Advancing pediatric drug development in South Asia: Current landscape and vision for the future.

ABSTRACT: The manuscript summarizes the outcomes of a one-day conference by the South Asian College of American College of Clinical Pharmacology (SAC-ACCP) in July 2023, at Bhopal. The theme of the conference was "Advancing pediatric drug development in South Asia." SAC-ACCP organized this event in Bhopal to foster the discipline of clinical pharmacology and to motivate researchers and physicians in the in the central part of India. The conference featured presentations on regional approaches to pediatric drug development in Asia by pediatric scientific experts from the pharmaceutical industry, regulatory agencies, as well as independent consultancies. The speakers highlighted several important aspects of the evolving regulatory landscape in India and proposed numerous actionable steps in acceleration of pediatric drug development. This commentary provides insights from presentations and the panel discussion at this conference and also makes an attempt to connect to similar discussions that occurred at the SAC-ACCP drug development conference in 2017.

Role of neurosurgeons In strengthening paediatric neuro-oncology In low- and middle-income countries: a narrative review with case examples.

Paediatric neuro-oncology in low- and middle-income countries (LMICs) accounts for a significant proportion of cancer-related mortalities in this age group. The current dearth of structured paediatric neurosurgery training programmes in LMICs requires multidisciplinary coordination; neurosurgeons play certain key roles, as discussed in this article, in ensuring safe and effective care for paediatric neuro-oncology patients. This document intends to elaborate through illustrative cases of the technical and structural nuances required by neurosurgeons in LMICs to provide appropriate surgical care.

Communicate to Care: Implementing Health Literacy in a Pediatric Ears, Nose, and Throat Clinic.

BACKGROUND: Despite positive outcomes in controlled trials, organizations have been slow to adopt health literacy practices. The purpose of the Communicate to CARE (Clear Communication, Achieve Understanding with Teach-Back, Receptive to our patient family needs, Empathetic care delivery) study was to use theories and strategies from implementation science to scale up health literacy practices in a pediatric Ears, Nose, and Throat (ENT) clinic. BRIEF DESCRIPTION OF ACTIVITY: Expanding on previous efforts that simply reflected on barriers, the CARE team identified barriers within the local context pre-implementation to select strategies to directly address barriers during health literacy implementation. The RE-AIM framework was used to evaluate the reach, effectiveness, adoption, implementation, and maintenance of health literacy practices. IMPLEMENTATION: Over 18 months, the CARE team delivered multiple implementation strategies, including external facilitator, microlessons, preparing champions, audit and feedback, local consensus discussions, and small test of change. We tailored health literacy practices to clinic team roles to accommodate the clinic workflow. RESULTS: ENT team mean ratings on acceptability, appropriateness, and feasibility remained >4 indicating a high likelihood of successful implementation. Caregiver always ratings significantly increased from baseline to 12 months for easy-to-understand medication instructions (74%-96%), test results (54%-96%), know what to do if had questions (89%-96%), and encouraged to talk about health problems (76%-90%). Caregiver ratings dropped slightly at 18 months, indicating a need for booster training. While one third of caregivers reported Teach-Back practice across all time periods, the ENT team reported increased practice from baseline (42%), 6 (61%) and 12 months (70%). LESSONS LEARNED: Over the first 12 months, the external facilitator delivered implementation strategies with weekly contact, tapering contact over the final 6 months. The local champion became engaged in the CARE study through a quality improvement project with meaningful outcomes for the clinic and an incentivization program for scholarly endeavors. Lunch and learn sessions helped build relationships between the CARE and ENT team to discuss and problem solve issues. The 5-item CAHPS health literacy composite proved to be sensitive to changes during implementation of health literacy practices. Integrating these items into standard follow up surveys with patients and families would help realize the return on investment for health literacy implementation. [HLRP: Health Literacy Research and Practice. 2024;8(3):e166-e174.].

