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Objective The purpose of this study was to develop a natural language processing (NLP) pipeline to identify incidental thyroid nodules (ITNs) meeting criteria for sonographic follow-up and to assess both adherence rates to white paper recommendations and downstream outcomes related to these incidental findings. Methods 21583 non-contrast chest CT reports from 2017 and 2018 were retrospectively evaluated to identify reports which included either an explicit recommendation for thyroid ultrasound, a description of a nodule ≥ 1.5 cm, or description of a nodule with suspicious features. Reports from 2018 were used to train an NLP algorithm called fastText for automated identification of such reports. Algorithm performance was then evaluated on the 2017 reports. Next, any patient from 2017 with a report meeting criteria for ultrasound follow-up was further evaluated with manual chart review to determine follow-up adherence rates and nodule-related outcomes. Results NLP identified reports with ITNs meeting criteria for sonographic follow-up with an accuracy of 96.5% (95% CI 96.2-96.7) and sensitivity of 92.1% (95% CI 89.8-94.3). In 10006 chest CTs from 2017, ITN follow-up ultrasound was indicated according to white paper criteria in 81 patients (0.8%), explicitly recommended in 46.9% (38/81) of patients, and obtained in less than half of patients in which it was appropriately recommended (17/35, 48.6%). Discussion NLP accurately identified chest CT reports meeting criteria for ITN ultrasound follow-up. Radiologist adherence to white paper guidelines and subsequent referrer adherence to radiologist recommendations showed room for improvement.

Purpose This study aimed to determine whether continual electronic patient-reported outcome (ePRO) measurements at home can capture the fluctuations in health-related quality of life (HRQOL) scores between visits. Methods We performed a randomized controlled trial to compare the scores obtained by standard practice (paper-based measurements in the hospital) to scores by continuous measurement of ePRO at home. Metastatic cancer patients were randomly assigned to either the paper-based ( n = 50) or the ePRO group ( n = 52). EQ-5D-5L and EORTC QLQ C-30 scores were obtained on 3 different chemotherapy days in the paper-based group. Meanwhile, scores were obtained on the chemotherapy day and on days 3, 7, 10, and 14 in the ePRO group during 2 cycles. The first hypothesis of our study was that both scores at the same time points would be equivalent despite different measurement frequency, place, or mode of measurement. The second hypothesis was that PRO score–adjusted time would be different between the groups. For equivalence, the endpoint was the mean EQ-5D-5L index value on the chemotherapy day before the outpatient treatment. Only if equivalence was shown, quality-adjusted life-days (QALDs) were considered using all the data. Results The adjusted mean difference in the EQ-5D-5L index was determined to be −0.013 (95% confidence interval [CI]: −0.049 to 0.022); the 95% CI did not exceed the equivalence margin. Similarly, the mean difference in global health status (2.28 [95% CI: −2.55 to 7.11]) also showed equivalence. However, the QALD by EQ-5D-5L was significantly lower in the ePRO group by 1.36 per 30 d (95% CI: −2.22 to −0.51; P = 0.0021). Conclusions Continual measurements of the HRQOL at home by ePRO may yield more detailed profiles of the HRQOL.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

Aβ42 is one of the most extensively studied blood and Cerebrospinal fluid (CSF) biomarkers for the diagnosis of symptomatic and prodromal Alzheimer’s disease (AD). Because of the heterogeneity and transient nature of Aβ42 oligomers (Aβ42Os), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aβ42 monomers (Aβ42Ms) and Aβ42Os is essential for the accurate diagnosis of AD. The currently commonly used Aβ42 ELISA test kits usually mis-detected the elevated Aβ42Os, leading to incomplete analysis and underestimation of soluble Aβ42, resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aβ42 monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of Aβ42Ms and Aβ42Os in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of Aβ42Ms or/and Aβ42Os in dLFI was 154 pg/mL. The test results for dLFI were similar to those observed in the enzyme-linked immunosorbent assay (ELISA). Therefore, this paper-based dLFI provides a practical and rapid method for the on-site detection of two biomarkers in blood or CSF samples without the need for additional expertise or equipment. Graphical Abstract

Although crucial in improving health outcomes in the preterm infants, parenteral nutrition (PN) is not without risk, especially if handled improperly. A growing body of evidence suggests that components of PN admixtures, including lipid injectable emulsions (ILEs), are susceptible to degradation, including oxidation when exposed to light (ie, photo-oxidation), resulting in the production of reactive oxygen species. Infants, especially those born preterm, are considered more susceptible to consequences of oxidative stress than children and adults. Oxidative stress is associated with bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intestinal failure-associated liver disease. The American Society for Parenteral and Enteral Nutrition (ASPEN) assembled a working group to provide recommendations on clinical practice surrounding photoprotection of PN.This Position Paper reviews the scientific literature on the formation of quantifiable peroxides and other degradation products when PN admixtures and ILEs are exposed to light and reports adverse clinical outcomes in premature infants exposed to PN. Recommendations for photoprotection of PN admixtures and ILEs are provided, as well as the challenges in achieving complete photoprotection with the equipment, supplies, and materials currently available in the US. ASPEN and the authors understand that the full implementation of complete photoprotection may not currently be feasible given current product availability; recommendations provided in this paper serve to represent the goal to which to strive as well as to highlight the importance of product availability to achieve these practices. This paper has been approved by the ASPEN Board of Directors.

The spread of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), resulting in a global pandemic with around four million deaths. Although there are a variety of nucleic acid-based tests for detecting SARS-CoV-2, these methods have a relatively high cost and require expensive supporting equipment. To overcome these limitations and improve the efficiency of SARS-CoV-2 diagnosis, we developed a microfluidic platform that collected serum by a pulling-force spinning top and paper-based microfluidic enzyme-linked immunosorbent assay (ELISA) for quantitative IgA/IgM/IgG measurements in an instrument-free way. We further validated the paper-based microfluidic ELISA analysis of SARS-CoV-2 receptor-binding domain (RBD)-specific IgA/IgM/IgG antibodies from human blood samples as a good measurement with higher sensitivity compared with traditional IgM/IgG detection (99.7% vs 95.6%) for early illness onset patients. In conclusion, we provide an alternative solution for the diagnosis of SARS-CoV-2 in a portable manner by this smart integration of pulling-force spinning top and paper-based microfluidic immunoassay.

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.

