Publications by authors named "Charles P Quesenberry"

302 Publications

Survival Associated With Consolidated Multidisciplinary Care in Head and Neck Cancer: A Retrospective Cohort Study.

Otolaryngol Head Neck Surg 2021 Nov 9:1945998211057852. Epub 2021 Nov 9.

Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.

Objective: To compare survival among patients with head and neck cancer before and after implementing a weekly multidisciplinary clinic and case conference.

Methods: 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.

Results: 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% ( = .07) and disease-specific survival was 84.9% and 87.5% ( = .05) among pre- and postimplementation patients, respectively. At 3 years, preimplementation patients had slightly poorer overall (hazard ratio, 1.20; 95% CI, 1.02-1.40) and disease-specific (hazard ratio, 1.26; 95% CI, 1.03-1.54) adjusted survival than postimplementation patients. In unadjusted and adjusted analyses, survival improvements were more pronounced among patients with advanced disease.

Discussion: A multidisciplinary clinic and case conference were associated with improved outcomes among patients with head and neck cancer, especially those with advanced tumors.

Implications For Practice: All patients with head and neck cancer should receive multidisciplinary team management, especially those with advanced tumors.
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http://dx.doi.org/10.1177/01945998211057852DOI Listing
November 2021

Cancer in People with and without Hepatitis C Virus Infection: Comparison of Risk Before and After Introduction of Direct-Acting Antivirals.

Cancer Epidemiol Biomarkers Prev 2021 Dec 28;30(12):2188-2196. Epub 2021 Sep 28.

Division of Research, Kaiser Permanente Northern California, Oakland, California.

Background: Chronic hepatitis C virus (HCV) infection is a leading cause of liver cancer. The association of HCV infection with extrahepatic cancers, and the impact of direct-acting antiviral (DAA) treatment on these cancers, is less well known.

Methods: We conducted a cohort study in a healthcare delivery system. Using electronic health record data from 2007 to 2017, we determined cancer incidence, overall and by type, in people with HCV infection and by DAA treatment status. All analyses included comparisons with a reference population of people without HCV infection. Covariate-adjusted Poisson models were used to estimate incidence rate ratios.

Results: 2,451 people with HCV and 173,548 people without HCV were diagnosed with at least one type of cancer. Compared with people without HCV, those with HCV were at higher risk for liver cancer [adjusted incidence rate ratio (aIRR) = 31.4, 95% confidence interval (CI) = 28.9-34.0], hematologic cancer (aIRR = 1.3, 95% CI = 1.1-1.5), lung cancer (aIRR = 1.3, 95% CI = 1.2-1.5), pancreatic cancer (aIRR = 2.0, 95% CI = 1.6-2.5), oral/oropharynx cancer (aIRR = 1.4, 95% CI = 1.1-1.8), and anal cancer (aIRR = 1.6, 95% CI = 1.1-2.4). Compared with people without HCV, the aIRR for liver cancer was 31.9 (95% CI = 27.9-36.4) among DAA-untreated and 21.2 (95% CI = 16.8-26.6) among DAA-treated, and the aIRR for hematologic cancer was 1.5 (95% CI = 1.1-2.0) among DAA-untreated and 0.6 (95% CI = 0.3-1.2) among DAA-treated.

Conclusions: People with HCV infection were at increased risk of liver cancer, hematologic cancer, and some other extrahepatic cancers. DAA treatment was associated with reduced risk of liver cancers and hematologic cancers.

Impact: DAA treatment is important for reducing cancer incidence among people with HCV infection.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0742DOI Listing
December 2021

Participant education, spousal education and dementia risk in a diverse cohort of members of an integrated health care delivery system in Northern California.

BMJ Open 2021 06 18;11(6):e040233. Epub 2021 Jun 18.

Behavioral Health and Aging, Kaiser Permanente Division of Research, Oakland, California, USA.

Objective: The role of spousal education on dementia risk and how it may differ by gender or race/ethnicity is unknown. This study examines the association between one's own education separate from and in conjunction with spousal education and risk of dementia.

Design: Cohort.

Setting: Kaiser Permanente Northern California (KPNC), an integrated health care delivery system.

Participants: 8835 members of KPNC who were aged 40-55, married and reported own and spousal education in 1964-1973.

Primary Outcome Measure: Dementia cases were identified through medical records from 1 January 1996 to 30 September 2017.

