Theoretical Behavior Substitutions during the 24-Hour Day in Pregnancy and Infant Growth Outcomes.

PURPOSE: To assess associations of theoretically reallocating time from sleep, sedentary behavior, or light intensity physical activity (LPA) to moderate/vigorous intensity physical activity (MVPA) during pregnancy with infant growth outcomes. METHODS: We used data from a cohort of pregnant individuals with overweight or obesity (n = 116). At 9-15 and 30-36 weeks gestation, waking movement was measured using wrist-worn accelerometers and sleep duration was self-reported. Outcomes were obtained from delivery electronic health records (birth) and study visits (12 months). We used compositional isotemporal substitution models. RESULTS: In early pregnancy, reallocating 10 minutes of sleep, sedentary behavior, or LPA to MVPA was associated with 20% (RR = 0.80; 95%CI: 0.75,0.85), 21% (RR = 0.79; 95%CI: 0.75,0.84), and 25% (RR = 0.75; 95%CI: 0.70,0.81) lower risk of large-for-gestational age (LGA) birthweight, respectively, and 17% (RR = 0.83; 95%CI: 0.75,0.91), 18% (RR = 0.82; 95%CI: 0.75,0.91), and 22% (RR = 0.78; 95%CI: 0.70,0.88) lower risk of rapid infant growth (birth to 12 months), respectively. In late pregnancy, reallocating 10 minutes to MVPA was associated with 18% to 22% lower risk of LGA birthweight, but was not associated with rapid infant growth. Reallocating time to MVPA in early or late pregnancy was not associated with high newborn body fat percent. CONCLUSIONS: Our findings suggest beneficial associations of theoretically reallocating time from sleep, sedentary behavior, or LPA to MVPA, especially during early pregnancy, for reducing LGA birthweight and rapid infant growth.

Racial Residential Segregation and Mental Health During Pregnancy.

Importance: Research suggests the social, physical, and socioeconomic contexts of residing in segregated neighborhoods may negatively affect mental health. Objective: To assess the association between racial residential segregation and prenatal mental health among Asian, Black, Hispanic, and White individuals. Design, Setting, and Participants: This population-based cross-sectional study was conducted in Kaiser Permanente Northern California (KPNC), an integrated health care delivery system. Participants included self-identified Asian, Black, Hispanic, and White pregnant individuals who attended at least 1 prenatal care visit at KPNC between January 1, 2014, and December 31, 2019. Data were analyzed from January 14, 2023, to August 15, 2024. Exposures: Racial residential segregation, defined by the local Getis-Ord Gi* statistic, was calculated in each racial and ethnic group and categorized as low (<0), medium (0-1.96), or high (>1.96). A positive Gi* statistic indicates overrepresentation (greater clustering or segregation) of the racial and ethnic group in an index census tract and neighboring tracts compared with the larger surrounding geographic area. Main Outcomes and Measures: Prenatal depression and anxiety defined by diagnoses codes documented in the electronic health record between the first day of the last menstrual period and the day prior to birth. Results: Among the 201 115 participants included in the analysis (mean [SD] age, 30.8 [5.3] years; 26.8% Asian, 6.6% Black, 28.0% Hispanic, and 38.6% White), prenatal depression and anxiety were highest in Black individuals (18.3% and 18.4%, respectively), followed by White (16.0% and 18.2%, respectively), Hispanic (13.0% and 14.4%, respectively), and Asian (5.7% and 6.4%, respectively) individuals. Asian (40.8% vs 31.1%) and Black (43.3% vs 22.6%) individuals were more likely to live in neighborhoods with high vs low segregation, while Hispanic individuals were equally likely (34.3% vs 34.7%). High compared with low segregation was associated with greater odds of prenatal depression (adjusted odds ratio [AOR], 1.25 [95% CI, 1.10-1.42]) and anxiety (AOR, 1.14 [95% CI, 1.00-1.29]) among Black individuals. High segregation was associated with lower odds of prenatal depression among Asian (AOR, 0.75 [95% CI, 0.69-0.82]), Hispanic (AOR, 0.88 [95% CI, 0.82-0.94]), and White (AOR, 0.91 [95% CI, 0.86-0.96]) individuals. Similar associations were found for anxiety among Asian (AOR, 0.80 [95% CI, 0.73-0.87]) and Hispanic (AOR, 0.88 [95% CI, 0.82-0.93]) but not White (AOR, 0.95 [95% CI, 0.90-1.00]) individuals. Conclusions and Relevance: In this cross-sectional study, racial and ethnic residential segregation was associated with worse prenatal mental health for Black individuals but better mental health for Asian, Hispanic, and White individuals. Policies reducing segregation and its impact may improve mental health outcomes in pregnant Black individuals.

A Tailored Postpartum eHealth Physical Activity Intervention for Individuals at High Risk of Postpartum Depression-the POstpartum Wellness Study (POW): Protocol and Data Overview for a Randomized Controlled Trial.

