Advanced Image-Guided Percutaneous Technique Versus Advanced Laparoscopic Surgical Technique for Peritoneal Dialysis Catheter Placement.

Rationale & Objective: Timely placement of a functional peritoneal dialysis (PD) catheter is crucial to long-term PD success. Advanced image-guided percutaneous and advanced laparoscopic techniques both represent best practice catheter placement options. Advanced image-guided percutaneous is a minimally invasive procedure that does not require general anesthesia. Study Design: Retrospective cohort study comparing time from referral to procedure, complication rate, and 1-year catheter survival between placement techniques. Setting & Participants: Patients who had advanced laparoscopic or advanced image-guided percutaneous PD catheter placement from January 1, 2011 to December 31, 2013 in an integrated Northern California health care delivery system. Exposure: PD catheter placement using advanced laparoscopic or advanced image-guided percutaneous techniques. Outcomes: One-year PD catheter survival; major, minor, and infectious complications; time from referral to PD catheter placement; and procedure time. Analytical Approach: Wilcoxon rank sum tests to compare referral and procedure times; χ2/Fisher exact tests to compare complications; and modified least-squares regression to compare adjusted 1-year catheter survival between PD placement techniques. Results: We identified 191 and 238 PD catheters placed through advanced image-guided percutaneous and advanced laparoscopic techniques, respectively. Adjusted 1-year PD catheter survival was 80% (95% CI, 74%-87%) using advanced image-guided percutaneous technique vs 91% (87%-96%) using advanced laparoscopic technique (P = 0.01). Major complications were <1% in both groups. Minor and infectious complications were 45.6% and 38.7% in advanced image-guided percutaneous and advanced laparoscopic techniques, respectively (P = 0.01). Median days from referral to procedure were 12 and 33 for patients undergoing advanced image-guided percutaneous and advanced laparoscopic techniques, respectively (P < 0.001). Median procedure time was 30 and 44.5 minutes for patients undergoing advanced image-guided percutaneous and advanced laparoscopic techniques, respectively (P < 0.001). Limitations: Retrospective study with practice preference influenced by timing, local expertise, and resources. Conclusions: Both advanced image-guided percutaneous and advanced laparoscopic techniques reported rare major complications and demonstrated excellent (advanced laparoscopic) and acceptable (advanced image-guided percutaneous) 1-year PD catheter survival. For patients referred for PD catheter placement at centers where advanced laparoscopic resources or expertise remain limited, the advanced image-guided percutaneous technique can provide a complementary and timely option to support the utilization of PD. Plain-Language Summary: Peritoneal dialysis is a preferred dialysis modality for many patients. However, the lack of available skilled surgeons can limit the placement of the peritoneal dialysis catheter in a timely manner. In the past decade, interventional radiology has developed expertise in placing peritoneal dialysis catheters. Using data from an integrated health care system, we compared the outcome of peritoneal dialysis catheters placed using laparoscopic surgery and interventional radiology techniques. Our results showed excellent 1-year patency of peritoneal dialysis catheters placed using laparoscopic surgery, whereas interventional radiology placement of catheters had lower but acceptable 1-year patency survival, based on best practice guideline criteria. Hence, interventional radiology placement of peritoneal dialysis catheters may be a viable alternative when laparoscopic surgery is not available or feasible.

Risks of Uterine Perforation and Expulsion Associated With Intrauterine Devices.

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. CLINICAL TRIAL REGISTRATION: EU PAS register, EUPAS33461.

Demographic, Reproductive, and Medical Risk Factors for Intrauterine Device Expulsion.

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.

Disparities in the Incidence of Ectopic Pregnancy in a Large Health Care System in California, 2010-2019.