Methods: Own and spousal education was self-reported in 1964-1973 and each was classified as four indicator variables (≤high school, trade school/some college, college degree and postgraduate) and as ≥college degree versus
Results: The cohort was 37% non-white, 46% men and 30% were diagnosed with dementia during follow-up from 1996 to 2017 (mean follow-up=12.7 years). Greater participant education was associated with lower dementia risk independent of spousal education, demographics and health indicators. Greater spousal education was associated with lower dementia adjusting for demographics but became non-significant after further adjustment for participant education. The same pattern was seen for spousal education ≥college degree (not adjusting for participant education HR=0.83 (95% CI: 0.76 to 0.90); adjusting for participant education HR=0.92 (95% CI: 0.83 to 1.01)). These associations did not vary by gender or race/ethnicity.

Conclusion: In a large diverse cohort, we found that higher levels of participant's own education were associated with lower dementia risk regardless of spousal education. An inverse association between spousal education and dementia risk was also present, however, the effects became non-significant after adjusting for participant education.
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http://dx.doi.org/10.1136/bmjopen-2020-040233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215232PMC
June 2021

Association of Type 1 Diabetes and Hypoglycemic and Hyperglycemic Events and Risk of Dementia.

Neurology 2021 Jun 2. Epub 2021 Jun 2.

Division of Research, Kaiser Permanente Oakland, CA, USA.

Objective: To determine whether severe hypoglycemic and hyperglycemic events are associated with longitudinal dementia risk in older adults with type 1 diabetes.

Methods: A longitudinal cohort study followed 2,821 members of an integrated healthcare delivery system with type 1 diabetes from 1997-2015. Hypoglycemic and hyperglycemic events requiring emergency room or hospitalization were abstracted from medical records beginning 1/1/1996 through cohort entry. Participants were followed for dementia diagnosis through 9/30/2015. Dementia risk was examined using Cox proportional hazard models adjusted for age (as timescale), sex, race/ethnicity, HbA1c, depression, stroke, and nephropathy.

Results: Among 2,821 older adults (mean age 56) with type 1 diabetes, 398 (14%) had a history of severe hypoglycemia, 335 (12%) severe hyperglycemia and 87 (3%) 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 (HR=1.66; 95% 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 versus those with neither (HR=6.20; 95% CI: 3.02, 12.70).

Conclusions: For older individuals with type 1 diabetes, severe hypoglycemic and hyperglycemic events are associated with increased future risk of dementia.
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http://dx.doi.org/10.1212/WNL.0000000000012243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302147PMC
June 2021

Patterns and Factors Associated With Adherence to Lung Cancer Screening in Diverse Practice Settings.

JAMA Netw Open 2021 04 1;4(4):e218559. Epub 2021 Apr 1.

Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill.

Importance: For lung cancer screening to confer mortality benefit, adherence to annual screening with low-dose computed tomography scans is essential. Although the National Lung Screening Trial had an adherence rate of 95%, current data are limited on screening adherence across diverse practice settings in the United States.

Objective: To evaluate patterns and factors associated with adherence to annual screening for lung cancer after negative results of a baseline examination, particularly in centralized vs decentralized screening programs.

Design, Setting, And Participants: This observational cohort study was conducted at 5 academic and community-based sites in North Carolina and California among 2283 individuals screened for lung cancer between July 1, 2014, and March 31, 2018, who met US Preventive Services Task Force eligibility criteria, had negative results of a baseline screening examination (American College of Radiology Lung Imaging Reporting and Data System category 1 or 2), and were eligible to return for a screening examination in 12 months.

Exposures: To identify factors associated with adherence, the association of adherence with selected baseline demographic and clinical characteristics, including type of screening program, was estimated using multivariable logistic regression. Screening program type was classified as centralized if individuals were referred through a lung cancer screening clinic or program and as decentralized if individuals had a direct clinician referral for the baseline low-dose computed tomography scan.

Main Outcomes And Measures: Adherence to annual lung cancer screening, defined as a second low-dose computed tomography scan within 11 to 15 months after baseline screening.

Results: Among the 2283 eligible individuals (1294 men [56.7%]; mean [SD] age, 64.9 [5.8] years; 1160 [50.8%] aged ≥65 years) who had negative screening results at baseline, overall adherence was 40.2% (n = 917), with higher adherence among those who underwent screening through centralized (46.0% [478 of 1039]) vs decentralized (35.3% [439 of 1244]) programs. The independent factor most strongly associated with adherence was type of screening program, with a 2.8-fold increased likelihood of adherence associated with centralized screening (adjusted odds ratio [aOR], 2.78; 95% CI, 1.99-3.88). Another associated factor was age (65-69 vs 55-59 years: aOR, 1.38; 95% CI, 1.07-1.77; 70-74 vs 55-59 years: aOR, 1.47; 95% CI, 1.10-1.96).

Conclusions And Relevance: After negative results of a baseline examination, adherence to annual lung cancer screening was suboptimal, although adherence was higher among individuals who were screened through a centralized program. These results support the value of centralized screening programs and the need to further implement strategies that improve adherence to annual screening for lung cancer.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.8559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087957PMC
April 2021

Healthy preconception and early-pregnancy lifestyle and risk of preterm birth: a prospective cohort study.

