bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-sectional analysis of caesarean sections according to the Robson 10-group classification system in Somalia
Authors: Barut Adil , Erkok Umut , Hassan Hiba Bashir
Published: January 2025

Background

Caesarean section (CS) is an important indicator of access to and quality of maternal health services. The WHO recommends the Robson 10-group classification system as a global standard for assessing, monitoring and comparing CS rates at all levels. Identification of the Robson groups that contribute the most to the overall CS is important to determine possible modifiable factors in our attempts to reduce the CS rate. This study was designed to analyse CS deliveries performed in a tertiary referral centre in Somalia according to the Robson 10-group classification system.

Design

This retrospective study included data on consecutive mothers who had deliveries from 1 January 2022 to 1 July 2023.

Methods

Data were categorised according to the Robson classification. Each patient’s data was coded according to Robson’s specifications.

Results

A total of 3030 deliveries were analysed. Of these, 1156 (38.2 %) were CS. Among the five largest Robson groups, the highest absolute contribution to CSs was found in group 5, with 11.4% followed by group 10 with a corresponding contribution of 9.4%. In the next three largest Robson groups (groups 1, 3, 4), the absolute contributions were 3.9%, 3.4% and 3.3%, respectively. The total percentages of CSs among all deliveries (n=3030) and among all CSs (n=1156) in the five largest Robson groups were 31.3% and 82.2%, respectively.

Conclusion

Our analysis showed that the overall caesarean section rate was 38.2%, and those major contributors were Robson groups 5 and 10.
Comparison of carbon dioxide control during pressure controlled versus pressure-regulated volume controlled ventilation in children (CoCO2): protocol for a pilot digital randomised controlled trial in a quaternary paediatric intensive care unit
Authors: Mozun Rebeca , Chopard Daphné , Zapf Florian , Baumann Philipp , Brotschi Barbara , Adam Anika , Jaeggi Vera , Bangerter Beat , Gibbons Kristen S , Burren Juerg , Schlapbach Luregn J
Published: January 2025

Introduction

Digital trials are a promising strategy to increase the evidence base for common interventions and may convey considerable efficiency benefits in trial conduct. Although paediatric intensive care units (PICUs) are rich in routine electronic data, highly pragmatic digital trials in this field remain scarce. There are unmet evidence needs for optimal mechanical ventilation modes in paediatric intensive care. We aim to test the feasibility of a digital PICU trial comparing two modes of invasive mechanical ventilation using carbon dioxide (CO2) control as the outcome measure.

Methods and analysis

Single-centre, open-labelled, randomised controlled pilot trial with two parallel treatment arms comparing pressure control versus pressure-regulated volume control. Patients are eligible if aged <18 years, weighing >2 kg, have an arterial line and require >60 min of mechanical ventilation during PICU hospitalisation at the University Children’s Hospital Zurich. Exclusion criteria include cardiac shunt lesions, pulmonary hypertension under treatment and intracranial hypertension. CO2is measured using three methods: end-tidal (continuous), transcutaneous (continuous) and blood gas analyses (intermittent). Baseline, intervention and outcome data are collected electronically from the patients’ routine electronic health records. The primary feasibility outcome is adherence to the assigned ventilation mode, while the primary physiological outcome is the proportion of time spent within the target range of CO2(end-tidal, normocarbia defined as CO2≥ 4.5 and ≤ 6 kPa). Both primary outcomes are captured digitally every minute from randomisation until censoring (at 48 hours after randomisation, extubation, discharge or death, whichever comes first). Analysis will occur on an intention-to-treat basis. We aim to enrol 60 patients in total. Recruitment started in January 2024 and continued for 9 months.

Ethics and dissemination

This study received ethical approval from the Cantonal Ethics Commission of Zurich (identification number: 2022–00829). Study results will be disseminated through publication in a peer-reviewed journal and other media like podcasts.

Trial registration number

NCT05843123.
Digital screening tool for the assessment of cognitive impairment in unsupervised setting—digiDEM-SCREEN: study protocol for a validation study
Authors: Zeiler Michael , Dietzel Nikolas , Kammerer Klaus , Frick Ulrich , Pryss Rüdiger , Heuschmann Peter , Prokosch Hans-Ulrich , Graessel Elmar , Kolominsky-Rabas Peter L
Published: January 2025

Introduction

Dementia is one of the most relevant widespread diseases, with a prevalence of currently 55 million people with dementia worldwide. However, about 60–75% of people with dementia have not yet received a formal diagnosis. Asymptomatic screening of cognitive impairments using neuropsychiatric tests has been proven to efficiently enhance diagnosis rates. Digital screening tools, in particular, provide the advantage of being accessible without spatial or time restrictions. The study aims to validate a digital cognitive screening test (digiDEM-SCREEN) as an app in the German language.

Methods and analysis

This is a multicentre study in Bavaria. Participants are people with mild cognitive impairment, people with dementia in an early stage and cognitively healthy people. Recruitment will take place in specialised diagnostic facilities (memory outpatient clinics). 135 participants are aimed based on a power analysis. Sociodemographic data, diagnosis and results of neuropsychiatric tests (Consortium to Establish a Registry for Alzheimer’s Disease, Montreal Cognitive Assessment, digiDEM-SCREEN) will be collected at one point per person via electronic data capturing. The sensitivity, specificity and corresponding cut-off values will be determined based on receiver-operating-characteristic curves. The correlation of the digiDEM-SCREEN test with existing cognitive screening/testing procedures will be analysed.

