Evaluating Artificial Intelligence in Clinical Settings-Let Us Not Reinvent the Wheel.

Given the requirement to minimize the risks and maximize the benefits of technology applications in health care provision, there is an urgent need to incorporate theory-informed health IT (HIT) evaluation frameworks into existing and emerging guidelines for the evaluation of artificial intelligence (AI). Such frameworks can help developers, implementers, and strategic decision makers to build on experience and the existing empirical evidence base. We provide a pragmatic conceptual overview of selected concrete examples of how existing theory-informed HIT evaluation frameworks may be used to inform the safe development and implementation of AI in health care settings. The list is not exhaustive and is intended to illustrate applications in line with various stakeholder requirements. Existing HIT evaluation frameworks can help to inform AI-based development and implementation by supporting developers and strategic decision makers in considering relevant technology, user, and organizational dimensions. This can facilitate the design of technologies, their implementation in user and organizational settings, and the sustainability and scalability of technologies.

CHRISTMAS: Chiral Pair Isobaric Labeling Strategy for Multiplexed Absolute Quantitation of Enantiomeric Amino Acids.

Amino acids (AAs) in the d-form are involved in multiple pivotal neurological processes, although their l-enantiomers are most commonly found. Mass spectrometry-based analysis of low-abundance d-AAs has been hindered by challenging enantiomeric separation from l-AAs, low sensitivity for detection, and lack of suitable internal standards for accurate quantification. To address these critical gaps, N,N-dimethyl-l-leucine (l-DiLeu) tags are first validated as novel chiral derivatization reagents for chromatographic separation of 20 pairs of d/l-AAs, allowing the construction of a 4-plex isobaric labeling strategy for enantiomer-resolved quantification through single step tagging. Additionally, the creative design of N,N-dimethyl-d-leucine (d-DiLeu) reagents offers an alternative approach to generate analytically equivalent internal references of d-AAs using d-DiLeu-labeled l-AAs. By labeling cost-effective l-AA standards using paired d- and l-DiLeu, this approach not only enables absolute quantitation of both d-AAs and l-AAs from complex biological matrices with enhanced precision but also significantly boosts the combined signal intensities from all isobaric channels, greatly improving the detection and quantitation of low-abundance AAs, particularly d-AAs. We term this quantitative strategy CHRISTMAS, which stands for chiral pair isobaric labeling strategy for multiplexed absolute quantitation. Leveraging the ion mobility collision cross section (CCS) alignment, interferences from coeluting isomers/isobars are effectively filtered out to provide improved quantitative accuracy. From wild-type and Alzheimer's disease (AD) mouse brains, we successfully quantified 20 l-AAs and 5 d-AAs. The significant presence and differential trends of certain d-AAs compared to those of their l-counterparts provide valuable insights into the involvement of d-AAs in aging, AD progression, and neurodegeneration.

Increased expression of SLC25A1/CIC causes an autistic-like phenotype with altered neuron morphology.

N ε-lysine acetylation within the lumen of the endoplasmic reticulum is a recently characterized protein quality control system that positively selects properly folded glycoproteins in the early secretory pathway. Overexpression of the endoplasmic reticulum acetyl-CoA transporter AT-1 in mouse forebrain neurons results in increased dendritic branching, spine formation and an autistic-like phenotype that is attributed to altered glycoprotein flux through the secretory pathway. AT-1 overexpressing neurons maintain the cytosolic pool of acetyl-CoA by upregulation of SLC25A1, the mitochondrial citrate/malate antiporter and ATP citrate lyase, which converts cytosolic citrate into acetyl-CoA. All three genes have been associated with autism spectrum disorder, suggesting that aberrant cytosolic-to-endoplasmic reticulum flux of acetyl-CoA can be a mechanistic driver for the development of autism spectrum disorder. We therefore generated a SLC25A1 neuron transgenic mouse with overexpression specifically in the forebrain neurons. The mice displayed autistic-like behaviours with a jumping stereotypy. They exhibited increased steady-state levels of citrate and acetyl-CoA, disrupted white matter integrity with activated microglia and altered synaptic plasticity and morphology. Finally, quantitative proteomic and acetyl-proteomic analyses revealed differential adaptations in the hippocampus and cortex. Overall, our study reinforces the connection between aberrant cytosolic-to-endoplasmic reticulum acetyl-CoA flux and the development of an autistic-like phenotype.

