bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency Domain Adjoint-Based Iterative Learning Control for MIMO Systems
Authors: Lee Yu-Hsiu , Chou Wei-Yi
Published: December 2024

The adjoint of the system is a linear operator that can be interpreted as the transposition of the unit pulse response matrix with a Toeplitz structure. In the context of iterative learning control, the system adjoint can be used as the learning filter by performing dedicated experiments on the system, resulting in monotonically convergent algorithms. However, the required number of experiments equals the product of input and output channels, and the convergence speed is limited by the system peak gain. This work aims to reduce the number of dedicated experiments for multivariate systems and improve the convergence speed of the adjoint-based iterative learning control. The proposed algorithm constructs the system adjoint in frequency domain and therefore the required number of experiments equals the number of input channels. Exploiting the independence of frequency response of linear-time-invariant systems, the learning gain can be frequency-dependent, which further accelerates the convergence speed. Algorithm convergence under frequency domain uncertainties are ensured with learning scalar or diagonal gain design. It is shown that for a single-input-single-output system, the proposed approach becomes the inversion-based algorithms. Convergence condition is also developed for multivariable systems through complex analysis. The developed approach is validated through experiments on a multi-axis galvanometer.
Detailed Analysis of Friction in Water-Lubricated Bearings Under Boundary Lubrication: Model Development and Experimental Validation
Authors: Yang Chaozhen , Liu Xueshen , Huang Zhangkai , Wang Ting , Chen Meixia
Published: December 2024

A novel friction model for water-lubricated bearings under boundary lubrication conditions is proposed. The effects of speed, load, surface roughness, and material properties on the friction coefficient are examined. The model is validated through experimental tests using nitrile-butadiene rubber (NBR) and ultrahigh molecular weight polyethylene (UHMWPE) materials, demonstrating reliability and applicability. The impact of varying speed and load on lubrication regimes is analyzed, with a focus on the behavior of micro-convex contact friction under boundary lubrication conditions. Based on the verified friction model, the influence of surface roughness and texture direction on bearing performance is also explored, offering actionable insights for optimizing bearing design. This model provides critical insights for enhancing friction management and noise reduction in water-lubricated bearings, offering valuable guidance for their design and manufacturing.
The
Chlamydia pneumoniae
inclusion membrane protein Cpn0308 interacts with host protein ACBD3
Authors: Ma Liang , Jia Xiao-hui , Gao Zhe , Zhou Yan , Cheng Yong-ting , Li Ping , Jia Tian-jun
Published: December 2024

Chlamydia pneumoniae
is an obligate intracellular bacterium of eukaryotic cells characterized by a unique biphasic life cycle; its biosynthesis and replication must occur within a cytoplasmic vacuole or inclusion. Certain inclusion membrane proteins have been demonstrated to mediate the interactions between intra-inclusion chlamydial organisms and the host cell. It has been demonstrated previously that the
C. pneumoniae
-encoded Cpn0308 localizes to the inclusion membrane; however, its function remains unknown. In the current study, a yeast two-hybrid assay was conducted to screen Cpn0308 as a bait against a HeLa cell cDNA library, revealing its binding to the host protein acyl-coenzyme A binding domain-containing 3 (ACBD3). The interaction between Cpn0308 and ACBD3 was confirmed through co-immunoprecipitation and GST (Glutathione S-transferase) pull-down assays. The two proteins were also co-localized in HeLa cells co-expressing Cpn0308 and ACBD3, as well as in
C. pneumoniae
-infected cells, as observed under confocal fluorescence microscopy. Given that ACBD3 plays a crucial role in maintaining host cell lipid homeostasis and its Golgi dynamic domain is responsible for interacting with Cpn0308, we hypothesize that the Cpn0308-ACBD3 interaction may facilitate
C. pneumoniae
’s acquisition of host lipids, thereby benefiting chlamydial survival. This study lays a foundation for further elucidating the mechanisms of Cpn0308-mediated
C. pneumoniae
pathogenesis.

IMPORTANCE

The biosynthesis and replication of
Chlamydia pneumoniae
(
Cpn
) must occur within the cytoplasmic vacuoles or inclusions of host cells. Inclusion bodies play a crucial role in mediating the interactions between
Cpn
and host cells. Cpn0308 is localized to the inclusion membrane; however, its function is unknown. In this study, Cpn0308 was found to bind to host protein acyl-coenzyme A binding domain-containing 3 (ACBD3) through some standard approaches. Co-localization of the two proteins was observed in both original HeLa cells and Cpn-infected HeLa cells. ACBD3 plays a significant role in maintaining lipid homeostasis in host cells; we speculate that the Cpn0308-ACBD3 interaction may facilitate the acquisition of host lipids by
C. pneumoniae
, thereby enhancing chlamydial survival.
Cervical fibroid presenting with heavy menstrual bleeding and symptomatic microcytic hypochromic anaemia
Authors: Dunphy Louise , Fowler Grace , Sukumar Vaiyapuri
Published: December 2024

