bluuebunny/crossref_metadata_2025 huggingface dataset:
Reimbursement of innovative pharmaceuticals in English and Spanish hospitals—The example of isavuconazole
Authors: Jeck Julia , Wingen‐Heimann Sebastian M. , Thielscher Christian , Kron Anna , Bonn Jennifer , Jakobs Florian , Grau Santiago , Enoch David A. , Micallef Christianne , Cornely Oliver A. , Kron Florian
Published: June 2021

Background

Kron et al (Mycoses, 64, 2021, 86) found cost savings for the use of the innovative pharmaceutical isavuconazole in the inpatient setting in Germany (Bismarck‐based healthcare system). Little is known about the reimbursement of innovative pharmaceuticals in the inpatient setting of Beveridge‐based healthcare systems.

Objectives

The aim of this study was to evaluate the market access process and reimbursement of isavuconazole, exemplary for innovative pharmaceuticals, in England and Spain.

Patients/Methods

Market access processes of both countries were described. Focussing on typical patient clusters for isavuconazole treatment, reimbursement data regarding inpatients with (i) allogeneic haematopoietic stem cell transplantation or (ii) acute myeloid leukaemia was considered. Data were publicly available and of high topicality (England 2020/2021, Spain 2018). Discounting and a currency conversion to Euro were applied.

Results

This study showed that market access processes of both countries are broadly similar. Further, full reimbursement of isavuconazole as an innovative pharmaceutical may lead to reduction in resource utilisation. Without medication costs, isavuconazole can thus result in cost savings for both patient clusters due to a reduction in length of stay.

Conclusions

Expenses for innovative pharmaceuticals may be balanced or even lead to cost savings due to a reduction in length of stay. The latter contributes to a greater patient benefit. For both healthcare system, the analyses highlighted drugs’ cost‐effectiveness and assessing its added value into reimbursement decisions is highly relevant.
Photosensitization Reactions of Biomolecules: Definition, Targets and Mechanisms
Authors: Baptista Maurício S. , Cadet Jean , Greer Alexander , Thomas Andrés H.
Published: June 2021

Photosensitization reactions have been demonstrated to be largely responsible for the deleterious biological effects of UV and visible radiation, as well as for the curative actions of photomedicine. A large number of endogenous and exogenous photosensitizers, biological targets and mechanisms have been reported in the past few decades. Evolving from the original definitions of the type I and type II photosensitized oxidations, we now provide physicochemical frameworks, classifications and key examples of these mechanisms in order to organize, interpret and understand the vast information available in the literature and the new reports, which are in vigorous growth. This review surveys in an extended manner all identified photosensitization mechanisms of the major biomolecule groups such as nucleic acids, proteins, lipids bridging the gap with the subsequent biological processes. Also described are the effects of photosensitization in cells in which UVA and UVB irradiation triggers enzyme activation with the subsequent delayed generation of superoxide anion radical and nitric oxide. Definitions of photosensitized reactions are identified in biomolecules with key insights into cells and tissues.
Devoting ourselves to the manifestly unattainable*
Authors: Southwood Nicholas , Wiens David
Published: June 2021

It is tempting to think (1) that we may sometimes have what we callhopelessly utopian dutiesand yet (2) that “ought” implies “can.” How might we square these apparently conflicting claims? A simple solution is to interpret hopelessly utopian duties as duties topursuethe achievement of manifestly unattainable outcomes (as opposed to duties toachievethe outcomes), thereby promising to vindicate the possibility of such duties in a way that is compatible with “ought” implies “can.” The main challenge for this simple solution is to say what the relevant “duties to pursue” are supposed to involve. We survey several existing candidates and argue that none of them succeeds in delivering on the promise of the simple solution. We then propose a previously untheorized class of duties that we call duties todevote ourselvesto achieving an outcome, and argue that such duties provide us with an interpretation of hopelessly utopian duties that is up to the task.
Longitudinal changes in total and regional body composition in patients with chronic obstructive pulmonary disease
Authors: Machado Felipe V. C. , Spruit Martijn A. , Coenjaerds Miranda , Pitta Fabio , Reynaert Niki L. , Franssen Frits M. E.
Published: June 2021

Background and objective

Low fat‐free mass (FFM) is common in patients with chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality. Few studies have evaluated longitudinal changes in body composition in patients with COPD compared with non‐COPD controls. This study aimed to compare longitudinal changes in total and regional body composition between patients with COPD and non‐COPD controls and investigate predictors of changes in body composition in COPD.

Methods

Patients with COPD and non‐COPD controls participating in the Individualized COPD Evaluation in relation to Ageing (ICE‐Age) study, a single‐centre, longitudinal, observational study, were included. Subjects were assessed at baseline and after 2 years of follow‐up. Among other procedures, body composition was measured by dual‐energy X‐ray absorptiometry scan. The number of exacerbations/hospitalizations 1 year before inclusion and during follow‐up were assessed in patients with COPD.

Results

A total of 405 subjects were included (205 COPD, 87 smoking and 113 non‐smoking controls). Patients with COPD and smoking controls presented a significant decline in total FFM (mean [95% CI]: −1173 [−1527/−820] g and −486 [−816/−156] g, respectively) while body composition remained stable in non‐smoking controls. In patients with COPD, the decline in FFM was more pronounced in legs (−174 [−361/14] g) and trunk (−675 [−944/406] g) rather than in arms (54 [−19/126] g). The predictors of changes in total and regional FFM in patients with COPD were gender, number of previous hospitalizations, baseline values of FFM and BMI.

