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Currently, all assays measuring acetylcholinesterase (AChE) activity following a suspected nerve agent exposure leverage methodologies that fail to identify the agent. This limits the overall effectiveness and ability to administer proper countermeasures. As such, there is an urgent need to identify novel, rapid, and more comprehensive approaches to establish AChE activity, including identification of the toxicant. Paper spray mass spectrometry was used to monitor the activity of acetylcholinesterase, both in-solution and on modified hydrophobic paper surface. Hydrophobic paper surfaces were prepared using vaporized trichloro(3,3,3-trifluoropropyl)silane. In both approaches, mixtures of diluted human whole blood with and without VX were mixed with a non-endogenous AChE specific substrate, 1,1-dimethyl-4-acetylthiomethylpiperidinium (MATP+). Formation of the cleaved MATP+ product was monitored over time and compared to MATP+ to determine relative AChE activity. This on-substrate assay was effective at determining AChE activity and identifying the toxicant; however, determination of AChE activity in-solution proceeded at a slower rate. The on-substrate assay serves as a pioneering example of an enzymatic reaction occurring on the surface of a paper spray ionization ticket. This work broadens the range of applications relating to paper spray ionization-based clinical diagnostic assays. Graphical Abstractᅟ Electronic supplementary material The online version of this article (10.1007/s13361-018-2072-1) contains supplementary material, which is available to authorized users.

Human access to safe water has become a major problem in many parts of the world as increasing human activities continue to spill contaminants into our water systems. To guarantee the protection of the public as well as the environment, a rapid and sensitive way to detect contaminants is required. In this work, a paper-based microbial fuel cell was developed to act as a portable, single-use, on-site water quality sensor. The sensor was fabricated by combining two layers of paper for a simple, low-cost, and disposable design. To facilitate the use of the sensor for on-site applications, the bacterial cells were pre-inoculated onto the device by air-drying. To eliminate any variations, the voltage generated by the microorganism before and after the air-drying process was measured and calculated as an inhibition ratio. Upon the addition of different formaldehyde concentrations (0%, 0.001%, 0.005%, and 0.02%), the inhibition ratios obtained were 5.9 &plusmn, 0.7%, 6.9 &plusmn, 0.7%, 8.2 &plusmn, 0.6%, and 10.6 &plusmn, 0.2%, respectively. The inhibition ratio showed a good linearity with the formaldehyde concentrations at R2 = 0.931. Our new sensor holds great promise in monitoring water quality as a portable, low-cost, and on-site sensor.

The development of viable point-of-care diagnostic formats is integral to achieving better patient care and improved outcomes. The need for robust and low-cost tests is especially important in under-resourced and rural settings. Perhaps the greatest challenge is ensuring that an untrained individual is capable of operating and interpreting the test, out with a care facility. Here we present a paper-based diagnostic device capable of sensing miR-29a using both colorimetric and surface enhanced Raman scattering (SERS) analysis. Rather, than carry out the two types of analyses in tandem, we envisage that the colorimetric output is easy enough to be interpreted by the untrained-individual administering the test to provide them with qualitative feedback. If deemed positive, the test can be further validated at a centralized care facility using a handheld-Raman spectrometer to provide a semi-quantitative result. Detection of miR-29a, a microRNA associated with myocardial infarction, was achieved at a level of pg μL-1 through the combination of three-dimensional paper-based microfluidics, colorimetric detection, and surface enhanced Raman scattering (SERS) analysis. RGB analysis of the colorimetric output generated from samples containing miR-29a at different concentrations (18-360 pg μL-1) showed differentiation from the control sample, however significant repeat variability indicated that it could not be used for quantifying miR-29a levels. However, the SERS analysis exhibited greater reproducibility at varying concentrations, achieving an LoD of 47 pg μL-1. The union of the paper-based device and the two analysis methods resulted in the production of a sensitive, reproducible and facile, point of care test (POCT), which paves the way for future implementation in the diagnosis of a range of diseases.

This ESC Council on Stroke/EAPCI/EBNI position paper summarizes recommendations for training of cardiologists in endovascular treatment of acute ischaemic stroke. Interventional cardiologists adequately trained to perform endovascular stroke interventions could complement stroke teams to provide the 24/7 on call duty and thus to increase timely access of stroke patients to endovascular treatment. The training requirements for interventional cardiologists to perform endovascular therapy are described in details and should be based on two main principles: (i) patient safety cannot be compromised, (ii) proper training of interventional cardiologists should be under supervision of and guaranteed by a qualified neurointerventionist and within the setting of a stroke team. Interdisciplinary cooperation based on common standards and professional consensus is the key to the quality improvement in stroke treatment.

The COVID-19 pandemic has had a huge influence in almost all areas of life, affecting societies, economics, and health care systems worldwide. The paediatric cardiology community is no exception. As the challenging battle with COVID-19 continues, professionals from the Association for the European Paediatric and Congenital Cardiology receive many questions regarding COVID-19 in a Paediatric and Congenital Cardiology setting. The aim of this paper is to present the AEPC position on frequently asked questions based on the most recent scientific data, as well as to frame a discussion on how to take care of our patients during this unprecedented crisis. As the times are changing quickly and information regarding COVID-19 is very dynamic, continuous collection of evidence will help guide constructive decision-making.

BackgroundSmartphones have become an essential part of everyday life and it is undeniable that apps offer enormous opportunities for dealing with future challenges in public health. Nevertheless, the exact patient requirements for medical apps in the field of orthopedic and trauma surgery are currently unknown. ObjectiveThe aim of this study was to define target groups, evaluate patient requirements, and the potential and pitfalls regarding medical apps specific for patients receiving orthopedic and trauma surgical care. MethodsA prospective multicenter study was conducted between August 2018 and December 2019 at a German trauma center and 3 trauma surgery/orthopedic practices. A paper-based survey consisting of 15 questions evaluated information regarding smartphone and medical app usage behavior. In addition, suggested app functions were rated using Likert scales. Descriptive statistics and binary log-binomial regression were performed. ResultsA total of 1055 questionnaires were included in our statistical analysis. Approximately 89.57% (945/1055) of the patients in this study owned a smartphone. Smartphone ownership probability decreased with every decade of life and increased with higher levels of education. Medical information was obtained via mobile web access by 62.65% (661/1055) of the patients; this correlated with smartphone ownership in regard to age and educational level. Only 11.18% (118/1055) of the patients reported previous medical app usage, and 3.50% (37/1055) of the patients received an app recommendation from a physician. More than half (594/1055, 56.30%) of the patients were unwilling to pay for a medical app. The highest rated app functions were information about medication, behavioral guidelines, and medical record archival. An improved treatment experience was reported through the suggested app features by 71.18% (751/1055) of the patients. ConclusionsMobile devices are a widely used source of information for medical content, but only a minority of the population reported previous medical app usage. The main target group for medical apps among patients receiving orthopedic and trauma surgical care tends to be the younger population, which results in a danger of excluding fringe groups, especially the older adults. Education seems to be one of the most important pull factors to use smartphones or a mobile web connection to obtain health information. Medical apps primarily focusing on an optimized patient education and flow of information seem to have the potential to support patients in health issues, at least in their subjective perception. For future target group–oriented app developments, further evidence on the clinical application, feasibility, and acceptance of app usage are necessary in order to avoid patient endangerment and to limit socioeconomic costs.