Ethics and dissemination

The study obtained ethical approval from the Ethics Committee of the Julius-Maximilians-Universität of Würzburg (JMU) (application number: 177/23-sc). The test will give feedback about the current cognitive status and possible cognitive impairments that should lead to the users seeking further diagnostic measures by medical professionals. It will be accessible free of charge in established app stores. The results of the validation study will be published in peer-reviewed journals.
Neoadjuvant adebrelimab combined with chemotherapy (cisplatin/carboplatin and etoposide) for limited-stage small-cell lung cancer: a study protocol of phase 2 trial (NIUS)
Authors: Liu Yanyang , Huang Qian , Tian Long , Zheng Xi , Chen Guizhi , Xu Hongyu , Li Mengxia , Zhu Daxing , Zhang Yan
Published: January 2025

Introduction

Small-cell lung cancer (SCLC) is a highly malignant neuroendocrine tumour, and concurrent chemoradiotherapy is the current recommended treatment for limited-stage SCLC. However, the overall survival (OS) of patients with SCLC remains poor. Therefore, improving the survival of patients with SCLC and benefitting more patients are urgent clinical requirements. Immunotherapy has achieved good efficacy in extensive-stage SCLC and non-SCLC. However, the use of neoadjuvant immunotherapy in limited-stage SCLC is unknown but promising. To this end, we plan to conduct a study on adebrelimab in combination with chemotherapy for the neoadjuvant treatment of limited-stage SCLC.

Methods and analysis

This will be a single-arm, prospective study. The primary endpoint of this study will be a pathological complete remission rate. The secondary endpoints will be a major pathological response, objective response rate, event-free survival, OS, R0 resection rate, safety and potential predictive biomarker parameters related to efficacy in peripheral blood samples, including minimal residual disease, circulating tumour cells and cluster of differentiation (CD) 4/CD8. This study will enrol 28 patients.

Ethics and dissemination

This study was approved by the Biomedical Ethics Review Committee of West China Hospital, Sichuan University, on 1 August 2023 (grant number 2023[987]). The version of this study protocol is V7.0. The patients have been enrolled since September 2023. This study will conclude in January 2026, and the results will be presented to peer-reviewed medical journals and international scientific conferences in 2027. This study will provide important data on whether neoadjuvant treatment with adebrelimab combined with chemotherapy is clinically beneficial in patients with limited-stage SCLC.

(Prospective study of neoadjuvant adebrelimab combined with chemotherapy in limited-stage SCLC; Chinese Clinical Trial Registry (ChiCTR),www.chictr.org.cn/; Number, ChiCTR2300074591.)

Trial registration number

ChiCTR2300074591
Safe Implementation of Treatments in Stroke: a study on intravenous thrombolysis in patients over 80 years of age with acute ischaemic stroke
Authors: Matusevicius Marius , Paiva Nunes Ana , Krishnan Manju , Egido Jose , Concari Letizia , Dixit Anand , Reggiani Monica , Pagès Alain , Danays Thierry , Toni Danilo , Ahmed Niaz
Published: January 2025

Objectives

To investigate the safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients aged >80 years with acute ischaemic stroke (AIS) after IVT was approved in this patient population in several European and non-European countries during 2018–2019.

Design

This is an observational registry study using prospectively collected data from the Safe Implementation of Treatment in Stroke (SITS) registry. Comparisons will be performed between patients treated post-approval (July 2018 to December 2021) period with those treated pre-approval (June 2015 to June 2018) period using propensity score matching (PSM).

Setting

This is a multicentre international study in hospitals treating AIS with IVT.

Participants

Patients aged >80 years who otherwise followed the IVT Summary of Product Characteristics of European countries as part of the mutual recognition procedure.

Primary and secondary outcomes

The main outcomes were symptomatic intracerebral haemorrhage per SITS monitoring study definition, death and functional independency as defined by a modified Rankin Scale score of 0–2 at 90 days.

Results

After PSM, 614 patients remained in each group (mean age 87 years, 39% males). All baseline data were well balanced after PSM. There were no statistically significant differences in outcomes between pre- and post-approval patients for SICH (2.5% vs 2.3%, risk ratio (RR) 1.064, 95% CI 0.345–1.784), death (25.3% vs 28.4%, RR 0.889, 0.699–1.08) and functional independency at 90 days (40.3% vs 37%, RR 1.089, 0.942–1.237).

Conclusions

In this observational study of IVT treatment in patients >80 years of age with AIS before and after formal approval for this treatment, we did not find any difference in outcomes between the pre- and post-approval periods.
Cost–utility analysis of MR imaging-guided transurethral ultrasound ablation for the treatment of low- to intermediate-risk localised prostate cancer
Authors: Muhler Paul , Akuamoa-Boateng Dennis , Rosenbrock Johannes , Stock Stephanie , Müller Dirk , Heidenreich Axel , Simões Corrêa Galendi Julia
Published: January 2025

Background

Magnetic resonance-guided transurethral ultrasound ablation (MR-TULSA) is a new focal therapy for treating localised prostate cancer that is associated with fewer adverse effects (AEs) compared with established treatments. To support large-scale clinical implementation, information about cost-effectiveness is required.

