bluuebunny/crossref_metadata_2025_split huggingface dataset:
Centralising acute stroke care within clinical practice in the Netherlands: lower bounds of the causal impact
Authors: Freriks Roel D. , Mierau Jochen O. , Buskens Erik , Pizzo Elena , Luijckx Gert-Jan , van der Zee Durk-Jouke , Lahr Maarten M. H. 
Published: February 2020

AbstractBackgroundAuthors in previous studies demonstrated that centralising acute stroke care is associated with an increased chance of timely Intra-Venous Thrombolysis (IVT) and lower costs compared to care at community hospitals. In this study we estimated the lower bound of the causal impact of centralising IVT on health and cost outcomes within clinical practice in the Northern Netherlands.MethodsWe used observational data from 267 and 780 patients in a centralised and decentralised system, respectively. The original dataset was linked to the hospital information systems. Literature on healthcare costs and Quality of Life (QoL) values up to 3 months post-stroke was searched to complete the input. We used Synthetic Control Methods (SCM) to counter selection bias. Differences in SCM outcomes included 95% Confidence Intervals (CI). To deal with unobserved heterogeneity we focused on recently developed methods to obtain the lower bounds of the causal impact.ResultsUsing SCM to assess centralising acute stroke 3 months post-stroke revealed healthcare savings of $US 1735 (CI, 505 to 2966) while gaining 0.03 (CI, − 0.01 to 0.73) QoL per patient. The corresponding lower bounds of the causal impact are $US 1581 and 0.01. The dominant effect remained stable in the deterministic sensitivity analyses with $US 1360 (CI, 476 to 2244) as the most conservative estimate.ConclusionsIn this study we showed that a centralised system for acute stroke care appeared both cost-saving and yielded better health outcomes. The results are highly relevant for policy makers, as this is the first study to address the issues of selection and unobserved heterogeneity in the evaluation of centralising acute stroke care, hence presenting causal estimates for budget decisions.
Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry
Authors: Holtze Colin H. , Freiheit Elizabeth A. , Limb Susan L. , Stauffer John L. , Raimundo Karina , Pan Wayne T. , Flaherty Kevin R. , Kim Hyun J. 
Published: February 2020

Abstract
Background
Pragmatic use of the anti-fibrotic medications pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) in the United States (US) has not been studied and may be different from international settings due to structural differences between health care systems. This study examined the relationship between patient- and site-level characteristics and anti-fibrotic (a) use and (b) selection.

Methods
Data from the Pulmonary Fibrosis Foundation Patient Registry was used to perform univariable and multivariable regressions with generalized linear mixed models. A random effects model examined registry site variation.

Results
703 of 1218 (57.7%) patients were taking a single anti-fibrotic of which 312 (44.4%) were taking nintedanib and 391 (55.6%) were taking pirfenidone. Up to 25% of patients using an anti-fibrotic may have been excluded from clinical trial participation due to having too severe disease as measured by diffusion limitation for carbon monoxide. Age (OR = 0.974, p = 0.0086) and diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 0.896, p = 0.0007) was negatively associated with anti-fibrotic use while time (in log of days) since diagnosis (OR = 1.138, p < 0.0001), recent patient clinical trial participation (OR = 1.569, p = 0.0433) and oxygen use (OR = 1.604, p = 0.0027) was positively associated with anti-fibrotic use. Time (log of days) since diagnosis (OR = 1.075, p = 0.0477), history of coronary artery disease (OR = 1.796, p = 0.0030), presence of pulmonary hypertension (OR = 2.139, p = 0.0376), patient clinical trial participation in the prior 12 months (OR = 2.485, p = 0.0002), diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 1.138, p = 0.0184), anticoagulant use (OR = 2.507, p = 0.0028), and enrollment at a registry site in the Midwest region (OR = 1.600, p = 0.0446) were associated with pirfenidone use. Anti-fibrotic use varied by registry site. Rates of discontinuation were modest and nearly identical for the two medications with side effects being the most common reason given for discontinuation. Twenty-three percent (23%, 274) of persons with IPF were using or had recently used an immunomodulatory agent.

Conclusions
This analysis provides a detailed characterization of IPF treatment patterns in the US; many users of anti-fibrotic medications may not have qualified for inclusion in clinical trials. More research is needed to understand variations in medical decision-making for use and selection of anti-fibrotic medication.
Relation of cardiac adipose tissue to coronary calcification and myocardial microvascular function in type 1 and type 2 diabetes
Authors: Zobel Emilie H. , Christensen Regitse Højgaard , Winther Signe A. , Hasbak Philip , Hansen Christian Stevns , von Scholten Bernt J. , Holmvang Lene , Kjaer Andreas , Rossing Peter , Hansen Tine W. 
Published: February 2020

Abstract
Background
Cardiac adipose tissue may have local paracrine effects on epicardial arteries and the underlying myocardium, promoting calcification and affecting myocardial microcirculation. We explored whether the total amount of cardiac adipose tissue was associated with coronary artery calcium score (CAC) and myocardial flow reserve in persons with type 1 or type 2 diabetes and healthy controls.

