bluuebunny/crossref_metadata_2025 huggingface dataset:
An Analysis of Past Florence Nightingale Medal Recipients: Insights Into Exceptional Nurses and the Evolution of Nursing
Authors: Wang Qian , Zhu Ruifang , Duan Zhiguang
Published: January 2021

Aim

To examine past Florence Nightingale Medal recipients’ parallels with the evolving nature of the nursing field as a whole.

Design

Descriptive research.

Method

The professional and demographic characteristics of 1,449 Florence Nightingale Medal recipients between 1920 and 2015 were analyzed to develop a high-level overview of the award recipient characteristics.

Result

Medal recipients were primarily female (98.07%), with 36% being Specialist nurses. Awards were mainly conferred for aid work (30.4%) in the context of war or armed conflict followed by Nursing education (17.2%) and disaster aid (14.9%). The majority of recipients were affiliated with the Red Cross and the majority of recipients were those conducting Red Cross duties.

Conclusion

Our results offer statistical validation for the dedication of these exceptional individuals, while also highlighting overall parallels with the ongoing development of the nursing field as it expands to better deliver culturally-sensitive care and to overcome outdated stereotypes that would otherwise constrain innovation.
PPARγ increases HUWE1 to attenuate NF-κB/p65 and sickle cell disease with pulmonary hypertension
Authors: Jang Andrew J. , Chang Sarah S. , Park Changwon , Lee Choon-Myung , Benza Raymond L. , Passineau Michael J. , Ma Jing , Archer David R. , Sutliff Roy L. , Hart C. Michael , Kang Bum-Yong
Published: January 2021

Sickle cell disease (SCD)-associated pulmonary hypertension (PH) causes significant morbidity and mortality. Here, we defined the role of endothelial specific peroxisome proliferator-activated receptor γ (PPARγ) function and novel PPARγ/HUWE1/miR-98 signaling pathways in the pathogenesis of SCD-PH. PH and right ventricular hypertrophy (RVH) were increased in chimeric Townes humanized sickle cell (SS) mice with endothelial-targeted PPARγ knockout (SSePPARγKO) compared with chimeric littermate control (SSLitCon). Lung levels of PPARγ, HUWE1, and miR-98 were reduced in SSePPARγKO mice compared with SSLitCon mice, whereas SSePPARγKO lungs were characterized by increased levels of p65, ET-1, and VCAM1. Collectively, these findings indicate that loss of endothelial PPARγ is sufficient to increase ET-1 and VCAM1 that contribute to endothelial dysfunction and SCD-PH pathogenesis. Levels of HUWE1 and miR-98 were decreased, and p65 levels were increased in the lungs of SS mice in vivo and in hemin-treated human pulmonary artery endothelial cells (HPAECs) in vitro. Although silencing of p65 does not regulate HUWE1 levels, the loss of HUWE1 increased p65 levels in HPAECs. Overexpression of PPARγ attenuated hemin-induced reductions of HUWE1 and miR-98 and increases in p65 and endothelial dysfunction. Similarly, PPARγ activation attenuated baseline PH and RVH and increased HUWE1 and miR-98 in SS lungs. In vitro, hemin treatment reduced PPARγ, HUWE1, and miR-98 levels and increased p65 expression, HPAEC monocyte adhesion, and proliferation. These derangements were attenuated by pharmacological PPARγ activation. Targeting these signaling pathways can favorably modulate a spectrum of pathobiological responses in SCD-PH pathogenesis, highlighting novel therapeutic targets in SCD pulmonary vascular dysfunction and PH.
Significant differences in single-platelet biophysics exist across species but attenuate during clot formation
Authors: Oshinowo Oluwamayokun , Copeland Renee , Sakurai Yumiko , Fay Meredith E. , Petrich Brian G. , Leong Traci , Brainard Benjamin , Lam Wilbur A.
Published: January 2021

Key Points

Human, canine, ovine, and porcine platelets exhibit disparate biophysical signatures, whereas human and murine platelets are similar. Multiple biophysical parameters integrate during clot formation, measured by bulk clot contraction, and attenuate biophysical differences.
Clinical characteristics and 3-month outcomes in cancer patients with incidentalversusclinically suspected and confirmed pulmonary embolism
Authors: Peris Marisa , López-Nuñez Juan J. , Maestre Ana , Jimenez David , Muriel Alfonso , Bikdeli Behnood , Weinberg Ido , Ay Cihan , Mazzolai Lucia , Lorenzo Alicia , Monreal Manuel ,   the RIETE Investigators
Published: January 2021

Background

Current guidelines suggest treating cancer patients with incidental pulmonary embolism (PE) similarly to those with clinically suspected and confirmed PE. However, the natural history of these presentations has not been thoroughly compared.

Methods

We used the data from the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the 3-month outcomes in patients with active cancer and incidental PEversusthose with clinically suspected and confirmed PE. The primary outcome was 90-day all-cause mortality. Secondary outcomes were PE-related mortality, symptomatic PE recurrences and major bleeding.

