Altered liver metabolism post-wean abolishes efficacy of vitamin D for breast cancer prevention in a mouse model.

Young women have increased risk of vitamin D deficiency, which may increase breast cancer incidence. Here, we assessed the anti-cancer efficacy of vitamin D in mouse models of young-onset breast cancer. In never-pregnant mice, vitamin D supplementation increased serum 25(OH)D and hepatic 1,25(OH)2D3, reduced tumor size, and associated with anti-tumor immunity. These anti-tumor effects were not replicated in a mouse model of postpartum breast cancer, where hepatic metabolism of vitamin D was suppressed post-wean, which resulted in deficient serum 25(OH)D and reduced hepatic 1,25(OH)2D3. Treatment with active 1,25(OH)2D3 induced hypercalcemia exclusively in post-wean mice, highlighting metabolic imbalance post-wean. RNAseq revealed suppressed CYP450 expression postpartum. In sum, we provide evidence that vitamin D anti-tumor activity is mediated through immunomodulatory mechanisms and is ineffective in the post-wean window due to altered hepatic metabolism. These findings have implications for suppressed xenobiotic metabolism in postpartum women beyond vitamin D.

Contraceptive services in Oregon's state-funded network during the COVID-19 pandemic.

OBJECTIVES: To understand how changes to in-person health care during the COVID pandemic impacted contraceptive use in Oregon's state-funded network. STUDY DESIGN: A retrospective cohort of 245,600 visits (virtual and in-person) among 70,295 women presenting to publicly funded family planning clinics in Oregon between January 2019 and June 2021. Data were abstracted from clinic records and restricted to visits of patients identifying as female, 12-51 years old, not using sterilization as a method. Contraception was grouped by effectiveness Tier (Tier 1: intrauterine device, implants; Tier 2: progestin injectable, pill/patch/ring). Multivariable logistic regression predicted the use of contraception by stage of the COVID pandemic which corresponded to service availability (prepandemic, acute: nonemergency services halted, subacute: restricted services), patient demographics, including insurance type, and clinic and geospatial characteristics. RESULTS: Overall during the acute stage, people with visits were more likely to leave with a method of contraception odds ratios (OR) 1.39 (95% confidence interval [CI] 1.24-1.57); however, it was significantly less likely to be a Tier 1 method (OR 0.82, 95% CI 0.74-0.91) as compared to prepandemic. This finding was particularly marked in rural areas (OR 0.69 [96% CI 0.58-0.83]) and among the publicly insured (OR 0.87 [95% CI 0.80-0.94]). CONCLUSIONS: Demand for contraception increased during the acute phase of the COVID pandemic, and shifts in method mix from Tier 1 to Tier 2 methods occurred. Disparities in contraceptive access persisted for those in rural locations or with public insurance. IMPLICATIONS: Lessons learned from the COVID-19 pandemic are critical to informing our future emergency response. The need for family planning services increased during the public health emergency.

Menstrual Technology Innovations and the Implications for Heavy Menstrual Bleeding.

Menstruation is a personal and cultural experience with financial and health implications. Menstruation historically has been managed with disposable commodities, including tampons and pads. New technologies, including underwear and menstrual cups and discs, have emerged to address diverse menstrual needs such as prioritization of sustainability, discretion, and inclusivity. New technologies are not routinely integrated into history taking or validated questionnaires, which currently rely on traditional tampon and pad use for identifying individuals with heavy menstrual bleeding. Review of menstrual technologies and accessories provides insight to empower gynecologists and other clinicians to take comprehensive menstrual histories, including strategies for identification of heavy menstrual bleeding and troubleshooting menstrual disturbances, within the context of new menstrual technologies.

Human Milk-Expression Technologies: A Primer for Obstetricians.

Lactation is a powerful tool for improving health trajectories and promoting reproductive justice. Multiple new human milk-expression technologies are available. Although direct feeding is optimal and feasible in many circumstances, understanding human milk-expression technology and counseling patients appropriately represents one of the ways physicians can support patients in meeting their feeding goals. Breast pumps and breast pump accessories may help patients establish and maintain breastfeeding, but these technologies continue to evolve and are not always intuitive. The core components of a pump are the attachment at the breast, valves, tubing, motor, device programming, and reservoir. Whereas closed systems can be used by multiple patients, open systems are single-user and they are not able to be sterilized. Mobile pumps may help support breastfeeding individuals who are unable to remain stationary for the time necessary to express milk. Nonelectric pumps represent an important adjuvant technology. There are a wide variety of pump accessories that may help patients overcome specific breastfeeding challenges. Obstetricians remain uniquely positioned to support patients in achieving their lactation goals, which is enhanced by familiarity with the supportive technologies available.

