Long-Term Follow-Up before and during Riluzole Treatment in Six Patients from Two Families with Spinocerebellar Ataxia Type 7.

BACKGROUND: Currently no curative treatment exists for spinocerebellar ataxias (SCAs). Riluzole repurposing was proposed as a symptomatic treatment in different types of cerebellar ataxia. We report a long-term-follow up under riluzole treatment in SCA type 7. METHODS: Six patients received Riluzole 50 mg twice daily on a compassionate use program for a mean of 4.8 years (range 3.5-9). We measured ataxia onset and progression through the Scale for the Assessment and Rating of Ataxia (SARA), and collected extensive ophthalmological data before and after Riluzole treatment. Electrocardiogram and laboratory profile for drug safety were performed every six months. RESULTS: Riluzole treatment showed no effect on visual function in two patients with an advanced retinal damage. Improvements of visual function occurred in four patients followed by ophthalmologic stability up to 5 years after starting treatment. Two patients had a less steep deterioration of ataxia after treatment compared to pre-treatment, during the first 2,5 years of therapy. One showed soon after therapy an improvement of the SARA score, and then overall stability lasting 3,5 years, followed by ataxia worsening. One visually impaired patient without neurological impairment did not worse until the last visit after 3,5 years of follow-up. The remaining 2 patients showed an improvement of SARA scores soon after therapy, and an overall stability lasting respectively 5 and 3 years. No adverse event was registered during the observation period. DISCUSSION: This study suggests a possible beneficial action of Riluzole in SCA7 and provides a detailed description of the ophthalmologic profile of these patients.

The incidence of fractures in children under two years of age: a systematic review.

BACKGROUND: Epidemiological research on fractures in children under the age of two is of great importance to help understand differences between accidental and abusive trauma. OBJECTIVE: This systematic review aimed to evaluate studies reporting on the incidence of fractures in children under two years of age, excluding birth injuries. Secondary outcome measures included fracture location, mechanisms of injury and fracture characteristics. METHODS: A systematic literature review (1946 to February 7th 2024), including prospective and retrospective cohort studies and cross-sectional cohort studies, was performed. Studies including children from other age groups were included if the actual measures for those aged 0-2 years could be extracted. We also included studies restricted to infants. Annual incidence rates of fractures were extracted and reported as the main result. Critical appraisal of was performed using the Appraisal tool for Cross-Sectional Studies. RESULTS: Twelve moderate to good quality studies met eligibility criteria, of which seven were based on data from medical records and five were registry studies. Studies investigated different aspects of fractures, making comprehensive synthesis challenging. There was an overall annual fracture incidence rate of 5.3 to 9.5 per 1,000 children from 0-2 years of age; with commonest sites being the radius/ulna (25.2-40.0%), followed by tibia/fibula (17.3-27.6%) and the clavicle (14.6-14.8%) (location based on 3 studies with a total of 407 patients). In infants, the reported incidence ranged between 0.7 to 4.6 per 1,000 (based on 3 studies), with involvement of the clavicle in 22.2% and the distal humerus in 22.2% of cases (based on 1 study). Only a single metaphyseal lesion was reported (proximal humerus of an 11-month-old infant). Fracture mechanisms were detailed in four studies, with fall from chair, bed, table, own height or fall following indoor activities causing 50-60% of fractures. CONCLUSIONS: There is a paucity of good quality data on fracture incidence in children under the age of two. Larger, prospective and unbiased studies would be helpful in determining normal pattern of injuries, so that differences from abusive trauma may be better understood.

Decision making for health-related research outcomes that alter diagnosis: A model from paediatric brain tumours.

