Late preterm antenatal corticosteroids in singleton and twin gestations: a retrospective cohort study.

BACKGROUND: In 2016, the American College of Obstetricians and Gynecologists recommended antenatal corticosteroids in the late preterm period for women at risk for preterm delivery. Limited real-world evidence exists on neonatal outcomes, particularly for twin gestations, following the guideline change. The study objective is to determine the association of antenatal corticosteroids in late preterm singleton and twin pregnancies with respiratory complications and hypoglycemia in a real-world clinical setting. METHODS: This is a retrospective cohort study comprising late preterm deliveries (4,341 mother-child pairs) within the Mount Sinai Health System, 2012-2018. The exposure of interest is antenatal corticosteroid administration of betamethasone during pregnancy between 34 0/7 and 36 6/7 weeks. Our primary outcomes are neonatal respiratory complications and hypoglycemia. Multivariable logistic regression was used to estimate the association between antenatal corticosteroid exposure and these two outcomes. We stratified the study population by singleton gestations and twins to minimize the potential confounding from different obstetric management between the two groups. RESULTS: Among a total of 4,341 mother-child pairs (3,309 singleton and 1,032 twin mother-child pairs), 745 mothers received betamethasone, of which 40.94% (305/745) received the full course. Relative to no treatment, a full course of betamethasone was associated with reduced odds of respiratory complications (OR = 0.53, 95% CI:[0.31-0.85], p < 0.01) and increased odds of hypoglycemia (OR = 1.86, 95%CI:[1.34-2.56], p < 0.01) in singletons; however, the association with respiratory complications was not significant in twins (OR = 0.42, 95% CI:[0.11-1.23], p = 0.16), but was associated with increased odds of hypoglycemia (OR = 2.18, 95% CI:[1.12-4.10], p = 0.02). A partial course of betamethasone (relative to no treatment) was not significantly associated with any of the outcomes, other than respiratory complications in twins (OR = 0.34, 95% CI:[0.12-0.82], p = 0.02). CONCLUSIONS: Exposure to antenatal corticosteroids in singletons and twins is associated with increased odds of hypoglycemia. Among singletons, exposure to the full dosage (i.e. two doses) was associated with decreased odds of respiratory complications but this was only the case for partial dose among twins. Twin gestations were not studied by the Antenatal Late Preterm Steroids trial. Therefore, our study findings will contribute to the paucity of evidence on the benefit of antenatal corticosteroids in this group. Health systems should systematically monitor guideline implementations to improve patient outcomes.

[The Effect of High Humidity Environments on Very Low Birth Weight Preterm Infants: A Systematic Review].

BACKGROUND: The scholarly evidence on the timing and practice of interventional care administered to preterm infants in high-humidity environments is unclear. This makes evaluating the prognosis of preterm infants with comorbidities difficult and means that clinical medical staff lack clear guidelines for care. PURPOSE: This systematic review was designed to explore the prognostic effects of interventions for comorbidities performed on very low birthweight preterm infants in high humidity environments to provide an empirical basis for developing related clinical-care guidelines. METHODS: An electronic database was searched for all relevant documents published between 1930 and September 2021. The keywords used were "premature infants" OR "very low weight premature infants" OR "very low weight premature infants" AND "humidity", and the target groups were premature infants weighing ≤ 1,500 grams or delivered at ≤ 34 weeks of gestation. The timing and practice of interventions in high humidity environments and the occurrence and prognosis of related comorbidities were explored. The main findings cover the issues of body weight, total water intake, electrolytes, urine output, insensitivity water loss, infection, common complications, and mortality in preterm infants. After reviewing the methods, quality, and efficacy of the research in the identified studies, 9 articles were selected for integrated synthesis. RESULTS: Recommendations for the use of high humidity with infants delivered at ≤ 30 weeks of gestation or at birth weights ≤ 1,000 grams were integrated. An environment with a relative humidity of 70%-80% should be used during the first postpartum week and 50%-60% during the second postpartum week. The recommended total duration of use of a high-humidity environment is two weeks to avoid delaying the development of the stratum corneum. Physiological indicators shown to exhibit significant improvement under this regimen include reduced total water intake, increased urine output, and a lower incidence of hypernatremia. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The appropriate timing and practice of high humidity intervention were integrated in this study. It is hoped that this review provides an evidence-based clinical practice guideline for preterm infant care.

