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OBJECTIVES: The use of ventricular assist devices in children is increasing. However, absolute numbers in individual centers and countries remain small. Collaborative efforts such as the Paedi-EUROMACS are therefore essential in order to combine international experience with paediatric ventricular assist devices. In this paper, the results from the fourth Paedi-EUROMACS report are presented. METHODS: All paediatric (<19 years) patients supported by a ventricular assist device from the EUROMACS database were included. Patients are stratified into a congenital heart disease group and a group with a non-congenital aetiology. Endpoints included mortality, transplantation and recovery. Cox proportional hazard models were used to explore associated factors for mortality, cerebrovascular accident, and pump thrombosis. RESULTS: 590 primary implantations were included. The congenital group was significantly younger (2.5 versus 8.0 years respectively, p < 0.001) and were more commonly supported by a pulsatile flow device (73.5% vs 59.9%, p < 0.001). Mortality was significantly higher in the congenital group (30.8 vs 20.4%; p = 0.009) than in the non-congenital group. However, in multivariable analyses, congenital heart disease was not significantly associated with mortality (HR 1.285, CI 0.8111-2.036, p = 0.740). Pump thrombosis was the most frequently reported adverse event (377 events in 132 patients; 0.925 events per patient-year) and was significantly associated with BSA (HR 0.524 CI 0.333-0.823, p = 0.005), congenital heart disease (HR 1.641 CI 1.054-2.555, p = 0.028) and pulsatile flow support (HR 2.345 CI 1.406-3.910, p = 0.001) in multivariable analyses. CONCLUSIONS: This fourth Paedi-EUROMACS report highlights the increasing use of paediatric ventricular assist devices. The patient populations with congenital and non-congenital aetiology exhibit distinct characteristics and clinical outcomes.
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AIM: Heart transplantation (HT) in patients with failing univentricular circulation is often challenging. This is compounded by the ever-increasing number of patients with prior Norwood-type reconstruction of the aorta, large aortic root, and often dense adhesions from multiple prior operations. We aimed to elucidate differences in outcomes of HT in patients with prior univentricular palliations, with and without prior Norwood-type aortic arch reconstruction (ArchRec). METHODS: All patients who underwent HT for failed univentricular palliation during the 1990-2022 period were included in the study. RESULTS: Of 45 patients, 18 had undergone ArchRec. Hospital mortality improved in the recent era (17.4% before 2006 vs 0% after 2006; p=0.11), despite a higher proportion of patients with ArchRec (17.4% before 2006 vs 60.8% after 2006, p=0.002). Patients with ArchRec had a higher number of prior cardiac surgeries (4.1±1.5 vs 3.2±1.3, p=0.04), longer cardiopulmonary bypass time (320±23 vs 242±21 min, p=0.02), more concomitant arch reconstruction (33.3% vs 0%, p=0.02), greater need for post-HT extracorporeal membrane oxygenation (33.3% vs 3.7%; p=0.01) and longer hospital stay (37.1±30.5 days vs 23.6±11.8 days, p=0.04). Freedom from death or retransplantation for all patients was 91%, 73%, 67%, and 53% at 1, 5, 10, and 15-years, respectively. Prior ArchRec, Fontan procedure, and earlier eras were not risk factors for death. CONCLUSIONS: The outcomes of HT after univentricular palliation have improved in recent times and low operative mortality can be achieved. Despite increased complexity, good similar outcomes can be achieved in patients with and without prior arch reconstruction regardless of the palliation stage.
