The ‘time-limited trial’ for patients with critical illness is a collaborative plan made by clinicians, patients and families to use life-sustaining therapies for a defined duration. After this period, the patient’s response to therapy informs decisions about continuing recovery-focused care or transitioning to comfort-focused care. The promise of time-limited trials to help navigate the uncertain limits and benefits of life-sustaining therapies has been extensively discussed in the palliative and critical care literature, leading to their dissemination into clinical practice. However, we have little evidence to guide clinicians in how to conduct time-limited trials, leading to substantial variation in how and why they are currently used. The overall purpose of this study is to characterise the features of an optimal time-limited trial through a rich understanding of how they are currently shaping critical care delivery.

We are conducting an observational, multicentre, focused ethnography of time-limited trials in patients with acute respiratory failure receiving invasive mechanical ventilation in six intensive care units (ICUs) within five hospitals across the US. Study participants include patients, their surrogate decision makers and ICU clinicians. We are pursuing two complementary analyses of this rich data set using the open-ended, inductive approach of constructivist grounded theory and, in parallel, the structured, deductive methods of systems engineering. This cross-disciplinary, tailored approach intentionally preserves the tension between time-limited trials’ conceptual formulation and their heterogeneous, real-world use.

This study has been reviewed and approved by the University of Wisconsin Institutional Review Board (IRB) as the single IRB (ID: 2022-1681; initial approval date 23 January 2023). Our findings will be disseminated through peer-reviewed publication, conference presentations, and summaries for the public.

NCT06042621.

Transoral robotic surgery (TORS) is a minimally invasive technique for surgical removal of tumours of the tonsil and lateral oropharynx. Surgical defects after TORS lateral oropharyngectomy are traditionally left open to heal by secondary intention, resulting in significant postoperative pain and secondarily resulting in delayed swallowing and discharge. Although multimodal analgesia can improve postoperative pain control, no studies to date have assessed the impact of adjunct surgical interventions for reducing postoperative pain after TORS. Buccal fat rotation flap is a regional reconstruction option after TORS lateral oropharyngectomy and provides immediate coverage of the open surgical wound. However, the impact of buccal fat rotation flap reconstruction on postoperative pain and swallowing remains unclear. This trial aims to compare postoperative pain outcomes in patients who undergo TORS lateral oropharyngectomy with and without buccal fat rotation reconstruction.

This protocol outlines a single centre, parallel, unblinded, phase II, randomised control trial. Inclusion criteria include adult patient (≥18 years) undergoing TORS lateral oropharyngectomy for early to intermediate stage tonsillar squamous cell carcinoma (T1-2N0-1 p16+/–) or early to intermediate stage salivary gland tumours of the palatine tonsils. Exclusion criteria include a history of prior head and neck squamous cell carcinoma, prior head and neck radiotherapy, retropharyngeal lymphadenopathy, bilateral lymphadenopathy, need for bilateral neck dissection, baseline trismus, opioid use or drug addiction, need for open surgery (transcervical lateral oropharyngectomy), free tissue transfer, or alternative regional flap, and pregnancy. All patients are planned for a TORS lateral oropharyngectomy. The intervention group will have a buccal fat rotation flap reconstruction, and the control group will be allowed to heal via secondary intention. The allocation sequence will be created using a computer-generated random sequence with a permuted block strategy. The allocation sequence will be concealed until the time of assignment. The primary outcome is postoperative pain intensity during rest and swallowing using the visualised analogue scale. Secondary outcomes include postoperative complications, other adverse events, patient-reported speech and swallowing, opioid usage, length of hospital stay, feeding tube dependence and blood glucose levels. The trial has a target sample size of 40 patients. Statistical analysis of the primary outcome will be analysed in an intention to treat analysis using a linear mixed effects model.

The study was approved by the University Health Network Coordinated Approval Process for Clinical Research. Study number CAPCR ID: 24-5894. All participants will be required to provide written informed consent to participate. Findings will be presented at national conferences and published in medical journals.

NCT06965738.

