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Background: Screening and eradication of Helicobacter pylori reduce the risk of gastric cancer in patients with a family history. We assessed patient perspectives on H. pylori screening and treatment within a diverse regional US population., Methods: Between July 2022 and August 2022, we conducted a cross-sectional study among patients with ≥1 first-degree relative(s) with gastric cancer. Eligible patients were between 18 and 75 years of age without history of H. pylori infection or gastric cancer. A survey assessed interest in testing and willingness to complete treatment for H. pylori. Interested patients were offered H. pylori testing and treatment. We examined interest and effectiveness of treatment by race and ethnicity., Results: We identified 15,255 eligible patients, and 1,500 patients were randomly selected for the survey; 280 (19%) patients, including two relatives not initially invited but asked to participate, responded following outreach. Respondents were 65% male and averaged 57 years (SD = 13) with 36% Hispanic, 36% non-Hispanic White, 15% Asian/Pacific Islander, and 9% non-Hispanic Black. Overall, 223 (80%) were interested in H. pylori screening; of these, 89% would take antibiotics as prescribed. Willingness to screen was consistent across racial and ethnic groups. Among 223 respondents interested in screening, 128 (57%) completed testing with 15 screen-detected cases; all 15 completed treatment, and 11 had confirmed eradication., Conclusions: Patients with family history of gastric cancer had a high level of interest in H. pylori screening and successful eradication when detected., Impact: A screen-and-treat strategy for H. pylori may be considered for patients with family history of gastric cancer., (©2024 American Association for Cancer Research.)

Objectives: The aim of this study was to examine the adherence, changes in weight, and, waist circumference associated with the daily consumption of a culturally preferred food, namely an avocado, among Hispanic/Latina females in the Habitual Diet and Avocado Trial (HAT). Methods: HAT was a multisite, randomized controlled trial conducted between 2018 and 2020. Participants in the Avocado-Supplemented Diet Group were provided with and instructed to consume one avocado/day (~2.2 servings) for 6 months; participants in the Habitual Diet Group were instructed to follow their usual diet and limit intake to ≤2 avocados/month. Avocado consumption was assessed using three random 24 h dietary recalls administered by dietitians. This analysis focused on women who self-identified as Hispanic/Latina. Results: Within HAT, 158 females self-identified as Hispanic/Latina (median age: 42 years, IQR: 36-54). Across the dietary recalls, the Avocado-Supplemented Group ( n = 80) consumed 1.9-2.1 avocado servings/day; the Habitual Diet Group ( n = 78) consumed 0.04-0.09 servings/day ( p < 0.001). The weight and waist circumference measurements were similar between groups. Hispanic/Latina females remained adherent to daily avocado consumption for the 6-month study period, without a significant change in their body weight or waist circumference measurements. Conclusions: Integrating a culturally preferred food into a dietary intervention enhanced adherence amongst Latina adults, with no impact significant impact on body composition.

Background/objectives: The Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) model relies primarily on fasting glucose values. Health systems have increasingly shifted practice towards use of glycated hemoglobin (HbA1c) measurement. We modified the ENDPAC model using patients with new onset hyperglycemia., Methods: Four cohorts of patients 50-84 years of age with HbA1c results ≥6.2-6.5 % in 2011-2018 were identified. A combine cohort was formed. A widened eligibility criterion was applied to form additional four individual cohorts and one combined cohort. The primary outcome was the diagnosis of pancreatic cancer within 3 years after the first elevated HbA1c testing. The performance of the modified ENDPAC model was evaluated by AUC, sensitivity, positive predictive value, cases detected, and total number of patients screened., Results: The individual and combined cohorts consisted of 39,001-79,060 and 69,334-92,818 patients, respectively (mean age 63.5-65.0 years). The three-year PC incidence rates were 0.47%-0.54 %. The AUC measures were in the range of 0.75-0.77 for the individual cohorts and 0.75 for the combined cohorts. When the four individual cohorts were combined, more PC cases can be identified (149 by the combined vs. 113-116 by individual cohorts when risk score was 5+). Performance measures were compromised in nonwhites. Asian and Pacific islanders had lower sensitivity compared to other racial and ethnic groups (29 % vs. 50-60 %) when risk score was 5+., Conclusions: The modified ENDPAC model targets a broader population and thus identifies more high-risk patients for cancer screening. The differential performance needs to be considered when the model is applied to non-white population., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Population-based screening for gastric cancer (GC) in low prevalence nations is not recommended. The objective of this study was to develop a risk-prediction model to identify high-risk patients who could potentially benefit from