Permanente Northern California Health Plan Research Articles

Survival by race and ethnicity among insured patients with early-onset colorectal cancer.

18 Background: Colorectal cancer (CRC) incidence and mortality have decreased in the United States over the past 3 decades, but the incidence is increasing in those <50 years of age (i.e., early-onset CRC). Studies have examined racial and ethnic differences in CRC incidence in this age group, but little is known about differences in survival. Examining survival by race and ethnicity among patients with early-onset CRC may provide insights about differences in risk factors, access to care, and treatment. Methods: This retrospective cohort study included Kaiser Permanente Northern California health plan members 18-49 years of age and diagnosed with CRC between 2006-2019. Race and ethnicity were self-reported as Asian/Pacific Islander, Black, Hispanic, or White. 5-year survival probability was assessed using Kaplan-Meier analyses. Cox regression with adjustment was used to evaluate associations between race and ethnicity and 5-year survival. Results: Of 1620 patients, median age was 45.4 years, 47% were female, 20% were Asian/Pacific Islander, 8% Black, 22% Hispanic, and 50% non-Hispanic White persons. Adjusted for age, sex, and comorbidities, Hispanic persons had a higher risk of death at 5 years compared to White persons (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.09-1.83) (Table). Sequentially adding annual household income and neighborhood deprivation index had no impact on the association; adding tumor stage decreased the HR to 1.14 (0.87-1.49) and adding tumor and treatment factors decreased the HR to 1.08 (0.82-1.42). Risk of death among Asian/Pacific Islander and Black patients did not differ from White patients. Conclusions: Among insured patients with early-onset CRC, Hispanic patients had a higher risk of death at 5 years than patients of White race. The higher risk was associated with differences in tumor stage at diagnosis, tumor factors, and treatment factors. Targeted interventions to improve CRC symptom awareness and remove barriers to CRC diagnosis and treatment among vulnerable populations may be needed to eliminate disparities in early-onset CRC survival. [Table: see text]

Risk factors for recurrent emergency care utilization for flares in inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) need frequent emergency care due to flares of their disease. However, understanding which patients are most vulnerable to repeat emergency care due to recurrent flares of their disease remains poor. This was a retrospective cohort study of Kaiser Permanente Northern California health plan members aged ≥18 years between 2009 and 2018. Our primary outcome was occurrence of repeat emergency department (ED) visits with a primary diagnosis code of IBD in the 6 months following their index ED visit. Baseline characteristics and clinical service use patterns were extracted. We used multivariable negative binomial regression analysis to measure the incident risk of a recurrent ED visit within 6 months. We found 2111 patients who met eligibility criteria, of whom 56.7% were female and 39.7% were non-White. During the 6-month observation period, 19.3% (n = 408) returned to the ED for a second IBD flare. In adjusted analyses, we found older age (incident risk ratio [IRR] 0.44, 95% confidence interval [CI] 0.31-0.62 for age 60+ compared to 18-30), higher neighborhood household income (IRR 0.80, 95% CI 0.65-0.98 for income ≥$85,000), and diagnosis of alcohol use disorder were associated with a lower risk of repeat ED utilization (IRR 0.62, 95% CI 0.41-0.93), while presence of mood disorder (IRR 1.26, 95% CI 1.03-1.58), history of opiate prescription (IRR 1.38, 95% CI 1.10-1.73), and corticosteroid prescription (IRR 1.57, 95% CI 1.27-1.95) were associated with increased risk of repeat ED utilization. Prompt outpatient follow-up was not associated with a lower odds of recurrent ED utilization (IRR 0.93, 95% CI 0.75-1.15). Our study identified multiple patient characteristics associated with higher recurrent short-term use of the ED for IBD care. Although we did not find prompt outpatient follow-up after initial ED visit to be protective, targeted interventions directed at high-risk individuals based on mood disorders, opiate use, or steroid use may help to optimize care and health care utilization.

Low- and High-Density Lipoprotein Cholesterol and Dementia Risk Over 17 Years of Follow-up Among Members of a Large Health Care Plan.