Compassionate End-of-Life Care: Mixed-Methods Multisite Evaluation of the 3 Wishes Project.

Background: The 3 Wishes Project (3WP) is an end-of-life program that aims to honor the dignity of dying patients by creating meaningful patient- and family-centered memories while promoting humanistic interprofessional care. Objective: To determine whether this palliative intervention could be successfully implemented-defined as demonstrating value, transferability, affordability, and sustainability-beyond the intensive care unit in which it was created. Design: Mixed-methods formative program evaluation. (ClinicalTrials.gov: NCT04147169). Setting: 4 North American intensive care units. Participants: Dying patients, their families, clinicians, hospital managers, and administrators. Intervention: Wishes from dying patients, family members, and clinicians were elicited and implemented. Measurements: Patient characteristics and processes of care; the number, type, and cost of each wish; and semistructured interviews and focus groups with family members, clinicians, and managers. Results: A total of 730 patients were enrolled, and 3407 wishes were elicited. Qualitative data were gathered from 75 family members, 72 clinicians, and 20 managers or hospital administrators. Value included intentional comforting of families as they honored the lives and legacies of their loved ones while inspiring compassionate clinical care. Factors promoting transferability included family appreciation and a collaborative intensive care unit culture committed to dignity-conserving end-of-life care. Staff participation evolved from passive support to professional agency. Program initiation required minimal investment for reusable materials; thereafter, the mean cost was $5.19 (SD, $17.14) per wish. Sustainability was demonstrated by the continuation of 3WP at each site after study completion. Limitation: This descriptive formative evaluation describes tertiary care center-specific experiences rather than aiming for generalizability to all jurisdictions. Conclusion: The 3WP is a transferrable, affordable, and sustainable program that provides value to dying patients, their families, clinicians, and institutions. Primary Funding Source: Greenwall Foundation.

[Improving the Completeness of Facilitated Tucking for Preterm Infants in the Neonatal Intensive Care Unit].

BACKGROUND & PROBLEMS: Facilitated tucking (containment) is a strategy that has been demonstrated to improve insufficient muscle tone, reduce procedural pain, and stabilize vital signs in premature infants. PURPOSE: The aim of this study was to improve the accuracy and implementation rate of nursing staffs` facilitated tucking. METHODS: Formulate and standardize nursing care to reduce the burden on nursing staff and make staff implementation consistent. Decomposition diagrams of the production steps were posted in patient units, on-the-job education courses were held, and a short video was used to provide care guidelines to nursing staff. RESULTS: Compared to pretest levels, the rate of facilitated tucking implementation in the early, middle, and late invasive medical treatment periods, respectively, increased from 0% to 53.5%, 1.2% to 50%, and 6% to 48.8%, while the accuracy rate of facilitated tucking cognition increased from 61.1% to 91.9%. CONCLUSIONS: This project effectively promoted the standardization of facilitated tucking in our hospital, provided preterm infants with better care and neurological development, and improved mother-infant attachment.

Passive Leg Raise: Feasibility and Safety of the Maneuver in Patients With Undifferentiated Shock.

