Pharmacotherapy for opioid use disorder in pregnancy.

PURPOSE OF REVIEW: Opioid use disorder (OUD) in pregnancy has significantly increased in the last decade, impacting 8.2 per 1000 deliveries. OUD carries significant risk of morbidity and mortality for both the birthing person and neonate, but outcomes for both are improved with opioid agonist treatment (OAT). Here, we describe the recommended forms of OAT in pregnancy, updates to the literature, and alternate OAT strategies, and share practical peripartum considerations for patients on OAT. RECENT FINDINGS: Recent studies comparing buprenorphine and methadone have reaffirmed previous findings that buprenorphine is associated with superior outcomes for the neonate, without clear differences in morbidity or mortality for the birthing person. Optimal initiation and dosing of OAT remains unclear, with several recent studies evaluating methods of initiation, as well as a potential role for higher and more rapid dosing in the fentanyl era. Alternative products such as buprenorphine-naloxone and extended-release buprenorphine are of significant research interest, though randomized prospective data are not yet available. SUMMARY: Buprenorphine and methadone are standard of care for treatment of OUD during pregnancy, and multiple patient factors impact the optimal choice. Insufficient data exist to recommend alternative agents as a primary strategy currently. All patients with OUD in pregnancy should be counseled regarding OAT. VIDEO: http://links.lww.com/COOG/A94.

Hepatitis C and obstetrical morbidity in a substance use disorder clinic: a role for telemedicine?

BACKGROUND: Hepatitis C infection often co-occurs with substance use disorders in pregnancy. Accessing hepatitis C treatment is challenging because of loss to follow-up in the postpartum period, attributable to social and financial barriers to care. Telemedicine has been explored as a means of increasing routine postpartum care, but the potential impact on retention in and completion of care for postpartum hepatitis C has not been assessed. OBJECTIVE: This study aimed to evaluate the impact of hepatitis C on obstetrical morbidity in a substance use disorder-specific prenatal clinic, and the effect of Infectious Disease telemedicine consultation on subsequent treatment delivery. STUDY DESIGN: We performed a retrospective cohort study of all patients in our substance use disorder prenatal clinic from June 2018 to February 2023. Telemedicine consults for hepatitis C diagnoses began in March 2020 and included electronic chart review by Infectious Disease when patients were unable to be seen. Our primary outcome was composite obstetrical morbidity (preterm birth, preeclampsia, fetal growth restriction, fetal anomaly, abruption, postpartum hemorrhage, or chorioamnionitis) compared between patients with and without active hepatitis C. We additionally evaluated rates of completed referral and initiation of hepatitis C treatment before and after implementation of telemedicine consult. RESULTS: A total of 224 patients were included. Of the 222 patients who underwent screening, 71 (32%) were positive for active hepatitis C. Compared with patients without hepatitis C, a higher proportion of patients with hepatitis C were White (80% vs 58%; P=.02), had a history of amphetamine use (61% vs 32%; P<.01), injection drug use (72% vs 38%; P<.01), or overdose (56% vs 29%; P<.01), and were on methadone (37% vs 18%; P<.01). There was no difference in the primary outcome of composite obstetrical morbidity. The rate of hepatitis C diagnosis was not statistically significantly different between the pre- and posttelemedicine cohorts (N=29 [41%], N=42 [27%]), and demographics of hepatitis C virus-positive patients were similar, with most being unemployed, single, and publicly insured. A lower proportion of patients in the posttelemedicine group reported heroin use compared with the pretelemedicine cohort (62% vs 90%; P=.013). After implementation of telemedicine, patients were more likely to attend the visit (19% vs 44%; P=.03), and positive patients were much more likely to receive treatment (14% vs 57%; P<.01); 100% of visits in the posttelemedicine group occurred via telemedicine. There were 7 patients who were prescribed treatment by their obstetrician after chart review by Infectious Disease. CONCLUSION: Patients with and without hepatitis C had similar maternal and neonatal outcomes, with multiple indicators of social and financial vulnerability. Telemedicine Infectious Disease consult was associated with increased follow-up and hepatitis C treatment, and obstetricians were able to directly prescribe. Because patients with substance use disorders and hepatitis C may have increased barriers to care, telemedicine may represent an opportunity for intervention.

Deficits in ultrasonic vocalization development and production following neonatal hypoxic ischemic insult.

