Systems-level barriers to treatment in a cervical cancer prevention program in Kenya: Several observational studies.

OBJECTIVE: To identify health systems-level barriers to treatment for women who screened positive for high-risk human papillomavirus (hrHPV) in a cervical cancer prevention program in Kenya. METHODS: In a trial of implementation strategies for hrHPV-based cervical cancer screening in western Kenya in 2018-2019, women underwent hrHPV testing offered through community health campaigns, and women who tested positive were referred to government health facilities for cryotherapy. The current analysis draws on treatment data from this trial, as well as two observational studies that were conducted: 1) periodic assessments of the treatment sites to ascertain availability of resources for treatment and 2) surveys with treatment providers to elicit their views on barriers to care. Bivariate analyses were performed for the site assessment data, and the provider survey data were analyzed descriptively. RESULTS: Seventeen site assessments were performed across three treatment sites. All three sites reported instances of supply stockouts, two sites reported treatment delays due to lack of supplies, and two sites reported treatment delays due to provider factors. Of the 16 providers surveyed, ten (67%) perceived lack of knowledge of HPV and cervical cancer as the main barrier in women's decision to get treated, and seven (47%) perceived financial barriers for transportation and childcare as the main barrier to accessing treatment. Eight (50%) endorsed that providing treatment free of cost was the greatest facilitator of treatment. CONCLUSION: Patient education and financial support to reach treatment are potential areas for intervention to increase rates of hrHPV+ women presenting for treatment. It is also essential to eliminate barriers that prevent treatment of women who present, including ensuring adequate supplies and staff for treatment.

Patient factors affecting successful linkage to treatment in a cervical cancer prevention program in Kenya: A prospective cohort study.

OBJECTIVE: To identify patient factors associated with whether women who screened positive for high-risk human papillomavirus (hrHPV) successfully accessed treatment in a cervical cancer prevention program in Kenya. METHODS: A prospective cohort study was conducted as part of a trial of implementation strategies for hrHPV-based cervical cancer screening in western Kenya from January 2018 to February 2019. In this larger trial, women underwent hrHPV testing during community health campaigns (CHCs), and hrHPV+ women were referred to government facilities for cryotherapy. For this analysis, we looked at rates of and predictors of presenting for treatment and presenting within 30 days of receiving positive hrHPV results ("timely" presentation). Data came from questionnaires completed at the time of screening and treatment. Multivariable logistic regression was used to identify factors associated with each outcome. RESULTS: Of the 505 hrHPV+ women, 266 (53%) presented for treatment. Cryotherapy was performed in 236 (89%) of the women who presented, while 30 (11%) were not treated: 15 (6%) due to gas outage, six (2%) due to pregnancy, five (2%) due to concern for cervical cancer, and four (2%) due to an unknown or other reason. After adjusting for other factors in the multivariable analysis, higher education level and missing work to come to the CHC were associated with presenting for treatment. Variables that were associated with increased likelihood of timely presentation were missing work to come to the CHC, absence of depressive symptoms, told by someone important to come to the CHC, and shorter distance to the treatment site. CONCLUSION: The majority of hrHPV+ women who did not get treated were lost at the stage of decision-making or accessing treatment, with a small number encountering barriers at the treatment sites. Patient education and financial support are potential areas for intervention to increase rates of hrHPV+ women seeking treatment.

Hepatitis C in pregnancy: screening, treatment, and management.

