bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of trimetazidine on ventricular remodeling in coronary artery disease patients with left ventricular hypertrophy: the rationale and design of a randomized controlled trial
Authors: Wu Lili , Luan Yi , Li Ya , Wang Min , He Jialin , Jin Chongying , Zhang Wenbin
Published: June 2020

Background

Trimetazidine is a metabolic anti-ischemic agent, which increases the tolerance of cardiomyocytes to ischemia. However, few studies have explored the effect of trimetazidine on ventricular remodeling in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) with left ventricular hypertrophy (LVH).

Methods

It is a randomized, placebo-controlled trial, and we propose to recruit one hundred and twenty-four CAD patients undergoing PCI with LVH during a 12-month period. They will be randomized to receive either trimetazidine (35 mg twice a day) or placebo in the following 12 months after PCI. Blood tests, echocardiography, symptom of angina and major adverse cardiovascular events (MACEs) will be collected at follow-up visit at 3 and 12 months. The primary end point will be the left ventricular remodeling measured by left ventricular mass index (LVMI) at 3- and 12-month follow-up compared with the baseline. The secondary end points will be the symptom of angina assessed by Seattle Angina Questionnaire, myocardial ischemia measured by 6-min walk test and exercise electrocardiography test, as well as MACEs (defined as a composite of death, myocardial infarction, stroke, recurrent angina, re-hospitalization, change of viable myocardium).

Discussion

This study aims to demonstrate the effect of trimetazidine on left ventricular remodeling and myocardial ischemia in CAD patients undergoing PCI with LVH. Trimetazidine treatment is likely to improve the left ventricular remodeling, symptoms of angina and myocardial ischemia. It might also reduce the risk of MACEs in CAD patients undergoing PCI with LVH.

Trial registration

http://www.chictr.org.cn, Chinese Clinical Trial Registry (ChiCTR1800017876). Registered on 19 Aug 2018.
Ventricular strain analysis in patients with no structural heart disease using a vendor-independent speckle-tracking software
Authors: Xia Hongmei , Yeung Darwin F. , Di Stefano Cristina , Cha Stephen S. , Pellikka Patricia A. , Ye Zi , Thaden Jeremy J. , Villarraga Hector R.
Published: June 2020

Background

Ventricular strain measurements vary depending on cardiac chamber (left ventricle [LV] or right ventricle [RV]), type of strain (longitudinal, circumferential, or radial), ventricular level (basal, mid, or apical), myocardial layer (endocardial or epicardial), and software used for analysis, among other demographic factors such as age and gender. Here, we present an analysis of ventricular strain taking all of these variables into account in a cohort of patients with no structural heart disease using a vendor-independent speckle-tracking software.

Methods

LV and RV full-thickness strain parameters were retrospectively measured in 102 patients (mean age 39 ± 15 years; 62% female). Within this cohort, we performed further layer-specific strain analysis in 20 subjects. Data were analyzed for global and segmental systolic strain, systolic strain rate, early diastolic strain rate, and their respective time-to-peak values.

Results

Mean LV global longitudinal, circumferential, and radial strain values for the entire cohort were − 18.4 ± 2.0%, − 22.1 ± 4.1%, and 43.9 ± 12.1% respectively, while mean RV global and free wall longitudinal strain values were − 24.2 ± 3.9% and − 26.1 ± 5.2% respectively. Women on average demonstrated higher longitudinal and circumferential strain and strain rate than men, and longer corresponding time-to-peak values. Longitudinal strain measurements were highest at the apex compared with the mid ventricle and base, and in the endocardium compared with the epicardium. Longitudinal strain was the most reproducible measure, followed closely by circumferential strain, while radial strain showed suboptimal reproducibility.

Conclusions

We present an analysis of ventricular strain in patients with no structural heart disease using a vendor-independent speckle-tracking software.
Compbdt: an R program to compare two binary diagnostic tests subject to a paired design
Authors: Roldán-Nofuentes J. A.
Published: June 2020

Background

The comparison of the performance of two binary diagnostic tests is an important topic in Clinical Medicine. The most frequent type of sample design to compare two binary diagnostic tests is the paired design. This design consists of applying the two binary diagnostic tests to all of the individuals in a random sample, where the disease status of each individual is known through the application of a gold standard.This article presents an R program to compare parameters of two binary tests subject to a paired design.

