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JAMA Network Open May 2024Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants.
OBJECTIVE
To determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks' gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death.
DESIGN, SETTING, AND PARTICIPANTS
This phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward. Two analysis cohorts, not breathing well and breathing well, were specified a priori based on assessment of breathing 30 seconds after birth.
INTERVENTION
After birth, all infants received stimulation and suctioning if needed. From 30 to 120 seconds, infants randomized to the intervention received continuous positive airway pressure if breathing well or positive-pressure ventilation if not, with cord clamping at 120 seconds. Control infants received 30 to 60 seconds of delayed cord clamping followed by standard resuscitation.
MAIN OUTCOMES AND MEASURES
The primary outcome was any grade IVH on head ultrasonography or death before day 7. Interpretation by site radiologists was confirmed by independent radiologists, all masked to study group. To estimate the association between study group and outcome, data were analyzed using the stratified Cochran-Mantel-Haenszel test for relative risk (RR), with associations summarized by point estimates and 95% CIs.
RESULTS
Of 1110 women who consented to participate, 548 were randomized and delivered infants at GA less than 29 weeks. A total of 570 eligible infants were enrolled (median [IQR] GA, 26.6 [24.9-27.7] weeks; 297 male [52.1%]). Intraventricular hemorrhage or death occurred in 34.9% (97 of 278) of infants in the intervention group and 32.5% (95 of 292) in the control group (adjusted RR, 1.02; 95% CI, 0.81-1.27). In the prespecified not-breathing-well cohort (47.5% [271 of 570]; median [IQR] GA, 26.0 [24.7-27.4] weeks; 152 male [56.1%]), IVH or death occurred in 38.7% (58 of 150) of infants in the intervention group and 43.0% (52 of 121) in the control group (RR, 0.91; 95% CI, 0.68-1.21). There was no evidence of differences in death, severe brain injury, or major morbidities between the intervention and control groups in either breathing cohort.
CONCLUSIONS AND RELEVANCE
This study did not show that providing assisted ventilation before cord clamping in extremely preterm infants reduces IVH or early death. Additional study around the feasibility, safety, and efficacy of assisted ventilation before cord clamping may provide additional insight.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02742454.
Topics: Humans; Infant, Newborn; Infant, Extremely Premature; Female; Male; Umbilical Cord Clamping; Canada; Respiration, Artificial; Cerebral Intraventricular Hemorrhage; Umbilical Cord; Continuous Positive Airway Pressure; Gestational Age; Time Factors; United States
PubMed: 38758557
DOI: 10.1001/jamanetworkopen.2024.11140 -
Frontiers in Pediatrics 2024Despite major advances in neonatal care, oxygen remains the most commonly used medication in the neonatal intensive care unit (NICU). Supplemental oxygen can be... (Review)
Review
Despite major advances in neonatal care, oxygen remains the most commonly used medication in the neonatal intensive care unit (NICU). Supplemental oxygen can be life-saving for term and preterm neonates in the resuscitation period and beyond, however use of oxygen in the neonatal period must be judicious as there can be toxic effects. Newborns experience substantial hemodynamic changes at birth, rapid energy consumption, and decreased antioxidant capacity, which requires a delicate balance of sufficient oxygen while mitigating reactive oxygen species causing oxidative stress. In this review, we will discuss the physiology of neonates in relation to hypoxia and hyperoxic injury, the history of supplemental oxygen in the delivery room and beyond, supporting clinical research guiding trends for oxygen therapy in neonatal care, current practices, and future directions.
PubMed: 38751747
DOI: 10.3389/fped.2024.1371710 -
Scientific Reports May 2024Severe intraventricular hemorrhage (IVH) in premature infants can lead to serious neurological complications. This retrospective cohort study used the Korean Neonatal...
Severe intraventricular hemorrhage (IVH) in premature infants can lead to serious neurological complications. This retrospective cohort study used the Korean Neonatal Network (KNN) dataset to develop prediction models for severe IVH or early death in very-low-birth-weight infants (VLBWIs) using machine-learning algorithms. The study included VLBWIs registered in the KNN database. The outcome was the diagnosis of IVH Grades 3-4 or death within one week of birth. Predictors were categorized into three groups based on their observed stage during the perinatal period. The dataset was divided into derivation and validation sets at an 8:2 ratio. Models were built using Logistic Regression with Ridge Regulation (LR), Random Forest, and eXtreme Gradient Boosting (XGB). Stage 1 models, based on predictors observed before birth, exhibited similar performance. Stage 2 models, based on predictors observed up to one hour after birth, showed improved performance in all models compared to Stage 1 models. Stage 3 models, based on predictors observed up to one week after birth, showed the best performance, particularly in the XGB model. Its integration into treatment and management protocols can potentially reduce the incidence of permanent brain injury caused by IVH during the early stages of birth.
