bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrospective examination of risk factors for central line‐associated bloodstream infections in home parenteral nutrition patients from a Queensland tertiary hospital
Authors: Hoey Paris , Roche Douglas , Chapman Paul , Kaushik Vishal , Llewellyn Stacey , Adris Niwansa
Published: November 2024

Background

Central line‐associated bloodstream infections (CLABSIs) are a potential complication for home parenteral nutrition (HPN) patients.

Aim

We sought to analyse risk factors of developing HPN‐related CLABSI and assess CLABSI management in the Australian context.

Methods

A retrospective observational cohort study was conducted on 34 adult patients receiving HPN via a central venous catheter (CVC) at a Queensland tertiary referral centre between 2016 and 2023. Patient charts were reviewed, and Kaplan–Meier analysis was employed to determine associations between characteristics and time to CLABSI in the first CVC using Peto‐Peto Prentice test.

Results

A total of 39 CLABSI episodes occurred in 19 patients. Patients with ≥1 CLABSI used regular opioids more than those without CLABSI (P = 0.016). Fourteen (41%, n = 14/34) patients developed a CLABSI in their first CVC. No patient or line characteristics were found to be predictive of CLABSI in their first CVC. The CLABSI rate was 1.02/1000 catheter days. Most CLABSIs were caused by Enterobacterales (22%, n = 12/55) and Candida sp. (22%, n = 12/55). Empiric antimicrobial therapy was adequate in only 25% (n = 7/28), and the median time to effective antibiotic therapy was 22.7 h (interquartile range 4.8–29.8). There were three successful CVC salvages (8%, n = 3/39).

Conclusions

In this cohort of patients, regular opioid use was associated with increased risk of developing CLABSI. Based on our findings, an empiric antimicrobial regime of vancomycin, cefepime and caspofungin will provide adequate coverage for most HPN‐related CLABSIs in Australian IF units with a similar antimicrobial distribution and resistance pattern.
Racial Disparities in a Teen Pregnancy Prevention Program: Abstinence‐Only Versus a Comprehensive Sexuality Education Program
Authors: Merritt Breanca , Green Jennifer , Sanchez Louisiana Montserrat , Fluhr Janene , Oman Roy F.
Published: November 2024

BACKGROUND

Despite overall declines in risky teen sexual activity, racial and ethnic disparities persist. This study compared abstinence‐only and comprehensive teen pregnancy prevention (TPP) programs to explore the effects of the programs on teen sexual activity‐related outcomes that may differ by race/ethnicity.

METHODS

Program evaluation data were collected from 7th‐grade students in comprehensive (N = 3244) and abstinence‐only (N = 3172) TPP programs. Differences between outcomes by TPP program were analyzed using chi‐square tests and logistic regression for each racial/ethnic group.

RESULTS

Black and Hispanic students were significantly less likely to indicate positive attitudes, intentions, and behaviors at baseline. Only white students significantly improved in both programs from pre‐ to post‐assessment. Native American students in the abstinence‐only program were significantly less likely than Native American students in the comprehensive sexuality programming to improve from pre‐ to post‐assessment regarding male sexuality, refusal skills, sex and teen norms, and sexual abstinence.

CONCLUSIONS

The findings suggest that youth of diverse racial/ethnic backgrounds do not enter TPP programs with similar attitudes, intentions, or behavior regarding appropriate sexual behavior and that the impact of such programs also may vary by race and ethnicity.
Clinical outcomes and profitability following rural hospital mergers and acquisitions
Authors: Tsai Thomas C. , Duggan Ciara E. , Zheng Jie , Orav E. John , Epstein Arnold M.
Published: November 2024

Purpose

As US hospital markets become increasingly consolidated, empirical evidence is needed on the clinical and financial impacts of mergers on care provided by rural hospitals. We identified characteristics of rural hospitals that underwent mergers or acquisitions and examined changes in profitability, clinical outcomes, and patient experience at acquired versus non‐acquired rural hospitals.

Methods

We identified 145 rural US hospitals that underwent merger or acquisition between 2009 and 2014 and 906 rural non‐acquired control hospitals. For each acquisition year, we used a difference‐in‐differences design to compare that year's acquired hospitals to a randomly chosen set of non‐acquired controls. Adjusted linear regression models were used to assess the relationship between acquisition and changes in profitability, patient experience, and clinical outcomes.

Findings

Compared to non‐acquired hospitals, acquired hospitals were more likely to be for‐profit (18.6% vs. 4.6%, p<0.001) and tended to have lower total margins (‐1.1% vs. 1.2%; p<0.05) despite higher average clinical volumes. Changes in acquired hospitals’ total margins, patient satisfaction, and risk‐adjusted 30‐day mortality rates were not different than changes among control hospitals. However, acquisition was associated with lower improvement in 30‐day risk‐adjusted readmission rates (‐0.58 percentage point [p.p.] difference‐in‐differences, 95% confidence interval ‐0.88 to ‐0.28 p.p., p<0.001).