Conclusion

Patients with COPD present a significant decline in FFM after 2 years of follow‐up, this decline is more pronounced in their legs and trunk.
Bruxism and type of breathing as factors associated with oral herpes lesion in Brazilian para‐athletes
Authors: Storrer Carmen Lucia Mueller , Costa Eugenio Esteves , Scariot Rafaela , Pivetta Petinati Maria Fernanda , Winckler Ciro , Deliberador Tatiana Miranda , Küchler Erika Calvano , Brancher João Armando
Published: June 2021

Aims

The present study investigated if recurrent manifestation of oral herpes lesions is associated with other factors and impacts the oral health‐related quality of life in para‐athletes.

Methods and results

The studied population was composed of a convenience sample of 370 Brazilian para‐athletes. All included individuals answered questionnaires and were submitted to an oral examination. A self‐reported questionnaire addressed demographic and oral health data, including the recurrent manifestation of oral herpes lesions. The Oral Health Impact Profile was also applied in its reduced version with 14 questions (OHIP‐14). The population was categorized according to results from previous competitions into a high‐performance level, medium‐performance level, and regional‐performance level. Chi‐square or Fisher's exact tests, odds ratio calculation, logistic regression analysis, and t‐tests were performed (α = 5%). Sixty (16.2%) para‐athletes reported recurrent manifestations of oral herpes lesions. Para‐athletes with sleep bruxism (p = .007) and awake bruxism (p = .048) had a higher chance of reporting oral herpes lesions. Type of breathing was also associated with oral herpes lesions (p = .031). The OHIP‐14 mean distribution among the groups was not statistically significant (p > .05).

Conclusion

Bruxism and type of breathing were associated with self‐reported oral herpes lesions in Brazilian para‐athletes.
Echocardiographic changes in the shape and size of the aortic cusps in dogs with confirmed systemic hypertension
Authors: Holland Merrilee , Hofmeister Erik , Hudson Judith
Published: June 2021

Systemic hypertension (SH) in dogs typically occurs secondary to renal disease, diabetes mellitus, hyperadrenocorticism, malignant adrenal tumors, or various medications. Echocardiography performed on people with SH has shown asymmetric dilation of the sinuses at the level of the aortic valves, previously undescribed in canine patients. The objective of this retrospective case‐control study was to determine if there was a difference in size and shape of the aortic cusps at the level of the sinus of Valsalva in dogs with SH compared to dogs with normal blood pressure. We reviewed echocardiographic findings in 74 dogs with SH and 37 dogs with normal blood pressure (NBP), defined as less than 150 mmHg. Systemic hypertension was classified as mild (150‐159 mm Hg), moderate (160‐179 mm Hg), or severe (greater than 180 mm Hg). There was a significant difference (P < .001) in the mean size of the aorta cusps at the level of the sinuses in 67 of 74 dogs with SH and none of 37 dogs with NBP. Of the 74 dogs with SH, 70 had left ventricular hypertrophy (18 asymmetric, 15 concentric, and 37 eccentric). Additionally, there was aortic root dilatation in 15 dogs, aortic insufficiency in 21, mitral regurgitation in 50, and left atrial enlargement in 71. The standard deviation of the three cusp measurements between the dogs with SH and dogs with NBP had a sensitivity of 92% and specificity of 97% for diagnosis of SH. Asymmetric size of the aortic cusps on echocardiography is therefore a reliable indicator of SH in dogs.
The Bending of Pretwisted Thin-Walled Beams of Symmetric Star-Shaped Cross Sections
Authors: Maunder L.
Published: June 2021

The customary method of determining the elastic bending deflections of pretwisted beams predicts that the deflections of a uniform beam with a cross section having equal principal moments of inertia will be independent of pretwist. Experimental deflections of a thin-walled pretwisted beam with a doubly symmetric cruciform cross section have been found, however, to be significantly larger than those thus predicted. Based on energy methods, an approximate analysis is developed for pretwisted thin-walled beams having symmetric star-shaped cross sections, which takes into account the effect of interactions between pretwist and distortions of cross sections. An equivalent bending stiffness is derived which is a function of pretwist. The principal theoretical and experimental results are shown in Fig. 4.
Torques on a Satellite Vehicle From Internal Moving Parts
Authors: Roberson R. E.
Published: June 2021

Many of the torques produced by the motion of parts within a body are negligibly small in most engineering applications. However, if the body is a satellite vehicle these small torques can be significant, even to playing a dominant role in the excitation of satellite attitude motions. This paper derives a complete expression for the attitude perturbation torque from this source, interpreting each of its terms. The atittude reference co-ordinate system is discussed. The nature of the torque is found for three simple cases.
Redundant Trusses of Elastic-Strain-Hardening Material
Authors: Ziegler Hans
Published: June 2021

W. Prager has given a geometric method for the determination of the load-carrying capacity of a redundant truss consisting of elastic, perfectly plastic bars. In the present paper this method is generalized for trusses consisting of elastic-strain-hardening bars with given limit loads in tension and compression.
Second Acceleration in Four-Bar Mechanisms as Related to Rotopole Motion
Authors: Carter W. J.
Published: June 2021

The second acceleration of the driven crank in a four-bar mechanism may be determined by an extension of the acceleration analysis given by Koenig.
The Effect of a Tangential Contact Force Upon the Rolling Motion of an Elastic Sphere on a Plane
Authors: Johnson K. L.
Published: June 2021

