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Concept: Kaiser Permanente

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Early puberty is associated with adverse health outcomes. We investigated whether in utero exposure to maternal obesity is associated with daughters' pubertal timing using 15,267 racially/ethnically diverse Kaiser Permanente Northern California members age 6-11 years with pediatrician-assessed Tanner staging (2003-2017). We extracted maternal body mass index (BMI) during pregnancy from the electronic health record. Using a proportional hazards model with interval censoring we examined the associations between maternal obesity and girl’s pubertal timing, and effect modification by race/ethnicity and mediation by pre-pubertal BMI. Maternal obesity (BMI ≥30 kg/m2) or overweight (BMI 25-29.9 kg/m2) was associated with earlier breast onset in girls [hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.30, 1.49; HR = 1.21, 95% CI: 1.13, 1.29, respectively], adjusting for girls' race/ethnicity, maternal age, education, parity and smoking during pregnancy. There was interaction by race/ethnicity for associations between maternal obesity and girls' pubic hair onset: associations were strongest among Asian and white girls [HR = 1.53, 95% CI: 1.24, 1.90; HR = 1.34, 95% CI: 1.18, 1.52, respectively] and absent for African-American girls. Adjustment for girls' pre-pubertal BMI only slightly attenuated associations. Our results suggest the importance of maternal metabolic factors during pregnancy on girls' pubertal timing and potential differences in the associations by race/ethnicity.

Concepts: Nutrition, Obesity, Body mass index, Kaiser Permanente, Puberty, Body shape, Electronic health record, Pubic hair

26

Ongoing growth in health care expenditures and changing patterns in the demand for health care challenge societies worldwide. The Chronic Care Model (CCM), combined with classification for care needs based on Kaiser Permanente (KP) Triangle, may offer a suitable framework for change. The aim of the present study is to investigate the effectiveness of Embrace, a population-based model for integrated elderly care, regarding patient outcomes, service use, costs, and quality of care.

Concepts: Present, Time, Health care, Medicine, Healthcare, Kaiser Permanente, Geriatrics, Permanente Creek

25

Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into 7 major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. PC and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed considering only non-adjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian-European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3,741 genetically-identified parent-child pairs, 93% were concordant for self-reported race/ethnicity; among 2,018 genetically-identified full-sib pairs, 96% were concordant; the lower rate for parent-child pairs was largely due to inter-marriage. The parent-child pairs revealed a trend towards increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories, creates interesting challenges and future opportunities for genetic epidemiologic studies.

Concepts: Genetics, Health, Epidemiology, Biology, United States, Kaiser Permanente, Native Americans in the United States, English American

20

Asthma is the most common chronic condition of childhood, yet the relationship between obesity and asthma risk and the impact of obesity on clinical asthma outcomes are not well understood. For this population-based, longitudinal study, demographic and clinical data were extracted from administrative and electronic health records of 623,358 patients aged 6-19 years who were enrolled in the Kaiser Permanente Southern California health plan in 2007-2011. Crude asthma incidence ranged from 16.9 per 1,000 person-years among normal-weight youth to 22.3 per 1,000 person-years among extremely obese youth. The adjusted risks of asthma for overweight, moderately obese, and extremely obese youth relative to those of normal weight youth were 1.16 (95% confidence interval: 1.13, 1.20), 1.23 (95% confidence interval: 1.19, 1.28), and 1.37 (95% confidence interval: 1.32, 1.42), respectively (Ptrend < 0.0001). The relationship between obesity and asthma risk was strongest in Asian/Pacific Islanders and in the youngest girls (aged 6-10 years), compared with other groups. Among youth who developed asthma, those who were moderately or extremely obese had more frequent asthma exacerbations requiring emergency department services and/or treatment with oral corticosteroids. In conclusion, obese youth are not only more likely to develop asthma, but they may be more likely to have severe asthma, resulting in a greater need for health care utilization and aggressive asthma treatment.

Concepts: Health care, Nutrition, Asthma, Obesity, Overweight, Kaiser Permanente, Body shape, Childhood obesity

20

Objectives. We examined the impact on patient safety if nurse practitioners (NPs), certified nurse midwives (CNMs), and physician assistants (PAs) were permitted to provide aspiration abortions in California. Methods. In a prospective, observational study, we evaluated the outcomes of 11 487 early aspiration abortions completed by physicians (n = 5812) and newly trained NPs, CNMs, and PAs (n = 5675) from 4 Planned Parenthood affiliates and Kaiser Permanente of Northern California, by using a noninferiority design with a predetermined acceptable risk difference of 2%. All complications up to 4 weeks after the abortion were included. Results. Of the 11 487 aspiration abortions analyzed, 1.3% (n = 152) resulted in a complication: 1.8% for NP-, CNM-, and PA-performed aspirations and 0.9% for physician-performed aspirations. The unadjusted risk difference for total complications between NP-CNM-PA and physician groups was 0.87 (95% confidence interval [CI] = 0.45, 1.29) and 0.83 (95% CI = 0.33, 1.33) in a propensity score-matched sample. Conclusions. Abortion complications were clinically equivalent between newly trained NPs, CNMs, and PAs and physicians, supporting the adoption of policies to allow these providers to perform early aspirations to expand access to abortion care. (Am J Public Health. Published online ahead of print January 17, 2013: e1-e8. doi:10.2105/AJPH.2012.301159).

