Reported Barriers to Hepatitis C Treatment among Pregnant and Early-Parenting Mothers Undergoing Substance Use Disorder Treatment in One U.S. State.

Nationwide, the prevalence of the hepatitis C virus (HCV) has risen in recent years. At least 90% of infected persons must be treated to achieve global elimination targets. The current study aimed to explore barriers to, and facilitators of, direct-acting antiviral (DAA) HCV treatment uptake amongst pregnant and early-parenting women undergoing comprehensive substance use treatment. Twenty participants with documented HCV antibody positivity were recruited from two substance use treatment centers in central Kentucky. Semi-structured interviews were conducted to explore knowledge about HCV, previous experiences, and intentions to seek care. Themes were extracted using an inductive analytical approach. Most participants were aware of the dangers posed by HCV infection. However, there was a high degree of misinformation about transmission mechanisms and treatment eligibility requirements. Low priority for HCV treatment also surfaced as a barrier to treatment uptake. Participants reported being unable to seek care due to time and resource limitations in the presence of a highly demanding treatment process. Findings from the current study suggest that more work is needed to eliminate residual barriers that limit access to HCV treatment among pregnant and early-parenting women in treatment for substance use disorder.

Care-by-parent model as a tool for reduction of neonatal opioid withdrawal syndrome in neonates exposed to buprenorphine maintenance therapy in-utero.

Objective: To determine if a structured care-by-parent (CBP) protocol is associated with a reduction in diagnosis of treatment-requiring Neonatal Opioid Withdrawal Syndrome (NOWS).Study design: We performed a pilot retrospective, case control study of pregnant women enrolled in a comprehensive prenatal care program for opioid-dependent patients during which they received buprenorphine for Medication Assisted Treatment (MAT) for Opioid Use Disorder (OUD). Patients who participated in the CBP program actively roomed-in with their infants even after maternal hospital discharge while infants continued to be monitored for development of treatment-requiring NOWS. The primary outcome was the rate of treatment-requiring NOWS in the CBP grouping.Results: Thirty-two (32) cases that were enrolled in the CBP model were compared with 32 matched controls that were not enrolled in this model. There was a significant reduction in the rate of treatment-requiring NOWS among cases compared to the controls (OR = 0.10; p = .001). Neonates undergoing CBP had a decreased length of stay and lower Finnegan scores compared to those who did not undergo CBPConclusion: Among infants born to mothers with OUD in pregnancy, CBP significantly reduces the rate of treatment-requiring NOWS.

Comparison of Serum and Cervical Cytokine Levels throughout Pregnancy between Preterm and Term Births.

Objective To assess differences in cytokine levels in cervicovaginal fluid (CVF) and serum across trimesters between women with preterm births (PTBs) and full-term births. Study Design This multicenter study enrolled 302 women with a singleton gestation. CVF and serum cytokines, interleukin 1α (IL-1α), IL-1ß, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-8, were measured. Women with at least one cytokine assessment and noted PTB status in their medical record were retained in the study ( N = 272). Data were analyzed using mixed modeling (main effects of PTBs and time/trimester). Results For the CVF values of IL-6, IL-8, IL-10, TNF-α, and CRP, and serum MMP-8, those who delivered preterm had significantly higher values than the full-term group regardless of trimester. For the serum values of IL-1ß, IL-6, and TNF-α, those delivering preterm had significantly lower values than those delivering full-term regardless of trimester. For IL-1ß in CVF, the cytokine was significantly higher in the PTB group for second and third trimesters only, relative to the full-term group. Conclusion For each CVF cytokine that differed by birth status, values were higher for PTB than term, averaged over trimester. Numerous cytokine profiles varied across trimesters in women delivering term versus preterm in both CVF and serum.

Buprenorphine for Medication-Assisted Treatment of Opioid Use Disorder in Pregnancy: Relationship to Neonatal Opioid Withdrawal Syndrome.