Topics: Humans; Machine Learning; Infant, Newborn; Republic of Korea; Female; Male; Retrospective Studies; Infant, Very Low Birth Weight; Databases, Factual; Cerebral Hemorrhage; Algorithms; Cerebral Intraventricular Hemorrhage; Infant, Premature
PubMed: 38750286
DOI: 10.1038/s41598-024-62033-y -
EClinicalMedicine Jun 2024Anemia is a significant contributor to the global disease burden, of which thalassemia is the most common hereditary anaemic disease. Previous estimates were based on...
BACKGROUND
Anemia is a significant contributor to the global disease burden, of which thalassemia is the most common hereditary anaemic disease. Previous estimates were based on data that were geographically limited and lacked comprehensive global analysis. This study provides the prevalence, incidence, mortality and disability-adjusted life years (DALYs) of thalassemia in 204 countries and regions of thalassemia between 1990 and 2021, focusing on the age structure and time trends of the disease burden. To provide effective information for health policy, allocation of medical resources and optimization of patient management programs.
METHODS
Using the standardised Global Burden of Disease (GBD) methodologies, we aimed to derive a more precise representation of the health burden posed by thalassemia by considering four distinct types of epidemiological data, namely the incidence at birth, prevalence, mortality and DALYs. The presented data were meticulously estimated and displayed both as numerical counts and as age-standardised rates per 100,000 persons of the population, accompanied by uncertainty interval (UI) to highlight potential statistical variability. The temporal trends spanning the years 1990-2021 were subjected to a rigorous examination utilizing Joinpoint regression analysis. This methodological approach facilitated the computation of the annual percentage change (APC) and the average annual percentage change (AAPC), along with their corresponding 95% confidence intervals (CIs).
FINDINGS
Globally, the age-standardized prevalence rates (ASPR), age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALYs rates for thalassemia in 2021 were 18.28 per 100,000 persons (95% UI 15.29-22.02), 1.93 per 100,000 persons (95% UI 1.51-2.49), 0.15 per 100,000 persons(95% UI 0.11-0.20), and 11.65 per 100,000 persons (95% UI 8.24-14.94), respectively. Compared to 1990, these rates have decreased by 0.18 (95% UI -0.22 to -0.14), 0.25 (95% UI -0.30 to -0.19), 0.48 (95% UI -0.60 to -0.28), and 0.49 (95% UI -0.62 to -0.29) respectively. In 2021, the ASIR of thalassemia was highest in East Asia at 7.35 per 100,000 persons (95% UI 5.37-10.04), and ASMR was highest in Southeast Asia at 0.37 per 100,000 persons (95% UI 0.29-0.45).Gender comparisons showed negligible differences in disease burden, with the highest prevalence noted in children under five, decreasing with age. The global ASPR and ASMR declined from 1990 to 2021 overall, though an increasing trend in prevalence was found among the elderly. Joinpoint analysis revealed that the global ASPR increased between 2018 and 2021 (APC = 9.2%, 95% CI: 4.8%-13.8%, P < 0.001), ASIR decreased (APC = -7.68%, 95% CI: -10.88% to -4.36%, P < 0.001), and there was a significant rise in ASMR from 2019 to 2021 (APC = 4.8%, 95% CI: 0.1%-9.6%, P < 0.05). Trends in ASPR and ASMR varied across regions, with notable changes in South Asia.
INTERPRETATION
The global burden of thalassemia, reflected in its prevalence, incidence, mortality, and DALYs, exhibits significant disparities. Geographic and demographic shifts in disease distribution have been observed from 1990 to 2021, with an overall decrease in burden, yet an increase in cases among the elderly population. Analysis of epidemiological trends over time highlights the influence of health policies and significant public health interventions on thalassemia outcomes. There data are crucial for healthcare professionals, policymakers, and researchers to refine and enhance management strategies, aiming to further mitigate thalassemia's global impact.