AIMS: The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro-oncology speciality. METHODS: As part of a previous research study, the diagnoses of 73 archival paediatric brain tumour samples were reclassified according to the WHO 2016 guidelines. To determine the disclosure threshold and clinical actionability of pathology-related findings, we conducted a result-evaluation approach within the ethical framework of BRAIN UK using a surrogate clinical multidisciplinary team (MDT) of neuro-oncology specialists. RESULTS: The MDT identified key determinants impacting decision-making, including anticipated changes to patient management, time elapsed since initial diagnosis, likelihood of the patient being alive and absence of additional samples since cohort inception. Ultimately, none of our research findings were considered clinically actionable, largely due to the cohort's historic archival and high-risk nature. From this experience, we developed a decision-making framework to determine if research findings indicating a change in diagnosis require reporting to the relevant clinical teams. CONCLUSIONS: Ethical issues relating to the use of archival tissue for research and the potential to identify actionable findings must be carefully considered. We have established a structured framework to assess the actionability of research data relating to patient diagnosis. While our specific findings are most applicable to the pathology of poor prognostic brain tumour groups in children, the model can be adapted to a range of disease settings, for example, other diseases where research is dependent on retrospective tissue cohorts, and research findings may have implications for patients and families, such as other tumour types, epilepsy-related pathology, genetic disorders and degenerative diseases.

Uses of infrared thermography in acute illness: a systematic review.

Introduction: Infrared thermography (IRT) is a non-contact, non-ionising imaging modality, providing a visual representation of temperature distribution across a surface. Methods: We conducted a systematic search of indexed and grey literature for studies investigating IRT applications involving patients in acute care settings. Studies were categorised and described along themes identified iteratively using narrative synthesis. Quality appraisal of included studies was performed using the Quality Assessment tool for Diagnostic Accuracy Studies. Results: Of 1,060 unique records, 30 studies were included. These were conducted in emergency departments and intensive care units involving adult, paediatric and neonatal patients. IRT was studied for the diagnosis, monitoring or risk stratification of a wide range of individual conditions. IRT was predominantly used to display thermal change associated with localised inflammation or microcirculatory dysfunction. Existing research is largely at an early developmental stage. Discussion: We recommend that high quality diagnostic validation studies are now required for some clinical applications. IRT has the potential to be a valuable tool in the acute care setting and represents an important area for future research particularly when combined with advances in machine learning technology. Systematic review registration: CRD 42022327619 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=327619).

Epidemiology, Treatment Patterns, and Cost Analysis of Immune Thrombocytopenia in Spain between 2014 and 2020: A Population-based Study.

Background Immune thrombocytopenia (ITP) is characterised by low platelet counts and often leads to bleeding, fatigue, and reduced health-related quality of life. Methods This observational, retrospective, population-based study using BIG-PAC® database included Spanish paediatric and adult patients with primary ITP diagnosed in primary care and hospitals between 2014 and 2020 (median follow-up: 4 years). Epidemiology, baseline/clinical characteristics, treatment trends, healthcare resources and costs were analysed. Results The BIG-PAC® database contains records of 1,818,588 patients; 170 adults and 27 children with ITP were included in our analysis. ITP prevalence and annual incidence per 100,000 were estimated in 10.8 (2.8 in chronic ITP [cITP] patients) and 1.5 (0.3 in cITP patients), respectively. Epistaxis was the most common bleeding event, followed by genitourinary and gastrointestinal bleeding; >50%/> 75% of ITP/cITP patients reported fatigue. Chronic patients had lower platelet counts at baseline and required more transfusions. Corticosteroids, immunosuppressants, and thrombopoietin receptor agonists were the most used agents in first-, second- and third-line treatment, respectively. Thirty-five patients, all of them in chronic phase, underwent splenectomy. Patients had on average 13.9, 6.6, and 1.2 visits/year to primary care, haematology/internal medicine, and emergency departments, respectively. More than one-fourth of adult patients took on average 16.3 days of sick leave annually. Mean annual total health care costs were €10,741 (ITP patients) and €19,809 (cITP patients). Conclusion This is the first study to provide an overall perspective on the situation of the Spanish ITP population in terms of epidemiology, treatment trends, health care resources and costs, highlighting unmet patient needs, and direct and indirect costs/resource use between 2014 and 2020.

Comparison of intranasal dexmedetomidine and ketamine for paediatric premedication: A randomized study.