Conclusions

Overall, mergers or acquisitions of rural hospitals were not associated with significant improvements in profitability, clinical outcomes, or patient experience. Policymakers may need to closely monitor rural hospital mergers in order to balance preserving access for rural patients with the consequences of health care consolidation.
Long‐term monitoring reveals sex‐ and age‐related survival patterns in griffon vultures
Authors: Gómez‐López G. , Martínez F. , Sanz‐Aguilar A. , Carrete M. , Blanco G.
Published: November 2024

Survival is a key demographic parameter for long‐lived bird species as it strongly influences their population dynamics and persistence. In recent decades, several studies have focused on unravelling differential patterns of survival by sex or age in bird populations, as each group may be affected by different ecological and anthropogenic pressures. Vultures are a highly threatened group of birds where age‐ and especially sex‐dependent survival patterns have been understudied, and therefore, obtaining robust estimates and understanding which factors modulate them is crucial for developing management and conservation strategies. Here, we used a long‐term dataset (1990–2023) from a wild colony of griffon vultures Gyps fulvus in central Spain and a capture‐mark‐recapture framework to address potential sex‐ and age‐mediated patterns of apparent survival and resighting. Resighting probabilities were lower for individuals in their first year of life than for older individuals. Apparent survival probabilities increased with age and were generally higher for males than for females, particularly in subadults. Disentangling whether an unequal survival between sexes is due to female‐biased dispersal or to true mortality is necessary to understand population dynamics and to be able to implement adequate conservation management actions. Our research underlines the importance of considering sex and age interactions in demographic analyses of long‐lived, usually threatened species.
Caudal block, high flow oxygen insufflation and dexmedetomidine sedation for inguinal hernia surgery in infants—A prospective evaluation of an alternative anesthesia technique
Authors: Taverner Fiona J. , Burgoyne Laura L. , Scott‐Weekly Ross , van der Griend Benjamin F. , Chooi Cheryl S. L. , Khurana Sanjeev , Humphreys Susan R. , Leemaqz Shalem , Morris Scott , Roberts Claire T. , von Ungern‐Sternberg Britta S.
Published: November 2024

Background

Inguinal hernia repair is the most common operation in infants, with well recognized anesthetic and perioperative risks. The aim was to investigate if the combination of caudal block, high‐flow nasal oxygen insufflation and intravenous dexmedetomidine sedation is suitable for infants undergoing inguinal hernia surgery.

Methods

A prospective multicenter international study was performed in three centers in Australia and New Zealand. Fifty infants less than 64 weeks post‐menstrual age undergoing inguinal hernia surgery were enrolled. Exclusion criteria were any condition that contraindicated the use of the anesthesia technique. The technique included intravenous dexmedetomidine with a loading dose of 1–2 mcg/kg over 10 min and maintenance of 0.2–3 mcg/kg/h, high‐flow nasal oxygen insufflation 2 L/kg/min with an oxygen blender, and a caudal block using 1 mL/kg 0.2% ropivacaine. The primary outcome was the successful completion of surgery without conversion to general anesthesia.

Results

Completion of surgery with the technique was successful in 41/50 (82%) infants. Care was provided by 22 anesthesiologists and 11 surgeons. Infants had a low incidence of intraoperative complications, including apnea [1 (2.4%)], bradycardia [2 (4.9%)], hypotension [2 (4.9%)], and desaturation [1 (2.4%)]. Postoperative complications included apnea [3 (7.3%)], bradycardia [3 (7.3%)], hypotension [3 (7.3%)], desaturation [4 (9.8%)]. No infants were intubated in the first 24 h postoperatively.

Conclusion

Caudal block, high‐flow nasal oxygen insufflation and intravenous dexmedetomidine sedation is a potential alternative to general anesthesia for infant inguinal hernia surgery with a low rate of complications in this small cohort of infants.
Comparative transcriptome analysis highlights resistance regulatory networks of maize in response to Exserohilum turcicum infection at the early stage
Authors: Li MingRui , Qi Xin , Li Dan , Wu Zhiqiang , Liu Meiyi , Yang Weiguang , Zang Zhenyuan , Jiang Liangyu
Published: November 2024

Northern corn leaf blight, caused by Exserohilum turcicum (E. turcicum), is one of the most destructive diseases in maize, leading to serious yield losses. However, the underlying molecular mechanisms of E. turcicum infection response in maize remain unclear. In this study, we performed comparative transcriptome analysis in resistant maize inbred line J9D207 (R) and susceptible maize inbred line PH4CV (S) after infecting with E. turcicum at 0 h, 24 h and 72 h, respectively. Compared with 0 h, 9656 (24 h) and 8748 (72 h) differentially expressed genes (DEGs) were identified in J9D207, and 7915 (24 h) and 7865 (72 h) DEGs were identified in PH4CV. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that alpha‐linolenic acid metabolism, benzoxazinoid biosynthesis, flavonoid biosynthesis and phenylpropanoid biosynthesis might be involved in maize defense reactions. Some DEGs coded for transcription factors, such as MYB‐related, ERF, NAC, bZIP, bHLH and WRKY families, which indicated that they may participate in resistance against E. turcicum. In addition, DEGs involved in SA, JA, ABA and ET signaling pathways were revealed. Moreover, 75 SOD activity‐related genes and 421 POD activity‐related genes were identified through weighted gene co‐expression network analysis (WGCNA), respectively. These results provide a novel insight into the resistance mechanism of maize in response to E. turcicum inoculation.
Identification of cambium stem cell factors and their positioning mechanism
Authors: Eswaran Gugan , Zhang Xixi , Rutten Jacob Pieter , Han Jingyi , Iida Hiroyuki , López Ortiz Jennifer , Mäkilä Riikka , Wybouw Brecht , Planterose Jiménez Benjamin , Vainio Leo , Porcher Alexis , Leal Gavarron Marina , Zhang Jing , Blomster Tiina , Wang Xin , Dolan David , Smetana Ondřej , Brady Siobhán M. , Kucukoglu Topcu Melis , ten Tusscher Kirsten , Etchells J. Peter , Mähönen Ari Pekka
Published: November 2024