Objective

To evaluate the cost–utility of MR-TULSA compared with robot-assisted radical prostatectomy (RARP), external beam radiation therapy (EBRT) and active surveillance (AS) for patients with low- to favourable intermediate-risk localised prostate cancer.

Design, setting and participants

A Markov model was developed targeting 60-year-old men diagnosed with low- to intermediate-risk localised prostate cancer over a time horizon of 40 years from the German Statutory Health Insurance (SHI) perspective. To assess the robustness of the results, deterministic and probabilistic sensitivity analyses were performed.

Intervention

Four different treatment strategies were compared: minimally invasive MR-TULSA, two definitive approaches (RARP and EBRT) and one observational strategy (AS).

Outcome measurements and statistical analysis

Outcomes were measured in overall costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER).

Results

AS generated the highest number of QALYs (12.67), followed by MR-TULSA (12.35), EBRT (12.35) and RARP (12.20). RARP generated the lowest costs (€ 46 997) over one patient’s lifetime, while MR-TULSA was a slightly more expensive alternative (€48 826). The incremental cost-effectiveness ratio (ICER) of AS compared with RARP was €11 600 per QALY and of MR-TULSA compared with RARP was €12 193 per QALY, while EBRT was dominated. At a willingness-to-pay of €20 000 per QALY, the probability of being cost-effective is 44% for AS, 25% for RARP, 25% for MR-TULSA and 6% for EBRT.

Conclusions

All treatment options for 60-year-old men diagnosed with low- to intermediate-risk localised prostate cancer are affected by considerable uncertainty. Accepting high follow-up costs by applying a higher willingness-to-pay, AS is the most favourable treatment option.
Understanding the work-related challenges of organ and tissue donation coordinators during the COVID-19 pandemic: a mixed-method study
Authors: Silva e Silva Vanessa , Minervini Alessandra , Dupuis Kendra-Lee , Lotherington Ken , Dhanani Sonny , Silva Amina
Published: January 2025

Objectives

This study aimed to explore the perceptions of donation coordinators in Canada and understand how the COVID-19 pandemic impacted their work activities.

Design

A sequential mixed-method design incorporating a cross-sectional survey investigating demographic data, substance use and abuse and perceived stress related to the pandemic and semistructured qualitative interviews to further investigate those.

Setting

Organ donation organisations across Canada.

Participants

Canadian organ and tissue donation coordinators working within deceased donation programmes. Participants were recruited using a purposive sampling technique for the survey and qualitative interviews. Recruitment and data collection took place between January 2022 and March 2023.

Analysis

The data were analysed using descriptive statistics for the quantitative findings and content analysis for the qualitative data.

Results

Of the 175 available coordinators, 120 participated in the survey, and 39 participated in the qualitative interviews. The great majority were female (n=98; 81.7%), registered nurses (n=117; 97.5%) and on average 42 years old (SD=9.64). The survey result for perceived stress showed that, on average, coordinators did not experience high stress levels during the pandemic. We also identified an increase in the consumption of substances to manage workplace stress near the pandemic’s beginning. The qualitative interviews yielded two main themes (Personal Life Changes and Workplace Adjustments) in which coordinators reported their views on challenges with uncertainties, effects on their personal lives, redeployment, stressors and among others.

Conclusion

Our study’s results provide a comprehensive understanding of the perceptions and experiences of coordinators in Canada during the COVID-19 pandemic. Using a combination of methods, we identified various ways coordinators were affected by the pandemic in their personal and professional lives. These findings highlight the need to support the development of adaptive strategies and promote resilience during crises.
Experiences of Māori and Pacific women recruited into a pregnancy clinical trial in Aotearoa, New Zealand: a Kaupapa Māori qualitative study
Authors: Enright Richard , Roskvist Rachel , Rahiri Jamie-Lee , Mullane Tania , Albert Benjamin B , Satokar Vidit Vinod , Harwood Matire
Published: January 2025

Objectives

To explore the perspectives of Māori and Pacific women who participated in the Fish Oil study to ascertain what barriers and facilitators may exist for successfully recruiting Māori and Pacific women into clinical trials.

Design

A Kaupapa Māori qualitative study.

Setting

Auckland, New Zealand.

Participants

16 Māori and Pacific women who participated in the fish oil supplementation during pregnancy study (ACTRN12617001078347p) between 1 January 2017 and 31 December 2020.

Main outcome measures

Semistructured in-depth interviews were conducted, recorded and transcribed and then subjected to inductive thematic analysis to identify key themes related to barriers and facilitators of successful Māori and Pacific women recruitment into a clinical trial.

Results

Of 37 eligible Māori and Pacific women who participated in the original Fish Oil study, 16 women consented to participate in this study. Three key themes were identified: (1) relationships matter, (2) privileges and barriers and (3) the study experience. Key facilitators for recruitment included having solid relationships with research team members, practising exemplary professionalism, having clear communication and having the ability to establish rapport and research team flexibility. The desire to create a better future for participants’ babies and to give back to Māori and Pacific communities through participating in a clinical trial were also key drivers of successful recruitment. In contrast, the major barriers described were time pressures and the distance to the research facility.