PURPOSE: Passive leg raise (PLR), in combination with technologies capable of capturing stroke volume changes, has been widely adopted in the management of shock. However, dedicated evaluation of safety, feasibility, and receptiveness of patients and nursing staff to PLR maneuver is missing. METHODS: A noninterventional, prospective trial recruited adult patients with onset of undifferentiated shock within 24 hours with persistent vasopressor requirements despite fluid resuscitation. A standardized PLR maneuver was used to compare two noninvasive hemodynamic monitoring systems, each without significant impact on the performance of the maneuver. Safety and efficacy of the PLR were evaluated via subjective and objective measures. Objective measures of patient comfort and tolerance were evaluated through changes in vital signs, sedation, and analgesia requirements. Nurses and awake patients completed surveys on their experience. RESULTS: Seventy-nine patients were enrolled. Testing was aborted in 2 cases for medical reasons (one patient developed rapid atrial fibrillation, second had profound desaturation). Of all, 5.4% of patients required additional vasopressor support after completion of the PLR maneuver due to persistent hypotension and 4.1% of patients required additional sedation. Among awake patients (N = 35), 6% reported pain and 29% reported discomfort. A total of 11% of nurses reported minor technical difficulties with the maneuver. CONCLUSION: Passive leg raise maneuver leads to a few serious but reversible complications in a selected population of hemodynamically unstable patients. Although it provides relevant diagnostic information, it may impact patient care. Treating physician should be aware of infrequent but possible complications and appreciate the impact of the maneuver on patients' comfort and nursing workload.

Targeting ENT1 and adenosine tone for the treatment of Huntington's disease.

Huntington's disease (HD) is caused by an abnormal CAG expansion in the exon 1 of huntingtin gene. The treatment of HD is an unmet medical need. Given the important role of adenosine in modulating brain activity, in this study, levels of adenosine and adenine nucleotides in the cerebral spinal fluid of patients with HD and in the brain of two mouse models of HD (R6/2 and Hdh150Q) were analysed. The expression and activity of ENT1 in the striatum of mice with HD were measured. Targeting adenosine tone for treating HD was examined in R6/2 mice by genetic removal of ENT1 and by giving an ENT1 inhibitor, respectively. The results showed that the adenosine homeostasis is dysregulated in the brain of patients and mice with HD. In patients, the ratio of adenosine/ATP in the cerebral spinal fluid was negatively correlated with the disease duration, and tended to have a positive correlation with independence scale and functional capacity. In comparison to controls, mRNA level of ENT1 was higher in the striatum of R6/2 and Hdh150Q mice. Intrastriatal administration of ENT1 inhibitors increased extracellular level of adenosine in the striatum of R6/2 mice to a much higher level than controls. Chronic inhibition of ENT1 or by genetic removal of ENT1 enhanced the survival of R6/2 mice. Collectively, adenosine homeostasis and ENT1 expression are altered in HD. The inhibition of ENT1 can enhance extracellular adenosine level and be a potential therapeutic approach for treating HD.

Potential Industrial Production of a Well-Soluble, Alkaline-Stable, and Anti-Inflammatory Isoflavone Glucoside from 8-Hydroxydaidzein Glucosylated by Recombinant Amylosucrase of Deinococcus geothermalis.

8-Hydroxydaidzein (8-OHDe), an ortho-hydroxylation derivative of soy isoflavone daidzein isolated from some fermented soybean foods, has been demonstrated to possess potent anti-inflammatory activity. However, the isoflavone aglycone is poorly soluble and unstable in alkaline solutions. To improve the aqueous solubility and stability of the functional isoflavone, 8-OHDe was glucosylated with recombinant amylosucrase of Deinococcus geothermalis (DgAS) with industrial sucrose, instead of expensive uridine diphosphate-glucose (UDP-glucose). One major product was produced from the biotransformation, and identified as 8-OHDe-7-α-glucoside, based on mass and nuclear magnetic resonance spectral analyses. The aqueous solubility and stability of the isoflavone glucoside were determined, and the results showed that the isoflavone glucoside was almost 4-fold more soluble and more than six-fold higher alkaline-stable than 8-OHDe. In addition, the anti-inflammatory activity of 8-OHDe-7-α-glucoside was also determined by the inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells. The results showed that 8-OHDe-7-α-glucoside exhibited significant and dose-dependent inhibition on the production of nitric oxide, with an IC50 value of 173.2 µM, which remained 20% of the anti-inflammatory activity of 8-OHDe. In conclusion, the well-soluble and alkaline-stable 8-OHDe-7-α-glucoside produced by recombinant DgAS with a cheap substrate, sucrose, as a sugar donor retains moderate anti-inflammatory activity, and could be used in industrial applications in the future.