Wood constitutes the largest reservoir of terrestrial biomass. Composed of xylem, it arises from one side of the vascular cambium, a bifacial stem cell niche that also produces phloem on the opposing side. It is currently unknown which molecular factors endow cambium stem cell identity. Here we show that TRACHEARY ELEMENT DIFFERENTIATION INHIBITORY FACTOR (TDIF) ligand–activated PHLOEM INTERCALATED WITH XYLEM (PXY) receptors promote the expression of CAMBIUM-EXPRESSED AINTEGUMENTA-LIKE (CAIL) transcription factors to define cambium stem cell identity in the
Arabidopsis
root. By sequestrating the phloem-originated TDIF, xylem-expressed PXY confines the TDIF signaling front, resulting in the activation of CAIL expression and stem cell identity in only a narrow domain. Our findings show how signals emanating from cells on opposing sides ensure robust yet dynamically adjustable positioning of a bifacial stem cell layer.
Revisiting the mid-Pleistocene transition ocean circulation crisis
Authors: Hines Sophia K. V. , Charles Christopher D. , Starr Aidan , Goldstein Steven L. , Hemming Sidney R. , Hall Ian R. , Lathika Nambiyathodi , Passacantando Mollie , Bolge Louise
Published: November 2024

The mid-Pleistocene transition (MPT) [~1.25 to 0.85 million years ago (Ma)] marks a shift in the character of glacial-interglacial climate (

1

,

2

). One prevailing hypothesis for the origin of the MPT is that glacial deep ocean circulation fundamentally changed, marked by a circulation “crisis” at ~0.90 Ma (marine isotope stages 24 to 22) (

3

). Using high-resolution paired neodymium, carbon, and oxygen isotope data from the South Atlantic Ocean (Cape Basin) across the MPT, we find no evidence of a substantial change in deep ocean circulation. Before and during the early MPT (~1.30 to 1.12 Ma), the glacial deep ocean variability closely resembled that of the most recent glacial cycle. The carbon storage facilitated by developing deep ocean stratification across the MPT required only modest circulation adjustments.
Total synthesis of (−)-cylindrocyclophane A facilitated by C−H functionalization
Authors: Bosse Aaron T. , Hunt Liam R. , Suarez Camila A. , Casselman Tyler D. , Goldstein Elizabeth L. , Wright Austin C. , Park Hojoon , Virgil Scott C. , Yu Jin-Quan , Stoltz Brian M. , Davies Huw M. L.
Published: November 2024

(−)-Cylindrocyclophane A is a 22-membered C
2
-symmetric [7.7]paracyclophane that bears bis-resorcinol functionality and six stereocenters. We report a synthetic strategy for (−)-cylindrocyclophane A that uses 10 C−H functionalization reactions, resulting in a streamlined route with high enantioselectivity and efficiency (17 steps). The use of chiral dirhodium tetracarboxylate catalysis enabled the C–H functionalization of primary and secondary positions, which was complemented by palladium-catalyzed C(sp
2
)–C(sp
2
) cross-couplings, resulting in the rapid formation of the macrocyclic core and all stereocenters with high regio-, diastereo-, and enantioselectivity. The use of a late-stage palladium-catalyzed fourfold C(sp
2
)–H acetoxylation installed the bis-resorcinol moieties. This research exemplifies how multilaboratory collaborations can produce substantial modernizations of complex total synthesis endeavors.
Regulated N-glycosylation controls chaperone function and receptor trafficking
Authors: Ma Mengxiao , Dubey Ramin , Jen Annie , Pusapati Ganesh V. , Singal Bharti , Shishkova Evgenia , Overmyer Katherine A. , Cormier-Daire Valérie , Fedry Juliette , Aravind L. , Coon Joshua J. , Rohatgi Rajat
Published: November 2024

One-fifth of human proteins are N-glycosylated in the endoplasmic reticulum (ER) by two oligosaccharyltransferases, OST-A and OST-B. Contrary to the prevailing view of N-glycosylation as a housekeeping function, we identified an ER pathway that modulates the activity of OST-A. Genetic analyses linked OST-A to HSP90B1, an ER chaperone for membrane receptors, and CCDC134, an ER luminal protein. During its translocation into the ER, an N-terminal peptide in HSP90B1 templates the assembly of a translocon complex containing CCDC134 and OST-A that protects HSP90B1 during folding, preventing its hyperglycosylation and degradation. Disruption of this pathway impairs WNT and IGF1R signaling and causes the bone developmental disorder osteogenesis imperfecta. Thus, N-glycosylation can be regulated by specificity factors in the ER to control cell surface receptor signaling and tissue development.
Analysis methods for large-scale neuronal recordings
Authors: Stringer Carsen , Pachitariu Marius
Published: November 2024

