Search

Background: Machine learning (ML) approaches facilitate risk prediction model development using high-dimensional predictors and higher-order interactions at the cost of model interpretability and transparency. We compared the relative predictive performance of statistical and ML models to guide modeling strategy selection for surveillance mammography outcomes in women with a personal history of breast cancer (PHBC). Methods: We cross-validated seven risk prediction models for two surveillance outcomes, failure (breast cancer within 12 months of a negative surveillance mammogram) and benefit (surveillance-detected breast cancer). We included 9,447 mammograms (495 failures, 1,414 benefits, and 7,538 nonevents) from years 1996 to 2017 using a 1:4 matched case–control samples of women with PHBC in the Breast Cancer Surveillance Consortium. We assessed model performance of conventional regression, regularized regressions (LASSO and elastic-net), and ML methods (random forests and gradient boosting machines) by evaluating their calibration and, among well-calibrated models, comparing the area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CI). Results: LASSO and elastic-net consistently provided well-calibrated predicted risks for surveillance failure and benefit. The AUCs of LASSO and elastic-net were both 0.63 (95% CI, 0.60–0.66) for surveillance failure and 0.66 (95% CI, 0.64–0.68) for surveillance benefit, the highest among well-calibrated models. Conclusions: For predicting breast cancer surveillance mammography outcomes, regularized regression outperformed other modeling approaches and balanced the trade-off between model flexibility and interpretability. Impact: Regularized regression may be preferred for developing risk prediction models in other contexts with rare outcomes, similar training sample sizes, and low-dimensional features.

To estimate the positive predictive value (PPV) of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes for identifying HF subtypes.We validated ICD-10-CM HF diagnosis codes among Kaiser Permanente Washington enrollees who were ≥18 years of age and had an ICD-10-CM HF diagnosis code during 2017-2018 and a procedure code for an echocardiogram in the 12 months before through 6 months after the HF code. Left ventricular ejection fraction (LVEF) ascertained from medical chart review was used as the gold standard for classifying patients as having reduced ejection fraction (rEF), mid-range ejection fraction (mEF), or preserved ejection fraction (pEF).Among 6194 eligible patients, we randomly sampled 1000 for medical chart review. A total of 974 patients had LVEF information in their chart. The ICD-10-CM HF code group with the highest PPV for rEF was I50.20-I50.23, "Systolic (congestive) heart failure," PPV = 41.4% (95% CI, 34.5-48.7%); and the highest PPV for mEF or rEF was also I50.20-I50.23, PPV = 70.2% (95% CI, 63.1-76.4%). The highest PPV for pEF was the I50.30-I50.33 group, "Diastolic (congestive) heart failure," PPV = 92.0% (95% CI, 88.1-94.7%); and the highest PPV for mEF or pEF was also I50.30-I50.33, PPV = 97.7% (95% CI, 95.1-99.0%).If the accuracy measure of greatest interest is PPV, our results suggest that ICD-10-CM HF codes alone may not be adequate for identifying patients with rEF but may be adequate for identifying patients with pEF. HF coding practices may vary across settings, which may impact generalizability of our findings.

Supplementary Table S1 shows the calibration assessment in a sensitivity analysis on LASSO and Elastic-net by enforcing the adjustment of the matching factor.

Supplementary Figure S1 shows frequency of predictor inclusion in regression-based models for surveillance failure and benefit across imputed datasets.

Background:Machine learning (ML) approaches facilitate risk prediction model development using high-dimensional predictors and higher-order interactions at the cost of model interpretability and transparency. We compared the relative predictive performance of statistical and ML models to guide modeling strategy selection for surveillance mammography outcomes in women with a personal history of breast cancer (PHBC).Methods:We cross-validated seven risk prediction models for two surveillance outcomes, failure (breast cancer within 12 months of a negative surveillance mammogram) and benefit (surveillance-detected breast cancer). We included 9,447 mammograms (495 failures, 1,414 benefits, and 7,538 nonevents) from years 1996 to 2017 using a 1:4 matched case–control samples of women with PHBC in the Breast Cancer Surveillance Consortium. We assessed model performance of conventional regression, regularized regressions (LASSO and elastic-net), and ML methods (random forests and gradient boosting machines) by evaluating their calibration and, among well-calibrated models, comparing the area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CI).Results:LASSO and elastic-net consistently provided well-calibrated predicted risks for surveillance failure and benefit. The AUCs of LASSO and elastic-net were both 0.63 (95% CI, 0.60–0.66) for surveillance failure and 0.66 (95% CI, 0.64–0.68) for surveillance benefit, the highest among well-calibrated models.Conclusions:For predicting breast cancer surveillance mammography outcomes, regularized regression outperformed other modeling approaches and balanced the trade-off between model flexibility and interpretability.Impact:Regularized regression may be preferred for developing risk prediction models in other contexts with rare outcomes, similar training sample sizes, and low-dimensional features.

Supplementary Methods show the detailed information of model fitting using the machine learning approaches in this work.

To explore to what extent intrauterine device (IUD) expulsion is associated with demographic and clinical risk factors.The APEX-IUD (Association of Perforation and Expulsion of IntraUterine Devices) study was a U.S. cohort study using electronic health records from three integrated health care systems (Kaiser Permanente Northern California, Southern California, and Washington) and a health care information exchange (Regenstrief Institute). These analyses included individuals aged 50 years or younger with IUD insertions from 2001 to 2018. Intrauterine device expulsion cumulative incidence and incidence rates were estimated. Using Cox regression models, hazard ratios with 95% CIs were estimated before and after adjustment for risk factors of interest (age, race and ethnicity, parity, body mass index [BMI], heavy menstrual bleeding, and dysmenorrhea) and potential confounders.In total, 228,834 individuals with IUD insertion and no delivery in the previous 52 weeks were identified (184,733 [80.7%] with levonorgestrel-releasing intrauterine system). Diagnosis of heavy menstrual bleeding-particularly a diagnosis in both recent and past periods-was the strongest risk factor for IUD expulsion. Categories with the highest risk of IUD expulsion within each risk factor included individuals diagnosed with overweight, obesity, and morbid obesity; those in younger age groups, especially among those aged 24 years or younger; and in those with parity of four or more. Non-Hispanic White individuals had the lowest incidence and risk, and after adjustment, Asian or Pacific Islander individuals had the highest risk. Dysmenorrhea was not independently associated with expulsion risk when adjusting for heavy menstrual bleeding.Most risk factors for expulsion identified in this study appear consistent with known physiologic factors that affect uterine anatomy and physiology (age, BMI, heavy menstrual bleeding, parity). The increased risk of IUD expulsion among individuals of color warrants further investigation. Intrauterine devices are an effective long-term contraceptive; expulsion is uncommon, but patients should be counseled accordingly.Bayer AG.EU PAS register, EUPAS33461.

Primary care providers prescribe most long-term opioid therapy and are increasingly asked to taper the opioid doses of these patients to safer levels. A recent systematic review suggests that multiple interventions may facilitate opioid taper, but many of these are not feasible within the usual primary care practice. To determine if opioid taper plans documented by primary care providers in the electronic health record are associated with significant and sustained opioid dose reductions among patients on long-term opioid therapy. A nested case-control design was used to compare cases (patients with a sustained opioid taper defined as average daily opioid dose of ≤ 30 mg morphine equivalent (MME) or a 50% reduction in MME) to controls (patients matched to cases on year and quarter of cohort entry, sex, and age group, who had not achieved a sustained taper). Each case was matched with four controls. Two thousand four hundred nine patients receiving a ≥ 60-day supply of opioids with an average daily dose of ≥ 50 MME during 2011–2015. Opioid taper plans documented in prescription instructions or clinical notes within the electronic health record identified through natural language processing; opioid dosing, patient characteristics, and taper plan components also abstracted from the electronic health record. Primary care taper plans were associated with an increased likelihood of sustained opioid taper after adjusting for all patient covariates and near peak dose (OR = 3.63 [95% CI 2.96–4.46], p < 0.0001). Both taper plans in prescription instructions (OR = 4.03 [95% CI 3.19–5.09], p < 0.0001) and in clinical notes (OR = 2.82 [95% CI 2.00–3.99], p < 0.0001) were associated with sustained taper. These results suggest that planning for opioid taper during primary care visits may facilitate significant and sustained opioid dose reduction.