Urinary tract infections (UTIs) make up a significant proportion of the global burden of disease in vulnerable groups and tend to substantially impair the quality of life of those affected, making timely detection of UTIs a priority for public health. However, economic and societal barriers drastically reduce accessibility of traditional lab-based testing methods for critical patient groups in low-resource areas, negatively affecting their overall healthcare outcomes. As a result, cellulose-based materials such as paper and thread have garnered significant interest among researchers as substrates for so-called frugal analytical devices which leverage the material’s portability and adaptability for facile and reproducible diagnoses of UTIs. Although the field may be only in its infancy, strategies aimed at commercial penetration can appreciably increase access to more healthcare options for at-risk people. In this review, we catalogue recent advances in devices that use cellulose-based materials as the primary housing or medium for UTI detection and chart out trends in the field. We also explore different modalities employed for detection, with particular emphasis on their ability to be ported onto discreet casings such as sanitary products. Graphical abstract

Oral corticosteroids (OCS) are frequently used for asthma treatment. This medication is highly effective for both acute and chronic diseases, but evidence indicates that indiscriminate OCS use is common, posing a risk of serious side effects and irreversible harm. There is now an urgent need to introduce OCS stewardship approaches, akin to successful initiatives that optimized appropriate antibiotic usage. The aim of this TSANZ (Thoracic Society of Australia and New Zealand) position paper is to review current knowledge pertaining to OCS use in asthma and then delineate principles of OCS stewardship. Recent evidence indicates overuse and over-reliance on OCS for asthma and that doses >1000 mg prednisolone-equivalent cumulatively are likely to have serious side effects and adverse outcomes. Patient perspectives emphasize the detrimental impacts of OCS-related side effects such as weight gain, insomnia, mood disturbances and skin changes. Improvements in asthma control and prevention of exacerbations can be achieved by improved inhaler technique, adherence to therapy, asthma education, smoking cessation, multidisciplinary review, optimized medications and other strategies. Recently, add-on therapies including novel biological agents and macrolide antibiotics have demonstrated reductions in OCS requirements. Harm reduction may also be achieved through identification and mitigation of predictable adverse effects. OCS stewardship should entail greater awareness of appropriate indications for OCS prescription, risk–benefits of OCS medications, side effects, effective add-on therapies and multidisciplinary review. If implemented, OCS stewardship can ensure that clinicians and patients with asthma are aware that OCS should not be used lightly, while providing reassurance that asthma can be controlled in most people without frequent use of OCS.

Urinary incontinence is a common problem among older adults that is often complicated by many nuanced ethical considerations. Unfortunately, there is a lack of guidance for healthcare professionals on how to navigate such concerns. This International Continence Society white paper aims to provide healthcare professionals with an ethical framework to promote best care practices in the care of older adults with urinary incontinence.

Cardiac arrhythmias are a major cause of death and disability. A large number of experimental cell and animal models have been developed to study arrhythmogenic diseases. These models have provided important insights into the underlying arrhythmia mechanisms and translational options for their therapeutic management. This position paper from the ESC Working Group on Cardiac Cellular Electrophysiology provides an overview of (i) currently available in vitro, ex vivo, and in vivo electrophysiological research methodologies, (ii) the most commonly used experimental (cellular and animal) models for cardiac arrhythmias including relevant species differences, (iii) the use of human cardiac tissue, induced pluripotent stem cell (hiPSC)-derived and in silico models to study cardiac arrhythmias, and (iv) the availability, relevance, limitations, and opportunities of these cellular and animal models to recapitulate specific acquired and inherited arrhythmogenic diseases, including atrial fibrillation, heart failure, cardiomyopathy, myocarditis, sinus node, and conduction disorders and channelopathies. By promoting a better understanding of these models and their limitations, this position paper aims to improve the quality of basic research in cardiac electrophysiology, with the ultimate goal to facilitate the clinical translation and application of basic electrophysiological research findings on arrhythmia mechanisms and therapies.

Patients with the dual burden of chronic kidney disease (CKD) and cardiovascular disease (CVD) experience unacceptably high rates of morbidity and mortality, which also entail unfavorable effects on healthcare systems. Currently, concerted efforts to identify, prevent and treat CVD in CKD patients are lacking at the institutional level, with emphasis still being placed on individual specialty views on this topic. The authors of this position paper endorse the need for a dedicated interdisciplinary team of subspecialists in cardio-nephrology that manages appropriate clinical interventions across the inpatient and outpatient settings. There is a critical need for training programs, guidelines and best clinical practice models, and research funding from nephrology, cardiology and other professional societies, to support the development of the subspecialty of cardio-nephrology. This position paper from the coordinating committee from the Working Group for Cardiorenal Medicine of the Spanish Society of Nephrology (S.E.N.) is intended to be the starting point to develop the subspecialty of cardio-nephrology within the S.E.N.. The implementation of the subspecialty in day-to-day nephrological practice will help to diagnose, treat, and prevent CVD in CKD patients in a precise, clinically effective, and health cost-favorable manner. Resumen: Los pacientes con enfermedad renal crónica (ERC) que presentan enfermedad cardiovascular (ECV) tienen índices de morbilidad y mortalidad inaceptablemente elevados, que impactan desfavorablemente sobre los sistemas de salud. En la actualidad, se requieren actuaciones multidisciplinares para identificar, prevenir y tratar la ECV en los pacientes con ERC, debiendo pues superarse la época de las actuaciones de las especialidades individuales. Los autores de este artículo respaldan la necesidad de un equipo interdisciplinar de subespecialistas en cardionefrología que gestione las intervenciones clínicas adecuadas en el entorno hospitalario y en el ambulatorio. Existe una gran necesidad de programas de formación, de guías y modelos de práctica clínica, y de fondos para la investigación en las sociedades de nefrología, cardiología y otras, para apoyar el desarrollo de la subespecialidad de cardio-nefrología. Este documento de opinión del comité coordinador del Grupo de Trabajo de Medicina Cardiorenal de la Sociedad Española de Nefrología (S.E.N.) pretende ser el inicio del desarrollo de la subespecialidad de Cardionefrología en el marco de la S.E.N. La implementación de la subespecialidad en la práctica nefrológica diaria contribuirá a diagnosticar, tratar y prevenir la ECV en los pacientes con ERC de una manera precisa, clínicamente efectiva y sanitariamente rentable.