IntroductionEctopic pregnancy leads to reproductive health morbidity, including greater risk of another ectopic pregnancy, infertility, and, in rare cases, mortality. Information on trends in the incidence of ectopic pregnancy in the last decade is limited. MethodsA population-based cross-sectional study of women aged 15-44 years enrolled at Kaiser Permanente Northern and Southern California 2010-2019 was conducted. Electronic health records were used to identify ectopic pregnancies. The crude ectopic pregnancy incidence per 1000 pregnancies (live births, induced abortions, and ectopic pregnancies) and 95% confidence interval (CI) was estimated per study year, overall, and stratified by age group. The age-adjusted incidence and 95% CI was estimated per study year, overall, and stratified by race/ethnicity. Temporal trend was assessed using Poisson regression. ResultsThere were 15,537 ectopic pregnancies among 979,027 pregnancies. The overall age-adjusted ectopic pregnancy incidence was 15.8 per 1000 pregnancies, 95% CI: 15.6, 16.1. The annual incidence increased from 15.2, 95% CI: 14.4, 16.1, in 2010 to 16.4, 95% CI: 15.6, 17.2, in 2019 (p < 0.001). The overall incidence was highest among women aged 40-44 years (24.2, 95% CI: 22.7, 25.6) and non-Hispanic Black women (21.9, 95% CI: 21.0, 22.8); compared to 30-34-year-old (16.2, 95% CI: 15.7, 16.6) and non-Hispanic White (14.6, 95% CI: 14.1, 15.0) women, respectively. DiscussionThe increase in ectopic pregnancy incidence during the studied period was largely driven by increasing incidence in younger women. However, disparities in the incidence by age and race/ethnicity persisted. ConclusionEctopic pregnancy remains a significant source of reproductive health morbidity, especially for older ( >40 years) and non-Hispanic Black women.

Intrauterine device-related uterine perforation incidence and risk (APEX-IUD): a large multisite cohort study.

BACKGROUND: 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. METHODS: 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). FINDINGS: 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). INTERPRETATION: 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. FUNDING: Bayer AG.

Association between intrauterine device type and risk of perforation and device expulsion: results from the Association of Perforation and Expulsion of Intrauterine Device study.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Association between menorrhagia and risk of intrauterine device-related uterine perforation and device expulsion: results from the Association of Uterine Perforation and Expulsion of Intrauterine Device study.

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 device-expulsion rate (40.01 vs 10.92 per 1000 person-years) 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.

Association of the Timing of Postpartum Intrauterine Device Insertion and Breastfeeding With Risks of Intrauterine Device Expulsion.

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 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. 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 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). 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.

Ectopic pregnancy prevention: Further evidence of benefits of prescription contraceptives.

OBJECTIVE: To estimate the incidence of ectopic pregnancy (EP) associated with prescription contraceptive use. STUDY DESIGN: We performed a retrospective cohort study of women aged 15 to 44 years at Kaiser Permanente Northern and Southern California during 2010 to 2019. We identified EPs and prescription contraceptive use from diagnosis, procedural, and medication codes, and natural language processing of clinical notes from electronic health records. Contraceptive use categories included combined hormonal contraceptives, intrauterine devices, depot-medroxyprogesterone acetate (DMPA), progestin-only pills (POPs), implants, no method after recent discontinuation of a prescription contraceptive in the last 12 months, and no method after discontinuation of a prescription contraceptive more than 12 months ago or no use of prescription contraceptives during the study period. Contraceptive use was updated as women started, stopped, or changed methods. An EP was attributed to a contraceptive method if it occurred 14 days after starting and up to 42 days after stopping a method. Age-adjusted EP incidence and 95% confidence intervals (CI) were estimated per 10,000 woman-years overall and by contraceptive category. RESULTS: There were 11,436 EPs among 3,204,118 women with 11,909,842 woman-years of follow-up for an overall EP incidence of 9.5 per 10,000 woman-years (95%CI 9.3-9.6). The majority of EPs (9662; 84.5%) occurred during no prescription contraceptive use. EP incidence was lowest during DMPA (1.8 per 10,000 woman-years [95%CI 1.2-2.5]) or implant (2.0 per 10,000 woman-years [95%CI 1.2-3.3]) use, and higher during POP use at 15.2 (95%CI 12.2-19.6); however, incidence was highest after recent discontinuation of a prescription contraceptive (20.6 per 10,000 woman-years [95%CI 19.7-21.4]). CONCLUSIONS: EP incidence is lower with prescription contraceptive use than with nonuse. IMPLICATIONS: All prescription contraceptives, including POPs are protective of EP.