Delays in cancer diagnosis for patients with non-specific symptoms (NSSs) lead to poorer outcomes. Rapid Diagnostic Clinics (RDCs) expedite care, but most NSS patients do not have cancer, highlighting the need for better risk stratification. This study aimed to develop biomarker-based clinical prediction scores to differentiate high-risk and low-risk NSS patients, enabling more targeted diagnostics.

Retrospective and prospective cohort study.

Secondary care RDC in London.

Adult patients attending an RDC between December 2016 and September 2023 were included. External validation used data from another RDC.

The primary outcome was a cancer diagnosis. Biomarker-based risk scores were developed using Latent Class Analysis (LCA) and Least Absolute Shrinkage and Selection Operator (LASSO). Model performance was assessed using logistic regression, receiver operating characteristic curves (AUROC) and decision curve analysis.

Among 5821 RDC patients, LCA identified high white cell count, low haemoglobin, low albumin, high serum lambda light chain, high neutrophil-to-lymphocyte ratio, high serum kappa light chain (SKLC), high erythrocyte sedimentation rate (ESR), high C-reactive protein (CRP) and high neutrophils as cancer risk markers. LASSO selected high platelets, ESR, CRP, SKLC, alkaline phosphatase and lactate dehydrogenase. Each one-point increase in score predicted higher odds of cancer (LCA: AOR 1.19, 95% CI 1.16 to 1.23; LASSO: AOR 1.29, 95% CI 1.25 to 1.34). Scores ≥2 predicted significantly higher cancer odds (LCA: AOR 3.79, 95% CI 2.91 to 4.95; LASSO: AOR 3.44, 95% CI 2.66 to 4.44). Discrimination was good (AUROC: LCA 0.74; LASSO 0.73). External validation in 573 patients confirmed predicted increases in cancer risk per one-point LASSO score rise (AOR 1.28, 95% CI 1.15 to 1.42), with a borderline increase for LCA (AOR 1.16, 95% CI 1.06 to 1.27).

Biomarker-based scores effectively identified NSS patients at higher cancer risk. LCA captured a broader biomarker range, offering higher sensitivity, while LASSO achieved higher specificity with fewer markers. These scores may also help detect severe benign conditions, improving RDC triage. Further validation is needed before broader clinical implementation.

Large differences exist in chronic kidney disease (CKD) rates between countries, but differences within diverse populations living in the same setting with universal healthcare are not well understood.

To compare dialysis prevalence, CKD risk factors and control, and CKD progression by ethnicity and birth country in an ethnoculturally diverse setting with high rates of kidney disease and universal healthcare.

Scarborough, Toronto’s most diverse region and site of Canada’s largest regional dialysis programme.

Double observational cohort study of 2397 participants: a retrospective cohort of 1116 residents who received dialysis between 2016–2019, and a prospective cohort of 1281 individuals with non-dialysis CKD followed for 3 years between 2010–2015 in Scarborough.

Dialysis prevalence, calculated by comparing frequencies of birth countries and ethnicities in the dialysis cohort with census-derived community frequencies. Secondary outcome measurements were traditional CKD risk factor prevalence (diabetes, hypertension, cardiovascular disease) and control (haemoglobin A1c, blood pressure); and CKD progression (estimated glomerular filtration rate decline, proteinuria) adjusted for socioeconomic status in the non-dialysis cohort.

Dialysis prevalence was 4.2 times higher in immigrants (p

Despite universal healthcare access, marked disparities in CKD risks and rates exist within ethnoculturally diverse immigrants living in this Canadian kidney disease hotspot. More focused research and tailored interventions are required.

Alcohol is consumed by an estimated 137.4 million people in the USA 12 years of age and older and, as a result, is estimated to have caused about 140 thousand deaths among people 20 to 64 years of age each year from 2015 up to and including 2019.

