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To compare survival among patients with head and neck cancer before and after implementing a weekly multidisciplinary clinic and case conference.A retrospective cohort study with chart review was conducted of 3081 patients (1431 preimplementation, 1650 postimplementation) diagnosed with stage I-IVB tumors in the oral cavity, oropharynx, hypopharynx, nasopharynx, or larynx. Pre- and postimplementation differences in overall and disease-specific survival 1, 2, and 3 years after diagnosis were assessed with unadjusted Kaplan-Meier curves and multivariable Cox proportional hazard regression models adjusted for demographic characteristics, comorbidity burden, smoking status, tumor site and stage, p16 status for oropharyngeal squamous cell cancer, and initial treatment modality.Patients less commonly presented with oropharyngeal squamous cell cancer and advanced tumors (III-IVB) and received primary treatment with surgery alone or with adjuvant therapy preimplementation than postimplementation. Overall survival at 3 years was 77.1% and 79.9% (A multidisciplinary clinic and case conference were associated with improved outcomes among patients with head and neck cancer, especially those with advanced tumors.All patients with head and neck cancer should receive multidisciplinary team management, especially those with advanced tumors.

PURPOSE: Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown. METHODS: We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2,152 HR+ BC patients diagnosed from 2006–2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at six-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture. RESULTS: Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although

Background Lactation is associated with lower risks for cardiovascular disease in women. Organ-related adiposity, which plays significant roles in the development of cardiometabolic diseases, could help explain this observation. We evaluated the association of lactation duration with visceral (VAT) and pericardial (PAT) fat volumes in women. Methods Data were obtained from 910 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study (1985-1986) without diabetes prior to pregnancy who had ≥1 birth during 25 years of follow-up and had VAT and PAT measured from computed tomographic scans in 2010-2011. Cumulative lactation duration across all births since baseline was calculated from self-reports collected at periodic exams. Results At baseline, the average age of women (48% black, 52% white) was 24 ± 3.7 years. After controlling for baseline age, race, smoking status, body mass index, fasting glucose, family history of diabetes, fat intake, total cholesterol, physical activity, and follow-up covariates (parity, gestational diabetes), the mean fat volumes across categories of lactation [none (n = 221), 1-5 months (n = 306), 6-11 months (n = 210), and ≥12 months (n = 173)] were 122.0, 113.7 105.0, and 110.1 cm3 for VAT and 52.2, 46.7, 44.5, and 43.4 cm3 for PAT, respectively. Changes in body weight from the first post-baseline birth to the end of follow-up mediated 21% and 18% of the associations of lactation with VAT and PAT, respectively. Conclusions In this prospective study, longer cumulative lactation duration was associated with lower VAT and PAT volumes, with weight gain partially mediating these associations.

Histone deacetylase inhibitors, including valproic acid, selectively induce cellular differentiation and apoptosis in melanoma cells. No published pharmacoepidemiologic studies have explored the association between valproic acid use and melanoma risk. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n = 2,213,845) from 1997 to 2012 to examine the association between valproic acid use and melanoma risk. Melanoma hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, adjusted for age, sex, calendar year, and healthcare use. Melanoma incidence was lower among exposed individuals (64.0 exposed vs. 96.2 unexposed per 100,000 person-years, P0.001). Exposed individuals had a lower incident melanoma risk (HR = 0.64; 95% CI = 0.51-0.79) in unadjusted analysis, and the estimate was attenuated but significant in adjusted analysis (HR = 0.76, 95% CI = 0.61-0.94). Cumulative exposure based on the number of fills revealed a biologically implausible inverse dose-effect. Exposed individuals were more likely to present with local than regional or distant disease at diagnosis (80/82; 97.6% exposed vs. 12,940/13,971; 92.6% unexposed). Our findings suggest that valproic acid exposure may be associated with decreased melanoma risk and progression, but the cumulative exposure analyses suggest that the observation may be owing to residual confounding.

Background Associations of excessive gestational weight gain (GWG) with greater birthweight and childhood obesity may be confounded by shared familial environment or genetics. Sibling comparisons can minimize variation in these confounders because siblings grow up in similar environments and share the same genetic predisposition for weight gain. Methods We identified 96 289 women with live births in 2008–2014 at Kaiser Permanente Northern California. Fifteen percent of women (N = 14 417) had at least two births during the study period for sibling analyses. We assessed associations of GWG according to the Institute of Medicine (IOM) recommendations with birthweight and obesity at age 3 years, using conventional analyses comparing outcomes between mothers and sibling analyses comparing outcomes within mothers, which control for stable within-family unmeasured confounders such as familial environment and genetics. We used generalized estimating-equations and fixed-effects models. Results In conventional analyses, GWG above the IOM recommendations was associated with 88% greater odds of large-for-gestational age birthweight [95% confidence interval (CI): 1.80, 1.97] and 30% greater odds of obesity at 3 years old (95% CI: 1.24, 1.37) compared with GWG within the IOM recommendations. In sibling analyses, GWG above the IOM recommendations was also associated with greater odds of large-for-gestational age [odds ratio (OR): 1.36; 95% CI: 1.20, 1.54], but was not associated with obesity at 3 years old (OR = 0.98; 95% CI: 0.84, 1.15). Conclusions GWG likely has a direct impact on birthweight; however, shared environmental and lifestyle factors within families may play a larger role in determining early-childhood weight status and obesity risk than GWG.

BACKGROUND: Maternal nutrition during pregnancy has a significant effect on the health of the offspring and mother, highlighting the need for identifying factors that may impact diet during pregnancy. Research in non-pregnant and pregnant populations suggest depression may play a role. OBJECTIVE: Investigate the relationship between prenatal depression and diet quality during pregnancy overall and by race/ethnicity and explore the relationships between prenatal depression and the 12 Healthy Eating Index (HEI-2010) dietary components. DESIGN: A cross-sectional secondary analysis of a cohort study of Kaiser Permanente Northern California women entering prenatal care between October 2011 and April 2013. PARTICIPANTS/SETTING: Participants included 1,160 adult pregnant women. MAIN OUTCOME MEASURES: Poor diet quality was defined as a HEI-2010 score in the lowest quartile. STATISTICAL ANALYSES PERFORMED: Logistic regression was used to assess the relationship between prenatal depression (defined as a depression diagnosis, PHQ-9 score of 10 or greater or antidepressant medication dispensing between the last menstrual period and completion of the FFQ) and poor diet quality overall and by race/ethnicity. T-tests and linear regression analyses were used to assess the relationships between prenatal depression and each of the 12 HEI-2010 dietary components. RESULTS: 159 (14%) of the participants had prenatal depression. Women with prenatal depression had nearly two times the odds of poor diet quality (OR:1.80;95%CI:1.23,2.60) compared to women without prenatal depression, after adjusting for potential confounders. Differences emerged by race/ethnicity; after adjusting for potential confounders the adjusted odds of poor diet quality were significant only among Hispanic women. Hispanic women with prenatal depression had an increased odds of poor diet quality compared to Hispanic women without prenatal depression (OR:2.66, 95%CI:1.15,6.06). Women with prenatal depression had a higher consumption of empty calories (from solid fats, alcohol, and added sugars; threshold for counting alcohol is greater than 13g/1,000 kcal ) (p=0.01) and lower consumption of greens and beans (p

INTRODUCTION AND OBJECTIVE:Historically, prognostic studies of intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC) have focused on the risk of initial recurrence, yet little is known ab...

INTRODUCTION AND OBJECTIVE:The transurethral resection of bladder tumor (TURBT) is a common urologic procedure with a reported complication rate of about 5% according to administrative data. Howeve...

