Kaiser Permanente Research Articles

Abstract PO5-25-10: Clinical and Epidemiologic Significance of HER2-Low Expression in Breast Cancer in the Pathways Study

Abstract Background: A subset of breast cancers (BC) typically classified as HER2-negative do express low levels of the protein and can be responsive to targeted therapy trastuzumab-deruxtecan. It is unclear if HER2-low tumors have a biology distinct from that in HER2 negative BC. The goal of this study was to evaluate the clinical and epidemiologic features of tumors with HER2-low expression compared with those classified as HER2-negative in a large population study. Material and methods: The Pathways Study is a prospective multi-ethnic cohort study of women with BC enrolled between 2006-2013 within Kaiser Permanente Northern California (KPNC). Breast biomarker results were extracted from pathology reports and underwent centralized pathology review. HER2-low was defined as 1+ or 2+ (negative by in situ hybridization); HER2-negative was defined as 0+. Other data were collected by self-report or extraction from electronic health records at the KPNC cancer registry, including BC risk factors, tumor characteristics [AJCC stage, ER/PR positive or negative status], treatment modality (chemotherapy, radiation therapy, hormonal therapy, and type of surgery), and survival outcomes [recurrence free survival (RFS), breast cancer specific mortality (BCSM), and overall survival (OS)]. The clinical and epidemiologic variables were tested in association with HER2 status (low/negative) by t-tests. Associations of HER2-low with survival outcomes were calculated by proportional hazards regression. Women were included in this analysis if they had a documented HER2 value that was not classified as HER2-positive. Results: Of the 2,200 eligible cases, 1,295 (57.2%) had tumors that were HER2-low. Hormone receptors (HR) were positive in 1,956 (88.9%) cases. HER2-low expression was observed more often in HR-positive cases than in HR-negative, 1,144 (58.4%) vs. 115 (47.1%), respectively (p=.0005). Patients with HER2-low tumors were less likely than those with HER2-negative BC to have family history: 232 of 1259 (18.6%) vs. 214 of 941 (22.8%), respectively (p=.015). This difference was true for patients with HR-positive tumors but not for HR-negative. HER2-low expression appeared to be more common in Asian patients in the HR-negative group than in patients from any other race or ethnicity group. In the HR-negative group, patients with HER2-low had better OS, BCSM, and RFS (p=.019, .014, and .034, respectively) than those with HER2-negative disease. Multivariable analyses were performed for the HR-negative group and adjusted for age at diagnosis, tumor AJCC stage, and type of treatment. Compared with patients with HER2-negative status, patients with HER2-low tumors had lower risk for OS (hazard ratio=0.48, 95% confidence interval: 0.28 to 0.81, p= .006); for RFS (hazard ratio=0.49, 95% confidence interval: 0.27 to 0.90, p= .021); and for BCSM (hazard ratio=0.36, 95% confidence interval: 0.17 to 0.76, p= .007). In analyses stratified by race and ethnicity and controlled for age at diagnosis, AJCC stage and treatment type, Black patients with HER2-low tumors had lower risk for RFS (hazard ratio=0.44, 95% confidence interval: 0.21 to 0.94, p= .035) compared with patients with HER2-negative tumors. Conclusions: In this large prospective study with well annotated epidemiologic, clinical, and outcome data, we observed some clinical and epidemiologic differences between HER2-low and HER2-negative patients, raising the possibility that HER2-low might be a unique biologic entity. Citation Format: Thaer Khoury, Rochelle Payne Ondracek, Song Yao, Lucas Mendocino, Warren Davis, Angela Omilian, Marilyn Kwan, Janise Roh, Lia D'Addario, Emily Valice, Daniel Fernandez, Isaac Ergas, Christine Ambrosone, Lawrence Kushi. Clinical and Epidemiologic Significance of HER2-Low Expression in Breast Cancer in the Pathways Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-25-10.

Abstract PO3-27-05: Racioethnic and Ancestral Differences in Risk of Cardiometabolic Conditions and Cardiovascular Disease in Women Treated for Breast Cancer: the Pathways Heart Study