Contemporary cardiovascular medicine is complex, dynamic, and interactive. Therefore, multidisciplinary dialogue between different specialists is required to deliver optimal and patient-centred care. This has led to the concept of explicit collaborations of different specialists caring for patients with complex cardiovascular diseases—that is ‘heart teams’. These teams are particularly valuable to minimize referral bias and improve guideline adherence as so to be responsive to patient preferences, needs, and values but may be challenging to coordinate, especially in the acute setting. This position paper—jointly developed by four cardiovascular associations—is intended to provide conceptual and practical considerations for the composition, structure, and function of multidisciplinary teams. It focuses on patients with complex coronary artery diseases in both elective and urgent setting and provide guidance on how to implement the heart team both in chronic and in acute coronary syndromes patients, including cases with mechanical complications and haemodynamic instability; it also discusses strategies for clear and transparent patient communication and provision of a patient-centric approach. Finally, gaps in evidence and research perspectives in this context are discussed.

Recognizing the increase in cancer incidence globally and the need for effective cancer control interventions, several organizations, professional bodies, and international institutions have proposed strategies to improve treatment options and reduce mortality along with minimizing overall incidence. Despite these efforts, an estimated 9.6 million deaths in 2018 was attributed to this noncommunicable disease, making it the second leading cause of death worldwide. Left unchecked, this will further increase in scale, with an estimated 29.5 million new cases and 16.3 million deaths occurring worldwide in 2040. Although it is known and generally accepted that cancer services must include radiotherapy, such access is still very limited in many parts of the world, especially in low- and middle-income countries. After thorough review of the current status of radiotherapy including programs worldwide, as well as achievements and challenges at the global level, the International Atomic Energy Agency convened an international group of experts representing various radiation oncology societies to take a closer look into the current status of radiotherapy and provide a road map for future directions in this field. It was concluded that the plethora of global and regional initiatives would benefit further from the existence of a central framework, including an easily accessible repository through which better coordination can be done. Supporting this framework, a practical inventory of competencies needs to be made available on a global level emphasizing the knowledge, skills, and behavior required for a safe, sustainable, and professional practice for various settings. This white paper presents the current status of global radiotherapy and future directions for the community. It forms the basis for an action plan to be developed with professional societies worldwide.

Aims Quality indicators (QIs) are tools to improve the delivery of evidence-base medicine. In 2017, the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) developed a set of QIs for acute myocardial infarction (AMI), which have been evaluated at national and international levels and across different populations. However, an update of these QIs is needed in light of the accumulated experience and the changes in the supporting evidence. Methods and results The ESC methodology for the QI development was used to update the 2017 ACVC QIs. We identified key domains of AMI care, conducted a literature review, developed a list of candidate QIs, and used a modified Delphi method to select the final set of indicators. The same seven domains of AMI care identified by the 2017 Study Group were retained for this update. For each domain, main and secondary QIs were developed reflecting the essential and complementary aspects of care, respectively. Overall, 26 QIs are proposed in this document, compared to 20 in the 2017 set. New QIs are proposed in this document (e.g. the centre use of high-sensitivity troponin), some were retained or modified (e.g. the in-hospital risk assessment), and others were retired in accordance with the changes in evidence [e.g. the proportion of patients with non-ST segment elevation myocardial infarction (NSTEMI) treated with fondaparinux] and the feasibility assessments (e.g. the proportion of patients with NSTEMI whom risk assessment is performed using the GRACE and CRUSADE risk scores). Conclusion Updated QIs for the management of AMI were developed according to contemporary knowledge and accumulated experience. These QIs may be applied to evaluate and improve the quality of AMI care.

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), “lower is better for longer”, and the recent data have strongly emphasized the need of also “the earlier the better”. In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual’s calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an ‘Extremely High Risk’ group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardio-vascular risk in these patients.

BACKGROUND: The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) position paper from 2015 on percutaneous endoscopic gastrostomy (PEG) required updating in the light of recent clinical knowledge and data published in medical journals since 2014. METHODS: A systematic review of medical literature from 2014 to 2020 was carried out. Consensus on the content of the manuscript, including recommendations, was achieved by the authors through electronic and virtual means. The expert opinion of the authors is also expressed in the manuscript when there was a lack of good scientific evidence regarding PEGs in children in the literature. RESULTS: The authors recommend that the indication for a PEG be individualized, and that the decision for PEG insertion is arrived at by a multidisciplinary team (MDT) having considered all appropriate circumstances. Well timed enteral nutrition is optimal to treat faltering growth to avoid complications of malnutrition and body composition. Timing, device choice and method of insertion is dependent on the local expertise and after due consideration with the MDT and family. Major complications such as inadvertent bowel perforation should be avoided by attention to good technique and by ensuring the appropriate experience of the operating team. Feeding can be initiated as early as 3 hours after tube placement in a stable child with iso-osmolar feeds of standard polymeric formula. Low-profile devices can be inserted initially using the single-stage procedure or after 2-3 months by replacing a standard PEG tube, in those requiring longer-term feeding. Having had a period of non-use and reliance upon oral intake for growth and weight gain-typically 8-12 weeks-a PEG may then safely be removed after due consultation. In the event of non-closure of the fistula the most successful method for closing it, to date, has been a surgical procedure, but the Over-The-Scope-Clip (OTSC) has recently been used with considerable success in this scenario. CONCLUSIONS: A multidisciplinary approach is mandatory for the best possible treatment of children with PEGs. Morbidity and mortality are minimized through team decisions on indications for insertion, adequate planning and preparation before the procedure, subsequent monitoring of patients, timing of the change to low-profile devices, management of any complications, and optimal timing of removal of the PEG.

Liver and kidney are strictly connected in a reciprocal manner, in both the physiological and pathological condition. The Italian Association for the Study of Liver, in collaboration with the Italian Society of Nephrology, with this position paper aims to provide an up-to-date overview on the principal relationships between these two important organs. A panel of well-recognized international expert hepatologists and nephrologists identified five relevant topics: 1) The diagnosis of kidney damage in patients with chronic liver disease; 2) Acute kidney injury in liver cirrhosis; 3) Association between chronic liver disease and chronic kidney disease; 4) Kidney damage according to different etiology of liver disease; 5) Polycystic kidney and liver disease. The discussion process started with a review of the literature relating to each of the five major topics and clinical questions and related statements were subsequently formulated. The quality of evidence and strength of recommendations were graded according to the GRADE system. The statements presented here highlight the importance of strong collaboration between hepatologists and nephrologists for the management of critically ill patients, such as those with combined liver and kidney impairment.