The motion and deformation of an elastic sphere rolling on an elastic plane under a normal contact pressure N have been studied for the case where a tangential force T is also sustained at the point of contact. Provided that T < μN (μ = coefficient of friction), the sphere rolls without sliding but exhibits a small velocity relative to the plane, termed “creep.” Following the work of Mindlin and Poritsky, it is shown that creep arises from slip over part of the area of contact, and further, that this slip takes place toward the trailing edge of the contact area. On the assumption of a locked region in which no slip occurs, of circular shape, tangential to the circle of contact at its leading point, surface tractions are found which satisfy the condition of no slip within the locked region and are approximately consistent with the laws of friction in the slip region. The variation of creep velocity with tangential force is thereby determined. Experimental measurements of the creep of a steel ball rolling on a flat steel surface are in reasonable agreement with the theoretical results.
The Vibration of a String Having a Uniform Motion Along Its Length
Authors: Archibald F. R. , Emslie A. G.
Published: June 2021

In calculating the natural frequencies of a power chain or belt it is usual to use the theory of vibrating strings. However, the speed of the chain or belt may be a considerable fraction of the wave velocity as given by (T/ρ)1/2. It might be expected hat this would have a marked effect on the natural frequencies. This is shown to be so and the formula for the natural frequencies of a moving string is obtained. The problem of the forced vibration of the string is also considered.
Unsteady Laminar Boundary Layers in an Incompressible Stagnation Flow
Authors: Yang Kwang-Tzu
Published: June 2021

The present study deals with unsteady laminar boundary layers in the immediate vicinity of the stagnation point of a heated blunt-nosed cylinder in an incompressible flow with unsteady velocity. An exact solution is presented for the special case of a flow velocity varying inversely with a linear function of time, together with calculated boundary-layer characteristics for different values of a flow parameter. Based on the results of this exact solution, an approximate method of solutions is proposed for a more general problem where the flow velocity changes arbitrarily with time. The results of five examples are shown and discussed in the light of other available solutions. Finally, the limitation of this approximate solution is pointed out and a possible remedy indicated.
Axially Symmetric Buckling of Shallow Spherical Shells Under External Pressure
Authors: Reiss Edward L.
Published: June 2021

A formula for the initial buckling loads for clamped, shallow spherical shells under uniform external pressure is obtained by combining the solutions of two linearized versions of the original nonlinear problem. One of these versions is a linear eigenvalue problem, while the other is the bending problem for a shallow cap in the linear theory of elasticity. The formula, which is obtained in a simple manner, yields buckling loads that are in better agreement with experiments than previous approximate solutions to the nonlinear problem.
Numerical and Experimental Investigation of a Low Order Radial Turbine Model for Engine-Level Optimization of Turbocharger Design
Authors: Hohenberg Karl , Martinez-Botas Ricardo , Łuczyński Piotr , Freytag Carola , Wirsum Manfred
Published: June 2021

This paper presents the development and validation of a meanline model by means of numerical and experimental methods, to determine it's feasibility as an optimization tool for turbocharger matching. Using a parametric turbine model, numerical experiments were conducted accounting for variations of several key turbine design parameters and a wide operating range. The resulting dataset was used to test the accuracy of the meanline model when calibrated to a baseline design and thus evaluate it's ability of extrapolating to different designs. The loss models were examined in more detail, and a set of loss models which provided the most accurate results is presented. The meanline model was further validated experimentally using dynamometer test results of 6 turbine designs from the same parametric turbine model. The result showed that for design point and high power operation, an error of less than 3.1% and 2.0% was achieved for efficiency and mass flow parameters, respectively. This led to the conclusion that the model would be sufficiently accurate to represent design changes relevant to turbocharger matching.
Unsteady Analysis of Heat Transfer Coefficient Distribution in a Static Ribbed Channel for An Established Flow
Authors: Perrot Aurélien , Gicquel Laurent , Duchaine Florent , Odier Nicolas , Dombard Jérôme , Grosnickel Thomas
Published: June 2021

Turbulent-ribbed channels are extensively used in turbomachinery to enhance convective heat transfer in internally cooled components such as turbine blades. One of the key aspects of such a problem is the distribution of the heat transfer coefficient (HTC) in fully developed flows, and many studies have addressed this problem by the use of computational fluid dynamics (CFD). In the present document, large eddy simulation (LES) is performed for a configuration from a test-rig at the Von Karman Institute representing a square channel with periodic square ribs. The whole channel is computed in an attempt to better understand HTC maps in this specific configuration. Resulting mean and unsteady flow features are captured, and predictions are used to further explain the obtained HTC distribution. More specifically turbulent structures are seen to bring cold gas from the main flow to the wall. A statistical analysis of these events using the joint velocity-temperature probability density function (PDF), and quadrant method allows to define four types of events happening at every location of the channel and which can then be linked to the HTC distribution. First, the HTC is very high where the flow impacts the wall with cold temperature whereas it is lower where the hot gas is ejected to the main flow. In an attempt to link the HTC trace on the channel wall with structures in the flow field far-off the wall, the main modes are identified performing power spectral density (PSD) analysis of the velocity along the channel. Dynamic mode decomposition (DMD) of the flow field data is then used to present the spatio-temporal characteristics of two of the identified most dominant modes: a vortex-street mode linked to the first rib and a rib-to-rib mode appearing because of the quasi-periodicity of the configuration. However, DMD analysis of the HTC trace on the wall does not emphasize any dominant mode. This indicates a weak link between the main flow large scale features and the instantaneous and more local HTC distribution.
Surface damage formation during atomic layer etching of silicon with chlorine adsorption
Authors: Tinacba Erin Joy Capdos , Isobe Michiro , Hamaguchi Satoshi
Published: June 2021

