Determinants of vessel contrast in BMI-adapted low dose CT coronary angiography with prospective ECG-triggering

We evaluated the determinants of vessel contrast in prospectively ECG-triggered CT coronary angiography (CTCA). Seventy patients underwent low-dose CTCA using Body Mass Index (BMI)-adapted tube parameters and a fixed contrast material bolus. Contrast to noise ratio (CNR) was calculated from contrast (between coronaries and perivascular tissue) and image noise (standard deviation of aortic attenuation). Cardiac output (CO) was calculated from gated 99mTc-tetrofosmin-SPECT. Mean radiation dose was 2.13±0.69mSv. Image noise was not affected by BMI (r=0.1, P=0.36), while CNR was inversely related to body surface area (BSA) (r=−0.5, P<0.001) and CO (r=−0.45, P<0.001). After successfully overcoming the impact of BMI on image noise by adapting tube parameters, CNR mainly depends on coronary vessel contrast. The latter reflects the dilution of the contrast material by blood volume and CO, which are both correlated to BSA. Therefore, BSA adapted contrast administration may help to compensate for this effec

Transcatheter Closure of Paravalvular Defects Using a Purpose-Specific Occluder

ObjectivesThis study sought to describe a method of paravalvular leak closure using a purpose-specific occlusion device.BackgroundTranscatheter closure of paravalvular leaks has been hampered by technical challenges, the limitations of available imaging modalities, and the lack of closure devices specifically designed for this purpose.MethodsPatients with severe symptomatic paravalvular regurgitation at high risk for repeat surgery underwent transcatheter leak closure. Both left ventricular puncture and retrograde transfemoral approaches were used with fluoroscopic and 3-dimensional transesophageal guidance. A purpose-specific occluder (Vascular Plug III, AGA Medical Corp., Plymouth, Minnesota) was used.ResultsFive patients with severe prosthetic mitral and aortic paravalvular leaks underwent attempted closure. Implantation of the device was successfully accomplished in all. In 1 patient, the plug interfered with closure of a mechanical valve leaflet and was removed and replaced with an alternate device. Complications included pericardial bleeding in 2 patients with a transapical approach. There was no procedural mortality. At a median follow-up of 191 days (interquartile range [IQR] 169 to 203 days) all patients were alive. New York Heart Association functional class fell from 4 (IQR 3 to 4) to 2 (IQR 2 to 3), hemoglobin rose from 89 g/l (IQR 87 to 108 g/l) to 115 g/l (IQR 104 to 118 g/l), creatinine fell from 109 μmol/l (IQR 106 to 132 μmol/l) to 89 μmol/l (IQR 89 to 126 μmol/l). Median echocardiographic follow-up at 58 days (IQR 56 to 70 days) reported residual regurgitation to be reduced from grade 4 to grade 2 (IQR 1.5 to 2.25).ConclusionsClosure of mitral and aortic prosthetic paravalvular leaks with the Vascular Plug III using either a transapical (mitral) or a retrograde (aortic) approach appears promising

Outcome of Patients After Transcatheter Aortic Valve Embolization

ObjectivesThis study aims to assess the mid- to long-term follow-up of patients after valve embolization at the time of transcatheter aortic valve implantation (TAVI).BackgroundTranscatheter heart valve (THV) embolization is a rare but serious complication during TAVI. Although various techniques have been developed to manage acute complications and reduce periprocedural morbidity/mortality, long-term clinical and hemodynamic consequences after these events are unknown.MethodsPatients who developed THV embolization after TAVI were prospectively assessed. Clinical and echocardiographic characteristics were recorded at baseline and after successful TAVI/surgical aortic valve replacement. The THV migration and strut fractures/degeneration were assessed by computed tomography.ResultsA total of 7 patients had THV embolization, all of which occurred immediately after valve deployment. The embolized THV was repositioned in the aortic arch proximal to the left subclavian artery (n = 2), immediately distal to the left subclavian artery (n = 2), and in the abdominal aorta (n = 3). A second THV was implanted successfully at the same sitting in 4 patients and at the time of a second procedure in 2 patients. Elective conventional aortic valve replacement was performed in 1 patient. Median follow-up was 1,085 days. One patient died during follow-up from an unrelated cause. The remaining 6 survivors were in New York Heart Association functional class I or II at final follow-up. Mid-term computed tomography follow-up (n = 4,591 to 1,548 days) showed that the leaflets of the embolized THV remain open in all phases of the cardiac cycle. There was also no strut fracture or migration of these valves.ConclusionsClinical outcomes remain good when THV embolization is managed effectively. There are no apparent hemodynamic consequences of a second valve placed in the series. These embolized valves remain in a stable position with no evidence of strut fractures at mid-term follow-up

