bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospitals’ financial performance across European countries: a scoping review protocol
Authors: Dubas‐Jakóbczyk Katarzyna , Ndayishimiye Costase , Szetela Przemysław , Sowada Christoph
Published: January 2024

Introduction

Hospitals remain the cornerstone of health systems in European countries. Therefore, the financial sustainability of hospitals constitutes an important determinant of healthcare provision security. The fragmentary data available indicate that hospitals in many European countries are continuously facing financial deficits and/or insolvency problems. Yet a comparative analysis of hospital financial performance across European countries has been lacking. The proposed review will, therefore, fill in an important research gap and build a knowledge base on the topic of assessing and monitoring the financial sustainability of hospitals in Europe. The general objective is to identify, synthetise and map existing evidence on hospital financial performance across European countries.

Methods and analysis

This scoping review will follow six stages: (1) defining the research question, (2) identifying relevant literature, (3) studies selection, (4) data extraction, (5) collating, summarising and reporting of results and (6) consultation process and involvement of knowledge users. The following databases will be searched:(1) Medline via PubMed, (2) Web of Science Core Collection, (3) Scopus and (4) ProQuest Central. In addition, a Google Engine search will also be performed. Furthermore, reference lists of relevant papers will be visually scanned to identify further studies of interest. The review will include both quantitative and qualitative empirical studies as well as theoretical papers and technical reports. The PRISMA extension for a Scoping Review checklist will be used for reporting.

Ethics and dissemination

Formal ethical approval is not required because no primary data will be collected in this study. Results will be published in a peer-reviewed journal. The findings will also be disseminated through conference presentations and summaries to key stakeholders.
RELEASE-HF study: a protocol for an observational, registry-based study on the effectiveness of telemedicine in heart failure in the Netherlands
Authors: van Eijk Jorna , Luijken Kim , Jaarsma Tiny , Reitsma Johannes B , Schuit Ewoud , Frederix Geert W J , Derks Lineke , Schaap Jeroen , Rutten Frans H , Brugts Jasper , de Boer Rudolf A , Asselbergs Folkert W , Trappenburg Jaap C A
Published: January 2024

Introduction

Meta-analyses show postive effects of telemedicine in heart failure (HF) management on hospitalisation, mortality and costs. However, these effects are heterogeneous due to variation in the included HF population, the telemedicine components and the quality of the comparator usual care. Still, telemedicine is gaining acceptance in HF management. The current nationwide study aims to identify (1) in which subgroup(s) of patients with HF telemedicine is (cost-)effective and (2) which components of telemedicine are most (cost-)effective.

Methods and analysis

The RELEASE-HF (‘REsponsible roLl-out of E-heAlth through Systematic Evaluation – Heart Failure’) study is a multicentre, observational, registry-based cohort study that plans to enrol 6480 patients with HF using data from the HF registry facilitated by the Netherlands Heart Registration. Collected data include patient characteristics, treatment information and clinical outcomes, and are measured at HF diagnosis and at 6 and 12 months afterwards. The components of telemedicine are described at the hospital level based on closed-ended interviews with clinicians and at the patient level based on additional data extracted from electronic health records and telemedicine-generated data. The costs of telemedicine are calculated using registration data and interviews with clinicians and finance department staff. To overcome missing data, additional national databases will be linked to the HF registry if feasible. Heterogeneity of the effects of offering telemedicine compared with not offering on days alive without unplanned hospitalisations in 1 year is assessed across predefined patient characteristics using exploratory stratified analyses. The effects of telemedicine components are assessed by fitting separate models for component contrasts.

Ethics and dissemination

The study has been approved by the Medical Ethics Committee 2021 of the University Medical Center Utrecht (the Netherlands). Results will be published in peer-reviewed journals and presented at (inter)national conferences. Effective telemedicine scenarios will be proposed among hospitals throughout the country and abroad, if applicable and feasible.

Trial registration number

NCT05654961.
Amantadine and/or transcranial magnetic stimulation for fatigue associated with multiple sclerosis (FETEM): study protocol for a phase 3 randomised, double-blind, cross-over, controlled clinical trial
Authors: Matias-Guiu Jordi A , González-Rosa Javier , Hernández Miguel Ángel , Martínez-Ginés Maria Luisa , Portolés Antonio , Pérez-Macías Natalia , Benito-León Julián , Padrón Iván , Prieto Julio , Matias-Guiu Jorge
Published: January 2024

Introduction

Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although its efficacy is under debate. Transcranial magnetic stimulation (TMS) is a promising intervention that has shown positive effects in some preliminary investigations. We aim to investigate the effect of 6 weeks of amantadine and/or TMS in fatigue due to MS.

Methods and analysis

The study is a national, multicentre, phase 3, randomised, double-blind, cross-over, placebo-controlled and sham-controlled clinical trial. Adult patients with relapsing-remitting MS, Expanded Disability Status Scale score of 1.5–4.5 and Fatigue Severity Score>4 are eligible for the trial. Participants will be randomised to one of the sequences of the study. Each sequence consists of four periods of 6 weeks of treatment and three washout periods of 12–18 weeks. All patients will receive all the combinations of therapies. The primary outcome is the Modified Fatigue Impact Scale. The secondary outcomes are the Symbol Digit Modalities Test (cognition), Beck Depression Inventory-II (depressive symptoms) and Short-Survey 12 (quality of life). Safety and cost-effectiveness will also be evaluated. An exploratory substudy including MRI and blood biomarkers will be conducted.

