Kaiser Permanente Southern California Members Research Articles

Primary Human Papillomavirus Screening: Women's Perceptions of New Cervical Cancer Screening Recommendations.

Background: Current clinical guidelines recommended primary human papillomavirus (HPV) screening for cervical cancer testing. Previous studies reported patient-level barriers (e.g., limited knowledge and attachment to Pap test) that may hinder wide adoption of primary HPV screening. We assessed these women-level factors following the implementation of primary HPV screening (July 2020) at Kaiser Permanente Southern California (KPSC). Methods: We administered a patient survey (mail and on-line) to female KPSC members aged 30-65 years who received primary HPV screening between October and December 2020. Those who preferred English vs. Spanish language were sampled separately. The survey included domains on knowledge about HPV and HPV screening, awareness of screening guidelines, and attitudes about HPV testing. Demographic data were collected using electronic health records. We used weighted multivariable logistic and modified Poisson regressions for associations between language preference and survey responses. Results: In total, 3,009 surveys were returned (38.0% response rate). Few women (7.0%) found HPV testing as an acceptable screening method. The majority of women (92.2%) remained unaware that HPV testing can replace Pap test for screening. The Pap test was the most preferred screening approach for 33.2% Spanish-speaking women vs. 19.9% English-speaking women. Only 20.6% knew that women aged 30-65 years can be screened every 5 years with cotest or primary HPV screening. Most women (96.4%) did not perceive stigma about taking the HPV test. Conclusion: Proactive patient education will help improve women's knowledge about primary HPV screening, which may facilitate its implementation in additional health care settings.

Thiazide Discontinuation in Chronic Kidney Disease Hypertension Management: A Retrospective Chart Review.

Thiazides are utilized in general hypertension management, however, their role in chronic kidney disease (CKD) hypertension management remains unclear. Although data support thiazide efficacy in advanced CKD, the adverse effect profile (including estimated glomerular filtration rate [eGFR] decline and electrolyte abnormalities) may lead to thiazide discontinuation. The authors assessed the thiazide discontinuation rate in Kaiser Permanente Southern California members with moderate-to-severe CKD and hypertension. This study was a multicenter retrospective analysis evaluating Kaiser Permanente Southern California members with hypertension and CKD 3B or 4 who filled a thiazide prescription in 2021, with follow-up through 2022. The outcomes were thiazide discontinuation rate, reason for thiazide discontinuation, time to thiazide discontinuation, and discontinuing practitioner specialty. Mean changes in blood pressure and eGFR from baseline were also evaluated. Of the 401 patients followed for 1 year after thiazide initiation, 65 patients discontinued a thiazide (discontinuation rate: 16.2%, mean time to discontinuation: 7.5 months). Of the 201 patients followed for 2 years after thiazide initiation, 57 patients discontinued a thiazide (discontinuation rate: 28.4%, mean time to discontinuation: 15.5 months). The most commonly documented thiazide discontinuation reason was increased serum creatinine (30% of total reasons at 1 year and 39% of total reasons at 2 years). Most patients with hypertension and CKD 3B or 4 continued on a thiazide with favorable blood pressure lowering effects and modest eGFR decline. Thiazides may be considered viable antihypertensive options with close renal function monitoring for patients with moderate-to-severe CKD.

Abstract P317: Patient Perceptions and Satisfactions of a Remote Blood Pressure Monitoring Program in an Integrated Healthcare System

Background: Uncontrolled high blood pressure (BP) is a leading contributor to cardiovascular disease. Remote BP monitoring (RBPM) can empower patients to participate in their healthcare which may be important for improving BP control. The aim of this study was to understand patients’ attitudes toward and satisfaction with a RBPM program. Methods: We identified Kaiser Permanente (KP) Southern California members aged 18 years and older enrolled in a RBPM program. Eligibility criteria include having uncontrolled BP (≥140/90 mmHg), a smartphone, and an email address. Between July 27 and August 17, 2023, we emailed a letter of invitation and link to an online survey to 716 eligible members followed by 2 reminder emails. The survey consisted of 5 domains to assess patients’ experiences with a BP monitor and the KP Health Ally app: ease of use, trust, perceived benefits, privacy and overall satisfaction. Responses to each question were rated on a scale from 1 (disagree) to 7 (agree). The average score for each domain was calculated as the weighted sum of the questions. Antihypertensive medication adherence was reported on a scale ranging from “all of the time” to “less than half the time”. Results: A total of 71 patients (9.9%) responded to the survey with 60 (8.4%) completing all questions. Respondents had a mean age of 60.4 (SD 13.1) years, with 70.4% being female and 50.5% African American. Overall satisfaction and perceived benefits were the highest scoring domains followed by ease of use and trust in the monitor and app (Figure). Privacy concerns were minimal. The overwhelming majority of respondents (89.7%) reported taking their BP medications all or nearly all of the time. Conclusion: Most respondents rated the RBPM program with a high level of satisfaction, perceived benefits and had limited concern about privacy with the potential opportunity to improve patients’ trust in the BP monitor and app functionality. This high level of patient satisfaction and acceptability should lead to increased implementation and scaling of the RBPM program.

