IntroductionThe predisposition to food allergy development and the induction of allergen-specific immune responses appears to be initiated early in infancy. Early exposure to food allergens, such as peanut and cashew nut, via human milk is likely important in initiating oral tolerance and reducing risk of food allergy development. This trial aims to determine if the risk of developing peanut and cashew nut allergy during infancy can be reduced by a high peanut and cashew nut maternal diet during lactation.Methods and analysisThis is a multisite, parallel, two-arm (1:1 allocation), single-blinded (outcome assessors, statistical analyst and investigators), randomised controlled trial. Target sample size is 4412 participants (2206 per group). Women (aged 18–50 years) with a singleton pregnancy, who are planning to breastfeed and do not have peanut and/or cashew nut allergies are eligible to participate. After obtaining written informed consent, participants are randomised to either a high peanut and cashew nut diet (at least 60 peanuts and 40 cashew nuts per week) or a low peanut and cashew nut diet (no more than 20 peanuts and 12 cashew nuts per week). Participants are asked to follow their allocated diet from birth to 6 months postnatal. Individual lactation consultant advice and support is provided as required. The study’s primary outcome is food challenge proven IgE-mediated peanut and/or cashew nut allergy during infancy (0–18 months). Key secondary outcomes include infant sensitisation to peanut and/or cashew nut. Analyses will be performed on an intention-to-treat basis according to a prespecified statistical analysis plan.Ethics and disseminationEthical approval has been granted from the Western Australian Child and Adolescent Health Service Human Research Ethics Committee (approval number RGS0000006685). Trial results will be presented at scientific conferences and published in peer-reviewed journals.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN ACTRN12624000134527)

Letermovir, a cytomegalovirus (CMV) terminase complex inhibitor, was first approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic hematopoietic cell transplant (HCT) recipients (R+). This study evaluated the pharmacokinetics (PK), efficacy, and safety of letermovir in pediatric R+ allogeneic HCT recipients. In this Phase 2b, single-arm, open-label study, 65 participants were enrolled sequentially in three age groups (AG; AG1, 12 to <18 years; AG2, 2 to <12 years; and AG3, birth to <2 years). PK was evaluated in an initial cohort in each AG using intensive PK data to confirm or modify dosing before enrolling the remaining participants. Adult HCT population PK (PopPK) data were used to establish the exposure reference range. The adult letermovir dose evaluated in AG1 and AG2 participants achieved exposures generally within the adult HCT reference range. In AG3, the initial cohort (letermovir with cyclosporin A) achieved exposures trending lower than the median exposure target; the letermovir dose was increased for the remaining participants. Efficacy and safety in pediatric participants were generally consistent with adult HCT data. A pediatric HCT PopPK model was developed to determine dose recommendations to be included in patient prescribing information. The doses evaluated achieved exposures generally within the adult HCT reference range. At exposures achieved, letermovir was efficacious and safe in preventing clinically significant CMV infection in pediatric allogeneic HCT recipients. The observed concentration data informed a pediatric PopPK model to optimize final letermovir dose recommendations in this population.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT03940586.

Abstract Literature suggests that there is a paucity of dedicated concussion clinics in Australia, with the ones that exist being privately owned and usually offering discipline specific services (e.g. physiotherapy) (Nguyen, McKay, Ponsford, Davies, Makdissi, Drummond, Reyes, Makovec Knight, Peverill, Brennan &amp; Willmott, 2023). Whilst the long-term impact of concussions, for instance, traumatic encephalopathy syndrome, dominates media coverage, everyday concussions, especially at the community level, require more consideration. Concussions need to be identified and managed appropriately using best practice care. This is usually provided initially, by a General Practitioner or Emergency Department. However, if concussion symptoms are prolonged, a multidisciplinary team of concussion experts are best placed to provide the required holistic care. Prior to 2022, there was no adult public concussion clinic in NSW and only one public paediatric concussion clinic at Sydney Children’s Hospital, Westmead. The need for more clinics was apparent, and overseas literature suggests that multidisciplinary management made the most gain in regard to patient outcomes (Jaganathan &amp; Sullivan, 2020). Therefore, the Northern Sydney Local Health District (NSLHD) established a multidisciplinary Concussion Clinic at Royal North Shore Hospital (RNSH) in 2022. This was the first of its kind in Australia, where a true multidisciplinary approach was at the centre of the model of care. While there are many multidisciplinary clinics in Australia, the difference is that this one had the multidisciplinary team (MDT) playing a combined role in the assessments and discussions with the patient, all seeing the patient together in real time. This made for better understanding of events, concussive mechanisms, recovery timelines, symptom causes, patient examination, and a diverse but cohesive evidence-based approach to treatment and management. There was less repetition for the patient, optimised resource and time allocation per patient, increasing quality and effectiveness of care while reducing wait times to access appropriate services, notwithstanding increased patient satisfaction.