Ethics and dissemination

The study is approved by the Ethics Committee of the Hospital Clinico San Carlos and the Spanish Agency of Medications and Medical Devices. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.

Trial registration number

EudraCT 2021-004868-95;NCT05809414.
The Tuberculosis Sentinel Research Network (TB-SRN) of the International epidemiology Databases to Evaluate AIDS (IeDEA): protocol for a prospective cohort study in Africa, Southeast Asia and Latin America
Authors: Enane Leslie A , Duda Stephany N , Chanyachukul Thida , Bolton-Moore Carolyn , Navuluri Neelima , Messou Eugène , Mbonze Nana , McDade LaQuita R , Figueiredo Marina Cruvinel , Ross Jeremy , Evans Denise , Diero Lameck , Akpata Robert , Zotova Natalia , Freeman Aimee , Pierre Marie Flore , Rupasinghe Dhanushi , Ballif Marie , Byakwaga Helen , de Castro Nathalie , Tabala Martine , Sterling Timothy R , Sohn Annette H , Fenner Lukas , Wools-Kaloustian Kara , Poda Armel , Yotebieng Marcel , Huebner Robin , Marcy Olivier
Published: January 2024

Introduction

Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium.

Methods and analysis

This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA’s global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses.

Ethics and dissemination

Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.
Study of postoperative laryngopharyngeal discomfort: protocol for a single-centre cohort study
Authors: Wang Li Fang , Zheng Meng-Tao , Liang Nan , Ma Hao Ning , Li Wei Xia
Published: January 2024

Introduction

Postoperative laryngopharyngeal discomfort after extubation can lead to severe throat pain, dysphagia, or postoperative tongue oedema. Possible mechanisms include increased oral pressure, obstruction of venous and lymphatic return in the neck, and increased capillary hydrostatic pressure, which leads to oedema of the tongue and upper airway. However, real-time monitoring indicators of anaesthesia are lacking. Therefore, we designed this study to accurately measure the contact force of the tracheal tube on the tongue in different surgical positions during general anaesthesia.

Methods and analysis

This prospective single-centre observational study will enrol 54 patients undergoing elective surgery under general anaesthesia for>2 hours with endotracheal tube application from 1 July 2023 to 30 June 2024. Patients will be divided into the supine (Supine group) and high-risk (Flexion group) groups. Dynamic changes in the contact force between the tracheal tube and tongue will be measured using T-Scan technology. All patients will be followed up for 7 days postoperatively. The primary endpoint is postoperative laryngopharyngeal discomfort. Secondary outcomes include the time to the first successful recovery of oral intake of fluids and solid food, and airway-related events.

Ethics and dissemination

Ethical approval was obtained from the Ethics Committee of Clinical Research of China-Japan Friendship Hospital (2023-KY-219, approved on 14 September 2023). Informed consent will be obtained during anaesthesia evaluation. This study aims to explore the characteristics of the contact force on the tongue caused by endotracheal intubation in different surgical positions and to provide a better understanding of the risk factors and prevention of postoperative laryngopharyngeal discomfort. The findings of this study will be presented at our hospital, reported on ClinicalTrials.gov, and published in peer-reviewed journals.

Trial registration number

NCT05987293.
Excess mortality during the COVID-19 pandemic in low-income and lower middle-income countries: protocol for a systematic review and meta-analysis
Authors: Gmanyami Jonathan Mawutor , Jarynowski Andrzej , Belik Vitaly , Lambert Oscar , Amuasi John , Quentin Wilm
Published: January 2024

Introduction

The COVID-19 pandemic has been marked by a massive death toll. However, the overall effect of the pandemic, including potential unintended negative impacts of some control measures, on mortality remains poorly understood in low-income and lower middle-income countries (LLMICs). This review aims to summarise the available literature on excess mortality in LLMICs, focusing on the methods and data sources used in estimating excess mortality and the drivers of excess mortality.

Methods and analysis

We will review the available literature and report results in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis. Searches will be conducted in PubMed, Embase, Web of Science, Cochrane Library, Google Scholar and Scopus. All published studies that report on the estimates of excess mortality in populations of LLMICs will be included. This will include those with a publication date from 2019 onwards and those with at least a 1-year non-COVID-19 period as the comparator in the estimation of excess mortality during the pandemic. There will be no language restrictions on the search. The meta-analysis will include studies with extractable data on excess mortality, methods, population size, and observed and expected deaths. We will use the Mantel-Haenszel method to estimate the pooled risk ratio with 95% CIs.

Ethics and dissemination

As there is no primary data collection, there is no requirement for ethical review. The results will be disseminated through peer-reviewed journal publication and conference presentations.

