bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why do they do it? A grounded theory study of the use of low-value care among primary health care physicians
Authors: Ingvarsson Sara , Augustsson Hanna , Hasson Henna , Nilsen Per , von Thiele Schwarz Ulrica , von Knorring Mia 
Published: October 2020

Abstract
Background
The use of low-value care (LVC) is widespread and has an impact on both the use of resources and the quality of care. However, few studies have thus far studied the factors influencing the use of LVC from the perspective of the practitioners themselves. The aim of this study is to understand why physicians within primary care use LVC.

Methods
Six primary health care centers in the Stockholm Region were purposively selected. Focus group discussions were conducted with physicians (n = 31) working in the centers. The discussions were coded inductively using a grounded theory approach.

Results
Three main reasons for performing LVC were identified. Uncertainty and disagreement about what not to do was related to being unaware of the LVC status of a practice, guidelines perceived as conflicting, guidelines perceived to be irrelevant for the target patient population, or a lack of trust in the guidelines. Perceived pressure from others concerned patient pressure, pressure from other physicians, or pressure from the health care system. A desire to do something for the patients was associated with the fact that the visit in itself prompts action, symptoms to relieve, or that patients' emotions need to be reassured. The three reasons are interdependent. Uncertainty and disagreement about what not to do have made it more difficult to handle the pressure from others and to refrain from doing something for the patients. The pressure from others and the desire to do something for the patients enhanced the uncertainty and disagreement about what not to do. Furthermore, the pressure from others influenced the desire to do something for the patients.

Conclusions
Three reasons work together to explain primary care physicians’ use of LVC: uncertainty and disagreement about what not to do, perceived pressure from others, and the desire to do something for the patients. The reasons may, in turn, be influenced by the health care system, but the decision nevertheless seemed to be up to the individual physician. The findings suggest that the de-implementation of LVC needs to address the three reasons from a systems perspective.
A modified frozen elephant trunk technique for acute Stanford type A aortic dissection
Authors: Song Shi-bo , Wu Xi-jie , Sun Yong , Cai Shi-hao , Hu Po-yuan , Qiang Hai-feng 
Published: October 2020

Abstract
Background
Acute Stanford type A aortic dissection is often fatal, with a high mortality rate and requiring emergency intervention. Salvage surgery aims to keep the patient alive by addressing severe aortic regurgitation, tamponade, primary tear, and organ malperfusion and, if possible, prevent the late dissection-related complications in the proximal and downstream aorta. Unfortunately, no optimal standard treatment or technique to treat this disease exists. Total arch replacement with frozen elephant trunk technique plays an important role in treating acute type A aortic dissection. We aim to describe a modified elephant trunk technique and report its short-term outcomes.

Methods
From February 2018 to August 2019, 16 patients diagnosed with acute Stanford type A aortic dissection underwent surgery with the modified frozen elephant trunk technique at Xiamen Heart Center (male/female: 9/7; average age: 56.1 ± 7.6 years). All perioperative variables were recorded and analyzed. We measured the diameters of the ascending aorta, aortic arch, and descending aorta on the bifurcation of the pulmonary and abdominal aortas and compared the diameters at admission, before discharge, and 3 months after discharge.

Results
Fifteen patients (93.8%) had hypertension. The primary tears were located in the lesser curvature of the aortic arch and ascending aorta in 5 (31.3%) and 9 patients (56.3%), respectively, and no entry was found in 2 patients (12.5%). The dissection extended to the iliac artery and distal descending aorta in 14 (87.6%) and 2 patients (12.5%), respectively. The duration of cardiopulmonary bypass (CPB), cross-clamping, and antegrade cerebral perfusion were 215.8 ± 40.5, 140.8 ± 32.3, and 55.1 ± 15.2 min, respectively. Aortic valve repair was performed in 15 patients (93.8%). Bentall procedure was performed in one patient (6.3%). Another patient received coronary artery repair (6.3%). The diameters at all levels were greater on discharge than those on admission, except the aortic arch. After 3 months, the true lumen diameter distal to the frozen elephant trunk increased, indicating false lumen thrombosis and/or aortic remodeling.

