bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibiotic therapy is associated with adverse drug events among older adults with advanced cancer: A cohort study
Authors: Datta Rupak , Han Ling , Doyle Margaret , Allore Heather , Sanft Tara , Quagliarello Vincent , Juthani-Mehta Manisha 
Published: March 2023

Background: Older adults with advanced cancer are exposed to antibiotics but estimates of adverse drug events associated with antibiotic therapy are lacking. Aim: Evaluate the association of antibiotic therapy with adverse drug events in older adults with advanced cancer. Design: Cohort study where the exposure was the ratio of days of therapy of an oral or intravenous antibiotic per patient-day and the outcome was an adverse drug event, defined as cardiotoxicity, hepatotoxicity, nephrotoxicity, Clostridioides difficile infection, or new detection of a multidrug-resistant organism. Setting/participants: Patients aged ⩾65 years with solid tumors from a tertiary care center who received palliative chemotherapy ( n = 914). Results: Mean age was 75 ± 6.6 years, and 52% were female. Common tumors were lung (31%, n = 284) and gastrointestinal (26%, n = 234). Mean time from first course of palliative chemotherapy to index admission was 128 days. Five-hundred thirty (58%) patients were exposed to antibiotics during the index admission; of these, 27% ( n = 143) met standardized criteria for infection. Patients were commonly exposed to cephalosporins (33%, n = 298) and vancomycin (30%, n = 276). Among patients exposed to antibiotics, 35% ( n = 183/530) developed an adverse drug event. In multivariable testing, antibiotic therapy was associated with development of an adverse drug event (>0 to <1 vs 0 days of therapy/patient-day: adjusted odds ratio [aOR] = 1.9; 95% confidence interval [CI], 1.2–2.8; ⩾1 vs 0 days of therapy/patient-day: aOR = 2.1, 95% CI, 1.4–3.0). Conclusion: Antibiotic therapy was independently associated with adverse drug events in hospitalized older adults with advanced cancer. These findings may inform antibiotic decision-making among palliative care providers.
A generalizable strategy for crosslinkable albumin-based hydrogels and application as potential anti-tumor nanoplatform
Authors: Lv WanWan , Yang Kai , Yu Jingwen , Wu Yiqing , Zhang Mengdi , Liu Zichuan , Wang Xixuan , Zhou Jiahui , Ma Haoran , Yi Rongyuan , Chu Hui , Chen Jian 
Published: March 2023

Albumin-based hydrogels have emerged as promising nanoparticle systems for the effective delivery of hydrophobic anticancer drugs. Anti-cancer drugs often cause some adverse effects, such as toxicity and rapid clearance by mononuclear phagocytic systems. Herein, a new strategy of synthesizing N-hydroxysuccinimide (NHS)-activated linker to form crosslinkable albumin-based hydrogels (CABH) is reported. The CABH favored physiochemical characteristics improvement of doxorubicin (Dox) and drug release. The CABH was constructed depending on the crosslinking reaction between NHS activated glycerol and albumin. The size of CABH was approximately 200 nm examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). It was found that the particle size and size distribution of the CABH remained stable in neutral PBS for 1 week. Dox loaded CABH would be controllably released in weak acidic environment verified by in vitro release and in vitro cell imaging. The Dox loaded hydrogel results in significant killing in the case of acidic culture medium. Our work provides a crosslinking method to formulate albumin nanoplatform and improve the size, stability, drug loading capacity and controlled release, which throws light on the potential application in drug delivery.
Barriers to nurses health advocacy role
Authors: Laari Luke , Duma Sinegugu E 
Published: March 2023