Coverage of immediate postpartum long-acting reversible contraception has improved birth intervals for at-risk populations.

BACKGROUND: In 2012, South Carolina revised the Medicaid policy to cover reimbursement for immediate postpartum long-acting reversible contraception. Immediate postpartum long-acting reversible contraception may improve health outcomes for populations at risk with a subsequent short-interval pregnancy. OBJECTIVES: We examined the impact of the Medicaid policy change on the initiation of long-acting and reversible contraception (immediate postpartum and postpartum) within key populations. We determined whether immediate postpartum long-acting and reversible contraception use varied by adequate prenatal care (>7 visits), metropolitan location, and medical comorbidities. We also tested the association of immediate postpartum and postpartum long-acting, reversible contraception on interpregnancy interval of less than 18 months. STUDY DESIGN: We conducted a historical cohort study of live births among Medicaid recipients in South Carolina between 2010 and 2017, 2 years before and 5 years after the policy change. We used birth certificate data linked with Medicaid claims. Our primary outcome was immediate postpartum long-acting and reversible contraception, and our secondary outcome was short interpregnancy interval. We characterize trends in long-acting and reversible contraception use and interpregnancy interval over the study period. We used logistic regression models to test the association of key factors (rural, inadequate prenatal care, and medical comorbidities) with immediate and outpatient postpartum long-acting and reversible contraception following the policy change and to test the association of immediate postpartum and postpartum long-acting and reversible contraception with short interpregnancy interval. RESULTS: Our sample included 187,438 births to 145,973 women. Overall, 44.7% of the sample was white, with a mean age of 25.0 years. A majority of the sample (61.5%) was multiparous and resided in metropolitan areas (79.5%). The odds of receipt of immediate postpartum long-acting and reversible contraception use increased after the policy change (adjusted odds ratio, 1.39, 95% confidence interval, 1.34-1.43). Women with inadequate prenatal care (adjusted odds ratio, 1.50, 95% confidence interval, 1.31-1.71) and medically complex pregnancies had higher odds of receipt of immediate postpartum long-acting and reversible contraception following the policy change (adjusted odds ratio, 1.47, 95% confidence interval, 1.29-1.67) compared with women with adequate prenatal care and normal pregnancies. Women residing in rural areas were less likely to receive immediate postpartum long-acting and reversible contraception (adjusted odds ratio, 0.36, 95% confidence interval, 0.30-0.44) than women in metropolitan areas. Utilization of immediate postpartum long-acting and reversible contraception was associated with a decreased odds of a subsequent short interpregnancy interval (adjusted odds ratio, 0.62, 95% confidence interval, 0.44-0.89). CONCLUSION: Women at risk of a subsequent pregnancy and complications (inadequate prenatal care and medical comorbidities) are more likely to receive immediate postpartum long-acting and reversible contraception following the policy change. Efforts are needed to improve access in rural areas.

A Geospatial Analysis of the Impact of the Baby-Friendly Hospital Initiative on Breastfeeding Initiation in North Carolina.

BACKGROUND:: Significant disparities in breastfeeding support and practice exist in North Carolina. The Baby-Friendly Hospital Initiative is a worldwide intervention that encourages birth facilities to adopt specific practices in support of breastfeeding. RESEARCH AIM:: This study aimed to evaluate the impact of the Baby-Friendly Hospital Initiative on breastfeeding initiation in North Carolina, with special attention to rural areas. METHODS:: To better understand disparities in breastfeeding initiation across North Carolina, we conducted a secondary analysis of birth certificate data from 2011 to 2014. Univariate and multivariate logistic regression models were used to estimate the association between breastfeeding initiation and (a) birth at a Baby-Friendly hospital and (b) maternal residence in a county with a Baby-Friendly hospital. Model residuals were aggregated by county and analyzed for spatial autocorrelation. RESULTS:: Birth at a Baby-Friendly hospital was associated with increased odds of breastfeeding initiation, adjusted odds ratio = 1.7, 95% confidence interval [1.65, 1.89]. Model residuals showed significant clustering by county, with some rural areas' rates systematically overestimated. Whereas presence of a Baby-Friendly hospital in a mother's community of residence was not associated with increased initiation, birth at a Baby-Friendly hospital was associated with smaller disparities in initiation between rural and urban births. CONCLUSION:: Birth at a Baby-Friendly hospital is associated with improved breastfeeding initiation and reduced disparities in initiation between rural and urban counties in North Carolina.