Adolescence is a period of rapid transformation when meeting targets for optimal diabetes care is often challenging due to competing life demands. For more than two decades a diabetes transition clinic in Sydney, Australia, has sustained positive outcomes and demonstrated aspects of resilience in the care of individuals living with type 1 diabetes (T1D) who have transitioned from paediatric to adult care. Many studies have focused on resilience in acute care setting showever, studies that examine the factors that support resilience in settings that care for individuals with long-term, chronic conditions such as T1D are lacking. This study aims to examine the contributions of relationships among stakeholders, including adolescents and young adults living with T1D, their carers and healthcare providers, to the resilience of a T1D transition clinic. Clinic observations at a paediatric clinic (transition preparation) and a T1D transition clinic located in an adult hospital, and interviews with eight providers comprising endocrinologists, diabetes educators, nurses and an administrator, and 17 adolescents/young adults (aged 16-25 years) living with T1D were conducted. Inductive and deductive analyses were performed using a framework of seven principles for Patient and Stakeholder Involvement in Resilience in Healthcare. There was evidence for all seven principles though three were strongly expressed in the data: (1) Individual factors, (2) Influence of leadership and (3) Relationships among young adults, carers, and healthcare providers. Overall, key contributions to the clinic's resilience included a stable and cohesive team, continuity of staff, strong leadership sustained over 20 years, presence of a clinic coordinator, open channels of communication, and a positive, supportive culture among clinic stakeholders. There was also evidence of situational resilience and established processes that were adapted to suit an individuals' needs such as transition timing, mode of service (e.g., telehealth) and appointment time (e.g., after hours). Resilience in transitional care settings such as those that support young adults living with T1D are contingent on person-centred care, relational leadership, and strong and supportive relationships. Similar transitional care clinics could seek to test this model in different contexts to assess the transferability of the findings described here.

Aim: To report the efficacy and safety of ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) from the phase III, 72-week, placebo-controlled period of Study 041. Materials & methods: Inclusion criteria: boys with nmDMD aged ≥5years, on a stable corticosteroid regimen for ≥12months, and baseline 6-minute walk distance (6MWD) ≥150m. Randomization: 1:1, ataluren (40mg/kg/day):placebo. Primary end point: slope of 6MWD change (average rate of change). Secondary end points: changes in 6MWD, time to 10% persistent worsening in 6MWD, North Star Ambulatory Assessment score, timed function tests and safety. Study populations: intention-to-treat; patients aged ≥7 to ≤16years with baseline 6MWD ≥300m and stand from supine ≥5s; patients with baseline 6MWD 300-400m. Results: In the intention-to-treat population (n=359), over 72weeks, ataluren reduced the rate of 6MWD decline by 21% (p = 0.0248), reduced the average 6MWD change (p = 0.0248), delayed time to 10% persistent worsening in 6MWD (p = 0.0078), and reduced North Star Ambulatory Assessment total score decline (p = 0.0235), change in 10m walk/run time (p=0.0422) and change in time to climb four stairs (p = 0.0293) versus placebo. In the 6MWD 300-400m subgroup (n=169), ataluren reduced the rate of 6MWD decline by 30% (p = 0.0310) versus placebo. Ataluren treatment benefits were seen in secondary end points in this subgroup, except for change in time to descend four stairs. In the 6MWD ≥300m and time to stand from supine ≥5s subgroup (n=185), there was a 9% slower rate of 6MWD decline for ataluren versus placebo over 72weeks (p = 0.3626). Ataluren reduced change in time to climb four stairs (p = 0.0179) versus placebo in this subgroup; no treatment benefits were seen for other secondary end points. Ataluren was well tolerated (serious adverse events: ataluren, 7.1%; placebo, 6.8%); no deaths occurred. Conclusion: Long-term ataluren treatment has a favorable benefit-risk profile, slowing motor function decline in the largest phase III nmDMD study to date.

To evaluate the predictive validity of best practice early detection tools for cerebral palsy (CP) in a high-risk cohort. Prospective longitudinal cohort study. Neonatal intensive care unit of a regional tertiary hospital in Bangladesh. Neonates with risk factors for CP admitted to Mymensingh Medical College Hospital Neonatal Intensive Care Unit between November 2019 and March 2020. General Movements Assessment (GMA) at writhing and fidgety periods; Hammersmith Infant Neurological Examination (HINE) and Peabody Developmental Motor Scales Second Edition (PDMS-2) conducted in person at 3, 12 and 24 months. The Developmental Assessment of Young Children (DAYC-2), Ages and Stages Questionnaire (ASQ-3) and Developmental Milestones Chart (DMC) were administered remotely at 6, 9, 12, 18 and 24 months. Due to the impact of COVID-19, a proportion of the cohort was not able to have GMA fidgety videos completed and the first HINE assessment was delayed. A total of 227 infants were enrolled. Of the surviving infants assessed at 24 months, 36 (29%) had a confirmed diagnosis of CP. The most accurate combination of tools for early detection was GMA and HINE at 3 months (sensitivity 0.91; specificity 1.00). The PDMS-2 Total Motor Quotient, with an optimised cut-off of 59, showed high accuracy at 24 months (sensitivity 0.94; specificity 0.99). Among the tools administered remotely, the DAYC-2 PD, DMC (Gross and Fine Motor domains) and ASQ-3 (Gross and Fine Motor domains) demonstrated strong predictive validity-both individually and in combination-at 9, 12, 18 and 24 months, supporting their use as practical alternatives when in-person assessments are not feasible. Despite pandemic-related disruptions, an accurate diagnosis was possible as early as 3 months of age using the best practice tools. Our findings support the practicability of scalable early detection models integrating in-person and remote assessments to improve access to timely diagnosis.

Objective: This study aimed to explore information needs and preferences of children with cancer and their parents about cancer-related symptoms. Methods: A systematic review of the literature was conducted using five databases and citation searches. The quality of eligible studies was assessed with the Mixed Methods Appraisal Tool. Results: Thirty studies were included (N=256 children and N=1778 parents/guardians). Children’s perspectives on their information needs were under examined and different from their parents. Both children and parents required more information about symptoms and late effects. Associations between participants’ characteristics and their information needs about symptoms and late effects were inconclusive. Parents preferred to receive information from doctors, in verbal and written formats, more than from online sources. Conclusions: Children with cancer and their parents need more tailored information about symptoms and late effects. Further research is required to identify how best to support individualized information needs and delivery preferences of children with cancer and their parents.