Am J Clin Nutr 2021 08;114(2):813-821

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Background: 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.

Objectives: We aimed to examine the associations of preconceptional and early-pregnancy low-risk modifiable factors (individually and in combination) with PTB risk.

Methods: 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 delivery <37 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 score <75th 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1093/ajcn/nqab089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326036PMC
August 2021

mHealth Mindfulness Intervention for Women with Moderate-to-Moderately-Severe Antenatal Depressive Symptoms: a Pilot Study Within an Integrated Health Care System.

Mindfulness (N Y) 2021 Mar 11:1-11. Epub 2021 Mar 11.

Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612 USA.

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 (<28 weeks of gestation) with moderate-to-moderately-severe depressive symptoms without a regular (<3 times/week) mindfulness/meditation practice. Participants were asked to follow a self-paced, 6-week mindfulness meditation program using a mobile app, Headspace™, 10-20 min/day. Outcome measures included feasibility, acceptability, and patient-reported outcomes (e.g., depression symptoms).

Results: Of the 27 women enrolled, 20 (74%) completed the study. Over half (55%) of participants used the app ≥50% of the days during the 6-week intervention. Responses to the semi-structured interviews indicated that women appreciated the convenience of the intervention and the ability to engage without having to attend classes or arrange childcare. We observed significant improvements in pre-postintervention scores for depression symptoms, perceived stress, sleep disturbance, and mindfulness.

Conclusions: Our study demonstrates the feasibility and acceptability of an mHealth mindfulness intervention for women with moderate-to-moderately-severe antenatal depression symptoms. The preliminary data further suggest that an efficacy trial is warranted.
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http://dx.doi.org/10.1007/s12671-021-01606-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947160PMC
March 2021

Mediating Effects of Cardiometabolic Risk Factors on the Association Between Maternal Race-Ethnicity and Cesarean Delivery Among Low-Risk Women.

J Womens Health (Larchmt) 2021 07 11;30(7):1028-1037. Epub 2021 Feb 11.

The Permanente Medical Group, Regional Offices, Kaiser Permanente Northern California, Oakland, California, USA.

While racial-ethnic disparities in cesarean delivery rates among nulliparous women delivering a term singleton in the vertex position (NTSV) exist, it remains unclear the extent to which potentially modifiable maternal cardiometabolic risk factors (obesity, maternal hyperglycemia and hypertensive disorders) underlie these disparities. We examined race-ethnicity and risk of NTSV cesarean deliveries and whether the associations were mediated by maternal cardiometabolic risk factors. A cohort study of 62,048 NTSV deliveries in Kaiser Permanente Northern California. The outcome was cesarean delivery. Black, Asian, and Hispanic women were at increased risk of having a NTSV cesarean delivery compared with White women (relative risks and 95% confidence intervals: 1.37 [1.28-1.45]; 1.11 [1.07-1.16]; 1.12 [1.07-1.16], respectively), independent of established risk factors and prenatal care utilization. The extent to which cardiometabolic risk factors mediated the associations between race-ethnicity (each group vs. White, in separate analyses) and NTSV cesarean delivery varied by race-ethnicity. Maternal overweight/obesity (body mass index ≥25.0) mediated the association between Black and Hispanic race-ethnicity and NTSV cesarean delivery (21.1% [15.8-26.4] and 24.7% [14.6-34.8, respectively), but not for Asian race. Maternal hyperglycemia (gestational diabetes mellitus or preexisting diabetes) mediated the association between Asian and Hispanic race and NTSV cesarean delivery (18.5% [9.8-27.2] and 9.8% [5.0-14.7], respectively), but not for Black race. Hypertensive disorders mediated 3.2% (0.70-5.8) of the association between Black race and cesarean delivery, but not for other race-ethnicities. Black, Asian, and Hispanic women are at increased risk for NTSV cesarean deliveries. Maternal cardiometabolic risk factors only partially mediate the associations between race-ethnicity and NSTV cesarean deliveries.
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http://dx.doi.org/10.1089/jwh.2019.8171DOI Listing
July 2021

A prospective study of lifestyle factors and bone health in breast cancer patients who received aromatase inhibitors in an integrated healthcare setting.

J Cancer Surviv 2021 Feb 9. Epub 2021 Feb 9.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

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 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-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 < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37).

Conclusions: Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy.

Implications For Cancer Survivors: Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies.
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http://dx.doi.org/10.1007/s11764-021-00993-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349930PMC
February 2021

The Association of Lactation Duration with Visceral and Pericardial Fat Volumes in Parous Women: The CARDIA Study.