Management of Intrauterine Contraception in Early Pregnancy.

OBJECTIVES: Women with rare intrauterine contraception (IUC) failures are advised to have their IUC removed because of the risk of poor obstetric outcomes with a retained IUC. Specifics regarding IUC removal in early pregnancy including techniques for removal, rates of success, and immediate pregnancy outcomes following removal are not well described, however. The objective of this study was to identify women with an IUC in early pregnancy examined at a tertiary care center with the primary objective of describing IUC removal attempts, IUC removal successes, and pregnancy outcomes at 20 weeks following IUC removal. METHODS: Case series of women with concurrent IUC and early pregnancy who presented to a tertiary care ultrasound center by 12 weeks' gestation. RESULTS: A total of 3116 women had an early pregnancy ultrasound during the study period. Nineteen (19/3116, 0.61%) women underwent ultrasounds that identified a pregnancy before 12 weeks and an IUC in the uterus. A copper IUC was identified in 11 women (11/19, 58%) on their first ultrasound, and a levonogestrel IUC was identified in 5 women (5/19, 26%). Seventeen (17/19, 88%) women attempted to remove their IUC; 11 of 69 (69%) were successfully removed on the first attempt. Fourteen (14/19; 74%) women with an IUC examined by 12 weeks' gestation had an ongoing pregnancy at 20 weeks compared with 1782 (1782/2678, 67%; P = 0.209) women without an IUC. CONCLUSIONS: Pregnancy with IUC is rare. Among the 19 women who were found to have an in situ IUC and early pregnancy, most had a successful IUC removal and had an ongoing pregnancy at 20 weeks' gestation. In our case series, IUC removal in the first trimester was a straightforward procedure and likely successful.

Pregnancy Outcomes in Patients with Glomerular Disease Attending a Single Academic Center in North Carolina.

BACKGROUND: Contemporary data regarding pregnancy outcomes in US patients with primary glomerular diseases are lacking. We aimed to report fetal and maternal outcomes among women with biopsy-proven primary glomerular disease who received obstetric care at a single large academic US center. METHODS: All women with a biopsy-confirmed primary glomerular disease diagnosis and without end-stage kidney disease who received obstetric care at the University of North Carolina (UNC) Hospitals (1996-2015) were identified using the Glomerular Disease Collaborative Network registry and the UNC Hospitals Perinatal Database. The primary study outcome was perinatal death (stillbirth at >20 weeks or neonatal death). Secondary outcomes included premature birth (<37 weeks), birth weight, preeclampsia, and kidney function changes (postpartum vs. baseline). Demographics, clinical characteristics, and outcomes were compared across glomerular disease subtypes. RESULTS: Among 48 pregnancies in 43 women (IgA nephropathy n = 17, focal segmental glomerulosclerosis [FSGS] n = 16, membranous nephropathy n = 6, minimal change disease n = 4), 13% of pregnancies resulted in perinatal death and 48% of babies were born prematurely. From a maternal perspective, 33% of pregnancies were complicated by preeclampsia, 39% by a doubling of urinary protein, and 27% by a ≥50% increase in serum creatinine. Outcome differences across glomerular disease subtypes were not statistically significant, although decline in kidney function appeared most frequent in FSGS. CONCLUSION: Adverse pregnancy outcomes are frequently observed in women with glomerular disease. The independent influence of glomerular disease subtype on outcomes requires further study. More widespread reporting and analysis of pregnancy outcomes in women with glomerular disease are urgently needed.

Association between hypoalbuminemia and surgical site infection in vulvar cancers.

