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Introduction: Stroke is a significant contributor to chronic impairment on a global scale, impacting millions of individuals each year. Despite the progress made in the field of stroke management, individuals frequently experience enduring sensorimotor and cognitive impairments that have a substantial influence on their quality of life and ability to live independently. Need of the study: Virtual Reality Training (VRT) consists of rigorous, repetitive sessions that promote cerebral-hemispheric integration through the creation of a stimulating environment that combines sensory and motor functions. It is anticipated that VRT and Transcranial Magnetic Stimulation (TMS) will stimulate the affected hemisphere while inhibiting the unaffected hemisphere. Voluntary movement is also crucial for interhemispheric interaction; therefore, the present research employs VRT for physical movements while stimulating across multiple regions of the brain. Aim: To investigate the combined efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) and Virtual Reality Training for sensorimotor and cognitive deficits among stroke patients. Materials and Methods: The present study will be a single-blind, prospective, randomised controlled trial recruiting 69 patients with unilateral stroke from Jaypee Hospital Noida, Uttar Pradesh, India for a continuous period of one year from July 2023 to June 2024 and will be allocated through block randomisation to one of the three treatment groups as per the inclusion and exclusion criteria. Group 1- Simultaneous repetitive TMS (rTMS) and VRT, Group 2- rTMS combined with Sham VRT, and Group 3- VRT protocol combined with Sham Stimulation. Fugl Meyer Assessment (FMA), Montreal Cognitive Assessment (MOCA), National Institutes of Health Stroke Scale (NIHSS), and Addenbrooke’s Cognitive Examination III (ACE III) will be measured at baseline and at the end of the fourth week.

Background: There are no established guidelines for the follow up of infants born after a prenatal diagnosis of a genomic copy number variant (CNV), despite their increased risk of developmental issues. The aims of this study were (i) to determine the perinatal outcomes of fetuses diagnosed with and without a CNV, and (ii) to establish a population-based paediatric cohort for long term developmental follow up. Methods: An Australian state-wide research database was screened for pregnant individuals who had a prenatal chromosomal microarray (CMA) between 2013–2019 inclusive. Following linkage to laboratory records and clinical referrer details, hospital records were manually reviewed for study eligibility. Eligible participants were mother–child pairs where the pregnancy resulted in a livebirth, the mother was able to provide informed consent in English (did not require a translator) and the mother was the primary caregiver for the child at hospital discharge after birth. Research invitations were sent by registered post at an average of six years after the prenatal diagnostic test. Statistical analysis was performed in Stata17. Results: Of 1832 prenatal records examined, 1364 (74.5%) mother–child pairs were eligible for recruitment into the follow up cohort. Of the 468 ineligible, 282 (60.3%) had 'no live pregnancy outcome' (209 terminations of pregnancy (TOP) and 73 miscarriages, stillbirths, and infant deaths), 157 (33.5%) required a translator, and 29 (6.2%) were excluded for other reasons. TOP rates varied by the type of fetal CNV detected: 49.3% (109/221) for pathogenic CNVs, 18.2% (58/319) for variants of uncertain significance and 3.3% (42/1292) where no clinically significant CNV was reported on CMA. Almost 77% of invitation letters were successfully delivered (1047/1364), and the subsequent participation rate in the follow up cohort was 19.2% (201/1047). Conclusions: This study provides Australia's first population-based data on perinatal outcomes following prenatal diagnostic testing with CMA. The relatively high rates of pregnancy loss for those with a prenatal diagnosis of a CNV presented a challenge for establishing a paediatric cohort to examine long term outcomes. Recruiting a mother–child cohort via prenatal ascertainment is a complex and resource-intensive process, but an important step in understanding the impact of a CNV diagnosis in pregnancy and beyond. Trial registration: ACTRN12620000446965p; Registered on April 6, 2020. [ABSTRACT FROM AUTHOR]

Introduction: Stroke is a significant contributor to chronic impairment on a global scale, impacting millions of individuals each year. Despite the progress made in the field of stroke management, individuals frequently experience enduring sensorimotor and cognitive impairments that have a substantial influence on their quality of life and ability to live independently. Need of the study: Virtual Reality Training (VRT) consists of rigorous, repetitive sessions that promote cerebral-hemispheric integration through the creation of a stimulating environment that combines sensory and motor functions. It is anticipated that VRT and Transcranial Magnetic Stimulation (TMS) will stimulate the affected hemisphere while inhibiting the unaffected hemisphere. Voluntary movement is also crucial for interhemispheric interaction; therefore, the present research employs VRT for physical movements while stimulating across multiple regions of the brain. Aim: To investigate the combined efficacy of Repetitive Transcranial Magnetic Stimulation (rTMS) and Virtual Reality Training for sensorimotor and cognitive deficits among stroke patients. Materials and Methods: The present study will be a singleblind, prospective, randomised controlled trial recruiting 69 patients with unilateral stroke from Jaypee Hospital Noida, Uttar Pradesh, India for a continuous period of one year from July 2023 to June 2024 and will be allocated through block randomisation to one of the three treatment groups as per the inclusion and exclusion criteria. Group 1- Simultaneous repetitive TMS (rTMS) and VRT, Group 2- rTMS combined with Sham VRT, and Group 3- VRT protocol combined with Sham Stimulation. Fugl Meyer Assessment (FMA), Montreal Cognitive Assessment (MOCA), National Institutes of Health Stroke Scale (NIHSS), and Addenbrooke’s Cognitive Examination III (ACE III) will be measured at baseline and at the end of the fourth week. [ABSTRACT FROM AUTHOR]

Many medicinal products are initially developed and tested in adults, and often, only a limited amount of data on their safety and efficacy in children exist. Consequently, paediatric healthcare providers sometimes need to make informed decisions about using medicinal products in children based on available fragmentary data. Ethical guidelines emphasise the importance of protecting children and ensuring they receive safe and effective medical treatments. Paediatric clinical trials should be conducted to provide evidence- based care with specific attention to minimise risks to children. This highlights the dilemma of finding a balance between protecting children and adolescents (and avoiding unnecessary clinical trials) and obtaining reliable, robust and justified data to treat them adequately and not in an off-label manner with unknown risks. For years, paediatricians maintained that children and adolescents are not treated based on up-to-date scientific knowledge and justification. The slogan "children are not small adults" summarised the concerns in a catch phrase. Different stakeholders have taken a variety of actions to address this concern. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Paediatric Clinical Care Pathways (CCPs) are developed for specific health conditions or patient populations and are designed to standardise care across different healthcare settings, including hospitals, clinics, and outpatient settings. These care pathways outline the clinical guidelines for diagnosis, treatment, and follow-up of specific medical conditions. They provide a framework for the delivery of care based on the best available evidence and tailored to each patient's individual needs. This overview is aimed at identifying the available evidence for the effective use of CCPs in paediatric patients with Lower Respiratory Tract Infection (LRTI). It reviews the nature of CCPs of LRTI, their benefits, strategies to implement them, steps involved in development of CCPs and the disease condition in paediatric population for whom the CCPs are used so far. The article also gives an account of limitations of using CCPs.