Abstract Background: Despite the established literature of racioethnic disparities in cardiovascular disease (CVD) in the general population, few studies have examined such differences in women after BC treatment, who are at higher risk due to cardiotoxic cancer treatment. Moreover, few prior studies have considered genetic similarity among the participants in the analyses, which can be objectively inferred to delineate the ancestral background of an individual. Methods: The Pathways Heart Study was established to investigate the incidence of cardiometabolic risk factors and CVD events in women with a history of BC at Kaiser Permanente Northern California (KPNC). The main study endpoints for this analysis were cardiometabolic risk factors (hypertension, diabetes, and dyslipidemia) and CVD events, identified by ICD and CPT codes from EHR. Prevalent conditions were identified within 3 years prior to the date of BC diagnosis, and incident conditions were from the date of BC diagnosis to December 31, 2021. Ethnicity was self-reported and classified as non-Hispanic White (NHW), non-Hispanic Black (NHB), Asian, Hispanic, other, or unknown. Global genetic ancestry was estimated to capture the proportion of continental ancestries genetically similar to the reference populations in Africa, Americas, Asia, and Europe from the 1000 Genome Project and Human Genome Diversity Project (HGDP), which, with the current lack of universally accepted labeling, are herein referred to as African, Native American, Asian, and European ancestry, respectively. Multivariable logistic and Cox proportional hazards regression models with all-cause mortality considered as competing risk were used to analyze the associations of race and ethnicity and genetic similarity with prevalent and incident cardiometabolic risk factors and CVD events. Results: Of the 4,071 women with BC in this analysis, 2,713 (66.6%) self-reported as NHW, 305 (7.5%) as NHB, 512 (12.6) as Asian, 447 (11.0%) as Hispanic, and 94 (2.3%) as other or unknown. NHB, Asian, and Hispanic women were more like to have prevalent diabetes than NHW women, the pattern of which persisted after BC diagnosis. Adjusted OR (95% CI) of risk of incident diabetes was 1.74 (1.21-2.49) for NHB, 3.63 (2.59-5.08) for Asian, and 2.19 (1.58-3.04) for Hispanic women, as compared to NHW. Analysis of genetic similarity revealed results consistent with self-reported race and ethnicity (sHR [95% CI] per 25% increment of African ancestry 1.19 [1.07-1.34], Asian ancestry 1.57 [1.44-1.72], and Native American ancestry 1.60 [1.29-2.00]), in comparison to European ancestry. For CVD risk, NHB women were more like to develop any prevalent and incident CVD than NHW women, particularly for ischemic heart disease (incident risk sHR=1.80 [1.10-2.94]). Genetic similarity analyses also showed higher risk of ischemic heart disease associated with African ancestry (incident risk per 25% increment, sHR=1.23 [1.06-1.43]). In contrast, Hispanic women were at lower risk of any incident CVD, serious CVD, arrhythmia, heart failure or cardiomyopathy, and ischemic heart disease. Similarly, lower risk of these CVD conditions was associated with Native American ancestry. Conclusions: Compared with women who self-reported as NHW, those self-reported as NHB, Asian, and Hispanic were at higher risk of diabetes prior to BC diagnosis and the elevated risk persisted after BC diagnosis. Moreover, Black women had higher risk of prevalent and incident CVD, whereas Hispanic women had lower risk of CVD, the latter of which might be related to the admixture of Native American ancestry. To our knowledge, this is the largest multi-ethnic study of disparities in CVD health in women post BC treatment, demonstrating corroborating findings between self-reported race and ethnicity and genetic similarity. The results highlight disparities in cardiometabolic risk factors and CVD among BC survivors that may warrant more research and clinical attentions. Citation Format: Song Yao, Haiyang Sheng, Peter Fiorica, Richard Cheng, Lucas Mendicino, Angela Omilian, Qianqian Zhu, Janise Roh, Cecile Laurant, Valerie Lee, Isaac Ergas, Carlos Iribarren, Jamal Rana, Mai Nguyen-Huynh, Eileen Rillamas-Sun, Dawn Hershman, Christine Ambrosone, Lawrence Kushi, Heather Greenlee, Marilyn Kwan. Racioethnic and Ancestral Differences in Risk of Cardiometabolic Conditions and Cardiovascular Disease in Women Treated for Breast Cancer: the Pathways Heart Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-05.

Lead Time and Immortal Time Biases Impact the Calculation of Post-colonoscopy Colorectal Cancer Survival

The World Endoscopy Organization (WEO) standardized the reporting of post-colonoscopy colorectal cancers (PCCRCs), which account for 7% to 10% of colorectal cancers (CRCs).1 PCCRCs are diagnosed 6 to 36 months after a false negative colonoscopy. Detected CRCs (dCRCs) are diagnosed ≤6 months after an index true positive colonoscopy.2 PCCRC prognosis is unclear, with outcomes reported as comparable,3 superior,4 or inferior5,6 to those of dCRC. Because WEO terminology defines cases relative to the index colonoscopy, conventional survival analyses of PCCRC are susceptible to lead time and immortal time biases. We evaluated the influence of these biases on mortality in a population-based retrospective cohort of 10,938 dCRCs (93.8%) and 717 PCCRCs (6.2%). This study was set within Kaiser Permanente Northern California (KPNC), a large integrated health system, whose members are similar in demographic and socioeconomic characteristics to the Northern California region.7.

