Integrated Health Care Delivery System Research Articles

Association of Cardiovascular Outcomes and Mortality With Sustained Long-Acting Insulin Only vs Long-Acting Plus Short-Acting Insulin Treatment

Cardiovascular events and mortality are the principal causes of excess mortality and health care costs for people with type 2 diabetes. No large studies have specifically compared long-acting insulin alone with long-acting plus short-acting insulin with regard to cardiovascular outcomes. To compare cardiovascular events and mortality in adults with type 2 diabetes receiving long-acting insulin who do or do not add short-acting insulin. This retrospective cohort study emulated a randomized experiment in which adults with type 2 diabetes who experienced a qualifying glycated hemoglobin A1c (HbA1c) level of 6.8% to 8.5% with long-acting insulin were randomized to continuing treatment with long-acting insulin (LA group) or adding short-acting insulin within 1 year of the qualifying HbA1c level (LA plus SA group). Retrospective data in 4 integrated health care delivery systems from the Health Care Systems Research Network from January 1, 2005, to December 31, 2013, were used. Analysis used inverse probability weighting estimation with Super Learner for propensity score estimation. Analyses took place from April 1, 2018, to June 30, 2019. Long-acting insulin alone or with added short-acting insulin within 1 year from the qualifying HbA1c level. Mortality, cardiovascular mortality, acute myocardial infarction, stroke, and hospitalization for heart failure. Among 57 278 individuals (39 279 with data on cardiovascular mortality) with a mean (SD) age of 60.6 (11.5) years, 53.6% men, 43.5% non-Hispanic White individuals, and 4 years of follow-up (median follow-up of 11 [interquartile range, 5-20] calendar quarters), the LA plus SA group was associated with increased all-cause mortality compared with the LA group (hazard ratio, 1.27; 95% CI, 1.05-1.49) and a decreased risk of acute myocardial infarction (hazard ratio, 0.89; 95% CI, 0.81-0.97). Treatment with long-acting plus short-acting insulin was not associated with increased risks of congestive heart failure, stroke, or cardiovascular mortality. Findings of this retrospective cohort study suggested an increased risk of all-cause mortality and a decreased risk of acute myocardial infarction for the LA plus SA group compared with the LA group. Given the lack of an increase in major cardiovascular events or cardiovascular mortality, the increased all-cause mortality with long-acting plus short-acting insulin may be explained by noncardiovascular events or unmeasured confounding.

Torsade de pointes: A nested case-control study in an integrated healthcare delivery system.

BackgroundTdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QT interval. There are limited data describing risk factors, treatment, and outcomes of this potentially fatal arrhythmia.ObjectiveOur goals were as follows: (1) to validate cases presenting with Torsade de Pointes (TdP), (2) to identify modifiable risk factors, and (3) to describe the management strategies used for TdP and its prognosis in a real‐world healthcare setting.MethodsCase–control study (with 2:1 matching on age, sex, and race/ethnicity) nested within the Genetic Epidemiology Research on Aging (GERA) cohort. Follow‐up of the cohort for case ascertainment was between January 01, 2005 and December 31, 2018.ResultsA total of 56 cases of TdP were confirmed (incidence rate = 3.6 per 100,000 persons/years). The average (SD) age of the TdP cases was 74 (13) years, 55 percent were female, and 16 percent were non‐white. The independent predictors of TdP were potassium concentration <3.6 mEq/L (OR = 10.6), prior history of atrial fibrillation/flutter (OR = 6.2), QTc >480 ms (OR = 4.4) and prior history of coronary artery disease (OR = 2.6). Exposure to furosemide and amiodarone was significantly greater in cases than in controls. The most common treatment for TdP was IV magnesium (78.6%) and IV potassium repletion (73.2%). The in‐hospital and 1‐year mortality rates for TdP cases were 10.7% and 25.0% percent, respectively.ConclusionsThese findings may inform quantitative multivariate risk indices for the prediction of TdP and could guide practitioners on which patients may qualify for continuous ECG monitoring and/or electrolyte replacement therapy.