Development and validation of a realistic type III esophageal atresia simulator for the training of pediatric surgeons.

BACKGROUND: The technical complexity and limited casuistry of neonatal surgical pathology limit the possibilities of developing the necessary technical competencies by specialists in training. Esophageal atresia constitutes the paradigm of this problem. The use of synthetic 3D models for training is a promising line of research, although the literature is limited. METHODS: We conceptualized, designed, and produced an anatomically realistic model for the open correction of type III oesophageal atresia. We validated it with two groups of participants (experts and non-experts) through face, construct, and content-validity questionnaires. RESULTS: The model was validated by nine experts and nine non-experts. The mean procedure time for the experts and non-experts groups was 34.0 and 38.4 min, respectively. Two non-experts did not complete the procedure at the designed time (45 min). Regarding the face validity questionnaire, the mean rating of the model was 3.2 out of 4. Regarding the construct validity, we found statistically significant differences between groups for the equidistance between sutures, 100% correct in the expert group vs. 42.9% correct in the non-expert group (p = 0.02), and for the item "Confirms that tracheoesophageal fistula closure is watertight before continuing the procedure", correctly assessed by 66.7% of the experts vs. by 11.1% of non-experts (p = 0.05). Concerning content validity, the mean score was 3.3 out of 4 for the experts and 3.4 out of 4 for the non-experts. CONCLUSIONS: The present model is a cost-effective, simple-to-produce, and validated option for training open correction of type III esophageal atresia. However, future studies with larger sample sizes and blinded validators are needed before drawing definitive conclusions.

The 2022-2023 Pediatric Respiratory Illness Surge: Survey of Acute and Critical Care Resource Use.

OBJECTIVE: A surge of pediatric respiratory illnesses beset the United States in late 2022 and early 2023. This study evaluated within-surge hospital acute and critical care resource availability and utilization. The study aimed to determine pediatric hospital acute and critical care resource use during a respiratory illness surge. METHODS: Between January and February 2023, an online survey was sent to the sections of hospital medicine and critical care of the American Academy of Pediatrics, community discussion forums of the Children's Hospital Association, and PedSCCM-a pediatric critical care website. Data were summarized with median values and interquartile range. RESULTS: Across 35 hospitals with pediatric intensive care units (PICU), increase in critical care resource use was significant. In the month preceding the survey, 26 (74%) hospitals diverted patients away from their emergency department (ED) to other hospitals, with 46% diverting 1-5 patients, 23% diverting 6-10 patients, and 31% diverting more than 10 patients. One in 5 hospitals reported moving patients on mechanical ventilation from the PICU to other settings, including the ED (n = 2), intermediate care unit (n = 2), cardiac ICU (n = 1), ward converted to an ICU (n = 1), and a ward (n = 1). Utilization of human critical care resources was high, with PICU faculty, nurses, and respiratory therapists working at 100% capacity. CONCLUSIONS: The respiratory illness surge triggered significant hospital resource use and diversion of patients away from hospitals. Pediatric public health emergency-preparedness should innovate around resource capacity.

Common errors in statistics and methods.

As statistical reviewers and editors for BMJ Paediatrics Open (BMJPO), we frequently see methodological and statistical errors in articles submitted to our journal. To make a list of these common errors and propose suitable corrections, and inspired by similar efforts at other leading journals, we surveyed the statistical reviewers and editors at BMJPO to collect their 'pet peeves' and examples of best practices.(1, 2) We have divided these into seven sections: graphics; statistical significance and related issues; presentation, vocabulary, textual and tabular presentation; causality; model building, regression and choice of methods; meta-analysis; and miscellaneous. Here, we present the common errors, with brief explanations. We hope that the guidance provided here will help guide authors as they prepare their submissions to the journal, leading to higher quality and more robust research reporting.

Evaluating the implementation of the Pediatric Acute Care Education (PACE) program in northwestern Tanzania: a mixed-methods study guided by normalization process theory.

