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Abstract Background Respiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-β is naturally produced in response to viral infection, limiting replication. This exploratory study aimed to demonstrate proof-of-mechanism, and evaluate the efficacy and safety of inhaled recombinant interferon-β1a (SNG001) in COPD. Part 1 assessed the effects of SNG001 on induced sputum antiviral interferon-stimulated gene expression, sputum differential cell count, and respiratory function. Part 2 compared SNG001 and placebo on clinical efficacy, sputum and serum biomarkers, and viral clearance. Methods In Part 1, patients (N = 13) with stable COPD were randomised 4:1 to SNG001 or placebo once-daily for three days. In Part 2, patients (N = 109) with worsening symptoms and a positive respiratory viral test were randomised 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e., acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]). Results In Part 1, SNG001 upregulated sputum interferon gene expression. In Part 2, there were minimal SNG001–placebo differences in the efficacy endpoints; however, whereas gene expression was initially upregulated by viral infection, then declined on placebo, levels were maintained with SNG001. Furthermore, the proportion of patients with detectable rhinovirus (the most common virus) on Day 7 was lower with SNG001. In Group B, serum C-reactive protein and the proportion of patients with purulent sputum increased with placebo (suggesting bacterial infection), but not with SNG001. The overall adverse event incidence was similar with both treatments. Conclusions Overall, SNG001 was well-tolerated in patients with COPD, and upregulated lung antiviral defences to accelerate viral clearance. These findings warrant further investigation in a larger study. Trial registration EU clinical trials register (2017-003679-75), 6 October 2017.

Introduction Central venous access devices (CVADs) are commonly used for the treatment of paediatric cancer patients. Catheter locking is a routine intervention that prevents CVAD-associated adverse events, such as infection, occlusion and thrombosis. While laboratory and clinical data are promising, tetra-EDTA (T-EDTA) has yet to be rigorously evaluated or introduced in cancer care as a catheter lock.Methods and analysis This is a protocol for a two-arm, superiority type 1 hybrid effectiveness-implementation randomised controlled trial conducted at seven hospitals across Australia and New Zealand. Randomisation will be in a 3:2 ratio between the saline (heparinised saline and normal saline) and T-EDTA groups, with randomly varied blocks of size 10 or 20 and stratification by (1) healthcare facility; (2) CVAD type and (3) duration of dwell since insertion. Within the saline group, there will be a random allocation between normal and heparin saline. Participants can be re-recruited and randomised on insertion of a new CVAD. Primary outcome for effectiveness will be a composite of CVAD-associated bloodstream infections (CABSI), CVAD-associated thrombosis or CVAD occlusion during CVAD dwell or at removal. Secondary outcomes will include CABSI, CVAD-associated-thrombosis, CVAD failure, incidental asymptomatic CVAD-associated-thrombosis, other adverse events, health-related quality of life, healthcare costs and mortality. To achieve 90% power (alpha=0.05) for the primary outcome, data from 720 recruitments are required. A mixed-methods approach will be employed to explore implementation contexts from the perspective of clinicians and healthcare purchasers.Ethics and dissemination Ethics approval has been provided by Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC) (HREC/22/QCHQ/81744) and the University of Queensland HREC (2022/HE000196) with subsequent governance approval at all sites. Informed consent is required from the substitute decision-maker or legal guardian prior to participation. In addition, consent may also be obtained from mature minors, depending on the legislative requirements of the study site. The primary trial and substudies will be written by the investigators and published in peer-reviewed journals. The findings will also be disseminated through local health and clinical trial networks by investigators and presented at conferences.Trial registration number ACTRN12622000499785.

The Expanded Endoscopic Endonasal Approach, one of the best examples of endoscopic neurosurgery, allows access to the skull base through the natural orifice of the nostril. Current standard instruments lack articulation limiting operative access and surgeon dexterity, and thus, could benefit from robotic articulation. In this study, a handheld robotic system with a series of detachable end-effectors for this approach is presented. This system is comprised of interchangeable articulated 2/3 degrees-of-freedom 3 mm instruments that expand the operative workspace and enhance the surgeon’s dexterity, an ergonomically designed handheld controller with a rotating joystick-body that can be placed at the position most comfortable for the user, and the accompanying control box. The robotic instruments were experimentally evaluated for their workspace, structural integrity, and force-delivery capabilities. The entire system was then tested in a pre-clinical context during a phantom feasibility test, followed up by a cadaveric pilot study by a cohort of surgeons of varied clinical experience. Results from this series of experiments suggested enhanced dexterity and adequate robustness that could be associated with feasibility in a clinical context, as well as improvement over current neurosurgical instruments.

Abstract There have been recent restrictions to the range of gambling products made available to UK children, with the industry association Bacta introducing a minimum age of 18 for Category D fruit machines, which can otherwise be legally used by children. Any potential government action on Category D fruit machines may want to consider limitations in the current evidence base. The present study addressed this issue, by conceptually replicating previous results associating recollected usage of Category D fruit machine usage as a child and adult gambling. Compared to previous studies, the present study used a younger adult sample, and also tested for potential moderation by subjective confidence. Three out of four main tested associations were significant and in the hypothesised direction, and a lack of significance on interaction terms yielded no evidence of potential moderation by subjective confidence. The present study therefore added to the limited evidence base on potential risks of legal Category D fruit machine usage as a child.

