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.

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.

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.

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 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 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 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%.

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.

Women with high plasma levels of PBDE-47 are at increased risk of preterm birth.

OBJECTIVES: Nearly 100% of North American women have detectable levels of flame retardants such as polybrominated diphenyl ethers (PBDEs) in their plasma. These molecules have structural homology to thyroid hormones and may function as endocrine disruptors. Thyroid dysfunction has previously been associated with increased risk for preterm birth. Therefore, we conducted a multi-center, case-cohort study to evaluate if high plasma concentrations of a common PBDE congener in the first trimester increases the risk of preterm birth and its subtypes. METHODS: Pregnant women were recruited at the onset of initiation of prenatal care at Kaiser-Permanente Southern California (KPSC)-West Los Angeles and KPSC-San Diego medical centers. Plasma samples from women whose pregnancies ended preterm and random subset of those delivering at term were assayed for PBDE-47 and thyroid-stimulating hormone (TSH) by immunoassay. Quartile cutoffs were calculated for the patients at term and used to determine if women with exposures in the 4th quartile are at increased risk for preterm birth using logistic regression. RESULTS: We found that high concentrations of PBDE-47 in the first trimester significantly increased the odds of both indicated (adjusted odds ratio, adjOR=2.35, 95% confidence interval [CI]: 1.31, 4.21) and spontaneous (adjOR=1.76, 95% CI: 1.02, 3.03) preterm birth. Regardless of pregnancy outcome, TSH concentrations did not differ between women with high and low concentrations of PBDE-47. CONCLUSIONS: These results suggest that high plasma concentrations of PBDE-47 in the first trimester, increases the risk of indicated and spontaneous preterm birth.

The Shieh Score as a Risk Assessment Tool for Hospital-Acquired Pressure Injuries: A Retrospective Cohort Study.

OBJECTIVE: To design a new risk assessment tool to identify patients at high risk for hospital-acquired pressure injuries. METHODS: The researchers developed the Shieh Score using retrospective data of 406,032 hospital admissions from January 2014 to December 2016 with 1,299 pressure injury cases from the pressure injury registry. A decision tree and best subset logistic regression were used to select predictors from demographic and clinical candidate variables, which were then used to construct the Shieh Score. RESULTS: The final Shieh Score included the following measures: sex, age, diabetes, glomerular filtration rate, albumin level, level of function, use of IV norepinephrine, mechanical ventilation, and level of consciousness. The Shieh Score had a higher Youden Index, specificity, and positive predictive value than the Braden Scale. However, the Braden Scale had a higher sensitivity compared with the Shieh Score. CONCLUSIONS: The Shieh Score is an alternative risk assessment tool that may effectively identify a smaller number of patients at high risk for hospital-acquired pressure injuries with a higher specificity and positive predictive value than the Braden Scale.

Low Rate of Cancer Detection by Colonoscopy in Asymptomatic, Average-Risk Subjects with Negative Results From Fecal Immunochemical Tests.

BACKGROUND & AIMS: Screening colonoscopies are of uncertain benefit for persons with negative results from a fecal immunochemical test (FIT). We investigated detection of CRC by colonoscopy in asymptomatic, average-risk, FIT-negative subjects. METHODS: We conducted a retrospective, population-based cohort study of 96,804 subjects with an initial negative result from a FIT at ages 50-75 years, from 2008 through 2014, who then underwent colonoscopy, using the Kaiser Permanente California databases. We identified participants diagnosed with CRC from January 1, 2008 through December 31, 2015 from a cancer registry. Subjects were followed until initial colonoscopy, health plan disenrollment, death, or December 31, 2015. We reviewed records from 400 randomly selected persons without CRC (controls) for risk features to estimate the proportion who underwent screening colonoscopy. We performed logistic regression to identify variables associated with CRC detection. RESULTS: Of 257 subjects with a diagnosis of CRC, 102 did not have a record of CRC risk factors; 86 of these patients (84.3%) had non-advanced-stage CRC (no regional node spread/distant metastases). Of the 400 controls, 299 (74.75%; 95% CI, 70.49%-79.01%) lacked CRC risk features, enabling estimation that 72,263 (mean age, 57.5 ± 7.0 y; 54.5% female) had undergone screening colonoscopy. CRC was detected in 1.4 per 1000 persons after 1 FIT, without association with increasing FITs (P = .97). CRC was detected in 1.3 per 1000 persons in 2 y or less after the last FIT and in 4.4 per 1000 persons more than 2 y after the last FIT (P < .001). When the last FIT was 2 y earlier or less, CRC increased from 0.7 per 1000 persons age 50-59 y to 3.1 per 1000 persons older than 70 y. Age and time from the last FIT were associated with CRC, with adjusted odds ratios of 1.08 (95% CI, 1.05-1.11) and 2.76 (95% CI, 1.28-5.95), respectively. CONCLUSIONS: In asymptomatic, average-risk persons with a negative result from a FIT, CRC is infrequent within 2 y after the last FIT (especially for persons younger than 60 y), usually non-advanced, and unrelated to the number of FITs performed.