Prevalence of depression and anxiety disorders following mild traumatic brain injury.

BACKGROUND: Previous studies have identified an association between traumatic brain injuries and the development of psychiatric disorders in general. However, these studies were subject to limitations that demonstrate the need for a study of a large, clearly defined mild traumatic brain injury (mTBI) population within an integrated healthcare system. OBJECTIVE: To determine the prevalence and relative risk of postinjury affective disorders over 4 years following mTBI. DESIGN: Cohort study of mTBI cases and matched controls, over a 4-year period. SETTING: An integrated healthcare delivery system in California. PATIENTS: A total of 9428 adult health plan members diagnosed with mTBI from 2000-2007 and enrolled in the year before injury, during which no TBI was ascertained. Control participants included 18,856 individuals selected based on the following criteria: Two unexposed health plan members per each mTBI-exposed patient were randomly selected and individually matched for age, gender, race/ethnicity, and medical comorbidities. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A diagnosis of affective disorder (depressive, anxiety, and adjustment disorders) in the 4 years after mTBI or the reference date, determined according to the International Classification of Diseases, Ninth Revision, Clinical Modification as well as the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. RESULTS: Affective disorders were most prominent during the first 12 months with 23% following mTBI and 14% in the control group. Four-year aggregate adjusted odds ratios for having an affective disorder following mTBI were 1.2 (95% CI: 1.1, 1.2; p < .001) and 1.5 (95% CI: 1.5, 1.6; p < .001) for patients with and without prior affective disorders, respectively. CONCLUSION: mTBI was associated with a significantly increased risk of having subsequent affective disorders. Screening for and addressing affective disorders at earlier stages following the injury is an important step to avoid persisting conditions that may pose a barrier to full recovery.

Association of Pregnancy Intentions With Substance Use During Early Pregnancy.

OBJECTIVES: The goal of this study was to evaluate the association between pregnancy intentions and substance use in early pregnancy among pregnant women receiving prenatal care in a large, integrated healthcare system. METHODS: The sample comprised 29,787 Kaiser Permanente Northern California pregnant women (12.1% aged <25, 36.4% non-Hispanic White) screened for prenatal substance use in 2018 via a self-reported questionnaire and urine toxicology test given as part of standard prenatal care (at ∼8 weeks gestation). Multivariable logistic regression models tested for associations of pregnancy intentions with prenatal substance use (any use and specific substances) by self-report and/or a positive urine toxicology test. RESULTS: Adjusting for covariates, women with an unintended pregnancy (23.9% of the sample) had higher odds of any prenatal substance use than women with an intended pregnancy (28.8% vs 16.1%; adjusted odds ratio [aOR] = 1.80, 95% confidence interval [CI]:1.67-1.93). Having an unintended pregnancy was also associated with higher odds of using alcohol (14.4% vs 10.4%; aOR = 1.73, 95%CI:1.59-1.89), cannabis (15.6% vs 5.6%; aOR = 1.91, 95%CI:1.73-2.11), nicotine (3.8% vs 1.3%; aOR = 2.33, 95%CI:1.92-2.82), pain medication (2.3% vs 1.2%; aOR = 1.64, 95%CI:1.32-2.03), and stimulants (0.8% vs 0.3%; aOR = 1.85, 95%CI:1.23-2.79) early in pregnancy. DISCUSSION: Having an unintended pregnancy was associated with higher odds of substance use during early pregnancy. Connecting women of reproductive age with health education about pregnancy prevention and recognition of early signs of pregnancy, effective contraception, and early screening and interventions for prenatal substance use may help to reduce prenatal substance use and its associated consequences.

Design of the Association of Uterine Perforation and Expulsion of Intrauterine Device study: a multisite retrospective cohort study.

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.

Identifying Ectopic Pregnancy in a Large Integrated Health Care Delivery System: Algorithm Validation.