Mary S Anthony,1 Mary Anne Armstrong,2 Darios Getahun,3 Delia Scholes,4 Jennifer Gatz,5 Renate Schulze-Rath,6 Debbie Postlethwaite,2 Maqdooda Merchant,2 Amy L Alabaster,2 Giulia Chillemi,2 Tina Raine-Bennett,2 Fagen Xie,3 Vicki Y Chiu,3 Theresa M Im,3 Harpreet S Takhar,3 Michael Fassett,3 Jane Grafton,4 David Cronkite,4 Laura Ichikawa,4 Susan D Reed,4,7 Siu Lui Hui,5 Mary E Ritchey,1 Catherine W Saltus,8 Elizabeth B Andrews,1 Kenneth J Rothman,8 Alex Asiimwe,6 Richard Lynen,9 Juliane Schoendorf101RTI Health Solutions, Research Triangle Park, NC, USA; 2Kaiser Permanente Northern California, Oakland, CA, USA; 3Kaiser Permanente Southern California, Pasadena, CA, USA; 4Kaiser Permanente Washington, Seattle, WA, USA; 5Regenstrief Institute, Indianapolis, IN, USA; 6Bayer AG, Berlin, Germany; 7University of Washington, Seattle, WA, USA; 8RTI Health Solutions, Waltham, MA, USA; 9Bayer HealthCare, Whippany, NJ, USA; 10Bayer OY, Espoo, FinlandObjective: To validate algorithms identifying uterine perforations and intrauterine device (IUD) expulsions and to ascertain availability of breastfeeding status at the time of IUD insertion.Study design and setting: Four health care systems with electronic health records (EHRs) participated: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Southern California (KPSC), Kaiser Permanente Washington (KPWA), and Regenstrief Institute (RI). The study included women ≤50 years of age with an IUD insertion. Site-specific algorithms using structured and unstructured data were developed and a sample validated by EHR review. Positive predictive values (PPVs) of the algorithms were calculated. Breastfeeding status was assessed in a random sample of 125 women at each research site with IUD placement within 52 weeks postpartum.Results: The study population included 282,028 women with 325,582 IUD insertions. The PPVs for uterine perforation were KPNC 77%, KPSC 81%, KPWA 82%, and RI 47%; PPVs for IUD expulsion were KPNC 77%, KPSC 87%, KPWA 68%, and RI 37%. Across all research sites, breastfeeding status at the time of IUD insertion was determined for 94% of those sampled.Conclusions: Algorithms with a high PPV for uterine perforation and IUD expulsion were developed at 3 of the 4 research sites. Breastfeeding status at the time of IUD insertion could be determined at all research sites. Our findings suggest that a study to evaluate the associations of breastfeeding and postpartum IUD insertions with risk of uterine perforation and IUD expulsion can be successfully conducted retrospectively; however, automated application of algorithms must be supplemented with chart review for some outcomes at one research site due to low PPV.Keywords: electronic health records, intrauterine device, breastfeeding, validation study, algorithm, postpartum

Reports of perforation risk related to intrauterine devices (IUDs) inserted immediately post partum and among non-post-partum individuals are scarce, and previous studies with only 12-month follow-ups underestimate the risk. Breastfeeding at IUD insertion and insertion within 36 weeks post partum have been associated with increased risk of uterine perforation. The aim of these analyses was to compare the incidence and risks of IUD-related uterine perforations by non-post-partum and post-partum intervals at IUD insertion, and among post-partum individuals, to assess the impact of breastfeeding on these outcomes.We did a multisite cohort study in the USA, using electronic health records (EHR). Study sites were three health-care systems and a site that used data from a health-care information exchange. The study population included individuals who were aged 50 years or younger and had an IUD insertion between Jan 1, 2001, and April 30, 2018. Individuals were excluded if they had not been in the health-care system for at least 12 months before IUD insertion. The primary outcome for this analysis was any IUD-related uterine perforation diagnosis for the first IUD insertion in this time period. Both complete and partial IUD-related perforations were identified. Chart abstraction was done to validate EHR-based algorithms or confirm perforations. The crude rate and cumulative incidence of uterine perforation were evaluated by non-post-partum and post-partum intervals at IUD insertion in the full cohort, and by breastfeeding status in a subcohort of post-partum individuals. Cox models estimated crude and adjusted hazard ratios (aHRs).Data from 326 658 individuals in the full cohort and 94 817 individuals in the post-partum subcohort were analysed. In the full cohort, we identified 1008 uterine perforations (51·2% complete), with the 5-year cumulative incidence being the lowest in the non-post-partum group (0·29%, 95% CI 0·26-0·34). The aHR for the post-partum interval relative to non-post partum ranged from 2·73 (95% CI 1·33-5·63; 0 to 3 days post partum) to 6·71 (4·80-9·38; 4 days to ≤6 weeks post partum). The post-partum subcohort of individuals with breastfeeding information had 673 uterine perforations (62% complete), with a 5-year cumulative incidence of 1·37% (95% CI 1·24-1·52) and an increased risk with breastfeeding (aHR 1·37, 95% CI 1·12-1·66).Although the risk for uterine perforation with IUD insertion 4 days to 6 weeks or less post partum is nearly seven times that of insertion non-post partum, perforation remains an incredibly rare event for all clinical time points. Despite a slight increased risk of perforation with breastfeeding at IUD insertion, the benefits of breastfeeding and effective contraception generally outweigh risks and should have little clinical impact. Therefore, IUD insertion timing should be based on individual desire for IUD contraception and patient convenience to assure an IUD insertion can occur. Careful follow-up of individuals at higher risk of uterine perforation is warranted.Bayer AG.

Intrauterine devices, including levonorgestrel-releasing and copper devices, are highly effective long-acting reversible contraceptives. The potential risks associated with intrauterine devices are low and include uterine perforation and device expulsion.This study aimed to evaluate the risk of perforation and expulsion associated with levonorgestrel-releasing devices vs copper devices in clinical practice in the United States.The Association of Perforation and Expulsion of Intrauterine Device study was a retrospective cohort study of women aged ≤50 years with an intrauterine device insertion during 2001 to 2018 and information on intrauterine device type and patient and medical characteristics. Of note, 4 research sites with access to electronic health records contributed data for the study: 3 Kaiser Permanente-integrated healthcare systems (Northern California, Southern California, and Washington) and 1 healthcare system using data from a healthcare information exchange in Indiana (Regenstrief Institute). Perforation was classified as any extension of the device into or through the myometrium. Expulsion was classified as complete (not visible in the uterus or abdomen or patient reported) or partial (any portion in the cervix or malpositioned). We estimated the crude incidence rates and crude cumulative incidence by intrauterine device type. The risks of perforation and expulsion associated with levonorgestrel-releasing intrauterine devices vs copper intrauterine devices were estimated using Cox proportional-hazards regression with propensity score overlap weighting to adjust for confounders.Among 322,898 women included in this analysis, the incidence rates of perforation per 1000 person-years were 1.64 (95% confidence interval, 1.53-1.76) for levonorgestrel-releasing intrauterine devices and 1.27 (95% confidence interval, 1.08-1.48) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 0.22% (95% confidence interval, 0.20-0.24) and 0.63% (95% confidence interval, 0.57-0.68) for levonorgestrel-releasing intrauterine devices and 0.16% (95% confidence interval, 0.13-0.20) and 0.55% (95% confidence interval, 0.44-0.68) for copper intrauterine devices, respectively. The incidence rates of expulsion per 1000 person-years were 13.95 (95% confidence interval, 13.63-14.28) for levonorgestrel-releasing intrauterine devices and 14.08 (95% confidence interval, 13.44-14.75) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 2.30% (95% confidence interval, 2.24-2.36) and 4.52% (95% confidence interval, 4.40-4.65) for levonorgestrel-releasing intrauterine devices and 2.30% (95% confidence interval, 2.18-2.44) and 4.82 (95% confidence interval, 4.56-5.10) for copper intrauterine devices, respectively. Comparing levonorgestrel-releasing intrauterine devices with copper intrauterine devices, the adjusted hazard ratios were 1.49 (95% confidence intervals, 1.25-1.78) for perforation and 0.69 (95% confidence intervals, 0.65-0.73) for expulsion.After adjusting for potential confounders, levonorgestrel-releasing intrauterine devices were associated with an increased risk of uterine perforation and a decreased risk of expulsion relative to copper intrauterine devices. Given that the absolute numbers of these events are low in both groups, these differences may not be clinically meaningful.