Objective The objective of this study was to develop the first edition of a Chinese evidence-based position paper on the management of oral leukoplakia (OLK). Study Design The consultant group for drafting the position paper consisted of 31 oral medicine specialists and 2 evidence-based medicine specialists. English studies (searched in PubMed, EMBASE, and the Cochrane Library) and Chinese studies (searched in China National Knowledge Infrastructure and WanFang) published before January 2018 were used. The quality of the study was assessed using the Grading of Recommendations Assessment, Development, and Evaluation grid, and the strength of the recommendations was determined based on the results of 3 rounds of voting among the consultant group members using the Delphi method. Results Twenty-two evidence-based guidelines for clinical management and monitoring of OLK were established in this position paper. A clinical path diagram for oral health practitioners was constructed based on the recommendations. Conclusion Current evidence suggests that management and monitoring of patients with OLK should be performed by experienced clinicians to control the lesion and for early detection of malignant transformation. However, all recommendations are based on evidence of low or extremely low quality and may require further modification as new evidence is produced.

Two novel methods of measuring the dimensions of oral lesions are described, which would be of help in deciding relative efficacies of different therapeutic agents when used in clinical trials after larger studies quantitatively assessed for inter/intraobserver variability.

Osteoporosis and associated fractures present a major challenge in improving global health outcomes. Key clinical aspects are the definition of osteoporosis and associated fractures, fracture risk prediction, stratification of risk of fracture, intervention thresholds and the most appropriate intervention based on integration of aforementioned. Correct understanding and application of these concepts are essential to stem the increasing tide of fragility fractures associated with an aging population. The role of muscle strength and function, sarcopenia, and the newly emerging concept of osteosarcopenia in maintaining bone health are discussed in detail.

The goal of this position paper on ventilatory support at home for children is to provide expert consensus from Australia and New Zealand on optimal care for children requiring ventilatory support at home, both non-invasive and invasive. It was compiled by members of the Thoracic Society of Australia and New Zealand (TSANZ) and the Australasian Sleep Association (ASA). This document provides recommendations to support the development of improved services for Australian and New Zealand children who require long-term ventilatory support. Issues relevant to providers of equipment and areas of research need are highlighted.

Highlights • Standard procedures and appropriate assessment of exercise are proposed for the commonly used animal models related to chronic exercise (e.g., treadmill running, voluntary wheel running, swimming exercise, and resistance exercise) in cardiovascular research. • Optimal design of animal exercise studies in cardiovascular research should consider the choice of exercise models, control of exercise protocols, exercise at different stages of disease, and other factors, such as age, sex, and genetic background. • An optimal design for studying exercise-induced physiological cardiac growth and its related beneficial effects against cardiovascular diseases is presented., Growing evidence has demonstrated exercise as an effective way to promote cardiovascular health and protect against cardiovascular diseases However, the underlying mechanisms of the beneficial effects of exercise have yet to be elucidated. Animal exercise studies are widely used to investigate the key mechanisms of exercise-induced cardiovascular protection. However, standardized procedures and well-established evaluation indicators for animal exercise models are needed to guide researchers in carrying out effective, high-quality animal studies using exercise to prevent and treat cardiovascular diseases. In our review, we present the commonly used animal exercise models in cardiovascular research and propose a set of standard procedures for exercise training, emphasizing the appropriate measurements and analysis in these chronic exercise models. We also provide recommendations for optimal design of animal exercise studies in cardiovascular research, including the choice of exercise models, control of exercise protocols, exercise at different stages of disease, and other considerations, such as age, sex, and genetic background. We hope that this position paper will promote basic research on exercise-induced cardiovascular protection and pave the way for successful translation of exercise studies from bench to bedside in the prevention and treatment of cardiovascular diseases., Graphical abstract Image, graphical abstract

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH. ispartof: JOURNAL OF HYPERTENSION vol:39 issue:9 pages:1742-1767 ispartof: location:Netherlands status: published

Technologic advancements and the evolving digital health landscape have offered innovative solutions to several of our health care system's issues as well as increased the number of digital interactions and type of personal health information that is generated and collected, both within and outside of traditional health care. This American College of Physicians' position paper discusses the state of privacy legislation and regulations, highlights existing gaps in health information privacy protections, and outlines policy principles and recommendations for the development of health information privacy and security protections that are comprehensive, transparent, understandable, adaptable, and enforceable. The principles and recommendations aim to improve on the privacy framework in which physicians have practiced for decades and expand similar privacy guardrails to entities not currently governed by privacy laws and regulations. The expanded privacy framework should protect personal health information from unauthorized, discriminatory, deceptive, or harmful uses and align with the principles of medical ethics, respect individual rights, and support the culture of trust necessary to maintain and improve care delivery.

Background Coronavirus Disease 2019 (COVID-19), firstly reported in China last November 2019, became a global pandemic. It has been shown that periods of isolation may induce a spike in alcohol use disorder (AUD). In addition, alcohol-related liver disease (ALD) is the most common consequence of excessive alcohol consumption worldwide. Moreover, liver impairment has also been reported as a common manifestation of COVID-19. Aims The aim of our position paper was to consider some critical issues regarding the management of ALD in patients with AUD in the era of COVID-19. Methods A panel of experts of the Italian Society of Alcohology (SIA) met via “conference calls” during the lockdown period to draft the SIA’s criteria for the management of ALD in patients with COVID-19 as follows: (a) liver injury in patients with ALD and COVID-19 infection; (b) toxicity to the liver of the drugs currently tested to treat COVID-19 and the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) reorganization of the management of compensated and decompensated ALD and liver transplantation in the COVID-19 era. Results and Conclusions The COVID-19 pandemic has rapidly carried us toward a new governance scenario of AUD and ALD which necessarily requires an in-depth review of the management of these diseases with a new safe approach (management of out-patients and in-patients following new rules of safety, telemedicine, telehealth, call meetings with clinicians, nurses, patients, and caregivers) without losing the therapeutic efficacy of multidisciplinary treatment.