Background/Objective: The relationship between heart rate and heart rate variability (HRV) indices has been repeatedly studied in adults but limited data are available on the relationship in paediatric populations. Methods: Continuous 12-lead electrocardiograms were recorded in 1016 healthy children and adolescents (534 females) aged 4 to 19 years during postural manoeuvres with rapid changes between 10-min positions of supine → sitting → standing → supine → standing → sitting → supine. In each position, the averaged RR interval was measured together with four HRV indices, namely the SDNN, RMSSD, quasi-normalised high-frequency components (qnHF), and the proportions of low- and high-frequency components (LF/HF). In each subject, the slope of the linear regression between the repeated HRV measurements and the corresponding RR interval averages was calculated. Results: The intra-subject regression slopes, including their confidence intervals, were related to the age and sex of the subjects. The SDNN/RR, RMSSD/RR, and qnHF/RR slopes were significantly steeper (p < 0.001) and the (LF/HF)/RR slopes were significantly shallower (p < 0.001) in younger children compared to older children and adolescents. Conclusions: The study suggests that sympathetic and vagal influences on heart rate are present in both younger and older children. With advancing age, the sympatho-vagal balance gradually develops and allows the vagal control to suppress the sympathetic drive towards higher heart rates seen in younger age children. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the oral health status among allogeneic transplant recipients who were seen in a multidisciplinary graft‐versus‐host disease paediatric clinic at the University of California, San Francisco (UCSF). Methods: This was a retrospective cohort study of patients who underwent allogeneic transplants and were seen in the graft‐versus‐host disease paediatric clinic between January 2010 and September 2021. Demographic, medical and oral health data were recorded and analysed using descriptive statistics. Results: A total of 25 patients were seen in the paediatric graft‐versus‐host disease clinic (68% males) with a median age of 12 years at the time of transplant were included. Among them, 12 patients (48%) were diagnosed with oral chronic GVHD, 11 (44%) with dry mouth, four (16%) with oral pseudomembranous candidiasis, one (4%) with recrudescent Herpes Simplex Virus (HSV) infection and one (4%) with mammalian target of rapamycin‐inhibitor stomatitis and were managed by the oral medicine team, accordingly with medications, such as topical steroids (44%) and anti‐fungal (20%). Conclusions: HSCT recipients may present with a variety of oral complications. Patients may benefit by a multi‐disciplinary approach including a dental specialist as part of the cancer care team. [ABSTRACT FROM AUTHOR]

Paediatric Clinical Care Pathways (CCPs) are developed for specific health conditions or patient populations and are designed to standardise care across different healthcare settings, including hospitals, clinics, and outpatient settings. These care pathways outline the clinical guidelines for diagnosis, treatment, and follow-up of specific medical conditions. They provide a framework for the delivery of care based on the best available evidence and tailored to each patient's individual needs. This overview is aimed at identifying the available evidence for the effective use of CCPs in paediatric patients with Lower Respiratory Tract Infection (LRTI). It reviews the nature of CCPs of LRTI, their benefits, strategies to implement them, steps involved in development of CCPs and the disease condition in paediatric population for whom the CCPs are used so far. The article also gives an account of limitations of using CCPs. [ABSTRACT FROM AUTHOR]

Many medicinal products are initially developed and tested in adults, and often, only a limited amount of data on their safety and efficacy in children exist. Consequently, paediatric healthcare providers sometimes need to make informed decisions about using medicinal products in children based on available fragmentary data. Ethical guidelines emphasise the importance of protecting children and ensuring they receive safe and effective medical treatments. Paediatric clinical trials should be conducted to provide evidence-based care with specific attention to minimise risks to children. This highlights the dilemma of finding a balance between protecting children and adolescents (and avoiding unnecessary clinical trials) and obtaining reliable, robust and justified data to treat them adequately and not in an off-label manner with unknown risks. For years, paediatricians maintained that children and adolescents are not treated based on up-to-date scientific knowledge and justification. The slogan “children are not small adults” summarised the concerns in a catch phrase. Different stakeholders have taken a variety of actions to address this concern.

This study aimed to evaluate the distribution of plasma troponin I concentration and establish the 99th percentile reference for hs-cTnI in a hospitalized population without a cardiovascular discharge diagnosis from the Shandong area.

Paediatric vision impairment is a significant public health issue because of the associated health and economic consequences. This study aimed to determine the clinical characteristics and causes of vision impairment in paediatric patients who presented to a university-based low vision eye clinic in KwaZulu-Natal. The study used a retrospective design and included all paediatric patients with vision impairment who were younger than 18 years and presented to the university-based low vision eye clinic between January 2015 and December 2019. The sample consisted of 156 children with vision impairment with a similar proportion of males (n = 82) and females (n = 74). The mean age of the children was 13.5 ± 2.8 years, with a range of 5–17 years. Based on the best-corrected visual acuity (VA), most of the children (n = 111) had moderate vision impairment (VA worse than 6/18 to 6/60). The most common causes of paediatric vision impairment included albinism (n = 54), refractive error (n = 11), cataract (n = 10), and glaucoma (n = 10). The retina (n = 74) and normal globe (n = 26) were the most affected anatomical sites. Spectacles were prescribed to almost half of the sample (n = 76). A total of 126 optical and non-optical devices were recommended with telescopes (n = 43) and sun-protective measures (n = 20) being the most common. Paediatric vision impairment can have a negative impact on the quality of life. Local data related to the characteristics of children with vision impairment can be used to enhance the services provided in this university-based low vision clinic. This is important as efforts aimed at early identification, management, and rehabilitation will help minimise functional limitations and improve the quality of life of affected children. [ABSTRACT FROM AUTHOR]

Introduction. In recent years, there has been an increase in anterior cruciate ligament (ACL) injuries during childhood and adolescence. Aim. The aim of this study is to observe the diameter and length of the graft change in the postoperative period. Materials and methods. The study group consisted of 21 adolescents (11 boys and 10 girls) who underwent ACL reconstruction using hamstring and gracilis tendon grafts. MRI evaluations were performed at 3-6 and 24-26 months postoperatively to assess the width and length of the graft. The graft cross-sectional dimension was measured at the mid-substance of the tendons on sagittal scans in T1 and T2-weighted sequences. Length measurement was performed on axial ACL scans at its central portion (assessing midsubstance length). The collected measurements from both postoperative periods were compared and statistically analysed. Results. MRI analysis conducted postoperatively showed a statistically significant decrease in graft crosssectional dimension, from an average 7.21-5.82 mm. The intra-articular graft length measured in MRI at 3-6 months post-surgery averaged 21.52 mm, while the length measured at 24-26 months post-surgery averaged 22.42 mm. Conclusions. Postoperative MRI analysis of reconstructed ACLs in adolescents with active growth plates demonstrated a reduction in graft cross-sectional dimension and a slight increase in graft length. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between serum vitamin D levels and febrile seizures in the paediatric patients. Study Design: Case-Control Study. Place and Duration of Study: Abbasi Shaheed Hospital, Karachi Pakistan, from Mar 2020 to Mar 2021. Methodology: The study included all pyrexia paediatric patients, both with and without febrile seizures, as cases and controls. Children aged below six months or older than 60 months, with a previous history of afebrile seizures, diagnosed with central nervous system infection, dehydration, or electrolyte disturbance, were excluded from the study. Serum vitamin D levels and other demographic data were documented. Results: The study included 86 cases and controls. The mean age of cases was 28.07±16.47, and the controls were 26.38±15.72 months. The rate of vitamin D insufficiency was three times more likely in cases compared to controls, i.e. [OR, 95% CI: 3.95 (2.084—7.489)] with p=0.0001. Conclusion: Vitamin D deficiency is substantially more likely in the case than in the control group. As a result, children with febrile seizures should have their serum vitamin D levels tested.

Introduction. In recent years, there has been an increase in anterior cruciate ligament (ACL) injuries during childhood and adolescence.Aim. The aim of this study is to observe the diameter and length of the graft change in the postoperative period.Materials and methods. The study group consisted of 21 adolescents (11 boys and 10 girls) who underwent ACL reconstruction using hamstring and gracilis tendon grafts. MRI evaluations were performed at 3-6 and 24-26 months postoperatively to assess the width and length of the graft. The graft cross-sectional dimension was measured at the mid-substance of the tendons on sagittal scans in T1 and T2-weighted sequences. Length measurement was performed on axial ACL scans at its central portion (assessing mid-substance length). The collected measurements from both postoperative periods were compared and statistically analysed. Results. MRI analysis conducted postoperatively showed a statistically significant decrease in graft cross-sectional dimension, from an average 7.21-5.82 mm. The intra-articular graft length measured in MRI at 3-6 months post-surgery averaged 21.52 mm, while the length measured at 24-26 months post-surgery averaged 22.42 mm. Conclusions. Postoperative MRI analysis of reconstructed ACLs in adolescents with active growth plates demonstrated a reduction in graft cross-sectional dimension and a slight increase in graft length.

