bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation outcomes of convergence action policy to accelerate stunting reduction in Pidie district, Aceh province, Indonesia: a qualitative study
Authors: Sufri Sofyan , Iskandar Iskandar , Nurhasanah Nurhasanah , Bakri Saiful , Jannah Misbahul , Rajuddin Rajuddin , Nainggolan Sarah Ika , Sirasa Fathima , Lassa Jonatan Anderias
Published: November 2024

Objectives

The research aims to understand the challenges and opportunities in policy and programme convergence to accelerate interventions for reducing stunting at the district, subdistrict and the 10 focused villages.

Design

Data were collected through qualitative methods (in-depth interviews and document reviews), and then analysed using thematic processes with NVivo V.11 software, by QSR International The process included coding, categorising and linking to the eight implementation outcome variables (as determined themes), namely acceptability, adoption, appropriateness, feasibility, compliance, implementation cost, coverage and sustainability. The variables of convergence action policies were implemented differently by stakeholders at different layers of governance.

Setting

Pidie district, Aceh province, Indonesia.

Participants

106 respondents from provincial to village levels were selected and interviewed, including leaders and policymakers (n=10); and convergence action implementers from the province to the villages (n=96).

Results

Stunting reduction policies were generally acceptable to local leaders and policymakers as a policy imperative. Implementation costs were considered sufficient by stakeholders, although focusing only on nutrition-specific interventions. However, in terms of adoption, feasibility, compliance, nutrition-sensitive intervention coverage and sustainability aspects were insufficiently implemented in all the focused villages due to inadequate collaboration between health and non-health sectors and limited experts.

Conclusions

This study offers key recommendations for policy and practice changes and considerations. The utilisation of methods and findings from this study in other areas in Indonesia or other low- and middle-income countries is important to explore more about the applicability, benefits and weaknesses of this study.
Tushirikiane-4-Uthabiti (Supporting Each Other For Resilience): study protocol of a mental health, HIV self-testing and livelihoods randomised controlled trial for advancing HIV prevention outcomes among urban refugee youth in Kampala, Uganda
Authors: Logie Carmen H , Okumu Moses , Tailor Lauren , MacKenzie Frannie , Admassu Zerihun , Hakiza Robert , Kibuuka Musoke Daniel , Katisi Brenda , Nakitende Aidah , Kyambadde Peter , Mbuagbaw Lawrence
Published: November 2024

Introduction

Research with urban refugee youth in Uganda has documented co-occurring social (e.g., poverty) and health (e.g., depression) disparities associated with HIV vulnerabilities. Benefits of HIV self-testing (HIVST) in increasing HIV testing uptake among youth are well established, yet limited interventions have examined if combining HIVST with mental health promotion, or with mental health promotion alongside poverty reduction, is associated with greater improvements in HIV prevention and testing outcomes.

Methods and analysis

The aim is to evaluate the effectiveness of: (1) HIVST alone (standard of care); (2) mobile health (mHealth) and graphic medicine (comic) programme for mental health alongside HIVST; and (3) the combination of HIVST, a livelihoods programme, and mHealth mental health programme, in advancing the primary outcome of HIV testing uptake and secondary outcomes (HIV status knowledge, linkage to confirmatory testing and HIV care, HIV knowledge, consistent condom use, condom use self-efficacy, sexual risk) with urban refugee youth in Kampala, Uganda. A three-arm randomised controlled trial will be implemented from 8 April 2024 to 31 October 2024 with youth across five informal settlements in Kampala, grouped into three sites based on proximity, and randomised in a 1:1:1 design. Approximately 330 participants (110 per arm) are enrolled and data collection will occur at three time points (baseline enrolment, 3-month follow-up and 6-month follow-up).

Ethics and dissemination

The study received ethical approval from the University of Toronto (#37496), Mildmay Uganda Research Ethics Committee (#MUREC-2021-41) and Uganda National Council for Science & Technology (#SS1021ES). The trial is registered at ClinicalTrials.gov (NCT06270160). Study findings will produce new knowledge of the impacts of a mental health programme, and a combined mental health and livelihoods programme, on improving HIV prevention outcomes among urban refugee youth in Kampala. Findings will be shared in peer-reviewed publications, conference presentations and in community dissemination.

Trial registration number

NCT06270160(date of registration: 13 February 2024).

Trial sponsor

Dr. Carmen Logie, carmen.logie@utoronto.ca.
Advanced Nurse Practitioner (ANPs) experiences of the Quality and Outcomes Framework (QOF) Scheme: a UK case study
Authors: Khan Nagina , Peckham Stephen
Published: November 2024

Objectives

The primary focus of pay-for-performance (P4P) schemes in the UK has traditionally been related to the public health and inclusion elements related to the activities of doctors with comparatively less attention given to nursing care as a component of the scheme. However, nursing is an integral part of healthcare delivery in the National Health Service and nurses constitute the major group of healthcare professionals in most countries. Our aim was to explore advanced nurse practitioner (ANPs) experiences of the Quality and Outcomes Framework (QOF), using the Implicit Leadership Theory (ILT) frame.