The associations of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) with dementia risk in later life may be complex, and few studies have sufficient data to model nonlinearities or adequately adjust for statin use. We evaluated the observational associations of HDL-C and LDL-C with incident dementia in a large and well-characterized cohort with linked survey and electronic health record (EHR) data. Kaiser Permanente Northern California health plan members aged 55 years and older who completed a health behavior survey between 2002 and 2007, had no history of dementia before the survey, and had laboratory measurements of cholesterol within 2 years after survey completion were followed up through December 2020 for incident dementia (Alzheimer disease-related dementia [ADRD]; Alzheimer disease, vascular dementia, and/or nonspecific dementia) based on ICD-9 or ICD-10 codes in EHRs. We used Cox models for incident dementia with follow-up time beginning 2 years postsurvey (after cholesterol measurement) and censoring at end of membership, death, or end of study period. We evaluated nonlinearities using B-splines, adjusted for demographic, clinical, and survey confounders, and tested for effect modification by baseline age or prior statin use. A total of 184,367 participants [mean age at survey = 69.5 years, mean HDL-C = 53.7 mg/dL (SD = 15.0), mean LDL-C = 108 mg/dL (SD = 30.6)] were included. Higher and lower HDL-C values were associated with elevated ADRD risk compared with the middle quantile: HDL-C in the lowest quintile was associated with an HR of 1.07 (95% CI 1.03-1.11), and HDL-C in the highest quintile was associated with an HR of 1.15 (95% CI 1.11-1.20). LDL-C was not associated with dementia risk overall, but statin use qualitatively modified the association. Higher LDL-C was associated with a slightly greater risk of ADRD for statin users (53% of the sample, HR per 10 mg/dL increase = 1.01, 95% CI 1.01-1.02) and a lower risk for nonusers (HR per 10 mg/dL increase = 0.98; 95% CI 0.97-0.99). There was evidence for effect modification by age with linear HDL-C (p = 0.003) but not LDL-C (p = 0.59). Both low and high levels of HDL-C were associated with elevated dementia risk. The association between LDL-C and dementia risk was modest.

Cross-Trait Mendelian Randomization Study to Investigate Whether Migraine Is a Risk Factor for Multiple Sclerosis.

Migraine is common among people with multiple sclerosis (MS), but the reasons for this are unknown. We tested 3 hypothesized mechanisms for this observed comorbidity, including migraine is a risk factor of MS, genetic variants are shared between the conditions, and migraine is because of MS. Data were from 2 sources: publicly available summary statistics from genome-wide association studies of MS (N = 115,748) and migraine (N = 375,752 and N = 361,141) and a case-control study of MS recruited from the Kaiser Permanente Northern California Health Plan (N = 1,991). For the latter participants, migraine status was ascertained using a validated electronic health record migraine probability algorithm or self-report. Using the public summary statistics, we used 2-sample Mendelian randomization to test whether a migraine genetic instrumental variable was associated with MS. We used linkage disequilibrium score regression and LOGODetect to ascertain whether MS and migraine shared genetic variants across the genome and regionally. Using the Northern California MS cohort, we used logistic regression to identify whether people with both MS and migraine had different odds of clinical characteristics (e.g., age at MS onset, Perceived Deficits Questionnaire, and depression) or MS-specific risk factors (e.g., body mass index, smoking status, and infectious mononucleosis status) compared with people with MS without migraine. We did not find evidence supporting migraine as a causal risk factor of MS (p = 0.29). We did, however, identify 4 major histocompatibility complex (MHC) loci shared between MS and migraine. Among the Northern California MS cohort, 774 (39%) experienced migraine. People with both MS and migraine from this cohort were more likely to ever smoke (odds ratio [OR] = 1.30, 95% CI: 1.08-1.57), have worse self-reported cognitive deficits (OR = 1.04, 95% CI: 1.02-1.06), and ever experience depression (OR = 1.48, 95% CI: 1.22-1.80). Our findings do not support migraine as a causal risk factor of MS. Several genetic variants, particularly in the MHC, may account for some of the overlap. It seems likely that migraine within the context of MS is because of MS. Identifying what increases the risk of migraine within MS might lead to an improved treatment and quality of life.

Comparison of coronary revascularization strategies in older adults presenting with acute coronary syndromes.

The optimal coronary revascularization strategy to maximize the patient-centered outcome of days alive and out of hospital (DAOH), in multimorbid older (≥65-years) adults after an acute coronary syndrome (ACS) is incompletely understood. Using Kaiser Permanente Northern California Health Plan databases, we identified 3871 patients ≥65-years presenting with ACS between 1/1/2010-3/1/2018 who underwent coronary revascularization with either coronary artery bypass grafting (CABG, N=1575) or multivessel percutaneous coronary intervention (PCI, N=2296). Selection bias was accounted for through propensity score modeling techniques and inverse probability of treatment weighting. Cox proportional hazards models were fit to evaluate the association of revascularization type with outcomes. Absolute DAOH and the relative risk of achieving ≥90%DAOH during three time intervals. All-cause mortality, recurrent MI, stroke, rehospitalization, repeat revascularization, and dialysis initiation. CABG (compared to PCI) was associated with greater absolute number of DAOH, significant after the first year (mean difference at 1-year: +5.8 days, 95% confidence interval [CI], -1.6 to 13 days; 3-years: +56 days, 95%CI, +25 to +88 days; 5-years: + 131 days, 95%CI, +57 to +205 days). The relative risk of achieving ≥90% DAOH significantly favored CABG after the first year (1-year:1.02, 95%CI, 0.98-1.05; 3-years:1.06, 95%CI 1.002-1.11, 5-years:1.12, 95%CI, 1.03-1.22), and was related to lower incidences of all-cause mortality, repeat revascularization, rehospitalization, incident dialysis, and nonfatal MI with CABG. In older adults with multivessel or left main coronary artery disease who presented with ACS, CABG, after the first year, was associated with a greater absolute number of DAOH-a geriatric and patient-centered outcome, compared to PCI. CABG patients also had a higher probability of achieving ≥90%DAOH-with lower all-cause mortality, recurrent MI, repeat revascularization, new dialysis, and rehospitalization rates. Future randomized trials should study the impact of optimal revascularization strategies on the quality of life of older adults with multimorbidity.