Abstract Background Children tend to have milder forms of COVID-19 than adults, however post-acute complications have been observed also in the paediatric population. In this study, we compared COVID-19-related outcomes and long-term complications between paediatric and adult patients infected by SARS-CoV-2. Methods The study is based on individuals enrolled from October 2020 to June 2021 in the DECO COVID-19 multicentre prospective study supported by the Italian Ministry of Health (COVID-2020–12371781). We included individuals with RT-PCR -confirmed SARS-CoV-2 infection, who were evaluated in the emergency department and/or admitted to COVID-dedicated wards. The severity of SARS-CoV-2 infection was compared across age groups (children/adolescents aged

Abstract Background The evaluation of clinical evidence takes account of health benefit (efficacy and safety) and the degree of certainty in the estimate of benefit. In orphan indications practical and ethical challenges in conducting clinical trials, particularly in paediatric patients, often limit the available evidence, rendering structured evaluation challenging. While acknowledging the paucity of evidence, regulators and reimbursement authorities compare the efficacy and safety of alternative treatments for a given indication, often in the context of the benefits of other treatments for similar or different conditions. This study explores the feasibility of using the Institute for Clinical and Economic Review (ICER) Evidence Rating Matrix for Comparative Clinical Effectiveness in structured assessment of both the magnitude of clinical benefit (net health benefit, NHB) and the certainty of the effect estimate in a sample of orphan therapies for paediatric indications. Results Eleven systemic therapies with European Medicines Agency (EMA) orphan medicinal product designation, licensed for 16 paediatric indications between January 2017 and March 2020 were identified using OrphaNet and EMA databases and were selected for evaluation with the ICER Evidence Rating Matrix: burosumab; cannabidiol; cerliponase alfa; chenodeoxycholic acid (CDCA); dinutuximab beta; glibenclamide; metreleptin; nusinersen; tisagenlecleucel; velmanase alfa; and vestronidase alfa. EMA European Public Assessment Reports, PubMed, EMBASE, the Cochrane Library, Clinical Key, and conference presentations from January 2016 to April 2021 were searched for evidence on efficacy and safety. Two of the identified therapies were graded as “substantial” NHB: dinutuximab beta (neuroblastoma maintenance) and nusinersen (Type I SMA), and one as “comparable” NHB (CDCA). The NHB grade of the remaining therapies fell between “comparable” and “substantial”. No therapies were graded as having negative NHB. The certainty of the estimate ranged from “high” (dinutuximab beta in neuroblastoma maintenance) to “low” (CDCA, metreleptin and vestronidase alfa). The certainty of the other therapies was graded between “low” and “high”. The ICER Evidence Rating Matrix overall rating “A” (the highest) was given to two therapies, “B+” to 6 therapies, “C+” to five therapies, and “I” (the lowest) to three therapies. The scores varied between rating authors with mean agreement over all indications of 71.9% for NHB, 56.3% for certainty and 68.8% for the overall rating. Conclusions Using the ICER Matrix to grade orphan therapies according to their treatment benefit and certainty is feasible. However, the assessment involves subjective judgements based on heterogenous evidence. Tools such as the ICER Matrix might aid decision makers to evaluate treatment benefit and its certainty when comparing therapies across indications.

Abstract Background Association of vitamin D (25(OH)D) deficiency with obesity and diabetes has been well-established in paediatric and adult populations. This study aims to report the association of 25(OH)D deficiency with body composition and prevalence of 25(OH)D deficiency in Emirati children and adolescents, who attended a diabetes centre in the United Arab Emirates. Methods Using Abu Dhabi Diabetes and Obesity Study cohort, type 1 diabetes (T1D) and normoglycaemic (NG) participants between 4–19 years of age were selected. WHO criteria were used to define 25(OH)D cut-offs: deficient ( 50 nmol/L). Based on CDC recommendations, BMI percentile was categorised as underweight, normal weight, overweight and obesity. Results After age and sex matching, 148 T1D cases and 296 NG controls were identified. 25(OH)D deficiency was observed in 22.3% (n = 33) T1D and 40.5% (n = 120) NG participants. 25(OH)D levels were lower in adolescents (15 – 19 years) than children (4 – 7 years) in both T1D and NG groups (p = 0.018 vs p

Introduction: Sepsis is an important cause of mortality and morbidity in children. Paediatric sepsis in India has a high mortality rate of 40%, which necessitates early risk stratification and timely escalation of level of care for improving survival. Biochemical markers such as serum lactate are helpful in such cases. Lactate is frequently measured to estimate the extent of hypoxia at cellular level, and it correlates well with indices of end organ perfusion. Serum lactate level can be measured at bed side with rapid turn around time. Lactate testing is simple, inexpensive and reasonably sensitive tool for prognostication. Very few studies regarding lactate and lactate clearance have been done in paediatric population. Materials and Methods: 46 children aged between 1 month and 14 years of age were studied. Arterial blood sample was collected, and lactate levels were measured bedside using Abbott i-STAT. 300 handheld blood analyser at admission, 6 hours, 12 hours, 18 hours, 24 hours, 36 hours and 48 hours. Lactate clearance was calculated. PRISM III score (Pediatric severity index) was done on all patients on admission. Chi-square test was applied to check the dependency of different parameters on outcome (survival or non-survival) of the patients. Unpaired t-test is used to compare the means of different parameters since the standard deviation of the population is unknown. Spearman's correlation coefficient between blood lactate on admission and PRISM III score was obtained. Sensitivity, specificity for diagnostic tests were obtained. Receiver's operative curve was also obtained to get the area under the curve and cut off point for prediction. Results: Out of 46 cases, 45.7% were males and 54.3% were females. Majority (45.7%) cases were in the age groups of 1 to 5 years and 21.7% belonged to age <1 year. Mean age was 5.3 years in nonsurvivors and 4.9 years in survivors group. Lower respiratory tract infection was the major cause of PICU admission (43.47%). Majority (78.3%) had PRISM III score of 1 to 5. Majority of study participants had PRISM III score ranging between 1-5, followed by 11-15. Among 46 cases 91.3% had hyperlactatemia (>2mmol/L) on admission. Among 46 cases, 19.6% were non-survivors. Inotropes usage was 18.9% in survivors and 66.7% in non-survivors. This difference was found to be statistically significant (P value <0.05). Conclusion: Mean lactate levels were always higher in non-survivors as compared to survivors at all points of time from admission till 48 hours. Area under the curve for lactate levels was significant at all time points for predicting mortality. The best cut off values of lactate for predicting mortality with maximum sensitivity and specificity were 4.94 mmol/l at admission, 4.15 mmol/l at 6 hours, 4 mmol/l at 12 hours, 3.75 mmol/l at 18 hours, 3.22 mmol/l at 24 hours, 2.85 mmol/l at 36 hours and 2.55 mmol/l at 48 hours. Mean PRISM III score was more in non-survivors (15.00) as compared to survivors (2.51) and this difference was found to be statistically significant. [ABSTRACT FROM AUTHOR]