PROSPERO registration number

CRD42022378267.
Factors that impact on the quality of life of intestinal failure patients treated with home parenteral nutrition: protocol for a multicentre, longitudinal observational study
Authors: Kirk Colette , Mathers John , Pearce Mark , Thompson Nicholas P , Jones David
Published: January 2024

Background

Home parenteral nutrition (HPN) refers to the intravenous administration of macronutrients, micronutrients and fluid. The aims of treatment are to increase survival and improve quality of life (QoL). However, patients struggle with physiological symptoms, time-consuming invasive therapy and an increased occurrence of depression and social isolation. Our aim is to understand how HPN impacts the QoL of patients, and the contribution played by the complications of treatment, for example, liver disease.

Methods and analysis

A multicentre, longitudinal, observational study will be conducted using routinely collected clinical data. Participants will also be asked to complete three QoL questionnaires (EuroQol-5 Dimensions, Short Form 36 and HPN-QoL) at baseline and 12 months. The primary outcome is mean change in QoL scores over 12 months. Secondary outcomes include how factors including liver function, gut microbiota, number of infusions of PN per week, nutritional composition of PN and nutritional status impact on QoL scores.

Ethics and dissemination

Ethical approval was obtained from HRA and Health and Care Research Wales Research Ethics Committee (21/SC/0316). The study was eligible for portfolio adoption, Central Portfolio Management System ID 50506. Results will be disseminated through peer-reviewed scientific journals and presented at national and international meetings.
Role of soluble urokinase plasminogen activator receptor in critically ill children with hospital-acquired pneumonia: an observational study in hospital with controls
Authors: Saleh Nagwan Yossery , Soliman Shimaa Elshafy , Aboukoura Mohammed Adel , Garib Mohamed Ibrahim
Published: January 2024

Background

Diagnosing hospital-acquired pneumonia (HAP) (ventilator-associated pneumonia (VAP) and non-ventilator associated pneumonia (Non-VAP)) is still a hot issue. Soluble urokinase plasminogen activator receptor (suPAR) is prognostic in critically ill children with sepsis regarding mortality prediction. Our aim was to evaluate suPAR levels in children with HAP.

Methods

An observational, prospective study was conducted on 45 children diagnosed HAP (VAP and Non-VAP) and 40 healthy controls. Paediatric Sequential Organ Failure assessment Score (pSOFA) was assessed for each patient. Plasma suPAR levels were measured with ELISA on the day of diagnosis.

Results

On comparison levels of plasma suPAR for the children with HAP with the healthy control group, no statistically significant difference was observed (148 pg/mL (22.4–1939.7) and 184.4 pg/mL (31.6–1311.7), respectively, (p=0.32). suPAR was significantly increased in children with elevated pSOFA score on the day of diagnosis of pneumonia (p=0.034). suPAR was significantly increased in children with shock (p=0.005). suPAR levels was negatively correlated with oxygen saturation (rs=0.31,p=0.048). suPAR was not significantly correlated with C reactive protein.

Conclusions

suPAR can be used as a predictor for severity of illness in children with HAP. We firmly know that plasma suPAR, a novel marker, could indicate the disease if carried out on larger patient groups.
Assessing prognosis in depression: comparing perspectives of AI models, mental health professionals and the general public
Authors: Elyoseph Zohar , Levkovich Inbar , Shinan-Altman Shiri
Published: January 2024

Background

Artificial intelligence (AI) has rapidly permeated various sectors, including healthcare, highlighting its potential to facilitate mental health assessments. This study explores the underexplored domain of AI’s role in evaluating prognosis and long-term outcomes in depressive disorders, offering insights into how AI large language models (LLMs) compare with human perspectives.

Methods

Using case vignettes, we conducted a comparative analysis involving different LLMs (ChatGPT-3.5, ChatGPT-4, Claude and Bard), mental health professionals (general practitioners, psychiatrists, clinical psychologists and mental health nurses), and the general public that reported previously. We evaluate the LLMs ability to generate prognosis, anticipated outcomes with and without professional intervention, and envisioned long-term positive and negative consequences for individuals with depression.

Results

In most of the examined cases, the four LLMs consistently identified depression as the primary diagnosis and recommended a combined treatment of psychotherapy and antidepressant medication. ChatGPT-3.5 exhibited a significantly pessimistic prognosis distinct from other LLMs, professionals and the public. ChatGPT-4, Claude and Bard aligned closely with mental health professionals and the general public perspectives, all of whom anticipated no improvement or worsening without professional help. Regarding long-term outcomes, ChatGPT 3.5, Claude and Bard consistently projected significantly fewer negative long-term consequences of treatment than ChatGPT-4.

Conclusions

This study underscores the potential of AI to complement the expertise of mental health professionals and promote a collaborative paradigm in mental healthcare. The observation that three of the four LLMs closely mirrored the anticipations of mental health experts in scenarios involving treatment underscores the technology’s prospective value in offering professional clinical forecasts. The pessimistic outlook presented by ChatGPT 3.5 is concerning, as it could potentially diminish patients’ drive to initiate or continue depression therapy. In summary, although LLMs show potential in enhancing healthcare services, their utilisation requires thorough verification and a seamless integration with human judgement and skills.
Advanced child tax credit payments and national child abuse hotline contacts, 2019–2022
Authors: Merrill-Francis Molly , Chen May S , Dunphy Christopher , Swedo Elizabeth A , Zhang Kudon Hui , Metzler Marilyn , Mercy James A , Zhang Xinjian , Rogers Tia M , Wu Shortt Joann
Published: January 2024

Background

Children in households experiencing poverty are disproportionately exposed to maltreatment. Income support policies have been associated with reductions in child abuse and neglect. The advance child tax credit (CTC) payments may reduce child maltreatment by improving the economic security of some families. No national studies have examined the association between advance CTC payments and child abuse and neglect. This study examines the association between the advance CTC payments and child abuse and neglect-related contacts to the Childhelp National Child Abuse Hotline.