Pain Without Prejudice: Examining Disparities in Endometriosis and Pelvic Pain Management Stratified by Race in an Integrative Health Care System [ID 2683558

INTRODUCTION: Approximately 10% of reproductive-aged women suffer from endometriosis; racial variations in prevalence and treatment are unknown. Black women are often undertreated for pain and medical conditions. This study assessed variations in pelvic pain and endometriosis management with particular emphasis on Black versus non-Black patients. METHODS: We conducted a retrospective cohort study of women 18 years and older with pelvic pain disorders, including endometriosis, pelvic pain, dysmenorrhea, and dyspareunia, coded within the Kaiser Permanente Northern California electronic medical record between 2012 and 2019. Demographic, clinical, and treatment characteristics were assessed overall and by patient race/ethnicity. RESULTS: Of 15,164 eligible study participants, 1,707 (11.3%) were Black, 6,735 (50.1%) White, 2,097 (15.6%) Asian, 3,762 (28%) Latinx, and 863 (6%) unknown. Black compared to non-Black women were younger (36 [interquartile range (IQR) 28–44] versus 37 [IQR 30–45]; P<.001), had a higher body mass index (29.8 [IQR 25.2–35.9] versus 26 [IQR 22.7–30.7] kg/m2; P<.001) and similar parity. A higher proportion of Black women received hormonal therapy (56.2% versus 51.9%; P<.001). When stratified by all races, this was explained by White women receiving the least amount of hormonal therapy (56.2% versus 49.8%; P<.001). Black women received more pain medications (55.4% versus 44.7%; P<.001), with no racial variations in rates of laparoscopic surgery (4.4 versus 4.9; P=.21). Fewer Black women received referrals to a pelvic pain specialist (14.5% versus 17.8%; P=.001), and when stratified by all races White women received more referrals (21%; P<.001). There were no racial variations in patients who received medical followed by surgical treatment. CONCLUSION: Black women received more hormonal, pain, and similar surgical management, in contrast to that reported in prior publications. However, all races had a lower pelvic pain specialist referral rate than White patients. These findings illustrate the need to better understand the allocation of care in patients with pelvic pain disorders, including endometriosis.

Cardiovascular and mortality benefits of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists as third-step glucose-lowering medicine in patients with type 2 diabetes: a retrospective cohort analysis

IntroductionStudies have found that sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP1) have cardiovascular benefits for patients with type 2 diabetes (DM2) and atherosclerotic cardiovascular disease...

Multiple Sclerosis, Rituximab, Hypogammaglobulinemia, and Risk of Infections.

B-cell-depleting therapies increase the risk of infections and hypogammaglobulinemia. These relationships are poorly understood. The objectives of these analyses were to estimate how much of this rituximab-associated infection risk is mediated by hypogammaglobulinemia and to identify other modifiable risk factors in persons with multiple sclerosis (pwMS). We conducted a retrospective cohort study of rituximab-treated pwMS from January 1, 2008, to December 31, 2020, in Kaiser Permanente Southern California. Cumulative rituximab dose was defined as ≤2, >2 and ≤4, or >4 g. Serious infections were defined as infections requiring or prolonging hospitalizations, and recurrent outpatient infections as seeking care for ≥3 within 12 months. Exposures, outcomes, and covariates were collected from the electronic health record. Adjusted hazard ratios (aHRs) were estimated using Andersen-Gill hazards models, and generalized estimating equations were used to examine correlates of IgG values. Cross-sectional causal mediation analyses of rituximab and hypogammaglobulinemia were conducted. We identified 2,482 pwMS who were treated with rituximab for a median of 2.4 years (interquartile range = 1.3-3.9). The average age at rituximab initiation was 43.0 years, 71.9% were female, 49.7% were White, non-Hispanic patients, and 29.6% had advanced disability (requiring walker or worse). Seven hundred patients (28.2%) developed recurrent outpatient infections, 155 (6.2%) developed serious infections, and only 248 (10.0%) had immunoglobulin G (IgG) < 700 mg/dL. Higher cumulative rituximab dose (>4 g) was correlated with lower IgG levels (Beta = -58.8, p < 0.0001, ref ≤2 g) and, in models mutually adjusted for hypogammaglobulinemia, both were independently associated with an increased risk of serious (>4 g, aHR = 1.56, 95% CI 1.09-2.24; IgG < 500, aHR = 2.98, 95% CI 1.56-5.72) and outpatient infections (>4 g, aHR = 1.73, 95% CI 1.44-2.06; IgG < 500 aHR = 2.06, 95% CI 1.52-2.80; ref = IgG ≥ 700). Hypogammaglobulinemia explained at most 17.9% (95% CI -47.2-119%) of serious infection risk associated with higher cumulative rituximab exposure but was not significant for outpatient infections. Other independent modifiable risk factors were advanced physical disability for serious (aHR = 5.51, 95% CI 3.71-8.18) and outpatient infections (aHR = 1.24, 95% CI 1.06-1.44) and COPD (aHR = 1.68, 95% CI 1.34-2.11) and obesity (aHR = 1.25, 95% CI 1.09-1.45) for outpatient infections. Higher cumulative rituximab doses increase the risk of infections even in this population where 90% of patients maintained normal IgG levels. Clinicians should strive to use minimally effective doses of rituximab and other B-cell-depleting therapies and consider important comorbidities to minimize risks of infections.