A New Triterpenoid Glucoside from a Novel Acidic Glycosylation of Ganoderic Acid A via Recombinant Glycosyltransferase of Bacillus subtilis.

Ganoderic acid A (GAA) is a bioactive triterpenoid isolated from the medicinal fungus Ganoderma lucidum. Our previous study showed that the Bacillus subtilis ATCC (American type culture collection) 6633 strain could biotransform GAA into compound (1), GAA-15-O-ß-glucoside, and compound (2). Even though we identified two glycosyltransferases (GT) to catalyze the synthesis of GAA-15-O-ß-glucoside, the chemical structure of compound (2) and its corresponding enzyme remain elusive. In the present study, we identified BsGT110, a GT from the same B. subtilis strain, for the biotransformation of GAA into compound (2) through acidic glycosylation. BsGT110 showed an optimal glycosylation activity toward GAA at pH 6 but lost most of its activity at pH 8. Through a scaled-up production, compound (2) was successfully isolated using preparative high-performance liquid chromatography and identified to be a new triterpenoid glucoside (GAA-26-O-ß-glucoside) by mass and nuclear magnetic resonance spectroscopy. The results of kinetic experiments showed that the turnover number (kcat) of BsGT110 toward GAA at pH 6 (kcat = 11.2 min-1) was 3-fold higher than that at pH 7 (kcat = 3.8 min-1), indicating that the glycosylation activity of BsGT110 toward GAA was more active at acidic pH 6. In short, we determined that BsGT110 is a unique GT that plays a role in the glycosylation of triterpenoid at the C-26 position under acidic conditions, but loses most of this activity under alkaline ones, suggesting that acidic solutions may enhance the catalytic activity of this and similar types of GTs toward triterpenoids.

The critical role of Nramp1 in degrading α-synuclein oligomers in microglia under iron overload condition.

Oligomeric α-synuclein is a key mediator in the pathogenesis of Parkinson's disease (PD) and is mainly cleared by autophagy-lysosomal pathway, whose dysfunction results in the accumulation and cell-to-cell transmission of α-synuclein. In this study, concomitant with the accumulation of iron and oligomeric α-synuclein, higher expression of a lysosomal iron transporter, natural resistance-associated macrophage protein-1 (Nramp1), was observed in microglia in post-mortem striatum of sporadic PD patients. Using Nramp1-deficient macrophage (RAW264.7) and microglial (BV-2) cells as in-vitro models, iron exposure significantly reduced the degradation rate of the administered human α-synuclein oligomers, which can be restored by the expression of the wild-type, but not mutant (D543N), Nramp1. Likewise, under iron overload condition, mice with functional Nramp1 (DBA/2 and C57BL/6 congenic mice carrying functional Nramp1) had a better ability to degrade infused human α-synuclein oligomers than mice with nonfunctional Nramp1 (C57BL/6) in the brain and microglia. The interplay between iron and Nramp1 exhibited parallel effects on the clearance of α-synuclein and the activity of lysosomal cathepsin D in vitro and in vivo. Collectively, these findings suggest that the function of Nramp1 contributes to microglial degradation of oligomeric α-synuclein under iron overload condition and may be implicated in the pathogenesis of PD.

5-Year Real-World Outcomes With Frontline Pembrolizumab Monotherapy in PD-L1 Expression ≥ 50% Advanced NSCLC.