Methods

A time series study of contacts to the Childhelp National Child Abuse Hotline between January 2019 and December 2022 was used to examine the association between the payments and hotline contacts. An interrupted time series (ITS) exploiting the variation in the advance CTC payments was estimated using fixed effects.

Results

The CTC advance payments were associated with an immediate 13.8% (95% CI −17.5% to −10.0%) decrease in contacts to the hotline in the ITS model. Following the expiration of the advance CTC payments, there was a significant and gradual 0.1% (95% CI +0.0% to +0.2%) daily increase in contacts. Sensitivity analyses found significant reductions in contacts following each payment, however, the reductions were associated with the last three of the six total payments.

Conclusion

These findings suggest the advance CTC payments may reduce child abuse and neglect-related hotline contacts and continue to build the evidence base for associations between income-support policies and reductions in child abuse and neglect.
Multistep tumor genetic evolution and changes in immunogenicity trigger immune-mediated disease eradication in stage IV melanoma: lessons from a single case
Authors: Vallacchi Viviana , Vergani Elisabetta , Cossa Mara , Gargiuli Chiara , Busico Adele , Devecchi Andrea , Dugo Matteo , Bergamaschi Laura , De Cecco Loris , Cavalieri Stefano , Valeri Barbara , Tamborini Elena , Gallino Gianfrancesco , Del Vecchio Michele , Santinami Mario , Sensi Marialuisa , Rivoltini Licia , Di Guardo Lorenza , Rodolfo Monica
Published: January 2024

Durable remissions are observed in 10%–20% of treated patients with advanced metastatic melanoma but the factors associated with long-term complete clinical responses are largely unknown. Here, we report the molecular characteristics of tumor evolution during disease progression along a 9-year clinical course in a patient with advanced disseminated melanoma who received different treatments, including trametinib, ipilimumab, radiation, vemurafenib, surgical tumor debulking and a second ipilimumab course, ultimately achieving complete long-term disease remission.

Longitudinal analyses of therapies-resistant metastatic tumors revealed the effects of different treatments on tumor’s microenvironment and immunogenicity, ultimately creating a milieu favorable to immunotherapy response. Monitoring of the temporal dynamics of T cells by analysis of the T cell receptor (TCR) repertoire in the tumor and peripheral blood during disease evolution indicated that T-cell clones with common TCR rearrangements, present at low levels at baseline, were maintained and expanded after immunotherapy, and that TCR diversity increased. Analysis of genetic, molecular, and cellular components of the tumor depicted a multistep process in which treatment with kinase inhibitors strongly conditioned the immune microenvironment creating an inflamed milieu converting cold into hot tumors, while ipilimumab impacted and increased the TCR repertoire, a requirement for tumor rejection.

Since the optimal sequencing of treatment with antibodies targeting immune checkpoints and kinase inhibitors for advanced melanoma is still clinically debated, this case indicates that immunotherapy success is possible even after progression on targeted therapy.
WEB for recurrent aneurysms: a case series to review technical nuances
Authors: Holland Ryan , Essibayi Muhammed Amir , Altschul David
Published: January 2024

Recurrent intracranial aneurysms (IAs) often present with more complex morphology such as irregular shape, shallow height, and wide neck, which can make for challenging endovascular treatments.1 Initial rupture and interventions are associated with fibrotic changes and considerable alteration in the aneurysm configuration, which limits retreatment options and increases the risk of complications during retreatment.2 The Woven Endobridge (WEB) embolization device has demonstrated high efficacy, flexibility, and safety for the treatment of wide-neck bifurcation IAs, including ruptured and recurrent IAs, as shown in multiple retrospective studies and meta-analyses.3–8 Due to its optimal barrel shape, the WEB device is useful in the setting of previously treated aneurysms, particularly with wide-neck previously coiled aneurysms.1 9 10 In this technical video of four cases (video 1), we describe the technical nuances of WEB embolization for recurrent IAs, which were initially either coiled or clipped and demonstrated progressive growth with a wide-neck presentation on follow-up.

Video 1

Management of recurrent intracranial aneurysms via WEB: This video describes four recurrent intracranial aneurysms, which were initially either coiled or clipped but demonstrated progressive growth with a wide-neck presentation on follow-up. All cases were successfully treated via WEB.
The pEGASUS-HPC stent system for stent-assisted coiling of cerebral aneurysms: a multicenter case series
Authors: Lobsien Donald , Holtmannspoetter Markus , Eff Florian , Berlis Ansgar , Maurer Christoph Johannes , Behme Daniel , Diamandis Elie , Gawlitza Matthias , Fiorella David , Princiotta Ciro , Cirillo Luigi , Dall'Olio Massimo , Keston Peter , Klisch Joachim , Nania Alberto
Published: January 2024

Background

Stent-assisted coiling (SAC) is a well-established method for treatment of wide-necked intracranial aneurysms. In this multicenter, retrospective case series we evaluated SAC with a new low-profile, laser-cut stent with an antithrombogenic hydrophilic polymer coating (pEGASUS-HPC) for the treatment of intracranial aneurysms.