Objectives: To examine the association between treatment status and mortality risk among patients with papillary thyroid cancer (PTC). Methods: We identified 3,679 adults with PTC. Thirty-one untreated patients were matched to 155 treated patients. Hazards ratios (HR) and 95% confidence intervals (CIs) were calculated to estimate all-cause and disease-specific mortality. A low-risk subgroup was analyzed for differences in all-cause mortality. Results: The adjusted HRs (95% CIs) for all-cause mortality at 5 and 10 years were 4.2 (1.7-10.3) and 4.1 (1.9-9.4) and for disease- specific mortality were 14.1 (3.4-59.3) and 10.2 (2.9-36.4), respectively, for untreated versus treated patients. The adjusted HRs (95% CIs) for all- cause mortality was 0.7 (0.1-6.4) for low-risk untreated versus matched treated patients. Conclusions: Compared to treated patients, untreated PTC patients were at higher risk of death while low-risk untreated PTC patients had comparable rate of metastasis and no increased risk of all-cause mortality. Level of evidence: 3

PURPOSE: To estimate risks of incident Type 2 Diabetes (T2D) and Stage 2 and greater hypertension associated with self-reported and accelerometer-determined moderate-vigorous physical activity (MVPA) separately and adjusted for each other. METHODS: The sample included 2,291 black and white men and women, ages 38–50, in the CARDIA (Coronary Artery Risk Development in Young Adults) Fitness Study, conducted during the Year 20 core CARDIA exam. Accelerometer-determined (Actigraph, LLC. model 7164) MVPA (MVPA-Acc), assessed at Year 20, was defined as mins/day of counts ≥2020/min. Self-reported MVPA (MVPA-SR) was assessed at Year 20 using the CARDIA Physical Activity History. Incident T2D was ascertained at Years 25 and 30 from fasting glucose, 2 hr GTT, HbA1c or diabetes medication; incident hypertension was ascertained at those same times from measured blood pressure or use of antihypertensive medications. Modified Poisson regression models estimated relative risk (RR) of incident (Years 25 and 30) T2D or hypertension, associated with middle and high tertiles of Year 20 MVPA-Acc alone, Year 20 MVPA-SR alone, and both, adjusted for each other, relative to bottom tertile. RESULTS: In men, MVPA-Acc, but not MVPA-SR, was associated with a 37–67% decreased risk of incident T2D in a dose response relation that persisted with adjustment for BMI, Similar associations were observed in women, although the risk reduction was similar in the second and third tertiles, relative to the bottom tertile. In both men and women, MVPA-Acc was marginally associated with reduced risk of incident Stage 2 and greater hypertension, but only after adjustment for BMI, while MVPA-SR was not associated in either sex. CONCLUSIONS: Accelerometer-determined MVPA may provide more consistent risk estimates for incident diabetes than self-reported MVPA.

ObjectiveWomen have >50% greater lifetime risk of dementia than men but the role of female-specific endocrine milieu is not well-understood. This study evaluates associations between indicators of estrogen exposure from women's reproductive period and dementia risk in a large diverse population.MethodsWe evaluated 15,754 female members (29.9% nonwhite) of Kaiser Permanente with clinical examinations and health survey data from 1964 to 1973 and were members as of January 1, 1996. In midlife (mean age 51.1 years), women reported age at menarche and menopause and hysterectomy status. Reproductive span was calculated as menopause age minus menarche age. Dementia diagnoses were abstracted from January 1, 1996 to September 30, 2017 medical records (mean age at start of dementia follow-up 76.5 years). Cox proportional hazard models evaluated associations between aspects of reproductive span and dementia risk adjusting for demographics and life course health indicators.ResultsForty-two percent of women developed dementia. Compared to menarche at age 13.0 (mean menarche age), menarche at ≥16 was associated with 23% greater dementia risk (adjusted hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.01–1.50) adjusting for demographics and life course health indicators. Natural menopause at age ConclusionIn this large prospective cohort study, endocrine events signaling less estradiol exposure (i.e., later age at menarche, younger age at menopause, shorter reproductive span, and hysterectomies) were associated with elevated risk of dementia.

Introduction Little is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence. Methods Incident dementia diagnoses from 1/1/2010 to 9/30/2015 were abstracted from medical records for 2350 members of an integrated health care system in California (n = 1702 whites, n = 375 blacks, n = 105 Latinos, n = 168 Asians) aged ≥90 in 2010. We estimated race/ethnicity-specific age-adjusted dementia incidence rates and implemented Cox proportional hazards models and Fine and Gray competing risk of death models adjusted for demographics and comorbidities in midlife and late-life. Results Dementia incidence rates (n = 771 cases) were lowest among Asians (89.9/1000 person-years), followed by whites (96.9/1000 person-years), Latinos (105.8/1000 person-years), and blacks (121.5/1000 person-years). Cox regression and competing risk models estimated 28% and 36% higher dementia risk for blacks versus whites adjusting for demographics and comorbidities. Discussion Patterns of racial/ethnic disparities in dementia seen in younger older adults continue after the age of 90 years, though smaller in magnitude.

Importance Birth in areas with high infant mortality rates (IMRs) has been linked to worse long-term health outcomes, yet it is completely unknown if it impacts dementia risk. Methods In total 6268 health care members were followed for dementia diagnosis from 1996 to 2015. Birth state IMRs from 1928 were ranked into quartile (worst IMRs quartile range, whites: 69 to 129 deaths/1000 live births, Non-whites: 129 to 277 deaths/1000 live births). Cox proportional hazard models estimated the dementia risk associated with birth state IMR quartile adjusting for demographics and lifecourse health indicators. Results Compared with whites born outside of states in the worst IMR quartile, African Americans born in states in the worst IMR quartile had 92% increased dementia risk (HR=1.92; 95% CI: 1.42, 2.59), and African Americans born outside those states had 36% increased risk (HR=1.36; 95% CI: 1.20, 1.53). There was no association between birth state IMR and dementia risk among whites. Conclusions Birth in states with the highest rates of infant mortality was associated with elevated dementia risk among African Americans but not whites. The large absolute difference in IMRs likely reflects harsher early childhood conditions experienced by African Americans. These findings suggest that childhood conditions may play a role in racial disparities in dementia rates.

Gestational diabetes (GDM) predisposes 7-10% of pregnant women in the U.S. to a myriad of adverse health sequelae. Early prediction is critical. By leveraging metabolomics and clinical data, we aimed to develop and validate predictive metabolic signatures in early to mid-pregnancy for GDM. In a nested matched case-controls study of 91 women with GDM and 180 non-GDM controls in the Pregnancy Environment and Lifestyle Study (PETALS) cohort (discovery set), 157 annotated primary metabolites were measured by gas chromatography/time-of-flight mass spectrometry using fasting serum at gestational weeks (GW) 10-13 and 16-19. Machine learning algorithm using 10-fold cross validated Lasso regression identified predictive metabolomics signatures for GDM risk in the discovery set. We validated the signature at GW 10-13 in a random PETALS subsample (42 GDM, 372 non-GDM; validation set 1) and a matched case-control study within the GLOW trial of overweight/obese women (35 GDM, 70 non-GDM; validation set 2) and the signature at GW 16-19 in validation set 1. Upregulated aromatic and acidic amino acids and purinones at both GW 10-13 and 16-19 and additionally hexoses at GW 16-19 were significantly associated with GDM risk (FDR-adjusted P Disclosure Y. Zhu: None. A. Ngo: None. S. Fan: None. D. Barupal: None. C. Quesenberry: None. O. Fiehn: None. A. Ferrara: None. Funding National Institutes of Health (K12HD052163); National Institute of Diabetes and Digestive and Kidney Diseases (K01DK120807)