Real-world effectiveness of recombinant zoster vaccine in self-identified Chinese individuals aged ≥50 years in the United States

ABSTRACT We evaluated the vaccine effectiveness (VE) of two doses of recombinant zoster vaccine (RZV) against herpes zoster (HZ) and postherpetic neuralgia (PHN) in Chinese adults at Kaiser Permanente Southern California (KPSC). Chinese KPSC members were identified based on self-reported ethnicity or self-reported preferred spoken/written language. Those aged ≥50 years who received two doses of RZV 4 weeks to ≤ 6 months apart were matched 1:4 to RZV unvaccinated Chinese members and followed through June 2022; second doses were accrued 6/1/2018–12/31/2020. We estimated incidence and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) comparing outcomes (HZ and PHN). Adjusted VE (%) was calculated as (1−aHR)×100. 3978 RZV vaccinated Chinese members were matched to 15,912 RZV unvaccinated Chinese members. The incidence per 1000 person-years (95% CI) of HZ in the vaccinated group was 1.5 (0.9–2.5) and 10.9 (9.8–12.1) in the unvaccinated group; aHR (95% CI) was 0.12 (0.07–0.21). Adjusted VE (95% CI) was 87.6% (78.9–92.7) against HZ. We identified 0 PHN cases in the vaccinated group and 19 in the unvaccinated group. Among Chinese adults aged ≥50 years, two doses of RZV provided substantial protection against HZ and PHN supporting the real-world effectiveness of the vaccine in this population.

Factors associated with uptake of bivalent mRNA COVID-19 vaccines in a large US health care system

BackgroundBivalent mRNA COVID-19 vaccines were developed to provide protection against the original SARS-CoV-2 strain and Omicron BA.4/BA.5 variants, but uptake in the United States has been low. Sociodemographic disparities in COVID-19 vaccine uptake have been documented, but it is unclear if similar disparities persist among individuals who previously completed a primary series of monovalent COVID-19 vaccine. MethodsWe conducted a retrospective cohort study at Kaiser Permanente Southern California (KPSC) including youth aged 5–17 years and adults aged ≥18 years who were KPSC members and had completed a primary series of monovalent COVID-19 vaccine. Individuals were followed from index date (date of eligibility for bivalent vaccine) to 03/31/2023 to ascertain receipt of any dose of bivalent mRNA COVID-19 vaccine or until disenrollment from KPSC or death. Multivariable robust Poisson regression was conducted to assess the adjusted relative risk and 95 % confidence intervals of factors associated with receipt of bivalent vaccine. ResultsThe final cohorts included 305,339 youth and 2,534,619 adults, of whom 19.5 % and 30.7 %, respectively, had received bivalent COVID-19 vaccine. Factors associated with being more likely to receive bivalent COVID-19 vaccine included older age, Asian race, more prior year outpatient and virtual visits, Charlson score ≥1, and immunocompromised status. Factors associated with being less likely to receive a bivalent COVID-19 vaccine included age 12–17 vs 5–11 years, Hispanic and non-Hispanic Black race/ethnicity, ≥1 prior year inpatient or emergency department visits, prior history of SARS-CoV-2 infection (adults only), Medicaid insurance, and higher neighborhood deprivation index. ConclusionEven among youth and adults who had previously received a primary series of monovalent COVID-19 vaccine, sociodemographic and clinical disparities were observed in receipt of bivalent COVID-19 vaccine. These findings are critical to inform equitable strategies for the implementation of the updated monovalent COVID-19 vaccine targeting the Omicron XBB strain.

Multiple Sclerosis, Disease-Modifying Therapies, and Infections.

The use of highly effective multiple sclerosis (MS) disease-modifying therapies (DMTs) is rapidly increasing. Yet, little is known about their real-world risks of infections. The goals of this study were to assess the comparative risk of outpatient and serious infections across DMTs in a large, diverse, U.S. cohort and determine whether such risks are attributable to DMTs, having MS, or other factors. We conducted a retrospective cohort study of Kaiser Permanente Southern California members from 2008 through 2020 with MS and non-MS controls matched on age, sex, race, and ethnicity. MS treatments, serious (those requiring hospitalization) and outpatient infections, and covariates were collected from the electronic health record. Adjusted hazard ratios (aHR) and risk ratios (aRR) were estimated using the Cox and Poisson regression, respectively. Six thousand, six hundred and twenty-six patients with MS with 11,929 treatment episodes (2,487 rituximab, 546 natalizumab, 298 fingolimod, 4,629 interferon-beta/glatiramer acetate, IFN/GLAT, and 3,969 untreated) and 33,550 population controls were included in the analyses. The average age at treatment start ranged from 38.9 to 49.2 years, and 74% were women. Untreated (aRR = 1.39, [95% CI = 1.35-1.44]) and IFN/GLAT-treated patients with MS (aRR = 1.60, [95% CI = 1.56-1.65]) had a higher risk of outpatient infections and serious infections (aHR = 2.97, [95% CI = 2.65-3.32 and aHR = 2.31, [95% CI = 2.04-2.62], respectively) compared with controls. Rituximab (aRR = 1.19, [95% CI = 1.14-1.25]), fingolimod (aRR = 1.22, [95% CI = 1.09-1.37]), and to a lesser extent, natalizumab treatment (aRR = 1.08, [95% CI = 0.97-1.20]) were associated with an increased risk of outpatient infections compared with IFN/GLAT. Rituximab (aHR = 1.41, [95% CI = 1.09-1.84]) and natalizumab (aHR = 1.40, [95% CI = 0.96-2.04]) treatment were associated with a similar increased risk of serious infections compared with IFN/GLAT. The only treatment-specific association identified was fingolimod with outpatient herpetic infections. Higher comorbidity index, previous hospitalization for infections, and advanced disability significantly increased the risk of serious infections independent of DMTs. Hospitalization for UTI-related pseudorelapses accounted for 24%-48% of serious infections. Patients with MS have higher risks of outpatient and serious infections compared with patients without MS. The risk of outpatient infections was similarly increased by rituximab and fingolimod and serious infections by rituximab and natalizumab compared with IFN/GLAT. Steps to minimize risks include optimizing bladder care, comorbidity prevention, varicella vaccination, and considering discontinuing or avoiding DMT use in patients with advanced disability and/or previous hospitalizations for infections.