Leiomyomas or fibroids occur in 20%–40% of women of reproductive age and are mostly located in the uterine corpus, with only 1%–2% in the cervix. Fibroids may present with abnormal uterine bleeding, pelvic pain, dysmenorrhoea and pressure-related or urinary symptoms, and diagnosis requires imaging studies. Hysterectomy or myomectomy remains the cornerstone of management but is challenging due to the increased risk of urinary tract injuries and intraoperative bleeding caused by distorted anatomy. We present the case of a perimenopausal woman in her early 50s who complained of heavy menstrual bleeding, was diagnosed with a cervical fibroid and, while on the waiting list for a hysterectomy, suffered a collapse and presented to the emergency department with anaemia requiring multiple blood transfusions. A cervical fibroid should be considered in the differential diagnosis of a woman presenting with heavy menstrual bleeding and symptomatic anaemia.
Questioning the rules of engagement: a critical analysis of the use of limb symmetry index for safe return to sport after anterior cruciate ligament reconstruction
Authors: Simonsson Rebecca , Sundberg Axel , Piussi Ramana , Högberg Johan , Senorski Carl , Thomeé Roland , Samuelsson Kristian , Della Villa Francesco , Hamrin Senorski Eric
Published: December 2024

Objective

To evaluate the association between limb symmetry index (LSI) in quadriceps and hamstrings strength together with hop tests, as a proxy of recovery, and the deviation from being symmetrical (LSI 100%), with a safe return to sport (RTS) after anterior cruciate ligament reconstruction (ACL-R).

Methods

Athletes between 15 and 30 years old with a preinjury Tegner activity level ≥6 were eligible for inclusion. Data were extracted from a rehabilitation-specific registry, Project ACL (Gothenburg, Sweden) at the time of or after RTS for each athlete. The outcome of interest in this study was a safe RTS—not suffering a second ACL injury within 2 years from RTS—addressed by using the LSI in five different ways with results from the test battery which include five tests of muscle function at or after the time of RTS. Logistic regression analyses were performed with safe RTS as a dependent variable and presented with ORs and 95% CIs.

Results

In total, 233 athletes (51.1% women) were included. The best-differentiating cut-offs for strength and hop tests showed non-significantly poor discriminatory ability between athletes who had a safe RTS and those who did not (Youden J 0.09–0.24 and area under the curve 0.50–0.59). Athletes who had ≥80% or ≥85% LSI had significantly lower odds of safe RTS compared with athletes who did not meet the cut-offs of safe RTS (OR=0.32 (95% CI 0.12 to 0.87) and OR=0.39 (95% CI 0.18 to 0.84), respectively). There was no effect of a 1% increase in LSI or deviation from 100% symmetry on safe RTS.

Conclusion

The use of LSI from tests of muscle function to determine safe RTS after ACL-R, that is, RTS without sustaining a second ACL injury within 2 years, cannot differentiate between athletes who had a safe RTS and those who did not, regardless of whether LSI was used as cut-offs, incremental or as deviation from symmetry. Thus, it is of clinical importance that clinicians do not solely rely on the LSI to clear athletes for RTS.
Six months of hybrid closed-loop therapy improves diabetes-specific positive well-being, and reduces diabetes distress and fear of hypoglycemia: secondary analysis of a randomized controlled trial
Authors: Halliday Jennifer A , Russell-Green Sienna , Lam Benjamin , Trawley Steven , McAuley Sybil A , Bach Leon A , Burt Morton G , Cohen Neale D , Colman Peter G , Davis Elizabeth A , Holmes-Walker Deborah Jane , Jenkins Alicia J , Kaye Joey , Keech Anthony C , Lee Melissa H , McCallum Roland W , Paldus Barbora , Stranks Stephen N , Sundararajan Vijaya , Ward Glenn , Jones Timothy W , O’Neal David , Speight Jane , Hendrieckx Christel
Published: December 2024

Introduction

This analysis aimed to investigate diabetes-specific psychological outcomes among adults with type 1 diabetes (T1D) using hybrid closed-loop (HCL) versus standard therapy.

Research design and methods

In this multicenter, open-label, randomized, controlled, parallel-group clinical trial, adults with T1D were allocated to 26 weeks of HCL (MiniMed™ 670G) or standard therapy (insulin pump or multiple daily injections without real-time continuous glucose monitoring). Psychological outcomes (awareness and fear of hypoglycemia; and diabetes-specific positive well-being, diabetes distress, diabetes treatment satisfaction, and diabetes-specific quality of life (QoL)) were measured at enrollment, mid-trial and end-trial. Linear mixed models were conducted, using restricted maximum likelihood estimation, unadjusted and adjusted (for covariates: age, sex, diabetes duration, glycated hemoglobin, recent severe hypoglycemia, pre-trial insulin delivery modality, enrollment and mid-study scores).

Results

120 participants (mean age 44±12 years) were randomized to intervention (n=61) or standard therapy (n=59). At 13 weeks, the HCL group had better diabetes-specific positive well-being than the standard therapy group (unadjusted: Δ=1.0, p=0.025; adjusted: Δ=1.1, p=0.01), which was maintained at 26 weeks (unadjusted: Δ=0.9, p=0.042; adjusted: Δ=1.0, p=0.023). At 26 weeks, the HCL group also had less diabetes distress (adjusted: Δ=−6.4, p=0.039), fear of hypoglycemia (“maintain high”: adjusted: Δ=−0.8, p=0.034; and “worry”: adjusted: Δ=−1.8, p=0.048), and perceived “unacceptably high glucose levels” (unadjusted: Δ=−1.1, p<0.001; adjusted: Δ=−1.1, p<0.001). HCL did not improve diabetes treatment satisfaction, diabetes-specific QoL, hypoglycemia awareness, or perceived frequency of unacceptably low glucose levels.