Results

The “compbdt” program estimates the sensitivity and the specificity, the likelihood ratios and the predictive values of each diagnostic test applying the confidence intervals with the best asymptotic performance. The program compares the sensitivities and specificities of the two diagnostic tests simultaneously, as well as the likelihood ratios and the predictive values, applying the global hypothesis tests with the best performance in terms of type I error and power. When the global hypothesis test is significant, the causes of the significance are investigated solving the individual hypothesis tests and applying the multiple comparison method of Holm. The most optimal confidence intervals are also calculated for the difference or ratio between the respective parameters. Based on the data observed in the sample, the program also estimates the probability of making a type II error if the null hypothesis is not rejected, or estimates the power if the if the alternative hypothesis is accepted. The “compbdt” program provides all the necessary results so that the researcher can easily interpret them. The estimation of the probability of making a type II error allows the researcher to decide about the reliability of the null hypothesis when this hypothesis is not rejected. The “compbdt” program has been applied to a real example on the diagnosis of coronary artery disease.

Conclusions

The “compbdt” program is one which is easy to use and allows the researcher to compare the most important parameters of two binary tests subject to a paired design. The “compbdt” program is available as supplementary material.
Hemorrhagic cholecystitis with rare imaging presentation: a case report and a lesson learned from neglected medication history of NSAIDs
Authors: Zhang Xin , Zhang Chunjun , Huang Haifeng , Wang Junsen , Zhang Yun , Hu Qida
Published: June 2020

Background

Gallbladder carcinogenesis, frequently occurredin chronic cholecystitis patients, requires radical resection. We herein describe a hemorrhagic cholecystitis case that failed to be differentiated from gallbladder cancer preoperatively owing to the neglected medication history of long term oral nonsteroidal anti-inflammatory drugs (NSIADs) intake.

Case presentation

A 57-year-old Chinese female was admitted for right upper quadrant pain with the initial diagnosis of cholecystitis. Radiological studies were unable to exclude the differential diagnosis of suspected gallbladder cancer. During the scheduled radical resection of the suspected lesions, the gross dissection showed an interesting presentation of hemorrhagic cholecystitis, without any pathological evidence of malignancies. Additional postoperative investigation revealed a neglected medication history of long-term NSAIDs use.

Conclusions

This case suggests the importance of preoperative review of medication history and patient education on prescription drug abuse.
Relationship between retinal blood flow and cytokines in central retinal vein occlusion
Authors: Noma Hidetaka , Yasuda Kanako , Mimura Tatsuya , Ofusa Akemi , Shimura Masahiko
Published: June 2020

Background

We evaluated the relationship between retinal blood flow and aqueous humor levels of cytokines/growth factors in patients with central retinal vein occlusion (CRVO).

Methods

In an observational study, 64 eyes of 64 CRVO patients were examined before anti-vascular endothelial growth factor (VEGF) therapy. Blood flow was assessed in large vessels around and at the optic disk by determining the mean blur rate using laser speckle flowgraphy. Aqueous humor samples were obtained from the patients during anti-VEGF therapy and levels of the following molecules were measured by the suspension array method: soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, VEGF, plancental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, IL-8, IL-12(p70), and IL-13.

Results

The mean blur rate of the affected eye was significantly lower than that of the unaffected eye. The mean blur rate showed a significant negative correlation with the log-transformed aqueous humor levels of PlGF, sICAM-1, and IL-8, but not VEGF.

Conclusions

These findings suggest that retinal blood flow velocity might be more strongly correlated with inflammatory factors than VEGF in patients with nonischemic CRVO and macular edema.
Prevalence and predictors of taking tetanus toxoid vaccine in pregnancy: a cross-sectional study of 8,722 women in Sierra Leone
Authors: Yaya Sanni , Kota Komlan , Buh Amos , Bishwajit Ghose
Published: June 2020

Background

Immunization of women during pregnancy to protect them and their infants against tetanus, pertussis and influenza is recommended by the World health Organization (WHO). However, there is limited information about the coverage rate and associated factors in low-income countries. The aim of this study was to measure the prevalence and predictors of taking tetanus toxoid among pregnant women in Sierra Leone.

Methods

This study was based on the fifth round of Multiple Indicator Cluster Survey (MICS 5) conducted in Sierra Leone in 2017. In total 8722 women aged between 15 and 49 years were included in this study. Outcome variable was taking of Tetanus Toxoid vaccination during the last pregnancy. Data were analyzed using cross-tabulation and logistic regression methods.

Results

The overall prevalence of receiving TT immunization during women’s last pregnancy was 96.3% and that of taking at least two doses was 82.12%. In the regression analysis, women from Mende ethnicity had a 0.48 fold lower chance of being immunized (OR = 0.480, 95% CI = 0.385,0.59768) than those from the other ethnicity. In addition, women who attended at least four ANC visits had higher odds of receiving TT vaccine (OR = 1.919, 95% CI = 1.639,2.245) compared to those who attended less ANC visits. Stratified by areas, this association was observed in both urban (OR = 2.661, 95% CI = 1.924,3.679) and rural areas (OR = 1.716, 95% CI = 1.430,2.059). Attending at least four ANC visits showed a positive association with receiving at least two doses TT (OR = 2.434, 95% CI = 1.711,3.464) in both urban (OR = 2.815, 95% CI = 1.413,5.610) and rural areas (OR = 2.216, 95% CI = 1.463,3.356) as well.