Timing of AKI after urgent percutaneous coronary intervention and clinical outcomes: a high-dimensional propensity score analysis

IntroductionAcute kidney injury is a common complication of percutaneous coronary intervention and has been associated with an increased risk of death and progressive chronic kidney disease. However, whether the timing of acute kidney injury after urgent percutaneous coronary intervention could be used to improve patient risk stratification is not known.MethodsWe conducted a retrospective cohort study in adults surviving an urgent percutaneous coronary intervention between 2008 and 2013 within Kaiser Permanente Northern California, a large integrated healthcare delivery system, to evaluate the impact of acute kidney injury during hospitalization at 12 (±6), 24 (±6) and 48 (±6) hours after urgent percutaneous coronary intervention and subsequent risks of adverse outcomes within the first year after discharge. We used multivariable Cox proportional hazards models with adjustment for a high-dimensional propensity score for developing acute kidney injury after percutaneous coronary intervention to examine the associations between acute kidney injury timing and all-cause death and worsening chronic kidney disease.ResultsAmong 7250 eligible adults undergoing urgent percutaneous coronary intervention, 306 (4.2%) had acute kidney injury at one or more of the examined time periods after percutaneous coronary intervention. After adjustment, acute kidney injury at 12 (±6) hours was independently associated with higher risks of death (adjusted hazard ratio [aHR] 3.55, 95% confidence interval [CI] 2.19–5.75) and worsening kidney function (aHR 2.40, 95% CI:1.24–4.63). Similar results were observed for acute kidney injury at 24 (±6) hours and death (aHR 3.90, 95% CI:2.29–6.66) and worsening chronic kidney disease (aHR 4.77, 95% CI:2.46–9.23). Acute kidney injury at 48 (±6) hours was associated with excess mortality (aHR 1.97, 95% CI:1.19–3.26) but was not significantly associated with worsening kidney function (aHR 0.91, 95% CI:0.42–1.98).ConclusionsTiming of acute kidney injury after urgent percutaneous coronary intervention may be differentially associated with subsequent risk of worsening kidney function but not death.

Physical, Mental Health and Developmental Conditions, and Sociodemographic Characteristics Associated With Adverse Childhood Experiences Among Young Children in Pediatric Primary Care

Introduction To examine associations between patient characteristics and adverse childhood experiences (ACEs) in a population-based sample of pediatric primary care patients, using electronic health records and clinical, administrative data. Method An observational study was conducted in an integrated health care delivery system. Children ages 1–5 years (N = 13,370) were screened for ACEs at routine well-child visits between September 1, 2018 and May 31, 2019 in three pediatrics clinics. Multivariate models examined associations between patient characteristics (age, gender, race/ethnicity, insurance type, neighborhood income and education level, physical, mental health and developmental diagnoses, weight status) and any ACEs, and ≥ 3 ACEs exposure. Results Prevalence and severity of ACE exposure varied by race/ethnicity. Older age, Medicaid insurance, epilepsy/seizure disorder, sleeping disorders, adjustment disorders, and feeding disorders were associated with higher odds of ACEs exposure, higher-income with lower odds. Discussion Understanding relationships between ACEs and patient features can provide information to clinicians for early detection and appropriate interventions. To examine associations between patient characteristics and adverse childhood experiences (ACEs) in a population-based sample of pediatric primary care patients, using electronic health records and clinical, administrative data. An observational study was conducted in an integrated health care delivery system. Children ages 1–5 years (N = 13,370) were screened for ACEs at routine well-child visits between September 1, 2018 and May 31, 2019 in three pediatrics clinics. Multivariate models examined associations between patient characteristics (age, gender, race/ethnicity, insurance type, neighborhood income and education level, physical, mental health and developmental diagnoses, weight status) and any ACEs, and ≥ 3 ACEs exposure. Prevalence and severity of ACE exposure varied by race/ethnicity. Older age, Medicaid insurance, epilepsy/seizure disorder, sleeping disorders, adjustment disorders, and feeding disorders were associated with higher odds of ACEs exposure, higher-income with lower odds. Understanding relationships between ACEs and patient features can provide information to clinicians for early detection and appropriate interventions. Stacy Sterling, Research Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, CA. Felicia Chi, Senior Data Consultant, Division of Research, Kaiser Permanente Northern California, Oakland, CA. Judy Lin, Physician, Department of Pediatrics, Kaiser Permanente Medical Center, San Leandro, CA. Padmaja Padalkar, Physician, Department of Pediatrics, Kaiser Permanente Medical Center, San Jose, CA. Uma Vinayagasundaram, Physician, Department of Pediatrics, Kaiser Permanente Medical Center, Fremont, CA. Esti Iturralde, Research Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, CA. Kelly Young-Wolff, Research Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, CA. Verena E. Metz, Staff Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, CA. Arnd Herz, Physician, Department of Pediatrics, Kaiser Permanente Medical Center, Hayward, CA. Rahel Negusse, Research Associate, Division of Research, Kaiser Permanente Northern California, Oakland, CA. Melanie Jackson-Morris, Morris, Research Associate, Division of Research, Kaiser Permanente Northern California, Oakland, CA. Paul Espinas, Physician, Department of Pediatrics, Kaiser Permanente Medical Center, Hayward, CA.

