The validity of self-reported SARS-CoV-2 results among postpartum respondents.

BACKGROUND: Rapid and reliable health data on SARS-CoV-2 infection among pregnant individuals are needed to understand the influence of the virus on maternal health and child development, yet the validity of self-reported COVID-19 testing and diagnosis remains unknown. OBJECTIVES: We assessed the validity of self-reported COVID-19 polymerase chain reaction (PCR) testing and diagnosis during delivery among postpartum respondents as well as how diagnostic accuracy varied by respondent characteristics. METHODS: We validated receipt of a COVID-19 PCR test and test results by comparing self-reported results obtained through an electronic survey to electronic medical record data (gold standard) among a cross-sectional sample of postpartum respondents who delivered at four New York City hospitals between March 2020 and January 2021. To assess validity, we calculated each indicator's sensitivity, specificity and the area under the receiver-operating curve (AUC). We examined respondent characteristics (age, race/ethnicity, education level, health insurance, nativity, pre-pregnancy obesity and birth characteristics) as predictors of reporting accuracy using modified Poisson regression. RESULTS: A total of 276 respondents had matched electronic record and survey data. The majority, 83.7% of respondents received a SARS-CoV-2 PCR test during their delivery stay. Of these, 12.1% had detected SARS-CoV-2. Among those tested, sensitivity (90.5%) and specificity (96.5%) were high for SARS-CoV-2 detection. The adjusted risk ratio (aRR) of accurate result reporting was somewhat lower among Hispanic women relative to white non-Hispanic women (aRR 0.90, 95% CI 0.90, 1.00) and among those who had public or no insurance vs. private (aRR 0.91, 95% CI 0.82, 1.01), controlling for recall time. CONCLUSION(S): High recall accuracy result reporting for COVID-19 PCR tests administered during labour and delivery suggest the potential for population-based surveys as a rapid mechanism to obtain accurate data on COVID-19 diagnostic history. Additional psychometric research is warranted to ensure accurate recall across respondent subgroups.

Outcomes in Critically Ill Patients With Traumatic Brain Injury: Ethnicity, Documentation, and Insurance Status.

OBJECTIVES: Disparities in traumatic brain injury outcomes for ethnic minorities and the uninsured have previously been demonstrated; however, outcomes in undocumented immigrants have not been examined. We wanted to determine whether ethnicity, insurance, and documentation status served as risk factors for disparities in traumatic brain injury outcomes between undocumented immigrants and documented residents. DESIGN: Retrospective study. SETTING: Patients diagnosed with traumatic brain injury admitted to the surgical/trauma ICU at a level 1 trauma center serving a large immigrant population in New York City from 2009 to 2016. PATIENTS: Four-hundred seventy-one traumatic brain injury patients requiring surgical/trauma ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Undocumented immigrants constituted 29% of the population, were younger (39 vs 57 yr old, respectively; p < 0.0001), Hispanic (83%; p < 0.0001), and uninsured (87%; p < 0.0001). Falls resulted in the majority of traumatic brain injuries in the total population, however, undocumented immigrants were almost twice as likely to be assaulted (p = 0.0032). There was no difference in presence of midline shifts, Injury Severity Score, Glasgow Coma Score, hypotension, hypoxia, and pupillary reactions between undocumented immigrants and documented residents. Undocumented immigrants presented with significantly more effaced basilar cisterns (p = 0.0008). There was no difference in hospital care between undocumented immigrants and documented residents as determined by emergency department to surgical/trauma ICU transfer times (p = 0.967). Undocumented immigrants were more likely to be discharged home (53% vs 33%, respectively; p = 0.0009) and less likely to be sent to rehabilitation (25% vs 32%, respectively; p = 0.0009). After adjusting length of stay and mortality for covariates, undocumented immigrants had shorter length of stay (p < 0.05) and there was no difference in hospital mortality between undocumented immigrants and documented residents. CONCLUSIONS: Undocumented immigrants with traumatic brain injuries were more likely to be younger, have shorter length of stay, and experience similar mortality rates to documented residents. Social economic status may play a role in events prior to hospitalization and likely does in disposition outcomes.

Aryl hydrocarbon receptor activation by dioxin targets phosphoenolpyruvate carboxykinase (PEPCK) for ADP-ribosylation via 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP-ribose) polymerase (TiPARP).

Effects of the environmental toxin and carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) include a wasting syndrome associated with decreased gluconeogenesis. TCDD is a potent activator of the aryl hydrocarbon receptor (AHR), a ligand activated transcription factor. The relationship between gene activation by the AHR and TCDD toxicities is not well understood. We recently identified a pathway by which the AHR target gene TiPARP (TCDD-inducible poly(ADP-ribose) polymerase) contributes to TCDD suppression of transcription of phosphoenolpyruvate carboxykinase (PEPCK), a key regulator of gluconeogenesis, by consuming NAD(+) and decreasing Sirtuin 1 activation of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), a transcriptional activator of PEPCK. We report here that TCDD-induced TiPARP also targets PEPCK for ADP-ribosylation. Both cytosolic and mitochondrial forms of PEPCK were found to undergo ADP-ribosylation. Unexpectedly, AHR suppression also enhanced ADP-ribosylation and did so by a poly(ADP-ribose) polymerase-independent mechanism. This report 1) identifies ADP-ribosylation as a new posttranslational modification for PEPCK, 2) describes a pathway by which transcriptional induction of TiPARP by the AHR can lead to a downstream posttranslational change in a TCDD target protein (PEPCK), and 3) reveals that the AHR exerts complex, previously unidentified modulatory effects on ADP-ribosylation.

Identification of the aryl hydrocarbon receptor target gene TiPARP as a mediator of suppression of hepatic gluconeogenesis by 2,3,7,8-tetrachlorodibenzo-p-dioxin and of nicotinamide as a corrective agent for this effect.

The environmental toxin TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, dioxin) produces diverse toxic effects including a lethal wasting syndrome whose hallmark is suppressed hepatic gluconeogenesis. All TCDD toxicities require activation of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor. Whereas the mechanism for AHR induction of target genes is well understood, it is not known how AHR activation produces any TCDD toxicity. This report identifies for the first time an AHR target gene, TiPARP (TCDD-inducible poly(ADP-ribose) polymerase, PARP7) that can mediate a TCDD toxicity, i.e. suppression of hepatic gluconeogenesis. TCDD suppressed hepatic glucose production, expression of key gluconeogenic genes, phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase), and NAD(+) levels, and increased PARP activity and TiPARP expression. TCDD also increased acetylation and ubiquitin-dependent proteosomal degradation of the peroxisome proliferator-activated receptor γ coactivator 1 α (PGC1α), a coactivator of PEPCK and G6Pase transcription. TiPARP overexpression reproduced TCDD effects on glucose output and NAD(+) levels whereas TiPARP silencing diminished them. TiPARP overexpression also increased PGC1α acetylation and decreased PGC1α levels. In contrast, silencing of cytochromes P450 (CYP) 1A, main AHR-induced genes, did not alter TCDD suppression of gluconeogenesis. The vitamin B3 constituent, nicotinamide (NAM), prevented TCDD suppression of glucose output, NAD(+), and gluconeogenic genes and stabilized PGC1α. The corrective effects of NAM could be attributed to increased NAD(+) levels and suppression of AHR target gene induction. The results reveal that TiPARP can mediate a TCDD effect, that the AHR is linked to PGC1α function and stability and that NAM has novel AHR antagonist activity.