Kaiser Permanente Southern California Health Research Articles

Mortality Outcomes in a Large Population with and without Covert Cerebrovascular Disease.

Covert cerebrovascular disease (CCD) is frequently reported on neuroimaging and associates with increased dementia and stroke risk. We aimed to determine how incidentally-discovered CCD during clinical neuroimaging in a large population associates with mortality. We screened CT and MRI reports of adults aged ≥50 in the Kaiser Permanente Southern California health system who underwent neuroimaging for a non-stroke clinical indication from 2009-2019. Natural language processing identified incidental covert brain infarcts (CBI) and/or white matter hyperintensities (WMH), grading WMH as mild/moderate/severe. Models adjusted for age, sex, ethnicity, multimorbidity, vascular risks, depression, exercise, and imaging modality. Of n=241,028, the mean age was 64.9 (SD=10.4); mean follow-up 4.46 years; 178,554 (74.1%) had CT; 62,474 (25.9%) had MRI; 11,328 (4.7%) had CBI; and 69,927 (29.0%) had WMH. The mortality rate per 1,000 person-years with CBI was 59.0 (95%CI 57.0-61.1); with WMH=46.5 (45.7-47.2); with neither=17.4 (17.1-17.7). In adjusted models, mortality risk associated with CBI was modified by age, e.g. HR 1.34 [1.21-1.48] at age 56.1 years vs HR 1.22 [1.17-1.28] at age 72 years. Mortality associated with WMH was modified by both age and imaging modality e.g., WMH on MRI at age 56.1 HR = 1.26 [1.18-1.35]; WMH on MRI at age 72 HR 1.15 [1.09-1.21]; WMH on CT at age 56.1 HR 1.41 [1.33-1.50]; WMH on CT at age 72 HR 1.28 [1.24-1.32], vs. patients without CBI or without WMH, respectively. Increasing WMH severity associated with higher mortality, e.g. mild WMH on MRI had adjusted HR=1.13 [1.06-1.20] while severe WMH on CT had HR=1.45 [1.33-1.59]. Incidentally-detected CBI and WMH on population-based clinical neuroimaging can predict higher mortality rates. We need treatments and healthcare planning for individuals with CCD.

Effectiveness of BNT162b2 BA.4/5 bivalent mRNA vaccine against a range of COVID-19 outcomes in a large health system in the USA: a test-negative case–control study

XBB-related omicron sublineages have recently replaced BA.4/5 as the predominant omicron sublineages in the USA and other regions globally. Despite preliminary signs of immune evasion of XBB sublineages, few data exist describing the real-world effectiveness of bivalent COVID-19 vaccines, especially against XBB-related illness. We aimed to investigate the effectiveness of the Pfizer--BioNTech BNT162b2 BA.4/5 bivalent vaccine against both BA.4/5-related and XBB-related disease in adults aged 18 years or older. In this test-negative case-control study, we estimated the effectiveness of the BNT162b2 BA.4/5 bivalent vaccine using data from electronic health records of Kaiser Permanente Southern California health system members aged 18 years or older who received at least two doses of the wild-type COVID-19 mRNA vaccines. Participants sought care for acute respiratory infection between Aug 31, 2022, and April 15, 2023, and were tested for SARS-CoV-2 via PCR tests. Relative vaccine effectiveness (≥2 doses of wild-type mRNA vaccine plus a BNT162b2 BA.4/5 bivalent booster vs ≥2 doses of a wild-type mRNA vaccine alone) and absolute vaccine effectiveness (vs unvaccinated individuals) was estimated against critical illness related to acute respiratory infection (intensive care unit [ICU] admission, mechanical ventilation, or inpatient death), hospital admission, emergency department or urgent care visits, and in-person outpatient encounters with odds ratios from logistic regression models adjusted for demographic and clinical factors. We stratified vaccine effectiveness estimates for hospital admission, emergency department or urgent care visits, and outpatient encounters by omicron sublineage (ie, likely BA.4/5-related vs likely XBB-related), time since bivalent booster receipt, age group, number of wild-type doses received, and immunocompromised status. This study is registered with ClinicalTrials.gov (NCT04848584). Analyses were conducted for 123 419 encounters (24 246 COVID-19 cases and 99 173 test-negative controls), including 4131 episode of critical illness (a subset of hospital admissions), 14 529 hospital admissions, 63 566 emergency department or urgent care visits, and 45 324 outpatient visits. 20 555 infections were BA.4/5 related and 3691 were XBB related. In adjusted analyses, relative vaccine effectiveness for those who received the BNT162b2 BA.4/5 bivalent booster compared with those who received at least two doses of a wild-type mRNA vaccine alone was an additional 50% (95% CI 23-68) against critical illness, an additional 39% (28-49) against hospital admission, an additional 35% (30-40) against emergency department or urgent care visits, and an additional 28% (22-33) against outpatient encounters. Waning of the bivalent booster from 0-3 months to 4-7 months after vaccination was evident for outpatient outcomes but was not detected for critical illness, hospital admission, and emergency department or urgent care outcomes. The relative effectiveness of the BNT162b2 BA.4/5 bivalent booster for XBB-related infections compared with BA.4/5-related infections was 56% (95% CI 12-78) versus 40% (27-50) for hospital admission; 34% (21-45) versus 36% (30-41) against emergency department or urgent care visits; and 29% (19-38) versus 27% (20-33) for outpatient encounters. By mid-April, 2023, individuals previously vaccinated only with wild-type vaccines had little protection against COVID-19-including hospital admission. A BNT162b2 BA.4/5 bivalent booster restored protection against a range of COVID-19 outcomes, including against XBB-related sublineages, with the most substantial protection observed against hospital admission and critical illness. Pfizer.

