Pediatric Research Articles

Technology-based gamification in sleep medicine: A useful tool for physicians?

In recent years, individuals’ nightly sleep quality, hygiene and duration have declined significantly. Gamification, the addition of game-based elements to non-game contexts, is an emerging tool in medical education and may be readily applicable to sleep medicine. Initially developed for use in retail and education, gamification increases productivity and knowledge acquisition and retention. Between the dates of 12/16/2023 and 03/27/2024, we conducted a focused review of eleven recent studies investigating the effectiveness, feasibility, and acceptability of technology-based gamification interventions in improving subjects’ sleep duration, quality, and hygiene. Some studies focused primarily on imparting information while others sought to gamify user incentives. Most interventions were effective in improving user knowledge and sleep hygiene, were feasible to implement, and had high acceptability among subjects, measured through qualitative and quantitative data metrics. Effective media included mobile applications, wearable technology, and console-based exercise games (“exergames”). Although valid concerns exist regarding use of technology near bedtime, technology-based games designed for daytime usage offer more immersive experiences and increased user engagement. In the future, we anticipate increased use of gamification by primary care physicians, sleep physicians, and psychologists, particularly in rural areas, within pediatric sleep medicine, and to augment traditional cognitive behavioral therapy. New research should examine the addition of gamification to sleep-focused telemedicine and school-based educational sleep interventions.

Comparison of Mean Hospital Stay after Nebulization with 3% Hypertonic Saline vs Salbutamol in Treatment of Bronchiolitis

Abstract: Background: With an estimated prevalence of 33% in children age >2years and owing to 1 in 10th cause of hospitalization in children, Bronchiolitis is a major factor for morbidity and mortality. Varying nebulization doses have been shown to produce different clinical outcomes in patients with bronchiolitis. Objective: To compare mean hospital stay after nebulization with 3% hypertonic saline compared to the salbutamol among patients of bronchiolitis Materials and Methods: This was a randomized control study done at pediatric medicine ward, Services Hospital, Lahore. The study was done during 8th May 2018 to 8th November 2018. Data was collected from 68 children of age >3 months to < 2 years of both genders i.e. (34 in each group) fulfilling inclusion criteria. SPSS software was used for data entry and analysis. For quantitative variables age, mean and standard deviation were used whereas for qualitative variables like gender, frequency and percentages were used. Independent sample t-test was used for comparing mean hospital stay among the two groups taking p-value<0.05 as significant. Result: Average age in Salbutamol group was 1.06 ± 0.50 years and in Hypertonic solution mean age was 1.24 ± 0.55 years. There was significant difference in mean hospital stay with relatively lesser in hypertonic solution vs the Salbutamol group [3.18 ± 1.11 vs 4.44 ± 1.08 ; p-value <0.001]. Upon post-stratification analysis, the mean hospital stay was found to be significantly lower in the Hypertonic group vs. Salbutamol group with respect to age, gender and the duration of the disease (p-values<0.05 for all). Conclusion: This study concludes that the mean hospital stay was statistically lower in the hypertonic solution group vs the Salbutamol group. Moreover, the clinical efficacy of the hypertonic saline can be utilized in future to gain early recovery of Bronchiolitis and hence it can reduce the hospital stay and related cost. Keywords: Bronchiolitis, Salbutamol, Hypertonic saline, Hospital stay, Severity, Duration, Treatment.

Association of Simple Febrile Seizure with Iron Deficiency Anemia in Children: A Case Control Study

Abstract: Background: Febrile seizure is an established entity in Pediatrics which characterizes with absence of any intracranial infection or metabolic disorders. Simple febrile seizure carries a favorable prognosis without any sequelae. Still, it emerges as the most common etiology of seizure till the age of five years. Iron deficiency anemia is a commonly witnessed micro-nutrient deficiency with a worldwide distribution. Objective: To establish relation of simple febrile seizure with iron deficiency anemia in paediatric population. Materials and Methods: Case-control study, conducted in Pediatric Medicine Department, King Fahad Armed Forces Hospital Southern Region, Khamis Mushayat, Kingdom of Saudi Arabia, from1st January 2022 to 30th June 2023. The 102 children, having age six months to five years, with a diagnosis of first simple febrile seizure were assessed. Likewise, the control group included 102 febrile children without convulsion. The hematological parameters evaluated for diagnosis of iron deficiency anemia included hemoglobin, mean corpuscular volume, serum ferritin, serum iron, total iron binding capacity & red cell distribution width. Result: The mean age for first simple febrile seizure was 23 months. Acute respiratory infection was the most common etiology (80%). Iron deficiency anemia was identified in 17% of cases of simple febrile seizure, in contrary to 6% of cases with febrile illness without seizure, with odds ratio of 3.2. Conclusion: This study demonstrated that the children with iron deficiency anemia are at significantly higher risk of having febrile convulsions compare to control group with fever but without anemia. Keywords: Fever, Febrile seizure, Iron Deficiency anemia, Serum ferritin, Hemoglobin, Convulsion, Mean corpuscular hemoglobin.

