Abstract Background Recognizing the limitations of pre-market clinical data, regulatory authorities have embraced total product lifecycle management with post-market surveillance (PMS) data to assess medical device safety and performance. One method of proactive PMS involves the analysis of real-world data (RWD) through retrospective review of electronic health records (EHR). Because EHRs are patient-centered and focused on providing tools that clinicians use to determine care rather than collecting information on individual medical products, the process of transforming RWD into real-world evidence (RWE) can be laborious, particularly for medical devices with broad clinical use and extended clinical follow-up. This study describes a method to extract RWD from EHR to generate RWE on the safety and performance of embolization coils. Methods Through a partnership between a non-profit data institute and a medical device manufacturer, information on implantable embolization coils’ use was extracted, linked, and analyzed from clinical data housed in an electronic data warehouse from the state of Indiana’s largest health system. To evaluate the performance and safety of the embolization coils, technical success and safety were defined as per the Society of Interventional Radiology guidelines. A multi-prong strategy including electronic and manual review of unstructured (clinical chart notes) and structured data (International Classification of Disease codes), was developed to identify patients with relevant devices and extract data related to the endpoints. Results A total of 323 patients were identified as treated using Cook Medical Tornado, Nester, or MReye embolization coils between 1 January 2014 and 31 December 2018. Available clinical follow-up for these patients was 1127 ± 719 days. Indications for use, adverse events, and procedural success rates were identified via automated extraction of structured data along with review of available unstructured data. The overall technical success rate was 96.7%, and the safety events rate was 5.3% with 18 major adverse events in 17 patients. The calculated technical success and safety rates met pre-established performance goals (≥ 85% for technical success and ≤ 12% for safety), highlighting the relevance of this surveillance method. Conclusions Generating RWE from RWD requires careful planning and execution. The process described herein provided valuable longitudinal data for PMS of real-world device safety and performance. This cost-effective approach can be translated to other medical devices and similar RWD database systems.