Pearls from a Clinician-Researcher in an Integrated Health care Delivery System.

Pearls from a Clinician-Researcher in an Integrated Health care Delivery System.

Aligning care with the personal values of patients with complex care needs.

To identify opportunities to align care with the personal values of patients from three distinct groups with complex medical, behavioral, and social needs. Between June and August 2019, we conducted semi-structured interviews with individuals with complex care needs in two integrated health care delivery systems. Qualitative study using semi-structured interviews. We interviewed three groups of patients at Kaiser Permanente Washington and Kaiser Permanente Colorado representing three distinct profiles of complex care needs: Group A ("obesity, opioid prescription, and low-resourced neighborhood"), Group B ("older, high medical morbidity, emergency department, and hospital use"), and Group C ("older, mental and physical health concerns, and low-resourced neighborhood"). These profiles were identified based on prior work and prioritized by internal primary care stakeholders. Interview transcripts were analyzed using thematic analysis. Twenty-four patients participated; eight from each complex needs profile. Mean age across groups was 71 (range 48-86) years. We identified five themes common across the three groups that captured patients' views regarding values-aligned care. These themes focused on the importance of care teams exploring and acknowledging a patient's values, providing access to nonphysician providers who have different perspectives on care delivery, offering values-aligned mental health care, ensuring connection to community-based resources that support values and address needs, and providing care that supports the patient plus their family and caregivers. Our results suggest several opportunities to improve how care is delivered to patients with different complex medical, behavioral, and social needs. Future research is needed to better understand how to incorporate these opportunities into health care.

Evaluation of Vaccination Strategies to Compare Efficient and Equitable Vaccine Allocation by Race and Ethnicity Across Time

Identifying the most efficient COVID-19 vaccine allocation strategy may substantially reduce hospitalizations and save lives while ensuring an equitable vaccine distribution. To simulate the association of different vaccine allocation strategies with COVID-19-associated morbidity and mortality and their distribution across racial and ethnic groups. We developed and internally validated the risk of COVID-19 infection and risk of hospitalization models on randomly split training and validation data sets. These were used in a computer simulation study of vaccine prioritization among adult health plan members who were drawn from an integrated health care delivery system. The study was conducted from January 3, 2021, to June 1, 2021, in Oakland, California, and the data were analyzed during the same period. We simulated the association of different vaccine allocation strategies, including (1) random, (2) a US Centers for Disease Control and Prevention (CDC) proxy, (3) age based, and (4) combinations of models for the risk of adverse outcomes (CRS) and COVID-19 infection (PROVID), with COVID-19-related hospitalizations between May 1, 2020, and December 31, 2020, that were randomly permuted by month across 250 simulations and assessed vaccine allocation by race and ethnicity and the neighborhood deprivation index across time. The study included 3 202 679 adult patients (mean [SD] age, 48.2 [18.0] years; 1 677 637 women [52.4%]; 1 525 042 men [47.6%]; 611 154 Asian [19.1%], 206 363 Black [6.4%], 642 344 Hispanic [20.1%], and 1 390 638 White individuals [43.4%]), of whom 36 137 (1.1%) were positive for SARS-CoV-2. A risk-based strategy (CRS/PROVID) showed the largest avoidable hospitalization estimates (4954; 95% CI, 3452-5878) followed by age-based (4362; 95% CI, 2866-5175) and CDC proxy (4085; 95% CI, 2805-5109) strategies. Random vaccination showed substantially lower reductions in adverse outcomes. Risk-based strategies also showed the largest number of avoidable COVID-19 deaths (joint CRS/PROVID) and household transmissions. Risk-based (PROVID) and CDC proxy strategies were estimated to vaccinate the highest percentage of Hispanic and Black patients in 8 months (joint CRS/PROVID: 642 570 [100%] Hispanic, 185 530 [90%] Black; PROVID: 642 570 [100%] Hispanic, 198 480 [96%] Black; CDC proxy: 605 770 [95%] Hispanic and 151 772 [74%] Black) compared with an age-based approach (438 423 [68%] Hispanic, 154 714 [75%] Black). Overall, the PROVID and joint CRS/PROVID risk-based strategies were estimated to be followed by the most patients from areas with high neighborhood deprivation index being vaccinated early. In this simulation modeling study of adults from a large integrated health care delivery system, risk-based strategies were associated with the largest estimated reductions in COVID-19 hospitalizations, deaths, and household transmissions compared with the CDC proxy and age-based strategies, with a higher proportion of Hispanic and Black patients were estimated to be vaccinated early in the process compared with the CDC strategy.