The proposed review of the evidence on alcohol’s impact on health aims to produce conclusions to inform the Dietary Guidelines for Americans, 2026–2030. A multi-method approach will be utilised to formulate conclusions on (i) weekly (ie, average) thresholds to minimise long-term and short-term risks of morbidity and mortality, (ii) daily thresholds to minimise the short-term risk of injury or acute illness due to per occasion drinking, (iii) alcohol use among vulnerable populations (eg, pregnant women) and (iv) situations and circumstances that are hazardous for alcohol use. To inform expert decisions, this project will also include a systematic review of existing low-risk drinking guidelines, a systematic review of meta-analyses which examine alcohol’s impact on key attributable disease and mortality outcomes, and of estimates of the lifetime absolute risk of alcohol-attributable mortality and morbidity based on a person’s sex and average level of alcohol use. The systematic reviews were designed in accordance with the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). The preliminary conclusions produced as a result of this project will undergo public consultation, and data from these consultations will be qualitatively analysed. The results of the public consultations will be used to further revise and refine the project’s conclusions.

The study was granted an ethics exemption as only secondary data sources and unidentifiable public consultation will be utilised. Systematic reviews are pre-registered with PROSPERO (registration numbers CRD42024584924 and CRD42024584948).

This project will establish a scientific consensus concerning alcohol’s impact on health. This consensus is imperative for informing the upcoming Dietary Guidelines for Americans, 2026–2030, and for better informing individuals about the health risks associated with alcohol use.

Streptococcus pneumoniae serotype 3 (SPN3) remains a significant contributor to invasive pneumococcal disease globally, despite its inclusion in widely administered vaccines. The next generation of pneumococcal vaccines may confer better protection against this serotype, reducing disease burden. We describe an ethically approved protocol for a double-blind randomised controlled trial assessing the impact of VAXNEUVANCE (15-valent pneumococcal conjugated vaccine (PCV15)) and 0.9% saline (placebo) on the acquisition, density and duration of SPN3 carriage using a controlled human infection model.

Healthy adults aged 18–50 years will be randomised 1:1 to receive PCV15 or placebo. Participants will be considered enrolled on the trial at vaccination. One month following vaccination, all participants will be intranasally inoculated with SPN3. Following inoculation, participants will be followed up on days 2, 7, 14 and 28 to monitor safety, SPN3 colonisation status, density and duration, as well as immune responses. The primary endpoint of the study is to assess the rate of SPN3 acquisition between vaccinated and unvaccinated participants defined by classical microbiological methods. Secondary endpoints will determine the density and duration of SPN3 colonisation and compare the immune responses between study groups. An exploratory cohort of 5 participants will be asked to consent to a nasal biopsy procedure during a screening visit and a second nasal biopsy 28 days after PCV15 vaccination. This cohort will only receive PCV15 and will not be challenged. Through this exploratory cohort, we will explore gene expression changes induced by PCV15 vaccination and their visualisation (spatial location) within the nasal tissue.

This protocol has been reviewed by the sponsor, funder and external peer reviewers. The study is approved by the NHS Research and Ethics Committee (Reference: 24/SC/0388) and by the Medicines and Healthcare Products Regulatory Agency (Reference: CTA 21584/0485/001-0001).

NCT06731374 – ISRCTN91656864.

Our study investigated the age-adjusted incidence rates of non-fatal overdoses by HIV status and sex, and examined trends over time.

We used data from the Comparative Outcomes and Service Utilization Trends study, a population-based cohort study that includes clinical and administrative health data on virtually all people with HIV (PWH) and a 10% random sample of people without HIV in the province.

British Columbia, Canada.

Between April 2012 and March 2020, 11 050 PWH (81.8% male) and 473 952 people without HIV (50.3% male) who were 19 years and older contributed 68 035 and 3 285 824 person years (PY) of follow-up, respectively.

The primary outcome was age-adjusted incidence rates of non-fatal overdose events stratified by sex and HIV status. Trends over time were also assessed.

Age-adjusted non-fatal overdose incidence rates among males with and without HIV were 36.4 and 3.12 per 1000 PY, respectively (incidence rate ratio (IRR) = 11.7, 95% CI 10.9 to 12.5). For females with and without HIV, the age-adjusted incidence rates were 61.4 and 2.33 per 1000 PY, respectively (IRR=26.3, 95% CI 24.0 to 28.7). Between 2013 and 2019 (calendar years with full-year data), the age-adjusted non-fatal overdose rate increased significantly among males and females without HIV but not among PWH.