In the United States, 1-2.5% of pregnant women are infected with hepatitis C virus, which carries an approximately 5% risk of transmission from mother to infant. Hepatitis C virus can be transmitted to the infant in utero or during the peripartum period, and infection during pregnancy is associated with increased risk of adverse fetal outcomes, including fetal growth restriction and low birthweight. The purpose of this document is to discuss the current evidence regarding hepatitis C virus in pregnancy and to provide recommendations on screening, treatment, and management of this disease during pregnancy. The following are Society for Maternal-Fetal Medicine recommendations: (1) We recommend that obstetric care providers screen women who are at increased risk for hepatitis C infection by testing for anti-hepatitis C virus antibodies at their first prenatal visit. If initial results are negative, hepatitis C screening should be repeated later in pregnancy in women with persistent or new risk factors for hepatitis C infection (eg, new or ongoing use of injected or intranasal illicit drugs) (GRADE 1B). (2) We recommend that obstetric care providers screen hepatitis C virus-positive pregnant women for other sexually transmitted diseases, including HIV, syphilis, gonorrhea, chlamydia, and hepatitis B virus (GRADE 1B). (3) We suggest that patients with hepatitis C virus, including pregnant women, be counseled to abstain from alcohol (Best Practice). (4) We recommend that direct-acting antiviral regimens only be used in the setting of a clinical trial or that antiviral treatment be deferred to the postpartum period as direct-acting antiviral regimens are not currently approved for use in pregnancy (GRADE 1C). (5) We suggest that if invasive prenatal diagnostic testing is requested, women be counseled that data on the risk of vertical transmission are reassuring but limited; amniocentesis is recommended over chorionic villus sampling given the lack of data on the latter (GRADE 2C). (6) We recommend against cesarean delivery solely for the indication of hepatitis C virus (GRADE 1B). (7) We recommend that obstetric care providers avoid internal fetal monitoring, prolonged rupture of membranes, and episiotomy in managing labor in hepatitis C virus-positive women (GRADE 1B). (8) We recommend that providers not discourage breast-feeding based on a positive hepatitis C virus infection status (GRADE 1A).

Preconception consultations with Maternal Fetal Medicine for obese women: a retrospective chart review.

BACKGROUND: Obesity is associated with impaired fertility and pregnancy complications, and preconception weight loss may improve some of these outcomes. The purpose of this study was to evaluate the quality and effectiveness of Maternal Fetal Medicine (MFM) preconception consults for obese women. METHODS: We performed a retrospective chart review examining 162 consults at an academic medical center from 2008 to 2014. The main outcome measures included consultation content - e.g. discussion of obesity-related pregnancy complications, screening for comorbidities, and referrals for weight loss interventions - and weight loss. RESULTS: Screening for diabetes and hypertension occurred in 48% and 51% of consults, respectively. Discussion of obesity-related pregnancy complications was documented in 96% of consults. During follow-up (median 11 months), 27% of patients saw a nutritionist, 6% saw a provider for a medically supervised weight loss program, and 6% underwent bariatric surgery. The median weight change was a loss of 0.6% body weight. CONCLUSIONS: In this discovery cohort, a large proportion of MFM preconception consultations lacked appropriate screening for obesity-related comorbidities. While the vast majority of consultations included a discussion of potential pregnancy complications, relatively few patients achieved significant weight loss. More emphasis is needed on weight loss resources and delaying pregnancy to achieve weight loss goals.

Hepatitis C in Pregnancy: Review of Current Knowledge and Updated Recommendations for Management.

IMPORTANCE: An estimated 1% to 2.5% of pregnant women in the United States are infected with hepatitis C virus (HCV), which carries approximately a 6% risk of mother-to-infant transmission. OBJECTIVES: The aims of this article are to review the current evidence on HCV in pregnancy and to provide updated recommendations for management. EVIDENCE ACQUISITION: Original research articles, review articles, and guidelines on HCV in general and specifically in pregnancy were reviewed, as were drug safety profiles from the Food and Drug Administration. RESULTS: Pregnancy appears to have a beneficial effect on the course of maternal chronic HCV infection. However, it is associated with an increased risk of adverse fetal outcomes, including fetal growth restriction and low birth weight, and can be transmitted to the infant in utero or during the peripartum period. No perinatal intervention has been shown to reduce the risk of vertical transmission, but some may increase this risk. To date, no treatment regimens for HCV have been approved for use in pregnancy, but the new ribavirin-free, direct-acting antiviral regimens are being used with high efficacy outside pregnancy. CONCLUSIONS AND RELEVANCE: Hepatitis C virus infection in pregnancy generally does not adversely affect maternal well-being but is associated with adverse effects on the fetus because of pregnancy complications and vertical transmission. There are currently no approved treatment regimens for HCV in pregnancy; this should be an active area of research in obstetrics.