Conclusions

These findings imply that HCL offers important psychological benefits. In particular, improvement in diabetes-specific positive well-being was observed 13 weeks after HCL initiation and maintained at 26 weeks. Reduction in the perceived frequency of hyperglycemia was also apparent by 26 weeks. Adjusted analyses showed significant reductions in diabetes distress and fear of hypoglycemia at 26 weeks, suggesting these benefits were apparent for people with particular characteristics.

Trial registration number

Australian New Zealand Clinical Trials Registry: ACTRN12617000520336.
Mixed-methods process evaluation of a proactive approach to healthcare in Parkinson’s disease—ParkProReakt: a protocol of a hybrid efficacy-implementation study
Authors: Altschuck Natalie , van Munster Marlena , Stümpel Johanne , Pedrosa David Jose , Wellach Ingmar , Boebinger Hannes , Geraedts Max
Published: December 2024

Introduction

People with Parkinson’s disease (PwPD) experience a wide range of motor and non-motor symptoms that have a significant impact on their health and quality of life. Effective care management for PwPD involves monitoring symptoms at home, involving specialised multidisciplinary care providers and enhancing self-management skills. This study protocol describes the process evaluation within a randomised clinical trial to assess the implementation and its impact on patient health outcomes of ParkProReakt—a proactive, multidisciplinary, digitally supported care model for community-dwelling PwPD.

Methods and analysis

The hybrid efficacy-implementation study will assess key implementation outcomes using the Medical Research Council framework for complex interventions alongside a randomised controlled trial. A combination of quantitative and qualitative methods will be used to assess process data from care providers and patients. The main process outcomes are fidelity, dose, feasibility and context. Context will be analysed through semistructured interviews and focus groups using the Consolidated Framework of Implementation Research. To elucidate potential facilitators and barriers to implementation and to gain deeper insights into the efficacy outcome data, quantitative and qualitative process data will be integrated at an interpretative level using mixed methods. In addition to process evaluation, potential indirect mechanisms of impact will be measured.

Ethics and dissemination

Ethical approval for this study was obtained from the responsible state medical ethics committees in Hesse and Hamburg, Germany. Results will be communicated to the funding body and disseminated through scientific publications.

Trial registration

This study was registered with the German Registry for Clinical Studies (DRKS)—number: DRKS00031092.
Systematic review of the impact of the National Medication Price Negotiated Policy on the accessibility of drugs in China, 2016–2024
Authors: Peng Nan , Du Chenyu , Gong Yiran , Long Xiang , Wang Caiyi , Liu Pengcheng
Published: December 2024

Objective

To alleviate the economic burden of innovative drugs on patients in China, the government has been negotiating drug prices since 2016 to enhance their accessibility. This systematic review aimed to discuss the impact of the National Medication Price Negotiation Policy (NMPNP) on the accessibility of drugs in China in the years 2016–2024.

Design

Systematically reviewed the studies’ findings and evaluated their quality using the Newcastle-Ottawa Scale (NOS) collaborative tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 were used to facilitate transparent and complete reporting of our systematic review.

Data sources

PubMed, Web of Science, CNKI and Wanfang were searched from 1 January 2016 to 1 October 2024.

Eligibility criteria for selecting studies

The inclusion criteria of this study is a quantitative study to evaluate the accessibility of negotiated drugs after the implementation of the NMPNP.

Data extraction and synthesis

Two researchers independently searched the literature, extracted the data and cross-checked them. Any disagreements were resolved by discussion or consultation with a third party. The quality of systematic reviews was assessed using the NOS.

Results

A total of 32 studies were included in this review, 8 of the studies were assessed to be high quality based on the NOS, 17 as moderate quality and the remaining 7 as low quality. Most of them showed that after the implementation of the NMPNP, the availability, affordability, defined daily doses, hospital purchase volume and expenditure of negotiated drugs increased, and the price and defined daily dose cost of negotiated drugs decreased. However, a few studies found that some drugs are difficult to be admitted to hospitals and consumption dropped after the implementation of the NMPNP due to low clinical demand and weak competitiveness.

Conclusions

The implementation of NMPNP improved drug accessibility for patients and most regions had good implementation effects which can provide some insights for other countries. However, the high utilisation of successfully negotiated drugs has increased health insurance expenditures, potentially affecting the fund’s stability. This necessitates government regulation of both the use of these drugs and health insurance funds. Moreover, different regions and medical institutions had different development levels and resource allocations, resulting in uneven effects of the NMPNP which need to be improved in the future.
StUdy of Gestational diabetes And Risk using Electronic Data (SUGARED): a population-based cohort study—study protocol
Authors: Randall Deborah , Ibiebele Ibinabo , Nippita Tanya , Torvaldsen Siranda , Morris Jonathan M , Gallimore Felicity , Weir Tessa L , Glastras Sarah
Published: December 2024

Introduction

The incidence of gestational diabetes mellitus (GDM) in Australia has tripled in the last 20 years. Consequently, over 40 000 pregnancies are now diagnosed as ‘higher risk’ each year. This has increased antenatal surveillance and obstetric intervention, often in the form of delivery earlier than 39 weeks gestation. The StUdy of Gestational diabetes And Risk using Electronic Data (SUGARED) project aims to use large population-based and routinely collected linked health data to (1) personalise risk prediction of adverse pregnancy outcomes for women undergoing glucose tolerance testing, (2) guide optimal birth timing for women with diet-controlled GDM and (3) examine variation in GDM management and pregnancy outcomes in New South Wales (NSW), Australia.