Introduction: Multiple society guidelines recommend placing pancreatic stents for post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis prophylaxis in select cases. There is limited data on spontaneous migration and time to migration of these devices. Methods: Data on consecutive patients where a pancreatic stent (Cook Medical, Bloomington, IN) was used during an ERCP procedure between September 2019 and December 2019 were collected from an Indiana state-wide medical records database. Data were collected as part of post-market clinical follow up efforts with the primary aims of establishing continuing safety and effectiveness for the drainage of obstructed pancreatic ducts in a real-world setting and to identify potential systematic off-label use. Data elements included indication for procedure, duct status during follow-up, time to migration or removal, clinical success, and any adverse events. Results: Pancreatic stent placement was attempted in 128 patients (mean age 57.3 years; 59.4% (76/128) female; 87.5% (112/118) were White) (Table 1). Successful stent placement was achieved among 98.4% (126/128) of patients. Clinical success was achieved among 92.9% (117/126) of patients. Thirty-four (26.6%) patients reported at least 1 adverse event with the most frequent being pain or discomfort associated with the procedure (20.3%, 26/128), most classified as mild. Post-ERCP pancreatitis related to the device or procedure was identified in 3.9% (5/128) of patients. Spontaneous migration was observed among 51.2% (22/43) of patients with PEP prophylaxis as the indication vs 11.8% (9/76) of patients with other indications. The mean days to confirmation of the stent spontaneously migrating out in the PEP prophylaxis patients was 28.2 days (range: 10 days-79 days) (Table 1). Conclusion: ESGE guidelines recommend pancreatic stents to be in place no longer than 10 days when placed for PEP prophylaxis. Spontaneous migration of the stents was noted only half the time in PEP prophylaxis patients (51.2%, 22/43) in this study. This is despite removal of internal flaps (Figure 1) to facilitate the spontaneous passage. Clinicians should be aware of the possibility for additional procedures to remove stents, when placed for PEP prophylaxis. Indications for use of Cook pancreatic stents currently do not include placement for PEP prophylaxis, and Cook does not recommend modifying devices. The study was not powered to detect changes in migration rate based on stent size, length, or modification.Figure 1.: A,B) Stent prior to modification with a flap; C,D) Flap being cut; E,F) Stent post modification without flap. Table 1. - Patient demographics, stent characteristics and migration features by indication 1. One hundred and forty-nine stents attempted for placement among 128 patients 2. Two stents among 2 patients fell off during the procedure and stent status at follow-up was unavailable for 7 patients PEP: Post-ERCP Pancreatitis Total PEP Prophylaxis Patients Therapeutic Patients Age 57.3 ± 15.5 (128, 15 - 90) 61.7 ± 16.6 (46, 18 - 90) 54.8 ± 14.4 (82, 15 - 81) Sex Female Male 59.4% (76/128)40.6% (52/128) 69.6% (32/46)30.4% (14/46) 53.7% (44/82)46.3% (38/82) Race American Indian Asian Black Native Hawaiian None of these apply Refused White 0.8% (1/128)2.3% (3/128)4.7% (6/128)0.8% (1/128)0.8% (1/128)3.1% (4/128)87.5% (112/128) 2.2% (1/46)2.2% (1/46)2.2% (1/46)2.2% (1/46)0% (0/46)0% (0/46)91.3% (42/46) 0% (0/82)2.4% (2/82)6.1% (5/82)0% (0/82)1.2% (1/82)4.9% (4/82)85.4% (70/82) Stent size (Fr, mean ± SD, range) 5.3 ± 1.3 (149, 4 - 10) 4.3 ± 0.5 (47, 4 - 6) 5.8 ± 1.3 (102, 4 - 10) Stent length (Cm, mean ± SD, range) 8 ± 3.1 (149, 2 - 15) 7 ± 2.7 (47, 2 - 12) 8.5 ± 3.2 (102, 2 - 15) Modification1 Internal flap removed External flap made Internal flap made Manually groomed for shape Stent shortened and internal flap made 28.2% (42/149)0.7% (1/149)0.7% (1/149)0.7% (1/149)0.7% (1/149) 70.2% (33/47)2.1% (1/47)0% (0/47)0% (0/47)2.1% (1/47) 8.8% (9/102)0% (0/102)1.0% (1/102)1.0% (1/102)0% (0/102) Pigtails1 External Internal none 96.0% (143/149)0.7% (1/149)3.4% (5/149) 89.4% (42/47)0% (0/47)10.6% (5/47) 99.0% (101/102)1.0% (1/102)0% (0/102) Flaps1 External Internal None 2.0% (3/149)67.1% (100/149)30.9% (46/149) 4.3% (2/47)17.0% (8/47)78.7% (37/47) 1.0% (1/102)90.2% (92/102)8.8% (9/102) Stent status2 Fall out Removed In place 26.1% (31/119)48.7% (58/119)25.2% (30/119) 51.2% (22/43)30.2% (13/43)18.6% (8/43) 11.8% (9/76)59.2% (45/76)28.9% (22/76) Days to Fall out Removal In place confirmation 34.4 ± 25.2 (31, 10 - 90)43.4 ± 20.3 (58, 3 - 84)40 ± 18.1 (30, 2 - 83) 28.2 ± 20 (22, 10 - 79)34.8 ± 15.4 (13, 10 - 77)33 ± 15.9 (8, 2 - 60) 49.6 ± 31 (9, 15 - 90)45.9 ± 21 (45, 3 - 84)42.5 ± 18.5 (22, 14 - 83)

Background Real-world performance of COVID-19 diagnostic tests under Emergency Use Authorization (EUA) must be assessed. We describe overall trends in the performance of serology tests in the context of real-world implementation. Methods Six health systems estimated the odds of seropositivity and positive percent agreement (PPA) of serology test among people with confirmed SARS-CoV-2 infection by molecular test. In each dataset, we present the odds ratio and PPA, overall and by key clinical, demographic, and practice parameters. Results A total of 15,615 people were observed to have at least one serology test 14–90 days after a positive molecular test for SARS-CoV-2. We observed higher PPA in Hispanic (PPA range: 79–96%) compared to non-Hispanic (60–89%) patients; in those presenting with at least one COVID-19 related symptom (69–93%) as compared to no such symptoms (63–91%); and in inpatient (70–97%) and emergency department (93–99%) compared to outpatient (63–92%) settings across datasets. PPA was highest in those with diabetes (75–94%) and kidney disease (83–95%); and lowest in those with auto-immune conditions or who are immunocompromised (56–93%). The odds ratios (OR) for seropositivity were higher in Hispanics compared to non-Hispanics (OR range: 2.59–3.86), patients with diabetes (1.49–1.56), and obesity (1.63–2.23); and lower in those with immunocompromised or autoimmune conditions (0.25–0.70), as compared to those without those comorbidities. In a subset of three datasets with robust information on serology test name, seven tests were used, two of which were used in multiple settings and met the EUA requirement of PPA ≥87%. Tests performed similarly across datasets. Conclusion Although the EUA requirement was not consistently met, more investigation is needed to understand how serology and molecular tests are used, including indication and protocol fidelity. Improved data interoperability of test and clinical/demographic data are needed to enable rapid assessment of the real-world performance of in vitro diagnostic tests.