ObjectiveTo determine whether severe hypoglycemic and hyperglycemic events are associated with longitudinal dementia risk in older adults with type 1 diabetes.MethodsA longitudinal cohort study followed up 2,821 members of an integrated health care delivery system with type 1 diabetes from 1997 to 2015. Hypoglycemic and hyperglycemic events requiring emergency room or hospitalization were abstracted from medical records beginning January 1, 1996, through cohort entry. Participants were followed up for dementia diagnosis through September 30, 2015. Dementia risk was examined with Cox proportional hazard models adjusted for age (as time scale), sex, race/ethnicity, hemoglobin A1c, depression, stroke, and nephropathy.ResultsAmong 2,821 older adults (mean age 56 years) with type 1 diabetes, 398 (14%) had a history of severe hypoglycemia, 335 (12%) had severe hyperglycemia, and 87 (3%) had both. Over a mean 6.9 years of follow-up, 153 individuals (5.4%) developed dementia. In fully adjusted models, individuals with hypoglycemic events had 66% greater risk of dementia than those without a hypoglycemic event (hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.09, 2.53), while those with hyperglycemic events had >2 times the risk (HR 2.11, 95% CI 1.24, 3.59) than those without a hyperglycemic event. There was a 6-fold greater risk of dementia in individuals with both severe hypoglycemia and hyperglycemia vs those with neither (HR 6.20, 95% CI 3.02, 12.70).ConclusionsFor older individuals with type 1 diabetes, severe hypoglycemic and hyperglycemic events are associated with increased future risk of dementia.

Highlights • 3% of high-risk midlife women participated in lifestyle-related resources. • Lifestyle-related resource use was associated with more physical activity. • Lifestyle-related resource use was associated with lower weight in obese women. • Lifestyle-related resource use was associated with lower glucose in some women., Health plan-based resources are promising avenues for decreasing cardiovascular disease risk. This study examined associations of lifestyle-related resource utilization within a healthcare delivery system and cardiovascular biomarkers among midlife women with low physical activity. Midlife women (45-55 years old) with

Magnetic field (MF) non-ionizing radiation is widespread and everyone is exposed to some degree. This prospective cohort study of 913 pregnant women examined the association between high MF exposure and miscarriage risk. Cox (proportional hazards) regression was used to examine the association. After controlling for multiple other factors, women who were exposed to higher MF levels had 2.72 times the risk of miscarriage (hazard ratio = 2.72, 95% CI: 1.42–5.19) than those with lower MF exposure. The increased risk of miscarriage associated with high MF was consistently observed regardless of the sources of high MF. The association was much stronger if MF was measured on a typical day of participants’ pregnancies. The finding also demonstrated that accurate measurement of MF exposure is vital for examining MF health effects. This study provides fresh evidence, directly from a human population, that MF non-ionizing radiation could have adverse biological impacts on human health.

Objectives Traditional mindfulness-based interventions have been shown to reduce depression symptoms in pregnant women, although in-person classes may pose significant accessibility barriers, particularly during the COVID-19 pandemic. Mobile technology offers greater convenience, but little is known regarding the efficacy of self-paced, mobile-delivered (mHealth) mindfulness interventions in this population. This study tested the feasibility and acceptability of offering such an intervention for pregnant women with moderate-to-moderately-severe depression symptoms. Methods We conducted a single-arm trial within Kaiser Permanente Northern California (KPNC). Participants were identified through KPNC’s universal perinatal depression screening program. Eligible participants included English-speaking pregnant women (

Preterm birth (PTB) remains a leading cause of neonatal mortality and long-term morbidity. Individual factors have been linked to PTB risk. The impact of a healthy lifestyle, with multiple modifiable prenatal factors, remains unknown.We aimed to examine the associations of preconceptional and early-pregnancy low-risk modifiable factors (individually and in combination) with PTB risk.This prospective cohort study included 2449 women with singleton pregnancies in the Pregnancy Environment and Lifestyle Study. PTB was defined as ultrasound-confirmed obstetric estimate-based gestational age at delivery37 wk. A set of low-risk modifiable factors were identified: healthy weight (prepregnancy BMI: 18.5-24.9 kg/m2) based on clinical measurements and high-quality diet (Alternate Healthy Eating Index-Pregnancy score ≥75th percentile) and low-to-moderate stress during early pregnancy (Perceived Stress Scale score75th percentile) assessed at gestational weeks 10-13. Poisson regression estimated adjusted relative risk (aRR) of PTB in association with individual and combined low-risk modifiable prenatal factors, adjusting for sociodemographic, clinical, and other prenatal factors.One hundred and sixty women (6.5%) delivered preterm. Risk of PTB was lower among women who had a healthy weight (aRR: 0.58; 95% CI: 0.39, 0.86), high-quality diet (aRR: 0.68; 95% CI: 0.39, 0.99), and low-to-moderate stress (aRR: 0.60; 95% CI: 0.41, 0.88). Women with 1, 2, or 3 low-risk modifiable prenatal factors compared with none had a 38% (aRR: 0.72; 95% CI: 0.45, 1.16), 51% (aRR: 0.49; 95% CI: 0.29, 0.84), or 70% (aRR: 0.30; 95% CI: 0.13, 0.70) lower PTB risk, respectively. Associations of having ≥1 low-risk factor with PTB risk were more pronounced for medically indicated than for spontaneous PTB and for late than for early or moderate PTB. Associations also varied by race or ethnicity, although with overlapping 95% CIs.A healthy prenatal lifestyle with multiple low-risk modifiable factors was associated with lower risk of PTB. Our findings may inform multicomponent preconceptional or early-pregnancy prevention strategies to mitigate PTB risk.

Low muscle is associated with an increased risk of chemotherapy-related dose limiting toxicities (DLT) in cancer patients. Resistance training (RT) improves muscle mass; however, the effects of RT on preventing DLTs and dose reductions in colon cancer patients has not been investigated. FOcus on Reducing dose-limiting toxicities in Colon cancer with resistance Exercise (FORCE) is a multicenter, randomized clinical trial examining the effects of RT on relative dose intensity (RDI; primary outcome) and moderate and severe chemotoxicities (primary outcome) in non-metastatic colon cancer patients receiving adjuvant chemotherapy. Patients (N = 180) will be recruited from Kaiser Permanente Northern California, Dana-Farber Cancer Institute, and Penn State Cancer Institute. This paper describes recruitment strategies and design considerations. Patients will be randomized in equal numbers to RT intervention or control. Patients have baseline and post completion of chemotherapy visits where information on anthropometry, physical function, body composition, quality of life, physical activity and dietary behaviors, and inflammatory blood markers will be collected. Patient-reported outcomes of chemotherapy side effects will be collected around the time of chemotherapy throughout the duration of the trial. Intervention participants will be prescribed a progressive RT program consisting of 4–6 visits with a certified exercise trainer, delivered either in-person or remotely by video conference, and will be asked to engage twice weekly in-home training sessions. Control patients at the end of the study receive a consult with a FORCE exercise trainer, an online exercise RT training program and a set of resistance bands. Results of this trial will provide information on the benefit of resistance exercise as a treatment to increase RDI.