How COVID-19 changed clinical research strategies: a global survey

Objective Clinical research has faced new challenges during the COVID-19 pandemic, leading to excessive operational demands affecting all stakeholders. We evaluated the impact of COVID-19 on clinical research strategies and compared different adaptations by regulatory bodies and academic research institutions in a global context, exploring what can be learned for possible future pandemics. Methods We conducted a cross-sectional online survey and identified and assessed different COVID-19-specific adaptation strategies used by academic research institutions and regulatory bodies. Results All 19 participating academic research institutions developed and followed similar strategies, including preventive measures, manpower recruitment, and prioritisation of COVID-19 projects. In contrast, measures for centralised management or coordination of COVID-19 projects, project preselection, and funding were handled differently amongst institutions. Regulatory bodies responded similarly to the pandemic by implementing fast-track authorisation procedures for COVID-19 projects and developing guidance documents. Quality and consistency of the information and advice provided was rated differently amongst institutions. Conclusion Both academic research institutions and regulatory bodies worldwide were able to cope with challenges during the COVID-19 pandemic by developing similar strategies. We identified some unique approaches to ensure fast and efficient responses to a pandemic. Ethical concerns should be addressed in any new decision-making process

European survey on national harmonization in clinical research

Background: Clinical trials remain key to the development of evidence-based medical practice. However, they are becoming increasingly complex, mainly in a multinational setting. To address these challenges, the European Union (EU) adopted the Clinical Trial Regulation EU No. 536/2014 (CTR). Once in force, the CTR will lead to more consistent rules and simplification of procedures for conducting clinical trials through-out the EU. Existing harmonization initiatives and “research infrastructures” for clinical trials may facilitate this process. This publication offers a snapshot of the current level of harmonization activities in academic clinical research in Europe. Methods: A survey was performed among the member and observer countries of the European Clinical Research Infrastructure Network (ECRIN), using a standardizedpublishersversionpublishe

Evolution to a Competency-Based Training Curriculum for Pharmaceutical Medicine Physicians in Switzerland

In Switzerland, Pharmaceutical Medicine has existed as one of 46 physician specialties accredited by the Federal Office of Public Health for more than 20 years. As a medical-scientific discipline, our goal is to enable best possible therapeutic coverage for the benefit of patients and society through a medical need-based development and optimal use of medicinal products. The role of the specialist in Pharmaceutical Medicine is to closely collaborate with various stakeholders of the healthcare system in the context of the discovery, research, development and approval of new medicinal products, as well as safe and effective use of new and established medicinal products in daily clinical practice. The post-graduate training consists of 2 years of patient-related clinical work, followed by 3 years of vocational training at certified training centers in Pharmaceutical Medicine. This also includes completion of an academic post-graduate diploma in Pharmaceutical Medicine (30 ECTS) according to the IFAPP/PharmaTrain syllabus and a 1 day board exam. As part of an ongoing revision of the training curriculum, we are developing a Swiss Catalog of Core Competencies in Pharmaceutical Medicine (SC3-PM), based on the IFAPP competency framework for drug development specialists in industry. In this article we discuss how we adapt the scope of the IFAPP competency framework to better reflect such roles in academic institutions or regulatory bodies in Switzerland

miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components

In animals, microRNAs (miRNAs) generally repress gene expression by binding to sites in the 3′-untranslated region (UTR) of target mRNAs. miRNAs have also been reported to repress or activate gene expression by binding to 5′-UTR sites, but the extent of such regulation and the factors that govern these different responses are unknown. Liver-specific miR-122 binds to sites in the 5′-UTR of hepatitis C virus (HCV) RNA and positively regulates the viral life cycle, in part by stimulating HCV translation. Here, we characterize the features that allow miR-122 to activate translation via the HCV 5′-UTR. We find that this regulation is a highly specialized process that requires uncapped RNA, the HCV internal ribosome entry site (IRES) and the 3′ region of miR-122. Translation activation does not involve a previously proposed structural transition in the HCV IRES and is mediated by Argonaute proteins. This study provides an important insight into the requirements for the miR-122–HCV interaction, and the broader consequences of miRNAs binding to 5′-UTR sites

Associations Between Eczema and Attention Deficit Hyperactivity Disorder Symptoms in Children

Background: Epidemiological studies suggest a link between eczema and attention deficit hyperactivity disorder (ADHD), but underlying mechanisms have not been examined.Objective: We aim to investigate the association between eczema and subsequent ADHD symptoms in the Growing Up in Singapore Towards healthy Outcomes cohort and explore the role of pro-inflammatory cytokines and gut microbiome.Methods: The modified International Study of Asthma and Allergies in Childhood questionnaire and Computerized Diagnostic Interview Schedule for Children Version IV were administered to assess reported eczema within the first 18 months and presence of ADHD symptoms at 54 months, respectively. Skin prick testing at 18 months, cytokines in maternal blood during pregnancy and cord blood and the mediating role of the gut microbiome at 24 months were assessed.Results: After adjusting for confounders, eczema with or without a positive skin prick test was associated with doubling the risk of ADHD symptoms. No differences in maternal and cord blood cytokines were observed in children with and without eczema, or children with and without ADHD. Gut microbiome dysbiosis was observed in children with eczema and children with ADHD. Children with eczema also had lower gut bacterial Shannon diversity. However, the relationship between eczema and ADHD was not mediated by gut microbiome.Conclusion: Early life eczema diagnosis is associated with a higher risk of subsequent ADHD symptoms in children. We found no evidence for underlying inflammatory mechanism or mediation by gut microbiome dysbiosis. Further research should evaluate other mechanisms underlying the link between eczema and ADHD.Peer reviewe

Legal and ethical framework for global health information and biospecimen exchange - an international perspective.

BACKGROUND: The progress of electronic health technologies and biobanks holds enormous promise for efficient research. Evidence shows that studies based on sharing and secondary use of data/samples have the potential to significantly advance medical knowledge. However, sharing of such resources for international collaboration is hampered by the lack of clarity about ethical and legal requirements for transfer of data and samples across international borders. MAIN TEXT: Here, the International Clinical Trial Center Network (ICN) reports the legal and ethical requirements governing data and sample exchange (DSE) across four continents. The most recurring requirement is ethical approval, whereas only in specific conditions approval of national health authorities is required. Informed consent is not required in all sharing situations. However, waiver of informed consent is only allowed in certain countries/regions and under certain circumstances. The current legal and ethical landscape appears to be very complex and under constant evolution. Regulations differ between countries/regions and are often incomplete, leading to uncertainty. CONCLUSION: With this work, ICN illuminates the unmet need for a single international collaborative framework to facilitate DSE. Harmonising requirements for global DSE will reduce inefficiency and waste in research. There are many challenges to realising this ambitious vision, including inconsistent terminology and definitions, and heterogeneous and dynamic legal constraints. Here, we identify areas of agreement and significant difference as a necessary first step towards facilitating international collaboration. We propose the establishment of a working group to continue the comparison across jurisdictions, create a standardised glossary and define a set of basic principles and fundamental requirements for DSE