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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.

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

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

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.

First two decades of the twenty-first century are characterised by epidemics of non-communicable diseases such as many hundreds of millions of patients diagnosed with cardiovascular diseases and the type 2 diabetes mellitus, breast, lung, liver and prostate malignancies, neurological, sleep, mood and eye disorders, amongst others. Consequent socio-economic burden is tremendous. Unprecedented decrease in age of maladaptive individuals has been reported. The absolute majority of expanding non-communicable disorders carry a chronic character, over a couple of years progressing from reversible suboptimal health conditions to irreversible severe pathologies and cascading collateral complications. The time-frame between onset of SHS and clinical manifestation of associated disorders is the operational area for an application of reliable risk assessment tools and predictive diagnostics followed by the cost-effective targeted prevention and treatments tailored to the person.This article demonstrates advanced strategies in bio/medical sciences and healthcare focused on suboptimal health conditions in the frame-work of Predictive, Preventive and Personalised Medicine (3PM/PPPM). Potential benefits in healthcare systems and for society at large include but are not restricted to an improved life-quality of major populations and socio-economical groups, advanced professionalism of healthcare-givers and sustainable healthcare economy. Amongst others, following medical areas are proposed to strongly benefit from PPPM strategies applied to the identification and treatment of suboptimal health conditions:Stress overload associated pathologiesMale and female healthPlanned pregnanciesPeriodontal healthEye disordersInflammatory disorders, wound healing and pain management with associated complicationsMetabolic disorders and suboptimal body weightCardiovascular pathologiesCancersStroke, particularly of unknown aetiology and in young individualsSleep medicineSports medicineImproved individual outcomes under pandemic conditions such as COVID-19.

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

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.

Approximately 10 years have passed since the Peritoneal Dialysis Guidelines were formulated in 2009. Much evidence has been reported during the succeeding years, which were not taken into consideration in the previous guidelines, e.g., the next peritoneal dialysis PD trial of encapsulating peritoneal sclerosis (EPS) in Japan, the significance of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), the effects of icodextrin solution, new developments in peritoneal pathology, and a new international recommendation on a proposal for exit-site management. It is essential to incorporate these new developments into the new clinical practice guidelines. Meanwhile, the process of creating such guidelines has changed dramatically worldwide and differs from the process of creating what were “clinical practice guides.” For this revision, we not only conducted systematic reviews using global standard methods but also decided to adopt a two-part structure to create a reference tool, which could be used widely by the society’s members attending a variety of patients. Through a working group consensus, it was decided that Part 1 would present conventional descriptions and Part 2 would pose clinical questions (CQs) in a systematic review format. Thus, Part 1 vastly covers PD that would satisfy the requirements of the members of the Japanese Society for Dialysis Therapy (JSDT). This article is the duplicated publication from the Japanese version of the guidelines and has been reproduced with permission from the JSDT.

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.

[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.

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.

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%.

Influenza virus infection is a major worldwide public health problem. Influenza virus infections are associated with a high hospitalization rate in children between the ages of 5 and 14. The predominant reason for poor influenza prognosis is the lack of any effective means for early diagnosis. Early diagnosis of severe illness is critical to improving patient outcome, and could be especially useful in areas with limited medical resources. Accurate, inexpensive, and easy-to-use diagnostic tools could improve early diagnosis and patient outcome, and reduce overall healthcare costs. We developed an interleukin-6 paper-based test strip that used colloidal gold-conjugated antibodies to detect human interleukin-6 protein. These complexes were captured on a paper-based test strip patterned with perpendicular T lines that were pre-coated with anti-human interleukin-6 antibodies. Applied serum samples interacted with these antibodies and presented as colored bands that could be read using a spectrum-based optical reader. The full-spectrum of the reflected light interleukin-6 protein signal could be obtained from the spectral optics module, and the standard could be used to quantitatively analyze interleukin 6 level in serum. We retrospectively evaluated 10 children (23 serum samples) with severe influenza virus infections, 26 children (26 serum samples) with mild influenza virus infections, and 10 healthy children (10 serum samples). Our system, the combined use of a paper-based test strip and a spectrum-based optical reader, provided both qualitative and quantitative information. When used with the optical reader, the detection limit was improved from a qualitative, naked-eye level of 400 pg/ml to a quantitative, optical reader level of 76.85 pg/ml. After monitoring serum interleukin-6 level via our system, we found a high correlation between our system results and those obtainable using a conventional sandwich enzyme-linked immunosorbent assay method (Rho = 0.706, p < 0.001). The sensitivity and specificity for differentiating between severe and mild influenza using our combined method (test strip coupled with optical reader) were 78.3 and 50.0%, respectively. When interleukin-6 was combined with serum C-reaction protein, the sensitivity and specificity were 85.7 and 95.5%, and the receiver operating characteristic area-under-the-curve was quite high (AUC = 0.911, p < 0.001). The potential advantages of our system, i.e., a paper-based test strip coupled with a spectrum-based optical reader, are as follows: 1) simple user operation; 2) rapid turnaround times–within 20 min; 3) high detection performance; and, 4) low-cost fabrication.

[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.