Results

From July 2012 to January 2019, 946 cancer patients with incidental asymptomatic PE and 2274 with clinically suspected and confirmed PE were enrolled. Most patients (95%versus90%) received low-molecular-weight heparin therapy. During the first 90 days, 598 patients died, including 42 from PE. Patients with incidental PE had a lower all-cause mortality rate than those with suspected and confirmed PE (11%versus22%; OR 0.43, 95% CI 0.34–0.54). Results were consistent for PE-related mortality (0.3%versus1.7%; OR 0.18, 95% CI 0.06–0.59). Multivariable analysis confirmed that patients with incidental PE were at lower risk of death (adjusted OR 0.43, 95% CI 0.34–0.56). Overall, 29 (0.9%) patients developed symptomatic PE recurrences, and 122 (3.8%) had major bleeding. There were no significant differences in PE recurrences (OR 0.62, 95% CI 0.25–1.54) or major bleeding (OR 0.78, 95% CI 0.51–1.18).

Conclusions

Cancer patients with incidental PE had a lower mortality rate than those with clinically suspected and confirmed PE. Further studies are required to validate these findings, and to explore optimal management strategies in these patients.
Genome-wide association study of asthma exacerbations despite inhaled corticosteroid use
Authors: Hernandez-Pacheco Natalia , Vijverberg Susanne J. , Herrera-Luis Esther , Li Jiang , Sio Yang Yie , Granell Raquel , Corrales Almudena , Maroteau Cyrielle , Lethem Ryan , Perez-Garcia Javier , Farzan Niloufar , Repnik Katja , Gorenjak Mario , Soares Patricia , Karimi Leila , Schieck Maximilian , Pérez-Méndez Lina , Berce Vojko , Tavendale Roger , Eng Celeste , Sardon Olaia , Kull Inger , Mukhopadhyay Somnath , Pirmohamed Munir , Verhamme Katia M.C. , Burchard Esteban G. , Kabesch Michael , Hawcutt Daniel B. , Melén Erik , Potočnik Uroš , Chew Fook Tim , Tantisira Kelan G. , Turner Steve , Palmer Colin N. , Flores Carlos , Pino-Yanes Maria , Maitland-van der Zee Anke H.
Published: January 2021

Rationale

Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies.

Methods

A genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 children of European descent treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed.

Results

10 independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10−6). Of those, one variant at theCACNA2D3-WNT5Alocus was nominally replicated in Europeans (rs67026078; p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found.

Conclusions

The intergenic region ofCACNA2D3andWNT5Awas revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response.
Dyspnoea, lung function and CT findings 3 months after hospital admission for COVID-19
Authors: Lerum Tøri Vigeland , Aaløkken Trond Mogens , Brønstad Eivind , Aarli Bernt , Ikdahl Eirik , Lund Kristine Marie Aarberg , Durheim Michael T. , Rodriguez Jezabel Rivero , Meltzer Carin , Tonby Kristian , Stavem Knut , Skjønsberg Ole Henning , Ashraf Haseem , Einvik Gunnar
Published: January 2021

The long-term pulmonary outcomes of coronavirus disease 2019 (COVID-19) are unknown. We aimed to describe self-reported dyspnoea, quality of life, pulmonary function and chest computed tomography (CT) findings 3 months following hospital admission for COVID-19. We hypothesised outcomes to be inferior for patients admitted to intensive care units (ICUs), compared with non-ICU patients.

Discharged COVID-19 patients from six Norwegian hospitals were enrolled consecutively in a prospective cohort study. The current report describes the first 103 participants, including 15 ICU patients. The modified Medical Research Council (mMRC) dyspnoea scale, the EuroQol Group's questionnaire, spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), 6-min walk test, pulse oximetry and low-dose CT scan were performed 3 months after discharge.

mMRC score was >0 in 54% and >1 in 19% of the participants. The median (25th–75th percentile) forced vital capacity and forced expiratory volume in 1 s were 94% (76–121%) and 92% (84–106%) of predicted, respectively.DLCOwas below the lower limit of normal in 24% of participants. Ground-glass opacities (GGO) with >10% distribution in at least one of four pulmonary zones were present in 25% of participants, while 19% had parenchymal bands on chest CT. ICU survivors had similar dyspnoea scores and pulmonary function as non-ICU patients, but higher prevalence of GGO (adjusted OR 4.2, 95% CI 1.1–15.6) and lower performance in usual activities.

3 months after admission for COVID-19, one-fourth of the participants had chest CT opacities and reduced diffusing capacity. Admission to ICU was associated with pathological CT findings. This was not reflected in increased dyspnoea or impaired lung function.
Viable virus aerosol propagation by positive airway pressure circuit leak and mitigation with a ventilated patient hood
Authors: Landry Shane A. , Barr Jeremy J. , MacDonald Martin I. , Subedi Dinesh , Mansfield Darren , Hamilton Garun S. , Edwards Bradley A. , Joosten Simon A.
Published: January 2021

Introduction

Nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major feature of the COVID-19 pandemic. Evidence suggests patients can auto-emit aerosols containing viable viruses; these aerosols could be further propagated when patients undergo certain treatments, including continuous positive airway pressure (PAP) therapy. Our aim was to assess 1) the degree of viable virus propagated from PAP circuit mask leak and 2) the efficacy of a ventilated plastic canopy to mitigate virus propagation.

Methods

Bacteriophage phiX174 (108 copies·mL−1) was nebulised into a custom PAP circuit. Mask leak was systematically varied at the mask interface. Plates containingEscherichia colihost quantified viable virus (viaplaque forming unit) settling on surfaces around the room. The efficacy of a low-cost ventilated headboard created from a tarpaulin hood and a high-efficiency particulate air (HEPA) filter was tested.