Conclusions

Sixteen Māori and Pacific women who participated in a double-blinded randomised controlled trial shared that successful recruitment of Māori and Pacific women into clinical trials can be promoted by research flexibility participants’ whānau/family responsibilities, effective and culturally safe communication, and research teams striving to build and maintain relationships with participants throughout the trial.

Trial registeration number

Australian New Zealand Clinical Trials Registry, ACTRN12617001078347p. Universal Trial Number (U1111-1199-5860).
Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial
Authors: Gaston David C , Humphries Romney M , Lewis Ariel A , Gatto Cheryl L , Wang Li , Nelson George E , Stollings Joanna L , Ereshefsky Benjamin J , Christensen Matthew A , Dear Mary Lynn , Banerjee Ritu , Miller Karen F , Self Wesley H , Semler Matthew W , Qian Edward T
Published: January 2025

Introduction

Patients with suspected bacterial infection frequently receive empiric, broad-spectrum antibiotics prior to pathogen identification due to the time required for bacteria to grow in culture. Direct-from-blood diagnostics identifying the presence or absence of bacteria and/or resistance genes from whole blood samples within hours of collection could enable earlier antibiotic optimisation for patients suspected to have bacterial infections. However, few randomised trials have evaluated the effect of using direct-from-blood bacterial testing on antibiotic administration and clinical outcomes. This manuscript describes the protocol and statistical analysis plan for a randomised trial designed to evaluate the effect of blood cultures plus direct-from-blood bacterial testing results compared with blood culture results alone on antibiotic administration and clinical outcomes.

Methods and analysis

We are conducting a prospective, single-centre, parallel-group, non-blinded, pragmatic, randomised trial. The trial will enrol 500 adult patients presenting to the emergency department at Vanderbilt University Medical Center with suspected bacterial infection who have been initiated on empiric intravenous vancomycin. Eligible patients are randomised 1:1 to receive Food and Drug Administration-approved direct-from-blood bacterial testing in addition to blood cultures or blood cultures alone. The primary outcome is the time to the last dose of intravenous vancomycin within 14 days of randomisation. The secondary outcome is the time to the last dose of systemic antipseudomonal beta-lactam antibiotics within 14 days of randomisation. Additional outcomes include highest stage of acute kidney injury, lowest platelet count and receipt of kidney replacement therapy within 14 days of randomisation, as well as hospital-free days, intensive care unit-free-days and all-cause, in-hospital mortality within 28 days of randomisation. Enrolment began on 13 December 2023.

Ethics and dissemination

The trial involves human participants and was approved by the Vanderbilt University Medical Center institutional review board with a waiver of informed consent (IRB#231229). Results will be submitted in a peer-reviewed journal and presented at scientific conferences.

Trial registration number

NCT06069206.
Brain health in Norwegian female former top-level football players: a protocol for a longitudinal cohort study
Authors: Dahlén Sara Christina , Bjørneboe John , Sandmo Stian Kirkerud , Bache-Mathisen Lena , Filipcik Peter , Howe Emilie Isager , Høgestøl Einar August , Selbæk Geir , Straume-Næsheim Truls , Westlye Lars T , Bahr Roald , Andersen Thor Einar
Published: January 2025

Introduction

Repetitive head impacts (RHI) in sports may represent a risk factor for long-term cognitive and neurological sequelae. Recent studies have identified an association between playing football at the top level and an elevated risk of cognitive impairment and neurodegenerative disease. However, these were conducted on men, and there is a knowledge gap regarding these risks in female athletes. This study aims to investigate the effect of head impacts on brain health in female former top-level football players.

Methods and analysis

This is a prospective cohort study, enroling female former football players and top-level athletes from sports without an inherent risk of RHI. All participants are born in 1980 or earlier. We plan to perform follow-up assessments at least three times over 20 years.

The protocol includes neurocognitive assessments, self-reported neurocognitive outcomes, neurological examination, advanced brain MRI, and fluid biomarkers.

Ethics and dissemination

The study has been approved by the South-East Regional Ethics Committee for Medical Research in Norway (2023/178330) and the Norwegian Agency for Shared Services in Education and Research (SIKT). A Data Protection Impact Assessment was developed by the research group and approved by SIKT and the Norwegian School of Sport Sciences. We will disseminate the results through peer-reviewed publications, academic conference presentations and webinars. We will communicate with the public and key stakeholders in football worldwide to inform and promote the development and implementation of potential preventive measures based on our study findings.
Cataract surgery has minimal effect on corneal shape
Authors: Alfaqawi Fadi , Pagano Luca , Arbabi Esmaeil M , Romano Vito , Al-Maskari Ahmed , McLean Keri , Czanner Gabriella , Kaye Stephen B
Published: January 2025

Purpose

To quantify the effect of cataract surgery on cornea shape.

Methods

Patients undergoing cataract surgery with standardised 2.75 mm surgical incisions at 110 degrees with a side port at 50 degrees were included. Repeat biometric measurements were taken before surgery and at 6 weeks on both operated and unoperated fellow eyes. Data were transformed into Long’s formalism for analysis. Device-specific measurement error was determined. The main outcome measure was the change in keratometry taking into account the change in keratometry of the unoperated fellow eye. Secondary outcome measures included the variability introduced due to location of the incision.