FUNDING
National Natural Science Foundation of China; Guizhou Province Science and Technology Project; Guizhou Province Science and Technology Foundation of Health Commission.
PubMed: 38745964
DOI: 10.1016/j.eclinm.2024.102619 -
Cellular & Molecular Biology Letters May 2024Aberrant mitochondrial fission, a critical pathological event underlying myocardial ischemia/reperfusion (MI/R) injury, has emerged as a potential therapeutic target....
BACKGROUND
Aberrant mitochondrial fission, a critical pathological event underlying myocardial ischemia/reperfusion (MI/R) injury, has emerged as a potential therapeutic target. The long non-coding RNA (lncRNA) Oip5-as1 is increasingly recognized for its regulatory roles, particularly in MI/R injury. However, its precise mechanistic role in modulating mitochondrial dynamics remains elusive. This study aims to elucidate the mechanistic role of Oip5-as1 in regulating mitochondrial fission and evaluate its therapeutic potential against MI/R injury.
METHODS
To simulate in vitro MI/R injury, HL-1 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R). Lentiviral vectors were employed to achieve overexpression or knockdown of Oip5-as1 in HL-1 cells by expressing Oip5-as1 or shRNA targeting Oip5-as1, respectively. The impact of Oip5-as1 on mitochondrial dynamics in HL-1 cells was assessed using CCK-8 assay, flow cytometry, immunofluorescence staining, and biochemical assays. MI/R injury was induced in mice by ligating the left anterior descending coronary artery. Conditional knockout mice for Oip5-as1 were generated using the CRISPR/Cas9 genome editing technology, while overexpression of Oip5-as1 in mice was achieved via intramyocardial administration of AAV9 vectors. In mice, the role of Oip5-as1 was evaluated through echocardiographic assessment, histopathological staining, and transmission electron microscopy. Furthermore, Western blotting, RNA pull-down, RNA immunoprecipitation, and co-immunoprecipitation assays were conducted to investigate Oip5-as1's underlying mechanisms.
RESULTS
The expression levels of Oip5-as1 are significantly decreased in MI/R-injured HL-1 cells and myocardium. In HL-1 cells undergoing H/R injury, overexpression of Oip5-as1 attenuated excessive mitochondrial fission, preserved mitochondrial functionality, and reduced cellular apoptosis, while knockdown of Oip5-as1 exhibited the opposite effects. Furthermore, in a mouse model of MI/R injury, overexpression of Oip5-as1 diminished mitochondrial fission, myocardial infarct size and improved cardiac function. However, knockout of Oip5-as1 exacerbated myocardial injury and cardiac dysfunction, which were significantly reversed by treatment with a mitochondrial division inhibitor-1 (Mdivi-1). Mechanistically, Oip5-as1 selectively interacts with AKAP1 and CaN proteins, inhibiting CaN activation and subsequent DRP1 dephosphorylation at Ser637, thereby constraining DRP1's translocation to the mitochondria and its involvement in mitochondrial fission.
CONCLUSIONS
Our study underscores the pivotal role of Oip5-as1 in mitigating excessive mitochondrial fission during MI/R injury. The findings not only enhance our comprehension of the molecular mechanisms underlying MI/R injury but also identify Oip5-as1 as a potential therapeutic target for ameliorating MI/R injury.
Topics: RNA, Long Noncoding; Animals; Mitochondrial Dynamics; Myocardial Reperfusion Injury; Dynamins; Mice; Phosphorylation; Myocytes, Cardiac; Cell Line; Mice, Knockout; Male; Mice, Inbred C57BL
PubMed: 38745296
DOI: 10.1186/s11658-024-00588-4 -
PloS One 2024The brachial plexus is a set of nerves that innervate the upper extremity and may become injured during the birthing process through an injury known as Neonatal Brachial...
