of evidence.

Therapeutic drug monitoring of posaconazole delayed-release tablets and injections in pediatric patients.

This study aimed to investigate the dose and trough concentration (Cmin) of posaconazole delayed-release tablets and injections, and their correlation with efficacy and safety in pediatric patients. Patients younger than 18 years old received posaconazole delayed-release tablets or injections for prophylaxis or treatment of invasive fungal disease (IFD). Blood samples were collected to determine the plasma Cmins, and dose regimen adjustments were made if necessary. Clinical data were collected. A total of 210 Cmins of 113 pediatric patients were detected. The median Cmins were 1.0 and 1.3 mg/L for tablets and injections, respectively (P < 0.05). The median doses required to achieve the target Cmin were about 6.0 mg/kg of body weight/day, and no statistical difference was observed between different age groups, formulations, or indications (P > 0.05). Concomitant treatment of tacrolimus and diarrhea were found to affect Cmins of tablets, while age, gender, and BMI were found to be correlated with Cmins of injections. IFD breakthrough occurred in 9.2% of patients with a median Cmins of 0.74 mg/L for prophylaxis, and infection progression occurred in 43.2% of patients with a median Cmins of 0.97 mg/L for treatment, respectively. Transaminitis was the most common adverse event. Posaconazole delayed-release tablets and injections are safe for prophylaxis and treatment of IFD in pediatric patients. An empirical initial dose of 6.0 mg/kg of body weight/day is appropriate for prophylaxis, while a higher dose should be required for the treatment of IFD. It is necessary to adjust the dose regimen according to the results of therapeutic drug monitoring.This study is registered with chictr.gov.cn under identifier ChiCTR2300070008.

The influencing factors of pediatric nurses' perception of patient safety culture and partnership with patients' parents on patient safety nursing activities in South Korea: a descriptive study.

This study aimed to identify the effects of pediatric nurses' perception of patient safety culture and their partnership with patients' parents on pediatric patient safety nursing activities. This descriptive study was conducted over a two-month period, from October to November 2022, utilizing self-reported questionnaires. The study included 165 nurses, each having at least 6 months of working experience in wards where children were admitted. These nurses were selected from 13 pediatric specialty hospitals, general hospitals, and university hospitals across seven regions. The data analysis was performed using the SPSS/WIN 26.0 program (IBM Corp.) for descriptive statistics, t-test, One-way ANOVA, Scheffé test, Pearson correlation coefficients, and multiple regression analysis. The average scores for awareness of patient safety culture, partnership with patients' parents, and pediatric patient safety nursing activities were 3.37±0.41, 3.94±0.41, and 4.50±0.38, out of 5 points respectively. The factors influencing pediatric patient safety nursing activities were identified as a partnership with patients' parents (β=.41, p<.001). Among hospital-related characteristics, safety management committee (β=.16, p=.029) and safety management regulations (β=.17, p=.016) were also analyzed as factors influencing patient safety nursing activities. These factors accounted for 29.2% of the explanatory power for pediatric patient safety nursing activities. Based on the above study results, we found that to promote safe nursing activities for pediatric patients, developing and implementing training programs that enhance partnerships with patient's parents was imperative, and establishing work regulations and a safety management committee to systematically manage safety management tasks was deemed important.

Agomelatine in pediatric patients with moderate to severe major depressive disorder: an open-label extension study.

