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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 programs, formulation research and development and approved drug dosing for children have been limited, particularly for neonates (aged <4 weeks). 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 summarize 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.

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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.

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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.

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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.

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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.

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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.

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Soil-transmitted helminth (STH) infections inflict disability worldwide, especially in the poorest communities. Current therapeutic options against STHs show limited efficacy, particularly against Trichuris trichiura. The empirical management of patients coming from high-prevalence areas has been suggested for non-endemic areas. This study aimed to describe the management of STH infections in a non-endemic setting using an individualised approach. We performed a retrospective, descriptive study of all patients up to 16 years of age with STH infections attended at an international health unit in a non-endemic area (2014-2018), including all T. trichiura, Necator americanus, Ancylostoma duodenale, and Ascaris lumbricoides infections diagnosed using a formol-ether concentration technique and direct visualisation. Patients were treated according to current international guidelines. Sixty-one stool samples from 48 patients testing positive for STHs were collected, with 96% (46/48) reporting a previous long-term stay in endemic areas. Cure rates with 3-day benzimidazole regimens were 72% for T. trichiura, 40% for hookworms, and 83% for A. lumbricoides. The results were not influenced by any reinfection risk due to the study being performed in a non-endemic area. Patients coming from STH-endemic areas should be evaluated with appropriate diagnostic tools and followed up until cure control results. Cure rates in our cohort were moderate to low, similar to those published in studies in endemic areas. The efficacy of current treatment options is insufficient to recommend a specific empirical approach in high-income countries' healthcare systems.

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Fixed-Dose antiretroviral Combinations (FDCs) are the most used drug regimes in adult patients with human-immunodeficiency virus 1 infection, since they increase adherence to antiretroviral therapy and enable good quality of life. The European AIDS Clinical Society guidelines recommend the use of FDCs in paediatrics. However, the use of FDCs in paediatric population is restricted since studies in children and adolescents are mostly conducted in small sample sizes and are heterogeneous in settings and design. This systematic review aims to summarize the current knowledge about the use of FDCs in paediatric population, highlighting the relevant outcomes regarding efficacy and effectiveness, adherence, safety, and adverse events of these regimens.

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Liquid formulations are mostly used in the paediatric population. However, with certain active pharmaceutical ingredients (APIs), it is very difficult to guarantee quality and stability; this is the case, for example, with omeprazole. Omeprazole is used as a model drug due to the lack of a paediatric formulation meeting gastro-resistance requirements, which remains a challenge today. In this experimental study, the development of enteric polymer-coated pellets is proposed. It is proposed to use aqueous coating dispersions without the use of organic solvents, which are commonly used in fluidised bed coatings. To do this, the design of experiments method is used as a statistical tool for experiment creation and the subsequent analysis of the responses. In particular, this study uses a randomised full factorial design. The mean weight increases of the protective layer and the enteric coating are chosen as factors. Each factor is assigned two levels. Therefore, the design of the used experiments is a 22 + 1 central point. Overall, the obtained pellets can be an alternative to the compounding formulas of omeprazole that are currently used in the paediatric population, which do not meet the gastro-resistance specifications necessary to guarantee the therapeutic efficacy of this active ingredient.

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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.

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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.

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AIMS: To assess the efficacy and safety of faster aspart (FIAsp) in paediatric population with type 1 diabetes mellitus (T1DM) and insulin pumps in real-world settings. METHODS: Of 44 patients, 20 used FIAsp, 16 of which switched from aspart to FIAsp and 24 used aspart/lispro. We performed within-groups and between-groups analyses in three time points for anthropometric data, % of 24-h time in range of 70-180 mg/dl (TIR), time < 70 mg/dl and <54 mg/dl and time > 180 mg/dl and >250 mg/dl, bolus and basal insulins doses (units/kg/day and %), total daily dose (TDD, units/kg/day), glycaemic variability, frequency of set changes, sensor wear per week and meals per day. RESULTS: Use of FIAsp over time increased TIR (P = 0.002) and TDD (P = 0.008 and P = 0.004, respectively for three months after the switch and recent use) and decreased time in hyperglycaemia (>180 P = 0.003 and > 250 mg/dl, P = 0.004). Frequency of set changes differ in the first 3 months (P = 0.042). Patients with FIAsp consumed more meals per day compared to those with aspart/lispro (P = 0.032). CONCLUSION: Real-world data confirm that use of FIAsp in insulin pumps in paediatric populations improves glycaemic control long-term.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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INTRODUCTION: 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. MATERIALS AND METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

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