Incidence of Diabetes Among Youth Before and During the COVID-19 Pandemic

Prior research found increases in diabetes among youth during the COVID-19 pandemic, but few studies examined variation across sociodemographics. To examine diabetes incidence rates among a diverse population of youth in the US before and during the COVID-19 pandemic. This cohort study included data from Kaiser Permanente Southern California (KPSC) between January 1, 2016, and December 31, 2021. KPSC members aged from birth to 19 years with no history of diabetes were included. Individuals were followed up using electronic health records for diabetes incidence defined using diagnoses, laboratory values, and medications. Analyses were conducted between November 2022 and January 2023. Age- and sex-standardized annual and quarterly incidence rates per 100 000 person-years (PYs) were calculated for type 1 diabetes and type 2 diabetes between 2016 and 2021. Rates were calculated within strata of age (<10 and 10-19 years), sex, and race and ethnicity (Asian/Pacific Islander, Hispanic, non-Hispanic Black, non-Hispanic White, and other/multiple/unknown). Using Poisson regression with robust error variances, incidence rate ratios (IRR) comparing 2020 to 2021 with 2016 to 2019 were calculated by diabetes type and within age, sex, and race and ethnicity strata and adjusting for health care utilization. Between 2016 to 2021, there were 1200, 1100, and 63 patients with type 1 diabetes (mean [SD] age, 11.0 [4.5] years; 687 [57.3%] male), type 2 diabetes (mean [SD] age, 15.7 [2.7] years; 516 [46.9%] male), and other diabetes, respectively. Incidence of type 1 diabetes increased from 18.5 per 100 000 PYs in 2016 to 2019 to 22.4 per 100 000 PYs from 2020 to 2021 with increased IRRs among individuals aged 10 to 19 years, male individuals, and Hispanic individuals. Incidence of type 2 diabetes increased from 14.8 per 100 000 PYs from 2016 to 2019 to 24.7 per 100 000 PYs from 2020 to 2021 with increased IRRs among individuals aged 10 to 19 years, male and female individuals, and those with Black, Hispanic, and other/unknown race and ethnicity. In this cohort study of youth in KPSC, incidence of diabetes increased during the COVID-19 pandemic and was more pronounced in specific racial and ethnic groups. Future research to understand differential impacts of physiologic and behavioral risk factors is warranted.

Risk of herpes zoster following mRNA COVID-19 vaccine administration

ABSTRACTBackgroundAdverse events following mRNA COVID-19 vaccines, including herpes zoster (HZ), have been reported. We conducted a cohort study to evaluate the association between mRNA COVID-19 vaccination and subsequent HZ at Kaiser Permanente Southern California (KPSC).Research design and methodsThe vaccinated cohort consisted of KPSC members who received their first dose of mRNA COVID-19 vaccine (mRNA-1273 and BNT162b2) during 12/2020–05/2021 and were matched to unvaccinated individuals on age and sex. Incident HZ cases occurring within 90 days of follow-up were identified by diagnosis codes and antiviral medications. Cox proportional hazards models estimated adjusted hazard ratios (aHR), comparing HZ incidence between the vaccinated and unvaccinated cohorts.ResultsCohort included 1,052,362 mRNA-1273 recipients, 1,055,461 BNT162b2 recipients, and 1,020,334 comparators. Compared to unvaccinated individuals, aHR for HZ up to 90 days after the second dose of mRNA-1273 and BNT162b2 was 1.14 (1.05–1.24) and 1.12 (1.03–1.22), respectively. In those aged ≥50 years not vaccinated with zoster vaccine, aHR was also increased after the second dose of mRNA-1273 (1.18 [1.06–1.33]) and BNT162b2 (1.15 [1.02–1.29]) vaccine vs. unvaccinated individuals.ConclusionsOur findings suggest a potential increased risk of HZ after a second dose of mRNA vaccines, potentially driven by the increased risk in individuals aged ≥50 years without history of zoster vaccination.

1275-P: Incident Diabetes Before and During the COVID-19 Pandemic among Youth in Kaiser Permanente Southern California

Background: Prior research found increases in type 1 and type 2 diabetes (T1D/T2D) among youth during the COVID-19 pandemic but did not focus on age, sex, or race/ethnicity variation. We examined incidence rates from 2016-2021 in Kaiser Permanente Southern California (KPSC), a large, integrated healthcare delivery system. Methods: KPSC members &amp;lt;20 years old, with no diabetes prior to their incidence year were followed using electronic health records for diabetes defined using diagnoses, labs, and diabetes medications. We calculated age- and sex-standardized incidence rates per 100,000 person-years (PY) for T1D and T2D between 2016-2021 overall and by age, sex, and race/ethnicity. We used Poisson regression to calculate incidence rate ratios (IRR) comparing 2020-2021 to 2016-2019. Results: Incidence of T1D increased from 18.5/100,000 PY in 2016-2019 to 22.4/100,000 PY in 2020-2021 with increased IRR among 10-19-year-olds, both sexes, and Hispanic individuals. (Table) Incidence of T2D increased from 14.8/100,000 PY in 2016-2019 to 24.7/100,000 PY in 2020-2021 with increased IRR among 10-19-year-olds, both sexes, and those with non-Hispanic Black, Hispanic, and other/unknown race/ethnicity. Conclusion: Incidence of both T1D and T2D increased following the start of the pandemic. Future research to understand potential underlying physiologic and behavioral risk factors is warranted. Disclosure M.T.Mefford: None. R.Wei: None. E.Lustigova: None. J.P.Martin: None. K.Reynolds: Research Support; Novartis Pharmaceuticals Corporation.