Background: Children tend to have milder forms of COVID-19 than adults, however post-acute complications have been observed also in the paediatric population. In this study, we compared COVID-19-related outcomes and long-term complications between paediatric and adult patients infected by SARS-CoV-2. Methods: The study is based on individuals enrolled from October 2020 to June 2021 in the DECO COVID-19 multicentre prospective study supported by the Italian Ministry of Health (COVID-2020–12371781). We included individuals with RT-PCR -confirmed SARS-CoV-2 infection, who were evaluated in the emergency department and/or admitted to COVID-dedicated wards. The severity of SARS-CoV-2 infection was compared across age groups (children/adolescents aged < 18 years, young/middle-aged adults aged 18–64 years and older individuals) through the relative risk (RR) of severe COVID-19. Severity was defined by: 1) hospitalization due to COVID-19 and/or 2) need or supplemental oxygen therapy. RR and corresponding 95% confidence intervals were estimated using log-binomial models. Results: The study included 154 individuals, 84 (54.5%) children/adolescents, 50 (32.5%) young/middle-aged adults and 20 (13%) older adults. Compared to young/middle-aged adults the risk of hospitalization was lower among paediatric patients (RR: 0.49, 95% CI: 0.32–0.75) and higher among older adults (RR: 1.52, 95% CI: 1.12–2.06). The RR of supplemental oxygen was 0.12 (95% CI: 0.05–0.30) among children/adolescents and 1.46 (95% CI: 0.97–2.19) among older adults. Three children developed multisystem inflammatory syndrome (MIS-C), none was admitted to intensive care unit or reported post-acute Covid-19 complications. Conclusions: Our study confirms that COVID-19 is less severe in children. MIS-C is a rare yet severe complication of SARS-CoV-2 infection in children and its risk factors are presently unknown. [ABSTRACT FROM AUTHOR]

Hypnoanalgesia is a promising non-pharmacologic adjunct technique in paediatric interventions. Its safety, efficiency, and impacts on paediatric cardiac catheterisation (CC) are unknown. Methods: In a prospective study, patients aged <16 years who underwent CC under hypnoanalgesia from January to December 2021 were included. Pain and anxiety were assessed using the analgesia nociception index (ANI) and the visual analogue scale (VAS). Results: Sixteen patients were included; the mean age was 10.5 years, and the mean weight was 37 kg. Catheterisations were interventional in 10 patients (62.5%). Hypnoanalgesia indications were general anaesthesia (GA) contraindication in four patients (25.0%), the need for accurate pressure measurements in three patients (18.7%), and interventionist/patient preferences in nine (56.3%). CC was accomplished in 15 patients (93.7%), even in complicated cases. In one case, pulmonary artery pressures were normalised compared to previous catheterisation under local anaesthesia alone. The VAS score was under 5/10 for all patients. The ANI remained above 50 (no painful zone) for all but one patient. There was no significant decrease in the ANI during the intervention compared to the baseline (p = 0.62). No complications were reported. Conclusion: Paediatric CC is feasible and safe under hypnoanalgesia, even in complicated cases. Hypnoanalgesia was efficient in managing pain and stress, and it ensures more reliable pressure measurements. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to identify which factors could determine endoscopic therapy's failure in the paediatric patients with primary vesicoureteral reflux (VUR). Methods: We reviewed data from patients who underwent endoscopic surgery for primary reflux. We performed a multivariate logistic regression analysis considering factors conditioning therapeutic failure. All the tests were performed considering significant values of p < 0.05. Statistical analysis was performed with the SPSS 19.0 program. Study sample was homogenised by just including patients with primary reflux and excluding both patients with secondary reflux and patients with functional lower urinary conditions. Results: A total of 96 patients were included for review. Median age at surgery was 28 months. The overall success rate of endoscopic surgery for vesicoureteral reflux was 57%. Female sex, age under 24 months at the time of surgical intervention and having suffered a urinary tract infection (UTI) despite antibiotic prophylaxis are statistically significant risk factors for therapy failure. Conclusions: Nonetheless, differences between series could explain these differences in success rates. The lack of standardisation of the definition of 'success', the heterogeneity of patients included, and variables such as the degree of reflux, the presence of dysfunctional voiding, age or follow-up make it difficult to compare the success rate between series. Therefore, homogenisation of study samples assessing the evolution of primary reflux and response to endoscopic therapy is warranted. Level of evidence: Not applicable [ABSTRACT FROM AUTHOR]

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.

Introduction: ENT problems are one of the common causes that warrant a visit to the doctor both in rural and urban set ups. Paediatric population constitutes 35 % of world's total population. Since India is a developing country with growing economy, its health system is still evolving. Ear, nose and throat diseases are serious public health problem with universal distribution affecting all age group especially paediatric age group. Materials and Methods: This study was conducted in the Department of Pediatrics, Maharaja Institute of Medical Science, Vizianagaram. 417 children between the ages of 0-15, attending the ENT department in our hospital were included in the study. Demographic details such as age, sex, socio-economic status were taken. Clinical history and examination for common ENT complaints and disorders was also taken for all patients. Results: There was a predominance of females over males in our study. 159 (38%) patients were males, 258 (62%) were females. More number of disorders was concentrated in the 6-15 years age group, with more than 45% of the cases. Among the 103 ear disorders, chronic suppurative otitis media was the most common disorder accounting for 27.1% of the total cases and 54.9% of the ear disorders. Otitis media with effusion accounted for 20% of the cases. There were very few cases of otomycosis which were 5.8% of the ear diseases. Rhinitis was the most common of the nasal disordes with 48.3% followed by chronicsinusitis (17.2%). Infective rhinitis accounted for 12.5% of the nasal diseases. Pharyngitis (38.2%) was the most common disorder of the throat followed by tonsillitis (33.3%). Conclusion: Our study suggests that Otitis media, pharyngitis, tonsillitis and rhinitis are the most common diseases of Ear, nose and Throat. Although many of the diseases are not much of a health concern, they are significant causes of pediatric morbidility. Therefore, this study provides the basic information of the prevalent disorders in ENT in our area, so that relevant development of the medical setup and treatment can be set up by the hospital. [ABSTRACT FROM AUTHOR]

Background: The evaluation of clinical evidence takes account of health benefit (efficacy and safety) and the degree of certainty in the estimate of benefit. In orphan indications practical and ethical challenges in conducting clinical trials, particularly in paediatric patients, often limit the available evidence, rendering structured evaluation challenging. While acknowledging the paucity of evidence, regulators and reimbursement authorities compare the efficacy and safety of alternative treatments for a given indication, often in the context of the benefits of other treatments for similar or different conditions. This study explores the feasibility of using the Institute for Clinical and Economic Review (ICER) Evidence Rating Matrix for Comparative Clinical Effectiveness in structured assessment of both the magnitude of clinical benefit (net health benefit, NHB) and the certainty of the effect estimate in a sample of orphan therapies for paediatric indications. Results: Eleven systemic therapies with European Medicines Agency (EMA) orphan medicinal product designation, licensed for 16 paediatric indications between January 2017 and March 2020 were identified using OrphaNet and EMA databases and were selected for evaluation with the ICER Evidence Rating Matrix: burosumab; cannabidiol; cerliponase alfa; chenodeoxycholic acid (CDCA); dinutuximab beta; glibenclamide; metreleptin; nusinersen; tisagenlecleucel; velmanase alfa; and vestronidase alfa. EMA European Public Assessment Reports, PubMed, EMBASE, the Cochrane Library, Clinical Key, and conference presentations from January 2016 to April 2021 were searched for evidence on efficacy and safety. Two of the identified therapies were graded as "substantial" NHB: dinutuximab beta (neuroblastoma maintenance) and nusinersen (Type I SMA), and one as "comparable" NHB (CDCA). The NHB grade of the remaining therapies fell between "comparable" and "substantial". No therapies were graded as having negative NHB. The certainty of the estimate ranged from "high" (dinutuximab beta in neuroblastoma maintenance) to "low" (CDCA, metreleptin and vestronidase alfa). The certainty of the other therapies was graded between "low" and "high". The ICER Evidence Rating Matrix overall rating "A" (the highest) was given to two therapies, "B+" to 6 therapies, "C+" to five therapies, and "I" (the lowest) to three therapies. The scores varied between rating authors with mean agreement over all indications of 71.9% for NHB, 56.3% for certainty and 68.8% for the overall rating. Conclusions: Using the ICER Matrix to grade orphan therapies according to their treatment benefit and certainty is feasible. However, the assessment involves subjective judgements based on heterogenous evidence. Tools such as the ICER Matrix might aid decision makers to evaluate treatment benefit and its certainty when comparing therapies across indications. [ABSTRACT FROM AUTHOR]