BACKGROUND: Surveillance of ectopic pregnancy (EP) using electronic databases is important. To our knowledge, no published study has assessed the validity of EP case ascertainment using electronic health records. OBJECTIVE: We aimed to assess the validity of an enhanced version of a previously validated algorithm, which used a combination of encounters with EP-related diagnostic/procedure codes and methotrexate injections. METHODS: Medical records of 500 women aged 15-44 years with membership at Kaiser Permanente Southern and Northern California between 2009 and 2018 and a potential EP were randomly selected for chart review, and true cases were identified. The enhanced algorithm included diagnostic/procedure codes from the International Classification of Diseases, Tenth Revision, used telephone appointment visits, and excluded cases with only abdominal EP diagnosis codes. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall performance (Youden index and F-score) of the algorithm were evaluated and compared to the validated algorithm. RESULTS: There were 334 true positive and 166 true negative EP cases with available records. True positive and true negative EP cases did not differ significantly according to maternal age, race/ethnicity, and smoking status. EP cases with only one encounter and non-tubal EPs were more likely to be misclassified. The sensitivity, specificity, PPV, and NPV of the enhanced algorithm for EP were 97.6%, 84.9%, 92.9%, and 94.6%, respectively. The Youden index and F-score were 82.5% and 95.2%, respectively. The sensitivity and NPV were lower for the previously published algorithm at 94.3% and 88.1%, respectively. The sensitivity of surgical procedure codes from electronic chart abstraction to correctly identify surgical management was 91.9%. The overall accuracy, defined as the percentage of EP cases with correct management (surgical, medical, and unclassified) identified by electronic chart abstraction, was 92.3%. CONCLUSIONS: The performance of the enhanced algorithm for EP case ascertainment in integrated health care databases is adequate to allow for use in future epidemiological studies. Use of this algorithm will likely result in better capture of true EP cases than the previously validated algorithm.

Development of a longitudinal two-biomarker algorithm for early detection of ovarian cancer in women with BRCA mutations.

OBJECTIVE: To develop a longitudinal algorithm combining two biomarkers, CA125 and HE4, for early detection of ovarian cancer in women with BRCA mutations. METHODS: Women with BRCA mutations and intact ovaries were invited to participate in a novel ovarian cancer early detection prospective study. The Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4 was performed every four months; abnormal risks triggered a subsequent ultrasound. The study first used a risk algorithm for only CA125, a second algorithm was developed for HE4 and finally a risk algorithm combining the two biomarkers was implemented. The ROCA strategy was compared to Standard of Care (SOC) surveillance strategy. RESULTS: A total of 149 women enrolled in the ROCA arm while 43 women enrolled in the SOC arm. Abnormal scores were found in 24% of ROCA CA125 tests, 16% if ROCA CA125 or the novel ROCA HE4 were used independently and reduced to 8% using the new two-marker ROCA, significantly lower than the 15% of abnormal tests seen in the SOC arm (p = 0.042). The average false positive rate among women without ovarian cancer for two-marker ROCA for referral to ultrasound was 6.6% (specificity 93.4%), and for the two-marker ROCA plus ultrasound for referral to surgical consultation was 1.7% (specificity 98.3%). CONCLUSION: A newly developed two-marker ROCA administered every 4 months had lower call-back rates than SOC surveillance. Having established high specificity, the two-marker ROCA score deserves further evaluation for sensitivity in a larger trial.

Trends and correlates of self-reported alcohol and nicotine use among women before and during pregnancy, 2009-2017.