Methods and analysis

This retrospective cohort study using linked, routinely collected health data includes all women who gave birth from January 2016 to December 2020 in NSW. The cohort will include approximately 475 000 pregnancies, with >70 000 diagnosed with GDM. The study will link birth data to hospital data and birth/death registry data. In addition, clinical pathology results and detailed clinical information from a subset of public hospital pregnancies in 13 of 15 area health services will be linked. To address the three main aims, we will use statistical methods including logistic regression and K-fold cross-validation for risk prediction, a propensity-score matching ‘target trial’ method to examine birth timing, and multilevel modelling to examine hospital variation.

Ethics and dissemination

Ethics approval for the study has been granted by the NSW Population and Health Services Research Ethics Committee. We will communicate evidence generated from SUGARED to the local health districts and their clinicians, as well as potentially optimising dissemination using existing digital infrastructure.
Specialist clinical pathways in audiology services for adults living with coexisting hearing loss and dementia: a scoping review protocol
Authors: Wenje Sophie Mai , Calvert Sian , Henshaw Helen , Spriggs Ruth V , Dening Tom , Hendron Elizabeth , Heffernan Eithne
Published: December 2024

Introduction

Both hearing loss and dementia are associated with ageing, and it is thought that many individuals living with dementia also live with hearing loss. Despite the large comorbidity between these two disorders, there remains a clear lack of established guidelines in audiological services for assessing and managing patients living with dementia. This scoping review aims to examine whether specialist clinical pathways exist in audiology services for people living with coexisting hearing loss and dementia and to describe the specific components and features of these pathways. This review will provide up-to-date information on clinical practice, identifying any gaps in care and in the literature to inform future research hypotheses and best practice guidelines.

Methods and analysis

The methods are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. The following electronic databases will be searched: CINAHL, EMBASE, MEDLINE, PsycINFO, PubMed, Scopus and Web of Science. The eligibility criteria are defined according to the domains of the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation and Research type) search strategy tool. Primary research studies and select grey literature sources (eg, practice guidelines) will be eligible if published within the last 15 years. Studies eligible for inclusion must contain adults living with suspected or confirmed dementia, their carers, or clinicians within audiology services. Initial searches were performed on 31 January 2024 and will be updated before completion and submission of the review. Article quality will be appraised using an established tool: the Mixed Methods Appraisal Tool. The results will be synthesised and reported in line with reflexive thematic analysis guidelines.

Ethics and dissemination

No ethical issues are foreseen as the review will collect secondary data only. Findings will be reported by peer-reviewed publication and by national and international academic conferences.
Association between immunosuppressive medications and COVID-19 hospitalisation and death: a retrospective cohort study
Authors: Sechrist Samantha J , Tang Emily , Arnold Benjamin F , Acharya Nisha R
Published: December 2024

Importance

Immunocompromised status is a risk factor for severe SARS-CoV-2 infection. Little is known about how systemic corticosteroid dose and concurrent use of immunosuppressants are associated with COVID-19 outcomes.

Objective

To assess the association between corticosteroid dose/duration and concurrent immunosuppressant use on COVID-19 hospitalisation and death in the era of COVID-19 vaccinations.

Design

This is a retrospective cohort study using a deidentified insurance claims database from 1 July 2020 to 30 June 30, 2022, with the risk period starting on 1 July 2021. Impact of corticosteroid exposures and concurrent use of other immunosuppressants was assessed with attributable risk analysis and Cox regression that included COVID-19 vaccination status and time-updated dichotomous immunosuppressive medication exposures.

Participants

There were 10 109 596 eligible patients enrolled during the risk period, each with at least 365 days of continuous enrolment prior to 1 July 2021.

Exposures

Systemic corticosteroids, disease-modifying antirheumatic drugs (DMARDs), tumour necrosis factor-alpha inhibitors (TNFis) and other immunosuppressive drug categories.

Main outcomes

Incidence rate ratios and hazard ratios for COVID-19 hospitalisation and death.

Results

Corticosteroids were prescribed to 1 379 049 (13.6%) of 10 109 596 individuals. After adjustment, corticosteroids were associated with an increased risk of COVID-19 hospitalisation (HR: 5.40; 95% CI 5.27 to 5.53; p<0.0001) and death (HR: 5.90; 95% CI 5.59 to 6.22; p<0.0001). Among individuals exposed to corticosteroids without a record of COVID-19 vaccination, risks for COVID-19 hospitalisation and death were increased by 3- and 14.5-fold. The population attributable risk of corticosteroid use for COVID-19 hospitalisations was 13.9% (95% CI 13.5 to 14.3%). There was a significantly increased risk of COVID-19 hospitalisation associated with the use of corticosteroids plus DMARDs (HR: 1.55; 95% CI 1.42 to 1.70; p<0.0001) or plus TNFis (HR: 1.60; 95% CI 1.15 to 2.22; p=0.005).

Conclusions

Corticosteroids are associated with greater risk of COVID-19 hospitalisation and death, especially among unvaccinated individuals. Concurrent use of DMARDs and TNFis with corticosteroids confers greater risk.
Exploring the factors associated with prelacteal feeds in Papua New Guinea: a population-based survey
Authors: Maviso McKenzie , Namosha Elias , Guldan Georgia S.
Published: December 2024

Background

Prelacteal feeding disrupts early breastfeeding initiation and exclusive breastfeeding, and increases the risk of childhood illnesses and under-five mortality. Despite its negative health outcomes, newborns are given prelacteal feeds in Papua New Guinea (PNG). This study investigated the factors associated with prelacteal feeding practices among women in PNG.