Particulate Matter and Cardiovascular Risk in Adults with Chronic Obstructive Pulmonary Disease.

Rationale: People with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular disease and may be more susceptible to air pollution exposure. However, no study has examined the association between long-term fine particulate matter exposure (≤2.5 μm in aerodynamic diameter) and risk of cardiovascular events in this potentially vulnerable population. Objectives: To estimate the association between long-term fine particulate matter and risk of cardiovascular events among adults with COPD. Methods: This retrospective cohort study included 169,714 adults with COPD who were members of the Kaiser Permanente Northern California health plan during 2007-2016. Electronic health record data were linked to 1 km modeled particulate matter ≤2.5 μm in aerodynamic diameter exposure estimates. We fit Cox proportional hazard models, adjusting for age, sex, race/ethnicity, calendar year, smoking, body mass index, comorbidities, medications, and socioeconomic status. In low exposure analyses, we examined effects below the current regulation limit (12 μg/m3). Measurements and Main Results: Among adults with COPD, a 10-μg/m3 increase in 1-year mean fine particulate matter exposure was associated with an elevated risk of cardiovascular mortality (hazard ratio, 1.10; 95% confidence interval [CI], 1.01-1.20). Effects were stronger in low exposure analyses (hazard ratio, 1.88; 95% CI, 1.56-2.27). Fine particulate matter exposure was not associated with acute myocardial infarction or stroke in overall analyses. Conclusions: Long-term fine particulate matter exposure was associated with an increased risk of cardiovascular mortality among adults with COPD. Current regulations may not sufficiently protect those with COPD.

Abstract 14363: Clustering of Multiple Cardiometabolic Risk Factors by Race/Ethnicity and Age

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among Americans. The burden of cardiometabolic risk factor clustering in ethnic subgroups is not well described for US Asians compared to other race/ethnicities. Methods: This cross-sectional study was conducted using electronic health data for White (N=634,200), Black (N=85,156), Hispanic (N=188,071), Filipino (N=78,000) and Chinese (N=72,545) Kaiser Permanente Northern California health plan members in 2016 who were aged 40-84y and had weight status assessed. We examined the proportions of men and women in each racial/ethnic group with clustered cardiometabolic risks (CCR), defined as having diabetes, hypertension, and obesity. Diabetes mellitus (DM) was based on a clinical DM diagnosis, lab criteria, or receipt of DM pharmacotherapy. Hypertension was defined by clinical diagnosis. Obesity was characterized by WHO standard (BMI ≥30 kg/m 2 ) and Asian-specific (BMI ≥27.5 kg/m 2 ) thresholds. Results: CCR prevalence varied by race/ethnicity, age, and the BMI criteria used for obesity (standard or Asian threshold). Use of the Asian threshold resulted in Filipinos having CCR prevalence that approached Blacks and Hispanics across all age groups (Figure). The Asian criterion nearly doubled the proportion of at-risk Filipinos, particularly older adults aged 65-84y. Filipinos had more than 2x higher CCR prevalence compared to Chinese. Among all ethnic groups except for Blacks, men were more likely than women to have CCR. Conclusion: Using an Asian-specific BMI obesity threshold, Filipino-Americans have a higher prevalence of cardiometabolic risk factor clustering than Chinese-Americans, resembling that of Blacks and Hispanics. Identifying Asian ethnicity in electronic health records could help facilitate earlier metabolic assessment and management to further reduce CVD burden, which may be especially important for men.

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

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. 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. 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. 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.