Simultaneous recordings from hundreds or thousands of neurons are becoming routine because of innovations in instrumentation, molecular tools, and data processing software. Such recordings can be analyzed with data science methods, but it is not immediately clear what methods to use or how to adapt them for neuroscience applications. We review, categorize, and illustrate diverse analysis methods for neural population recordings and describe how these methods have been used to make progress on longstanding questions in neuroscience. We review a variety of approaches, ranging from the mathematically simple to the complex, from exploratory to hypothesis-driven, and from recently developed to more established methods. We also illustrate some of the common statistical pitfalls in analyzing large-scale neural data.
A two-faced membrane channel
Authors: Yang Xing , Jandaghian Mohammad Hossein
Published: November 2024

Contrasting surface properties activate a feedback loop system for a complete oil-and-water separation
Collateral effects of pandemic control
Authors: Rohani Pejman , Bahl Justin
Published: November 2024

The response to COVID-19 altered global dispersal of influenza viruses
A case for altruistic cities
Authors: Bai Xuemei
Published: November 2024

Intercity cooperation appears to be thriving, as evidenced by the growing number of regional and international intercity networks. However, a closer examination of these interactions reveals that their scope and depth are often limited, with information sharing, delegation visits, and mutual learning being the most common forms of engagement. Consequently, cities are frequently perceived as participating in intercity networks to “add flowers to the brocade”—a gesture of enhancement—rather than to achieve any substantial improvement in their functional capacities.
Effects of immunoproteasome inhibition on acute respiratory infection with murine hepatitis virus strain 1
Authors: Steigmann Jacob C. , Zhou Xiaofeng , Suttenberg Lauren N. , Salman Irha , Rehmathullah Zainab F. , Weinberg Jason B.
Published: November 2024

The immunoproteasome (IP) is a predominantly inducible component of the ubiquitin proteasome system that plays key roles in multiple aspects of immune function, inflammation, and protein homeostasis. We used murine hepatitis virus strain 1 (MHV-1), a mouse coronavirus, to define the role of IP activity during acute coronavirus respiratory infection. Expression of the β5i subunit of the IP and cytokines that induce IP activity, including IFN-γ, TNF-α, and IFN-β, increased in lungs and livers of CH3/HeJ mice following intranasal infection with MHV-1. IP inhibition using ONX-0914 did not affect MHV-1 replication in bone marrow-derived dendritic cells
in vitro
. IP inhibition
in vivo
exacerbated virus-induced weight loss and mortality but had no effect on virus replication in lungs or livers. IP inhibition had minimal effect on virus-induced pulmonary inflammation but led to substantially increased liver pathology, including greater upregulation of pro-inflammatory cytokines and histological evidence of inflammation and necrosis. Those findings were associated with evidence of increased endoplasmic reticulum stress although not with accumulation of ubiquitinated protein. Our results indicate that the IP is a protective host factor during acute MHV-1 infection.

IMPORTANCE

Inflammatory responses triggered by acute infection by respiratory viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drive morbidity and mortality. Infection of mice with murine hepatitis virus strain 1 (MHV-1), a mouse coronavirus, is a useful model to study the pathogenesis of coronavirus respiratory infections. The immunoproteasome is an inducible component of the ubiquitin proteasome system that is poised to contribute to multiple aspects of immune function, inflammation, and protein homeostasis during an infection. We used the MHV-1 model to define the role of the immunoproteasome in coronavirus pathogenesis. We found that immunoproteasome subunit expression increases in the lungs and the liver during acute MHV-1 respiratory infection. Inhibition of immunoproteasome activity did not affect MHV-1 replication but increased MHV-1-induced weight loss, mortality, and inflammation in lungs and livers. Thus, our findings indicate that the immunoproteasome is a critical protective host factor during coronavirus respiratory infection.
Identification of stimuli that enhance human herpesvirus 6A (HHV-6A) replication and reconstitution
Authors: Reich Jana , Serdar Dilan , Weißmann Ann-Christin , Kaufer Benedikt B.
Published: November 2024

Despite the availability of bacterial artificial chromosome (BAC) systems for human herpesvirus 6A (HHV-6A), reconstitution of infectious viruses is very challenging and time consuming. In this study, we developed approaches to improve the reconstitution process and enhance virus replication to overcome these technical challenges. Using dimethyl sulfoxide and exonuclease V, we significantly increased the efficiency of BAC transfections into JJHan T cells. We tested several stimulation strategies to enhance lytic replication and identified mitogens and glucocorticoids that, in combination, improve virus replication. In addition, we demonstrated that the interferon-mediated response impairs virus reconstitution and that the JAK1/JAK2 inhibitor ruxolitinib resulted in an immense improvement. Furthermore, hypoxia-inducible factor 1 alpha stabilization by IOX2 drastically accelerated virus reconstitution, indicating that the hypoxic response is a crucial regulator of HHV-6A replication. Our study sheds light on strategic approaches that improve replication and reconstitution of this ubiquitous human herpesvirus.