Subject(s)
Heart Transplantation , Humans , Heart Transplantation/methods , Male , Female , Hospital Mortality/trends , Infant , Retrospective Studies , Palliative Care/methods , Univentricular Heart/surgery , Norwood Procedures/methods , Survival Rate/trends , Infant, Newborn , Follow-Up StudiesABSTRACT
Health institutions recommend that young infants be exclusively breastfed on demand, and it is widely held that parents who can breastfeed have an obligation to do so. This has been challenged in recent philosophical work, especially by Fiona Woollard. Woollard's work critically engages with two distinct views of parental obligation that might ground such an obligation-based on maximal benefit and avoidance of significant harm-to reject an obligation to breastfeed. While agreeing with Woollard's substantive conclusion, this paper (drawing on philosophical discussion of the 'right to rear') argues that there are several more moderate views of parental obligation which might also be thought to ground parental obligation. We first show that an obligation to breastfeed might result not from a general obligation to maximally benefit one's child, but from what we call 'choice-specific' obligations to maximise benefit within particular activities. We then develop this idea through two views of parental obligation-the Dual Interest view, and the Best Custodian view-to ground an obligation to exclusively breastfeed on demand, before showing how both these more moderate views fail. Finally, we argue that not only is there no general obligation to breastfeed children, but that it is often morally right not to do so. Since much advice from health institutions on this issue implies that exclusive breastfeeding on demand is the best option for all families, our argument drives the feeding debate forward by showing that this advice often misrepresents parents' moral obligations in potentially harmful ways.
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Healthcare practitioners have access to a range of ethical guidance. However, the normative role of this guidance in ethical decision-making is underexplored. This paper considers two ways that healthcare practitioners could approach ethics guidance. We first outline the idea of deference to ethics guidance, showing how an attitude of deference raises three key problems: moral value; moral understanding; and moral error. Drawing on philosophical literature, we then advocate an alternative framing of ethics guidance as a form of moral testimony by colleagues and suggest that a more promising attitude to ethics guidance is to approach it in the spirit of 'critical engagement' rather than deference.
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Dipeptide repeat proteins are a major pathogenic feature of C9orf72 amyotrophic lateral sclerosis (C9ALS)/frontotemporal dementia (FTD) pathology, but their physiological impact has yet to be fully determined. Here we generated C9orf72 dipeptide repeat knock-in mouse models characterized by expression of 400 codon-optimized polyGR or polyPR repeats, and heterozygous C9orf72 reduction. (GR)400 and (PR)400 knock-in mice recapitulate key features of C9ALS/FTD, including cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction. Quantitative proteomics revealed an increase in extracellular matrix (ECM) proteins in (GR)400 and (PR)400 spinal cord, with the collagen COL6A1 the most increased protein. TGF-ß1 was one of the top predicted regulators of this ECM signature and polyGR expression in human induced pluripotent stem cell neurons was sufficient to induce TGF-ß1 followed by COL6A1. Knockdown of TGF-ß1 or COL6A1 orthologues in polyGR model Drosophila exacerbated neurodegeneration, while expression of TGF-ß1 or COL6A1 in induced pluripotent stem cell-derived motor neurons of patients with C9ALS/FTD protected against glutamate-induced cell death. Altogether, our findings reveal a neuroprotective and conserved ECM signature in C9ALS/FTD.