Aggregation of Asian-American subgroups masks meaningful differences in health and health risks among Asian ethnicities: an electronic health record based cohort study

BackgroundFew large cohort studies have examined the prevalence of diabetes mellitus (DM), hypertension (HTN), coronary artery disease (CAD), obesity, and smoking among middle-aged and older adults in the major Asian-American ethnic groups and Native Hawaiian/Pacific Islanders (PIs). The aim of this study was to evaluate how prevalence of these conditions and risk factors differs across Asian-American and PI ethnic groups and compares with an aggregated All Asian-American racial group.MethodsThis study used a cohort of 1.4 million adults aged 45 to 84 who were Kaiser Permanente Northern California health plan members during 2016. The cohort included approximately 274,910 Asian-Americans (Chinese, Filipino, Japanese, Korean, Southeast Asian, South Asian, other), 8450 PIs, 795,080 non-Hispanic whites, 107,200 blacks, and 210,050 Latinos. We used electronic health record data to produce age-standardized prevalence estimates of DM, HTN, CAD, obesity (using standard and Asian thresholds), and smoking for men and women in all racial/ethnic subgroups and compared these subgroups to an aggregated All Asian-American racial group and to whites, blacks, and Latinos.ResultsWe found large differences in health burden across Asian-American ethnic subgroups. For both sexes, there were 16 and > 22 percentage point differences between the lowest and highest prevalence of DM and HTN, respectively. Obesity prevalence among Asian subgroups (based on an Asian BMI ≥ 27.5 kg/m2 threshold) ranged from 14 to 39% among women and 21 to 45% among men. Prevalence of smoking ranged from 1 to 4% among women and 5 to 14% among men. Across all conditions and risk factors, prevalence estimates for Asian-American and PI ethnic groups significantly differed from those for the All Asian-American group. In general, Filipinos and PIs had greater health burden than All Asians, with prevalence estimates approaching those of blacks.ConclusionsIn a population of middle-aged and older adult Northern California health plan members, we found substantive differences in prevalence of chronic cardiovascular conditions, obesity, and smoking across Asian-American ethnic groups and between Asian-American ethnic groups and an aggregated All Asian racial group. Our study confirms that reporting statistics for an aggregated Asian-American racial group masks meaningful differences in Asian-American ethnic group health.

Trends in the Prevalence and Incidence of Attention-Deficit/Hyperactivity Disorder Among Adults and Children of Different Racial and Ethnic Groups

An increasing prevalence of adult attention-deficit/hyperactivity disorder (ADHD) diagnosis and treatment has been reported in clinical settings and administrative data in the United States. However, there are limited data on recent trends of adult ADHD diagnosis among racial/ethnic subgroups. To examine trends, including associated demographic characteristics, psychiatric diagnoses, and negative outcomes, in the prevalence and incidence of adult ADHD diagnosis among 7 racial/ethnic groups during a 10-year period. This cohort study investigated trends in the diagnosis of ADHD in adults who identified as African American or black, Native American, Pacific Islander, Latino or Hispanic, non-Hispanic white, Asian American, or other using the Kaiser Permanente Northern California health plan medical records. A total of 5 282 877 adult patients and 867 453 children aged 5 to 11 years who received care at Kaiser Permanente Northern California from January 1, 2007, to December 31, 2016, were included. Data analysis was performed from January 2017 through September 2019. Period of ADHD diagnosis. Prevalence and incidence of licensed mental health clinician-diagnosed ADHD in adults and prevalence of licensed mental health clinician-diagnosed ADHD in children aged 5 to 11 years. Of 5 282 877 adult patients (1 155 790 [21.9%] aged 25-34 years; 2 667 562 [50.5%] women; 2 204 493 [41.7%] white individuals), 59 371 (1.12%) received diagnoses of ADHD. Prevalence increased from 0.43% in 2007 to 0.96% in 2016. Among 867 453 children aged 5 to 11 years (424 449 [48.9%] girls; 260 236 [30.0%] white individuals), prevalence increased from 2.96% in 2007 to 3.74% in 2016. During the study period, annual adult ADHD prevalence increased for every race/ethnicity, but white individuals consistently had the highest prevalence rates (white individuals: 0.67%-1.42%; black individuals: 0.22%-0.69%; Native American individuals: 0.56%-1.14%; Pacific Islander individuals: 0.11%-0.39%; Hispanic or Latino individuals: 0.25%-0.65%; Asian American individuals: 0.11%-0.35%; individuals from other races/ethnicities: 0.29%-0.71%). Incidence of ADHD diagnosis per 10 000 person-years increased from 9.43 in 2007 to 13.49 in 2016. Younger age (eg, >65 years vs 18-24 years: odds ratio [OR], 0.094; 95% CI, 0.088-0.101; P < .001), male sex (women: OR, 0.943; 95% CI, 0.928-0.959; P < .001), white race (eg, Asian patients vs white patients: OR, 0.248; 95% CI, 0.240-0.257; P < .001), being divorced (OR, 1.131; 95% CI, 1.093-1.171; P < .001), being employed (eg, retired vs employed persons: OR, 0.278; 95% CI, 0.267-0.290; P < .001), and having a higher median education level (OR, 2.156; 95% CI, 2.062-2.256; P < .001) were positively associated with odds of ADHD diagnosis. Having an eating disorder (OR, 5.192; 95% CI, 4.926-5.473; P < .001), depressive disorder (OR, 4.118; 95% CI, 4.030-4.207; P < .001), bipolar disorder (OR, 4.722; 95% CI, 4.556-4.894; P < .001), or anxiety disorder (OR, 2.438; 95% CI, 2.385-2.491; P < .001) was associated with higher odds of receiving an ADHD diagnosis. Adults with ADHD had significantly higher odds of frequent health care utilization (OR, 1.303; 95% CI, 1.272-1.334; P < .001) and sexually transmitted infections (OR, 1.289; 95% CI 1.251-1.329; P < .001) compared with adults with no ADHD diagnosis. This study confirmed the reported increases in rates of ADHD diagnosis among adults, showing substantially lower rates of detection among minority racial/ethnic subgroups in the United States. Higher odds of negative outcomes reflect the economic and personal consequences that substantiate the need to improve assessment and treatment of ADHD in adults.