Background Speaking up to safeguard patients is a crucial ethical and moral obligation for nurses, but it is also a difficult and potentially dangerous component of nursing work. Health advocacy is gaining impetus in the medical literature, despite being hampered by barriers resulting in many nurses in Ghana remaining mute when faced with advocacy-required situations. We explored situations that thwart nurses from performing their health advocacy role. Research question What would cause nurses to take no action when they witness situations that require them to act as health advocates for their clients or communities? Research Design An inductive, descriptive qualitative design was used to collect and analyse data on barriers that prevent nurses from practising their health advocacy role in Ghana. Individual one-on-one in-depth interviews were conducted using a semi-structured interview guide. The data were analysed using qualitative content analysis. Participants and research context Twenty-four professional nurses and midwives registered with the Nursing and Midwifery Council were recruited from three regional hospitals in Ghana. These public hospitals were chosen from the upper, middle and coastal regions. Ethical considerations The UKZN Ethics Review Committee in South Africa and the GHS Ethics Review Committee in Ghana both gave their approval for this study. Findings Intrapersonal barriers, interpersonal barriers, and structural barriers emerged as major obstacles that nurses experience when performing their health advocacy role. Conclusions Barriers to health advocacy have undermined nurses' ability to function as health advocates and are preventing them from utilising their health advocacy position in nursing practise. Giving nursing students positive role models in the classroom and in the clinic can help them become more effective health advocates.
Thoracoscopic Left Atrial Appendage Exclusion for Atrial Fibrillation Patients Intolerant to Anticoagulation
Authors: Sharaf Omar M. , Falasa Matheus P. , Jones Todd E. , Khanna Anna Y. , Xiang Kun , George Philip , Torres Vilma , Miles William M. , Beaver Thomas M. 
Published: March 2023

Objective: Outcomes associated with isolated epicardial left atrial appendage (LAA) exclusion in atrial fibrillation (AF) patients with a contraindication or intolerance to anticoagulation are not clearly defined, especially in patients with prior stroke. This study evaluated the perioperative safety, medication use, and stroke outcomes for isolated thoracoscopic LAA exclusion for stroke prevention. Methods: A single-center retrospective study was performed of adults undergoing isolated thoracoscopic LAA exclusion with an epicardial exclusion device without a concomitant surgical procedure. Descriptive statistics were performed. Results: Twenty-five patients met the inclusion criteria. The cohort was 68% male ( n = 17) with a mean age of 76.4 ± 6.5 years, a mean preoperative CHA2DS2-VASc score of 4.2 ± 1.4, and a mean preoperative HAS-BLED score of 2.68 ± 1.03. Seventeen patients (68%) had nonparoxysmal AF. There were 11 patients with intolerance of anticoagulation due to intracranial hemorrhage (44%), 6 due to gastrointestinal bleeding (24%), and 4 due to genitourinary bleeding (16%). All procedures were performed thoracoscopically with 100% technical success—the mean LAA stump length was 5.5 ± 2.3 mm on intraoperative transesophageal echocardiography. The median hospital length of stay was 2 (interquartile range [IQR] 1, 6.5) days. The median follow-up time was 430 (IQR 125, 972) days. During follow-up, 1 patient with cerebral angiopathy had temporary neurologic deficits at an outside institution, with brain imaging showing no evidence of ischemic injury. There were no other thromboembolic events over the 38.8 postoperative patient-years examined. All patients were off anticoagulation at last follow-up. Conclusions: This study shows the perioperative safety, technical success, freedom from anticoagulation, and stroke outcomes of isolated thoracoscopic LAA exclusion in patients with AF at high risk for thromboembolic disease.
Hyperprogressive disease during atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma from Japanese real-world practice
Authors: Yumita Sae , Ogasawara Sadahisa , Nakagawa Miyuki , Maruta Susumu , Okubo Tomomi , Itokawa Norio , Iino Yotaro , Obu Masamichi , Haga Yuki , Seki Atsuyoshi , Kogure Tadayoshi , Ishino Takamasa , Ogawa Keita , Fujiwara Kisako , Iwanaga Terunao , Fujita Naoto , Sakuma Takafumi , Kojima Ryuta , Kanzaki Hiroaki , Koroki Keisuke , Inoue Masanori , Kobayashi Kazufumi , Kiyono Soichiro , Nakamura Masato , Kanogawa Naoya , Saito Tomoko , Kondo Takayuki , Nakagawa Ryo , Nakamoto Shingo , Muroyama Ryosuke , Chiba Tetsuhiro , Itobayashi Ei , Atsukawa Masanori , Koma Yoshihiro , Azemoto Ryosaku , Ito Kenji , Mizumoto Hideaki , Kato Jun , Kato Naoya 
Published: March 2023

Abstract
Background
Hyperprogressive disease (HPD) is a phenomenon with greatly accelerated tumor growth and clinical deterioration rates compared to pre-therapy, in patients treated with immune checkpoint inhibitors (ICI). The aim of this study is to clarify the reality of HPD in patients with advanced hepatocellular carcinoma (HCC) who were treated with atezolizumab plus bevacizumab (Atez/Bev) using tumor dynamics.