Methods

We used a case study approach. Six articles on the QOF work were synthesised, focused on ANPs and their leadership potential in healthcare. Evidence showed that despite having importance in delivering the activities of QOF, nursing activities overlooked. We undertook a thematic synthesis of these papers, with a specific focus ANPs’ leadership development in Long Term Conditions (LTC) care within general practice and capacity to influence the healthcare system.

Findings

Six themes were identified: (1) sensitivity, patient-centred care, context and continuity of care; (2) intelligence—leaders capable of making strategic decisions in healthcare settings, (3) dedication, trust, equity and equality, (4) dynamism of nursing, (5) tyranny, guise of teamwork, collaboration and (6) nursing and healthcare leadership.

Conclusions

Nurses in leadership roles created good working relationships, coped with conflicts and contributed to shared objectives and were sympathetic collaborators. Using the six ILT characteristics, we found that nurses were collaborators. Future P4P schemes should benefit from a collective lens of healthcare personnel when focusing on quality initiatives and improving the delivery of healthcare activities.
Patient discourses on real-time access to test results via hospital portals: a discourse analysis of semistructured interviews with Dutch patients
Authors: Hulter Pauline , Weggelaar-Jansen Anne Marie J W M , Ahaus Kees , Pluut Bettine
Published: November 2024

Objective

Real-time access to test results on patient portals can have advantages and disadvantages for patients. It confronts patients with a complicated decision, namely whether to consult results before the medical consultation. To gain a deep understanding of patients’ decision-making processes, we unravelled three discourses about real-time access to test results, each of which articulates a different set of values, assumptions and arguments. Our research question was what patient discourses on real-time access to test results can be distinguished?

Design

We conducted discourse analysis on 28 semistructured interviews.

Setting

Interviews were conducted with patients who had (no) experience with real-time access to test results. Our participants were treated in different hospitals, and therefore, used different portals since Dutch hospitals can choose from suppliers for their patient portals.

Participants

Patients with experience (n=15) and without experience (n=13) of real-time access to test results on a patient portal.

Results

We identified three discourses: (1) real-time access as a source of stress, which highlighted how real-time access could cause stress due to the complexity of deciding whether to access test results, the incomprehensibility of medical language and the urge to repeatedly check if test results were available, (2) anxiety reduction through real-time access showed how real-time access can reduce stress by reducing waiting times and (3) real-time access for self-management showed how real-time access can give patients an opportunity for self-management because they can make informed decisions and are better prepared for the medical consultation.

Conclusion

Our study shows the plurality in opinions on real-time access, which helps in forming different strategies to inform and support patients in order to realise optimal use of real-time access.
Online health literacy resources for people with intellectual disability: protocol for a grey literature scoping review
Authors: Yeap Zhenmei , Keeley Jessica , Skoss Rachel , Hunt Susan , Kickett Angela , Saldaris Jacinta , Nevill Thomas , Downs Jenny
Published: November 2024

Introduction

People with intellectual disability are at risk of poor physical and mental health. Risks to health are compounded by poor health literacy, that is, reduced capacity to access health services, respond quickly to changes in health status and navigate care pathways. Building health literacy skills is a strength-based way to increase health and optimise the use of healthcare services. The internet is a primary source of health information for many people, including people with intellectual disability and their families. This scoping review will aim to identify and collate online lay healthcare resources available to and developed for people with intellectual disability and their families and evaluate whether domains of health literacy are addressed.

Methods and analysis

This review will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews guidelines. The proposed search strategy has three components. Resources will be identified by (1) reviewing disability organisation websites, (2) searching key disability and health terms in the Google search engine and (3) snowball sampling to identify additional resources through links in identified websites and resources. Resources will be selected if they are freely available, presented in or translatable into English, provide health information and are directed to people with intellectual disability or their family members. Extracted data will include descriptors of the source, format, area of health and targeted age range. Content relevant to domains of health literacy will be documented and gaps in available health information will be identified. Study findings will be presented in narrative, tabular and visual forms.

Ethics and dissemination

Ethical approval will not be sought because primary data will not be collected. The results will be disseminated in peer-reviewed literature, as conference presentations, as a synthesised resource for people with intellectual disability and their families and in summary documents for health service managers and policymakers.
Low-value practices in primary care: a cross-sectional study comparing data between males and females in Spain
Authors: Mira José Joaquín , Carratalá-Munuera Concepción , García-Torres Daniel , Soriano Cristina , Sánchez-García Alicia , Gil-Guillen Vicente F , Vicente María Asunción , Pérez-Jover Mª Virtudes , Lopez-Pineda Adriana
Published: November 2024

Introduction

Overuse of medical services is a challenge worldwide, posing a threat to the quality of care, patient safety and the sustainability of healthcare systems. Some data suggest that females receive more low-value practices (LVPs)—defined as medical interventions that provide little or no benefit to patients and can even cause harm—than males. This study aims to evaluate and compare the occurrence of LVPs in primary care among both males and females.

Design

A retrospective study was conducted.

Setting

Primary care in the Alicante province (Spain) during 2022.

Participants

Data were extracted from the digital medical records of 978 936 patients attended by 1125 family physicians across 262 primary healthcare centres in the Alicante province.