Introduction: adolescence is a critical stage of rapid biological, emotional and social change and development. Adolescents and young adults (AYA) with asthma and allergies need to develop the knowledge and skills to self-manage their health independently. Healthcare professionals (HCP), parents and their wider network play an essential role in supporting AYA in this process. Previous work showed significant limitations in transition care across Europe. In 2020, the first evidence-based guideline on effective transition for AYA with asthma and allergies was published by EAACI.Aim: we herein summarize practical resources to support this guideline's implementation in clinical practice.Methods: for this purpose, multi-stakeholder Task Force members searched for resources in peer review journals and grey literature. These resources were included if relevant and of good quality and were pragmatically rated for their evidence-basis and user friendliness.Results: resources identified covered a range of topics and targeted healthcare professionals, AYA, parents/carers, schools, workplace and wider community. Most resources were in English, web-based and had limited evidence-basis.Conclusions: this position paper provides a valuable selection of practical resources for all stakeholders to support effective transitional care for AYA with asthma and allergies. Future research should focus on developing validated, patient-centred tools to further assist evidence-based transition care.

Executive SummaryWith an increasing variety of radiopharmaceuticals for diagnostic or therapeutic nuclear medicine as valuable diagnostic or treatment option, radiobiology plays an important role in supporting optimizations. This comprises particularly safety and efficacy of radionuclide therapies, specifically tailored to each patient. As absorbed dose rates and absorbed dose distributions in space and time are very different between external irradiation and systemic radionuclide exposure, distinct radiation-induced biological responses are expected in nuclear medicine, which need to be explored. This calls for a dedicated nuclear medicine radiobiology. Radiobiology findings and absorbed dose measurements will enable an improved estimation and prediction of efficacy and adverse effects. Moreover, a better understanding on the fundamental biological mechanisms underlying tumor and normal tissue responses will help to identify predictive and prognostic biomarkers as well as biomarkers for treatment follow-up. In addition, radiobiology can form the basis for the development of radiosensitizing strategies and radioprotectant agents. Thus, EANM believes that, beyond in vitro and preclinical evaluations, radiobiology will bring important added value to clinical studies and to clinical teams. Therefore, EANM strongly supports active collaboration between radiochemists, radiopharmacists, radiobiologists, medical physicists, and physicians to foster research toward precision nuclear medicine.

Background The COVID-19 pandemic has caused unprecedented global demand for personal protective equipment (PPE). A paucity of data on PPE burn rate (PPE consumption over time) in pandemic situations exacerbated these issues as there was little historic research to indicate volumes of PPE required to care for surges in infective patients and thus plan procurement requirements. Methods To better understand PPE requirements for care of suspected or confirmed COVID-19 patients in our Australian quaternary referral hospital, the number of staff-to-patient interactions in a 24-h period for three patient groups (ward-based COVID suspect, ward-based COVID confirmed, intensive care COVID confirmed) was audited prospectively from 1st to 30th April 2020. Results The average number of staff-to-patient interactions in a 24-h period was: 13.1 ± 5.0 (mean ± SD) for stable ward-managed COVID-19 suspect patients; 11.9 ± 3.8 for stable ward-managed confirmed COVID-19 patients; and 30.0 ± 5.3 for stable, mechanically ventilated, ICU-managed COVID-19 patients. This data can be used in PPE demand simulation modelling for COVID-19 and potentially other respiratory illnesses. Conclusion Data on the average number of staff-to-patient interactions needed for the care of COVID-19 patients is presented. This data can be used for PPE demand simulation modelling.

According to a recent World Health Organization estimate, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which originated in China in 2019, has spread globally, infecting nearly 100 million people worldwide by January 2021. Patients with chronic liver diseases (CLD), particularly cirrhosis, hepatobiliary malignancies, candidates for liver transplantation, and immunosuppressed individuals after liver transplantation appear to be at increased risk of infections in general, which in turn translates into increased mortality. This is also the case for SARS-CoV-2 infection, where patients with cirrhosis, in particular, are at high risk of a severe COVID-19 course. Therefore, vaccination against various pathogens including SARS-CoV-2, administered as early as possible in patients with CLD, is an important protective measure. However, due to impaired immune responses in these patients, the immediate and long-term protective response through immunisation may be incomplete. The current SARS-CoV-2 pandemic has led to the exceptionally fast development of several vaccine candidates. A small number of these SARS-CoV-2 vaccine candidates have already undergone phase III, placebo-controlled, clinical trials in healthy individuals with proof of short-term safety, immunogenicity and efficacy. However, although regulatory agencies in the US and Europe have already approved some of these vaccines for clinical use, information on immunogenicity, duration of protection and long-term safety in patients with CLD, cirrhosis, hepatobiliary cancer and liver transplant recipients has yet to be generated. This review summarises the data on vaccine safety, immunogenicity, and efficacy in this patient population in general and discusses the implications of this knowledge on the introduction of the new SARS-CoV-2 vaccines.

Atherosclerotic plaques prone to rupture may cause acute myocardial infarction (MI) but can also heal without causing an event. Certain common histopathological features, including inflammation, a thin fibrous cap, positive remodelling, a large necrotic core, microcalcification, and plaque haemorrhage are commonly found in plaques causing an acute event. Recent advances in imaging techniques have made it possible to detect not only luminal stenosis and overall coronary atherosclerosis burden but also to identify such adverse plaque characteristics. However, the predictive value of identifying individual adverse atherosclerotic plaques for future events has remained poor. In this Position Paper, the relationship between vulnerable plaque imaging and MI is addressed, mainly for non-invasive assessments but also for invasive imaging of adverse plaques in patients undergoing invasive coronary angiography. Dynamic changes in atherosclerotic plaque development and composition may indicate that an adverse plaque phenotype should be considered at the patient level rather than for individual plaques. Imaging of adverse plaque burden throughout the coronary vascular tree, in combination with biomarkers and biomechanical parameters, therefore holds promise for identifying subjects at increased risk of MI and for guiding medical and invasive treatment.

Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized, and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate-type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.

The coronavirus disease 2019 (COVID‐19) pandemic is a case that can be used as a biochemistry learning resource in relation to the topic of viruses. Learning to use cases will be effective if students are assigned to produce reports, articles, or other scientific papers. Self‐assessment can be used to assess the competencies that have been learnt in the writing process. This study aims to analyze the scientific papers and self‐assessment of students using the COVID‐19 pandemic case. It includes qualitative research with scientific paper and self‐assessment questionnaire analyses. The research sample was chemistry education study program students (N = 57) following biochemistry course, out of a population of 87 students. The results show that the students have a good understanding of explaining COVID‐19. Self‐assessment analysis shows that 80% of the students responded positively to eight statements; those who gave positive responses to each questionnaire statement were able to produce scientific papers. Good self‐assessment is in line with the ability of students to compile good scientific papers.

Significance: Cardiac troponin I (cTnI) is a primary biomarker for diagnosis of myocardial infarction (MI). In contrast to central laboratory tests for cTnI, point-of-care (POC) testing has the advantage of providing results when the patient is first encountered, which helps high-risk patients to be treated more rapidly and low-risk patients to be released in a timely fashion. A paper fluidic platform is good for POC testing because the paper is abundant, low cost, and disposable. However, current cTnI assays on paper platforms use antibodies as the recognition element, which has limitations due to the high cost of production and antibody stability issues at the POC. Aim: To develop an aptamer-based assay on a paper strip using surface-enhanced resonance Raman spectroscopy (SERRS) for detection of cTnI in the clinically relevant range at the POC. Approach: Gold nanoparticles (AuNPs) were functionalized with a Raman reporter molecule, malachite green isothiocyanate. The functionalized AuNPs were encapsulated in a silica shell and provided a SERRS signal using a handheld Raman system with a 638-nm excitation wavelength. A primary aptamer and a secondary aptamer of cTnI were used in a sandwich assay format to bind the cTnI on a test line of a paper fluidic platform. By measuring the SERRS signal from the test line, the concentration of cTnI was quantitatively determined. Results: The aptamer-based SERRS assay on a paper strip had a detection range of 0.016 to 0.1 ng/ml for cTnI, had good selectivity for cTnI compared to three other markers, had good stability over 10 days, and had good performance in the more complex serum sample matrix. Conclusions: The aptamer-based SERRS assay on a paper strip has the potential to provide a sensitive, selective, stable, repeatable, and cost-effective platform for the detection of cTnI toward eventual use in diagnosis of MI at the POC.