Importance Topical calcineurin inhibitors (TCIs), primarily used to treat atopic dermatitis (AD), carry a black box label warning users about the potential for increased skin cancer risk. The risk associated with keratinocyte carcinoma (KC), the most common cancer, defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), remains poorly defined because findings from large-scale postmarketing surveillance studies have not been reported. Objectives To examine KC risk overall and by subtype (BCC and SCC) among adults with AD exposed to TCIs compared with those exposed to topical corticosteroids (primary comparator group) and those unexposed to TCIs or topical corticosteroids (alternative comparator group) as well as alterations in risk with TCI dose, frequency, and duration of exposure. Design, Setting, and Participants A retrospective cohort study was conducted at Kaiser Permanente Northern California, a large, integrated health care delivery system, of adults 40 years or older (n = 93 746) with a physician-rendered diagnosis of AD or dermatitis. Patients who were diagnosed from January 1, 2002, to December 31, 2013, were included, with follow-up through December 31, 2017. Data analysis was conducted from June 1, 2016, to October 1, 2018. Exposures Time-varying pharmacy-dispensed TCI exposure (n = 7033) over the study period was compared with topical corticosteroids (n = 73 674) and no TCI or topical corticosteroid exposure (n = 46 141). Main Outcomes and Measures Electronic pathologic testing–validated incident KCs (n = 7744). Results Among a cohort of 93 746 members, the mean (SD) age was 58.5 (12.7) years, and 55 023 patients (58.7%) were women. Multivariable Cox proportional hazards regression revealed no association between TCI exposure and KC risk (adjusted hazard ratio [aHR], 1.02; 95% CI, 0.93-1.13) compared with topical corticosteroid exposure. Similarly, there were no significant differences in BCC risk (aHR, 1.01; 95% CI, 0.90-1.14, TCI vs topical corticosteroids) or SCC risk (aHR, 0.94; 95% CI, 0.82-1.08, TCI vs topical corticosteroids). Changing the comparator group to unexposed individuals yielded similar findings (aHR, 1.04; 95% CI, 0.91-1.19, TCI vs unexposed for basal cell carcinoma). There were no associations between TCI dose, frequency, and duration of use and BCC, SCC, or overall KC risk. Conclusions and Relevance The results of this postmarketing surveillance study of adult health plan members with AD revealed no apparent association between TCI exposure and overall KC, BCC, or SCC risk. Secondary analyses examining dose, frequency, and duration of TCI exposure revealed no associations. These findings suggest that use of TCIs may be safe with respect to KC risk among adults with AD.

Importance Azithromycin is one of the most commonly prescribed antibiotics in the US. It has been associated with an increased risk of cardiovascular death in some observational studies. Objective To estimate the relative and absolute risks of cardiovascular and sudden cardiac death after an outpatient azithromycin prescription compared with amoxicillin, an antibiotic not known to increase cardiovascular events. Design, Setting, and Participants This retrospective cohort study included 2 large, diverse, community-based integrated care delivery systems with comprehensive capture of encounters and prescriptions from January 1, 1998, to December 31, 2014. The cohort included patients aged 30 to 74 years who had at least 12 months of health-plan enrollment prior to antibiotic exposure. The exclusion criteria were absence of prescription benefits, prescription for more than 1 type of study antibiotic within 10 days, hospitalization or nursing home residence, and serious medical conditions. Risk of cardiovascular death associated with azithromycin vs amoxicillin exposure was calculated after controlling for confounding factors using a propensity score. Data were analyzed from December 1, 2016, to March 30, 2020. Exposures Outpatient prescription of azithromycin or amoxicillin. Main Outcomes and Measures The primary outcomes were cardiovascular death and sudden cardiac death. An a priori subgroup analysis quantified the effects of azithromycin exposure among patients with increased baseline cardiovascular risk. The secondary outcomes were noncardiovascular death and all-cause mortality. Results The study included 7 824 681 antibiotic exposures, including 1 736 976 azithromycin exposures (22.2%) and 6 087 705 amoxicillin exposures (77.8%), among 2 929 008 unique individuals (mean [SD] age, 50.7 [12.3] years; 1 810 127 [61.8%] women). Azithromycin was associated with a significantly increased hazard of cardiovascular death (hazard ratio [HR], 1.82; 95% CI, 1.23-2.67) but not sudden cardiac death (HR, 1.59; 95% CI, 0.90-2.81) within 5 days of exposure. No increases in risk were found 6 to 10 days after exposure. Similar results were observed in patients within the top decile of cardiovascular risk (HR, 1.71; 95% CI, 1.06-2.76). Azithromycin was also associated with an increased risk of noncardiovascular death (HR, 2.17; 95% CI, 1.44-3.26) and all-cause mortality (HR, 2.00; 95% CI, 1.51-2.63) within 5 days of exposure. Conclusions and Relevance These findings suggest that outpatient azithromycin use was associated with an increased risk of cardiovascular death and noncardiovascular death. Causality cannot be established, particularly for noncardiovascular death, owing to the likelihood of residual confounding.

Women with a history of gestational diabetes (GDM) are at high risk for developing type 2 diabetes, which may be further increased with weight gain after pregnancy. Our objective was to determine associations of long-term weight changes after a GDM pregnancy and type 2 diabetes risk. We used data on a cohort of 139 women with a GDM pregnancy identified though the Kaiser Permanente Northern California (KPNC) GDM registry (1986-2009) who completed a follow-up study visit an average of 16 years later (2011-2013). Type 2 diabetes was identified through the KPNC diabetes registry, self-report during follow-up visit recruitment, or at least one abnormal value on a 75-gram, 2-hour oral glucose tolerance test (2015 ADA criteria) conducted at the follow-up visit. Clinically measured weights extracted from the electronic health record were used to calculate average BMI change per year between delivery and either type 2 diabetes identification date or follow-up visit date. We used modified Poisson regression to estimate relative risks of type 2 diabetes associated with BMI change categories. Twenty-six percent of women lost weight [mean -0.3 BMI units/year, equivalent to -0.8 kg/year for a woman of the average height in our cohort (1.6 m)], 24% maintained their weight ( Disclosure S.E. Badon: None. F. Xu: None. C. Quesenberry: None. A. Ferrara: None. M.M. Hedderson: None. Funding National Institutes of Health (R01HD065904)

Hypertensive disorders in pregnancy and GDM are among the leading causes of maternal and perinatal morbidity. In 2017, the American College of Cardiology/American Heart Association released a new guideline for hypertension: systolic/diastolic blood pressure (SBP/DBP) ≥130/80 vs. previous 140/90 mmHg. However, these new cut-points have not been applied to pregnant women due to the lack of evidence on its impact on perinatal outcomes. We examined in women with and without GDM whether the risk of perinatal complications increased across SBP/DBP levels: normal ( Disclosure Y. Zhu: None. J. Feng: None. A. Ngo: None. C. Quesenberry: None. A. Ferrara: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K01DK120807)

Introduction Data on the comparative effectiveness of Diabetes Prevention Programs (DPPs) in the workplace are limited. Methods Between September 2015 and July 2016, employees of the City and County of San Francisco who were at risk for type 2 diabetes (N = 158) were randomly assigned to one of 2 DPP-derived programs recognized by the Centers for Disease Control and Prevention: an in-person YMCA-DPP (n = 78) or an online virtual lifestyle management DPP (VLM-DPP) offered through Canary Health (n = 80). The primary outcome was change in body weight assessed at 6 and 12 months. Follow-up ended in August 2017. Results Both the YMCA-DPP and VLM-DPP yielded a significant reduction in percentage body weight at 6 months. For the YMCA-DPP, mean percentage change at 6 months was -2.70% (95% confidence interval [CI], -3.91% to -1.48%) and at 12 months was -2.46% (95% CI, -4.24% to -0.68%). For the VLM-DPP, mean percentage change at 6 months was -2.41% (95% CI, -4.07% to -0.77%) and at 12 months was -1.59% (95% CI, -3.51% to 0.33%). The mean between-condition difference at 6 months was -0.25% (95% CI, -2.04% to 1.55%) and at 12 months was -0.84% (95% CI, -3.03% to 1.34%). No significant differences were observed between conditions. The YMCA-DPP had a slightly higher reduction in waist circumference than VLM-DDP at 6 months (mean between-condition difference -2.00 cm [95% CI, -4.24 to 0.25 cm]). Participant engagement, expressed as mean number of completed core program sessions, was significantly higher for the YMCA-DPP than the VLM-DPP. Participants of the YMCA-DPP completed an average of 10.2 sessions (95% CI, 9.0 to 11.4), and participants of the VLM-DPP completed an average of 5.9 sessions (95% CI, 4.7 to 7.1). The adjusted mean between-condition difference was 4.2 sessions (95% CI, 2.54 to 5.99). Conclusion Both the YMCA-DPP and VLM-DPP yielded weight loss at 6 months, which was maintained at 12 months in the YMCA-DPP. The workplace may be an effective setting to offer DPPs.