Influence of a New Diabetes Diagnosis on the Health Behaviors of the Patient’s Partner

When a person is given a diagnosis of diabetes, the changes in his or her health behaviors may influence the behaviors of his or her partner. The diabetes diagnosis may affect household members' perceptions of their own health risks, which could trigger behavioral change. The purpose of this study was to assess whether partners of persons with newly diagnosed diabetes changed their health behaviors compared with partners of persons without diabetes. The study population consisted of Kaiser Permanente Northern California health plan members from 2007 to 2011. This cohort study assessed differences in change of 8 health behaviors. The study compared coresiding partners of persons with newly diagnosed diabetes before and after a diabetes diagnosis with a 5 to 1 matched sample of coresiding partners of persons without diabetes. A total of 180,910 couples were included in the analysis. After adjusting for baseline characteristics, partners of persons with newly diagnosed diabetes had significantly higher rates of participation in weight management-related health education classes (risk ratio [RR] = 1.50; 95% CI, 1.39-1.63); smoking cessation medication use (RR = 1.25; 95% CI, 1.05-1.50); glucose screening (RR = 1.07; 95% CI, 1.05-1.08); clinically meaningful weight loss (RR = 1.06; 95% CI, 1.02-1.11); lipid screening (RR = 1.05; 95% CI, 1.04-1.07); influenza vaccination (RR = 1.03; 95% CI, 1.02-1.04); and blood pressure screening (RR = 1.02; 95% CI, 1.02-1.03) compared with partners of persons without diabetes. There were small but significant differences in health-related behavioral changes among partners of persons with newly diagnosed diabetes compared with partners of persons without diabetes, even when no intervention occurred. This finding suggests a diabetes diagnosis within a family may be a teachable moment to improve health behaviors at the household level.

Feasibility of analyzing DNA copy number variation in breast cancer tumor specimens from 1950 to 2010: how old is too old?

The purpose of the study was to assess the feasibility of quantifying long-term trends in breast tumor DNA copy number variation (CNV) profiles. We evaluated CNV profiles in formalin-fixed paraffin-embedded (FFPE) tumor specimens from 30 randomly selected Kaiser Permanente Northern California health plan women members diagnosed with breast cancer from 1950 to 2010. Assays were conducted for five cases per decade who had available tumor blocks and pathology reports. As compared to the tumors from the 1970s to 2000s, the older tumors dating back to the 1950s and 1960s were much more likely to (1) fail quality control, and (2) have fewer CNV events (average 23 and 31 vs. 58 to 69), fewer CNV genes (average 5.1 and 3.7k vs. 8.1to 10.3k), shorter CNV length (average 2,440 and 3,300k vs. 5,740to 9,280k), fewer high frequency Del genes (37 and 25% vs. 54to 76%), and fewer high frequency high_Amp genes (20% vs. 56to73%). On average, assay interpretation took an extra 60min/specimen for cases from the 1960s versus 20min/specimen for the most recent tumors. Assays conducted in the mid-2010s for CNVs may be feasible for FFPE tumor specimens dating back to the 1980s, but less feasible for older specimens.

Serious infections among a large cohort of subjects with systemically treated psoriasis

Biologic therapy is effective for treatment of moderate-to-severe psoriasis but may be associated with an increased risk for serious infection. To estimate the serious infection rate among patients with psoriasis treated with biologic as compared with nonbiologic systemic agents within a community-based health care delivery setting. We identified 5889 adult Kaiser Permanente Northern California health plan members with psoriasis who had ever been treated with systemic therapies and calculated the incidence rates and 95% confidence intervals (CIs) for serious infections over 29,717 person-years of follow-up. Adjusted hazard ratios (aHRs) were calculated using Cox regression. Adjusting for age, sex, race or ethnicity, and comorbidities revealed a significantly increased risk for overall serious infection among patients treated with biologics as compared with those treated with nonbiologics (aHR, 1.31; 95% CI, 1.02-1.68). More specifically, there was a significantly elevated risk for skin and soft tissue infection (aHR, 1.75; 95% CI, 1.19-2.56) and meningitis (aHR, 9.22; 95% CI, 1.77-48.10) during periods of active biologic use. Risk associated with individual drugs was not examined. We found an increased rate of skin and soft tissue infections among patients with psoriasis treated with biologic agents. There also was a signal suggesting increased risk for meningitis. Clinicians should be aware of these potential adverse events when prescribing biologic agents.