Design

A population-based cross-sectional study based on Demographic and Health Survey (DHS) data. Multivariable logistic regression using complex sample analysis was performed to control for the effects of potential confounders. Variables with p ≤ 0.05 were considered statistically significant.

Setting

Papua New Guinea.

Participants

A total weighted sample of 4399 women was included in the study.

Outcome measure

Prelacteal feeds.

Results

About 10% of women provided prelacteal feeds to their infants. The most frequently reported prelacteal feed was plain water (71.7%), followed by grain-based (eg, noodles) (47.1%), dark green leafy vegetables (42.1%) and soup (39.7%). Women with no formal (Adjusted Odds Ratio (AOR) 1.4, 95% CI: 1.0–3.0) or primary (AOR 1.5, 95% CI: 1.0–2.9) education, who had a caesarean section (AOR 4.1, 95% CI: 2.4–7.2), had given birth at home or in the village (AOR 3.7, 95% CI: 2.1–6.8) and from the Islands region (AOR 2.3, 95% CI: 1.5–3.5) had higher odds of providing prelacteal feeds.

Conclusion

Our study revealed that providing prelacteal feeds is common in PNG. Tailored health education and behaviour change communication are necessary to address this harmful infant feeding practice. Furthermore, the promotion of facility-based births and early breastfeeding practices should be prioritised using existing strategies, especially for disadvantaged and rural women.
Longitudinal cholesterol trends across socioeconomic groups in Norway: the influence of lipid-lowering drugs in the population-based Tromsø Study 1994–2016
Authors: Vo Chi Quynh , Wilsgaard Tom , Samuelsen Per-Jostein , Mathiesen Ellisiv B , Sommerseth Hilde L , Eggen Anne Elise , Wisløff Torbjørn
Published: December 2024

Objectives

There is limited evidence regarding the impact of lipid-lowering drugs (LLDs) on the socioeconomic gradient in a longitudinal perspective. The study investigates the longitudinal socioeconomic gradient in total cholesterol levels and whether this is affected by the use of LLDs.

Design

Population-based cohort study.

Setting

Sample from adult inhabitants of Tromsø municipality, Norway, who participated in the Tromsø Study (1994–2016).

Participants

17 550 participants of the population-based Tromsø Study in 1994–1995 who were non-users of LLD, aged 25–78 years at baseline and who attended one or more of three subsequent surveys in 2001, 2007–2008 and 2015–2016 were included in the study.

Outcome measure

Socioeconomic gradient in total cholesterol levels was compared among participants treated and not treated with LLDs during the observation period.

Results

The total cholesterol levels across all educational groups increased from 1994–1995 to 2015–2016 among untreated women (+0.33 mmol/L to +0.48 mmol/L), except for those with primary education (−0.12 mmol/L). Total cholesterol levels decreased among untreated men (−0.40 mmol/L to −0.06 mmol/L, from lowest education to highest education), treated women (−1.88 mmol/L to −1.35 mmol/L) and men (−2.21 mmol/L to −1.84 mmol/L) across all educational groups. At baseline, we observed a significant inverse association between education and total cholesterol levels among non-users of LLDs. There was no clear educational gradient in total cholesterol levels among users of LLDs.

Conclusions

Users of LLDs experienced a more substantial decrease in total cholesterol levels over time compared with non-users. The educational gradient in total cholesterol levels observed among non-users of LLD was not apparent among users.
Paediatric Personalized Research Network Switzerland (SwissPedHealth): a joint paediatric national data stream
Authors: Mozun Rebeca , Belle Fabiën N , Agostini Andrea , Baumgartner Matthias R , Fellay Jacques , Forrest Christopher B , Froese D Sean , Giannoni Eric , Goetze Sandra , Hofmann Kathrin , Latzin Philipp , Lauener Roger , Martin Necker Aurélie , Ormond Kelly , Pachlopnik Schmid Jana , Pedrioli Patrick G A , Posfay-Barbe Klara M , Rauch Anita , M Schulzke Sven , Stocker Martin , Spycher Ben D , Vayena Effy , Welzel Tatjana , Zamboni Nicola , Vogt Julia E , Schlapbach Luregn J , Bielicki Julia A , Kuehni Claudia E
Published: December 2024

Introduction

Children represent a large and vulnerable patient group. However, the evidence base for most paediatric diagnostic and therapeutic procedures remains limited or is often inferred from adults. There is an urgency to improve paediatric healthcare provision based on real-world evidence generation. Digital transformation is a unique opportunity to shape a data-driven, agile, learning healthcare system and deliver more efficient and personalised care to children and their families. The goal of Paediatric Personalized Research Network Switzerland (SwissPedHealth) is to build a sustainable and scalable infrastructure to make routine clinical data from paediatric hospitals in Switzerland interoperable, standardised, quality-controlled, and ready for observational research, quality assurance, trials and health-policy creation. This study describes the design, aims and current achievements of SwissPedHealth.

Methods and analysis

SwissPedHealth was started in September 2022 as one of four national data streams co-funded by the Swiss Personalized Health Network (SPHN) and the Personalized Health and Related Technologies (PHRT). SwissPedHealth develops modular governance and regulatory strategies and harnesses SPHN automatisation procedures in collaboration with clinical data warehouses, the Data Coordination Center, Biomedical Information Technology Network, and other SPHN institutions and funded projects. The SwissPedHealth consortium is led by a multisite, multidisciplinary Steering Committee, incorporating patient and family representatives. The data stream contains work packages focusing on (1) governance and implementation of standardised data collection, (2) nested projects to test the feasibility of the data stream, (3) a lighthouse project that enriches the data stream by integrating multi-omics data, aiming to improve diagnoses of rare diseases and 4) engagement with families through patient and public involvement activities and bioethics interviews.

