Outcome measures for use in trials of paediatric otorrhoea:A systematic review

Introduction:Paediatric otorrhoea (PO) describes a middle ear infection that results in a perforation of the tympanic membrane and ear discharge, in children and young people (CYP). Prolonged infection may be associated with hearing loss and developmental delay. The current management of paediatric otorrhoea is variable, including non-invasive treatments (conservative, oral antibiotics, topical antibiotics) and surgery, reflecting the lack of a sufficiently strong evidence base. Outcome reporting is fundamental to producing reliable and meaningful evidence to inform best practice.Objectives:Primary objective: to determine which outcome measures are currently used to evaluate treatment success in studies of non-surgical treatments for paediatric otorrhoea. Secondary objectives: to identify outcome measurement instruments used in the literature and assess their applicability for use in clinical trials of PO.Methods:This systematic review was registered with PROSPERO (CRD42023407976). Database searches of EMBASE, MEDLINE and Cochrane was performed on June 6, 2023, covering from Jan 1995 to May 2023. Randomised controlled trials or study protocols involving CYP with PO were included following PRISMA guidelines. Risk of bias was assessed with Cochrane's tool.Results:Of the 377 papers identified, six were included in the systematic review. The primary outcome of five of the studies related to otorrhoea cessation; both time to cessation and proportion recovered at various time points were used as measures. Two measurement instruments were identified: Otitis Media-6 Questionnaire and the Institute for Medical Technology Assessment Productivity Cost Questionnaire. Both were shown to be applicable measurement instruments when used in clinical trials of PO.Conclusions:To promote homogeneity and facilitate meaningful comparison and combination of studies, we propose that time to cessation of otorrhoea from onset of otorrhoea should be used as the primary outcome in future studies. Further research is needed to establish if this is the most important outcome to children and their caregivers

Computerised speechreading training for deaf children: A randomised controlled trial

Purpose: We developed and evaluated in a randomised controlled triala computerised speechreading training programme to determine a) whether it is possible to train speechreading in deaf children and b) whether speechreading training results in improvements in phonological and reading skills.Previous studies indicate a relationship between speechreading and reading skill and further suggest this relationshipmay be mediated by improved phonological representations. This is important since many deaf children find learning to read to be very challenging. Method: Sixty-six deaf 5-7 year olds were randomised into speechreading and maths training arms. Each training programme was comprised of10 minutesessionsa day, 4 days a week for 12 weeks. Children were assessed on a battery of language and literacy measures before training, immediately after training, 3 months and 10 months after training. Results: We found no significant benefits for participants who completed the speechreading training, compared to those who completed the maths training, on the speechreading primary outcome measure. However, significantly greater gains were observed in the speechreading training group on one of the secondary measures of speechreading. There was also some evidence of beneficial effects of the speechreading training on phonological representations, however these effects were weaker. No benefits were seen toword reading. Conclusions: Speechreading skill is trainable in deaf children. However, to support early reading, training may need to be longer or embedded in a broader literacy programme. Nevertheless, a training tool that can improve speechreading is likely to be of great interest to professionals working with deaf children

Managing female athlete health : Auditing the representation of female versus male participants among research in supplements to manage diagnosed micronutrient issues

Micronutrient deficiencies and sub-optimal intakes among female athletes are a concern and are commonly prevented or treated with medical supplements. However, it is unclear how well women have been considered in the research underpinning current supplementation practices. We conducted an audit of the literature supporting the use of calcium, iron, and vitamin D. Of the 299 studies, including 25,171 participants, the majority (71%) of participants were women. Studies with exclusively female cohorts (37%) were also more prevalent than those examining males in isolation (31%). However, study designs considering divergent responses between sexes were sparse, accounting for 7% of the literature. Moreover, despite the abundance of female participants, the quality and quantity of the literature specific to female athletes was poor. Just 32% of studies including women defined menstrual status, while none implemented best-practice methodologies regarding ovarian hormonal control. Additionally, only 10% of studies included highly trained female athletes. Investigations of calcium supplementation were particularly lacking, with just two studies conducted in highly trained women. New research should focus on high-quality investigations specific to female athletes, alongside evaluating sex-based differences in the response to calcium, iron, and vitamin D, thus ensuring the specific needs of women have been considered in current protocols involving medical supplements

Protocol for a Randomized Multiple Center Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children (Oxy-PICU): Oxygen in Paediatric Intensive Care