Air pollution and the sequelae of COVID-19 patients: A multistate analysis

ImportanceRecent evidence links air pollution to the severity COVID-19 symptoms and to death from the disease. To date, however, few studies have assessed whether air pollution affects the sequelae to more severe states or recovery from COVID-19 in a cohort with individual data. ObjectiveTo assess how air pollution affects the transition to more severe COVID-19 states or to recovery from COVID-19 infection in a cohort with detailed patient information. Design and OutcomesWe used a cohort design that followed patients admitted to hospital in the Kaiser Permanente Southern California (KPSC) Health System, which has 4.7 million members with characteristics similar to the general population. Enrollment began on 06/01/2020 and ran until 01/30/2021 for all patients admitted to hospital while ill with COVID-19. All possible states of sequelae were considered, including deterioration to intensive care, to death, discharge to recovery, or discharge to death. Transition risks were estimated with a multistate model. We assessed exposure using chemical transport model that predicted ambient concentrations of nitrogen dioxide, ozone, and fine particulate matter (PM2.5) at a 1 km scale. ResultsEach increase in PM2.5 concentration equivalent to the interquartile range was associated with increased risk of deterioration to intensive care (HR of 1.16; 95% CI: 1.12–1.20) and deterioration to death (HR of 1.11; 95% CI: 1.04–1.17). Results for ozone were consistent with PM2.5 effects, but ozone also affected the transition from recovery to death: HR of 1.24 (95% CI: 1.01–1.51). NO2 had weaker effects but displayed some elevated risks. ConclusionsPM2.5 and ozone were significantly associated with transitions to more severe states while in hospital and to death after discharge from hospital. Reducing air pollution could therefore lead to improved prognosis for COVID-19 patients and a sustainable means of reducing the health impacts of coronaviruses now and in the future.

Burden of Lower Respiratory Tract Infections Preventable by Adult Immunization With 15- and 20-Valent Pneumococcal Conjugate Vaccines in the United States.

Updated recommendations of the US Advisory Committee on Immunization Practices indicate that all adults aged ≥65 years and adults aged <65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults. We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California from 2016 through 2019. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against LRTI to model potential direct effects of PCV15/20 by age group and risk status. Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval, 41.3-131.8) and 108.6 (50.4-159.1) medically attended LRTI cases; 21.9 (10.1-32.0) and 26.6 (12.4-38.7) hospitalized LRTI cases; and 7.1 (3.3-10.5) and 8.7 (4.0-12.7) excess LRTI-associated deaths, each per 10 000 person-years. Among at-risk adults aged <65 years, use of PCV15 and PCV20 could prevent 85.7 (39.6-131.5) and 102.7 (47.8-156.7) medically attended LRTI cases per 10 000 person-years; 5.1 (2.4-8.6) and 6.2 (2.8-10.2) LRTI hospitalizations per 10 000 person-years, and 0.9 (0.4-1.4) and 1.1 (0.5-1.7) excess LRTI-associated deaths per 10 000 person-years. Our findings suggest recent recommendations, including PCV15/20 within adult pneumococcal vaccine series, may substantially reduce LRTI burden.

Assessment of Disruptive Life Events for Individuals Diagnosed With Schizophrenia or Bipolar I Disorder Using Data From a Consumer Credit Reporting Agency