BackgroundAs diagnostic tests for COVID-19 were broadly deployed under Emergency Use Authorization, there emerged a need to understand the real-world utilization and performance of serological testing across the United States. MethodsSix health systems contributed electronic health records and/or claims data, jointly developed a master protocol, and used it to execute the analysis in parallel. We used descriptive statistics to examine demographic, clinical, and geographic characteristics of serology testing among patients with RNA positive for SARS-CoV-2. ResultsAcross datasets, we observed 930,669 individuals with positive RNA for SARS-CoV-2. Of these, 35,806 (4%) were serotested within 90 days; 15% of which occurred <14 days from the RNA positive test. The proportion of people with a history of cardiovascular disease, obesity, chronic lung, or kidney disease; or presenting with shortness of breath or pneumonia appeared higher among those serotested compared to those who were not. Even in a population of people with active infection, race/ethnicity data were largely missing (>30%) in some datasets-limiting our ability to examine differences in serological testing by race. In datasets where race/ethnicity information was available, we observed a greater distribution of White individuals among those serotested; however, the time between RNA and serology tests appeared shorter in Black compared to White individuals. Test manufacturer data was available in half of the datasets contributing to the analysis. ConclusionOur results inform the underlying context of serotesting during the first year of the COVID-19 pandemic and differences observed between claims and EHR data sources-a critical first step to understanding the real-world accuracy of serological tests. Incomplete reporting of race/ethnicity data and a limited ability to link test manufacturer data, lab results, and clinical data challenge the ability to assess the real-world performance of SARS-CoV-2 tests in different contexts and the overall U.S. response to current and future disease pandemics.

ABSTRACT Intrauterine device (IUD) expulsion is more common among women with heavy menstrual bleeding, parity, higher body mass index (BMI), younger age, dysmenorrhea, or immediate postabortion or postpartum insertion. The APEX-IUD study was an observational cohort study of 326,658 individuals examining the association with breastfeeding, IUD type, and timing of postpartum IUD insertion with IUD expulsion and uterine perforation. This data set provides an opportunity to examine specific demographic, reproductive, and medical risk factors associated with IUD expulsion. This analysis of APEX-IUD data aimed to determine the associations of 6 risk factors (age, race/ethnicity, parity, BMI, heavy menstrual bleeding, and dysmenorrhea) and IUD expulsion, as well as the extent to which these associations differed for LNG-IUD compared with copper IUD users. Individuals aged 50 years or younger at the time of IUD insertion without a delivery 52 weeks or less before insertion were included. Individuals were followed from IUD insertion until IUD expulsion, uterine perforation, removal, reinsertion, expiration, pregnancy, hysterectomy, death, disenrollment from the health care system, or end of study period (June 2018). Crude incidence rates for each risk factor category were calculated using the number of expulsions during the time at risk divided by the total person-years at risk and were reported as the number of expulsions per 1000 person-years at risk. Hazards ratios (HRs) and 95% confidence intervals from Cox regression models were used to evaluate associations of the risk factors with IUD expulsion. These models were adjusted for potential confounding effects and were separately used to assess the association of covariates with IUD expulsion varied by IUD type. The total study cohort included 228,834 individuals (LNG-IUD: 184,733 [80.7%]; copper IUD: 41,123 [18.0%]; unknown type: 2978 [1/3%]). The average length of follow-up was 2.0 years, and there were 6762 expulsions with a crude incidence rate of 14.9 per 1000 person-years (95% confidence interval, 14.6–15.3). Adjusted hazards ratios (aHRs) showed the younger age groups having a higher risk of IUD expulsion and a trend toward lower aHRs with increasing age. Individuals with parity of 4 or more had the highest risk of IUD expulsion, and a parity of 2 was associated with the lowest risk on adjusted analysis. Adjusted analysis revealed a greater risk of IUD expulsion among individuals with higher BMI or heavy menstrual bleeding diagnosis compared with the comparator group. Multiple racial and ethnic groups including non-Hispanic Black, Hispanic Black, Hispanic White, Asian, or Pacific Islander were associated with a greater risk of IUD expulsion compared with non-Hispanic Whites when adjusting for covariates. When comparing aHRs by copper IUD or LNG-IUD; younger age was more strongly associated with expulsion among copper IUD users than LNG-IUD users, the risk for expulsion associated with obesity was significantly attenuated for copper IUD users compared with LNG-IUD users, and the risk of expulsion for those with heavy menstrual bleeding was partially attenuated by copper IUDs. Adjusted analysis revealed no association between dysmenorrhea and IUD expulsion. The results of this study show that, among the 6 risk factors investigated here, the risk of IUD expulsion was highest among individuals with a diagnosis of heavy menstrual bleeding, particularly in recent and past periods.