BACKGROUND: Postpartum depression (PPD) is associated with significant health consequences for the parent and child. Current recommendations for PPD prevention require intense health care system resources. Evidence-based interventions for PPD prevention that do not further burden the health care system are needed. Evidence suggests that physical activity (PA) can generally reduce depressive symptoms. Technology-based interventions may help decrease common barriers to PA. OBJECTIVE: This study aims to report the protocol and provide a data overview of the POstpartum Wellness study (POW)-an effectiveness trial evaluating whether an eHealth PA intervention tailored for postpartum individuals increased PA and decreased depressive symptoms among individuals at high PPD risk. METHODS: This remote parallel-group randomized controlled trial included postpartum individuals with a history of depression or at least moderate current depressive symptoms not meeting the PPD diagnostic threshold and with low PA levels from an integrated health care delivery system. Participants were randomized to an eHealth PA intervention or usual care. The intervention group received access to a library of web-based workout videos designed for postpartum individuals, which included interaction with their infants. At baseline and follow-up (3 and 6 months), PA was measured using questionnaires and a wrist-worn accelerometer. Depressive symptoms were measured using the Patient Health Questionnaire-8 (PHQ-8). Data were collected to assess exploratory outcomes of sleep, perceived stress, anxiety, parent-infant bonding, and infant development. RESULTS: The study was funded in January 2020. Participants were enrolled via REDCap (Research Electronic Data Capture) or telephonically between November 2020 and September 2022; data collection ended in April 2023. Randomized participants (N=99) were 4 months post partum at baseline with moderately severe depressive symptoms (mean PHQ-8 score 12.6, SD 2.2). Intervention (n=50) and usual care (n=49) groups had similar sociodemographic characteristics, months post partum, baseline depressive symptoms, number of children at home, and prepregnancy PA levels. Retention in assessments was ≥66% for questionnaires and ≥48% for accelerometry, with modest differences by group. At 3-month follow-up, 73 of 99 (74%) participants (intervention: 35/50, 70%; usual care: 38/49, 78%) completed questionnaires; 53 of 99 (54%) wore the accelerometer for 7 days (27 of 50 (54%) intervention, 26 of 49 (53%) usual care). At 6-month follow-up, 66 of 99 (67%) participants (30 of 50 (60%) intervention, 36 of 49 (73%) usual care) completed questionnaires and 43 of 99 (43%) wore the accelerometer for 7 days (21 of 50 (42%) intervention, 22 of 49 (45%) usual care). Data analysis is completed, and a manuscript with these findings is currently under review for publication. CONCLUSIONS: The POW trial evaluates the effectiveness of an eHealth PA intervention for improving depressive symptoms and increasing PA among postpartum individuals at high PPD risk. Results have implications for the design and delivery of behavioral interventions among vulnerable patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04414696; https://clinicaltrials.gov/ct2/show/NCT04414696. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56882.

Function, cognition, and quality of life among older adults with lung cancer who live alone: A prospective cohort study.

INTRODUCTION: Among older adults without cancer, living alone is associated with poor health outcomes. However, among older adults with non-small cell lung cancer (NSCLC) who live alone, data on function, cognition, and quality of life (QOL) during systemic treatment remain limited. MATERIALS AND METHODS: We enrolled adults aged ≥65 with advanced NSCLC starting a new chemotherapy, immunotherapy, and/or targeted therapy regimen with non-curative intent. Patients completed geriatric assessments including instrumental activities of daily living (IADL), Montreal Cognitive Assessment, and QOL pretreatment and at 1, 2, 4, and 6 months, or until treatment discontinuation, whichever occurred earlier. We categorized change in IADL, cognition, and QOL as stable/improved, declined with recovery, or declined without recovery using clinically meaningful definitions of change. We used multinomial logistic regression to compare change between patients who lived alone versus with others. RESULTS: Among 149 patients, median age was 73; 21% lived alone. Pretreatment IADL, cognition, and QOL scores were similar between older adults who lived alone versus with others. During NSCLC treatment, older adults who lived alone had similar trajectories of function (52% functional decline vs 38%), cognition (43% cognitive decline vs 50%), and QOL (45% QOL decline vs 44%) compared with those who lived with others. In unadjusted analyses, patients who lived alone were more likely to develop functional decline with recovery (reference category: stable/improved function) than those who lived with others (relative risk ratio 4.07, 95% CI 1.14-14.6, p = 0.03). However, this association was not observed after adjusting for age, race, prior NSCLC treatment, current treatment group, and pretreatment geriatric assessment differences. There were no differences in cognitive or QOL trajectories in unadjusted or adjusted analyses. DISCUSSION: Approximately half of older adults with advanced NSCLC who lived alone were able to maintain their function, cognition, and QOL during NSCLC treatment, which was similar to older adults who lived with others. Many older adults with advanced NSCLC who live alone can receive systemic treatment with individualized supportive care.