Outcome measures

Data on age, sex, diagnosis and treatment were extracted. The primary outcome measure was the frequency of 12 selected LVPs prescribed to male and female patients. These LVPs were expected to be relatively frequent occurrences with the potential to cause harm.

Results

A total of 45 955 LVPs were identified, of which 28 148 (5.27% of 534 603, CI95% 5.20–5.32) were prescribed to female patients and 17 807 (4.00% of 444 333, CI95% 3.95–4.06) to male patients (x², p value <0.0001). The most common LVPs were prescribing treatment for overactive bladder without excluding other pathologies that may cause similar symptoms (30.87%), using hypnotics without having a previous aetiological diagnosis in patients with difficulty maintaining sleep (14%) and recommending analgesics (NSAIDs, paracetamol and others) for more than 15 days per month in primary headaches that do not respond to treatment (13.33%).

Conclusions

Future clinical training, management and research must consider biological differences or those based on gender factors when analysing the frequency and causes of LVP.

Trial registration number

NCT05233852.
Tubal flushing with oil-based contrast during hysterosalpingography versus tubal flushing by hysterosalpingo-foam sonography in infertile women undergoing fertility work-up: study protocol of a randomised controlled trial (FOil study)
Authors: Kamphuis Danah , Huijser Janette P M , van Welie Nienke , Verhoeve Harold R , Kuijper Esther , de Bruin Jan Peter , van Dongen Angelique J C M , Gielen Susanne C J P , de Krom Guusje , Janse Femi , Koks Carolien A M , Nap Annemiek W , Anema Johannes R , Bosmans Judith E , Stoker Jaap , van Wely Madelon , Mol Ben Willem J , Mijatovic Velja , Dreyer Kim
Published: November 2024

Introduction

Hysterosalpingography (HSG) and hysterosalpingo-foam sonography (HyFoSy) are commonly used tubal patency tests during the fertility work-up. Besides its diagnostic purpose, HSG with oil-based contrast can also be applied for its fertility-enhancing effect, by tubal flushing. HyFoSy is considered as less painful compared with HSG, it lacks exposure to iodinated contrast medium and ionising radiation. The fertility-enhancing effects of HyFoSy are less studied and randomised controlled trials comparing pregnancy rates after HSG and HyFoSy are lacking. This study (FOil study) is initiated to compare the effectiveness of tubal flushing during HSG with oil-based contrast and HyFoSy.

Methods and analysis

The FOil study is a nationwide, multicentre, open label, randomised controlled trial with a superiority design. Infertile women with an indication for tubal patency testing during their fertility work-up will be randomly assigned to HSG with oil-based contrast medium or HyFoSy. The primary outcome is conception within 6 months after randomisation leading to live birth. To demonstrate or refute an 8% difference in conception leading to live birth in favour of HSG with oil-based contrast, 1102 women will be included in the trial. A cost-effectiveness analysis from a societal perspective will be performed alongside the trial.

Ethics and dissemination

The trial is approved by the Medical Ethics Review Committee of the Amsterdam University Medical Centers (Ref. No. 2022.0884, date: 17 March 2023) and by the boards of the participating hospitals. The findings will be disseminated in peer-reviewed journals and participants will be informed through the patient organisation.

Trial registration number

NCT05882188.
Plasmodium falciparummolecular surveillance to inform the Mozambican National Malaria Control Programme strategy: protocol
Authors: da Silva Clemente , Matambisso Gloria , Boene Simone , Rovira-Vallbona Eduard , Pujol Arnau , Comiche Kiba , Sánchez Antoni , Greenhouse Bryan , Chidimatembue Arlindo , Aranda-Díaz Andrés , Arnaldo Paulo , Ariani Cristina , Walker Patrick , Mbeve Henriques , Ndimande Nelo , Tembisse Dário , Ruybal-Pesántez Shazia , Verity Robert , Rafael Bernardete , Candrinho Baltazar , Mayor Alfredo
Published: November 2024

Introduction

Malaria molecular surveillance has the potential to generate information on biological threats that compromise the effectiveness of antimalarial interventions. This study aims to streamline surveillance activities to inform the new strategic plan of the Mozambican National Malaria Control Programme (2023–2030) for malaria control and elimination.

Methods and analyses

This prospective genomic surveillance study aims to generatePlasmodium falciparumgenetic data to monitor diagnostic failures due topfhrp2/3deletions and molecular markers of antimalarial drug resistance, to characterise transmission sources and to inform the implementation of new antimalarial approaches to be introduced in Mozambique (chemoprevention and child malaria vaccination). The study, to be conducted between 2024 and 2026, will use three sampling schemes: a multicluster probabilistic health facility survey in the 10 provinces of the country to detectpfhrp2/3deletions and markers of antimalarial drug resistance; dense sampling of all clinical cases in representative districts in the south targeted for elimination to characterise malaria importation and identify sources of transmission; and testing of pregnant women for malaria at their first antenatal care visit to assess malaria burden and molecular trends. Using a multiplex amplicon-based sequencing approach, the study will target microhaplotypes informative of genomic diversity and relatedness, as well as key drug resistance-associated genes,pfhrp2/3deletion and malaria vaccine targets. Key genomic information will be visualised in a dashboard integrated into the District Health Information System V.2-based Malaria Information Storage System for programmatic use.