Methods

Patients treated with pEGASUS-HPC SAC for one or more intracranial aneurysms were retrospectively included. Clinical, imaging, and procedural parameters as well as clinical and imaging follow-up data were recorded.

Results

We treated 53 aneurysms in 52 patients in six neurovascular centers between August 2021 and November 2022. Thirty-seven patients (69.8%) were female. Mean age was 57 (±11.7) years. Twenty-nine patients were treated electively, 23 in the acute phase (22 with aneurysmal subarachnoid hemorrhage (SAH), and 1 with a partially thrombosed aneurysm causing ischemic events). One intraprocedural thromboembolic event and three postprocedural ischemic complications occurred in two (8.7 %) of the SAH patients and in one of the elective patients (3.45%). Overall aneurysm occlusion was Raymond Roy (RR) I in 36 (69.2%), RR II in 9, and RR III in 9 cases. Follow-up imaging was available for 23 patients after an average of 147.7 (±59.6) days demonstrating RR I occlusion in 22 (95.5%) and RR II in 1 patient.

Conclusion

SAC with the pEGASUS-HPC stent system demonstrates rates of periprocedural safety and effectiveness that are comparable with previously reported series for stent-assisted coil embolization.
Risk of unruptured aneurysms in subarachnoid hemorrhage patients with multiple intracranial aneurysms: a multicenter, longitudinal, comparative study from China
Authors: Liu Jian , Zhang Yiping , Levitt Michael R , Mossa-Basha Mahmud , Wang Chao , Turhon Mirzat , Zhang Ying , Zhang Yisen , Wang Kun , Zhu Chengcheng , Yang Xinjian
Published: January 2024

Background

In aneurysmal subarachnoid hemorrhage patients with multiple intracranial aneurysms (aSAH-MIA patients), the risk of secondary unruptured intracranial aneurysms is inconsistent. This study aimed to explore the risk of unruptured aneurysms in Chinese aSAH-MIA patients.

Methods

The medical records and angiographic images of aSAH-MIA patients from eight cerebrovascular centers in China were retrospectively reviewed and analyzed. Patients with a single unruptured intracranial aneurysm (UIA) and no prior aSAH were used as controls. Propensity score matching (PSM) was employed to balance the differences in age, gender, aneurysm size, aneurysm site, and follow-up duration between the two groups.

Results

The study included 267 unruptured aneurysms from 204 aSAH-MIA patients and 769 single UIA. After PSM, 201 aneurysms were enrolled in the aSAH-MIA group and 201 aneurysms in the control group. The mean follow-up was 2.2 years. Thirty-four aneurysm instability events (28 growth and 6 rupture, 16.9%) occurred during follow-up in the aSAH-MIA group and 16 instability events (13 growth and 3 rupture, 8%) occurred in the control group. Risk factors for aneurysmal instability were aneurysm irregularity (OR 2.53; 95% CI 1.18 to 4.31), higher size ratio (OR 1.23; 95% CI 1.37 to 4.39), and middle cerebral artery location (OR 1.86; 95% CI 1.03 to 3.17). The risk of aneurysmal instability was substantially elevated in the aSAH-MIA group (HR 2.07; 95% CI 1.12 to 3.02).

Conclusions

Unruptured aneurysms in Chinese aSAH-MIA patients exhibited higher risks of growth and rupture than in patients with a single UIA. Middle cerebral artery location, higher size ratio and irregular shape were associated with higher risk of growth or rupture.
Azathioprine metabolite levels and outcomes during pregnancies with rheumatic disease
Authors: Balevic Stephen , Sims Catherine A , Eudy Amanda , Smith Valerie , Clowse Megan
Published: January 2024

Objective

Despite widespread use of azathioprine (AZA) during pregnancy, no studies evaluated the impact of pregnancy on AZA metabolites 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine nucleotide (6-MMPN) disposition in rheumatic diseases. This study characterises changes in AZA metabolite concentrations throughout pregnancy in women with rheumatic disease and explores relationships between metabolite concentrations, maternal disease activity, and neonatal outcomes.

Methods

Patients with rheumatic disease from a single centre prescribed AZA prior to pregnancy and ≥1 blood sample during pregnancy (5/2016 to 4/2022) were included. Commercial laboratories quantified AZA metabolite concentrations. The upper safety limit for 6-MMPN was >5700 pmol/8×108RBC. The therapeutic target for 6-TGN was ≥159 pmol/8×108RBC. Repeated correlation measures were used to evaluate the relationship between metabolite concentrations and pregnancy duration, and the relationship between 6-TGN concentration and SLE Physician Global Assessment (PGA). The relationship between pregnancy average 6-TGN and neonatal gestational age at birth was analysed using linear regression.