Prevalence of depression and anxiety disorders following mild traumatic brain injury.

Previous studies have identified an association between traumatic brain injuries and the development of psychiatric disorders in general. However, these studies were subject to limitations that demonstrate the need for a study of a large, clearly defined mild traumatic brain injury (mTBI) population within an integrated healthcare system. To determine the prevalence and relative risk of postinjury affective disorders over 4 years following mTBI. Cohort study of mTBI cases and matched controls, over a 4-year period. An integrated healthcare delivery system in California. A total of 9428 adult health plan members diagnosed with mTBI from 2000-2007 and enrolled in the year before injury, during which no TBI was ascertained. Control participants included 18,856 individuals selected based on the following criteria: Two unexposed health plan members per each mTBI-exposed patient were randomly selected and individually matched for age, gender, race/ethnicity, and medical comorbidities. Not applicable. A diagnosis of affective disorder (depressive, anxiety, and adjustment disorders) in the 4 years after mTBI or the reference date, determined according to the International Classification of Diseases, Ninth Revision, Clinical Modification as well as the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Affective disorders were most prominent during the first 12 months with 23% following mTBI and 14% in the control group. Four-year aggregate adjusted odds ratios for having an affective disorder following mTBI were 1.2 (95% CI: 1.1, 1.2; p < .001) and 1.5 (95% CI: 1.5, 1.6; p < .001) for patients with and without prior affective disorders, respectively. mTBI was associated with a significantly increased risk of having subsequent affective disorders. Screening for and addressing affective disorders at earlier stages following the injury is an important step to avoid persisting conditions that may pose a barrier to full recovery.

Influenza vaccination and mortality among adults with heart failure in an integrated healthcare delivery system, 2009-2018.

Influenza infection can result in decompensation or exacerbation of heart failure (HF) symptoms, hospitalization, and death. To examine the association of influenza vaccination with mortality and hospitalization during influenza and non-influenza seasons between 2009 and 2018. In this prospective, observational cohort study, we included Kaiser Permanente Southern California members with a HF diagnosis prior to September 1 each year from 2009 to 2017. The first influenza vaccination in each season (September 1 to May 31) was recorded. Vaccinated/unvaccinated patients were matched 1:1 on age, sex, and ejection fraction at the vaccination date (n-total = 74,870). Patients were followed through the end of each influenza season for all-cause mortality. Secondary outcomes included cardiovascular mortality and all-cause hospitalization. In a sensitivity analysis, we examined mortality in the non-influenza season. Influenza vaccinated vs unvaccinated patients had more comorbidities and higher healthcare utilization. After multivariable adjustment for utilization, sociodemographics, comorbidities, and medications, influenza vaccinated vs unvaccinated patients had a lower risk of all-cause mortality and cardiovascular mortality during the influenza season (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.63, 0.70 and HR 0.68, 95% CI 0.63, 0.74, respectively) but a higher risk of all-cause hospitalization (HR 1.27, 95% CI 1.21, 1.31). There was no association between influenza vaccination and all-cause or cardiovascular mortality during the non-influenza season (HR 0.99, 95% CI 0.89, 1.09 and HR 1.00, 95% CI 0.84, 1.21, respectively). Influenza vaccination in HF patients was associated with a lower risk of mortality during the influenza season. Our findings provide support for recommendations of universal influenza vaccination in patients with HF.