J Clin Endocrinol Metab 2021 05;106(6):1821-1831

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

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.
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http://dx.doi.org/10.1210/clinem/dgaa980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118361PMC
May 2021

Early life household intactness and timing of pubertal onset in girls: a prospective cohort study.

BMC Pediatr 2020 10 28;20(1):464. Epub 2020 Oct 28.

Kaiser Permanente Division of Research, 2000 Broadway, CA, 94612, Oakland, USA.

Background: Girls who experience early-life familial stress may have heightened risk of early puberty, which has adverse implications for adolescent and adult health. We assessed the association between household intactness and pubertal onset using a racially/ethnically diverse cohort of girls from Northern California.

Methods: A prospective cohort study of 26,044 girls born in 2003-10. Girls living with both parents from birth up to 6 years were considered to come from "intact" households while others constituted "non-intact" households. Pubertal development was measured using pediatrician-assessed Tanner staging for breast and pubic hair. Pubertal onset was defined as the transition from Tanner Stage 1 to 2+ for breast (thelarche) and pubic hair (pubarche). Menarche data was collected from routine well-child questionnaires. Weibull regression models accommodating left, right, and interval censoring were used to determine risk of earlier thelarche and pubarche, and logistic regressions were used to assess the risk of early menarche (age < 12).

Results: Girls exposed to non-intact households before age 2 years were at increased risk for earlier thelarche and pubarche with significant effect modification by race/ethnicity, compared with girls from intact households. The associations were strongest among Black girls (adjusted hazard ratio [HR]: 1.60, 95% confidence interval [CI]: 1.29,1.98; HR: 1.42, 95%CI: 1.15,1.77 for thelarche and pubarche, respectively). There were no significant associations among Asian/Pacific Islanders. Girls who lived in non-intact households before age 2 years were also at increased risk for earlier menarche, but without race/ethnic interaction. Adjustment for prepubertal obesity did not change these associations. Associations between living in non-intact households after age 2 years and early puberty were weaker but still significant.

Conclusions: Exposure to a non-intact household early in life may increase the risk of early puberty in girls. Future psychosocial interventions focused on improving family cohesiveness and efforts to reduce childhood stress among families that are non-intact may mitigate these negative associations, thereby preventing future adverse health effects of early puberty and health disparities.
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http://dx.doi.org/10.1186/s12887-020-02345-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592583PMC
October 2020

Gestational weight gain, birthweight and early-childhood obesity: between- and within-family comparisons.

Int J Epidemiol 2020 10;49(5):1682-1690

Kaiser Permanente Northern California Division of Research, Oakland, CA, USA.

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.
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http://dx.doi.org/10.1093/ije/dyaa110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746402PMC
October 2020

Association Between Topical Calcineurin Inhibitor Use and Keratinocyte Carcinoma Risk Among Adults With Atopic Dermatitis.

JAMA Dermatol 2020 10;156(10):1066-1073

Division of Research, Kaiser Permanente Northern California, Oakland.

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.
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http://dx.doi.org/10.1001/jamadermatol.2020.2240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557510PMC
October 2020

Early Screening of African Americans (45-50 Years Old) in a Fecal Immunochemical Test-Based Colorectal Cancer Screening Program.

Gastroenterology 2020 11 20;159(5):1695-1704.e1. Epub 2020 Jul 20.

Division of Research, Kaiser Permanente Northern California, Oakland, California.

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 who were 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%-7.1%) were similar.

Conclusions: Proportions of African Americans who participated in early (aged 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.
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http://dx.doi.org/10.1053/j.gastro.2020.07.011DOI Listing
November 2020

Comparative Effectiveness of 2 Diabetes Prevention Lifestyle Programs in the Workplace: The City and County of San Francisco Diabetes Prevention Trial.

Prev Chronic Dis 2020 05 28;17:E38. Epub 2020 May 28.

Division of Research, Kaiser Permanente Northern California, Oakland, California.

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.
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http://dx.doi.org/10.5888/pcd17.190396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279062PMC
May 2020

A telehealth lifestyle intervention to reduce excess gestational weight gain in pregnant women with overweight or obesity (GLOW): a randomised, parallel-group, controlled trial.

Lancet Diabetes Endocrinol 2020 06;8(6):490-500

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

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/m, 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.
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http://dx.doi.org/10.1016/S2213-8587(20)30107-8DOI Listing
June 2020

Caesarean delivery and the risk of atopic dermatitis in children.

Clin Exp Allergy 2020 07 11;50(7):805-814. Epub 2020 Jun 11.

School of Community Health Sciences, University of Nevada, Reno, NV, USA.