Results

Mask leak was associated with virus contamination in a dose-dependent manner (χ2=58.24, df=4, p<0.001). Moderate mask leak (≥21 L·min−1) was associated with virus counts equivalent to using PAP with a vented mask. The highest frequency of viruses was detected on surfaces <1 m away; however, viable viruses were recorded up to 3.86 m from the source. A plastic hood with HEPA filtration significantly reduced viable viruses on all plates. HEPA exchange rates ≥170 m3·h−1eradicated all evidence of virus contamination.

Conclusions

Mask leak from PAP may be a major source of environmental contamination and nosocomial spread of infectious respiratory diseases. Subclinical mask leak levels should be treated as an infectious risk. Low-cost patient hoods with HEPA filtration are an effective countermeasure.
Does the use of inhaled corticosteroids in asthma benefit lung function in the long-term? A systematic review and meta-analysis
Authors: Tan Daniel J. , Bui Din S. , Dai Xin , Lodge Caroline J. , Lowe Adrian J. , Thomas Paul S. , Jarvis Deborah , Abramson Michael J. , Walters E. Haydn , Perret Jennifer L. , Dharmage Shyamali C.
Published: January 2021

While asthma is known to be associated with an increased risk of progressive lung function impairments and fixed airflow obstruction, there is ongoing debate on whether inhaled corticosteroids (ICS) modify these long-term risks.

Searches were performed of the PubMed, Embase and CENTRAL databases up to 22 July 2019 for studies with follow-up ≥1 year that investigated the effects of maintenance ICS on changes in lung function in asthma.

Inclusion criteria were met by 13 randomised controlled trials (RCTs) (n=11 678) and 11 observational studies (n=3720). Median (interquartile range) follow-up was 1.0 (1–4) and 8.4 (3–28) years, respectively. In the RCTs, predominantly in individuals with mild asthma, ICS use was associated with improved pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1) across all age groups (2.22% predicted (95% CI 1.32–3.12), n=8332), with similar estimates of strength in association for children and adults. Improvements in post-BD FEV1were observed in adults (1.54% (0.87–2.21), n=3970), but not in children (0.20% (−0.49–0.90), n=3924) (subgroup difference, p=0.006). Estimates were similar between smokers and nonsmokers. There were no RCT data on incidence of fixed airflow obstruction. In the observational studies, ICS use was associated with improved pre-BD FEV1in children and adults. There were limited observational data for post-BD outcomes.

In patients with mild asthma, maintenance ICS are associated with modest, age-dependent improvements in long-term lung function, representing an added benefit to the broader clinical actions of ICS in asthma. There is currently insufficient evidence to determine whether treatment reduces incidence of fixed airflow obstruction in later life.
Update on biology and management of mesothelioma
Authors: Asciak Rachelle , George Vineeth , Rahman Najiib M.
Published: January 2021

Malignant pleural mesothelioma is an aggressive, incurable cancer that is usually caused by asbestos exposure several decades before symptoms arise. Despite widespread prohibition of asbestos production and supply, its incidence continues to increase. It is heterogeneous in its presentation and behaviour, and diagnosis can be notoriously difficult. Identification of actionable gene mutations has proven challenging and current treatment options are largely ineffective, with a median survival of 10–12 months.

However, the past few years have witnessed major advances in our understanding of the biology and pathogenesis of mesothelioma. This has also revealed the limitations of existing diagnostic algorithms and identified new treatment targets.

Recent clinical trials have re-examined the role of surgery, provided new options for the management of associated pleural effusions and heralded the addition of targeted therapies. The increasing complexity of mesothelioma management, along with a desperate need for further research, means that a multidisciplinary team framework is essential for the delivery of contemporary mesothelioma care.

This review provides a synthesised overview of the current state of knowledge and an update on the latest research in the field.
Mesenchymal stem cells as a double-edged sword in tumor growth: focusing on MSC-derived cytokines
Authors: Liang Wenqing , Chen Xiaozhen , Zhang Songou , Fang Jian , Chen Meikai , Xu Yifan , Chen Xuerong
Published: January 2021

Mesenchymal stem cells (MSCs) show homing capacity towards tumor sites. Numerous reports indicate that they are involved in multiple tumor-promoting processes through several mechanisms, including immunosuppression; stimulation of angiogenesis; transition to cancer-associated fibroblasts; inhibition of cancer cell apoptosis; induction of epithelial–mesenchymal transition (EMT); and increase metastasis and chemoresistance. However, other studies have shown that MSCs suppress tumor growth by suppressing angiogenesis, incrementing inflammatory infiltration, apoptosis and cell cycle arrest, and inhibiting the AKT and Wnt signaling pathways. In this review, we discuss the supportive and suppressive impacts of MSCs on tumor progression and metastasis. We also discuss MSC-based therapeutic strategies for cancer based on their potential for homing to tumor sites.
circRNA_0005529 facilitates growth and metastasis of gastric cancer via regulating miR-527/Sp1 axis
Authors: Zhang Xing , Yang Hongwei , Jia Yingdong , Xu Zhengwen , Zhang Liuping , Sun Meng , Fu Jing
Published: January 2021

