Mode of Detection of Second Breast Cancers in Patients Undergoing Surveillance After Treatment of Ductal Carcinoma in Situ.

BACKGROUND: For patients undergoing posttreatment surveillance after ductal carcinoma in situ (DCIS), the NCCN Guidelines for Breast Cancer recommend annual breast imaging and physical examination every 6 to 12 months for 5 years, and then annually. The aim of our study was to evaluate the modes of detection (imaging, patient reported, or physical examination) of second cancers in a cohort of patients undergoing surveillance after primary DCIS treatment to better inform surveillance recommendations. METHODS: We performed a retrospective cohort study of patients with DCIS treated between January 1, 2008, and December 31, 2011, within a large integrated health care system. Information on patient demographics, index DCIS treatment, tumor characteristics, and mode of detection of second breast cancer was obtained from the electronic health record or chart review. RESULTS: Our study cohort consisted of 1,550 women, with a median age of 59 years at diagnosis. Surgical treatment of DCIS included lumpectomy (75.0%; n=1,162), unilateral mastectomy (21.1%; n=327), or bilateral mastectomy (3.9%; n=61), with or without sentinel lymph node biopsy. Additionally, 44.4% (n=688) and 28.3% (n=438) received radiation and endocrine therapies, respectively. Median follow-up was 10 years, during which 179 (11.5%) women were diagnosed with a second breast cancer. Of the second cancers, 43.0% (n=77) were ipsilateral and 54.8% (n=98) contralateral, and 2.2% (n=4) presented with distant metastases; 61.5% (n=110) were invasive, 36.3% (n=65) were DCIS, and 2.2% (n=4) were Paget's disease. Second breast cancers were imaging-detected in 74.3% (n=133) of cases, patient-detected in 20.1% (n=36), physician-detected in 2.2% (n=4), and detected incidentally on imaging or pathology from procedures unrelated to oncologic care in 3.4% (n=6). CONCLUSIONS: In our cohort of patients undergoing surveillance following diagnosis and treatment of DCIS, 2% of second breast cancers were detected by a clinical breast examination. This suggests that survivorship care should prioritize mammography and patient education regarding breast self-examination and symptoms that warrant evaluation to detect second breast cancers.

Development and validation of an expanded panel of progestins using liquid chromatography-tandem triple quadrupole mass spectrometry to monitor protocol compliance in hormonal contraceptive pharmacokinetic/pharmacodynamic studies.

We developed and validated the use of ultra-high-performance liquid chromatography-heated electrospray ionization-tandem triple quadrupole mass spectrometry to simultaneously analyze serum concentrations of ethinylestradiol, dienogest, norelgestromin, norethindrone, gestodene, levonorgestrel, etonogestrel, segesterone acetate, medroxyprogesterone acetate, and drospirenone. The calibration range for all targets was 0.009-10 ng/mL, with lower limit of quantification of 0.009 ng/mL for all analytes except gestodene (0.019 ng/mL). We used our assay to check compliance among participants in a clinical trial, confirmed the use of drospirenone in 11 of 13 study participants, and evidence of noncompliant progestins in 2 (levonorgestrel = 1, norethindrone = 1). We conclude that this approach provides an accurate method to check protocol compliance in contraceptive clinical trials. IMPLICATIONS: The availability of a liquid chromatography-tandem triple quadrupole mass spectrometry multiprogestin analysis panel for simultaneous evaluation of the most common contraceptive steroids approved worldwide could improve monitoring of compliance and protocol adherence in clinical trials.

Delivery timing in dichorionic diamniotic twin pregnancies complicated by preeclampsia: a decision analysis.

OBJECTIVE: To determine the optimal timing of delivery in Dichorionic-diamniotic (DCDA) pregnancies complicated by preeclampsia without severe features. METHODS: A decision-analytic model was created to compare outcomes of expectant management vs. delivery from 34 to 37w0d. Outcomes included quality-adjusted life years (QALYs), development of severe preeclampsia, maternal mortality, maternal stroke, small for gestational age (SGA) due to fetal growth restriction (FGR) detected antenatally, stillbirth, cerebral palsy (CP), and neonatal mortality. Probabilities, utilities, and life expectancies were derived from the literature. Univariate analysis was used to evaluate the impact of delivery at various gestational ages. Maternal and neonatal outcomes were calculated for a theoretical cohort of 10,000 DCDA pregnancies with preeclampsia. RESULTS: The optimal gestational age for delivery was 36w0d when the total QALYs (868,112) were highest. Delivery at 34w0d resulted in the fewest cases of severe preeclampsia, maternal mortality, and maternal stroke (0, 4, and 15 cases per 10,000, respectively). The incidence of each of these adverse outcomes increased with gestational age, with the greatest number of adverse outcomes at 37w0d (2452 cases of severe preeclampsia, eight maternal deaths, and 31 cases of maternal stroke per 10,000). Delivery at 34w0d resulted in the fewest cases of severe preeclampsia (0), maternal stroke (15), maternal mortality (4), stillbirth (0), and SGA (1183). However, this strategy was also associated with most cases of neonatal CP (91) and neonatal mortality (87). CONCLUSION: DCDA twin pregnancies complicated by preeclampsia without severe features appear to have the best outcomes when delivered at 36w0d. Specifically, when compared to delivery at 37w0d, this strategy reduced maternal and neonatal morbidity and mortality.