BACKGROUND: In low- and middle-income countries (LMICs), such as Tanzania, the competency of healthcare providers critically influences the quality of pediatric care. To address this issue, we introduced Pediatric Acute Care Education (PACE), an adaptive learning program to enhance provider competency in Tanzania's guidelines for managing seriously ill children. Adaptive learning is a promising alternative to current in-service education, yet optimal implementation strategies in LMIC settings are unknown. OBJECTIVES: (1) To evaluate the initial PACE implementation in Mwanza, Tanzania, using the construct of normalization process theory (NPT); (2) To provide insights into its feasibility, acceptability, and scalability potential. METHODS: Mixed-methods study involving healthcare providers at three facilities. Quantitative data was collected using the Normalization MeAsure Development (NoMAD) questionnaire, while qualitative data was gathered through in-depth interviews (IDIs) and focus groups discussions (FGDs). RESULTS: Eighty-two healthcare providers completed the NoMAD survey. Additionally, 24 senior providers participated in IDIs, and 79 junior providers participated in FGDs. Coherence and cognitive participation were high, demonstrating that PACE is well understood and resonates with existing healthcare goals. Providers expressed a willingness to integrate PACE into their practices, distinguishing it from existing educational methods. However, challenges related to resources and infrastructure, particularly those affecting collective action, were noted. Early indicators point toward the potential for long-term sustainability of the PACE, but assessment of reflexive monitoring was limited due to the study's focus on PACE's initial implementation. CONCLUSION: This study offers vital insights into the feasibility and acceptability of implementing PACE in a Tanzanian context. While PACE aligns well with healthcare objectives, addressing resource and infrastructure challenges as well as conducting a longer-term study to assess reflexive monitoring is crucial for its successful implementation. Furthermore, the study underscores the value of the NPT as a framework for guiding implementation processes, with broader implications for implementation science and pediatric acute care in LMICs.

Exploring the perspectives of health care professionals on digital health technologies in pediatric care and rehabilitation.

BACKGROUND: Digital health technologies are increasingly used by healthcare professionals working in pediatric hospital and rehabilitation settings. Multiple factors may affect the implementation and use of digital health technologies in these settings. However, such factors have not been identified in a multidisciplinary, pediatric context. The objective of this study was to describe actual use and to identify the factors that promote or hinder the intention to use digital health technologies (mobile learning applications, virtual/augmented reality, serious games, robotic devices, telehealth applications, computerized assessment tools, and wearables) among pediatric healthcare professionals. METHODS: An online survey evaluating opinions, current use, and future intentions to use digital health technologies was completed by 108 professionals at one of Canada's largest pediatric institutes. Mann-Whitney U tests were used to compare the attitudes of healthcare professionals who intend to increase their use of digital health technologies and those who do not. Linear regression analyses were used to determine predictors of usage success. RESULTS: Healthcare professionals reported mostly using mobile and tablet learning applications (n = 43, 38.1%), telehealth applications (n = 49, 43.4%), and computerized assessment tools (n = 33, 29.2%). Attitudes promoting the intention to increase the use of digital health technologies varied according to technology type. Healthcare professionals who wished to increase their use of digital health technologies reported a more positive attitude regarding benefits in clinical practice and patient care, but were also more critical of potential negative impacts on patient-professional relationships. Ease of use (ß = 0.374; p = 0.020) was a significant predictor of more favorable usage success. The range of obstacles encountered was also a significant predictor (ß = 0.342; p = 0.032) of less favorable evaluation of usage success. Specific factors that hinder successful usage are lack of training (ß = 0.303; p = 0.033) and inadequate infrastructure (ß = 0.342; p = 0.032). CONCLUSIONS: When working with children, incorporating digital health technologies can be effective for motivation and adherence. However, it is crucial to ensure these tools are implemented properly. The findings of this study underscore the importance of addressing training and infrastructure needs when elaborating technology-specific strategies for multidisciplinary adoption of digital health technologies in pediatric settings.