Gender differences in the association between education and late-life cognitive function in the LifeAfter90 Study: A multiethnic cohort of the oldest-old.

INTRODUCTION: Few studies have examined the relationship between education and cognition among the oldest-old. METHODS: Cognitive assessments were conducted biannually for 803 participants (62.6% women) of LifeAfter90, a longitudinal study of individuals ≥ 90 years old. Gender differences in associations between education (< high school, high school, some college, and ≥ college) and cognition (verbal episodic memory, semantic memory, and executive function) were examined at baseline and longitudinally using linear mixed models. RESULTS: Higher education levels were associated with better cognitive performance at baseline for both men and women. College completion was more strongly associated with better baseline executive function among women. Education-cognition associations for baseline verbal episodic memory and baseline semantic memory did not differ by gender. Education was not associated with a decline in any domain-specific cognitive scores, regardless of gender. DISCUSSION: Education is associated with cognitive function among the oldest-old and varies by gender and cognitive domain at baseline but not over time. HIGHLIGHTS: In the oldest-old, higher education was associated with better cognitive function. College completion was more strongly associated with executive function in women. Education was not associated with cognitive decline after age 90 regardless of gender. Improving education could decrease gaps in cognitive level among older individuals.

Representativeness of Patients With Lung Cancer in an Integrated Health Care Delivery System.

INTRODUCTION: Observational research is important for understanding the real-world benefits of advancements in lung cancer care. Integrated health care systems, such as Kaiser Permanente Northern California, have extensive electronic health records suitable for such research, but the generalizability of their populations is often questioned. METHODS: Leveraging data from the California Cancer Registry, the authors compared distributions of demographic and clinical characteristics, in addition to neighborhood and environmental conditions, between patients diagnosed with lung cancer from 2015 through 2019 at Kaiser Permanente Northern California, National Cancer Institute-designated cancer centers (NCICCs), and all other non-NCICC hospitals within the same catchment area. RESULTS: Of 20,178 included patients, 30% were from Kaiser Permanente Northern California, 8% from NCICCs, and 62% from other non-NCICC hospitals. Compared to NCICC patients, Kaiser Permanente Northern California patients were more similar to other non-NCICC patients on most characteristics. Compared to other non-NCICC patients, Kaiser Permanente Northern California patients were slightly older, more likely to be female, and less likely to be Hispanic or Asian/Pacific Islander and to reside in lower socioeconomic status (SES) neighborhoods. In contrast, NCICC patients were younger, less likely to be female or from non-Asian/Pacific Islander minoritized racial groups, and more likely to present with early-stage disease and adenocarcinoma and to reside in neighborhoods with higher SES and lower air pollution than Kaiser Permanente Northern California or other non-NCICC patients. DISCUSSION: Patients from Kaiser Permanente Northern California, compared to NCICCs, are more broadly representative of the underlying patient population with lung cancer. CONCLUSION: Research using electronic health record data from integrated health care systems can contribute generalizable real-world evidence to benchmark and improve lung cancer care.

HbA1c variability associated with dementia risk in people with type 2 diabetes.

INTRODUCTION: Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A1c (HbA1c) levels, increases dementia risk. METHODS: Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long-term HbA1c variability using five operationalizations, including standard deviation (SD), adjusting for demographics and comorbidities. RESULTS: The mean baseline age was 61 years (48% women). Greater HbA1c SD was associated with greater dementia hazard (adjusted hazard ratio = 1.15 [95% confidence interval: 1.12, 1.17]). In stratified analyses, higher HbA1c SD quintiles were associated with greater dementia hazard among those with a mean HbA1c < 6% (P = 0.0004) or 6% to 8% (P < 0.0001) but not among those with mean HbA1c ≥ 8% (P = 0.42). DISCUSSION: Greater HbA1c variability is associated with greater dementia risk, even among those with HbA1c concentrations at ideal clinical targets. These findings add to the importance and clinical impact of recommendations to minimize glycemic variability. HIGHLIGHTS: We observed a cohort of 171,964 people with type 2 diabetes (mean age 61 years). This cohort was based in Northern California between 1996 and 2018. We examined the association between glycosylated hemoglobin A1c (HbA1c) variability and dementia risk. Greater HbA1c variability was associated with greater dementia hazard. This was most evident among those with normal-low mean HbA1c concentrations.

The Influence of Dietary Isothiocyanates on the Effectiveness of Mitomycin C and Bacillus Calmette-Guérin in Treating Nonmuscle-Invasive Bladder Cancer.