BACKGROUND: In clinical trials, frontline pembrolizumab for advanced NSCLC has demonstrated durable, clinically meaningful, long-term survival benefits over chemotherapy. Our objective was to evaluate 5-year survival rates outside the idealized setting of clinical trials for advanced/metastatic NSCLC treated with frontline pembrolizumab monotherapy. METHODS: Using a nationwide, electronic health record-derived, deidentified database in the United States, we studied adult patients with advanced/metastatic NSCLC (unresectable stage IIIB/IIIC, or stage IV), with PD-L1 expression ≥ 50%, no documented EGFR, ALK, or ROS1 genomic alteration, and ECOG performance status of 0-1 initiating frontline pembrolizumab monotherapy from November 1, 2016, through March 31, 2020, excluding those in clinical trials. Kaplan-Meier was used to determine overall survival (OS). Data cutoff was May 31, 2023. RESULTS: A total of 804 patients were eligible for the study, including 404 women (50%); median age was 72 years (range, 38-85 years), with 310 patients (39%) ≥ 75 years old. Median follow-up time from pembrolizumab initiation to data cutoff was 60.5 months (range, 38.0-78.7). At data cutoff, 549 patients (68%) had died. Median OS was 19.2 months (95% CI, 16.6-21.4), and survival rate at 5 years was 25.1% (95% CI, 21.7-28.7). Overall, 266 patients (33%) received 1 or more subsequent regimens, most commonly an anti-PD-(L)1 agent (as monotherapy or combination therapy) or platinum-based chemotherapy. CONCLUSIONS: With 5-year follow-up in a real-world population, frontline pembrolizumab monotherapy continues to demonstrate long-term effectiveness, with survival outcomes consistent with those of pivotal clinical trials, for treating patients with advanced NSCLC with PD-L1 expression of ≥ 50% and no EGFR, ALK, or ROS1 genomic alteration.

Real-World Treatment Patterns and Outcomes of First-Line Immunotherapy Among Patients With Advanced Nonsquamous NSCLC Harboring BRAF, MET, or HER2 Alterations.

Introduction: Data on utilization and clinical outcomes of programmed cell death protein or programmed death-ligand 1 (PD-[L]1) inhibitors in NSCLC with uncommon oncogenic alterations is limited. Methods: This retrospective study used a deidentified U.S. nationwide clinicogenomic database to select patients with advanced nonsquamous NSCLC without EGFR, ALK, or ROS1 alterations, diagnosed from January 1, 2016 to September 30, 2020, who initiated first-line therapy. Our objectives were to summarize characteristics and treatment patterns for patients with four little-studied genomic alterations or driver-negative NSCLC. We estimated Kaplan-Meier real-world time on treatment (rwTOT) and time to next treatment for patients receiving PD-(L)1 inhibitors. The data cutoff was September 30, 2021. Results: Of the 3971 eligible patients, 84 (2%) had NSCLC with BRAF V600E mutation, 117 (3%) had MET exon 14 skipping mutation, 130 (3%) had MET amplification, 91 (2%) had ERBB2 activation mutation, and 691 patients (17%) had driver-negative NSCLC. Patient characteristics differed among cohorts as expected. The most common first-line regimen in each cohort was a PD-(L)1 inhibitor as monotherapy or in combination with chemotherapy. The median rwTOT with anti-PD-(L)1 monotherapy was 4.6 months in the driver-negative cohort and ranged from 2.9 months (ERBB2 mutation) to 7.6 months (BRAF V600E mutation). The median rwTOT with anti-PD-(L)1-chemotherapy combination was 5.2 months in the driver-negative cohort and 6 months in all but the BRAF V600E cohort (17.5 mo). The patterns of real-world time to next treatment results were similar. Conclusions: Substantial use of anti-PD-(L)1 therapy and associated clinical outcomes are consistent with previous real-world findings and suggest no detriment from PD-(L)1 inhibitors for advanced nonsquamous NSCLC harboring one of these four genomic alterations relative to driver-negative NSCLC.

Who is pregnant? Defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C).

