Effect size and event rate estimation is necessary for sample size calculation in randomised clinical trials. Overestimation of the effect size and event rate can lead to inadequately powered studies and increased probability of false negative results. This is common in trials involving critically ill patients. However, such overestimation has not been systematically evaluated in trials involving neurocritical care. We aimed to conduct a systematic review of published randomised clinical trials involving critically ill neurological patients, to determine the accuracy of effect size and event rate estimation.

We will review randomised clinical trials involving adult critically ill neurological patients that were published from 2015 onwards in selected clinically useful and high-impact journals. We will include randomised clinical trials reporting a binary or time to event outcome, using two study groups, and a superiority design testing the efficacy of diagnostic, monitoring, therapeutic or process interventions. All eligible studies must report an estimated event rate in the control group and estimated effect size. All relevant studies will be identified through database searches. All study selection and data extraction will be conducted by two independent reviewers. We will use a random-effects model for pooling data. This review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Accuracy of effect size and event rate estimation will be evaluated by comparing the estimated and observed values. The association between the accuracy of the individual randomised clinical trial effect size and event rate estimation and rejection of the null hypothesis will be evaluated using logistic regression analysis. Multivariable linear regression analysis will be used to explore the factors associated with accuracy of effect size and event rate estimation. In addition, we will perform subgroup analysis by impact factor of the published journals, sample size of the studies and risk of bias.

As this systematic review will use data from previously published studies, it does not require ethics approval. Findings of this systematic review will be published in a peer-reviewed journal and will be presented at specialty-based conferences. The study will be included in the higher degree research thesis of the primary author.

CRD420251106394.

To compare costs and health consequences and to assess the cost-effectiveness of using low-dose oral long-acting morphine in people with chronic breathlessness.

Within-trial planned cost-consequences and cost-effectiveness analysis of data from a multisite, parallel-group, double-blind, randomised, placebo-controlled trial of low-dose, long-acting morphine.

11 hospital outpatients across the UK.

Consenting adults with chronic breathlessness due to long-term cardiorespiratory conditions.

5–10 mg two times a day oral long-acting morphine with a blinded laxative for 56 days.

Mean and SD of healthcare resource use (HRU) by trial arm; mean differences and 95% CI of costs between trial arms.

Mean differences in 28- and 56-day quality-adjusted life years (QALYs based on EuroQol five-dimension five-level score), Short Form-six dimensional scores and ICEpop CAPability-Supportive Care Measure scores; cost-utility of long-acting morphine for chronic breathlessness.

143 participants (75 morphine and 67 placebo) were randomised; 140 (90% power, males 66%, mean age 70.5 (SD 9.4)) formed the modified intention-to-treat population (participants receiving at least one dose of study medication). There were more inpatient and fewer outpatient services used by the morphine group versus the placebo. In the base-case analysis at 56 days, long-acting morphine was associated with similar mean per-patient costs and QALYs. There was an increase of £24 (95% CI –£395 to £552) and 0.002 (95% CI –0.004 to 0.008) QALYs. Hospitalisations were the main driver of cost differences. The corresponding incremental cost-effectiveness ratio was £12 000/QALY, with a probability of cost-effectiveness of 54% at a £20 000 willingness-to-pay threshold. In the scenario analysis that excluded costs of adverse events considered unrelated to long-acting morphine by site investigators and researchers, the probability of cost-effectiveness increased to 73%.

Oral morphine for chronic breathlessness is likely to be a cost-effective intervention provided adverse events are minimised, but the effect on outcome is small and cautious interpretation is warranted.

ISRCTN87329095.

The management of severe traumatic brain injury (sTBI) in the intensive care unit (ICU) is focused on preventing secondary brain insults, by ensuring adequate cerebral perfusion, oxygenation and substrate delivery. Despite optimisation of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) using evidence-based guidelines, brain tissue hypoxia can still occur and is strongly associated with adverse functional outcomes post sTBI.