Wildfire Exposure and Health Care Use Among People Who Use Durable Medical Equipment in Southern California.

People using electricity-dependent durable medical equipment (DME) may be vulnerable to health effects from wildfire smoke, residence near wildfires, or residence in evacuation zones. To our knowledge, no studies have examined their healthcare utilization during wildfires. We obtained 2016-2020 counts of residential Zip Code Tabulation Area (ZCTA) level outpatient, emergency department (ED), and inpatient visits made by DME-using Kaiser Permanente Southern California members 45+. We linked counts to daily ZCTA-level wildfire particulate matter (PM) 2.5 and wildfire boundary and evacuation data from the 2018 Woolsey and 2019 Getty wildfires. We estimated the association of lagged (up to 7 days) wildfire PM 2.5 and residence near a fire or in an evacuation zone and healthcare visit frequency with negative binomial and difference-in-differences models. Among 236,732 DME users, 10 µg/m 3 increases in wildfire PM 2.5 concentration were associated with the reduced rate (RR = 0.96; 95% confidence interval [CI] = 0.94, 0.99) of all-cause outpatient visits 1 day after exposure and increased rate on 4 of 5 subsequent days (RR range 1.03-1.12). Woolsey Fire proximity (<20 km) was associated with reduced all-cause outpatient visits, whereas evacuation and proximity were associated with increased inpatient cardiorespiratory visits (proximity RR = 1.45; 95% CI = 0.99, 2.12, evacuation RR = 1.72; 95% CI = 1.00, 2.96). Neither Getty Fire proximity nor evacuation was associated with healthcare visit frequency. Our results support the hypothesis that wildfire smoke or proximity interrupts DME users' routine outpatient care, via sheltering in place. However, wildfire exposures were also associated with increased urgent healthcare utilization in this vulnerable group.

Impact of California's Senate Bill 27 on Antimicrobial-Resistant Escherichia coli Urinary Tract Infection in Humans: Protocol for a Study of Methods and Baseline Data.

Overuse of antibiotics contributes to antimicrobial resistance (AMR) and is a growing threat to human health worldwide. Previous work suggests a link between antimicrobial use in poultry and human AMR extraintestinal pathogenic Escherichia coli (E coli) urinary tract infections (UTIs). However, few US-based studies exist, and none have comprehensively assessed both foodborne and environmental pathways using advanced molecular and spatial epidemiologic methods in a quasi-experimental design. Recently, California enacted Senate Bill 27 (SB27), which changed previous policy to require a veterinarian's prescription for the use of antibiotic drugs, and which banned antibiotic use for disease prevention in livestock. This provided an opportunity to evaluate whether SB27 will result in a reduction in antimicrobial-resistant infections in humans. We describe in detail the methods implemented to achieve the overarching objective of this study to evaluate the impact of SB27 on downstream antibiotic resistance rates in human UTIs. A summary of the overall approach and the partnerships between Columbia University, George Washington University (GWU), Johns Hopkins Bloomberg School of Public Health, Kaiser Permanente Southern California (KPSC) Research and Evaluation, the Natural Resources Defense Council, Sanger Institute at Stanford University, Sutter Health Center for Health Systems Research, the University of Cambridge, and the University of Oxford is presented. The collection, quality control testing, and shipment of retail meat and clinical samples are described. Retail meat (chicken, beef, turkey, and pork) was purchased from stores throughout Southern California from 2017 to 2021. After processing at KPSC, it was shipped to GWU for testing. From 2016 to 2021, after clinical specimens were processed for routine clinical purposes and immediately before discarding, those with isolated colonies of E coli, Campylobacter, and Salmonella from KPSC members were collected and processed to be shipped for testing at GWU. Detailed methods of the isolation and testing as well as the whole-genome sequencing of the meat and clinical samples at GWU are described. KPSC electronic health record data were used to track UTI cases and AMR patterns among the cultured specimens. Similarly, Sutter Health electronic health record data were used to track UTI cases in its Northern California patient population. From 2017 to 2021, overall, 12,616 retail meat samples were purchased from 472 unique stores across Southern California. In addition, 31,643 positive clinical cultures were collected from KPSC members during the same study period. Here, we presented data collection methods for the study, which was conducted to evaluate the impact of SB27 on downstream antibiotic resistance rates in human UTI. To date, it is one of the largest studies of its kind to be conducted. The data collected during this study will be used as the foundation for future analyses specific to the various objectives of this large body of work. DERR1-10.2196/45109.