INTRODUCTION AND OBJECTIVES: Paediatric patients are given premedication in order to decrease preoperative anxiety, allow smooth induction, and prevent postoperative psychological insult and behavioural changes. A child friendly method of administration is desirable. We compared intranasal administration of dexmedetomidine and ketamine in the operating room environment, to evaluate the Faces, Legs, Activity, Cry and Consolability (FLACC) score at the time of establishing intravenous access for induction of general anaesthesia. METHODS: This prospective, double-blind, randomized controlled trial was conducted at a tertiary care center. One hundred patients, 2-10 years of age, ASA physical status 1 & 2, scheduled for general anaesthesia were enrolled. Patient's presedation behaviour was assessed by the modified Yale Preoperative Anxiety Scale Short Form (mYPAS-SF). Patients in Group D received Dexmedetomidine 1 mcg/kg intranasally, and patients in Group K received Ketamine 5 mg/kg intranasally. After 45 minutes, patients were transferred to the operating table where intravenous cannulation was carried out and the response to needle insertion was assessed by FLACC scale. Vital signs, including the pulse-oximetry, heart rate and respiratory rate were monitored. Side effects such as nausea, vomiting, and agitation were also recorded. RESULTS: A significantly higher FLACC score was seen in Group D as compared to Group K (p = 0.001). The mean heart rate between two groups was found to be significantly (p = 0.001) lower in Group D compared to Group K. However, the proportion of adverse events was 8% in patients who received ketamine. CONCLUSIONS: Intranasal ketamine in a dose of 5 mg/kg is clinically more effective as premedication in children aged 2-10 years in comparison with intranasal dexmedetomidine in a dose of 1 mcg/kg.

Assessing the predictors for paediatric intensive care unit for inter-hospital transfer patients on high-flow nasal cannula or continuous positive airway pressure ventilation at a tertiary Australian paediatric hospital.

OBJECTIVE: The aim of the present study was to assess the predictors of need for paediatric intensive care unit (PICU) admission for inter-hospital transfer patients to a tertiary paediatric hospital ED on high flow (HF) or continuous positive airway pressure (CPAP) ventilation. METHODS: Single-centre retrospective study of patients transferred to the state's tertiary paediatric hospital. Demographic information and disease management information was obtained. RESULTS: Between October 2021 and September 2022, 53 patients were transferred to the tertiary hospital on HF or CPAP. Of these, 23 required admission to PICU. Those admitted to PICU had a higher median fraction of inspired oxygen than those not admitted (0.4 vs 0.3, respectively, P = 0.013). Patients transported by road (vs flight) were more likely (20/23 patients, RR = 3.15, P = 0.016) to be admitted to PICU (56% vs 18%). Those who had received CPAP prior to or during transfer were more likely to require PICU admission (P = 0.012). CONCLUSION: We have demonstrated that children who require CPAP to manage their respiratory disease are more likely to require PICU care on transfer to the tertiary paediatric hospital. In addition, those patients being transferred from secondary metropolitan hospitals after a trial of HF are also likely to require PICU care. This suggests that these patients should be directly admitted to PICU, allowing for improved patient experience and flow as well as reducing unnecessary ED resource utilisation.

Retinoblastoma: An update on genetic origin, classification, conventional to next-generation treatment strategies.

The most prevalent paediatric vision-threatening medical condition, retinoblastoma (RB), has been a global concern for a long time. Several conventional therapies, such as systemic chemotherapy and focal therapy, have been used for curative purposes; however, the search for tumour eradication with the least impact on surrounding tissues is still ongoing. This review focuses on the genetic origin, classification, conventional treatment modalities, and their combination with nano-scale delivery systems for active tumour targeting. In addition, the review also delves into ongoing clinical trials and patents, as well as emerging therapies such as gene therapy and immunotherapy for the treatment of RB. Understanding the role of genetics in the development of RB has refined its treatment strategy according to the genetic type. New approaches such as nanostructured drug delivery systems, galenic preparations, nutlin-3a, histone deacetylase inhibitors, N-MYC inhibitors, pentoxifylline, immunotherapy, gene therapy, etc. discussed in this review, have the potential to circumvent the limitations of conventional therapies and improve treatment outcomes for RB. In summary, this review highlights the importance and need for novel approaches as alternative therapies that would ultimately displace the shortcomings associated with conventional therapies and reduce the enucleation rate, thereby preserving global vision in the affected paediatric population.

Single-leg versus double-leg hip spica casts in the management of paediatric femoral shaft fractures? A systematic review and meta-analysis.