As semiconductor device structures continue to approach the nanometer size range, new challenges in the fabrication of such devices have arisen. For example, the need for high-aspect-ratio, highly selective, controllable, and isotropic or anisotropic etching at the nanometer scale are some of them. Recently, atomic layer etching (ALE) has attracted much attention as an alternative to the conventional reactive ion etching (RIE) to address these issues. In comparison with RIE, ALE offers highly uniform etching over a large area with a precise etched depth and little damage to the underlying material surface. However, the extent of the surface damage formation in ALE processes has not been extensively reported yet. In this study, molecular dynamics simulation is used to examine the surface damages and reaction mechanisms during plasma-assisted (PA-) ALE of silicon (Si) with chlorine (Cl) radical adsorption and low-energy Ar+ ion irradiation for desorption. Several ALE cycles have been simulated and reproducible etched depths per cycle have been obtained. Based on the depth profiles, a damaged surface layer with a thickness of about 1.5 nm is found to be caused by the ALE process even at a very low ion incident energy of 20 eV in the simulation. The thickness of a damaged-layer on the etched surface slightly increases with the ion incident energy for the energy range examined in this study (20–60 eV), and Cl atoms deposited on the surface in the ALE adsorption step are transported deeper in the damaged-layer by the ion bombardment. Our simulation results indicate that a certain damage formation cannot be avoided on the “as-etched” surface of a PA-ALE process and, if the damaged-layer inadvertently affects the device performance, further action to mitigate the damage needs to be taken.
Attenuation of Rayleigh waves due to surface roughness
Authors: Sarris Georgios , Haslinger Stewart G. , Huthwaite Peter , Nagy Peter B. , Lowe Michael J. S.
Published: June 2021

Rayleigh waves are well known to attenuate due to scattering when they propagate over a rough surface. Theoretical investigations have derived analytical expressions linking the attenuation coefficient to statistical surface roughness parameters, namely, the surface's root mean squared height and correlation length and the Rayleigh wave's wavenumber. In the literature, three scattering regimes have been identified—the geometric (short wavelength), stochastic (short to medium wavelength), and Rayleigh (long wavelength) regimes. This study uses a high-fidelity two-dimensional finite element (FE) modelling scheme to validate existing predictions and provide a unified approach to studying the problem of Rayleigh wave scattering from rough surfaces as the same model can be used to obtain attenuation values regardless of the scattering regime. In the Rayleigh and stochastic regimes, very good agreement is found between the theory and FE results both in terms of the absolute attenuation values and for asymptotic power relationships. In the geometric regime, power relationships are obtained through a combination of dimensional analysis and FE simulations. The results here also provide useful insight into verifying the three-dimensional theory because the method used for its derivation is analogous.
Macrophage depletion induces edema through release of matrix-degrading proteases and proteoglycan deposition
Authors: Bissinger Stefan , Hage Carina , Wagner Vinona , Maser Ilona-Petra , Brand Verena , Schmittnaegel Martina , Jegg Anna-Maria , Cannarile Michael , Watson Carl , Klaman Irina , Rieder Natascha , González Loyola Alejandra , Petrova Tatiana V. , Cassier Philippe A. , Gomez-Roca Carlos , Sibaud Vincent , De Palma Michele , Hoves Sabine , Ries Carola H.
Published: June 2021

Macrophage depletion by colony-stimulating factor 1 receptor blockade alters extracellular matrix homeostasis and promotes skin edema.
A helicase-primase drug candidate with sufficient target tissue exposure affects latent neural herpes simplex virus infections
Authors: Gege Christian , Bravo Fernando J. , Uhlig Nadja , Hagmaier Timo , Schmachtenberg Rosanne , Elis Julia , Burger-Kentischer Anke , Finkelmeier Doris , Hamprecht Klaus , Grunwald Thomas , Bernstein David I. , Kleymann Gerald
Published: June 2021

Treatment with the helicase-primase inhibitor IM-250 affects chronic neural HSV infections in mice and guinea pigs.
Cyanochelins, an Overlooked Class of Widely Distributed Cyanobacterial Siderophores, Discovered by Silent Gene Cluster Awakening
Authors: Galica Tomáš , Borbone Nicola , Mareš Jan , Kust Andreja , Caso Alessia , Esposito Germana , Saurav Kumar , Hájek Jan , Řeháková Klára , Urajová Petra , Costantino Valeria , Hrouzek Pavel
Published: June 2021

All living organisms depend on iron as an essential cofactor for indispensable enzymes. However, the sources of bioavailable iron are often limited.
Comparative Performances of Vitek-2, Disk Diffusion, and Broth Microdilution for Antimicrobial Susceptibility Testing of Canine Staphylococcus pseudintermedius
Authors: Rampacci Elisa , Trotta Michele , Fani Caterina , Silvestri Serenella , Stefanetti Valentina , Brachelente Chiara , Mencacci Antonella , Passamonti Fabrizio
Published: June 2021

Staphylococcus pseudintermedius
is the primary cause of canine cutaneous infections and is sporadically isolated as a pathogen from humans. Rapidly emerging antibiotic-resistant strains are creating serious health concerns so that accurate and timely antimicrobial susceptibility testing (AST) is crucial for patient care.
One-Step Detection and Classification of Bacterial Carbapenemases in 10 Minutes Using Fluorescence Identification of β-Lactamase Activity
Authors: Feng Yanfang , Swain Joseph W. R. , Palanisami Akilan , Ashraf Shoaib , Hasan Tayyaba
Published: June 2021