Background Since 2007, digital mammography and digital breast tomosynthesis (DBT) replaced screen-film mammography. Whether these technologic advances have improved diagnostic performance has, to the knowledge of the authors, not yet been established. Purpose To evaluate the performance and outcomes of surveillance mammography (digital mammography and DBT) performed from 2007 to 2016 in women with a personal history of breast cancer and compare with data from 1996 to 2007 and the performance of digital mammography screening benchmarks. Materials and Methods In this observational cohort study, five Breast Cancer Surveillance Consortium registries provided prospectively collected mammography data linked with tumor registry and pathologic outcomes. This study identified asymptomatic women with American Joint Committee on Cancer anatomic stages 0-III primary breast cancer who underwent surveillance mammography from 2007 to 2016. The primary outcome was a second breast cancer diagnosis within 1 year of mammography. Performance measures included the recall rate, cancer detection rate, interval cancer rate, positive predictive value of biopsy recommendation, sensitivity, and specificity. Results Among 32 331 women who underwent 117 971 surveillance mammographic examinations (112 269 digital mammographic examinations and 5702 DBT examinations), the mean age at initial diagnosis was 59 years ± 12 (standard deviation). Of 1418 second breast cancers diagnosed, 998 were surveillance-detected cancers and 420 were interval cancers. The recall rate was 8.8% (10 365 of 117 971; 95% CI: 8.6%, 9.0%), the cancer detection rate was 8.5 per 1000 examinations (998 of 117 971; 95% CI: 8.0, 9.0), the interval cancer rate was 3.6 per 1000 examinations (420 of 117 971; 95% CI: 3.2, 3.9), the positive predictive value of biopsy recommendation was 31.0% (998 of 3220; 95% CI: 29.4%, 32.7%), the sensitivity was 70.4% (998 of 1418; 95% CI: 67.9%, 72.7%), and the specificity was 98.1% (114 331 of 116 553; 95% CI: 98.0%, 98.2%). Compared with previously published studies, interval cancer rate was comparable with rates from 1996 to 2007 in women with a personal history of breast cancer and was higher than the published digital mammography screening benchmarks. Conclusion In transitioning from screen-film to digital mammography and digital breast tomosynthesis, surveillance mammography performance demonstrated minimal improvement over time and remained inferior to the performance of screening mammography benchmarks. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moy and Gao in this issue.

Intrauterine device (IUD) expulsion increases the risk of unintended pregnancy; how timing of postpartum IUD insertion and breastfeeding are associated with risk of expulsion is relevant to the benefit-risk profile.To evaluate the association of postpartum timing of IUD insertion and breastfeeding status with incidence and risk of IUD expulsion.The Association of Perforation and Expulsion of Intrauterine Devices (APEX-IUD) cohort study included women aged 50 years or younger with an IUD insertion between 2001 and 2018. The breastfeeding analysis focused on a subcohort of women at 52 or fewer weeks post partum with known breastfeeding status. The study was conducted using data from electronic health records (EHRs) at 4 research sites with access to EHR: 3 Kaiser Permanente sites (Northern California, Southern California, Washington) and the Regenstrief Institute (Indiana). Data analysis was conducted from June to November 2019.Timing of IUD insertion post partum was categorized into discrete time periods: 0 to 3 days, 4 days to 6 or fewer weeks, more than 6 weeks to 14 or fewer weeks, more than 14 weeks to 52 or fewer weeks, and non-post partum (52 weeks or no evidence of delivery). Breastfeeding status at the time of insertion was determined from clinical records, diagnostic codes, or questionnaires from well-baby visits.Incidence rates and adjusted hazard ratios (aHRs) were estimated using propensity scores to adjust for confounding.The full cohort included 326 658 women (mean [SD] age, 32.0 [8.3] years; 38 911 [11.9%] Asian or Pacific Islander; 696 [0.2%] Hispanic Black; 56 180 [17.2%] Hispanic other; 42 501 [13.0%] Hispanic White; 28 323 [8.7%] non-Hispanic Black; 137 102 [42.0%] non-Hispanic White), and the subcohort included 94 817 women. Most IUDs were levonorgestrel-releasing (259 234 [79.4%]). There were 8943 expulsions. The 5-year cumulative incidence of IUD expulsion was highest for insertions 0 to 3 days post partum (10.73%; 95% CI, 9.12%-12.61%) and lowest for insertions more than 6 weeks to 14 or fewer weeks post partum (3.18%; 95% CI, 2.95%-3.42%). Adjusted HRs using women with non-post partum IUD insertion as the referent were 5.34 (95% CI, 4.47-6.39) for those with postpartum insertion at 0 to 3 days; 1.22 (95% CI, 1.05-1.41) for those with postpartum insertion at 4 days to 6 or fewer weeks; 1.06 (95% CI, 0.95-1.18) for those with postpartum insertion at more than 6 to 14 or fewer weeks; and 1.43 (95% CI, 1.29-1.60) for those with postpartum insertion at more than 14 to 52 or fewer weeks. In the subcohort, 5-year cumulative incidence was 3.49% (95% CI, 3.25%-3.73%) for breastfeeding women and 4.57% (95% CI, 4.22%-4.95%) for nonbreastfeeding women; the adjusted HR for breastfeeding vs not breastfeeding was 0.71 (95% CI, 0.64-0.78).In this study of real-world data, IUD expulsion was rare but more common with immediate postpartum insertion. Breastfeeding was associated with lower expulsion risk.

Purpose To compare screening magnetic resonance (MR) imaging performance in the Breast Cancer Surveillance Consortium (BCSC) with Breast Imaging Reporting and Data System (BI-RADS) benchmarks. Materials and Methods This study was approved by the institutional review board and compliant with HIPAA and included BCSC screening MR examinations collected between 2005 and 2013 from 5343 women (8387 MR examinations) linked to regional Surveillance, Epidemiology, and End Results program registries, state tumor registries, and pathologic information databases that identified breast cancer cases and tumor characteristics. Clinical, demographic, and imaging characteristics were assessed. Performance measures were calculated according to BI-RADS fifth edition and included cancer detection rate (CDR), positive predictive value of biopsy recommendation (PPV2), sensitivity, and specificity. Results The median patient age was 52 years; 52% of MR examinations were performed in women with a first-degree family history of breast cancer, 46% in women with a personal history of breast cancer, and 15% in women with both risk factors. Screening MR imaging depicted 146 cancers, and 35 interval cancers were identified (181 total-54 in situ, 125 invasive, and two status unknown). The CDR was 17 per 1000 screening examinations (95% confidence interval [CI]: 15, 20 per 1000 screening examinations; BI-RADS benchmark, 20-30 per 1000 screening examinations). PPV2 was 19% (95% CI: 16%, 22%; benchmark, 15%). Sensitivity was 81% (95% CI: 75%, 86%; benchmark, >80%), and specificity was 83% (95% CI: 82%, 84%; benchmark, 85%-90%). The median tumor size of invasive cancers was 10 mm; 88% were node negative. Conclusion The interpretative performance of screening MR imaging in the BCSC meets most BI-RADS benchmarks and approaches benchmark levels for remaining measures. Clinical practice performance data can inform ongoing benchmark development and help identify areas for quality improvement. © RSNA, 2017.