Aims The epidemiologic Study of Women's Health Across the Nation (SWAN) includes urinary incontinence (UI) questionnaire items. We introduced an independently self-administered paper towel test (PTT-ISA; invention disclosure #2021-347) to objectively demonstrate UI. Aims were to determine: (1) PTT-ISA compliance and (2) relationship to questionnaire results. Methods 276 community women were invited to complete both SWAN questionnaire and PTT-ISA. For PTT-ISA, a woman holds a trifold brown paper towel against her perineum while coughing hard three times. She checks the towel for wetness and compares it with pictorial showing wetted area gradations (dry towel through >6 ml/saturated). She then selects the best photo match for her towel. A newly conceptualized variable constructed as PTT-ISA plus questionnaire results was formed. Results Of 276 women, noncompliance with PTT-ISA was 2.2% (6 women). Four others (1.5%) were missing questionnaires. For the remaining 266 women, conceptual cohesiveness between questionnaire-only and PTT-ISA + questionnaire was demonstrated in 165 (62.0%). Lack of cohesiveness occurred in 101 (38.9%), including 41 women who said "no" to the questionnaire item indicative of stress UI and had leakage on PTT-ISA; leakage degree varied across the full pictorial spectrum from drops to saturated. Conclusion PTT-ISA demonstrates high compliance, with rate comparable to survey compliance. It is a novel measure for objective sign of urine loss when independently self-administered by community women outside of a clinic environment. Further research comparing PTT-ISA with clinician-observed cough test is warranted. As independently self-administered, PTT-ISA is simple, noninvasive, inexpensive, and an acceptable test that adds value to otherwise survey-dependent research.

This White Paper by the European Society for Swallowing Disorders (ESSD) reports on the current state of screening and non-instrumental assessment for dysphagia in adults. An overview is provided on the measures that are available, and how to select screening tools and assessments. Emphasis is placed on different types of screening, patient-reported measures, assessment of anatomy and physiology of the swallowing act, and clinical swallowing evaluation. Many screening and non-instrumental assessments are available for evaluating dysphagia in adults; however, their use may not be warranted due to poor diagnostic performance or lacking robust psychometric properties. This white paper provides recommendations on how to select best evidence-based screening tools and non-instrumental assessments for use in clinical practice targeting different constructs, target populations and respondents, based on criteria for diagnostic performance, psychometric properties (reliability, validity, and responsiveness), and feasibility. In addition, gaps in research that need to be addressed in future studies are discussed. The following recommendations are made: (1) discontinue the use of non-validated dysphagia screening tools and assessments; (2) implement screening using tools that have optimal diagnostic performance in selected populations that are at risk of dysphagia, such as stroke patients, frail older persons, patients with progressive neurological diseases, persons with cerebral palsy, and patients with head and neck cancer; (3) implement measures that demonstrate robust psychometric properties; and (4) provide quality training in dysphagia screening and assessment to all clinicians involved in the care and management of persons with dysphagia.

The role of certain viruses in the etiology of some tumors is today indisputable, but there is a lack, however, of annoverview of the relationship between viruses and cancer with amultidisciplinary approach. For this reason, the Health Sciences Foundation has convened a group of professionals from different areas of knowledge to discuss the relationship between viruses and cancer, and the present document is the result of these deliberations. Although viruses cause only 10-15% of cancers, advances in oncology research are largely due to the work done during the last century on tumor viruses. The clearest cancer-inducing viruses are: HPV, HBV, HCV, EBV and, depending on the geographical area, HHV-8, HTLV-1 and HIV. HPVs, for example, are considered to be the causative agents of cervical carcinomas and, more recently, of a proportion of other cancers. Among the Herpes viruses, the association with the development of neoplasms is well established for EBV and HHV-8. Viruses can also be therapeutic agents in certain neoplasms and, thus, some oncolytic viruses with selective tropism for tumor cells have been approved for clinical use in humans. It is estimated that the prophylaxis or treatment of viral infections could prevent at least 1.5 million cancer deaths per year.

Intra-operative ultrasound has become a relevant imaging modality in neurosurgical procedures. While B-mode, with its intrinsic limitations, is still considered the primary ultrasound modality, intra-operative contrast-enhanced ultrasound (ioCEUS) has more recently emerged as a powerful tool in neurosurgery. Though still not used on a large scale, ioCEUS has proven its utility in defining tumor boundaries, identifying lesion vascular supply and mapping neurovascular architecture. Here we propose a step-by-step procedure for performing ioCEUS analysis of the brain, highlighting its neurosurgical applications. Moreover, we provide practical advice on the use of ultrasound contrast agents and review technical ultrasound parameters influencing ioCEUS imaging.

Atherosclerosis often affects the coronary arterial tree. Frequently the disease does not translate in significant narrowing of the vessels, thus determining only a non-obstructive disease. This condition that is described as non-obstructive coronary artery disease (NobsCAD) should be distinguished from the absence of disease (i.e. smooth coronary arteries) as it carries a specific prognostic value. The detection and reporting of NobsCAD should prompt preventive measures that can be individualized upon the degree of the underlying burden of disease. The accompanying clinical condition, the other cardiovascular risk factors present, and the description of the severity and extent of NobsCAD should provide the framework for an individualized treatment that should also consider the best available scientific evidence and guidelines. The description of NobsCAD represents important information to be collected whenever a coronary angiogram (both invasive and non-invasive) is performed. Treating the patient according to the presence and extent of NobsCAD offers prognostic benefits well beyond those offered by considering only the traditional cardiovascular risk factors. In order to reach this goal, NobsCAD should not be confused with the absence of coronary atherosclerosis or even ignored when detected as if it was a trivial information to provide.

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).Die Multiple Sklerose ist eine komplexe, autoimmun vermittelte Erkrankung des zentralen Nervensystems, charakterisiert durch inflammatorische Demyelinisierung sowie axonalen/neuronalen Schaden. Die Zulassung verschiedener verlaufsmodifizierender Therapien und unser verbessertes Verständnis der Krankheitsmechanismen und -entwicklung in den letzten Jahren haben die Prognose und den Verlauf der Erkrankung deutlich verändert. Diese Aktualisierung der Behandlungsempfehlung der Multiple Sklerose Therapie Konsensus Gruppe konzentriert sich auf die wichtigsten Empfehlungen für verlaufsmodifizierende Therapien der Multiplen Sklerose im Jahr 2021. Unsere Empfehlungen basieren auf aktuellen wissenschaftlichen Erkenntnissen und gelten für diejenigen Medikamente, die in weiten Teilen Europas, insbesondere in den deutschsprachigen Ländern (Deutschland, Österreich, Schweiz), zugelassen sind.