OBJECTIVE: To examine trends and correlates of frequency of self-reported alcohol and nicotine use among pregnant women. METHODS: Cross-sectional study of 363,240 pregnancies from 2009 to 2017 screened for self-reported substance use at their first prenatal visit in Kaiser Permanente Northern California. Poisson regression with a log link function was used to estimate the annual prevalences of self-reported daily, weekly, and ≤ monthly alcohol and nicotine use, adjusting for socio-demographics. Generalized estimating equation models were used to estimate the adjusted odds ratios (aOR) of any self-reported prenatal alcohol or nicotine use among those who self-reported use in the year prior to pregnancy, by frequency of pre-pregnancy substance use and socio-demographics. RESULTS: The sample was 64 % non-White [mean (SD) age = 30.1 (5.6)]. From 2009-2017, alcohol use before pregnancy increased from 63.4%-65.9% (trend p-value = .008), and prenatal alcohol use decreased from 11.6%-8.8% (trend p-value<.0001). Nicotine use before pregnancy decreased from 12.7 % to 7.7 % (trend p-value<.0001), and prenatal use decreased from 4.3 % to 2.0 % (trend p-value<.0001). Trends by use frequency were similar to overall trends. The odds of continued use of alcohol and nicotine during pregnancy were higher among those who used daily or weekly (versus monthly or less) in the year before pregnancy and varied with socio-demographics. DISCUSSION: Prenatal alcohol and nicotine use decreased from 2009 to 2017. More frequent pre-pregnancy use predicted higher odds of prenatal use. Results suggest that interventions and education about the harms of prenatal substance use for frequent users prior to conception may reduce substance use during pregnancy.

Variation in physician-directed immunohistochemistry screening among women with endometrial cancer.

OBJECTIVE: Immunohistochemistry screening is a reliable method for identifying women with endometrial cancer who are at risk for Lynch syndrome, but clinical workflows used to implement immunohistochemistry screening protocols can vary by institution. The goal of this study was to investigate variation in performance of immunohistochemistry screening when a physician order is required. METHODS: Retrospective study from an integrated healthcare system with a risk-based immunohistochemistry screening policy for Lynch syndrome from January 2015 to December 2016. Immunohistochemistry screening was indicated for all women with endometrial cancer aged <60 years and women with endometrial cancer aged ≥60 years who had a personal/family history suggestive of Lynch syndrome. However, a physician order was needed to have immunohistochemistry screening performed on the tumor specimen as our health system did not have reflex screening in the clinical workflow. Demographics and tumor characteristics were reviewed, and patients were stratified by immunohistochemistry screening status. Multivariable regression was performed to identify factors associated with immunohistochemistry performance and reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: There were 1399 eligible patients in the study. With a required physician order, immunohistochemistry screening rates (20% overall, 34% aged <60 years) were significantly lower than previous reports (36% overall, 90% aged <60 years, p≤0.0001 for both comparisons). Significant factors associated with immunohistochemistry screening performance identified by multivariable analysis included age, race, body mass index, personal/family cancer history, diabetes, endometrioid histology, and tumor grade. Asian women were most likely to have immunohistochemistry screening (OR 1.58, 95% CI 1.07 to 2.34) whereas black women were least likely (OR 0.43, 95% CI 0.22 to 0.91). CONCLUSIONS: Immunohistochemistry screening rates in women with endometrial cancer were lower in our health system compared with prior reports in the literature, and there were variations in screening performance according to patient age, race, and body mass index. Requiring a physician order for immunohistochemistry screening likely creates a barrier in screening uptake, therefore automated immunohistochemistry screening is recommended.

Comparison of two Lynch screening strategies in endometrial cancer in a California health system.

OBJECTIVE: Compare detection of Lynch syndrome in endometrial cancer between regions of a health care system with different screening strategies. METHODS: A retrospective study of endometrial cancer (EC) cases from 2 regions of an integrated health care system (Kaiser Permanente Northern (KPNC) and Southern (KPSC) California). Within KPNC, immunohistochemistry tumor screening (IHC) was physician ordered and risk-based; within KPSC, IHC was universal and automated. Clinical risk factors associated with abnormal IHC and Lynch Syndrome (LS) were identified. RESULTS: During the study, there were 2045 endometrial cancers: 1399 in the physician-order group and 646 in the universal testing group. In the physician-order group: among women < age 60, 34% underwent IHC; 9.6% were abnormal, and 3% were possible LS after methylation testing; among women ≥60, 11% underwent IHC, 3% were abnormal and <1% were possible LS. In the universal group, 87% of women age <60 had IHC, 19.4% were abnormal, and 6% were possible LS; Among women age ≥60, 82% underwent IHC, 26% were abnormal, and 2% were possible LS. There were no differences in LS cases between the physician-order group and the universal group in either age strata (<60: 3% vs. 3.6%, p=0.62; ≥60: <1% vs. 1%, p=0.63) Factors associated with LS were younger age (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.04-0.29) and lower body mass index (BMI), (OR 0.38 95% CI 0.18-0.80). CONCLUSIONS: Universal IHC screening did not result in increased LS detection in EC.