There is a dearth of population-level data on major disruptive life events (defined here as arrests by a legal authority, address changes, bankruptcy, lien, and judgment filings) for patients with bipolar I disorder (BPI) or schizophrenia, which has limited studies on mental health and treatment outcomes. To conduct a population-level study on disruptive life events by using publicly available data on disruptive life events, aggregated by a consumer credit reporting agency in conjunction with electronic health record (EHR) data. This study used EHR data from 2 large, integrated health care systems, Kaiser Permanente Southern California and Henry Ford Health. Cohorts of patients diagnosed from 2007 to 2019 with BPI or schizophrenia were matched 1:1 by age at analysis, age at diagnosis (if applicable), sex, race and ethnicity, and Medicaid status to (1) an active comparison group with diagnoses of major depressive disorder (MDD) and (2) a general health (GH) cohort without diagnoses of BPI, schizophrenia, or MDD. Patients with diagnoses of BPI or schizophrenia and their respective comparison cohorts were matched to public records data aggregated by a consumer credit reporting agency (98% match rate). Analysis took place between November 2020 and December 2022. The differences in the occurrence of disruptive life events among patients with BPI or schizophrenia and their comparison groups. Of 46 167 patients, 30 008 (65%) had BPI (mean [SD] age, 42.6 [14.2] years) and 16 159 (35%) had schizophrenia (mean [SD], 41.4 [15.1] years). The majoriy of patients were White (30 167 [65%]). In addition, 18 500 patients with BPI (62%) and 6552 patients with schizophrenia (41%) were female. Patients with BPI were more likely to change addresses than patients in either comparison cohort (with the incidence ratio being as high as 1.25 [95% CI, 1.23-1.28]) when compared with GH cohort. Patients with BPI were also more likely to experience any of the financial disruptive life events with odds ratio ranging from 1.15 [95% CI, 1.07-1.24] to 1.50 [95% CI, 1.42-1.58]). The largest differences in disruptive life events were seen in arrests of patients with either BPI or schizophrenia compared with GH peers (3.27 [95% CI, 2.84-3.78] and 3.04 [95% CI, 2.57-3.59], respectively). Patients with schizophrenia had fewer address changes and were less likely to experience a financial event than their matched comparison cohorts. This study demonstrated that data aggregated by a consumer credit reporting agency can support population-level studies on disruptive life events among patients with BPI or schizophrenia.

Racial Disparities in Severe Maternal Morbidity in an Integrated Health Care System, Southern California, 2008-2017.

The study's objectives were to examine rates of severe maternal morbidity (SMM) over a 10-year period and assess racial/ethnic disparities in SMM among insured women in a large, integrated health care system in Southern California. We included Kaiser Permanente Southern California (KPSC) health plan members who gave birth at ≥20weeks' gestation in a KPSC-owned hospital during 2008-2017. An SMM case was defined as presence of one or more indicators of an SMM event during a birth hospitalization, identified using maternal electronic health records. Crude SMM rates/10,000 births were calculated by year and maternal race/ethnicity. Modified Poisson regression models were used to assess the association between race/ethnicity and SMM adjusted for other maternal demographics, pregnancy characteristics, and preexisting conditions. We identified 5,915 SMM cases among 335,310 births. Crude SMM rates increased from 94.7 per 10,000 in 2008 to 192.6 in 2015 and 249.5 in 2017. Non-Hispanic Black (adjusted risk ratio [aRR] 1.52; 95% confidence interval [CI] 1.37-1.69), Asian/Pacific Islander (aRR 1.29, 95% CI 1.18-1.41), and Hispanic (aRR 1.18, 95% CI 1.10-1.27) women had greater likelihood of SMM than non-Hispanic White women. After further adjusting for preexisting health conditions, differences in SMM by race/ethnicity remained. SMM rates increased during 2008-2017 and women of racial and ethnic minority groups, particularly non-Hispanic Black women, were more likely to experience an SMM event than non-Hispanic White women. Multilevel approaches to understanding structural and social factors that may be associated with racial and ethnic disparities in SMM are needed to develop and test effective interventions to reduce SMM.

BNT162b2 Against COVID-19-Associated Emergency Department and Urgent Care Visits Among Children 5-11 Years of Age: A Test Negative Design.

In a 1:1 matched test-negative design among 5- to 11-year-olds in the Kaiser Permanente Southern California health system (n = 3984), BNT162b2 effectiveness against the omicron-related emergency department or urgent care encounters was 60% [95%CI: 47-69] <3 months post-dose-two and 28% [8-43] after ≥3 months. A booster improved protection to 77% [53-88].

Analysis of mRNA COVID-19 Vaccine Uptake Among Immunocompromised Individuals in a Large US Health System