Ethics and dissemination

The protocol was reviewed and approved by the national ethics committee of Mozambique (Comité Nacional de Bioética para Saúde, Ref: 680/CNBS/23). Project results will be presented to all stakeholders using study-specific brochures and published in open-access journals.

Trial registration number

NCT06529237.
Study protocol: Return to Country, an Australia-wide prospective observational study about returning First Nations renal patients home
Authors: Jones Yomei , Truong Mandy , Preece Cecilia , Cass Alan , Heerink Fiona , McDonald Stephen , Jones Scott , Mallett Andrew John , Majoni Sandawana William , Sajiv Cherian , Patankar Khalil , Mulholland Eddie , Woldeyohannes Solomon , Lawton Paul
Published: November 2024

Introduction

In Australia, kidney failure treatment disparities exist between Aboriginal and/or Torres Strait Islander (First Nations) and non-First Nations people. Despite persistent calls from First Nations patients with kidney failure, they are less likely to have treatment that allows them to live at home.

Methods and analysis

This is a prospective, multicentre study based in Australia. The aim of the study is to characterise the socioeconomic, environmental, health service and biomedical factors driving the health outcomes and patterns of health service utilisation experienced by First Nations patients and investigate whether health service changes to address these identified barriers can achieve higher rates of renal replacement therapy at home on country. This will be achieved by mixed-methods data collection at health service (audit and process data), staff (surveys and qualitative interviews) and patient (survey testing, feedback sessions, health outcomes) levels. A process evaluation will identify barriers and enablers to health services changes in relation to cultural safety. Baseline and follow-up data will be compared to assess the extent to which health services change their service delivery and the impact on health outcomes for First Nations patients with kidney failure. Qualitative and quantitative data will be integrated to provide an in-depth understanding of project outcomes and impacts.

Ethics and dissemination

This study is funded by the National Health and Medical Research Council of Australia (GNT1158075). Ethics approval has been obtained so far from the Human Research Ethics Committee (HREC) of the Northern Territory Department of Health and Menzies School of Health Research (2019-3530), Far North Queensland HREC (2023/QCH/99606 (Nov ver 4)-1732), the Central Adelaide Local Health Network HREC (2023/HRE00209), the Aboriginal Health Council of South Australia (AHREC Protocol #: 04-23-1078), the Aboriginal Health and Medical Research Council of New South Wales (AH&MRC HREC reference: 2230/24) and the Far North Queensland Human Research Ethics Committee (FNQ HREC reference: HREC/2023/QCH/99606 (Nov ver 4)-1732). Study participants, policy makers and community organisations will be provided with updates of study findings. Dissemination of study findings will be through peer-reviewed publications and conference presentations.

Trial registration number

ACTRN12623001241628.
Implementing group consultations in a lower limb musculoskeletal outpatient service to improve efficiency and maintain positive patient outcomes
Authors: Wigham Lisa , Richardson Annette , Moore Kathryn , Martin Michael
Published: November 2024

Background

Group consultations (GCs) in healthcare have been shown to improve clinical outcomes with greater efficiency. This project aimed to develop a more efficient musculoskeletal (MSK) physiotherapy-led GC approach for common lower limb problems. This was to help manage an anticipated increase in demand while maintaining high patient satisfaction and ensuring clinical effectiveness.

Methods

Three ‘Plan-Do-Study-Act’ (PDSA) cycles were undertaken to test out the new approach of virtual group consultations (VGCs) and face-to-face GCs with MSK patients. These two approaches were tested and refined on four common lower limb conditions: patellofemoral pain syndrome, Achilles tendinopathy, plantar fasciopathy and knee osteoarthritis. We measured the number of patients seen, staff time, patients’ experience and patient outcome scores.

Results

Each patient used 45 min of physiotherapy time via the traditional one-to-one physiotherapy consultation approach, this was reduced to 22 min in the VGCs and 12 min for the face-to-face GCs. We found a significant increase in EQ-5D scores (PDSA 1: +0.19, p=0.004 and PDSA 2: +0.17, p=0.002) and the Visual Analogue Score for Pain (PDSA 1: −1.95, p=0.001 and PDSA 2: −2.6, p=0.007) from the first to the second virtual GC sessions.

Conclusion

GCs were shown to be an efficient way of providing physiotherapy to patients with lower limb conditions. Feedback from patients attending GCs has shown a good level of effectiveness and patient satisfaction. This alternative way to review and treat patients has yielded a reduction in physiotherapist contact time per patient, improving the efficiency of our MSK service. We did not compare these groups to the one-to-one face-to-face consultations, therefore whether they are better, is unknown.
Life course socio-demographic circumstances and the association between housing tenure and disability-free life expectancy in Australia: a longitudinal cohort study
Authors: Hambisa Mitiku Teshome , Kiely Kim M
Published: November 2024

Introduction

This study aimed to assess the extent to which the association between housing tenure and disability-free life years is independent of socio-demographic circumstances from earlier in life.