Neonatal hypoxic ischemia encephalopathy (HIE) leads to major deficits in language development. While clinically there is a known correlation in the degree of HIE injury and subsequent language disability, there are no treatments beyond speech and language therapy; therefore, experimental studies with a HIE animal model to test new interventions and therapeutics are warranted. Neonatal rodents normally ultrasonically vocalize at postnatal day 7 (PND 7) to PND 14 in response to removal from their mothers. At 6-8 weeks of age juvenile male rodents ultrasonically vocalize in response to exposure to a mature female mouse. Changes in ultrasonic vocalization (USV) production after neonatal brain injury, such ashypoxic ischemia (HI), have not been studied. This study examines the acute and long-term ultrasonic vocalization ability of mice after HI at PND 10. Pups were subjected to HI, sham, or naïve conditions; where in HI and sham surgeries the right common carotid artery was exposed, in the HI this artery was double ligated. The HI and sham pups were then exposed to60minof hypoxia. Naïve pups did not undergo surgery and were subjected to60minof room air. At 3 days following surgery, HI and sham pups vocalize less than nonsurgical naïve controls; yet "juvenile" mice of 6-8 weeks old that underwent HI at PND 10 vocalize less than sham and naïve mice. We conclude that HI injury has significant impact on later adult vocalization.

The Role of Pyruvate Dehydrogenase Kinase-4 (PDK4) in Bladder Cancer and Chemoresistance.

Advanced bladder cancer remains a major source of mortality, with poor treatment options. Cisplatin-based chemotherapy is the standard treatment, however many patients are or become resistant. One potential cause of chemoresistance is the Warburg effect, a metabolic switch to aerobic glycolysis that occurs in many cancers. Upregulation of the pyruvate dehydrogenase kinase family (PDK1-PDK4) is associated with aerobic glycolysis and chemoresistance through inhibition of the pyruvate dehydrogenase complex (PDH). We have previously observed upregulation of PDK4 in high-grade compared with low-grade bladder cancers. We initiated this study to determine if inhibition of PDK4 could reduce tumor growth rates or sensitize bladder cancer cells to cisplatin. Upregulation of PDK4 in malignant bladder cancer cell lines as compared with benign transformed urothelial cells was confirmed using qPCR. Inhibition of PDK4 with dichloroacetate (DCA) resulted in increased PDH activity, reduced cell growth, and G0-G1 phase arrest in bladder cancer cells. Similarly, siRNA knockdown of PDK4 inhibited bladder cancer cell proliferation. Cotreatment of bladder cancer cells with cisplatin and DCA did not increase caspase-3 activity but did enhance overall cell death in vitro Although daily treatment with 200 mg/kg DCA alone did not reduce tumor volumes in a xenograft model, combination treatment with cisplatin resulted in dramatically reduced tumor volumes as compared with either DCA or cisplatin alone. This was attributed to substantial intratumoral necrosis. These findings indicate inhibition of PDK4 may potentiate cisplatin-induced cell death and warrant further studies investigating the mechanism through which this occurs. Mol Cancer Ther; 17(9); 2004-12. ©2018 AACR.

Ultrasonic vocalization changes and FOXP2 expression after experimental stroke.

Speech impairments affect one in four stroke survivors. However, animal models of post-ischemic vocalization deficits are limited. Male mice vocalize at ultrasonic frequencies when exposed to an estrous female mouse. In this study we assessed vocalization patterns and quantity in male mice after cerebral ischemia. FOXP2, a gene associated with verbal dyspraxia in humans, with known roles in neurogenesis and synaptic plasticity, was also examined after injury. Using a transient middle cerebral artery occlusion (MCAO) model, we assessed correlates of vocal impairment at several time-points after stroke. Further, to identify possible lateralization of vocalization deficits induced by left and right hemispheric strokes were compared. Significant differences in vocalization quantity were observed between stroke and sham animals that persisted for a month after injury. Injury to the left hemisphere reduced early vocalizations more profoundly than those to the right hemisphere. Nuclear expression of Foxp2 was elevated early after stroke (at 6h), but significantly decreased 24h after injury in both the nucleus and the cytoplasm. Neuronal Foxp2 expression increased in stroke mice compared to sham animals 4 weeks after injury. This study demonstrates that quantifiable deficits in ultrasonic vocalizations (USVs) are seen after stroke. USV may be a useful tool to assess chronic behavioral recovery in murine models of stroke.