Conclusions
The modified frozen elephant trunk technique for acute Stanford type A aortic dissection is safe and feasible and could be used for organ malperfusion. Short-term outcomes are encouraging, but long-term outcomes require further investigation.
Discovery of a dual inhibitor of NQO1 and GSTP1 for treating glioblastoma
Authors: Lei Kecheng , Gu Xiaoxia , Alvarado Alvaro G. , Du Yuhong , Luo Shilin , Ahn Eun Hee , Kang Seong Su , Ji Bing , Liu Xia , Mao Hui , Fu Haian , Kornblum Harley I. , Jin Lingjing , Li Hua , Ye Keqiang 
Published: October 2020

Abstract
Background
Glioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation.

Methods
High-throughput screen was used for agents selectively active against GBM cells with EGFRvIII mutations. Co-crystal structures were revealed molecular details of target recognition. Pharmacological and gene knockdown/overexpression approaches were used to investigate the oxidative stress in vitro and in vivo.

Results
We identified a small molecular inhibitor, “MNPC,” that binds to both NQO1 and GSTP1 with high affinity and selectivity. MNPC inhibits NQO1 and GSTP1 enzymes and induces apoptosis in GBM, specifically inhibiting the growth of cell lines and primary GBM bearing the EGFRvIII mutation. Co-crystal structures between MNPC and NQO1, and molecular docking of MNPC with GSTP1 reveal that it binds the active sites and acts as a potent dual inhibitor. Inactivation of both NQO1 and GSTP1 with siRNA or MNPC results in imbalanced redox homeostasis, leading to apoptosis and mitigated cancer proliferation in vitro and in vivo.

Conclusions
Thus, MNPC, a dual inhibitor for both NQO1 and GSTP1, provides a novel lead compound for treating GBM via the exploitation of specific vulnerabilities created by mutant EGFR.
Letter on Predicting the number of sites needed to deliver a multicentre clinical trial within a limited time frame in the UK
Authors: Greenwood Rosemary , Pell Julie , Foscarini-Craggs Paula , Wale Katharine , Thomas Ian , Bradbury Charlotte 
Published: October 2020

Abstract
When planning a multicentre clinical trial, it can be difficult to predict the time needed to open individual sites, and this in turn impacts on the total number of sites needed, the budget and the time frame for a clinical trial to be delivered successfully. This is of particular importance for funding applications with a limited time frame and budget such as NIHR RfPB. It is more efficient and cost-effective to open the total number of sites needed at the outset of a trial, rather than to respond later to slow site opening and recruitment. Here, we share our experience of successfully delivering a multicentre clinical trial for a rare disease within a limited time frame and budget by approximately doubling the number of sites initially predicted to be needed. We initially predicted 20 sites would be needed to deliver the clinical trial, but early on in the trial, the number of sites was more than doubled to allow successful recruitment of the target sample size within the desired time frame. Of the 48 ethically approved sites, the median time from ethical approval of a site to opening for recruitment was 182 days (95% confidence interval [143 to 245 days]) and ranged from 18 to 613 days. In four (9%) of these sites, part of the delay was due to pharmacy sign off not being given when R&D had issued capacity and capability (C&C). Delays due to pharmacy sign off varied from 10 days to over 3 months delay in two sites (94 days and 102 days). A mathematical solution to the problem of planning a study with a short recruitment window has been given to support the planning and costing of grants with fixed time constraints: number of sites = required sample size divided by (number of eligible patients per site per month times recruitment rate times (the number of months accrual minus 6 months)). We expect these results to help others who are planning multicentre clinical trials in the UK. Ethical approval from NRES Committee South West (IRAS number 225959).