COVID-19 and Risk of VTE in Ethnically Diverse Populations

BackgroundLimited existing data suggest that the novel COVID-19 may increase risk of VTE, but information from large, ethnically diverse populations with appropriate control participants is lacking.Research QuestionDoes the rate of VTE among adults hospitalized with COVID-19 differ from matched hospitalized control participants without COVID-19?Study Design and MethodsWe conducted a retrospective study among hospitalized adults with laboratory-confirmed COVID-19 and hospitalized adults without evidence of COVID-19 matched for age, sex, race or ethnicity, acute illness severity, and month of hospitalization between January 2020 and August 2020 from two integrated health care delivery systems with 36 hospitals. Outcomes included VTE (DVT or pulmonary embolism ascertained using diagnosis codes combined with validated natural language processing algorithms applied to electronic health records) and death resulting from any cause at 30 days. Fine and Gray hazards regression was performed to evaluate the association of COVID-19 with VTE after accounting for competing risk of death and residual differences between groups, as well as to identify predictors of VTE in patients with COVID-19.ResultsWe identified 6,319 adults with COVID-19 and 6,319 matched adults without COVID-19, with mean ± SD age of 60.0 ± 17.2 years, 46% women, 53.1% Hispanic, 14.6% Asian/Pacific Islander, and 10.3% Black. During 30-day follow-up, 313 validated cases of VTE (160 COVID-19, 153 control participants) and 1,172 deaths (817 in patients with COVID-19, 355 in control participants) occurred. Adults with COVID-19 showed a more than threefold adjusted risk of VTE (adjusted hazard ratio, 3.48; 95% CI, 2.03-5.98) compared with matched control participants. Predictors of VTE in patients with COVID-19 included age ≥ 55 years, Black race, prior VTE, diagnosed sepsis, prior moderate or severe liver disease, BMI ≥ 40 kg/m2, and platelet count > 217 k/μL.InterpretationAmong ethnically diverse hospitalized adults, COVID-19 infection increased the risk of VTE, and selected patient characteristics were associated with higher thromboembolic risk in the setting of COVID-19.

Association of Lifetime TBI and Military Employment with Late Life ADL Functioning: A Population-Based Prospective Cohort Study

ObjectiveTo determine associations of traumatic brain injury (TBI) and military employment with activities of daily living (ADL) in late life. DesignPopulation-based prospective cohort study with biennial follow-up and censoring at the time of dementia diagnosis. SettingCommunity-based integrated health care delivery system. ParticipantsParticipants (N=4953) were men (n=2066) and women (n=2887) aged ≥65 years who were dementia free. InterventionsNot applicable. Main Outcome MeasuresADL difficulties at baseline and accumulation during follow-up. ResultsTBI with loss of consciousness (LOC) before the age of 40 years was associated with slightly higher ADL difficulty at baseline for women (rate ratio [RR], 1.44; 95% confidence interval [CI], 1.08-1.93; P=.01). For men, TBI with LOC at any age was associated with greater ADL difficulty at baseline (age <40y: RR, 1.58; 95% CI, 1.20-2.08; P=.001; age ≥40y: RR, 2.14; 95% CI, 1.24-3.68; P=.006). TBI with LOC was not associated with the rate of accumulation of ADL difficulties over time in men or women. There was no evidence of an association between military employment and either outcome, nor of an interaction between military employment and TBI with LOC. Findings were consistent across a variety of sensitivity analyses. ConclusionsFurther investigation into factors underlying greater late life functional impairment among survivors of TBI is warranted.

Use of a mobile app to capture supplemental health information during pregnancy: Implications for clinical research.

Mobile applications ("apps") may be efficient tools for improving the quality of clinical research among pregnant women, but evidence is sparse. We assess the feasibility and generalizability of a mobile app for capturing supplemental data during pregnancy. In 2017, we conducted a pilot study of the FDA MyStudies mobile app within a pregnant population identified through Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system. We ascertained health conditions, medications, and substance use through app-based questionnaires. In a post-hoc analysis, we utilized electronic health records (EHR) to summarize sociodemographic and health characteristics of pilot participants and, for comparison, a pregnant population identified using similar methods. Six percent (64/1070) of contacted women enrolled in the pilot study. Nearly half (23/53) reported taking medication for headaches and one-fourth for constipation (13/53) and nausea (12/53) each. Few instances (2/92) of over-the-counter medication use were identified in electronic dispensing records. One-quarter to one-third of participants with depression and anxiety/panic, respectively, reported recently discontinuing medications for these conditions. Eighty-eight percent of pilot participants reported White race (95%CI: 81-95%), versus 67% of the comparison population (N=2065). More pilot participants filled ≥1 prescription for antianxiety medication (22% [95%CI: 13-35%]) and antidepressants (19% [95%CI 10-31%]) pre-pregnancy than the comparison population (10 and 9%, respectively). Mobile apps may be a feasible tool for capturing health data not routinely available in EHR. Pregnant women willing to use a mobile app for research may differ from the general pregnant population, but confirmation is needed.