Background

Circular RNAs (circRNAs) are endogenous non-coding RNAs, which are associated with various biological processes, including microRNA (miRNA) interaction, protein binding and regulatory splicing. circRNA_0005529 (circ_0005529) is derived from vacuolar protein sorting 33 homologue B (VPS33B), and its biological role in gastric cancer (GC) has not been examined. In this study, the expression and location of circ_0005529 and microRNA-527 (miR-527) were determined by qRT-PCR and fluorescence in situ hybridization (FISH). Cell proliferation and cell migration were determined by MTT, EdU incorporation, colony formation, wound scratch and transwell assays. In addition, immunohistochemistry and western blotting were performed to determine the expressions of specificity protein 1 (Sp1), PCNA, c-myc, E-cadherin and N-cadherin. Western blotting and luciferase reporter assay were performed to study the interaction between circ_0005529 and miR-527 or miR-527 and Sp1. The functional effects of circ_0005529 on GC through regulating Sp1 were further evaluated using xenograft and metastatic mouse models in vivo.

Results

Our results showed that circ_0005529 was upregulated in GC tissues and cells, and had promoting effects on cell proliferation and cell migration. Mechanism analysis suggested that circ_0005529 could bind to microRNA-527 (miR-527) and reduce its expression. The interaction between miR-527 and Sp1 in GC was systematically studied. In addition, the results indicated that Sp1 upregulation could rescue the effects on cell proliferation and migration caused by circ_0005529. Moreover, the inhibitory effects of circ_0005529 downregulation on GC growth and metastasis were evaluated in mouse models. These findings suggested that the axis of circ_0005529/miR-527/Sp1 may serve as a promising treatment target for GC diagnosis and treatment.

Conclusions

These findings suggested that the signal axis of circ_0005529/miR-527/Sp1 may has the potential to be explored as a novel therapeutic target for GC diagnosis and treatment.

Graphical abstract

Mechanism diagram: During GC development, overexpressed circ_0005529 sponged miR-527 and then upregulated the expression of Sp1. Subsequently, epithelial-mesenchymal transition (EMT), cell proliferation and cell migration were promoted, which ultimately facilitated the tumor metastasis
Systematic comparison of high-throughput single-cell RNA-seq methods for immune cell profiling
Authors: Yamawaki Tracy M. , Lu Daniel R. , Ellwanger Daniel C. , Bhatt Dev , Manzanillo Paolo , Arias Vanessa , Zhou Hong , Yoon Oh Kyu , Homann Oliver , Wang Songli , Li Chi-Ming
Published: January 2021

Background

Elucidation of immune populations with single-cell RNA-seq has greatly benefited the field of immunology by deepening the characterization of immune heterogeneity and leading to the discovery of new subtypes. However, single-cell methods inherently suffer from limitations in the recovery of complete transcriptomes due to the prevalence of cellular and transcriptional dropout events. This issue is often compounded by limited sample availability and limited prior knowledge of heterogeneity, which can confound data interpretation.

Results

Here, we systematically benchmarked seven high-throughput single-cell RNA-seq methods. We prepared 21 libraries under identical conditions of a defined mixture of two human and two murine lymphocyte cell lines, simulating heterogeneity across immune-cell types and cell sizes. We evaluated methods by their cell recovery rate, library efficiency, sensitivity, and ability to recover expression signatures for each cell type. We observed higher mRNA detection sensitivity with the 10x Genomics 5′ v1 and 3′ v3 methods. We demonstrate that these methods have fewer dropout events, which facilitates the identification of differentially-expressed genes and improves the concordance of single-cell profiles to immune bulk RNA-seq signatures.

Conclusion

Overall, our characterization of immune cell mixtures provides useful metrics, which can guide selection of a high-throughput single-cell RNA-seq method for profiling more complex immune-cell heterogeneity usually found in vivo.
The transverse diameter of right common femoral vein by ultrasound in the supine position for predicting post-spinal hypotension during cesarean delivery
Authors: Yao Shi-Fa , Zhao Yan-Hong , Zheng Jing , Qian Jie-Yan , Zhang Chen , Xu Zifeng , Xu Tao
Published: January 2021

Background

Post-spinal anesthesia hypotension during cesarean delivery is caused by decreased systemic vascular resistance due to the blockage of the autonomic nerves, which is further worsened by inferior vena cava (IVC) compression by the gravid uterus. This study aimed to assess whether peak velocity and diameter of the IVC below the xiphoid or right common femoral vein (RCFV) in the inguinal region, as measured on ultrasound, could reflect the degree of IVC compression and further identify parturients at risk of post-spinal hypotension.

Methods

Fifty-six parturients who underwent elective cesarean section with spinal anesthesia were included in this study; peak velocities and anteroposterior diameters of the IVC and peak velocities and transverse diameters of the RCFV were measured using ultrasound before anesthesia. The primary outcome was the ultrasound measurements of IVC and RCFV acquired before spinal anesthesia and their association with post-spinal hypotension. Hypotension was defined as a drop in systolic arterial pressure by > 20% from the baseline. Multinomial logistic regression analysis was used to identify the association between the measurements of IVC, RCFV, and post-spinal hypotension during cesarean delivery. Receiver operating characteristic curves were used to test the abilities of the identified parameters to predict post-spinal hypotension; the areas under the curve and optimum cut-off values for the predictive parameters were calculated.