Methods
Medical records of consecutive patients with advanced HCC who were treated with Atez/Bev were retrospectively reviewed. HPD was defined as a more than two- or fourfold increase in tumor growth rate (TGR) or tumor growth kinetics rate (TGKR) before and after treatment. Overall survival (OS) and baseline characteristics with or without HPD were analyzed.

Results
A total of 85 patients were included in the analysis. When HPD was defined as a twofold of TGR or TGKR, 8 patients (8/85, 9.4%) had HPD and 11 had PD without HPD. A total of 5 patients (5/85, 5.9%) were diagnosed with HPD and 14 with PD without HPD when HPD was defined as a fourfold of TGR or TGKR. No significant difference was observed in the baseline characteristics between HPD and non-HPD.

Conclusion
The prevalence of HPD in patients with advanced HCC treated with Atez/Bev was lower than those treated with nivolumab monotherapy. The HPD mechanism in ICI combined with antibodies targeting vascular endothelial growth factor (VEGF) remains to be elucidated.
Aspartate beta-hydroxylase domain containing 1 as a prognostic marker associated with immune infiltration in skin cutaneous melanoma
Authors: Sun Shiquan , Deng Min , Wen Juan , Chen Xiaoyuan , Xu Jiaqi , Liu Yu , Wan Huanhuan , Wang Jin , Yan Leping , He Yong , Xu Yunsheng 
Published: March 2023

Abstract
Background
Skin cutaneous melanoma (SKCM) is an extremely malignant tumor and accounts for the majority of skin cancer deaths. Aspartate beta-hydroxylase domain containing 1 (ASPHD1) may participate in cancer progression through controlling α-ketoglutarate-dependent dioxygenases. However, its role in skin cutaneous melanoma (SKCM) has not been well studied.

Methods
The gene expression data of ASPDH1 and differentially expressed genes (DEGs) from TCGA and GTEx were evaluated, and verified via the GEO database. Then, we performed GO/KEGG, GSEA, PPI network analysis to analyze the functional implications of the DEGs related to ASPHD1. Then, the association between the ASPHD1 expression and clinical parameters was investigated by Cox regression analysis. Subsequently, the survival time of SKCM patients was evaluated by plotting Kaplan-Meier curves. Moreover, we investigated the correlation between the ASPHD1 expression and lymphocytic infiltration by using the data from TISIDB and TIMER 2.0. Next, we explored the association between ASPHD1 expression and drug sensitivity. Finally, we validate the expression differences by analyzing the results of qPCR, Western blot from human normal epidermal melanocytes and melanoma cells, and immunohistochemistry (IHC) from non-tumor skin as well as melanoma tissues.

Results
The ASPHD1 expression level was significantly upregulated in several cancers, including SKCM especially SKCM-metastasis tissues, and patients with an increased ASPHD1 expression had longer overall survival time than low expression ones. The functional enrichment analysis of ASPHD1-related DEGs showed an association with cell development regulation and tumorigenic pathways. Furthermore, the increased ASPHD1 expression level was associated with the level of immunostimulors, immunoinhibitors, chemokines, and TILs, such as CD4+, CD8+ T cell, mast cell, Th2 cell, and dendritic cell. More interesting, we found that ASPHD1 expression was tightly associated with CTLA4 and CD276 which are immune checkpoint markers. Moreover, the upregulated expression of ASPHD1 exhibited higher IC50 values for 24 chemotherapy drugs, including doxorubicin, and masitinib. Finally, the differential expression of ASPHD1 in SKCM was validated by the results of qPCR, Western blot, and IHC.