Conclusion

Higher number of ANC visits, mass media exposure and higher wealth quintile increased the odds of receiving TT immunization. In addition, minimum two doses which were identified to reduce neonatal mortality. Therefore, immunization campaigns targeting improved utilization of healthcare and immunization services by women of childbearing age in Sierra Leone are strongly recommended.
Involvement of personal and professional relations among men bothered by lower urinary tract symptoms: a population-based cross-sectional study
Authors: Knudsen Marianne Møldrup , Balasubramaniam Kirubakaran , Haastrup Peter Fentz , Jarbøl Dorte Ejg , Rasmussen Sanne
Published: June 2020

Background

Lower urinary tract symptoms (LUTS) are common among men worldwide and despite frequently of benign origin, the symptoms often influence quality of life. Most men experiencing LUTS manage their symptoms in private settings without consulting their general practitioner (GP). Therefore, the purpose of this study was to identify who in the personal and professional relations Danish men discussed their bothersome LUTS with, to analyse factors associated with discussing LUTS with personal and professional relations, and to analyse how having a social network influenced healthcare seeking.

Methods

A nationwide population-based, cross-sectional survey representative of the Danish population. A total of 46,647 randomly selected men aged 20+ were invited to participate. Data were collected in 2012. The main outcome measures were odds ratios between involvement of personal and professional relations, GP contact and different characteristics (age, number of symptoms, available social network, and involvement of personal relations) among men experiencing bothersome LUTS. We used multivariate logistic regression models.

Results

Overall, 22,297 men completed the questionnaire. Of those, 4885 (21.9%) had experienced at least one LUTS, 23.5% had not discussed their symptoms with either personal nor professional relations and 59.1% had not discussed their LUTS with any professional relation. The symptoms were most often discussed with personal relations, primarily the spouse/partner who was involved in more than half of the cases. Odds of consulting the GP, another doctor and other healthcare professionals were two to four-fold higher when the symptoms were discussed with a personal relation. Having an available social network was significantly associated with lower odds of consulting the GP regarding frequent urination.

Conclusions

Despite the high prevalence of bothersome LUTS more than one-fifth of men did not discuss their symptoms with either personal nor professional relations, and more than half did not discuss the symptoms with any professional relations. Discussing the symptoms with personal relations was generally associated with higher odds of seeking professional help, and for frequent urination, having an available social network was associated with lower odds of consulting the GP. The results may be useful for detecting and treating men bothered by LUTS.
Control of antimicrobial resistance in Iran: the role of international factors
Authors: Mehtarpour Mojtaba , Takian Amirhossein , Eshrati Babak , Jaafaripooyan Ebrahim
Published: June 2020

Background

Antimicrobial resistance (AMR) is currently causing various challenges for all countries around the world. Accordingly, the WHO is placing a great emphasis on the global partnership and allinaces to drive countries towards developing policy guidances and a strategic framework for AMR contatiment. This study thus seeks to elaborate on the international factors underlying AMR management in Iran.

Methods

Semi-structured interviews were conducted with managers from the Ministry of health (n = 14), Iran veterinary organization (n = 4), the national professional associations (n = 3) and researchers (n = 3), between November 2018 and July 2019. Participants were selected using purposeful and snowball sampling. Interviews were recorded and transcribed verbatim and were subsequently coded and analyzed thematically using MAXQDA software (V.18) and reported.

Results

International enabling and predisposing factors were identified in relation to the AMR control in the country. Enabling factors included knowledge transfer, facilitation in policy agenda setting, formulation and implementaion process, and AMR monitoring. Predisposing factors, alternatively, encompassed the migration of infectious patients, trafficking of medicine and livestock from neighboring countries, and the imposed sanctions.

Conclusion

Nowadays, AMR is taken cognizance of as a global challenge, thus to be addressed effectively, needs an international consensus more than ever. This harmony would not certainly underrate national efforts, but instead, is needed to reinforce such efforts through e.g. technical and financial assistance. It is suggested for policymakers to use all available political and legal means such as health diplomacy to establish humanitarian channels in order to enhance global convention and remove possible barriers as the sanctions and reduce their adverse consequences for AMR control.
High manganese exposure decreased the risk of high triglycerides in workers: a cross-sectional study
Authors: Luo Xiaoyu , Liu Zhenfang , Ge Xiaoting , Huang Sifang , Zhou Yanting , Li Defu , Li Longman , Chen Xiang , Huang Lulu , Hou Qingzhi , Cheng Hong , Xiao Lili , Liu Chaoqun , Zou Yunfeng , Yang Xiaobo
Published: June 2020

Background

Manganese (Mn) participates in lipid metabolism. However, the associations between Mn exposure and dyslipidaemia is unclear.