The brachial plexus is a set of nerves that innervate the upper extremity and may become injured during the birthing process through an injury known as Neonatal Brachial Plexus Palsy. Studying the mechanisms of these injuries on infant cadavers is challenging due to the justifiable sensitivity surrounding testing. Thus, these specimens are generally unavailable to be used to investigate variations in brachial plexus injury mechanisms. Finite Element Models are an alternative way to investigate the response of the neonatal brachial plexus to loading. Finite Element Models allow a virtual representation of the neonatal brachial plexus to be developed and analyzed with dimensions and mechanical properties determined from experimental studies. Using ABAQUS software, a two-dimensional brachial plexus model was created to analyze how stresses and strains develop within the brachial plexus. The main objectives of this study were (1) to develop a model of the brachial plexus and validate it against previous literature, and (2) to analyze the effect of stress on the nerve roots based on variations in the angles between the nerve roots and the spinal cord. The predicted stress for C5 and C6 was calculated as 0.246 MPa and 0.250 MPa, respectively. C5 and C6 nerve roots experience the highest stress and the largest displacement in comparison to the lower nerve roots, which correlates with clinical patterns of injury. Even small (+/- 3 and 6 degrees) variations in nerve root angle significantly impacted the stress at the proximal nerve root. This model is the first step towards developing a complete three-dimensional model of the neonatal brachial plexus to provide the opportunity to more accurately assess the effect of the birth process on the stretch within the brachial plexus and the impact of biological variations in structure and properties on the risk of Neonatal Brachial Plexus Palsy.
Topics: Brachial Plexus; Finite Element Analysis; Humans; Infant, Newborn; Stress, Mechanical; Biomechanical Phenomena
PubMed: 38743738
DOI: 10.1371/journal.pone.0303511 -
Frontiers in Pediatrics 2024According to Bangladesh Demographic and Health Survey (2022), neonatal mortality, comprising 67% of under-5 deaths in Bangladesh, is significantly attributed to...
Vayu bubble continuous positive airway pressure is a promising solution with favorable treatment outcomes for respiratory distress syndrome in newborns: a qualitative study in Bangladesh.
BACKGROUND
According to Bangladesh Demographic and Health Survey (2022), neonatal mortality, comprising 67% of under-5 deaths in Bangladesh, is significantly attributed to prematurity and low birth weight (LBW), accounting for 32% of neonatal deaths. Respiratory distress syndrome (RDS) is a prevalent concern among preterm and LBW infants, leading to substantial mortality. The World Health Organization (WHO) recommends bubble continuous positive airway pressure (bCPAP) therapy, but the affordability and accessibility of conventional bCPAP devices for a large number of patients become major hurdles in Bangladesh due to high costs and resource intensiveness. The Vayu bCPAP, a simple and portable alternative, offers a constant flow of oxygen-enriched, filtered, humidified, and pressurized air. Our study, conducted in five health facilities, explores the useability, acceptability, and perceived treatment outcome of Vayu bCPAP in the local context of Bangladesh.
METHODS
A qualitative approach was employed in special care newborn units (SCANUs) of selected facilities from January to March 2023. Purposive sampling identified nine key informants, 40 in-depth interviews with service providers, and 10 focus group discussions. Data collection and analysis utilized a thematic framework approach led by trained anthropologists and medical officers.
RESULTS
Service providers acknowledged Vayu bCPAP as a lightweight, easily movable, and cost-effective device requiring minimal training. Despite challenges such as consumable shortages and maintenance issues, providers perceived the device as user-friendly, operable with oxygen cylinders, and beneficial during referral transportation. Treatment outcomes indicated effective RDS management, reduced hospital stays, and decreased referrals. Though challenges existed, healthcare providers and facility managers expressed enthusiasm for Vayu bCPAP due to its potential to simplify advanced neonatal care delivery.
CONCLUSIONS
The Vayu bCPAP device demonstrated useability, acceptability, and favorable treatment outcomes in the care of neonates with RDS. However, sustained quality service necessitates continuous monitoring, mentoring and retention of knowledge and skills. Despite challenges, the enthusiasm among healthcare providers underscores the potential of Vayu bCPAP to save lives and simplify neonatal care delivery. Development of Standard Operating procedure on Vayu bCPAP is required for systematic implementation. Further research is needed to determine how the utilization of Vayu bCPAP devices enhances accessibility to efficient bCPAP therapy for neonates experiencing RDS.
PubMed: 38742241
DOI: 10.3389/fped.2024.1359406 -
European Journal of Midwifery 2024Perineal trauma is associated with both short- and long-term morbidity which in turn relates to the degree of trauma. The objective of this study was to understand...
INTRODUCTION
Perineal trauma is associated with both short- and long-term morbidity which in turn relates to the degree of trauma. The objective of this study was to understand midwives' practices regarding perineal protection during the second phase of labor, emphasizing decision-making to perform an episiotomy.