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.
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http://dx.doi.org/10.1111/cea.13668DOI Listing
July 2020

Association of Valproic Acid Use, a Potent Histone Deacetylase Inhibitor, and Melanoma Risk.

J Invest Dermatol 2020 12 28;140(12):2353-2358. Epub 2020 Apr 28.

Division of Research, Kaiser Permanente Northern California, Oakland, California, USA; Department of Dermatology, Massachusetts General Hospital and Department of Population Medicine, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

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, P < 0.001). 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.
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http://dx.doi.org/10.1016/j.jid.2020.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606214PMC
December 2020

Proton Pump Inhibitor Use and Risk of Gastric, Colorectal, Liver, and Pancreatic Cancers in a Community-Based Population.

Am J Gastroenterol 2020 05;115(5):706-715

Department of Gastroenterology, Kaiser Permanente San Francisco, San Francisco, California, USA.

Introduction: Proton pump inhibitors (PPIs) are commonly used for gastrointestinal disorders; given they increase the systemic levels of gastrin, a trophic hormone, there is a concern about their carcinogenicity. This study evaluated the association between PPI use and gastrointestinal cancers.

Methods: We performed a nested case-control study in a large, community-based integrated healthcare setting. Cases were adults with gastric (n = 1,233), colorectal (n = 18,595), liver (n = 2,329), or pancreatic cancers (n = 567). Each case was matched with up to 10 controls by age, sex, race/ethnicity, medical facility, and enrollment duration. The primary exposure was defined as ≥2-year cumulative PPI supply. Data were obtained from pharmacy, cancer registry, and electronic medical record databases. Associations were evaluated using conditional logistic regression and adjusted for multiple confounders. We also evaluated the cancer risks separately by PPI dose, duration of use, and dose and duration.

Results: PPI use of ≥2-years was not associated with the risks of gastric (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.81-1.42), colorectal (OR: 1.05, 95% CI: 0.99-1.12), liver (OR: 1.14, 95% CI: 0.91-1.43), or pancreatic cancers (OR: 1.22, 95% CI: 0.89-1.67), compared to non-users. In exploratory analyses, elevated cancer risks were primarily restricted to those with ≥10 years of PPI use, but no consistent associations were found for increasing PPI dose and/or duration of use.

Discussion: PPI use of ≥2 years was not associated with increased risks of gastrointestinal cancers. The cancer risks associated with PPI use of ≥10 years requires further study.
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http://dx.doi.org/10.14309/ajg.0000000000000591DOI Listing
May 2020

Life Expectancy of Insured People With and Without Hepatitis C Virus Infection, 2007-2017.

Open Forum Infect Dis 2020 Feb 5;7(2):ofaa044. Epub 2020 Feb 5.

Kaiser Permanente Division of Research, Oakland, California, USA.

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.
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http://dx.doi.org/10.1093/ofid/ofaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043807PMC
February 2020

Long-term Risk of Colorectal Cancer and Related Death After Adenoma Removal in a Large, Community-based Population.

Gastroenterology 2020 03 4;158(4):884-894.e5. Epub 2019 Oct 4.

Department of Gastroenterology, Kaiser Permanente San Francisco, San Francisco, California; Division of Research, Kaiser Permanente Northern California, Oakland, California.

Background & Aims: The long-term risks of colorectal cancer (CRC) and CRC-related death following adenoma removal are uncertain. Data are needed to inform evidence-based surveillance guidelines, which vary in follow-up recommendations for some polyp types. Using data from a large, community-based integrated health care setting, we examined the risks of CRC and related death by baseline colonoscopy adenoma findings.

Methods: Participants at 21 medical centers underwent baseline colonoscopies from 2004 through 2010; findings were categorized as no-adenoma, low-risk adenoma, or high-risk adenoma. Participants were followed until the earliest of CRC diagnosis, death, health plan disenrollment, or December 31, 2017. Risks of CRC and related deaths among the high- and low-risk adenoma groups were compared with the no-adenoma group using Cox regression adjusting for confounders.

Results: Among 186,046 patients, 64,422 met eligibility criteria (54.3% female; mean age, 61.6 ± 7.1 years; median follow-up time, 8.1 years from the baseline colonoscopy). Compared with the no-adenoma group (45,881 patients), the high-risk adenoma group (7563 patients) had a higher risk of CRC (hazard ratio [HR] 2.61; 95% confidence interval [CI] 1.87-3.63) and related death (HR 3.94; 95% CI 1.90-6.56), whereas the low-risk adenoma group (10,978 patients) did not have a significant increase in risk of CRC (HR 1.29; 95% CI 0.89-1.88) or related death (HR 0.65; 95% CI 0.19-2.18).

