Retrospective study of preterm infants exposed to inhaled nitric oxide in Kaiser Permanente Southern California: morbidity, mortality and follow-up.

OBJECTIVE: Describe characteristics of preterm infants exposed to inhaled nitric oxide (iNO) in Kaiser Permanente Southern California. STUDY DESIGN: Case review of preterm infants <34-weeks exposed to iNO during 2010-2020 including respiratory and echocardiographic status, NICU course, and 12-month follow-up. RESULTS: 270 infants, 2.63% of births<34 weeks, (median, range: 26.1, 225/7-336/7 weeks gestation) were exposed to iNO. Median FiO2 at iNO initiation was 1.0 (IQR 0.94-1.0). Pulmonary hypertension (PH) was not associated with risk-adjusted 2 h oxygenation response or improved survival. Mortality to NICU discharge was 37.4%. Median cost of iNO was $7,695/patient. Discharged survivors experienced frequent rehospitalization (34.9%), use of supplemental oxygen, sildenafil, diuretics, bronchodilators, and steroids. Four infants had persistent PH. Five infants died after NICU discharge. CONCLUSIONS: Preterm infants receiving iNO have high mortality and 1st year morbidity. As currently used, iNO may be an indicator of respiratory disease severity rather than mediator of improved outcomes.

Coding of Childhood Psychiatric and Neurodevelopmental Disorders in Electronic Health Records of a Large Integrated Health Care System: Validation Study.

Background: Mental, emotional, and behavioral disorders are chronic pediatric conditions, and their prevalence has been on the rise over recent decades. Affected children have long-term health sequelae and a decline in health-related quality of life. Due to the lack of a validated database for pharmacoepidemiological research on selected mental, emotional, and behavioral disorders, there is uncertainty in their reported prevalence in the literature. objectives: We aimed to evaluate the accuracy of coding related to pediatric mental, emotional, and behavioral disorders in a large integrated health care system's electronic health records (EHRs) and compare the coding quality before and after the implementation of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) coding as well as before and after the COVID-19 pandemic. Methods: Medical records of 1200 member children aged 2-17 years with at least 1 clinical visit before the COVID-19 pandemic (January 1, 2012, to December 31, 2014, the ICD-9-CM coding period; and January 1, 2017, to December 31, 2019, the ICD-10-CM coding period) and after the COVID-19 pandemic (January 1, 2021, to December 31, 2022) were selected with stratified random sampling from EHRs for chart review. Two trained research associates reviewed the EHRs for all potential cases of autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), major depression disorder (MDD), anxiety disorder (AD), and disruptive behavior disorders (DBD) in children during the study period. Children were considered cases only if there was a mention of any one of the conditions (yes for diagnosis) in the electronic chart during the corresponding time period. The validity of diagnosis codes was evaluated by directly comparing them with the gold standard of chart abstraction using sensitivity, specificity, positive predictive value, negative predictive value, the summary statistics of the F-score, and Youden J statistic. κ statistic for interrater reliability among the 2 abstractors was calculated. Results: The overall agreement between the identification of mental, behavioral, and emotional conditions using diagnosis codes compared to medical record abstraction was strong and similar across the ICD-9-CM and ICD-10-CM coding periods as well as during the prepandemic and pandemic time periods. The performance of AD coding, while strong, was relatively lower compared to the other conditions. The weighted sensitivity, specificity, positive predictive value, and negative predictive value for each of the 5 conditions were as follows: 100%, 100%, 99.2%, and 100%, respectively, for ASD; 100%, 99.9%, 99.2%, and 100%, respectively, for ADHD; 100%, 100%, 100%, and 100%, respectively for DBD; 87.7%, 100%, 100%, and 99.2%, respectively, for AD; and 100%, 100%, 99.2%, and 100%, respectively, for MDD. The F-score and Youden J statistic ranged between 87.7% and 100%. The overall agreement between abstractors was almost perfect (κ=95%). Conclusions: Diagnostic codes are quite reliable for identifying selected childhood mental, behavioral, and emotional conditions. The findings remained similar during the pandemic and after the implementation of the ICD-10-CM coding in the EHR system.

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.