OBJECTIVES: Oxygen administration is a fundamental part of pediatric critical care, with supplemental oxygen offered to nearly every acutely unwell child. However, optimal targets for systemic oxygenation are unknown. Oxy-PICU aims to evaluate the clinical effectiveness and cost-effectiveness of a conservative peripheral oxygen saturation (Spo2) target of 88-92% compared with a liberal target of more than 94%. DESIGN: Pragmatic, open, multiple-center, parallel group randomized control trial with integrated economic evaluation. SETTING: Fifteen PICUs across England, Wales, and Scotland. PATIENTS: Infants and children age more than 38 week-corrected gestational age to 16 years who are accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. INTERVENTION: Adjustment of ventilation and inspired oxygen settings to achieve an Spo2 target of 88-92% during invasive mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Randomization is 1:1 to a liberal Spo2 target of more than 94% or a conservative Spo2 target of 88-92% (inclusive), using minimization with a random component. Minimization will be performed on: age, site, primary reason for admission, and severity of abnormality of gas exchange. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred to after randomization. The primary clinical outcome is a composite of death and days of organ support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support, and discharge outcomes. This trial received Health Research Authority approval on December 23, 2019 (reference: 272768), including a favorable ethical opinion from the East of England-Cambridge South Research Ethics Committee (reference number: 19/EE/0362). Trial findings will be disseminated in national and international conferences and peer-reviewed journals

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis : a pilot project of the ENIGMA–DTI working group

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/)

Evaluation of a Medical and Mental Health Unit compared with standard care for older people whose emergency admission to an acute general hospital is complicated by concurrent 'confusion': a controlled clinical trial. Acronym: TEAM: Trial of an Elderly Acute care Medical and mental health unit

Background: Patients with delirium and dementia admitted to general hospitals have poor outcomes, and their carers report poor experiences. We developed an acute geriatric medical ward into a specialist Medical and Mental Health Unit over an eighteen month period. Additional specialist mental health staff were employed, other staff were trained in the ‘person-centred’ dementia care approach, a programme of meaningful activity was devised, the environment adapted to the needs of people with cognitive impairment, and attention given to communication with family carers. We hypothesise that patients managed on this ward will have better outcomes than those receiving standard care, and that such care will be cost-effective. Methods/design: We will perform a controlled clinical trial comparing in-patient management on a specialist Medical and Mental Health Unit with standard care. Study participants are patients over the age of 65, admitted as an emergency to a single general hospital, and identified on the Acute Medical Admissions Unit as being ‘confused’. Sample size is 300 per group. The evaluation design has been adapted to accommodate pressures on bed management and patient flows. If beds are available on the specialist Unit, the clinical service allocates patients at random between the Unit and standard care on general or geriatric medical wards. Once admitted, randomised patients and their carers are invited to take part in a follow up study, and baseline data are collected. Quality of care and patient experience are assessed in a non-participant observer study. Outcomes are ascertained at a follow up home visit 90 days after randomisation, by a researcher blind to allocation. The primary outcome is days spent at home (for those admitted from home), or days spent in the same care home (if admitted from a care home). Secondary outcomes include mortality, institutionalisation, resource use, and scaled outcome measures, including quality of life, cognitive function, disability, behavioural and psychological symptoms, carer strain and carer satisfaction with hospital care. Analyses will comprise comparisons of process, outcomes and costs between the specialist unit and standard care treatment groups. Trial Registration number: ClinicalTrials.gov: NCT0113614

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Uptake and impact of vaccinating primary school-age children against influenza: experiences of a live attenuated influenza vaccine programme, England, 2015/16.

The 2015/16 influenza season was the third season of the introduction of an intra-nasally administered live attenuated influenza vaccine (LAIV) for children in England. All children aged 2‒6 years were offered LAIV, and in addition, a series of geographically discrete areas piloted vaccinating school-age children 7‒11 years old. Influenza A(H1N1)pdm09 was the dominant circulating strain during 2015/16 followed by influenza B. We measured influenza vaccine uptake and the overall and indirect effect of vaccinating children of primary school -age, by comparing cumulative disease incidence in targeted and non-targeted age groups in vaccine pilot and non-pilot areas in England. Uptake of 57.9% (range: 43.6-72.0) was achieved in the five pilot areas for children aged 5‒11 years. In pilot areas, cumulative emergency department respiratory attendances, influenza-confirmed hospitalisations and intensive care unit admissions were consistently lower, albeit mostly non-significantly, in targeted and non-targeted age groups compared with non-pilot areas. Effect sizes were less for adults and more severe endpoints. Vaccination of healthy primary school-age children with LAIV at moderately high levels continues to be associated with population-level reductions in influenza-related respiratory illness. Further work to evaluate the population-level impact of the programme is required