Spanish Society of Hospital Pharmacy and the Spanish Society of Pediatric Infectious Diseases (SEFH-SEIP) National Consensus Guidelines for therapeutic drug monitoring of antibiotic and antifungal drugs in pediatric and newborn patients. / Documento nacional de consenso de monitorización terapéutica de antibióticos y antifúngicos en el paciente pediátrico y neonatal de la Sociedad Española de Farmacia Hospitalaria (SEFH) y la Sociedad Española de Infectología Pediátrica (SEIP).

Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic parameters, is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised host. In neonates and children, infections account for a high percentage of hospital admissions and anti-infectives are the most used drugs. However, pediatric pharmacokinetic and pharmacodynamic studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals -usually used off-label in pediatrics- to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the pharmacokinetic parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treatment success. In addition, pediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring. The aim of this document, developed jointly between the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Pediatric Infectious Diseases (SEIP), is to describe the available evidence on the indications for therapeutic drug monitoring of antibiotics and antifungals in newborn and pediatric patients and to provide practical recommendations for therapeutic drug monitoring in routine clinical practice to optimize pharmacokinetic and pharmacodynamic parameters, efficacy and safety of antibiotics and antifungals in the pediatric population.

Precision adjuvants for pediatric vaccines.

Elucidating optimal vaccine adjuvants for harnessing age-specific immune pathways to enhance magnitude, breadth, and durability of immunogenicity remains a key gap area in pediatric vaccine design. A better understanding of age-specific adjuvants will inform precision discovery and development of safe and effective vaccines for protecting children from preventable infectious diseases.

The creation of a pediatric surgical checklist for adult providers.

PURPOSE: To address the need for a pediatric surgical checklist for adult providers. BACKGROUND: Pediatric surgery is unique due to the specific needs and many tasks that are employed in the care of adults require accommodations for children. There are some resources for adult surgeons to perform safe pediatric surgery and to assist such surgeons in pediatric emergencies, we created a straightforward checklist based on current literature. We propose a surgical checklist as the value of surgical checklists has been validated through research in a variety of applications. METHODS: Literature review on PubMed to gather information on current resources for pediatric surgery, all papers on surgical checklists describing their outcomes as of October 2023 were included to prevent a biased overview of the existing literature. Interviews with multiple pediatric surgeons were conducted for the creation of a checklist that is relevant to the field and has limited bias. RESULTS: Forty-two papers with 8,529,061 total participants were included. The positive impact of checklists was highlighted throughout the literature in terms of outcomes, financial cost and team relationship. Certain care checkpoints emerged as vital checklist items: antibiotic administration, anesthetic considerations, intraoperative hemodynamics and postoperative resuscitation. The result was the creation of a checklist that is not substitutive for existing WHO surgery checklists but additive for adult surgeons who must operate on children in emergencies. CONCLUSION: The outcomes measured throughout the literature are varied and thus provide both a nuanced view of a variety of factors that must be taken into account and are limited in the amount of evidence for each outcome. We hope to implement the checklist developed to create a standard of care for pediatric surgery performed in low resource settings by adult surgeons and further evaluate its impact on emergency pediatric surgery outcomes. FUNDING: Fulbright Fogarty Fellowship, GHES NIH FIC D43 TW010540.

Global survey on point-of-care ultrasound (pocus) use in child surgery.