Gender-Affirming Hysterectomies: Analysis of Temporal Trends and Characteristics Pre- and Post-Expansion of Health Care Coverage at a Large Integrated California Health Care System [ID 2683540

INTRODUCTION: Despite expansion of gender-affirming health care coverage in 2013, few studies have investigated temporal trends in gender-affirming surgeries (GAS) including hysterectomies. Our study aims to investigate the temporal trends of hysterectomies for transgender men and gender-diverse persons (TGD) compared to cisgender women between 2010–2012 and 2013–2019, and annually from 2010 to 2019. METHODS: We conducted an observational retrospective cohort study on TGD and cisgendered patients, aged 18 and older, within Kaiser Permanente Northern California (KPNC) between 2010 and 2019. Data on demographics, surgical characteristics, concurrent procedures, and postoperative complications were extracted from electronic medical records. Bivariate comparisons were performed using chi-squared analysis for categorical variables and t-tests for continuous variables. RESULTS: This study included 41,341 hysterectomies performed within KPNC between 2010 and 2019. Among all hysterectomies, 461 (1.1%) were for TGD. TGD who underwent hysterectomies were more likely to be younger, White, and nulliparous compared to their cisgender counterparts (P&lt;.05). The incidence of hysterectomies remained similar in cisgender women—from 3,750 (99.7%) in 2010 to 4,361 (98.4%) in 2019. For TGD, the incidence of hysterectomies increased gradually—from 10 (0.3%) in 2010 to 70 (1.6%) in 2019, with the largest increase occurring from 40 (1.0%) hysterectomies in 2014 to 62 (1.5%) in 2015. After expansion of GAS coverage, hysterectomy rates increased eightfold from 55 (0.5%) in 2010–2012 to 406 (1.4%) in 2013–2019. CONCLUSION: Gender-affirming hysterectomies have increased substantially because of changes in GAS policies. Future data will evaluate trends of ovarian conservation during concurrent GAS hysterectomy.

Economic Burden of Acute Gastroenteritis among Members of Integrated Healthcare Delivery System, United States, 2014-2016.

We conducted a large surveillance study among members of an integrated healthcare delivery system in Pacific Northwest of the United States to estimate medical costs attributable to medically attended acute gastroenteritis (MAAGE) on the day care was sought and during 30-day follow-up. We used multivariable regression to compare costs of MAAGE and non-MAAGE cases matched on age, gender, and index time. Differences accounted for confounders, including race, ethnicity, and history of chronic underlying conditions. Analyses included 73,140 MAAGE episodes from adults and 18,617 from children who were Kaiser Permanente Northwest members during 2014-2016. Total costs were higher for MAAGE cases relative to non-MAAGE comparators as were costs on the day care was sought and costs during follow-up. Costs of MAAGE are substantial relative to the cost of usual-care medical services, and much of the burden accrues during short-term follow-up.

Emergency Department Use in Adolescent and Young Adult Cancer Early Survivors from 2006 to 2020.

Purpose: Understanding emergency department (ED) use in adolescent and young adult (AYA) survivors could identify gaps in AYA survivorship. Methods: We conducted a cohort study of 7925 AYA survivors (aged 15-39 years at diagnosis) who were 2-5 years from diagnosis in 2006-2020 at Kaiser Permanente Southern California. We calculated ED utilization rates overall and by indication of the encounter (headache, cardiac issues, and suicide attempts). We estimated rate changes by survivorship year and patient factors associated with ED visit using a Poisson model. Results: Cohort was 65.4% women, 45.8% Hispanic, with mean age at diagnosis at 31.3 years. Overall, 38% of AYA survivors had ≥1 ED visit (95th percentile: 5 ED visits). Unadjusted ED rates declined from 374.2/1000 person-years (PY) in Y2 to 327.2 in Y5 (p change < 0.001). Unadjusted rates declined for headache, cardiac issues, and suicide attempts. Factors associated with increased ED use included: age 20-24 at diagnosis [relative risk (RR) = 1.30, 95% CI 1.09-1.56 vs. 35-39 years]; female (RR = 1.27, 95% CI 1.11-1.47 vs. male); non-Hispanic Black race/ethnicity (RR 1.64, 95% CI 1.38-1.95 vs. non-Hispanic white); comorbidity (RR = 1.34, 95% CI 1.16-1.55 for 1 and RR 1.80, 95% CI 1.40-2.30 for 2+ vs. none); and public insurance (RR = 1.99, 95% CI 1.70-2.32 vs. private). Compared with thyroid cancer, cancers associated with increased ED use were breast (RR = 1.45, 95% CI 1.24-1.70), cervical (RR = 2.18, 95% CI 1.76-2.71), colorectal (RR = 2.34, 95% CI 1.94-2.81), and sarcoma (RR = 1.39, 95% CI 1.03-1.88). Conclusion: ED utilization declined as time from diagnosis elapsed, but higher utilization was associated with social determinants of health and cancer types.

Association between particulate air pollution and hypertensive disorders in pregnancy: A retrospective cohort study.

Epidemiological findings regarding the association of particulate matter ≤2.5 μm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 μg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.

Association between SARS-CoV-2 Infection and Adverse Perinatal Outcomes by Race/Ethnicity in a Large Integrated Health Care System.