A commitment to marginalized children in the European Union: The hope and challenges of the EU Child Guarantee.

While children in general are usually seen as a societal priority, many children are disadvantaged by marginalization, with adverse effects on health and development. Following feasibility studies, the European Commission has now adopted a formal Child Guarantee of service access. This paper links the Feasibility Studies to other reports on the need to address marginalized and institutionalized children. The problems in identifying and quantifying such children are outlined, as are the challenges of planning for these groups of children and the difficulty of finding universal definitions and data. This European Union initiative is timely, given that around a quarter of European children are marginalized, while the effects of Covid-19 will add to this marginalization.

European Union Child Guarantee-challenges raised by the welcome promise of free healthcare for marginalized children.

BACKGROUND: Children are dependent on the way in which society provides healthcare, with primary and preventive care being initial components. They also have a generally acclaimed right to health, and to lack of impediment to access to healthcare. In a major initiative, the European Parliament has proposed a Child Guarantee to include free access to healthcare for marginalized children, and a Feasibility Study has been completed with positive results. However, there has been little analysis of national policies toward free access to healthcare for children, including longer-term treatment, mental health or adolescent health services, or of charges and indirect financial barriers to access. METHODS: Data on policies for children's access to healthcare from two recent European Community wide studies were re-analyzed and matched. Primary care, immunization, surveillance screening, minor illness, a more significant medium-term condition, and reproductive health were included. Additionally, data from a European survey of children reported as having unmet medical needs were revisited. Composite summaries relating to all 28 EU countries as of 2019 were produced. RESULTS: Only three EU-28 countries provided totally free services, though 26 countries provide free primary and preventive services. There is evidence of some children having unmet medical needs in 21 countries, with Expense being the main quoted factor. CONCLUSION: There is widespread variation across Europe in free access for children to healthcare, little comparative study of policies and their effects on enabling or hindering access, and minimal data collection. This compromises achievement of the Guarantee, and initiatives are needed.

Tailored communication methods as key to implementation of evidence-based solutions in primary child health care.

BACKGROUND: Evidence-based policies should underpin successful implementation of innovations within child health care. The EU-funded Models of Child Health Appraised project enabled research into effective methods to communicate research evidence. The objective of this study was to identify and categorize methods to communicate evidence-based research recommendations and means to tailor this to stakeholder audiences. METHODS: We conducted an online survey among national stakeholders in child health. Analysis of the most effective strategies to communicate research evidence and reach the target audience was carried out in order to ensure implementation of optimal child health care models at a national level. RESULTS: Representatives of stakeholders from 21 of the then 30 EU MS and EEA countries responded to the questionnaire. Three main approaches in defining the strategies for effective communication of research recommendations were observed, namely: dissemination of information, involvement of stakeholders and active attitude towards change expressed in actions. The target audience for communicating recommendations was divided into two layers: proximal, which includes those who are remaining in close contact with the child, and distal, which contains those who are institutionally responsible for high quality of child health services. They should be recipients of evidence-based results communicated by different formats, such as scientific, administrative, popular and personal. CONCLUSIONS: Influential stakeholders impact the process of effective research dissemination and guide necessary actions to strengthen the process of effective communication of recommendations. Communication of evidence-based results should be targeted to each audience's profile, both professional and non-professionals, by adjusting appropriate communication formats.

Factors influencing the uptake of evidence in child health policy-making: results of a survey among 23 European countries.