Safety Net Program to Improve Statin Initiation Among Adults With High Low-Density Lipoprotein Cholesterol

Despite their effectiveness in reducing low-density lipoprotein cholesterol and cardiovascular disease risk, high-intensity statins are underutilized among adults with low-density lipoprotein cholesterol ≥190 mg/dL. This study determined whether a safety net program (SureNet) facilitating medication and laboratory test orders improved statin initiation and laboratory test completions after (SureNet period: April 2019-September 2021) and before implementation (pre-SureNet period: January 2016-September 2018). Kaiser Permanente Southern California members aged 20-60 years with low-density lipoprotein cholesterol ≥190 mg/dL and no statin use in previous 2-6 months were included in this retrospective cohort study. Statin orders within 14 days and statin fills, laboratory test completions, and improved low-density lipoprotein cholesterol within 180 days of the high low-density lipoprotein cholesterol (pre-SureNet) or outreach (SureNet period) were compared. Analyses were conducted in 2022. Overall, 3,534 and 3,555 adults were eligible for statin initiation during the pre-SureNet and SureNet periods, respectively. Overall, 759 (21.5%) and 976 (27.5%) had a statin approved by their physician during pre-SureNet and SureNet periods, respectively (p<0.001). After multivariable adjustment for demographics and clinical characteristics, adults during the SureNet period had a higher likelihood of receiving a statin order (prevalence ratio=1.36, 95% CI=1.25, 1.48), filling their statin (prevalence ratio=1.32, 95% CI=1.26, 1.38), completing their laboratories (prevalence ratio=1.41, 95% CI=1.26, 1.58), and improving low-density lipoprotein cholesterol (prevalence ratio=1.21, 95% CI=1.07, 1.37) than in pre-Surenet period. The SureNet program was able to improve prescription orders, fills, laboratory test completions, and lower low-density lipoprotein cholesterol. Optimizing both physician adherence to treatment guidelines; and patient adherence to the program may improve low-density lipoprotein cholesterol lowering.

Effectiveness of Lower Rituximab Doses in Neuromyelitis Optica Spectrum Disorder: A Population-based Cohort Study (S50.006)

<h3>Objective:</h3> To describe effectiveness and safety outcomes in neuromyelitis optica spectrum disorder (NMOSD) patients treated with &lt;4g of rituximab per year <h3>Background:</h3> Optimal dosing of rituximab for NMOSD has not been established. The most common published regimens are 4 grams or 3g/m2 annually in divided doses. <h3>Design/Methods:</h3> We conducted a retrospective cohort study utilizing the electronic medical record among Kaiser Permanente Southern California members who met NMOSD diagnostic criteria and were treated with at least one rituximab infusion 1/1/2010–9/22/2022. <h3>Results:</h3> We identified 116 NMOSD patients who were treated with a median annual dose of 2,077 milligrams of rituximab (IQR=1673–2710mg) for a median of 4.6 years (IQR=2.4–8.0). The majority (88%) were aquaporin-4 IgG seropositive. Fifty-eight (50%) patients received an induction dose of 1g or less. The most common initial rituximab maintenance dose was 1g every 6 months (n=80, 69%), with 22 (19%) receiving lower and 14 (12%) higher doses. Rituximab dosing was lowered in 34 (29%) and increased in 6 (5.2%) patients. Twenty-one (18%) relapsed following rituximab treatment, of which 7 occurred within 6 months of initiation. Patients who relapsed had similar demographic and clinical characteristics at rituximab initiation and there were no significant differences in induction, initial maintenance or median annual doses compared to relapse-free patients. Six patients (5.2%) died within 2 years of their most recent rituximab dose, 3 from advanced NMO and 1 from COVID-19 pneumonia. Rituximab was discontinued in 28 (24%) patients, 10 (8.6%) for infections, 5 relapses, 2 hypogammaglobulinemia, 2 infusion reactions and 2 for disease stability. <h3>Conclusions:</h3> We found that annual rituximab dose of ~2gm adequately controlled disease activity in &gt;95% of NMOSD patients yet led to discontinuation from infections or hypogammaglobulinemia in 10.3% in this diverse, population-based cohort. Taken together with the existing literature, these findings indicate that even lower rituximab doses may result in an improved risk/benefit profile. <b>Disclosure:</b> Dr. Iordanova has nothing to disclose. Ms. Smith has nothing to disclose. Ms. Gonzales has nothing to disclose. Dr. Lee has nothing to disclose. Bonnie Li has nothing to disclose. An immediate family member of Dr. Langer-Gould has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of American Thoracic Society. The institution of Dr. Langer-Gould has received research support from PCORI. The institution of an immediate family member of Dr. Langer-Gould has received research support from PCORI, ARQ, NIH. Dr. Langer-Gould has a non-compensated relationship as a Voting Member with ICER CTAF Panel that is relevant to AAN interests or activities.

How much of the increased infection risk from higher rituximab doses is mediated by hypogammaglobulinemia in patients with multiple sclerosis? (S46.006)