targeted screening in a racial/ethnically diverse regional US population., Methods: We performed a retrospective cohort study from Kaiser Permanente Southern California from January 2008-June 2018 among individuals age ≥50 years. Patients with prior GC or follow-up <30 days were excluded. Censoring occurred at GC, death, age 85 years, disenrollment, end of 5-year follow-up, or study conclusion. Cross-validated LASSO regression models were developed to identify the strongest of 20 candidate predictors (clinical, demographic, and laboratory parameters). Records from 12 of the medical service areas were used for training/initial validation while records from a separate medical service area were used for testing., Results: 1,844,643 individuals formed the study cohort (1,555,392 training and validation, 289,251 testing). Mean age was 61.9 years with 53.3% female. GC incidence was 2.1 (95% CI 2.0-2.2) cases per 10,000 person-years (pyr). Higher incidence was seen with family history: 4.8/10,000 pyr, history of gastric ulcer: 5.3/10,000 pyr, H. pylori: 3.6/10,000 pyr and anemia: 5.3/10,000 pyr. The final model included age, gender, race/ethnicity, smoking, proton-pump inhibitor, family history of gastric cancer, history of gastric ulcer, H. pylori infection, and baseline hemoglobin. The means and standard deviations (SD) of c-index in validation and testing datasets were 0.75 (SD 0.03) and 0.76 (SD 0.02), respectively., Conclusions: This prediction model may serve as an aid for pre-endoscopic assessment of GC risk for identification of a high-risk population that could benefit from targeted screening., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Aims: The yield of various endoscopic biopsy sampling methods for detection of precursor lesions of noncardia gastric cancer in a real-world setting remains unclear. Our objective was to evaluate the association of endoscopic biopsy sampling methods with detection of gastric intestinal metaplasia (GIM) and gastric dysplasia (GD)., Methods: We conducted a case-control study of adult patients who underwent EGD with biopsy sampling between 2010 and 2021 in a racially and ethnically diverse U.S. healthcare system. Cases were patients with histopathologic findings of GIM and/or GD. Control subjects were matched 1:1 by age, procedure date, and medical center. We compared the detection of GIM and GD using 4 different biopsy sampling methods: unspecified, specified stomach location, 2+2, and the Sydney protocol. Additionally, we assessed trends in use of sampling methods (Cochrane-Armitage) and identified patient and endoscopist factors associated with their use (logistic regression)., Results: We identified 20,938 GIM and 455 GD matched pairs. A greater proportion of GIM cases were detected using 2+2 (31.3% vs 25.3%, P < .0001) and the Sydney protocol (9.1% vs 1.0%, P < .0001) compared with control subjects. Similarly, a greater proportion of GD cases were detected using the Sydney protocol (15.6% vs .4%, P < .0001). We observed an increasing trend in the use of the Sydney protocol during the study period (3.8%-16.1% in cases, P < .0001; 1%-1.1% in control subjects, P = .005). Male and Asian American patients were more likely to undergo 2+2 or the Sydney protocol, whereas female and Hispanic endoscopists were more likely to perform sampling using these protocols., Conclusions: The application of the Sydney protocol is associated with an increased detection of precursor lesions of gastric cancer in routine clinical practice., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background/objectives: There is currently no widely accepted approach to identify patients at increased risk for sporadic pancreatic cancer (PC). We aimed to compare the performance of two machine-learning models with a regression-based model in predicting pancreatic ductal adenocarcinoma (PDAC), the most common form of PC., Methods: This retrospective cohort study consisted of patients 50-84 years of age enrolled in either Kaiser Permanente Southern California (KPSC, model training, internal validation) or the Veterans Affairs (VA, external testing) between 2008 and 2017. The performance of random survival forests (RSF) and eXtreme gradient boosting (XGB) models were compared to that of COX proportional hazards regression (COX). Heterogeneity of the three models were assessed., Results: The KPSC and the VA cohorts consisted of 1.8 and 2.7 million patients with 1792 and 4582 incident PDAC cases within 18 months, respectively. Predictors selected into all three models included age, abdominal pain, weight change, and glycated hemoglobin (A1c). Additionally, RSF selected change in alanine transaminase (ALT), whereas the XGB and COX selected the rate of change in ALT. The COX model appeared to have lower AUC (KPSC: 0.737, 95% CI 0.710-0.764; VA: 0.706, 0.699-0.714), compared to those of RSF (KPSC: 0.767, 0.744-0.791; VA: 0.731, 0.724-0.739) and XGB (KPSC: 0.779, 0.755-0.802; VA: 0.742, 0.735-0.750). Among patients with top 5% predicted risk from all three models (N = 29,663), 117 developed PDAC, of which RSF, XGB and COX captured 84 (9 unique), 87 (4 unique), 87 (19 unique) cases, respectively., Conclusions: The three models complement each other, but each has unique contributions., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest for this study., (Copyright © 2023 IAP and EPC. All rights reserved.)