The Shieh Score as a Risk Assessment Instrument for Reducing Hospital-Acquired Pressure Injuries: A Prospective Cohort Study.

PURPOSE: The purpose of this study was to evaluate the Shieh Score's effectiveness in decreasing the rate of hospital-acquired pressure injuries when combined with an early warning notification system and standard order set of preventative measures. DESIGN: This was a prospective cohort study. SUBJECTS AND SETTING: This target population was nonpregnant, adult, hospitalized patients on inpatient and observation status at a tertiary hospital (Kaiser Permanente, Baldwin Park, California) during the 2020 year of the COVID-19 pandemic. METHODS: A new, risk assessment instrument, the Shieh Score, was developed in 2019 to predict hospitalized patients at high risk for pressure injuries. Data collection occurred between January 21, 2020, and December 31, 2020. When a hospital patient met the high-risk criteria for the Shieh Score, a provider-ordered pink-colored sheet of paper titled "Skin at Risk" was hung at the head of the bed and a standard order set of pressure injury preventative measures was implemented by nursing staff. RESULTS: Implementation of the program (Shieh Score, early warning system, and standard order set for preventive interventions) resulted in a 38% reduction in the annual hospital-acquired pressure injury rate from a mean incidence rate of 1.03 to 0.64 hospital-acquired pressure injuries per 1000 patient-days measured for the year 2020. CONCLUSION: The Shieh Score is a pressure injury risk assessment instrument, which effectively identifies patients at high risk for hospital-acquired pressure injuries and decreases the hospital-acquired pressure injury rate when combined with an early warning notification system and standard order set.

Association of Labor Epidural Analgesia, Oxytocin Exposure, and Risk of Autism Spectrum Disorders in Children.

Importance: Maternal labor epidural analgesia (LEA) and oxytocin use for labor and delivery have been reported to be associated with child autism spectrum disorders (ASD). However, it remains unclear whether these 2 common medications used during labor and delivery have synergistic associations with ASD risk in children. Objective: To assess the independent associations of LEA and oxytocin during labor and delivery with ASD, as well as outcome modification associated with the concurrent use of both interventions. Design, Setting, and Participants: Data for this cohort study included 205 994 singleton births with vaginal deliveries in a single integrated health care system in Southern California from calendar years 2008 to 2017. Children were followed up to December 31, 2021. Data on use of LEA and oxytocin, covariates, and ASD outcome in children were obtained from electronic medical records. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) adjusting for covariates. Exposures: Labor epidural analgesia and/or oxytocin use during labor and delivery. Main Outcomes and Measures: A child's clinical diagnosis of ASD during follow-up and at age of diagnosis. Results: Among the cohort, 153 880 children (74.7%) were exposed to maternal LEA and 117 808 children (57.2%) were exposed to oxytocin during labor and delivery. The population of children was approximately half boys and half girls. The median (IQR) age of the mothers was 30.8 (26.8-34.5) years for those not exposed to LEA, 30.0 (25.9-33.8) years for those exposed to LEA, 30.4 (26.5-34.1) years for those unexposed to oxytocin, and 30.0 (25.9-33.9) years for those exposed to oxytocin during labor and delivery. A total of 5146 children (2.5%) had ASD diagnosed during follow-up. Oxytocin exposure was higher among LEA-exposed (67.7%) than -unexposed (26.1%) children. The ASD risk associated with LEA was independent of oxytocin exposure (HR, 1.28; 95% CI, 1.18-1.38); however, the ASD risk associated with oxytocin was not significant after adjusting for LEA exposure (HR, 1.05; 95% CI, 0.99-1.12). A significant interaction of LEA and oxytocin on child ASD risk was found (P = .02 for interaction). Compared with no exposure, HRs were 1.20 (95% CI, 1.09-1.32) for LEA alone, 1.30 (95% CI, 1.20-1.42) for both LEA and oxytocin, and 0.90 (95% CI, 0.78-1.04) for oxytocin alone. Conclusions and Relevance: The findings of this cohort study suggest an association between maternal LEA and ASD risk in children, and the risk appeared to be further increased if oxytocin was also administered. Oxytocin exposure without LEA exposure was not associated with ASD risk in children. These findings must be interpreted with caution. Further studies are needed to replicate or refute the study results and examine biological plausibility.