Methods

This was a cross-sectional study. Data were collected from the 2017 the Mn-exposed workers healthy cohort (MEWHC). Finally, 803 occupationally Mn-exposed workers included in the study. The workers were divided into two groups. The grouping of this study was based on Mn-Time Weighted Averages (Mn-TWA). The high-exposure group included participants with Mn-TWA greater than 0.15 mg/m3. The low-exposure group included participants with Mn-TWA less than or equal to 0.15 mg/m3. Mn-TWA levels and dyslipidaemia were assessed.

Results

After adjustment for seniority, sex, cigarette consumption, alcohol consumption, high-fat diet frequency, medicine intake in the past two weeks, egg intake frequency, drinking tea, WHR, and hypertension, Mn-TWA levels was negatively correlated with high triglycerides (TG) risk in workers overall (OR = 0.51; 95% CI: 0.36, 0.73; p <  0.01). The results of males and females were consistent (OR = 0.53; 95% CI: 0.34, 0.81; p <  0.01) and (OR = 0.47; 95% CI: 0.24, 0.94; p <  0.01), respectively. By performing interactions analyses of workers overall, we observed no significant interactions among confounders. Mn-TWA levels and pack-years on high TG risk (relative excess risk for the interactions (RERI = 2.29, 95% CI: − 2.07, 6.66), (RERI) = 2.98, 95% CI: − 2.30, 8.26). Similarly, smoking status, drinking status, high-fat diet frequency, and Waist-to-Hip Ratio (WHR) showed non-significant interactions with Mn-TWA levels on high TG risk.

Conclusions

This research indicates that high Mn exposure was negatively related to high TG risk in workers.
Management of initial colonisations with Burkholderia species in France, with retrospective analysis in five cystic fibrosis Centres: a pilot study
Authors: Gruzelle Vianney , Guet-Revillet Hélène , Segonds Christine , Bui Stéphanie , Macey Julie , Chiron Raphaël , Michelet Marine , Murris-Espin Marlène , Mittaine Marie
Published: June 2020

Background

Whereas Burkholderia infections are recognized to impair prognosis in cystic fibrosis (CF) patients, there is no recommendation to date for early eradication therapy. The aim of our study was to analyse the current management of initial colonisations with Burkholderia cepacia complex (BCC) or B. gladioli in French CF Centres and its impact on bacterial clearance and clinical outcome.

Methods

We performed a retrospective review of the primary colonisations (PC), defined as newly positive sputum cultures, observed between 2010 and 2018 in five CF Centres. Treatment regimens, microbiological and clinical data were collected.

Results

Seventeen patients (14 with BCC, and 3 with B. gladioli) were included. Eradication therapy, using heterogeneous combinations of intravenous, oral or nebulised antibiotics, was attempted in 11 patients. Six out of the 11 treated patients, and 4 out of the 6 untreated patients cleared the bacterium. Though not statistically significant, higher forced expiratory volume in 1 second and forced vital capacity at PC and consistency of treatment with in vitro antibiotic susceptibility tended to be associated with eradication. The management of PC was shown to be heterogeneous, thus impairing the statistical power of our study. Large prospective studies are needed to define whom to treat, when, and how.

Conclusions

Pending these studies, we propose, due to possible spontaneous clearance, to check the presence of Burkholderia 1 month after PC before starting antibiotics, at least in the milder cases, and to evaluate a combination of intravenous beta-lactam + oral or intravenous fluoroquinolone + inhaled aminoglycoside.
Iridoid glycosides from Morinda officinalis How. exert anti-inflammatory and anti-arthritic effects through inactivating MAPK and NF-κB signaling pathways
Authors: Zhang Qi , Zhang Jian-hua , He Yu-qiong , Zhang Quan-long , Zhu Bo , Shen Yi , Liu Meng-qin , Zhu Lu-lin , Xin Hai-liang , Qin Lu-ping , Zhang Qiao-yan
Published: June 2020

Background

The root of Morinda officinalis How. (MO, the family of Rubiaceae) has long been used to treat inflammatory diseases in China and other eastern Asian countries, and iridoid glycosides extracted from MO (MOIG) are believed to contribute to this anti-inflammatory effect. However, the mechanism underlying the anti-inflammatory and anti-arthritic activities of MOIG has not been elucidated. The aim of the present study was to determine how MOIG exerted anti-inflammatory and anti-arthritic effects in vivo and in RAW 264.7 macrophages.

Methods

MOIG were enriched by XDA-1 macroporous resin. The maximum feasible dose method was adopted to evaluate its acute toxicity. The analgesic effect of MOIG was evaluated by acetic acid writhing test and the anti-inflammatory effect was evaluated by cotton-pellet granuloma test in rats and air pouch granuloma test in mice. The anti-arthritic effect was evaluated by establishing an adjuvant arthritis model induced by Complete Freund’s Adjuvant (CFA). The viability of the cultured RAW 264.7 macrophages was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was evaluated by measuring NO, IL-1β, IL-6 and TNF-α levels in LPS-stimulated RAW 264.7 cells. The protein level of inflammatory responsive genes was evaluated by Western blot analysis.