Results

132 patients were included. The mean change in keratometry of the operated eye was −0.23@111/+0.21@21 (95% CI −1.43@122/+0.04@32 to +1.04@135/+0.30@45). The flattening effect of the surgical incision was greater and more variable than the steepening effect (p<0.01), particularly if the incision was in the flat meridian. Coupling, defined as ratio of the keratometric change in the preoperative meridians of K2 and K1, varied from 0.91 (SD 2.31) for eyes with an incision in the steep meridian, 0.75 (SD 1.81) for an incision in the flat meridian to 0.28 (SD 2.06) when the incision was made in a neutral meridian.

Conclusion

Cataract surgery has a slightly greater flattening than steepening effect on corneal shape. Although the effects are very small and variable with incomplete coupling, it is preferable to place the incision in the steep meridian. Greater emphasis, however, should be placed on eye-specific factors, such as biometry, or patient-related factors to optimise refractive outcomes.
Integration of a specialist pharmacist-led multidisciplinary team in primary care: preventing strokes in people with atrial fibrillation across North East London
Authors: Patel Mital , Chahal Jagjot Kaur , Robson John , Ali Shabana , Clements Richard , Theodoulou Angela , Kearney Matt , Sohaib Afzal , Patel Riyaz , Antoniou Sotiris , Wright Paul
Published: January 2025

Public Health England outlines a national ambition of anticoagulating 90% of eligible patients with atrial fibrillation (AF) by 2029. In 2019/2020, two out of three boroughs reviewed in this study were in the bottom 10% of boroughs compared with others within England. Stroke National Audit data for these three boroughs from 2019 to 2020 identified that in patients with known AF admitted to hospital with strokes, 37% were not anticoagulated. Evidence shows that one stroke can be prevented for every 25 patients with AF treated with anticoagulation, reducing the burden of stroke and stroke-related disabilities.

In 2020, hospital specialist cardiovascular pharmacists were commissioned to identify patients with AF at high ischaemic risk (CHA2DS2VASc≥2) in three boroughs by working with general practitioners (GPs) and practice-based pharmacists. Using digital ‘proactive care frameworks’ created by UCLPartners and the Clinical Effectiveness Group, Queen Mary University of London, baseline searches of GP records enabled clinical teams to risk stratify and prioritise patients with AF for review. Patients not on anticoagulation were categorised as high risk and were reviewed for initiation of anticoagulation. The second priority was patients on dual antithrombotic therapy to determine if antiplatelet therapy could be stopped to minimise bleeding risk.

At baseline (March 2020), nationally available data (extracted from CVDPREVENT) showed that 81% of patients with AF at high ischaemic risk across the three selected boroughs were anticoagulated. Repeated data extraction in March 2023, showed 94% of patients with AF at high ischaemic risk were anticoagulated, an absolute improvement of 13%, with 415 patients initiated on anticoagulant therapy over 3 years, translating to 17 strokes prevented. There was a 52% reduction in dual antithrombotic therapy, preventing an estimated three major bleeds.

Improvements were achieved through a combination of specialist pharmacist reviews, GP and practice-based pharmacist training and virtual multidisciplinary reviews supporting the integration of specialists into a primary care setting to enable joined-up pathways for effective stroke prevention.
Implementation of patient-reported outcome dashboards within the electronic health record to support shared decision-making in serious chronic illness
Authors: Perry Laura M , Mohindra Nisha A , Coughlin Ava , Bedjeti Katy , Barnard Cynthia , Garcia Sofia F , Peipert Devin , Kircher Sheetal M , Aggarwal Vikram , Linder Jeffrey , Weitzel Melissa , Morken Victoria , Patten Elijah , Torres Jissell , O'Connor Mary , Metzger Susan , O’daniel Alesia , Chmiel Ryan , Modi Reena , Munroe Michelle , Xinos Stavroula , Elwyn Glyn , Nelson Eugene , Van Citters Aricca , Cella David , Hirschhorn Lisa
Published: January 2025

Background

Attending to patient-reported outcomes (PROs) using data visualisation dashboards could enhance shared decision-making (SDM) and care delivery for serious chronic illnesses. However, few studies have evaluated real-world strategies and resulting implementation outcomes of PRO dashboards.

Method

From June 2020 to January 2022, we implemented an electronic health record (EHR)-integrated PRO dashboard for advanced cancer and chronic kidney disease. Based on implementation science guidelines (eg, Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies, Reach, Effectiveness, Adoption, Implementation, Maintenance), we monitored use and captured adaptations in implementation strategies. Clinicians (n=7) and patients (n=30) responded to a 6-month survey that included appropriateness, acceptability, adoption and sustainability.

Results

Out of 1450 eligible patients, 748 (52%) completed at least one PRO invitation (reach). 37% of PRO questionnaire invitations (1421/3882) were completed (fidelity to PRO completion), with higher rates occurring when more implementation strategies were adopted. Among completed postvisit surveys from patients, 57% indicated that the dashboard was discussed at an eligible visit (fidelity to dashboard use). In the 6-month survey, patients endorsed the dashboard’s acceptability and appropriateness: 77% felt it frequently provided clear information and 63% felt it frequently met their needs. Most patients (77%) and clinicians (86%) valued the dashboard for increasing SDM, and 57% of clinicians endorsed the dashboard’s clinical sustainability.