Surrogate measures of infectious exposures have been consistently associated with lower childhood acute lymphoblastic leukemia (ALL) risk. However, recent reports have suggested that physician-diagnosed early-life infections increase ALL risk, thereby raising the possibility that stronger responses to infections might promote risk. We examined whether medically diagnosed infections were related to childhood ALL risk in an integrated health-care system in the United States. Cases of ALL (n = 435) diagnosed between 1994–2014 among children aged 0–14 years, along with matched controls (n = 2,170), were identified at Kaiser Permanente Northern California. Conditional logistic regression was used to estimate risk of ALL associated with history of infections during first year of life and across the lifetime (up to diagnosis). History of infection during first year of life was not associated with ALL risk (odds ratio (OR) = 0.85, 95% confidence interval (CI): 0.60, 1.21). However, infections with at least 1 medication prescribed (i.e., more “severe” infections) were inversely associated with risk (OR = 0.42, 95% CI: 0.20, 0.88). Similar associations were observed when the exposure window was expanded to include medication-prescribed infections throughout the subjects’ lifetime (OR = 0.52, 95% CI: 0.32, 0.85).

Among 25 291 and 4 921 830 people with and without hepatitis C, life expectancy at age 20 increased 1.8 years and 0.3 years from the interferon to interferon-free era, respectively. Increases were highest for racial and/or ethnic minority groups with hepatitis C.

OBJECTIVE This study examined the associations of central obesity measures, waist to hip ratio (WHR) and waist circumference (WC), in early pregnancy with subsequent risk of gestational diabetes mellitus (GDM) and evaluated the potential mediating role of insulin resistance markers. METHODS Within the prospective Pregnancy Environment and Lifestyle Study cohort of 1,750 women, WC and hip circumference were measured at gestational weeks 10 to 13. In a nested case-control study within the cohort, 115 GDM cases and 230 controls had fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and adiponectin measurements at gestational weeks 16 to 19. Poisson and conditional logistic regression models were used, adjusting for established risk factors for GDM, including prepregnancy overweight or obesity. RESULTS For women with WHR

Context Previous studies have not examined the ability of multiple preconception biomarkers, considered together, to improve prediction of gestational diabetes mellitus (GDM). Objective To develop a preconception biomarker risk score and assess its association with subsequent GDM. Design A nested case-control study among a cohort of women with serum collected as part of a health examination (1984 to 1996) and subsequent pregnancy (1984 to 2009). Biomarkers associated with GDM were dichotomized into high/low risk. Setting Integrated health care system. Participants Two controls were matched to each GDM case (n = 256 cases) on year and age at examination, age at pregnancy, and number of pregnancies between examination and index pregnancy. Main Outcome Measure GDM. Results High-risk levels of sex hormone-binding globulin (SHBG; 90 mg/dL), total adiponectin (3.9) were independently associated with 2.34 [95% confidence interval (CI): 1.50, 3.63], 2.03 (95% CI: 1.29, 3.19), 1.83 (95% CI: 1.16, 2.90), and 1.67 (95% CI: 1.07, 2.62) times the odds of GDM and included in the biomarker risk score. For each unit increase in the biomarker risk score, odds of GDM were 1.94 times greater (95% CI: 1.59, 2.36). A biomarker risk score including only SHBG and glucose was sufficient to improve prediction beyond established risk factors (age, race/ethnicity, body mass index, family history of diabetes, previous GDM; area under the curve = 0.73 vs 0.67, P = 0.002). Conclusions The improved, predictive ability of the biomarker risk score beyond established risk factors suggests clinical use of the biomarker risk score in identifying women at risk for GDM before conception for targeted prevention strategies.

OBJECTIVE Individuals with type 1 diabetes have experienced an increase in life expectancy, yet it is unknown what level of glycemic control is ideal for maintaining late-life brain health. We investigated the association of long-term glycemic control with dementia in older individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS We followed 3,433 members of a health care system with type 1 diabetes, aged ≥50 years, from 1996 to 2015. Repeated measurements of hemoglobin A1c (HbA1c), dementia diagnoses, and comorbidities were ascertained from health records. Cox proportional hazards models were fit to evaluate the association of time-varying glycemic exposure with dementia, with adjustment for age, sex, race/ethnicity, baseline health conditions, and frequency of HbA1c measurement. RESULTS Over a mean follow-up of 6.3 years, 155 individuals (4.5%) were diagnosed with dementia. Patients with ≥50% of HbA1c measurements at 8–8.9% (64–74 mmol/mol) and ≥9% (≥75 mmol/mol) had 65% and 79% higher risk of dementia, respectively, compared with those with CONCLUSIONS Among older patients with type 1 diabetes, those with majority exposure to HbA1c 8–8.9% and ≥9% had increased dementia risk, while those with majority exposure to HbA1c 6–6.9% and 7–7.9% had reduced risk. Currently recommended glycemic targets for older patients with type 1 diabetes are consistent with healthy brain aging.

BACKGROUND & AIMS: Treatment with the combination of ledipasvir and sofosbuvir for 12 weeks has been approved by the Food and Drug Administration for patients with genotype 1 hepatitis C virus (HCV) infection; some patients can be treated with an 8-week course. Guidelines recommend a 12-week treatment course for black patients, but studies have not compared the effectiveness of 8 vs 12 weeks in black patients who are otherwise eligible for an 8-week treatment regimen. METHODS: We conducted an observational study of Kaiser Permanente Northern California members with HCV genotype 1 infection who were eligible for 8 weeks of treatment with ledipasvir and sofosbuvir (treatment-naive, no cirrhosis, no HIV infection, level of HCV RNA

Objectives: The cost of direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection may contribute to treatment disparities. However, few data exist on factors associated with DAA initiation. Methods: We conducted a retrospective cohort study of HCV-infected Kaiser Permanente Northern California members aged ≥18 during October 2014 to December 2016, using Poisson regression models to evaluate demographic, behavioral, and clinical factors associated with DAA initiation. Results: Of 14 790 HCV-infected patients aged ≥18 (median age, 60; interquartile range, 53-64), 6148 (42%) initiated DAAs. DAA initiation was less likely among patients who were non-Hispanic black (adjusted rate ratio [aRR] = 0.7; 95% confidence interval [CI], 0.7-0.8), Hispanic (aRR = 0.8; 95% CI, 0.7-0.9), and of other minority races/ethnicities (aRR = 0.9; 95% CI, 0.8-1.0) than among non-Hispanic white people and among those with lowest compared with highest neighborhood deprivation index (ie, a marker of socioeconomic status) (aRR = 0.8; 95% CI, 0.7-0.8). Having maximum annual out-of-pocket health care costs >$3000 compared with ≤$3000 (aRR = 0.9; 95% CI, 0.8-0.9) and having Medicare (aRR = 0.8; 95% CI, 0.8-0.9) or Medicaid (aRR = 0.7; 95% CI, 0.6-0.8) compared with private health insurance were associated with a lower likelihood of DAA initiation. Behavioral factors (eg, drug abuse diagnoses, alcohol use, and smoking) were also significantly associated with a lower likelihood of DAA initiation (all P < .001). Clinical factors associated with a higher likelihood of DAA initiation were advanced liver fibrosis, HCV genotype 1, previous HCV treatment (all P < .001), and HIV infection ( P = .007). Conclusions: Racial/ethnic and socioeconomic disparities exist in DAA initiation. Substance use may also influence patient or provider decision making about DAA initiation. Strategies are needed to ensure equitable access to DAAs, even in insured populations.