Results

MOIG had no significant toxicity at maximum feasible dose of 22.5 g/kg. MO extracts and MOIG (50,100 and 200 mg/kg) all evoked a significantly inhibitory effects on the frequency of twisting induced by acetic acid in mice compared with the model control group. Administration of MO extracts and MOIG markedly decreased the dry and wet weight of cotton pellet granuloma in rats and air pouch granuloma in mice. MOIG significantly attenuated the paw swelling and decreased the arthritic score, weight loss, spleen index, and the serum level of inflammatory factors IL-1β, IL-6 and IL-17a in CFA-induced arthritic rats. MOIG inhibited the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells, and the expressions of iNOS, COX-2 and proteins related to MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 macrophages.

Conclusion

MOIG exerted anti-inflammatory and anti-arthritic activities through inactivating MAPK and NF-κB signaling pathways, and this finding may provide a sound experimental basis for the clinical treatment of rheumatoid arthritis with MOIG.
Online yoga to reduce post traumatic stress in women who have experienced stillbirth: a randomized control feasibility trial
Authors: Huberty Jennifer , Sullivan Mariah , Green Jeni , Kurka Jonathan , Leiferman Jenn , Gold Katherine , Cacciatore Joanne
Published: June 2020

Background

About 1 in every 150 pregnancies end in stillbirth. Consequences include symptoms of post traumatic stress disorder (PTSD), depression, and anxiety. Yoga has been used to treat PTSD in other populations and may improve health outcomes for stillbirth mothers. The purpose of this study was to determine: (a) feasibility of a 12-week home-based, online yoga intervention with varying doses; (b) acceptability of a “stretch and tone” control group; and (c) preliminary efficacy of the intervention on reducing symptoms of PTSD, anxiety, depression, perinatal grief, self-compassion, emotional regulation, mindfulness, sleep quality, and subjective health.

Methods

Participants (N = 90) were recruited nationally and randomized into one of three groups for yoga or exercise (low dose (LD), 60 min per week; moderate dose (MD), 150 min per week; and stretch-and-tone control group (STC)). Baseline and post-intervention surveys measured main outcomes (listed above). Frequency analyses were used to determine feasibility. Repeated measures ANCOVA were used to determine preliminary efficacy. Multiple regression analyses were used to determine a dose-response relationship between minutes of yoga and each outcome variable.

Results

Over half of participants completed the intervention (n = 48/90). Benchmarks (≥70% reported > 75% satisfaction) were met in each group for satisfaction and enjoyment. Participants meeting benchmarks (completing > 90% of prescribed minutes 9/12 weeks) for LD and MD groups were 44% (n = 8/18) and 6% (n = 1/16), respectively. LD and MD groups averaged 44.0 and 77.3 min per week of yoga, respectively. The MD group reported that 150 prescribed minutes per week of yoga was too much. There were significant decreases in PTSD and depression, and improvements in self-rated health at post-intervention for both intervention groups. There was a significant difference in depression scores (p = .036) and grief intensity (p = .009) between the MD and STC groups. PTSD showed non-significant decreases of 43% and 56% at post-intervention in LD and MD groups, respectively (22% decrease in control).

Conclusions

This was the first study to determine the feasibility and preliminary efficacy of an online yoga intervention for women after stillbirth. Future research warrants a randomized controlled trial.

Trial registration

ClinicalTrials.gov. NCT02925481. Registered 10–04-16.
Towards a comprehensive and interoperable representation of consent-based data usage permissions in the German medical informatics initiative
Authors: Bild Raffael , Bialke Martin , Buckow Karoline , Ganslandt Thomas , Ihrig Kristina , Jahns Roland , Merzweiler Angela , Roschka Sybille , Schreiweis Björn , Stäubert Sebastian , Zenker Sven , Prasser Fabian
Published: June 2020

Background

The aim of the German Medical Informatics Initiative is to establish a national infrastructure for integrating and sharing health data. To this, Data Integration Centers are set up at university medical centers, which address data harmonization, information security and data protection. To capture patient consent, a common informed consent template has been developed. It consists of different modules addressing permissions for using data and biosamples. On the technical level, a common digital representation of information from signed consent templates is needed. As the partners in the initiative are free to adopt different solutions for managing consent information (e.g. IHE BPPC or HL7 FHIR Consent Resources), we had to develop an interoperability layer.

Methods

First, we compiled an overview of data items required to reflect the information from the MII consent template as well as patient preferences and derived permissions. Next, we created entity-relationship diagrams to formally describe the conceptual data model underlying relevant items. We then compared this data model to conceptual models describing representations of consent information using different interoperability standards. We used the result of this comparison to derive an interoperable representation that can be mapped to common standards.