IMPORTANCE

HHV-6A is a betaherpesvirus that infects a wide range of human tissues and establishes lifelong latency in the host. Its reactivation has been implicated in several diseases, including multiple sclerosis, encephalitis, myocarditis, and chronic fatigue syndrome, although its pathogenetic role remains elusive. The efficacy of common antiviral drugs is limited, and no specific drugs target HHV-6A infection. The data of this study shed light on stimuli and potential pathways that influence HHV-6A replication and reconstitution. Our strategies not only simplify virus propagation and reconstitution to study HHV-6A biology but also provide the basis for the development of therapeutic strategies.
Re-expansion pulmonary oedema: two case reports and review of the current literature
Authors: Kwan How Foong , Ng Boon Hau , Nik Abeed Nik Nuratiqah , Ban Andrea Yu-Lin
Published: November 2024

Re-expansion pulmonary oedema (RPE) is an uncommon complication that occurs when a collapsed lung suddenly re-expands, resulting in an osmotic shift of fluid from the blood vessels into the air spaces within the lungs. This condition can develop following thoracocentesis or intercostal chest drainage. We report two cases of RPE that developed after varying volumes of pleural drainage and at different times. Both patients responded well to non-invasive ventilation and hydrocortisone, making a full recovery. Early detection is crucial as RPE is associated with higher mortality rates, but a positive prognosis is attainable with prompt identification and intervention.
Incomplete superficial palmar arch and gangrene in the hand in a neonate with DOCK6 mutation
Authors: Naaz Aisha , Ahmad Shahbaj , Patra Saikat , Gupta Girish
Published: November 2024

The superficial palmar arch, formed by the branches of radial and ulnar arteries, supplies the blood to the hand. In cases of incomplete superficial palmar arch, the radial and ulnar branches fail to join. Any compromise to the ulnar blood supply in an incomplete superficial palmar arch can lead to subsequent gangrene. This baby presented with blackish discolouration and gangrene on the left hand, primarily affecting the little, ring, middle and index fingers. Timely intervention with antibiotics and heparinisation led to salvage of the ring, middle and index fingers, while the little finger underwent auto-amputation. On clinical exome sequencing, the baby was found to have DOCK6 mutation. This case highlights the importance of vascular involvement in DOCK6 mutation and the need for careful evaluation and management in cases of incomplete superficial palmar arch.
SGLT-2 inhibitors and mortality among patients with heart failure with reduced ejection fraction: linked database study
Authors: Svanström Henrik , Mkoma George Frederick , Hviid Anders , Pasternak Björn
Published: November 2024

Objective

To investigate the association between sodium-glucose cotransporter-2 (SGLT-2) inhibitor use and risk of all cause mortality among patients with heart failure with reduced ejection fraction.

Design

Linked database study.

Setting

National registers in Denmark, July 2020 to June 2023.

Participants

Patients with heart failure, aged ≥45 years, with left ventricular ejection fraction ≤40%.

Main outcome measures

The primary outcome was all cause mortality comparing initiation and continued treatment with SGLT-2 inhibitors versus continued treatment with other standard-of-care heart failure drugs and non-use of SGLT-2 inhibitors; secondary outcomes were the composite of cardiovascular mortality or admission to hospital with heart failure and its individual components. Hazard ratios were estimated using Cox regression adjusted using inverse probability of treatment weighting based on propensity scores.

Results

The study included 6776 patients who started SGLT-2 inhibitors (79% dapagliflozin; 21% empagliflozin) and 14 686 patients who remained on other standard-of-care heart failure drugs and did not use SGLT-2 inhibitors. Most SGLT-2 inhibitor users were male (70%), the mean age was 71.2 (standard deviation 10.6) years, and 20% had type 2 diabetes. During follow-up, 374 deaths occurred among SGLT-2 inhibitor users (incidence rate 5.8 per 100 person years) and 1602 among non-users (8.5 per 100 person years). The weighted hazard ratio for all cause mortality was 0.75 (95% confidence interval 0.66 to 0.85); the weighted incidence rate difference was −1.6 (95% confidence interval −2.5 to −0.8) per 100 person years. Secondary outcomes showed a weighted hazard ratio of 0.94 (0.85 to 1.04) for cardiovascular mortality or hospital admission with heart failure, 0.77 (0.64 to 0.92) for cardiovascular mortality, and 1.03 (0.92 to 1.15) for hospital admission with heart failure. The weighted hazard ratios for all cause mortality were consistent in patients with and without diabetes (0.73 (0.58 to 0.91) and 0.73 (0.63 to 0.85); P=0.99).