We observed a significantly higher non-fatal overdose rate among PWH compared to people without HIV. The rate was highest among females with HIV. These findings underline the need for policies and programmes oriented towards PWH to mitigate overdoses, especially for females.

Tobacco use is the most significant modifiable risk factor for adverse health outcomes, and early research indicates there are also significant harms associated with vaping. National targets aim to reduce smoking and vaping during pregnancy for Aboriginal and Torres Strait Islander people. While most Aboriginal and Torres Strait Islander people want to quit, cessation is frequently attempted without support, increasing the chance of relapse. Group-based smoking cessation programmes increase quit success by 50%–130% in the general population; however, they have never been evaluated in Aboriginal and/or Torres Strait Islander communities.

The Gulibaa study is an Indigenous-led and community-embedded project that will co-design, implement and evaluate a group-based model of care to support Aboriginal and Torres Strait Islander women to be smoke- and vape-free. Staff of Health Services in New South Wales, Australia, will receive training to deliver a face-to-face group-based smoking and vaping cessation intervention. Aboriginal and/or Torres Strait Islander people who identify as a woman or non-binary, are pregnant or of reproductive age (16 to 49 years), currently smoke or vape at least once per day and are willing to attend the programme are eligible to participate. Up to 500 participants will be recruited. A mixed method evaluation approach will be implemented guided by the RE-AIM framework. Outcomes will include intervention reach, intervention effectiveness (determined primarily by self-reported 7-day point prevalence abstinence at 6 months follow-up), acceptability and feasibility of the intervention, programme fidelity and maintenance and cost effectiveness.

Embedding culturally safe support to quit during pregnancy can result in improved outcomes for both mother and child and immediately improve intergenerational health and well-being. Ethics approval has been provided by the Aboriginal Health and Medical Research Council and the University of Newcastle. Study findings will be disseminated to Aboriginal and Torres Strait Islander communities in ways that are meaningful to them, as well as through Aboriginal health services, key national bodies, relevant state and federal government departments.

ACTRN12625001050448.

Radioembolisation (RE) is gaining traction as a robust treatment option for patients with hepatocellular cancer (HCC) across all cancer stages. RE allows the delivery of targeted high-dose radiation directly to tumours, with relative sparing of the surrounding liver tissue. Traditionally, radiation has been delivered using ⁹⁰Yttrium ([⁹⁰Y]Y)-labelled microspheres, either glass or resin. The success of RE is dependent on the dose delivered to the tumour. When using [⁹⁰Y]Y microspheres, dose prediction is calculated through a ^99mTechnitium ([^99mTc]Tc)-macroaggregated albumin (MAA) scan, which allows the calculation of the dose to be administered to the tumour. However, [^99mTc]Tc-MAA is not a true surrogate of [⁹⁰Y]Y microspheres, and this will impact on the final dose delivered. [¹⁶⁶Ho]Ho, like [⁹⁰Y]Y, is a beta emitter but unlike [⁹⁰Y]Y also emits gamma-radiation, allowing for quantitative nuclear imaging. The primary aim of this pilot study was to investigate the safety and efficacy of dosimetry-based individualised ¹⁶⁶Holmium ([¹⁶⁶Ho]Ho-RE) in patients with HCC.

15 eligible participants will be recruited to receive [¹⁶⁶Ho]Ho-RE. The primary objective is to establish the toxicity profile of dosimetry-based individualised [¹⁶⁶Ho]Ho-RE. The secondary objective is to assess efficacy as measured by modified Response Evaluation Criteria in Solid Tumours (mRECIST) and Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria. Additional exploratory objectives include quality of life assessment and identification of a radiomic signature of response. The results from this study will be combined with the prospective iHEPAR study to form a larger analysis.

The study has received approval from the East Midlands—Nottingham 1 Research Ethics Committee—approval number 23/EM/0239. The study will be performed in compliance with the Declaration of Helsinki and the principles of Good Clinical Practice. Signed informed consent will be obtained from each patient before study entry. The results will be disseminated through publication in a peer-reviewed scientific journal.

Clinicaltrials.gov NCT06302400.