Rapid and accurate diagnosis of bacterial carbapenemases remains a major challenge for clinical laboratories. A novel assay was developed here using fluorescence identification of β-lactamase activity (FIBA) to permit rapid detection and classification of bacterial carbapenemases.
Binding of the Andes Virus Nucleocapsid Protein to RhoGDI Induces the Release and Activation of the Permeability Factor RhoA
Authors: Gorbunova Elena E. , Mackow Erich R.
Published: June 2021

HPS-causing hantaviruses infect pulmonary endothelial cells (ECs), causing vascular leakage, pulmonary edema, and a 35% fatal acute respiratory distress syndrome (ARDS). Hantaviruses do not lyse or disrupt the endothelium but dysregulate normal EC barrier functions and increase hypoxia-directed permeability.
Contribution of SARS-CoV-2 Accessory Proteins to Viral Pathogenicity in K18 Human ACE2 Transgenic Mice
Authors: Silvas Jesus A. , Vasquez Desarey Morales , Park Jun-Gyu , Chiem Kevin , Allué-Guardia Anna , Garcia-Vilanova Andreu , Platt Roy Neal , Miorin Lisa , Kehrer Thomas , Cupic Anastasija , Gonzalez-Reiche Ana S. , Bakel Harm van , García-Sastre Adolfo , Anderson Tim , Torrelles Jordi B. , Ye Chengjin , Martinez-Sobrido Luis
Published: June 2021

Despite great efforts put forward worldwide to combat the current coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a human health and socioeconomic threat. Insights into the pathogenesis of SARS-CoV-2 and the contribution of viral proteins to disease outcome remain elusive.
Specific Interaction of DDX6 with an RNA Hairpin in the 3′ UTR of the Dengue Virus Genome Mediates G
1
Phase Arrest
Authors: Choksupmanee Opas , Tangkijthavorn Worapol , Hodge Kenneth , Trisakulwattana Krittanai , Phornsiricharoenphant Worawich , Narkthong Veerakorn , Tulakarnwong Sarun , Ngamphiw Chumpol , Tongsima Sissades , Chimnaronk Sarin
Published: June 2021

Dengue virus (DENV) is transmitted by mosquitoes to humans, infecting 390 million individuals per year globally. About 20% of infected patients shows a spectrum of clinical manifestation, ranging from a mild flu-like syndrome, to dengue fever, to life-threatening severe dengue diseases, including dengue hemorrhagic fever and dengue shock syndrome.
Conserved Gammaherpesvirus Protein Kinase Counters the Antiviral Effects of Myeloid Cell-Specific STAT1 Expression To Promote the Establishment of Splenic B Cell Latency
Authors: Sylvester P. A. , Jondle C. N. , Stoltz K. P. , Lanham J. , Dittel B. N. , Tarakanova V. L.
Published: June 2021

IFN signaling is a major antiviral system of the host that suppresses replication of diverse viruses, including acute and chronic gammaherpesvirus infection. STAT1 is a critical member and the primary antiviral effector of IFN signaling pathways.
The Classical, Yet Controversial, First Enzyme of Lipid Synthesis: Escherichia coli Acetyl-CoA Carboxylase
Authors: Cronan John E.
Published: June 2021

Escherichia coli
acetyl-CoA carboxylase (ACC), the enzyme responsible for synthesis of the malonyl-CoA, the building block of fatty acid synthesis, is the paradigm bacterial ACC. Many reports on the structures and stoichiometry of the four subunits comprising the active enzyme as well as on regulation of ACC activity and expression have appeared in the almost 20 years since this subject was last reviewed. This review seeks to update and expand on these reports.
Cold Atmospheric Plasma Promotes Killing of Staphylococcus aureus by Macrophages
Authors: Duchesne Constance , Frescaline Nadira , Blaise Océane , Lataillade Jean-Jacques , Banzet Sébastien , Dussurget Olivier , Rousseau Antoine
Published: June 2021

Staphylococcus aureusis the most frequent cause of skin and soft tissue infections. Treatment failures are increasingly common due to antibiotic resistance and the emergence of resistant strains.
Pyoverdine Inhibitors and Gallium Nitrate Synergistically Affect Pseudomonas aeruginosa
Authors: Kang Donghoon , Revtovich Alexey V. , Deyanov Alexander E. , Kirienko Natalia V.
Published: June 2021

P. aeruginosa
is one of the most common causative agents for ventilator-associated pneumonia and nosocomial bacteremia and is a leading cause of death in patients with cystic fibrosis. Pandrug-resistant strains of
P. aeruginosa
are increasingly identified in clinical samples and show resistance to virtually all major classes of antibiotics, including aminoglycosides, cephalosporins, and carbapenems.
Comparison of SIRS criteria and qSOFA score for identifying culture-positive sepsis in the emergency department: a prospective cross-sectional multicentre study
Authors: Mignot-Evers Lisette , Raaijmakers Vivian , Buunk Gerba , Brouns Steffie , Romano Lorenzo , van Herpt Thijs , Gharbharan Arvind , Dieleman Jeanne , Haak Harm
Published: June 2021

Objective

To compare the daily practice of two emergency departments (ED) in the Netherlands, where systemic inflammatory response syndrome (SIRS) criteria and quick Sequential Organ Failure Assessment (qSOFA) score are used differently as screening tools for culture-positive sepsis.