Major depressive disorder (MDD) in young people is a common psychiatric disorder, but treatment options are limited. Agomelatine has demonstrated short-term efficacy and safety in pediatric patients. We report here the results of a 92-week open-label extension (OLE). The international, multicenter, double-blind, study randomized 400 patients (80 children, 320 adolescents) with moderate-to-severe MDD to one of four treatment groups: agomelatine 10mg (n = 102), agomelatine 25mg (n = 95), placebo (n = 103), and fluoxetine 10-20mg (n = 100). After 12weeks, patients who could benefit from treatment continuation were offered entry into an optional OLE during which they received agomelatine 10 or 25mg for a further 92weeks. A total of 339 patients (271 adolescents) entered the OLE. Treatment groups considered for the OLE analysis reflected those received in the double-blind and OLE periods: agomelatine (10 or 25mg) in both (ago/ago, n = 170); placebo then agomelatine 10-25mg (pcb/ago, n = 85); or fluoxetine then agomelatine 10-25mg (fluox/ago, n = 84). Mean age (± SD) at entry into the double-blind phase (Week 0) was 13.6 ± 2.7years and 61.9% were female. Mean changes in Children's Depression Rating Scale revised (CDRS-R) raw total score from Week 12 to last post-Week 12 value in the three groups were - 16.3 ± 12.2 (ago/ago), - 18.9 ± 16.1 (pcb/ago), and - 16.1 ± 15.5 (fluox/ago), reflecting the difference in efficacy between treatments during the double-blind period, and heterogeneity at W12 between the treatment groups. Adverse events considered related to treatment occurred in 14.5% of patients: 15.3% ago/ago, 16.5% pcb/ago, and 10.7% fluox/ago. Three patients (all adolescents) experienced treatment-related severe adverse events: two treated with ago/ago and one treated with pcb/ago. Among the adolescents, one treatment-related severe adverse event in a patient in the pcb/ago group led to study withdrawal. Agomelatine was associated with continuous improvement in depressive symptoms without unexpected safety signals. These findings support the safe use of agomelatine in a pediatric population with moderate-to-severe MDD for up to 104weeks.Trial registration No: EUDRACT No. 2015-002181-23.

CT-scan-guided-irrigated trans-catheter ablation of epicardial accessory pathways in the coronary sinus: safety and feasibility in pediatric patients.

The most common site of epicardial APs is posterior-septal, and ablation from the coronary sinus (CS) or its main tributaries is needed. However, particularly in children, it can carry a considerable risk of complications, such as coronary artery (CA) injury, CS damage, and perforation. This study aims to assess the efficacy and safety of computed tomography (CT)-scan-guided-irrigated trans-catheter (TC) ablation of epicardial APs through the CS in children. Twenty-four children (19 males; mean age 13.8 ± 2.6) with posterior-septal and left posterior epicardial APs who underwent an endocavitary electrophysiological study (EPS) and TC ablation from the CS were enrolled in this study. All patients underwent a CT scan to visualize the CS and its branches and their proximity to the CAs before the ablation. Clinical, electrophysiological and follow-up data were collected. Acute success rate was 87.5% (21 out of 24 procedures). No complications occurred. In 16 (66.7%) patients, the ablation site was detected at the proximal CS, in two (8.3%) patients in the mid-proximal CS and in six (25%) in the middle cardiac vein (MCV). Ablation was achieved using an irrigated radiofrequency (RF) catheter in all patients and without the use of fluoroscopy in 20 patients (83.3%). Over a median follow-up of 15.1months (IQR 2.5-32.3), no recurrences or complications occurred. Epicardial posterior-septal and left posterior APs, in the area of CS or MCV, can be definitively eliminated in most children using CT-scan-guided electro-anatomical mapping and transvenous irrigated RF ablation.

Intermittent micafungin dosing schedule in pediatric oncology patients ‐ safe for outpatient parenteral antimicrobial therapy?

IntroductionAntifungal prophylaxis is an important preventative strategy for high-risk pediatric oncology patients. When triazoles are contraindicated, micafungin is an alternative to polyenes, due to improved tolerability and limited drug-drug interactions. An intermittent dosing schedule is advantageous for outpatient parenteral antimicrobial therapy (OPAT), but studies assessing safety in pediatric patients are limited. MethodsThis single-centre, retrospective, observational study compared the safety and tolerability of daily (1 mg/kg) and intermittent (3 mg/kg) dosing of amphotericin B liposomal (AmB) and micafungin in children under 18 years, with high-risk leukemia. ResultsOf 51 patients, with 76 individual dosing schedules, hepatoxicity and nephrotoxicity were comparable across all four dosing schedules. Severity of hypokalemia was significantly higher amongst patients receiving AmB (p = 0.041), with higher rates of intravenous electrolyte supplementation required. Infusion-related reactions occurred only in the AmB group (22 %). Intermittent administration and dosing of micafungin was well tolerated, with similar effects on liver function and reduced rates of hypokalemia. ConclusionThis study supports the positive safety profile of intermittent micafungin compared with AmB and describes successful OPAT implementation. Prospective studies assessing efficacy are needed to validate these findings.