Results

Thirty-seven pregnancies in 35 women with 108 serum samples were included. There was no significant difference in dose-adjusted 6-TGN concentrations across pregnancy and peripartum, whereas 6-MMPN concentrations appeared higher during pregnancy. No elevated transaminases or cholestasis were observed concurrently with 6-MMPN above 5700 pmol/8×108RBC. Metabolite concentrations were related to total AZA dosage, weight-based dosage and TPMT phenotype. In pregnant women with SLE achieving average 6-TGN in the therapeutic range, we observed a non-significant reduction in PGA and increase in neonatal gestational age at birth.

Conclusions

In this exploratory study, we did not observe systematic changes in 6-TGN concentrations throughout pregnancy and peripartum, whereas 6-MMPN concentrations were higher during pregnancy. Monitoring AZA metabolite concentrations in pregnancy is a potential tool to identify medication non-adherence as well as patients with high 6-MMPN in whom dosage adjustment or close laboratory monitoring may optimise safety.
Circulating neutrophil extracellular trap remnants as a biomarker to predict outcomes in lupus nephritis
Authors: Whittall-Garcia Laura Patricia , Naderinabi Farnoosh , Gladman Dafna D , Urowitz Murray , Touma Zahi , Konvalinka Ana , Wither Joan
Published: January 2024

Objective

To determine if the serum levels of neutrophil extracellular trap (NET) remnants (Elastase-DNA and HMGB1-DNA complexes) at the time of a lupus nephritis (LN) flare predict renal outcomes in the following 24 months.

Methods

This was a retrospective study performed in prospectively followed cohorts. The study included two cohorts: an exploratory cohort to assess the association between NET remnant levels and the presence of active LN, and a separate LN cohort to determine the utility of NET remnants to predict renal outcomes over the subsequent 24 months.

Results

Ninety-two individuals were included in the exploratory cohort (49 active systemic lupus erythematosus (SLE), 23 inactive SLE and 20 healthy controls (HC)). NET remnants were significantly higher in patients with SLE patients compared with HC (p<0.0001 for both complexes) and those with active LN (36%) had significantly higher levels of NET remnants compared with active SLE without LN (Elastase-DNA: p=0.03; HMGB1-DNA: p=0.02). The LN cohort included 109 active LN patients. Patients with proliferative LN had significantly higher levels of NET remnants than non-proliferative LN (Elastase-DNA: p<0.0001; HMGB1-DNA: p=0.0003). Patients with higher baseline levels of NET remnants had higher odds of not achieving complete remission (Elastase-DNA: OR 2.34, p=0.007; HMGB1-DNA: OR 2.61, p=0.009) and of progressing to severe renal impairment (Elastase-DNA: OR 2.84, p=0.006; HMGB1-DNA: OR 2.04, p=0.02) at 24 months after the flare.

Conclusions

Elastase-DNA and HMGB1-DNA complexes predict renal outcomes, suggesting they could be used to identify patients requiring more aggressive therapy at flare onset.
Comparative evaluation of microprobe versus conventional transoesophageal echocardiography for PFO closure guidance
Authors: Lanki Jemina , Tuohinen Suvi , Simonen Piia , Jalanko Mikko , Sinisalo Juha
Published: January 2024

Background

Patent foramen ovale (PFO) closure is traditionally guided by transoesophageal echocardiography (TEE) under general anaesthesia, which prolongs procedure duration and increases costs and risks. A transnasal echocardiography with a microTEE-probe (microTNE) is tolerated under conscious sedation and offers an effective alternative to TEE. The aim of this study was to compare the feasibility, safety and time expenditure of PFO closure using conventional TEE versus microTNE guidance.

Methods

Consecutive patients assigned for PFO losure in Helsinki University Hospital from 2003 to 2021 were included in the study (n=336). TEE with general anaesthesia was used until November 2018 (n=167) while microTNE-guided PFO closure (n=169) under conscious sedation was the principal method thereafter. Patients were followed for 3 months after PFO closure.

Results

The microTNE-route success rate was 97.2% vs TEE 100% (p=0.06) and procedure success rate was 97.7% with microTNE and 96.0% with TEE-guidance (p=0.54). The procedure time was significantly shorter with microTNE 21±7 min than with TEE 30±13 min (p<0.001). At the beginning of microTNE era, nasal bleeding complication was quite frequent; however, overall complication rates were equal between the groups. However, C reactive protein (CRP) increase was significantly milder with microTNE than TEE 1.0±2.9 vs 3.0±4.0 mg/L (p<0.001). An increase in CRP was independently associated with procedure type (p=0.004) and time (p=0.003).