Cardiovascular disease is one of the main causes of morbidity and sick leave in Belgium, imposing a great socio-economic burden on the contemporary healthcare system and society. Cardiac rehabilitation is an evidence-based treatment strategy that not only improves the cardiac patients' health state but also holds promise so as to facilitate vocational reintegration in the society. This position paper was developed and endorsed by the Belgian Working Group of Cardiovascular Prevention and Rehabilitation. It provides an overview of the currently available Belgian data with regard to the role of cardiac rehabilitation in return to work after an initial cardiac event. It identifies the relevant barriers and facilitators of vocational integration of cardiac patients and summarises the contemporary Belgian legal and medical framework in this regard. Cardiac rehabilitation remains a primordial component of the post-acute event management of the cardiac patient, facilitating vocational reintegrating and thereby decreasing the pressure on social security. Despite the availability of a relevant legislative framework, there is a need for well-defined algorithms to assess readiness for return to work that can be used in daily clinical practice. ispartof: ACTA CARDIOLOGICA vol:75 issue:5 pages:388-397 ispartof: location:England status: published

Contains fulltext : 225338.pdf (Publisher’s version ) (Open Access) OBJECTIVES: The number of older people dying in long-term care facilities (LTCFs) is increasing globally, but care quality may be variable. A framework was developed drawing on empirical research findings from the Palliative Care for Older People (PACE) study and a scoping review of literature on the implementation of palliative care interventions in LTCFs. The PACE study mapped palliative care in LTCFs in Europe, evaluated quality of end-of-life care and quality of dying in a cross-sectional study of deceased residents of LTCFs in 6 countries, and undertook a cluster-randomized control trial that evaluated the impact of the PACE Steps to Success intervention in 7 countries. Working with the European Association for Palliative Care, a white paper was written that outlined recommendations for the implementation of interventions to improve palliative and end-of-life care for all older adults with serious illness, regardless of diagnosis, living in LTCFs. The goal of the article is to present these key domains and recommendations. DESIGN: Transparent expert consultation. SETTING: International experts in LTCFs. PARTICIPANTS: Eighteen (of 20 invited) international experts from 15 countries participated in a 1-day face-to-face Transparent Expert Consultation (TEC) workshop in Bern, Switzerland, and 21 (of 28 invited) completed a follow-up online survey. METHODS: The TEC study used (1) a face-to-face workshop to discuss a scoping review and initial recommendations and (2) an online survey. RESULTS: Thirty recommendations about implementing palliative care for older people in LTCFs were refined during the TEC workshop and, of these, 20 were selected following the survey. These 20 recommendations cover domains at micro (within organizations), meso (across organizations), and macro (at national or regional) levels addressed in 3 phases: establishing conditions for action, embedding in everyday practice, and sustaining ongoing change. CONCLUSIONS AND IMPLICATIONS: We developed a framework of 20 recommendations to guide implementation of improvements in palliative care in LTCFs.

Cognitive modeling involves the creation of computer simulations that emulate the internal processes of the mind. This set of papers are the five best representatives of the papers presented at the 17th International Conference on Cognitive Modeling, ICCM 2019. While they represent a diversity of techniques and tasks, they all also share a striking similarity: They make strong statements about the importance of accounting for individual differences.

Summary: The International Osteoporosis Foundation (IOF) Capture the Fracture® Campaign with the Fragility Fracture Network (FFN) and National Osteoporosis Foundation (NOF) has developed eleven patient-level key performance indicators (KPIs) for fracture liaison services (FLSs) to guide quality improvement. Introduction: Fracture Liaison Services (FLSs) are recommended worldwide to reduce fracture risk after a sentinel fracture. Given not every FLS is automatically effective, the IOF Capture the Fracture working group has developed and implemented the Best Practice Framework to assess the organisational components of an FLS. We have now developed a complimentary KPI set that extends this assessment of performance to the patient level. Methods: The Capture the Fracture working group in collaboration with the Fragility Fracture Network Secondary Fragility Fracture Special Interest Group and National Osteoporosis Foundation adapted existing metrics from the UK-based Fracture Liaison Service Database Audit to develop a patient-level KPI set for FLSs. Results: Eleven KPIs were selected. The proportion of patients: with non-spinal fractures; with spine fractures (detected clinically and radiologically); assessed for fracture risk within 12 weeks of sentinel fracture; having DXA assessment within 12 weeks of sentinel fracture; having falls risk assessment; recommended anti-osteoporosis medication; commenced of strength and balance exercise intervention within 16 weeks of sentinel fracture; monitored within 16 weeks of sentinel fracture; started anti-osteoporosis medication within 16 weeks of sentinel fracture; prescribed anti-osteoporosis medication 52 weeks after sentinel fracture. The final KPI measures data completeness for each of the other KPIs. For these indicators, levels of achievement were set at the < 50%, 50–80% and > 80% levels except for treatment recommendation where a level of 50% was used. Conclusion: This KPI set compliments the existing Best Practice Framework to support FLSs to examine their own performance using patient-level data. By using this KPI set for local quality improvement cycles, FLSs will be able to efficiently realise the full potential of secondary fracture prevention and improved clinical outcomes for their local populations.

International audience; AIM: The families of hospitalised preterm infants risk depression and post-traumatic stress and the preterm infants risk re-hospitalisation. The French neonatal society's aim was to review the literature on how the transition from hospital to home could limit these risks and to produce a position paper.METHODS: A systematic literature review was performed covering 1 January 2000 to 1 January 2018, and multidisciplinary experts examined the scientific evidence.RESULTS: We identified 939 English and French papers and 169 are quoted in the position paper. Most studies stressed the importance of early, personalised and progressive involvement of the family. Healthcare staff and families should assess discharge preparations jointly. This evaluation should assess the capacities of the newborn infant, with regard to its physiological maturity. It should also assess the family's ability to supply the medical, psychological and social assistance required before and after discharge. There should be a structured follow-up process that includes effective communication, various tools, interventions, networks, health and social professionals.CONCLUSION: Discharge preparations may improve the transition from hospital to home and the outcomes for the parents and newborn preterm infant. This early family-centred approach should be structured, coordinated and based on individual needs and circumstances.