OBJECTIVE:The APEX-IUD (Association of Perforation and Expulsion of Intrauterine Devices) study evaluated the association of postpartum timing of intrauterine device (IUD) insertion, breastfeeding, heavy menstrual bleeding, and IUD type (levonorgestrel-releasing vs copper) with risks of uterine perforation and IUD expulsion in usual clinical practice. We summarize the clinically important findings to inform counseling and shared decision making.METHODS:APEX-IUD was a real-world (using U.S. health care data) retrospective cohort study of individuals aged 50 years and younger with IUD insertions between 2001 and 2018 and with electronic health record data. Cumulative incidences of uterine perforation and IUD expulsion were calculated. Adjusted hazard ratios (aHRs) and 95% CIs were estimated from proportional hazards models with control of confounding.RESULTS:Among the study population of 326,658, absolute risk of uterine perforation was low overall (cumulative incidence, 0.21% [95% CI 0.19-0.23%] at 1 year and 0.61% [95% CI 0.56-0.66% at 5 years]) but was elevated for IUDs inserted during time intervals within 1 year postpartum, particularly among those between 4 days and 6 weeks postpartum (aHR 6.71, 95% CI 4.80-9.38), relative to nonpostpartum insertions. Among postpartum insertions, IUD expulsion risk was greatest for insertions in the immediate postpartum period (0-3 days after delivery) compared with nonpostpartum (aHR 5.34, 95% CI 4.47-6.39). Postpartum individuals who were breastfeeding had a slightly elevated risk of perforation and lowered risk of expulsion than those not breastfeeding. Among nonpostpartum individuals, those with a heavy menstrual bleeding diagnosis were at greater risk of expulsion than those without (aHR 2.84, 95% CI 2.66-3.03); heavy menstrual bleeding also was associated with a slightly elevated perforation risk. There was a slightly elevated perforation risk and slightly lower expulsion risk associated with levonorgestrel-releasing IUDs compared with copper IUDs.CONCLUSION:Absolute risk of adverse outcomes with IUD insertion is low. Clinicians should be aware of the differences in risks of uterine perforation and expulsion associated with IUD insertion during specific postpartum time periods and with a heavy menstrual bleeding diagnosis. This information should be incorporated into counseling and decision making for patients considering IUD insertion.FUNDING SOURCE:Bayer AG.

Abstract Background We evaluated the frequency of genomic testing and treatment patterns by age category in patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated in both academic‐ and community‐based health systems within a single Midwestern State. Methods Retrospective analysis of data from the Indiana University Health System Enterprise Data Warehouse and two local cancer registries, of 629 patients aged ≥18 years with ND AML during 2011–2018. Primary outcome variables were, proportion of patients with genomic analysis and frequency of mutations. Chemotherapy was categorized as “standard induction” or “other chemotherapy”/targeted therapy, and hypomethylating agents. Results Overall, 13% of ND AML patients between 2011 and 2018 had evidence of a genomic sequencing report with a demonstrated increase to 37% since 2016. Genomic testing was more likely performed in patients: aged ≤60 years than >60 years (45% vs. 30%; p = 0.03), treated in academic versus community hospitals (44% vs. 26%; p = 0.01), and in chemotherapy recipients than non‐therapy recipients (46% vs. 19%; p < 0.001). Most common mutations were ASXL1, NPM1, and FLT3. Patients ≥75 years had highest proportion (46%) of multiple (≥3) mutations. Overall, 31.2% of patients with AML did not receive any therapy for their disease. This subgroup was older than chemotherapy recipients (mean age: 71.4 vs. 55.7 years, p < 0.001), and was highest (66.2%) in patients ≥75 years. Conclusions Our results highlight the unmet medical need to increase access to genomic testing to afford treatment options, particularly to older AML patients in the real‐world setting, in this new era of targeted therapies.

OBJECTIVE:To explore to what extent intrauterine device (IUD) expulsion is associated with demographic and clinical risk factors.METHODS: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.RESULTS: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.CONCLUSION: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.FUNDING SOURCE:Bayer AG.CLINICAL TRIAL REGISTRATION:EU PAS register, EUPAS33461.