Update on the Use of Thrombopoietin-Receptor Agonists in Pediatrics.

This review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children, and adolescents. It focuses on substances that have been approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for pediatric patients. Romiplostim and eltrombopag are already established as second-line treatment for persistent or chronic immune thrombocytopenia (ITP). As in adults, TPO-RAs are currently also evaluated in severe aplastic anemia (SAA), chemotherapy-induced thrombocytopenia (CIT), myelodysplastic syndromes (MDS), and poor engraftment after hematopoietic stem cell transplantation in pediatric and adolescent patients. Moreover, studies on the implication of TPO-RA in treating rare inherited thrombocytopenias, such as Wiskott-Aldrich syndrome (WAS), congenital amegakaryocytic thrombocytopenia (CAMT), or MYH9-associated thrombocytopenia, deserve future attention. Current developments include testing of avatrombopag and lusutrombopag that are approved for the treatment of thrombocytopenia associated with chronic liver disease (CLD) in adult patients. In pediatric and adolescent medicine, we expect in the near future a broader use of TPO-RAs as first-line treatment in primary ITP, thereby considering immunomodulatory effects that increase the rate of sustained remission off-treatment, and a selective use in rare inherited thrombocytopenias based on current clinical trials.

Evolution of Pediatric Critical Care Medicine Physicians Clinical and Academic Profile by Gender.

To examine career trajectory and academic profile of Pediatric Critical Care Medicine (PCCM) physicians, with special focus on gender differences. Observational cross-sectional study of PCCM fellowship graduates using publicly available data. Publicly available databases including National Provider Identifier registry, American Board of Pediatrics, Doximity, official hospital websites, and Scopus. Two thousand one hundred twenty-nine PCCM fellowship graduates employed in clinical positions in U.S. practice locations. None. Physician demographic characteristics included gender and time since fellowship completion. Current career and academic characteristics included employment data, publication productivity (h-index), and academic rank. Data from 2129 career PCCM physicians was included, with recent graduates showing a notable increase in female representation. Workplace characteristics revealed that most PCCM physicians worked in university-affiliated hospitals, with higher percentages of female physicians working in university-affiliated hospitals compared with male physicians. The study also highlighted significant gender disparities in academic metrics, with male physicians having higher h-indices (3 vs. 2; p < 0.001) and more publications (6 vs. 4; p < 0.001) than their female counterparts across various career phases. Additionally, the analysis showed gender differences in academic rank, with a higher proportion of female faculty holding assistant and associate professor ranks (58.2% vs. 47.5%; p < 0.001), while a greater percentage of male faculty held the rank of professor (20.2% vs. 11.1%; p < 0.001). Multiple variable regression analysis identified both male gender and time since fellowship graduation as independently associated with a physician's h-index, while only time since fellowship graduation was linked to current academic rank. This is the first analysis of career and academic characteristics of practicing PCCM physicians, additionally studying the association of gender and career trajectory. Gender discrepancy was seen in employment hospital characteristics, h-indices, and academic rank. Additional studies are required to further explore the impact of gender on career trajectory.

Beyond laryngoscopy: Trends in advanced technique endotracheal intubation in pediatric intensive care units across the United States

ObjectivesEndotracheal intubation (ETI) is a lifesaving procedure in critically ill children. Direct laryngoscopy (DL) is the most utilized method for ETI, however advanced techniques beyond DL are indicated in some patients. The purpose of this study is to describe trends of advanced ETI techniques in the critical care setting. Materials and methodsUsing the National Emergency Airway Registry for Children (NEAR4KIDS), advanced technique ETI quality improvement data were prospectively collected for ETIs in PICUs from April 2018 to September 2021. Those who underwent ETI with only DL or who underwent exchange of an existing endotracheal tube were excluded. ResultsA total of 79 patients underwent advanced technique ETI with a median age of 8 (IQR 1–17) years. Advanced technique ETI was successful on the first attempt in 46.8 % of cases, with an overall success rate of 91.1 %. 1.3 % of patients received emergent surgical airway management. The most utilized advanced ETI technique was video laryngoscopy, followed by flexible bronchoscopy, and intubation through a laryngeal mask airway (LMA). The provider discipline ultimately successful in performing advanced technique ETI was most often pediatric critical care medicine (n = 26, 32.9 %), followed by anesthesia (n = 20, 25.3 %), and otolaryngology (n = 16, 20.3 %). ConclusionWhile often indicated in challenging clinical scenarios, advanced ETI techniques are ultimately successful in the vast majority of cases. Advanced technique ETI is a highly multidisciplinary process.