Microfluidic paper-based analytical devices (µPADs) have become promising tools offering various analytical applications for chemical and biological assays at the point-of-care (POC). Compared to traditional microfluidic devices, µPADs offer notable advantages; they are cost-effective, easily fabricated, disposable, and portable. Because of our better understanding and advanced engineering of µPADs, multistep assays, high detection sensitivity, and rapid result readout have become possible, and recently developed µPADs have gained extensive interest in parallel analyses to detect biomarkers of interest. In this review, we focus on recent developments in order to achieve µPADs with high-throughput capability. We discuss existing fabrication techniques and designs, and we introduce and discuss current detection methods and their applications to multiplexed detection assays in relation to clinical diagnosis, drug analysis and screening, environmental monitoring, and food and beverage quality control. A summary with future perspectives for µPADs is also presented.

International audience; The population of patients with congenital heart disease (CHD) is continuously increasing, and a significant proportion of these patients will experience arrhythmias because of the underlying congenital heart defect itself or as a consequence of interventional or surgical treatment. Arrhythmias are a leading cause of mortality, morbidity and impaired quality of life in adults with CHD. Arrhythmias may also occur in children with or without CHD. In light of the unique issues, challenges and considerations involved in managing arrhythmias in this growing, ageing and heterogeneous patient population and in children, it appears both timely and essential to critically appraise and synthesize optimal treatment strategies. The introduction of catheter ablation techniques has greatly improved the treatment of cardiac arrhythmias. However, catheter ablation in adults or children with CHD and in children without CHD is more technically demanding, potentially causing various complications, and thus requires a high level of expertise to maximize success rates and minimize complication rates. As French recommendations regarding required technical competence and equipment are lacking in this situation, the Working Group of Pacing and Electrophysiology of the French Society of Cardiology and the Affiliate Group of Paediatric and Adult Congenital Cardiology have decided to produce a common position paper compiled from expert opinions from cardiac electrophysiology and paediatric cardiology. The paper details the features of an interventional cardiac electrophysiology centre that are required for ablation procedures in adults with CHD and in children, the importance of being able to diagnose, monitor and manage complications associated with ablations in these patients and the supplemental hospital-based resources required, such as anaesthesia, surgical back-up, intensive care, haemodynamic assistance and imaging. Lastly, the need for quality evaluations and French registries of ablations in these populations is discussed. The purpose of this consensus statement is therefore to define optimal conditions for the delivery of invasive care regarding ablation of arrhythmias in adults with CHD and in children, and to provide expert and - when possible - evidence-based recommendations on best practice for catheter-based ablation procedures in these specific populations.

More than 10,000 preterm infants have participated in randomised controlled trials on probiotics worldwide, suggesting that probiotics in general could reduce rates of necrotising enterocolitis (NEC), sepsis, and mortality. Answers to relevant clinical questions as to which strain to use, at what dosage, and how long to supplement are, however, not available. On the other hand, an increasing number of commercial products containing probiotics are available from sometimes suboptimal quality. Also, a large number of units around the world are routinely offering probiotic supplementation as the standard of care despite lacking solid evidence. Our recent network meta-analysis identified probiotic strains with greatest efficacy regarding relevant clinical outcomes for preterm neonates. Efficacy in reducing mortality and morbidity was found for only a minority of the studied strains or combinations. In the present position paper, we aim to provide advice, which specific strains might potentially be used and which strains should not be used. In addition, we aim to address safety issues of probiotic supplementation to preterm infants, who have reduced immunological capacities and occasional indwelling catheters. For example, quality reassurance of the probiotic product is essential, probiotic strains should be devoid of transferable antibiotic resistance genes, and local microbiologists should be able to routinely detect probiotic sepsis. Provided all safety issues are met, there is currently a conditional recommendation (with low certainty of evidence) to provide either Lactobacillus rhamnosus GG ATCC53103 or the combination of Bifidobacterium infantis Bb-02, Bifidobacterium lactis Bb-12, and Streptococcus thermophilus TH-4 in order to reduce NEC rates.

Background Invasive fungal disease is a life-threatening condition that can be challenging to treat due to pathogen resistance, drug toxicity, and therapeutic failure secondary to suboptimal drug concentrations. Frequent therapeutic drug monitoring (TDM) is required for some anti-fungal agents to overcome these issues. Unfortunately, TDM at the institutional level is difficult, and samples are often sent to a commercial reference laboratory for analysis. To address this gap, the first paper spray-mass spectrometry assay for the simultaneous quantitation of five triazoles was developed. Methods Calibration curves for fluconazole, posaconazole, itraconazole, hydroxyitraconazole, and voriconazole were created utilizing plasma-based calibrants and four stable isotopic internal standards. No sample preparation was needed. Plasma samples were spotted on a paper substrate in pre-manufactured plastic cartridges, and the dried plasma spots were analyzed directly utilizing paper spray-mass spectrometry (paper spray MS/MS). All experiments were performed on a Thermo Scientific TSQ Vantage triple quadrupole mass spectrometer. Results The calibration curves for the five anti-fungal agents showed good linearity (R2 = 0.98–1.00). The measured assay ranges (lower limit of quantification [LLOQ]–upper limit of quantitation [ULOQ]) for fluconazole, posaconazole, itraconazole, hydroxyitraconazole, and voriconazole were 0.5–50 μg/mL, 0.1–10 μg/mL, 0.1–10 μg/mL, 0.1–10 μg/mL, and 0.1–10 μg/mL, respectively. The inter- and intra-day accuracy and precision were less than 25% over the respective ranges. Conclusions We developed the first rapid paper spray-MS/MS assay for simultaneous quantitation of five triazole anti-fungal agents in plasma. The method may be a powerful tool for near-point-of-care TDM aimed at improving patient care by reducing the turnaround time and for use in clinical research.

Coronavirus Disease 2019 (COVID‐19) has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020. In this White Paper, we address the cardiovascular co‐morbidities of COVID‐19 infection; the diagnosis and treatment of standard cardiovascular conditions during the pandemic; and the diagnosis and treatment of the cardiovascular consequences of COVID‐19 infection. In addition, we will also address various issues related to the safety of healthcare workers and the ethical issues related to patient care in this pandemic.

A graphene and poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) modified conductive paper-based electrochemical impedance spectroscopy (EIS) aptasensor has been successfully fabricated by a simple and continuous coating process. A graphene/PEDOT:PSS modified paper electrode forms the nanocomposite providing a conductive and sensitive substrate for further aptamer functionalization of the biosensor. This low-cost paper-based aptasensor exhibits its sensitivity to carcinoembryonic antigens (CEA) in standard buffer solutions and human serum samples in a linear range of 0.77&ndash, 14 ng&middot, mL&minus, 1. The limit of detection (LOD) is found to be 0.45 ng&middot, 1 and 1.06 ng&middot, 1 for CEA in both samples, separately. This aptamer-based sensing device was also evaluated and received a good correlation with the immunoassay detection method. The proposed paper-based aptasensor has demonstrated its potential as a rapid simple point-of-care analytical platform for early cancer diagnosis in less developed areas where manufacturing facilities, analytical instruments, and trained specialists are limited.