BACKGROUND Breastfeeding (BF) may protect against obesity and type 2 diabetes mellitus in children exposed to maternal diabetes in utero, but its effects on infant growth among this high-risk group have rarely been evaluated. OBJECTIVES The objective of this study was to evaluate BF intensity and duration in relation to infant growth from birth through 12 months among offspring of mothers with gestational diabetes mellitus (GDM). METHODS Prospective cohort of 464 GDM mother-infant dyads (28% White, 36% Hispanic, 26% Asian, 8% Black, 2% other). Weight and length measured at birth, 6-9 weeks, 6 months and 12 months. Categorized as intensive BF or formula feeding (FF) groups at 6-9 weeks (study baseline), and intensity from birth through 12 months as Group 1: consistent exclusive/mostly FF, Group 2: transition from BF to FF within 3-9 months and Group 3: consistent exclusive/mostly BF. Multivariable mixed linear regression models estimated adjusted mean (95% confidence interval) change in z-scores; weight-for-length (WLZ), weight-for-age and length-for-age. RESULTS Compared with intensive BF at 6-9 weeks, FF showed greater increases in WLZ-scores from 6 to 9 weeks to 6 months [+0.38 (0.13 to 0.62) vs. +0.02 (-0.15 to 0.19); p = 0.02] and birth to 12 months [+1.11 (0.87 to 1.34) vs. +0.53 (0.37 to 0.69); p

Objective Retinopathy impacts over one-third of those with diabetes mellitus and is associated with impaired cognitive performance and cerebrovascular lesions in middle-aged adults with type 1 diabetes. However, the association between diabetic retinopathy (DR) and risk of dementia in type 1 diabetes is unknown. We investigated the association between DR and incident dementia in a large, elderly population with type 1 diabetes. Methods A cohort of 3742 patients with type 1 diabetes aged 50 years and above was followed from January 1, 1996 to September 30, 2015 for incident dementia. DR diagnoses were identified from electronic medical records. Age as timescale Cox proportional hazard models evaluated associations between time-updated DR and dementia risk. Models were adjusted for demographics, severe glycemic events, glycosylated hemoglobin, and vascular comorbidities. Results Among 3742 patients with type 1 diabetes (47% female, 21% nonwhite), 182 (5%) were diagnosed with dementia during a mean follow-up of 6.2 years. No significant association was found between DR and incident dementia in the main analyses [adjusted Hazard Ratio=1.12; 95% confidence interval, 0.82-1.54), nor among subgroup restricted to those aged 60 years and above or 70 years and above. Conclusions DR was not associated with risk of dementia, suggesting that pathophysiological processes underlying dementia may be different in type 1 versus type 2 diabetes.

A 17-gene biopsy-based reverse transcription polymerase chain reaction assay, which provides a Genomic Prostate Score (GPS-scale 0-100), has been validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP) in men with low- and intermediate-risk prostate cancer (PCa).To evaluate GPS as a predictor of PCa metastasis and PCa-specific death (PCD) in a large cohort of men with localized PCa and long-term follow-up.A retrospective study using a stratified cohort sampling design was performed in a cohort of men treated with RP within Kaiser Permanente Northern California. RNA from archival diagnostic biopsies was assayed to generate GPS results.We assessed the association between GPS and time to metastasis and PCD in prespecified uni- and multivariable statistical analyses, based on Cox proportional hazard models accounting for sampling weights.The final study population consisted of 279 men with low-, intermediate-, and high-risk PCa between 1995 and 2010 (median follow-up 9.8 yr), and included 64 PCD and 79 metastases. Valid GPS results were obtained for 259 (93%). In univariable analysis, GPS was strongly associated with time to PCD, hazard ratio (HR)/20 GPS units=3.23 (95% confidence interval [CI] 1.84-5.65; p0.001), and time to metastasis, HR/20 units=2.75 (95% CI 1.63-4.63; p0.001). The association between GPS and both end points remained significant after adjusting for National Comprehensive Cancer Network, American Urological Association, and Cancer of the Prostate Risk Assessment (CAPRA) risks (p0.001). No patient with low- or intermediate-risk disease and a GPS of20 developed metastases or PCD (n=31). In receiver operating characteristic analysis of PCD at 10 yr, GPS improved the c-statistic from 0.78 (CAPRA alone) to 0.84 (GPS+CAPRA; p0.001). A limitation of the study was that patients were treated during an era when definitive treatment was standard of care with little adoption of active surveillance.GPS is a strong independent predictor of long-term outcomes in clinically localized PCa in men treated with RP and may improve risk stratification for men with newly diagnosed disease.Many prostate cancers are slow growing and unlikely to spread or threaten a man's life, while others are more aggressive and require treatment. Increasingly, doctors are using new molecular tests, such as the17-gene Genomic Prostate Score (GPS), which can be performed at the time of initial diagnosis to help determine how aggressive a given patient's cancer may be. In this study, performed in a large community-based healthcare network, GPS was shown to be a strong predictor as to whether a man's prostate cancer will spread and threaten his life after surgery, providing information that may help patients and their doctors decide on the best course of management of their disease.

OBJECTIVE Severe hyperglycemia and hypoglycemia (“severe dysglycemia”) are serious complications of type 1 diabetes (T1D). Depression has been associated with severe dysglycemia in type 2 diabetes but has not been thoroughly examined specifically in T1D. We evaluated bidirectional associations between depression and severe dysglycemia among older people with T1D. RESEARCH DESIGN AND METHODS We abstracted depression and severe dysglycemia requiring emergency room visit or hospitalization from medical health records in 3,742 patients with T1D during the study period (1996–2015). Cox proportional hazards models estimated the associations between depression and severe dysglycemia in both directions, adjusting for demographics, micro- and macrovascular complications, and HbA1c. RESULTS During the study period, 41% had depression and 376 (11%) and 641 (20%) had hyperglycemia and hypoglycemia, respectively. Depression was strongly associated with a 2.5-fold increased risk of severe hyperglycemic events (hazard ratio [HR] 2.47 [95% CI 2.00, 3.05]) and 89% increased risk of severe hypoglycemic events (HR 1.89 [95% CI 1.61, 2.22]). The association was strongest within the first 6 months (HRhyperglycemia 7.14 [95% CI 5.29, 9.63]; HRhypoglycemia 5.58 [95% CI 4.46, 6.99]) to 1 year (HRhyperglycemia 5.16 [95% CI 3.88, 6.88]; HRhypoglycemia 4.05 [95% CI 3.26, 5.04]) after depression diagnosis. In models specifying severe dysglycemia as the exposure, hyperglycemic and hypoglycemic events were associated with 143% (HR 2.43 [95% CI 2.03, 2.91]) and 74% (HR 1.75 [95% CI 1.49, 2.05]) increased risk of depression, respectively. CONCLUSIONS Depression and severe dysglycemia are associated bidirectionally among patients with T1D. Depression greatly increases the risk of severe hypoglycemic and hyperglycemic events, particularly in the first 6 months to 1 year after diagnosis, and depression risk increases after severe dysglycemia episodes.