Methods

We analysed nationally representative data from the Household Income and Labour Dynamics in Australia survey. Participants were followed up for 14 years (2001–2014). Housing tenure was measured by the question, “Do you (or any other members of this household) own this home, rent it, or do you live here rent-free?” Disability was defined by the SF-36 physical function subscale. We used multistate modelling and inverse probability weighting to estimate the association between housing tenure (home ownership vs renting) and disability-free life expectancy (DFLE), adjusting for a range of socio-demographic indicators.

Results

The sample included 6164 participants (52.5% women) aged 45 years and older in 2001. In weighted analyses that adjusted for earlier life circumstances, for men, the estimated total life expectancy (TLE) at age 65 among renters was 16.7 years, 2.3 (95% CI −3.7 to −0.7) years shorter than the TLE of 19.0 years for owner-occupiers. DFLE was 1.8 years shorter for renters than owner-occupiers. For women at age 65, the weighted TLE was estimated to be 20.6 years, 2.3 (95% CI −3.9 to −0.6) years shorter than the 22.9 years estimated for owner-occupiers. Compared with owner-occupiers, DFLE was 3.1 years shorter for women renters.

Conclusions

Both men and women renters had shorter disability-free and TLE than owner-occupiers independent of earlier life circumstances. There is a need for policies addressing potential health disparities linked to housing tenure.
Burnout, motivation and job satisfaction among community health workers recruited for a depression training in Madhya Pradesh, India: a cross-sectional study
Authors: Mitchell Lauren M , Anand Aditya , Muke Shital , Hollon Steven D , Joshi Udita , Khan Azaz , Haney Juliana , Shrivastava Ritu , Singh Abhishek , Singla Daisy , Teja G Sai , Tugnawat Deepak , Bhan Anant , Patel Vikram , Naslund John A
Published: November 2024

Introduction

Burnout, low motivation and poor job satisfaction among community health workers (CHWs) have negative impacts on health workers and on patients. This study aimed to characterise levels of burnout, motivation and job satisfaction in CHWs in Madhya Pradesh, India and to determine the relation between these levels and participant characteristics. This study can inform efforts to promote well-being and address stress in this population.

Methods

In this cross-sectional study, we recruited participants via simple random sampling without replacement. We administered two validated questionnaires, the Copenhagen Burnout Inventory and a Motivation and Job Satisfaction Assessment, to CHWs who had enrolled in a training programme to deliver a brief psychological intervention for depression. We calculated mean scores for each questionnaire item, examined the reliability of the measures and analysed associations between participant demographic characteristics and questionnaire scores.

Results

339 CHWs completed the questionnaires. The personal burnout domain had the highest mean burnout score (41.08, 95% CI 39.52 to 42.64, scale 0–100) and 33% of participants reported moderate or greater levels of personal burnout. Items that reflected physical exhaustion had the highest item-test correlations. The organisation commitment domain had the highest mean motivation score (mean 3.34, 95% CI 3.28 to 3.40, scale 1–4). Items describing pride in CHWs’ work had the highest item-test correlations. Several pairwise comparisons showed that higher education levels were associated with higher motivation levels (degree or higher vs eighth standard (p=0.0044) and 10th standard (p=0.048) and 12th standard versus eighth standard (p=0.012)). Cronbach’s alpha was 0.82 for the burnout questionnaire and 0.86 for the motivation and job satisfaction questionnaire.

Conclusion

CHWs report experiencing burnout and feeling physically tired and worn out. A sense of pride in their work appears to contribute to motivation. These findings can inform efforts to address burnout and implement effective task-sharing programmes in low-resource settings.
Prospective cohort study exploring the neurodevelopmental outcomes following documented neonatal sepsis in Nepal: study protocol
Authors: Vaidya Swechhya , Raj Manu , Sudevan Remya , Chandramathi Jayasree , Karmacharya Shailendra Bir , Subedi Kalpana , Raya Ganendra Bhakta , Shrestha Dhruba
Published: November 2024

Introduction

Neonatal sepsis, a significant contributor to global neonatal mortality, poses substantial risks to infant health, particularly in low-resource countries like Nepal. Despite its high prevalence, there is a lack of clarity in defining and understanding neonatal sepsis, leading to challenges in diagnosing and managing the condition effectively. The probable impact of neonatal sepsis on long-term neurodevelopmental outcomes, including motor and cognitive delays, remains under-explored in Nepal. The primary objective of this study is to report the prevalence of neurodevelopmental delay in neonates with documented sepsis. The secondary objective is to report significant associations of the same with selected probable risk factors.