Subject(s)
Amyotrophic Lateral Sclerosis , Frontotemporal Dementia , Induced Pluripotent Stem Cells , Animals , Humans , Mice , Frontotemporal Dementia/pathology , Amyotrophic Lateral Sclerosis/metabolism , Transforming Growth Factor beta1 , C9orf72 Protein/genetics , C9orf72 Protein/metabolism , Induced Pluripotent Stem Cells/metabolism , Motor Neurons/metabolism , Drosophila , Extracellular Matrix/metabolism , Dipeptides/metabolism , DNA Repeat Expansion/geneticsABSTRACT
OBJECTIVE: This study evaluates the long-term results of tetralogy of Fallot repair and assesses the risk factors for adverse outcomes. METHODS: This retrospective study included 960 patients who underwent transatrial transpulmonary tetralogy of Fallot repair between 1990 and 2020. RESULTS: A transannular patch was placed in 722 patients, and pulmonary valve preservation was achieved in 233 patients. The median age at tetralogy of Fallot repair was 9.4 (interquartile range, 6.2-14.2) months. The median follow-up duration was 10.6 (interquartile range, 5.4-16.3) years. There were 8 early deaths (0.8%) and 20 late deaths (2.1%). Genetic syndrome and pulmonary valve annulus Z score less than -3 were risk factors for mortality. The survival was 97.7% (95% confidence interval, 96.4-98.5) and 94.5% (95% confidence interval, 90.9-96.7) at 10 and 30 years, respectively. Freedom from any reoperation was 86.4% (95% confidence interval, 83.6-88.7) and 65.4% (95% confidence interval, 59.8-70.4) at 10 and 20 years, respectively. Postoperative right ventricular outflow tract peak gradient of 25 mm Hg or greater correlated with reoperation. Propensity score-matched analysis demonstrated that freedom from pulmonary valve replacement at 15 years was higher in the pulmonary valve preservation group compared with the transannular patch group (98.2% vs 78.4%, P = .004). Freedom from reoperation for right ventricular outflow tract obstruction at 15 years was lower in the pulmonary valve preservation group compared with the transannular patch group (P = .006). CONCLUSIONS: The long-term outcomes of tetralogy of Fallot repair are excellent. A postoperative right ventricular outflow tract peak gradient less than 25 mm Hg appears to be optimal to prevent reoperation. If the pulmonary valve size is suitable, pulmonary valve preservation reduces the risk of pulmonary valve replacement, yet increases the reoperation rate for right ventricular outflow tract obstruction.
Subject(s)
Pulmonary Valve , Tetralogy of Fallot , Ventricular Outflow Obstruction, Right , Humans , Infant , Retrospective Studies , Treatment Outcome , Pulmonary Valve/surgery , Reoperation , Follow-Up StudiesABSTRACT
Purpose: The withdrawal of HVAD in 2021 created a concern for the pediatric population. The alternative implantable centrifugal blood pump HeartMate 3 has since been used more frequently in children. This paper analyses the outcome of children on LVAD support provided with an HVAD or HM3. Methods: A retrospective analysis of the EUROMACS database on children supported with VAD < 19 years of age from 1 January 2009 to 1 December 2021 was conducted. All patients with an LVAD and either an HVAD or HM3 were included. Patients with missing data on VAD status and/or missing baseline and/or follow up information were excluded. Kaplan-Meier survival analysis was performed to evaluate survival differences. Analyses were performed using Fisher's exact test. Results: The study included 150 implantations in 142 patients with 128 implants using an HVAD compared to 28 implants using an HM3. Nine patients (6%) needed temporary right ventricular mechanical support, which was significantly higher in the HM3 group, with 25% (p: 0.01). Patients in the HVAD group were significantly younger (12.7 vs. 14.5 years, p: 0.01), weighed less (45.7 vs. 60 kg, p: <0.000) and had lower BSA values (1.3 vs. 1.6 m2, p: <0.000). Median support time was 204 days. Overall, 98 patients (69%) were discharged and sent home, while 87% were discharged in group HM3 (p: ns). A total of 123 children (86%) survived to transplantation, recovery or are ongoing, without differences between groups. In the HVAD group, 10 patients (8%) died while on support, whereas in 12% of HM3 patients died (p: 0.7). Conclusions: Survival in children implanted with an HM3 was excellent. Almost 90% were discharged and sent home on the device.
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I introduce a distinction between health need and medical need, and raise several questions about their interaction. Health needs are needs that relate directly to our health condition. Medical needs are needs which bear some relation to medical institutions or processes. I suggest that the question of whether medical insurance or public care should cover medical needs, health needs, or only needs which fit both categories is a political question that cannot be resolved definitionally. I also argue against an overly strict definition of medical need on the grounds that this presupposes, wrongly, that medical intervention should always be a last resort.