Background: Paediatric femoral shaft fractures can be managed with single- or double-leg hip spica casting between ages six-months and six-years. The aim of this review was to determine if single-leg hip spicas reduce the impact on family life without compromising fracture stability. Methods: The study was registered on PROSPERO (CRD42023454309). MEDLINE, Embase, Web of Science, Cochrane Library, and clinical trial registers were searched to May 2023 for level I-III evidence. Primary outcomes were impact on family life and fracture stability. Where appropriate, Meta-analysis was completed using RevMan v5.4. Risk of bias was assessed using RoB 2.0 (RCTs) and ROBINS-I (non-RCTs). Certainty of evidence was measured with GRADE. Results: From 234 identified papers, four met the inclusion criteria (two RCTs; two non-RCTs). A total of 339 children were included (single-leg spica: 176; double-leg spica: 163). Three studies were 'high risk' and one study 'moderate risk' of bias. Impact on family life parameters were too heterogenous for pooled meta-analysis. Non-pooled data identified significantly more missed work days in the double-leg spica group and the 'Impact on Family' Scale significantly favoured single-leg spicas. For fracture stability, meta-analysis identified that (i) mal-union rates were significantly lower in single-leg spica: OR 0.08 (95 % CI 0.01 to 0.69; p = 0.02); (ii) MUA in theatre was not significantly different: OR 0.97 (95 % CI 0.19 to 4.86; p = 0.97); and (iii) wedge adjustment was not significantly different: OR 3.46 (95 % CI 0.48 to 24.92; p = 0.22). Certainty of evidence was assessed as 'very low'. Conclusion: Single-leg hip spicas may be associated with reduced impact on family life without compromising fracture stability compared with double-leg hip spicas. However, the evidence is weak. Therefore, a propensity score matched observational study is required to understand if subgroups of patients (age, fracture pattern, mechanism of injury) would benefit from a single- or double-leg hip spica.

Approaches to supratentorial brain tumours in children.

The differential diagnosis of supratentorial brain tumours in children can be challenging, especially considering the recent changes to the WHO classification of CNS tumours published in 2021. Many new tumour types have been proposed which frequently present in children and young adults and their imaging features are currently being described by the neuroradiology community. The purpose of this article is to provide guidance to residents and fellows new to the field of paediatric neuroradiology on how to evaluate an MRI of a patient with a newly diagnosed supratentorial tumour. Six different approaches are discussed including: 1. Tumour types, briefly discussing the main changes to the recent WHO classification of CNS tumours, 2. Patient age and its influence on incidence rates of specific tumour types, 3. Growth patterns, 4. Tumour location and how defining the correct location helps in narrowing down the differential diagnoses and 5. Imaging features of the tumour on DWI, SWI, FLAIR and post contrast sequences.

A novel experiential work-based learning model in paediatric secondary care using entrustable professional activities to develop clinical knowledge and communication skills.

BACKGROUND: Initial education and training standards for pharmacists in Great Britain require early clinical exposure to patients using experiential work-based learning. However, there is poor evidence of this approach in some settings, such as paediatric care. The aim of this study was therefore to explore a novel model of experiential work-based learning for student pharmacists in a paediatric setting. METHODS: Fourth-year student pharmacists enrolled on a Master of Pharmacy programme were allocated five three-hour placement sessions at a paediatric hospital. Sessions consisted of a briefing, ward activities, scaffolded consultations with children and their carers, followed by a debriefing session with a clinical supervisor. Data were collected relating to the ward, patient details, student reported activities, learning outcomes and if follow up was required by a member of the clinical team. Data were cleaned, quality checked, then descriptive statistical analysis and inductive content analysis were conducted. MAIN FINDINGS: Seventy-four students took part in 28 individual sessions and 233 consultations were recorded. Consultations included a best-possible medical history (76%, n = 177), a satisfactory drug history (45%, n = 104), or discussed hospital discharge (11%, n = 26). Students were exposed to patients with diagnosed acute conditions (41%, n = 96) and chronic conditions (33%, n = 76), as well as children awaiting diagnosis (13%, n = 30). Students reported learning about the pathology, diagnosis and symptoms of paediatric conditions (48%, n = 81), medicines used in children (24%, n = 41), patient experiences of recieving care (15%, n = 25), carer experiences (2%, n = 3), the hospital environment (2%, n = 4), career progression (2%, n = 4), and experiences of social care (11%, n = 18). Findings were synthesised with existing entrustable professional activities from the literature to generate novel EPAs specific to paediatric settings. CONCLUSIONS: A paediatric setting offers a suitable environment to host experiential work-based learning in pharmacy education. Standards of initial education and training which require pharmacists to prescribe in Great Britain must recognise the importance of exposure to the health needs and experiences of children, young people's and carers prior to graduation.