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

Child nutrition has always been a global concern. This study performed visual analysis of 1,398 child nutrition highly cited papers (HCPs) from 2009 to 2019. The purpose of the study was to evaluate and present the performances of authors, journals, countries, institutions, top cited papers; to explore the hot topics, prospects, and to propose the future research directions on child nutrition. We used bibliometric methods to conduct in-depth statistical analysis of HCPs on child nutrition, showing research progress, trends and hot spots. We included HCPs on child nutrition from the Science Citation Index-Expanded (SCI-E) database February 7, 2020. Two tools, CiteSpace and VOSviewer, were used to conduct the bibliometric analyses. The results showed that, since 2011, the number of HCPs on child nutrition has increased rapidly. The top three contributors in this field were the USA, the UK and Canada. However, the contribution of developing countries was very limited. Intestinal microflora, food allergy, overweight and obesity were the three major research hotspots in this field. Results of this study provide valuable references for ongoing child nutrition related research, which may be interesting and noteworthy to the researchers involved.

Simple Summary Although secondary enucleation (SE) is the treatment of choice for retinoblastoma eyes that did not respond favorably to conservative therapies, clear criteria for its indication are, however, currently missing. In this position paper on behalf of the European Retinoblastoma Group (EURbG), we discuss the available literature on SE, including its influence on metastases rate and survival, and propose guidelines to assist decision-making to interrupt eye-preserving therapies depending on the availabilities of advanced diagnostic and therapeutic modalities. Absolute indications to SE may be restricted to eyes with refractory tumor activity resisting all salvage treatments or eyes under apparent tumor control but no visual potential and irreducible complications. In contrast, eyes with an obscured optic nerve head and/or ocular complications amenable to specific surgical or medical management can be considered relative indications, provided that appropriate follow-up can be implemented and that parents are fully aware of a residual risk. Abstract Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future.

This study investigates the efficacy of using discarded textile (cotton and polycotton) and paper waste (newspaper and corrugated cardboard) as substrates to form sheets with optimum tensile strength. The effect of alkali treatment (sodium hydroxide (NaOH) and sodium bicarbonate (NaHCO3)), compressive loads (200 N and 500 N), and the use of binding agents (blackstrap molasses, sodium alginate, and cornstarch) were studied to optimize the tensile strength of homogeneous sheets. The alkali treatment using 5% NaOH for 5 h of soaking demonstrated the highest increase in tensile strength of 21% and 19% for cotton and newspaper, respectively. Increasing compressive load from 200 N to 500 N showed the highest increase in tensile strength of 37% and 42% for cotton and newspaper, respectively. Remarkably, among the binders, cornstarch at 20% concentration obtained an increase in tensile strength of 395%, 320%, 310%, and 185% for cotton, polycotton, corrugated cardboard, and newspaper sheets, respectively. The optimum results obtained from this study will be utilized to develop biodegradable seedling pots using discarded textile and paper waste.

Urine bags are commonly used to collect urine samples from neonates. However, the sample can be contaminated by stool, or detachment of the bag due to body movement can lead to failure of the collection. A qualitative urine collection kit containing ten filter papers of 3.2 mm diameter was developed and clinically verified among 138 neonates. During a single diaper change (approximately 3 h), the rate of urine collection was calculated. Urine collection was considered to be successful if any filter paper in the urine collection sheet turned from blue to white. Of the 127 neonates who passed urine, 122 had a change in the filter paper. The urine collection rate was 96%, with changes in all 10 filter papers observed in 98 neonates (80%). Urine collection rate was not influenced by sex (p = 1.00), age at collection (p = 0.72), preterm birth (p = 1.00), low birth weight (p = 0.92), or fecal contamination (p = 1.00). The incidence of dermatitis was not higher than in the group in which urine bags were used (urine collection kit: 2/68 [3%]; urine bag: 5/68 [7%]; p = 0.44). Novel urine collection kits using filter paper can collect samples from neonates safely and with a high probability of success.

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.

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.

We report on an immunofluorescent paper-based assay for the detection of severe acute respiratory symptom coronavirus 2 (SARS-CoV-2) humanized antibody. The paper-based device was fabricated by using lamination technique for easy and optimized handling. Our approach utilises a two-step strategy that involves (i) initial coating of the paper-electrode with recombinant SARS-CoV-2 nucleocapsid antigen to capture the target SARS-CoV-2 specific antibodies, and (ii) subsequent detection of SARS-CoV-2 antibodies using fluorophore-conjugated IgG antibody. The fluorescence readout was observed with fluorescence microscopy. The images were processed and quantified using a MATLAB program. The assay can selectively detect SARS-CoV-2 humanized antibodies spiked in PBS and healthy human serum samples with the relative standard deviation of approximately 6.4% (for n = 3). It has broad dynamic ranges (1 ng to 50 ng/µL in PBS and 5 to 100 ng/µL in human serum samples) for SARS-CoV-2 humanized antibodies with the detection limits of 2 ng/µL (0.025 IU/mL) and 10 ng/µL (0.125 IU/mL) in PBS and human serum samples, respectively. We believe that our assay has the potential to be used as a simple, rapid, and inexpensive paper-based diagnostic device with a portable fluorescent reader to provide point-of-care diagnosis. This assay can be used for rapid examination of a large batch of samples toward clinical screening of SARS-CoV-2 specific antibodies as a confirmed infected active case or to evaluate the immune response to a SARS-CoV-2 vaccine.