Magnetic field (MF) non-ionizing radiation is widespread and everyone is exposed to some degree. This prospective cohort study of 913 pregnant women examined the association between high MF exposure and miscarriage risk. Cox (proportional hazards) regression was used to examine the association. After controlling for multiple other factors, women who were exposed to higher MF levels had 2.72 times the risk of miscarriage (hazard ratio = 2.72, 95% CI: 1.42–5.19) than those with lower MF exposure. The increased risk of miscarriage associated with high MF was consistently observed regardless of the sources of high MF. The association was much stronger if MF was measured on a typical day of participants’ pregnancies. The finding also demonstrated that accurate measurement of MF exposure is vital for examining MF health effects. This study provides fresh evidence, directly from a human population, that MF non-ionizing radiation could have adverse biological impacts on human health.

Objective To evaluate 25-year physical activity (PA) trajectories from young to middle age and assess associations with the prevalence of coronary artery calcification (CAC). Patients and Methods This study includes 3175 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who self-reported PA by questionnaire at 8 follow-up examinations over 25 years (from March 1985-June 1986 through June 2010-May 2011). The presence of CAC (CAC>0) at year 25 was measured using computed tomography. Group-based trajectory modeling was used to identify PA trajectories with increasing age. Results We identified 3 distinct PA trajectories: trajectory 1, below PA guidelines (n=1813; 57.1%); trajectory 2, meeting PA guidelines (n=1094; 34.5%); and trajectory 3, 3 times PA guidelines (n=268; 8.4%). Trajectory 3 participants had higher adjusted odds of CAC>0 (adjusted odds ratio [OR], 1.27; 95% CI, 0.95-1.70) vs those in trajectory 1. Stratification by race showed that white participants who engaged in PA 3 times the guidelines had higher odds of developing CAC>0 (OR, 1.80; 95% CI, 1.21-2.67). Further stratification by sex showed higher odds for white males (OR, 1.86; 95% CI, 1.16-2.98), and similar but nonsignificant trends were noted for white females (OR, 1.71; 95% CI, 0.79-3.71). However, no such higher odds of CAC>0 for trajectory 3 were observed for black participants. Conclusion White individuals who participated in 3 times the recommended PA guidelines over 25 years had higher odds of developing coronary subclinical atherosclerosis by middle age. These findings warrant further exploration, especially by race, into possible biological mechanisms for CAC risk at very high levels of PA.

Objective:To evaluate the association of early-adulthood and mid-adulthood hypertension with dementia in men and women.Methods:We evaluated 5,646 members of a diverse integrated health care delivery system who had clinical examinations and health survey data from 1964 to 1973 (mean age 32.7 years; early adulthood) and 1978–1985 (mean age 44.3 years; mid-adulthood) and were members as of January 1, 1996 (mean age 59.8 years). Hypertension categories based on measurements of blood pressure (BP) and change in hypertension categories between the 2 examinations (e.g., onset hypertension) were used to predict dementia incidence from January 1, 1996, to September 30, 2015. Cox proportional hazard models were adjusted for demographics, vascular comorbidities, and hypertension treatment; inverse probability weighting accounted for differential attrition between first BP measurement and start of follow-up.Results:A total of 532 individuals (9.4%) were diagnosed with dementia. Early adulthood hypertension was not associated with dementia, though effect estimates were elevated among women. Mid-adulthood hypertension was associated with 65% (95% confidence interval [CI] 1.25–2.18) increased dementia risk among women but not men. Onset of hypertension in mid-adulthood predicted 73% higher dementia risk in women (95% CI 1.24–2.40) compared to stable normotensive. There was no evidence that hypertension or changes in hypertension increased dementia risk among men.Conclusions:Though midlife hypertension was more common in men, it was only associated with dementia risk in women. Sex differences in the timing of dementia risk factors have important implications for brain health and hypertension management.

Background Asian Americans are a rapidly growing and diverse population. Prior research on dementia among Asian Americans focused on Japanese Americans or Asian Americans overall, although marked differences in cardiometabolic conditions between subgroups have been documented. Materials and methods We compared dementia incidence among 4 Asian American subgroups (n=8384 Chinese; n=4478 Japanese; n=6210 Filipino; n=197 South Asian) and whites (n=206,490) who were Kaiser Permanente Northern California members aged 64 years and above with no dementia diagnoses as of January 1, 2000. Dementia diagnoses were collected from medical records January 1, 2000 to December 31, 2013. Baseline medical utilization and comorbidities (diabetes, depression, hypertension, stroke, cardiovascular disease) were abstracted from medical records January 1, 1996 to December 31, 1999. We calculated age-standardized dementia incidence rates and Cox models adjusted for age, sex, medical utilization, and comorbidities. Results Mean baseline age was 71.7 years; mean follow-up was 9.6 years. Age-standardized dementia incidence rates were higher among whites than "All Asian-Americans" or any subgroup. Compared with Chinese (13.7/1000 person-years), dementia incidence was slightly higher among Japanese [14.8/1000 person-years; covariate-adjusted hazard ratio (adjusted-HR)=1.08; 95% confidence interval (CI), 0.99-1.18] and Filipinos (17.3/1000 person-years; adjusted-HR=1.20; 95% CI, 1.11-1.31), and lower among South Asians (12.1/1000 person-years; adjusted-HR=0.81; 95% CI, 0.53-1.25). Conclusions Future studies are needed to understand how immigration history, social, environmental, and genetic factors contribute to dementia risk in the growing and diverse Asian American population.

Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival. Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan–Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I–III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer–specific mortality (CRCsM). Results: Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09–1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05–2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and Conclusions: Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker. Impact: Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008–15. ©2017 AACR.

OBJECTIVE The objective is to clarify the role of immunodeficiency and pneumonia in elevated lung cancer risk among HIV-infected individuals. DESIGN Cohort study of HIV-infected and HIV-uninfected adults in a large integrated healthcare system in California during 1996-2011. METHODS We used Poisson models to obtain rate ratios for lung cancer associated with HIV infection, overall and stratified by recent CD4 cells/μl (HIV-uninfected as reference group), with χ tests for trends across CD4 strata. Fully adjusted models included demographics, cancer risk factors (smoking, drug/alcohol abuse, overweight/obesity), and prior pneumonia. RESULTS Among 24 768 HIV-infected and 257 600 HIV-uninfected individuals, the lung cancer rate per 100 000 person-years was 66 (n = 80 events) for HIV-infected and 33 (n = 506 events) for HIV-uninfected individuals [rate ratio 2.0, 95% confidence interval (CI): 1.7-2.2]. Overall, HIV-infected individuals were at increased risk of lung cancer after adjustment for demographics and cancer risk factors (rate ratio 1.4, 95% CI: 1.1-1.7), but not after additional adjustment for pneumonia (rate ratio 1.2, 95% CI: 0.9-1.6). Lower CD4 cell counts were associated with higher risk of lung cancer in unadjusted and demographics-adjusted models (P