Clinical Effectiveness of an Outpatient Multidisciplinary Chronic Pain Management Telementoring Service.

The objective of this study was to assess the effectiveness of a Pain E-Consult Program (PEP), a multidisciplinary telementoring service based on the Extension for Community Healthcare Outcomes (ECHO) model to reduce opioid use in the outpatient setting. This was a retrospective matched cohort study conducted in an integrated health care delivery system. Adult patients without cancer and with a 90-day morphine milligram equivalent (MME) ≥30 mg/d between April 1, 2016, and June 30, 2017, were included. Patients whose primary care clinician received the PEP (observation) were compared with usual care (control) patients. Observation patients were matched up to 1:5 to control patients. Outcomes included change in MME and initiation of nonopioid alternative medications. Multivariable regression analyses were performed. A total of 665 patients were matched: 125 and 540 in the observation and control groups, respectively. Patients were primarily female, white, and Medicare beneficiaries. The observation group had a statistically significantly greater decrease in median MME/day during the 6-month (-7.4 vs. 1.5 mg, P=0.002) and 12-month (-15.1 vs. -2.8 mg, P<0.001) follow-up and rates of ≥20% decrease (6 mo: 41.6% vs. 24.6%, P=0.003; 12 mo: 48.0% vs. 32.6%, P=0.017). There were no differences in the rates of initiation of nonopioid alternative medications. A PEP was associated with greater reductions in MME/day compared with usual care despite similar rates of nonopioid alternative medication initiation. A prospective randomized study of this program should be undertaken to confirm these findings.

Retrospective Cohort Study Comparing Infliximab-dyyb and Infliximab in Biologic-Naive Patients With Inflammatory Bowel Disease in the United States.

Real-world assessments of biosimilars are needed to understand their effectiveness and safety in practice settings that may differ from those seen in clinical trials or healthcare systems in different countries. To assess the effectiveness and safety of a biosimilar (infliximab-dyyb) and its reference product (infliximab) in patients with inflammatory bowel disease (IBD) in the United States. We conducted a retrospective cohort study of biologic-naive patients with IBD who started treatment with infliximab-dyyb or infliximab. The study included 3206 patients identified through electronic health records in a US integrated healthcare delivery system. The effectiveness outcome was a composite of IBD-related surgery, IBD-related emergency room visit, and IBD-related hospitalization within 12 months of initiation. Safety outcomes included incidence of any or serious infection, cancer, acute liver dysfunction, and tuberculosis. We used a non-inferiority test with an upper-limit margin of 10% to analyze effectiveness. Doubly robust methods incorporating Cox proportional hazard regression with standardized inverse probability of treatment weighting were used to analyze both effectiveness and safety outcomes. The composite effectiveness outcome occurred in 107 of 870 patients (12.3%) in the infliximab-dyyb and 379 of 2336 patients (16.2%) in the infliximab groups. Infliximab-dyyb was non-inferior (P < .01) and was not different (hazard ratio [HR] 0.81; confidence interval [CI] 0.65-1.01; P = .06) to infliximab. Safety outcomes were not different between infliximab-dyyb and infliximab for any infections (HR 1.01; CI 0.86-1.17; P = .95), serious infections (HR 0.83; CI 0.54-1.26; P = .38), cancers (HR 0.83; CI 0.44-1.54; P = .55), and tuberculosis (HR 0.59; CI 0.10-3.55; P = .57). Initiation of infliximab-dyyb was non-inferior to infliximab among biologic-naive patients with IBD in an US integrated healthcare delivery system.