The Brain Oxygen Neuromonitoring in Australia and New Zealand Assessment – Global Trial (BONANZA-GT) is an international, two-arm, open-label, parallel group, randomised controlled trial comparing sTBI management incorporating early brain tissue oxygen (PbtO₂) monitoring and optimisation, with ICP/CPP-based management alone. A total of 860 adults admitted to participating institutions with non-penetrating sTBI and requiring insertion of an ICP monitor (as determined by the treating neurosurgeon) will be enrolled. The primary outcome is the proportion of patients with favourable neurological outcomes, as defined by a Glasgow Outcome Score-Extended (GOS-E) >4, at 6 months following injury. Key secondary outcomes include all-cause mortality at ICU discharge, hospital discharge, adverse events, as well as hospital and ICU length of stay and GOS-E at 12 months. The BONANZA-GT will determine whether a protocolised therapeutic strategy guided by continuous PbtO₂ monitoring in addition to ICP/CPP targets results in improved neurological outcomes when compared with standard care using ICP/CPP-guided management alone.

Approval has been obtained from relevant ethics boards in every jurisdiction that is participating in the trial. Inclusion of adults who lack capacity for informed consent will be governed in accordance with the legal requirements of each participating site. Study findings will be presented at scientific meetings and disseminated via peer-review publications.

Australian and New Zealand Clinical Trials Registry (ACTRN 12619001328167).

Spironolactone is a useful and effective acne treatment option for adult female patients. We aim to establish whether spironolactone could be a safe treatment for the management of acne in the female adolescent population as well. The objective of this scoping review is to provide an evidence map of the safety profile of spironolactone in the paediatric population aged 0–17 across all clinical indications.

This scoping review will be conducted according to the Joanna Briggs Institute scoping review protocol. Relevant publications will be searched on the MEDLINE, Embase and Web of Science databases from inception until July 2025. The authors of included studies will be contacted using contact details provided in the manuscript to check for any further published or unpublished data on the review question. An initial search will be conducted using keywords to identify relevant articles. After identifying the research strategy, articles will be extracted into a reference management tool, and a two-part study selection process will be systematically applied by two reviewers. The first part consists of screening titles and abstracts to define the eligibility of each article. In the second part, the full texts will be screened and only relevant articles will be kept. All articles related to the safety of spironolactone in children and adolescents across all clinical indications will be included. Data will be extracted using a scoping review management software such as Covidence, collated and charted to summarise all the relevant methods, outcomes and key findings in the articles.

This scoping review will provide an extensive overview of the available safety evidence for the use of spironolactone in children and teenagers. Since the scoping review methodology consists of reviewing and collecting data from publicly available materials, this study does not require ethics approval. The results will be disseminated in a peer-reviewed publication.

Aphasia is a language impairment that affects one-third of people who experience a stroke. Aphasia can impact all facets of language: speaking, understanding, reading and writing. Around 60% of people with aphasia have persistent language impairments 1 year after their stroke, requiring ongoing healthcare and support. In recent years, the internet has become a key resource for the self-management of chronic health conditions. Navigating web content, however, requires language use, and as such, people living with aphasia are more likely to be excluded from digital health and support services. Web Content Accessibility Guidelines exist; however, they do not fully address the unique and diverse needs of people with aphasia, and a significant proportion of websites (over 90%) do not fully adhere to them. This protocol paper describes the first two stages of the Bridging the Digital Divide project, which aims to codesign and develop (a) a web-browser extension to re-render webpages to an ‘aphasia-friendly’ (accessible) format, (b) training tools to help users and health professionals customise the web-browser extension and (c) guidelines for developing communication-accessible websites.

The research will be conducted using experience-based codesign. In Stage 1a, focus groups will be held with (1) people with aphasia, (2) family members or significant others and (3) health professionals working with people with aphasia. Participants will be asked to share their experiences of accessing (or supporting a person with aphasia to access) healthcare, information and support services on the web. The nominal group technique (NGT) will be used to identify priorities for improving web accessibility for people with aphasia. Focus group data will be analysed using reflexive thematic analysis, and prioritisation data will be analysed using inductive qualitative content analysis. In Stage 1b, eight codesign workshops will be held with representatives of the three key stakeholder groups to iteratively codesign and develop a web-browser extension, training tools and guidelines to support web accessibility.