BACKGROUND: The ability to successfully transfer knowledge across international boundaries to improve health across the European Region is dependent on an in-depth understanding of the many factors involved in policy creation. Across countries we can observe various approaches to evidence usage in the policy-making process. This study, which was a part of the Models of Child Health Appraised (MOCHA) project assessing patterns of children's primary care in Europe, focused on how and what kind of evidence is used in child health policy-making processes in European countries and how it is applied to inform policy and practice. METHOD: In this study, a qualitative approach was used. The data were analysed in accordance with the thematic analysis protocol. The MOCHA project methodology relies on experienced country agents (CA) recruited for the project and paid to deliver child health data in each of 30 European countries. CAs are national experts in the child health field who defined the country-specific structured information and data. A questionnaire designed as a semi-structured survey instrument asked CAs to indicate the sources of evidence used in the policy-making process and what needed to be in place to support evidence uptake in policy and practice. RESULTS: In our data we observed two approaches to evidence usage in child health policy formulation. The scientific approach in our understanding refers to the so-called bottom-up initiatives of academia which identify and respond to the population's needs. Institutional approaches can be informed by scientific resources as well; however, the driving forces here are governmental institutions, whose decisions and choices are based not only on the population needs but also on political, economic and organizational factors. The evidence used in Europe can also be of an external or internal nature. Various factors can affect the use of evidence in child health policy-making. Facilitators are correlated with strong scientific culture development, whereas barriers are defined by a poor tradition of implementing changes based on reliable evidence. CONCLUSIONS: Focusing on the facilitators and actively working to reduce the barriers can perceivably lead to faster and more robust policy-making, including the development of a culture of scientific grounding in policy creation.

After the European Global Vaccination Summit-The need for practical policies to boost vaccination delivery to children in Europe.

BACKGROUND: Low childhood vaccination rates in Europe continue to cause concern and have triggered much policy study. However, regarding children, making immunisation a stand-alone issue cuts across integrated child health services. Most initiatives, including the 10 Action Points from the 2019 European-hosted Global Vaccination Summit, are all laudable but high level enablement policies. Delivery processes have been ignored, and key stakeholders not involved in discussions. METHODS: Reviews of policies, literature and planned actions, leading to identification of further delivery policies needed to facilitate and stimulate practical accomplishments. RESULTS: 10 aspects are identified where European coordinated action to develop policies, share evidence and increase standards, would be beneficial. These also fit in with established European Commission strengths, and the incoming Commission's policies and priorities. CONCLUSION: The European Commission, Member States and child health stakeholders should pursue a holistic approach, taking immunisation as a component of integrated child health. Service delivery should be compatible with modern societal challenges and related parenting patterns, and public health processes modernised and reinvigorated. Nursing and societal stakeholders should be brought in, and fit-for-purpose digital support facilitated. This is even more urgent following the diversion of the Covid-19 pandemic.

The endoplasmic reticulum acetyltransferases ATase1/NAT8B and ATase2/NAT8 are differentially regulated to adjust engagement of the secretory pathway.

Nε-lysine acetylation of nascent glycoproteins within the endoplasmic reticulum (ER) lumen regulates the efficiency of the secretory pathway. The ER acetylation machinery consists of the membrane transporter, acetyl-CoA transporter 1 (AT-1/SLC33A1), and two acetyltransferases, ATase1/NAT8B and ATase2/NAT8. Dysfunctional ER acetylation is associated with severe neurological diseases with duplication of AT-1/SLC33A1 being associated with autism spectrum disorder, intellectual disability, and dysmorphism. Neuron-specific AT-1 over-expression in the mouse alters neuron morphology and function, causing an autism-like phenotype, indicating that ER acetylation plays a key role in neurophysiology. As such, characterizing the molecular mechanisms that regulate the acetylation machinery could reveal critical information about its biology. By using structure-biochemistry approaches, we discovered that ATase1 and ATase2 share enzymatic properties but differ in that ATase1 is post-translationally regulated via acetylation. Furthermore, gene expression studies revealed that the promoters of AT-1, ATase1, and ATase2 contain functional binding sites for the neuron-related transcription factors cAMP response element-binding protein and the immediate-early genes c-FOS and c-JUN, and that ATase1 and ATase2 exhibit additional modes of transcriptional regulation relevant to aging and Alzheimer's disease. In vivo rodent gene expression experiments revealed that Atase2 is specifically induced following activity-dependent events. Finally, over-expression of either ATase1 or ATase2 was sufficient to increase the engagement of the secretory pathway in PC12 cells. Our results indicate important regulatory roles for ATase1 and ATase2 in neuron function with induction of ATase2 expression potentially serving as a critical event that adjusts the efficiency of the secretory pathway for activity-dependent neuronal functions.