<h3>Objective:</h3> To estimate to what extent increased infection risk from more rituximab exposure is mediated by hypogammaglobulinemia in multiple sclerosis (MS) patients. <h3>Background:</h3> Prolonged treatment with B-cell depleting therapies increase the risk of hypogammaglobulinemia and infections. These relationships are poorly understood. <h3>Design/Methods:</h3> We conducted a retrospective cohort study utilizing the electronic medical record among Kaiser Permanente Southern California members who met MS diagnostic criteria and were treated with at least two rituximab infusions, 2008–2020. Multivariable Andersen-Gill hazards models were used to assess risk of recurrent outpatient (≥4/year) or serious/hospitalized infections and linear regression to examine correlates of IgG values. <h3>Results:</h3> We identified 2477 MS patients who were treated with rituximab for a median of 2.0 years (IQR=1.0–3.0). 405 patients (16.4%) developed recurrent outpatient infections, 153 (6.2%) serious infections and 249 (10.1%) IgG &lt;700 mg/dL. Higher cumulative rituximab dose (&gt;4g) was correlated with lower IgG levels (Beta=−57.0, p&lt;0.0001, ref≤2g) and, in models mutually adjusted for hypogammaglobulinemia, both were independently associated with an increased risk of serious (&gt;4g, aHR=1.57, 95%CI=1.08–2.28, p=.018; IgG&lt;500, aHR=2.90, 95%CI=1.52–5.54, p=0.001) and outpatient infections (&gt;4g, aHR=2.09, 95%CI=1.64–2.66, p&lt;.0001; IgG&lt;500 aHR=2.48, 95%CI=1.64–3.75, p&lt;.0001; ref=IgG≥700). Mediation analyses showed that hypogammaglobulinemia accounted for 12.6% of serious infection risk associated with higher cumulative rituximab exposure but was not significant for outpatient infections. Other independent modifiable risk factors were advanced physical disability for serious infections (aHR=5.86, p&lt;.0001), obesity (aHR=1.38, p=.0017) and chronic obstructive pulmonary disease (aHR=1.88, p=.0001) for outpatient infections. Black (16.6% of population) or Asian (2.8%) race or Hispanic (31.0%) ethnicity was correlated with significantly higher IgG levels (Betas=260.7, 252.7, 67.3, respectively, p’s&lt;.0001, ref=white) but had no independent influence on infection risks. <h3>Conclusions:</h3> Higher cumulative rituximab doses increase the risk of infections primarily via mechanisms independent of hypogammaglobulinemia. Important factors that influence these relationships include selected comorbidities, race and ethnicity, advanced physical disability, and age. <b>Disclosure:</b> An immediate family member of Dr. Langer-Gould has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Annals of American Thoracic Society. The institution of Dr. Langer-Gould has received research support from PCORI. The institution of an immediate family member of Dr. Langer-Gould has received research support from PCORI, ARQ, NIH. Dr. Langer-Gould has a non-compensated relationship as a Voting Member with ICER CTAF Panel that is relevant to AAN interests or activities. Bonnie Li has nothing to disclose. Ms. Smith has nothing to disclose. Ms. Gonzales has nothing to disclose. Dr. Xu has nothing to disclose.

2233. Clinical Risk Scores (CRSs) to Predict Resistance to Trimethoprim-Sulfamethoxazole (TMP-SMX), Fluoroquinolone (FQ), Nitrofurantoin (NIT), or Third Generation Cephalosporins (3GC) among Adult Outpatients (OPs) with Complicated Urinary Tract Infections (cUTIs)

Abstract Background Increased resistance rates to available oral antibiotics (ABs) contribute to delays in receipt of appropriate treatment and adverse outcomes among patients with cUTI in the OP setting. To optimize empiric AB selection in adult OPs with cUTIs, we developed CRSs using information available at presentation to estimate the risk of having a cUTI that was resistant to TMP-SMX, FQ, NIT, or 3GC. Methods Retrospective cohort study among Kaiser Permanente Southern California members from 2017-2020. Inclusion criteria: age ≥18 yrs; cUTI diagnosis during an OP visit; positive urine culture with antibiotic susceptibility results; receipt of antibiotic ±3 days of index urine culture, and not hospitalized on day of OP visit. Resistance to TMP-SMX, FQ, NIT, and 3GC on index urine culture was quantified. OPs were randomly split (60:40) into training and validation datasets. Covariates present on clinical presentation were collected. Least absolute shrinkage and selection operator logistic regression (LR) were used to develop separate models to estimate the likelihood of resistance to TMP-SMX, FQ, NIT, and 3GC. The prediction models were developed using training and validation datasets. For all 4 LR models, CRSs were calculated as the weighted sums of regression coefficients. Variables in each of the final LR models were assigned point(s), and an OP’s CRS for cUTI resistant to TMP-SMX, FQ, NIT, or 3GC was based on total points in each of the respective models. Results A total of 30,450 cUTIs among 26,326 OPs met study criteria. Mean age was 61, 54% were female, and E. coli (66%) was the most common pathogen. Resistance to TMP-SMX, FQ, NIT, and 3GC was 37%, 27%, 24%, and 19%, respectively. Baseline covariates and associated points for the 4 LR models are shown in Table 1. A CRS of 0, 5, 8, 12 corresponded to a &amp;gt;20% risk of resistance to TMP-SMX, FQ, NIT, or 3GC, respectively (Figure 1). Table 1.Baseline Clinical Covariates and Associated Point Values in Each of the 4 Clinical Risk Scores Covariates in each of the Final ResistanceFigure 1.Clinical Risk Scores for Resistance to TMP-SMX, FQ, NIT, and 3GC Conclusion We developed a high-performing parsimonious CRS to aid clinicians in appropriate treatment selection of adult OPs with cUTI. This tool can be used to facilitate empiric antibiotic selection and ensure adult OPs with cUTI have a greater probability of receiving early appropriate therapy. Given its high baseline resistance, TMP/SMX should not be considered for empiric therapy. Disclosures Thomas P. Lodise, PharmD, PhD, Spero Therapeutics: Advisor/Consultant Lie Hong H. Chen, DrPH, MSPH, Spero Therapeutics: Grant/Research Support Katia J. Bruxvoort, PhD, MPH, Dynavax: Grant/Research Support|Gilead: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support Rong Wei, MA, Spero Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support Theresa M. Im, MPH, Spero Therapeutics: Grant/Research Support Richard Contreras, MS, Spero Therapeutics: Grant/Research Support Mauricio Rodriguez, PharmD, MS-HEOR, BCPS, BCCCP, BCIDP, Spero Therapeutics: Employee Larry Friedrich, PharmD, Spero Therapeutics: Employee Jennifer Reese, PharmD, Spero Therapeutics: Employee Sara Y. Tartof, PhD MPH, Pfizer: Grant/Research Support|Spero: Grant/Research Support.

