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.

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.

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.

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.

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.

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.

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).

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.

Neighborhood Disadvantage, Race and Ethnicity, and Postpartum Depression.

Importance: Postpartum depression (PPD) is a debilitating condition with higher rates among Black individuals. Increasingly, neighborhood disadvantage is being recognized as a contributor to poor health and may be associated with adverse postpartum mental health; however, associations between neighborhood disadvantage, race and ethnicity, and PPD have not been examined. Objective: To investigate the association between neighborhood disadvantage and PPD and evaluate the extent to which these associations may differ by race and ethnicity. Design, Setting, and Participants: This population-based cross-sectional study included 122 995 postpartum Kaiser Permanente Northern California members 15 years or older with a live birth between October 7, 2012, and May 31, 2017, and an address in the electronic health record. Analyses were conducted from June 1, 2022, through June 30, 2023. Exposures: Neighborhood disadvantage defined using quartiles of the Neighborhood Deprivation Index (NDI), a validated census-based socioeconomic status measure; self-reported race and ethnicity ascertained from Kaiser Permanente Northern California electronic health records. Main Outcomes and Measures: Multivariable Poisson regression was conducted to assess associations between neighborhood disadvantage, race and ethnicity, and a diagnosis of PPD. Results: Of 122 995 included postpartum individuals, 17 554 (14.3%) were younger than 25 years, 29 933 (24.3%) were Asian, 8125 (6.6%) were Black, 31 968 (26.0%) were Hispanic, 47 527 (38.6%) were White, 5442 (4.4%) were of other race and ethnicity, and 15 436 (12.6%) had PPD. Higher neighborhood disadvantage and race and ethnicity were associated with PPD after covariate adjustment. Compared with White individuals, Black individuals were more likely to have PPD (adjusted relative risk [ARR], 1.30; 95% CI, 1.24-1.37), whereas Asian (ARR, 0.48; 95% CI, 0.46-0.50), and Hispanic (ARR, 0.92; 95% CI, 0.89-0.96) individuals and those identified as having other race and ethnicity (ARR, 95% CI, 0.90; 0.85-0.98) were less likely to have PPD. Associations between NDI and PPD differed by race and ethnicity (likelihood ratio test for interaction, χ212 = 41.36; P < .001). Among Black individuals, the risk of PPD was the greatest overall and increased with neighborhood disadvantage in a dose-response manner (quartile [Q] 2 ARR, 1.39 [95% CI, 1.13-1.71]; Q3 ARR, 1.50 [95% CI, 1.23-1.83]; Q4 ARR, 1.60 [95% CI, 1.32-1.93]; Cochrane-Armitage test for trend, P < .001). Neighborhood disadvantage was associated with PPD among Asian (Q2 ARR, 1.17 [95% CI, 1.04-1.31]; Q3 ARR, 1.20 [95% CI, 1.06-1.35]) and White (Q3 ARR, 1.14 [95% CI, 1.07-1.21]; Q4 ARR, 1.17 [95% CI, 1.09-1.26]) individuals and those of other race and ethnicity (Q3 ARR, 1.34 [95% CI, 1.09-1.63]; Q4 ARR, 1.28 [95% CI, 1.03-1.58]), but the magnitude of risk was lower. Neighborhood disadvantage was not associated with PPD among Hispanic individuals (eg, Q2 ARR, 1.04 [95% CI, 0.94-1.14]; Q3 ARR, 1.00 [95% CI, 0.91-1.10]; Q4 ARR, 0.98 [95% CI, 0.90-1.08]). Conclusions and Relevance: In this cross-sectional study of postpartum individuals, residing in more disadvantaged neighborhoods was associated with PPD, except among Hispanic individuals. Neighborhood disadvantage may be associated with racial and ethnic differences in postpartum mental health. Geographic targeting of mental health interventions may decrease postpartum mental health inequities.

Intrinsic motivation for physical activity, healthy eating, and self-weighing in association with corresponding behaviors in early pregnancy.