PURPOSE: Nonmuscle-invasive bladder cancer (NMIBC) has high recurrence rates and is often treated with mitomycin C (MMC) and bacillus Calmette-Guérin (BCG). Their efficacy relies on phase 2 enzyme metabolism and immune response activation, respectively. Dietary isothiocyanates, phytochemicals in cruciferous vegetables, are phase 2 enzyme inducers and immunomodulators, and may impact treatment outcomes. We investigated the modifying effects of cruciferous vegetable and isothiocyanate intake on recurrence risk following MMC or BCG treatment. MATERIALS AND METHODS: Self-reported cruciferous vegetable intake, estimated isothiocyanate intake, and urinary isothiocyanate metabolites were collected from 1158 patients with incident NMIBC in the prospective Be-Well Study. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazards regression models for risk of first recurrences, and random effects Cox shared frailty models for multiple recurrences. RESULTS: Over median follow-up of 23 months, 343 (30%) recurrences occurred. Receipt of MMC and BCG was associated with decreased risks of first recurrence (MMC: HR = 0.58; 95% CI: 0.46-0.73; BCG: HR = 0.66; 95% CI: 0.49-0.88) and multiple recurrences (MMC: HR = 0.55; 95% CI: 0.44-0.68; BCG: HR = 0.72; 95% CI: 0.55-0.95). Patients receiving BCG and having high intake (>2.4 servings/mo), but not low intake, of raw cruciferous vegetables had reduced risk of recurrence (HR: 0.56; 95% CI: 0.36-0.86; P for interaction = .02) and multiple recurrences (HR: 0.51; 95% CI: 0.34-0.77; P for interaction < .001). The inverse association between MMC receipt and recurrence risk was not modified. CONCLUSIONS: For NMIBC patients who receive induction BCG, increasing consumption of raw cruciferous vegetables could be a promising strategy to attenuate recurrence risk.

Relative contribution of COVID-19 vaccination and SARS-CoV-2 infection to population-level seroprevalence of SARS-CoV-2 spike antibodies in a large integrated health system.

BACKGROUND: Understanding the relative contributions of SARS-CoV-2 infection-induced and vaccine-induced seroprevalence is key to measuring overall population-level seroprevalence and help guide policy decisions. METHODS: Using a series of six population-based cross-sectional surveys conducted among persons aged ≥7 years in a large health system with over 4.5 million members between May 2021 and April 2022, we combined data from the electronic health record (EHR), an electronic survey and SARS-CoV-2 spike antibody binding assay, to assess the relative contributions of infection and vaccination to population-level SARS-CoV-2 seroprevalence. EHR and survey data were incorporated to determine spike antibody positivity due to SARS-CoV-2 infection and COVID-19 vaccination. We used sampling and non-response weighting to create population-level estimates. RESULTS: We enrolled 4,319 persons over six recruitment waves. SARS-CoV-2 spike antibody seroprevalence increased from 83.3% (CI 77.0-88.9) in May 2021 to 93.5% (CI 89.5-97.5) in April 2022. By April 2022, 68.5% (CI 61.9-74.3) of the population was seropositive from COVID-19 vaccination only, 13.9% (10.7-17.9) from COVID-19 vaccination and prior diagnosed SARS-CoV-2 infection, 8.2% (CI 4.5-14.5) from prior diagnosed SARS-CoV-2 infection only and 2.9% (CI 1.1-7.6) from prior undiagnosed SARS-CoV-2 infection only. We found high agreement (≥97%) between EHR and survey data for ascertaining COVID-19 vaccination and SARS-CoV-2 infection status. CONCLUSIONS: By April 2022, 93.5% of persons had detectable SARS-CoV-2 spike antibody, predominantly from COVID-19 vaccination. In this highly vaccinated population and over 18 months into the pandemic, SARS-CoV-2 infection without COVID-19 vaccination was a small contributor to overall population-level seroprevalence.

Group Multimodal Prenatal Care and Postpartum Outcomes.