Methods and analysis

This is a dual-centric prospective cohort study that is ongoing at two hospitals—Paropakar Maternity and Women’s Hospital and Siddhi Memorial Hospital in Nepal, over a 2-year period. Neonates diagnosed with sepsis will be assessed using the Developmental Assessment Scale for Indian Infants at 6 months and 1 year, postdiagnosis. Statistical analyses will include prevalence estimation and logistic regression.
Financial incentives and motivational intervention to improve gastric cancer screening in China: a randomized controlled trial study protocol
Authors: Wang Quan , Gong Chao , Lv Yumeng , Tan Yiyang , Liu Siqi , Yang Li
Published: November 2024

Gastric cancer (GC) remains a significant global health challenge, with high mortality rates, particularly in low- and middle-income countries, like China. Early detection through screening is crucial for improving prognosis and reducing mortality. However, uptake of GC screening remains suboptimal, highlighting the need for effective interventions to promote screening participation. This study employs an experimental design to evaluate the effectiveness of two interventions, financial incentives and motivational interventions, in promoting GC screening uptake at the individual level. A large sample size will be recruited from high GC-burden provinces in China, and participants will be randomly assigned to intervention and control groups. Statistical analyses, including the χ² test and interrupted time series analysis, will be used to assess the impact of interventions on screening uptake and adherence. The research protocol was reviewed by the ethical review committee of the Peking University Health Science Center (2024097) and registered at the ClinicalTrials.gov. Findings from this study will be disseminated through peer-reviewed publications, conference presentations, and engagement with stakeholders to inform evidence-based strategies for improving GC screening and reducing GC-related morbidity and mortality.
Propafenone facilitates mitochondrial-associated ferroptosis and synergizes with immunotherapy in melanoma
Authors: Zhou Qian , Dian Yating , He Yi , Yao Lei , Su Hui , Meng Yu , Sun Yuming , Li Daishi , Xiong Yixiao , Zeng Furong , Liang Xiaowei , Liu Hong , Chen Xiang , Deng Guangtong
Published: November 2024

Background

Despite the successful application of immunotherapy, both innate and acquired resistance are typical in melanoma. Ferroptosis induction appears to be a potential strategy to enhance the effectiveness of immunotherapy. However, the relationship between the status of ferroptosis and the effectiveness of immunotherapy, as well as viable strategies to augment ferroptosis, remains unclear.

Methods

A screening of 200 cardiovascular drugs obtained from the Food and Drug Administration-approved drug library was conducted to identify the potential ferroptosis sensitizer. In vitro and in vivo experiments explored the effects of propafenone on ferroptosis in melanoma. Animal models and transcriptomic analyses evaluated the therapeutic effects and survival benefits of propafenone combined with immune checkpoint blockades (ICBs). The relationship between propafenone targets and the efficacy of ICBs was validated using the Xiangya melanoma data set and publicly available clinical data sets.

Results

Through large-scale drug screening of cardiovascular drugs, we identified propafenone, an anti-arrhythmia medication, as capable of synergizing with ferroptosis inducers in melanoma. Furthermore, we observed that propafenone, in combination with glutathione peroxidase 4 inhibitor RSL3, collaboratively induces mitochondrial-associated ferroptosis. Mechanistically, propafenone transcriptionally upregulates mitochondrial heme oxygenase 1 through the activation of the Jun N-terminal kinase (JNK)/JUN signaling pathway under RSL3 treatment, leading to overloaded ferrous iron and reactive oxygen species within the mitochondria. In xenograft models, the combination of propafenone and ferroptosis induction led to nearly complete tumor regression and prolonged survival. Consistently, propafenone enhances immunotherapy-induced tumorous ferroptosis and antitumor immunity in tumor-bearing mice. Significantly, patients exhibiting high levels of ferroptosis/JUN/HMOX1 exhibited improved efficacy of immunotherapy and prolonged progression-free survival.

Conclusions

Taken together, our findings suggest that propafenone holds promise as a candidate drug for enhancing the efficacy of immunotherapy and other ferroptosis-targeted therapies in the treatment of melanoma.
Neoadjuvant immunotherapy in the evolving landscape of sarcoma treatment
Authors: Cai Qiyan , Que Yi , Zhang Xing
Published: November 2024

Soft tissue sarcoma is characterized by its rarity and complexity, making it more difficult to conduct large clinical trials compared with other solid tumors. Also known as ‘cold tumors,’ sarcomas, especially advanced sarcomas, have poor responses to immunotherapy. Based on that, the results of two groundbreaking phase 2 clinical trials about neoadjuvant immunotherapy in patients with liposarcoma or undifferentiated pleomorphic sarcoma are encouraging. In this paper, we discuss the results of these clinical trials and the challenges we are facing to conduct neoadjuvant immunotherapy in sarcomas and call for further research to promote the development of it.
Integrated single-cell transcriptome and TCR profiles of hepatocellular carcinoma highlight the convergence on interferon signaling during immunotherapy
Authors: Li Tianhao , Guo Shengnan , Xu Chang , Zhang Mingjie , Lyu Cheng , Xu Huanhuan , Hou Zepeng , Zhang Mingshuo , Li Xiaobo , Ren Jing , Liu Changqing , Kong Dan , Hao Dapeng , Wang Guangyu
Published: November 2024

Background

Despite the success of immune checkpoint inhibitor (ICI)-based combination therapies in hepatocellular carcinoma (HCC), its effectiveness remains confined to a subset of patients. The development of reliable, predictive markers is important for accurate patient stratification and further mechanistic understanding of therapy response.

Methods

We comprehensively analyzed paired single-cell RNA transcriptome and T-cell repertoire profiles from 14 HCC ascites samples, collected from 7 patients before and after treatment with the combination of sintilimab (anti-PD-1) and bevacizumab (anti-VEGF).