Immunocompromised individuals are at increased risk for severe outcomes due to SARS-CoV-2 infection. Given the varying and complex nature of COVID-19 vaccination recommendations, it is important to understand COVID-19 vaccine uptake in this vulnerable population. To assess mRNA COVID-19 vaccine uptake and factors associated with uptake among immunocompromised individuals from December 14, 2020, through August 6, 2022. This cohort study was conducted with patients of Kaiser Permanente Southern California (KPSC), an integrated health care system in the US. The study included patients aged 18 years or older who were immunocompromised (individuals with an immunocompromising condition or patients who received immunosuppressive medications in the year prior to December 14, 2020) and still met criteria for being immunocompromised 1 year later. Age, sex, self-identified race and ethnicity, prior positive COVID-19 test result, immunocompromising condition, immunomodulating medication, comorbidities, health care utilization, and neighborhood median income. Outcomes were the number of doses of mRNA COVID-19 vaccine received and the factors associated with receipt of at least 4 doses, estimated by hazard ratios (HRs) and 95% Wald CIs via Cox proportional hazards regression. Statistical analyses were conducted between August 9 and 23, 2022. Overall, 42 697 immunocompromised individuals met the study eligibility criteria. Among these, 18 789 (44.0%) were aged 65 years or older; 20 061 (47.0%) were women and 22 635 (53.0%) were men. With regard to race and ethnicity, 4295 participants (10.1%) identified as Asian or Pacific Islander, 5174 (12.1%) as Black, 14 289 (33.5%) as Hispanic, and 17 902 (41.9%) as White. As of the end of the study period and after accounting for participant censoring due to death or disenrollment from the KPSC health plan, 78.0% of immunocompromised individuals had received a third dose of mRNA COVID-19 vaccine. Only 41.0% had received a fourth dose, which corresponds to a primary series and a monovalent booster dose for immunocompromised individuals. Uptake of a fifth dose was only 0.9% following the US Centers for Disease Control and Prevention (CDC) recommendation to receive a second monovalent booster (ie, fifth dose). Adults aged 65 years or older (HR, 3.95 [95% CI, 3.70-4.22]) were more likely to receive at least 4 doses compared with those aged 18 to 44 years or 45 to 64 years (2.52 [2.36-2.69]). Hispanic and non-Hispanic Black adults (HR, 0.77 [95% CI, 0.74-0.80] and 0.82 [0.78-0.87], respectively, compared with non-Hispanic White adults), individuals with prior documented SARS-CoV-2 infection (0.71 [0.62-0.81] compared with those without), and individuals receiving high-dose corticosteroids (0.88 [0.81-0.95] compared with those who were not) were less likely to receive at least 4 doses. These findings suggest that adherence to CDC mRNA monovalent COVID-19 booster dose recommendations among immunocompromised individuals was low. Given the increased risk for severe COVID-19 in this vulnerable population and the well-established additional protection afforded by booster doses, targeted and tailored efforts to ensure that immunocompromised individuals remain up to date with COVID-19 booster dose recommendations are warranted.

Association of Incidentally Discovered Covert Cerebrovascular Disease Identified Using Natural Language Processing and Future Dementia.

Background Covert cerebrovascular disease (CCD) has been shown to be associated with dementia in population-based studies with magnetic resonance imaging (MRI) screening, but dementia risk associated with incidentally discovered CCD is not known. Methods and Results Individuals aged ≥50 years enrolled in the Kaiser Permanente Southern California health system receiving head computed tomography (CT) or MRI for nonstroke indications from 2009 to 2019, without prior ischemic stroke/transient ischemic attack, dementia/Alzheimer disease, or visit reason/scan indication suggestive of cognitive decline or stroke were included. Natural language processing identified incidentally discovered covert brain infarction (id-CBI) and white matter disease (id-WMD) on the neuroimage report; white matter disease was characterized as mild, moderate, severe, or undetermined. We estimated risk of dementia associated with id-CBI and id-WMD. Among 241 050 qualified individuals, natural language processing identified 69 931 (29.0%) with id-WMD and 11 328 (4.7%) with id-CBI. Dementia incidence rates (per 1000 person-years) were 23.5 (95% CI, 22.9-24.0) for patients with id-WMD, 29.4 (95% CI, 27.9-31.0) with id-CBI, and 6.0 (95% CI, 5.8-6.2) without id-CCD. The association of id-WMD with future dementia was stronger in younger (aged <70 years) versus older (aged ≥70 years) patients and for CT- versus MRI-discovered lesions. For patients with versus without id-WMD on CT, the adjusted HR was 2.87 (95% CI, 2.58-3.19) for older and 1.87 (95% CI, 1.79-1.95) for younger patients. For patients with versus without id-WMD on MRI, the adjusted HR for dementia risk was 2.28 (95% CI, 1.99-2.62) for older and 1.48 (95% CI, 1.32-1.66) for younger patients. The adjusted HR for id-CBI was 2.02 (95% CI, 1.70-2.41) for older and 1.22 (95% CI, 1.15-1.30) for younger patients for either modality. Dementia risk was strongly correlated with id-WMD severity; adjusted HRs compared with patients who were negative for id-WMD by MRI ranged from 1.41 (95% CI, 1.25-1.60) for those with mild disease on MRI to 4.11 (95% CI, 3.58-4.72) for those with severe disease on CT. Conclusions Incidentally discovered CCD is common and associated with a high risk of dementia, representing an opportunity for prevention. The association is strengthened when discovered at younger age, by increasing id-WMD severity, and when id-WMD is detected by CT scan rather than MRI.