Parents' perceptions of patient safety in paediatric hospital care-A mixed-methods systematic review.

To identify and summarize evidence on paediatric patient safety in a hospital setting from parents' point of view. A mixed-methods systematic review. ID number CRD42023453626. PubMed, Scopus, ScienceDirect, the Cochrane Library and the Wiley database were searched in July 2023. Two researchers independently applied eligibility criteria, selected studies and conducted a quality appraisal. Data-based convergent synthesis and thematic content analysis were employed. Twelve studies were included: eight qualitative research studies, two cross-sectional studies, one non-randomized experimental study and one mixed-methods study. The results were grouped into two themes-parental perceptions of inclusion in paediatric patient safety and parental perceptions of exclusion from paediatric patient safety-and comprised seven main subthemes: comfort in communication, parental engagement, communication difficulties, withdrawal from activity, uncertainty about available information and threats to patient safety. Parents are willing to be engaged in care but require support from healthcare professionals, as they are often anxious about the condition of their children and actions they believe might be helpful. They need to be treated as valuable partners and be engaged in communication and decision processes. The development and implementation of interventions involving parents in ensuring the safety of hospitalized paediatric patients should be of the utmost priority to healthcare organizations, as the common theme throughout the included studies was the need for improved communication with and recognition of parents as allies. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist was followed. No Patient or Public Contribution.

LARINGOESPASMO EM CRIANÇAS DURANTE PROCEDIMENTOS SOB ANESTESIA

Introduction: Laryngospasm can result in partial or complete loss of the patient’s airway. It is an anesthetic emergency caused by an exacerbated reflex that can occur with the closure of the vocal cords, accompanied by the descent of the epiglottis over the laryngeal orifice, and which is still responsible for significant morbidity and mortality in pediatric patients. It is most common in children under two years of age. The management of laryngospasm consists of its prevention, recognition, treatment and post-anesthetic care. Objective: To identify recent approaches to laryngospasm in children during anesthetic procedures in the literature. Methodology: This is a literature review, highlighting laryngospasm in children undergoing anesthetic procedures. Final considerations: Laryngospasm in children during anesthesia is a critical situation. Effective management is important with rapid and appropriate interventions to restore airway patency and ensure adequate oxygenation of the child, avoiding complications. The anesthesiologist must pay attention to the risk factors involved, and an in-depth understanding of these aspects is crucial for doctors, who, together with the surgical team, can guarantee the safety and well-being of pediatric patients during anesthetic procedures.

Hospital and Patient Characteristics Associated with Neonatal Blood Stream Infection in Inpatient Care: Insights from the 2019 HCUP KID Database.

This study explores the associations between pediatric adverse events (PAEs) and both hospital and patient characteristics within the inpatient hospital setting, specifically focusing on Neonatal Blood Stream Infection (NBSI) as defined by pediatric quality indicators (PDIs) from the Agency for Healthcare Research and Quality (AHRQ). This research aims to answer questions regarding the relationship between hospital characteristics and patient demographics with the occurrence of NBSI. This study utilized discharge data from the Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Databases (KID) for the year 2019. Bivariate and multivariate logistic regression models were employed to analyze patient-level encounters of NBSIs. The analysis examined various factors including hospital size, location, and teaching status, as well as patient-specific variables such as gender, age, race, service lines, payment sources, and major operating room procedures. The results indicate that Public and Private not-for-profit hospitals showed significantly lower odds of experiencing NBSIs when compared to Private investor-owned hospitals, as did smaller, rural, and nonteaching hospitals when compared to large hospitals. Additionally, individual factors such as gender, age, race, service lines, payment sources, and types of major operating room procedures were found to have varying levels of significance in relation to NBSI. This study provides important insights into PAEs within the inpatient hospital setting, particularly focusing on NBSIs within the PDI framework. The findings highlight critical areas for the development of evidence-based interventions and guidelines, which are essential for clinicians and policymakers. Ultimately, this study contributes to the understanding and improvement of pediatric patient safety by emphasizing the necessity for targeted strategies to mitigate the risk of NBSI.