CUMULATIVE EXPOSURE TO ELEVATED BLOOD PRESSURE THROUGHOUT ADULTHOOD AND LATE-LIFE DEMENTIA RISK

Hypertension, particularly in midlife, is associated with increased dementia risk. Cumulative exposure to elevated blood pressure is likely relevant, but few studies have data to estimate cumulative exposure to elevated blood pressure throughout midlife, particularly in ethnically diverse populations. The objective of this study was to examine the association of cumulative exposure to elevated systolic blood pressure between ages 30 and 50 with late-life dementia risk among black and white Americans. This is a cohort study of n=6,168 black (35%) and white (65%) Kaiser Permanente Northern California health plan members who were ages 30–35 in 1964–1973 and remained members as of January 1, 1996. Blood pressure was measured at clinical exams between1964–1985. Late-life dementia diagnosis was collected from medical records January 1, 1996-October 15, 2015. Cumulative exposure to elevated systolic blood pressure at ages 30–50 years was estimated with “area under the curve” for each person's systolic blood pressure trajectory from linear mixed effects models with age as the timescale and restricted cubic splines to account for nonlinearities. We examined the association between cumulative years of hypertension (systolic blood pressure >= 140 mmHg) and pre-hypertension (systolic blood pressure 120–139mmHg) between ages 30–50 years with late-life dementia incidence with Cox proportional hazards models adjusting for age (as timescale), sex, race, and education. Blood pressure was measured an average of 3.3 times (range 1–13) between 1964–1985. Between ages 30–50, estimated cumulative exposure to prehypertension was high (mean=12.7 years); estimated cumulative exposure to hypertension was lower (mean=1.2 years). Mean age at the start of dementia follow up in 1996 was 59 years (range 53–67 years). Over a mean of 15.2 years of follow-up, there were n=522 dementia cases. For every 5 years of cumulative exposure to pre-hypertension, dementia risk increased by 8% (hazard ratio (HR)=1.08; 95% CI=1.02–1.14). For every 5 years of cumulative exposure to hypertension, dementia risk increased by 24% (HR=1.24; 95% CI=1.12–1.36). The association between cumulative exposure to elevated systolic blood pressure did not differ by race. Cumulative exposure to elevated systolic blood pressure throughout adulthood is associated with late-life dementia risk in an ethnically diverse population.

Malignancy rates in a large cohort of patients with systemically treated psoriasis in a managed care population

Moderate to severe psoriasis often requires treatment with systemic agents, many of which have immunosuppressive properties and could increase cancer risk, including nonmelanoma skin cancer (NMSC). We sought to estimate the overall malignancy rate (excluding NMSC) and NMSC rate among 5889 patients with systemically treated psoriasis. We identified a cohort of adult Kaiser Permanente Northern California health plan members with psoriasis diagnosed from 1998 to 2011 and treated with at least 1 systemic antipsoriatic agent and categorized them into ever-biologic or nonbiologic users. Malignancy rates were calculated per 1000 person-years of follow-up with 95% confidence intervals (CI). Crude and confounder-adjusted hazard ratios (aHRs) were calculated using Cox regression. Most biologic-exposed members were treated with TNF-alfa inhibitors (n=2214, 97%). Overall incident cancer rates were comparable between ever-biologic as compared to nonbiologic users (aHR 0.86, 95% CI 0.66-1.13). NMSC rates were 42% higher among individuals ever exposed to a biologic (aHR 1.42, 95% CI 1.12-1.80), largely driven by increased cutaneous squamous cell carcinoma risk (aHR 1.81, 95% CI 1.23-2.67). No information was available on disease severity. We found increased incidence of cutaneous squamous cell carcinoma among patients with systemically treated psoriasis who were ever exposed to biologics, the majority of which were TNF-alfa inhibitors. Increased skin cancer surveillance in this population may be warranted.

Differences in Access to and Preferences for Using Patient Portals and Other eHealth Technologies Based on Race, Ethnicity, and Age: A Database and Survey Study of Seniors in a Large Health Plan.

