Feeding Infants: Choice-Specific Considerations, Parental Obligation, and Pragmatic Satisficing.

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.

Heart Transplantation after Univentricular Palliation: Improved Outcomes and Increased Complexity.

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.

Use of implantable cardioverter-defibrillator in children supported with ventricular assist device: An analysis of data from the EUROMACS registry.

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% (7♀, 15♂) 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.

Rationing, Responsibility, and Vaccination during COVID-19: A Conceptual Map.

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.

Serosurveillance of SARS-CoV-2 in Welsh Blood Donors: Establishment of the surveillance system and results up to November 2022.

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.

Recombinant Factor VIIa in Pediatric Cardiac Surgery.

OBJECTIVES: Recombinant activated factor VIIa (rVIIa) is used off-label for refractory bleeding after cardiac surgery. This study reviewed the indications, usage rates, and complications of rVIIa. DESIGN: A retrospective case-control observational study. SETTING: A single quaternary pediatric hospital. PARTICIPANTS: All children undergoing cardiac surgery with cardiopulmonary bypass over a three-year period. INTERVENTIONS: Administration of rVIIa as rescue therapy for refractory bleeding after weaning from cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Onethousand, five hundred fifteen cardiopulmonary bypass procedures were reviewed. Patients receiving rVIIa were each matched to two control patients by age, procedure type, and bypass time. Data collected included weight, crossclamp time, anticoagulant and antifibrinolytic dose, return to the operating room for bleeding, thrombotic events, and extracorporeal membrane oxygenation (ECMO) circuit interventions. Forty-two patients received rVIIa (2.8%). Major systemic thrombotic complications were observed in 19% (controls 12.5%) of patients; 80% of recombinant factor VIIa patients requiring postoperative ECMO had interventions for circuit thrombosis (controls 31.25%); 4.76% of rVIIa recipients required reexploration for intractable bleeding (controls 1.39%). CONCLUSIONS: This study added to understanding regarding the use of recombinant factor VIIa in pediatric cardiac surgery and reported increased thrombotic complications, especially for children who progress to ECMO. Prospective studies to better understand the pathophysiology of coagulopathy and hemorrhage in pediatric cardiac surgery and the role of hemostatic agents, such as rVIIa, are required.

Affirmative action in healthcare resource allocation: Vaccines, ventilators and race.

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.

Healthcare Priorities: The "Young" and the "Old".

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.

Doctors as Appointed Fiduciaries: A Supplemental Model for Medical Decision-Making.

How should we respond to patients who do not wish to take on the responsibility and burdens of making decisions about their own care? In this paper, we argue that existing models of decision-making in modern healthcare are ill-equipped to cope with such patients and should be supplemented by an "appointed fiduciary" model where decision-making authority is formally transferred to a medical professional. Healthcare decisions are often complex and for patients can come at time of vulnerability. While this does not undermine their capacity, it can be excessively burdensome. Most existing models of decision-making mandate that patients with capacity must retain ultimate responsibility for decisions. An appointed fiduciary model provides a formalized mechanism through which those few patients who wish to defer responsibility can hand over decision-making authority. By providing a formal structure for deferring to an appointed fiduciary, the confusions and risks of the informal transfers that can occur in practice are avoided. Finally, we note how appropriate governance and law can provide safeguards against risks to the welfare of patients and medical professionals.

The Right Not to Know: some Steps towards a Compromise.

There is an ongoing debate in medicine about whether patients have a 'right not to know' pertinent medical information, such as diagnoses of life-altering diseases. While this debate has employed various ethical concepts, probably the most widely-used by both defenders and detractors of the right is autonomy. Whereas defenders of the right not to know typically employ a 'liberty' conception of autonomy, according to which to be autonomous involves doing what one wants to do, opponents of the right not to know often employ a 'duty' understanding, viewing autonomy as involving an obligation to be self-governing. The central contribution of this paper is in showing that neither view of autonomy can reasonably be said to support the extreme stances on the right not to know that they are sometimes taken to. That is, neither can a liberty view properly defend a right not to know without limits, nor can a duty view form the basis of an absolute rejection of the right not to know. While there is still theoretical distance between these two approaches, we conclude that the views are considerably closer on this issue than they first appear, opening the way for a possible compromise.

The right not to know and the obligation to know.

There is significant controversy over whether patients have a 'right not to know' information relevant to their health. Some arguments for limiting such a right appeal to potential burdens on others that a patient's avoidable ignorance might generate. This paper develops this argument by extending it to cases where refusal of relevant information may generate greater demands on a publicly funded healthcare system. In such cases, patients may have an 'obligation to know'. However, we cannot infer from the fact that a patient has an obligation to know that she does not also have a right not to know. The right not to know is held against medical professionals at a formal institutional level. We have reason to protect patients' control over the information that they receive, even if in individual instances patients exercise this control in ways that violate obligations.