An articulated shape model to predict paediatric lower limb bone geometry using sparse landmarks.

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.

Association between socioeconomic deprivation, ethnicity and health outcomes in preschool children with recurrent wheeze in England: a retrospective cohort study.

BACKGROUND: Preschool-aged children have among the highest burden of acute wheeze. We investigated differences in healthcare use, treatment and outcomes for recurrent wheeze/asthma in preschoolers from different ethno-socioeconomic backgrounds. METHODS: Retrospective cohort study using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics in England. We reported number of acute presentations and hospitalisations stratified by index of multiple deprivation (IMD) and ethnicity; and factors associated with treatment non-escalation, and hospitalisation rates using multivariable logistic and Poisson regression models. RESULTS: 194 291 preschool children were included. In children not trialled on asthma preventer medications, children from the most deprived IMD quintile (adjusted OR 1.67; 95% CI 1.53 to 1.83) and South Asian (1.77; 1.64 to 1.91) children were more likely to have high reliever usage and where specialist referral had not occurred, the odds of referral being indicated was higher in the most deprived quintile (1.39; 1.28 to 1.52) and South Asian (1.86; 1.72 to 2.01) children compared with the least deprived quintile and white children, respectively.Hospitalisation rates for wheeze/asthma were significantly higher in children from the most deprived quintile (adjusted IRR 1.20; 95% CI 1.13 to 1.27) compared with the least, and in South Asian (1.57; 1.44 to 1.70) and black (1.32; 1.22 to 1.42) compared with white children. CONCLUSIONS: We identified inequalities in wheeze/asthma treatment and morbidity in preschool children from more deprived, and non-white backgrounds. A multifaceted approach to tackle health inequality at both the national and local levels, which includes a more integrated and standardised approach to treatment, is needed to improve health outcomes in children with preschool wheeze/asthma.

Health care safety incidents in paediatric emergency care.

OBJECTIVE: To characterize safety incidents in paediatric emergency departments (PEDs): frequency, sources, root causes, and consequences. MATERIALS AND METHODS: We conducted a cross-sectional, observational and descriptive study in the PED of the Clinical University Hospital XX (blinded for review). Patients were recruited through opportunity sampling and the data were collected during care delivery and one week later through a telephone survey. The methodology was based on the ERIDA study on patient safety incidents related to emergency care, which in turn was based on the ENEAS and EVADUR studies. RESULTS: The study included a total of 204 cases. At least one incident was detected in 25 cases, with two incidents detected in 3 cases, for a total incidence of 12.3%. Twelve incidents were detected during care delivery and the rest during the telephone call. Ten percent did not reach the patient, 7.1% reached the patient but caused no harm, and 82.1% reached the patient and caused harm. Thirteen incidents (46.4%) did not have an impact on care delivery, 8 (28.6%) required a new visit or referral, 6 (21.4%) required additional observation and 1 (3.6%) medical or surgical treatment. The most frequent root causes were health care delivery and medication. Incidents related to procedures and medication were most frequent. Of all incidents, 78.6% were considered preventable, with 50% identified as clear failures in health care delivery. CONCLUSIONS: Safety incidents affected 12.3% of children managed in the PED of the HCUVA, of which 78.6% were preventable.

Estimated compared with actual plans of paediatric dental treatment performed under deep sedation: A retrospective cohort study.