Introduction: There is currently no widely accepted approach to screening for pancreatic cancer (PC). We aimed to develop and validate a risk prediction model for pancreatic ductal adenocarcinoma (PDAC), the most common form of PC, across 2 health systems using electronic health records., Methods: This retrospective cohort study consisted of patients aged 50-84 years having at least 1 clinic-based visit over a 10-year study period at Kaiser Permanente Southern California (model training, internal validation) and the Veterans Affairs (VA, external testing). Random survival forests models were built to identify the most relevant predictors from >500 variables and to predict risk of PDAC within 18 months of cohort entry., Results: The Kaiser Permanente Southern California cohort consisted of 1.8 million patients (mean age 61.6) with 1,792 PDAC cases. The 18-month incidence rate of PDAC was 0.77 (95% confidence interval 0.73-0.80)/1,000 person-years. The final main model contained age, abdominal pain, weight change, HbA1c, and alanine transaminase change (c-index: mean = 0.77, SD = 0.02; calibration test: P value 0.4, SD 0.3). The final early detection model comprised the same features as those selected by the main model except for abdominal pain (c-index: 0.77 and SD 0.4; calibration test: P value 0.3 and SD 0.3). The VA testing cohort consisted of 2.7 million patients (mean age 66.1) with an 18-month incidence rate of 1.27 (1.23-1.30)/1,000 person-years. The recalibrated main and early detection models based on VA testing data sets achieved a mean c-index of 0.71 (SD 0.002) and 0.68 (SD 0.003), respectively., Discussion: Using widely available parameters in electronic health records, we developed and externally validated parsimonious machine learning-based models for detection of PC. These models may be suitable for real-time clinical application., (Copyright © 2022 by The American College of Gastroenterology.)

Background and Aims: Identifying factors associated with increased short-term risk of pancreatic cancer in the setting of acute pancreatitis (AP) can inform clinical care decisions and expedite cancer diagnosis., Methods: A retrospective cohort study of patients hospitalized for AP between 2007 and 2017 in an integrated health-care system in Southern California. AP cases were identified by diagnosis code with laboratory confirmation. Multivariable Cox proportional hazards regression model was used to assess risk of pancreatic cancer within 3 years of AP, adjusting for patient demographics, clinical parameters (body mass index, AP etiology, chronic pancreatitis, diabetes) and radiographic imaging features., Results: Among 9,490 patients hospitalized with AP, the mean (standard deviation) age was 55.8 (17.8) years, 55% were women, and 42% were Hispanic. Majority of AP cases were biliary (64%), 12% were alcohol-related, 5% were hypertriglyceridemia-induced, and 19% were other/unknown etiology. Ninety-five (1%) patients were diagnosed with pancreatic cancer within 3 years of AP (4.2 cases/1000 person-years). Risk factors for pancreatic cancer were age ≥65 years (hazard risk [HR]: 2.5, 95% confidence interval [CI]: 1.2-5.3), male sex (HR: 1.9, 95% CI: 1.2-2.8), Asian/Pacific Islander race (HR: 2.0, 95% CI: 1.1-3.6), and underweight body mass index (HR: 2.6, 95% CI: 1.1-6.5). In addition, other/unknown AP etiology (HR: 2.0, 95% CI: 1.3-3.1) and dilatation of the main pancreatic duct (HR: 6.6, 95% CI: 4.2-10.5) were independently associated with increased risk of pancreatic cancer., Conclusion: In addition to older age, the lack of well-established etiology, underweight body habitus, and main pancreatic duct dilatation were independently associated with increased short-term risk of pancreatic cancer among patients hospitalized for AP., (© 2022 The Authors.)