No Blame No Gain? From a No Blame Culture to a Responsibility Culture in Medicine.

Healthcare systems need to consider not only how to prevent error, but how to respond to errors when they occur. In the United Kingdom's National Health Service, one strand of this latter response is the 'No Blame Culture', which draws attention from individuals and towards systems in the process of understanding an error. Defences of the No Blame Culture typically fail to distinguish between blaming someone and holding them responsible. This article argues for a 'responsibility culture', where healthcare professionals are held responsible in cases of foreseeable and avoidable errors. We demonstrate how healthcare professionals can justifiably be held responsible for their errors even though they work in challenging circumstances. We then review the idea of 'responsibility without blame', applying this to cases of error in healthcare. Sensitive to the undesirable effects of blaming healthcare professionals and to the moral significance of holding individuals accountable, we argue that a responsibility culture has significant advantages over a No Blame Culture due to its capacity to enhance patient safety and support medical professionals in learning from their mistakes, while also recognising and validating the legitimate sense of responsibility that many medical professionals feel following avoidable error, and motivating medical professionals to report errors.

Permanent pacemaker implantation after pediatric heart transplantation: Risk factors, indications, and outcomes.

BACKGROUND: Permanent pacemaker (PPM) placement in adults following orthotopic heart transplantation (OHT) has been well documented. However, studies concerning the need for PPM implantation in pediatric heart transplant recipients are less common. METHODS: Institutional transplant and pacing databases as well as patient medical records were reviewed for all pediatric patients undergoing OHT (n = 314; all with bicaval connection) at our institution between January 2000 and March 2018. RESULTS: A total of 16 patients (5.1%) were implanted with a pacemaker after transplantation. Donor age was the only significant risk factor for post-transplant PPM implantation, with a median age of 28.5 years (7.0-49.0) in the pacing group vs 15.5 years (0.4-56.0) in the non-pacing group (P = 0.009). Indication for pacemaker insertion was more often complete heart block (CHB) (12/16, 75%) than sinus node dysfunction (SND) (4/16, 25%). There was no significant difference in mortality between recipients who received a PPM and those who did not (log-rank test; P = 0.345). CONCLUSIONS: Increasing donor age is associated with increased PPM placement following pediatric heart transplantation. Interestingly, a high proportion of CHB patients recovered sinus rhythm, and long-term outcomes for paced patients are similar to other heart transplant recipients.

Successful lung donation at the age of 6 weeks: Challenges and lessons learned.

A clinical case of successful procurement and transplantation of bilateral lungs from 6-week-old infant with sepsis secondary to bacterial meningitis is reported. Forty-one-day-old male infant (height 60 cm, weight 4 kg) died of cerebral edema secondary to Escherichia coli meningitis and bacteremia. Preretrieval assessment included the following: arterial gases; pO2 50.4 kPa (378 mm Hg), pCO2 4.9 kPa (37 mm Hg), on FiO2 100%, PEEP 5 cm H2 O. Fiberoptic bronchoscopy showed no secretions nor mucosal inflammation; CXR revealed clear lung fields and pleural spaces. Inspection revealed dense adhesions in pericardial cavity and purulent left hemithorax effusion (urgent Gram-stain came back as negative) but there was no consolidation in the lung. Good compliance of the lungs on inflation/deflation test was observed. The lungs were retrieved using the technique described. The recipient was a 4-month-old infant with alveolar capillary dysplasia and malaligned pulmonary veins. Implantation of the lungs was performed via bilateral thoracosternotomy on cardiopulmonary bypass, cooling to 30°C. Elective support with nitric oxide was used postoperatively. Two years after the transplantation, the recipient doing well with normal lung function. Lung procurement from a 6-week donor with infectious complications and prolonged ventilation is a challenging undertaking but can be successful and should be attempted whenever possible given the paucity of organs available for pediatric recipients.

Glycine Amidinotransferase (GATM), Renal Fanconi Syndrome, and Kidney Failure.