Conclusions

MicroTNE is a feasible and safe alternative for PFO closure guidance. MicroTNE under conscious sedation shortens procedure duration and induces a milder inflammatory reaction than conventional TEE under general anaesthesia.
Systematic review and meta-analysis of early aortic valve replacement versus conservative therapy in patients with asymptomatic aortic valve stenosis with preserved left ventricle systolic function
Authors: Senguttuvan Nagendra Boopathy , Srinivasan Nishok Victory , Panchanatham Manokar , Abdulkader Rizwan Suliankatchi , Anandaram Asuwin , Polareddy Dinesh Reddy , Ramesh Sankaran , Singh Harsimran , Yallanki Hanumath , Kaliyamoorthi Dhamodaran , Chidambaram Sundar , Ramalingam Vadivelu , Rajendran Ravindran , Muralidharan Thoddi Ramamurthy , Rao Ravindar , Seth Ashok , Claessen Bimmer , Krishnamoorthy Parasuram
Published: January 2024

Background

A quarter of patients with severe aortic stenosis (AS) were asymptomatic, and only a third of them survived at the end of 4 years. Only a select subset of these patients was recommended for aortic valve replacement (AVR) by the current American College of Cardiology/American Heart Association guidelines. We intended to study the effect of early AVR (eAVR) in this subset of asymptomatic patients with preserved left ventricle function.

Methods and results

We searched PubMed and Embase for randomised and observational studies comparing the effect of eAVR versus conservative therapy in patients with severe, asymptomatic AS and normal left ventricular function. The primary outcome was all-cause mortality. The secondary outcomes were composite major adverse cardiac events (MACE) (study defined), myocardial infarction (MI), stroke, cardiac death, sudden death, the development of symptoms, heart failure hospitalisations and major bleeding. We used GRADEPro to assess the certainty of the evidence. In the randomised controlled trial (RCT) only analysis, we found no significant difference in all-cause mortality between the early aortic intervention group versus the conservative arm (CA) (incidence rate ratio, IRR (CI): 0.5 (0.2 to 1.1), I2=31%, p=0.09). However, in the overall cohort, we found mortality benefit for eAVR over CA (IRR (CI): 0.4 (0.3 to 0.7), I2=84%, p<0.01). There were significantly lower MACE, cardiac death, sudden death, development of symptoms and heart failure hospitalisations in the eAVR group. We noticed no difference in MI, stroke and major bleeding.

Conclusion

We conclude that there is no reduction in all-cause mortality in the eAVR arm in patients with asymptomatic AS with preserved ejection fraction. However, eAVR reduces heart failure related hospitalisations and death or heart failure hospitalisations.

PROSPERO registration number

CRD42022306132.
Psychosocial screening instruments to assist support consultants in patients with cancer
Authors: Driessen Helen Pieternel Antonie , van der Rijt Carin C D , Busschbach Jan J V , Elfrink Erna J , Kranenburg Leonieke W
Published: January 2024

Objectives

Around 30% of patients with cancer suffer from psychosocial problems requiring formal care; however, these problems are often not identified. Support consultants may play a role in identifying these problems. This study investigates the feasibility of using validated screening instruments to assist support consultants in identifying psychosocial problems.

Methods

Prospective observational study focusing on patients visiting support consultants at hospital-affiliated centres for information and support. The feasibility of using screening instruments was assessed based on the percentage of patients willing to participate. For these patients, possible psychosocial problems were objectified, and referral to formal care was assessed.

Results

Out of 227 eligible patients at IntermeZZo, 48 participated (21.1%). At PATIO, over 141 consultations took place and 27 patients participated. Main reason for non-participation was that patients did not feel such a need. The majority showed elevated scores, indicating possible psychosocial problems and around half were referred. Respecting the individual needs of patients and offering them with what benefits them is crucial, including screening instruments does not match their needs nor did support consultants feel it was appropriate in certain cases.

Conclusion

Given the low percentage of questionnaires administered, it does not seem feasible to systematically administer them to patients visiting support consultants.
Emergency preparedness for mass casualty events: South Texas commentary on the development of a statewide emergency response system
Authors: Harrell Kelly , Cirone Justin , Hill Alexandra , Johnson Abigail , McClary Caleb , Myers John C , Ngamsuntikul Samantha , Mendoza Adriene , Quesada Jose , Epley Eric , Eastridge Brian , Nicholson Susannah , Brigmon Erika P , Jenkins Donald H
Published: January 2024

Mass casualty incidents (MCIs) are on the rise in the USA, and hemorrhage is the leading cause of preventable death in trauma. The need for rapid access to life-saving blood and blood products is essential for preventing death due to hemorrhage. It is well established that most major cities in the USA are underprepared to meet blood transfusion requirements in the event of an MCI. The South Texas Whole Blood Consortium sought to rectify this and vowed to be prepared to provide low-titer type O-positive whole blood (LTOWB) and blood components to the people who need it, where and when they need it. This system was able to transport 25 units of LTOWB and packed red blood cells almost 100 miles away to Uvalde Memorial Hospital within just 67 minutes after notification of an active shooter. The regional consortium has created a pool of dedicated LTOWB donors affectionately called Heroes in Arms who can be called on to instantly augment locoregional blood supply. Previously pregnant women have historically been excluded from donating plasma and LTOWB due to the increased rates of human leukocyte antigen (HLA) antibody (Ab) positivity, which is associated with transfusion-related acute lung injury. However, the South Texas Blood and Tissue Center in San Antonio had a large number of qualified, previously pregnant females desire to join the Heroes in Arms program prompting them to assess the feasibility of providing HLA Ab testing for this demographic and the results were promising. This is the first report of previously pregnant women being included in the pool for donation of LTOWB.
Walking blood bank: a plan to ensure self-sufficiency in an era of blood shortage
Authors: Brigmon Erika Paola , Cirone Justin , Harrell Kelly , Greebon Leslie , Ngamsuntikul Samantha , Mendoza Adriene , Epley Eric , Eastridge Brian , Nicholson Susannah , Jenkins Donald H
Published: January 2024