Does smoke from biomass fuel contribute to anemia in pregnant women in Nagpur, India? A cross-sectional study.

BACKGROUND: Anemia affects upwards of 50% of pregnant women in developing countries and is associated with adverse outcomes for mother and child. We hypothesized that exposure to smoke from biomass fuel--which is widely used for household energy needs in resource-limited settings--could exacerbate anemia in pregnancy, possibly as a result of systemic inflammation. OBJECTIVE: To evaluate whether exposure to smoke from biomass fuel (wood, straw, crop residues, or dung) as opposed to clean fuel (electricity, liquefied petroleum gas, natural gas, or biogas) is an independent risk factor for anemia in pregnancy, classified by severity. METHODS: A secondary analysis was performed using data collected from a rural pregnancy cohort (N = 12,782) in Nagpur, India in 2011-2013 as part of the NIH-funded Maternal and Newborn Health Registry Study. Multinomial logistic regression was used to estimate the effect of biomass fuel vs. clean fuel use on anemia in pregnancy, controlling for maternal age, body mass index, education level, exposure to household tobacco smoke, parity, trimester when hemoglobin was measured, and receipt of prenatal iron and folate supplements. RESULTS: The prevalence of any anemia (hemoglobin < 11 g/dl) was 93% in biomass fuel users and 88% in clean fuel users. Moderate-to-severe anemia (hemoglobin < 10 g/dl) occurred in 53% and 40% of the women, respectively. Multinomial logistic regression showed higher relative risks of mild anemia in pregnancy (hemoglobin 10-11 g/dl; RRR = 1.38, 95% CI = 1.19-1.61) and of moderate-to-severe anemia in pregnancy (RRR = 1.79, 95% CI = 1.53-2.09) in biomass fuel vs. clean fuel users, after adjusting for covariates. CONCLUSION: In our study population, exposure to biomass smoke was associated with higher risks of mild and moderate-to-severe anemia in pregnancy, independent of covariates. TRIAL REGISTRATION: ClinicalTrials.gov NCT 01073475.

Exocyclic carbons adjacent to the N6 of adenine are targets for oxidation by the Escherichia coli adaptive response protein AlkB.

The DNA and RNA repair protein AlkB removes alkyl groups from nucleic acids by a unique iron- and α-ketoglutarate-dependent oxidation strategy. When alkylated adenines are used as AlkB targets, earlier work suggests that the initial target of oxidation can be the alkyl carbon adjacent to N1. Such may be the case with ethano-adenine (EA), a DNA adduct formed by an important anticancer drug, BCNU, whereby an initial oxidation would occur at the carbon adjacent to N1. In a previous study, several intermediates were observed suggesting a pathway involving adduct restructuring to a form that would not hinder replication, which would match biological data showing that AlkB almost completely reverses EA toxicity in vivo. The present study uses more sensitive spectroscopic methodology to reveal the complete conversion of EA to adenine; the nature of observed additional putative intermediates indicates that AlkB conducts a second oxidation event in order to release the two-carbon unit completely. The second oxidation event occurs at the exocyclic carbon adjacent to the N(6) atom of adenine. The observation of oxidation of a carbon at N(6) in EA prompted us to evaluate N(6)-methyladenine (m6A), an important epigenetic signal for DNA replication and many other cellular processes, as an AlkB substrate in DNA. Here we show that m6A is indeed a substrate for AlkB and that it is converted to adenine via its 6-hydroxymethyl derivative. The observation that AlkB can demethylate m6A in vitro suggests a role for AlkB in regulation of important cellular functions in vivo.