Recent studies have reported associations between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy and adverse perinatal outcomes but the extent to which these associations vary by race/ethnicity remains uncertain. Therefore, we examined how the association between prenatal SARS-CoV-2 infection and adverse perinatal outcomes may be modified by race/ethnicity. A retrospective cohort study was performed using data on 67,986 pregnant women extracted from the Kaiser Permanente Southern California electronic health records between April 6, 2020, and December 31, 2021. Upon admission to labor and delivery, all women were routinely tested for coronavirus disease 2019 (COVID-19) using real-time reverse-transcriptase polymerase chain reaction test. Adjusted odds ratios (aORs) were used to estimate associations. During the study period, COVID-19 was diagnosed in 4,960 (7%) of singleton pregnancies, with the highest rates observed among Hispanics (9.4%) and non-Hispanic Blacks (6.2%). Compared with non-Hispanic Whites, Hispanics (aOR: 1.12, 95% CI: 1.03, 1.21) with SARS-CoV-2 infection had the highest odds of a pregnancy associated with nonreassuring fetal heart rate tracing. Neonates of all races/ethnicities, except for non-Hispanic Blacks, showed significantly increased odds of SARS-CoV-2 infection, with the highest risk observed among Asians/Pacific Islanders (aOR: 10.88, 95% CI: 1.33, 89.04). Non-Hispanic White mothers who tested positive were admitted to intensive care unit (ICU) at a higher rate at delivery and within 7 days of delivery (aOR: 34.77, 95% CI: 11.3, 107.04; aOR: 26.48, 95% CI: 9.55, 73.46, respectively). Hispanics were also at a significantly higher odds of admission to ICU (aOR: 4.62, 95% CI: 2.69, 7.94; aOR: 4.42, 95% CI: 2.58, 7.56, respectively). Non-Hispanic Black, Hispanic, and Asian/Pacific Islander mothers who tested positive for SARS-CoV-2 prenatally, were at increased risk for preeclampsia/eclampsia, and preterm birth as compared to non-Hispanic White mothers. The findings highlight racial/ethnic disparities in the association between SARS-CoV-2 infection and adverse perinatal outcomes. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. We also observed a remarkably high risk of ICU admission for non-Hispanic White mothers infected with SARS-CoV-2. · Race/ethnicity influences perinatal outcomes in pregnancies impacted by SARS-CoV-2.. · The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders.. · White mothers had a notably high risk of ICU admission at delivery following SARS-CoV-2 infection..

Latching Medical Students onto a Virtual Breastfeeding Elective During the COVID-19 Pandemic.

Objectives: To describe the implementation of a successful two-week virtual breastfeeding elective for medical students during the COVID-19 pandemic and characterize student demographics, objective knowledge, and perspectives on breastfeeding before and after the elective. Study Design: We adapted the Santa Rosa Kaiser Permanente Family Medicine breastfeeding residency curriculum to create a two-week virtual medical student elective using Kern's six steps of curriculum development and a competency-based education framework. Educational components included self-paced modules, shadowing experiences, and group didactics. Objective knowledge was assessed with multiple-choice tests before and after the elective compared using a paired t-test. Reflective writing pieces were qualitatively analyzed using the six phases of thematic analysis developed by Braun and Clarke. Results: From 2020 to 2023, 40 medical students completed the elective. Breastfeeding knowledge increased significantly from the pre-test 72% (95% CI: 52-92%) to post-test 91% (95% CI: 81-100%) (p < 0.001). Over 90% of students felt that learning objectives were met well or very well and agreed or strongly agreed that the elective increased their knowledge and confidence in providing anticipatory guidance to breastfeeding parents. Similar themes were shared across students' reflective writing pieces, with nearly 30% (n = 23) of the student essays addressing socio-cultural and racial differences in beliefs surrounding breastfeeding. Conclusion: A virtual breastfeeding curriculum for medical students is well-received by stakeholders (patients, lactation consultants, students, etc.) and improves breastfeeding knowledge and confidence. A virtual elective is an innovative and effective way to deliver breastfeeding education and can be used even when institutional breastfeeding or lactation support is unavailable.

Adverse Childhood Experiences and Sleep Disturbances Among Puerto Rican Young Adults