Cardiovascular (CV) engagement in coronavirus disease 2019 (COVID‐19) is a huge determinant of prognosis during the acute phase of the disease. However, little is known about the potential chronic implications of the late phase of COVID‐19 and about the appropriate approach to these patients. Heart failure, type 1 and type 2 myocardial infarction, arrhythmias, myocarditis, pulmonary fibrosis, and thrombosis have been shown to be related to severe acute respiratory syndrome coronavirus 2 infection, and a ‘long COVID‐19’ illness has been recognized with fatigue, chest pain, and dyspnoea among the most frequent symptoms reported after discharge from hospital. This paper focuses on some open questions that cardiologists are going to face during the next months in a general cardiology outpatient clinic, in particular how to evaluate a ‘post‐COVID’ patient during follow‐up of CV complications of the acute phase and how to manage new CV symptoms that could be the consequence, at least in part, of heart/vessels and/or lung involvement of the previous virus infection. Present symptoms and signs, history of previous CV disease (both preceding COVID‐19 and occurring during viral infection), and specific laboratory and imaging measurements during the acute phase may be of interest in focusing on how to approach the clinical evaluation of a post‐COVID patient and how to integrate in our standard of care the new information on COVID‐19, possibly in a multidisciplinary view. Dealing with the increased COVID‐associated CV risk burden and becoming acquainted with potential new e‐cardiology approaches aimed at integrating the cardiology practice are relevant new challenges brought by severe acute respiratory syndrome coronavirus 2 infection and its sequelae.

Minimal invasive extracorporeal circulation (MiECC) systems have initiated important efforts within science and technology to further improve the biocompatibility of cardiopulmonary bypass components to minimize the adverse effects and improve end-organ protection. The Minimal invasive Extra-Corporeal Technologies international Society was founded to create an international forum for the exchange of ideas on clinical application and research of minimal invasive extracorporeal circulation technology. The present work is a consensus document developed to standardize the terminology and the definition of minimal invasive extracorporeal circulation technology as well as to provide recommendations for the clinical practice. The goal of this manuscript is to promote the use of MiECC systems into clinical practice as a multidisciplinary strategy involving cardiac surgeons, anaesthesiologists and perfusionists.

The personalized medicine is in a rapidly evolving scenario. The identification of actionable mutations is revolutionizing the therapeutic landscape of tumors. The morphological and histological tumor features are enriched by the extensive genomic profiling, and the first tumor-agnostic drugs have been approved regardless of tumor histology, guided by predictive and druggable genetic alterations. This new paradigm of "mutational oncology", presents a great potential to change the oncologic therapeutic scenario, but also some critical aspects need to be underlined. A process governance is mandatory to ensure the genomic testing accuracy and homogeneity, the economic sustainability, and the regulatory issues, ultimately granting the possibility of translating this model in the "real world". In this position paper, based on experts' opinion, the AIOM-SIAPEC-IAP-SIBIOC-SIF Italian Scientific Societies revised the new agnostic biomarkers, the diagnostic technologies available, the current availability of agnostic drugs and their present indication.

International audience; Button batteries (BB) remain a health hazard to children as ingestion might lead to life-threatening complications, especially if the battery is impacted in the esophagus. Worldwide initiatives have been set up in order to prevent and also timely diagnose and manage BB ingestions. A European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) task force for BB ingestions has been founded, which aimed to contribute to reducing the health risks related to this event. It is important to focus on the European setting, next to other worldwide initiatives, to develop and implement effective management strategies. As one of the first initiatives of the ESPGHAN task force, this ESPGHAN position paper has been written. The literature is summarized, and prevention strategies are discussed focusing on some controversial topics. An algorithm for the diagnosis and management of BB ingestions is presented and compared to previous guidelines (NASPGHAN, National Poison Center). In agreement with earlier guidelines, immediate localization of the BB is important and in case of esophageal impaction, the BB should be removed instantly (preferably 12 hours after ingestion or time point of removal >12 hours after ingestion) and esophageal impaction the guideline suggests to perform a CT scan in order to evaluate for vascular injury before removing the battery. In delayed diagnosis, even if the battery has passed the esophagus, endoscopy to screen for esophageal damage and a CT scan to rule out vascular injury should be considered even in asymptomatic children. In asymptomatic patients with early diagnosis (

The term liquid biopsy (LB) refers to the use of various biological fluids as a surrogate for neoplastic tissue to achieve information for diagnostic, prognostic and predictive purposes. In the current clinical practice, LB is used for the identification of driver mutations in circulating tumor DNA derived from both tumor tissue and circulating neoplastic cells. As suggested by a growing body of evidence, however, there are several clinical settings where biological samples other than tissue could be used in the routine practice to identify potentially predictive biomarkers of either response or resistance to targeted treatments. New applications are emerging as useful clinical tools, and other blood derivatives, such as circulating tumor cells, circulating tumor RNA, microRNAs, platelets, extracellular vesicles, as well as other biofluids such as urine and cerebrospinal fluid, may be adopted in the near future. Despite the evident advantages compared with tissue biopsy, LB still presents some limitations due to both biological and technological issues. In this context, the absence of harmonized procedures corresponds to an unmet clinical need, ultimately affecting the rapid implementation of LB in clinical practice. In this position paper, based on experts’ opinions, the AIOM–SIAPEC-IAP–SIBIOC–SIF Italian Scientific Societies critically discuss the most relevant technical issues of LB, the current and emerging evidences, with the aim to optimizing the applications of LB in the clinical setting., Highlights • In the current clinical practice LB is used for the identification of driver mutations in circulating tumor DNA (ctDNA). • New applications in tumors other than non-small-cell lung cancer (NSCLC) are emerging as useful clinical tools. • Other blood derivatives, together with other biofluids, are an active field of research and may be adopted in the near future. • Despite the evident advantages, liquid biopsy still presents limitations due to both biological and technological issues. • Standardization of the procedures needs to be addressed to ensure widespread implementation in clinical practice.