Background: Association of vitamin D (25(OH)D) deficiency with obesity and diabetes has been well-established in paediatric and adult populations. This study aims to report the association of 25(OH)D deficiency with body composition and prevalence of 25(OH)D deficiency in Emirati children and adolescents, who attended a diabetes centre in the United Arab Emirates. Methods: Using Abu Dhabi Diabetes and Obesity Study cohort, type 1 diabetes (T1D) and normoglycaemic (NG) participants between 4–19 years of age were selected. WHO criteria were used to define 25(OH)D cut-offs: deficient (< 30 nmol/L), insufficient (30-50 nmol/L) and sufficient (> 50 nmol/L). Based on CDC recommendations, BMI percentile was categorised as underweight, normal weight, overweight and obesity. Results: After age and sex matching, 148 T1D cases and 296 NG controls were identified. 25(OH)D deficiency was observed in 22.3% (n = 33) T1D and 40.5% (n = 120) NG participants. 25(OH)D levels were lower in adolescents (15 – 19 years) than children (4 – 7 years) in both T1D and NG groups (p = 0.018 vs p < 0.001). Females were more likely to be 25(OH)D deficient in both groups. Children and adolescents with BMI ≥ 95th percentile were more likely to be 25(OH)D deficient than those with normal weight (OR: 2.69; 95% CI: 1.56, 4.64). Adiposity measures and 25(OH)D levels correlated negatively in both groups (T1D p < 0.01, NG p < 0.001). Conclusion: Vitamin D 25(OH)D deficiency is notably prevalent in Emirati children and adolescents despite adequate sunlight throughout the year. The prevalence was lower in those with T1D which may be indicative of treatment compliance in this population. This study also confirms important negative association of serum 25(OH)D levels with body mass and obesity in this population. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence and repeatability of high‐order aberrations (HOAs) from non‐cyclopleged eyes in 1515 children and adolescents 2.5–18 years of age. Methods: The Leipzig Research Centre for Civilization Diseases (LIFE)‐Child study is a population‐based, prospective, observational single‐centre study that investigates the development of children and adolescents in Germany. Wavefront measurements were repeated three times in each eye of 1515 healthy subjects. Results were described by 36 Zernike coefficients for a 5 mm reference pupil diameter. Short‐term repeatability is given for each coefficient. The impact on vision is described by the root mean squared (RMS) value of the HOA Zernike coefficients. Results: High‐order aberrations were dominated by five contributions. For 1004 right eyes: spherical aberration (c12 = 0.06 ± 0.07 μm), coma (c7 = 0.03 ± 0.09 μm, c8 = 0.03 ± 0.06 μm) and trefoil (c6 = −0.01 ± 0.07 μm, c9 = 0.008 ± 0.06 μm). The RMS value was 0.18 ± 0.06 μm. Modes higher than fourth order do not contribute clinically to the aberrations. HOAs show no clinically significant dependency with age. Instead, HOA values agree well with previous results on aberrations in adult eyes. Spherical aberration was highly correlated between the two eyes. Repeatability was worst for coma, 0.033 μm, due to variability in the alignment of the pupil centre. The left eye showed, on average, a 0.08 mm larger pupil diameter than the right eye (p < 0.02). Conclusions: Across the age span from 2.5 to 18 years, we see the same distribution of HOA as for adults. We established that only five Zernike coefficients, spherical aberration, coma and trefoil were of clinical significance in healthy eyes. A high correlation between the two eyes for spherical aberration suggests a common blueprint for each eye in any one subject. [ABSTRACT FROM AUTHOR]

Background: Morphological differences that can lead to cerebellar volume changes are associated with the pathogenesis of paediatric diseases. The aim of this study was to examine cerebellum volume in a healthy paediatric population. Materials and methods: To provide MRI‐based volumetric measurements of the cerebellum, images from the years 2019 to 2021 were scanned retrospectively. A total of 100 images, including the paediatric population aged 0–15 years, were imported into the volBrain software. Volumetric segmentations were obtained automatically, and each lobular cerebellar volume was obtained. The samples were divided into groups of 0–2 years (n = 18), 3–5 years (n = 24), 6–11 years (n = 34) and 12–15 years (n = 24). Obtained cerebellar volumes, age groups, gender and bilateral side comparisons were made. Results: In the comparative analyses performed for the total cerebellum and each of the 12 lobular segments, statistically significant differences were found between the age groups in all measurements except Crus II, lobules VIIB, VIIIA and VIIIB (p < 0.05). In multiple comparison tests, statistically significant differences were found between defined age groups, especially infants and toddlers and early adolescence groups (p < 0.05). There was a significant positive correlation between the ages of the subjects and their cerebellum volumes (p < 0.05). Statistically significant differences were found in lobules I–II, VI, VIIIB, IX and X in right and left side volumes (p < 0.05). Conclusion: There is a tendency to increase in cerebellar volume during the transition from childhood to adolescence. The cerebellum has volumetric differences in the first years of life and during adolescence. When the development of a healthy cerebellum is analysed based on volumetric segmentation, differences are observed. The findings of this study may be useful in confirming various theories attributed to the cerebellum in the clinic. [ABSTRACT FROM AUTHOR]

Key message Treatment with pollen allergen specific-immunotherapy improved health-related quality of life in children. Higher symptom scores were associated with lower perceived health-related quality of life. The proportion of children with severe or very severe symptoms from eyes, Nose and/or lungs had significantly decreased after 1 year of pollen SCIT and was maintained during the treatment years

Carbamazepine is a medicine used to manage epilepsy and partial or tonic-clonic seizures. This study aimed at formulating and obtaining carbamazepine orodispersible tablets for paediatric use at a 50 mg dose, with a diameter not greater than 6 mm and a tablet weight of 80 mg, through a direct compression process. The SeDeM pre-formulation/formulation method was used to define the characteristics of both carbamazepine and the selected excipients for direct compression. This study succeeded in formulating and obtaining the proposed tablets. Following the application of the SeDeM method, the tablets met the mass uniformity test and showed appropriate hardness values for orodispersible tablets. The tablets also met the United States Pharmacopeia (USP) test specifications at t = 60 min. The orodispersible tablets obtained may improve compliance with paediatric treatment with carbamazepine, ensuring the safety and effectiveness of the medicine.