Discussion

This pilot study demonstrated the clinical appropriateness, acceptability and feasibility of implementing an EHR-integrated PRO dashboard for advanced cancer and chronic kidney disease. Results also point to areas for improvement, including strategies to further support patient and clinician engagement, PRO completion and sustainability in real-world implementation.
Improving 1-year liver allograft survival hazard ratios
Authors: Ramkissoon Resham­ , Rosier Ashley , Iyengar Savitha , Taner Timucin , Sanchez William
Published: January 2025

Background

The Scientific Registry for Transplant Recipients (SRTR) publishes outcomes of all transplant centres in the USA two times a year. The outcomes are publicly available and used by insurance payers and patients to assess the performance of a programme. Poor performance can result in temporary suspension or termination of a transplant programme. The estimated 1-year survival hazard ratio (EHR) is an important metric publicly reported by the SRTR.

Problem

The EHR at our institution was 1.13, indicating a graft loss rate that was 13% higher than the national average.

Methods/INTERVENTION

We defined an improvement in this metric as achieving an EHR of <1.0. Our balance measure was maintaining similar liver transplant volumes and avoiding limiting access to transplant. Using a causality tree, we identified there was no ‘real time’ assessment of programme risk or objective metric to assess this. An affinity diagram was used to determine high and intermediate risk factors for mortality and graft loss and, using a REDCap form (a web application used to manage our database) to track actual and potential complications, we calculated a weekly ‘risk metric’ that was introduced at multidisciplinary selection conference meetings.

Results

We remeasured our EHR at each interval release of the SRTR outcomes and found it to be 0.98 and 0.65 after implementing the ‘risk metric.’ During the intervention period, annual liver transplant volume remained above the baseline measure.

Conclusion

By implementing a ‘risk metric’ to prospectively assess the risk of a low EHR at transplant selection committee meetings, we were able to reduce the EHR well below the national average without limiting access to liver transplants.
Insights from a codesigned dynamic modelling study of child and adolescent obesity in Australia
Authors: Chiu Simon Keith , Baur Louise A , Occhipinti Jo-An , Carrello Joseph , Golley Rebecca K , Hayes Alison , Hunter Kylie E , Kreuger L Kurt , Lawson Kenny , Okely Anthony D , Seidler Anna Lene , Wyse Rebecca , Freebairn Louise
Published: January 2025

Introduction

Child and adolescent obesity is associated with a range of immediate health issues and influences obesity in adulthood. The complex nature of health determinants that contribute to obesity makes it challenging to deliver effective public health interventions. This research presents insights from a system dynamics model of childhood and adolescent obesity aimed at supporting evidence-based decision-making.

Methods

A system dynamics model was developed using the best available evidence and data, with input from research and industry experts to map the hypothetical causal structure of the factors contributing to childhood and adolescent obesity in Australia. The model was calibrated to fit the historical prevalence of obesity (R2=0.97, mean squared error (MSE)=4.94E-04). Intervention-based scenarios were simulated to examine how changes in environmental factors and health-related behaviours may affect the prevalence of obesity. The potential economic benefits of the scenarios were estimated from changes in population healthcare spending and quality of life compared with base model projections.

Results

A series of interventions were explored in the model, including changes in early childhood behaviours, changes to diet and physical activity in childcare and school settings, financial support for organised sports and sugar-sweetened beverage taxation. The most promising individually implemented intervention scenario for reducing the prevalence of childhood and adolescent obesity was a sugar-sweetened beverage tax (0.57 percentage points and 0.61 percentage points, respectively) and government funding of organised sports (0.42 percentage points and 0.63 percentage points, respectively). When all interventions were implemented in combination, childhood obesity was reduced by 1.43 percentage points and 1.81 percentage points in adolescents.

Conclusions

The findings highlight the challenges faced by policy-makers and public health practitioners working to reduce childhood and adolescent obesity. Insights from the model emphasise the value of public health programmes over the life course. Implementing initiatives with broad reach that support healthy choices may reduce obesity, resulting in a healthier Australian population.
Individual versus group exercise effect on youth physical activity levels: a randomised controlled trial
Authors: Novak Dario , Čule Marko , Kim Jinseo , Kim Rockli , Subramanian S V
Published: January 2025

Objectives

To explore the effects of two different types of exercise (individual vs group) on physical activity (PA) among Croatian university students.

Methods

A total of 976 university students between the ages of 19 and 20 years (age 19.4±1.1 years, body mass index 21.9±2.9 kg/m2) were randomly assigned to either the control group (individual exercise) (n=504) or the intervention group, which received group exercise (n=472). Pre- and postintervention measures included: self-rated health, parents’ occupation, psychological distress, nutritional status and PA levels. The overall intervention effect was estimated using linear regression method, and heterogeneity in intervention effect was assessed by modelling complex variance.

Results

Group-based exercise intervention significantly increased total PA time by more than 10 metabolic equivalents (METS) hours per week compared with individual-based exercise control group. When considering different types of activities, the intervention effect was stronger for vigorous activity (increase by almost 6 METS hours per week) than walking activity (2.5 METS hours per week). The change in moderate activity level was not significant after covariate adjustment. In addition, intervention was also effective in reducing sedentary hours. Finally, when complex level-1 heterogeneity was modelled by intervention status, we found substantially larger variance in the intervention group compared with the controls, indicating presence of heterogeneous treatment effect.