Rationale and Objectives Evidence is inconsistent about whether radiologists' interpretive performance on a screening mammography test set reflects their performance in clinical practice. This study aimed to estimate the correlation between test set and clinical performance and determine if the correlation is influenced by cancer prevalence or lesion difficulty in the test set. Materials and Methods This institutional review board-approved study randomized 83 radiologists from six Breast Cancer Surveillance Consortium registries to assess one of four test sets of 109 screening mammograms each; 48 radiologists completed a fifth test set of 110 mammograms 2 years later. Test sets differed in number of cancer cases and difficulty of lesion detection. Test set sensitivity and specificity were estimated using woman-level and breast-level recall with cancer status and expert opinion as gold standards. Clinical performance was estimated using women-level recall with cancer status as the gold standard. Spearman rank correlations between test set and clinical performance with 95% confidence intervals (CI) were estimated. Results For test sets with fewer cancers (N = 15) that were more difficult to detect, correlations were weak to moderate for sensitivity (woman level = 0.46, 95% CI = 0.16, 0.69; breast level = 0.35, 95% CI = 0.03, 0.61) and weak for specificity (0.24, 95% CI = 0.01, 0.45) relative to expert recall. Correlations for test sets with more cancers (N = 30) were close to 0 and not statistically significant. Conclusions Correlations between screening performance on a test set and performance in clinical practice are not strong. Test set performance more accurately reflects performance in clinical practice if cancer prevalence is low and lesions are challenging to detect.

ObjectiveWe sought to identify and characterize examinations in women with a personal history of breast cancer likely performed for asymptomatic surveillance.MethodsWe included surveillance mammograms (1997-2017) in asymptomatic women with a personal history of breast cancer diagnosed at age ≥18 years (1996-2016) from 103 Breast Cancer Surveillance Consortium facilities. We examined facility-level variability in examination indication. We modeled the relative risk (RR) and 95% confidence intervals (CIs) at the examination level of a (1) nonscreening indication and (2) surveillance interval ≤9 months using Poisson regression with fixed effects for facility, stage, diagnosis age, surgery, examination year, and time since diagnosis.ResultsAmong 244,855 surveillance mammograms, 69.5% were coded with a screening indication, 12.7% short-interval follow-up, and 15.3% as evaluation of a breast problem. Within a facility, the proportion of examinations with a screening indication ranged from 6% to 100% (median 86%, interquartile range 79%-92%). Facilities varied the most for examinations in the first 5 years after diagnosis, with 39.4% of surveillance mammograms having a nonscreening indication. Within a facility, breast conserving surgery compared with mastectomy (RR= 1.64; 95% CI= 1.60-1.68) and less time since diagnosis (1 year versus 5 years; RR= 1.69; 95% CI= 1.66-1.72; 3 years versus 5 years= 1.20; 95% CI= 1.18-1.23) were strongly associated with a nonscreening indication with similar results for ≤9-month surveillance interval. Screening indication and >9-month surveillance intervals were more common in more recent years.ConclusionVariability in surveillance indications across facilities in the United States supports including indications beyond screening in studies evaluating surveillance mammography effectiveness and demonstrates the need for standardization.

Background There is lack of consensus regarding the use of breast MRI for routine surveillance for second breast cancer events in women with a personal history of breast cancer. Purpose To compare performance of surveillance mammography with breast MRI. Materials and Methods This observational cohort study used prospectively collected data and included 13 266 women age 18 years and older (mean age, 60 years ± 13) with stage 0-III breast cancer who underwent 33 938 mammographic examinations and 2506 breast MRI examinations from 2005 to 2012 in the Breast Cancer Surveillance Consortium. Women were categorized into two groups: mammography alone (n = 11 745) or breast MRI (n = 1521). Performance measures were calculated by using end-of-day assessment and occurrence of second breast cancer events within 1 year of imaging. Logistic regression was used to compare performance for breast MRI versus mammography alone, adjusting for women, examination, and primary breast cancer characteristics. Analysis was conducted on a per-examination basis. Results Breast MRI was associated with younger age at diagnosis, chemotherapy, and higher education and income. Raw performance measures for breast MRI versus mammography were as follows, respectively: cancer detection rates, 10.8 (95% confidence interval [CI]: 6.7, 14.8) versus 8.2 (95% CI: 7.3, 9.2) per 1000 examinations; sensitivity, 61.4% (27 of 44; 95% CI: 46.5%, 76.2%) versus 70.3% (279 of 397; 95% CI: 65.8%, 74.8%); and biopsy rate, 10.1% (253 of 2506; 95% CI: 8.9%, 11.3%) versus 4.0% (1343 of 33 938; 95% CI: 3.7%, 4.2%). In multivariable models, breast MRI was associated with higher biopsy rate (odds ratio [OR], 2.2; 95% CI: 1.9, 2.7; P < .001) and cancer detection rate (OR, 1.7; 95% CI: 1.1, 2.7; P = .03) than mammography alone. However, there were no differences in sensitivity (OR, 1.1; 95% CI: 0.4, 2.9; P = .84) or interval cancer rate (OR, 1.1; 95% CI: 0.6, 2.2; P = .70). Conclusion Comparison of the performance of surveillance breast MRI with mammography must account for patient characteristics. Whereas breast MRI leads to higher biopsy and cancer detection rates, there were no significant differences in sensitivity or interval cancers compared with mammography. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Newell in this issue.

Background Annually, more than 250 000 US women are diagnosed with breast cancer and are recommended for yearly surveillance mammography for second cancers after treatment completion. Many also receive breast magnetic resonance imaging (MRI), without evidence of effectiveness. Objectives (1) Assess patient and provider perspectives on surveillance breast imaging; (2) compare effectiveness of breast MRI with or without mammography to mammography only; (3) develop patient decision aids with education on breast imaging and results from imaging tests. Methods The research was based within 5 breast imaging registries in the US Breast Cancer Surveillance Consortium. Using a structured interview guide we conducted 6 focus groups with 41 women who had a personal history of breast cancer. We conducted a systematic literature review, following all relevant standards. We identified 33 938 surveillance mammograms and 2506 breast MRIs from 13 266 women following treatment for stage 0 to III breast cancer diagnosed in 2003-2012; second cancer events were ascertained within 1 year after imaging. We estimated performance measures using end-of-day radiologic assessment and compared them using multivariable logistic regression to adjust for potential confounders. Finally, we developed a prototype, web-based surveillance decision tool with information about breast imaging and results, incorporating women’s personal characteristics. Results Women reported anxiety when anticipating surveillance results and discomfort but high trust in imaging. Our systematic review indicated need for robust analyses, including comparative studies in breast imaging. We observed 397 second breast cancers within 1 year of mammogram (286 invasive, 108 ductal carcinoma in situ [DCIS], 3 unknown) and 44 cancers within 1 year of breast MRI (30 invasive cancers, 13 DCIS, 1 unknown). Unadjusted performance measures comparing breast MRI to mammography only (respectively, per 1000 examinations), were cancer detection rates (within 1 year of exam): 10.8 (95% confidence interval [CI], 9.6-12.0) vs 8.2 (95% CI, 7.98.5); and interval cancer rates: 6.8 (95% CI, 5.8-7.8) vs 3.5 (95% CI, 3.3-3.7). Sensitivity was 61.4% (95% CI, 46.5-76.2) vs 70.3% (95% CI, 65.8-74.8); specificity was 88.2% (95% CI, 86.9-89.5) vs 88.5% (95% CI, 88.1-88.8); and positive predictive value of cancer among biopsied women was 19.5% (95% CI, 12.3-26.7) vs 30.5% (95% CI, 27.0-34.0). By multivariable logistic regression, breast MRI was associated with improved cancer detection rate (OR = 1.68; 95% CI, 1.04-2.69; p = 0.03) and specificity (OR = 1.20; 95% CI, 1.03-1.40; p = 0.02), with no statistically significant difference in sensitivity (OR = 1.10; 95% CI, 0.45-2.72) and a 2.23-fold increased biopsy rate (95% CI, 1.86-2.66). Conclusions Women are challenged to understand surveillance breast imaging. Surveillance breast MRI compared with mammography in community practice had 2-fold higher biopsy rates with improved cancer detection, without improvement in sensitivity or a decrease in interval cancer rates. Our promising prototype decision aid provides women and clinicians with information about surveillance imaging. In sum, our results fill a gap about breast imaging for women with a personal history of breast cancer and can facilitate survivorship care planning after a breast cancer diagnosis.

