Increasing demand for haematological specialist care makes the optimisation of referrals and outpatient workflow a priority. Automated placing of standardised test orders prior to the first appointment may provide haematologists with necessary information to reach diagnoses and initiate treatment at the first patient encounter, reducing low-value follow-up appointments. We aimed to evaluate rates of patient participation in an initiative using artificial intelligence to place standardised test orders as well as reasons for non-participation, differences in the number of participants and non-participants discharged back to primary care with a diagnosis or appropriate treatment plan, and potentially avoidable referrals.

A retrospective, multicentric cohort study.

Four academic hospitals in Madrid, Spain.

18 190 patients referred for a first haematologist appointment for 11 included presenting complaints.

Referral notes from primary care were classified using natural language processing and automated placement of standardised test order sets was carried out prior to first appointment for participating patients.

We compared demographic differences between participants and non-participants, the main motives for not participating, and the number of patients discharged back to primary care at first appointment with a diagnosis and treatment plan. Most frequent International Classification of Diseases, tenth revision codes for each of the included presenting complaints were described.

During the study period, 18 190 (41%) patients were referred for a first haematologist appointment for presenting complaints included in the intervention (‘eligible patients’), of which 612 (3.3%) patients agreed to participate in the intervention. Participants were significantly younger than non-participants. Most common motives for not participating were administrative reasons (6268, 76.9%). Only 122 (1.5%) patients expressed explicit unwillingness to participate. A significant increase in the number of patients discharged upon first appointment was observed for participants (146 (23.9%) vs 3375 (19.36%); p=0.041), signifying a 22% relative reduction in avoidable follow-up. The diagnosis ‘haematological disorders ruled out’ was constantly observed as one of the ten most common diagnoses made by the haematology specialist for all but one of the included presenting complaints.

Natural language processing of referrals from primary to specialist haematology care with automated placing of standardised test orders can decrease low-value follow-up appointments. Explicit refusal to participate was low. Participants tended to be younger than non-participants, underlining the importance of designing strategies to target the older population in order to improve participation.

The aims of this study were (1) to develop and validate the interactive CLAIM Test (iCLAIM Test) to measure children’s ability to assess claims about treatment effects and make informed health choices and (2) to measure this ability in Spanish primary school children using the developed test.

We followed a multistep process including (1) definition of the test scope, (2) selection of the questions, (3) translation process, (4) design and development of the online test, (5) external review with experts, (6) user-test with children and (7) cross-sectional validation study with Rasch analysis.

Spanish primary schools.

Twelve experts (75% women) participated in the review, 11 children (45% girls) participated in the user-test and 480 Spanish primary school children (46.5% girls) from fourth to sixth grades (9–12 years old) participated in the cross-sectional validation study.

The iCLAIM Test is an online, interactive and user-friendly test in Spanish that measures children’s ability to understand and apply key concepts of the informed health choices (IHC) Project when assessing claims about treatment effects and making IHCs. The test includes 30 questions: six demographic questions and 24 questions from the Claim Evaluation Tools item bank. Less than 40% of the students who participated in the cross-sectional validation study showed basic knowledge of the IHC Key Concepts and how to apply them, and less than 4% showed a clear knowledge. The test showed a good fit to the Rasch model and was acceptable to the target audience.

The iCLAIM Test is the first instrument validated for measuring children’s ability to assess treatment claims in Spain. In the future, we can tailor IHC education interventions and improve critical thinking skills about the health of Spanish children.

Cancer is the leading cause of death and morbidity among children and adolescents worldwide. Functionality-based interventions are relevant among children and adolescents with an oncological diagnosis, whence studies summarising evidence on this topic are needed. This systematic review will summarise evidence on the effect of interventions to improve functionality indicators among paediatric patients diagnosed with cancer.