Pregnancy attempts among adolescent and young adult cancer survivors

To examine whether demographic and cancer-related characteristics and factors such as fertility discussion with a medical provider and fertility preservation use are associated with attempting pregnancy after adolescent and young adult cancer. Cross-sectional online survey. Not applicable. Women with lymphoma, breast cancer, thyroid cancer, or gynecologic cancer diagnosed at 15-39 years from 2004 to 2016 were identified from the North Carolina Cancer Registry and the Kaiser Permanente Northern and Southern California health care systems and responded to an online survey addressing survivorship concerns, including fertility and reproductive outcomes. Demographic characteristics, cancer characteristics, fertility discussion with a medical provider or fertility specialist between cancer diagnosis and starting cancer treatment, use of fertility preservation strategies (freezing embryos or oocytes) after cancer diagnosis. Pregnancy attempt after cancer diagnosis, defined by either a pregnancy or 12 months of trying to become pregnant without pregnancy. Among 801 participants who had not reached their desired family size at diagnosis, 77% had a fertility discussion with any medical provider between cancer diagnosis and treatment initiation, and 8% used fertility preservation after cancer diagnosis. At survey (median =7 years after diagnosis; interquartile range, 4-10), 32% had attempted pregnancy. Neither fertility discussion with any medical provider nor fertility counseling with a fertility specialist was significantly associated with pregnancy attempts. However, the use of fertility preservation was significantly associated with attempting pregnancy (prevalence ratios = 1.74; 95% confidence interval: 1.31-2.32). Other characteristics positively associated with pregnancy attempts included younger age at diagnosis, longer time since diagnosis, having a partner (at diagnosis or at survey), and having a history of infertility before cancer diagnosis. Use of fertility preservation strategies was uncommon in our cohort but was associated with attempting pregnancy after cancer. Ensuring access to fertility preservation methods may help adolescent and young adult cancer survivors to plan and initiate future fertility.

The Correlation of Diabetes Mellitus and Urinary Retention From Intravesical OnabotulinumtoxinA Injection for Overactive Bladder.

The objective was to determine whether patients with diabetes mellitus (DM) treated with intravesical onabotulinumtoxinA (BoNT) injection for overactive bladder (OAB) had increased urinary retention requiring clean intermittent catheterization (CIC), as well as the impact of disease duration and severity. We hypothesize that patients with DM will have higher rates of retention after BoNT injection. We performed a retrospective cohort analysis of women in the Kaiser Permanente Southern California Health System who underwent BoNT injection for OAB, excluding women with a history of urinary retention or neurogenic bladder. We identified 565 patients, 410 in the control group and 155 in the DM group. No significant difference was found in the rate of CIC (9% in the control group versus 5.8% in the DM group, P = 0.2), voiding dysfunction, and peak postprocedure postvoid residual volume (PVR). Patients with diabetes had a significantly increased rate of postprocedure urinary tract infection (UTI; 27.6% versus 38.1%, P = 0.02). Urinary tract infection was significantly associated with urinary retention (adjusted odds ratio [OR], 2.26; 95% confidence interval [CI], 1.02-4.99; P = 0.045) and peak PVR ≥200 mL (adjusted OR, 2.42; 95% CI, 1.15-5.06; P = 0.019). Diabetic disease duration and severity were not a predictor of urinary retention, elevated PVR, or voiding dysfunction; however, the presence of ≥1 disease-related complication was a predictor of UTI (adjusted OR, 2.81; 95% CI, 1.34-5.91; P = 0.006). Diabetic patients had a similar rate of urinary retention requiring CIC after BoNT injection for OAB compared with nondiabetic patients. Diabetic patients had an increased risk of UTI based on disease severity.

Abstract 14139: Differential Benefit of Non-Invasive Cardiac Stress Testing by HEART Score Risk Stratification

Introduction: AHA guidelines recommend non-invasive cardiac testing (NIT) within 72 hours after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS), after acute myocardial infarction (AMI) has been excluded. However, the effectiveness of this strategy to reduce the risk of future AMI or death, in low-risk patients is contested. Hypothesis: We hypothesized that in patients with low risk based on history, electrocardiogram, age, risk factors and troponin (HEART) based scoring, early NIT may not be beneficial compared to higher risk. Methods: We compared the effectiveness of early NIT vs. no early testing, in a retrospective cohort of adult (age ≥18) members of the Kaiser Permanente Southern California health system from 05/2016-12/2020. We included all adults presenting at EDs with suspected ACS and who had data to compute HEART score. We stratified the cohort into low risk (score 0-3); intermediate risk (score 4-6) and high-risk (score ≥7) based on HEART score. Within each group, confounder adjusted instrumental variables models were used to evaluate the marginal effect of early NIT, and the number needed to treat (NNT) was calculated as the inverse of the absolute composite risk reduction in death/AMI within 30 days of ED discharge. Results: The cohort included 174,936 patients [61% Low risk (mean age 53; female 58%; early NIT 5%), 36% intermediate risk (mean age 71; female 72%; early NIT 18%), and 3% high risk (mean age 74, female 45%; early NIT 23%)]. The risk reduction in 30-day death/AMI due to early NIT increased progressively through the intermediate-risk (NNT = 59) and high-risk groups (NNT = 24) (Table 1). Risk reduction in the low-risk group was not statistically significant. Conclusions: HEART score based high risk patients may benefit the most from early NIT. However, the majority of the suspected ACS cohort was classified as low risk and the benefit of early NIT on 30-day death/AMI was uncertain in this low-risk group.