Results

The digital representation needs to capture the following information: (1) version of the consent, (2) consent status for each module, and (3) period of validity of the status. We found that there is no generally accepted solution to represent status information in a manner interoperable with all relevant standards. Hence, we developed a pragmatic solution, comprising codes which describe combinations of modules with a basic set of status labels. We propose to maintain these codes in a public registry called ART-DECOR. We present concrete technical implementations of our approach using HL7 FHIR and IHE BPPC which are also compatible with the open-source consent management software gICS.

Conclusions

The proposed digital representation is (1) generic enough to capture relevant information from a wide range of consent documents and data use regulations and (2) interoperable with common technical standards. We plan to extend our model to include more fine-grained status codes and rules for automated access control.
Co-production in health policy and management: a comprehensive bibliometric review
Authors: Fusco Floriana , Marsilio Marta , Guglielmetti Chiara
Published: June 2020

Background

Due to an increasingly elderly population, a higher incidence of chronic diseases and higher expectations regarding public service provision, healthcare services are under increasing strain to cut costs while maintaining quality. The importance of promoting systems of co-produced health between stakeholders has gained considerable traction both in the literature and in public sector policy debates. This study provides a comprehensive map of the extant literature and identifies the main themes and future research needs.

Methods

A quantitative bibliometric analysis was carried out consisting of a performance analysis, science mapping, and a scientific collaboration analysis. Web of Science (WoS) was chosen to extract the dataset; the search was refined by language, i.e. English, and type of publication, i.e. journal academic articles and reviews. No time limitation was selected.

Results

The dataset is made up of 295 papers ranging from 1994 to May 2019. The analysis highlighted an annual percentage growth rate in the topic of co-production of about 25%. The articles retrieved are split between 1225 authors and 148 sources. This fragmentation was confirmed by the collaboration analysis, which revealed very few long-lasting collaborations. The scientific production is geographically polarised within the EU and Anglo-Saxon countries, with the United Kingdom playing a central role. The intellectual structure consists of three main areas: public administration and management, service management and knowledge translation literature. The co-word analysis confirms the relatively low scientific maturity of co-production applied to health services. It shows few well-developed and central terms, which refer to traditional areas of co-production (e.g. public health, social care), and some emerging themes related to social and health phenomena (e.g. the elderly and chronic diseases), the use of technologies, and the recent patient-centred approach to care (patient involvement/engagement).

Conclusions

The field is still far from being mature. Empirical practices, especially regarding co-delivery and co-management as well as the evaluation of their real impacts on providers and on patients are lacking and should be more widely investigated.
Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD: results on cardiovascular safety from the IMPACT trial
Authors: Day Nicola C. , Kumar Subramanya , Criner Gerard , Dransfield Mark , Halpin David M. G. , Han MeiLan K. , Jones C. Elaine , Kaisermann Morrys C. , Kilbride Sally , Lange Peter , Lomas David A. , Martin Neil , Martinez Fernando J. , Singh Dave , Wise Robert , Lipson David A.
Published: June 2020

Background

This analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy.

Methods

IMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death.

Results

Baseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments.

Conclusions

In a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10–11% and 1–3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI.

Trial registration

NCT02164513 (GSK study number CTT116855).
RETRACTED ARTICLE: CircTLK1 promotes the proliferation and metastasis of renal cell carcinoma by sponging miR-136-5p
Authors: Li Jianfa , Huang Chenchen , Zou Yifan , Ye Jing , Yu Jing , Gui Yaoting
Published: June 2020

Background

Circular RNAs (circRNAs), a novel type of noncoding RNA (ncRNA), are covalently linked circular configurations that form via a loop structure. Accumulating evidence indicates that circRNAs are potential biomarkers and key regulators of tumor development and progression. However, the precise roles of circRNAs in renal cell carcinoma (RCC) remain unknown.

Methods

Through circRNA high-throughput sequencing of RCC cell lines, we identified the circRNA TLK1 (circTLK1) as a novel candidate circRNA derived from the TLK1 gene. qRT-PCR detected the mRNA, circRNA and miRNA expression levels in RCC tissues and cells. Loss-of function experiments were executed to detect the biological roles of circTLK1 in the RCC cell phenotypes in vitro and in vivo. RNA-FISH, RNA pull-down, dual-luciferase reporter, western blot and immunohistochemistry assays were used to investigate the molecular mechanisms underlying the functions of circTLK1.