BackgroundPatients are being encouraged to go online to obtain health information and interact with their health care systems. However, a 2014 survey found that less than 60% of American adults aged 65 and older use the Internet, with much lower usage among black and Latino seniors compared with non-Hispanic white seniors, and among older versus younger seniors.ObjectiveOur aims were to (1) identify race/ethnic and age cohort disparities among seniors in use of the health plan’s patient portal, (2) determine whether race/ethnic and age cohort disparities exist in access to digital devices and preferences for using email- and Web-based modalities to interact with the health care system, (3) assess whether observed disparities in preferences and patient portal use are due simply to barriers to access and inability to use the Internet, and (4) learn whether older adults not currently using the health plan’s patient portal or website have a potential interest in doing so in the future and what kind of support might be best suited to help them.MethodsWe conducted two studies of seniors aged 65-79 years. First, we used administrative data about patient portal account status and utilization in 2013 for a large cohort of English-speaking non-Hispanic white (n=183,565), black (n=16,898), Latino (n=12,409), Filipino (n=11,896), and Chinese (n=6314) members of the Kaiser Permanente Northern California health plan. Second, we used data from a mailed survey conducted in 2013-2014 with a stratified random sample of this population (final sample: 849 non-Hispanic white, 567 black, 653 Latino, 219 Filipino, and 314 Chinese). These data were used to examine race/ethnic and age disparities in patient portal use and readiness and preferences for using digital communication for health-related purposes.ResultsAdults aged 70-74 and 75-79 were significantly less likely than 65-69 year olds to be registered to use the patient portal, and among those registered, to have used the portal to send messages, view lab test results, or order prescription refills. Across all age groups, non-Hispanic whites and Chinese seniors were significantly more likely than black, Latino, and Filipino seniors to be registered and to have performed these actions. The survey found that black, Latino, and Filipino seniors and those 75 years old and older were significantly less likely to own digital devices (eg, computers, smartphones), use the Internet and email, and be able and willing to use digital technology to perform health care-related tasks, including obtaining health information, than non-Hispanic whites, Chinese, and younger seniors (aged 65-69), respectively. The preference for using non-digital modalities persisted even among Internet users.ConclusionsHealth plans, government agencies, and other organizations that serve diverse groups of seniors should include social determinants such as race/ethnicity and age when monitoring trends in eHealth to ensure that eHealth disparities do not induce greater health status and health care disparities between more privileged and less privileged groups.

Analyzing historical trends in breast cancer biomarker expression: a feasibility study (1947-2009).

Background/Objectives:Determining long-term trends in tumor biomarker expression is essential for understanding aspects of tumor biology amenable to change. Limiting the availability of such data, currently used assays for biomarkers are relatively new. For example, assays for the estrogen receptor (ER), which are the oldest, extend back only to the 1970s.Methods:To extend scant knowledge about the feasibility of obtaining long-term data on tumor biomarkers, we randomly selected 60 breast cancer cases (10 per decade) diagnosed between 1947–2009 among women members of the Kaiser Permanente Northern California health plan to obtain and analyze their formalin-fixed paraffin-embedded (FFPE) tumor specimens. For each tumor specimen, we created duplicate tissue microarrays for analysis.Results:We located tumor blocks and pathology reports for 50 of the 60 cases (83%), from which we randomly sampled 5 cases per decade for biomarker analysis (n=30). All 30 cases displayed excellent morphology and exhibited biomarkers compatible with histologic type and grade. Test–retest reliability was also excellent: 100% for ER; 97% for human epidermal growth factor receptor 2 and epidermal growth factor receptor; 93% for progesterone receptor and cytokeratin 5/6; and 90% for Ki67 and molecular phenotype; the kappa statistic was excellent (>0.9) for 4 of the 7 biomarkers, strong (0.6–0.8) for 2, and fair for only 1 (owing to low prevalence).Conclusions:These results indicate immunostaining for biomarkers commonly used to evaluate breast cancer biology and assign surrogate molecular phenotypes can reliably be employed on archival FFPE specimens up to 60 years old.