Summary Background Excess gestational weight gain (GWG) among women with overweight or obesity synergistically increases their already elevated risk of having gestational diabetes, a caesarean delivery, a large for gestational age infant, and post-partum weight retention, and increases their child's risk of obesity. We investigated whether a primarily telehealth lifestyle intervention reduced excess GWG among women with overweight or obesity. Methods We did a randomised controlled trial in five antenatal clinics of Kaiser Permanente; Oakland, San Leandro, Walnut Creek, Fremont, and Santa Clara, CA, USA. Women at 8–15 weeks' gestation with singletons, pre-pregnancy BMI 25·0–40·0 kg/m2, and aged 18 years or older were randomly assigned (1:1) to receive the telehealth lifestyle intervention or usual antenatal care. Randomisation was adaptively balanced for age, BMI, and race and ethnicity. Data collectors and investigators were masked to group assignments. The core lifestyle intervention consisted of two in-person and 11 telephone sessions on behavioural strategies to improve weight, diet, and physical activity, and stress management to help women meet a trial goal of gaining at the lower limit of the Institute of Medicine (IOM) guidelines range for total GWG: 7 kg for women with overweight and 5 kg for women with obesity. Usual antenatal care included an antenatal visit at 7–10 weeks' gestation, an additional seven antenatal visits, on average, and periodic health education newsletters, including the IOM GWG guidelines and information on healthy eating and physical activity in pregnancy. The primary outcome was weekly rate of GWG expressed as excess GWG, per Institute of Medicine guidelines and mean assessed in the intention-to-treat population. The trial is registered at ClinicalTrials.gov , NCT02130232 . Findings Between March 24, 2014, and Sept 26, 2017, 5329 women were assessed for eligibility and 200 were randomly assigned to the lifestyle intervention group and 198 to the usual care group. Analyses included 199 women in the lifestyle intervention group (one lost to follow-up) and 195 in the usual care group (three lost to follow-up). 96 (48%) women in the lifestyle intervention group and 134 (69%) women in the usual care group exceeded Institute of Medicine guidelines for rate of GWG per week (relative risk 0·70, 95% CI 0·59 to 0·83). Compared with usual care, women in the lifestyle intervention had reduced weekly rate of GWG (mean 0·26 kg per week [SD 0·15] vs 0·32 kg per week [0·13]; mean between-group difference −0·07 kg per week, 95% CI −0·09 to −0·04). No between-group differences in perinatal complications were observed. Interpretation Our evidence-based programme showed that health-care delivery systems could further adapt to meet the needs of their clinical settings to prevent excess GWG and improve healthy behaviours and markers of insulin resistance among women with overweight or obesity by using telehealth lifestyle interventions. Funding US National Institutes of Health.

Background Caesarean delivery (C-section) may disrupt maternal-infant microbial transfer and alter immune system development and subsequent risk for atopic dermatitis. Objective Investigate the association between C-section and atopic dermatitis by age four and examine potential sources of bias in the relationship in a large cohort study. Methods Maternal and child information was collected through Kaiser Permanente Northern California's (KPNC) integrated healthcare system. Data sources included electronic medical records, pharmacy databases, state birth records, and prospectively collected breastfeeding surveys. Children were eligible if they were born in a KPNC or contracting hospital between 2005 and 2014 and had continuous enrolment in the KPNC system for at least four years (n = 173 105). Modified Poisson regression with robust variance estimation was used to estimate the association between C-section and atopic dermatitis overall and when stratified by demographic and labour and delivery characteristics. Results Although unadjusted analyses showed a positive association between C-section and atopic dermatitis [RR(95%CI): 1.06(1.03, 1.10)], this effect was attenuated towards the null after adjustment [aRR(95%CI): 1.02(0.99, 1.05)]. In stratified analyses, there was evidence that C-section increased atopic dermatitis risk among certain subgroups (eg firstborns, overweight/obese pre-pregnancy BMI), but associations were weak. C-section delivery conditions indicative of the least exposure to maternal microbiome (ie no labour, short interval between membrane rupture and delivery) showed no evidence of association with atopic dermatitis. Estimated associations were not strongly influenced by intrapartum antibiotics, breastfeeding, missing data, or familial factors. Conclusion Caesarean delivery was not associated with atopic dermatitis by age four in this large US cohort. This association did not appear to be biased by intrapartum antibiotics, breastfeeding behaviour, C-section indication, missing covariates, or familial factors.

Background & Aims Some guidelines recommend starting colorectal cancer (CRC) screening before age 50 years for African Americans, but there are few data on screening uptake and yield in this population. Methods We performed a prospective study of fecal immunochemical test (FIT) screening among African American members of the Kaiser Permanente Northern California health plan. We compared data from African American members screened when they were 45–50 years old (early screening group) in 2018 with data from previously unscreened African American, white, Hispanic, and Asian/Pacific Islander health plan members, 51–56 years old. Screening outreach was performed with mailed FIT kits. Logistic regression models, adjusted for sex, were used to evaluate differences among groups in screening uptake, colonoscopy follow up of abnormal test results, and test yield. Results Among 10,232 African Americans in the early screening group who were mailed a FIT, screening was completed by 33.1%. Among the 4% with positive test results, 85.3% completed a follow-up colonoscopy: 57.8% had any adenoma, 33.6% had an advanced adenoma (adenoma with advanced histology or polyp ≥10 mm), and 2.6% were diagnosed with CRC. African Americans in the early screening group were modestly more likely to have completed screening than previously unscreened African Americans, whites, and Hispanics 51–56 years old. The groups did not differ significantly in positive results from the FIT (range, 3.8%–4.6%) and more than 74% received a follow-up colonoscopy after a positive test result. The test yields for any adenoma (range, 56.7%–70.7%), advanced adenoma (range, 20.0%–33.6%), and CRC (range, 0 to 7.1%) were similar. Conclusions Proportions of African Americans who participated in early (ages 45–50 years) FIT screening, and test yield, were comparable to those of previously unscreened African Americans, whites, Hispanics, and Asian/Pacific islanders who were 51–56 years old.

Background: Depression is associated with weight change outside of pregnancy. We assessed associations of prepregnancy or early pregnancy onset depression with gestational weight gain (GWG) rate overall and according to Institute of Medicine (IOM) recommendations. Materials and Methods: Depression from 6 months prepregnancy through 20 weeks gestation was identified in a health care system in northern California with perinatal depression screening (2011–2016; n = 87,600). GWG rate (lbs/week) was calculated using weight at delivery and at diagnosis or depression screening ≤20 weeks. Results: Compared to women without prepregnancy or early pregnancy depression, women with prepregnancy onset depression had 11% greater risk of GWG rate IOM recommendations (95% CI: 1.01–1.05), with a stronger association for >IOM in normal weight women. Early pregnancy onset depression was associated with 0.04 lbs/week greater GWG rate (95% CI: 0.02–0.07) and 4% greater risk of GWG rate >IOM recommendations (95% CI: 1.02–1.07) compared to no prepregnancy or early pregnancy depression, with stronger associations in obese women. Conclusions: Women with prepregnancy onset depression may be at higher risk for GWG both below and above recommendations. Women with early onset prenatal depression may be at slightly higher risk for GWG rate above recommendations. Our results suggest that the relationship between depression and GWG may vary based on timing of depression onset, prepregnancy body mass index category, and antidepressant use. Additional research should identify factors that predict how a woman's lifestyle behaviors and weight change after depression diagnosis.

Early puberty is associated with adverse health outcomes, but little is known regarding early-life determinants influencing pubertal timing. We examined the associations between maternal gestational weight gain (GWG) and the timing of the onset of breast development (thelarche) and pubic hair development (pubarche) in a cohort of 2,070 girls born in a Kaiser Permanente Northern California facility between 2005 and 2006. Using Weibull regression models accommodating interval censoring and adjusting for important confounders, we found that excess GWG was associated with increased risk of early thelarche (hazard ratio (HR) = 1.50, 95% confidence interval (CI): 1.26, 1.78) and early pubarche (HR = 1.35, 95% CI: 1.10, 1.66). Inadequate GWG was associated with early thelarche (HR = 1.36, 95% CI: 1.08, 1.71). The associations between excess or inadequate GWG and risk of earlier thelarche were stronger if mothers were obese before or at the beginning of pregnancy (body mass index ≥30 kg body weight per m height squared) (HR = 2.01, 95% CI: 1.53, 2.63; HR = 2.08, 95% CI: 1.45, 2.98, respectively). Similar associations were found for pubarche outcome. Inclusion of girls’ prepubertal body mass index slightly attenuated these associations, but they remained significant. Monitoring of maternal weight before and throughout pregnancy might help prevent early pubertal onset and subsequent negative health outcomes.