Racial and Ethnic Disparities in the Management of Postdural Puncture Headache With Epidural Blood Patch for Obstetric Patients in New York State.

Importance: Characterizing and addressing racial and ethnic disparities in peripartum pain assessment and treatment is a national priority. Objective: To evaluate the association of race and ethnicity with the provision and timing of an epidural blood patch (EBP) for management of postdural puncture headache in obstetric patients. Design, Setting, and Participants: This cross-sectional study used New York State hospital discharge records from January 1, 1998, to December 31, 2016, from mothers 15 to 49 years of age with a postdural puncture headache after neuraxial analgesia or anesthesia for childbirth. Statistical analysis was performed from February 2020 to February 2022. Exposures: Patients' race and ethnicity (reported as provided by each participating hospital; the method of determining race and ethnicity [ie, self-reported or not] cannot be determined from the data) were categorized into non-Hispanic White (reference group), non-Hispanic Black, Hispanic, and other race and ethnicity (including Asian and Pacific Islander, American Indian, Alaskan Native, and other). Main Outcomes and Measures: The primary outcome was the rate of EBP use. The secondary outcome was the interval (days) between hospital admission and provision of EBP. Odds ratios (ORs) and 95% CIs of EBP use associated with race and ethnicity were estimated using mixed-effect logistic regression models, adjusting for patient and hospital characteristics. Results: During the study period, 8921 patients (mean [SD] age, 30 [6] years; 1028 [11.5%] Black; 1301 [14.6%] Hispanic; 4960 [55.6%] White; and 1359 [15.2%] other race and ethnicity) with postdural puncture headache were identified among 1.9 million deliveries with a neuraxial procedure. Of these 8921 patients, 4196 (47.0%; 95% CI, 46.0%-48.1%) were managed with an EBP. A total of 2650 White patients (53.4%; 95% CI, 52.0%-54.8%) used an EBP; this rate was significantly higher than that among Hispanic patients (41.7% [543]; 95% CI, 39.9%-44.5%), Black patients (35.7% [367]; 95% CI, 32.8%-38.7%), or patients of other race and ethnicity (35.2% [478]; 95% CI, 32.6%-37.8%). Timing of EBP was at a median of 2 days (IQR, 2-3 days) after hospital admission for White patients compared with a median of 3 days (IQR, 2-4 days) for Hispanic patients, Black patients, and patients of other race and ethnicity (P < .001 for the comparison with White patients). After adjustment for patient and hospital characteristics, the EBP rate was not different between White and Hispanic patients (adjusted OR, 1.11; 95% CI, 0.94-1.30). It was significantly lower for Black patients (adjusted OR, 0.80; 95% CI, 0.67-0.94) and patients of other races and ethnicities (adjusted OR, 0.85; 95% CI, 0.73-0.99). Conclusions and Relevance: In this study, significant racial and ethnic disparities in the management of postdural puncture headache with EBP were observed, with both lower rates and delayed timing, which may be associated with long-term adverse effects.

Structural and functional characterization of nonstructural protein 2 for its role in hepatitis C virus assembly.

The hepatitis C virus (HCV) is a flavivirus replicating in the cytoplasm of infected cells. The HCV genome is a single-stranded RNA encoding a polyprotein that is cleaved by cellular and viral proteases into 10 different products. While the structural proteins core protein, envelope protein 1 (E1) and E2 build up the virus particle, most nonstructural (NS) proteins are required for RNA replication. One of the least studied proteins is NS2, which is composed of a C-terminal cytosolic protease domain and a highly hydrophobic N-terminal domain. It is assumed that the latter is composed of three trans-membrane segments (TMS) that tightly attach NS2 to intracellular membranes. Taking advantage of a system to study HCV assembly in a hepatoma cell line, in this study we performed a detailed characterization of NS2 with respect to its role for virus particle assembly. In agreement with an earlier report ( Jones, C. T., Murray, C. L., Eastman, D. K., Tassello, J., and Rice, C. M. (2007) J. Virol. 81, 8374-8383 ), we demonstrate that the protease domain, but not its enzymatic activity, is required for infectious virus production. We also show that serine residue 168 in NS2, implicated in the phosphorylation and stability of this protein, is dispensable for virion formation. In addition, we determined the NMR structure of the first TMS of NS2 and show that the N-terminal segment (amino acids 3-11) forms a putative flexible helical element connected to a stable alpha-helix (amino acids 12-21) that includes an absolutely conserved helix side in genotype 1b. By using this structure as well as the amino acid conservation as a guide for a functional study, we determined the contribution of individual amino acid residues in TMS1 for HCV assembly. We identified several residues that are critical for virion formation, most notably a central glycine residue at position 10 of TMS1. Finally, we demonstrate that mutations in NS2 blocking HCV assembly can be rescued by trans-complementation.