Objectives:The purpose of this position paper is two-fold: first, to describe the state of extracorporeal membrane oxygenation education worldwide, noting current limitations and challenges; and second, to put forth an educational agenda regarding opportunities for an international collaborative approach toward standardization.Design:Relevant medical literature was reviewed through literature search, and materials from national organizations were accessed through the Internet. Taskforce members generated a consensus statement using an iterative consensus process through teleconferences and electronic communication.Setting:In 2018, the Extracorporeal Life Support Organization convened the ECMOed Taskforce at two structured, face-to-face meetings of 40 healthcare practitioners and educators with expertise in caring for the extracorporeal membrane oxygenation patient and in extracorporeal membrane oxygenation education.Patients:None.Interventions:None.Measurements and Main Results:The ECMOed Taskforce identified seven educational domains that would benefit from international collaborative efforts. Of primary importance, the Taskforce outlined actionable items regarding 1) the creation of a standardized extracorporeal membrane oxygenation curriculum; 2) defining criteria for an extracorporeal membrane oxygenation course as a vehicle for delivering the curriculum; 3) outlining a mechanism for evaluating the quality of educational offerings; 4) utilizing validated assessment tools in the development of extracorporeal membrane oxygenation practitioner certification; and 5) promoting high-quality educational research to guide ongoing educational and competency assessment development.Conclusions:Significant variability and limitations in global extracorporeal membrane oxygenation education exist. In this position paper, we outline a road map for standardizing international extracorporeal membrane oxygenation education and practitioner certification. Ongoing high-quality educational research is needed to evaluate the impact of these initiatives.

We propose a flexible, binder-free and free-standing carbonaceous paper fabricated via electrostatic spray deposition using reduced graphene oxide/carbon nanotube (rGO/CNT) as a promising electrode material for flexible sodium-ion batteries (NIBs). The as-prepared rGO/CNT paper exhibits a three-dimensional (3D) layered structure by employing rGO as conductive frameworks to provide sodium-storage active sites and CNT as spacer to increase rGO interlayer distance and benefit the diffusion kinetics of sodium ions. Consequently, the rGO/CNT paper delivers an enhanced sodium ion storage capacity of 166.8 mAh g&minus, 1 at 50 mA g-1, retaining an average capacity of 101.4 mAh g&minus, 1 when current density sets back 100 mA g&minus, 1 after cycling at various current rates. An average capacity of 50 mAh g&minus, 1 at 200 mA g&minus, 1 was stabilized when cycling up to 300 cycles. The well-maintained electrochemical performance of free-standing rGO/CNT paper is due to the well-established hybrid 3D nanostructures, which demonstrates our carbon based material fabricated by a facile approach can be applied as one of the high-performance and low-cost electrode materials for applications in flexible energy storage devices.

© 2020 John Wiley & Sons, Ltd. Drug misuse in prisons contributes to increased disruption and violence and negatively impacts prisoner safety, rehabilitation, and recovery. Synthetic cannabinoid receptor agonists (SCRAs), colloquially known as “spice”, are infused into papers and are of particular concern in a prison setting where they are commonly vaped. Methods for the qualitative and quantitative analysis of SCRA infused papers, including impurity profiling, were developed using gas chromatography–mass spectrometry (GC–MS) with qualitative confirmation by ultra high pressure liquid chromatography with photodiode array and quadrupole time of flight mass spectrometry detection (UPLC-PDA-QToF-MS) and applied to 354 individual seized paper samples originating from 168 seizures from three Scottish prisons. Of these samples, 41% (146 samples from 101 seizures) contained at least one SCRA and multiple SCRAs were detected on 23% of these papers. Concentrations ranged from < 0.05–1.17 mg/cm2 paper, representing the first reported quantitative data for SCRA infused papers. An evolution in the SCRAs detected was demonstrated; 5F-MDMB-PINACA (5F-ADB) predominated until late 2018, after which time 5F-MDMB-PICA and 4F-MDMB-BINACA became increasingly more prevalent, followed by the arrival of MDMB-4en-PINACA in June 2019. Concentration mapping data from two seized paper samples demonstrated that SCRA concentrations across larger papers were highly variable (0.47–2.38 mg/cm2 paper) making consistent dosing by users, and representative sampling by laboratory analysts, difficult. Near real-time qualitative and quantitative information on SCRAs circulating in prisons acts as an early warning system for SCRAs emerging on the wider illicit market, inform the methods used to detect them and limit supply, and provide information to support harm reduction measures.

The traditional view on the cerebellum is that it controls motor behavior. Although recent work has revealed that the cerebellum supports also nonmotor functions such as cognition and affect, only during the last 5 years it has become evident that the cerebellum also plays an important social role. This role is evident in social cognition based on interpreting goal-directed actions through the movements of individuals (social "mirroring") which is very close to its original role in motor learning, as well as in social understanding of other individuals' mental state, such as their intentions, beliefs, past behaviors, future aspirations, and personality traits (social "mentalizing"). Most of this mentalizing role is supported by the posterior cerebellum (e.g., Crus I and II). The most dominant hypothesis is that the cerebellum assists in learning and understanding social action sequences, and so facilitates social cognition by supporting optimal predictions about imminent or future social interaction and cooperation. This consensus paper brings together experts from different fields to discuss recent efforts in understanding the role of the cerebellum in social cognition, and the understanding of social behaviors and mental states by others, its effect on clinical impairments such as cerebellar ataxia and autism spectrum disorder, and how the cerebellum can become a potential target for noninvasive brain stimulation as a therapeutic intervention. We report on the most recent empirical findings and techniques for understanding and manipulating cerebellar circuits in humans. Cerebellar circuitry appears now as a key structure to elucidate social interactions. Frank Van Overwalle, Elien Heleven, Qianying Ma, and Min Pu were supported by an SRP57 grant from the Vrije Universiteit Brussel, and Elien Heleven was additionally supported by an FWO G002319N/AL907 grant from the Flemish government. Zaira Cattaneo was supported by a Bando Ricerca Finalizzata (GR2016-02363640) by the Italian Ministry of Health. Marco Michelutti and Arseny A. Sokolov were supported by aMille E Una Lode fellowship from the University of Padua to MM, and fellowships from the Leenaards Foundation and the Swiss National Science Foundation, and a grant from the Helmut Horten Foundation to AAS. Catherine Stoodley and Laura C. Rice were supported by an NIH R15MH106957 grant. Van Overwalle, F (corresponding author), Vrije Univ Brussel, Dept Psychol, Pl Laan 2, B-1050 Brussels, Belgium; Vrije Univ Brussel, Ctr Neurosci, Pl Laan 2, B-1050 Brussels, Belgium. Frank.VanOverwalle@vub.ac.be; mmanto@ulb.ac.be; zaira.cattaneo@unimib.it; silvia.clausi@uniroma1.it; chiara.ferrari@unipv.it; gabrieli@mit.edu; xguellparadis@mgh.harvard.edu; Elien.Heleven@vub.be; m.lupo@hsantalucia.it; Qianying.Ma@vub.be; michelutti.marco.m@gmail.com; g.olivito@hsantalucia.it; Min.Pu@vub.be; laura.blevins@student.american.edu; jschmahmann@mgh.harvard.edu; libera.siciliano@uniroma1.it; Arseny.Sokolov@chuv.ch; stoodley@american.edu; kim.vandun@uhasselt.be; LVandervert@aol.com; maria.leggio@uniroma1.it

Renal denervation is a device-based procedure for hypertension for which safety and efficacy has been demonstrated. At present, its clinical use is still matter of debate, despite the most recent clinical trials have shown promising results with new-generation devices in various hypertensive populations. This position paper was deemed necessary by the Italian Society of Arterial Hypertension, in order to provide indications about the applications of renal denervation in the clinical setting. A state-of-the art review of the literature, focusing on safety and efficacy data, is provided. Furthermore, based on current evidence and expert consensus, clinical profiles of possible candidates for renal denervation are proposed. The selection process should take into account not only blood pressure values, global cardiovascular risk profile, but also drug adherence and tolerability and patient preferences. This position paper also defines minimum requirements for renal denervation selection centers and a flowchart for the difficult-to-treat hypertensive patient. Further studies are needed to support these preliminary indications, which are based on expert-consensus only.