Results

circTLK1 is overexpressed in RCC, and expression is positively correlated with distant metastasis and unfavorable prognosis. Silencing circTLK1 significantly inhibited RCC cell proliferation, migration and invasion in vitro and in vivo. circTLK1 was mainly distributed in the cytoplasm and positively regulated CBX4 expression by sponging miR-136-5p. Forced CBX4 expression reversed the circTLK1 suppression-induced phenotypic inhibition of RCC cells. Moreover, CBX4 expression was positively correlated with VEGFA expression in RCC tissues. CBX4 knockdown significantly inhibited VEGFA expression in RCC cells.

Conclusion

Collectively, our findings demonstrate that circTLK1 plays a critical role in RCC progression by sponging miR-136-5p to increase CBX4 expression. circTLK1 may act as a diagnostic biomarker and therapeutic target for RCC.
Burnout in nursing: a theoretical review
Authors: Dall’Ora Chiara , Ball Jane , Reinius Maria , Griffiths Peter
Published: June 2020

Background

Workforce studies often identify burnout as a nursing ‘outcome’. Yet, burnout itself—what constitutes it, what factors contribute to its development, and what the wider consequences are for individuals, organisations, or their patients—is rarely made explicit. We aimed to provide a comprehensive summary of research that examines theorised relationships between burnout and other variables, in order to determine what is known (and not known) about the causes and consequences of burnout in nursing, and how this relates to theories of burnout.

Methods

We searched MEDLINE, CINAHL, and PsycINFO. We included quantitative primary empirical studies (published in English) which examined associations between burnout and work-related factors in the nursing workforce.

Results

Ninety-one papers were identified. The majority (n= 87) were cross-sectional studies; 39 studies used all three subscales of the Maslach Burnout Inventory (MBI) Scale to measure burnout. As hypothesised by Maslach, we identified high workload, value incongruence, low control over the job, low decision latitude, poor social climate/social support, and low rewards as predictors of burnout. Maslach suggested that turnover, sickness absence, and general health were effects of burnout; however, we identified relationships only with general health and sickness absence. Other factors that were classified as predictors of burnout in the nursing literature were low/inadequate nurse staffing levels, ≥ 12-h shifts, low schedule flexibility, time pressure, high job and psychological demands, low task variety, role conflict, low autonomy, negative nurse-physician relationship, poor supervisor/leader support, poor leadership, negative team relationship, and job insecurity. Among the outcomes of burnout, we found reduced job performance, poor quality of care, poor patient safety, adverse events, patient negative experience, medication errors, infections, patient falls, and intention to leave.

Conclusions

The patterns identified by these studies consistently show that adverse job characteristics—high workload, low staffing levels, long shifts, and low control—are associated with burnout in nursing. The potential consequences for staff and patients are severe. The literature on burnout in nursing partly supports Maslach’s theory, but some areas are insufficiently tested, in particular, the association between burnout and turnover, and relationships were found for some MBI dimensions only.
Inhibition of lysine acetyltransferases impairs tumor angiogenesis acting on both endothelial and tumor cells
Authors: Di Martile Marta , Gabellini Chiara , Desideri Marianna , Matraxia Marta , Farini Valentina , Valentini Elisabetta , Carradori Simone , Ercolani Cristiana , Buglioni Simonetta , Secci Daniela , Andreazzoli Massimiliano , Del Bufalo Donatella , Trisciuoglio Daniela
Published: June 2020

Background

Understanding the signalling pathways involved in angiogenesis, and developing anti-angiogenic drugs are one of the major focuses on cancer research. Herein, we assessed the effect of CPTH6, a lysine acetyltransferase inhibitor and anti-tumoral compound, on angiogenesis-related properties of both endothelial and cancer cells.

Methods

The in vitro effect of CPTH6 on protein acetylation and anti-angiogenic properties on endothelial and lung cancer cells was evaluated via wound healing, trans-well invasion and migration, tube formation, immunoblotting and immunofluorescence. Matrigel plug assay, zebrafish embryo and mouse xenograft models were used to evaluate in vivo anti-angiogenic effect of CPTH6.

Results

CPTH6 impaired in vitro endothelial angiogenesis-related functions, and decreased the in vivo vascularization both in mice xenografts and zebrafish embryos. Mechanistically, CPTH6 reduced α-tubulin acetylation and induced accumulation of acetylated microtubules in the perinuclear region of endothelial cells. Interestingly, CPTH6 also affected the angiogenesis-related properties of lung cancer cells, and conditioned media derived from CPTH6-treated lung cancer cells impaired endothelial cells morphogenesis. CPTH6 also modulated the VEGF/VEGFR2 pathway, and reshaped cytoskeletal organization of lung cancer cells. Finally, anti-migratory effect of CPTH6, dependent on α-tubulin acetylation, was also demonstrated by genetic approaches in lung cancer cells.