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BackgroundIn 2020, Wales experienced some of the highest rates of confirmed COVID-19 cases in Europe. We set up a serosurveillance scheme using residual samples from blood donations to inform the pandemic response in Wales.AimTo identify changes in SARS-CoV-2 antibody seroprevalence in Wales by time, demography and location.MethodsResidual samples from blood donations made in Wales between 29 June 2020 and 20 November 2022 were tested for antibodies to the nucleocapsid antigen (anti-N) of SARS-CoV-2, resulting from natural infection. Donations made between 12 April 2021 and 20 November 2022 were also tested for antibodies to the spike antigen (anti-S) occurring as a result of natural infection and vaccination.ResultsAge-standardised seroprevalence of anti-N antibodies in donors remained stable (4.4-5.5%) until November 2020 before increasing to 16.7% by February 2021. Trends remained steady until November 2021 before increasing, peaking in November 2022 (80.2%). For anti-S, seroprevalence increased from 67.1% to 98.6% between May and September 2021, then remained above 99%. Anti-N seroprevalence was highest in younger donors and in donors living in urban South Wales. In contrast, seroprevalence of anti-S was highest in older donors and was similar across regions. No significant difference was observed by sex. Seroprevalence of anti-N antibodies was higher in Black, Asian and other minority ethnicities (self-reported) compared with White donors, with the converse observed for anti-S antibodies.ConclusionWe successfully set up long-term serological surveillance of SARS-CoV-2 using residual samples from blood donations, demonstrating variation based on age, ethnicity and location.
Subject(s)
Blood Donors , COVID-19 , Aged , Humans , Antibodies, Viral , COVID-19/epidemiology , Ethnicity , SARS-CoV-2 , Seroepidemiologic Studies , Wales/epidemiologyABSTRACT
Throughout the COVID-19 pandemic, shortages of scarce healthcare resources consistently presented significant moral and practical challenges. While the importance of vaccines as a key pharmaceutical intervention to stem pandemic scarcity was widely publicized, a sizable proportion of the population chose not to vaccinate. In response, some have defended the use of vaccination status as a criterion for the allocation of scarce medical resources. In this paper, we critically interpret this burgeoning literature, and describe a framework for thinking about vaccine-sensitive resource allocation using the values of responsibility, reciprocity, and justice. Although our aim here is not to defend a single view of vaccine-sensitive resource allocation, we believe that attending critically with the diversity of arguments in favor (and against) vaccine-sensitivity reveals a number of questions that a vaccine-sensitive approach to allocation should answer in future pandemics.
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BACKGROUND: Data on the use and outcome of children on ventricular assist device (VAD) support provided with an implantable cardioverter-defibrillator (ICD) remains poor. METHODS: A retrospective analysis of the EUROMACS database on children supported with VAD < 19 years of age from January 1, 2009 to April 1, 2020. Patients with missing data on status of ICD, missing baseline and/or follow up information were excluded. The primary independent variable of interest was the concomitant presence or absence of an ICD at the time of VAD placement. Kaplan-Meier survival analysis was performed to evaluate survival differences between children on VAD with and without an ICD. RESULTS: Out of 303 patients provided with a VAD, 7% (7â, 15â) had an ICD implanted and formed the study group. Median age was 14 years, median weight was 43.5 kg, and median BSA was 1.39. Median Intermacs stage was 2 (range: 1-7). Seventeen patients (77%) were transplanted, 4 (18%) died while on support, and 1 (5%) was weaned from device after myocardial recovery. Median time on support was 68 days compared to 361 days in the control group (p: 0.01). Three patients underwent device exchange due to thrombus formation in the pump. There was no difference in survival between groups (p = 0.342). CONCLUSION: The presence of ICD in pediatric patients supported with a VAD is low (7%). Children on VAD support provided with an ICD do not have a survival benefit compared to children without an ICD.