Since the first statement of the German Society of Oto-Rhino-Laryngology, hypoglossal nerve stimulation (HNS) is meanwhile an established treatment option for obstructive sleep apnea (OSA). There are three HNS systems available in Germany which differ in their technical details of the underlying comparable basic principle. For the unilateral HNS with respiratory sensing, several comparative studies, high-volume register analysis and long-term reports exist. The continuous HNS without respiratory sensing does not require a sleep endoscopy for indication. For the bilateral continuous HNS as the single partially implantable device, a feasibility study exists. For indication, the assessment of positive airway pressure failure by sleep medicine is crucial, and the decision for HNS should be made in discussion of other treatment options for at least moderate OSA. The implantation center holds primarily responsibility among the interdisciplinary sleep team and is primary contact for the patient in problems. This depicts why structural processes are required to secure outcome quality and minimize the complications. The aftercare of HNS patients can be provided interdisciplinary and by different medical institutions, whereat, minimal reporting standards to document outcome and usage are recommended.

[Abstract] The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of the LVAD-supported patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD-supported patients. The expected and non-expected device-related and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of the LVAD implanting centres. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to experience comorbidities common in the older population. The probability of an LVAD-supported patient presenting with medical emergency to a local emergency department, internal, or surgical ward of a non-LVAD implanting centre is increasing. The purpose of this trilogy is to supply the immediate tools needed by the non-LVAD specialized physician: ambulance clinicians, emergency ward physicians, general cardiologists, internists, anaesthesiologists, and surgeons, to comply with the medical needs of this fast-growing population of LVAD-supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department and from the emergency department to the internal or surgical wards and eventually to the discharge home from the hospital back to the general practitioner. In this first part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, after the introduction on the assist devices technology in general, definitions and structured approach to the assessment of the LVAD-supported patient in the ambulance and emergency department is presented including cardiopulmonary resuscitation for LVAD-supported patients.

The Veterans Health Administration (VHA) is the United States' largest integrated health care delivery system, serving over 9 million enrollees at nearly 1300 health care facilities. In addition to providing health care to the nation's military veterans, the VHA has a research and development program, trains thousands of medical residents and other health care professionals, and conducts emergency preparedness and response activities. The VHA has been celebrated for delivering high-quality care to veterans, early adoption of electronic medical records, and high patient satisfaction. However, the system faces challenges, including implementation of an expanded community care program, modernization of its electronic medical records system, and providing care to a population with complex needs. The position paper offers policy recommendations on VHA funding, the community care program, medical and health care professions training, and research and development.

The steady growth of corporate interest and influence in the health care sector over the past few decades has created a more business-oriented health care system in the United States, helping to spur for-profit and private equity investment. Proponents say that this trend makes the health care system more efficient, encourages innovation, and provides financial stability to ensure access and improve care. Critics counter that such moves favor profit over care and erode the patient-physician relationship. American College of Physicians (ACP) underscores that physicians are permitted to earn a reasonable income as long as they are fulfilling their fiduciary responsibility to provide high-quality, appropriate care within the guardrails of medical professionalism and ethics. In this position paper, ACP considers the effect of mergers, integration, private equity investment, nonprofit hospital requirements, and conversions from nonprofit to for-profit status on patients, physicians, and the health care system.

Human trafficking is a pandemic human rights violation with an emerging paradigm shift that reframes an issue traditionally seen through a criminal justice lens to that of a public health crisis, particularly for children. Children and adolescents who are trafficked or are at risk for trafficking should receive evidence-based, trauma-informed, and culturally responsive care from trained health care providers (HCPs). The purpose of this article was to engage and equip pediatric HCPs to respond effectively to human trafficking in the clinical setting, improving health outcomes for affected and at-risk children. Pediatric HCPs are ideally positioned to intervene and advocate for children with health disparities and vulnerability to trafficking in a broad spectrum of care settings and to optimize equitable health outcomes.

Background: The cost-effectiveness of using a mobile diary app as an adjunct in dialectical behavior therapy (DBT) in patientswith borderline personality disorder is unknown.Objective: This study aims to perform an economic evaluation of a mobile diary app compared with paper-based diary cardsin DBT treatment for patients with borderline personality disorder in a psychiatric outpatient facility.Methods: This study was conducted alongside a pragmatic, multicenter, randomized controlled trial. The participants wererecruited at 5 Danish psychiatric outpatient facilities and were randomized to register the emotions, urges, and skills used in amobile diary app or on paper-based diary cards. The participants in both groups received DBT delivered by the therapists. Acost-consequence analysis with a time horizon of 12 months was performed. Consequences included quality-adjusted life years(QALYs), depression severity, borderline severity, suicidal behavior, health care use, treatment compliance, and system usability.All relevant costs were included. Focus group interviews were conducted with patients, therapists, researchers, and industryrepresentatives to discuss the potential advantages and disadvantages of using a mobile diary app.Results: A total of 78 participants were included in the analysis. An insignificantly higher number of participants in the papergroup dropped out before the start of treatment (P=.07). Of those starting treatment, participants in the app group had an averageof 37.1 (SE 27.55) more days of treatment and recorded an average of 3.16 (SE 5.10) more skills per week than participants inthe paper group. Participants in both groups had a QALY gain and a decrease in depression severity, borderline severity, andsuicidal behavior. Significant differences were found in favor of the paper group for both QALY gain (adjusted difference −0.054;SE 0.03) and reduction in depression severity (adjusted difference −1.11; SE 1.57). The between-group difference in total costsranged from US $107.37 to US $322.10 per participant during the 12 months. The use of services in the health care sector wassimilar across both time points and groups (difference: psychiatric hospitalization and 2.02; SE 3.19). Overall, the patients showed high acceptability and considered the app as being easy to use. Therapists worriedabout potential negative influences on the therapist-patient interaction from new work tasks accompanying the introduction ofthe new technology but pointed at innovation potential from digital database registrations.Conclusions: This study suggests both positive and negative consequences of mobile diary apps as adjuncts to DBT comparedwith paper diary cards. More research is needed to draw conclusions regarding its cost-effectiveness. Background:The cost-effectiveness of using a mobile diary app as an adjunct in dialectical behavior therapy (DBT) in patients with borderline personality disorder is unknown.Objective:This study aims to perform an economic evaluation of a mobile diary app compared with paper-based diary cards in DBT treatment for patients with borderline personality disorder in a psychiatric outpatient facility.Methods:This study was conducted alongside a pragmatic, multicenter, randomized controlled trial. The participants were recruited at 5 Danish psychiatric outpatient facilities and were randomized to register the emotions, urges, and skills used in a mobile diary app or on paper-based diary cards. The participants in both groups received DBT delivered by the therapists. A cost-consequence analysis with a time horizon of 12 months was performed. Consequences included quality-adjusted life years (QALYs), depression severity, borderline severity, suicidal behavior, health care use, treatment compliance, and system usability. All relevant costs were included. Focus group interviews were conducted with patients, therapists, researchers, and industry representatives to discuss the potential advantages and disadvantages of using a mobile diary app.Results:A total of 78 participants were included in the analysis. An insignificantly higher number of participants in the paper group dropped out before the start of treatment (P=.07). Of those starting treatment, participants in the app group had an average of 37.1 (SE 27.55) more days of treatment and recorded an average of 3.16 (SE 5.10) more skills per week than participants in the paper group. Participants in both groups had a QALY gain and a decrease in depression severity, borderline severity, and suicidal behavior. Significant differences were found in favor of the paper group for both QALY gain (adjusted difference −0.054; SE 0.03) and reduction in depression severity (adjusted difference −1.11; SE 1.57). The between-group difference in total costs ranged from US $107.37 to US $322.10 per participant during the 12 months. The use of services in the health care sector was similar across both time points and groups (difference: psychiatric hospitalization Conclusions:This study suggests both positive and negative consequences of mobile diary apps as adjuncts to DBT compared with paper diary cards. More research is needed to draw conclusions regarding its cost-effectiveness.