Evidence-Based Antibiotic Prophylaxis in Clean Hand Surgeries: An Educational Intervention to Decrease Use.

PURPOSE: Evidence for the use of prophylactic antibiotics in clean hand surgery is limited, yet surgeons continue to administer antibiotics to prevent postoperative infections. We sought to assess the effect of a program directed at reducing the use of antibiotic prophylaxis in carpal tunnel release surgery and elicit reasons for continued use. METHODS: A surgeon leader implemented a program between September 1, 2018 and September 30, 2019 to reduce antibiotic prophylaxis in clean hand surgeries in a hospital system of 10 medical centers. It consisted of (1) an evidence-based educational session for all participating orthopedic and hand surgeons during which the elimination of the use of antibiotics in clean hand surgeries was requested and (2) a year-long, monthly antibiotic use audit and feedback cycle using carpal tunnel release (CTR) as a proxy for clean hand surgery. The rate of antibiotic use in the year of the intervention was compared to the rate prior to the intervention. Multivariable regression was used to determine patient-related risk factors for receiving antibiotics. Participating surgeons completed a survey to elucidate factors that contributed to continued use. RESULTS: Antibiotic prophylaxis decreased from 1223/2379 (51%) in 2017-2018 to 531/2550 (21%) in 2018-2019. During the last month of evaluation, the rate decreased to 28/208 (14%). Logistic regression revealed a higher rate of antibiotic use during the period after the intervention among patients who had diabetes mellitus or who were operated upon by an older surgeon. The follow-up surgeon survey revealed a strong positive correlation between surgeon willingness to administer antibiotics and patient hemoglobin A1c and body mass index. CONCLUSIONS: The rate of antibiotic use in carpal tunnel release decreased from 51% the year prior to 14% the final month of implementing a surgeon-led program to reduce antibiotic prophylaxis. Multiple barriers to the implementation of evidence-based practice were identified. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Cost-effectiveness of a 3-year tele-messaging intervention for positive airway pressure use.

OBJECTIVES: To evaluate the cost-effectiveness of a 3-year tele-messaging intervention for positive airway pressure (PAP) use in obstructive sleep apnea (OSA). STUDY DESIGN: A post hoc cost-effectiveness analysis (from US payers' perspective) of data from a 3-month tele-OSA trial, augmented with 33 months of epidemiologic follow-up. METHODS: Cost-effectiveness was compared among 3 groups of participants with an apnea-hypopnea index of at least 15 events/hour: (1) no messaging (n = 172), (2) messaging for 3 months (n = 124), and (3) messaging for 3 years (n = 46). We report the incremental cost (2020 US$) per incremental hour of PAP use and the fraction probability of acceptability based on a willingness-to-pay threshold of $1825 per year ($5/day). RESULTS: The use of 3 years of messaging had similar mean annual costs ($5825) compared with no messaging ($5889; P = .89) but lower mean cost compared with 3 months of messaging ($7376; P = .02). Those who received messaging for 3 years had the highest mean PAP use (4.11 hours/night), followed by no messaging (3.03 hours/night) and 3 months of messaging (2.84 hours/night) (all P < .05). The incremental cost-effectiveness ratios indicated that 3 years of messaging showed lower costs and greater hours of PAP use compared with both no messaging and 3 months of messaging. Based on a willingness-to-pay threshold of $1825, there is a greater than 97.5% chance (ie, 95% confidence) that 3 years of messaging is acceptable compared with the other 2 interventions. CONCLUSIONS: Long-term tele-messaging is highly likely to be cost-effective compared with both no and short-term messaging, with an acceptable willingness-to-pay threshold. Future long-term cost-effectiveness studies in a randomized controlled trial setting are warranted.

Association Between Positive Airway Pressure Adherence and Health Care Costs Among Individuals With OSA.