Conclusions: With up to 14 years of follow-up, high-risk adenomas were associated with an increased risk of CRC and related death, supporting early colonoscopy surveillance. Low-risk adenomas were not associated with a significantly increased risk of CRC or related deaths. These results can inform current surveillance guidelines for high- and low-risk adenomas.
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http://dx.doi.org/10.1053/j.gastro.2019.09.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083250PMC
March 2020

Correction to: Breastfeeding and timing of pubertal onset in girls: a multiethnic population-based prospective cohort study.

BMC Pediatr 2019 Sep 5;19(1):317. Epub 2019 Sep 5.

Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA, 94612, USA.

Following publication of the original article [1], the authors reported that Table 4 was incorrectly presented. The revised and corrected version is shown below.
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http://dx.doi.org/10.1186/s12887-019-1671-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6729063PMC
September 2019

Breastfeeding and timing of pubertal onset in girls: a multiethnic population-based prospective cohort study.

BMC Pediatr 2019 08 9;19(1):277. Epub 2019 Aug 9.

Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA, 94612, USA.

Background: Early puberty is associated with higher risk of adverse health and behavioral outcomes throughout adolescence and adulthood. US girls are experiencing earlier puberty with substantial racial/ethnic differences. We examined the association between breastfeeding and pubertal timing to identify modifiable risk factors of early puberty and potential sources of racial/ethnic differences in the timing of pubertal development.

Methods: A prospective cohort study of 3331 racially/ethnically diverse girls born at Kaiser Permanente Northern California (KPNC) between 2004 and 06. All data were obtained from KPNC electronic clinical and administrative datasets. Mother-reported duration of breastfeeding was obtained from questionnaires administered at each 'well-baby' check-up exam throughout the baby's first year and categorized as 'Not breastfed', 'Breastfed < 6 months', and 'Breastfed ≥ 6 months'. Pubertal development data used Tanner stages assessed by pediatricians during routine pediatric checkups starting at age 6. Pubertal onset was defined as transition from Tanner Stage 1 to Tanner Stage 2+ for breast (thelarche) and pubic hair (pubarche). Weibull regression models accommodating for left, right, and interval censoring were used in all analyses. Models were adjusted for maternal age, education, race/ethnicity, parity and prepubertal body mass index (BMI). We also examined race/ethnicity as a potential effect modifier of these associations.

Results: Not breastfeeding was associated with earlier onset of breast and pubic hair development compared to breastfeeding ≥6 months (adjusted hazard ratio [HR]: 1.25; 95% confidence interval [CI]: 1.07-1.46; HR: 1.24; 95% CI: 1.05-1.46, respectively). Breastfeeding for < 6 months was also associated with the risk of earlier pubic hair development (HR: 1.14; 95% CI: 1.00-1.30, compared to breastfeeding ≥6 months). Inclusion of girls' prepubertal BMI slightly attenuated the association between breastfeeding and timing of breast onset but remained significant. The association between not breastfeeding and early breast development may be stronger among African American girls (HR: 1.92; 95% CI: 1.01-3.66, no breastfeeding vs. ≥6 months) than other racial/ethnic groups.

Conclusions: Breastfeeding is an independent predictor of pubertal onset in girls, and the strength of the association may vary by race/ethnicity. Providing breastfeeding support and lactation education for high risk mothers may help prevent earlier pubertal onset and promote positive health outcomes later in life.
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http://dx.doi.org/10.1186/s12887-019-1661-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688234PMC
August 2019

Risk Estimates for Diabetes and Hypertension with Different Physical Activity Methods.

Med Sci Sports Exerc 2019 12;51(12):2498-2505

Division of Research, Kaiser Permanente, Oakland, CA.

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 2291 black and white men and women, ages 38-50 yr, in the Coronary Artery Risk Development in Young Adults (CARDIA) fitness study, conducted during the year 20 core CARDIA examination. Accelerometer-determined (Actigraph, LLC. model 7164) MVPA (MVPA-Acc), assessed at year 20, was defined as minutes per 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 h glucose tolerance test, 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% to 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, whereas 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.
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http://dx.doi.org/10.1249/MSS.0000000000002083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138450PMC
December 2019

A Randomized Study of Values Affirmation to Promote Interest in Diabetes Prevention Among Women With a History of Gestational Diabetes.

Med Care 2019 07;57(7):528-535

Division of Research, Kaiser Permanente Northern California, Oakland.

Objective: The objective of this study was to test whether 2 interventions promote interest in diabetes prevention among women with a history of gestational diabetes mellitus, who face high lifetime risk for diabetes.