Among children who sustain mild traumatic brain injury (mTBI), 10–30% develop a cluster of cognitive, physical, and emotional symptoms commonly referred to as post-concussion syndrome (PCS). Symptoms typically resolve within 7–10 days, but a minority of patients report symptoms that persist for months or even years. The aim of our study was to identify a neurobiochemical marker after mTBI that can predict the presence of post-concussion syndrome three months after head injury in paediatric patients. Children between 7 and 16 years of age who had head trauma and no other complaints were included. Three months after the initial visit, participants or parents/guardians were interviewed in person about the children's PCS symptoms using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The mean value of S100B protein in serum in 38 patients without signs of PCS was 0.266 μg L−1, with a 95% confidence interval (CI) of 0.221 − 0.310 μg L−1. Among the 22 patients with signs of PCS, the mean value of S100B protein in serum was 0.845 μg L−1, with a 95% CI of 0.745–0.945 μg L−1. Patients with signs of PCS had higher S100B protein levels than those without signs of PCS (p < 0.0001). Our prospective study showed that S100B protein is a useful neurobiomarker for detecting paediatric patients at risk for post-concussion syndrome. We found that the biomarker S100B correlated with the severity of traumatic brain injury (number of lesions on CT) and the presence of post-concussion syndrome. [ABSTRACT FROM AUTHOR]

Although the safety profiles of mRNA COVID-19 vaccines (mRNA-1273 and BNT162b2) were evaluated in pre-authorization clinical trials, real-world data allow us to better define their benefit/risk ratio in the paediatric population. The current study aimed to evaluate the safety profiles of mRNA COVID-19 vaccines in children by analysing the pharmacovigilance data of the European spontaneous reporting system database EudraVigilance (EV) in the period from 1 January 2021, to 1 October 2022. During our study period, overall 4838 ICSRs related to mRNA COVID-19 vaccines referring to 5–11-year-old subjects were retrieved from EV, of which 96.9% were related to BNT162b2 and 49.3% were related to males. A total of 12,751 Adverse Events Following Immunization (AEFIs) were identified, of which 38.7% were serious. The most frequently reported AEFIs were pyrexia, headache, and vomiting. Only 20 Individual Case Safety Reports (ICSRs) reported Multisystem Inflammatory Syndrome (MIS) as an AEFI, all related to BNT162b2. The majority of MIS cases were females, and six cases were completely resolved at the time of reporting. Our results show a favourable risk–benefit profile for all mRNA COVID-19 vaccines in this paediatric sub-population, supporting their use in children. Considering the peculiarity and fragility of children, continuous safety monitoring of COVID-19 vaccines is required. [ABSTRACT FROM AUTHOR]

Background: The immunological effect of allergen-specific immunotherapy is well documented, but few studies have examined the long-term effects of pollen subcutaneous immunotherapy (SCIT) on health-related quality of life (HRQoL) in children and adolescents. Therefore, the aims of this study were to evaluate the effect of pollen SCIT on HRQoL and to assess the association between HRQoL and symptoms among children and adolescents with allergic rhinoconjunctivitis in a 3-year follow-up. Methods: A prospective cohort study was conducted at a paediatric clinic in Sweden, including 158 children (5–16 years) on SCIT (birch and/or grass). Health-related quality of life, measured with DISABKIDS, symptom scores and allergen-specific IgE and IgG4 antibodies (blood test), were assessed at start, and after 1, 2 and 3 years of treatment. ANOVA and t-test were used to analyse differences over time, between groups and linear mixed model for the association between HRQoL and influencing factors. Results: After 1 year of pollen SCIT, HRQoL improved from 79.5 to 85.1 (p < 0.001), and the improvements were maintained (mean 1 years, 84.8, 3 years 87.2). Symptom scores decreased after 1 year, mean 19.9 to 11.5 (p < 0.001) and were maintained for year two (11.9) and year three (10.3). The proportion of children with severe or very severe symptoms decreased from 35.6% to 4.5% after 1 year of SCIT. Health-related quality of life was associated with symptoms at all measured timepoints (p = 0.001–0.031); higher symptom scores were associated with lower perceived HRQoL. Allergen-specific IgE antibodies decreased, birch from 151.0 to 76.8 kU/L (p < 0.001), and IgG4 antibodies increased, birch from 2.2 to 17.6 g/L (p < 0.001), grass from 0.5 to 14.3 g/L (p < 0.001), during the study period. Conclusion: After 1 year of pollen SCIT, HRQoL improved, and symptoms decreased; these changes were maintained during the study period. The proportion of severe and very severe symptoms significantly decreased. Key message: Treatment with pollen allergen specific-immunotherapy improved health-related quality of life in children. Higher symptom scores were associated with lower perceived health-related quality of life. The proportion of children with severe or very severe symptoms from eyes, Nose and/or lungs had significantly decreased after 1 year of pollen SCIT and was maintained during the treatment years [ABSTRACT FROM AUTHOR]

Cardiovascular involvement has a great impact on morbidity and mortality in sickle cell disease (SCD). Currently, few studies are available regarding the paediatric setting and, moreover, current guidelines for the echocardiogram screening program in the asymptomatic paediatric population are controversial. We performed a retrospective observational monocentric study on 64 SCD patients (37 male and 27 female, median age 10) at the Bambino Gesù Childrens' Hospital, who had undergone a routine transthoracic echocardiogram. In total, 46 (72%) patients had at least one cardiac abnormality. Left atrial dilatation (LAD) was present in 41 (65%) patients and left ventricular hypertrophy (LVH) was found in 29 (45%) patients. Patients with LAD showed lower median haemoglobin levels (p = 0.009), and a higher absolute reticulocyte count (p = 0.04). LVH was negatively correlated with the median haemoglobin value (p = 0.006) and positively with the reticulocyte count (p = 0.03). Moreover, we found that patients with cardiac anomalies had higher transfusion needs and a lower frequency of pain crises. In our setting, cardiac involvement has a high prevalence in the paediatric cohort and seems to be associated with specific laboratory findings, and with a specific clinical phenotype characterized by complications related to high haemodynamic load. [ABSTRACT FROM AUTHOR]

Background: Early childhood caries (ECC) remains one of the most prevalent childhood diseases in Australia, disproportionately affecting disadvantaged populations. Aim: To investigate the ECC experience including risk factors, incidence of caries, pain and infection as well as relapse rates of caries and secondary dental general anaesthesia (GA). Design: A retrospective cohort study included dental records of children with ECC, aged <72 months at an Australian public dental hospital paediatric dentistry department from 2013 to 2015 (n = 102). Dental caries, pain, infection, referral patterns, demographic and caries risk factor data were recorded for 24 months. Descriptive statistics were used for patient characteristics and clinical data, and Kaplan–Meier curves and parametric exponential survival models for time‐to‐event series. Results: The study population demonstrated higher‐than‐national average dmft and disease progression at baseline. Major risk factors for the development of caries, pain and infection were daily consumption of sweetened beverages, poor oral hygiene, residing in lower socio‐economic areas, older age and being male. Rates of caries relapse and new referral for secondary treatment under general anaesthesia were relatively high. Conclusion: A high degree of ECC progression and recurrence in this population indicates a need for a more comprehensive approach to ECC addressing multilevel root causes and systemic risk factors. [ABSTRACT FROM AUTHOR]

Introduction. Pineal region pathologies are heterogenous, spectrum ranging from benign, infective to malignant in nature such as parenchymal, germ cell, glial, melanomas, metastatic, tubercular, etc. These lesions are commoner in the pediatric age group and have a variable outcome. The goal of this study is to present our experience regarding the surgical outcomes of pineal region lesions in the paediatric population. Objective. The objective of this study is to access the surgical outcome of pineal region lesions in the paediatric population Methods and Material. Eighty cases of pineal region lesions in the paediatric population (up to 15 years of age) operated in the neurosurgery department, G.B Pant Hospital New Delhi via either Occipital transtentorial or Supracerebellar Infratentorial approaches were retrospectively analysed. Results. There were four main groups of lesions with pineal parenchymal tumours (35 cases) being the commonest. Glial tumours were the next most common contributing 29 cases. Germ cell tumours comprise 7 and miscellaneous 9 cases. The outcome showed graded improvement with the extent of tumour removal and 57 patients (71.25%) improved following surgery. The clinical status of 20 patients (25%) remained unchanged and 3(3.75%) deteriorated from their pre-operative status. 3 patients (3.75%) died in the immediate post-operative period and 11(13.75%) died due to recurrent disease. Conclusion. A graded increase in survival was noted with increasing the degree of resection and postoperative adjuvant therapy in malignant pineal tumours whereas benign pineal lesions can be managed with surgery. Pure germinomas are the only tumour for which the survival rate was unrelated to extent of tumour resection. [ABSTRACT FROM AUTHOR]