Healthy lifestyle behaviors influence maternal cardiovascular health, but motivation for them in pregnancy is poorly understood. We examined whether intrinsic motivation (assessed on 5-point scales for each behavior) is associated with three lifestyle behaviors in early pregnancy: physical activity, by intensity level; healthy eating, quantified with the Alternate Healthy Eating Index for Pregnancy (AHEI-P); and weight self-monitoring, a standard weight management technique. Participants in the Northern California Pregnancy, Lifestyle and Environment Study (PETALS) population-based cohort completed validated surveys in early pregnancy (2017-18; N = 472; 22 % Asian, 6 % Black, 30 % Hispanic, 13 % multiracial, 30 % White). Cross-sectional data were analyzed in 2021-22. Overall, 40.7 % (n = 192) met United States national physical activity guidelines; the average AHEI-P score was 62.3 out of 130 (SD 11.4); and 36.9 % reported regular self-weighing (≥once/week; n = 174). In models adjusted for participant characteristics, 1-unit increases in intrinsic motivation were associated with increased likelihood of meeting physical activity guidelines (risk ratio [95 % CI]: 1.66 [1.48, 1.86], p < 0.0001); meeting sample-specific 75th percentiles for vigorous physical activity (1.70 [1.44, 1.99], p < 0.0001) and AHEI-P (1.75 [1.33, 2.31], p < 0.0001); and regular self-weighing (2.13 [1.92, 2.37], p < 0.0001). A 1-unit increase in intrinsic motivation lowered the risk of meeting the 75th percentile for sedentary behavior (0.79 [0.67, 0.92], p < 0.003). Intrinsic motivation was not associated with reaching 75th percentiles for total, light, or moderate activity. Intrinsic motivation is associated with physical activity, healthy eating, and self-weighing among diverse individuals in early pregnancy. Results can inform intervention design to promote maternal health via increased enjoyment of lifestyle behaviors.

Challenges and Opportunities of Epidemiological Studies to Reduce the Burden of Cancers in Young Adults.

There are >1.9 million survivors of adolescent and young adult cancers (AYA, diagnosed at ages 15-39) living in the U.S. today. Epidemiologic studies to address the cancer burden in this group have been a relatively recent focus of the research community. In this article, we discuss approaches and data resources for cancer epidemiology and health services research in the AYA population. We consider research that uses data from cancer registries, vital records, healthcare utilization, and surveys, and the accompanying challenges and opportunities of each. To illustrate the strengths of each data source, we present example research questions or areas that are aligned with these data sources and salient to AYAs. Integrating the respective strengths of cancer registry, vital records, healthcare data, and survey-based studies sets the foundation for innovative and impactful research on AYA cancer treatment and survivorship to inform a comprehensive understanding of diverse AYA needs and experiences.

Alcohol consumption and prognosis and survival in breast cancer survivors: The Pathways Study.

BACKGROUND: The impact of alcohol consumption on breast cancer (BC) prognosis remains unclear. METHODS: The authors examined short-term alcohol intake in relation to recurrence and mortality in 3659 women who were diagnosed with stage I-IV BC from 2003 to 2013 in the Pathways Study. Alcohol drinking in the past 6 months was assessed at cohort entry (mean, 2 months postdiagnosis) and 6 months later using a food-frequency questionnaire. Study end points were recurrence and death from BC, cardiovascular disease, and all causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. RESULTS: Over an average follow-up of 11.2 years, 524 recurrences and 834 deaths (369 BC-specific and 314 cardiovascular disease-specific) occurred. Compared with nondrinkers (36.9%), drinkers were more likely younger, more educated, and current or past smokers. Overall, alcohol consumption was not associated with recurrence or mortality. However, women with higher body mass index (BMI ≥ 30 kg/m2 ) had lower risk of overall mortality with increasing alcohol consumption for occasional drinking (HR, 0.71; 95% CI, 0.54-0.94) and regular drinking (HR, 0.77; 95% CI, 0.56-1.08) around the time of diagnosis, along with 6 months later, in a dose-response manner (p < .05). Women with lower BMI (<30 kg/m2 ) were not at higher risk of mortality but were at possibly higher, yet nonsignificant, risk of recurrence for occasional drinking (HR, 1.29; 95% CI, 0.97-1.71) and regular drinking (HR, 1.19; 95% CI, 0.88-1.62). CONCLUSIONS: Alcohol drinking around the time of and up to 6 months after BC diagnosis was associated with lower risk of all-cause mortality in obese women. A possible higher risk of recurrence was observed in nonobese women.

Prenatal Health Care Outcomes Before and During the COVID-19 Pandemic Among Pregnant Individuals and Their Newborns in an Integrated US Health System.