The Ventilatory Changes of Pediatric Peroral Endoscopic Myotomy Patients.

Peroral endoscopic myotomy (POEM) has proven to be a successful treatment method for achalasia in both adult and pediatric patients. Yet, there is a lack of evidence for anaesthetic management of pediatric patients who underwent POEM procedure. In this study, we aim to present perioperative and postoperative management strategies for pediatric patients with achalasia from in anaesthesia aspect. Medical records were reviewed for 16 pediatric patients at a single center who underwent POEM procedure for achalasia between 2017 and 2020. Patients' data regarding demographics, preoperative diet, body mass index, perioperative monitoring and vitals, airway management, anaesthesia maintenance, mechanical ventilation settings duration of recovery, length of stay, pain management and adverse events were evaluated. The study cohort included 7 female and 9 male patients with a mean age of 5.5 years. Anaesthesia maintenance was provided with 0.8-1.2 minimum alveolar concentration sevoflurane in a 40-60% O2-air mixture, Remifentanil infusion and bolus doses of Rocuronium. The median age was 3 years for patients ventilated in pressure controlled ventilation mode and 10 years in volume controlled ventilation mode. Respiration rate and minute ventilation were adjusted to maintain end tidal carbon dioxide (ETCO2) below 45 mmHg. Needle decompression was applied for 14 patients (87.5%) for treatment of capnoperitoneum. The mean procedure duration and recovery room duration were 66 (±22.9) minutes and 62 (±21) minutes, respectively. Postoperative pain management is provided with paracetamol and tramadol in total 8 patients (50%). There was no adverse event during postoperative period and all patients discharged in a mean time of 3 days. POEM has demonstrated encouraging outcomes in terms of safety and effectiveness in pediatric patients. Due to challenging nature of the pediatric patients, it is important to acknowledge that the procedure requires specialized anaesthesia management. Management of perioperative complications of increased ETCO2 requires understanding the physiologic results of pneumo-mediastinum and pneumo-peritoneum. Beside the known anaesthetic management strategies, a tailored approach should be adopted for each patient. Further investigations should be conducted to develop standardized management.

Dupilumab for the treatment of alopecia areata in pediatric patients with atopic dermatitis: A scoping review.

Our study aims to synthesize existing evidence of dupilumab for alopecia areata (AA) in pediatric patients with atopic dermatitis (AD). We searched MEDLINE and Embase on March 1, 2024, using keywords related to AD, AA, dupilumab, and pediatric patient populations per PRISMA-ScR guidelines. A mean SALT score reduction of 42.6 following dupilumab treatment (p < .01) over an average of 3.21 months, and a mean reduction of Investigator Global Assessment (IGA) levels of 2.14 units (p < .01) demonstrates the efficacy of dupilumab in pediatric AA when there is concurrent AD. Our findings in combination with dupilumab's favorable safety profile in pediatric AD makes it an appealing option for AA treatment, however, a greater understanding of the underlying mechanisms, optimal pediatric patient selection criteria, long-term efficacy, and safety profile of dupilumab in this context is warranted.

Nusinersen effectiveness and safety in pediatric patients with 5q-spinal muscular atrophy: a multi-center disease registry in China

ObjectiveTo evaluate the effectiveness and safety of nusinersen for the treatment of 5q-spinal muscular atrophy (SMA) among Chinese pediatric patients.MethodsUsing a longitudinal, multi-center registry, both prospective and retrospective data were collected from pediatric patients with 5q-SMA receiving nusinersen treatment across 18 centers in China. All patients fulfilling the eligibility criteria were included consecutively. Motor function outcomes were assessed post-treatment by SMA type. Safety profile was evaluated among patients starting nusinersen treatment post-enrollment. Descriptive analyses were used to report baseline characteristics, effectiveness, and safety results.ResultsAs of March 2nd, 2023, 385 patients were included. Most patients demonstrated improvements or stability in motor function across all SMA types. Type II patients demonstrated mean changes [95% confidence interval (CI)] of 4.4 (3.4–5.4) and 4.1 (2.8–5.4) in Hammersmith Functional Motor Scale-Expanded (HFMSE), and 2.4 (1.7–3.1) and 2.3 (1.2–3.4) in Revised Upper Limb Module (RULM) scores at months 6 and 10. Type III patients exhibited mean changes (95% CI) of 3.9 (2.5–5.3) and 4.3 (2.6–6.0) in HFMSE, and 2.1 (1.2–3.0) and 1.5 (0.0–3.0) in RULM scores at months 6 and 10. Of the 132 patients, 62.9% experienced adverse events (AEs). Two patients experienced mild AEs (aseptic meningitis and myalgia) considered to be related to nusinersen by the investigator, with no sequelae.ConclusionsThese data underscore the significance of nusinersen in Chinese pediatric patients with SMA regarding motor function improvement or stability, and support recommendations on nusinersen treatment by Chinese SMA guidelines and continuous coverage of nusinersen by basic medical insurance.