Child health research and planning in Europe disadvantaged by major gaps and disparities in published statistics.

BACKGROUND: Population data, such as mortality and morbidity statistics, are essential for many reasons, including giving context for research, supporting action on health determinants, formulation of evidence-based policy for health care and outcome evaluation. However, when considering children, it is difficult to find such data, despite children comprising one-fifth of the European population and being in a key formative life stage and dependent on societal support. Moreover, it would be expected that there should be confidence in the key child health data available, with little to no discrepancy between recognized health statistic databases. METHODS: This study explored the main health databases in or including Europe to collate child mortality data, for both all-cause and specific-cause mortality. Tables were constructed for comparison of values and rankings. RESULTS: The results show that there are major differences in reported mortality data between two prominent health statistic databases, difference in coding systems, and unannounced changes within one of the databases. CONCLUSIONS: The lack of health data for children seems compounded by challenges to the trust and credibility, which are vital if these data are to have utility. Children and society are the losers, and resolution is needed as a priority.

European Union initiatives in child immunization-the need for child centricity, e-health and holistic delivery.

BACKGROUND: Low childhood immunization rates in Europe are causing concern and have triggered several EU initiatives. However, these are counter-factual as they make immunization a stand-alone issue and cut across best practice in integrated child health services. They also focus unduly on 'anti-vax' pressures, generalize 'vaccine hesitancy' and overlook practical difficulties and uncertainties encountered by parents in real world situations about presenting children for immunization. Meanwhile European expertize in child health electronic record systems and relevant standards are ignored despite their being a potentially sound foundation ripe for enhancement. METHODS: Situation and literature reviews, and cohesion of two European research projects, led to shared investigation. As a result, two cross-sectoral expert workshops were held to consider digital health standards for harmonizing integrated preventive child health including immunization, and the work of other stakeholders such as the World Health Organisation and the European Centre for Disease Control. RESULTS: Progress in child health information models and digital health standards was assessed, areas needing further standards development identified and desirable steps towards innovation in service delivery and record keeping agreed. CONCLUSION: The European Commission, member states and child health stakeholders should take an integrated approach to child health with immunization as a component. Service delivery should be sensitive to parental concerns and challenges, and the way child- and family-centric data are recorded and used should be enhanced. Services should be enabled by the International Patient Summary and related electronic health record standards and linkages, and evaluated to assess most effective systems and practice.

Potentially over 3 million children in EU Europe believed not to be receiving needed medical and dental treatment-and parents' reasons why.

BACKGROUND: Children have the right to health and countries a duty under the United Nations Convention on the Rights of the Child to facilitate this. The European Union has emphasized the importance of investing in children, but at times this seems more wish than pragmatism. Furthermore, European statistical systems do not provide any relevant data, and the degree of unmet need has hitherto been unknown. However, new ad hoc household survey data have now been published by Eurostat showing the percentage of children with a purported unmet medical or dental need and the expressed reasons for this. METHOD: This paper critically reviews these data on children with a reported unmet medical or dental need to create an indication of the number of European children with unmet medical and dental needs, and the contributory factors. RESULTS: This paper calculates that some 1 million European children can be estimated to have an unmet medical need and 2 million children an unmet dental need, though the survey approach has some weaknesses. A probable overestimate of children affected in sample households offsets the likely failure to capture data about children in institutions, homeless, or in fractured families, or about multiple needs. The reported reasons for not obtaining treatments are a valuable first step in highlighting an important issue for Europe's children-measurement of service accessibility. CONCLUSION: Potentially over 3 million European Union children are failing to have their health needs and their rights met. If the incoming European Commission is serious about its predecessor's promise to invest in children and to take seriously their rights, action is needed to improve quantification of unmet need and to reduce suffering and potential lasting damage.