This protocol will follow Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA)-Protocols reporting guidelines. The systematic review will be conducted according to the Cochrane Handbook and PRISMA 2020. Studies will be searched in MEDLINE (PubMed), Embase, Web of Science, CENTRAL, LILACS and PEDro. Additional searches will include Google Scholar, reference lists of included studies, relevant reviews and trial registries. Studies will be included if they implement a functionality-based intervention. They must evaluate effects among paediatric patients with an oncological diagnosis. Secondary outcomes will include health-related quality of life. There will be no limits to language or year of publication, and articles published in peer-reviewed journals will be accepted. Only randomised controlled trials will be included. Risk of bias will be assessed using the Cochrane Risk of Bias Tool 2. Two independent reviewers will select studies, extract data and assess risk of bias. A narrative synthesis and meta-analysis will be conducted if studies are clinically and methodologically homogeneous. Statistical heterogeneity will be assessed using Higgins’ inconsistency test (I^²). Meta-analysis may estimate combined effects using random-effects and the inverse variance method. The R statistical software will be used. The certainty of evidence will be evaluated for each outcome using the Grading of Recommendations Assessment, Development and Evaluation system.

This study used data from previously published studies, thus waiving submission to an Ethics Committee. Scientific dissemination strategies will include publication in peer-reviewed journals, conference presentations and workshops for the public.

CRD42024462833.

Sodium-glucose cotransporter (SGLT) inhibitors have shown substantial benefit in reducing cardiovascular and kidney events across diverse clinical populations, but the underlying physiological mechanisms remain unclear. However, existing mechanistic studies on renal and cardiovascular haemodynamics show variability in design, have limited statistical power and yield inconsistent outcomes, thus limiting the ability to draw generalisable conclusions. To address this gap, we conducted a systematic review and proposed the first meta-analysis to aggregate individual participant-level data from mechanistic studies to identify consistent physiological patterns and enhance understanding of the therapeutic effects of SGLT inhibition.

Gold-standard measured glomerular filtration rate (mGFR) was selected as the primary outcome for this systematic review, which aimed to identify all completed mechanistic studies investigating the effects of SGLT inhibition. Electronic databases including Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews; and Cochrane Central Register of Controlled Trials were searched using a detailed search strategy. In total, 24 studies (n=1296) were identified. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Key variables including demographics, medical history, concomitant medications, vital signs, mGFR, renal haemodynamics, urine and plasma biochemistry, tubular sodium handling, echocardiography, cardiac output monitoring, arterial stiffness and fluid volume will be extracted. A one-stage individual participant data meta-analysis under a Bayesian framework will be conducted, using hierarchical models to simultaneously analyse data from all eligible studies. The risk of bias due to missing results will be assessed. Sensitivity analyses and subgroup evaluations will be incorporated to explore sources of heterogeneity and assess robustness of findings.

Ethics approval was obtained from University Health Network, Toronto, Canada. Findings from the Mechanisms of SGLT Inhibitor Action and Physiological Mediators (MOSAIC) meta-analysis will be published in peer-reviewed journals and results will be disseminated at scientific conferences.

CRD420251001413.

Early childhood caries (ECC) continues to be a public health problem. The application of silver diamine fluoride (SDF) is a simple, non-invasive procedure. This study aims to evaluate SDF’s effectiveness, acceptability and oral health-related quality of life (OHRQoL) compared with atraumatic restorative treatment in managing ECC.

An open-label parallel superiority randomised clinical trial will be conducted involving children aged 2–5 years. Participants will include children with at least one active cavitated lesion (ICDAS 5+) of their primary teeth, with no signs of pulp involvement. The trial will occur at preschools in the La Araucanía and Metropolitan Regions of Chile from 2025 to 2027. The primary outcome variable will be the caries lesion arrest, acceptability and OHRQoL. We will also determine the presence of any adverse effects. Evaluations will be carried out at 6 and 12 months. A sample of 234 teeth with carious lesions per group is estimated. The primary inferential analysis will be performed on an intention-to-treat basis; a per-protocol analysis will be conducted for adverse effects. For caries lesion arrest, a multilevel logistic regression model adjusted for significant covariates will be used to account for within-child clustering. The acceptability will be assessed through quantitative and qualitative methods. The magnitude of change in OHRQoL between baseline and follow-up will be quantified using effect size estimates derived from the early childhood health impact scale survey data.

This study’s implementation benefits the study population, and the ethical principles of research have been considered and approved by the Science Committee of the University, Resolution N°049_19. The results and conclusions of the clinical trial will be published in academic conferences and peer-reviewed journals.

NCT06786975.

Inflammatory bowel disease (IBD) is associated with worse major adverse liver outcomes (MALO) in patients with chronic liver disease (CLD). Although the interplay between these conditions is recognised, the contribution of external factors such as race and socioeconomic status (SES) remains unclear. We aimed to assess the association of race and socioeconomic factors with MALO in patients with IBD and CLD.