Results

We identify a widespread convergence on interferon (IFN) signaling across various immune cell lineages in treatment-responsive patients with HCC, indicating a common transcriptional state transition in the immune microenvironment linked to immunotherapy response in HCC. Strong IFN signaling marks CD8+T cells with larger clonal expansion and enhanced cytotoxicity, macrophages toward M1-like polarization and strong T-cell recruitment ability, dendritic cells with increased antigen presentation capacity, as well as highly cytotoxic natural killer cells and activated B cells. By translating our finding to cohorts of patients with HCC, we demonstrate the specificity of IFN-signaling in the prognosis of patients with HCC and its ability to predict immunotherapy response.

Conclusions

This study provides a unique single-cell resource with clonal and longitudinal resolution during ICI therapy and reveals IFN signaling as a biomarker of immunotherapy response in HCC, suggesting a beneficial effect by combining IFN inducers with ICIs for patients with HCC.
Treatment of iatrogenic vertebral artery injury during C1-C2 arthrodesis with a covered stent
Authors: Bram Richard , Mehta Ankit I , Atwal Gursant
Published: November 2024

Iatrogenic vertebral artery injury (VAI) has been described in the context of both anterior and posterior approaches to the cervical spine.1 2 Endovascular treatment of VAI primarily entails vessel sacrifice or vascular reconstruction. The latter option offers the advantage of achieving hemostasis while maintaining parent vessel patency.3 In this video (video 1) we describe the case of a patient in their 20s undergoing C1-C2 arthrodesis with Harms technique. A V3 segment VAI was successfully treated with two overlapping covered stents which provided hemostasis and parent vessel reconstruction. Follow-up angiography demonstrated robust flow in the parent vertebral artery with no in-stent stenosis. The patient remained at neurological baseline with no ischemic or hemorrhagic complications. To our knowledge, this is the first technical video demonstrating this technique in the setting of iatrogenic VAI.

Video 1

 Endovascular treatment of iatrogenic vertebral artery injury with a covered stent.
Recurrent intrathecal catheter-tip granuloma formation on a replaced system delivering low dose/concentration fentanyl and bupivacaine: a case report
Authors: Feldheim Timothy V , Hayek Salim M
Published: November 2024

Background

Intrathecal drug delivery (IDD) is a well-established treatment modality for refractory chronic pain. Intrathecal catheter-tip granuloma (ICTG) formation is a known possible complication of opiate IDD and is likely triggered by mast cell degranulation. The use of low concentration and dosage of opioids that do not induce mast cell degranulation has been advised to mitigate the risk of ICTG formation.

Case presentation

A patient in their 50s with history of multiple lumbar spine surgeries and refractory low back pain who was treated with IDD developed an initial ICTG while receiving intrathecal hydromorphone and bupivacaine. The patient’s catheter was thus replaced and repositioned. The pump was also replaced due to repeat motor stall, and the infusate was changed from hydromorphone with bupivacaine to low-dose fentanyl with bupivacaine. Five years later, the patient developed myelopathic symptoms, and on imaging a new mass believed to be an ICTG was detected at the new thoracic catheter tip location. The patient was placed on normal saline infusion for 4 months before system explant, with some improvement of symptoms.

Conclusions

ICTG formation is uncommon but can be a devastating complication of IDD if not properly diagnosed in a timely fashion. Repeat ICTG has only been documented twice in the literature, and ICTG with low dose fentanyl in combination with bupivacaine has not been reported. Despite using regimens and techniques to reduce the risk of ICTG formation, one must judiciously surveil their patients for the dreaded ICTG complication.
Inflammatory biomarker analysis confirms reduced disease severity in heterozygous patients with familial Mediterranean fever
Authors: Elhani Inès , Backes Stefan , Kallinich Tilmann , Amaryan Gayane , Belot Alexandre , Berendes Rainer , Berger Thomas , Dressler Frank , Foell Dirk , Fühner Sabrina , Giese Arnd , Hinze Claas , Hitzegrad Anna Lisa , Horneff Gerd , Jansson Annette , Klotsche Jens , Lainka Elke , Niehues Tim , Oommen Prasad , Haas Johannes-Peter , Rietschel Christoph , Theodoropoulo Katerina , Vinit Caroline , Weissbarth-Riedel Elisabeth , Hentgen Véronique , Wittkowski Helmut
Published: November 2024

Introduction

Familial Mediterranean fever (FMF) is a genetic disease leading to recurrent episodes of inflammation. Two pathogenic variants are required for classical disease, but the disease can occur in heterozygous patients. Patients are treated continuously with colchicine to prevent amyloid A (AA) amyloidosis, including heterozygous patients who display a moderate form of FMF and rarely develop AA amyloidosis. The need for lifelong colchicine treatment in heterozygous FMF is therefore controversial. We aimed to characterise genotype-specific levels of inflammatory biomarkers, and to focus on heterozygous patients who discontinued colchicine.

Methods

All patients with FMF from the European databases AIDnet and JIRcohort who received colchicine during follow-up were included. Demographics, C reactive protein (CRP), serum amyloid A (SAA), S100A8/A9 and S100A12 levels, leucocyte and neutrophil counts were extracted. Visits were classified as active, subclinical or inactive according to symptoms, CRP and SAA levels.