BACKGROUND: Planning the extent of paediatric dental treatment under deep sedation is highly important, as the duration of the sedation should be limited to approximately 1 h, and the amount of local anesthesia is limited by the children's body weight. AIM: To compare treatment plans estimated at initial examinations with actual dental treatments under intravenous deep sedation. We examined factors that could affect the differences. DESIGN: For this retrospective cohort study, data were collected from the medical records of all the children younger than 18 years who underwent dental treatment under intravenous deep sedation during 2019-2021 at the Department of Pediatric Dentistry. RESULTS: In total, 108 children were included. During the actual versus the estimated treatment under deep sedation, more teeth were treated (p < .001), and the treatment was more complex (p < .001). A longer waiting period for dental treatment was found to be correlated with a greater number of treated teeth than was estimated (p = .003) and with greater complexity of the actual than the estimated treatment (p = .003). CONCLUSION: Actual compared with estimated dental treatment under deep sedation involved more teeth and was of greater complexity. This suggests that referrals should include children with limited estimated treatment plans.

Flexible bronchoscopy for foreign body aspiration in children: A single-centre experience.

BACKGROUND: The technological evolution of bronchoscopy has led to the widespread adoption of flexible techniques and their use for both diagnostic and therapeutic purposes. Currently, there is an active debate regarding the comparative efficacy and safety of rigid vs flexible bronchoscopy in the treatment of foreign body aspiration. AIM: To evaluate our experience with tracheobronchial foreign body extraction using flexible bronchoscopy and provide a literature overview. METHODS: This was a single-centre retrospective study. Twenty-four patients were enrolled between January 2017 and January 2023. Medical records of patients aged below 18 years who were admitted to authors' affiliated institution with a suspected diagnosis of foreign body aspiration were collected from hospital's database to Microsoft Excel 2019. Data were analysed using MedCalc Statistical Software. RESULTS: Patient ages varied from 9 months to 11 years. The median age was 23.5 months, 95% confidence interval (CI) 19.49-44.77. We observed age clustering in children with foreign body aspiration at our institution with three age subgroups: (1) 0-25 months; (2) 40-60 months; and (3) 120-140 months. We expectancy of an organic tracheobronchial foreign body was significantly higher in 0-25 months subgroup than that in older ones when subgroups 40-60 and 120-140 months were combined together (odds ratio = 10.0, 95%CI: 1.44-29.26, P = 0.0197). Successful foreign body extraction was performed in all cases. Conversion to a rigid bronchoscope was not required in any of the cases. No major complications (massive bleeding, tracheobronchial tree perforation, or asphyxia) were observed. CONCLUSION: Flexible bronchoscopy is an effective and safe method for tracheobronchial foreign body extraction in children.

Impact of tonsillectomy on the efficacy of Alt-RAMEC/PFM treatment protocols in children with class III malocclusion and tonsillar hypertrophy: protocol for a cluster randomised controlled trial.

INTRODUCTION: Orthodontic treatment using face mask protraction combined with an alternate rapid maxillary expansion and constriction/protraction face mask (Alt-RAMEC/PFM) protocol is effective in the early treatment of patients with class III malocclusion, but the stability of treatment outcomes represents a major concern. Previous studies have suggested that tonsillar hypertrophy can be a risk factor for class III malocclusion and tonsillectomy may prompt the normalisation of dentofacial growth. However, these studies had a low-to-moderate level of evidence. This study was designed to identify the impact of tonsillectomy before orthodontic treatment on the efficacy and stability of Alt-RAMEC/PFM protocols and the sleep quality and oral health in children with anterior crossbite and tonsillar hypertrophy. METHODS AND ANALYSIS: This is a two-arm, parallel-group, superiority cluster randomised controlled trial, with four clinics randomly assigned to the surgery-first arm and the orthodontic-first arm in a 1:1 ratio. The Alt-RAMEC protocol involves alternate activation and deactivation of the expander's jet screw over 6 weeks to stimulate maxillary suture distraction. Patients will be instructed to wear the PFM for a minimum of 14 hours per day. The primary outcomes are changes in Wits appraisal and the degree of maxillary advancement from baseline to the end of orthodontic treatment. Lateral cephalometric radiographs, polysomnography, Obstructive Sleep Apnoea-18 questionnaire and Oral Health Impact Profile-14 questionnaire will be traced, collected and measured. We will recruit 96 patients intofor the study. To assess differences, repeated multilevel linear mixed modelling analyses will be used. ETHICS AND DISSEMINATION: This study has been granted ethical approval by the Ethics Committee of the School & Hospital of Stomatology, Wuhan University (approval No. 2023-D10). Written informed consent will be obtained from the participants and their guardians. The results of the trial will be disseminated through academic conferences and journal publications. TRIAL REGISTRATION NUMBER: ChiCTR2300078833.