Results

A longer transverse diameter of the RCFV was associated with the occurrence of post-spinal hypotension (odds ratio = 2.022, 95% confidence interval [CI] 1.261–3.243). The area under the receiver operating characteristics curve for the prediction of post-spinal hypotension was 0.759 (95% CI 0.628–0.890, P = 0.001). A transverse diameter of > 12.2 mm of the RCFV could predict post-spinal hypotension during cesarean delivery.

Conclusions

A longer transverse diameter of RCFV was associated with hypotension and could predict parturients at a major risk of hypotension before anesthesia.

Trial registration

This study was registered at http://www.chictr.org.cn on 16, May, 2018. No. ChiCTR1800016163.
Clinical characteristics of 14 COVID-19 deaths in Tianmen, China: a single-center retrospective study
Authors: Hu Jijia , Zhang Yingang , Wang Wei , Tao Zhihe , Tian Juan , Shao Ning , Liu Nian , Wei Hui , Huang Hao
Published: January 2021

Background

The treatment of critically ill patients with COVID-19 who were hospitalized in Wuhan has been reported. However, the clinical characteristics of patients who died of COVID-19 in regions with relatively scarce healthcare resources remain unknown.

Methods

In this retrospective study, a total of 14 patients who were admitted from January 18 to February 11, 2020 and died of COVID-19 were evaluated. The epidemiological, symptomatic, laboratory, radiological and treatment records were reviewed and analyzed.

Results

The mean age of the 14 patients was 56.7 (SD 15.3) years, and 8 (57.1%) were older than 50 years. Eight (57.1%) were men, and 11 (78.6%) had one or more high risk factors. The most common chronic diseases among these patients were cardiovascular disease (7, 50.0%), hypertension (6, 42.9%), and chronic kidney disease (5, 35.7%). General symptoms included cough (12, 85.7%), fever (11, 78.6%), and dyspnea (10, 71.4%). The median duration from the onset of symptoms to death was 11 (IQR 6.5–19.5) days, and the median duration from admission to death was 4.5 (1.0–11.8) days. Patients who died within 4.5 days had more severe pulmonary lesions, significantly reduced lymphocytes and elevated C-reactive protein (CRP). Most patients had organ dysfunction, including 13 (92.9%) with acute respiratory distress syndrome (ARDS), 4 (28.6%) with cardiac injury, 3 (21.4%) with acute kidney injury, and 3 (21.4%) with liver dysfunction.

Conclusions

Elderly SARS-CoV-2-infected patients with comorbidities, especially those with ARDS and severe chest CT findings on admission, are at increased risk of death and deserve special attention and quality medical treatment.
The different manifestations of COVID-19 in adults and children: a cohort study in an intensive care unit
Authors:   on behalf of the KIDS-Corona study group, Girona-Alarcon Mònica ,   Kids Corona Platform, Bobillo-Perez Sara , Sole-Ribalta Anna , Hernandez Lluisa , Guitart Carmina , Suarez Ricardo , Balaguer Mònica , Cambra Francisco-Jose , Jordan Iolanda
Published: January 2021

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has collapsed health systems worldwide. In adults, the virus causes severe acute respiratory distress syndrome (ARDS), while in children the disease seems to be milder, although a severe multisystem inflammatory syndrome (MIS-C) has been described. The aim was to describe and compare the characteristics of the severe COVID-19 disease in adults and children.

Methods

This prospective observational cohort study included the young adults and children infected with SARS-CoV-2 between March–June 2020 and admitted to the paediatric intensive care unit. The two populations were analysed and compared focusing on their clinical and analytical characteristics and outcomes.

Results

Twenty patients were included. There were 16 adults (80%) and 4 children (20%). No mortality was recorded.

All the adults were admitted due to ARDS. The median age was 32 years (IQR 23.3–41.5) and the most relevant previous pathology was obesity (n = 7, 43.7%). Thirteen (81.3%) needed mechanical ventilation, with a median PEEP of 13 (IQR 10.5–14.5). Six (37.5%) needed inotropic support due to the sedation. Eight (50%) developed a healthcare-associated infection, the most frequent of which was central line-associated bloodstream infection (n = 7, 71.4%). One patient developed a partial pulmonary thromboembolism, despite him being treated with heparin.

All the children were admitted due to MIS-C. Two (50%) required mechanical ventilation. All needed inotropic support, with a median vasoactive-inotropic score of 27.5 (IQR 17.5–30).

The difference in the inotropic requirements between the two populations was statistically significant (37.5% vs. 100%, p < 0.001). The biomarker values were higher in children than in adults: mid-regional pro-adrenomedullin 1.72 vs. 0.78 nmol/L (p = 0.017), procalcitonin 5.7 vs. 0.19 ng/mL (p = 0.023), and C-reactive protein 328.2 vs. 146.9 mg/L (p = 0.005). N-terminal pro-B-type natriuretic peptide and troponins were higher in children than in adults (p = 0.034 and p = 0.039, respectively).