Abstract 13239: Variation in Cost by HEART Score in Patients With Suspected Acute Coronary Syndrome

Introduction: The variation in medical cost by risk stratification using history, electrocardiogram, age, risk factors and troponin (HEART), after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS), is not well understood. Hypothesis: We hypothesized that annual total all cause cost will increase significantly with increasing HEART score and the primary driver of the total cost will be cardiovascular disease (CVD) related care. Methods: This was a retrospective cohort study of adults (age ≥18) with chest pain and complete data for HEART score, presenting at EDs within the Kaiser Permanente Southern California health system from 1/2016-12/2018. We analyzed direct medical cost associated with medical office visits, hospital facility and ED visits, pharmacy utilization, hospice stays, skilled nursing stays, home health, dialysis, laboratory, and radiology utilization during the 1-year following the index ED visit. Stratified by HEART score categories, we used one part and two part generalized linear models (log link &amp; gamma family distribution) adjusted for socio-demographics, cardiovascular disease (CVD) history and treatment and non-CVD comorbidities, to estimate average adjusted total all cause expenditure as well as subgroups of utilization. Results: The cohort included 33,990 patients (60% Low risk; 37% intermediate risk and 3% high risk). The adjusted annual total cost varied from $6,544 (95% CI $6,228 to $6,860) in the low risk to $21,210 ($19,458 to $22,962) in the high-risk group (Table 1). In each group, the primary driver of total cost was CVD related care accounting for 41% to 46% of total cost. CVD care provided in a hospital setting accounted for 44%-76% of CVD total cost. Conclusions: Increased follow-up medical office visits, improved medications and lifestyle management may reduce the near exponential increase in cost driven by catastrophic hospital utilization, in higher HEART risk stratified patients.

Ambient temperature and risk of urinary tract infection in California: A time-stratified case-crossover study using electronic health records.

Background:In the United States (US), urinary tract infections (UTI) lead to more than 10 million office visits each year. Temperature and season are potentially important risk factors for UTI, particularly in the context of climate change.Methods:We examined the relationship between ambient temperature and outpatient UTI diagnoses among patients followed from 2015 to 2017 in two California healthcare systems: Kaiser Permanente Southern California (KPSC) and Sutter Health in Northern California. We identified UTI diagnoses in adult patients using diagnostic codes and laboratory records from electronic health records. We abstracted patient age, sex, season of diagnosis, and linked community-level Index of Concentration at the Extremes (ICE-I, a measure of wealth and poverty concentration) based on residential address. Daily county-level average ambient temperature was assembled from the Parameter-elevation Regressions on Independent Slopes Model (PRISM). We implemented distributed lag nonlinear models (DLNM) to assess the association between UTI and lagged daily temperatures. Main analyses were confined to women. In secondary analyses, we stratified by season, healthcare system, and community-level ICE-I.Results:We observed 787,186 UTI cases (89% among women). We observed a threshold association between ambient temperature and UTI among women: an increase in daily temperature from the 5th percentile (6.0 °C) to the mean (16.2 °C) was associated with a 3.2% (95% CI: 2.4, 3.9%) increase in same-day UTI diagnosis rate, whereas an increase from the mean to 95th percentile was associated with no change in UTI risk (0.0%, 95% CI: −0.7, 0.6%). In secondary analyses, we observed the clearest monotonic increase in the rate of UTI diagnosis with higher temperatures in the fall. Associations did not differ meaningfully by healthcare system or community-level ICE-I. Results were robust to alternate model specifications.Discussion:Increasing temperature was related to higher rate of outpatient UTI, particularly in the shoulder seasons (spring, autumn).

Risk Factors for Silent Brain Infarcts and White Matter Disease in a Real-World Cohort Identified by Natural Language Processing