AimsTo highlight the need for the development of effective and realistic workforce strategies for critical care nurses, in both a steady state and pandemic.BackgroundIn acute care settings, there is an inverse relationship between nurse staffing and iatrogenesis, including mortality. Despite this, there remains a lack of consensus on how to determine safe staffing levels. Intensive care units (ICU) provide highly specialised complex healthcare treatments. In developed countries, mortality rates in the ICU setting are high and significantly varied after adjustment for diagnosis. The variability has been attributed to systems, patient and provider issues including the workload of critical care nurses.DesignDiscursive paper.FindingsNursing workforce is the single most influential mediating variable on ICU patient outcomes. Numerous systematic reviews have been undertaken in an effort to quantify the effect of critical care nurses on mortality and morbidity, invariably leading to the conclusion that the association is similar to that reported in acute care studies. This is a consequence of methodological limitations, inconsistent operational definitions and variability in endpoint measures. We evaluated the impact inadequate measurement has had on capturing relevant critical care data, and we argue for the need to develop effective and realistic ICU workforce measures.ConclusionCOVID-19 has placed an unprecedented demand on providing health care in the ICU. Mortality associated with ICU admission has been startling during the pandemic. While ICU systems have largely remained static, the context in which care is provided is profoundly dynamic and the role and impact of the critical care nurse needs to be measured accordingly. Often, nurses are passive recipients of unplanned and under-resourced changes to workload, and this has been brought into stark visibility with the current COVID-19 situation. Unless critical care nurses are engaged in systems management, achieving consistently optimal ICU patient outcomes will remain elusive.Relevance to clinical practiceObjective measures commonly fail to capture the complexity of the critical care nurses' role despite evidence to indicate that as workload increases so does risk of patient mortality, job stress and attrition. Critical care nurses must lead system change to develop and evaluate valid and reliable workforce measures.

International audience; Multidisciplinary management of worsening heart failure (HF) in the elderly improves survival. To ensure patients have access to adequate care, the current HF and French health authority guidelines advise establishing a clearly defined HF patient pathway. This pathway involves coordinating multiple disciplines to manage decompensating HF. Yet, recent registry data indicate that insufficient numbers of patients receive specialised cardiology care, which increases the risk of rehospitalisation and mortality. The patient pathway in France involves three key stages: presentation with decompensated HF, stabilisation within a hospital setting and transitional care back out into the community. In each of these three phases, HF diagnosis, severity and precipitating factors need to be promptly identified and managed. This is particularly pertinent in older, frail patients who may present with atypical symptoms or coexisting comorbidities and for whom geriatric evaluation may be needed or specific geriatric syndrome management implemented. In the transition phase, multi-professional post-discharge management must be coordinated with community health care professionals. When the patient is discharged, HF medication must be optimised, and patients educated about self-care and monitoring symptoms. This review provides practical guidance to clinicians managing worsening HF in the elderly.

The disruptive force of the COVID-19 pandemic is lessening in power and plans are being made for the postcrisis period, among which increasing the sustainability of higher education is of significant importance. The study aims at establishing students’ existing environment-related routines during their home confinement, as a basis for applying green measures to campus living once academic life is resumed with the physical presence of students. The collected data rely on self-reported information provided by 816 students from Politehnica University of Timisoara (Romania), collected via an online, anonymous survey. The novelty of the approach is that household environment-related routines are investigated during a crisis period, with the possibility to build upon the results to implement tailored measures to encourage or diminish environmentally relevant consumption by young, highly skilled individuals. The students display a moderate awareness of environmental issues and indicate consumption routines that may be steered towards an increased sustainability-conscious campus life, through the combined intervention of the university, city administration, and stakeholder involvement. The findings are used to explore the possible directions for action towards increasing or contributing to the territorial sustainability in the socio-ecological context of Timisoara, the largest university city in the western part of Romania via educational, managerial and policy interventions.

Background One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. Management Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. Current Issues The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. Perspectives There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). Conclusion The “PDA strategy” integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.

Costela Lacrimioara Serban,1 Ancuta Mioara Banu,2 Sandra Putnoky,3 Stefania Ioana Butica,4 Mihai Dinu Niculescu,5 Salomeia Putnoky6 1Department of Functional Sciences, University of Medicine and Pharmacy “Victor Babes” Timișoara, Timișoara, Romania; 2Department 2, Maxilo-Facial Surgery Discipline, Faculty of Dental Medicine, University of Medicine and Pharmacy “Victor Babes” Timișoara, Timișoara, Romania; 3Psychiatric Clinic, Emergency Clinical County Hospital, Timișoara, Romania; 4University of Medicine and Pharmacy “Victor Babes” Timișoara, Timișoara, Romania; 5Advanced Nutrigenomics, Cary, NC, 27511, USA; 6Department of Microbiology, University of Medicine and Pharmacy “Victor Babes” Timișoara, Timișoara, RomaniaCorrespondence: Ancuta Mioara BanuDepartment 2, Maxilo-Facial Surgery Discipline, Faculty of Dental Medicine, University of Medicine and Pharmacy “Victor Babes” Timișoara, Take Ionescu Bvd 5, Timi&scedil;oara, 300890, RomaniaTel +40722273268Email banu.ancuta@umft.roPurpose: This study assessed potential differences in estimating short-term dietary intake of energy and nutrients and food consumption, between 4-week food frequency questionnaires (FFQs) and 7-day food records in Romanian adults.Patients and Methods: A total of 116 participants (age range 18– 74 years, 31% males and 28.4% of participants being overweight and obese) were recruited. Estimates for energy and macro- and micronutrient intakes, and food group intakes were compared between the two methods using Wilcoxon-sign-rank test, correlation coefficients, Cohen’s Kappa, Bland–Altman plots with 95% limits of agreement, and quartile classifications.Results: Cohen’s Kappa values for energy and macronutrient intakes indicated moderate agreement, ranging from 0.402 (protein) to 0.470 (fat), fair agreement for most micronutrients (0.2– 0.4) and poor agreement for most food groups (< 0.2). When data were cross-classified into quartiles for energy and macronutrients, about 58% of participants were cross-classified in the same quartile using both methods, while 33% of participants were cross-classified in adjacent quartiles of one method versus the other. Micronutrients (such Na, Mg, Ca, K, Fe, vitamins) had the highest degree of misclassification, on average 40% being cross-classified in the same quartile and another 40% in adjacent quartiles. Bland–Altman plots suggested that both methods were comparable for energy and all macronutrients. When the consumption of food groups was compared, correlation coefficients between methods ranged from 0.09 (legumes) to 0.26 (whole grain), indicating poor correlation.Conclusion: These results showed that the relative match of a standard FFQ, as compared to the 7-day food records, was moderate in estimating macronutrient and energy, fair for most micronutrient intakes and poor for others and as for food groups.Keywords: food-frequency questionnaire, FFQ, validation, adults, dietary assessment, food-record