Conclusions

In this large database study among patients with heart failure with reduced ejection fraction, SGLT-2 inhibitor use was associated with a 25% lower risk of all cause mortality, supporting their effectiveness in routine clinical practice.
Regulation (EU) 536/2014 and the role of ethics committees: a proposal for a review system model
Authors: Riva Luciana , Petrini Carlo
Published: November 2024

Independent ethics committees play an important role in clinical trials as well as in all health-related research. Internationally, the national laws of the individual countries have guided their local development and organisation over the decades. Directive 2001/20/EC of the European Parliament and of the Council explicitly recognised the ethics committees’ duty to protect the rights, safety and well-being of human subjects involved in trials and to provide public assurance of that protection. Regulation (EU) 536/2014, which repealed the aforesaid directive, provides that a clinical trial must be subjected to scientific and ethical review, without specifically defining what they consist in. The divide between the evaluation of the ethical value and the scientific value of a study is very faint and, for some, it may even appear a meaningless distinction. While Regulation (EU) 536/2014 requires Member States to ensure that ethics committees are involved in the assessment process within their national territory, it does not require such ethical assessment to be binding. This article proposes a possible system for interaction between ethics committees and local regulatory authorities in which the meaning and purpose of the ethical assessment are conceptually clearly defined and not narrow.
Cost-effectiveness analysis of trifluridine/tipiracil in the treatment of heavily pretreated metastatic gastric cancer from the perspective of Chinese healthcare system
Authors: Ying Ting , Xia Runan , Zhang Yuanyuan , Dai Jiahui , Wang Yadong , Xie Xuefeng
Published: November 2024

Objectives

The aim of this study was to evaluate the cost-effectiveness of trifluridine/tipiracil (FTD/TPI) for heavily pretreated metastatic gastric cancer from the perspective of the Chinese healthcare system.

Designs

Based on the overall survival and progression-free survival (PFS) data from the Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS) trial (NCT02500043), a three-state Markov model (PFS, progressed disease and death) was constructed to analyse the cost-effectiveness of FTD/TPI compared with the placebo in heavily pretreated metastatic gastric cancer. Cost and utility were from pricing records and the literature. The model was simulated for 5 years with monthly cycles. Costs and health outcomes were discounted by 5%. We then conducted sensitivity analyses to evaluate the robustness of the parameters. The model results were from the Chinese healthcare system.

Outcome measures

The output results were the quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER).

Results

According to the model results, FTD/TPI generated an additional cost of US$26 855.66 and 0.88 QALYs compared with the placebo. ICER of FTD/TPI compared with the placebo was US$30 494.89 per QALY. Sensitivity analyses revealed that the utility value of the PFS stage and FTD/TPI adverse event costs were the main influencing parameters, and the results were stable. At a threshold of three times per capita gross domestic product of China (US$35 559.34 in 2022), the probability of FTD/TPI being cost-effective compared with placebo was 99.2%.

Conclusion

From the perspective of the Chinese healthcare system, FTD/TPI is a more cost-effective option compared with the placebo for the treatment of heavily pretreated metastatic gastric cancer in patients who have received at least two prior advanced treatment regimens.

Trial registration number

The Chinese population registered in the Chinese Clinical Trial Registry (ChiCTR2400080940) and clinical trial (NCT05029102).
Avoiding anti-inflammatories: a randomised controlled trial testing the effect of an eHealth information package on primary healthcare patient medication knowledge and behaviour in Aotearoa New Zealand
Authors: Leitch Sharon , Zeng Jiaxu , Smith Alesha , Stokes Tim
Published: November 2024

Background

Patient medication knowledge and health literacy affect patient safety. Taking angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin II receptor blockers (ARBs), with diuretics and non-steroidal anti-inflammatory medications (NSAIDs) is nephrotoxic. Patients may not know of this risk. An eHealth information package was developed to inform patients at risk of taking this combination of medication.

Objective

To assess the impact of the eHealth information package on patient knowledge and behaviour.

Design

This was a two-arm, parallel, randomised control trial. A knowledge quiz and NSAID use survey were undertaken at baseline, and repeated after two weeks. The intervention group accessed the information package after completing the baseline assessment. The control group received normal care.

Setting and participants

Primary healthcare patients prescribed an ACE-i or ARB plus a diuretic in Aotearoa New Zealand.

Intervention

A novel eHealth information package was made available to participants in the intervention group consisting of a downloadable PDF and online education activity. This took approximately 15 min for participants to complete.

Primary outcome measures

Change in knowledge scores and in NSAID use between pre-intervention and post-intervention assessment.

Secondary outcome measures

Self-reported patient intentions regarding future NSAID use

Results

The 201 participants who completed the study had high baseline NSAID medication knowledge, which did not substantially change at follow-up. The intervention group had a 0.35 (95% CI: -0.18, 0.88) higher knowledge score than the control group. NSAID use decreased over the study; the intervention group had 62% lower odds of NSAID use at follow-up assessment compared with the control group (OR=0.37, 95% CI: 0.14, 1.03). There was no substantial difference between study groups at follow-up for self-reported action. The information package was considered acceptable and useful.

Conclusion

This tailored eHealth information package may reduce NSAID use in patients at increased risk from NSAID-related harm.

Trial registration number

Australian New Zealand Clinical Trial Registry (ACTRN:12622001132730).
Anxiety, depression and access to mental health services among internally displaced persons in Mogadishu, Somalia: a cross-sectional survey
Authors: Dahie Hassan Abdullahi , Osman Mohamed Abdullahi , Jimale Yusuf Ali , Mohamud Falis Ibrahim , Hussein Hamdi Ahmed , Alasow Mohamed Osman , Osman Abukar Abdi , Abdullahi Abdirahman Mohamed
Published: November 2024

Objective

The study aims to evaluate anxiety and depression levels and access to mental health services among internally displaced persons (IDPs) in Mogadishu, Somalia.