METHODS
A descriptive and explanatory study was conducted with an intentional sample of twenty-two midwives working in the labor ward of a tertiary hospital in a metropolitan location and in the public service, in Portugal. A semi-open interview was applied to collect the data from 5 to 15 January 2019. The computer software package, NVivo version 10, was used to perform the thematic analysis.
RESULTS
Four main themes arose from the midwives' data: 1) Factors affecting the application of perineal protection techniques', 2) Birth position, 3) Techniques for perineal protection, and 4) Episiotomy. The reasons for performing an episiotomy were the presence of tense perineum, large weight baby, previous obstetric anal sphincter injury, and Kristeller maneuver.
CONCLUSIONS
Midwives' practices regarding perineal protection techniques and reasons for performing an episiotomy were not all in line with the evidence. Perineal massage was not mentioned as a perineal protection technique.
PubMed: 38736456
DOI: 10.18332/ejm/174126 -
Biological Psychiatry May 2024Body dysmorphic disorder (BDD) is thought to be associated with considerable suicide risk. This nationwide cohort study quantified the risks of intentional self-harm -...
OBJECTIVES
Body dysmorphic disorder (BDD) is thought to be associated with considerable suicide risk. This nationwide cohort study quantified the risks of intentional self-harm - including non-suicidal self-injuries and suicide attempts - and death by suicide in BDD.
METHODS
Individuals with a validated ICD-10 diagnosis of BDD in the Swedish National Patient Register, registered between January 1, 1997 and December 31, 2020, were matched with 10 unexposed individuals from the general population on birth year, sex, and county of residence. Conditional Poisson regression models estimated incidence rate ratios (IRR) and 95% confidence intervals (CIs) for intentional self-harm and stratified Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs for death by suicide. Models adjusted for sociodemographic variables and lifetime psychiatric comorbidities.
RESULTS
Among 2,833 individuals with BDD and 28,330 unexposed matched individuals, 466 (16.45%) and 1,071 (3.78%) had at least one record of intentional self-harm during the study period, respectively (IRR=3.37; 95% CI, 3.02-3.76). In the BDD cohort, about two thirds (n=314; 67%) had their first recorded self-harm event before their first BDD diagnosis. A total of 17 (0.60%) individuals with BDD and 27 (0.10%) unexposed individuals died by suicide (HR=3.47; 95% CI, 1.76-6.85). All results remained robust to additional adjustment for lifetime psychiatric comorbidities. A higher proportion of individuals with BDD who died by suicide had at least one previous record of intentional self-harm, compared to unexposed individuals (52.94% vs. 22.22%; p=0.0363).
CONCLUSIONS
BDD was associated with a three-fold increased risk of intentional self-harm and death by suicide.
PubMed: 38734199
DOI: 10.1016/j.biopsych.2024.05.006 -
Transplantation Proceedings May 2024Deterioration of kidney function after orthotopic liver transplantation is a common complication that may occur after perioperative acute kidney injury (AKI) and...
Deterioration of kidney function after orthotopic liver transplantation is a common complication that may occur after perioperative acute kidney injury (AKI) and preexisting or developing chronic kidney disease (CKD). AKI is described in the early postoperative period in more than half of recipients, whereas the main cause of CKD is pharmacotherapy. When end-stage renal failure occurs, patients may be qualified for additional transplantations. We present a rare case of a 27-year-old woman who, as a teenager, underwent 2 liver transplantations due to Wilson's disease. Surgeries were complicated by systemic infection and multiple organ failure. The kidneys did not regain their function, and therefore, after 6 months of dialysis, the organ was transplanted. Three organ transplantations were performed. Due to the patient's willingness and good graft functions, the patient started trying to conceive. Three months before successful conception, immunosuppressive therapy was changed to tacrolimus and azathioprine. Pregnancy was complicated by pregnancy-induced hypertension, and its course was closely monitored. Organ functions and immunosuppressive therapy were regularly assessed. Due to the pre-eclampsia developed in the 35th week of gestation, a Cesarean delivery was performed, and she gave birth to a daughter weighing 2350 g (Apgar 7-7-8). The patient decided to breastfeed. There were no obstetric complications or graft function deterioration in the early postpartum period. Mother and daughter left home after 7 days of hospitalization. The presented clinical situation proves that multiorgan transplantation recipients can have a successful pregnancy without impairing graft functions. Therefore, the pregnancy requires adequate preparation and increased care.
PubMed: 38729837
DOI: 10.1016/j.transproceed.2024.03.033