In daily clinical practice, clinicians integrate available data to ascertain the diagnostic and prognostic probability of a disease or clinical outcome for their patients. For patients with suspected or known cardiovascular disease, several anatomical and functional imaging techniques are commonly performed to aid this endeavor, including coronary computed tomography angiography (CCTA) and nuclear cardiology imaging. Continuous improvement in positron emission tomography (PET), single-photon emission computed tomography (SPECT), and CT hardware and software has resulted in improved diagnostic performance and wide implementation of these imaging techniques in daily clinical practice. However, the human ability to interpret, quantify, and integrate these data sets is limited. The identification of novel markers and application of machine learning (ML) algorithms, including deep learning (DL) to cardiovascular imaging techniques will further improve diagnosis and prognostication for patients with cardiovascular diseases. The goal of this position paper of the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI) is to provide an overview of the general concepts behind modern machine learning-based artificial intelligence, highlights currently prefered methods, practices, and computational models, and proposes new strategies to support the clinical application of ML in the field of cardiovascular imaging using nuclear cardiology (hybrid) and CT techniques.

Pancreatic cancer (PC) is a common cause of cancer-related death, due to difficulties in detecting early-stage disease, to its aggressive behaviour, and to poor response to systemic therapy. Therefore, developing strategies for early diagnosis of resectable PC is critical for improving survival. Diabetes mellitus is another major public health problem worldwide. Furthermore, diabetes can represent both a risk factor and a consequence of PC: nowadays, the relationship between these two diseases is considered a high priority for research. New-onset diabetes can be an early manifestation of PC, especially in a thin adult without a family history of diabetes. However, even if targeted screening for patients at higher risk of PC could be a promising approach, this is not recommended in asymptomatic adults with new-onset diabetes, due to the much higher incidence of hyperglycaemia than PC and to the lack of a safe and affordable PC screening test. Prompted by a well-established and productive multidisciplinary cooperation, the Italian Association of Medical Oncology (AIOM), the Italian Medical Diabetologists Association (AMD), the Italian Society of Endocrinology (SIE), and the Italian Society of Pharmacology (SIF) here review available evidence on the mechanisms linking diabetes and PC, addressing the feasibility of screening for early PC in patients with diabetes, and sharing a set of update statements with the aim of providing a state-of-the-art overview and a decision aid tool for daily clinical practice., Highlights • The incidence of PC is increasing and its prognosis is very poor; therefore, early detection is fundamental. • New-onset diabetes may be an early manifestation of PC, often disappearing after its resection. • Screening for PC is not currently recommended among people with new-onset diabetes, due to its high incidence. • Thin subjects >50 years old at the time of diabetes onset, with sudden weight loss and severe hyperglycaemia are at higher risk. • Currently some clinical models are promising for stratifying cancer risk in people with new-onset diabetes.

© 2021 Sociedade Portuguesa de Cardiologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/), Heart failure (HF) with reduced ejection fraction (HFrEF) is associated with high rates of hospitalization and death. It also has a negative impact on patients' functional capacity and quality of life, as well as on healthcare costs. In recent years, new HFrEF prognosis-modifying drugs have emerged, leading to intense debate within the international scientific community toward a paradigm shift for the management of HFrEF. In this article, we report the contribution of a Portuguese HF expert panel to the ongoing debate. Based on the most recently published clinical evidence, and the panel members' clinical judgment, three key principles are highlighted: (i) sacubitril/valsartan should be preferred as first-line therapy for HFrEF, instead of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker; (ii) the four foundation HFrEF drugs are the angiotensin receptor/neprilysin inhibitor, beta-adrenergic blocking agents, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors, regardless of the presence of type-2 diabetes mellitus; (iii) these four HFrEF drug classes should be introduced over a short-term period of four to six weeks, guided by a safety protocol, followed by a dose up-titration period of 8 weeks., A insuficiência cardíaca (IC) com fração de ejeção reduzida (ICFEr) está associada a níveis elevados de hospitalização e mortalidade. A ICFEr também tem um impacto negativo na capacidade funcional e na qualidade de vida dos doentes, bem como na despesa em saúde. Nos últimos anos, surgiram novos medicamentos modificadores do prognóstico da ICFEr, originando um intenso debate na comunidade científica internacional em relação a uma mudança de paradigma para o tratamento da ICFEr. Neste artigo, relatamos a contribuição de um painel de especialistas portugueses em IC para o debate em curso. Com base na evidência clínica publicada mais recentemente e no julgamento clínico dos membros do painel, três princípios-chave são destacados: (i) sacubitril/valsartan deve ser preferido como terapia de primeira linha para a ICFEr, em vez de um inibidor da enzima de conversão da angiotensina ou um bloqueador do recetor da angiotensina; (ii) os quatro medicamentos básicos para a ICFEr são o inibidor do recetor da angiotensina e da neprilisina, os agentes bloqueadores beta-adrenérgicos, os antagonistas do recetor mineralocorticoide e os inibidores do cotransportador sódio-glucose 2, independentemente da presença de diabetes mellitus tipo 2; (iii) essas quatro classes de medicamentos para a ICFEr devem ser rapidamente introduzidas num período curto de 4-6 semanas, seguindo um protocolo de segurança, e depois tituladas durante as oito semanas seguintes.