2232. Association between Inappropriate Empiric Therapy (IET) and 30-Day Emergency Department/Inpatient (ED/IP) Visits Among Adult Outpatients (OPs) with Complicated Urinary Tract Infections (cUTIs)

Abstract Background Deleterious outcomes associated with IET are well documented among hospitalized patients with infections. However, scant data exist on the consequences of IET among adult OPs with cUTIs. This study evaluated the association between receipt of IET and 30-day ED/IP visits among adult OPs with cUTIs. Methods Retrospective cohort study among Kaiser Permanente Southern California members from 2017-20. Inclusion criteria were age ≥18 years; cUTI diagnosis during an OP visit; positive urine culture with antibiotic (AB) susceptibility results; receipt of AB ±3 days of index urine culture; and not hospitalized on day of OP visit. For OPs with multiple cUTIs, only the index cUTI was considered. IET was defined as failure to receive an AB with in vitro microbiologic activity against all recovered cUTI pathogens ±3 days of culture collection date. Outcomes included all-cause and cUTI-related ED/IP visits ≥3 days to ≤30 days from index culture date. Logistic regression was used to adjust for baseline differences between appropriateness groups. Results During study period, 25,980 OPs with cUTIs met study criteria. Mean age was 60 years, majority female (57%), and E. coli (66%) was the most common pathogen. IET was noted in 2656 (10%) of patients. Comparison of baseline characteristics between appropriateness groups is shown in Table. Comparison of 30-day all-cause and cUTI-related ED/IP visits between IET and appropriate empiric therapy (AET) is shown in Figure. In the logistic regression, receipt of IET was associated with an increase odds of 30-day all-cause ED/IP visits (adjusted odds ratio (aOR)= 1.3; 95% CI: 1.2-1.4) and 30-day cUTI-related ED/IP visits (aOR=1.5; 95% CI: 1.4-1.7), respectively. Figure Conclusion Thirty-day all-cause and cUTI-related ED/IP visits were significantly higher among adult OPs with cUTI who received IET. As culture and susceptibility results are frequently unknown at the time of empiric therapy selection, the findings highlight the critical need to use institution-specific antibiotic resistance risk stratification tools, in tandem with rapid diagnostic tests, to guide empiric antibiotic decisions among OPs with cUTIs as measures to ensure patients receive AET and maximize chances of a successful clinical outcome. Disclosures Thomas P. Lodise, PharmD, PhD, Spero Therapeutics: Advisor/Consultant Lie Hong H. Chen, DrPH, MSPH, Spero Therapeutics: Grant/Research Support Katia J. Bruxvoort, PhD, MPH, Dynavax: Grant/Research Support|Gilead: Grant/Research Support|Glaxosmithkline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Seqirus: Grant/Research Support Rong Wei, MA, Spero Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support Theresa M. Im, MPH, Spero Therapeutics: Grant/Research Support Richard Contreras, MS, Spero Therapeutics: Grant/Research Support Mauricio Rodriguez, PharmD, MS-HEOR, BCPS, BCCCP, BCIDP, Spero Therapeutics: Employee Larry Friedrich, PharmD, Spero Therapeutics: Employee Jennifer Reese, PharmD, Spero Therapeutics: Employee Sara Y. Tartof, PhD MPH, Pfizer: Grant/Research Support|Spero: Grant/Research Support.

Investigating Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Congenital Anomalies.

This observational retrospective matched cohort study evaluated the safety of a prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination, Boostrix. We previously reported on the risk of maternal and neonatal outcomes; here we report on the risk of congenital anomalies in infants at birth through 6months of age. The study included pregnant Kaiser Permanente Southern California members. Women who received the Tdap vaccine on or after the 27th week of pregnancy between January 2018 and January 2019 were matched to women who were pregnant between January 2012 and December 2014 and were not vaccinated with Tdap during pregnancy. Unadjusted and adjusted relative risks (aRRs) with 95% confidence intervals were estimated by Poisson regression. Quantitative secular trend analyses, from 2011 to 2017, were conducted on congenital anomalies with a statistically significant aRR > 1. The analysis consisted of 16,350 and 16,088 live-born infants in the Tdap-exposed and unexposed cohorts, respectively. Of the 14 congenital anomaly body systems evaluated, 8 (eye, ear/face/neck, respiratory, upper gastrointestinal, genital, renal, musculoskeletal, integument) had statistically significant elevated aRRs, with point estimates ranging from 1.17 to 2.02. The observed elevated aRRs were consistent with their respective secular increases over time. Cautious interpretation of these findings is warranted as these increases may have resulted from improved identification and diagnosis. Furthermore, the biological plausibility of an association between maternal vaccine exposure in the third trimester of pregnancy and birth defects is low. The overall study findings support the safety of maternal immunization with Boostrix during the third trimester of pregnancy. ClinicalTrials.gov identifier, NCT03463577.