Research Design And Methods: We designed an email outreach message promoting an existing preventive lifestyle program. The message incorporated values affirmation, a theory-based intervention that can improve openness to health information but typically relies on a writing exercise less practical in health care settings. In a 3-arm randomized study, 237 women with elevated body mass index and a history of gestational diabetes mellitus were randomized to read an outreach message containing either no affirmation (control) or 1 of 2 affirmations, streamlined to remove the typical writing exercise: either a values affirmation prompting reflection on any personal value, or a parenting affirmation prompting reflection on caregiving-related values. Outcomes included demonstrating interest in the lifestyle program (seeking information about it or intending to join) and seeking publicly-available health information about diabetes prevention.

Results: Compared with control, participants randomized to the values affirmation more frequently demonstrated interest in the lifestyle program (59.0% vs. 74.4%; adjusted relative risk: 1.31; 95% confidence interval: 1.04-1.66) and sought information about diabetes prevention (59.0% vs. 73.4%; adjusted relative risk: 1.22; 95% confidence interval: 0.97-1.54). The parenting affirmation yielded no significant differences in either outcome.

Conclusions: A streamlined values affirmation, designed for feasibility in a health care setting, can promote interest in diabetes prevention among women at high risk. Research is needed to evaluate its effects on diabetes prevention program enrollment and clinical outcomes.
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http://dx.doi.org/10.1097/MLR.0000000000001133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565448PMC
July 2019

Pre- and Early Pregnancy Onset Depression and Subsequent Rate of Gestational Weight Gain.

J Womens Health (Larchmt) 2019 09 7;28(9):1237-1245. Epub 2019 May 7.

Division of Research, Kaiser Permanente Northern California, Oakland, California.

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. 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;  = 87,600). GWG rate (lbs/week) was calculated using weight at delivery and at diagnosis or depression screening ≤20 weeks. 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. 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.
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http://dx.doi.org/10.1089/jwh.2018.7497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743087PMC
September 2019

Stressors in Midlife and Risk of Dementia: The Role of Race and Education.

Alzheimer Dis Assoc Disord 2019 Jul-Sep;33(3):200-205

Kaiser Permanente Division of Research, Oakland.

Background: Posttraumatic stress disorder is associated with increased dementia risk but less is known about stress because of everyday problems in diverse populations.

Methods: A total of 9605 health care plan members who provided information regarding midlife stressors in 1972 to 1973 (ages, 40 to 55 y) were followed for dementia diagnosis between 1996 and 2017. Cox proportional hazard models evaluated associations between midlife stressors and dementia adjusting for demographics and lifecourse health indicators.

Results: Reporting at least 1 midlife stressor was associated with 17% greater dementia risk [hazard ratio (HR), 1.17; 95% confidence interval (CI),1.07-1.27] versus 0 midlife stressors and 26% increased risk among those with less than equal to high school education (HR, 1.26; 95% CI,1.09-1.44) adjusting for demographics. Compared with whites without stressors, whites with ≥1 stressor had 13% greater dementia risk (HR, 1.13; 95% CI, 1.02-1.24), blacks without stressors 19% greater risk (HR, 1.19; 95% CI,1.08-1.32), and blacks with ≥1 stressors 47% greater risk (HR, 1.47; 95% CI,1.27-1.69) in fully adjusted models. Resource problems were associated with 20% greater risk (HR, 1.20; 95% CI, 1.01-1.42) than interpersonal problems.

Conclusion: Reporting ≥1 serious midlife stressor was associated with elevated dementia risk, especially stressors related to resources problems and for those with less than equal to high school education. Everyday stressors can impact brain health over the long term and may contribute to racial inequities in dementia rates, though education can be a mitigating factor.
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http://dx.doi.org/10.1097/WAD.0000000000000313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710152PMC
July 2020

Hepatitis C treatment uptake and response among human immunodeficiency virus/hepatitis C virus-coinfected patients in a large integrated healthcare system.

Int J STD AIDS 2019 06 2;30(7):689-695. Epub 2019 May 2.

10 Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

U.S. guidelines recommend that patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) be prioritized for HCV treatment with direct-acting antiviral agents (DAAs), but the high cost of DAAs may contribute to disparities in treatment uptake and outcomes. We evaluated DAA initiation and effectiveness in HIV/HCV-coinfected patients in a U.S.-based healthcare system during October 2014-December 2017. Of 462 HIV/HCV-coinfected patients, 276 initiated DAAs (70% cumulative proportion treated over three years). Lower likelihood of DAA initiation was observed among patients with Medicare (government-sponsored insurance) versus commercial insurance (adjusted rate ratio [aRR] = 0.62, 95% CI = 0.46-0.84), patients with drug abuse diagnoses (aRR = 0.72, 95% CI = 0.54-0.97), patients with CD4 cell count <200 cells/µl versus ≥500 (aRR = 0.45, 95% CI = 0.23-0.91), and patients without prior HCV treatment (aRR = 0.68, 95% CI = 0.48-0.97). There were no significant differences in DAA initiation by age, gender, race/ethnicity, socioeconomic status, HIV transmission risk, alcohol use, smoking, fibrosis level, HIV RNA levels, antiretroviral therapy use, hepatitis B infection, or number of outpatient visits. Ninety-five percent of patients achieved sustained virologic response (SVR). We found little evidence of sociodemographic disparities in DAA initiation among HIV/HCV-coinfected patients, and SVR rates were high. Efforts are needed to increase DAA uptake among coinfected Medicare enrollees, patients with drug abuse diagnoses, patients with low CD4 cell count, and patients receiving first-time HCV treatment.
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http://dx.doi.org/10.1177/0956462419836520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529258PMC
June 2019