PURPOSE: To undertake a global assessment of existing ultrasound practices, barriers to access, point-of-care ultrasound (POCUS) training pathways, and the perceived clinical utility of POCUS in Child Surgery. METHODS: An electronic survey was disseminated via the GICS (Global Initiative of Children's Surgery) network. 247 anonymized responses from 48 countries were collated. 71.3% (176/247) worked in child surgery. RESULTS: Ultrasound was critical to practice with 84% (147/176) of requesting one daily or multiple times per week. Only 10% (17/176) could access emergency ultrasound < 1 h from request. The main barrier was a lack of trained personnel. HIC surgeons were more likely to have ultrasound training (24/29; 82.8%) compared with LMICs (74/147; 50.3%) (p = .001319; CI 95%). Self-perceived POCUS competence was associated with regularity of POCUS use (p < 0.001; CI 95%). Those who already practice POCUS most commonly use it for trauma, intussusception, and ultrasound-guided procedures. Majority (90%; 159/176) of child surgeons would attend formal POCUS training if available. CONCLUSIONS: Ultrasound is critically important in children's surgery globally, however, many surgeons experience barriers to timely access. There is a strong interest in learning POCUS for relevant pediatric surgical applications. Further research is needed to evaluate the best methods of training, accreditation, and governance.

Improving outcomes for uncomplicated gastroschisis: clinical practice guidelines from the American Pediatric Surgical Association Outcomes and Evidence-based Practice Committee.

BACKGROUND: The authors sought better outcomes for uncomplicated gastroschisis through development of clinical practice guidelines. METHODS: The authors and the American Pediatric Surgical Association Outcomes and Evidenced-based Practice Committee used an iterative process and chose two questions to develop clinical practice guidelines regarding (1) standardized nutrition protocols and (2) postnatal management strategies. An English language search of PubMed, MEDLINE, OVID, SCOPUS, and the Cochrane Library Database identified literature published between January 1, 1970, and December 31, 2019, with snowballing to 2022. The Appraisal of Guideline, Research and Evaluation reporting checklist was followed. RESULTS: Thirty-three studies were included with a Level of Evidence that ranged from 2 to 5 and recommendation Grades B-D. Nine evaluated standardized nutrition protocols and 24 examined postnatal management strategies. The adherence to gastroschisis-specific nutrition protocols promotes intestinal feeding and reduces TPN administration. The implementation of a standardized postnatal clinical management protocol is often significantly associated with shorter hospital stays, less mechanical ventilation use, and fewer infections. CONCLUSIONS: There is a lack of comparative studies to guide practice changes that improve uncomplicated gastroschisis outcomes. The implementation of gastroschisis-specific feeding and clinical care protocols is recommended. Feeding protocols often significantly reduce TPN administration, although the length of hospital stay may not consistently decrease.

The management of testicular torsion: A survey of Turkish pediatric surgeons and pediatric urologists.

BACKGROUND: This study aimed to evaluate the approaches of pediatric surgeons and pediatric urologists in Türkiye regarding the diagnosis and treatment of testicular torsion (TT) and their adherence to the European Association of Urology (EAU) pediatric urology guideline. METHODS: A survey consisting of 19 questions, accompanied by an annotation describing the objective of the study, was emailed to pediatric surgeons and pediatric urologists in June and July 2023. RESULTS: Of the 95 respondents, 62.1% had over 10 years of experience, and 48.4% treated more than five cases of TT annually. Of the participants, 87.4% stated that scrotal Doppler ultrasonography (US) was always used, and 12.6% stated that US was used in cases of doubtful diagnosis. Concerning treatment, 14.7% reported performing manual detorsion, 70.5% never did, and 14.7% did so only if the operating room was unavailable soon. A total of 92.6% of participants opted for emergency surgery. Among participants who perform manual detorsion, 71.4% perform surgery within 24 hours after successful manual detorsion. Regarding fixation of the contralateral testicle, 14.7% never performed it, and 27.4% did so only when they performed an orchiectomy on the torsion testicle. CONCLUSION: While most participants follow EAU pediatric urology guidelines by performing emergency surgery, the rate of manual detorsion is low. Few participants stated that emergency surgery may not be performed after manual detorsion. While all of the participants performed fixation of the torsion testicle in accordance with the guidelines, the same adherence was not observed in the contralateral testicle.