Background Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006–2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration–mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device–related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. Objective We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. Study Design APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. Results The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74–177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. Conclusion Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.

ObjectiveThe purpose of this study was to evaluate concordance between BI-RADS assessments and management recommendations for breast MRI in community practice.Materials and methodsBreast MRI data were collected from four regional Breast Cancer Surveillance Consortium registries from 2005 to 2011 for women who were 18-79 years old. Assessments and recommendations were compared to determine concordance according to BI-RADS guidelines. Concordance was compared by assessment category as well as by year of examination and clinical indication.ResultsIn all, 8283 MRI examinations were included in the analysis. Concordance was highest (93% [2475/2657]) in examinations with a BI-RADS category 2 (benign) assessment. Concordance was also high in examinations with category 1 (negative) (87% [1669/1909]), category 0 (incomplete) (83% [348/417]), category 5 (highly suggestive of malignancy) (83% [208/252]), and category 4 (suspicious) (74% [734/993]) assessments. Examinations with categories 3 (probably benign) and 6 (known biopsy-proven malignancy) assessments had the lowest concordance rates (36% [302/837] and 56% [676/1218], respectively). The most frequent discordant recommendation for a category 3 assessment was routine follow-up. The most frequent discordant recommendation for a category 6 assessment was biopsy. Concordance of assessments and management recommendations differed across clinical indications (p < 0.0001), with the lowest concordance in examinations to assess disease extent.ConclusionBreast MRI BI-RADS management recommendations were most concordant for assessments of negative, incomplete, suspicious, and highly suggestive of malignancy. Lower concordance for assessments of probably benign and known biopsy-proven malignancy and for examinations performed to assess disease extent highlight areas for interventions to improve breast MRI reporting.

BACKGROUND Current data on the pathologic diagnoses of breast biopsy after mammography can inform patients, clinicians, and researchers about important population trends. METHODS Breast Cancer Surveillance Consortium data on 4,020,140 mammograms between 1996 and 2008 were linked to 76,567 pathology specimens. Trends in diagnoses in biopsies by time and risk factors (patient age, breast density, and family history of breast cancer) were examined for screening and diagnostic mammography (performed for a breast symptom or short-interval follow-up). RESULTS Of the total mammograms, 88.5% were screening and 11.5% diagnostic; 1.2% of screening and 6.8% of diagnostic mammograms were followed by biopsies. The frequency of biopsies over time was stable after screening mammograms, but increased after diagnostic mammograms. For biopsies obtained after screening, frequencies of invasive carcinoma increased over time for women ages 40-49 and 60-69, Ductal carcinoma in situ (DCIS) increased for those ages 40-69, whereas benign diagnoses decreased for all ages. No trends in pathology diagnoses were found following diagnostic mammograms. Dense breast tissue was associated with high-risk lesions and DCIS relative to nondense breast tissue. Family history of breast cancer was associated with DCIS and invasive cancer. CONCLUSIONS Although the frequency of breast biopsy after screening mammography has not changed over time, the percentages of biopsies with DCIS and invasive cancer diagnoses have increased. Among biopsies following mammography, women with dense breasts or family history of breast cancer were more likely to have high-risk lesions or invasive cancer. These findings are relevant to breast cancer screening and diagnostic practices. Cancer 2015;121:1369–1378. © 2015 American Cancer Society.

© 2016, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.Purpose: Breast cancer risk prediction models are used to plan clinical trials and counsel women; however, relationships of predicted risks of breast cancer incidence and prognosis after breast cancer diagnosis are unknown. Methods: Using largely pre-diagnostic information from the Breast Cancer Surveillance Consortium (BCSC) for 37,939 invasive breast cancers (1996-2007), we estimated 5-year breast cancer risk (

ContextOral contraceptive (OC) use is common, but bone changes associated with use of contemporary OC remain unclear.ObjectiveThe objective of the study was to compare bone mineral density (BMD) change in adolescent and young adult OC users and discontinuers of two estrogen doses, relative to nonusers.Design and settingThis was a prospective cohort study, Group Health Cooperative.ParticipantsParticipants included 606 women aged 14-30 yr (50% adolescents aged 14-18 yr): 389 OC users [62% 30-35 μg ethinyl estradiol (EE)] and 217 age-similar nonusers; there were 172 OC discontinuers. The 24-month retention was 78%.Main outcome measureThe main outcome measure was BMD measured at 6-month intervals for 24-36 months.ResultsAfter 24 months, adolescents using 30-35 μg EE OCs, but not those using lower-dose OCs, had significantly smaller adjusted mean percentage BMD gains than nonusers at the spine [group means (95% confidence interval for between group differences) 1.32 vs. 2.26% (-1.89, -0.13%)] and whole body [1.45 vs. 2.03% (-1.29%, -0.13%)]. Adolescents who discontinued 30-35 μg EE OC showed significantly smaller gains than nonusers at the spine after 12 months [0.51 vs. 1.72% (-2.38%, -0.30%)]. Young adult OC users did not differ from nonusers. However, OC discontinuers of both doses differed significantly from nonusers at the spine 12 months after discontinuation [-1.32% < 30 μg EE, -0.92% 30-35 μg EE vs. +0.27% nonusers (-2.48, -0.54, and -1.94%, -0.55%, respectively)]. Results were similar for mean absolute BMD change (grams per square centimeter).ConclusionsBoth OC use and discontinuation were associated with BMD losses/smaller gains relative to nonusers (differences < 2% after 12-24 months for all skeletal sites). The clinical significance of these results regarding future fracture risk is unknown. Study of longer-term trends after discontinuation is needed.

Purpose MRI is increasingly used for the detection of breast carcinoma. Little is known about breast MRI techniques among community practice facilities. The aim of this study was to evaluate equipment and acquisition techniques used by community facilities across the United States, including compliance with minimum standards by the ACRIN ® 6667 Trial and the European Society of Breast Imaging. Methods Breast Cancer Surveillance Consortium facilities performing breast MRI were identified and queried by survey regarding breast MRI equipment and technical parameters. Variables included scanner field strength, coil type, acquisition coverage, slice thickness, and the timing of the initial postcontrast sequence. Results were tallied and percentages of facilities meeting ACRIN ® and European Society of Breast Imaging standards were calculated. Results From 23 facilities performing breast MRI, results were obtained from 14 (61%) facilities with 16 MRI scanners reporting 18 imaging parameters. Compliance with equipment recommendations of ≥1.5-T field strength was 94% and of a dedicated breast coil was 100%. Eighty-three percent of acquisitions used bilateral postcontrast techniques, and 78% used slice thickness ≤ 3 mm. The timing of initial postcontrast sequences ranged from 58 seconds to 8 minutes 30 seconds, with 63% meeting recommendations for completion within 4 minutes. Conclusions Nearly all surveyed facilities met ACRIN and European Society of Breast Imaging standards for breast MRI equipment. The majority met standards for acquisition parameters, although techniques varied, in particular for the timing of initial postcontrast imaging. Further guidelines by the ACR Breast MRI Accreditation Program will be of importance in facilitating standardized and high-quality breast MRI.

Menopausal status is a common covariate in epidemiologic studies. Still, there are no standard definitions for menopausal status using observational data. This study assesses distinctions between menopausal status definitions using commonly collected epidemiologic data, and explores their impact on study outcomes using breast cancer rates as an example.Using survey data from 227,700 women aged 40-64 who received screening mammograms from the Breast Cancer Surveillance Consortium, we classified menopausal status under five different definitions: one complex definition combining multiple variables, two definitions using age as a proxy for menopausal status, one based only on menstrual period status, and one based on age and menstrual period status.We compared the distribution of menopausal status and menopausal status-specific breast cancer incidence and detection rates across definitions for menopausal status.Overall, 36% and 29% of women were consistently classified as postmenopausal and premenopausal, respectively, across all definitions. Menopausal status-specific breast cancer incidence and detection rates were similar across definitions. Rates were unchanged when information regarding natural menopause, bilateral oophorectomy, hormone therapy, and timing of last menstrual period were sequentially added to definitions of postmenopausal status.Distinctions in menopausal status definitions contribute to notable differences in how women are classified, but translate to only slight differences in menopausal status-specific breast cancer rates.