Subject(s)
Defibrillators, Implantable , Heart Failure , Heart-Assist Devices , Humans , Child , Adolescent , Heart Failure/surgery , Retrospective Studies , Registries , Treatment OutcomeABSTRACT
Sufficientarians face a problem of arbitrariness: why place a sufficiency threshold at any particular point? One response is to seek universal goods to justify a threshold. However, this faces difficulties (despite sincere efforts) by either being too low, or failing to accommodate individuals with significant cognitive disabilities. Some sufficientarians have appealed to individuals' subjective evaluations of their lives. I build on this idea, considering another individualized threshold: 'tolerability'. I respond to some traditional challenges to individualistic approaches to justice: 'expensive' tastes, and adaptive preferences. Finally, I end by offering some suggestions about how this relates to policymaking.
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Subjectivists think that our well-being is grounded in our subjective attitudes. Many such views are vulnerable to variations on the 'paradox of desire', where theories cannot make determinate judgements about the well-being of agents who take a positive valuing attitude towards their life going badly. However, this paradox does not affect all subjectivist theories; theories grounded on agents' prudential values can avoid it. This paper suggests a new paradox for subjectivist theories which has a wider scope, and includes such prudential judgement theories. I outline the new paradox and show how two plausible idealisztions (coherence and consideration) will not help. Subjectivists about well-being must either add an additional idealization that can solve the paradox of judgement or explain why such paradoxes do not constitute serious objections to a theory of well-being.
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Some philosophers and segments of the public think age is relevant to healthcare priority-setting. One argument for this is based in equity: "Old" patients have had either more of a relevant good than "young" patients or enough of that good and so have weaker claims to treatment. This article first notes that some discussions of age-based priority that focus in this way on old and young patients exhibit an ambiguity between two claims: that patients classified as old should have a low priority, and that patients classified as young should have high priority. The author next argues, drawing on a problem raised by Christine Overall, that equity cannot justify giving "old" patients low priority, since there is wide variety in the total lifetime experiences of older people, partly influenced by gender, race, class, and disability injustice. Finally, the author suggests that there might be a limited role for age-based prioritization in the context of infant and childhood death, since those who die in childhood are always and uncontroversially among the worst-off.
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A considerable literature has emerged around the idea of using 'personal responsibility' as an allocation criterion in healthcare distribution, where a person's being suitably responsible for their health needs may justify additional conditions on receiving healthcare, and perhaps even limiting access entirely, sometimes known as 'responsibilisation'. This discussion focuses most prominently, but not exclusively, on 'luck egalitarianism', the view that deviations from equality are justified only by suitably free choices. A superficially separate issue in distributive justice concerns the two-way relationship between health and other social goods: deficits in health typically undermine one's abilities to secure advantage in other areas, which in turn often have further negative effects on health. This paper outlines the degree to which this latter relationship between health and other social goods exacerbates an existing problem for proponents of responsibilisation (the 'harshness objection') in ways that standard responses to this objection cannot address. Placing significant conditions on healthcare access because of a person's prior responsibility risks trapping them in, or worsening, negative cycles where poor health and associated lack of opportunity reinforce one another, making further poor yet ultimately responsible choices more likely. It ends by considering three possible solutions to this problem.
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This article is about the potential justification for deploying some form of affirmative action (AA) in the context of healthcare, and in particular in relation to the pandemic. We call this Affirmative Action in healthcare Resource Allocation (AARA). Specifically, we aim to investigate whether the rationale and justifications for using prioritization policies based on race in education and employment apply in a healthcare setting, and in particular to the COVID-19 pandemic. We concentrate in this article on vaccines and ventilators because these are both highly scarce resources in the pandemic, and there has been a need to develop policies for allocating them. However, as will become clear, the ethical considerations relating to them may diverge. We first set out two rationales for AAs and what they might entail in a healthcare setting. We then consider some disanalogies between AA and AARA, as well as the different implications of AARA for allocating ventilators as opposed to vaccines. Finally, we consider some of the practical ways in which AARA could be implemented, and conclude by responding to some key objections.