Abstract Purpose The aim of this study was to evaluate the safety and efficacy of zero-fluoroscopy (ZF) catheter ablation (CA) for supraventricular tachycardias (SVT). Methods 584 consecutive patients referred to our institution for CA of SVT were analysed. Patients were categorised into two groups; zero-fluoroscopy (ZF) group and conventional fluoroscopy (CF) group. The ZF group was further divided into two subgroups (adults and paediatric). Patient characteristics, procedural information, and follow-up data were compared. Results The ZF group had a higher proportion of paediatric patients (42.2% vs 0.0%; p

• Paediatric anti-infective therapy development lags greatly behind that for adults. • Adolescents should be included in parallel with adults in phase 3 trials. • Model-informed drug development approaches can expedite development. • Innovative statistical methodologies and trial designs can reduce sample sizes. • Partnerships can overcome barriers to access in low- and middle-income countries. The HIV treatment landscape for adults has progressed dramatically in recent decades; however, paediatric populations continue to experience delayed and limited access to effective and safe antiretroviral therapy options. Despite current incentive programmes, formulation research and development and approved drug dosing for children have been limited, particularly for neonates (aged <4 wk). Regulatory approval of drug formulations and dosing in children may lag behind adult approvals by years. Formulation and trial design adjustments complicate paediatric drug development, all of which are vital to accommodate for physiological differences, organ maturation, and rapid weight gain, which are most significant in the youngest children. To facilitate more rapid anti-infective drug development for paediatric populations, regulatory agencies provide guidelines that include extrapolating efficacy and safety data from relevant populations; using pharmacokinetic (PK) bridging and modelling to reduce sample sizes and limit the number of PK studies needed before efficacy analyses; and enrolling age- or weight-based cohorts in parallel rather than sequentially for clinical trials. Ensuring access to approved drugs poses an additional challenge, as uncertainty in demand leads to manufacturing and supply complexity with potentially higher costs that can be a barrier to uptake. Here we summarise challenges in drug development for children living with HIV, which are not unique to antiretrovirals. We aim to propose strategies for how model-based approaches and global partnerships can overcome some of these barriers to accelerate paediatric drug development, with particular reference to HIV, and how lessons learnt from HIV could be extended to other anti-infectives. [ABSTRACT FROM AUTHOR]

Introduction. Pineal region pathologies are heterogenous, spectrum ranging from benign, infective to malignant in nature such as parenchymal, germ cell, glial, melanomas, metastatic, tubercular, etc. These lesions are commoner in the pediatric age group and have a variable outcome. The goal of this study is to present our experience regarding the surgical outcomes of pineal region lesions in the paediatric population. Objective. The objective of this study is to access the surgical outcome of pineal region lesions in the paediatric population Methods and Material. Eighty cases of pineal region lesions in the paediatric population (upto 15 years of age) operated in the neurosurgery department, G.B Pant Hospital New Delhi via either Occipital transtentorial or Supracerebellar Infratentorial approaches were retrospectively analyzed. Results. There were four main groups of lesions with pineal parenchymal tumours (35 cases) being the commonest. Glial tumours were the next most common contributing 29 cases. Germ cell tumours comprise 7 and miscellaneous 9 cases. The outcome showed graded improvement with the extent of tumour removal and 57 patients(71.25%) improved following surgery. The clinical status of 20 patients(25%) remained unchanged and 3(3.75%) deteriorated from their pre-operative status. 3 patients(3.75%) died in the immediate post-operative period and 11(13.75%) died due to recurrent disease. Conclusion. A graded increase in survival was noted with increasing the degree of resection and postoperative adjuvant therapy in malignant pineal tumours whereas benign pineal lesions can be managed with surgery. Pure germinomas are the only tumour for which the survival rate was unrelated to extent of tumour resection.

Carbamazepine is a medicine used to manage epilepsy and partial or tonic-clonic seizures. This study aimed at formulating and obtaining carbamazepine orodispersible tablets for paediatric use at a 50 mg dose, with a diameter not greater than 6 mm and a tablet weight of 80 mg, through a direct compression process. The SeDeM pre-formulation/formulation method was used to define the characteristics of both carbamazepine and the selected excipients for direct compression. This study succeeded in formulating and obtaining the proposed tablets. Following the application of the SeDeM method, the tablets met the mass uniformity test and showed appropriate hardness values for orodispersible tablets. The tablets also met the United States Pharmacopeia (USP) test specifications at t = 60 min. The orodispersible tablets obtained may improve compliance with paediatric treatment with carbamazepine, ensuring the safety and effectiveness of the medicine. [ABSTRACT FROM AUTHOR]

General anaesthesia could affect various immune responses, including Th1 and Th2 immunity, which might also affect cells that play an important role in the pathogenesis of atopic dermatitis. However, the relationship between general anaesthesia exposure and atopic dermatitis remains unknown. The aim of this study was to investigate the risk of developing atopic dermatitis after first exposure to general anaesthesia in the paediatric population (18 years or under). A retrospective cohort study, including those exposed (n = 7,681) and unexposed (n = 38,405; control participants) to general anaesthesia (1:5 ratio), was conducted using national sample cohort data from 2002 to 2015. All participants were followed up for 2 years after cohort entry. The 2-year cumulative incidences of atopic dermatitis in the exposed and unexposed groups were 2.3% and 2.2%, respectively. In the subgroup analysis by age, the cumulative incidence was not significantly different between these cohorts. The risks of atopic dermatitis were not significant in the exposed group in the univariate model (hazard ratio 1.05; confidence interval 0.88–1.24) and in the multivariate model, wherein all covariates were adjusted (adjusted hazard ratio, 1.03; 95% confidence interval 0.87–1.23). The results suggest that children’s exposure to general anaesthesia was not associated with increased or decreased risk of atopic dermatitis.

This study highlights the management of a grossly depressed frontal bone fracture with obvious deformity in a paediatric patient as facial fracture management is frequently intricate and challenging, particularly within the paediatric population as compared to adult. Paediatric fractures have a greater capacity to remodel, but the paediatric brain and craniofacial skeleton are still developing which puts the children at risk for unique complications, such as growing skull fractures. [ABSTRACT FROM AUTHOR]

Abstract Objective To provide the latest evidence of performance and robustness of waist-to-height ratio (WHtR) in discriminating clusters of cardiometabolic risk factors (CMRs) and promote WHtR in routine primary health care practice in children, a meta-analysis was used. Methods Searches was performed in eight databases from inception to July 03, 2020. Inclusion criteria were: (1) observational study, (2) children and adolescents, (3) provided WHtR measurements, (4) had CMRs as outcomes, and (5) diagnostic studies. Exclusion criteria were: (1) non-original articles, (2) unable to extract 2 × 2 contingency tables, (3) not in English or Chinese language, (4) populations comprising clinical patients, or (5) duplicate articles. WHtR cutoff points, 2 × 2 contingency tables were extracted from published reports. Outcomes included: CMR clusters of at least three CMRs (CMR3), two (CMR2), one (CMR1), and CMR components. Bivariate mixed-effects models were performed to estimate the summarised area under the curves (AUSROC) with 95% CIs and related indexes. We conducted subgroup analyses by sex and East Asian ethnicity. Results Fifty-three observational studies were included. The AUSROC reached 0.91 (95% CI: 0.88–0.93), 0.85 (95% CI: 0.81, 0.88) and 0.75 (95% CI: 0.71, 0.79) for CMR3, CMR2, and CMR1, respectively. The pooled sensitivity and specificity for CMR3 reached 0.84 and exceeded 0.75 for CMR2. For CMR1, the sensitivity achieved 0.55 with 0.84 for specificity. We had similar findings for our subgroup and sensitivity analyses. Conclusions WHtR shows good and robust performance in identifying CMRs clustering across racial populations, suggesting its promising utility in public health practice globally.