Importance: An increasing body of evidence suggests equivalent if not improved postpartum outcomes of in-person group prenatal care compared with individual prenatal care. However, research is needed to evaluate outcomes of group multimodal prenatal care (GMPC), with groups delivered virtually in combination with individual in-person office appointments to collect vital signs and conduct other tests compared with individual multimodal prenatal care (IMPC) delivered through a combination of remotely delivered and in-person visits. Objective: To compare postpartum outcomes between GMPC and IMPC. Design, Setting, and Participants: A frequency-matched longitudinal cohort study was conducted at Kaiser Permanente Northern California, an integrated health care delivery system. Participants included 424 individuals who were pregnant (212 GMPC and 212 frequency-matched IMPC controls (matched on gestational age, race and ethnicity, insurance status, and maternal age) receiving prenatal care between August 17, 2020, and April 1, 2021. Participants completed a baseline survey before 14 weeks' gestation and a follow-up survey between 4 and 8 weeks post partum. Data analysis was performed from January 3, 2022, to March 4, 2024. Exposure: GMPC vs IMPC. Main Outcome Measures: Validated instruments were used to ascertain postpartum psychosocial outcomes (stress, depression, anxiety) and perceived quality of prenatal care. Self-reported outcomes included behavioral outcomes (breastfeeding initiation, use of long-acting reversible contraception), satisfaction with prenatal care, and preparation for self and baby care after delivery. Primary analyses included all study participants in the final cohort. Three secondary dose-stratified analyses included individuals who attended at least 1 visit, 5 visits, and 70% of visits. Log-binomial regression and linear regression analyses were conducted. Results: The final analytic cohort of 390 participants (95.6% follow-up rate of 408 singleton live births) was racially and ethnically diverse: 98 (25.1%) Asian/Pacific Islander, 88 (22.6%) Hispanic, 17 (4.4%) non-Hispanic Black, 161 (41.3%) non-Hispanic White, and 26 (6.7%) multiracial participants; median age was 32 (IQR, 30-35) years. In the primary analysis, after adjustment, GMPC was associated with a 21% decreased risk of perceived stress (adjusted risk ratio [ARR], 0.79; 95% CI, 0.67-0.94) compared with IMPC. Findings were consistent in the dose-stratified analyses. There were no significant differences between GMPC and IMPC for other psychosocial outcomes. While in the primary analyses there was no significant group differences in perceived quality of prenatal care (mean difference [MD], 0.01; 95% CI, -0.12 to 0.15) and feeling prepared to take care of baby at home (ARR, 1.09; 95% CI, 0.96-1.23), the dose-stratified analyses documented higher perceived quality of prenatal care (MD, 0.16; 95% CI, 0.01-0.31) and preparation for taking care of baby at home (ARR, 1.27; 95% CI, 1.13-1.43) for GMPC among those attending 70% of visits. No significant differences were noted in patient overall satisfaction with prenatal care and feeling prepared for taking care of themselves after delivery. Conclusions: In this cohort study, equivalent and, in some cases, better outcomes were observed for GMPC compared with IMPC. Health care systems implementing multimodal models of care may consider incorporating virtual group prenatal care as a prenatal care option for patients.

Pubertal Timing Across Asian American, Native Hawaiian, and Pacific Islander Subgroups.

Importance: Earlier puberty is associated with adverse health outcomes, such as mental health issues in adolescence and cardiometabolic diseases in adulthood. Despite rapid growth of the Asian American, Native Hawaiian, and Pacific Islander populations in the US, limited research exists on their pubertal timing, potentially masking health disparities. Objective: To examine pubertal timing among Asian American, Native Hawaiian, and Pacific Islander children and adolescents by disaggregating ethnic subgroups. Design, Setting, and Participants: This retrospective cohort study included Asian American, Native Hawaiian, and Pacific Islander youths aged 5 to 18 years assessed for pubertal development at Kaiser Permanente Northern California, a large, integrated health care delivery system. Follow-up occurred from March 2005, through December 31, 2019. Data were analyzed in October 2023. Exposure: Race and ethnicity, categorized into 11 ethnic subgroups: Asian Indian, Chinese, Filipino, Japanese, Korean, Native Hawaiian and Pacific Islander, Other South Asian, Other Southeast Asian, Vietnamese, multiethnic, and multiracial. Main Outcomes and Measures: Pubertal timing was determined using physician-assessed sexual maturity ratings (SMRs). Outcomes included the median age at transition from SMR 1 (prepubertal) to SMR 2 or higher (pubertal) for onset of genital development (gonadarche) in boys, breast development (thelarche) in girls, and pubic hair development (pubarche) in both boys and girls. Results: In this cohort of 107 325 Asian American, Native Hawaiian, and Pacific Islander children and adolescents (54.61% boys; 12.96% Asian Indian, 22.24% Chinese, 26.46% Filipino, 1.80% Japanese, 1.66% Korean, 1.96% Native Hawaiian and Pacific Islander, 0.86% Other South Asian, 3.26% Other Southeast Asian, 5.99% Vietnamese, 0.74% multiethnic, and 22.05% multiracial), the overall median ages for girls' pubarche and thelarche were 10.98 years (95% CI, 10.96-11.01 years) and 10.13 years (95% CI, 10.11-10.15 years), respectively. For boys' pubarche and gonadarche, median ages were 12.08 years (95% CI, 12.06-12.10 years) and 11.54 years (95% CI, 11.52-11.56 years), respectively. Differences between subgroups with earliest and latest median age at onset were 14 months for girls' pubarche, 8 months for thelarche, 8 months for boys' pubarche, and 4 months for gonadarche. In general, Asian Indian, Native Hawaiian and Pacific Islander, and Other South Asian subgroups had the earliest ages at onset across pubertal markers, while East Asian youths exhibited the latest onset. Restricting to those with healthy body mass index did not substantially change the findings. Conclusions and Relevance: In this cohort study of Asian American, Native Hawaiian, and Pacific Islander children and adolescents, pubertal timing varied considerably across ethnic subgroups. Further investigation is warranted to assess whether these differences contribute to observed health disparities in adulthood, such as type 2 diabetes and cardiovascular diseases.

Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study.