Ethics and dissemination

The health database regulation of SwissPedHealth was approved by the ethics committee (AO_2022-00018). Research findings will be disseminated through national and international conferences and publications in peer-reviewed journals, and in lay language via online media and podcasts.
Pragmatic non-inferiority Randomised trial Investigating Needle aspiration versus ChEst drain for Secondary Spontaneous Pneumothorax (the PRINCE-SSP study): study protocol for a randomised non-inferiority trial
Authors: Walker Steven , Taylor Ellie , McAndrew Amy , Carlton Edward , Chaudhuri Ella , Ghorpade Pooja , Goodwin Charlotte , Connors James , Cook Heather , Luengo-Fernandez Ramon , Creanor Siobhan , Maskell Nick A
Published: December 2024

Introduction

Secondary spontaneous pneumothorax (SSP) is a medical emergency where the lung collapses in the presence of underlying chronic lung disease. Current international clinical guidelines advise intercostal drain (ICD) insertion for SSP. However, in a previous small study needle aspiration (NA) has been shown to reduce length of hospital stay (LOHS) and reduce complications. We are evaluating the clinical and cost-effectiveness of an initial NA approach to the management of patients with SSP in the United Kingdom.

Methods and analysis

The PRINCE-SSP (Pragmatic non-inferiority Randomised trial Investigating Needle aspiration vs ChEst drain for Secondary Spontaneous Pneumothorax) trial is a pragmatic, multicentre, open-label, parallel, two-group, randomised, non-inferiority trial to establish whether NA for SSP is non-inferior in terms of LOHS compared with ICD. We aim to recruit 110 patients from at least 15 UK NHS hospitals, over 18 months. Participants allocated to the intervention (NA) group will have an NA inserted at the presentation. Those allocated to the comparator (usual care) group will have an ICD inserted. Participants are followed up for 30 days. The primary outcome measure is initial LOHS, up to day 30 postrandomisation. Secondary outcomes include (but are not limited to) total LOHS including readmissions, complications, cost-effectiveness and patient-reported quality of life.

Ethics and dissemination

This trial received Health Research Authority (HRA) approval from Wales Research Ethics Committee seven ethics committee (23/WA/0085). Results will be submitted for publication in a peer-reviewed journal. A plain English summary of the trial results will be prepared and disseminated with the help of our patient advisory group, including via social media, and provided to trial participants via post or email according to their preference.

Trial registration number

ISRCTN12644940.
Pelvis Or Involved Node Treatment: Eradicating Recurrence in Prostate Cancer (POINTER-PC) – study protocol paper for a phase III multicentre, open-label randomised controlled trial
Authors: Slevin Finbar , Alexander Sophie , Brown Sarah R , Carter Matthew , Choudhury Ananya , Clipson Alexandra , Din Omar , Dive Caroline , Gilbert Alexandra , Girvan Sean , Hingorani Mohan , Jain Suneil , Khoo Vincent , Lilley John , Murray Louise J , Naismith Olivia , Noutch Samantha , Oliveira Pedro , Pagett Christopher J H , Smith Alexandra , Talbot James , Webster Joanne , Henry Ann M
Published: December 2024

Introduction

Prostate cancer (PCa) is the most common cancer in men. Recurrence may occur in up to half of patients initially treated with curative intent for high-risk localised/locally advanced PCa. Pelvic nodal recurrence is common in this setting, but no clear standard of care exists for these patients, with potential therapeutic approaches including stereotactic body radiotherapy (SBRT) to the involved node(s) alone, extended nodal irradiation (ENI) to treat sites of potential micrometastatic spread in addition to involved node(s) and androgen deprivation therapy with or without additional systemic anticancer therapies. Based on observational studies, ENI is associated with promising metastasis-free survival (MFS) compared with SBRT and appears to result in low rates of severe late toxicity.

Methods and analysis

Pelvis Or Involved Node Treatment: Eradicating Recurrence in Prostate Cancer is a UK multicentre, open-label, phase III randomised controlled trial, which will deliver much needed, high-quality evidence of the impact on metastatic progression from ENI compared with SBRT in patients with PCa pelvic nodal recurrence. The trial will also evaluate the long-term toxicity of 5-fraction ENI compared with a standard 20-fraction schedule. The trail will randomise 480 participants in a ratio of 2:1:1 to SBRT, 5-fraction ENI or 20-fraction ENI from 35 to 40 UK radiotherapy sites over 4 years. Coprimary endpoints are MFS at 3 years and participant-reported late bowel toxicity at 3 years. Secondary endpoints include overall survival, biochemical progression-free survival, failure-free survival, patterns of failure, participant-reported/clinician-reported toxicity and health-related quality of life. Collection of blood and tissue samples will enable future evaluation of biomarkers of disease and toxicity and support stratification of salvage therapeutic approaches.

Ethics and dissemination

Ethical approval was obtained from NHS Health Research Authority, East of England – Cambridgeshire and Hertfordshire Research Ethics Committee (24/EE/0099). Trial results will be published in peer-reviewed journals and adhere to International Committee of Medical Journal Editors guidelines.