Ethical clearance for Stage 1a and Stage 1b of this project has been approved by the University of Queensland Human Research Ethics Committee (Stage 1a approval number: 2023/HE000528, Stage 1b approval number: 2024/HE000721). The outcomes of this research will be disseminated in peer-reviewed journals and presented at national and international conferences. A dissemination and celebration event will be held at the completion of the project.

International consensus guidelines support the initial administration of 30 mL/kg of intravenous fluids for haemodynamic resuscitation of newly diagnosed septic shock. Practice variation exists between the volume of fluids administered and timing of vasopressor commencement. The optimal approach in patients with septic shock is uncertain.

Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In emergency Department Sepsis is a 1000-participant multicentre, randomised, open-label, parallel group clinical trial conducted in patients with septic shock presenting to the emergency department in participating sites in Australia, New Zealand and Ireland. Participants are randomised (1:1) to either restricted fluids and early vasopressors or a larger initial intravenous fluid volume and later vasopressors. The primary outcome is days alive and out of hospital at day 90 postrandomisation. Secondary outcomes are all-cause mortality at day 90, time from randomisation until death (to day 90), days alive and at home at day 90 and ventilator-free, vasopressor-free and renal replacement-free days to day 28 postrandomisation and death or disability at 6-month and 12-month postrandomisation. Health-related quality of life will be assessed at day 180 and 12 months following randomisation.

The study was approved by Northern Sydney Local Health District Human Research Ethics Committee (HREC2020/ETH02874) on 21 January 2021. Patients will be enrolled under a waiver of prior consent. The patient or next-of-kin (or equivalent according to local jurisdiction) is approached at the first available opportunity and given a trial information sheet. According to local approvals, the patient or next-of-kin chooses to either continue in the trial or opt-out/decline continued participation. Results will be disseminated in peer-reviewed journals and presented at academic conferences.

NCT04569942

Pain is one of the most bothersome symptoms that affects patients with inflammatory bowel disease (IBD) but is often inadequately treated. Inadequate pain control in the inpatient setting not only impacts patients’ experience but increases opioid use and hospital length of stay. Opioids are often considered first-line treatment for severe pain but are associated with significant morbidity and mortality in IBD. Non-steroidal anti-inflammatory drugs are a non-opioid analgesic option, but concerns regarding their contribution to IBD flares have limited their use. Brain-gut behavioural therapies (BGBT), such as cognitive behavioural therapy, meditation and gut-directed hypnotherapy, are effective for pain management and have a role in the treatment of IBD symptoms. However, the use of BGBT in IBD is challenging, given limited access to behavioural health specialists, especially in the inpatient setting. Virtual reality (VR)-directed BGBT programmes can bridge this gap and enhance pain treatment for inpatients with IBD. Therefore, in this study, we aim to establish feasibility and acceptability for a VR-directed BGBT inpatient programme for patients with IBD.

We will recruit 40 patients with IBD who are hospitalised at Michigan Medicine and who endorse IBD-related pain. We will assess patient-reported outcomes (pain rating, IBD-specific symptoms, perceived stress, mood) before and after treatment, cumulative inpatient analgesic requirements and hospital length of stay. Our primary objective will be to establish intervention feasibility defined by the frequency and percentage of enrolled participants that use the VR-directed BGBT inpatient intervention in any capacity. Our secondary objective will be to evaluate intervention acceptability by conducting semistructured interviews with study participants. We will also explore the preliminary effectiveness of VR-directed BGBT on patient-reported outcomes and healthcare utilisation as compared with historic controls.

The study was approved by the institutional review board of the University of Michigan Medical School on 10 October 2023 (HUM00240999). All human subjects will be required to sign an informed consent document prior to study participation. Study findings will be reported through peer-reviewed publication.

NCT06188793.