Development of the Children’s ACuTe UltraSound (CACTUS) point-of-care ultrasound (POCUS)-accredited training in the UK: a descriptive study

Point-of-care ultrasound (POCUS) is an established, evidence-supported tool that can be used in neonatal and paediatric medicine, offering clinicians immediate diagnostic insights, assessment of interventions and improved safety profiles and...

MDB-61. STARVING TUMORS OF POLYAMINES: A NOVEL APPROACH IN TREATING AGGRESSIVE PEDIATRIC MEDULLOBLASTOMA

Abstract BACKGROUND Polyamines, essential intracellular polycations, govern fundamental cell processes and drive oncogenesis. Our research unveiled the dependency of pediatric Diffuse Midline Gliomas (DMG) on the polyamine pathway (Khan et al.,2021). Disruption of this pathway with the synthesis inhibitor DFMO, and the transport inhibitor AMXT1501, potently inhibited DMG tumors, yielding unprecedented survival in-vivo. We hypothesized that dual polyamine pathway targeting could similarly suppress growth in other aggressive pediatric brain tumors. METHODS/RESULTS We analyzed the expression of polyamine pathway regulators in high-risk pediatric brain cancers ZERO precision medicine platform and found elevated expression in medulloblastoma. ODC1, a polyamine synthesis driver, was found to have significant correlation in high-grade gliomas with four key functional tumor states—stemness, cell cycle, hypoxia, and angiogenesis. Medulloblastoma cells were sensitive to treatment with DFMO but showed a compensatory increase in polyamine transporter expression. Conversely, treatment with AMXT1501 increased ODC1 expression. Dual targeting of the polyamine pathway potently and synergistically inhibited cell proliferation and clonogenic potential in Group-3 medulloblastoma cells. Flow cytometric analysis of Annexin V-stained cells showed that treatment with DFMO and AMXT1501 in combination led to induction of apoptosis. Critically, dual polyamine inhibition potently sensitized medulloblastoma cells to the topoisomerase-I inhibitor, SN-38, leading to complete eradication of medulloblastoma cell proliferation and colony formation at nanomolar chemotherapeutic concentrations, with the effect most pronounced in Group-3 medulloblastoma. In triple combination-treated cells, over-representation analysis revealed heightened mitotic DNA damage, macroautophagy, and apoptosis, coupled with diminished neuron/synapse development, glycosylation, and cellular signaling pathways. We are currently testing this treatment strategy in aggressive orthotopic medulloblastoma models. CONCLUSION These findings suggest targeting the polyamine pathway as a promising strategy to sensitize aggressive pediatric medulloblastoma tumors to chemotherapy. DFMO/AMXT1501 is in Phase I evaluation for adults (NCT05500508) and advancing to a Phase I/II trial for children through the CONNECT consortium.

Advances in Point-of-Care Ultrasound in Pediatric Acute Care Medicine.

Pediatric point-of-care ultrasonography (POCUS) has grown in utilization and is now an integral part of pediatric acute care. Applications within the pediatric critical care, neonatology and pediatric emergency were once limited to evaluation of undifferentiated shock states, abdominal free fluid assessments in trauma resuscitation and procedural guidance. The body of pediatric POCUS literature is ever expanding and recently published international consensus guidelines are available to guide implementation into clinical practice. The authors present a review of emerging applications and controversies within thoracic, hemodynamic, neurologic, and ocular POCUS in pediatric acute care medicine.

Optimizing paediatric specialist referrals for short stature in an era of multiple growth hormone indications.

The assessment of growth during infancy and childhood is an essential component of paediatric medicine, as atypical growth may point to the existence of an underlying health condition. To reduce morbidity, it is vital that treatment for growth disorders is provided in a timely fashion. However, although there are guidelines regarding referral criteria for short stature in Europe and the USA, there are no such guidelines in Canada. To address this, a series of consultations and workshops with paediatricians, paediatric endocrinologists, family physicians and nurses were held, with the aim of developing a consensus-based set of recommendations for children in Canada showing atypical growth and to identify red flags for children who might benefit from early referral. To achieve this, a referral algorithm and referral form for primary care providers were developed to ensure timely and appropriate referrals, and transmission of the most relevant details to the secondary care consultant.