Design

A prospective cross-sectional multicentre study.

Setting

Two EDs at two European clinical teaching hospitals in the Netherlands.

Participants

760 patients with suspected infection who met SIRS criteria or had a qualifying qSOFA score who were treated at two EDs in the Netherlands from 1 January to 1 March 2018 were included.

Methods

SIRS criteria and qSOFA score were calculated for each patient. The first hospital treated the patients who met SIRS criteria following the worldwide Surviving Sepsis Campaign protocol. At the second hospital, only patients who met the qualifying qSOFA score received this treatment. Therefore, patients could be divided into five groups: (1) SIRS+, qSOFA−, not treated according to protocol (reference group); (2) SIRS+, qSOFA−, treated according to protocol; (3) SIRS+, qSOFA+, treated according to protocol; (4) SIRS−, qSOFA+, not treated according to protocol; (5) SIRS−, qSOFA+, treated according to protocol.

Primary and secondary outcome measures

To prove culture-positive sepsis was present, cultures were used as the primary outcome. Secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission.

Results

98.9% met SIRS criteria and 11.7% met qSOFA score. Positive predictive values of SIRS criteria and qSOFA score were 41.2% (95% CI 37.4% to 45.2%) and 48.1% (95% CI 37.4% to 58.9%), respectively. HRs were 0.79 (95% CI 0.40 to 1.56, p=0.500), 3.42 (95% CI 1.82 to 6.44, p<0.001), 18.94 (95% CI 2.48 to 144.89, p=0.005) and 4.97 (95% CI 1.44 to 17.16, p=0.011) for groups 2–5, respectively.

Conclusion

qSOFA score performed as well as SIRS criteria for identifying culture-positive sepsis and performed significantly better for predicting in-hospital mortality and ICU admission. This study shows that SIRS criteria are no longer necessary and recommends qSOFA score as the standard for identifying culture-positive sepsis in the ED.

Trial registration number

NL8315.
Addressing maternal and child health equity through a community health worker home visiting intervention to reduce low birth weight: retrospective quasi-experimental study of the Arizona Health Start Programme
Authors: Sabo Samantha , Wightman Patrick , McCue Kelly , Butler Matthew , Pilling Vern , Jimenez Dulce J , Celaya Martín , Rumann Sara
Published: June 2021

Objective

To test if participation in the Health Start Programme, an Arizona statewide Community Health Worker (CHW) maternal and child health (MCH) home visiting programme, reduced rates of low birth weight (LBW), very LBW (VLBW), extremely LBW (ELBW) and preterm birth (PTB).

Design

Quasi-experimental retrospective study using propensity score matching of Health Start Programme enrolment data to state birth certificate records for years 2006–2016.

Setting

Arizona is uniquely racially and ethnically diverse with comparatively higher proportions of Latino and American Indian residents and a smaller proportion of African Americans.

Participants

7212 Health Start Programme mothers matched to non-participants based on demographic, socioeconomic and geographic characteristics, health conditions and previous birth experiences.

Intervention

A statewide CHW MCH home visiting programme.

Primary and secondary outcome measures

LBW, VLBW, ELBW and PTB.

Results

Using Health Start Programme’s administrative data and birth certificate data from 2006 to 2016, we identified 7212 Health Start Programme participants and 53 948 matches. Programme participation is associated with decreases in adverse birth outcomes for most subgroups. Health Start participation is associated with statistically significant lower rates of LBW among American Indian women (38%; average treatment-on-the-treated effect (ATT): 2.30; 95% CI −4.07 to –0.53) and mothers with a pre-existing health risk (25%; ATT: -3.06; 95% CI −5.82 to –0.30). Among Latina mothers, Health Start Programme participation is associated with statistically significant lower rates of VLBW (36%; ATT: 0.35; 95% CI −0.69 to –0.01) and ELBW (62%; ATT: 0.31; 95% CI (−0.52 to –0.10)). Finally, Health Start Programme participation is associated with a statistically significant lower rate of PTB for teen mothers (30%; ATT: 2.81; 95% CI −4.71 to –0.91). Other results were not statistically significant.

Conclusion

A state health department-operated MCH home visiting intervention that employs CHWs as the primary interventionist may contribute to the reduction of LBW, VLBW, ELBW and PTB and could improve birth outcomes statewide, especially among women and children at increased risk for MCH inequity.
Intravenous liposomal amphotericin B efficacy and safety for cutaneous and mucosal leishmaniasis: a systematic review and meta-analysis protocol
Authors: Naeem Faheel , Nathan Keren , Chivinski Jeffrey , Ekmekjian Taline , Libman Michael , Barkati Sapha
Published: June 2021

Introduction

Treatment of cutaneous and mucosal leishmaniasis (CL and ML, respectively) must be individualised as there is no universal therapeutic approach. Intravenous liposomal amphotericin B (L-AmB) is an accessible and relatively safe treatment that has been increasingly used for the treatment of CL and ML. While several descriptive studies have been published on the efficacy and safety of L-AmB, there are no interventional studies. Moreover, the findings from published studies have not yet been integrated and synthesised. Therefore, we aim to evaluate and consolidate the descriptive evidence on the efficacy and the safety of Intravenous L-AmB treatment for CL and ML in both the New and Old World.