Introduction Muscular dystrophies present a group of inherited degenerative disorder that are characterized by progressive muscular weakness. This evidence-based position paper represents the official position of the European Union through the UEMS PRM Section. The aim of the paper is to evaluate the role of the physical and rehabilitation medicine (PRM) physician and PRM practice for people with muscular dystrophies. Evidence acquisition A systematic review of the literature and a consensus procedure by means of a Delphi process have been performed involving the delegates of all European countries represented in the UEMS PRM Section. Evidence synthesis The systematic literature review is reported together with thirty-three recommendations resulting from the Delphi procedure. Conclusions The role of the PRM physician is to assess the functional status of persons with muscular dystrophy and to plan, monitor and lead PRM program in an interdisciplinary setting within a multiprofessional team.

Proteinuria is a condition in which an excessive amount of protein is excreted in urine. It is, among others, an indicator of kidney disease or risk of cardiovascular disease. Rapid and reliable diagnosis and monitoring of proteinuria is of great importance for both patients and their physicians. For that reason, a paper-based sensor for proteinuria diagnosis was designed, optimized, and validated utilizing smartphone-assisted signal acquisition. In the first step, a few commonly employed protein assays were optimized and compared in terms of analytical performance on paper matrix. The tetrabromophenol blue method was selected as the one providing a sufficiently low limit of detection (39 mg·L−1) on the one hand and appropriate long-term stability (up to 3 months) on the other hand. The optimized assay was employed for protein-to-creatinine ratio (PCR) determination on a single paper-based sensor. For both analytes the linear ranges were within the clinically relevant range. The analytical usefulness of the developed sensors was demonstrated by a PCR recovery study in artificial urine. The obtained PCR recoveries were from ca. 80 to 150%.

[Abstract] The improvement in left ventricular assist device (LVAD) technology and scarcity of donor hearts have increased dramatically the population of the LVAD-supported patients and the probability of those patients to present to the emergency department with expected and non-expected device-related and patient-device interaction complications. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to suffer from other co-morbidities common in the older population. In this second part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the LVAD-supported patient presenting to the emergency department with bleeding, neurological event, pump thrombosis, chest pain, syncope, and other events are presented. The very challenging issue of declaring death in an LVAD-supported patient, as the circulation is artificially preserved by the device despite no other signs of life, is also discussed in detail.

Purpose The purpose of the study was to appraise the methodological quality of the highest impact blepharoplasty research and to describe prevalent research themes. Methods The 100 most highly cited research papers relevant to blepharoplasty were obtained from Web of Science, with no journal or date limitations applied. Data extraction included the study design, main research topic and specialty, outcome measures, and citation count. Each paper's level of evidence was independently evaluated by 2 authors according to the Oxford Centre for Evidence-Based Medicine system. Results Overall, the 100 most cited blepharoplasty research papers were cited by 4,194 papers. The mean number of citations for each paper was 73 (range: 42-239). Most of the papers presented level 4 (n = 51) or level 5 (n = 35) evidence, which is consistent with the predominance of case series (n = 47) and expert opinions (n = 18) amongst study designs. No papers achieved level 1 (highest) evidence. Six papers presented level 2 evidence and 8 papers presented level 3. Significant research foci included innovative surgical techniques (n = 65) and anatomical considerations (n = 10), with reconstructive and cosmetic implications. Senior authors were mainly affiliated with centers of plastic (n = 53) or ophthalmic/oculoplastic (n = 34) surgery. Only 3 papers used validated subjective or objective cosmetic outcome measures. Conclusions Despite a significant impact on current practice, the level of evidence of the highly cited blepharoplasty research was predominantly low. Robust research methodology, through well-designed studies and standardized outcome measures, is necessary to facilitate evidence synthesis and guide clinical practice.