CACHD1 is an α2δ-Like Protein That Modulates CaV3 Voltage-Gated Calcium Channel Activity.

The putative cache (Ca2+ channel and chemotaxis receptor) domain containing 1 (CACHD1) protein has predicted structural similarities to members of the α2δ voltage-gated Ca2+ channel auxiliary subunit family. CACHD1 mRNA and protein were highly expressed in the male mammalian CNS, in particular in the thalamus, hippocampus, and cerebellum, with a broadly similar tissue distribution to CaV3 subunits, in particular CaV3.1. In expression studies, CACHD1 increased cell-surface localization of CaV3.1, and these proteins were in close proximity at the cell surface, consistent with the formation of CACHD1-CaV3.1 complexes. In functional electrophysiological studies, coexpression of human CACHD1 with CaV3.1, CaV3.2, and CaV3.3 caused a significant increase in peak current density and corresponding increases in maximal conductance. By contrast, α2δ-1 had no effect on peak current density or maximal conductance in CaV3.1, CaV3.2, or CaV3.3. A comparison of CACHD1-mediated increases in CaV3.1 current density and gating currents revealed an increase in channel open probability. In hippocampal neurons from male and female embryonic day 19 rats, CACHD1 overexpression increased CaV3-mediated action potential firing frequency and neuronal excitability. These data suggest that CACHD1 is structurally an α2δ-like protein that functionally modulates CaV3 voltage-gated calcium channel activity.SIGNIFICANCE STATEMENT This is the first study to characterize the Ca2+ channel and chemotaxis receptor domain containing 1 (CACHD1) protein. CACHD1 is widely expressed in the CNS, in particular in the thalamus, hippocampus, and cerebellum. CACHD1 distribution is similar to that of low voltage-activated (CaV3, T-type) calcium channels, in particular to CaV3.1, a protein that regulates neuronal excitability and is a potential therapeutic target in conditions such as epilepsy and pain. CACHD1 is structurally an α2δ-like protein that functionally increases CaV3 calcium current. CACHD1 increases the presence of CaV3.1 at the cell surface, forms complexes with CaV3.1 at the cell surface, and causes an increase in channel open probability. In hippocampal neurons, CACHD1 causes increases in neuronal firing. Thus, CACHD1 represents a novel protein that modulates CaV3 activity.

Contextual determinants of CHILDREN'S health care and policy in Europe.

BACKGROUND: The main objective of this study was to explore the contextual determinants of child health policies. METHODS: The Horizon 2020 Models of Child Health Appraised (MOCHA) project has one Country Agent (CA) in all 30 EU and EEA countries. A questionnaire designed by MOCHA researchers as a semi-structured survey instrument asked CAs to identify and report the predominating public and professional discussions related to child health services within the last 5 years in their country and the various factors which may have influenced these. The survey was issued to CAs following validation by an independent Expert Advisory Board. The data were collected between July and December 2016. The data was qualitatively analysed using software Nvivo11 for data coding and categorization and constructing the scheme for identified processes or elements. RESULTS: Contextual determinants of children's health care and policy were grouped into four categories. 1) Socio-cultural determinants: societal activation, awareness, communication, trust, freedom, contextual change, lifestyle, tolerance and religion, and history. 2) Structural determinants which were divided into: a) external determinants related to elements indirectly correlated with health care and b) internal determinants comprising interdependent health care and policy processes. 3) International determinants such as cross-nationality of child health policy issues. 4) The specific situational determinants: events which contributed to intensification of debates which were reflected by behavioural, procedural, institutional and global factors. CONCLUSIONS: The influence of context across European countries, in the process of children's health policy development is clearly evident from our research. A number of key categories of determinants which influence child health policy have been identified and can be used to describe this context. Child health policy is often initiated in reaction to public discontentment. The multiple voices of society resulted, amongst others, in the introduction of new procedures, action plans and guidelines; raising levels of awareness, intensifying public scrutiny, increasing access and availability of services and provoking introduction of structural changes or withdrawing unfavourable changes.