Creating musculoskeletal models in a paediatric population currently involves either creating an image-based model from medical imaging data or a generic model using linear scaling. Image-based models provide a high level of accuracy but are time-consuming and costly to implement, on the other hand, linear scaling of an adult template musculoskeletal model is faster and common practice, but the output errors are significantly higher. An articulated shape model incorporates pose and shape to predict geometry for use in musculoskeletal models based on existing information from a population to provide both a fast and accurate method. From a population of 333 children aged 4–18 years old, we have developed an articulated shape model of paediatric lower limb bones to predict bone geometry from eight bone landmarks commonly used for motion capture. Bone surface root mean squared errors were found to be 2.63 ± 0.90 mm, 1.97 ± 0.61 mm, and 1.72 ± 0.51 mm for the pelvis, femur, and tibia/fibula, respectively. Linear scaling produced bone surface errors of 4.79 ± 1.39 mm, 4.38 ± 0.72 mm, and 4.39 ± 0.86 mm for the pelvis, femur, and tibia/fibula, respectively. Clinical bone measurement errors were low across all bones predicted using the articulated shape model, which outperformed linear scaling for all measurements. However, the model failed to accurately capture torsional measures (femoral anteversion and tibial torsion). Overall, the articulated shape model was shown to be a fast and accurate method to predict lower limb bone geometry in a paediatric population, superior to linear scaling. [ABSTRACT FROM AUTHOR]

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Purpose: The aim of this study was to evaluate the safety and efficacy of zero-fluoroscopy (ZF) catheter ablation (CA) for supraventricular tachycardias (SVT).Methods: 584 consecutive patients referred to our institution for CA of SVT were analysed. Patients were categorised into two groups; zero-fluoroscopy (ZF) group and conventional fluoroscopy (CF) group. The ZF group was further divided into two subgroups (adults and paediatric). Patient characteristics, procedural information, and follow-up data were compared.Results: The ZF group had a higher proportion of paediatric patients (42.2% vs 0.0%; p < 0.001), resulting in a younger age (30.9 ± 20.3 years vs 52.7 ± 16.5 years; p < 0.001) and lower BMI (22.8 ± 5.7 kg/m2 vs 27.0 ± 5.4 kg/m2; p < 0.001). Procedure time was shorter in the ZF group (94.2 ± 50.4 min vs 104.0 ± 54.0 min; p = 0.002). There were no major complications and the rate of minor complications did not differ between groups (0.0% vs 0.4%; p = 0.304). Acute procedural success as well as the long-term success rate when only the index procedure was considered did not differ between groups (92.5% vs 95.4%; p = 0.155; 87.1% vs 89.2%; p = 0.422). When repeated procedures were included, the long-term success rate was higher in the ZF group (98.3% vs 93.5%; p = 0.004). The difference can be partially explained by the operators' preferences.Conclusion: The safety and efficacy of ZF procedures in adult and paediatric populations are comparable to that of CF procedures. [ABSTRACT FROM AUTHOR]

Introduction: Epilepsy is considered as the most common neurological disorder. Aim: To compare the effectiveness of Antiepileptic Drugs (AED) under British National Formula (BNF) guidelines and regular practice for different oral antiepileptic medications in enhancing and controlling the patient’s disease state and tolerability. Materials and Methods: The prospective longitudinal cohort study was conducted at Department of Paediatrics of DR. B.C. Roy Postgraduate Institute of Paediatric Sciences, Kolkata, West Bengal, between May 2018 and April 2019 where all the patients (70) were randomly divided into two groups; group I patients were on regular practice medication while group II patients followed BNF guidelines. The doses of the treatment plan was formulated and changed according to the subsequent follow-up. The formulation of doses was done by either increasing the current AED or adding a new AED to the treatment regimen. The Paediatric Quality of Life Inventory (PedsQL) was used to assess the adverse effects in epileptic patients. The data was analysed by using Microsoft Excel database and Statistical Package for the Social Sciences (SPSS) Version 21.0 was used for data computation, p-value< 0.05 was considered as statistically significant. Results: About 23.5% patients of group II had seizures whereas, 53.1% patients of group I had convulsions after six months follow-up. Patients on levetiracetam 10 mg/kg once daily then increased in steps up to 10 mg per kg twice daily (max. per dose 30 mg/kg) monotherapy were experiencing poor seizure control with a number of seizure incidence in group I patients (n=10) compared to patients (n=4) who followed the BNF guidelines. Adverse effects of AEDs such as headache, skin rash, weight loss, weight gain, diarrhoea, dizziness etc., were more in 53.12% patients of group I following regular practice medicines (n=17) compared to 23.5% patients (n=8) of group II followed BNF guidelines. In normal procedure for physical, physiological and overall functioning, there was a decrease in the PedsQL score of group I patients; while in BNF recommendation for physical, physiological and overall functioning, there was an insignificant difference in the PedsQL score of group II patients. Conclusion: The present study concluded that unbiased individualisation of patients for the selection AEDs and its doses according to BNF guidelines has been found to be significantly effective in reducing the adverse effects as well as improved seizure control in paediatric population.

Introduction: Enuresis or bedwetting is the most common urological problem seen in children from the age of 5-15 years. Various diagnostic procedures like urodynamics study, urinary system ultrasonography and Electromyography (EMG) are widely used. In most cases, endoanal probe is used for the procedure of EMG which is an invasive technique but surface EMG is pain free and easier. Aim: To assess the activity of perianal muscle in children with enuresis using surface EMG. Materials and Methods: Present study was a cross-sectional study in which 20 healthy children and 20 enuretic children in the age group of 5-15 years participated. Both boys and girls without central nervous system disorder were included. Surface EMG of the perianal muscles were performed. The homogenecity of demographic data like age, weight and height were checked using Student’s t-test. Normality of the data was established using Shapiro-Wilk’s test. Results: On analysis, the mean age (years) of normal children was 8.75±2.09 and for enuretic children was 9.3±2.63. The mean value of amplitudes of surface EMG (Quotient of Motor Unit action Potential-QMUP) in normal children was 428.6±118.6 μV and for enuretic children was 248.01±45.85 μV (p

Although the safety profiles of mRNA COVID-19 vaccines (mRNA-1273 and BNT162b2) were evaluated in pre-authorization clinical trials, real-world data allow us to better define their benefit/risk ratio in the paediatric population. The current study aimed to evaluate the safety profiles of mRNA COVID-19 vaccines in children by analysing the pharmacovigilance data of the European spontaneous reporting system database EudraVigilance (EV) in the period from 1 January 2021, to 1 October 2022. During our study period, overall 4838 ICSRs related to mRNA COVID-19 vaccines referring to 5–11-year-old subjects were retrieved from EV, of which 96.9% were related to BNT162b2 and 49.3% were related to males. A total of 12,751 Adverse Events Following Immunization (AEFIs) were identified, of which 38.7% were serious. The most frequently reported AEFIs were pyrexia, headache, and vomiting. Only 20 Individual Case Safety Reports (ICSRs) reported Multisystem Inflammatory Syndrome (MIS) as an AEFI, all related to BNT162b2. The majority of MIS cases were females, and six cases were completely resolved at the time of reporting. Our results show a favourable risk–benefit profile for all mRNA COVID-19 vaccines in this paediatric sub-population, supporting their use in children. Considering the peculiarity and fragility of children, continuous safety monitoring of COVID-19 vaccines is required.