Methods and analyses

A systematic review of all relevant study types with no restriction on date or language of publication will be conducted. Online databases including MEDLINE, The Cochrane Library, EMBASE, EBSCO, Scopus, Ovid and WHO databases were searched on 3 April 2020. The search included all study types that assess Intravenous L-AmB treatment for CL and ML in humans. The Population, Intervention, Comparison, Outcome and Study Design strategy and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be used to determine which studies will be selected for final inclusion. The quality of included case series and case reports will be assessed using modified quality assessment tools. A narrative synthesis of the findings will be provided and the primary outcome and secondary outcome of interest, response rate and adverse events rate, respectively, and the 95% CI will be ascertained. Estimates from individual studies will be pooled using random-effects model.

Ethics and dissemination

This systematic review does not require formal ethical approval since no primary data will be collected. Findings will be disseminated through a peer-reviewed publication and relevant conferences.

PROSPERO registration number

CRD42020173440.
Global and regional overview of the inclusion of paediatric surgery in the national health plans of 124 countries: an ecological study
Authors: Landrum Kelsey , Cotache-Condor Cesia F , Liu Yingling , Truche Paul , Robinson Julia , Thompson Nealey , Granzin Ryann , Ameh Emmanuel , Bickler Steve , Samad Lubna , Meara John G , Rice Henry E , Smith Emily R
Published: June 2021

Objective

This study evaluates the priority given to surgical care for children within national health policies, strategies and plans (NHPSPs).

Participants and setting

We reviewed the NHPSPs available in the WHO’s Country Planning Cycle Database. Countries with NHPSPs in languages different from English, Spanish, French or Chinese were excluded. A total of 124 countries met the inclusion criteria.

Primary and secondary outcome measures

We searched for child-specific and surgery-specific terms in the NHPSPs’ missions, goals and strategies using three analytic approaches: (1) count of the total number of mentions, (2) count of the number of policies with no mentions and (3) count of the number of policies with five or more mentions. Outcomes were compared across WHO regional and World Bank income-level classifications.

Results

We found that the most frequently mentioned terms were ‘child*’, ‘infant*’ and ‘immuniz*’. The most frequently mentioned surgery term was ‘surg*’. Overall, 45% of NHPSPs discussed surgery and 7% discussed children’s surgery. The majority (93%) of countries did not mention selected essential and cost-effective children’s procedures. When stratified by WHO region and World Bank income level, the West Pacific region led the inclusion of ‘pediatric surgery’ in national health plans, with 17% of its countries mentioning this term. Likewise, low-income countries led the inclusion of surg* and ‘pediatric surgery’, with 63% and 11% of countries mentioning these terms, respectively. In both stratifications, paediatric surgery only equated to less than 1% of the total terms.

Conclusion

The low prevalence of children’s surgical search terms in NHPSPs indicates that the influence of surgical care for this population remains low in the majority of countries. Increased awareness of children’s surgical needs in national health plans might constitute a critical step to scale up surgical system in these countries.
Development and validation of a patient-reported measure of compassion in healthcare: the Sinclair Compassion Questionnaire (SCQ)
Authors: Sinclair Shane , Hack Thomas F , MacInnis Cara C , Jaggi Priya , Boss Harrison , McClement Susan , Sinnarajah Aynharan , Thompson Genevieve
Published: June 2021

Objectives

Compassion is a key indicator of quality care that is reportedly eroding from patients’ care experience. While the need to assess compassion is recognised, valid and reliable measures are lacking. This study developed and validated a clinically informed, psychometrically rigorous, patient-reported compassion measure.

Design

Data were collected from participants living with life-limiting illnesses over two study phases across four care settings (acute care, hospice, long term care (LTC) and homecare). In phase 1, data were analysed through exploratory factor analysis (EFA), with the final items analysed via confirmatory factor analysis (CFA) in phase 2. The Schwartz Center Compassionate Care Scale (SCCCS), the revised Edmonton Symptom Assessment Scale (ESAS-r) and Picker Patient Experience Questionnaire (PPEQ) were also administered in phase 2 to assess convergent and divergent validity.

Setting and participants

633 participants were recruited over two study phases. In the EFA phase, a 54-item version of the measure was administered to 303 participants, with 330 participants being administered the final 15-item measure in the CFA phase.

Results

Both EFA and CFA confirmed compassion as a single factor construct with factor loadings for the 15-item measure ranging from 0.76 to 0.86, with excellent test–retest reliability (intraclass correlation coefficient range: 0.74–0.89) and excellent internal reliability (Cronbach’s alpha of 0.96). The measure was positively correlated with the SCCCS (r=0.75, p<0.001) and PPEQ (r=0.60, p<0.001). Participants reporting higher experiences of compassion had significantly greater well-being and lower depression on the ESAS-r. Patients in acute care and hospice reported significantly greater experiences of compassion than LTC residents.

Conclusions

There is strong initial psychometric evidence for the Sinclair Compassion Questionnaire (SCQ) as a valid and reliable patient-reported compassion measure. The SCQ provides healthcare providers, settings and administrators the means to routinely measure patients experiences of compassion, while providing researchers a robust measure to conduct high-quality research.
Costs of hospital trauma team simulation training: a prospective cohort study
Authors: Rosqvist Eerika , Ylönen Marika , Torkki Paulus , Repo Jussi P , Paloneva Juha
Published: June 2021

Objectives

This study investigated the costs of 2-hour multiprofessional in situ hospital trauma team simulation training and its effects on teams’ non-technical skills using the T-NOTECHS instrument.

Background

Simulation is a feasible and effective teaching and learning method. Calculating the costs of simulated trauma team training in medical emergency situations can yield valuable information for improving its overall cost-effectiveness.

