Search

BackgroundElectronic health record (EHR) data provide a unique opportunity to study the epidemiology of COVID-19, clinical outcomes of the infection, comparative effectiveness of therapies, and vaccine effectiveness but require a well-defined computable phenotype of COVID-19–like illness (CLI). ObjectiveThe objective of this study was to evaluate the performance of pathogen-specific and other acute respiratory illness (ARI) International Statistical Classification of Diseases-9 and -10 codes in identifying COVID-19 cases in emergency department (ED) or urgent care (UC) and inpatient settings. MethodsWe conducted a retrospective observational cohort study using EHR, claims, and laboratory information system data of ED or UC and inpatient encounters from 4 health systems in the United States. Patients who were aged ≥18 years, had an ED or UC or inpatient encounter for an ARI, and underwent a SARS-CoV-2 polymerase chain reaction test between March 1, 2020, and March 31, 2021, were included. We evaluated various CLI definitions using combinations of International Statistical Classification of Diseases-10 codes as follows: COVID-19–specific codes; CLI definition used in VISION network studies; ARI signs, symptoms, and diagnosis codes only; signs and symptoms of ARI only; and random forest model definitions. We evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of each CLI definition using a positive SARS-CoV-2 polymerase chain reaction test as the reference standard. We evaluated the performance of each CLI definition for distinct hospitalization and ED or UC cohorts. ResultsAmong 90,952 hospitalizations and 137,067 ED or UC visits, 5627 (6.19%) and 9866 (7.20%) were positive for SARS-CoV-2, respectively. COVID-19–specific codes had high sensitivity (91.6%) and specificity (99.6%) in identifying patients with SARS-CoV-2 positivity among hospitalized patients. The VISION CLI definition maintained high sensitivity (95.8%) but lowered specificity (45.5%). By contrast, signs and symptoms of ARI had low sensitivity and positive predictive value (28.9% and 11.8%, respectively) but higher specificity and negative predictive value (85.3% and 94.7%, respectively). ARI diagnoses, signs, and symptoms alone had low predictive performance. All CLI definitions had lower sensitivity for ED or UC encounters. Random forest approaches identified distinct CLI definitions with high performance for hospital encounters and moderate performance for ED or UC encounters. ConclusionsCOVID-19–specific codes have high sensitivity and specificity in identifying adults with positive SARS-CoV-2 test results. Separate combinations of COVID-19-specific codes and ARI codes enhance the utility of CLI definitions in studies using EHR data in hospital and ED or UC settings.

Abstract Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P

A growing body of neurobiological and psychological research sheds light on the mechanisms underlying the development and maintenance of opioid use disorder and its relation to parenting behavior. Perinatal opioid use is associated with risks for women and children, including increased risk of child maltreatment. Drawing from extant data, here we provide an integrated mechanistic model of perinatal opioid use, parenting behavior, infant attachment, and child well-being to inform the development and adaptation of behavioral interventions for opioid-exposed mother–infant dyads. The model posits that recurrent perinatal opioid use may lead to increased stress sensitivity and reward dysregulation for some mothers, resulting in decreased perceived salience of infant cues, disengaged parenting behavior, disrupted infant attachment, and decreased child well-being. We conclude with a discussion of Mindfulness-Oriented Recovery Enhancement as a means of addressing mechanisms undergirding perinatal opioid use, parenting, and attachment, presenting evidence on the efficacy and therapeutic mechanisms of mindfulness. As perinatal opioid use increases in the United States, empirically informed models can be used to guide treatment development research and address this growing concern.

Birthweight has been found to associate with later-life health outcomes. Here the authors perform a meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, identifying differentially methylated CpGs in neonatal blood that associate with birthweight.

Folic acid is routinely recommended for women trying to conceive to ensure proper fetal development. Here, the authors perform a large epigenomics study to examine which fetal epigenetic changes are associated with varied maternal plasma folate levels.

BACKGROUND RBC transfusion effectiveness varies due to donor, component, and recipient factors. Prior studies identified characteristics associated with variation in hemoglobin increments following transfusion. We extended these observations, examining donor genetic and nongenetic factors affecting transfusion effectiveness.METHODS This is a multicenter retrospective study of 46,705 patients and 102,043 evaluable RBC transfusions from 2013 to 2016 across 12 hospitals. Transfusion effectiveness was defined as hemoglobin, bilirubin, or creatinine increments following single RBC unit transfusion. Models incorporated a subset of donors with data on single nucleotide polymorphisms associated with osmotic and oxidative hemolysis in vitro. Mixed modeling accounting for repeated transfusion episodes identified predictors of transfusion effectiveness.RESULTS Blood donor (sex, Rh status, fingerstick hemoglobin, smoking), component (storage duration, γ irradiation, leukoreduction, apheresis collection, storage solution), and recipient (sex, BMI, race and ethnicity, age) characteristics were associated with hemoglobin and bilirubin, but not creatinine, increments following RBC transfusions. Increased storage duration was associated with increased bilirubin and decreased hemoglobin increments, suggestive of in vivo hemolysis following transfusion. Donor G6PD deficiency and polymorphisms in SEC14L4, HBA2, and MYO9B genes were associated with decreased hemoglobin increments. Donor G6PD deficiency and polymorphisms in SEC14L4 were associated with increased transfusion requirements in the subsequent 48 hours.CONCLUSION Donor genetic and other factors, such as RBC storage duration, affect transfusion effectiveness as defined by decreased hemoglobin or increased bilirubin increments. Addressing these factors will provide a precision medicine approach to improve patient outcomes, particularly for chronically transfused RBC recipients, who would most benefit from more effective transfusion products.FUNDING Funding was provided by HHSN 75N92019D00032, HHSN 75N92019D00034, 75N92019D00035, HHSN 75N92019D00036, and HHSN 75N92019D00037; R01HL126130; and the National Institute of Child Health and Human Development (NICHD).