OBJECTIVE: To determine if preoperative hypoalbuminemia is associated with postoperative wound complications among patients with vulvar cancer. METHODS: The National Surgical Quality Improvement Program database was queried for cases of vulvar cancer undergoing vulvectomy with or without lymphadenectomy (LND) from 2008 to 2013. Primary outcome was major wound complication. Secondary outcome was minor wound complication. Hypoalbuminemia was defined as albumin<3.5g/dL. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Of 777 vulvar cancer patients, 514 (66.2%) had vulvar surgery alone and 263 (30.3%) had a LND. Median age was 66 (range 20-90) and median BMI was 28.9kg/m(2) (range 14.3-65.5). The incidence of wound complication was 10.4% (81/777) with 48 minor and 39 major complications. There was no difference in major wound complications when a LND was performed (p=1.0). Preoperative albumin was recorded in 429 patients (55.2%). Patients with hypoalbuminemia were more likely to have a major wound complication (OR 2.9 95% CI 1.1-7.3, p=0.02), even after adjusting for BMI, age, preoperative hematocrit, and diabetes (aOR 2.7 95% CI 1.1-7.1, p=0.04). In bivariable analysis, age, diabetes, and BMI were not associated with wound complication. Patients with a wound infection had 10 times the odds of being readmitted within 30days (OR 9.5, 95% CI 4.9-18.4, p<0.01). CONCLUSIONS: Low preoperative albumin is associated with major postoperative wound complications in women undergoing surgery for vulvar cancer. When obtaining informed consent, patients with low albumin should be counseled regarding higher risks of postoperative wound complication.

Patient characteristics associated with treatment choice for pelvic organ prolapse and urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Women with pelvic organ prolapse (POP) and stress urinary incontinence (SUI) frequently undergo more than one treatment prior to settling on their final strategy. We hypothesize that women who are younger, with worse POP and SUI symptoms will desire and choose surgical treatment. METHODS: A retrospective cohort study was performed over 1 year identifying new patients presenting with POP and/or SUI at a university hospital. Our aim was to determine patient desire for either surgical or conservative treatment, as well as the actual treatment chosen and received after the first visit and 1 year later. To identify predictors of choice, baseline demographic characteristics were obtained. RESULTS: Of the 203 women who met the inclusion criteria, 44.3 % (90/203) desired surgery and 55.7 % (113/203) desired conservative treatment at their first visit. Women who desired surgery were more likely to be younger (p = 0.003), sexually active (p = 0.001), have more advanced prolapse (p = 0.006), and have more bothersome symptoms (p = 0.05). Of the women who desired surgery at their first visit, 12.2 % (11/90) actually chose conservative treatment. These women were less likely to be insured (p = 0.01). By 1 year, of the women who initially desired and subsequently chose conservative treatment, 26.5 % (30/113) had undergone surgery. The women who changed from conservative to surgical treatment were more likely to be younger (p = 0.01), non-White (p = 0.03), and sexually active (p = 0.04). CONCLUSIONS: In this study, younger, sexually active women were more likely to either opt for surgery initially or to change their treatment plan from conservative to surgical.

Decreasing time to antibiotics in febrile patients with central lines in the emergency department.

BACKGROUND AND OBJECTIVE: Rapid antibiotic administration is essential for the successful management of patients who have central lines and present with fever. We conducted an emergency department (ED) improvement initiative to deliver antibiotics to 90% of patients within 60 minutes and to minimize process variation. METHODS: Our setting was an academic ED. We assembled a multidisciplinary team, identified contributing factors to the care delivery problem, determined key drivers and intervention steps, implemented changes, and used strategies to engage ED staff and promote sustainability. Outcomes were analyzed by using a time series design with baseline data and continuous postintervention monitoring. Outcomes included percentage of patients receiving antibiotics within 60 minutes, time to antibiotic administration, and accuracy for triage acuity and chief complaint. RESULTS: An 8-month baseline period revealed that 63% of patients received antibiotics within 60 minutes of arrival, with a mean time to antibiotics of 65 minutes. Multiple Plan-Do-Study-Act (PDSA) cycles were used to improve patient identification and initial management processes. The percentage of patients receiving antibiotics within 60 minutes of arrival was increased to 99% (297 of 301), and mean time to administration decreased to 30 minutes (95% confidence interval: 28-32). These gains were sustained for 24 months. Subanalysis identified a racial discrepancy, with African American patients experiencing significantly longer delays than patients of other races (95 vs 61 minutes; P < .05); this discrepancy was eliminated with our initiative. CONCLUSIONS: Our initiative exceeded our goal of 90% antibiotic delivery within 60 minutes for a sustained period of at least 24 months, decreased process variation and mean time to antibiotic administration, and eliminated race-based discrepancies in care.