Background Obesity and depression may each be associated with lower rates of cervical and breast cancer screening. Studies have examined obesity or depression alone, but not together, despite the established link between them. Purpose This article aims to disentangle the effects of depression and obesity on receipt of breast and cervical cancer screening. Methods A stratified sampling design was used to recruit women aged 40–65 years with information on BMI from an integrated health plan in Washington State in 2003–2005. A telephone survey included the Patient Health Questionnaire–9 for depression, weight, and height. Automated data assessed Paps for 3097 women over a 3-year period and screening mammograms over a 2-year period for 2163 women aged ≥51 years. Logistic regression models (conducted in 2008) examined the association between obesity and depression and receipt of screening tests. Results In univariate logistic regression models, women were less likely to receive a Pap if they were obese (OR=0.53, 95% CI=0.41, 0.69) or depressed (OR=0.60, 95% CI=0.42, 0.87). Further, women were less likely to receive a screening mammogram if they were depressed (OR=0.45, 95% CI=0.30, 0.67). In multivariable models, only obesity remained significantly associated with a lower likelihood of Pap screening (OR=0.67, 95% CI=0.0.49, 0.93), and only depression remained significantly associated with lower rates of screening mammography (OR=0.49, 95% CI=0.31, 0.76). Obesity and depression did not interact significantly in either model. Conclusions Obesity and depression appear to have specific effects on receipt of different cancer-screening tests.

Most of the millions of oral contraceptive (OC) users are under 30 years of age and in the critical period for bone mass accrual.This cross-sectional study of 606 women aged 14-30 years examined both OC duration and estrogen dose and their association with bone mineral density (BMD) at the hip, spine, and whole body (dual-energy X-ray absorptiometry).Of 389 OC users and 217 nonusers enrolled, 50% were adolescents (14-18 years). Of OC users, 38% used "low-dose" OCs [30 mcg ethinyl estradiol (EE)]. In adolescents, mean BMD differed by neither OC duration nor EE dose. However, 19- to 30-year-old women's mean BMD was lower with longer OC use for spine and whole body (p=.004 and p=.02, respectively) and lowest for12 months of low-dose OCs for the hip, spine and whole body (p=.02, .003 and .002, respectively).Prolonged use of today's OCs, particularly30 mcg EE, may adversely impact young adult women's bone density while using these agents.

ObjectiveThe effect of oral contraceptive (OC) use on risk of fracture remains unclear, and use during later reproductive life may be increasing. To determine the association between OC use during later reproductive life and risk of fracture across the menopausal transition, we conducted a population-based case-control study in a Pacific Northwest HMO, Group Health Cooperative.MethodsFor the January 2008 to March 2013 interval, 1,204 case women aged 45 to 59 years with incident fractures, and 2,275 control women were enrolled. Potential cases with fracture codes in automated data were adjudicated by electronic health record review. Potential control women without fracture codes were selected concurrently, sampling based on age. Participants received a structured study interview. Using logistic regression, associations between OC use and fracture risk were calculated as odds ratios (ORs) and 95% confidence intervals (CIs).ResultsParticipation was 69% for cases and 64% for controls. The study sample was 82% white; mean age was 54 years. The most common fracture site for cases was the wrist/forearm (32%). Adjusted fracture risk did not differ between cases versus controls for OC use in the 10 years before menopause (OR 0.90, 95% CI 0.74, 1.11); for OC use after age 38 (OR 0.94, 95% CI 0.78, 1.14); for duration of use, or for other OC exposures.ConclusionsThe current study does not show an association between fractures near the menopausal transition and OC use in the decade before menopause or after age 38. For women considering OC use at these times, fracture risk does not seem to be either reduced or-reassuringly-increased.

Using a combination of performance measures, we updated previously proposed criteria for identifying physicians whose performance interpreting screening mammography may indicate suboptimal interpretation skills.In this study, six expert breast imagers used a method based on the Angoff approach to update criteria for acceptable mammography performance on the basis of two sets of combined performance measures: set 1, sensitivity and specificity for facilities with complete capture of false-negative cancers; and set 2, cancer detection rate (CDR), recall rate, and positive predictive value of a recall (PPV1) for facilities that cannot capture false-negative cancers but have reliable cancer follow-up information for positive mammography results. Decisions were informed by normative data from the Breast Cancer Surveillance Consortium (BCSC).Updated combined ranges for acceptable sensitivity and specificity of screening mammography are sensitivity≥80% and specificity≥85% or sensitivity 75-79% and specificity 88-97%. Updated ranges for CDR, recall rate, and PPV1 are: CDR≥6 per 1000, recall rate 3-20%, and any PPV1; CDR 4-6 per 1000, recall rate 3-15%, and PPV1≥3%; or CDR 2.5-4.0 per 1000, recall rate 5-12%, and PPV1 3-8%. Using the original criteria, 51% of BCSC radiologists had acceptable sensitivity and specificity; 40% had acceptable CDR, recall rate, and PPV1. Using the combined criteria, 69% had acceptable sensitivity and specificity and 62% had acceptable CDR, recall rate, and PPV1.The combined criteria improve previous criteria by considering the interrelationships of multiple performance measures and broaden the acceptable performance ranges compared with previous criteria based on individual measures.

Background: Opportunities to prevent late-stage breast cancer within the course of usual care are needed. We evaluate whether clinical encounters offer such opportunities. Methods: Within seven health care plans, we identifi ed 1298 women aged more than 50 years with early (

Although adolescent women are actively acquiring bone, there has been little study of the possible effects of depot medroxyprogesterone acetate (DMPA) injectable contraception use on bone density in adolescents. We conducted a cross-sectional evaluation of the association between DMPA use and bone mineral density in adolescent women, ages 14-18 years. Of 174 study participants, 81 were DMPA users (range, 1-13 injections, median = 3) and 93 were not. Mean bone density at all anatomic sites (hip, spine and whole body) was lower for DMPA users than nonusers, but differences were not statistically significant (e.g., hip, 0.940 vs. 0.970 g/cm2, p = 0.10; spine, 0.970 vs. 0.992 g/cm2, p = 0.19). Duration of DMPA use showed a trend toward lower spine bone density (p-value for trend = 0.06). This study did not find a strong association between DMPA use and bone density. Further prospective evaluation of bone density changes with DMPA use and after DMPA discontinuation are needed in this age group.

The objective of our study was to evaluate organized breast cancer screening implementation by measuring the association between screening program enrollment and late-stage disease. Our setting was a health plan using mailed mammography reminders to women ages ≥40. We conducted yearly cross-sectional summaries of mammography experience and late-stage (regional or distant Surveillance Epidemiology and End Results Reporting (SEER) stage) breast cancer occurrence for all of the health-plan women ages ≥40 (1986–1998). We estimated the odds of late-stage breast cancer among health-plan and surrounding community women because it was too early to compare changes in mortality. We also estimated the odds of late-stage disease (1995–1998) associated with program enrollment and mammography screening among health-plan women. We found that mammography-within-two-years increased within the health plan from 25.9% to 51.2% among women ages 40–49 and from 32.9% to 74.7% among women ages ≥50. Health-plan late-stage rates were lower than those in the surrounding community [ages 40–49: odds ratio (OR), 0.87; 95% confidence interval (CI), 0.77–0.99; ages 50–79: OR, 0.86; 95% CI, 0.80–0.92] and declined parallel to the community. Among health-plan cancer cases, women ages ≥43 who were enrolled in the screening program and who had at least one program mammogram were less likely to have late-stage disease compared with the women not enrolled in the program (OR, 0.31; 95% CI, 0.16–0.61) but the odds of late-stage was also reduced among program-enrolled women not receiving program mammograms (OR, 0.45; 95% CI, 0.21–0.95). We concluded that enrollment in organized screening is associated with increased likelihood of mammography and reduced odds of late-stage breast cancer. Addressing the concerns of un-enrolled women and those without mammograms offers an opportunity for further late-stage disease reduction.