BACKGROUND: Women with breast cancer are at higher risk of cardiovascular disease (CVD) compared with women without breast cancer. Whether higher diet quality at breast cancer diagnosis lowers this risk remains unknown. We set out to determine if higher diet quality at breast cancer diagnosis was related to lower risk of CVD and CVD-related death. METHODS: This analysis included 3415 participants from the Pathway Study, a prospective cohort of women diagnosed with invasive breast cancer at Kaiser Permanente Northern California between 2005 and 2013 and followed through December 31, 2021. Scores from 5 diet quality indices consistent with healthy eating were obtained at the time of breast cancer diagnosis. Scores were categorized into ascending quartiles of concordance for each diet quality index, and multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. P values were 2-sided. RESULTS: The Dietary Approaches to Stop Hypertension diet quality index was associated with lower risk of heart failure (HR = 0.53, 95% CI = 0.33 to 0.87; Ptrend = .03), arrhythmia (HR = 0.77, 95% CI = 0.62 to 0.94; Ptrend = .008), cardiac arrest (HR = 0.77, 95% CI = 0.61 to 0.96; Ptrend = .02), valvular heart disease (HR = 0.79, 95% CI = 0.64 to 0.98; Ptrend = .046), venous thromboembolic disease (HR = 0.75, 95% CI = 0.60 to 0.93; Ptrend = .01), and CVD-related death (HR = 0.70, 95% CI = 0.50 to 0.99; Ptrend = .04), when comparing the highest with lowest quartiles. Inverse associations were also found between the healthy plant-based dietary index and heart failure (HR = 0.60, 95% CI = 0.39 to 0.94; Ptrend = .02), as well as the alternate Mediterranean dietary index and arrhythmia (HR = 0.74, 95% CI = 0.60 to 0.93; Ptrend = .02). CONCLUSION: Among newly diagnosed breast cancer patients, higher diet quality at diagnosis was associated with lower risk of CVD events and death.

Modifying Effects of Genetic Variations on the Association Between Dietary Isothiocyanate Exposure and Non-muscle Invasive Bladder Cancer Prognosis in the Be-Well Study.

SCOPE: Dietary isothiocyanate (ITC) exposure from cruciferous vegetable (CV) intake may improve non-muscle invasive bladder cancer (NMIBC) prognosis. This study aims to investigate whether genetic variations in key ITC-metabolizing/functioning genes modify the associations between dietary ITC exposure and NMIBC prognosis outcomes. METHODS AND RESULTS: In the Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study), a prospective cohort of 1472 incident NMIBC patients, dietary ITC exposure is assessed by self-reported CV intake and measured in plasma ITC-albumin adducts. Using Cox proportional hazards regression models, stratified by single nucleotide polymorphisms (SNPs) in nine key ITC-metabolizing/functioning genes, it is calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression. The rs15561 in N-acetyltransferase 1 (NAT1) is alter the association between CV intake and progression risk. Multiple SNPs in nuclear factor E2-related factor 2 (NRF2) and nuclear factor kappa B (NFκB) are modify the associations between plasma ITC-albumin adduct level and progression risk (pint < 0.05). No significant association is observed with recurrence risk. Overall, >80% study participants are present with at least one protective genotype per gene, showing an average 65% reduction in progression risk with high dietary ITC exposure. CONCLUSION: Despite that genetic variations in ITC-metabolizing/functioning genes may modify the effect of dietary ITCs on NMIBC prognosis, dietary recommendation of CV consumption may help improve NMIBC survivorship.

Relative contribution of COVID-19 vaccination and SARS-CoV-2 infection to population-level seroprevalence of SARS-CoV-2 spike antibodies in a large integrated health system.

Background: Understanding the relative contributions of SARS-CoV-2 infection-induced and vaccine- induced seroprevalence is key to measuring overall population-level seroprevalence and help guide policy decisions. Methods: Using a series of six population-based cross-sectional surveys conducted among persons aged ≥7 years in a large health system with over 4.5 million members between May 2021 and April 2022, we combined data from the electronic health record (EHR), an electronic survey and SARS-CoV-2 spike antibody binding assay, to assess the relative contributions of infection and vaccination to population- level SARS-CoV-2 seroprevalence. EHR and survey data were incorporated to determine spike antibody positivity due to SARS-CoV-2 infection and COVID-19 vaccination. We used sampling and non-response weighting to create population-level estimates. Results: We enrolled 4,319 persons over six recruitment waves. SARS-CoV-2 spike antibody seroprevalence increased from 83.3% (CI 77.0-88.9) in May 2021 to 93.5% (CI 89.5-97.5) in April 2022. By April 2022, 68.5% (CI 61.9-74.3) of the population was seropositive from COVID-19 vaccination only, 13.9% (10.7-17.9) from COVID-19 vaccination and prior diagnosed SARS-CoV-2 infection, 8.2% (CI 4.5- 14.5) from prior diagnosed SARS-CoV-2 infection only and 2.9% (CI 1.1-7.6) from prior undiagnosed SARS-CoV-2 infection only. We found high agreement (≥97%) between EHR and survey data for ascertaining COVID-19 vaccination and SARS-CoV-2 infection status. Conclusions: By April 2022, 93.5% of persons had detectable SARS-CoV-2 spike antibody, predominantly from COVID-19 vaccination. In this highly vaccinated population and over 18 months into the pandemic, SARS-CoV-2 infection without COVID-19 vaccination was a small contributor to overall population-level seroprevalence. Article summary: By April 2022, >93% of people had antibodies to SARS-CoV-2 with COVID-19 vaccination as the main driver of overall population-level seroprevalence in our healthcare system. SARS-CoV-2 infection without vaccination made a small contribution to population-level seroprevalence in our healthcare system.