BACKGROUND: The impact of positive airway pressure (PAP) therapy for OSA on health care costs is uncertain. RESEARCH QUESTION: Are 3-year health care costs associated with PAP adherence in participants from the Tele-OSA clinical trial? STUDY DESIGN AND METHODS: Participants with OSA and prescribed PAP in the Tele-OSA study were stratified into three PAP adherence groups based on usage patterns over 3 years: (1) high (consistently ≥ 4 h/night), (2) moderate (2-3.9 h/night or inconsistently ≥ 4 h/night), and (3) low (< 2 h/night). Using data from 3 months of the Tele-OSA trial and 33 months of posttrial follow up, average health care costs (2020 US dollars) in 6-month intervals were derived from electronic health records and analyzed using multivariable generalized linear models. RESULTS: Of 543 participants, 25% were categorized as having high adherence, 22% were categorized as having moderate adherence, and 52% were categorized as having low adherence to PAP therapy. Average PAP use mean ± SD was 6.5 ± 1.0 h, 3.7 ± 1.2 h, and 0.5 ± 0.5 h for the high, moderate, and low adherence groups, respectively. The high adherence group had the lowest average covariate-adjusted 6-month health care costs ± SE ($3,207 ± $251) compared with the moderate ($3,638 ± $363) and low ($4,040 ± $304) adherence groups. Significant cost differences were observed between the high and low adherence groups ($832; 95% CI, $127 to $1,538); differences between moderate and low adherence were nonsignificant ($401; 95% CI, -$441 to $1,243). INTERPRETATION: In participants with OSA, better PAP adherence was associated with significantly lower health care costs over 3 years. Findings support the importance of strategies to enhance long-term PAP adherence.

Clinical Outcomes of Telehealth in Patients With Coronary Artery Disease and Heart Failure During the COVID-19 Pandemic.

The COVID-19 pandemic necessitated a rapid adoption of telehealth (TH); however, its safety in subspecialty clinical practice remains uncertain. To assess the clinical outcomes associated with TH use in patients with coronary artery disease and/or heart failure during the initial phase of the COVID-19 pandemic, eligible adult patients who saw cardiologists from March 1, 2020, to August 31, 2020 (TH period) were identified. Patients were divided into two 3-month subcohorts (TH1, TH2) and compared with corresponding 2019 prepandemic subcohorts. The primary outcome was cardiovascular (CV) events within 3 months after index visits. Secondary analysis was CV events in patients aged ≥75 years within 3-month follow-up associated with TH use. Multivariable logistic regression was used to evaluate the association between TH use and CV outcomes. The study cohort included 6,485 TH and 7,557 prepandemic patients. The mean age was 70 years, with 40% of patients aged ≥75 years and 35% women. TH visits accounted for 0% of visits during the prepandemic period, compared with 68% during the TH period. Telephone visits comprised ≥92% of all TH encounters. Compared with the prepandemic period, patients seen during the TH period had fewer overall CV events (adjusted odds ratio 0.78, 95% confidence interval 0.67 to 0.90). Patients aged ≥75 years had similar findings (adjusted odds ratio 0.70, 95% confidence interval 0.55 to 0.89). Additional analysis of CV outcome events within 6 months after index visits showed similar findings. In conclusion, TH largely by way of telephone encounters can be safely incorporated into the ambulatory cardiology practice regardless of age.

Examining recent trends in spontaneous and iatrogenic preterm birth across race and ethnicity in a large managed care population.

