Arterial Structure and Stiffness Are Altered in Young Adults Born Preterm.

OBJECTIVE: Preterm birth has been associated with changes in arterial structure and function. Association with complications occurring during the neonatal period, including bronchopulmonary dysplasia, on vascular outcomes in adulthood is unknown. Approach and Results: We evaluated a cohort of 86 adults born preterm (below 30 weeks of gestation), compared to 85 adults born term, at a mean age of 23 years. We performed ultrasonographic assessment of the dimensions of the ascending aorta, carotid and brachial arteries, and estimated flow-mediated dilation, carotid-femoral pulse wave velocity, augmentation index corrected for heart rate, and carotid intima-media thickness. All analyses were performed with and without adjustment for potential confounding variables, including height, sex, and body mass index. Ascending aorta diameter in diastole was smaller in the preterm group, but carotid and brachial arteries were similar. Carotid and brachial strain, a marker of arterial distensibility, was smaller in the preterm group, while carotid-femoral pulse wave velocity, was similar between groups, indicating similar aortic stiffness. Carotid intima-media thickness, endothelial function flow-mediated dilation, blood nitrite, and nitrate levels were similar between groups. Individuals with bronchopulmonary dysplasia had lower brachial artery strain suggesting long-term association of this neonatal complication with vascular structure. Diastolic blood pressure was higher in the preterm group and was associated with decreased brachial and carotid distensibility. CONCLUSIONS: Young adults born preterm display alterations in arterial distensibility that are associated with a history of bronchopulmonary dysplasia.

Association of antenatal magnesium sulfate with reduced late-onset sepsis in extreme preterm infants.

OBJECTIVES: Neonatal intensive care has changed extensively over the last decades resulting in improved survival of extreme preterm infants. However, improved survival is associated with prolonged hospitalization, mechanical ventilation and use of invasive devices, which are all predisposing factors for LOS. LOS is known to increase short- and long-term morbidities resulting in impaired neurodevelopmental outcome. Besides treatment with antibiotics and supportive care, there is an unmet need for adjunctive therapies to prevent neonatal sepsis and hereby improve outcome. METHODS: In a retrospective single-center design, we explored underlying pre-, peri- and postnatal factors in extreme preterm infants with and without LOS to potentially identify future strategies in the prevention of LOS in these infants. RESULTS: Associations formerly published could be confirmed, such as lower birth weight, longer duration of respiratory support, parenteral nutrition and NICU stay and a higher incidence of almost all neonatal morbidities. A new interesting finding was the fact that infants with LOS received more antenatal magnesium sulfate (p = 0.002). After nearest neighbor matching based on birth weight, gestational age, gender and multiplicity increased duration of parenteral nutrition and NICU stay, the incidence of PVL remained significantly different between the two groups (LOS/no LOS), but also the association between antenatal magnesium sulfate administration and less LOS held true (p = 0.004). CONCLUSION: In this study, extreme preterm infants receiving antenatal magnesium sulfate developed less LOS. Whether this is merely an associative factor reflecting illness severity or an interesting link for new preventive strategies for LOS, should be further explored.

What do we talk about when we talk about "equipoise"? Stakeholder interviews assessing the use of equipoise in clinical research ethics.

INTRODUCTION: Equipoise, generally defined as uncertainty about the relative effects of the treatments being compared in a trial, is frequently referenced as an ethical standard for the conduct of randomized clinical trials. However, it seems to be defined in several different ways and may be used differently by different individuals. We explored how clinical researchers, chairs of research ethics boards, and philosophers of science define and reason with this term. METHODS: We completed semi-structured interviews about clinical trial ethics with 15 clinical researchers, 15 research ethics board chairs, and 15 philosophers of science/bioethicists. Each participant was asked a standardized set of 10 questions, 4 of which were specifically about equipoise. All interviews were conducted telephonically and transcribed. Responses were grouped and analysed via a modified grounded theory method. RESULTS: Forty-three respondents defined equipoise in 7 logically distinct ways, and 2 respondents could not explicitly define it. The most common definition, offered by 14 respondents (31%), defined "equipoise" as a disagreement at the level of a community of physicians. There was significant variability in definitions offered between and within groups. When asked how they would "operationalize" equipoise - i.e. check or test for its presence - respondents provided 7 alternatives, the most common being in relation to a literature review (15/45, 33%). The vast majority of respondents (35/45, 78%) felt the concept was helpful, though many acknowledged that the lack of a clear definition or operationalization was problematic. CONCLUSION: There is significant variation in definitions of equipoise offered by respondents, suggesting that parties within groups and between groups may be referring to different concepts when they reference "equipoise". This non-uniformity may impact fairness and transparency and opens the door to potential ethical problems in the evaluation of clinical trials - for instance, a patient may understand equipoise very differently than the researchers enrolling her in a trial, which could cause her agreement to participate to be based upon false premises.