How does societal reaction to children's health issues contribute to health policy in Europe? Results of a survey.

BACKGROUND: In the European context the awareness of societal responsibility for children's health has increased with greater attention to children's rights and child empowerment processes. Child health issues are considered particularly sensitive; thus, they often provoke strong societal reactions, which, as a consequence, influence national health policies across Europe. Effectiveness of societal influences increases with the involvement of various actors in the context. METHODS: A qualitative approach was used to identify the level of societal involvement in health decision-making. A questionnaire was sent to the Country Agents (CAs) of the Models of Child Health Appraised (MOCHA) project. CAs are contact points in each of the 30 participating in the project countries and were asked to identify strong public and professional discussions related to child health services in their countries. Data collection was undertaken between July and December 2016. RESULTS: Based on 71 case studies, we identified eight thematic patterns, which characterize societal reactions to the currently worrisome child health issues across Europe. We devoted our attention to the three most controversial: child vaccination, child poverty and child abuse. The cases described by the CAs show the broad perspective in the perception of child health problems. Child health issues involve the public and raise nationwide debates. Public concerns were directly or indirectly related to child health and depicted the national overtone. CONCLUSIONS: Concerns in Europe about child health care are twofold: they are devoted to systemic issues (indirect patient orientation) and to child health and well-being (direct patient orientation). The phenomenon of societal responsibility for children's health is important for the support of public acceptance of child health policy.

DEDICATE: proposal for a conceptual framework to develop dementia-friendly integrated eCare support.

BACKGROUND: Evidence shows that the implementation of information and communication technologies (ICT) enabled services supporting integrated dementia care represents an opportunity that faces multi-pronged challenges. First, the provision of dementia support is fragmented and often inappropriate. Second, available ICT solutions in this field do not address the full spectrum of support needs arising across an individual's whole dementia journey. Current solutions fail to harness the potential of available validated e-health services, such as telehealth and telecare, for the purposes of dementia care. Third, there is a lack of understanding of how viable business models in this field can operate. The field comprises both professional and non-professional players that interact and have roles to play in ensuring that useful technologies are developed, implemented and used. METHODS: Starting from a literature review, including relevant pilot projects for ICT-based dementia care, we define the major requirements of a system able to overcome the limitations evidenced in the literature, and how this system should be integrated in the socio-technical ecosystem characterizing this disease. From here, we define the DEDICATE architecture of such a system, and the conceptual framework mapping the architecture over the requirements. RESULTS: We identified three macro-requirements, namely the need to overcome: deficient technology innovation, deficient service process innovation, and deficient business models innovation. The proposed architecture is a three level architecture in which the center (data layer) includes patients' and informal caregivers' preferences, memories, and other personal data relevant to sustain the dementia journey, is connected through a middleware (service layer), which guarantees core IT services and integration, to dedicated applications (application layer) to sustain dementia care (formal support services, FSS), and to existing formal care infrastructures, in order to guarantee care coordination (care coordination services, CCS). CONCLUSIONS: The proposed DEDICATE architecture and framework envisages a feasible means to overcome the present barriers by: (1) developing and integrating technologies that can follow the patient and the caregivers throughout the development of the condition, since the early stages in which the patient is able to build up preferences and memories will be used in the later stages to maximise personalization and thereby improve efficacy and usability (technology innovation); (2) guaranteeing the care coordination between formal and informal caregivers, and giving an active yet supported role to the latter (service innovation); and (3) integrating existing infrastructures and care models to decrease the cost of the overall care pathway, by improving system interoperability (business model innovation).

Left circumflex coronary artery from the pulmonary artery in scimitar syndrome.

