Quality Initiative to Reduce Failed Trial of Labor after Cesarean Using Calculated VBAC Success Likelihood.

OBJECTIVE: Vaginal birth after cesarean can reduce morbidity associated with multiple cesarean deliveries. Failed vaginal birth after cesarean is associated with increased maternal and neonatal morbidity. The Maternal-Fetal Medicine Units Vaginal Birth After Cesarean calculator is a validated tool to predict the likelihood of successful trial of labor after cesarean. Predicted likelihood < 60% has been associated with increased maternal and neonatal morbidity. We sought to determine if formal incorporation of calculated vaginal birth after cesarean likelihood into patient-centered counseling would reduce failed vaginal birth after cesarean. STUDY DESIGN: This is a quality improvement intervention at a single tertiary-care academic medical center, in which standardized patient counseling was implemented, facilitated by an electronic medical record template featuring patient-specific likelihood of vaginal birth after cesarean success. Term singleton pregnancies with history of one to two cesareans were included; those with contraindication to labor were excluded. Historical controls (January 2016-December 2018, n = 693) were compared with a postimplementation cohort (January 2019-April 2020, n = 328). Primary outcome was failed vaginal birth after cesarean. RESULTS: Fewer patients in the postintervention cohort had a history of an arrest disorder (PRE: 48%, 330/693 vs. POST: 40%, 130/326, p = 0.03); demographics were otherwise similar, including the proportion of patients with <60% likelihood of success (PRE: 39%, 267/693, vs. POST: 38%, 125/326). Following implementation, induction of labor in patients with a <60% likelihood of successful vaginal birth after cesarean decreased from 17% (45/267) to 5% (6/125, p < 0.01). The proportion of failed vaginal birth after cesarean decreased from 33% (107/329) to 22% (32/143, p = 0.04). Overall vaginal birth after cesarean rate did not change (PRE: 32%, 222/693, vs. POST: 34%, 111/326, p = 0.52). CONCLUSION: An intervention targeting provider counseling that included a validated vaginal birth after cesarean success likelihood was associated with decreased risk of failed trial of labor after cesarean without affecting overall vaginal birth after cesarean rate. KEY POINTS: · Labored cesarean increases maternal morbidity.. · Application of the Maternal-Fetal Medicine Units (MFMU) calculator to antenatal counseling decreased labored cesarean.. · Application of the MFMU calculator to antenatal counseling did not decrease overall vaginal birth after cesarean rate..

Caring for Pregnant Women with Opioid Use Disorder in the USA: Expanding and Improving Treatment.

PURPOSE OF THE REVIEW: Opioid use disorder in the USA is rising at an alarming rate, particularly among women of childbearing age. Pregnant women with opioid use disorder face numerous barriers to care, including limited access to treatment, stigma, and fear of legal consequences. This review of opioid use disorder in pregnancy is designed to assist health care providers caring for pregnant and postpartum women with the goal of expanding evidence-based treatment practices for this vulnerable population. RECENT FINDINGS: We review current literature on opioid use disorder among US women, existing legislation surrounding substance use in pregnancy, and available treatment options for pregnant women with opioid use disorder. Opioid agonist treatment (OAT) remains the standard of care for treating opioid use disorder in pregnancy. Medically assisted opioid withdrawal ("detoxification") is not recommended in pregnancy and is associated with high maternal relapse rates. Extended release naltrexone may confer benefit for carefully selected patients. Histories of trauma and mental health disorders are prevalent in this population; and best practice recommendations incorporate gender-specific, trauma-informed, mental health services. Breastfeeding with OAT is safe and beneficial for the mother-infant dyad. SUMMARY: Further research investigating options of OAT and the efficacy of opioid antagonists in pregnancy is needed. The US health care system can adapt to provide quality care for these mother-infant dyads by expanding comprehensive treatment services and improving access to care.

Downregulation of homologous recombination DNA repair genes by HDAC inhibition in prostate cancer is mediated through the E2F1 transcription factor.

BACKGROUND: Histone deacetylase inhibitors (HDACis) re-express silenced tumor suppressor genes and are currently undergoing clinical trials. Although HDACis have been known to induce gene expression, an equal number of genes are downregulated upon HDAC inhibition. The mechanism behind this downregulation remains unclear. Here we provide evidence that several DNA repair genes are downregulated by HDAC inhibition and provide a mechanism involving the E2F1 transcription factor in the process. METHODOLOGY/PRINCIPAL FINDINGS: Applying Analysis of Functional Annotation (AFA) on microarray data of prostate cancer cells treated with HDACis, we found a number of genes of the DNA damage response and repair pathways are downregulated by HDACis. AFA revealed enrichment of homologous recombination (HR) DNA repair genes of the BRCA1 pathway, as well as genes regulated by the E2F1 transcription factor. Prostate cancer cells demonstrated a decreased DNA repair capacity and an increased sensitization to chemical- and radio-DNA damaging agents upon HDAC inhibition. Recruitment of key HR repair proteins to the site of DNA damage, as well as HR repair capacity was compromised upon HDACi treatment. Based on our AFA data, we hypothesized that the E2F transcription factors may play a role in the downregulation of key repair genes upon HDAC inhibition in prostate cancer cells. ChIP analysis and luciferase assays reveal that the downregulation of key repair genes is mediated through decreased recruitment of the E2F1 transcription factor and not through active repression by repressive E2Fs. CONCLUSIONS/SIGNIFICANCE: Our study indicates that several genes in the DNA repair pathway are affected upon HDAC inhibition. Downregulation of the repair genes is on account of a decrease in amount and promoter recruitment of the E2F1 transcription factor. Since HDAC inhibition affects several pathways that could potentially have an impact on DNA repair, compromised DNA repair upon HDAC inhibition could also be attributed to several other pathways besides the ones investigated in this study. However, our study does provide insights into the mechanism that governs downregulation of HR DNA repair genes upon HDAC inhibition, which can lead to rationale usage of HDACis in the clinics.