Prognos (R) in the diagnosis of amalgam hypersensitivity - A diagnostic case-control study

Objective: We aimed to investigate whether the Prognos (R) device might be a useful tool in the diagnosis of disorders suspected to be due to dental amalgam fillings. Participants and Methods: A diagnostic case-control study was performed in 27 patients who complained about health problems attributed to amalgam ( cases), 27 healthy volunteers with amalgam fillings ( controls I), and 27 healthy amalgam-free volunteers ( controls II). All participants were tested before and after application of 300 mg DMPS (2.3-dimercapto-1-propanesulfonic acid) with Prognos, a diagnostic device for the energetic measurement of Traditional Chinese Medicine meridians. In addition, mercury was measured in blood, urine, and saliva, and a lymphocyte transformation test (LTT) was performed. Results: Diagnoses derived from the first and second Prognos testing did not agree above chance (Cohen's Kappa = -0.11, 95% confidence interval -0.33 to 0.10; p = 0.30). Agreement for secondary outcome measures was poor, too. Prognos measurements did not differ between cases and controls. Correlations with measurements in urine, blood and saliva were low. Conclusion: In this study Prognos could not be shown to be a useful tool in the diagnosis of disorders suspected to be due to dental amalgam fillings

Improving lipid management in patients with acute coronary syndrome : The ACS Lipid EuroPath tool

Post-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. In 2018, the ACS EuroPath Survey, performed in collaboration with 555 European cardiologists, identified a sub-optimal LDL-C management in post-ACS patients. Based on these premises, the ACS EuroPath II project led to the development of a self-assessment tool to improve lipid management in these very high risk patients, taking into consideration the new 2019 ESC/EAS guidelines. This tool is built in 3 sections. The first is a questionnaire to assess the lipid management practice from the acute phase up to 12 months of follow-up. The main topics covered in this section relate to 1) acute phase (lipid management of ACS patients during hospitalization; 2) discharge (lipid management at discharge, with focus on follow-up plan); 3) follow-up (lipid management at the time of first and subsequent follow-ups); 4) referral pathway for definitive lipid management care of post-ACS patients; 5) evaluation of the achieved goal at 6 months to 1 year and key implications. The second section is a brief report to position the results against other European Union clinical practice and European guidelines. The last section allows the physician to evaluate and consider the implementation of one or more strategies, successfully developed in leading European centers, in order to optimize their own clinical practice

The effect of the 2019 ESC/EAS dyslipidaemia guidelines on low-density lipoprotein cholesterol goal achievement in patients with acute coronary syndromes: the ACS EuroPath IV project

AimsTo evaluate the effect of the ESC/EAS 2019 dyslipidaemia guidelines on patient management of lipid-lowering therapy in patients with acute coronary syndrome (ACS), through a survey designed to compare post-ACS patient management in 2022 with that in 2018.MethodsOnline questionnaires focused on lipid profile and medications were used to gather data from 2650 ACS patients in 6 European countries, treated between March–June 2022 (ACS EuroPath IV survey). These data were compared with data collected from 2650 patients who participated in the ACS EuroPath I survey (conducted in 2018).ResultsLipid testing was performed in 90% of patients and was done sooner after admission in 2022 versus 2018 (mean 1.4 vs 1.7 days). Increased testing for non-HDL-C, lipoprotein(a), and ApoB was observed over time. At discharge, most patients (≥90%) were receiving lipid-lowering therapy. Prescribing patterns differed, with a higher proportion of patients receiving statin plus ezetimibe combination therapy in 2022 versus 2018 (34% vs 13%). LDL-C levels were lower in 2022 versus 2018 at admission and at 1st, 2nd and 3rd post-discharge follow-up points. More patients achieved low-density lipoprotein cholesterol (LDL-C) goals in 2022 versus 2018 at the first follow-up (average 14 vs 16 weeks since discharge; ConclusionLDL-C goal achievement has improved since the release of the 2019 guidelines, but lipid management in post-ACS patients remains suboptimal.Cardiolog

Stories can change the world – citizen science communication in practice

Citizen science, the active participation of the public in scientific research projects, is a rapidly expanding field in open science and open innovation. It provides an integrated model of public knowledge production and engagement with science. As a growing worldwide phenomenon, it is invigorated by evolving new technologies that connect people easily and effectively with the scientific community. Catalysed by citizens’ wishes to be actively involved in scientific processes, as a result of recent societal trends, it also offers contributions to the rise in tertiary education. In addition, citizen science provides a valuable tool for citizens to play a more active role in sustainable development. This book identifies and explains the role of citizen science within innovation in science and society, and as a vibrant and productive science-policy interface. The scope of this volume is global, geared towards identifying solutions and lessons to be applied across science, practice and policy. The chapters consider the role of citizen science in the context of the wider agenda of open science and open innovation, and discuss progress towards responsible research and innovation, two of the most critical aspects of science today

Emergence of 3D Printed Dosage Forms: Opportunities and Challenges

The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such as extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, including design flexibility and control and manufacture which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry

Embracing open innovation to acquire external ideas and technologies and to transfer internal ideas and technologies outside

The objective of this dissertation is to increase understanding of how organizations can embrace open innovation in order to acquire external ideas and technologies from outside the organization, and to transfer internal ideas and technologies to outside the organization. The objective encompasses six sub-objectives, each addressed in one or more substudies. Altogether, the dissertation consists of nine substudies and a compendium summarizing the substudies. An extensive literature review was conducted on open innovation and crowdsourcing literature (substudies 1–4). In the subsequent empirical substudies, both qualitative research methods (substudies 5–7) and quantitative research methods (substudies 8–9) were applied. The four literature review substudies provided insights on the body of knowledge on open innovation and crowdsourcing. These substudies unveiled most of the influential articles, authors, and journals of open innovation and crowdsourcing disciplines. Moreover, they identified research gaps in the current literature. The empirical substudies offer several insightful findings. Substudy 5 shows how non-core ideas and technologies of a large firm can become valuable, especially for small firms. Intermediary platforms can find solutions to many pressing problems of large organizations by engaging renowned scientists from all over world (substudy 6). Intermediary platforms can also bring breakthrough innovations with novel mechanisms (substudy 7). Large firms are not only able to garner ideas by engaging their customers through crowdsourcing but they can also build long-lasting relations with their customers (substudies 8 and 9). Embracing open innovation brings challenges for firms too. Firms need to change their organizational structures in order to be able to fully benefit from open innovation. When crowdsourcing is successful, it produces a very large number of new ideas. This has the consequence that firms need to allocate a significant amount of resources in order to identify the most promising ideas. In an idea contest, customarily, only one or a few best ideas are rewarded (substudy 7). Sometimes, no reward is provided for the selected idea (substudies 8 and 9). Most of the ideas that are received are not implemented in practice

A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety

Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAF(cases) = 0.431, MAF(controls) = 0.368) upstream of MIR579 was associated with panic disorder in patients (p(allelic) = 0.004, n(cases) = 506, n(controls) = 506) and with higher trait anxiety in healthy individuals (p(ASI) = 0.029, p(ACQ) = 0.047, n = 3112). Compared to the major (A)allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%