Subject(s)
COVID-19 , Vaccines , Humans , Pandemics , COVID-19/prevention & control , Ventilators, Mechanical , Public Policy , Delivery of Health Care , Resource AllocationABSTRACT
Current genetic tools designed to target macrophages in vivo often target cells from all myeloid lineages. Therefore, we sought to generate a novel transgenic mouse which has a tamoxifen inducible Cre-recombinase under the control of the human CD68 promoter (hCD68-CreERT2). To test the efficiency and specificity of the of Cre-recombinase activity we crossed the hCD68-CreERT2 mice with a loxP-flanked STOP cassette red fluorescent protein variant (tdTomato) mouse. We established that orally dosing mice with 2 mg of tamoxifen for 5 consecutive days followed by a 5-day induction period resulted in robust expression of tdTomato in CD11b+ F4/80+ tissue resident macrophages. Using this induction protocol, we demonstrated tdTomato expression within peritoneal, liver and spleen macrophages and blood Ly6Clow monocytes. Importantly there was limited or no inducible tdTomato expression within other myeloid cells (neutrophils, monocytes, dendritic cells and eosinophils), T cells (CD4+ and CD8+) and B cells (CD19+). We also demonstrated that the level of tdTomato expression can be used as a marker to identify different populations of peritoneal and liver macrophages. We next assessed the longevity of tdTomato expression in peritoneal macrophages, liver and splenic macrophages and demonstrated high levels of tdTomato expression as long as 6 weeks after the last tamoxifen dose. Importantly, hCD68-CreERT2 expression is more restricted than that of LysM-Cre which has significant expression in major myeloid cell types (monocytes and neutrophils). To demonstrate the utility of this novel macrophage-specific Cre driver line we demonstrated tdTomato expression in recruited CD11b+CD64+F4/80+ monocyte-derived macrophages within the atherosclerotic lesions of AAV8-mPCSK9 treated mice, with limited expression in recruited neutrophils. In developing this new hCD68-CreERT2 mouse we have a tool that allows us to target tissue resident macrophages, with the advantage of not targeting other myeloid cells namely neutrophils and inflammatory monocytes.
Subject(s)
Integrases , Tamoxifen , Animals , Humans , Integrases/genetics , Macrophages/metabolism , Mice , Mice, Transgenic , Tamoxifen/pharmacologyABSTRACT
BACKGROUND: Standards generally reported in the literature about informing children and respecting their consent or refusal before elective heart surgery may differ from actual practice. This research aims to summarize the main themes in the literature about paediatric anaesthesia and compare these with research findings on how health professionals counsel young children before elective heart surgery, respect their consent or refusal, and maintain patient-centred care. METHODS: This qualitative research involved: literature reviews about children's consent to surgery and major interventions; observations of wards, clinics and medical meetings in two paediatric cardiology departments, October 2019 to February 2020; audio-recorded semi-structured interviews with 45 hospital staff, including 5 anaesthetists, and related experts, November 2019 to April 2021; interviews with 16 families, with children aged 6- to 15-years and their parents shortly after elective heart surgery, and some months later (reported in other papers); thematic data analysis; and research reports on how different professions contribute to children's informed decisions for heart surgery. RESULTS: The medical, ethics and English legal literature tend to assume legal minors cannot refuse major recommended treatment, and cannot consent until they are 12 years or older. Little is said about informing pre-competent children. If children resist, some anaesthetists rely on sedation and distraction, and avoid much informed discussion, aiming to reduce peri-operative anxiety. However, interviewees reported informing young children, and respecting their consent or refusal before elective surgery. They may delay elective surgery and provide further information and support, aiming to reduce fear and promote trust. Six years of age was commonly cited as the threshold for respecting consent to heart transplantation. CONCLUSION: Differing views about younger children's competence, anxiety and best interests support different reactions to children's consent and refusal before elective heart surgery. This paper reports the zero-restraint policy followed for over a decade in at least one leading surgery centre. The related law and literature need to be updated, to take more account of evidence of actual practice.