Trial registration number

ISRCTN11089334, registered on 23 September 2024.
Endoplasmic reticulum protein TXNDC5 modulates thyroid eye disease TGF-β1-induced myofibroblast transdifferentiation
Authors: Chiu Hsun-I , WU Shi-Bei , Wu Albert Y , Tsai Chieh-Chih
Published: December 2024

Aim

There remain limited therapies to treat thyroid eye disease (TED) orbital fibrosis, highlighting the urgency to develop novel targets. Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts are important pathogenetic factor of TED. Endoplasmic reticulum (ER) stress may play a role in TED pathogenesis since it has been linked to liver, kidney, heart and lung fibrotic remodelling. We would evaluate the role of thioredoxin domain containing 5 (TXNDC5), a fibroblast-enriched ER protein, in TGF-β1-induced myofibroblast transdifferentiation from TED orbital fibroblasts.

Methods

Orbital fibroblasts from patients with TED were treated with TGF-β1 to investigate ER stress-relative gene expression especially for TXNDC5. To determine if TXNDC5 is involved in TGF-β1-induced fibrosis, we transfected TED orbital fibroblasts by lentivirus with a small hairpin RNA of pLKO-TXNDC5 gene (shTXNDC5) to knockdown TXNDC5 protein expression levels. After transfection of shTXNDC5 in TED orbital fibroblast followed by TGF-β1 treatment, we analysed TGF-β1-induced fibrosis protein expression.

Results

We measured increased TXNDC5 gene and protein expression in primary TED orbital fibroblasts. TXNDC5 protein levels were increased in TED orbital fibroblasts under TGF-β1 stimulation (2.5, 5, 10 and 20 ng/mL). Moreover, TXNDC5 knockdown of attenuated TGFβ1 (5 ng/mL)-induced myofibroblast transdifferentiation and extracellular matrix protein upregulation whereas increasing TXNDC5 expression by a recombinant protein of TXNDC5 (rhTXNDC5) addition increased alpha smooth muscle actin, fibronectin and connective tissue growth factor protein expression.

Conclusion

In conclusion, targeting TXNDC5 may be a novel therapeutic approach against TGF-β1-induced myofibroblast transdifferentiation in TED orbital fibroblasts.
Empowering professionals: a multidisciplinary approach to supporting people seeking asylum and refugees
Authors: Harris Philippa , Twose Olivia , Ni Chaoilte Aileen , Cinardo Paola , Bradbeer Lucy , Longley Nicky , Eisen Sarah , Ward Allison
Published: December 2024

People seeking asylum and refugees living in initial accommodation in the UK can experience significant barriers to accessing care. They often have complex health and social needs and may experience fragmentation in the delivery of services. The Respond Integrated Refugee Health Service, hosted by University College London Hospital and operating across North Central London, has been created to address some of these challenges. In addition to offering in-person holistic health and well-being assessments, infection screening and onward care planning, Respond has developed an online multidisciplinary team (MDT) forum to support professionals working with the most complex of cases. Key professional groups from across the network are invited to contribute to multidisciplinary care planning, providing an efficient and streamlined multiagency model of care, improved access to interdisciplinary pathways and opportunities for interprofessional learning. Here, we describe the creation of the Respond Complex Refugee Health Advice and Guidance MDT and discuss the perceived benefits and limitations of the MDT approach in improving the care of people seeking asylum and refugees.
Incidence and outcomes of in-hospital resuscitation for cardiac arrest among paediatric patients in Jordan: a retrospective observational study
Authors: Alrawashdeh Ahmad , Alkhatib Zaid I
Published: December 2024

Objective

To investigate the incidence and survival rates of paediatric patients receiving resuscitation for in-hospital cardiac arrest (IHCA) in a teaching hospital in Northern Jordan, comparing initial pulseless rhythms and bradycardia rhythm with poor perfusion.

Design

Retrospective observational study

Setting

An university-affiliated tertiary hospital in Northern Jordan, covering January 2015 to December 2022.

Patients

All hospitalised paediatric patients aged 1 month–18 years who received cardiopulmonary resuscitation (CPR) for cardiac arrest were included in the study. Resuscitation attempts were categorised into initial pulseless rhythm events and bradycardia with poor perfusion events.

Main outcome measures

Incidence rate of paediatric CPR and the survival to hospital discharge rate.

Results

A total of 504 paediatric patients received CPR during the study period, with an incidence rate of 6.26 per 1000 paediatric admissions. The annual incidence rate was significantly reduced by an average of 5.5% for the total sample but increased by 25.0% for bradycardia events (n=110, 21.8%). The percentage of patients who sustained return of spontaneous circulation (ROSC) was 25.0%. Survival to hospital discharge was low at 4.8% while showing an increasing trend by an average of 24.0% per year. Bradycardia events had a significantly higher ROSC rate (34.6% vs 22.3%); but an insignificant higher survival rate (6.4 vs 4.3). Patients with neurological or cardiovascular medical conditions, those in non-intensive care unit departments, and those with respiratory causes had higher odds of survival to discharge.

Conclusion

While the incidence rate of paediatric IHCA in Jordan is comparable to developed countries, the survival rate is much poorer. The study highlights the importance of strengthening healthcare infrastructure, establishing national legal and ethical frameworks around resuscitation policies and establishing robust data registries to monitor and optimise care practices.
Coming in hot: a qualitative investigation into perceptions of parents and doctors of reasons for the presentation of children with fever to the emergency department in England
Authors: Franklin Courtney , Taylor-Robinson David , Carrol Enitan D , Moran Paul , Carter Bernie
Published: December 2024

Introduction

Paediatric emergency department (ED) attendances and admissions in England are increasing. Fever is a common presenting problem for these attendances. Anxiety and misperceptions surrounding appropriate management of fever persist among parents. Little evidence exists on the pathways to ED for fever, and doctors’ perceptions of why parents present their child to the ED.