Objectives: To define pregnancy episodes and estimate gestational age within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods: We developed a comprehensive approach, named Hierarchy and rule-based pregnancy episode Inference integrated with Pregnancy Progression Signatures (HIPPS), and applied it to EHR data in the N3C (January 1, 2018-April 7, 2022). HIPPS combines: (1) an extension of a previously published pregnancy episode algorithm, (2) a novel algorithm to detect gestational age-specific signatures of a progressing pregnancy for further episode support, and (3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated pregnancy cohorts based on gestational age precision and pregnancy outcomes for assessment of accuracy and comparison of COVID-19 and other characteristics. Results: We identified 628 165 pregnant persons with 816 471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, abortions), and 23.3% had unknown outcomes. Clinician validation agreed 98.8% with HIPPS-identified episodes. We were able to estimate start dates within 1 week of precision for 475 433 (58.2%) episodes. 62 540 (7.7%) episodes had incident COVID-19 during pregnancy. Discussion: HIPPS provides measures of support for pregnancy-related variables such as gestational age and pregnancy outcomes based on N3C data. Gestational age precision allows researchers to find time to events with reasonable confidence. Conclusion: We have developed a novel and robust approach for inferring pregnancy episodes and gestational age that addresses data inconsistency and missingness in EHR data.

The Agile Clinical Nurse Specialist: Navigating the Challenges of the COVID-19 Pandemic.

PURPOSE/OBJECTIVES: This article describes the contributions of the clinical nurse specialist in navigating the challenges of the COVID-19 pandemic to ensure patient and staff safety while providing science-based quality of care. DESCRIPTION: The group of clinical nurse specialists using advanced practice knowledge and skills within the 3 spheres of impact (ie, patient, organization, and nurse) developed and implemented strategies that supported frontline clinicians and met emerging organizational needs during the COVID-19 pandemic. OUTCOMES: The clinical nurse specialist's agility was imperative in navigating the challenges of the pandemic to ensure the safety of patients and staff by providing strategies and standardization to workflow processes across the organization. CONCLUSION: The group's combined clinical expertise and support of frontline nurses positioned the clinical nurse specialist to rapidly escalate the bedside nurse's concerns and provide recommendations to improve workflow while maintaining patient and staff safety.

A comprehensive digital phenotype for postpartum hemorrhage.

OBJECTIVE: We aimed to establish a comprehensive digital phenotype for postpartum hemorrhage (PPH). Current guidelines rely primarily on estimates of blood loss, which can be inaccurate and biased and ignore complementary information readily available in electronic medical records (EMR). Inaccurate and incomplete phenotyping contributes to ongoing challenges in tracking PPH outcomes, developing more accurate risk assessments, and identifying novel interventions. MATERIALS AND METHODS: We constructed a cohort of 71 944 deliveries from the Mount Sinai Health System. Estimates of postpartum blood loss, shifts in hematocrit, administration of uterotonics, surgical interventions, and diagnostic codes were combined to identify PPH, retrospectively. Clinical features were extracted from EMRs and mapped to common data models for maximum interoperability across hospitals. Blinded chart review was done by a physician on a subset of PPH and non-PPH patients and performance was compared to alternate PPH phenotypes. PPH was defined as clinical diagnosis of postpartum hemorrhage documented in the patient's chart upon chart review. RESULTS: We identified 6639 PPH deliveries (9% prevalence) using our phenotype-more than 3 times as many as using blood loss alone (N = 1,747), supporting the need to incorporate other diagnostic and intervention data. Chart review revealed our phenotype had 89% accuracy and an F1-score of 0.92. Alternate phenotypes were less accurate, including a common blood loss-based definition (67%) and a previously published digital phenotype (74%). CONCLUSION: We have developed a scalable, accurate, and valid digital phenotype that may be of significant use for tracking outcomes and ongoing clinical research to deliver better preventative interventions for PPH.

Inpatient Administration of Alpha-1-Adrenergic Receptor Blocking Agents Reduces Mortality in Male COVID-19 Patients.