This retrospective cohort study analysed hospitalised adults with IBD and CLD using the National Inpatient Sample database (2015–2021). Demographic variables included age, sex and race. SES included household income. Clinical variables included length of hospital stay, in-hospital mortality and comorbidities. A multivariate logistic regression analysis was performed to assess the independent associations between MALO and patient demographics, comorbidities and social determinants of health.

Among 97 628 hospitalised adult patients with IBD, 4.11% (4011/97 628) had secondary CLD. The majority of patients with IBD-CLD were white (74.94% or 2928/3907), and over half (53.83% or 2118/3934) resided in lower-income households with incomes below US$35 000. Racial disparities were evident, with significant differences in comorbidities such as sepsis, cholangitis and hepatocellular carcinoma. Among white patients, the prevalence of depression and anxiety was 20.18% (591/2928) and 24.21% (709/2928), respectively, which was higher compared with other racial groups. In adjusted analyses, African American race (OR 1.42, p=0.003) and lowest SES (OR 1.19, p=0.04) were independently associated with increased odds of MALO.

African American race and lower SES are independently associated with higher odds of MALO in patients with IBD-CLD. These findings highlight disparities that warrant further investigation and suggest that targeted interventions may help improve liver-related outcomes. Interventions reducing health inequities are desperately needed to mitigate disparities in this patient population.

Suicide rates have increased over the last couple of decades globally, particularly in the United States and among populations with lower economic status who present at safety-net healthcare systems. Recently, predictive models for suicide risk have shown promise; however, a model for this specific population does not exist.

To develop a predictive risk model of suicide and intentional self-harm (ISH) for patients presenting at the psychiatric emergency department (ED) of JPS Health Network, a safety net medical and mental healthcare system in Texas.

The study used structured and unstructured electronic medical record (EMR) data (2015–2019) and local medical examiner data (2015–2020) to create predictors and outcome variables. All psychiatric ED notes during calendar years 2018 and 2019 were reviewed using natural language processing to identify presentations for any level of self-harm and subsequent manual review of identified visits to accurately classify ED presentations for treatment of an act of intentional self-harm meeting study criteria. Data from 15 987 patients were used to develop and validate a machine learning-based predictive model that leverages rolling window methodology to predict risk repeatedly across a patient’s trajectory. Feature engineering played a prominent role in defining new predictors.

The best model (XGBoost) achieved the area under the receiver operating characteristic curve of 0.81 for 30-day predictions and demonstrated concentration of ISH and suicide attempt events in high-risk quantiles of risk (65% had events in top 0.1% quantile). The predicted risk can be translated into a propensity of events (80% at the highest predicted risk) to facilitate clinical interpretation.

Machine learning-based models can be used with standard EMRs to identify patients presenting at the psychiatric ED with a high risk of ISH and suicide attempts within the next 30 days.

Integration of a predictive model can significantly aid clinical decision-making in safety-net psychiatric EDs.

Students enrolling in higher education often adopt lifestyles linked to worse mental health, potentially contributing to the peak age onset of mental health problems in early adulthood. However, extensive research is limited by focusing on single lifestyle behaviours, including single time points, within limited cultural contexts, and focusing on a limited set of mental health symptoms.

The UNIversity students’ LIFEstyle behaviours and Mental health cohort (UNILIFE-M) is a prospective worldwide cohort study aiming to investigate the associations between students’ lifestyle behaviours and mental health symptoms during their college years. The UNILIFE-M will gather self-reported data through an online survey on mental health symptoms (ie, depression, anxiety, mania, sleep problems, substance abuse, inattention/hyperactivity and obsessive/compulsive thoughts/behaviours) and lifestyle behaviours (ie, diet, physical activity, substance use, stress management, social support, restorative sleep, environment and sedentary behaviour) over 3.5 years. Participants of 69 universities from 28 countries (300 per site) will be assessed at university admission in the 2023 and/or the 2024 academic year and followed up for 1, 2 and 3.5 years.

The study was first approved at a national level in Brazil (CAE:63025822.8.1001.5346). Study sites outside Brazil obtained additional ethics approval from their institutions using the main approval. Results from the UNILIFE-M cohort will be disseminated through scientific publications, presentations at scientific meetings, press releases, the general media and social media.

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.

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.

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.