Randomized Trial of Patient Outreach Approaches to De-implement Outdated Colonoscopy Surveillance Intervals.

BACKGROUND AND AIMS: Guidelines now recommend patients with low-risk adenomas receive colonoscopy surveillance in 7-10 years and those with the previously recommended 5-year interval be re-evaluated. We tested 3 outreach approaches for transitioning patients to the 10-year interval recommendation. METHODS: This was a 3-arm pragmatic randomized trial comparing telephone, secure messaging, and mailed letter outreach. The setting was Kaiser Permanente Northern California, a large integrated healthcare system. Participants were patients 54-70 years of age with 1-2 small (<10 mm) tubular adenomas at baseline colonoscopy, due for 5-year surveillance in 2022, without high-risk conditions, and with access to all 3 outreach modalities. Patients were randomly assigned to the outreach arm (telephone [n = 200], secure message [n = 203], and mailed letter [n = 201]) stratified by age, sex, and race/ethnicity. Outreach in each arm was performed by trained medical assistants (unblinded) communicating in English with 1 reminder attempt at 2-4 weeks. Participants could change their assigned interval to 10 years or continue their planned 5-year interval. RESULTS: Sixty-day response rates were higher for telephone (64.5%) and secure messaging outreach (51.7%) vs mailed letter (31.3%). Also, more patients adopted the 10-year surveillance interval in the telephone (37.0%) and secure messaging arms (32.0%) compared with mailed letter (18.9%) and rate differences were significant for telephone (18.1%; 97.5% confidence interval: 8.3%-27.9%) and secure message outreach (13.1%; 97.5% confidence interval: 3.5%-22.7%) vs mailed letter outreach. CONCLUSIONS: Telephone and secure messaging were more effective than mailed letter outreach for de-implementing outdated colonoscopy surveillance recommendations among individuals with a history of low-risk adenomas in an integrated healthcare setting. (ClinicalTrials.gov, Number: NCT05389397).

Effect of home-based resistance training on chemotherapy relative dose intensity and tolerability in colon cancer: The FORCE randomized control trial.

BACKGROUND: Many patients with colon cancer cannot fully adhere to postoperative chemotherapy due to dose-limiting toxicities, resulting in lower relative dose intensity (RDI) and potentially compromising overall survival. This study examined whether home-based resistance training (RT) during adjuvant chemotherapy improves RDI and patient-reported toxicities versus usual care (UC) in colon cancer patients. METHODS: Multicenter, randomized control trial (RCT) conducted at community and academic practices. Enrollment of patients receiving postoperative chemotherapy for colon cancer occurred between February 23, 2018, and September 29, 2021; final follow-up was March 21, 2022. Participants were randomized to RT (n = 90) or UC (n = 91) for the duration of chemotherapy. Participants in the RT group engaged in twice weekly home-based progressive RT. At the end of the study, UC was given an online exercise program. RESULTS: Among 181 randomized patients (mean age, 55.2 [SD, 12.8] years, 95 [52.5%] were men), there were no differences in the mean RDI among those in RT (79% [SD, 19%]) and those in UC (82% [SD, 19%]); (mean difference -0.04 [95% confidence interval (CI), -0.09 to 0.02]). Assignment to RT did not significantly reduce the number of moderate/severe symptoms per week across follow-up (relative rate: 0.94 [95% CI, 0.72-1.22]). Additionally, time since randomization did not significantly modify the effect of RT on the overall number of symptoms (p = .06). CONCLUSIONS: Among patients with colon cancer, these results do not support home-based RT as an adjunct to chemotherapy specifically to improve planned treatment intensity.

Digital health outreach to promote postpartum screening after gestational diabetes: A randomized factorial pilot study.