Background For many patients with kidney failure, the cause and underlying defect remain unknown. Here, we describe a novel mechanism of a genetic order characterized by renal Fanconi syndrome and kidney failure.Methods We clinically and genetically characterized members of five families with autosomal dominant renal Fanconi syndrome and kidney failure. We performed genome-wide linkage analysis, sequencing, and expression studies in kidney biopsy specimens and renal cells along with knockout mouse studies and evaluations of mitochondrial morphology and function. Structural studies examined the effects of recognized mutations.Results The renal disease in these patients resulted from monoallelic mutations in the gene encoding glycine amidinotransferase (GATM), a renal proximal tubular enzyme in the creatine biosynthetic pathway that is otherwise associated with a recessive disorder of creatine deficiency. In silico analysis showed that the particular GATM mutations, identified in 28 members of the five families, create an additional interaction interface within the GATM protein and likely cause the linear aggregation of GATM observed in patient biopsy specimens and cultured proximal tubule cells. GATM aggregates-containing mitochondria were elongated and associated with increased ROS production, activation of the NLRP3 inflammasome, enhanced expression of the profibrotic cytokine IL-18, and increased cell death.Conclusions In this novel genetic disorder, fully penetrant heterozygous missense mutations in GATM trigger intramitochondrial fibrillary deposition of GATM and lead to elongated and abnormal mitochondria. We speculate that this renal proximal tubular mitochondrial pathology initiates a response from the inflammasome, with subsequent development of kidney fibrosis.

A randomised trial of the influence of racial stereotype bias on examiners' scores, feedback and recollections in undergraduate clinical exams.

BACKGROUND: Asian medical students and doctors receive lower scores on average than their white counterparts in examinations in the UK and internationally (a phenomenon known as "differential attainment"). This could be due to examiner bias or to social, psychological or cultural influences on learning or performance. We investigated whether students' scores or feedback show influence of ethnicity-related bias; whether examiners unconsciously bring to mind (activate) stereotypes when judging Asian students' performance; whether activation depends on the stereotypicality of students' performances; and whether stereotypes influence examiner memories of performances. METHODS: This is a randomised, double-blinded, controlled, Internet-based trial. We created near-identical videos of medical student performances on a simulated Objective Structured Clinical Exam using British Asian and white British actors. Examiners were randomly assigned to watch performances from white and Asian students that were either consistent or inconsistent with a previously described stereotype of Asian students' performance. We compared the two examiner groups in terms of the following: the scores and feedback they gave white and Asian students; how much the Asian stereotype was activated in their minds (response times to Asian-stereotypical vs neutral words in a lexical decision task); and whether the stereotype influenced memories of student performances (recognition rates for real vs invented stereotype-consistent vs stereotype-inconsistent phrases from one of the videos). RESULTS: Examiners responded to Asian-stereotypical words (716 ms, 95% confidence interval (CI) 702-731 ms) faster than neutral words (769 ms, 95% CI 753-786 ms, p < 0.001), suggesting Asian stereotypes were activated (or at least active) in examiners' minds. This occurred regardless of whether examiners observed stereotype-consistent or stereotype-inconsistent performances. Despite this stereotype activation, student ethnicity had no influence on examiners' scores; on the feedback examiners gave; or on examiners' memories for one performance. CONCLUSIONS: Examiner bias does not appear to explain the differential attainment of Asian students in UK medical schools. Efforts to ensure equality should focus on social, psychological and cultural factors that may disadvantage learning or performance in Asian and other minority ethnic students.

Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a devastating neurodegenerative disorder characterized by the progressive loss of spinal motor neurons. While the aetiological mechanisms underlying the disease remain poorly understood, oxidative stress is a central component of amyotrophic lateral sclerosis and contributes to motor neuron injury. Recently, oxidation resistance 1 (OXR1) has emerged as a critical regulator of neuronal survival in response to oxidative stress, and is upregulated in the spinal cord of patients with amyotrophic lateral sclerosis. Here, we tested the hypothesis that OXR1 is a key neuroprotective factor during amyotrophic lateral sclerosis pathogenesis by crossing a new transgenic mouse line that overexpresses OXR1 in neurons with the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Interestingly, we report that overexpression of OXR1 significantly extends survival, improves motor deficits, and delays pathology in the spinal cord and in muscles of SOD1(G93A) mice. Furthermore, we find that overexpression of OXR1 in neurons significantly delays non-cell-autonomous neuroinflammatory response, classic complement system activation, and STAT3 activation through transcriptomic analysis of spinal cords of SOD1(G93A) mice. Taken together, these data identify OXR1 as the first neuron-specific antioxidant modulator of pathogenesis and disease progression in SOD1-mediated amyotrophic lateral sclerosis, and suggest that OXR1 may serve as a novel target for future therapeutic strategies.

Fair Innings and Time-Relative Claims.

Greg Bognar has recently offered a prioritarian justification for 'fair innings' distributive principles that would ration access to healthcare on the basis of patients' age. In this article, I agree that Bognar's principle is among the strongest arguments for age-based rationing. However, I argue that this position is incomplete because of the possibility of 'time-relative' egalitarian principles that could complement the kind of lifetime egalitarianism that Bognar adopts. After outlining Bognar's position, and explaining the attraction of time-relative egalitarianism, I suggest various ways in which these two kinds of principle could interact. Since various options have very different implications for age-based rationing, proponents of such a rationing scheme must take a position on time-relative egalitarianism to complement a lifetime prioritarian view like Bognar's.