Association Between Gender and Salary Among Pediatric Hospital Medicine Physicians.

Gender-based disparities in salary exist in multiple fields of medicine. However, there is limited data examining gender inequities in salary in pediatric hospital medicine (PHM). Our primary objective was to assess whether gender-based salary differences exist in PHM. The secondary objective was to assess if, among women, the differences in salary varied on the basis of leadership positions or self-identified race and ethnicity. We conducted a survey-based, cross-sectional study of pediatric hospitalists in December 2021. Our primary outcomes were base and total salary, adjusted for the reported number of average weekly work hours. We performed subanalyses by presence of a leadership position, as well as race. We used a weighted t test using inverse probability weighting to compare the outcomes between genders. A total of 559 eligible people responded to our survey (51.0%). After propensity score weighting, women's mean base salary was 87.7% of men's base (95% confidence interval [CI] 79.8%-96.4%, P < .01), and women's total salary was 85.6% of men's total (95% CI 73.2%-100.0%, P = .05) salary. On subgroup analysis of respondents with a leadership position, women's total salary was 80.6% of men's total salary (95% CI 68.7%-94.4%, P < .01). Although women who identified as white had base salaries that were 86.6% of white men's base salary (95% CI 78.5%-95.5%, P < .01), there was no gender-based difference noted between respondents that identified as nonwhite (88.4% [69.9%-111.7%] for base salary, 80.3% [57.2% to 112.7%]). Gender-based discrepancies in salary exists in PHM, which were increased among those with leadership roles. Continued work and advocacy are required to achieve salary equity within PHM.

Empfehlungen der Österreichischen Gesellschaft für Kinder- und Jugendheilkunde zur Prophylaxe einer RSV-Infektion mit Nirsevimab

ZusammenfassungSeit dem Jahr 2023 ist der langwirksame monoklonale RSV(Respiratory Syncytial Virus)-Antikörper Nirsevimab in der EU zugelassen, der eine 75–80 %ige Effektivität zur Reduktion schwerer RSV-Infektionen mit oder ohne Hospitalisierung bewiesen hat. Ein österreichischer Expertinnenkreis diskutierte zu fünft und anschließend in mehreren Delphi-Runden diese signifikante Verbesserung der RSV-Prophylaxe (Palivizumab fünf Injektionen monatlich über die Saison nur für Risikokinder verglichen mit Einmalgabe von Nirsevimab). Es bestand Konsens, dass alle Kinder diesen Schutz ab Oktober/November vor Beginn oder während der Saison bis März des Folgejahres erhalten sollen. Die ÖGKJ fordert aufgrund des derzeitigen Wissensstandes, dass alle Neugeborenen und Säuglinge vor einer schweren RSV-Infektion in der ersten Saison geschützt werden, Risikokinder in Einzelfällen auch über eine 2. Saison, und empfiehlt zur Prophylaxe von RSV-Infektionen die Gabe von Nirsevimab, sofern die Kindesmutter keinen RSV-Impfstoff während der Schwangerschaft erhalten hat. Diese Empfehlungen können sich ändern, wenn mehr Daten zur Effektivität bei Risikokindern vorliegen.

Paediatric gender medicine: Longitudinal studies have not consistently shown improvement in depression or suicidality.

Systematic literature reviews have found the evidence for hormonal interventions in paediatric-age patients with gender dysphoria is of low certainty. Studies in this field have all been observational, and generally of low quality. Nevertheless, some experts assert that the observational studies in this field have consistently found improvement in mental health, and therefore constitute sufficient evidentiary basis for hormonal interventions. The present review sought to characterise results of the longitudinal clinical research studies that have reported depression and suicidality outcomes. The present review collated, from examination of six existing reviews, 14 longitudinal clinical research studies that have specifically investigated depression and/or suicidality outcomes. Significantly positive depression outcomes were reported in six studies, and significantly positive suicidality outcomes in two studies. Outcomes were negative in the largest study. Notably, some studies articulated positive conclusions about hormonal interventions even in the setting of insignificant, small or negative findings. Analysis of longitudinal clinical research in this field showed inconsistent demonstration of benefit with respect to depression and suicidality. This analysis suggests that, contrary to assertions of some experts and North American professional medical organisations, the impact of hormonal interventions on depression and suicidality in this population is unknown.