BACKGROUND: Intrauterine devices are effective instruments for contraception, and 1 levonorgestrel-releasing device is also indicated for the treatment of heavy menstrual bleeding (menorrhagia). OBJECTIVE: To compare the incidence of intrauterine device expulsion and uterine perforation in women with and without a diagnosis of menorrhagia within the first 12 months before device insertion STUDY DESIGN: This was a retrospective cohort study conducted in 3 integrated healthcare systems (Kaiser Permanente Northern California, Southern California, and Washington) and a healthcare information exchange (Regenstrief Institute) in the United States using electronic health records. Nonpostpartum women aged <= 50 years with intrauterine device (eg, levonorgestrel or copper) insertions from 2001 to 2018 and without a delivery in the previous 12 months were studied in this analysis. Recent menorrhagia diagnosis (ie, recorded <= 12 months before insertion) was ascertained from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes. The study outcomes, viz, device expulsion and device-related uterine perforation (complete or partial), were ascertained from electronic medical records and validated in the data sources. The cumulative incidence and crude incidence rates with 95% confidence intervals were estimated. Cox proportional hazards models estimated the crude and adjusted hazard ratios using propensity score overlap weighting (13-16 variables) and 95% confidence intervals. RESULTS: Among 228,834 nonpostpartum women, the mean age was 33.1 years, 44.4% of them were White, and 31,600 (13.8%) had a recent menorrhagia diagnosis. Most women had a levonorgestrel-releasing device (96.4% of those with and 78.2% of those without a menorrhagia diagnosis). Women with a menorrhagia diagnosis were likely to be older, obese, and have dysmenorrhea or fibroids. Women with a menorrhagia diagnosis had a higher intrauterine deviceeexpulsion rate (40.01 vs 10.92 per 1000 personyears) than those without, especially evident in the first few months after insertion. Women with a menorrhagia diagnosis had a higher cumulative incidence (95% confidence interval) of expulsion (7.00% [6.70-7.32] at 1 year and 12.03% [11.52-12.55] at 5 years) vs those without (1.77% [1.70-1.84] at 1 year and 3.69% [3.56-3.83] at 5 years). The risk of expulsion was increased for women with a menorrhagia diagnosis vs for those without (adjusted hazard ratio, 2.84 [95% confidence interval, 2.66-3.03]). The perforation rate was low overall (<1/1000 person-years) but higher in women with a diagnosis of menorrhagia vs in those without (0.98 vs 0.63 per 1000 person-years). The cumulative incidence (95% confidence interval) of uterine perforation was slightly higher for women with a menorrhagia diagnosis (0.09% [0.06-0.14] at 1 year and 0.39% [0.29-0.53] at 5 years) than those without it (0.07% [0.06-0.08] at 1 year and 0.28% [0.24-0.33] at 5 years). The risk of perforation was slightly increased in women with a menorrhagia diagnosis vs in those without (adjusted hazard ratio, 1.53; 95% confidence interval, 1.10-2.13). CONCLUSION: The risk of expulsion is significantly higher in women with a recent diagnosis of menorrhagia. Patient education and counseling regarding the potential expulsion risk is recommended at insertion. The absolute risk of perforation for women with a recent diagnosis of menorrhagia is very low. The increased expulsion and perforation rates observed are likely because of causal factors of menorrhagia.

IMPORTANCE 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. OBJECTIVE To evaluate the association of postpartum timing of IUD insertion and breastfeeding status with incidence and risk of IUD expulsion. DESIGN, SETTING, AND PARTICIPANTS The Association of Perforation and Expulsion of Intrauterine Devices (APEX-IUD) cohort study includedwomen 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. EXPOSURES 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. MAIN OUTCOMES AND MEASURES Incidence rates and adjusted hazard ratios (aHRs) were estimated using propensity scores to adjust for confounding. RESULTS 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 fewerweeks; 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). CONCLUSIONS AND RELEVANCE 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.

Introduction: Studies have found that AML pts treated at high pt volume, academic or NCI-designated cancer centers have improved outcomes compared to pts treated at smaller community hospitals. But little is known about the treatment patterns and outcomes as related to a combined academic and community based health system. Therefore, in a real-world cohort that included both academic and community hospitals that collaborate with one another, we evaluated pt characteristics, frequency of genomic testing, frequency of chemotherapy treatment (Tx) or any targeted therapy as a function of age, and outcomes in ND AML pts.

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/m(2), 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.