Objectives

To understand perceptions of parents and doctors of the reasons for ED presentation for children (0–18 years) with fever in England.

Design

This forms the first part of a qualitative study, using reflective thematic analysis.

Participants

15 parents (12 mothers and 3 fathers) who had taken their febrile child to hospital (2015–2023), and 5 ED doctors (4 consultants and 1 resident doctor) who had experienced treating a febrile child in an ED in England.

Methods

Semistructured remote (Zoom) interviews were conducted (2022–2023).

Results

Reflexive thematic analysis facilitated investigation into current parental concerns regarding fever and decision-making leading to ED attendance. The overarching theme ‘factors influencing unscheduled care’ comprised four key themes that reflected the complex interplay between factors influencing parental decision-making to seek emergency care, at the individual and wider structural level. These were parental proficiency and experience; social networks and access to services; fever phobia, uncertainty and anxiety; and reassurance. Doctors also acknowledged the importance of these factors, such as reassurance and showing compassion and further indicated a persistent educational gap surrounding fever between doctors and parents.

Conclusions

We widen the evidence base of why parents attend ED for paediatric fever and their perceptions of other health services. Parents face challenges when seeking care and perceived ED as a last resort. Interventions to support parental decision-making and management of fever could help to alleviate these challenges, as well as potentially reducing the demand for emergency care.
Neonatal death prediction scores: a systematic review and meta-analysis
Authors: Veloso Felipe C S , Barros Carine R A , Kassar Samir B , Gurgel Ricardo Q
Published: December 2024

Objective

To compare, through a systematic review and meta-analysis of observational accuracy studies, the main existing neonatal death prediction scores.

Method

Systematic review and meta-analysis of observational accuracy studies. The databases accessed were MEDLINE, ELSEVIER, LILACS, SciELO, OpenGrey, Open Access Thesis and Dissertations, EMBASE, Web of Science, SCOPUS and Cochrane Library. For qualitative analysis, Quality Assessment of Diagnostic Accuracy Studies 2 was used. For the quantitative analysis, the area under the curve and the SE were used, as well as the inverse of the variance as a weight measure, DerSimonian and Laird as a measure of random effects, Higgins’ I² as an estimate of heterogeneity, Z as a final measure with a 95% confidence level.

Results

55 studies were analysed, 8 scores were compared in a total of 193 849 newborns included. The most accurate neonatal death prediction score was Score for Neonatal Acute Physiology Perinatal Extension II (SNAPPE II) (0.89 (95% CI 0.86 to 0.92)) and the least accurate was gestational age (0.75 (95% CI 0.71 to 0.79)).

Conclusion

SNAPPE II was the most accurate score found in this study. Despite this, the choice of score depends on the situation and setting in which the newborn is inserted, and it is up to the researcher to analyse and decide which one to use based on practicality and the possibility of local implementation. Given this, it is interesting to carry out new prospective studies to improve the prediction of neonatal deaths around the world.

PROSPERO registration number

CRD42023462425.
Mutational signatures define immune and Wnt-associated subtypes of ampullary carcinoma
Authors: Zhuravleva Ekaterina , Lewinska Monika , O'Rourke Colm J , Pea Antonio , Rashid Asif , Hsing Ann W , Taranta Andrzej , Chang David , Gao Yu-Tang , Koshiol Jill , Oliveira Rui Caetano , Andersen Jesper B
Published: December 2024

Background and objective

Ampullary carcinoma (AMPAC) taxonomy is based on morphology and immunohistochemistry. This classification lacks prognostic reliability and unique genetic associations. We applied an approach of integrative genomics characterising patients with AMPAC exploring molecular subtypes that may guide personalised treatments.

Design

We analysed the mutational landscapes of 170 patients with AMPAC. The discovery included 110 tumour/normal pairs and the validation comprised 60 patients. In a tumour subset, we interrogated the transcriptomes and DNA methylomes. Patients were stratified based on mutational signatures and associated with molecular and clinical features. To evaluate tumour and immune cellularity, 22 tumours were independently assessed histomorphologically and by digital pathology.

Results

We defined three patient clusters by mutational signatures independent of histomorphology. Cluster 1 (C1) was defined by spontaneous deamination of DNA 5-methylcytosine and defective mismatch repair. C2 and C3 were related to the activity of transcription-coupled nucleotide excision repair but C3 was further defined by the polymerase eta mutational process. C1–2 showed enrichment of Wnt pathway alterations, aberrant DNA methylation profiles, immune cell exclusion and patients with poor prognosis. These features were associated with a hypermutator phenotype caused by C>T alterations at CpGs. C3 patients with improved overall survival were associated with activation of immune-related pathways, immune infiltration and elevated expression of immunoinhibitory checkpoint genes.

Conclusion

Immunogenicity and Wnt pathway associations, emphasised by the mutational signatures, defined patients with prospective sensitivity to either immunotherapy or Wnt pathway inhibitors. This emphasises a novel mutational signature-based AMPAC classification with prognostic potential, suggesting prospective implications for subgroup-specific management of patients with AMPAC.