Design

A prospective cohort study.

Setting

Trauma resuscitation room in Central Finland Hospital, Finland.

Participants

475 medical professionals in 81 consecutive, simulated trauma teams.

Primary and secondary outcome measures

Team simulation training costs in 2017 and 2018 were analysed in the following two phases: (1) start-up costs and (2) costs of education. Primary outcome measures were training costs per participant and training costs per team. Secondary outcome measures were non-technical skills, which were measured on a 5–25-point scale using the T-NOTECHS instrument.

Results

The annual mean total costs of trauma team simulation training were €58 000 for 40 training sessions and 238 professionals. Mean cost per participant was €203. Mean cost per team was €1220. The annual costs of simulation training markedly decreased when at least 70–80 teams participated in the training. Mean change in T-NOTECHS score after simulation training was +2.86 points (95% CI 1.97 to 3.75;+14.5%).

Conclusions

The greater the number of teams trained per year, the lower the costs per trauma team. In this study, we developed an activity-based costing method to calculate the costs of trauma team simulation training to help stakeholders make decisions about whether to initiate or increase existing trauma team simulation training or to obtain these services elsewhere.
Extent of awareness and attitudes on plagiarism among post-graduate resident doctors and junior medical faculty in India: a cross-sectional, multicentric study
Authors: Raj Jeffrey Pradeep , Venkatachalam Shreeraam , Amaravati Rajkumar S , Siby Noel , Oommen Aswathy Maria , Jose Jesin Elsa , George Melvin , Ramraj Balaji , Penumutsa Vijay Subbaraju , Bodda Deepthi Rani , Rajad R , Reshmi R , Inbaraj Leeberk Raja , Rajiv S , Bhandare Basavaraj , Aiyappan Rajalakshmy , Mathew Philip , Saleem Ahammed K , Shetty Robin , Bhuvaneswari G , Suresh Kumar T , Prasanna B Lakshmi , Manderwad Guru Prasad
Published: June 2021

Objectives

Though dissertation is mandatory for postgraduates (PG), it is unknown if adequate knowledge on plagiarism exists at that level. Thus, we intended to study the knowledge and attitude towards plagiarism among junior doctors in India.

Design

Cross-sectional study

Setting

PG medical residents and Junior faculty from various teaching institutions across south India.

Participants

A total of N=786 doctors filled the questionnaires of which approximately 42.7% were from government medical colleges (GMCs) and the rest from private institutions.

Methods

Participants were given a pretested semistructured questionnaire which contained: (1) demographic details; (2) a quiz developed by Indiana University, USA to assess knowledge and (3) Attitudes towards Plagiarism Questionnaire (ATPQ).

Outcome measures

The Primary outcome measure was knowledge about plagiarism. The secondary outcome measure was ATPQ scores.

Results

A total of N=786 resident doctors and junior faculty from across 11 institutions participated in this study. Of this, 42.7% were from GMCs and 60.6% were women. The mean (SD) knowledge score was 4.43 (1.99) out of 10. The factors (adjusted OR; 95% CI; p value) that emerged as significant predictors of knowledge were number of years in profession (−0.181; −0.299 to –0.062; 0.003), no previous publication (0.298; 0.099 to 0.498; 0.003) and working in a GMC (0.400; 0.106 to 0.694; 0.008). The overall mean (SD) scores of the three attitude components were: Permissive attitudes—37.33 (5.33), critical attitudes —20.32 (4.82) and subjective norms—31.05 (4.58), all of which corresponded to the moderate category.

Conclusion

Participants lacked adequate knowledge on how to avoid plagiarism suggesting a need for a revamp in medical education curriculum in India by incorporating research and publication ethics.
Adjuvant effects of vitamin A and vitamin D supplementation on treatment of children with attention-deficit/hyperactivity disorder: a study protocol for a randomised, double-blinded, placebo-controlled, multicentric trial in China
Authors: Zhou Ping , Wolraich Mark Lee , Cao Ai-hua , Jia Fei-Yong , Liu Bin , Zhu Lin , Liu Yongfang , Li Xiaoli , Li Chao , Peng Bin , Yang Ting , Chen Jie , Cheng Qian , Li Tingyu , Chen Li
Published: June 2021

Introduction

Approximately 7.2% of children in the world suffer from attention-deficit/hyperactivity disorder (ADHD). Due to the availability of the osmotic-release oral-system methylphenidate, ADHD currently has a remission rate of up to 30.72%. Nevertheless, it has been reported that patients with ADHD tend to exhibit vitamin A and vitamin D deficiency, which may aggravate the symptoms of ADHD. This study aims to determine the effect of vitamin A and vitamin D supplementation as adjunctive therapy to methylphenidate on the symptoms of ADHD.

Methods and analysis

This is a parallel, prospective, interventional multicentric study. Patients will be enrolled from the southern, central and northern parts of China. A target of 504 patients will be followed for 8 weeks. They will be allocated into three groups (vitamin AD, vitamin D and placebo) and administered the interventions accordingly. Data on changes in the symptoms of ADHD as well as changes in the serum concentrations of vitamin A and vitamin D will be recorded. Both responders and nonresponders based on the sociodemographic and clinical data will also be described to mitigate selection bias.

Ethics and dissemination

This study is performed in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Children’s Hospital of Chongqing Medical University, China (approval number: (2019) IRB (STUDY) number 262). The results of the trial will be reported in peer-reviewed scientific journals and academic conferences regardless of the outcomes.

Trial registration number

NCT04284059.