Trends in neonatal morbidity and mortality for very low birthweight infants: a 20-year single-center experience.

OBJECTIVE: To describe trends in mortality and morbidity rates of very low birth weight infants as well as their pre-, peri- and postnatal characteristics over a period of 20 years' time. METHODS: Retrospective study in all very low birth weight infants admitted to the neonatal intensive care unit of the University Hospitals Ghent from 1 January 2000, to 31 December 2020. Mortality was the primary outcome variable with major morbidities being co-primary outcome variables. Pre-, peri- and postnatal characteristics are secondary outcome variables. We compared pre-, peri- and postnatal characteristics, as well as major morbidities between different groups with comparable rates of mortality. RESULTS: We included a total of 2037 very low birth weight infants and divided them in 3 epochs based on stepwise reductions in mortality in 2008 and 2013: 2000-2007 (n = 718), 2008-2012 (n = 506) and 2013-2020 (n = 813). Mortality decreased significantly over the years in all gestational ages, but predominantly in those with the youngest gestational age. Changes in obstetric and neonatal care were observed over time. Most significant changes were the increased use of antenatal corticosteroids, magnesium sulfate and surfactant. Intraventricular hemorrhage grade III/IV decreased significantly in all gestational ages. Significant increase in retinopathy of prematurity was observed. Bronchopulmonary dysplasia at 36 weeks and discharge home with oxygen is increasing in the total group. In those born below 26 weeks a slight increase in all major morbidities was observed especially of patent ductus arteriosus and retinopathy of prematurity. Increase of all other major morbidities seems to stabilize in epoch 3. The number of infants surviving without any major morbidity increases to almost 1/2 in all very low birth weight infants and to 1/10 in those born 24-25 weeks gestation. CONCLUSION: Analysis of the real-life experience showed that survival in very low birth weight infants significantly increased over time. Evolution of major morbidities will have to be carefully watched in the future.

Parental participation in the care of hospitalized neonates in low- and middle-income countries: A systematic review and meta-analysis.

Introduction: To determine the effect of parental participation in hospital care on neonatal and parental outcomes in low- and middle-income countries (LMICs) and to identify the range of parental duties in the care of hospitalized neonates in LMICs. Methods: We searched CINAHL, CENTRAL, LILACs, MEDLINE, EMBASE and Web of Science from inception to February 2022. Randomized and non-randomized studies from LMICs were eligible if parents performed one or more roles traditionally undertaken by healthcare staff. The primary outcome was hospital length-of-stay. Secondary outcomes included mortality, readmission, breastfeeding, growth, development and parental well-being. Data was extracted in duplicate by two independent reviewers using a piloted extraction form. Results: Eighteen studies (eight randomized and ten non-randomized) were included from seven middle-income countries. The types of parental participation included hygiene and infection prevention, feeding, monitoring and documentation, respiratory care, developmental care, medication administration and decision making. Meta-analyses showed that parental participation was not associated with hospital length-of-stay (MD -2.35, 95% CI -6.78-2.07). However, parental involvement was associated with decreased mortality (OR 0.46, 95% CI 0.22-0.95), increased breastfeeding (OR 2.97 95% CI 1.65-5.35) and decreased hospital readmission (OR 0.36, 95% CI 0.16-0.81). Narrative synthesis demonstrated additional benefits for growth, short-term neurodevelopment and parental well-being. Ten of the eighteen studies had a high risk of bias. Conclusion: Parental participation in neonatal hospital care is associated with improvement in several key neonatal outcomes in middle-income countries. The lack of data from low-income countries suggests that there remains barriers to parental participation in resource-poor settings. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=187562], identifier [CRD42020187562].

The Community Health and Social Medicine Incubator: a service-learning framework for medical student-led projects.