The primary aim of this 36-month prospective cohort study was to evaluate the association between use of oral contraceptives (OCs) and bone mineral density in reproductive-age women. The 36-month bone density (g/cm2) at the spine, hip and whole body and percent change from baseline (measured at 6-month intervals) were evaluated among 245 women 18-39 years of age; 89 were using OCs (median duration: 3.7 years at study entry) and 156 were not using any hormonal contraception. Before and after adjustment for covariates (baseline bone density, age, race, ever pregnant, exercise, body mass and calcium intake), women using OCs did not differ significantly from comparison women in percent change in bone density over 36 months or in absolute bone density at 36 months. All p-values for between-group differences were >0.55. In conclusion, within the limitations of this study, OCs did not appear to impact bone density over time in this cohort of reproductive-age women.

Author(s): Ott, Susan M; LaCroix, Andrea Z; Ichikawa, Laura E; Scholes, Delia; Barlow, William E | Abstract: OBJECTIVES:To determine the effects of low doses of hydrochlorothiazide (HCTZ) on plasma lipids in healthy older men and women. DESIGN:Randomized, double-blind, placebo-controlled clinical trial for 3 years followed by a 1 year extension without medication. SETTING:Research clinic of a nonprofit health maintenance organization. PARTICIPANTS:Two hundred five women and 115 men aged 60 to 79 with normal blood pressure, bone density within two standard deviations of mean for age, and low-density lipoprotein cholesterol (LDL-C) levels less than 190 mg/dL. INTERVENTION:Placebo or HCTZ 12.5 or 25 mg/d. MEASUREMENTS:Plasma cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides. RESULTS:There were no significant differences in the change in the plasma lipids between placebo and either group. The mean changes +/- standard deviation in LDL-C after 3 years in men were -5.2 +/- 3.9 mg/dL (placebo), -4.6 +/- 3.7 (12.5 mg), and 1.1 +/- 3.8 (25 mg) and in women were 1.3 +/- 2.8 (placebo), -1.1 +/- 2.8 (12.5 mg), and -6.8 +/- 2.8 (25 mg). No significant differences were seen when analysis was done only for subjects who adhered to study medication. CONCLUSION:This study provides evidence that low doses of thiazide diuretics have minimal effects on cholesterol metabolism in healthy older adults. Therefore, effects on lipid levels need not limit use of thiazides for prevention of osteoporotic fractures.

Purpose Oral contraceptive (OC) use can occur throughout a woman's reproductive life span with the potential for long-term impacts on health. To assess potential measurement error in prior OC use, this study compared level of agreement between self-reported prior OC use and pharmacy dispensing data in perimenopausal and/or early postmenopausal women. Methods The study's 1399 women (ages, 45–59 years) were participants in a population-based case-control study of the association between OC use and fracture risk. Episodes of lifetime self-reported OC use (in months) were collected, by telephone interview, for January 1, 2008 through November 25, 2012. Pharmacy fills, back to 1980, were collected from automated data. Agreement was measured using the prevalence-adjusted and bias-adjusted kappa index. Results The number of women with OC pharmacy fills was 11% to 45% higher than those who reported OC use during each time period. Between-measures agreement was better for more recent use. Prevalence-adjusted and bias-adjusted kappa index values ranged from 0.88 (95% confidence interval, 0.85–0.90) within 5 years from the reference date to 0.65 (95% confidence interval, 0.59–0.71) within 15 to 20 years. Conclusions For studies designed to assess the long-term effects of OC use, the current results are reassuring in noting moderate agreement between self-reported OC use and pharmacy data for up to 15 to 20 years before the interview.

Depot medroxyprogesterone acetate (DMPA) injectable contraception may decrease bone density and increase the risk for osteoporosis in later life. Prospective data are scarce, especially of the effects of DMPA discontinuation on bone.Between 1994 and 1999, we conducted a population-based prospective cohort study among women enrollees of a Washington State health maintenance organization. We enrolled 457 nonpregnant women, ages 18-39 years (183 DMPA users and 274 non-users). Bone density was measured by dual-energy x-ray absorptiometry every 6 months for 3 years.Bone density decreased notably among DMPA-exposed women at the spine (adjusted mean bone density was -0.0053 gm/cm for DMPA users compared with +0.0023 gm/cm for non-users for each 6-month interval) and total hip (-0.0060 compared with -0.0002 gm/cm ). This represents an annualized mean rate of change at the spine of -0.87% compared with +0.40% and, at the hip, -1.12% compared with -0.05%. Discontinuers of this method (N = 110) showed sizable increases in bone density over comparison women (for each 6-month interval, adjusted mean spine bone density was +0.0067 gm/cm compared with +0.0023 gm/cm, respectively; adjusted mean hip bone density was +0.0035 compared with -0.0002 gm/cm ). Estimated annualized mean rates of change were +1.41% compared with +0.40% [corrected] at the spine and +1.03% [corrected] compared with -0.05% at the hip. After 30 months, mean bone density for discontinuers was similar to that of non-users.In this study, DMPA use was strongly associated with bone density loss. Substantial postdiscontinuation recovery of bone provides evidence that the effects may be largely reversible.

This abstract was withdrawn by the authors.

Rationale and Objectives As breast magnetic resonance imaging (MRI) use grows, benchmark performance parameters are needed for auditing and quality assurance purposes. We describe the variation in breast MRI abnormal interpretation rates (AIRs) by clinical indication among a large sample of US community practices. Materials and Methods We analyzed data from 41 facilities across five Breast Cancer Surveillance Consortium imaging registries. Each registry obtained institutional review board approval for this Health Insurance Portability and Accountability Act compliant analysis. We included 11,654 breast MRI examinations conducted in 2005–2010 among women aged 18–79 years. We categorized clinical indications as 1) screening, 2) extent of disease, 3) diagnostic (eg, breast symptoms), and 4) other (eg, short-interval follow-up). We characterized assessments as positive (ie, Breast Imaging Reporting and Data System [BI-RADS] 0, 4, and 5) or negative (ie, BI-RADS 1, 2, and 6) and provide results with BI-RADS 3 categorized as positive and negative. We tested for differences in AIRs across clinical indications both unadjusted and adjusted for patient characteristics and registry and assessed for changes in AIRs by year within each clinical indication. Results When categorizing BI-RADS 3 as positive, AIRs were 21.0% (95% confidence interval [CI], 19.8–22.3) for screening, 31.7% (95% CI, 29.6–33.8) for extent of disease, 29.7% (95% CI, 28.3–31.1) for diagnostic, and 27.4% (95% CI, 25.0–29.8) for other indications (P

The purpose of this study was to compare biochemical markers of bone resorption and formation in young women using different hormonal contraceptive methods. Women aged 18-39 yr who were using depot medroxyprogesterone acetate (DMPA) contraception were recruited for the study; comparison women were matched by age and clinic location. There were 116 women using DMPA, 39 using oral contraceptives containing estrogen and progestin, and 72 not currently using hormonal contraceptives. Biochemical measurements were serum calcium, PTH and osteocalcin, and urine N-telopeptide. Bone density was measured using dual-energy x-ray absorptiometry. The N-telopeptide levels, adjusted for age and other risk factors, were 42.4 +/- 2.3 nmol/mmol creatinine in the DMPA group, 26.2 +/- 3.3 nmol/mmol in the oral contraceptive group, and 35.4 +/- 2.9 nmol/mmol in the nonusers; significant differences were seen in all pairwise comparisons. Osteocalcin levels showed the same pattern, although the difference between the DMPA users and nonusers was not statistically significant. There were no differences among groups in the PTH levels. The bone density at the spine was 1.086 +/- 0.085 g/cm(2) in the DMPA group, 1.103 +/- 0.095 g/cm(2) in the oral contraceptive group, and 1.093 +/- 0.090 g/cm(2) in nonusers (P = 0.051). The results suggest that in women using DMPA bone resorption exceeded bone formation.