Safely Doing Less in Pediatrics and Pediatric Hospital Medicine

Safely Doing Less in Pediatrics and Pediatric Hospital Medicine

The clinical application and laboratory management of molecular genetic diagnosis in children's hospital

AbstractBackgroundMolecular diagnostic technology is the foundation of precision medicine, which has the advantages of good specificity, high sensitivity, strong targeting, rapiddiagnosis, etc. It has a wide range of applications in the field of pediatrics. However, molecular diagnostic technology is characterized by complicated experimental operation, high difficulty in data analysis and interpretation, in consistent standards among laboratories, and difficult standardization of technical processes. Enhancing the application value of molecular diagnostic technology in pediatrics and promoting the high‐quality development of the discipline requires careful consideration by relevant management and professionals.MethodsThis study firstly outlines the development history of molecular diagnostic technology. Then, it analyzes the application of molecular diagnostic technology in the field of pediatrics. Finally, it explores the countermeasures for the management of molecular diagnostic laboratories.ResultsThis study highlights the importance of molecular diagnostic technology in providing information and decision‐making basis for disease prevention, prediction,diagnosis, treatment and regression. It has a wide range of applications in the molecular diagnosis of pediatric hereditary diseases, malignant tumors and infectious diseases. In addition, the countermeasures for the management of molecular diagnostic laboratories are proposed from the five aspects of laboratory, personnel team construction, standardized management,multidisciplinary cross‐discipline, research and translation, safety managementand ethical supervision, and management upgrading and modernization.ConclusionsMolecular diagnostic technology, as the basis of precision medicine, has become one of the important frontier fields in the development of contemporary pediatric medicine. Enhanced laboratory capacity in molecular diagnostic techniques can improve outcomes in the prevention, prediction, diagnosis, treatment, prognosis and research of pediatricdiseases, and lay the groundwork for child healthcare.

The Positive Impact of Physical Activity Programs on Overall Child Health and Wellbeing

Background One of the most remarkable and significant topics of interest in the field of pediatric medicine is the positive impact of physical activity programs on overall child health and wellbeing. This review article aims to highlight the physical, mental and social aspects of physical activity programs and explore how movement programs can contribute to a healthier next generation by highlighting their benefits for children's health. Materials and Methods In the search for scientific literature for this review, data from the US National Library of Medicine (PubMed), PsycINFO, MEDLINE, and SportDiscus were used, and the terms “movement programs’’,’’ overall health’’, ‘’ physical activity programs’’, and “children’s psychological health” were used. The relevant literature has also taken its source from the research of relevant articles from reference lists derived from data searches. Results In today's modern world, where children are becoming increasingly sedentary and spending more time indoors in front of screens, it is becoming increasingly clear how physical activity programs play a vital role in improving children's health. Therefore, physical activity programs appear to have an extremely important health impact on children's physical, socioemotional, and psychological health by providing them with opportunities to participate in structured physical activities such as sports, games, and exercise. Conclusion It is recommended that movement programs be introduced in early childhood to help children develop a habit of physical activity. These physical activity programs should be designed in a way that encourages children to engage in physical activity in a playful and non-competitive manner. It is also important to recognize that movement programs can contribute to the physical and psychological health of children, while also fostering their social development.

Avulsion and Soft Tissue Injuries of the Ulnar Collateral Ligament in Children and Adolescents