First trimester fasting plasma glucose screen in advanced maternal age women: a cost-effectiveness analysis.

BACKGROUND: The prevalence of preexisting type 2 diabetes mellitus (T2DM) in the United States is on the rise. Women of advanced maternal age (AMA, ≥35 years) are more likely to have preexisting T2DM in pregnancy because glucose intolerance increases with age. Diabetes in pregnancy is associated with significant maternal and neonatal morbidity and mortality, and earlier treatment initiation improves pregnancy outcomes. However, maternal age is not currently recognized as an independent risk factor that warrants diabetes screening prior to the traditional screen at 24-28 weeks gestation. OBJECTIVE: To evaluate the cost-effectiveness of screening all AMA women with a first trimester fasting plasma glucose (FPG) test for earlier diagnosis and management of preexisting T2DM. STUDY DESIGN: A decision-analytic model was created to compare pregnancy outcomes in AMA women who undergo a first trimester FPG test vs third trimester oral glucose tolerance test alone. Probabilities were obtained from the literature. Outcomes examined included preeclampsia, preterm delivery, macrosomia, shoulder dystocia, brachial plexus injury (BPI), intrauterine fetal demise (IUFD), cerebral palsy, and neonatal death. The cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio of the first trimester screening strategy were examined as well. Sensitivity analyses and a Monte Carlo simulation were performed to test the model's robustness. RESULTS: In AMA women, screening for preexisting T2DM in the first trimester with an FPG test resulted in fewer cases of preeclampsia, preterm delivery, BPI, IUFD, cerebral palsy, and neonatal death compared to performing a third trimester oral glucose tolerance test alone, and is cost-effective. Monte Carlo analysis incorporating the distribution of all probabilities showed that first trimester FPG screening remained cost-effective as long as the incremental cost of initiating diabetes treatment in the first trimester was less than $150,000 and the cost of the FPG screen was less than $2700. CONCLUSION: Compared to third trimester oral glucose tolerance test alone, performing a first trimester FPG screen in AMA women is cost-saving and more effective.

The impact of extremes of maternal age on maternal and neonatal pregnancy outcomes in women with pregestational diabetes mellitus.

Background:. Diabetes mellitus (DM) during pregnancy increases the risk for many complications such as preeclampsia and cesarean section. Teen (age <20) and advanced maternal age (AMA, age ≥35) pregnancies are both at increased risk for maternal and neonatal morbidity and mortality. Understanding the risks and complications unique to teen and AMA women with pregestational DM is imperative to providing care and improving outcomes.Objective:. This study sought to determine how maternal and neonatal outcomes are affected by pregestational DM in teen and AMA pregnancies.Study design:. This is a retrospective cohort study of 1.58 million pregnancies in California from 2005 through 2008s, of which 10,034 diabetic women with nonanomalous, singleton pregnancies were identified. Women with gestational DM were excluded. Maternal outcomes examined include preeclampsia, placental abruption, chorioamnionitis, preterm delivery, and cesarean section. Neonatal outcomes include size for gestational age, birth weight >4000 g, shoulder dystocia, brachial plexus injury, jaundice, and intrauterine fetal demise (IUFD). Multivariate regression analyses and chi-squared test were used for statistical comparisons and a p-value of less than .05 was used to indicate statistical significance.Results:. Compared to women of age 20-34 years with pregestational DM as the reference group, women <20 years old with DM had higher rates of preeclampsia (aOR 1.72; 95% CI 1.29-2.29; p-value < .001) and lower rates of cesarean delivery (aOR 0.63; 95% CI 0.47-0.85; p < .001). Neonates of teen mothers were more likely to be large for gestational age (LGA; > 90%ile; aOR 1.60; 95% CI 1.14-2.23; p = .006), whereas neonates in the maternal age category of 35-39 years had lower rates of LGA >90%ile (aOR 0.81; 95% CI 0.70-0.92; p = .001). Odds of IUFD were greatest in women age 35-39 years old (aOR 1.73; 95% CI 1.05-2.85; p = .031). Analysis examining women >40 years old showed no statistically significant difference in outcomes.Conclusion: Pregnancy outcomes in women with pregestational diabetes differ depending on maternal age category. Teens are at higher risk for preeclampsia and LGA neonates, but at lower risk for cesarean. Women aged 35-39 years are at higher risk for cesarean delivery, are less likely to have LGA neonates, and more likely to experience IUFD. Understanding the etiologies behind these differences may lead to improvements in these clinical outcomes.