Mass casualty incidents and massive transfusion requirements continue to plague the USA with hemorrhage remaining the number one cause of death in trauma. The unfortunate reality of numerous mass shootings in Southwest Texas has led to the need for a way in which to provide blood during these events as rapidly as it is required. Multiple agencies within the Southwest Texas system have united to help provide this life-saving blood to people when they need it most. This effort began with the development of a system for safe, efficient, and now widespread use of whole blood in the region. After demonstrating the success of delivering large quantities of blood during the Uvalde shooting, we have begun to develop a walking blood bank that is similar to what the miliary uses on the battlefield. The concept behind this initiative is to have a cohort of whole blood donors who are preselected to join the program which is now dubbed ‘Heroes in Arms’. These donors will be called upon to donate whole blood during a massive transfusion event. Their blood will be rapidly screened prior to transfusion to the patient. This blood will still undergo the normal rigorous testing and, should any potentially transmissible diseases by discovered post-transfusion, the individual who received that product will be treated accordingly. Given the low rate of transmissible disease among this preselected population, combined with rapid screening prior to transfusion, the risk of a person receiving a transmissible disease is insignificant in comparison to the benefit of having blood to transfuse during hemorrhage. This model is a promising collaborative effort to provide in a timely and sufficient blood product in cases of major need which will consequently minimize the number of traumatically injured civilian patients who die from hemorrhage.
Expanding single-trace YMS amplitudes with gauge-invariant coefficients
Authors: Wei Fang-Stars , Zhou Kang
Published: January 2024

In this note, we use the new bottom-up method based on soft theorems to recursively construct the expansion of single-trace Yang–Mills-scalar amplitudes. The resulting expansion manifests the gauge invariance for any polarization carried by external gluons, as well as the permutation symmetry among external gluons. Our result is equivalent to that found by Clifford Cheung and James Mangan via the so-called covariant color–kinematics duality approach.
Everything you always wanted to know about how causal set theory can help with open questions in cosmology, but were afraid to ask
Authors: Yazdi Yasaman K.
Published: January 2024

In this paper, we briefly survey open questions in cosmology that either have been or could potentially be addressed with the help of the causal set theory approach to quantum gravity. Our discussion includes topics ranging from dark matter and dark energy to primordial quantum fluctuations and horizon entropy. By putting together all in one place, these cosmologically relevant directions of work within causal set theory, we hope to impart a bird’s-eye view of this important research theme.
Perinatal Western-style diet exposure associated with decreased microglial counts throughout the arcuate nucleus of the hypothalamus in Japanese macaques
Authors: Papadakis Samantha , Thompson Jacqueline R. , Feczko Eric , Miranda-Dominguez Oscar , Dunn Geoffrey A. , Selby Matthew , Mitchell AJ , Sullivan Elinor L. , Fair Damien A.
Published: January 2024

Prenatal Western-style diet exposure is associated with increased microglial activity in utero. However, we found a potentially neuroprotective reduction in microglia count during early postnatal development. This trajectory could inform the timing of disruptions to microglia-mediated neuronal circuit formation. Additionally, this is the first study in juvenile macaques to characterize the distribution of microglia along the rostral-caudal axis of the arcuate nucleus of the hypothalamus. Nearby neuronal populations may be greater targets during inflammatory insults.
Local vibration induces changes in spinal and corticospinal excitability in vibrated and antagonist muscles
Authors: Amiez Nicolas , Martin Alain , Gaveau Jérémie , Julliand Sophie , Papaxanthis Charalambos , Paizis Christos
Published: January 2024

Spinal disturbances confound the interpretation of excitability changes in motor areas and compromise the conclusions reached by previous studies using only a corticospinal marker for both vibrated and antagonist muscles. The time course recovery suggests that the H-reflex perturbations for the vibrated muscle do not only depend on changes in alpha motoneurons excitability. Local vibration induces neuromuscular changes in both vibrated and antagonist muscles at the spinal and cortical levels.
Comparison of Resonance Modes in Two-Dimensional and Three-Dimensional Microsphere Structures
Authors: Heshmati Sajjad , Rahmani Abolfazl
Published: January 2024

In this article, we have investigated the performance of a resonator in 2D, in an asymmetric form using the physical method and using the Matlab software, we have analyzed it in 3D. According to the simulation results, in asymmetric 2D and 3D structures, whispering gallery modes, or resonances appeared at similar wavelengths for the same radial and polar mode number. Also, the results obtained from the simulations indicated that the resonances of the asymmetric 2D structure would occur at wavelengths close to the wavelengths of 3D structure and the resonance wavelengths for transverse electric (TE) and while transverse magnetic (TM) modes would not change by altering the lateral mode number. Accordingly, 2D structures can be used to obtain resonance wavelengths in microsphere resonators. Achieving results with high accuracy, as well as faster speed offered by smaller meshing volume is one of the advantages of 2D structures in the physical method.