Results

Data from 747 patients were extracted (233 homozygous, 201 compound heterozygous, 224 heterozygous patients, 49 heterozygous with one class III variant and 40 compound heterozygous with two class III variants). During active visits, all biomarker levels were higher compared with inactive visits (p<0.001). Heterozygous patients showed lower levels of CRP, SAA, S100A8/A9 and S100A12 during inactive and subclinical visits than patients with two class IV-V variants. Colchicine was discontinued in 52 heterozygous patients and reintroduced in 23 of them (44%).

Conclusion

S100A8/A9 and S100A12 proteins are biomarkers that can be used to assess disease activity. Heterozygous patients have lower levels of inflammatory biomarkers and some of them can sustainably discontinue colchicine treatment.
Stability of symptom-based subtypes in Sjogren’s disease
Authors: Berry Joe Scott , Tarn Jessica , Casement John , Lendrem Dennis , Thompson Kyle , Mariette Xavier , Gottenberg Jacques-Eric , Ng Wan-Fai
Published: November 2024

Objectives

The Newcastle Sjogren’s Stratification Tool (NSST) stratifies Sjogren’s disease patients into four subtypes. Understanding the stability of the subtypes is vital if symptom-based stratification is to be more broadly adopted. In this study, we stratify patients longitudinally to understand how symptom-based subtypes vary over time and factors influencing subtype change.

Methods

274 patients from the United Kingdom Primary Sjögren’s Syndrome Registry (UKPSSR) with data permitting NSST subtype assignment from two study visits were included. The French Assessment of Systemic Signs and Evolution of Sjogren’s Syndrome (ASSESS) cohort (n=237) acted as an independent comparator. Group analyses of significant differences were performed, with logistic regression models used to assess covariates of subtype stability.

Results

UKPSSR and ASSESS cohorts showed a broadly similar proportion of subjects in each subtype and similar baseline clinical characteristics except body mass index (BMI). Several baseline characteristics differ significantly between the subtypes, most notably anti-Ro status and BMI. Subtype membership was reasonably stable in both cohorts with 60% and 57% retaining subtype. The high-symptom burden subtype was the most stable over time with 70% and 67% retaining subtype. Higher baseline probability score was the greatest predictor of subtype stability with higher C4 levels, antidepressant use, and a higher CCI score also predicting increased stability.

Conclusion

NSST subtype membership remains stable over time in a large proportion of patients. When subtype transition is associated with factors at baseline, it is most strongly associated with an uncertain subtype allocation. Our findings support the hypothesis that symptom-based subtypes reflect genuine pathobiological endotypes and therefore maybe important to consider in trial design and clinical management.
Gradient boosting MUST taggers for highly-boosted jets
Authors: Aguilar-Saavedra J. A. , Arganda E. , Joaquim F. R. , Sandá Seoane R. M. , Seabra J. F.
Published: November 2024

The Mass Unspecific Supervised Tagging (MUST) method has proven to be successful in implementing generic jet taggers capable of discriminating various signals over a wide range of jet masses. We implement the MUST concept by using eXtreme Gradient Boosting () classifiers instead of neural networks (NNs) as previously done. We build both fully-generic and specific multi-pronged taggers, to identify 2, 3, and/or 4-pronged signals from SM QCD background. We show that -based taggers are not only easier to optimize and much faster than those based in NNs, but also show quite similar performance, even when testing with signals not used in training. Therefore, they provide a quite efficient alternative machine-learning implementation for generic jet taggers.
Toward Understanding the Effects of Intelligence of a Virtual Character during an Immersive Jigsaw Puzzle Co-Solving Task
Authors: Choi Minsoo , Cui Dixuan , Volonte Matias , Koilias Alexandros , Kao Dominic , Mousas Christos
Published: November 2024

In virtual reality, creating intelligent virtual characters has been a long-lasting endeavor. However, while researchers have investigated several aspects of a virtual character’s intelligence, little attention has been paid to the impact of the implemented intelligence levels assigned to a virtual character during human–virtual character collaboration. Thus, we conducted a within-group study (

\(N=24\)

) to explore how three different intelligence levels (low vs. medium vs. high) assigned to a virtual character can impact how study participants perceive that virtual character and interact with the task they are instructed to complete. Specifically, for our study, we developed a jigsaw puzzle game and instructed our participants to solve it with the help of a virtual character. During the jigsaw puzzle solving process, we collected application logs related to how the participants executed the task and observed the virtual environment. Moreover, after each condition, we asked the participants to respond using a questionnaire that examined their social presence, how they perceived the character’s intelligence and compared it with their own, and how they rated the virtual character’s realism. Our results indicated that the different intelligence levels assigned to the virtual characters impacted participants’ responses on several variables, including co-presence, perceived intelligence, intelligence comparison, and character interaction and behavior realism. Moreover, based on the collected logged data, we found that the intelligence levels assigned to our virtual character significantly impacted the performance of our participants. Our results could be valuable to the research community for creating more engaging experiences with intelligent virtual characters for collaborative tasks in immersive environments.