Exposure-Response and Subgroup Analyses to Support Body Weight-Based Dosing of Brentuximab Vedotin in Children and Young Adults with Newly Diagnosed High-risk Classical Hodgkin Lymphoma.

The purpose of the study was to evaluate the relationships between brentuximab vedotin (BV) pharmacokinetics, age, and body weight (BW) with efficacy and safety in pediatric and young adult patients with previously untreated, high-risk classical Hodgkin lymphoma in the phase III AHOD1331 study. Overall, 296 patients (age 2-21 years) in the overall population were randomized to and received BV + chemotherapy; the pharmacokinetic subpopulation comprised 24 patients (age <13 years). Age- and/or BW-based (pharmacokinetic surrogates) subgroup analyses of efficacy and safety were conducted for the overall population. Exposure-response analyses were limited to the pharmacokinetic subpopulation. There were no visible trends in disease characteristics across pediatric age subgroups, whereas BW increased with age. Observed antibody-drug conjugate exposures in patients ages <12 years were lower than those in adults administered BV 1.8 mg/kg every 3 weeks, as exposure increased with BW. Nevertheless, no detrimental impact on event-free survival was seen in younger subgroups: 3-year event-free survival rates were 96.2% (2-<12 years) and 92.0% (12-<18 years), with no events observed in those ages <6 years. Neither early response nor lack of need for radiation therapy was associated with high pharmacokinetic exposure. No evidence of exposure-driven grade ≥2 or ≥3 peripheral neuropathy or grade ≥3 neutropenia was seen in exposure-safety and BW-based subgroup analyses; the incidence of these safety events was comparable across pediatric age subgroups, despite lower exposure in younger children. No further adjustments based on age or BW are required for the BV dosage (1.8 mg/kg every 3 weeks) approved in children.

Enhance the management of perioperative crisis events, improve the safety and quality of pediatric anesthesia

Perioperative crisis events refer to unexpected seriously life-threatening when the patient is during or after surgery, and require rapid identification, evaluation, and management by clinical teams to minimize harm. The pediatric anesthesia management during perioperative period is special and challenging for anesthesiologists, requiring professional technical and non-technical skills. The article mainly elaborates on the incidence and risk factors of pediatric anesthesia crisis events during perioperative period and introduces the concept of anesthesia crisis resource management and strategies. The anesthesiologist team needs to adopt a crisis resource management strategy, taking a typical crisis event of malignant hyperthermia as an example, including identification of crisis signs immediately, termination of trigger drugs rapidly, intravenous injection of the special drug dantrolene, physical cooling, and symptomatic support treatment, seeking assistance from other teams actively, recording and feeding back. This study aims to improve the cognitive decision-making ability and teamwork ability of anesthesiologists and their teams, effectively preventing and responding to potential crisis events effectively, and ensuring the safety of pediatric patients during perioperative period.

Phase I trial of chidamide, an oral HDAC inhibitor, in combination with oral etoposide in patients with refractory/recurrent neuroblastoma.