Objective To examine the relationship between antepartum buprenorphine dose for medication-assisted treatment (MAT) of opioid use disorder (OUD) and incident neonatal opioid withdrawal syndrome (NOWS). Study Design We performed a prospective cohort study of pregnant women with a singleton gestation diagnosed with OUD and receiving buprenorphine for MAT at a tertiary care academic institution from July 2015 to January 2017. We divided the study cohort into two groups-pregnancies with versus without NOWS. Substance abuse patterns in pregnancy, maternal, and neonatal clinical outcomes were compared. Results The incidence of NOWS was 31.11% ( n = 28/90) in our study cohort. Pregnancies with NOWS had a significantly higher rate of benzodiazepine positive urine tests and number of positive urine drug screen (UDS) results for illicit opioids. The group without NOWS had significantly higher number of patients with an appropriate UDS result at delivery through postpartum. Rates of neonatal intensive care unit (NICU) admission, length of NICU stay, and maximum Finnegan score were significantly higher in the group with NOWS. Neither the initial (10.6 ± 5.2 versus 10.3 ± 4.8 mg, p = 0.80) nor the final buprenorphine doses (13.3 ± 5.1 versus 13.0 ± 4.6 mg, p = 0.81) were significantly different between study groups. Conclusion The occurrence of NOWS was not related to buprenorphine dose used for MAT.

Intrahepatic Cholestasis of Pregnancy with Severe Elevation of Bile Acids in the Setting of Acute Hepatitis C Infection.

Intrahepatic cholestasis of pregnancy (ICP) is a complication of pregnancy resulting in elevation of serum bile acid levels. ICP is often associated with underlying liver disease, including hepatitis C. Bile acids in relationship to the acute infection of hepatitis C virus have not yet been delineated in the literature. A 26-year-old gravida 4 para 2103 with dichorionic, diamniotic twin gestation and history of intravenous drug abuse developed ICP in the setting of acute hepatitis C infection. In addition to clinical symptoms of pruritus and right upper quadrant pain, she developed severe elevation in bile acids, 239 micromol/L, and transaminitis aspartate aminotransferase 1033 U/L, and alanine aminotransferase 448 U/L. She received ursodeoxycholic acid and antenatal testing was performed. Patient delivered vaginally at 33-week gestation following preterm rupture of membranes. Neonates were admitted to NICU and had uncomplicated neonatal courses. In the setting of ICP with significant transaminitis and severe elevation of bile acids, consideration of acute viral hepatitis is important, especially considering the worsening opioid epidemic and concurrent increase in intravenous drug use in the United States. Further study is needed regarding the acute form of HCV infection and its effect on ICP and associated bile acids.

Biocompatibility of a sonicated silk gel for cervical injection during pregnancy: in vivo and in vitro study.

OBJECTIVE: To evaluate the biocompatibility of silk gel for cervical injection. STUDY DESIGN: Silk gel was injected into the cervix of pregnant rats on day 13 (n = 11) and harvested at day 17. Histology of silk gel was compared with suture controls. Also, human cervical fibroblasts were cultured on silk gel and tissue culture plastic (TCP) in vitro. Cell viability, proliferation, metabolic activity, gene expression (COL1A1, COL3A1, and COX2), and release of proinflammatory mediators (interleukin [IL] 6 and IL-8) were evaluated. RESULTS: In vivo, a mild foreign body response was seen surrounding the silk gel and suture controls. In vitro, cervical fibroblasts were viable, metabolically active, and proliferating at 72 hours. Release of IL-6 and IL-8 was similar on silk gel and TCP. Collagen and COX2 gene expression was similar or slightly decreased compared with TCP. CONCLUSIONS: Silk gel was well tolerated in vivo and in vitro, which supports continuing efforts to develop silk gels as an alternative to cervical cerclage.

Cervical mucus properties stratify risk for preterm birth.