Health Disparities in Kidney Failure Among Patients With Autosomal Dominant Polycystic Kidney Disease: A Cross-Sectional Study

Understanding potential differences in patterns of kidney failure among patients with autosomal dominant polycystic kidney disease (ADPKD) may provide insights into improving disease management. We sought to characterize patients with ADPKD and kidney failure across different race/ethnicities. Cross-sectional study. Kaiser Permanente Southern California members diagnosed with ADPKD between January1, 2002, and December 31,2018. ADPKD. Kidney failure, dialysis, or receipt of kidney transplant. Differences in characteristics by race/ethnicity were assessed using analysis of variance F test and χ2 test. To compare the range and distribution of the average age at onset of kidney failure by race/ethnicity and sex, we used box plots and confidence intervals. Multivariable logistic regression was used to estimate OR for kidney transplant. Among 3,677 ADPKD patients, 1,027 (27.3%) had kidney failure. The kidney failure cohort was comprised of Black (n=138; 30.7%), White (n=496; 30.6%), Hispanic (n=306; 24.7%), and Asian (n=87; 23.6%) patients. Hispanic patients had the youngest mean age of kidney failure onset (50 years) compared to Black (56 years) and White (57 years) patients. Black (44.2%; OR, 0.72) and Hispanic (49.7%; OR, 0.65) patients had lower rates of kidney transplantation compared to White (53.8%) patients. Preemptive kidney transplantations occurred in 15.0% of patients. Retrospective study design and possible misclassification of ADPKD cases. Kidney function calculations were based on equations incorporating race, potentially overestimating kidney function in African Americans. The study was conducted within a single, integrated health care system in 1 geographic region and may not be generalizable to all ADPKD patients. Among a large diverse ADPKD population, we observed racial/ethnic differences in rates of kidney failure, age of kidney failure onset, and rates of kidney transplantation. Our real-world ADPKD cohort provides insight into racial/ethnic variation in clinical features of disease and potential disparities in care, which may affect ADPKD outcomes.

Health Literacy and Treatment Satisfaction Among Patients with Venous Thromboembolism.

Venous thromboembolism (VTE) treatment requires complex management, and patients with limited health literacy (HL) may perceive higher burden and lower benefits associated with their treatment. To examine the association of HL with treatment satisfaction among patients with VTE. Retrospective cohort study PARTICIPANTS: Kaiser Permanente Southern and Northern California members who were taking oral anticoagulants (OAC) for incident VTE between 2015 and 2018 were surveyed. Main Measures HL was assessed using a 3-item HL assessment and dichotomized as having adequate or limited HL. High treatment burden and low treatment benefit were defined as Anti-Clot Treatment Scale (ACTS) scores below the 25th percentile of the distributions for ACTS Burdens and Benefits survey components, respectively. Using Poisson regression, multivariable adjusted risk ratios (RR) and 95% confidence intervals (CI) were calculated for the association of HL with high treatment burden and low treatment benefits. Among 2154 respondents, 397 (18.4%) had limited HL. Patients with limited vs adequate HL were older (47.9% vs 27.5% aged ≥ 75 years, p<0.001), more likely to use a non-English language when discussing their health (10.8% vs 1.7%, p<0.001), to have less than high school education (10.1% vs 1.7%, p<0.001), and to self-rate their health as fair or poor (47.6% vs 25.5%, p<0.001). After multivariable adjustment, patients with limited HL were more likely to have higher perceived treatment burden (RR 1.24, 95% CI 1.07, 1.45) and lower perceived treatment benefits (RR 1.21, 95% CI 1.08, 1.37). Limited HL was associated with lower OAC treatment satisfaction, though absolute differences in satisfaction scores were small. Further examination of the intersection of HL with VTE treatment satisfaction and compliance among older and non-English speaking patients is warranted.

Wildfire exposure and health care use among people who use durable medical equipment in Southern California

Background: Climate change-induced wildfires cause trauma, stress, and injury in affected communities, while exposing 70% of the US population to smoke particulate matter (PM2.5) annually and exacerbating cardiorespiratory disease. Few studies examine wildfire smoke exposure in vulnerable populations, and none evaluate residence near a fire. Methods: We identified 236,732 Kaiser Permanente Southern California members who used electricity-dependent durable medical equipment (DME). DME use is associated with respiratory illness and disability, indicating vulnerability to smoke exposure and difficulty evacuating disaster zones. Daily counts of outpatient, inpatient, and emergency healthcare visits made by DME users from 2016-2020 were linked with daily estimates of wildfire generated PM2.5 by residential ZIP code. We used historical maps to identify ZIPs within 20 km of the the 2018 and 2019 Getty and Woolsey fires. We performed negative binomial regression analyses using direct and lagged effects of wildfire PM2.5 and difference-in-differences analyses to evaluate the association between direct wildfire exposure and health care visit frequency. We adjusted for temperature, temporal effects, non-wildfire PM2.5, and spatial confounders. Results: Residence within 20 km of the Woolsey Fire was associated with fewer outpatient and more inpatient visits (RR = 0.98, 95% CI: 0.78, 0.87, RR = 1.45, 95% CI: 1.01, 2.11), while Getty Fire evacuation exposure was not associated with visit frequency. In contrast, increases in wildfire PM2.5 were associated with small and constant increases in outpatient visits 2-6 days after a change. Wildfire PM2.5 was not associated with frequency of inpatient or emergency visits at any lag. Conclusion: DME users, presumed vulnerable to wildfire smoke exposure, may have sheltered in place during fires or took other precautions. However, the Woolsey Fire (which was 10 times larger than the Getty) may have produced health concerns in those directly affected when evacuation was necessary and sheltering in place impossible.