Abstract 881: Benchmarking genome-wide polygenic risk score development techniques in colorectal cancer risk prediction

Abstract Colorectal cancer (CRC) is a leading cause of cancer death, yet many CRC deaths are preventable via CRC screening. Currently only age and family history are used to define screening eligibility. However, CRC risk varies substantially in the population. In recent years polygenic risk scores (PRS) have gained attention as powerful risk prediction tool to personalize interventions. PRS provides a quantitative measure of an individual's inherited risk based on the cumulative effect of many genetic risk variants. Here, we benchmark several genome wide PRS techniques to select the best performing models in CRC risk prediction. We built CRC risk prediction models that incorporate genome-wide genotype data from large-scale research studies (55,105 cases and 65,079 controls, European ancestries) with the imputed genetic data on over 40 million variants. The risk prediction models were externally evaluated in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, including 101,987 genotyped individuals within the Kaiser Permanente Northern California (KPNC) integrated healthcare delivery system. We built genome-wide PRS using various methods including known CRC risk variants, thresholding and pruning followed by machine learning approaches (ML), LDpred, improved LDpred2, SBayesR, PRS-CS, Lassosum and empirical Bayes. Among 55,033 individuals of European ancestry in the GERA cohort, we evaluated the performance of models in terms of the age and sex-adjusted AUC. We showed that LDpred, LDpred2, LDpred2-sparse, SBayesR and PRS-CS perform equally well in terms of discriminatory accuracy (AUC=0.65). In addition, the PRS developed using the above-mentioned techniques identified the top 30% of the GERA European population has a hazard ratio estimate of ~2.2 on CRC risk, which is comparable to that for having an affected first-degree relative. The developed CRC PRSs will provide way for risk-stratified CRC screening and other targeted interventions. PRS derivation methodsNo. of variantsAUC(1,311 cases and 53,722 controls)Hazard ratio estimates (CI)Top 30% of population vs. remainingKnown variants1400.631.92 (1.75-2.23)PT Clumping + ML (Ridge)10,0000.631.94 (1.72-2.19)LDpred1.2M0.652.20 (1.94-2.47)LDPred21.2M0.652.20 (1.93-2.45)LDpred2 Sparse530K0.652.20 (1.90-2.41)SBayesR1.2M0.652.20 (1.88-2.38)PRS-CS1.2M0.652.20 (1.91-2.43)Lassosum1.2M0.621.76 (1.56-2.58)EBPRS1.2M0.621.81 (1.66-2.11)AUC based on family history in GERA cohort is 0.54 Citation Format: Minta Thomas, Lori C Sakoda, Jeffrey K Lee, Mark A Jenkins, Andrea Burnett-Hartman, Heather Hampel, Elisabeth A Rosenthal, Hermann Brenner, Jenny Chang-Claude, Marc J Gunter, Polly A Newcomb, Steven Gallinger, Tabitha A Harrison, Graham Casey, Victor Moreno, Gail P Jarvik, Stephen B Gruber, Robert E Schoen, Andrew T Chan, Richard B Hayes, Douglas A Corley, Ulrike Peters, Li Hsu. Benchmarking genome-wide polygenic risk score development techniques in colorectal cancer risk prediction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 881.

Primary Nephrotic Syndrome and Risks of ESKD, Cardiovascular Events, and Death: The Kaiser Permanente Nephrotic Syndrome Study.

Little population-based data exist about adults with primary nephrotic syndrome. To evaluate kidney, cardiovascular, and mortality outcomes in adults with primary nephrotic syndrome, we identified adults within an integrated health care delivery system (Kaiser Permanente Northern California) with nephrotic-range proteinuria or diagnosed nephrotic syndrome between 1996 and 2012. Nephrologists reviewed medical records for clinical presentation, laboratory findings, and biopsy results to confirm primary nephrotic syndrome and assigned etiology. We identified a 1:100 time-matched cohort of adults without diabetes, diagnosed nephrotic syndrome, or proteinuria as controls to compare rates of ESKD, cardiovascular outcomes, and death through 2014, using multivariable Cox regression. We confirmed 907 patients with primary nephrotic syndrome (655 definite and 252 presumed patients with FSGS [40%], membranous nephropathy [40%], and minimal change disease [20%]). Mean age was 49 years; 43% were women. Adults with primary nephrotic syndrome had higher adjusted rates of ESKD (adjusted hazard ratio [aHR], 19.63; 95% confidence interval [95% CI], 12.76 to 30.20), acute coronary syndrome (aHR, 2.58; 95% CI, 1.89 to 3.52), heart failure (aHR, 3.01; 95% CI, 2.16 to 4.19), ischemic stroke (aHR, 1.80; 95% CI, 1.06 to 3.05), venous thromboembolism (aHR, 2.56; 95% CI, 1.35 to 4.85), and death (aHR, 1.34; 95% CI, 1.09 to 1.64) versus controls. Excess ESKD risk was significantly higher for FSGS and membranous nephropathy than for presumed minimal change disease. The three etiologies of primary nephrotic syndrome did not differ significantly in terms of cardiovascular outcomes and death. Adults with primary nephrotic syndrome experience higher adjusted rates of ESKD, cardiovascular outcomes, and death, with significant variation by underlying etiology in the risk for developing ESKD.