Conclusions

Adults and children had different clinical manifestations. Adults developed severe ARDS requiring increased respiratory support, whereas children presented MIS-C with greater inotropic requirements. Biomarkers could be helpful in identifying susceptible patients, since they might change depending on the clinical features.
Correction to: HIV infection and multidrug resistant tuberculosis: a systematic review and meta-analysis
Authors: Sultana Zeeba Zahra , Hoque Farhana Ul , Beyene Joseph , Akhlak-Ul-Islam Md. , Khan Md Hasinur Rahman , Ahmed Shakil , Hawlader Delwer Hossain , Hossain Ahmed
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
Causal effect between total cholesterol and HDL cholesterol as risk factors for chronic kidney disease: a mendelian randomization study
Authors: Miao Liu , Min Yan , Qi Bin , Zhu Chuan-Meng , Chen Jian-Hong , Deng Guo-Xiong , Wang Yong , Li Jian-Fei , Li Rong-Shan
Published: January 2021

Background

While observational studies show an association between serum lipid levels and cardiovascular disease (CVD), intervention studies that examine the preventive effects of serum lipid levels on the development of CKD are lacking.

Methods

To estimate the role of serum lipid levels in the etiology of CKD, we conducted a two-sample mendelian randomization (MR) study on serum lipid levels. Single nucleotide polymorphisms (SNPs), which were significantly associated genome-wide with serum lipid levels from the GLGC and CKDGen consortium genome-wide association study (GWAS), including total cholesterol (TC, n = 187,365), triglyceride (TG, n = 177,861), HDL cholesterol (HDL-C, n = 187,167), LDL cholesterol (LDL-C, n = 173,082), apolipoprotein A1 (ApoA1, n = 20,687), apolipoprotein B (ApoB, n = 20,690) and CKD (n = 117,165), were used as instrumental variables. None of the lipid-related SNPs was associated with CKD (all P > 0.05).

Results

MR analysis genetically predicted the causal effect between TC/HDL-C and CKD. The odds ratio (OR) and 95% confidence interval (CI) of TC within CKD was 0.756 (0.579 to 0.933) (P = 0.002), and HDL-C was 0.85 (0.687 to 1.012) (P = 0.049). No causal effects between TG, LDL-C- ApoA1, ApoB and CKD were observed. Sensitivity analyses confirmed that TC and HDL-C were significantly associated with CKD.

Conclusions

The findings from this MR study indicate causal effects between TC, HDL-C and CKD. Decreased TC and elevated HDL-C may reduce the incidence of CKD but need to be further confirmed by using a genetic and environmental approach.
Perspectives of pregnant and breastfeeding women on longitudinal clinical studies that require non-invasive biospecimen collection – a qualitative study
Authors: Lemas Dominick J. , Wright Lauren , Flood-Grady Elizabeth , Francois Magda , Chen Lynn , Hentschel Austen , Du Xinsong , Hsiao Chu J. , Chen Huan , Neu Josef , Theis Ryan P. , Shenkman Elizabeth , Krieger Janice
Published: January 2021

Background

Investigation of the microbiome during early life has stimulated an increasing number of cohort studies in pregnant and breastfeeding women that require non-invasive biospecimen collection. The objective of this study was to explore pregnant and breastfeeding women’s perspectives on longitudinal clinical studies that require non-invasive biospecimen collection and how they relate to study logistics and research participation.

Methods

We completed in-depth semi-structured interviews with 40 women who were either pregnant (n = 20) or breastfeeding (n = 20) to identify their understanding of longitudinal clinical research, the motivations and barriers to their participation in such research, and their preferences for providing non-invasive biospecimen samples.

Results

Perspectives on research participation were focused on breastfeeding and perinatal education. Participants cited direct benefits of research participation that included flexible childcare, lactation support, and incentives and compensation. Healthcare providers, physician offices, and social media were cited as credible sources and channels for recruitment. Participants viewed lengthy study visits and child protection as the primary barriers to research participation. The barriers to biospecimen collection were centered on stool sampling, inadequate instructions, and drop-off convenience.

Conclusion

Women in this study were interested in participating in clinical studies that require non-invasive biospecimen collection, and motivations to participate center on breastfeeding and the potential to make a scientific contribution that helps others. Effectively recruiting pregnant or breastfeeding participants for longitudinal microbiome studies requires protocols that account for participant interests and consideration for their time.
The lifetime prevalence and impact of generalized anxiety disorders in an epidemiologic Italian National Survey carried out by clinicians by means of semi-structured interviews
Authors: Preti Antonio , Demontis Roberto , Cossu Giulia , Kalcev Goce , Cabras Federico , Moro Maria Francesca , Romano Ferdinando , Balestrieri Matteo , Caraci Filippo , Dell’Osso Liliana , Di Sciascio Guido , Drago Filippo , Hardoy Maria Carolina , Roncone Rita , Faravelli Carlo , Gonzalez Cesar Ivan Aviles , Angermayer Matthias , Carta Mauro Giovanni
Published: January 2021

Background

Generalized anxiety disorder (GAD) is one of the most reported diagnoses in psychiatry, but there is some discrepancy between the cases identified in community studies and those identified in tertiary care. This study set out to evaluate whether the use of clinicians as interviewers may provide estimates in a community survey close to those observed in primary or specialized care.

Methods

This is a community survey on a randomly selected sample of 2338 adult subjects. The Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS) was administered by clinicians, providing lifetime diagnosis based on the DSM-IV-TR. Health-related quality of life (HR-QoL) was measured with the Short-Form Health Survey (SF-12).