Twins versus singleton pregnancies: outcomes in small for gestational age late preterm deliveries.

Background: Compared to singleton pregnancies, small for gestational age (SGA) and twin gestations experience adverse maternal and neonatal outcomes. Specific data regarding outcomes in late preterm SGA twin gestations are lacking.Objective: This study sought to compare pregnancy outcomes of late preterm (≥34 and <37 weeks) SGA twins versus singletons. In addition, we sought to stratify the comparisons by <10 and <5 percentile categories.Study design: In this retrospective cohort of 1.85 million pregnancies, we identified 10,646 nonanomalous, SGA, late preterm singleton and twin pregnancies. Births at gestational ages <34 and ≥37 weeks were excluded. Multivariate regression analyses and Chi-squared test were used for statistical comparisons and a p-value of less than 0.05 was used to indicate statistical significance.Results: After controlling for race, education, parity, prenatal care, diabetes, and hypertensive disease, twin pregnancies were less likely to experience neonatal death (aOR 0.14; 95% CI 0.03-0.63; p = .01) and intrauterine fetal demise (IUFD) (aOR 0.16; 95% CI 0.08-0.31; p < .001) compared to SGA <10 percentile singletons. Cesarean rates were higher in SGA <10 [percentile twin pregnancies (aOR 3.40; 95% CI 3.01-3.90; p < .001) as were postpartum hemorrhage (aOR 2.01; 95% CI 1.52-2.67; p < .001) and transfusion (aOR 1.54; 95% CI 1.52-2.67; p = .024).Conclusion: Late preterm SGA twin pregnancies were more like to be complicated by cesarean delivery, postpartum hemorrhage, and maternal transfusion compared to singleton pregnancies. However, neonatal death and IUFD were less common in SGA twin gestations.

Practice Gap in Atrial Fibrillation Oral Anticoagulation Prescribing at Emergency Department Home Discharge.

INTRODUCTION: Current U.S. cardiology guidelines recommend oral anticoagulation (OAC) to reduce stroke risk in selected patients with atrial fibrillation (AF), but no formal AF OAC recommendations exist to guide emergency medicine clinicians in the acute care setting. We sought to characterize emergency department (ED) OAC prescribing practices after an ED AF diagnosis. METHODS: This retrospective study included index visits for OAC-naive patients ≥18 years old who were discharged home from the ED at an urban, academic, tertiary hospital with a primary diagnosis of AF from 2012-2014. Five hypothesis-blinded, chart reviewers abstracted data from patient problem lists and medical history in the electronic health record to assess stroke (CHA2DS2-VASc) and bleeding risk (HAS-BLED). The primary outcome was the provision of an OAC prescription at discharge in OAC-naive patients with high stroke risk. Descriptive statistics and multivariable logistic regression assessed associations between OAC prescription and patient characteristics. RESULTS: We included 138 patient visits in our analysis, of whom 39.9% (n = 55) were low stroke risk (CHA2DS2-VASc = 0 in males and 1 in females), 15.9% (n = 22) were intermediate risk (CHA2DS2-VASc = 1 in males), and 44.2% (n = 61) were high risk (CHA2DS2-VASc ≥ 2). Of patients with high stroke risk and low-to-intermediate bleeding risk (n = 57), 80.7% were not prescribed an OAC at discharge. Cardiology consultation and female gender, but not stroke risk (CHA2DS2-VASc score), were predictors of an ED provider prescribing an OAC to an OAC-naive AF patient at ED discharge. CONCLUSION: The majority of OAC-eligible patients were discharged home without an OAC prescription. In OAC-naive patients discharged home from the ED, cardiology consultation and female gender were associated with OAC prescription. Our findings suggest that access to expert opinion may improve provider comfort with OAC prescribing and highlight the need for improved guidelines specific to ED-management of AF.