BACKGROUND: For the past several decades, epidemiological studies originating from the United States have consistently reported increasing rates of preterm birth (PTB). Despite the implementation of several clinical and public health interventions to reduce PTB rates, it remains the leading cause of infant morbidity and mortality in the United States and around the world. OBJECTIVE: This study aimed to examine recent trends in preterm birth and its clinical subtypes by maternal race and ethnicity among singleton births. STUDY DESIGN: Kaiser Permanente Southern California electronic health records for all singleton births between 2009 and 2020 (n=427,698) were used to examine preterm birth trends and their subtypes (spontaneous and iatrogenic preterm births). Data on preterm labor triage extracted from electronic health records using natural language processing were used to define preterm birth subtypes. Maternal race and ethnicity are categorized as non-Hispanic White, non-Hispanic Black, Hispanic, and non-Hispanic Asian or Pacific Islander. Multiple logistic regression was used to quantify the linear trend for preterm birth and its subtypes. Racial and ethnic trends were further examined by considering statistical interactions and stratifications. RESULTS: From 2009 to 2020, the overall preterm birth rate decreased by 9.12% (from 8.04% to 7.31%; P<.001). The rates decreased by 19.29% among non-Hispanic Whites (from 7.23% to 5.83%; P<.001), 6.15% among Hispanics (from 7.82% to 7.34%; P=.036), and 12.60% among non-Hispanic Asian or Pacific Islanders (from 8.90% to 7.78%; P<.001), whereas a nonsignificantly increased preterm birth rate (8.45%) was observed among non-Hispanic Blacks (from 9.91% to 10.75%; P=.103). Between 2009 and 2020, overall spontaneous preterm birth rates decreased by 28.85% (from 5.75% to 4.09%; P<.001). However, overall iatrogenic preterm birth rates increased by 40.45% (from 2.29% to 3.22%; p<.001). Spontaneous preterm birth rates decreased by 34.73% among non-Hispanic Whites (from 5.44% to 3.55%; P<.001), 19.75% among non-Hispanic Blacks (from 6.82% to 5.47%; P<.001), 22.96% among Hispanics (from 5.55% to 4.28%; P<.001), and 28.19% among non-Hispanic Asian or Pacific Islanders (from 6.50% to 4.67%; P<.001). Iatrogenic preterm birth rates increased by 52.42% among non-Hispanic Whites (from 1.88% to 2.61%; P<.001), 107.89% among non-Hispanic Blacks (from 3.18% to 6.13%; P<.001), 46.88% among Hispanics (from 2.29% to 3.26%; P<.001), and 42.21% among non-Hispanic Asian or Pacific Islanders (from 2.45% to 3.44%; P<.001). CONCLUSION: The overall preterm birth rate decreased over time and was driven by a decrease in the spontaneous preterm birth rate. There is racial and ethnic variability in the rates of spontaneous preterm birth and iatrogenic preterm birth. The observed increase in iatrogenic preterm birth among all racial and ethnic groups, especially non-Hispanic Blacks, is disconcerting and needs further investigation.

Urgent and non-emergent telehealth care for seniors: Findings from a multi-site impact study.

INTRODUCTION: The global pandemic has raised awareness of the need for alternative ways to deliver care, notably telehealth. Prior to this study, research has been mixed on its effectiveness and impact on downstream utilization, especially for seniors. Our multi-institution study of more than 300,000 telehealth visits for seniors evaluates the clinical outcomes and healthcare utilization for urgent and non-emergent symptoms. METHODS: We conducted a retrospective cohort study from November 2015 to March 2019, leveraging different models of telehealth from three health systems, comparing them to in-person visits for urgent and non-emergent needs of seniors based on International Classification of Diseases, 10th edition diagnoses. The study population was adults aged 60 years or older who had access to telehealth and were affiliated with and resided in the geographic region of the healthcare organization providing telehealth. The primary outcomes of interest were visit resolution and episodes of care for those that required follow-up. RESULTS: In total, 313,516 telehealth visits were analysed across three healthcare organizations. Telehealth encounters were successful in resolving urgent and non-emergent needs in 84.0-86.7% of cases. When visits required follow-up, over 95% were resolved in less than three visits for both telehealth and in-person cohorts. DISCUSSION: While in-person visits have traditionally been the gold standard, our results suggest that when deployed within the confines of a patient's existing primary care and health system provider, telehealth can be an effective alternative to in-person care for urgent and non-emergent needs of seniors without increasing downstream utilization.

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.

Association between SARS-CoV-2 Infection and Adverse Perinatal Outcomes in a Large Health Maintenance Organization.