Conclusions

This study discusses major implications of different ways of exercising among youths from a health, educational and sport perspective. Intervention and policies that leverage school social capital might serve as an avenue for health promotion in youth.
Healthcare spending and factors associated with fall injury in Australia residential aged care: a cohort analysis
Authors: Okafor Charles , Balasooriya Namal N. , Page Amy T , Hill Anne-Marie , Etherton-Beer Christopher D , Comans Tracy
Published: January 2025

Background

Given that fall injury is a critical public health concern in Australia, understanding the economic implications of falls among older adults is crucial to allocating healthcare resources efficiently to reduce falls and improve quality of life. This study therefore aimed to estimate the cost and identify factors associated with fall-related injuries within residential aged care (RAC).

Methods

A cohort analysis from the healthcare system perspective based on data from a double-blinded randomised controlled trial—the Opti-Med trial. The trial participants were 303 people aged ≥65 years. Identification of in-scope data from the trial dataset was achieved using the falls description note and the National Hospital Cost Data Collection diagnostic related group classification system. Data analyses were performed using STATA V.17. All costs were adjusted to 2022 Australian dollars.

Results

On average, the cost of an injurious fall per incident was $2494 (SD=$6199), while the average cost of falls per resident annum was $1798 (SD=$6002). The potential cost of injurious falls per annum in Australia’s RAC system was $325 million. Sex and body mass index (BMI) were identified factors associated with fall injury. There was an inverted U-shaped relationship between BMI and falls risk in RAC.

Conclusions

The healthcare spending on fall injury per resident annum in RAC represents 20% of the 2021–2022 healthcare expenditure per capita. The high cost and inverted U-shaped relationship between BMI and falls risk underscores the need for more effective and RAC-tailored falls prevention strategies in this setting.

Trial registration numbers

Australian New Zealand Clinical Trial Registry (ACTRN12613001204730); WHO Universal Trial (U1111-1148-6094).
Radiomics signature for dynamic monitoring of tumor inflamed microenvironment and immunotherapy response prediction
Authors: Bernatowicz Kinga , Amat Ramon , Prior Olivia , Frigola Joan , Ligero Marta , Grussu Francesco , Zatse Christina , Serna Garazi , Nuciforo Paolo , Toledo Rodrigo , Escobar Manel , Garralda Elena , Felip Enriqueta , Perez-Lopez Raquel
Published: January 2025

Background

The efficacy of immune checkpoint inhibitors (ICIs) depends on the tumor immune microenvironment (TIME), with a preference for a T cell-inflamed TIME. However, challenges in tissue-based assessments via biopsies have triggered the exploration of non-invasive alternatives, such as radiomics, to comprehensively evaluate TIME across diverse cancers. To address these challenges, we develop an ICI response signature by integrating radiomics with T cell-inflamed gene-expression profiles.

Methods

We conducted a pan-cancer investigation into the utility of radiomics for TIME assessment, including 1360 tumors from 428 patients. Leveraging contrast-enhanced CT images, we characterized TIME through RNA gene expression analysis, using the T cell-inflamed gene expression signature. Subsequently, a pan-cancer CT-radiomic signature predicting inflamed TIME (CT-TIME) was developed and externally validated. Machine learning was employed to select robust radiomic features and predict inflamed TIME. The study also integrated independent cohorts with longitudinal CT images, baseline biopsies, and comprehensive immunohistochemistry panel evaluation to assess the pan-cancer biological associations, spatiotemporal landscape and clinical utility of the CT-TIME.

Results

The CT-TIME signature, comprising four radiomic features linked to a T-cell inflamed microenvironment, demonstrated robust performance with AUCs (95% CI) of 0.85 (0.73 to 0.96) (training) and 0.78 (0.65 to 0.92) (external validation). CT-TIME scores exhibited positive correlations with CD3, CD8, and CD163 expression. Intrapatient analysis revealed considerable heterogeneity in TIME between tumors, which could not be assessed using biopsies. Evaluation of aggregated per-patient CT-TIME scores highlighted its promising clinical utility for dynamically assessing the immune microenvironment and predicting immunotherapy response across diverse scenarios in advanced cancer. Despite demonstrating progression disease at the first follow-up, patients within the inflamed status group, identified by CT-TIME, exhibited significantly prolonged progression-free survival (PFS), with some surpassing 5 months, suggesting a potential phenomenon of pseudoprogression. Cox models using aggregated CT-TIME scores from baseline images revealed a statistically significant reduction in the risk of PFS in the pan-cancer cohort (HR 0.62, 95% CI 0.44 to 0.88, p=0.007), and Kaplan-Meier analysis further confirmed substantial differences in PFS between patients with inflamed and uninflamed status (log-rank test p=0.009).

Conclusions

The signature holds promise for impacting clinical decision-making, pan-cancer patient stratification, and treatment outcomes in immune checkpoint therapies.
MAF1 inhibits hepatocarcinogenesis by fostering an immunostimulatory tumor microenvironment
Authors: Cao Di , Wang Yue-Ning , Sun Chao-Yue , Li Haojiang , Ren Ge , Zhou Yu-Feng , Zhang Mei-Yin , Wang Shuo-Cheng , Mai Shi-Juan , Wang Hui-Yun
Published: January 2025

Background

The biological significance of MAF1, a tumor suppressor, in carcinogenesis and immune response of hepatocellular carcinoma (HCC) remains unreported. Understanding the underlying mechanisms by which MAF1 enhances anti-tumor immunity in HCC is crucial for developing novel immunotherapy strategies and enhancing clinical responses to treatment for patients with HCC.