Results

Overall, 55 (2.3%) subjects met the criteria for GAD, with greater prevalence in women (3.6%) than in men (0.9%): OR = 4.02; 95%CI: 1.96–8.26. Up to 40% of those with GAD had at least another diagnosis of mood, anxiety, or eating disorders. The mean score of SF-12 in people with GAD was 32.33 ± 6.8, with a higher attributable burden than in other conditions except for major depressive disorder.

Conclusions

We found a relatively lower lifetime prevalence of GAD than in community surveys based on lay interviewers and a structured interview. The identified cases of GAD showed a strong impact on the quality of life regardless of co-morbidity and high risk in women, suggesting a profile similar to the one identified from studies in primary and specialized care.
Serum bilirubin and chronic obstructive pulmonary disease (COPD): a systematic review
Authors: MacDonald David M. , Kunisaki Ken M. , Wilt Timothy J. , Baldomero Arianne K.
Published: January 2021

Background

Bilirubin is a potent antioxidant and higher serum bilirubin levels have been associated with improved COPD outcomes. We performed a systematic review to evaluate the association between serum bilirubin levels and lung function (FEV1), prevalence/incidence of COPD, acute exacerbations of COPD, respiratory health status, and mortality.

Methods

MEDLINE® and Embase were searched using Ovid® (search updated October 1st, 2019). We included studies that measured serum bilirubin levels and outcomes of interest in adults with or without underlying lung disease. We excluded studies of those with liver disease or drug-induced elevations in bilirubin. We used the Newcastle–Ottawa scale to assess individual study risk of bias (ROB) and the US Agency for Healthcare Research and Quality—Evidence Based Practice tool to assess overall strength of evidence (SOE). Two authors independently determined eligibility, performed data abstraction, assessed ROB, and determined SOE.

Results

Thirteen studies (5 low risk of bias, 3 moderate and 5 high risk) were included. We found low strength of evidence for the association between higher bilirubin levels and lower risk of acute exacerbations of COPD (2 studies), mortality (3 studies), COPD diagnosis (4 studies), and lung function (FEV1) (8 studies). We found insufficient evidence on the relationship between serum bilirubin and respiratory health status/exercise capacity (1 study) and airflow obstruction (FEV1/FVC ratio) (4 studies).

Conclusion

Higher bilirubin levels may be associated with lower mortality and improved COPD outcomes. Randomized trials are needed to evaluate the effect of medications that raise serum bilirubin on COPD outcomes.

PROSPERO registration: CRD42019145747.
Variation in practice and outcomes after inguinal hernia repair: a nationwide observational study
Authors: Latenstein Carmen S. S. , Thunnissen Floris M. , Harker Mitchell , Groenewoud Stef , Noordenbos Mark W. , Atsma Femke , de Reuver Philip R.
Published: January 2021

Background

Inguinal hernia repair has often been used as a showcase to illustrate practice variation in surgery. This study determined the degree of hospital variation in proportion of patients with an inguinal hernia undergoing operative repair and the effect of this variation on clinical outcomes.

Methods

A nationwide, longitudinal, database study was performed in all hospitals in the Netherlands between 2013 and 2015. Patients with inguinal hernias were collected from the Diagnosis-Related-Group (DRG) database. The case-mix adjusted operation rate in patients with a new DRG determines the observed variation. Hospital variation in case-mix adjusted inguinal hernia repair-rates was calculated per year. Clinical outcomes after surgery were compared between hospitals with high and low adjusted operation-rates.

Results

In total, 95,637 patients were included. The overall operation rate was 71.6%. In 2013–2015, the case-mix adjusted performance of inguinal hernia repairs in hospitals with high rates was 1.6–1.9 times higher than in hospitals with low rates. Moreover, in hospitals with high adjusted rates of inguinal hernia repair the time to surgery was shorter, more laparoscopic procedures were performed, less emergency department visits were recorded post-operatively, while more emergency department visits were recorded when patients were treated conservatively compared to hospitals with low adjusted operation rates.

Conclusion

Hospital variation in inguinal hernia repair in the Netherlands is modest, operation-rates vary by less than two-fold, and variation is stable over time. Hernia repair in hospitals with high adjusted rates of inguinal hernia repair are associated with improved outcomes.
Comparing various protocols of human and bovine ovarian tissue decellularization to prepare extracellular matrix-alginate scaffold for better follicle development in vitro
Authors: Nikniaz Hossein , Zandieh Zahra , Nouri Mohammad , Daei-farshbaf Neda , Aflatoonian Reza , Gholipourmalekabadi Mazaher , Jameie Seyed Behnamedin
Published: January 2021

Background

Nowadays, the number of cancer survivors is significantly increasing as a result of efficient chemo/radio therapeutic treatments. Female cancer survivors may suffer from decreased fertility. In this regard, different fertility preservation techniques were developed. Artificial ovary is one of these methods suggested by several scientific groups. Decellularized ovarian cortex has been introduced as a scaffold in the field of human fertility preservation. This study was carried out to compare decellularization of the ovarian scaffold by various protocols and evaluate the follicle survival in extracellular matrix (ECM)-alginate scaffold.