10034 Background: Chidamide, an oral subtype-selective histone deacetylase (HDAC) inhibitor, has been shown to be effective in adult patients with hematological tumors. However, there is no data on its safety and efficacy in pediatric cancer patients. Combination of HDAC inhibitors and etoposide have shown synergistic anti-tumor effects in preclinical studies of neuroblastoma. We conducted a phase I trial in pediatric patients with recurrent or refractory neuroblastoma to determine the maximum tolerable dose (MTD) of chidamide combined with oral etoposide treatment. Methods: Daily oral etoposide 35 mg/m2/dose was administered on days 1–21 in combination with escalating doses of chidamide (14 and 17 mg/m2/d) twice weekly in each 28-day cycle using the standard 3 + 3 design. Patients with response or stable disease after two cycles would maintain treatment until disease progression or unacceptable toxicity occurred. Chidamide pharmacokinetic testing was performed. Results: 31 patients were enrolled in this study. The median age was 7 years (range 3 – 18). 14 patients were included in the dose escalation phase (Ia), 17 patients in the expansion cohort (Ib). The MTD of chidamide was 14 mg/m2/d, with dose limiting neutropenia and thrombocytopenia observed at 17 mg/m2/d. Median number of cycles completed was 2.5 (range 1–11). A total of 19 patients (61.3%) experienced treatment-related grade 3/4 hematologic toxicity, and no grade 3/4 non-hematological toxicity was observed. No objective responses were seen. Conclusions: In children with refractory/recurrent neuroblastoma, chidamide is well-tolerated at 14 mg/m2/d twice weekly when combining with oral etoposide 35 mg/m2/d daily. Prolonged disease stability achieved in patients with minimal residual diseases deserves further investigation. Clinical trial information: NCT05338541 .

Patient-focused programable release indomethacin tablets prepared via conjugation of hot melt extrusion (HME) and fused depositional modeling (FDM) -3D printing technologies

Indomethacin (IND) eases the chronic pain caused by Juvenile idiopathic arthritis (JIA) in clinic, but it was reported that it has dose-related side effects such as gastrointestinal irritations and potential damage to nervous system. So, there is a considerable demand for offering effective, safety, and quality IND dosages for individual pediatric and youth patients. The main aim of this work is to on-demand manufacture personalized and programmable release IND tablets via combining hot melt extrusion (HME) and 3D printing technologies based on the structure-release correlations. IND loaded filaments were extruded and then the tablets were designed and printed. A series of physical and chemical characterization studies were also conducted, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), hot stage polarized light microscopy (PLM), texture analysis, and in vitro drug release studies. The results showed that IND was dispersed in HPMCAS matrix and formed amorphous solid dispersions (ASDs). Additionally, the in vitro drug release studies demonstrated that the release of IND can be programmed via manipulating 3D structure design. The mathematical model to predict the IND from structural designed tablets was obtained and two tablets (T-v1 and T-v2) were printed to validate such model, where the fitting coefficient are 0.9964 and 0.9965, respectively. This study suggested that combining HME and 3D printing technologies could be an optimal approach for personalized and precision drug delivery dosage development.

What do patients and families observe aboutpediatric safety?: A thematic analysis of real-time narratives.

Data on inpatient safety are documented by hospital staff through incident reporting (IR) systems. Safety observations from families or patients are rarely captured. The Family Input for Quality and Safety (FIQS) study created a mobile health tool for pediatric patients and their families to anonymously report safety observations in real time during hospitalization. The study objectives were to describe these observations and identify domains salient to safety. In this observational study, we analyzed pediatric patient safety reports from June 2017 to April 2018. Participants were: English-speaking family membersand hospitalized patients ≥13 years old. The analysis had two stages: (1) assessment of whether narratives met established safety event criteria and whether there were companion IRs; (2) thematic analysis to identify domains. Of 248 enrolled participants, 58 submitted 120 narrative reports. Of the narratives, 68 (57%) met safety event criteria, while only 1 (0.8%) corresponded to a staff-reported IR. Twenty-five percent of narratives shared positive feedback about patient safety efforts; 75% shared constructive feedback. We identified domains particularly salient to safety:(1) patients and families as safety actors; (2) emotional safety; (3) system-centered care; and (4) shared safety domains, including medication, communication, and environment of care. Some domains capture data that is otherwise difficult to obtain (#1-3), while others fit within standard healthcare safety domains (#4). Patients and families observe and report salient safety events that can fill gaps in IR data. Healthcare leaders should consider incorporating patient and family observations-collected with an option for anonymity and eliciting both positive and constructive comments.