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

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

Association of Real-time Continuous Glucose Monitoring With Glycemic Control and Acute Metabolic Events Among Patients With Insulin-Treated Diabetes

Continuous glucose monitoring (CGM) is recommended for patients with type 1 diabetes; observational evidence for CGM in patients with insulin-treated type 2 diabetes is lacking. To estimate clinical outcomes of real-time CGM initiation. Exploratory retrospective cohort study of changes in outcomes associated with real-time CGM initiation, estimated using a difference-in-differences analysis. A total of 41 753 participants with insulin-treated diabetes (5673 type 1; 36 080 type 2) receiving care from a Northern California integrated health care delivery system (2014-2019), being treated with insulin, self-monitoring their blood glucose levels, and having no prior CGM use were included. Initiation vs noninitiation of real-time CGM (reference group). Ten end points measured during the 12 months before and 12 months after baseline: hemoglobin A1c (HbA1c); hypoglycemia (emergency department or hospital utilization); hyperglycemia (emergency department or hospital utilization); HbA1c levels lower than 7%, lower than 8%, and higher than 9%; 1 emergency department encounter or more for any reason; 1 hospitalization or more for any reason; and number of outpatient visits and telephone visits. The real-time CGM initiators included 3806 patients (mean age, 42.4 years [SD, 19.9 years]; 51% female; 91% type 1, 9% type 2); the noninitiators included 37 947 patients (mean age, 63.4 years [SD, 13.4 years]; 49% female; 6% type 1, 94% type 2). The prebaseline mean HbA1c was lower among real-time CGM initiators than among noninitiators, but real-time CGM initiators had higher prebaseline rates of hypoglycemia and hyperglycemia. Mean HbA1c declined among real-time CGM initiators from 8.17% to 7.76% and from 8.28% to 8.19% among noninitiators (adjusted difference-in-differences estimate, -0.40%; 95% CI, -0.48% to -0.32%; P < .001). Hypoglycemia rates declined among real-time CGM initiators from 5.1% to 3.0% and increased among noninitiators from 1.9% to 2.3% (difference-in-differences estimate, -2.7%; 95% CI, -4.4% to -1.1%; P = .001). There were also statistically significant differences in the adjusted net changes in the proportion of patients with HbA1c lower than 7% (adjusted difference-in-differences estimate, 9.6%; 95% CI, 7.1% to 12.2%; P < .001), lower than 8% (adjusted difference-in-differences estimate, 13.1%; 95% CI, 10.2% to 16.1%; P < .001), and higher than 9% (adjusted difference-in-differences estimate, -7.1%; 95% CI, -9.5% to -4.6%; P < .001) and in the number of outpatient visits (adjusted difference-in-differences estimate, -0.4; 95% CI, -0.6 to -0.2; P < .001) and telephone visits (adjusted difference-in-differences estimate, 1.1; 95% CI, 0.8 to 1.4; P < .001). Initiation of real-time CGM was not associated with statistically significant changes in rates of hyperglycemia, emergency department visits for any reason, or hospitalizations for any reason. In this retrospective cohort study, insulin-treated patients with diabetes selected by physicians for real-time continuous glucose monitoring compared with noninitiators had significant improvements in hemoglobin A1c and reductions in emergency department visits and hospitalizations for hypoglycemia, but no significant change in emergency department visits or hospitalizations for hyperglycemia or for any reason. Because of the observational study design, findings may have been susceptible to selection bias.

PBI2 Real-World Evaluation of Biosimilar Bevacizumab-awwb versus Reference Bevacizumab in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer in a U.S. Integrated Healthcare Delivery System: 6-Month Interim Analysis

The objective of this study was to evaluate the real-world effectiveness and safety outcomes of patients with advanced non-squamous non-small cell lung cancer (NSCLC) initiated on bevacizumab-awwb versus bevacizumab in a U.S. integrated healthcare delivery system.

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

ObjectiveThe role of spousal education on dementia risk and how it may differ by gender or race/ethnicity is unknown. This study examines the association between one’s own education separate from...