Methods

Mice were subjected to hydrodynamic tail vein injections of transposon vectors to overexpress AKT/NRas, or c-Myc, with or without wild-type (WT) or mutant-activated (−4A) MAF1, or short-hairpin MAF1 (shMAF1). Liver tissues and tumors were harvested and analyzed using histology, immunohistochemistry, immunoblotting, quantitative reverse-transcription PCR, and flow cytometry. MAF1 was overexpressed or knocked down in HCC cells via lentiviral transfection. Cell lines were analyzed using RNA sequencing, immunoblotting, dual luciferase reporter, and chromatin precipitation assays.

Results

Both MAF1-WT and MAF1-4A proteins significantly inhibit hepatocarcinogenesis in mice, with the mutant form exhibiting a stronger suppressive effect. Although MAF1 knockdown alone does not induce abnormalities in the mouse liver, it accelerates c-Myc-induced carcinogenesis. Our results provide the first in vivo evidence that MAF1 plays a tumor suppressor role by activating PTEN to suppress the AKT-mammalian target of rapamycin signaling pathway during hepatocarcinogenesis in physiologically relevant tumor models. More importantly, we found that MAF1 not only enhances the intratumoral infiltration of CD8+T cells by increasing CXCL10 secretion but also enhances their functional activity by inhibiting PDL1 transcription in mouse liver cancer, which were confirmed in human HCC or in vitro experiments. Furthermore, PDL1 overexpression accelerates mouse hepatocarcinogenesis by antagonizing the tumor-suppressive role of MAF1.

Conclusions

Our study uncovers a novel anti-tumor immunity of MAF1 in hepatocarcinogenesis and human HCC. These findings suggest that the stimulated MAF1 could potentially improve immunotherapy in combination with immune checkpoint inhibitors in HCC patients, especially in those with an absence of T cells in HCC tissues.
Predictive value of ENLIGHT-DP in patients with metastatic lung adenocarcinoma treated with immune checkpoint inhibitors and platinum chemotherapy directly from histopathology slides using inferred transcriptomics
Authors: Arnon Johnathan , Dinstag Gal , Tirosh Omer , Gugel Leon , Kinar Yaron , Gottlieb Tzivia , Elia Anna , Rottenberg Yakir , Nechushtan Hovav , Tabi Michael , Blumenfeld Philip , Pikarsky Eli , Beker Tuvik , Aharonov Ranit , Popovtzer Aron
Published: January 2025

Introduction

Immune checkpoint inhibitors (ICI) have improved outcomes in non-small cell lung cancer (NSCLC). Nevertheless, the clinical benefit of ICI as monotherapy or in combination with chemotherapy remains widely varied and existing biomarkers have limited predictive value. We present an analysis of ENLIGHT-DP, a novel transcriptome-based biomarker directly from histopathology slides, in patients with lung adenocarcinoma (LUAD) treated with ICI and platinum-based chemotherapy.

Methods

We retrospectively scanned high-resolution H&E slides from pretreatment tumor-tissue samples of 50 patients with metastatic LUAD treated with first-line ICI with (46) or without (4) platinum-based chemotherapy and applied our ENLIGHT-DP pipeline to generate, in a blinded manner, an individual prediction score. ENLIGHT-DP predicts response to ICI and targeted therapies given H&E slide scans in two steps: (1) predict individual messenger RNA expression directly from high-resolution H&E scanned slides using DeepPT, a digital-pathology-based algorithm. (2) Use these values as input to ENLIGHT, a transcriptome-based platform that predicts response to ICI and targeted therapies derived from drug-specific networks of gene expressions. We then unblinded the clinical outcomes and evaluated the predictive value of ENLIGHT-DP in comparison to programmed death ligand (PD-L)-1 and tumor mutational burden (TMB).

Results

ENLIGHT-DP is predictive of response to treatment with receiver operating characteristic (ROC) area under the curve (AUC) of 0.69 (p=0.01) and outperforms both TMB and PD-L1 expression with ROC AUC of 0.52 and 0.46, respectively. Using a predetermined binary cut-off (established on independent cohorts) for patients predicted to respond to ICI, ENLIGHT-DP achieves 100% positive predictive value (PPV) and 44% sensitivity, superior to both PD-L1>50% (65% PPV and 38% sensitivity) and TMB-high (82% PPV and 26% sensitivity). ENLIGHT-DP was highly predictive in PD-L1<1% and TMB-low outlier groups with ROC AUC of 0.88 and 0.80, respectively (p value<0.05). ENLIGHT-DP is the only biomarker in this cohort significantly correlated with progression-free survival (HR: 0.45, 95% CI: 0.2 to 0.99, p=0.048).

Conclusion

We demonstrate the application of ENLIGHT-DP, a transcriptome-based biomarker for accurate prediction of treatment of LUAD with ICI and platinum-based chemotherapy, outperforming PD-L1 and TMB, and relying solely on accessible H&E scanned slides. Further studies on different tumor types, ICI monotherapy and bigger NSCLC cohorts are warranted.