BACKGROUND: Scimitar syndrome is a rare combination of cardiopulmonary abnormalities found in 1-3 per 1000 live births. Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is only found in 1 in 250-400 congenital heart disease patients. OBJECTIVE: We aimed to investigate the incidence of left circumflex ALCAPA within our referral center's cohort of scimitar syndrome patients. MATERIALS AND METHODS: A review of medical records, cardiac imaging and operative notes from all patients diagnosed with scimitar syndrome at our center between 1992 and 2016 was undertaken and all imaging reviewed. RESULTS: Fifty-four patients with scimitar syndrome and imaging were identified. Of these, 3 patients (1 male and 2 female) with ALCAPA were identified, representing an incidence of 5.5% (95% confidence interval [CI] 0-11.67%). In all three cases, the anomalous coronary arising from the pulmonary artery was the left circumflex coronary artery (LCx) and the point of origin was close to the pulmonary arterial bifurcation. CONCLUSION: We hypothesize that the prevalence of LCx-ALCAPA, in the setting of scimitar syndrome, may be greater than previously thought. We suggest that any patient with scimitar syndrome, especially with evidence of ischaemia, should be investigated for ALCAPA. Given its noninvasive nature and simultaneous imaging of the lungs, we suggest that cardiovascular CT is the most appropriate first-line investigation for these patients.

Outcome after transcatheter occlusion of patent ductus arteriosus in infants less than 6 kg: A national study from United Kingdom and Ireland.

OBJECTIVES: This study aimed to report our national experience with transcatheter patent ductus arteriosus (PDA) occlusion in infants weighing <6 kg. BACKGROUND: The technique of transcatheter PDA closure has evolved in the past two decades and is increasingly used in smaller patients but data on safety and efficacy are limited. METHODS: Patients weighing < 6 kg in whom transcatheter PDA occlusion was attempted in 13 tertiary paediatric cardiology units in the United Kingdom and Ireland were retrospectively analyzed to review the outcome and complications. RESULTS: A total of 408 patients underwent attempted transcatheter PDA closure between January 2004 and December 2014. The mean weight at catheterization was 4.9 ± 1.0 kg and mean age was 5.7 ± 3.0 months. Successful device implantation was achieved in 374 (92%) patients without major complication and of these, complete occlusion was achieved in 356 (95%) patients at last available follow-up. Device embolization occurred in 20 cases (5%). The incidence of device related obstruction to the left pulmonary artery or aorta and access related peripheral vascular injury were low. There were no deaths related to the procedure. CONCLUSIONS: Transcatheter closure of PDA can be accomplished in selected infants weighing <6 kg despite the manufacturer's recommended weight limit of 6 kg for most ductal occluders. The embolization rate is higher than previously reported in larger patients. Retrievability of the occluder and duct morphology needs careful consideration before deciding whether surgical ligation or transcatheter therapy is the better treatment option.

Oral Enoximone as an Alternative to Protracted Intravenous Medication in Severe Pediatric Myocardial Failure.

Phosphodiesterase 3 inhibitors have been used successfully in pediatric patients with acute or chronic myocardial dysfunction over the last two decades. Their protracted continuous intravenous administration is associated with risk of infectious and thromboembolic complications. Weaning intravenous medication and starting oral angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers can be challenging. We reviewed retrospectively hospital records of 48 patients receiving oral enoximone treatment in a single tertiary pediatric cardiac center between November 2005 and April 2014. Failure to wean from intravenous milrinone infusion and/or intolerance of ACE inhibitors and/or beta-blockers was indications for oral enoximone treatment. Age of the patients ranged between 0.5 and 191 months (median 7.5 months) at the time of starting enoximone treatment. There were 14 patients (29 %) with left ventricular dysfunction due to myocarditis or dilated cardiomyopathy and 34 patients (71 %) with myocardial dysfunction complicating congenital heart disease. Fifteen (44 %) of these 34 patients had left ventricular dysfunction, 13 (38 %) right ventricular dysfunction, and in 6 (18 %) both ventricles were failing. Duration of oral enoximone treatment was between 3 days and 34 months (median of 2.3 months). Myocardial functional recovery allowed for weaning of enoximone treatment in 15 patients (31 %) after 6 days-15 months (median 5 months). No adverse hemodynamic effects were noted. Blood stained gastric aspirates encountered in two patients resolved with concomitant milk administration. Based on our limited experience, oral enoximone is a well-tolerated and promising alternative to intravenous medication and/or other commonly used oral medications in selected pediatric patients with chronic heart failure.