Conclusion
The expression of ASPHD1 in SKCM patients is closely related to patient survival. ASPHD1 may participate in the regulation of tumor immune microenvironment. Additionally, it may serve as a prognostic biomarker for SKCM and future in-depth studies are necessary to explore its value.
How public health insurance expansion affects healthcare utilizations in middle and low-income households: an observational study from national cross-section surveys in Vietnam
Authors: Nguyen Chi M. , Nguyen Mai P. , Luc Lan D. P. 
Published: March 2023

AbstractPublic health insurance (PHI) has been implemented with different levels of participation in many countries, from voluntary to mandatory. In Vietnam, a law amendment made PHI compulsory nationwide in 2015 with a tolerance phase allowing people a flexible time to enroll. This study aims to examine mechanisms under which the amendment affected the enrollment, healthcare utilization, and out-of-pocket (OOP) expenditures by middle- and low-income households in this transitioning process.Using the biennial Vietnam Household Living Standard Surveys, the study applied the doubly robust difference-in-differences approach to compare outcomes in the post-amendment period from the 2016 survey with those in the pre-amendment period from the 2014 survey. The approach inheriting advantages from its predecessors, i.e., the difference-in-differences and the augmented inverse-probability weighting methods, can mitigate possible biases in policy evaluations due to the changes within the group and between groups over time in the cross-section observational study.The results showed health insurance expansion with extensive subsidies in premiums and medical coverage for persons other than the full-time employed, young children or elderly members in the family, significantly increased enrollments in the middle- and low-income groups by 9% and 8%, respectively. The number of visits for PHI-eligible services also increased, approximately 0.5 more visit per person in the middle-income and 1 more visit per person in the low-income. The amendment, however, so far did not show any significant effect on reducing OOP payments, neither for the low nor the middle-income groups. To further expand PHI coverage and financial protections, policymakers should focus on improving public health facilities, contracting PHI to more accredited private health providers, and motivating the high-income group’s enrollments.
Nurses’ promotion of Mental Health First Aid Training Programmes for upper secondary students: a modified Delphi approach
Authors: Costa Tiago Filipe Oliveira , Moreno Poyato Antonio Rafael , Sampaio Francisco Miguel Correia , Lluch Canut María Teresa , Sequeira Carlos Alberto da Cruz 
Published: March 2023

Abstract
Background
Mental Health First Aid Training Programmes can be carried out by nurses in schools. Adolescents have reported the importance of these interventions, the contents to be addressed, and intervention strategies that should be used. Mental health nurses have also discussed the characteristics of these training programmes. This study sought to create a consensus on the features of Mental Health First Aid Training Programmes promoted by nurses aimed at upper secondary students.

Methods
A descriptive mixed method study was developed using the modified e-Delphi technique. Original statements on the topic were drawn from the results section of previous studies with nurses and adolescents. The statements were included in a structured online questionnaire. An expert panel of 78 mental health nurses participated in the two-rounds online survey from October to December 2021. Absolute and relative frequencies of responses were analysed. The experts’ comments were also considered.

Results
In the first round, experts suggested 4 new ideas about training programmes. Experts took a position on a total of 59 declarations. At least 75% of participants agreed with 58 statements about training programmes, namely about facilitators, intervention foci, evaluation methodology, participants, the implementation context, period and regularity, intervention strategies and content. The experts’ opinions differed only in one statement that expressed the impaired sexual behaviour as a mental health problem to be addressed in the training programmes.

Conclusions
Mental health nurses can lead the delivery of training programmes in upper secondary schools, improving adolescent competencies in mental health. Several educational approaches can be used to teach about mental health, related problems and actions underlying these conditions. Valid and appropriate assessment methods must be used. Our findings guide the planning, implementation and evaluation of these interventions in upper secondary schools and encourage nurses to explore these programmes and include them in their educational curricula.
Health system readiness to manage maternal death data and avail evidence for decision-making through the Maternal Death Surveillance System in Ethiopia, 2020
Authors: Endris Abduilhafiz A. , Tilahun Tizita 
Published: March 2023

Abstract
Background
Maternal mortality remains a major health problem in Ethiopia. To generate contextual evidence on the burden and distribution of existing causes and contributing factors for programmatic and individual-level decision-making, the Maternal Death Surveillance and Response System was introduced in 2013. This assessment describes the Ethiopian health system's readiness to avail evidence for decision-making through the MDSR system.

Method
A cross-sectional study designed using the WHO framework for evaluating surveillance systems was used. By employing a multistage sampling, 631 health facilities and 539 health posts were included. ODK collect data entry software was used to collect data from September 2019 to April 2020. Findings are presented in text descriptions, graphs, maps, and tables.