The term neuromyths refers to misconceptions about learning and the brain. Educator neuromyths may result in inappropriate instruction, labelling of learners, and wasted resources. To date, little research has considered the sources of these beliefs. We surveyed 1359 Australian preservice educators (M = 22.7, SD = 5.7 years) about their sources of information for 15 neuromyth and 17 general brain knowledge statements. Consistent with previous studies, neuromyth beliefs were prevalent. Predictors of neuromyth accuracy included general brain knowledge and completion of university classes addressing neuromyths, although effects were modest. Depending on the belief, participants relied on general knowledge, academic staff, school staff, and popular media. Recommendations for teacher education are presented.

Objective Develop a process map of when patients learn about their proposed surgery and what resources patients use to educate themselves.Design A mixed methods design, combining semistructured stakeholder interviews, quantitative validation using electronic healthcare records (EHR) in a retrospective cohort and a cross-sectional patient survey.Setting A single surgical centre in the UK.Participants Fourteen members of the spinal multidisciplinary team were interviewed to develop the process map.This process map was validated using the EHR of 50 patients undergoing elective spine surgery between January and June 2022. Postprocedure, feedback was gathered from 25 patient surveys to identify which resources they used to learn about their spinal procedure. Patients below the age of 18 or who received emergency surgery were excluded.Interventions Elective spine surgery and patient questionnaires given postoperatively either on the ward or in follow-up clinic.Primary and secondary outcome measures The primary outcome was the percentage of the study cohort that was present at encounters on the process map. Key timepoints were defined if >80% of patients were present. The secondary outcome was the percentage of the study cohort that used educational resources listed in the patient questionnaire.Results There were 342 encounters which occurred across the cohort, with 16 discrete event categories identified. The initial surgical clinic (88%), anaesthetic preoperative assessment (96%) and admission for surgery (100%) were identified as key timepoints. Surveys identified that patients most used verbal information from their surgeon (100%) followed by written information from their surgeon (52%) and the internet (40%) to learn about their surgery.Conclusions Process mapping is an effective method of illustrating the patient pathway. The initial surgical clinic, anaesthetic preoperative assessment and surgical admission are key timepoints where patients receive information. This has future implications for guiding patient education interventions to focus at key timepoints.

IntroductionGroup A streptococcus (GAS) infections, such as pharyngitis and impetigo, can lead to rheumatic fever and rheumatic heart disease (RHD). Australian Aboriginal and Torres Strait Islander populations experience high rates of RHD and GAS skin infection, yet rates of GAS pharyngitis are unclear. Anecdotally, clinical presentations of pharyngitis, including tonsillar hypertrophy and sore throat, are uncommon. This study aimed to develop a standardised set of tonsil photographs and determine tonsil size distribution from an urban paediatric population.MethodsA prospective cohort of children aged 3–15 years were recruited at the public events “Discover Day” and “Telethon Weekend” (October 2017) in Perth, Western Australia, Australia. Tonsil photographs, symptomatology, and GAS rapid antigen detection tests (RADT) were collected. Tonsil size was graded from the photographs using the Brodsky Grading Scale of tonsillar hypertrophy (Brodsky) by two independent clinicians, and inter-rater reliability calculated. Pharyngitis symptoms and GAS RADT were correlated, and immediate results provided.ResultsFour hundred and twenty-six healthy children participated in the study over three days. The median age was seven years [interquartile range (IQR) 5.9–9.7 years]. Tonsil photographs were collected for 92% of participants, of which 62% were rated as good-quality photographs and 79% were deemed of adequate quality for assessment by both clinicians. When scored by two independent clinicians, 57% received the same grade. Average Brodsky grades (between clinicians) were 11%, 35%, 28%, 22% and 5% of grades 0,1,2,3 and 4, respectively. There was moderate agreement in grading using photographs, and minimal to weak agreement for signs of infection. Of 394 participants, 8% reported a sore throat. Of 334 GAS RADT performed,

Abstract l-DOPA is deficient in the developing albino eye, resulting in abnormalities of retinal development and visual impairment. Ongoing retinal development after birth has also been demonstrated in the developing albino eye offering a potential therapeutic window in humans. To study whether human equivalent doses of l-DOPA/Carbidopa administered during the crucial postnatal period of neuroplasticity can rescue visual function, OCA C57BL/6 J-c2J OCA1 mice were treated with a 28-day course of oral l-DOPA/Carbidopa at 3 different doses from 15 to 43 days postnatal age (PNA) and for 3 different lengths of treatment, to identify optimum dosage and treatment length. Visual electrophysiology, acuity, and retinal morphology were measured at 4, 5, 6, 12 and 16 weeks PNA and compared to untreated C57BL/6 J (WT) and OCA1 mice. Quantification of PEDF, βIII-tubulin and syntaxin-3 expression was also performed. Our data showed impaired retinal morphology, decreased retinal function and lower visual acuity in untreated OCA1 mice compared to WT mice. These changes were diminished or eliminated when treated with higher doses of l-DOPA/Carbidopa. Our results demonstrate that oral l-DOPA/Carbidopa supplementation at human equivalent doses during the postnatal critical period of retinal neuroplasticity can rescue visual retinal morphology and retinal function, via PEDF upregulation and modulation of retinal synaptogenesis, providing a further step towards developing an effective treatment for albinism patients.