Concepts: Pregnancy, Birth control, General practitioner, Kaiser Permanente, Iatrogenesis, Healthcare occupations, Pro-choice, Physician assistant

19

In June 2010, Kaiser Permanente Northern California replaced all 7-valent pneumococcal conjugate vaccine (PCV7) vaccines with the 13-valent pneumococcal conjugate vaccine (PCV13). Our objectives were to compare the incidence of bacteremia in children 3 to 36 months old by 3 time periods: pre-PCV7, post-PCV7/pre-PCV13, and post-PCV13.

Concepts: Pneumonia, Streptococcus pneumoniae, Vaccine, Vaccination schedule, Pneumococcal conjugate vaccine, Pneumococcal vaccine, Kaiser Permanente, Vaccines

19

Objective To examine the association between exposures to perinatal factors and autism spectrum disorders (ASD). Study Design A retrospective cohort study of ASD among children born in Kaiser Permanente Southern California hospitals between 1991 and 2009 (n = 594,638). Medical records were used to determine exposure to perinatal (antepartum and intrapartum) complications. ASD was diagnosed using DSM-IV criteria. Multivariable Cox regression was used to estimate hazard ratios (HRs). Result Children with ASD were more likely to be exposed to perinatal complications (HR = 1.15, 95% confidence interval [CI]: 1.09-1.21) than neurotypical children. Children exposed to antepartum (HR = 1.22, 95% CI: 1.10-1.36) and intrapartum (HR = 1.10, 95% CI: 1.04-1.17) complications were at increased risk of ASD. The risk was even greater when both antepartum and intrapartum conditions were present (HR = 1.44, 95% CI: 1.26-1.63). Conclusion Exposure to antepartum or intrapartum complications increases the risk of ASD in the offspring. Therefore, pregnancy complications may help identify children who could benefit from early screening and intervention for this common neurodevelopmental condition.

Concepts: Cohort study, Autism, Pervasive developmental disorder, Asperger syndrome, Autism spectrum, PDD-NOS, Kaiser Permanente, Neurodevelopmental disorder

17

Optimal cardiovascular risk factors control among individuals with diabetes remains a challenge. We evaluated changes in glucose, lipid, and blood pressure control among diabetes patients after implementation of a large-scale population management program, known as Preventing Heart Attacks and Strokes Everyday, at Kaiser Permanente Northern California (KPNC), during 2004-2013.

Concepts: Blood, Myocardial infarction, Heart, Blood vessel, Stroke, Circulatory system, Artery, Kaiser Permanente

11

The Kaiser Permanente (KP) Research Program on Genes, Environment and Health (RPGEH), in collaboration with the University of California, San Francisco, undertook genome-wide genotyping of over 100,000 subjects that constitute the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. The project, which generated over 70 billion genotypes, represents the first large scale use of the Affymetrix Axiom Genotyping Solution. Because genotyping took place over a short 14-month period, creating a near-real time analysis pipeline for experimental assay quality control and final optimized analyses was critical. Because of the multi-ethnic nature of the cohort, four different ethnic-specific arrays were employed to enhance genome-wide coverage. All assays were performed on DNA extracted from saliva samples. To improve sample call rates and significantly increase genotype concordance, we partitioned the cohort into disjoint packages of plates with similar assay contexts. Using strict QC criteria, the overall genotyping success rate was 103,067 out of 109,837 samples assayed (93.8%), with a range of 92.1% to 95.4% for the four different arrays. Similarly, the SNP genotyping success rate ranged from 98.1% to 99.4% across the four arrays, the variation mostly depending on how many SNPs were included as single copy versus double copy on a particular array. The high quality and large scale of genotype data created on this cohort, in conjunction with comprehensive longitudinal data from the KP electronic health records of participants will enable a broad range of highly powered genome-wide association studies on a diversity of traits and conditions.

Concepts: DNA, Gene, Genetics, Epidemiology, Biology, Quality control, Genome-wide association study, Kaiser Permanente

11

We conducted a nested case-control study including 407 cases and 2,075 frequency matched controls to investigate the association between maternal infections during pregnancy and risk of autism spectrum disorders (ASD). Cases, controls, and maternal infections were ascertained from Kaiser Permanente Northern California clinical databases. No overall association between diagnoses of any maternal infection during pregnancy and ASD was observed [adjusted odds ratio (ORadj) = 1.15, 95 % confidence interval (CI) 0.92-1.43]. However, women with infections diagnosed during a hospital admission (ORadj = 1.48, 95 % CI 1.07-2.04), particularly bacterial infections (ORadj = 1.58, 95 % CI 1.06-2.37), were at increased risk of delivering a child with ASD. Multiple infections during pregnancy were associated with ASD (ORadj = 1.36, 95 % CI 1.05-1.78).

Concepts: Immune system, Experimental design, Epidemiology, Bacteria, Infection, Odds ratio, Autism, Kaiser Permanente