Apha-1-adrenergic receptor antagonists (α1-blockers) can suppress pro-inflammatory cytokines, thereby potentially improving outcomes among patients with COVID-19. Accordingly, we evaluated the association between α1-blocker exposure (before or during hospitalization) and COVID-19 in-hospital mortality. We identified 2,627 men aged 45 or older who were admitted to Mount Sinai hospitals with COVID-19 between February 24 and May 31, 2020, in New York. Men exposed to α1-blockers (N = 436) were older (median age 73 vs. 64 years, P < 0.001) and more likely to have comorbidities than unexposed men (N = 2,191). Overall, 777 (29.6%) patients died in hospital, and 1,850 (70.4%) were discharged. Notably, we found that α1-blocker exposure was independently associated with improved in-hospital mortality in a multivariable logistic analysis (OR 0.699; 95% CI, 0.498-0.982; P = 0.039) after adjusting for patient demographics, comorbidities, and baseline vitals and labs. The protective effect of α1-blockers was stronger among patients with documented inpatient exposure to α1-blockers (OR 0.624; 95% CI 0.431-0.903; P = 0.012). Finally, age-stratified analyses suggested variable benefit from inpatient α1-blocker across age groups: Age 45-65 OR 0.483, 95% CI 0.216-1.081 (P = 0.077); Age 55-75 OR 0.535, 95% CI 0.323-0.885 (P = 0.015); Age 65-89 OR 0.727, 95% CI 0.484-1.092 (P = 0.124). Taken together, clinical trials to assess the therapeutic value of α1-blockers for COVID-19 complications are warranted.

Improving preeclampsia risk prediction by modeling pregnancy trajectories from routinely collected electronic medical record data.

Preeclampsia is a heterogeneous and complex disease associated with rising morbidity and mortality in pregnant women and newborns in the US. Early recognition of patients at risk is a pressing clinical need to reduce the risk of adverse outcomes. We assessed whether information routinely collected in electronic medical records (EMR) could enhance the prediction of preeclampsia risk beyond what is achieved in standard of care assessments. We developed a digital phenotyping algorithm to curate 108,557 pregnancies from EMRs across the Mount Sinai Health System, accurately reconstructing pregnancy journeys and normalizing these journeys across different hospital EMR systems. We then applied machine learning approaches to a training dataset (N = 60,879) to construct predictive models of preeclampsia across three major pregnancy time periods (ante-, intra-, and postpartum). The resulting models predicted preeclampsia with high accuracy across the different pregnancy periods, with areas under the receiver operating characteristic curves (AUC) of 0.92, 0.82, and 0.89 at 37 gestational weeks, intrapartum and postpartum, respectively. We observed comparable performance in two independent patient cohorts. While our machine learning approach identified known risk factors of preeclampsia (such as blood pressure, weight, and maternal age), it also identified other potential risk factors, such as complete blood count related characteristics for the antepartum period. Our model not only has utility for earlier identification of patients at risk for preeclampsia, but given the prediction accuracy exceeds what is currently achieved in clinical practice, our model provides a path for promoting personalized precision therapeutic strategies for patients at risk.

Who is pregnant? defining real-world data-based pregnancy episodes in the National COVID Cohort Collaborative (N3C).

Objective: To define pregnancy episodes and estimate gestational aging within electronic health record (EHR) data from the National COVID Cohort Collaborative (N3C). Materials and Methods: We developed a comprehensive approach, named H ierarchy and rule-based pregnancy episode I nference integrated with P regnancy P rogression S ignatures (HIPPS) and applied it to EHR data in the N3C from 1 January 2018 to 7 April 2022. HIPPS combines: 1) an extension of a previously published pregnancy episode algorithm, 2) a novel algorithm to detect gestational aging-specific signatures of a progressing pregnancy for further episode support, and 3) pregnancy start date inference. Clinicians performed validation of HIPPS on a subset of episodes. We then generated three types of pregnancy cohorts based on the level of precision for gestational aging and pregnancy outcomes for comparison of COVID-19 and other characteristics. Results: We identified 628,165 pregnant persons with 816,471 pregnancy episodes, of which 52.3% were live births, 24.4% were other outcomes (stillbirth, ectopic pregnancy, spontaneous abortions), and 23.3% had unknown outcomes. We were able to estimate start dates within one week of precision for 431,173 (52.8%) episodes. 66,019 (8.1%) episodes had incident COVID-19 during pregnancy. Across varying COVID-19 cohorts, patient characteristics were generally similar though pregnancy outcomes differed. Discussion: HIPPS provides support for pregnancy-related variables based on EHR data for researchers to define pregnancy cohorts. Our approach performed well based on clinician validation. Conclusion: We have developed a novel and robust approach for inferring pregnancy episodes and gestational aging that addresses data inconsistency and missingness in EHR data.