The Community Health and Social Medicine (CHASM) Incubator is a social impact venture that gives medical and other health care students the opportunity to develop initiatives that sustainably promote health equity for, and in partnership with, community partners and historically marginalized communities. Students learn how to develop projects with project management curricula, are paired with community health mentors, and are given seed micro-financing. As the first community health incubator driven by medical students, CHASM provides a framework for students interested in implementing sustainable solutions to local health disparities which extends the service-learning opportunities offered in existing curricula.

L'incubateur CHASM (Community Health and Social Medicine) est une initiative visant à créer un impact social en donnant aux étudiants en médecine et des autres sciences de la santé la possibilité de développer des initiatives durables en collaboration avec des partenaires communautaires et des communautés historiquement marginalisées. CHASM met en valeur l'équité en matière de santé. Les étudiants apprennent à élaborer des projets via un cursus de gestion de projet, sont jumelés à des mentors en santé communautaire et bénéficient de micro-financement de départ. Ce premier incubateur de santé communautaire mené par des étudiants en médecine fournit un cadre aux étudiants qui souhaitent mettre en œuvre des solutions durables aux inégalités en matière de santé. Il élargit également les possibilités d'apprentissage par le service offertes dans les cursus existants.

Many randomized clinical trials may not be justified: a cross-sectional analysis of the ethics and science of randomized clinical trials.

OBJECTIVE: We have proposed that three scientific criteria are important for the ethical justification of randomized clinical trials (RCTs): (1) they should be designed around a clear hypothesis; (2) uncertainty should exist around that hypothesis; (3) that uncertainty should be as established through a systematic review. We hypothesized that the majority of a sample of recently published RCTs would not explicitly incorporate these criteria, therefore rendering them potentially unjustified on scientific grounds. STUDY DESIGN AND SETTING: Cross-sectional analysis of all RCTs published in the New England Journal of Medicine and the Journal of the American Medical Association in 2015. Each article and protocol was reviewed for: (1) a clearly stated central hypothesis; (2) references to "equipoise," or "consensus;" (3) some indication of evidentiary uncertainty; (4) a meta-analysis or systematic review surrounding the hypothesis or study question. RESULTS: We included 208 RCT articles and 199 protocols. Among combined articles and protocols, 76% had a clearly stated hypothesis, 99% referenced some form of uncertainty, and 54% cited a relevant systematic review or meta-analysis. Only 44% of combined texts contained all three scientific criteria. There were few references to "equipoise" (10%) or "consensus" (11%), and those references to equipoise were most often inconsistent with accepted definitions. CONCLUSION: The majority of RCTs (56%) did not meet the three scientific criteria described previously and therefore may be scientifically and therefore ethically unjustified. We recommend that "equipoise," "clinical equipoise," and "lack of consensus" be abandoned as scientific criteria for RCTs and be replaced by an expectation that RCTs have a clearly stated, meaningful hypothesis around which uncertainty has been established through a systematic review of the literature.

Respiratory adaptation in term infants following elective caesarean section.

OBJECTIVE: To determine respiratory rate (RR), tidal volume (TV) and end-tidal carbon dioxide (EtCO2) values in full-term infants immediately after caesarean section, and to assess whether infants that develop transient tachypnoea of the newborn (TTN) follow the same physiological patterns. DESIGN AND PATIENTS: A Respironics NM3 Monitor (Philips, Netherlands) continuously measured RR, TV and EtCO2 for 7 min in infants >37 weeks' gestation following elective caesarean section (ECS). Monitoring was repeated at 2 hours of age for 2 min. Gestation, birth weight, Apgar scores and admissions to neonatal unit were documented. SETTING: The operative delivery theatre of Cork University Maternity Hospital, Ireland. RESULTS: There were 95 term infants born by ECS included. Median (IQR) gestation was 39 weeks (38.2-39.1) and median (IQR) birth weight 3420 g (3155-3740). Median age at initiation of monitoring was 26.5 s (range: 20-39). Data were analysed for the first 7 min of life. Mean breaths per minute (bpm) increased over the first 7 min of life (44.31-61.62). TV and EtCO2 values were correlated and increased from 1 min until maximum mean values were recorded at 3 min after delivery (5.18 mL/kg-6.44 mL/kg, and 4.32 kPa-5.64 kPa, respectively). Infants admitted to the neonatal unit with TTN had significantly lower RRs from 2 min of age compared with infants not admitted for TTN. CONCLUSIONS: TV and EtCO2 values are correlated and increase significantly over the first few minutes following ECS. RR increases gradually from birth, and rates were lower in infants that develop TTN.