Sleep quality is a known marker of overall health. Studies suggest that adverse childhood experiences (ACEs) are associated with sleep disturbances among children and adults. To examine the association of retrospective and prospective ACEs with sleep quality among a cohort of Puerto Rican young adults from 2 sociocultural contexts. This prospective cohort study used data from the Boricua Youth Study (BYS), a population-based study representing Puerto Rican children from the South Bronx, New York, and Puerto Rico conducted from August 2000 to August 2003. Participants who were 5 to 9 years of age at enrollment in the BYS and who participated in wave 4 of the BYS took part in the Health Assessment (HA) when they were 18 to 29 years of age, from April 2013 to August 2017. Of the eligible 982 participants, 813 (82.8%) participated in the HA. Statistical analysis was conducted from January 2023 to January 2024. Prospective ACEs measured from parent and youth responses and retrospective ACEs measured among young adults using questions from the validated ACE questionnaire from the original ACEs study conducted by Kaiser Permanente and the Centers for Disease Control and Prevention and published in 1998. Analysis included 8 overlapping items from both questionnaires. Sleep quality was assessed in the HA with the Pittsburgh Sleep Quality Index. The summary score included 7 components of the Pittsburgh Sleep Quality Index. The hypothesis was formulated after data collection. Sleep quality information was gathered at the same time as retrospective ACEs in the HA. Of the 813 participants, 438 (53.9%) lived in Puerto Rico as children, 411 (50.6%) identified as female, and the mean (SE) age of participants was 22.9 (0.07) years. After adjusting for sociodemographic factors, retrospective ACEs had a significant association with worse sleep outcomes (β [SE] = 0.29 [0.07]; 95% CI, 0.15-0.44; P < .001). Prospective ACEs did not have a significant association with sleep quality, after adjusting for sociodemographic factors (β [SE] = 0.05 [0.10]; 95% CI, -0.14 to 0.24; P = .59). This study suggests that there is a significant association between retrospective ACEs and sleep quality among Puerto Rican young adults, after adjusting for sociodemographic factors. Prospective ACEs were not significantly associated with sleep disturbances, after adjusting for sociodemographic factors. Addressing ACEs reported in young adulthood may help reduce sleep disorders.

Reducing Firearm Access for Suicide Prevention: Implementation Evaluation of the Web-Based "Lock to Live" Decision Aid in Routine Health Care Encounters.

"Lock to Live" (L2L) is a novel web-based decision aid for helping people at risk of suicide reduce access to firearms. Researchers have demonstrated that L2L is feasible to use and acceptable to patients, but little is known about how to implement L2L during web-based mental health care and in-person contact with clinicians. The goal of this project was to support the implementation and evaluation of L2L during routine primary care and mental health specialty web-based and in-person encounters. The L2L implementation and evaluation took place at Kaiser Permanente Washington (KPWA)-a large, regional, nonprofit health care system. Three dimensions from the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) model-Reach, Adoption, and Implementation-were selected to inform and evaluate the implementation of L2L at KPWA (January 1, 2020, to December 31, 2021). Electronic health record (EHR) data were used to purposefully recruit adult patients, including firearm owners and patients reporting suicidality, to participate in semistructured interviews. Interview themes were used to facilitate L2L implementation and inform subsequent semistructured interviews with clinicians responsible for suicide risk mitigation. Audio-recorded interviews were conducted via the web, transcribed, and coded, using a rapid qualitative inquiry approach. A descriptive analysis of EHR data was performed to summarize L2L reach and adoption among patients identified at high risk of suicide. The initial implementation consisted of updates for clinicians to add a URL and QR code referencing L2L to the safety planning EHR templates. Recommendations about introducing L2L were subsequently derived from the thematic analysis of semistructured interviews with patients (n=36), which included (1) "have an open conversation," (2) "validate their situation," (3) "share what to expect," (4) "make it accessible and memorable," and (5) "walk through the tool." Clinicians' interviews (n=30) showed a strong preference to have L2L included by default in the EHR-based safety planning template (in contrast to adding it manually). During the 2-year observation period, 2739 patients reported prior-month suicide attempt planning or intent and had a documented safety plan during the study period, including 745 (27.2%) who also received L2L. Over four 6-month subperiods of the observation period, L2L adoption rates increased substantially from 2% to 29% among primary care clinicians and from <1% to 48% among mental health clinicians. Understanding the value of L2L from users' perspectives was essential for facilitating implementation and increasing patient reach and clinician adoption. Incorporating L2L into the existing system-level, EHR-based safety plan template reduced the effort to use L2L and was likely the most impactful implementation strategy. As rising suicide rates galvanize the urgency of prevention, the findings from this project, including L2L implementation tools and strategies, will support efforts to promote safety for suicide prevention in health care nationwide.

A care coordination program to support patients with hepatitis B virus at Kaiser Permanente Mid-Atlantic States

BackgroundEliminating hepatitis B virus (HBV) is a significant worldwide challenge requiring innovative approaches for vaccination, screening, disease management, and the prevention of related conditions. Programs that support patients in accessing needed clinical services can help optimize access to preventive services and treatment resources for hepatitis B.MethodsHere, we outline a coordinator-supported program (HBV Pathway) that connects patients infected with HBV to laboratory testing, imaging, and specialty care for treatment initiation and/or liver cancer surveillance (screening of high-risk patients for liver cancer). This study describes the HBV Pathway steps and reports sociodemographic factors of patients by initiation and completion.ResultsResults showed a 72.5% completion rate (defined as completing all Pathway steps including the final specialty visit) among patients who initiated the Pathway. Differences in completion were observed by age, race, ethnicity, and service area, with higher rates for younger ages, Asian race, non-Hispanic ethnicity, and lower rates for patients within one service area. Of those who completed the specialty visit, 59.5% were referred for hepatocellular carcinoma surveillance.ConclusionsThe HBV Pathway offers dual benefits– care coordination support for patients to promote Pathway completion and a standardized testing and referral program to reduce physician burden. This program provides an easy and reliable process for patients and physicians to obtain updated clinical information and initiate treatment and/or liver cancer screening if needed.