Acute and chronic physical exercises may enhance the development of statin-related myopathy. In this context, the recent (2019) guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) for the management of dyslipidemias recommend that, although individuals with dyslipidemia should be advised to engage in regular moderate physical exercise (for at least 30 min daily), physicians should be alerted with regard to myopathy and creatine kinase (CK) elevation in statin-treated sport athletes. However it is worth emphasizing that abovementioned guidelines, previous and recent ESC/EAS consensus papers on adverse effects of statin therapy as well as other previous attempts on this issue, including the ones from the International Lipid Expert Panel (ILEP), give only general recommendations on how to manage patients requiring statin therapy on regular exercises. Therefore, these guidelines in the form of the Position Paper are the first such an attempt to summary existing, often scarce knowledge, and to present this important issue in the form of step-by-step practical recommendations. It is critically important as we might observe more and more individuals on regular exercises/athletes requiring statin therapy due to their cardiovascular risk.

Bonertz, Andreas/0000-0002-6846-9265; Brough, Helen/0000-0001-7203-0813; Hoffmann, Hans Jurgen/0000-0002-6743-7931; Hoffmann-Sommergruber, Karin/0000-0002-8830-058X; Schmid-Grendelmeier, Peter/0000-0003-3215-3370 WOS:000569864500002 PubMed: 32306414 Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high-quality diagnostic allergens for in vivo diagnosis of IgE-mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies. With the need to ensure the availability of high-quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens. Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.

Aim. To evaluate in vitro the antibacterial effect of a paper made of silver phosphate cellulose fibers (SPCF) on Staphylococcus aureus, the most common diabetic foot ulceration (DFU) pathogen when compared with other common commercial products. Methods. The antibacterial activity of SPCF samples was evaluated through time with cell counting on agar plates. SPCF samples were then compared with commercial wound care products currently in use in DFU treatments (Silvercel™, Acticoat 7, and Aquacel Ag ExtraTM) through time on agar plates (growth inhibition zones). Results. After 6 hours, there was no viable bacterial cell detected on either plate (p<0.05). There was a net growth inhibition zone for SPCF samples but no significant difference between the two silver concentrations. Compared with common commercial products, SPCF paper provides results equal to Acticoat 7 (p<0.05) and superior to Aquacel AG ExtraTM and Silvercel™ at lower silver concentrations (p<0.001). Conclusions. These results have shown the efficiency of SPCF paper to eliminate Staphylococcus aureus in these conditions. SPCF papers are effective when compared with other common commercial products and could have an industrial potential in wound care. Infected DFU could benefit from the antibacterial effectiveness of SPCF, but more relevant experimentations related to foot ulcers are needed.

Assessment of vitamin and trace element status (VTE) is important in the clinical management of the sick child. In this position paper, we present the various assessment methods available to the clinical practitioner, and critically discuss pitfalls with interpretation of their results. There are 4 main approaches to assess the VTE body status of an individual patient including clinical examination, dietary assessment, and measurement of direct and indirect biomarkers of VTE in biological samples. Clinical signs of VTE deficiencies usually present only when body stores are substantially depleted and are often difficult to detect or differentiate from other nonnutrient-related causes. In isolation, dietary assessment of micronutrients can be inaccurate and imprecise, in disease and in individual patient assessment but may be useful to complement findings from other VTE assessment methods. Use of biomarkers is the most common approach to assess VTE status in routine practice but in the presence of systemic inflammatory response and in the absence of appropriate paediatric reference intervals, interpretation of biomarker results might be challenging and potentially mislead clinical practice. The use of a multimodal approach, including clinical examination, dietary assessment, and laboratory biomarkers is proposed as the optimal way to ascertain the VTE status of individual patients. In the presence of acute inflammatory conditions, VTE measurements in plasma should be replaced by biomarkers not affected by systemic inflammatory response or delayed until inflammatory state is resolved.

The separation of plasma from whole blood is the first step in many diagnostic tests. Point-of-care tests often rely on integrated plasma filters, but protein retention in such filters limits their performance. Here, we investigate plasma separation on interlocked micropillar scaffolds ("synthetic paper") by the local agglutination of blood cells coupled with the capillary separation of the plasma. We separated clinically relevant volumes of plasma with high efficiency in a separation time on par with that of state of the art techniques. We investigated different covalent and non-covalent surface treatments (PEGMA, HEMA, BSA, O2 plasma) on our blood filter and their effect on protein recovery, and identified O2 plasma treatment and 7.9 μg/cm2 agglutination antibody as most suitable treatments. Using these treatments, we recovered at least 82% of the blood plasma proteins, more than with state-of-the-art filters. The simplicity of our device and the performance of our approach could enable better point-of-care tests. QC 20200427 EU Project ND4ID

As the treatment landscape continues to evolve towards the application of precision medicine in multiple myeloma (MM), there is a clear need to identify those patients who are at risk of not achieving the maximum benefit whilst exposed to the highest level of toxicity. This group of patients, defined as frail, is an unmet clinical need. However, how we define such a vulnerable group of patients with MM remains to be clarified. An integral aspect of this is to define the physiological age and capacity of patients with MM to deal with the burden of their disease and it’s treatment. Such assessments may include not only functional and clinical assessments but also laboratory-based biomarkers of frailty, aging and senescent cellular burden. A need to develop, test and validate clinical screening scores before their adoption into clinical practice is mandated. This position paper from the European Myeloma Network aims to review what is known about defining frailty in MM, and how we can advance this knowledge for the design of clinical trials and ultimately how we deliver treatment in the clinic.

In this work, we have developed a paper-based microfluidic device capable of remote biofluid collection followed by an analysis of the dried clinical samples using a miniature mass spectrometer. We have evaluated a portable mass spectrometer as a possible surveillance platform by analyzing the clinical malaria samples (whole blood) collected from Ghana. We synthesized pH-sensitive ionic probes and coupled them with monoclonal antibodies specific to theiPlasmodium falciparum/ihistidine-rich protein 2 (iPf/iHRP2) malaria antigen. We then used the antibody-ionic probe conjugates in a paper-based immunoassay to captureiPf/iHRP2 antigen from untreated whole blood. After the immunoassay, the bound ionic probes were cleaved, and the released mass tags were analyzed through an on-chip paper spray mass spectrometry strategy. During process optimization, we determined the detection limit foriPf/iHRP2 in untreated human serum to be 0.216 nmol/L when using the miniature mass spectrometer. This sensitivity is comparable to the World Health Organization's suggested threshold of 0.227 nmol/L foriPf/iHRP2, proving that our method will be applicable to diagnose symptomatic malaria infection (≥200 parasites per μL blood). The paper device can be stored at room temperature for at least 25 days without affecting the clinical outcome, with each stored paper chip offering good repeatability and reproducibility (RSD = 4-12%). The stability and sensitivity of the developed paper-based immunoassay platform will allow miniature mass spectrometers to be used for point-of-care malaria detection as well as in large-scale surveillance screening to aid eradication programs.