Trial registration
EudraCT Number 2017-001171-23. Registered on 26 June 2017
Use of spinal anaesthesia in neonates and infants in Antananarivo, Madagascar: a retrospective descriptive study
Authors: Randriamizao Harifetra M. R. , Rakotondrainibe Aurélia , Razafindrabekoto Lova D. E. , Ravoaviarivelo Prisca F. , Rajaonera Andriambelo T. , Andriamanarivo Mamy L. 
Published: October 2020

Abstract
Objective
The aim of this study was to present the first cases of spinal anesthesia, in newborns and infants, preterm/ex-prematures, in order to determine its feasibility and its potential harmlessness, in Antananarivo—Madagascar. Indeed, spinal anesthesia is a low cost technique and can limit respiratory complications, postoperative apnea a contrario with pediatric general anesthesia which can lead to perioperative risks.

Results
In a retrospective, descriptive, 7-year (2013 to 2019) period study, conducted in the University Hospital Joseph Ravoahangy Andrianavalona, 69 patients’ data files planned to have spinal anesthesia were recorded. These pediatric patients were predominantly male (sex ratio = 2.8) and 37 [28–52] days old. The smallest anesthetized child weighed 880 g; the youngest was 4 days old. Twenty-seven (27) of them were premature and 20.3% presented respiratory diseases. They were mostly scheduled for hernia repair (90%). Spinal anesthesia was performed, with a Gauge 25 Quincke spinal needle, after 2 [1–2] attempts with hyperbaric bupivacaine of 4 [3.5–4] mg. Failure rate was 5.8%. The heart rate was stable throughout perioperative period and no complications were observed.
Explicit solutions of some equations and systems of mathematical physics
Authors: Slavova Angela , Popivanov Petar 
Published: October 2020

AbstractThis paper deals at first with a fully integrable evolution system of nonlinear partial differential equations (PDEs) which is a generalization of the classical Heisenberg ferromagnet equation. Then the scalar variant of this system is considered. Looking for solutions of special form, the problem of finding explicit solutions of the above-mentioned equations is reduced to the global solvability of overdetermined real-valued systems of nonlinear PDEs. In many cases particular solutions which are not solitons are expressed by classical functions including some special ones as Jacobi elliptic functions, Legendre elliptic functions, and Weierstrass normal elliptic integrals. A geometrical visualization of several solutions is also proposed.
Identification of repurposable cytoprotective drugs in vanishing white matter disease patient-derived cells
Authors: Ng Neville , Cabral-da-Silva Mauricio Castro , Maksour Simon , Berg Tracey , Engel Martin , Silva Dina M. , Do-Ha Dzung , Lum Jeremy S. , Muñoz Sonia Sanz , Suarez-Bosche Nadia , Stevens Claire H. , Ooi Lezanne 
Published: October 2020

Abstract
Background
Vanishing white matter disease (VWMD) is a rare disease caused by mutations of the guanine exchange factor eIF2B. VWMD typically presents with juvenile onset, and there are few treatments for the disease. Recent progress in the field has established mitochondrial dysfunction and endoplasmic reticulum (ER) stress to be strongly implicated in observed glial cell pathology. Drug repurposing offers a rapid approach toward translation of therapeutics using already-licensed drugs.

Objective
The aim of this study was to use fibroblasts and induced pluripotent stem cell (iPSC)-derived astrocytes from patients bearing the EIF2B5R113H/A403V or EIF2B2G200V/E213G VWMD mutations to identify potential repurposable FDA-approved drugs based on in vitro assays.

Methods
Cell viability in the presence or absence of stress was assessed by resazurin reduction activity and assays for mitochondrial membrane potential and oxidative stress by tetramethylrhodamine and dichlorofluorescein-based assays, respectively. Integrated stress response markers, including eIF2α phosphorylation, GADD34 and CHOP were quantified by fluorescent western blot.