Prior acupuncture experience among elderly participants enrolled in a clinical trial of acupuncture for chronic low back pain: Implications for future trials

BackgroundThe effectiveness of acupuncture for chronic low back pain (cLBP) has not been studied specifically in the 65-and-older population. To inform the validity and generalizability of future acupuncture studies among older adults, we characterized elderly participants’ prior experience with and views toward acupuncture and tested for clinical and sociodemographic differences between acupuncture-naïve and non-naïve participants. MethodsData for this study were collected during the baseline telephone interview from the participants enrolled in the Kaiser Permanente Northern California site of an NIH-funded, multicenter clinical trial of acupuncture for cLBP in older adults. ResultsNearly two-thirds (65.6 %) of participants surveyed reported they had previously received acupuncture treatment with the vast majority seeking acupuncture treatment for pain-related issues (84.8 %). The majority of these participants reported relatively modest levels of exposure to acupuncture with most participants (63.1 %) reporting fewer than 10 treatment sessions over their lifetimes. There were no significant differences in age, sex, race, ethnicity, disability scores, income levels, or pain levels between the acupuncture-naïve and non-naïve groups. ConclusionContextual consideration for prior acupuncture utilization rates is warranted and may be higher than expected or previously reported. We found few differences in baseline characteristics between participants who were acupuncture-naïve and those with prior acupuncture experience; thus, future pragmatic clinical trials might relax previous acupuncture-use considerations in their recruitment criteria. For trials focused on acupuncture-naive patients, it may be more feasible to expand the definition of "acupuncture-naive" based on lifetime acupuncture visits or time since last treatment. Trial registrationThe protocol was registered at clinicaltrials.gov (#NCT04982315).

Colorectal Cancer Screening After Sequential Outreach Components in a Demographically Diverse Cohort

Organized screening outreach can reduce differences in colorectal cancer (CRC) incidence and mortality between demographic subgroups. Outcomes associated with additional outreach, beyond universal outreach, are not well known. To compare CRC screening completion by race and ethnicity, age, and sex after universal automated outreach and additional personalized outreach. This observational cohort study included screening-eligible individuals aged 50 to 75 years assessed during 2019 in a community-based organized CRC screening program within the Kaiser Permanente Northern California (KPNC) integrated health care delivery setting. For KPNC members who are not up to date with screening by colonoscopy, each year the program first uses automated outreach (mailed prescreening notification postcards and fecal immunochemical test [FIT] kits, automated telephone calls, and postcard reminders), followed by personalized components for nonresponders (telephone calls, electronic messaging, and screening offers during office visits). Data analyses were performed between November 2021 and February 2023 and completed on February 5, 2023. Completed CRC screening via colonoscopy, sigmoidoscopy, or FIT. The primary outcome was the proportion of participants completing an FIT or colonoscopy after each component of the screening process. Differences across subgroups were assessed using the χ2 test. This study included 1 046 745 KPNC members. Their mean (SD) age was 61.1 (6.9) years, and more than half (53.2%) were women. A total of 0.4% of members were American Indian or Alaska Native, 18.5% were Asian, 7.2% were Black, 16.2% were Hispanic, 0.8% were Native Hawaiian or Other Pacific Islander, and 56.5% were White. Automated outreach significantly increased screening participation by 31.1%, 38.1%, 29.5%, 31.9%, 31.8%, and 34.5% among these groups, respectively; follow-up personalized outreach further significantly increased participation by absolute additional increases of 12.5%, 12.4%, 13.3%, 14.4%, 14.7%, and 11.2%, respectively (all differences P < .05 compared with White members). Overall screening coverage at the end of the yearly program differed significantly among members who were American Indian or Alaska Native (74.1%), Asian (83.5%), Black (77.7%), Hispanic (76.4%), or Native Hawaiian or Other Pacific Islander (74.4%) compared with White members (82.2%) (all differences P < .05 compared with White members). Screening completion was similar by sex; older members were substantially more likely to be up to date with CRC screening both before and at the end of the screening process. In this cohort study of a CRC screening program, sequential automated and personalized strategies each contributed to substantial increases in screening completion in all demographic groups. These findings suggest that such programs may potentially reduce differences in CRC screening completion across demographic groups.

Hospital-associated venous thromboembolism prophylaxis use by risk assessment at a large integrated health care network in Northern California.