Findings
Four hundred (77.1%) health facilities (332 (74.6%) health centers and 68 (91.9%) hospitals) and 264 (71.5%) health posts reported implementing the MDSR system. Of the implementing health facilities, 349 (87.3%) had a death review committee, and only 42 (12.4%) were functional. About 89.4% of health centers and 79.4% of hospitals had sub-optimal maternal death identification and notification readiness. Only 23 (6.96%) and 18 (26.47%) MDSR-implementing health centers and hospitals had optimal readiness to investigate and review maternal deaths, respectively. Moreover, only 39 (14.0%) health posts had locally translated case definitions and 28 (10.6%) had verbal autopsy format to investigate maternal deaths. Six (1.5%) facility officers and 24 (9.1%) health extension workers were engaged in data analysis and evidence generation at least once during 2019/20. Regional variation is observed in system implementation.

Conclusions and recommendations
Sub-optimal MDSR system implementation is recorded. Revitalizing the system by addressing all system components is critical. Having a national-level roadmap for MDSR system implementation and mobilizing all available resources and stakeholders to facilitate this is vital. Establishing a system for routine data quality monitoring and assurance by integrating with the existing PHEM structure, having a system for routine capacity building, advocacy, and monitoring and evaluating the availability and functionality of MDSR committees at health facilities are all critical. Digitalization, designing a system to fit emerging regions' health service delivery, and availing required resources for the system is key.
Lessons learnt while integrating services for children: qualitative interviews with professional stakeholders
Authors: Baxter Vanessa , Speed Ewen , Ioakimidis Vasilios , Ross Matthew 
Published: March 2023

Abstract
Background
In the English NHS, integrated care is seen as an opportunity to deliver joined-up care for children and families. This paper examines the lessons learnt by professional stakeholders in the process of developing different examples of integrated models of care/frameworks for children’s services.

Methods
Initial desk research was undertaken to identify different examples of integrated care models and systems/frameworks for children’s services. This identified forty-three examples in England. Of these, twelve examples were shortlisted after consultation with the senior managers within the Health and Care Partnership that had commissioned the research, and a more detailed online search for published documents was undertaken. Semi-structured qualitative interviews were then conducted with sixteen professional stakeholders in eight of these examples, ranging from one to four interviewees per example. Interviews focused on the lessons learnt from integrating and transforming services. Data were analysed using framework analysis.

Results
The eight examples vary in their design but have several broad commonalities. A number of common themes and learning have emerged, of which two were identified within all eight examples: the first is about focusing on children and young people; the second is about focusing on partner engagement and collaboration and the importance of building trust and relationships between partners. A number of other important themes also emerged together with several challenges.

Conclusions
A number of common factors were identified that are essential to success in integrating health and care systems. Common across all localities were being child-centric and focusing on child outcomes plus the importance of building trust, engagement and relationships with partners. The findings can help health and care system leaders transform services to ensure efficiency, improvement in services and integration.
Reduced virulence in tigecycline-resistant Klebsiella pneumoniae caused by overexpression of ompR and down-regulation of ompK35
Authors: Park Suyeon , Kim Hyunkeun , Ko Kwan Soo 
Published: March 2023

Abstract
Background
The development of tigecycline resistance in hypervirulent Klebsiella pneumoniae strains has resulted in decreased virulence that is associated with reduced production of capsular polysaccharides (CPS). In this study, we investigated the mechanisms that link tigecycline susceptibility to decreased virulence.

Methods
We compared transcriptomes from tigecycline-susceptible wild-type strains and tigecycline-resistant mutants using mRNA sequencing. ompR-overexpressed and ompR-deleted mutants were constructed from wild-type strains and tigecycline-resistant mutants, respectively. Antibiotic susceptibility tests were performed, and string tests and precipitation assays were conducted to identify phenotypic changes related to tigecycline susceptibility and ompR expression. Bacterial virulence was assessed by serum resistance and Galleria mellonella infection assays.

Results
Transcriptomic analyses demonstrated a significant decrease in the expression of ompK35 in the tigecycline-resistant mutants. We observed that tigecycline-resistant mutants overexpressed ompR, and that the expression of ompK35 was regulated negatively by ompR. While tigecycline-resistant mutants and ompR-overexpressed mutants exhibited reduced hypermucoviscosity and virulence, deletion of ompR from tigecycline-resistant mutants restored their hypermucoviscosity and virulence.

Conclusions
In hypervirulent K. pneumoniae strains, ompR expression, which is regulated by exposure to tigecycline, may affect the production of CPS, leading to bacterial virulence.