Feasibility, patient compliance and acceptability of ovarian cancer surveillance using two serum biomarkers and Risk of Ovarian Cancer Algorithm compared to standard ultrasound and CA 125 among women with BRCA mutations.

OBJECTIVE: We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months. METHODS: Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale. RESULTS: There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034). CONCLUSIONS: This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer.

Correlates of Pregnant Women's Participation in a Substance Use Assessment and Counseling Intervention Integrated into Prenatal Care.

INTRODUCTION: Screening and referral for substance use are essential components of prenatal care. However, little is known about barriers to participation in substance use interventions that are integrated within prenatal care. METHODS: Our study examines demographic and clinical correlates of participation in an initial assessment and counseling intervention integrated into prenatal care in a large healthcare system. The sample comprised Kaiser Permanente Northern California pregnant women with a live birth in 2014 or 2015 who screened positive for prenatal substance use via a self-reported questionnaire and/or urine toxicology test given as part of standard prenatal care (at ~ 8 weeks gestation). RESULTS: Of the 11,843 women who screened positive for prenatal substance use (median age = 30 years; 42% white; 38% screened positive for alcohol only, 20% for cannabis only, 5% nicotine only, 17% other drugs only, and 19% ≥ 2 substance categories), 9836 (83%) completed the initial substance use assessment and counseling intervention. Results from multivariable logistic regression analyses indicated that younger age, lower income, single marital status, and a positive urine toxicology test predicted higher odds of participation, while other/unknown race/ethnicity, greater parity, receiving the screening later in pregnancy, and screening positive for alcohol only or other drugs only predicted lower odds of participation (all Ps < .05). DISCUSSION: Findings suggest that integrated substance use interventions can successfully reach vulnerable populations of pregnant women (e.g., younger, lower income, racial/ethnic minorities). Future research should address whether differences in participation are due to patient (e.g., type of substance used, perceived stigma) or provider factors (e.g., working harder to engage traditionally underserved patients).

Validity of Self-reported Cannabis Use Among Pregnant Females in Northern California.

BACKGROUND: Most clinical and epidemiologic estimates of prenatal cannabis use are based on self-report, and the validity of self-reported cannabis use has not been examined in a large, representative population of pregnant women. We determined the validity of self-reported prenatal cannabis use and predictors of nondisclosure using data from Kaiser Permanente Northern California's (KPNC) healthcare system with universal prenatal cannabis screening during prenatal care. METHODS: Validation study using data from 281,025 pregnancies in KPNC among females aged ≥11 years who completed a self-administered questionnaire on prenatal cannabis use and a cannabis urine toxicology test from 2009 to 2017. We calculated sensitivity, specificity, positive predictive value, and negative predictive value of self-reported prenatal cannabis use using urine toxicology testing as the criterion standard, and sensitivity of urine toxicology testing using self-reported use as the criterion standard. We compared sociodemographics of those who disclosed versus did not disclose prenatal cannabis use. RESULTS: Urine toxicology testing identified more instances of prenatal cannabis use than self-report (4.9% vs 2.5%). Sensitivity of self-reported use was low (33.9%). Sensitivity of the toxicology test was higher (65.8%), with greater detection of self-reported daily (83.9%) and weekly (77.4%) than monthly or less use (54.1%). Older women, those of Hispanic race/ethnicity, and those with lower median neighborhood incomes were most likely to be misclassified as not using cannabis by self-reported screening. CONCLUSIONS: Given that many women choose not to disclose prenatal cannabis use, clinicians should educate all prenatal patients about the potential risks and advise them to quit cannabis use during pregnancy.