OBJECTIVE: This study aimed to examine whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy is associated with increased odds of perinatal complications and viral transmission to the infant. STUDY DESIGN: A retrospective cohort study of women who delivered at Kaiser Permanente Southern California hospitals (April 6, 2020-February 28, 2021) was performed using data extracted from electronic health records (EHRs). During this time polymerize chain reaction (PCR)-based tests for SARS-CoV-2 was universally offered to all pregnant women at labor and delivery admission, as well as earlier in the pregnancy, if they were displaying symptoms consistent with SARS-CoV-2 infection or a possible exposure to the virus. Adjusted odds ratio (aOR) was used to estimate the strength of associations between positive test results and adverse perinatal outcomes. RESULTS: Of 35,123 women with a singleton pregnancy, 2,203 (6%) tested positive for SARS-CoV-2 infection with 596 (27%) testing positive during the first or second trimester and 1,607 (73%) during the third trimester. Women testing positive were younger than those who tested negative (29.7 [5.4] vs. 31.1 [5.3] years; mean [standard deviation (SD)]; p < .001). The SARS-CoV-2 infection tended to increase the odds of an abnormal fetal heart rate pattern (aOR: 1.10; 95% confidence interval [CI]: 1.00, 1.21; p = 0.058), spontaneous preterm birth (aOR: 1.28; 95% CI: 1.03, 1.58; p = 0.024), congenital anomalies (aOR: 1.69; 95% CI: 1.15, 2.50; p = 0.008), and maternal intensive care unit admission at delivery (aOR: 7.44; 95% CI: 4.06, 13.62; p < 0.001) but not preeclampsia/eclampsia (aOR: 1.14; 95% CI: 0.98, 1.33; p = 0.080). Eighteen (0.8%) neonates of mothers who tested positive also had a positive SARS-CoV-2 test after 24 hours of birth, but all were asymptomatic during the neonatal period. CONCLUSION: These findings suggest that prenatal SARS-CoV-2 infection increases the odds of some adverse perinatal outcomes. The likelihood of vertical transmission from the mother to the fetus was low (0.3%), suggesting that pregnancy complications resulting from SARS-CoV-2 infection pose more risk to the baby than transplacental viral transmission. KEY POINTS: · SARS-CoV-2 infection is associated with increased odds of adverse perinatal outcomes.. · The odds of specific adverse outcomes were greater when a mother was infected earlier in pregnancy.. · The proportion of vertical transmission from mother to fetus was 0.3%.

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.

Population-Based Incidence, Severity, and Risk Factors Associated with Treated Acute-Onset COVID-19 mRNA Vaccination-Associated Hypersensitivity Reactions.

BACKGROUND: COVID-19 mRNA vaccination-associated acute-onset hypersensitivity reactions have caused anxiety and may be contributing to vaccine hesitancy. OBJECTIVE: To determine the incidence, severity, and risk factors for treated acute-onset COVID-19 mRNA vaccination-associated hypersensitivity reactions in a well-characterized population. METHODS: All Kaiser Permanente Southern California (KPSC) members who received COVID-19 mRNA vaccinations between December 15, 2020, and March 11, 2021, at a KPSC facility were identified and characterized, along with all treated acute-onset vaccination-associated hypersensitivity events. RESULTS: We identified 391,123 unique vaccine recipients (59.18% female, age 64.19 ± 17.86 years); 215,156 received 2 doses (53.54% Moderna), 157,615 only a first dose (50.13% Moderna) (1961 [1.46%] >2 weeks late getting a second dose), and 18,352 (74.43% Moderna) only a second dose. Only 104 (0.028%) (85.58% female, age 53.18 ± 15.96 years) had treated first dose events, 68 (0.030%) Moderna. Only 32 (0.014%) (93.75% female, age 57.28 ± 17.09 years) had treated second dose events, 21 (0.016%) Moderna. Only 2 (0.00033%) vaccinations resulted in anaphylaxis. Only 27 (20.77%) of those with treated first dose reactions failed to get a second dose. Only 6 of 77 (7.8%) with first dose reactions also had second dose reactions. Individuals with treated events were more likely to be female (P < .0001), younger (P < .0001), and had more pre-existing drug "allergies" (2.11 ± 2.12 vs 1.02 ± 1.41 [P < .0001] for average recipients). CONCLUSIONS: Treated acute-onset hypersensitivity events were mostly benign, more common with first COVID-19 mRNA vaccine doses, more likely to occur in younger females with typical risk factors associated with multiple drug intolerance syndrome, and very unlikely to be primarily immunologically mediated.

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.