BACKGROUND: Ascending infection from the colonized vagina to the normally sterile intrauterine cavity is a well-documented cause of preterm birth. The primary physical barrier to microbial ascension is the cervical canal, which is filled with a dense and protective mucus plug. Despite its central role in separating the vaginal from the intrauterine tract, the barrier properties of cervical mucus have not been studied in preterm birth. METHODS AND FINDINGS: To study the protective function of the cervical mucus in preterm birth we performed a pilot case-control study to measure the viscoelasticity and permeability properties of mucus obtained from pregnant women at high-risk and low-risk for preterm birth. Using extensional and shear rheology we found that cervical mucus from women at high-risk for preterm birth was more extensible and forms significantly weaker gels compared to cervical mucus from women at low-risk of preterm birth. Moreover, permeability measurements using fluorescent microbeads show that high-risk mucus was more permeable compared with low-risk mucus. CONCLUSIONS: Our findings suggest that critical biophysical barrier properties of cervical mucus in women at high-risk for preterm birth are compromised compared to women with healthy pregnancy. We hypothesize that impaired barrier properties of cervical mucus could contribute to increased rates of intrauterine infection seen in women with preterm birth. We furthermore suggest that a robust association of spinnbarkeit and preterm birth could be an effectively exploited biomarker for preterm birth prediction.

Neurotensin and CRH interactions augment human mast cell activation.

Stress affects immunity, but the mechanism is not known. Neurotensin (NT) and corticotropin-releasing hormone (CRH) are secreted under stress in various tissues, and have immunomodulatory actions. We had previously shown that NT augments the ability of CRH to increase mast cell-dependent skin vascular permeability in rodents. Here we show that NT triggered human mast cell degranulation and significantly augmented CRH-induced vascular endothelial growth factor (VEGF) release. Investigation of various signaling molecules indicated that only NF-κB activation was involved. These effects were blocked by pretreatment with the NTR antagonist SR48692. NT induced expression of CRH receptor-1 (CRHR-1), as shown by Western blot and FACS analysis. Interestingly, CRH also induced NTR gene and protein expression. These results indicate unique interactions among NT, CRH, and mast cells that may contribute to auto-immune and inflammatory diseases that worsen with stress.

Group B Streptococcus prophylaxis in patients who report a penicillin allergy: a follow-up study.

OBJECTIVE: The purpose of this study was to compare adherence to the 2002 Centers for Disease Control (CDC) guidelines for the prevention of perinatal group B Streptococcus (GBS) disease in patients who are allergic to penicillin during the years 2004-2006 and 2008. STUDY DESIGN: Previous data from our institution revealed suboptimal adherence to the 2002 CDC guidelines for GBS prophylaxis among women who are allergic to penicillin. These data caused the hospital to implement a series of interventions. The original cohort (2004-2006) was compared with a cohort of women who delivered between April 2008 and January 2009 (n = 74) to determine whether the proportion of women who had antimicrobial sensitivity testing and who had received an appropriate antibiotic had improved. RESULTS: In 2008, 76% (95% confidence interval, 66-84%) of GBS-positive women who are allergic to penicillin received an appropriate antibiotic (compared with 16.2% in 2004-2006; P < .001). Antimicrobial sensitivity testing was performed in 79.4% of cases (95% confidence interval, 68-87%), compared with 11.4% in 2004-2006 (P < .001). CONCLUSION: With directed intervention, adherence to the 2002 CDC guidelines for GBS prophylaxis in women who are allergic to penicillin improved dramatically.

Current practice of thromboprophylaxis in the burn population: a survey study of 84 US burn centers.

While there is limited prospective data on the incidence of venous thromboembolism (VTE) in the burn population, there are no prospective studies on the efficacy and safety of VTE prophylaxis in these patients. Despite lack of such data, we hypothesized that most burn centers practice some form of prophylaxis. Eighty-four US burn centers were contacted regarding their modality of VTE prophylaxis, if any. Of the 84 US burn centers, 71 were enrolled in this survey. 76.1% centers reported routine VTE prophylaxis. Modalities included sequential compression device (SCD) (33), subcutaneous heparin (31), enoxaparin (13), dalteparin (3), and intravenous heparin infusion (1). Twenty-one reported combined modalities of SCD and subcutaneous heparin (19), SCD and enoxaparin (1), or SCD and dalteparin (1). Survey results underscore the need to definitively establish risk factors for VTE in the burn population and to prospectively define an evidence-based standard of care in prophylaxis for those patients.