Ventilation Strategies During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure: Current Approaches Among Level IV Neonatal ICUs

To describe ventilation strategies used during extracorporeal membrane oxygenation (ECMO) for neonatal respiratory failure among level IV neonatal ICUs (NICUs). Design: Cross-sectional electronic survey. Setting: Email-based Research Electronic Data Capture survey. Patients: Neonates undergoing ECMO for respiratory failure at level IV NICUs. Interventions: A 40-question survey was sent to site sponsors of regional referral neonatal ECMO centers participating in the Children\u27s Hospitals Neonatal Consortium. Reminder emails were sent at 2- and 4-week intervals. Measurements and main results: Twenty ECMO centers responded to the survey. Most primarily use venoarterial ECMO (65%); this percentage is higher (90%) for congenital diaphragmatic hernia. Sixty-five percent reported following protocol-based guidelines, with neonatologists primarily responsible for ventilator management (80%). The primary mode of ventilation was pressure control (90%), with synchronized intermittent mechanical ventilation (SIMV) comprising 80%. Common settings included peak inspiratory pressure (PIP) of 16-20 cm H2O (55%), positive end-expiratory pressure (PEEP) of 9-10 cm H2O (40%), I-time 0.5 seconds (55%), rate of 10-15 (60%), and Fio2 22-30% (65%). A minority of sites use high-frequency ventilation (HFV) as the primary mode (5%). During ECMO, 55% of sites target some degree of lung aeration to avoid complete atelectasis. Fifty-five percent discontinue inhaled nitric oxide (iNO) during ECMO, while 60% use iNO when trialing off ECMO. Nonventilator practices to facilitate decannulation include bronchoscopy (50%), exogenous surfactant (25%), and noninhaled pulmonary vasodilators (50%). Common ventilator thresholds for decannulation include PEEP of 6-7 (45%), PIP of 21-25 (55%), and tidal volume 5-5.9 mL/kg (50%). Conclusions: The majority of level IV NICUs follow internal protocols for ventilator management during neonatal respiratory ECMO, and neonatologists primarily direct management in the NICU. While most centers use pressure-controlled SIMV, there is considerable variability in the range of settings used, with few centers using HFV primarily. Future studies should focus on identifying respiratory management practices that improve outcomes for neonatal ECMO patients

Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n1⁄42,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n1⁄43,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombinedo5108) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist

Outcomes of Moderately Preterm Infants of Insulin-Dependent Diabetic Mothers

Objective Little is known about the hospital outcomes of moderately preterm (MPT; 29 0/7–33 6/7 weeks gestational age) infants born to insulin-dependent diabetic mothers (IDDMs). We evaluated characteristics and outcomes of MPT infants born to IDDMs compared with those without IDDM (non-IDDM). Study Design Cohort study of infants from 18 centers included in the MPT infant database from 2012 to 2013. We compared characteristics and outcomes of infants born to IDDMs and non-IDDMs. Results Of 7,036 infants, 527 (7.5%) were born to IDDMs. Infants of IDDMs were larger at birth, more often received continuous positive pressure ventilation in the delivery room, and had higher risk of patent ductus arteriosus (adjusted relative risk or aRR: 1.49, 95% confidence interval [CI]: 1.20–1.85) and continued hospitalization at 40 weeks postmenstrual age (aRR: 1.55, 95% CI: 1.18–2.05). Conclusion MPT infants of IDDM received more respiratory support and prolonged hospitalizations, providing further evidence of the important neonatal health consequences of maternal diabetes. Key Points </jats:p

Linked electronic health records for research on a nationwide cohort including over 54 million people in England

ABSTRACTObjectivesDescribe a new England-wide electronic health record (EHR) resource enabling whole population research on Covid-19 and cardiovascular disease whilst ensuring data security and privacy and maintaining public trust.DesignCohort comprising linked person-level records from national healthcare settings for the English population accessible within NHS Digital’s new Trusted Research Environment.SettingEHRs from primary care, hospital episodes, death registry, Covid-19 laboratory test results and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular and Covid-19 vaccination data.Participants54.4 million people alive on 1st January 2020 and registered with an NHS general practitioner in England.Main measures of interestConfirmed and suspected Covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack (TIA) and incident myocardial infarction (MI)) and all-cause mortality between 1st January and 31st October 2020.ResultsThe linked cohort includes over 96% of the English population. By combining person-level data across national healthcare settings, data on age, sex and ethnicity are complete for over 95% of the population. Among 53.2M people with no prior diagnosis of stroke/TIA, 98,721 had an incident stroke/TIA, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.1M people with no prior history of MI, 62,966 had an incident MI, of which 8% were recorded only in primary care and 12% only in death records. A total of 959,067 people had a confirmed or suspected Covid-19 diagnosis (714,162 in primary care data, 126,349 in hospital admission records, 776,503 in Covid-19 laboratory test data and 48,433 participants in death registry records). While 58% of these were recorded in both primary care and Covid-19 laboratory test data, 15% and 18% respectively were recorded in only one.ConclusionsThis population-wide resource demonstrates the importance of linking person-level data across health settings to maximize completeness of key characteristics and to ascertain cardiovascular events and Covid-19 diagnoses. Although established initially to support research on Covid-19 and cardiovascular disease to benefit clinical care and public health and to inform health care policy, it can broaden further to enable a very wide range of research.</jats:sec

Team Stress and Adverse Events during Neonatal Tracheal Intubations: A Report from NEAR4NEOS

Objective This study aimed to examine the association between team stress level and adverse tracheal intubation (TI)-associated events during neonatal intubations. Study Design TIs from 10 academic neonatal intensive care units were analyzed. Team stress level was rated immediately after TI using a 7-point Likert scale (1 = high stress). Associations among team stress, adverse TI-associated events, and TI characteristics were evaluated. Result In this study, 208 of 2,009 TIs (10%) had high stress levels (score &lt; 4). Oxygenation failure, hemodynamic instability, and family presence were associated with high stress level. Video laryngoscopy and premedication were associated with lower stress levels. High stress level TIs were associated with adverse TI-associated event rates (31 vs. 16%, p &lt; 0.001), which remained significant after adjusting for potential confounders including patient, provider, and practice factors associated with high stress (odds ratio: 1.90, 96% confidence interval: 1.36–2.67, p &lt; 0.001). Conclusion High team stress levels during TI were more frequently reported among TIs with adverse events.</jats:p

Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

AbstractAlthough two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.</jats:p