Methods
We studied three groups: (1) 30 controls, (2) 60 persons with type 1 diabetes and (3) 60 persons with type 2 diabetes. The three groups were matched for sex and age. The three groups derived from retrospective analysis of two clinical studies. All underwent cardiac 82Rb positron emission tomography/computed tomography (PET/CT) scanning. Cardiac adipose tissue volume (the sum of epicardial and pericardial fat), CAC, and myocardial flow reserve (ratio of pharmacological stress flow and rest flow) were evaluated using semiautomatic software. We applied linear regression to assess the association between cardiac adipose tissue, CAC and myocardial flow reserve.

Results
Mean (SD) cardiac adipose tissue volume was 99 (61) mL in the control group, 106 (78) mL in the type 1 diabetes group and 228 (97) mL in the type 2 diabetes group. Cardiac adipose tissue was positively associated with body mass index in all three groups (p ≤ 0.02). In the controls, cardiac adipose tissue was positively associated with CAC score (p = 0.008) and negatively associated with myocardial flow reserve (p = 0.005). However, cardiac adipose tissue was not associated with CAC or myocardial flow reserve in the groups including persons with type 1 or type 2 diabetes (p ≥ 0.50).

Conclusions
In contrast to what was found in healthy controls, we could not establish a relation between cardiac adipose tissue and coronary calcification or myocardial microvascular function in person with type 1 or type 2 diabetes. The role of cardiac adipose tissue in cardiovascular disease in diabetes remains unclear.
Zoledronic acid inhibits TSC2-null cell tumor growth via RhoA/YAP signaling pathway in mouse models of lymphangioleiomyomatosis
Authors: Zhao Dandan , Wu Jing , Zhao Yinjuan , Shao Wei , Cheng Qi , Shao Xiaoyan , Yuan Xianwen , Ye Juan , Gao Jianpu , Jin Meiling , Li Chaojun , Chen Xiaolin , Zhao Yue , Xue Bin 
Published: February 2020

Abstract
Background
This study is to investigate the effects of zoledronic acid (ZA) on TSC2-null cell proliferation and on the tumor progression and recurrence in mouse models of lymphangioleiomyomatosis (LAM).

Methods
Subcutaneous mouse models and LAM mouse models were established. Immunohistochemistry and immunofluorescence were performed to detect the protein expression levels. TUNEL assay was conducted to detect cell apoptosis. Immunoprecipitation was carried out to determine the interaction between proteins.

Results
ZA prevented the growth of TSC2-null cells both in culture and in LAM mouse models. Compared with rapamycin, ZA more effectively promoted the apoptosis of TSC2-null cells. Moreover, combined with the rapamycin, ZA effectively suppressed the tumor recurrence after drug withdrawal and ZA inhibited the activity of GTPase RhoA by decreasing protein geranylgeranylation, resulting in changes of Yap nucleus translocation.

Conclusion
ZA promotes cell apoptosis in TSC2-null cells through the RhoA/YAP signaling pathway. ZA may be used for the clinical treatment of LAM.
Ubiquitin-specific peptide 22 acts as an oncogene in gastric cancer in a son of sevenless 1-dependent manner
Authors: Lim ChitChoon , Xu Jia-Cheng , Chen Tian-Yin , Xu Jia-Xin , Chen Wei-Feng , Hu Jian-Wei , Li Quan-Lin , Zhang Yi-Qun 
Published: February 2020