Intrauterine lidocaine for pain control during laminaria insertion: a randomized controlled trial.

OBJECTIVE: To determine if intrauterine administration of 5 cc of 2% lidocaine in addition to paracervical block reduces pain during laminaria insertion, when compared with paracervical block and saline placebo. STUDY DESIGN: This was a randomized, double blind placebo-controlled trial. Women presenting for abortion by dilation and evacuation (D&E) at 14-24 weeks gestational age were randomized to receive an intrauterine instillation of either 5 mL of 2% lidocaine or 5 mL of normal saline, in addition to standard paracervical block with 20 cc of 0.25% bupivacaine. Our primary outcome was self-reported pain scores on a 100mm Visual Analogue Scale (VAS) immediately following laminaria insertion. Secondary outcome was self-reported VAS pain score indicating the maximum level of pain experienced during the 24-48-h interval between laminaria insertion and D&E procedure. RESULTS: Seventy-two women were enrolled, and data for 67 women were analyzed, only two of whom were more than 21 weeks on gestation. The range of pain scores at both time points was large (1-90 mm at laminaria insertion; 0-100mm in laminaria-D&E interval). Mean pain scores were not different between treatment groups at laminaria insertion, (33 vs. 32, p=.8) or in the laminaria - D&E interval (43 vs. 44, p=.9). CONCLUSION: Intrauterine administration of 5 cc of 2% lidocaine in addition to paracervical block did not reduce pain with laminaria insertion when compared to paracervical block with saline placebo. IMPLICATIONS: Intrauterine lidocaine combined with paracervical block does not improve pain control at laminaria insertion when compared with paracervical block and saline placebo. Wide variation in pain scores and persistent pain after laminaria insertion suggests patient would benefit from more effective methods of pain control at laminaria insertion and during the post-laminaria interval.

Awareness is not enough: the need to increase meningococcal vaccine uptake.

OBJECTIVE: Adolescent meningococcal vaccine uptake remains low. We examined vaccine awareness among parents of adolescents and uptake. METHODS: Parents of adolescents aged 11 to 17 years (n = 1281) participated in a statewide survey. Logistic regression with weighted data provided population-based estimates. RESULTS: In all, 65% had heard of meningococcal vaccine; parents more likely to report awareness had adolescents aged 16 to 17 years, in private school, or with health insurance. In total, 44% of aware parents reported vaccination; vaccinated teens were more likely to be black (odds ratio [OR] = 2.17), had a preventive checkup within 12 months (OR = 3.03), or resided with another child ≤18 years (OR = 1.83). Many parents of unvaccinated adolescents (38.5%) did not plan to vaccinate them within 12 months. The most common reasons for not vaccinating were providers not recommending it and believing adolescents did not need it. CONCLUSION: Many parents aware of meningococcal vaccine did not vaccinate their adolescents. Interventions that include increasing provider recommendation and annual visits may increase uptake.

Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection.

HIV type 1 (HIV-1) persists within resting CD4(+) T cells despite antiretroviral therapy (ART). To better understand the kinetics by which resting cell infection (RCI) is established, we developed a mathematical model that accurately predicts (r = 0.65, P = 2.5 × 10(-4)) the initial frequency of RCI measured about 1 year postinfection, based on the time of ART initiation and the dynamic changes in viremia and CD4(+) T cells. In the largest cohort of patients treated during acute seronegative HIV infection (AHI) in whom RCI has been stringently quantified, we found that early ART reduced the generation of latently infected cells. Although RCI declined after the first year of ART in most acutely infected patients, there was a striking absence of decline when initial RCI frequency was less than 0.5 per million. Notably, low-level viremia was observed more frequently as RCI increased. Together these observations suggest that (i) the degree of RCI is directly related to the availability of CD4(+) T cells susceptible to HIV, whether viremia is controlled by the immune response and/or ART; and (ii) that two pools of infected resting CD4(+) T cells exist, namely, less stable cells, observable in patients in whom viremia is not well controlled in early infection, and extremely stable cells that are established despite early ART. These findings reinforce and extend the concept that new approaches will be needed to eradicate HIV infection, and, in particular, highlight the need to target the extremely small but universal, long-lived latent reservoir.