INfluenza VaccInation To mitigate typE 1 Diabetes (INVITED): a study protocol for a randomised, double-blind, placebo-controlled clinical trial in children and adolescents with recent-onset type 1 diabetes.

INTRODUCTION: Children and adolescents with recent-onset type 1 diabetes (T1D) commonly maintain a certain level of insulin production during the remission phase, which can last months to years. Preserving ß-cell function can reduce T1D complications and improve glycaemic control. Influenza vaccination has pleiotropic effects and administration of the vaccine during the early phases of T1D may offer ß-cell protection. This study aims to assess the effect of influenza vaccination on preserving ß-cell function in children and adolescents with recent-onset T1D. METHODS AND ANALYSIS: The INfluenza VaccInation To mitigate typE 1 Diabetes trial is a randomised, double-blind, placebo-controlled, multicentre trial in paediatric patients with recent-onset T1D aged 7-17 years. 100 participants will be randomised in a 1:1 ratio to receive either a standard inactivated quadrivalent influenza vaccine or a placebo within 14 days of diagnosis. The primary outcome is a difference in mean change (from baseline to 12 months) in C-peptide level between groups during a 2-hour mixed-meal tolerance test. Secondary outcomes include mean change (from baseline to 6 months) in C-peptide levels, haemoglobin A1c, ambulatory glucose profiles and insulin requirements. Exploratory outcomes are diabetes-related autoantibodies, inflammatory markers and serum haemagglutinin inhibition antibody titres against the influenza viruses. The current treatment for T1D is largely symptomatic, relying on insulin administration. There is a pressing need for novel pharmacological approaches aimed at modulating the immune system to preserve residual ß-cell function. Existing immunotherapies are cost-prohibitive and associated with multiple side effects, whereas influenza vaccination is inexpensive and generally well tolerated. A positive outcome of this study holds potential for immediate implementation into standard care for children and adolescents with recent-onset T1D and may guide future research on immune modulation in T1D. ETHICS AND DISSEMINATION: Ethical approval was obtained from Danish Health Authorities prior to participant enrollment. The trial results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05585983 and EudraCT Number 2022-500906-17-01.

Dose to organs at risk for total body irradiation: Single-institution data using the modulated arc total body irradiation technique.

BACKGROUND: Organs at risk (OAR) dose reporting for total body irradiation (TBI) patients is limited, and standardly reported only as mean doses to the lungs and kidneys. Consequently, dose received and effects on other OAR remain unexplored. To remedy this gap, this study reports dose data on an extensive list of OAR for patients treated at a single institution using the modulated arc total body irradiation (MATBI) technique. METHOD: An audit was undertaken of all patients treated with MATBI between January 2015 and March 2021 who had completed their course of treatment. OAR were contoured on MATBI patient treatment plans, with 12 Gy in six fraction prescription. OAR dose statistics and dose volume histogram data are reported for the whole body, lungs, kidneys, bones, brain, lens, heart, liver and bowel bag. RESULTS: The OAR dose data for 29 patients are reported. Mean dose results are body 11.77 Gy, lungs 9.86 Gy, kidneys 11.84 Gy, bones 12.03 Gy, brain 12.12 Gy, right lens 12.31 Gy, left lens 12.64 Gy, heart 11.07 Gy, liver 11.81 Gy and bowel bag 12.06 Gy. Dose statistics at 1-Gy intervals of V6-V13 for lungs and V10-V13 for kidneys are also included. CONCLUSION: This is the first time an extensive list of OAR data has been reported for any TBI technique. Due to the paucity of reporting, this information could be used by centres implementing the MATBI technique, in addition to aiding comparison between TBI techniques, with the potential for greater understanding of the relationship between dose volume data and toxicity.