AbstractBackgroundAberrant expression of ubiquitin-specific peptide 22 (USP22) has been detected in various cancers. This study aimed to investigate the role of USP22 and the underlying mechanism in human gastric cancer.MethodsThe expression pattern of USP22 in human gastric cancer was detected in a tissue microarray containing 88 pairs of gastric cancer tissue and adjacent normal tissue samples from patients with primary gastric cancer using immunohistochemical staining. The correlation of USP22 expression with clinical characteristics of patients, as well as their prognostic values in the overall survival of patients, were evaluated. USP22-overexpressing SGC7901 and USP22-silencing AGS cells were used to explore the role of USP22 in gastric cancer cell behavior in vitro and in vivo. Chromatin immunoprecipitation was performed to identify differentially expressed genes induced by USP22 overexpression. Western blot analysis was conducted to detect the activation of RAS/ERK and PI3K/AKT signaling in USP22-overexpressing SGC7901 cells and xenograft tumor tissues. Knockdown of RAS activator son of sevenless 1 (SOS1) was performed to investigate the role of SOS1 in USP22-regulated gastric cancer cell behavior and RAS signaling both in vitro and in vivo.ResultsUSP22 protein expression was significantly increased in human gastric cancer tissues, compared with adjacent normal tissues, and was positively correlated with local tumor stage. Gain- and loss-of-function assays showed that USP22 promoted gastric cancer cell growth and cell cycle transition while suppressing apoptosis in vitro. Consistent results were observed in a xenograft mouse model. Chromatin immunoprecipitation revealed that the overexpression of USP22 induced the upregulation of RAS activator son of sevenless 1 (SOS1) in SGC7901 cells. Western blot analysis showed that USP22 overexpression also induced activation of the RAS/ERK and PI3K/AKT pathways in SGC7901 cells and xenograft tumor tissues. Furthermore, SOS1 silencing could reverse the effects of USP22 on gastric cancer cell behavior and RAS signaling both in vitro and in vivo.ConclusionsOur results suggest that USP22 acts as an oncogene in gastric cancer in a SOS1-dependent manner, identifying the USP22/SOS1/RAS axis as a potential therapeutic target in gastric cancer.
Healthcare professionals’ perspective can guide post-marketing surveillance of artemisinin-based combination therapy in Uganda
Authors: Ndagije Helen Byomire , Kiguba Ronald , Manirakiza Leonard , Kirabira Elijah , Sserwanga Allan , Nabirye Leah , Mukonzo Jackson , Olsson Sten , Spinewine Anne , D’Hoore William , Speybroeck Niko 
Published: February 2020

Abstract
Background
Efficient testing to identify poor quality artemisinin-based combination therapy (ACT) is important to optimize efforts to control and eliminate malaria. Healthcare professionals interact with both ACT and malaria patients they treat and hence could observe, first-hand, suspect poor quality artemisinin-based combinations linked to poor malaria treatment outcomes and the factors associated with inappropriate use or treatment failure.

Methods
A cross-sectional study of 685 HCP perspectives about the efficacy of ACT between June and July 2018 at selected health facilities in Uganda. Medicine samples were obtained from the seven regions of Uganda and tested for quality using the Germany Pharma Health Fund™ minilabs.

Results
The average age of the 685 respondents was 30 (SD = 7.4) years. There was an almost equal distribution between male and female respondents (51:49), respectively. Seventy percent (n = 480) were diploma holders and the nurses contributed to half (49%, n = 334) of the study population. Sixty-one percent of the HCPs reported having ever encountered ACT failures while treating uncomplicated malaria. Nineteen percent of HCPs thought that dihydroartemisinin/piperaquine gave the most satisfactory patient treatment outcomes, while 80% HCPs thought that artemether/lumefantrine gave the least satisfactory patient treatment outcomes, possibly due to dosing schedule and pill burden. Healthcare professionals from the Central region (OR = 3.0, CI 0.3–1.0; P = 0.0001), Eastern region (OR = 5.4, CI 2.9–9.8; P = 0.0001) and Northern region (OR = 5.3, CI 2.9–9.9; P = 0.0001) had a higher chance of encountering ACT failure in 4 weeks prior to the survey as compared to those from the western region. Healthcare professionals from private health facilities also had higher chances of encountering ACT failures in past 4 weeks as compared to those from public health facilities (OR = 2.7, CI 1.7–3.9; P = 0.0001). All 192 samples passed the quality screening tests. The random sample of 10% of all samples randomly obtained by the laboratory staff also passed the chemical content analysis and dissolution tests.

Conclusion
ACT medicines are widely available over-the-counter to the public and it is very difficult to report and monitor a decrease in efficacy or treatment failure. The perspectives of HCPs on treatment failure or lack of efficacy may potentially guide optimization efforts of sampling methodologies for the quality survey of ACT medicines.
Prolonged health worker strikes in Kenya- perspectives and experiences of frontline health managers and local communities in Kilifi County
Authors: Waithaka Dennis , Kagwanja Nancy , Nzinga Jacinta , Tsofa Benjamin , Leli Hassan , Mataza Christine , Nyaguara Amek , Bejon Philip , Gilson Lucy , Barasa Edwine , Molyneux Sassy 
Published: February 2020

Abstract
Background
While health worker strikes are experienced globally, the effects can be worst in countries with infrastructural and resource challenges, weak institutional arrangements, underdeveloped organizational ethics codes, and unaffordable alternative options for the poor. In Kenya, there have been a series of public health worker strikes in the post devolution period. We explored the perceptions and experiences of frontline health managers and community members of the 2017 prolonged health workers’ strikes.