Approaches for rapid reviews that focus on streamlining systematic review methods are not always suitable for exploring complex policy questions, as developing and testing theories to explain these complexities requires configuring diverse qualitative, quantitative, and mixed methods studies. Our objective was therefore to provide a guide to selecting approaches for rapidly (i.e., within days to months) addressing complex questions related to health policy and system issues. We provide a two-stage, transdisciplinary collaborative process to select a rapid review approach to address complex policy questions, which consists of scoping the breadth and depth of the literature and then selecting an optimal approach to synthesis. The first stage (scoping the literature) begins with a discussion with the stakeholders requesting evidence to identify and refine the question for the review, which is then used to conduct preliminary searches and conceptually map the documents identified. In the second stage (selection of an optimal approach), further stakeholder consultation is required to refine and tailor the question and approach to identifying relevant documents to include. The approach to synthesizing the included documents is then guided by the final question, the breadth and depth of the literature, and the time available and can include a static or evolving conceptual framework to code and analyze a range of evidence. For areas already covered extensively by existing systematic reviews, the focus can be on summarizing and integrating the review findings, resynthesizing the primary studies, or updating the search and reanalyzing one or more of the systematic reviews. The choice of approaches for conducting rapid reviews is intertwined with decisions about how to manage projects, the amount of work to be done, and the knowledge already available, and our guide offers support to help make these strategic decisions. Supplementary Information The online version contains supplementary material available at 10.1186/s13643-021-01834-y.

The short-term mortality and rehospitalization rates after admission for acute heart failure (AHF) remain high, despite the high level of adherence to contemporary practice guidelines. Observational data from non-randomized studies in AHF strongly support the in-hospital administration of oral evidence-based modifying chronic heart failure (HF) medications (i.e., b-blockers, ACE inhibitors, mineralocorticoid receptor antagonists) to reduce morbidity and mortality. Interestingly, a well-designed prospective randomized multicenter study (PIONEER-HF) showed an improved clinical outcome and stress/injury biomarker profile after in-hospital administration of sacubitril/valsartan (sac/val) as compared to enalapril, in hemodynamically stable patients with AHF. However, sac/val implementation during hospitalization remains suboptimal due to the lack of an integrated individualized plan or well-defined appropriateness criteria for transition to oral therapies, an absence of specific guidelines regarding dose selection and the up-titration process, and uncertainty regarding patient eligibility. In the present expert consensus position paper, clinical practical recommendations are proposed, together with an action plan algorithm, to encourage and facilitate sac/val administration during hospitalization after an AHF episode with the aim of improving efficiencies of care and resource utilization.

Objective The aim of the study was to determine the response rate to a mixed-mode survey using email compared with that to a paper survey in survivors of critical illness. Design This is a prospective randomised controlled trial. Setting The study was conducted at a single-centre quaternary intensive care unit (ICU) in Adelaide, Australia. Participants Study participants were patients admitted to the ICU for ≥48 h and discharged from the hospital. Interventions The participants were randomised to receive a survey by paper (via mail) or via online (via email, or if a non-email user, via a letter with a website address). Patients who did not respond to the initial survey received a reminder paper survey after 14 days. The survey included quality of life (EuroQol-5D-5L), anxiety and depression (Hospital Anxiety and Depression Scale), and post-traumatic symptom (Impact of Event Scale-Revised) assessment. Main outcome measures Survey response rate, extent of survey completion, clinical outcomes at different time points after discharge, and survey cost analysis were the main outcome measures. Outcomes were stratified based on follow-up time after ICU discharge (3, 6, and 12 months). Results A total of 239 patients were randomised. The response rate was similar between the groups (mixed-mode: 78% [92/118 patients] vs. paper: 80% [97/121 patients], p = 0.751) and did not differ between time points of follow-up. Incomplete surveys were more prevalent in the paper group (10% vs 18%). The median EuroQol-5D-5L index value was 0.83 [0.71–0.92]. Depressive symptoms were reported by 25% of patients (46/187), anxiety symptoms were reported by 27% (50/187), and probable post-traumatic stress disorder was reported by 14% (25/184). Patient outcomes did not differ between the groups or time points of follow-up. The cost per reply was AU$ 16.60 (mixed-mode) vs AU$ 19.78 (paper). Conclusion The response rate of a mixed-mode survey is similar to that of a paper survey and may provide modest cost savings.

Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB-BUTINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1H-indazole-3-carbox-amide). ADB-BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB-BUTINACA was detected in SCRA-infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA-infused papers tested between January and July 2021. In this work, ADB-BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono-hydroxylation on the n-butyl tail) and B16 (mono-hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB-4en-PINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-[pent-4-en-1-yl]-1H-indazole-3-carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB-BUTINACA, prevalence has remained low. ADB-4en-PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB-BUTINACA (EC50, 11.5 nM and ADB-4en-PINACA (EC50, 11.6 nM) are similar to that of MDMB-4en-PINACA (EC50, 4.3 nM). A third tert-leucinamide SCRA, ADB-HEXINACA was also detected in prison samples and warrants further investigation. Funding Agencies|Linkopings Universitet; Dubai Police Force [2427681]; Leverhulme TrustLeverhulme Trust [RC-2015-01]; Scottish Prison Service [01865]; Linkoping University; VINNOVAVinnova [2019-03566]; European CommissionEuropean CommissionEuropean Commission Joint Research Centre [E! 113377]

Digital, Background: Hypertension, hyperglycemia, dyslipidemia, overweight, obesity, and tobacco (smoking, chewing, and vaping), together with a pro-inflammatory and procoagulant state, are the main risk factors related to atherosclerotic cardiovascular disease. Objective and methods: A group of experts from the Americas, based on their clinical expertise in cardiology, cardiovascular prevention, and cardiometabolic (CM) diseases, joined together to develop these practical recommendations for the optimal evaluation and treatment of residual CM risk factors in Latin America, using a modified Delphi methodology (details in electronic TSI) to generate a comprehensive CM risk reduction guideline, and through personalized medicine and patient-centered decision, considering the cost-benefit ratio The process was well defined to avoid conflicts of interest that could bias the discussion and recommendations. Results: Residual risk reduction should consider therapeutic options adapted to specific patient needs, based on five treatment objectives: triglyceride-rich lipoproteins, inflammation, impaired glucose metabolism, high blood pressure, and prothrombotic status. Comprehensive control of all CM risk factors should be a priority to deal with this important public health problem and prevent premature deaths. The recommendations in this paper address the evidence-based treatment of CM risk and are intended for clinical application in Latin American countries., Antecedentes: Un grupo de factores de riesgo cardiometabólicos (hipertensión, hiperglucemia, dislipidemia, sobrepeso, obesidad y tabaco (fumado, masticado, vaporizado), junto con un estado proinflamatorio y procoagulante, son los principales factores de riesgo relacionados con la enfermedad cardiovascular aterosclerótica. Objetivo y métodos: Basándose en su experiencia en cardiología, prevención cardiovascular y enfermedades cardiometabólicas, un grupo de expertos de las Américas se unió para desarrollar estas recomendaciones prácticas para la evaluación y tratamiento óptimos de los factores de riesgo cardiometabólicos residuales en América Latina, utilizando una metodología Delphi modificada con el objetivo de generar una guía integral de pautas para la reducción del riesgo cardiometabólico, mediante la medicina personalizada y la decisión centrada en el paciente teniendo en cuenta la relación costo-beneficio. El proceso fue bien definido para evitar conflictos de intereses que podrían sesgar la discusión y las recomendaciones. Resultados: La reducción del riesgo residual debe considerar opciones terapéuticas adaptadas a las necesidades específicas del paciente, basadas en 5 objetivos de tratamiento: lipoproteínas ricas en triglicéridos inflamación, metabolismo de la glucosa, presión arterial alta y estado protrombótico. El Control integral de todos los factores de riesgo cardiometabólicos debe ser una prioridad para hacer frente a este importante problema de salud pública y prevenir las muertes prematuras. Las recomendaciones de este documento abordan el tratamiento basado en evidencia del riesgo cardiometabólico y están destinadas a la aplicación clínica en los países de América Latina., Ciencias Médicas y de la Salud

Despite years of study, controversy remains regarding the optimal graft for anterior cruciate ligament reconstruction (ACLR), suggesting that a single graft type is not ideal for all patients. A large community based ACLR Registry that collects prospective data is a powerful tool that captures information and can be analyzed to optimize surgery for individual patients. The studies highlighted in this paper were designed to optimize and individualize ACLR surgery and have led to changes in surgeon behavior and improvements in patient outcomes. Kaiser Permanente (KP) is an integrated health care system with 10.6 million members and more than 50 hospitals. Every KP member who undergoes an ACLR is entered into the Registry, and prospectively monitored. The Registry uses a variety of feedback mechanisms to disseminate Registry findings to the ACLRR surgeons and appropriately influence clinical practices and enhance quality of care. Allografts were found to have a 3.0 times higher risk of revision than bone-patellar tendon-bone (BPTB) autografts. Allograft irradiation >1.8 Mrad, chemical graft processing, younger patients, BPTB allograft, and male patients were all associated with a higher risk of revision surgery. By providing feedback to surgeons, overall allograft use has decreased by 27% and allograft use in high-risk patients ≤21 years of age decreased 68%. We have identified factors that influence the outcomes of ACLR. Statement of Clinical Significance: We found that information derived from an ACLR Registry and shared with the participating surgeons directly decreased the use of specific procedures and implants associated with poor outcomes.