Does Providing Positive Airway Pressure for Sleep Apnea Change Health Care Utilization?

BACKGROUND: Sleep apnea is underdiagnosed and thus undertreated. If therapy for sleep apnea results in reduced health care utilization in an entire treated population, then decision-makers will have key information for allocating limited health care resources. OBJECTIVES: To determine whether positive airway pressure (PAP) for sleep apnea was associated with reduced health care utilization in an entire treated population. RESEARCH DESIGN: This was a retrospective cohort; propensity score-matched cases and noncases; pre-post analyses of individual subject utilization. SUBJECTS: Electronic health records were used to identify adult subjects diagnosed with sleep apnea and dispensed PAP therapy (cases) and those without either diagnosed sleep apnea or dispensed PAP therapy (noncases). MEASURES: Acute care hospital days and dispensed medication days supply were compared in cases and noncases. Negative binomial regression was used to model utilization for up to 5 years before and 7 years after PAP dispensation (cases) or a random date (noncases). The association of PAP with changing annual utilization was estimated. RESULTS: There were 13,271 cases and 13,271 matched noncases from 2008 to 2012 for analyses. Trends in the annual rate of acute care utilization were no different between cases and noncases (rate ratio, 0.98, P=0.543). Trends in the annual rate of medication utilization were no different between cases and noncases (rate ratio, 1.008, P=0.112). CONCLUSIONS: PAP dispensation for sleep apnea did not appear to reduce the rate of acute care and medication utilization over several years of follow-up in a large integrated health care system.

Risk of Gastric Cancer Among Patients With Intestinal Metaplasia of the Stomach in a US Integrated Health Care System.

BACKGROUND & AIMS: Gastric intestinal metaplasia (GIM) is a common finding from routine endoscopies. Although GIM is an early step in gastric carcinogenesis, there is controversy regarding routine surveillance of patients with GIM in regions with a low prevalence of gastric cancer. We aimed to determine the incidence of gastric cancer among patients with GIM and risk factors for gastric cancer. METHODS: We performed a retrospective cohort study of patients from the Kaiser Permanente Southern California region diagnosed with GIM from 2000 through 2011. GIM was identified by a keyword search of pathology reports; gastric cancer cases were identified by cross-reference with an internal cancer registry. The incidence of gastric cancer in patients with GIM (n = 923; median age at diagnosis, 68 y) was compared with that of an age- and sex-matched reference population (controls). Risk factors such as ethnicity, smoking status, history of Helicobacter pylori infection, and family history of gastric cancer were evaluated by individual Cox proportional hazards regression. We then performed a second case-cohort study to evaluate the risk of gastric cancer based on the location and extent of GIM. The median duration of follow-up evaluation was 4.6 years (interquartile range, 3.0-6.7 y). RESULTS: We identified 25 patients with GIM who developed gastric cancers. Seventeen cases of cancer were diagnosed at the same time as the diagnosis of GIM. Eight cases of cancer were identified within a median time period of 4.6 years after a diagnosis of GIM (interquartile range, 2-5.7 y). The overall incidence rate for the cohort was 1.72 (95% confidence interval, 0.74-3.39). Among the risk factors evaluated, only family history (hazard ratio, 3.8; 95% confidence interval, 1.5-9.7; P = .012) and extent of GIM (odds ratio, 9.4; 95% confidence interval, 1.8-50.4) increased the risk for gastric cancer. The incidence rate for gastric cancer in patients with a positive family history was 8.12 (95% confidence interval, 1.67-23.73). CONCLUSIONS: In an analysis of patients with GIM listed in the Kaiser Permanente Southern California database, 2.7% were diagnosed with gastric cancer; almost 70% of cases of gastric cancer were detected at the time of GIM diagnosis. Family history and extensive metaplasia were associated with an increased risk of subsequent gastric cancer. Targeted surveillance of patients with these criteria could increase early detection of gastric cancer.