Methods
We employed an embedded research approach in one county in the Kenyan Coast. We collected in-depth qualitative data through informal observations, reflective meetings, individual and group interviews and document reviews (n = 5), and analysed the data using a thematic approach. Individual interviews were held with frontline health managers (n = 26), and group interviews with community representatives (4 health facility committee member groups, and 4 broader community representative groups). Interviews were held during and immediately after the nurses’ strike.

Findings
In the face of major health facility and service closures and disruptions, frontline health managers enacted a range of strategies to keep key services open, but many strategies were piecemeal, inconsistent and difficult to sustain. Interviewees reported huge negative health and financial strike impacts on local communities, and especially the poor. There is limited evidence of improved health system preparedness to cope with any future strikes.

Conclusion
Strikes cannot be seen in isolation of the prevailing policy and health systems context. The 2017 prolonged strikes highlight the underlying and longer-term frustration amongst public sector health workers in Kenya. The health system exhibited properties of complex adaptive systems that are interdependent and interactive. Reactive responses within the public system and the use of private healthcare led to limited continued activity through the strike, but were not sufficient to confer resilience to the shock of the prolonged strikes. To minimise the negative effects of strikes when they occur, careful monitoring and advanced planning is needed. Planning should aim to ensure that emergency and other essential services are maintained, threats between staff are minimized, health worker demands are reasonable, and that governments respect and honor agreements.
Vulnerability in health and social capital: a qualitative analysis by levels of marginalization in Mexico
Authors: Martínez-Martínez Oscar A. , Rodríguez-Brito Anidelys 
Published: February 2020

AbstractBackgroundSocial capital is employed as an asset when there is a lack of an efficient health-care system. However, this relationship is not homogeneous and can differ according to the characteristics of individuals and their context. In this paper, we aim to analyze the role of social capital in the solution of healthcare problems among individuals with different levels of marginalization and unequal access to health services.MethodsThis qualitative study examines the role of social capital in the demand for healthcare among Mexican individuals with different levels of marginalization. The research draws data from semi-structured interviews (N = 247) that were collected in four Mexican states with different social welfare benefits: Mexico City, Tamaulipas, the State of Mexico, and Oaxaca. The interviewees were selected using the snowball method and other eligibility criteria such as education, age, and gender.ResultsFindings suggest that social capital is a relevant factor in solving healthcare problems, depending on the level of marginalization. The role of social capital can be explained by the precariousness of medical service delivery, the poor health infrastructure, and the difficult access to health care in Mexico. Networks are the main resource to deal with health related issues, food, medicine, and out-of-the-pocket medical expenses in contexts of high levels of marginalization. In the middle level of marginalization, networks also help in raising funds for more-specialized medical services and higher quality hospitals. In the least-marginalized levels, social capital is used as companionship for sick individuals, while support networks act as emotional relief. At this level, most individuals have private health insurance, and many of them have major medical healthcare coverage.ConclusionsParticipants reported low levels of trust in the health care system because of the poor infrastructure and quality of medical service delivery. Although the main criticism is focused on public healthcare institutions, there is a lack of trust in private medical services as well. These facts are related to the access and quality of medical service delivery and turn social capital into a significant asset. Despite that social bonds or links are valuable resources that individuals can use to solve healthcare related issues, the use of social capital is not homogenous. Indeed, it can be influenced by several factors that were represented in this study through the municipal marginalization index.
Application of the Food Quality Protection Act children’s health safety factor in the U.S. EPA pesticide risk assessments
Authors: Naidenko Olga V. 
Published: February 2020

Abstract
Background
The Food Quality Protection Act of 1996, or FQPA, required the Environmental Protection Agency to set allowable levels for pesticides in a way that would “ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue.” The act stipulated that an additional tenfold margin of safety for pesticide risk assessments shall be applied to account for pre- and postnatal toxicity and for any data gaps regarding pesticide exposure and toxicity, unless there are reliable data to demonstrate that a different margin would be safe for infants and children.

Discussion
To examine the implementation of the FQPA-mandated additional margin of safety, this analysis reviews 59 pesticide risk assessments published by the EPA between 2011 and 2019. The list includes 12 pesticides used in the largest amount in the U.S.; a group of 35 pesticides detected on fruits and vegetables; and 12 organophosphate pesticides. For the non-organophosphate pesticides reviewed here, the EPA applied an additional children’s health safety factor in 13% of acute dietary exposure scenarios and 12% of chronic dietary exposure scenarios. For incidental oral, dermal and inhalation exposures, additional FQPA factors were applied for 15, 31, and 41%, respectively, of the non-organophosphate pesticides, primarily due to data uncertainties. For the organophosphate pesticides as a group, a tenfold children’s health safety factor was proposed in 2015. Notably, in 2017 that decision was reversed for chlorpyrifos.

Conclusions
For the majority of pesticides reviewed in this study, the EPA did not apply an additional FQPA safety factor, missing an opportunity to fully use the FQPA authority for protecting children’s health.