Gestational weight gain and optimal wellness (GLOW): rationale and methods for a randomized controlled trial of a lifestyle intervention among pregnant women with overweight or obesity.

BMC Pregnancy Childbirth 2019 Apr 30;19(1):145. Epub 2019 Apr 30.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94612, USA.

Background: Excess gestational weight gain (GWG) is common among women with overweight or obesity, increasing their risks for pregnancy complications, delivering a large infant, and postpartum weight retention. To date, only intensive interventions have had success and few interventions have been designed for implementation in healthcare settings.

Methods: We describe the development, rationale, and methods of GLOW (GestationaL Weight Gain and Optimal Wellness), a randomized controlled trial evaluating the efficacy of a lifestyle intervention to prevent excess GWG among racially/ethnically diverse women with overweight or obesity in an integrated healthcare delivery system. Participants in Kaiser Permanente Northern California will be randomized, within 2 weeks of completing a study baseline clinic visit at 10 weeks' gestation, to either usual medical care or a multi-component pregnancy lifestyle intervention adapted from the Diabetes Prevention Program (target N = 400). Informed by focus groups with patients and designed to be feasible in a clinical setting, the intervention will include 13 weekly individual sessions (11 delivered by telephone) focused on behavior change for weight management, healthy eating, physical activity, and stress management. Outcomes will be assessed in women and their infants from randomization to 12 months postpartum. The primary outcome is GWG. Secondary outcomes include changes in diet and physical activity during pregnancy and infant birthweight. Exploratory outcomes include cardiometabolic profile assessed via pregnancy blood samples and cord blood samples; and postpartum weight retention and infant anthropometrics up to 12 months of age. The trial includes systematic approaches to enhance intervention fidelity, intervention adherence, and participant retention in trial assessments.

Discussion: GLOW is among few trials targeting excess GWG among diverse women with overweight or obesity in a healthcare setting, with long-term maternal and infant outcomes assessed up to 12 months after delivery. This evaluation of a multi-component intervention is designed to produce generalizable results to inform potential adoption of the intervention in clinical settings.

Trial Registration: ClinicalTrials.gov ( NCT02130232 ): submitted April 30, 2014; posted May 5, 2014.
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http://dx.doi.org/10.1186/s12884-019-2293-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492416PMC
April 2019

Telomere length and socioeconomic status at neighborhood and individual levels among 80,000 adults in the Genetic Epidemiology Research on Adult Health and Aging cohort.

Environ Epidemiol 2019 Jun 1;3(3):e049. Epub 2019 May 1.

Division of Research, Oakland, Kaiser Permanente Northern California, Oakland, California.

Background: Telomere length (TL) may serve as a biologic marker of aging. We examined neighborhood and individual-level socioeconomic status (SES) in relation to TL.

Methods: The study included 84,996 non-Hispanic white subjects from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, part of the Research Program on Genes, Environment and Health. Relative TL (T/S) was log transformed to improve normality and standardized to have mean 0 and variance 1. Neighborhood SES was measured using the Neighborhood Deprivation Index (NDI), and individual SES was measured by self-reported education level. We fit linear regression models of TL on age, sex, smoking, body mass index, comorbidities, NDI, and education level. We tested for differences in the associations by sex and nonlinearity in the association of NDI with TL.

Results: Each SD increase in NDI was associated with a decrease of 0.0192 in standardized TL, 95% confidence interval (CI) = -0.0306, -0.0078. There was no evidence of nonlinearity in the association of NDI with TL. We further found that less than high school education was associated with a decrease of 0.1371 in standardized TL, 95% CI = -0.1919, -0.0823 as compared to a college education. There were no differences in the associations by sex.

Conclusions: We found evidence that both lower neighborhood SES and lower individual-level SES are associated with shorter TL among non-Hispanic whites. Our findings suggest that socioeconomic factors may influence aging by contributing to shorter TL.
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http://dx.doi.org/10.1097/EE9.0000000000000049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939422PMC
June 2019
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