The Association of Refractive Error with Glaucoma in a Multiethnic Population

To evaluate the association between refractive error and the prevalence of glaucoma by race or ethnicity. Cross-sectional study. Kaiser Permanente Northern California Health Plan members with refractive error measured at 35 years of age or older between 2008 and 2014 and with no history of cataract surgery, refractive surgery, or a corneal disorder. We identified 34 040 members with glaucoma or ocular hypertension (OHTN; cases) and 403 398 members without glaucoma (controls). Glaucoma cases were classified as primary angle-closure glaucoma (PACG); 1 of the 4 forms of open-angle glaucoma: primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), pigmentary glaucoma (PIGM), and pseudoexfoliation glaucoma (PEX); or OHTN. Refractive error, expressed as spherical equivalent (SE), was coded as a continuous trait and also as categories. Logistic regression analyses were used to estimate theassociation between refractive error and the prevalence of glaucoma overall and in specific racial or ethnic groups. The association between refractive error and glaucoma subtypes evaluated as odds ratios (ORs) with 95% confidence intervals (CIs). In controls, the mean SE was-0.59 diopters (D) (standard deviation, 2.62 D). Each 1-D reduction in SE was associated with a 22% decrease in the odds of PACG (OR, 0.78; 95% CI, 0.77-0.80) and with increases in the odds of open-angle glaucoma ranging from 1.23 (95% CI, 1.20-1.26) for PIGM, to 1.07 (95% CI, 1.03-1.11) for PEX, and to 1.05 (95% CI, 1.04-1.06) for OHTN. In addition, we observed a stronger association between myopia and POAG among non-Hispanic whites (OR, 1.12; 95% CI, 1.11-1.13) and NTG among Asians (OR, 1.17; 95% CI, 1.15-1.20) and non-Hispanic whites (OR, 1.19; 95% CI, 1.15-1.22). Myopia was associated with an increased prevalence of all forms of open-angle glaucoma and OHTN, whereas hyperopia was associated with a substantially increased prevalence of PACG. Although high myopia is a strong risk factor for glaucoma subtypes, low and moderate myopia also have a significant effect on glaucoma risk. Additionally, there were moderate racial differences in the association of myopia with the risk of POAG and NTG.

Validity of diagnostic codes and laboratory tests of liver dysfunction to identify acute liver failure events

Identification of acute liver failure (ALF) is important for post-marketing surveillance of medications, but the validity of using ICD-9 diagnoses and laboratory data to identify these events within electronic health records is unknown. We examined positive predictive values (PPVs) of hospital ICD-9 diagnoses and laboratory tests of liver dysfunction for identifying ALF within a large, community-based integrated care organization. We identified Kaiser Permanente Northern California health plan members (2004-2010) with a hospital diagnosis suggesting ALF (ICD-9 570, 572.2, 572.4, 572.8, 573.3, 573.8, or V42.7) plus an inpatient international normalized ratio ≥1.5 (off warfarin) and total bilirubin ≥5.0 mg/dL. Hospital records were reviewed by hepatologists to adjudicate ALF events. PPVs for confirmed outcomes were determined for individual ICD-9 diagnoses, diagnoses plus prescriptions for hepatic encephalopathy treatment, and combinations of diagnoses in the setting of coagulopathy and hyperbilirubinemia. Among 669 members with no pre-existing liver disease, chart review confirmed ALF in 62 (9%). Despite the presence of co-existing coagulopathy and hyperbilirubinemia, individual ICD-9 diagnoses had low PPVs (range, 5-15%); requiring prescriptions for encephalopathy treatment did not increase PPVs of these diagnoses (range, 2-23%). Hospital diagnoses of other liver disorders (ICD-9 573.8) plus hepatic coma (ICD-9 572.2) had high PPV (67%; 95%CI, 9-99%) but only identified two (3%) ALF events. Algorithms comprising relevant hospital diagnoses, laboratory evidence of liver dysfunction, and prescriptions for hepatic encephalopathy treatment had low PPVs for confirmed ALF events. Studies of ALF will need to rely on medical records to confirm this outcome.

The Impact of Central Corneal Thickness on the Risk for Glaucoma in a Large Multiethnic Population

To investigate the relationship between central corneal thickness (CCT) and demographics, and determine whether CCT may be a substantial mediator of the relationships between glaucoma and its demographic risk factors. This cross-sectional study included patients in the Kaiser Permanente Northern California health plan from January 1, 2007 to December 31, 2011 who were 40 years and older and had a documented CCT measurement (N=81,082). Those with any cornea-related diagnoses or a history of corneal refractive surgery were excluded. Demographic characteristics, including age, sex, and race/ethnicity, as well as clinical information including glaucoma-related diagnosis, diabetic status, CCT, and intraocular pressure were gathered from the electronic medical record. Multivariate linear regression analysis indicated that female sex, increased age, and black race were significantly associated with thinner corneas. A subgroup analysis among Asians revealed that Chinese, Japanese, and Koreans had corneas 6 to 13 µm thicker than South and Southeast Asians, Filipinos, and Pacific Islanders for each diagnosis (P<0.001). In our population, 24.5% (N=19878) had some form of open-angle glaucoma; 21.9% (N=17,779) did not have any glaucoma-related diagnosis. Variation in CCT accounted for only 6.68% [95% confidence interval (CI), 6.14%-7.24%] of the increased risk of open-angle glaucoma seen with increasing age, but explained as much as 29.4% (95% CI, 27.0%-32.6%) of the increased risk of glaucoma seen among blacks, and 29.5% (95% CI, 23.5%-37.0%) of the increased risk of glaucoma seen among Hispanics. CCT seems to explain a substantial portion of the increased risk of glaucoma seen among blacks and Hispanics.