Conclusion

Overall, this study indicates that α-tubulin acetylation could play a role in the anti-angiogenic effect of CPTH6 and, more in general, it adds information to the role of histone acetyltransferases in tumor angiogenesis, and proposes the inhibition of these enzymes as an antiangiogenic therapy of cancer.
Biomarkers of sepsis: time for a reappraisal
Authors: Pierrakos Charalampos , Velissaris Dimitrios , Bisdorff Max , Marshall John C. , Vincent Jean-Louis
Published: June 2020

Introduction

Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers.

Methods

Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms “Biomarker” AND “Sepsis.” There were no restrictions by age or language, and all studies, clinical and experimental, were included.

Results

We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis.

Conclusions

The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.
CTCF loss mediates unique DNA hypermethylation landscapes in human cancers
Authors: Damaschke Nathan A. , Gawdzik Joseph , Avilla Mele , Yang Bing , Svaren John , Roopra Avtar , Luo Jian-Hua , Yu Yan P. , Keles Sunduz , Jarrard David F.
Published: June 2020

Background

The chromatin insulator CCCTC-binding factor (CTCF) displays tissue-specific DNA binding sites that regulate transcription and chromatin organization. Despite evidence linking CTCF to the protection of epigenetic states through barrier insulation, the impact of CTCF loss on genome-wide DNA methylation sites in human cancer remains undefined.

Results

Here, we demonstrate that prostate and breast cancers within The Cancer Genome Atlas (TCGA) exhibit frequent copy number loss of CTCF and that this loss is associated with increased DNA methylation events that occur preferentially at CTCF binding sites. CTCF sites differ among tumor types and result in tissue-specific methylation patterns with little overlap between breast and prostate cancers. DNA methylation and transcriptome profiling in vitro establish that forced downregulation of CTCF leads to spatially distinct DNA hypermethylation surrounding CTCF binding sites, loss of CTCF binding, and decreased gene expression that is also seen in human tumors. DNA methylation inhibition reverses loss of expression at these CTCF-regulated genes.

Conclusion

These findings establish CTCF loss as a major mediator in directing localized DNA hypermethylation events in a tissue-specific fashion and further support its role as a driver of the cancer phenotype.
Immunopathology in schistosomiasis is regulated by TLR2,4- and IFN-γ-activated MSC through modulating Th1/Th2 responses
Authors: Liu Chao , Zhang Yi-shu , Chen Fang , Wu Xiao-ying , Zhang Bei-bei , Wu Zhong-dao , Lei Jun-xia
Published: June 2020

Background and aims

A marked egg-induced CD4+ T cell programmed inflammation and subsequent hepatic fibrosis characterize the pathogenesis of schistosomiasis. Mesenchymal stem cell (MSC) has been extensively studied for the treatment of schistosomiasis. However, the mechanism by which MSCs modulate the pathogenesis of schistosomiasis has not been clarified. Furthermore, the local inflammatory milieu may greatly influence the immunoregulatory properties of MSCs, and our early experiments demonstrated that Toll-like receptor (TLR)2/TLR4 agonist effected immune modulation of MSC. Here, we further investigated their modulation on the pathogenesis of schistosomiasis.

Methods

Adult BALB/c male mice were percutaneously infected with 16 ± 2 pairs S. japonicum cercariae and received intravenously pretreated MSC at 1 week and 3 weeks post-infection, respectively. At 8 weeks post-infection, effects of MSC on liver histology were shown by hematoxylin and eosin (H&E) staining and Masson staining and quantitatively compared by the hepatic hydroxyproline content; α-smooth muscle actin (α-SMA), collagen type I(Col-1), transforming growth factor β (TGF-β), and tumor necrosis factor-α (TNF-α) gene expression in the liver were assessed by semi-quantitative polymerase chain reaction (PCR); the Th1/Th2 dominance among different groups was compared by analyzing CD4+ interferon-γ (IFN-γ)+ and CD4+interleukin-4 (IL-4)+T cells in the liver by flow cytometry and serum level of IFN-γ and IL-5 using enzyme-linked immunosorbent assay (ELISA). Effects of different kinds of MSC were further evaluated in vitro by the coculture system.

Results

Results showed TLR4- and IFN-γ-activated MSC alleviated liver fibrosis in infected mice, without a significant increase of mortality, and unpretreated MSC showed no clear improvement; however, TLR2- and IFN-γ-activated MSC displayed aggravated immunopathology. In accord with the pathological results, TLR4- and IFN-γ-activated MSC groups showed moderate enhancement of Th1 response in vitro and clear Th1 dominance in vivo without leading to extreme inflammation, whereas TLR2- and IFN-γ-activated MSC not only induced Th1 response, but also triggered excessive inflammation as evidenced by atrophy of the thymus and higher TNF level in the coculture system.

Conclusions

This study demonstrates that TLR4 combined with IFN-γ can activate the MSC group with positive effects on the pathology of schistosomiasis by modulating Th subsets at some degree. This result suggests that when MSC is being used to treat different immuno-disturbance complications, subtle pretreatment methods should be seriously considered.