Results
Dysregulated GADD34 and CHOP were identified in patient fibroblasts and iPSC-derived astrocytes under induced stress conditions. A drug screen from a 2400 FDA-approved drug library with EIF2B5R113H/A403V VWMD patient fibroblasts identified 113 anti-inflammatory drugs as a major class of hits with cytoprotective effects. A panel of candidate drugs, including berberine, deflazacort, ursodiol, zileuton, guanabenz and Anavex 2–73, and preclinical ISRIB, increased cell survival of EIF2B5R113H/A403V or EIF2B2G200V/E213G VWMD astrocytes, and were further investigated for their effect on the integrated stress response and mitochondrial stress. Ursodiol demonstrated capacity to ameliorate oxidative stress and loss of mitochondrial membrane potential in VWMD patient iPSC-derived astrocytes in the presence or absence of stress conditions.

Conclusion
Patient-derived cells can be used to identify cellular phenotypes and for large-scale drug screening. Anti-inflammatory compounds, such as berberine, deflazacort, ursodiol and zileuton are potentially repurposable drug candidates for VWMD that should be further investigated for translation in vivo.
The roles of iodized oil-based lymphangiography and post-lymphangiographic computed tomography for specific lymphatic intervention planning in patients with postoperative lymphatic fistula: a literature review and case series
Authors: Pan F. , Loos M. , Do T. D. , Richter G. M. , Kauczor H. U. , Hackert T. , Sommer C. M. 
Published: October 2020

AbstractIn the management of patients with postoperative lymphatic fistula (LF) in different locations, iodized oil-based lymphangiography (LAG) from trans-pedal or intranodal route is an established diagnostic approach with the potential to plan further interventional treatments. However, specific lymphatic interventions are indicated depending on different locations and morphologies of the LF. After a systematic literature review, four types of interventions can be considered, including direct leakage embolization/sclerotherapy (DLE/DLS), percutaneous afferent lymphatic vessel embolization (ALVE), percutaneous afferent lymphatic vessels disruption/sclerotherapy (ALVD/ALVS), and trans-afferent nodal embolization (TNE). In the iodized oil-based LAG, three potential lymphatic targets including confined leakage, definite afferent LVs, and definite closest afferent LNs should be comprehensively assessed. For optimal prospective treatment planning for LF, iodized oil-based post-lymphangiographic computed tomography (post-LAG CT) is a useful complement to the conventional iodized oil-based LAG, which can be performed easily after LAG. This review article summarized the current evidence of the specific lymphatic interventions in patients with postoperative LF and explored the potential benefits of post-LAG CT in the intervention planning from a case series.
Reliability and validity of 3 different Chinese versions of the Oxford knee score (OKS)
Authors: Ngwayi James Reeves Mbori , Tan Jie , Liang Ning , Porter Daniel Edward 
Published: October 2020

Abstract
Background
Different Chinese versions of the Oxford Knee Score (OKS) are available for knee arthritis assessment. These include the Malaysian, Hong Kong and Singaporean Chinese versions with slight variations in wordings and use of Cantonese in the Hong Kong Version. This study evaluated the validity and reliability of the different Chinese OKS versions in Mainland China.

Methods
One hundred ninety four China mainland-based patients participated in the study, each being diagnosed with knee osteoarthritis. The patients were randomly assigned into 3 groups: Group A completed the Malaysian OKS; Group B completed the Singaporean OKS; Group C completed the Hong Kong OKS. Participants also completed the 36-item Short Form Survey (SF 36). The electronic versions of the questionnaires completed by the patients were sent to smart devices via a social media platform.

Results
Interclass coefficients for test-retest reliability of the groups were 0.917 in group A, 0.921 in group B, 0.824 in group C. Cronbach alpha results for internal consistency of the 3 groups were: 0.912 in group A, 0.896 in group B, 0.846 in group C. Spearson correlation results with individual SF-36 domains were as follows: Group A showed strong negative correlations with bodily pain and physical function domains; group B exhibited moderate negative correlations with the bodily pain and physical function domains; group C revealed strong negative correlations with the bodily pain and physical function domains and weak negative correlations with vitality domain.