PURPOSE Generalizability, reproducibility and objectivity are critical elements that need to be considered when translating machine learning models into clinical practice. While a large body of literature has been published on machine learning methods for segmentation of brain tumors, a systematic evaluation of paper quality and reproducibility has not been done. We investigated the use of “Transparent Reporting of studies on prediction models for Individual Prognosis Or Diagnosis” (TRIPOD) items, among papers published in this relatively new and growing field. METHODS According to PRISMA a literature review was performed on four databases, Ovid Embase, Ovid MEDLINE, Cochrane trials (CENTRAL) and Web of science core-collection first in October 2020 and a second time in February 2021. Keywords and controlled vocabulary included artificial intelligence, machine learning, deep learning, radiomics, magnetic resonance imaging, glioma, and glioblastoma. The publications were assessed in order to the TRIPOD items. RESULTS 37 publications from our database search were screened in TRIPOD and yielded an average score of 12.08 with the maximum score being 16 and the minimum score 7. The best scoring item was interpretation (item 19) where all papers scored a point. The lowest scoring items were the title, the abstract, risk groups and the model performance (items number 1, 2, 11 and 16), where no paper scored a point. Less than 1% of the papers discussed the problem of missing data (item 9) and the funding of research (item 22). CONCLUSION TRIPOD analysis showed that a majority of the papers do not score high on critical elements that allow reproducibility, translation, and objectivity of research. An average score of 12.08 (40%) indicates that the publications usually achieve a relatively low score. The categories that were consistently poorly described include the ML network description, measuring model performance, title details and inclusion of information into the abstract.

Purpose of Review Osteoarthritis (OA) is the most common forms of arthritis in the general population, accounting for more pain and functional disability than any other musculoskeletal disease. There are currently no approved disease modifying drugs for OA. In the absence of effective pharmacotherapy, many patients with OA turn to nutritional supplements and nutraceuticals, including collagen derivatives. Collagen hydrolyzates and ultrahydrolyzates are terms used to describe collagens that have been broken down into small peptides and amino acids in the presence of collagenases and high pressure. Recent Findings This article reviews the relevant literature and serves as a White Paper on collagen hydrolyzates and ultrahydrolyzates as emerging supplements often advertised to support joint health in OA. Collagen hydrolyzates have demonstrated some evidence of efficacy in a handful of small scale clinical trials, but their ability to treat and reverse advanced joint disease remains highly speculative, as is the case for other nutritional supplements. Summary The aim of this White Paper is to stimulate research and development of collagen-based supplements for patients with OA and other musculoskeletal diseases at academic and industrial levels. This White Paper does not make any treatment recommendations for OA patients in the clinical context, but simply aims to highlight opportunities for scientific innovation and interdisciplinary collaboration, which are crucial for the development of novel products and nutritional interventions based on the best available and published evidence.

Introduction: Although calcium pyrophosphate deposition (CPPD) is common, there are no published outcome domains or validated measurement instruments for CPPD studies. In this paper, we describe the framework for development of the Outcome Measures in Rheumatology (OMERACT) CPPD Core Domain Sets. Methods: The OMERACT CPPD working group performed a scoping literature review and qualitative interview study. Generated outcomes were presented at the 2020 OMERACT CPPD virtual Special Interest Group (SIG) meeting with discussion focused on whether different core domain sets should be developed for different calcium pyrophosphate deposition (CPPD) clinical presentations and how the future CPPD Core Domain Set may overlap with already established osteoarthritis (OA) domains. These discussions informed development of a future work plan for development of the OMERACT CPPD Core Domain Sets. Findings: Domains identified from a scoping review of 112 studies and a qualitative interview study of 36 people (28 patients with CPPD, 7 health care professionals, one stakeholder) were mapped to core areas of OMERACT Filter 2.1. The majority of SIG participants agreed there was need to develop separate core domain sets for "short term" and "long term" studies of CPPD. Although CPPD + OA is common and core domain sets for OA have been established, participants agreed that existing OA core domain sets should not influence the development of OMERACT core domain sets for CPPD. Prioritization exercises (using Delphi methodology) will consider 40 potential domains for short term studies of CPPD and 47 potential domains for long term studies of CPPD. Conclusion: Separate OMERACT CPPD Core Domain Sets will be developed for "short term" studies for an individ-ual flare of acute CPP crystal arthritis and for "long term" studies that may include participants with any clinical presentation of CPPD (acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and/or CPPD + OA). (c) 2021 Elsevier Inc. All rights reserved.

IntroductionFront-line health workers in remote health facilities are the first contact of the formal health sector and are confronted with life-saving decisions. Health information systems (HIS) support the collection and use of health related data. However, HIS focus on reporting and are unfit to support decisions. Since data tools are paper-based in most primary healthcare settings, we have produced an innovative Paper-based Health Information System in Comprehensive Care (PHISICC) using a human-centred design approach. We are carrying out a cluster randomised controlled trial in three African countries to assess the effects of PHISICC compared with the current systems.Methods and analysisStudy areas are in rural zones of Côte d’Ivoire, Mozambique and Nigeria. Seventy health facilities in each country have been randomly allocated to using PHISICC tools or to continuing to use the regular HIS tools. We have randomly selected households in the catchment areas of each health facility to collect outcomes’ data (household surveys have been carried out in two of the three countries and the end-line data collection is planned for mid-2021). Primary outcomes include data quality and use, coverage of health services and health workers satisfaction; secondary outcomes are additional data quality and use parameters, childhood mortality and additional health workers and clients experience with the system. Just prior to the implementation of the trial, we had to relocate the study site in Mozambique due to unforeseen logistical issues. The effects of the intervention will be estimated using regression models and accounting for clustering using random effects.Ethics and disseminationEthics committees in Côte d’Ivoire, Mozambique and Nigeria approved the trials. We plan to disseminate our findings, data and research materials among researchers and policy-makers. We aim at having our findings included in systematic reviews on health systems interventions and future guidance development on HIS.Trial registration numberPACTR201904664660639; Pre-results.