ObjectiveTo assess the frequency of silent brain infarcts (SBIs) and white matter disease (WMD) and associations with stroke risk factors (RFs) in a real-world population. Patients and MethodsThis was an observational study of patients 50 years or older in the Kaiser Permanente Southern California health system from January 1, 2009, through June 30, 2019, with head computed tomography or magnetic resonance imaging for nonstroke indications and no history of stroke, transient ischemic attack, or dementia. A natural language processing (NLP) algorithm was applied to the electronic health record to identify individuals with reported SBIs or WMD. Multivariable Poisson regression estimated risk ratios of demographic characteristics, RFs, and scan modality on the presence of SBIs or WMD. ResultsAmong 262,875 individuals, the NLP identified 13,154 (5.0%) with SBIs and 78,330 (29.8%) with WMD. Stroke RFs were highly prevalent. Advanced age was strongly associated with increased risk of SBIs (adjusted relative risks [aRRs], 1.90, 3.23, and 4.72 for those aged in their 60s, 70s, and ≥80s compared with those in their 50s) and increased risk of WMD (aRRs, 1.79, 3.02, and 4.53 for those aged in their 60s, 70s, and ≥80s compared with those in their 50s). Magnetic resonance imaging was associated with a reduced risk of SBIs (aRR, 0.87; 95% CI, 0.83 to 0.91) and an increased risk of WMD (aRR, 2.86; 95% CI, 2.83 to 2.90). Stroke RFs had modest associations with increased risk of SBIs or WMD. ConclusionAn NLP algorithm can identify a large cohort of patients with incidentally discovered SBIs and WMD. Advanced age is strongly associated with incidentally discovered SBIs and WMD.

Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Medically Attended Lower Respiratory Tract Infection and Pneumonia Among Older Adults.

Among older adults, 13-valent pneumococcal conjugate vaccine (PCV13) has been found efficacious against nonbacteremic pneumonia associated with vaccine-serotype pneumococci. However, the burden of lower respiratory tract infection (LRTI) and pneumonia preventable by direct immunization of older adults continues to be debated. We analyzed data from an open cohort of adults aged ≥65 years enrolled in Kaiser Permanente Southern California health plans from 2016 to 2019 who received PCV13 concordant with US Advisory Committee on Immunization Practices guidelines. We estimated PCV13 vaccine effectiveness (VE) via the adjusted hazard ratio for first LRTI and pneumonia episodes during each respiratory season, comparing PCV13-exposed and PCV13-unexposed time at risk for each participant using a self-matched inference framework. Analyses used Cox proportional hazards models, stratified by individual. Among 42700 adults who met inclusion criteria, VE was 9.5% (95% confidence interval [CI], 2.2% to 16.3%) against all-cause medically attended LRTI and 8.8% (95% CI, -.2% to 17.0%) against all-cause medically attended pneumonia. In contrast, we did not identify evidence of protection against LRTI and pneumonia following receipt of the 23-valent pneumococcal polysaccharide vaccine. PCV13 prevented 0.7 (95% CI, .2 to 1.4) and 0.5 (95% CI, .0 to 1.0) cases of LRTI and pneumonia, respectively, per 100 vaccinated persons annually; over 5 years, 1 case of LRTI and 1 case of pneumonia were prevented for every 27 and 42 individuals vaccinated, respectively. PCV13 vaccination among older adults substantially reduced incidence of medically attended respiratory illness. Direct immunization of older adults is an effective strategy to combat residual disease burden associated with PCV13-type pneumococci.

Abstract 10157: Incremental Medical Expenditure and Effectiveness of Early Non-invasive Cardiac Testing in Suspected Acute Coronary Syndrome

Introduction: The relationship between medical expenditure and long-term effectiveness of early (within 72 hours) non-invasive cardiac stress testing (NIT) in reducing future acute myocardial infraction (AMI) is not well understood. We estimated the value of early NIT after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS). Methods: This was a retrospective cohort study of adult (18+) patients with chest pain, presenting at EDs within the Kaiser Permanente Southern California health system from 10/2015-12/2018. We analyzed the direct medical expenditure associated with medical office visits, hospital facility and ED visits, pharmacy utilization, hospice stays, skilled nursing stays, home health, dialysis, laboratory and radiology utilization during the one year following the index chest pain ED visit. We also identified incidence of AMI during the 1-year follow-up. We used 2-stage residual inclusion instrumental variables (IV) techniques to evaluate the marginal effect of early NIT on total all cause expenditure as well as subgroups of utilization. We used control functions IV techniques to evaluate the marginal effect of NIT on AMI and calculated the number needed to treat (NNT) as the inverse of the absolute risk reduction. All models adjusted for socio-demographics, cardiovascular disease (CVD) history and treatment and non-CVD comorbidities. Results: The cohort included 91250 patients (mean age 58 years, female 58%) and 19% received early NIT. The marginal difference in total expenditure between the early NIT vs controls was $2,583 (95% CI $591 to $4,575) and was mainly related to the index ED visit (Table 1). Those who received early NIT had slightly lower risk of AMI during the 1-year follow-up (risk reduction 1.3% (-1.9% to -0.7%) resulting in NNT of 75. Conclusions: Early NIT offers minor risk reduction of AMI but with an increase of $2583 in expenditure. With a NNT of 75, the cost to avoid one AMI is estimated to be $193,725.