BACKGROUND: Patient-reported outcome measures (PROMs) are validated questionnaires that are completed by patients. Arthroplasty registries vary in PROM collection and use. Current information about registry collection and use of PROMs is important to help improve methods of PROM data analysis, reporting, comparison, and use toward improving clinical practice. QUESTIONS/PURPOSES: To characterize PROM collection and use by registries, we asked: (1) What is the current practice of PROM collection by arthroplasty registries that are current or former members of the International Society of Arthroplasty Registries, and are there sufficient similarities in PROM collection between registries to enable useful international comparisons that could inform the improvement of arthroplasty care? (2) How do registries differ in PROM administration and demographic, clinical, and comorbidity index variables collected for case-mix adjustment in data analysis and reporting? (3) What quality assurance methods are used for PROMs, and how are PROM results reported and used by registries? (4) What recommendations to arthroplasty registries may improve PROM reporting and facilitate international comparisons? METHODS: An electronic survey was developed with questions about registry structure and collection, analysis, reporting, and use of PROM data and distributed to directors or senior administrators of 39 arthroplasty registries that were current or former members of the International Society of Arthroplasty Registries. In all, 64% (25 of 39) of registries responded and completed the survey. Missing responses from incomplete surveys were captured by contacting the registries, and up to three reminder emails were sent to nonresponding registries. Recommendations about PROM collection were drafted, revised, and approved by the International Society of Arthroplasty Registries PROMs Working Group members. RESULTS: Of the 25 registries that completed the survey, 15 collected generic PROMs, most frequently the EuroQol-5 Dimension survey; 16 collected joint-specific PROMs, most frequently the Knee Injury and Osteoarthritis Outcome Score and Hip Disability and Osteoarthritis Outcome Score; and 11 registries collected a satisfaction item. Most registries administered PROM questionnaires within 3 months before and 1 year after surgery. All 16 registries that collected PROM data collected patient age, sex or gender, BMI, indication for the primary arthroplasty, reason for revision arthroplasty, and a comorbidity index, most often the American Society of Anesthesiologists classification. All 16 registries performed regular auditing and reporting of data quality, and most registries reported PROM results to hospitals and linked PROM data to other data sets such as hospital, medication, billing, and emergency care databases. Recommendations for transparent reporting of PROMs were grouped into four categories: demographic and clinical, survey administration, data analysis, and results. CONCLUSION: Although registries differed in PROM collection and use, there were sufficient similarities that may enable useful data comparisons. The International Society of Arthroplasty Registries PROMs Working Group recommendations identify issues that may be important to most registries such as the need to make decisions about survey times and collection methods, as well as how to select generic and joint-specific surveys, handle missing data and attrition, report data, and ensure representativeness of the sample. CLINICAL RELEVANCE: By collecting PROMs, registries can provide patient-centered data to surgeons, hospitals, and national entities to improve arthroplasty care.

INTRODUCTION Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that affects both upper and lower motor neurons and is fatal in its course. This evidence-based position paper represents the official position of the UEMS PRM Section. The aim of the paper is to define the role of the physical and rehabilitation medicine (PRM) physician and PRM professional practice for people with ALS. EVIDENCE ACQUISITION A systematic review of the literature and a consensus procedure by means of a Delphi process have been performed involving the delegates of all European countries represented in the UEMS PRM Section. EVIDENCE SYNTHESIS The systematic literature review is reported together with thirty-two recommendations resulting from the Delphi procedure. CONCLUSIONS The responsibility of the PRM physician is functional assessment of persons with ALS and delivering the optimal and most effective PRM program of care. The rehabilitation program of patients with ALS should be delivered and monitored by the multiprofessional team, with the PRM physician as principal coordinator.

Children are seldom affected by severe forms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2) infection; however, the impact of comorbidities in the clinical presentation and outcome of SARS-CoV2 in children is poorly characterized including that of chronic liver disease (CLD) and those taking immunosuppressive medications for autoimmune liver disease or following liver transplantation (LT). Although not the main target organ, a spectrum of liver involvement has been described in children infected with SARS-CoV2 and those presenting with Multisystem Inflammatory Syndrome in Children (MIS-C). The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the Society of Pediatric Liver Transplantation (SPLIT) present an evidence-based position paper on liver involvement in children with SARS-CoV2 infection and its impact on those with CLD as well as LT recipients. All children may exhibit acute liver injury from SARS-CoV2 infection, and those with CLD and may experience hepatic decompensation. Preventative and therapeutic measures are discussed.

The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as ‘post-acute COVID-19’ may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance., Graphical Abstract Graphical Abstract

The clinical importance of blood group (BG) antigens is related to their ability to induce immune antibodies that can cause hemolysis. Yet, ABO and D (Rh) are still considered to be the key antigens for healthy blood transfusion and secondary antigens are the next priority. Serological typing is the most widely used typing method. Rapid and accurate blood grouping plays an important role in some clinical conditions, rather than conventional techniques. Hence, developing a simple and economical model for rapid blood grouping would facilitate these tests. In recent decades, paper-based microfluidics such as μPADs has gained much interest in wide application areas such as point-of-care diagnostic. In this study, we evaluated μPADs that are performed for blood grouping and its recent progress. A comprehensive literature search was performed using databases including PUBMED, SCOPUS, Web of Science and Google Scholar. Keywords were blood grouping or typing, paper analytical device, rapid test, etc. After investigation of search results, 16 papers from 2010 to 2020 were included. Further information in detail was classified in Table 1. Generally, two principles for blood typing μPADs are introduced. The lateral chromatographic flow method and the vertical flow-through method that detects BG in a visual-based manner. To detect results with acceptable clarity many factors and challenges like paper, blood sample, buffer, Ab and RBC interaction and also μPADs stability need to be considered, which are discussed. In conclusion, the simplicity, stability, cheapness, portability and biocompatibility of μPADs for blood grouping confirming its utility and also they have the capability to robust, universal blood-grouping platform. Table 1 Summary of blood grouping tests using paper-based analytical devices Antigens Type of diagnosis Validation method Sample No Accuracy Action time Paper type Stability Sample dilution Buffer Ref A, B, Rh Forward volunteers records 5 - - Whatman No. 4 - 1/2 PBS* (Khan et al. 2010) A, B, Rh Forward gel assay test and conventional slide test 100 100% 1 min Whatman No. 4 and Kleeenex paper towel 7 Days in 4 °C 1/1 NSS (Al-Tamimi et al. 2012) A, B, Rh Forward gel card assay 99 100% 20 Sec + Washing Kleeenex paper towel - 1/1 NSS (Li et al. 2012) A, B, Rh Forward - - - - Kleeenex paper towel - 45/100 PSS (Li et al. 2013) A, B, Rh Forward gel card assay 98 100% 1.5 min Kleeenex paper towel - 85/100 PBS (Guan et al. 2014b) C, E, c, e, K, Jka, Jkb, M, N, S, P1, and Lea Forward gel card assay 266 100% - Kleeenex paper towel - 1/1 NSS (Li et al. 2014b) A, B, Rh Forward and Reverse conventional slide test 96 ≈ 91% 10 min Whatman No. 1 21 Days in 4 °C 1/2 NSS (Noiphung et al. 2015) C, c, E, e, K, k, Fya, Fyb, Jka, Jkb, M, N, S and s, P1, Lea and Leb Forward - 478 - - Kleeenex paper towel - 1/1 NSS, PBS (Then et al. 2015) A, B Forward and Reverse conventional slide test 76 100% 5-8 min Whatman No. 4 38 Days in 4 °C 1/4, 1/1 NSS (Songjaroen and Laiwattanapaisal 2016) D, K Forward volunteers records 210 - 7.5 min Kleenex paper towel - 1/1 NSS (Yeow et al. 2016) A, B, c, e, D, C, E, M, N, S, s, P1, Jka, Jkb, Lea, Leb, Fya, and Fyb Forward and Reverse gel card assay 3550 ≈100% 30 s Fiber glass and cotton linter 180 Days in 25 °C 45/100, 1/1 PBS (Zhang et al. 2017) A, B Forward conventional slide test 598 100% 3 min Whatman No. 113 14 Day in 4 °C 1/1 NSS (Songjaroen et al. 2018) A, B, Rh Forward conventional slide test - - 30 Sec + Washing Unrefined sisal paper - 1/2 NSS (Casals-Terré et al. 2019) A, B, Rh Forward - - - - Whatman No.1 - 1/1 NSS (Ansari et al. 2020) ABORh Forward and Reverse conventional slide test - 100% Unrefined Eucalyptus papers - 1/2 NSS, PBS (Casals-Terré et al. 2020) A, B, Rh Forward - - - 30 Sec + Washing Whatman No. 4 modified with chitosan ≥ 100 days in 25 °C 1/1 NSS (Parween et al. 2020)

Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field. ESM-U, CG, GV, GJ, IVB, MvR, and VvS, are members of the “IMMPROVE” consortium (Innovative Measurements and Markers for Prostate Cancer Diagnosis and Prognosis using Extracellular Vesicles), which is sponsored by an Alpe d'HuZes grant of the Dutch Cancer Society (grant #EMCR2015-8022). AL is supported by Norges Forskningsråd, Kreftforeningen and Helse Sør-Øst RHF (NO). UE is supported by the NIH, National Heart, Lung, and Blood Institute, Award number K23-HL-126101. CJB and EJH are supported by the Dutch Kidney Foundation (Nierstichting), Award number: CP18.05.

The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded in 2018, with the aim to promote cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic peripheral artery was selected as the very first topic to be investigated by the federation. In this second paper, different experiences from delegates of participating countries were shared to define common strategies to harmonize, standardize, and optimize education and training in the Vascular Surgery specialty.

Coronavirus disease 2019 (COVID‐19) first emerged in China in November 2019. Most governments have responded to the COVID‐19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID‐19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID‐19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID‐19 era (group activities, telemedicine, outpatients treatment, alcohol‐related liver disease and liver transplantation, collecting samples); (d) AUD and SARS‐CoV‐2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID‐19 disease will need implementation. Thus, the COVID‐19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in‐depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment., All health care systems need to be reorganized during and after the COVID‐19 pandemic, and also the CAATs in order to combine operator safety with patient safety and care. The multi‐disciplinary intervention involving experts in the treatment of AUD and ALD with specialists in the treatment of COVID‐19 disease will need implementation and the contribution of the family and of care‐givers in the management of AUD and ALD patients will play a significant role.

Background: The WHO definition of palliative care includes bereavement support as integral to palliative care, yet a previous survey of bereavement support in palliative care in Europe has shown a range of service responses to loss. A rigorous approach to agreeing and implementing a palliative care bereavement framework was required. Aim: The aim of this study was to develop consensus on best-practice recommendations for bereavement care principles, structures, processes and delivery based on current practice and evidence. Design: In accordance with Guidance on Conducting and Reporting Delphi Studies, a consensus-building five-round Delphi technique was performed. A scoping review of research literature informed drafting of 54 statements by the EAPC Bereavement Task Force. Evaluation of the statements was performed by an expert panel using a 5-point Likert scale. ⩾80% agreement were defined as essential items and 75%–79% agreement were defined as desirable items. Items with a consensus rating Setting/participants: The Delphi study was carried out by an expert panel among membership organisations of the European Association for Palliative Care. Results: In total, 376 email requests to complete Delphi questionnaire were distributed with a response rate of 23% ( n = 87) and a follow-up response-rate of 79% ( n = 69). Of the initial 54 statements in six dimensions, 52 statements were endorsed with 26 essential statements and 26 desirable statements. Conclusions: The six dimensions and 52 statements agreed through this Delphi study clarify a coherent direction for development of bereavement services in palliative care in Europe.

Background Brucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable. Methodology/Principal findings In this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen. Conclusions B cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations., Author summary Brucellosis is one of the most important zoonosis in the world and has caused tremendous economic losses in agriculture and animal husbandry in many countries. Developing rapid, sensitive and specific diagnostic methods is very important for early detection and treatment of brucellosis patients. In this study, a novel diagnostic technique, nano-ZnO modified paper ELISA, was established. The antigen used in this technique was a fusion protein containing multiple B cell epitopes, which were predicted from Brucella major outer membrane proteins such as Bp26, Omp31, Omp16, Omp2b and Omp25. Comparing to traditional LPS antigen, this multiepitope based antigen displayed considerably higher sensitivity and higher specificity in laboratory. With the strategy described in this paper, more efficient epitopes and protein antigen can be identified in the future. Currently, LPS antigen is only prepared from live Brucella, while protein antigen can be produced in large quantities in prokaryotic expression system. In addition to nano-p-ELISA, this protein antigen can also be used for development other methods such as fluorescent polarization assay (FPA) and immunochromatographic assay (ICA) to meet the varied demand for brucellosis testing.

Recent research breakthroughs have emerged from applied basic research throughout all scientific areas, including adult and paediatric gastroenterology, hepatology and nutrition (PGHAN). The research landscape within the European Society of Paediatric Gastroenterology and Nutrition (ESPGHAN) is also inevitably changing from clinical research to studies involving applied laboratory research. This position paper aims to depict the current status quo of basic science and translational research within ESPGHAN, and to delineate how the society could invest in research in the present and future time. The paper also explores which research areas in the field of PGHAN represent the current and future priorities, and what type of support is needed across the ESPGHAN working groups (WGs) and special interest groups (SIGs) to fulfil their research goals.