To evaluate the possible effects of depot medroxyprogesterone acetate (DMPA) injectable contraception on depressive symptoms, we conducted a population-based prospective study with women aged 18-39 years old enrolled at a health maintenance organization. At baseline, 183 women used DMPA and 274 were non-users. Data on depressive symptoms and on factors potentially related to DMPA use and depression were collected by questionnaire at 6-month intervals for up to 3 years. In multivariate longitudinal analysis, we found an increased likelihood of reporting depressive symptoms among continuous DMPA users (OR = 1.44; 95% CI = 1.00-2.07) and discontinuers (OR = 1.60; 95% CI = 1.03-2.48) when compared to non-users. Women who discontinued DMPA use had elevated depressive symptoms prior to discontinuation (OR = 2.30; 95% CI = 1.42-3.70) and immediately following discontinuation (OR = 2.46; 95% CI = 1. 46-4.14), and depressive symptoms subsided at subsequent visits relative to non-users. Our prospective analyses found an association between DMPA use and depressive symptoms but further research is needed to determine whether the relationship is causal.

This paper examines the relationships among reports of depressive symptoms, BMI and frequency of consumption of 30 foods in 4655 middle-aged women. Food was grouped into three categories: high-calorie sweet, high-calorie nonsweet, and low-calorie. Controlling for total energy intake, BMI and depressive symptoms were both inversely associated with a higher frequency of consumption of low-calorie foods. BMI was positively associated with consumption of high-calorie nonsweet foods and negatively related to consumption of high-calorie sweet foods. Depressive symptoms were positively associated with sweet foods consumption and negatively associated with nonsweet foods consumption. These findings suggest that the positive association between BMI and depression in women may be mediated by sweets consumption. This is consistent with the hypothesis that eating sweet foods reduces negative affect.

The case-cohort design is most useful in analyzing time to failure in a large cohort in which failure is rare. Covariate information is collected from all failures and a representative sample of censored observations. Sampling is done without respect to time or disease status, and, therefore, the design is more flexible than a nested case-control design. Despite the efficiency of the methods, case-cohort designs are not often used because of perceived analytic complexity. In this article, we illustrate computation of a simple variance estimator and discuss model fitting techniques in SAS. Three different weighting methods are considered. Model fitting is demonstrated in an occupational exposure study of nickel refinery workers. The design is compared to a nested case-control design with respect to analysis and efficiency in a small simulation. In this example, case-cohort sampling from the full cohort was more efficient than using a comparable nested case-control design.

Objective: This study was undertaken to determine the results and complications of stents placed for initially unsuccessful or complicated iliac percutaneous transluminal angioplasty (PTA), the effect of location (external iliac or common iliac) on outcome, and the influence of superficial femoral artery patency on benefit. Design: From 1992 through 1997, 350 patients underwent iliac artery PTA at the authors' institutions. Of this group, 88 patients (88 arteries) had one or more stents placed after PTA (140 stents in total) for residual stenosis or pressure gradient (63 patients), iliac dissection (12 patients), long-segment occlusion (10 patients), or recurrent stenosis (3 patients). Thirty patients required the placement of more than one stent. The indications for PTA in these 88 patients were claudication (48 patients) and limb-threatening ischemia (40 patients). Forty-seven patients had stents placed in the common iliac, 29 patients had stents placed in the external iliac, and 12 patients had stents placed in both. Seventy-one arteries (81%) were stenotic, and 17 (19%) were occluded before PTA. Sixty-six arteries were treated by interventional radiologists, 15 by a vascular surgeon, and 7 jointly. Main outcome measure: Criteria for success included (1) increase of at least one clinical category of chronic limb ischemia from baseline or satisfactory wound healing, (2) maintenance of an ankle/brachial index increase of more than 0.10 above the preprocedure index, and (3) residual angiographic stenosis less than 25% and, for patients with pressure gradient measurements, a residual gradient less than 10 mm Hg. Results: Stent placement was accomplished in all 88 patients with 16 (18%) major complications. Mean follow-up was 17 months (range, 3 to 48 months). By life-table analysis, success was 75% at 1 year, 62% at 2 years, and 57% at 3 years. No cardiovascular risk factor or independent variable was statistically significant in predicting success. There was no difference in success rates for common iliac or external iliac lesions. Superficial femoral artery patency did not correlate with outcome. Conclusions: Although stents can eliminate residual lesions and arterial dissection, these patients are likely to require adjuvant or subsequent procedures to attain clinical success. By controlling the PTA complication and treating the emergent problem, stents may allow for subsequent elective intervention. (J Vasc Surg 1998;28:104-14)

Objective: To evaluate the association between vaginal douching and cervical Chlamydia trachomatis infection. Methods: We analyzed cross-sectional data from a study conducted at Group Health Cooperative of Puget Sound, a nonprofit health maintenance organization in western Washington state. Participants were nonpregnant women Group Health enrollees between the ages of 18 and 34 years who were attending two primary care clinics either for nonurgent visits, primarily routine preventive health visits, or in response to an invitation from the study. Before the clinical examination, all completed a self-administered survey assessing demographic and behavioral characteristics, including the timing, frequency, products used, and reasons for douching. Chlamydial infection was ascertained via cell culture isolation of C trachomatis from endocervical specimens obtained at the same visit. Results: Chlamydia trachomatis was isolated from cervical cultures in 58 (3.4%) of 1692 study participants. Women who reported douching in the 12 months before their clinic visit had an increased likelihood of chlamydial infection compared with women who did not douche (prevalence odds ratio [OR] 2.29, 95% confidence interval [CI] 1.22, 4.30, after adjusting for confounding factors). The likelihood was higher for women who reported douching more often: OR 2.60 (95% CI 1.29, 5.24) for women who douched one to three times per month, and OR 3.84 (95% CI 1.26, 11.70) for those douching four times or more per month. These associations were slightly stronger when women who reported douching because of an infection were excluded from the analysis. Conclusion: These results support the hypothesis that vaginal douching predisposes to acquisition of cervical chlamydial infection and are compatible with previous studies that report associations between douching and sequelae of chlamydial infection, including pelvic inflammatory disease, ectopic pregnancy, and infertility.

ImportanceBreast magnetic resonance imaging (MRI) is increasingly used for breast cancer screening, diagnostic evaluation, and surveillance. However, we lack data on national patterns of breast MRI use in community practice.ObjectiveTo describe patterns of breast MRI use in US community practice during the period 2005 through 2009.Design, setting, and participantsObservational cohort study using data collected from 2005 through 2009 on breast MRI and mammography from 5 national Breast Cancer Surveillance Consortium registries. Data included 8931 breast MRI examinations and 1,288,924 screening mammograms from women aged 18 to 79 years.Main outcomes and measuresWe calculated the rate of breast MRI examinations per 1000 women with breast imaging within the same year and described the clinical indications for the breast MRI examinations by year and age. We compared women screened with breast MRI to women screened with mammography alone for patient characteristics and lifetime breast cancer risk.ResultsThe overall rate of breast MRI from 2005 through 2009 nearly tripled from 4.2 to 11.5 examinations per 1000 women, with the most rapid increase from 2005 to 2007 (P = .02). The most common clinical indication was diagnostic evaluation (40.3%), followed by screening (31.7%). Compared with women who received screening mammography alone, women who underwent screening breast MRI were more likely to be younger than 50 years, white non-Hispanic, and nulliparous and to have a personal history of breast cancer, a family history of breast cancer, and extremely dense breast tissue (all P < .001). The proportion of women screened using breast MRI at high lifetime risk for breast cancer (>20%) increased during the study period from 9% in 2005 to 29% in 2009.Conclusions and relevanceUse of breast MRI for screening in high-risk women is increasing. However, our findings suggest that there is a need to improve appropriate use, including among women who may benefit from screening breast MRI.