Importance: The COVID-19 pandemic accelerated the use of telemedicine. However, data on the integration of telemedicine in prenatal health care and health outcomes are sparse. Objective: To evaluate a multimodal model of in-office and telemedicine prenatal health care implemented during the COVID-19 pandemic and its association with maternal and newborn health outcomes. Design, Setting, and Participants: This cohort study of pregnant individuals using longitudinal electronic health record data was conducted at Kaiser Permanente Northern California, an integrated health care system serving a population of 4.5 million people. Individuals who delivered a live birth or stillbirth between July 1, 2018, and October 21, 2021, were included in the study. Data were analyzed from January 2022 to May 2023. Exposure: Exposure levels to the multimodal prenatal health care model were separated into 3 intervals: unexposed (T1, birth delivery between July 1, 2018, and February 29, 2020), partially exposed (T2, birth delivery between March 1, 2020, and December 5, 2020), and fully exposed (T3, birth delivery between December 6, 2020, and October 31, 2021). Main Outcomes and Measures: Primary outcomes included rates of preeclampsia and eclampsia, severe maternal morbidity, cesarean delivery, preterm birth, and neonatal intensive care unit (NICU) admission. The distributions of demographic and clinical characteristics, care processes, and health outcomes for birth deliveries within each of the 3 intervals of interest were assessed with standardized mean differences calculated for between-interval contrasts. Interrupted time series analyses were used to examine changes in rates of perinatal outcomes and its association with the multimodal prenatal health care model. Secondary outcomes included gestational hypertension, gestational diabetes, depression, venous thromboembolism, newborn Apgar score, transient tachypnea, and birth weight. Results: The cohort included 151 464 individuals (mean [SD] age, 31.3 [5.3] years) who delivered a live birth or stillbirth. The mean (SD) number of total prenatal visits was similar in T1 (9.41 [4.75] visits), T2 (9.17 [4.50] visits), and T3 (9.15 [4.66] visits), whereas the proportion of telemedicine visits increased from 11.1% (79 214 visits) in T1 to 20.9% (66 726 visits) in T2 and 21.3% (79 518 visits) in T3. NICU admission rates were 9.2% (7014 admissions) in T1, 8.3% (2905 admissions) in T2, and 8.6% (3615 admissions) in T3. Interrupted time series analysis showed no change in NICU admission risk during T1 (change per 4-week interval, -0.22%; 95% CI, -0.53% to 0.09%), a decrease in risk during T2 (change per 4-week interval, -0.91%; 95% CI, -1.77% to -0.03%), and an increase in risk during T3 (change per 4-week interval, 1.75%; 95% CI, 0.49% to 3.02%). There were no clinically relevant changes between T1, T2, and T3 in the rates of risk of preeclampsia and eclampsia (change per 4-week interval, 0.76% [95% CI, 0.39% to 1.14%] for T1; -0.19% [95% CI, -1.19% to 0.81%] for T2; and -0.80% [95% CI, -2.13% to 0.55%] for T3), severe maternal morbidity (change per 4-week interval , 0.12% [95% CI, 0.40% to 0.63%] for T1; -0.39% [95% CI, -1.00% to 1.80%] for T2; and 0.99% [95% CI, -0.88% to 2.90%] for T3), cesarean delivery (change per 4-week interval, 0.06% [95% CI, -0.11% to 0.23%] for T1; -0.03% [95% CI, -0.49% to 0.44%] for T2; and -0.05% [95% CI, -0.68% to 0.59%] for T3), preterm birth (change per 4-week interval, 0.23% [95% CI, -0.11% to 0.57%] for T1; -0.37% [95% CI, -1.29% to 0.55%] for T2; and -0.15% [95% CI, -1.41% to 1.13%] for T3), or secondary outcomes. Conclusions and Relevance: These findings suggest that a multimodal prenatal health care model combining in-office and telemedicine visits performed adequately compared with in-office only prenatal health care, supporting its continued use after the pandemic.

Associations of dietary isothiocyanate exposure from cruciferous vegetable consumption with recurrence and progression of non-muscle-invasive bladder cancer: findings from the Be-Well Study.

BACKGROUND: High recurrence and progression rates are major clinical challenges for non-muscle-invasive bladder cancer (NMIBC). Dietary isothiocyanates (ITCs), phytochemicals primarily from cruciferous vegetables (CV), show strong anticancer activities in preclinical BC models, yet their effect on NMIBC prognosis remains unknown. OBJECTIVES: This study aimed to investigate the associations of dietary ITC exposure at diagnosis with NMIBC recurrence and progression. METHODS: The study analyzed 1143 participants from the Be-Well study, a prospective cohort of newly diagnosed NMIBC cases in 2015-2019 with no prior history of BC. Dietary ITC exposure was indicated by self-reported CV intake, estimated ITC intake, urinary metabolites, and plasma ITC-albumin adducts. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression, and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for delayed and multiple recurrence. RESULTS: Over a mean follow-up of 25 mo, 347 (30%) developed recurrence and 77 (6.7%) had disease progression. Despite no significant associations with the overall risk of recurrence, urinary ITC metabolites (OR: 1.96; 95% CI: 1.01, 4.43) and dietary ITC intake (OR: 2.13; 95% CI: 1.03, 4.50) were associated with late recurrence after 12-mo postdiagnosis compared with before 12-mo postdiagnosis. Raw CV intake was associated with reduced odds of having ≥2 recurrences compared with having one (OR: 0.34; 95% CI: 0.16, 0.68). Higher plasma concentrations of ITC-albumin adducts were associated with a reduced risk of progression, including progression to muscle-invasive disease (for benzyl ITC, HR: 0.40; 95% CI: 0.17, 0.93; for phenethyl ITC, HR: 0.40; 95% CI: 0.19, 0.86). CONCLUSIONS: Our findings indicate the possible beneficial role of dietary ITCs in NMIBC prognosis. Given the compelling preclinical evidence, increasing dietary ITC exposure with CV intake could be a promising strategy to attenuate recurrence and progression risks in patients with NMIBC.