Background: Although pediatric medial epicondylar fractures and apophysitis are well studied, patterns of subapophyseal avulsion and ligamentous injuries of the medial elbow in this population merit investigation to inform optimal treatment strategies. Purpose: To describe the occurrence and demographic correlates of ulnar collateral ligament (UCL) avulsion and soft tissue injuries of the pediatric and adolescent elbow. Study Design: Cross-sectional study; Level of evidence, 3. Methods: An institutional review board–approved review was conducted to identify consecutive patients with medial elbow injuries treated in a tertiary pediatric sports medicine practice between 2016 and 2021. Radiographs were obtained during injury evaluation, and patients with nondisplaced medial epicondylar apophysitis and complete epicondylar fracture were excluded, resulting in 150 patients with soft tissue injuries occurring distal to the medial epicondyle apophysis (subapophyseal) for study. Radiographs were evaluated for bony avulsion of the UCL from either the medial epicondyle proximally or the ulnar sublime tubercle distally. Injuries without radiographic evidence of bony avulsion, but with clinical examination findings consistent with ligamentous injury, were classified as radiographically negative UCL injuries, and magnetic resonance imaging (MRI) was performed to further evaluate these injuries if moderate to severe medial swelling of the elbow or significant concern for medial structural injury was present on examination. These MRI scans were evaluated to classify the UCL injury and assess for periosteal or cartilaginous avulsions. Results: A total of 150 patients (mean age, 12.5 ± 3.4 years; 70 female), 55% (150/274) of the entire medial elbow injury population, had a subapophyseal injury. Of these patients, 62 had a bony avulsion detected on radiograph, and 88 had a radiographically negative injury. In addition to the 62 radiographic avulsions, the 61 MRI scans obtained on those radiographically negative injuries revealed 33 complete UCL disruptions, resulting in 63.3% (95/150) of patients sustaining a complete ligamentous disruption. With the MRI scans, 37 (61%) cases of cartilaginous or periosteal avulsion of the UCL were diagnosed. Overall, 66% of all 150 subapophyseal injuries had a bony, cartilaginous, or periosteal UCL avulsion. Patients with cartilaginous (mean age, 10.3 years) and bony (mean age, 10.6 years) avulsions were younger than those with central ligament injury (mean age, 14.2 years) or periosteal (mean age, 14.2 years) avulsions (P = .005). There was a significant association between the mechanism of injury and the location of UCL tear identified on MRI scans: traumatic falls were associated with distal tears, and throwing injuries were associated with proximal tears (P < .001). Conclusion: UCL central ligament and avulsion lesions may be frequently diagnosed after injury to the pediatric medial elbow, the majority of which are complete injuries, and may require MRI for diagnosis. The mechanism of injury may predict the location of ligamentous injury, and osteocartilaginous avulsions are more likely to present at younger ages than injuries to the soft tissue of the UCL or periosteum. The prevalence of these injuries merits further investigation into best protocols of nonoperative treatment or surgical repair techniques and outcomes.

Leading Paediatric Infectious Diseases-Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions.

Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.

Assessment of Bitterness in Non-Charged Pharmaceuticals with a Taste Sensor: A Study on Substances with Xanthine Scaffold and Allopurinol.

Taste sensors with an allostery approach have been studied to detect non-charged bitter substances, such as xanthine derivatives, used in foods (e.g., caffeine) or pharmaceuticals (e.g., etofylline). In this study, the authors modified a taste sensor with 3-bromo-2,6-dihydroxybenzoic acid and used it in conjunction with sensory tests to assess the bitterness of non-charged pharmaceuticals with xanthine scaffolds (i.e., acefylline and doxofylline), as well as allopurinol, an analogue of hypoxanthine. The results show that the sensor was able to differentiate between different levels of sample bitterness. For instance, when assessing a 30 mM sample solution, the sensor response to acefylline was 34.24 mV, which corresponded to the highest level of bitterness (τ = 3.50), while the response to allopurinol was lowest at 2.72 mV, corresponding to relatively weaker bitterness (τ = 0.50). Additionally, this study extended the application of the sensor to detect pentoxifylline, an active pharmaceutical ingredient in pediatric medicines. These results underscore the taste sensor's value as an additional tool for early-stage assessment and prediction of bitterness in non-charged pharmaceuticals.

Advanced Chemical and Imaging Methods for Studying Structure Morphology and Excipients Solid State Transformations in Pharmaceutical Multiparticulate Formulations

The formulation of paediatric medicines faces significant challenges to meet the requirements for safe and accurate administration, while maintaining a suitable taste. Multiparticulate formulations have a strong potential to address these challenges because they combine dose flexibility with ease of administration. Understanding the stability of multiparticulate formulations over storage as a function of time and environmental parameters, such as humidity and temperature, is important to manage their commercialisation and use. In this work, we have expanded the toolkit of available techniques for studying multiparticulates beyond those such as scanning electron microscopy (SEM) and confocal laser scanning microscopy. We include advanced methods of environmentally-controlled SEM to monitor temperature- and humidity-induced changes in-situ, and a variety of Raman spectroscopies including stimulated Raman scattering microscopy to identify and localise the different ingredients at the surface and inside the multiparticulates. These techniques allowed unprecedented monitoring of specific changes to the particulate structure and distribution of individual ingredients due to product aging. These methods should be considered as valuable novel tools for in-depth characterisation of multiparticulate formulations to further understand chemical changes occurring during their development, manufacturing and long-term storage. We envisage these techniques to be useful in furthering the development of future medicine formulations.