Abstract 10173: Risk Factors of Cardiovascular Disease in Breast Cancer Patients

Introduction: Cardiovascular disease (CVD) events during cancer treatment can interfere with the delivery of curative therapy. In adult cancer survivors, CVD mortality is second only to cancer recurrence related mortality. We evaluated the demographic and clinical risk factors of CVD in breast cancer patients. Methods: A retrospective cohort study was conducted at Kaiser Permanente Southern California (KPSC) health system. We identified adult members (18+) diagnosed with primary breast cancer from 01/2000-12/2019 using the KPSC cancer registry. We only included patient who had at least one year of continuous health plan enrollment prior to their cancer diagnosis to determine risk factors status and to ensure they did not have any history of CVD (defined as cardiac arrest, cardiomyopathy, congestive heart failure, coronary atherosclerosis, heart valve disorders, myocardial infarction, ventricular fibrillation, dysrhythmias or stroke) prior to their cancer diagnosis. We evaluated the association of age at cancer diagnosis; race; ethnicity; obesity; cancer stage; and history of depression, drug abuse, renal failure, liver disease, lipid disorder, diabetes and hypertension using a proportional hazard model. All patients were followed from their cancer diagnosis to the earliest date of CVD (failure event) diagnosis or death or health plan disenrollment or end of study (12/2020). Results: In the cohort of 36,840 patients (Table 1), 11,993 (33%) had a CVD diagnosis during follow-up (average follow-up 5.3 years). The hazard rate of CVD increased significantly with age. Distant metastatic disease was associated with 7-fold higher CVD hazard as compared to in-situ cancer. Most other clinical factors significantly increased the hazard rate (Table 1). Conclusions: In breast cancer patients naïve to CVD disease prior to cancer diagnosis, the hazard rate of CVD post cancer diagnosis is significantly higher in older individuals and those with metastatic disease.

Advances in Understanding Early-Onset Colorectal Cancer.

Since the 1990s, the incidence of early-onset colorectal cancer (at <50 years of age) in the US has increased by more than 50%; similar increases have also been observed internationally. These increases are found particularly among individuals born during and after the 1960s, raising the possibility that the increased rates of early-onset colorectal cancer are attributable to changes in risk-factor patterns throughout successive generations. The reasons for these alarming epidemiologic patterns for early-onset colorectal cancer worldwide are only recently being investigated and major gaps in our knowledge remain. In the current issue of this journal, Arif and colleagues differentiated characteristics and outcomes of early-onset colorectal cancer in patients with the predisposing conditions of inflammatory bowel disease or hereditary genetic syndromes, compared with patients who have sporadic disease. Also, in this issue, Schumacher and colleagues investigated risk factors for early-onset colorectal adenocarcinoma in a nested case-control study among Kaiser Permanente Southern California (KPSC) health plan members. The research presented on characteristics and outcomes points to the importance of sporadic disease in the rise of early-onset colorectal cancer, while the research presented on risk factors points to the importance of obesity as a potential explanatory factor for this rise.See related articles by Arif et al., p. 1785 and by Schumacher et al., p. 1792.

Association of Silent Cerebrovascular Disease Identified Using Natural Language Processing and Future Ischemic Stroke.

Silent cerebrovascular disease (SCD), comprising silent brain infarction (SBI) and white matter disease (WMD), is commonly found incidentally on neuroimaging scans obtained in routine clinical care. Their prognostic significance is not known. We aimed to estimate the incidence of and risk increase in future stroke in patients with incidentally discovered SCD. Patients in the Kaiser Permanente Southern California (KPSC) health system aged ≥50 years, without prior ischemic stroke, transient ischemic attack (TIA), or dementia/Alzheimer disease receiving a head CT or MRI between 2009 and 2019 were included. SBI and WMD were identified by natural language processing (NLP) from the neuroimage report. Among 262,875 individuals receiving neuroimaging, NLP identified 13,154 (5.0%) with SBI and 78,330 (29.8%) with WMD. The incidence of future stroke was 32.5 (95% confidence interval [CI] 31.1, 33.9) per 1,000 patient-years for patients with SBI: 19.3 (95% CI 18.9, 19.8) for patients with WMD and 6.8 (95% CI 6.7, 7.0) for patients without SCD. The crude hazard ratio (HR) associated with SBI was 3.40 (95% CI 3.25 to 3.56) and for WMD 2.63 (95% CI 2.54 to 2.71). With MRI-discovered SBI, the adjusted HR was 2.95 (95% CI 2.53 to 3.44) for those <65 years of age and 2.15 (95% CI 1.91 to 2.41) for those ≥65. With CT scan, the adjusted HR was 2.48 (95% CI 2.19 to 2.81) for those <65 and 1.81 (95% CI 1.71 to 1.91) for those ≥65. The adjusted HR associated with a finding of WMD was 1.76 (95% CI 1.69 to 1.82) and was not modified by age or imaging modality. Incidentally discovered SBI and WMD are common and associated with increased risk of subsequent symptomatic stroke, representing an important opportunity for stroke prevention.