Hospital-acquired venous thromboembolism (HA VTE) is a preventable complication in hospitalized patients. We aimed to examine the use of pharmacologic prophylaxis (pPPX) and compare two risk assessment methods for HA VTE: a retrospective electronic Padua Score (ePaduaKP) and admitting clinician's choice of risk within the admission orderset (low, moderate, or high). We retrospectively analyzed prophylaxis orders for adult medical admissions (2013-2019) at Kaiser Permanente Northern California, excluding surgical and ICU patients. ePaduaKP was calculated for all admissions. For a subset of these admissions, clinician-assigned HA VTE risk was extracted. Descriptive pPPX utilization rates between ePaduaKP and clinician-assigned risk as well as concordance between ePaduaKP and clinician-assigned risk. Among 849,059 encounters, 82.2% were classified as low risk by ePaduaKP, with 42.3% receiving pPPX. In the subset with clinician-assigned risk (608,512 encounters), low and high ePaduaKP encounters were classified as moderate risk in 87.5% and 92.0% of encounters, respectively. Overall, 56.7% of encounters with moderate clinician-assigned risk received pPPX, compared to 7.2% of encounters with low clinician-assigned risk. pPPX use occurred in a large portion of low ePaduaKP risk encounters. Clinicians frequently assigned moderate risk to encounters at admission irrespective of their ePaduaKP risk when retrospectively examined. We hypothesize that the current orderset design may have negatively influenced clinician-assigned risk choice as well as pPPX utilization. Future work should explore optimizing pPPX for high-risk patients only.

Automated CT Analysis of Body Composition as a Frailty Biomarker in Abdominal Surgery

Prior studies demonstrated consistent associations of low skeletal muscle mass assessed on surgical planning scans with postoperative morbidity and mortality. The increasing availability of imaging artificial intelligence enables development of more comprehensive imaging biomarkers to objectively phenotype frailty in surgical patients. To evaluate the associations of body composition scores derived from multiple skeletal muscle and adipose tissue measurements from automated segmentation of computed tomography (CT) with the Hospital Frailty Risk Score (HFRS) and adverse outcomes after abdominal surgery. This retrospective cohort study used CT imaging and electronic health record data from a random sample of adults who underwent abdominal surgery at 20 medical centers within Kaiser Permanente Northern California from January 1, 2010, to December 31, 2020. Data were analyzed from April 1, 2022, to December 1, 2023. Body composition derived from automated analysis of multislice abdominal CT scans. The primary outcome of the study was all-cause 30-day postdischarge readmission or postoperative mortality. The secondary outcome was 30-day postoperative morbidity among patients undergoing abdominal surgery who were sampled for reporting to the National Surgical Quality Improvement Program. The study included 48 444 adults; mean [SD] age at surgery was 61 (17) years, and 51% were female. Using principal component analysis, 3 body composition scores were derived: body size, muscle quantity and quality, and distribution of adiposity. Higher muscle quantity and quality scores were inversely correlated (r = -0.42; 95% CI, -0.43 to -0.41) with the HFRS and associated with a reduced risk of 30-day readmission or mortality (quartile 4 vs quartile 1: relative risk, 0.61; 95% CI, 0.56-0.67) and 30-day postoperative morbidity (quartile 4 vs quartile 1: relative risk, 0.59; 95% CI, 0.52-0.67), independent of sex, age, comorbidities, body mass index, procedure characteristics, and the HFRS. In contrast to the muscle score, scores for body size and greater subcutaneous and intermuscular vs visceral adiposity had inconsistent associations with postsurgical outcomes and were attenuated and only associated with 30-day postoperative morbidity after adjustment for the HFRS. In this study, higher muscle quantity and quality scores were correlated with frailty and associated with 30-day readmission and postoperative mortality and morbidity, whereas body size and adipose tissue distribution scores were not correlated with patient frailty and had inconsistent associations with surgical outcomes. The findings suggest that assessment of muscle quantity and quality on CT can provide an objective measure of patient frailty that would not otherwise be clinically apparent and that may complement existing risk stratification tools to identify patients at high risk of mortality, morbidity, and readmission.

Comparative analysis of two disaster risk assessment tools for primary health care centers: The case of Iran

AimAssessing disaster risk in primary health care (PHC) centers is essential for ensuring continuity of operations during disasters. There is a lack of internationally recognized methods for conducting this assessment in PHC centers. In Iran, the SARA tool, a modified version of the Hospital Safety Index, has been utilized, but its effectiveness is being questioned. This study aims to evaluate the SARA by comparing it with the Kaiser Permanente Hazard Vulnerability Analysis (KP HVA) tool to identify differences and potential issues. Methodology: The cross-sectional study was conducted in two stages. First, the expert panel was used to compare the two tools' instructions and inputs and extract similarities and differences. In the second phase, the outputs of the two tools were compared by implementing them in 156 PHC centers supervised by Semnan University of Medical Sciences. Data was collected using SARA and KP HVA tools and analyzed using Excel software. ResultsThe findings illustrated the disparities in the results obtained from the two tools. Although significant similarities exist in the instructions and inputs, the SARA results indicated the safety and preparedness of PHC centers without considering the hazards. On the other hand, the KP HVA results highlighted hazard risk priorities based on comparable dimensions. ConclusionThe leading cause of the differences is the multiple-hazard and all-hazard approaches of KP HVA and SARA tools. It is recommended that the SARA tool be upgraded based on the advantages of the KP HVA tool for better resource allocation.