Objective: We examined the acceptability and feasibility of a multi-component digital health outreach intervention to promote uptake of guideline-recommended postpartum screening for type 2 diabetes among patients with gestational diabetes (GDM). Methods: We conducted a 24 randomized factorial experiment as part of the Multiphase Optimization Strategy (MOST) preparation phase for developing behavioral interventions. Participants with current or recent GDM in an integrated healthcare system were randomized to receive an outreach message with up to four intervention components, designed to be self-administered in about 10 min and efficiently delivered online via REDCap: a streamlined values affirmation, personalized information on diabetes risk, an interactive motivational interviewing-based component, and an interactive action planning component. Patient-reported acceptability and feasibility outcomes were assessed via survey. Results: Among 162 participants, 72% self-identified with a racial/ethnic minority group. Across components, acceptability scores averaged 3.9/5; ≥91% of participants read most or all of the outreach message; ≥89% perceived the amount of information as "about right"; and ≥ 87% completed ≥1 interactive prompt. Conclusion: Each intervention component was acceptable to diverse patients and feasible to deliver in a brief, self-directed, online format. Innovation: These novel components target unaddressed barriers to patient engagement in guideline-recommended postpartum diabetes screening and adapt theory-based behavior change techniques for large-scale use.

Behavior reallocations within 24-h movement profiles and change in cardiometabolic biomarkers during pregnancy.

OBJECTIVE: The goal of this study was to investigate associations of reallocations within 24-h movement profiles and changes in cardiometabolic biomarkers from early to late pregnancy. METHODS: In 137 individuals with prepregnancy overweight/obesity, waking movement was measured using wrist-worn accelerometers, sleep was self-reported, and biomarkers were measured in fasting serum samples at 12 and 32 weeks' gestation. We used compositional isotemporal substitution models. RESULTS: On average, biomarkers increased 21%-83% across pregnancy. For those with guideline-recommended moderate/vigorous-intensity physical activity (MVPA) in early pregnancy, reallocating 30 min from MVPA to sleep, sedentary behavior, or light-intensity physical activity (LPA) was associated with a 0.6 mmol/L greater increase in total cholesterol (95% CI: -0.1 to 1.2) and a 0.7 mmol/L greater increase in low-density lipoprotein (LDL) cholesterol (95% CI: 0.1 to 1.3) from early to late pregnancy. For those with low MVPA in early pregnancy, reallocating 30 min from sleep, sedentary behavior, or LPA to MVPA was associated with a 0.6 mmol/L lower increase in total cholesterol (95% CI: -1.3 to 0.1) and a 0.8 mmol/L lower increase in LDL cholesterol (95% CI: -1.4 to -0.1) from early to late pregnancy. There were no associations with change in glucose, insulin, homeostatic model assessment for insulin resistance, very low-density lipoprotein, or high-density lipoprotein cholesterol, triglycerides, or free fatty acids. CONCLUSIONS: Maintaining or achieving a 24-h movement profile with guideline-recommended amounts of MVPA may be beneficial for reducing pregnancy-induced increases in total and LDL cholesterol.

Timing and level of educational attainment and late-life cognition in the KHANDLE study.

INTRODUCTION: The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point. METHODS: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N = 554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized). RESULTS: Compared to low educational attainment, high (ß= 0.59 SD units; 95% confidence interval [CI]: 0.39, 0.79) and later-life high educational attainment (ß = 0.22; 95% CI: 0.00, 0.44) were associated with higher executive function. Only high educational attainment was associated with higher verbal episodic memory (ß = 0.27; 95% CI: 0.06, 0.48). DISCUSSION: Level and timing of educational attainment are both associated with domain-specific cognition. A single assessment for educational attainment may inadequately characterize protective associations with late-life cognition. HIGHLIGHTS: Few studies have examined both level and timing of educational attainment on cognition. Marginalized populations are more likely to attain higher education in adulthood. Higher educational attainment in late life is also associated with higher cognition.

Environmental and Occupational Exposures and Prognosis in Patients with Non-Muscle Invasive Bladder Cancer in the Be-Well Study.

Bladder cancer is primarily diagnosed as non-muscle invasive bladder cancer (NMIBC) with high recurrence and progression rates. Environmental and occupational exposures to carcinogens are well-known risk factors for developing bladder cancer, yet their effects on prognosis remain unknown. In the Be-Well Study, a population-based prospective cohort study of 1,472 patient with newly diagnosed NMIBC from 2015 to 2019, we examined history of environmental and occupational exposures in relation to tumor stage and grade at initial diagnosis by multivariable logistic regression, and subsequent recurrence and progression by Cox proportional hazards regression. Exposure to environmental and occupational carcinogens was significantly associated with increased risk of progression (HR = 1.79; 95% CI: 1.04, 3.09), specifically increased progression into muscle-invasive disease (HR = 2.28; 95% CI: 1.16, 4.50). Exposure to asbestos and arsenic were associated with increased odds of advanced stage at diagnosis (asbestos: OR = 1.43; 95% CI: 1.11, 1.84; arsenic, OR = 1.27; 95% CI: 1.01, 1.63), and formaldehyde exposure was associated with increased risk of recurrence (HR = 1.38; 95% CI: 1.12, 1.69). Our findings suggest that history of these exposures may benefit current risk stratification systems to tailor clinical care and improve prognosis in patients with NMIBC.