Effectiveness of bisphosphonate use and risk of contralateral breast cancer and recurrence in women with early-stage breast cancer treated with tamoxifen.

The effectiveness of bisphosphonates (BP) in reducing risk of second breast cancer and recurrence in observational studies has been minimally studied. We examined the association of oral BP use on risk of contralateral breast cancer (CBC) and recurrence in 16,781 women diagnosed with early-stage breast cancer from 1996 to 2007, treated with tamoxifen, and followed through December 31, 2009 at Kaiser Permanente Northern California (KPNC, n = 8857) and Southern California (KPSC, n = 7924). Sociodemographic, clinical, and pharmacy information were extracted from electronic medical records and cancer registries. CBC was identified from cancer registries, and recurrences from electronic health records and chart reviews. Multivariate Cox regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) treating BP use and hormonal therapy as time-varying variables. After mean 6.4 years of follow-up, 494 (3.0 %) women developed CBC. BP use post-breast cancer diagnosis (>93 % alendronate) ranged from 14.5 to 24.9 % at both study sites. Overall, there was no association of BP use with reduced risk of CBC (ever use, HR = 0.96; 95 % CI 0.67-1.38 and continuous use, HR = 1.03; 95 % CI 0.88, 1.20). Similar null associations were observed for recurrence (ever use, HR = 0.98; 95 % CI 0.82, 1.17 and continuous use, HR = 1.00; 95 % CI 0.92, 1.09). Associations varied somewhat by site yet confidence intervals overlapped. BP use was not associated with reduced risk of recurrence or new primary disease among women diagnosed with early breast cancer and treated with tamoxifen.

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.

Racial differences in estimated GFR decline, ESRD, and mortality in an integrated health system.

BACKGROUND: Current evidence does not clearly identify the contribution of kidney function decline and mortality to racial disparities in end-stage renal disease (ESRD) incidence. We used observed estimated glomerular filtration rate (eGFR) to project the time of onset of kidney failure and examined mortality to better understand these racial disparities. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: Adult members of Kaiser Permanente Southern California in 2003-2009 with more than 2 serum creatinine tests and more than 180 days between tests: 526,498 whites, 350,919 Hispanics, 136,923 blacks, and 105,476 Asians. PREDICTOR: Race/ethnicity. OUTCOMES: ESRD (dialysis or transplantation); mortality. MEASUREMENTS: eGFR decline was modeled using linear regression. Kidney failure was projected based on predicted eGFR <15 mL/min/1.73 m² at specified times. Racial differences in projected kidney failure and mortality in those with projected kidney failure were estimated with adjustment for age, sex, and entry eGFR. RESULTS: Blacks had more extreme rates of eGFR decline (1st percentile, -23.6 mL/min/1.73 m² per year), followed by Hispanics (-20.9 mL/min/1.73 m² per year), whites (-20.1 mL/min/1.73 m² per year), and Asians (-17.6 mL/min/1.73 m² per year; P < 0.001). There were 25,065 whites, 11,368 Hispanics, 6,785 blacks, and 3,176 Asians with projected kidney failure during the study period. The ORs for projected kidney failure versus whites during CKD stages 3 and 4 were 1.54 (95% CI, 1.46-1.62) in blacks, 1.49 (95% CI, 1.42-1.56) in Hispanics, and 1.41 (95% CI, 1.32-1.51) in Asians. For those with projected kidney failure, the HRs of death versus whites during CKD stages 3 and 4 were 0.82 (95% CI, 0.77-0.88) in blacks, 0.67 (95% CI, 0.63-0.72) in Hispanics, and 0.58 (95% CI, 0.52-0.65) in Asians. LIMITATIONS: Results may not generalize to the uninsured or subgroups within a race. Projected kidney failure was based on linear trends from clinically obtained eGFR. CONCLUSIONS: We found more extreme rates of eGFR decline in blacks. Projected kidney failure during CKD stages 3 and 4 was high in blacks, Hispanics, and Asians relative to whites. Mortality for those with projected kidney failure was highest in whites. Differences in eGFR decline and mortality contributed to racial disparities in ESRD incidence.

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.

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.

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.

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.