Results

The micrographs of H&E and DAPI staining confirmed successful decellularization of the ovarian cortex in all experimental groups, but residual DNA content in SDS-Triton group was significantly higher than other groups (P < 0.05). SEM images demonstrated that complex fiber network and porosity structure were maintained in all groups. Furthermore, elastin and collagen fibers were observed in all groups after decellularization process. MTT test revealed higher cytobiocompatibility of the SDS-Triton-Ammonium and SDS-Triton decellularized scaffolds compared with SDS groups. Compared to the transferred follicles into the sodium alginate (81%), 85.9% of the transferred follicles into the decellularized scaffold were viable after 7 days of cultivation (P = 0.04).

Conclusion

Although all the decellularization procedures was effective in removal of cells from ovarian cortex, SDS-Triton-Ammonium group showed less residual DNA content with higher cytobiocompatibility for follicles when compared with other groups. In addition, the scaffold made from ovarian tissues decellularized using SDS-Triton-Ammonium and sodium alginate is suggested as a potential 3D substrate for in vitro culture of follicles for fertility preservation.
Survival of silver diamine fluoride among patients treated in community dental clinics: a naturalistic study
Authors: Raskin Sarah E. , Tranby Eric P. , Ludwig Sharity , Okunev Ilya , Frantsve-Hawley Julie , Boynes Sean
Published: January 2021

Background

Silver diamine fluoride (SDF) is a minimally-invasive preventive service used in the U.S. to avert and arrest caries since 2014. No studies document survival outcomes based in real world delivery. We analyzed 12-month survival outcomes of SDF applied independently or concurrently with other restorative procedures among a population receiving community dental care.

Methods

We analyzed data on SDF applications from de-identified dental claims on Oregon Health Plan patients served by Advantage Dental in 2016, who had been seen in 2015 (patient n = 2269; teeth n = 7787). We compared survival rates of SDF alone, SDF applied with a sedative filling, and SDF with a same-day restoration. Failure was defined as a restoration or extraction of the tooth 7 to 365 days after initial application. Survival was defined as a patient returning 180 or more days after application whose tooth did not have a restoration or extraction. Differences were assessed through Wilcoxon equality of survivor function tests and log-rank equality of survivor tests to compare failure rates, Cox Proportional Hazards models to assess factors associated with survival of SDF, and Kaplan–Meier survival estimate to calculate the probability of survival over time.

Results

SDF alone had an overall survival rate of 76%. SDF placed with sedative filling and with a same-day restoration had survival rates of 50% and 84% respectively, likely reflecting treatment intent. SDF alone survived exceptionally well on primary cuspids, permanent molars, and permanent bicuspids and among patients aged 10 to 20 years, with modest variation across caries risk assessment categories. A single annual application of SDF was successful in 75% of cases. Among SDF failures on permanent dentition, more than two-thirds of teeth received a minor restoration.

Conclusion

SDF is a minimally invasive non-aerosolizing option that prevented non-cavitated lesions and arrested early decay among community dentistry patients when applied independently or concurrently with restorative procedures. Professional organizations, policy makers, providers, and payors should broaden optional SDF use by informing clinical guidelines, reimbursement policies, and treatment decisions. Future research should address clinical, social, service delivery, workforce, and economic outcomes using diverse population-based samples, and the mechanisms underlying single application success and caries prevention potential.
What should we report? Lessons learnt from the development and implementation of serious adverse event reporting procedures in non-pharmacological trials in palliative care
Authors: Dunleavy Lesley , Collingridge Moore Danni , Korfage Ida , Payne Sheila , Walshe Catherine , Preston Nancy
Published: January 2021

Background/aims

Serious adverse event reporting guidelines have largely been developed for pharmaceutical trials. There is evidence that serious adverse events, such as psychological distress, can also occur in non-pharmaceutical trials. Managing serious adverse event reporting and monitoring in palliative care non-pharmaceutical trials can be particularly challenging. This is because patients living with advanced malignant or non-malignant disease have a high risk of hospitalisation and/or death as a result of progression of their disease rather than due to the trial intervention or procedures. This paper presents a number of recommendations for managing serious adverse event reporting that are drawn from two palliative care non-pharmacological trials.

Methods

The recommendations were iteratively developed across a number of exemplar trials. This included examining national and international safety reporting guidance, reviewing serious adverse event reporting procedures from other pharmacological and non-pharmacological trials, a review of the literature and collaboration between the ACTION study team and Data Safety Monitoring Committee. These two groups included expertise in oncology, palliative care, statistics and medical ethics and this collaboration led to the development of serious adverse event reporting procedures.

Results

The recommendations included; allowing adequate time at the study planning stage to develop serious adverse event reporting procedures, especially in multi-national studies or research naïve settings; reviewing the level of trial oversight required; defining what a serious adverse event is in your trial based on your study population; development and implementation of standard operating procedures and training; refining the reporting procedures during the trial if necessary and publishing serious adverse events in findings papers.

Conclusions

There is a need for researchers to share their experiences of managing this challenging aspect of trial conduct. This will ensure that the processes for managing serious adverse event reporting are continually refined and improved so optimising patient safety.

Trial registration

ACTION trial registration number: ISRCTN63110516 (date of registration 03/10/2014).

Namaste trial registration number: ISRCTN14948133 (date of registration 04/10/2017).
Correction to: Addressing the interaction between food insecurity, depression risk and informal work: findings of a cross-sectional survey among informal women workers with young children in South Africa
Authors: Horwood Christiane , Haskins Lyn , Hinton Rachael , Connolly Catherine , Luthuli Silondile , Rollins Nigel
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.