Conclusions
Different Chinese versions of the OKS showed good reliability and convergent validity in mainland samples of patients with knee osteoarthritis, supporting their use in research and other related studies.
Aspirin Use Is Associated With Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients With Coronavirus Disease 2019
Authors: Chow Jonathan H. , Khanna Ashish K. , Kethireddy Shravan , Yamane David , Levine Andrea , Jackson Amanda M. , McCurdy Michael T. , Tabatabai Ali , Kumar Gagan , Park Paul , Benjenk Ivy , Menaker Jay , Ahmed Nayab , Glidewell Evan , Presutto Elizabeth , Cain Shannon , Haridasa Naeha , Field Wesley , Fowler Jacob G. , Trinh Duy , Johnson Kathleen N. , Kaur Aman , Lee Amanda , Sebastian Kyle , Ulrich Allison , Peña Salvador , Carpenter Ross , Sudhakar Shruti , Uppal Pushpinder , Fedeles Benjamin T. , Sachs Aaron , Dahbour Layth , Teeter William , Tanaka Kenichi , Galvagno Samuel M. , Herr Daniel L. , Scalea Thomas M. , Mazzeffi Michael A. 
Published: October 2020

BACKGROUND:
Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk in critically ill patients. To our knowledge, no studies have evaluated whether aspirin use is associated with reduced risk of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality.

METHODS:
A retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions.

RESULTS:
Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin, P = .03) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, P = .04), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin, P = .51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, 95% confidence interval [CI], 0.37-0.85, P = .007), ICU admission (adjusted HR, 0.57, 95% CI, 0.38-0.85, P = .005), and in-hospital mortality (adjusted HR, 0.53, 95% CI, 0.31-0.90, P = .02). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users.

CONCLUSIONS:
Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.
Applicability of European Union Competition Law to Health Care Providers: The Dividing Line between Economic and Noneconomic Activities
Authors: Nikolić Bruno 
Published: October 2020

Abstract
Ever-increasing health spending, which, according to future projections, continues to outpace economic growth, will further endanger the financial sustainability of health systems. In a quest to improve the efficacy and efficiency of the health system and thus strengthen its financial sustainability, member states are employing market-based mechanisms to finance, manage, and provide health care. However, the introduction of elements of competition is constrained by the application of EU competition law, which raises significant concerns regarding the applicability of competition law and its limits in the field of health care. Due to the lack of a clear definition in EU legislation, the applicability and scope of competition law are determined on a case-by-case basis, which reveals an inconsistent approach by the European Commission and the CJEU regarding the application of competition law to health care providers and has created legal uncertainty. The aim of this article is to analyze relevant decisions by the commission and the CJEU case law in the pursuit of “boundaries” that may trigger the applicability of competition law with regard to health care providers. Based on the findings of the analysis, the article proposes a set of principles or guidelines for determining whether a health care provider should be considered as an undertaking and, as such, subject to EU competition law.
Health Technology Assessment and Health Care Reimbursement in the European Union: Permissive Dissensus and the Limits of Harmonization through the Backdoor
Authors: Löblová Olga 
Published: October 2020

Abstract
Member states have consistently limited the European Union's competences in the area of health care reimbursement. Despite these efforts, there has been a slow but steady tendency toward harmonization of a key tool in reimbursement decision-making: health technology assessment (HTA), a multidisciplinary evaluation of “value for money” of medicines, devices, diagnostics, and interventions, which provides expert advice for reimbursement decisions. This article examines the origins of this paradoxical appetite for harmonization as well as of the dissensus that has, at the moment, somewhat stalled further integration in HTA. It finds that the prointegration neofunctionalist “permissive dissensus” is still present in decision making on HTA but potentially offset by dissensus or outright opposition from key actors, including member states and the medical device industry. These actors are able to decipher the potential consequences of highly technical issues, such as HTA, for national systems of social protection. Despite that, they have little interest in politicizing the issue, potentially opening the door to integrative policy solutions in the future.