Rapid Mortality Review in the Intensive Care Unit: An In-Person, Multidisciplinary Improvement Initiative.

BACKGROUND: Significant resources have been allocated to decreasing the number of preventable deaths in hospitals, but identifying preventable factors and then leveraging them to effect system-wide change remains challenging. OBJECTIVE: To determine the ability of a novel in-person, multidisciplinary "rapid mortality review" process to identify deaths that are preventable and action items that lead to improvements in care. METHODS: Rapid mortality review sessions were conducted weekly for patients who died in the medical intensive care unit. Patient data and clinician opinions regarding preventable deaths were discussed and recorded. Bivariate analyses were done to detect associations between case variables and the formation of an action item. RESULTS: From 2013 to 2018, 542 patient deaths were reviewed; of those, 36 deaths (7%) were deemed potentially preventable. Facilitators identified issues in 294 cases (54%). A total of 253 action items were identified for 175 cases (32%); 60% of those action items were subsequently completed and led to tangible systemic change in 29 instances (11%). Action items were more likely to be identified for patients who had not been receiving comfort care (P < .001), for patients who had received cardiopulmonary resuscitation (P < .001), when the treatment team (P < .001) or the rapid mortality review facilitator (P < .001) had care-related concerns, and when the patient's death had been preventable (P < .001). CONCLUSIONS: Even in settings with low reported rates of preventable deaths, an in-person multidisciplinary mortality review can successfully identify areas where care can be improved, leading to systemic change.

In-hospital use of ACE inhibitors/angiotensin receptor blockers associates with COVID-19 outcomes in African American patients.

BACKGROUNDThe angiotensin-converting enzyme (ACE) D allele is more prevalent among African Americans compared with other races and ethnicities and has previously been associated with severe coronavirus disease 2019 (COVID-19) pathogenesis through excessive ACE1 activity. ACE inhibitors/angiotensin receptor blockers (ACE-I/ARB) may counteract this mechanism, but their association with COVID-19 outcomes has not been specifically tested in the African American population.METHODSWe identified 6218 patients who were admitted into Mount Sinai hospitals with COVID-19 between February 24 and May 31, 2020, in New York City. We evaluated whether the outpatient and in-hospital use of ACE-I/ARB is associated with COVID-19 in-hospital mortality in an African American compared with non-African American population.RESULTSOf the 6218 patients with COVID-19, 1138 (18.3%) were ACE-I/ARB users. In a multivariate logistic regression model, ACE-I/ARB use was independently associated with a reduced risk of in-hospital mortality in the entire population (OR, 0.655; 95% CI, 0.505-0.850; P = 0.001), African American population (OR, 0.44; 95% CI, 0.249-0.779; P = 0.005), and non-African American population (OR, 0.748, 95% CI, 0.553-1.012, P = 0.06). In the African American population, in-hospital use of ACE-I/ARB was associated with improved mortality (OR, 0.378; 95% CI, 0.188-0.766; P = 0.006), whereas outpatient use was not (OR, 0.889; 95% CI, 0.375-2.158; P = 0.812). When analyzing each medication class separately, ARB in-hospital use was significantly associated with reduced in-hospital mortality in the African American population (OR, 0.196; 95% CI, 0.074-0.516; P = 0.001), whereas ACE-I use was not associated with impact on mortality in any population.CONCLUSIONIn-hospital use of ARB was associated with a significant reduction in in-hospital mortality among COVID-19-positive African American patients.FUNDINGNone.

Rapid implementation of ultraviolet germicidal irradiation and reuse processes for N95 respirators at a health system during the coronavirus disease 2019 (COVID-19) pandemic.

An N95 respirator ultraviolet germicidal irradiation and reuse program was rapidly implemented at an academic health system in the United States during the coronavirus disease 2019 pandemic. This process continues to be a safe and effective way to slow the consumption rate of N95 respirators.