Design

A community-based, cross-sectional survey was carried out in IDP camps. Face-to-face interviews were conducted using a modified Hospital Anxiety and Depression Scale. Data were analysed using SPSS V.25.0, incorporating univariate and logistic regression analyses.

Setting

The study was conducted in 10 IDP camps located in the districts of Daynile and Kahda in the Banadir region of Somalia between November and December 2023.

Participants

The study included 522 randomly sampled individuals aged 18–70 years living in the selected IDP camps.

Results

The study revealed high prevalence rates of anxiety (43.7%) and depression (35.8%) among IDPs in the selected districts. Of those with anxiety, 54% were categorised as borderline cases and 46% as severe cases. Similarly for depression, 72.7% were classified as borderline cases and 27.3% as severe cases. Significant associations were found between anxiety symptoms and variables such as camp residence (OR: 3.872, 95% CI 2.333 to 6.424), female gender (OR: 2.387, 95% CI 1.604 to 3.552), young age (OR: 6.319, 95% CI 4.309 to 9.267), marriage contract (OR: 4.569, 95% CI 2.850 to 7.325), lack of education (OR: 1.92, 95% CI 1.349 to 2.737) and past experiences of trauma (OR: 5.207, 95% CI 3.274 to 8.281). Depressive symptoms were significantly associated with younger age (OR: 1.536, 95% CI 1.069 to 2.208), lack of formal education (OR: 1.661, 95% CI 1.153 to 2.395) and history of trauma (OR: 3.695, 95% CI 2.529 to 5.400). Additionally, the study highlighted a grave shortage of mental health and psychosocial support (MHPSS) services. User evaluations of MHPSS services varied, indicating room for improvement.

Conclusion

The study revealed elevated levels of anxiety and depression among IDPs in the districts of Kahda and Daynile in the Banadir region of Somalia, underscored by a critical shortage of MHPSS services, emphasising the need for tailored mental health interventions.
Efficacy of an mHealth intervention to support pain self-management and improve analgesia in patients with rib fractures: protocol for a randomised controlled trial
Authors: Ashton-James Claire Elizabeth , Doane Matthew , McNeilage Amy Gray , Gholamrezaei Ali , Glare Paul , Finniss Damien
Published: November 2024

Introduction

In light of the risks of over-reliance on opioid analgesia during recovery from rib fractures, there is increased interest in the efficacy of non-pharmacological approaches to pain management. This paper describes the protocol for a double-blind randomised controlled trial to evaluate the efficacy of an mHealth intervention for reducing pain intensity, pain-related distress and opioid use during early recovery from rib fractures.

Methods and analysis

Adults (N=120) with isolated rib fractures will be recruited within 24 hours of admission to a large public hospital in Sydney, Australia (single site), and randomised (1:1 allocation) to an intervention or active control group. Clinicians, participants and statisticians will be blind to participants’ group allocation. The intervention (PainSupport) consists of a brief pain self-management educational video, followed by twice daily supportive Short Message Service (SMS) text messages for 14 days. Participants in the active control group receive the same video but not the supportive text messages. Participants in both groups continue to receive usual care throughout the trial. The primary outcome will be self-reported pain intensity on respiration measured using a Numerical Rating Scale. Secondary outcomes will include opioid use, pain-related distress, adherence to behavioural pain management strategies and the acceptability and feasibility of the intervention. Participants will complete questionnaires at baseline and then on days 1–7 and day 14 of the trial. A feedback survey will be completed at the end of the trial (day 15). Linear mixed models will be used to evaluate the main effect of the group on the primary and secondary outcomes and to explore differences between outcome trends recorded over the trial. Analyses will be based on the intention-to-treat principle to minimise bias secondary to missing data or dropouts.

Ethics and dissemination

The study protocol has been reviewed and approved by the Northern Sydney Local Health District Human Research Ethics Committee (Australia). Informed consent is a requirement for participation in the study. Study results will be published in peer-reviewed journals and presented at scientific and professional meetings.

Trial registration number

ACTRN12623000006640.
Association between weight and body composition changes with falls risk in the Malaysian Elders Longitudinal Research (MELoR) study
Authors: Hashim Nurul Nabilah Akmal , Mat Sumaiyah , Myint Phyo Kyaw , Kioh Sheng Hui , Delibegovic Mirela , Chin Ai-Vyrn , Kamaruzzaman Shahrul Bahyah , Hairi Noran Naqiah , Khoo Selina Phaik Kin , Tan Maw Pin
Published: November 2024

Objective

Both changes in body composition and increased fall risk occur with increasing age. While weight management may be considered a component of falls prevention, the long-term consequences of changes in weight, however, remain uncertain. This prospective study aimed to evaluate the relationship between weight and body composition changes over 5 years with fall occurrence.

Design

Prospective cohort study.

Setting

Community-dwelling older adults interviewed at baseline (2013–2016) and follow-up (2020–2022) as a part of the Malaysian Elders Longitudinal Research study were included.

Participants

Participants who attended face-to-face follow-up visits.

Primary and secondary outcome measures

Fall occurrence over 12 months preceding the follow-up visit was determined. Anthropometric, bioimpedance analysis and physical performance measurements were obtained at both time points. Participants were categorised into three groups according to changes in weight and body composition using≥5% increase or decrease in weight to determine loss or gain.

