Postpartum readmission in Maryland by race and ethnicity, 2016-2019.

BACKGROUND: The majority of maternal deaths occur in the postpartum period. We sought to compare postpartum readmission by race and ethnicity to better understand whether there are disparities in maternal health in the postpartum period as indicated by readmission to the hospital. OBJECTIVE: This study aimed to use state-wide Maryland data to identify postpartum readmission rates by race and ethnicity, as well as the major risk factors, indications, and timing of readmission. STUDY DESIGN: In this retrospective study (2016-2019), childbirth hospitalizations for patients of childbearing age were identified from the Maryland State Inpatient Database, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. Indication for readmission was described. Multivariable logistic regression models were employed to determine racial and ethnic differences in postpartum readmissions, adjusting for maternal and obstetrical characteristics. RESULTS: Among total deliveries (n=260,778), 3914 patients (1.5%) were readmitted within 60 days of delivery. The most common primary diagnoses at readmission were hypertension and infection. The prevalence of readmission was 1.2% (1306/111,325) for White patients, 2.3% (1786/79,412) for Black patients, 1.2% (485/40,862) for Hispanic patients and 1.2% (337/29,179) for patients of Other race or ethnicity (P<.0001). Black patients had the highest rates of readmission for hypertensive disorders as compared with all other races (37%, P<.0001). In adjusted models, Black patients were more likely to be readmitted than White patients (odds ratio, 1.64; confidence interval, 1.52-1.77). The majority of all readmissions occurred in the first week after delivery with Black patients having higher rates of readmission in the second week relative to all other groups (P<.0001). CONCLUSION: Hypertension is a leading cause of postpartum readmission in Maryland. Black patients were more likely to be readmitted for hypertensive disorders of pregnancy and to have delayed readmission relative to other race or ethnic groups. Maryland public health officials should address disparities with interventions targeting racial and ethnic minorities, patients at risk for hypertensive disorders, and barriers to timely care.

Short-term treatment of golden retriever muscular dystrophy (GRMD) dogs with rAAVrh74.MHCK7.GALGT2 induces muscle glycosylation and utrophin expression but has no significant effect on muscle strength.

We have examined the effects of intravenous (IV) delivery of rAAVrh74.MHCK7.GALGT2 in the golden retriever muscular dystrophy (GRMD) model of Duchenne Muscular Dystrophy (DMD). After baseline testing, GRMD dogs were treated at 3 months of age and reassessed at 6 months. This 3-6 month age range is a period of rapid disease progression, thus offering a relatively short window to establish treatment efficacy. Measures analyzed included muscle AAV transduction, GALGT2 transgene expression, GALGT2-induced glycosylation, muscle pathology, and muscle function. A total of five dogs were treated, 4 at 2x1014vg/kg and one at 6x1014vgkg. The 2x1014vg/kg dose led to transduction of regions of the heart with 1-3 vector genomes (vg) per nucleus, while most skeletal muscles were transduced with 0.25-0.5vg/nucleus. GALGT2-induced glycosylation paralleled levels of myofiber vg transduction, with about 90% of cardiomyocytes having increased glycosylation versus 20-35% of all myofibers across the skeletal muscles tested. Conclusions from phenotypic testing were limited by the small number of dogs. Treated dogs had less pronounced fibrosis and overall lesion severity when compared to control groups, but surprisingly no significant changes in limb muscle function measures. GALGT2-treated skeletal muscle and heart had elevated levels of utrophin protein expression and GALGT2-induced expression of glycosylated α dystroglycan, providing further evidence of a treatment effect. Serum chemistry, hematology, and cardiac function measures were largely unchanged by treatment. Cumulatively, these data show that short-term intravenous treatment of GRMD dogs with rAAVrh74.MHCK7.GALGT2 at high doses can induce muscle glycosylation and utrophin expression and may be safe over a short 3-month interval, but that such treatments had only modest effects on muscle pathology and did not significantly improve muscle strength.

rAAVrh74.MCK.GALGT2 Demonstrates Safety and Widespread Muscle Glycosylation after Intravenous Delivery in C57BL/6J Mice.

rAAVrh74.MCK.GALGT2 is a surrogate gene therapy that inhibits muscular dystrophy in multiple animal models. Here, we report on a dose-response study of functional muscle GALGT2 expression as well as toxicity and biodistribution studies after systemic intravenous (i.v.) delivery of rAAVrh74.MCK.GALGT2. A dose of 4.3 × 1014vg/kg (measured with linear DNA standard) resulted in GALGT2-induced glycosylation in the majority of skeletal myofibers throughout the body and in almost all cardiomyocytes, while several lower doses also showed significant muscle glycosylation. No adverse clinical signs or treatment-dependent changes in tissue or organ pathology were noted at 1 or 3 months post-treatment. Blood cell and serum enzyme chemistry measures in treated mice were all within the normal range except for alkaline phosphatase (ALP) activity, which was elevated in serum but not in tissues. Some anti-rAAVrh74 capsid T cell responses were noted at 4 weeks post-treatment, but all such responses were not present at 12 weeks. Using intramuscular delivery, GALGT2-induced muscle glycosylation was increased in Cmah-deficient mice, which have a humanized sialoglycome, relative to wild-type mice, suggesting that use of mice may underestimate GALGT2 activity in human muscle. These data demonstrate safety and high transduction of muscles throughout the body plan with i.v. delivery of rAAVrh74.MCK.GALGT2.