While there is a clear clinical benefit of oral anticoagulation in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision for initiating and continuing anticoagulation is often based on a careful assessment of both thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug–drug and food–drug interactions. Bleeding risk is also not a static “one-off” assessment based on baseline factors but is dynamic, being influenced by aging, incident comorbidities, and drug therapies. In this executive summary of a European and Asia-Pacific Expert Consensus Paper, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with a view to summarizing “best practice” when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, and review established bleeding risk factors and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism, are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.

The British Society for Haematology (BSH) produces Good Practice Papers to recommend good practice in areas where there is a limited evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org. This Good Practice Paper was produced as a collaboration with the European Hematology Association (EHA) compiled according to the (BSH) process at http://scanmail.trustwave.com/?c=8248&d=68DV3b1jbPPsVn-8nm3kGS2D_-Hms9YWMWrrk5K8Eg&u=http%3a%2f%2fb-s-h%2eorg.uk. This guideline group included UK-based medical experts representing the BSH and members of the Red Cell and Iron Scientific Working Group (SWG) of EHA. Literature review details: MEDLINE, EMBASE and PubMED were searched systematically for publications in English from 2000 to 2019 using the following key words. ‘NGS’ and ‘next-generation sequencing’ or ‘high throughput sequencing’ AND ‘haemolytic anaemia’ or ‘DBA or ‘Diamond Blackfan anaemia’ or ‘CDA’ or ‘congenital dyserythropoietic anaemia’ or ‘sideroblastic anaemia’ or ‘HS' or ‘hereditary spherocytosis’ or ‘red cell membrane disorders’ or ‘red cell enzyme disorders’ or ‘PK deficiency’ or ‘PKD’. References from relevant publications were also searched. Conference abstracts were included if deemed to be of particular relevance. Review of the manuscript: Review of the manuscript was performed by the BSH Guidelines Committee General Haematology Task Force, the BSH Guidelines Committee and the General Haematology sounding board of the BSH. It was also on the members section of the BSH website for comment. It has also been reviewed by members of the EHA Red Cell and Iron SWG and the EHA Guidelines Executive Committee. info:eu-repo/semantics/publishedVersion

Objective To determine whether or not displaying the cost of tests can help reduce charges on test ordering in Japan. Methods This study was conducted under the setting of a simulated first visit of an outpatient for general internal medicine in a secondary medical institution in Japan. We randomly assigned 27 residents and clinical fellows to Team A or B. The first half, without charges displayed on the ordering system, was designated the "non-display group," and the participants of Team A selected tests for each paper-based simulated case (Q1-Q14), while the participants of Team B selected tests for Q15-Q28. The second half, which had charges displayed, was designated the "display group," and the participants of Team A selected tests for Q15-Q28, while the participants of Team B selected tests for Q1-Q14. The main outcome measure was the difference in the cost of tests per paper-based simulated case between the non-display and display groups. Results The median (interquartile range) cost of tests per paper-based simulated case was 12,255 yen (5,040-23,695 yen) in the non-display group versus 9,425 yen (2,320-21,700 yen) in the display group, showing a decrease of 2,830 yen with charges being displayed (p=0.002). Conclusion Displaying the charges when ordering tests in paper-based simulated cases resulted in cost reduction. The adoption of this intervention may reduce health insurance costs under the health insurance system in Japan, which has features such as universal health coverage and universal access to care.

In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting (‘Microbial Based Cancer Therapy’) at the US National Cancer Institute in the summer of 2017. Here, we define ‘Microbial Therapy’ to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields. The authors of this paper include many primary researchers in this field. In this paper, we discuss the potential, status and opportunities for microbial therapy as well as strategies attempted to date and important questions that need to be addressed. The main areas that we think will have the greatest impact are immune stimulation, control of efficacy, control of delivery, and safety. There is much excitement about the potential of this field to treat currently intractable cancer. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other biological or small molecule drugs. By better understanding and controlling these mechanisms, we will create new therapies that will become integral components of cancer care.

Purpose Patient-reported outcome (PRO) measures originally developed for paper administration are increasingly being administered electronically in clinical trials and other health research studies. Three published meta-analyses of measurement equivalence among paper and electronic modes aggregated findings across hundreds of PROs, but there has not been a similar meta-analysis that addresses a single PRO, partly because there are not enough published measurement equivalence studies using the same PRO. Because the SF-36(R) Health Survey (SF-36) is a widely used PRO, the aim of this study was to conduct a meta-analysis of measurement equivalence studies of this survey. Methods A literature search of several medical databases used search terms for variations of “SF-36” or “SF-12” and “equivalence” in the title or abstract of English language publications. The eight scale scores and two summary measures of the SF-36 and SF-12 were transformed to norm-based scores (NBS) using developer guidelines. A threshold of within ± 2 NBS points was set as the margin of equivalence. Comprehensive meta-analysis software was used. Results Twenty-five studies were included in the meta-analysis. Results indicated that mean differences across domains and summary scores ranged from 0.01 to 0.39 while estimates of agreement ranged from 0.76 to 0.91, all well within the equivalence threshold. Moderator analyses showed that time between administration, survey language, and type of electronic device did not influence equivalence. Conclusions The results of the meta-analysis support equivalence of paper-based and electronic versions of the SF-36 and SF-12 across a variety of disease populations, countries, and electronic modes.

Purpose: Dried blood spot (DBS) specimen simplifies blood collection, processing, storage and shipment and may reduce the cost of testing for hepatitis C virus (HCV) infection. We wanted to see if DBS using a cheap filter paper is reliable alternative to serum for detection of anti-HCV and HCV RNA. Materials and Methods: At a tertiary care hospital in Northeast India, we collected 91 paired DBS and serum specimens from patients at risk of HCV infection from July 2014 to June 2015. DBS was collected on Whatman No. 1 filter paper. After processing, the specimens were subjected to anti-HCV detection by a third-generation Enzyme-Linked Immunosorbent Assay (ELISA). The reactive DBS and serum specimens were further subjected to HCV RNA detection by polymerase chain reaction. The results were analysed in paired screen-positive study design. Results: Anti-HCV was detected in 9 (9.9%) DBS specimens and 10 (10.9%) serum specimens. There was statistically significant (P < 0.0001) correlation between the optical density values of DBS and serum specimens (Pearson r = 0.9181, 95% confidence interval: 0.8781–0.9453). HCV RNA was detected in 5/9 (55.6%) reactive DBS and 9/10 (90.0%) reactive serum specimens. There was no correlation between HCV RNA levels in the DBS and the serum specimens. The relative sensitivity rate and the relative false-positive rate of DBS anti-HCV ELISA were 0.89 and 1.00, respectively. Conclusions: DBS using Whatman No. 1 filter paper is quite reliable as serum for detection of anti-HCV. It can be useful in effective surveillance. However, it is not suitable for confirmation of chronic HCV infection.