Results

Of the 225 participants, aged 71.8±6.8 years, 128 (56.9%) were women. Weight gain was associated with increased fall risk at follow-up compared with stable weight (adjusted rate ratio, aRR (95% confidence interval, CI)=2.86 (1.02–8.02)) following adjustments for age and body mass index (BMI), but this relationship was attenuated by low baseline percentage lean body mass (%LBM) in women. The association was strenghtened after adjusting for age, BMI, and low muscle strength (aRR (95% CI)=2.89 (1.01–8.28)). Weight change did not influence falls risk in men. No difference was observed with changes in percentage body fat and %LBM over time with fall occurrence for both genders.

Conclusion

Lower baseline lean body mass influenced the relationship between weight gain and falls longitudinally. Interventions addressing low lean body mass should be considered in the prevention of weight-gain-related falls in older women.
Systematic review and network meta-analysis of non-invasive respiratory support in paediatric patients with acute hypoxaemic respiratory failure: a protocol
Authors: Feng Yan-Dong , Li Yu-Xia , Qin Jin , Yin Yang-Qi , Ling Ji-Zu
Published: November 2024

Introduction

Acute hypoxic respiratory failure (AHRF) is one of the most common causes of admission to paediatric intensive care units (PICUs) around the world, posing a serious health concern for the global community. Non-invasive respiratory support (NRS) is considered effective in reducing mortality and intubation rates in adults. However, it is not yet clear whether NRS is beneficial for children and which NRS modalities are most effective. This network meta-analysis aims to summarise existing evidence and compare the efficacy and safety of different NRS modalities in paediatric patients with acute hypoxaemic respiratory failure.

Methods and analysis

To identify randomised controlled trials, we will perform a systematic search of key databases (Embase, PubMed, CENTRAL, CINAHL Complete and Web of Science) and registered clinical trials (ClinicalTrials.gov, WHO ICTRP and ISRCTN). To ensure the inclusion of the latest literature, an initial pilot search was conducted on 8 July 2024, and an updated search will be conducted after the main research work of this study. AHRF in children treated with NRS will be included. Hospital mortality, intubation rate, treatment failure rate and serious adverse events are critical outcomes closely related to patient-centredness and importance. Two authors will independently select the studies and extract the data. The risk of bias will be assessed using the Cochrane risk of bias tool V.2.0. In order to compare the effects of different NRS modalities, pairwise meta-analysis and network meta-analysis will be conducted using R software. Several subgroup analyses will be conducted, including analyses of different causes of AHRF. We will conduct sensitivity analyses by excluding studies with a high risk of bias and those involving neonates. Using the Grading of Recommendations Assessment, Development and Evaluation methodology, we will assess the certainty of the evidence for the effect estimates of all the outcomes.

Ethics and dissemination

Since this research is a network meta-analysis based on published literature, no formal ethics approval is required. The results will be disseminated through a peer-reviewed journal for publication.

PROSPERO registration number

CRD42024529804.
Systematic review of child maltreatment screening tools used by different occupational groups: a study protocol
Authors: Colley Denise , Seidler Jenny , Rollbühler Philipp , Rasch Lena , Küppers Lisa , Gahr Britta , Mayatepek Ertan , De Bock Freia
Published: November 2024

Background

Child maltreatment (CM) encompasses physical, emotional or sexual abuse, physical or emotional/psychological neglect or intimate partner (or domestic) violence and is associated with adverse cognitive, behavioural, physical and social outcomes that often continue shaping adulthood. The early and valid detection of CM is essential to initiate treatment and intervention as well as to avoid continued violence against the child. Various occupational groups, such as healthcare providers, teachers, social workers, psychotherapists and others, encounter maltreated children in their professional settings. Systematic reviews on instruments to assess suspected CM often report on retrospective measurement via caregiver’s or child’s self-report and are frequently limited to the health system as a setting. The purpose of this Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review is to synthesise the evidence on psychometric properties of instruments to assess suspected CM at the presentation to a broad range of different occupational groups who work with children inside and outside the healthcare system.

Method

A systematic search will be performed in Scopus, PsycInfo, Medline and Web of Science with no limit on the earliest publication until January 2022. Eligibility criteria include studies that investigate psychometric properties of instruments to assess suspected CM in children and adolescents under 18 years by a professional proxy. After the independent screening of studies by two reviewers, quality assessment and data extraction will be performed using an adaptation of the COnsensus‐based Standards for the selection of health Measurement INstruments Risk of Bias checklist, Strengthening the Reporting of Observational Studies in Epidemiology: Explanation and Elaboration report and Downs and Black checklist for measuring study quality. Screening, quality assessment and data extraction will be done using Covidence. The results will be presented in narrative form and, if adequate, a meta-analysis will be performed.

Discussion

This review aims to give an overview of the psychometric properties of different instruments designed to screen suspected CM by professional proxies. The results will be of interest to different occupational groups who need information about methodological quality and characteristics of instruments to make decisions about the best-suited tool for a specific purpose. Furthermore, the results of this review will support the development of novel instruments and might improve the existing ones.

Ethics and dissemination

Ethics approval will not be required. The results of this systematic review will be submitted for publication in a peer-reviewed journal.

PROSPERO registration number

CRD42022297997.