Importance: COVID-19 is associated with systemic vascular damage; however, the risk posed to the retinal vasculature remains incompletely understood., Objective: To assess if there is a change in the incidence of retinal vascular occlusions after COVID-19 infection., Design, Setting, and Participants: This cohort study at an integrated health care organization (Kaiser Permanente Southern California) included patients without a history of retinal vascular occlusion who were diagnosed with COVID-19 infection between January 20, 2020, and May 31, 2021. Patients were excluded if they had a history of retinal artery occlusions (RAOs) or retinal vein occlusions (RVOs) more than 6 months before their COVID-19 diagnosis or if they were enrolled in Kaiser Permanente Southern California for less than 6 months before COVID-19 diagnosis., Exposures: COVID-19 infection., Main Outcomes and Measures: The change in the average biweekly incidence of new RAOs and RVOs after COVID-19 diagnosis. Adjusted incidence rate ratios (IRRs) were calculated to compare the incidence of retinal vascular occlusions before and after COVID-19 diagnosis after accounting for baseline demographic characteristics, medical history, and hospitalization., Results: A total of 432 515 patients diagnosed with COVID-19 infection were included in this study. The mean (SD) age was 40.9 (19.2) years, and 231 767 patients (53.6%) were women. Sixteen patients had an RAO (crude incidence rate, 3.00 per 1 000 000 patients), and 65 had an RVO (crude incidence rate, 12.20 per 1 000 000 patients) in the 6 months after COVID-19 diagnosis. The incidence of new RVOs was higher in the 6 months after COVID-19 infection compared with the 6 months before infection after adjusting for age; sex; self-reported race and ethnicity; body mass index; history of diabetes, hypertension, or hyperlipidemia; and hospitalization (adjusted IRR, 1.54; 95% CI, 1.05-2.26; P = .03). There was a smaller increase in the incidence of RAOs after COVID-19 diagnosis (IRR, 1.35; 95% CI, 0.64-2.85; P = .44). The peak incidence of RAOs and RVOs occurred 10 to 12 weeks and 6 to 8 weeks after COVID-19 diagnosis, respectively., Conclusions and Relevance: The findings of this study suggest that there was an increase in the incidence of RVOs after COVID-19 infection; however, these events remain rare, and in the absence of randomized controls, a cause-and-effect relationship cannot be established. Further large, epidemiologic studies are warranted to better define the association between retinal thromboembolic events and COVID-19 infection.

Purpose: The purpose of this study was to understand individual-, social-, and system-level factors that affect compliance with recommended diabetic retinopathy (DR)-evaluations, and how these factors vary between English and Spanish speakers., Patients and Methods: We conducted a qualitative study using semi-structured interviews. Study subjects included Kaiser Permanente Southern California members with type II diabetes mellitus at least aged 26 years who spoke English or Spanish. Patients were divided into groups based on their adherence with DR evaluations. Our main outcome measure was the major themes expressed by patients that explained their compliance with DR evaluation., Results: Fifty-one participants were enrolled: 30 English speakers (11 nonadherent, 19 adherent) and 21 Spanish speakers (8 nonadherent, 13 adherent). Adherent patients were more likely to have had experience with diabetes and identify as being responsible for their own care. Substantially more non-adherent patients suggested that beliefs and attitudes were the reasons people missed retinopathy appointments. More English-speaking participants tended to be self-directed in managing their healthcare, whereas more Spanish speakers relied on others for help. English speakers also noted better relationships with their physicians. Spanish speakers outlined problems with insurance coverage and costs as barriers., Conclusion: These data suggest two specific intervention strategies that eye care providers could implement to improve adherence with diabetic retinopathy screening and follow up: incorporating a person with DR-related visual loss into the team of staff delivering diabetes support programs and communication campaigns including specific messaging to address fears related to vision loss., Competing Interests: Dr Bobeck S Modjtahedi reports grants from Genentech and grants from VoxelCloud outside the submitted work. Ms Tiffany Q Luong reports grants from Regeneron, during the conduct of the study, and grants from Allergan plc, outside the submitted work. Dr Donald S Fong reports grants from Regeneron, Inc, during the conduct of the study. The author reports no other conflicts of interest in this work., (© 2022 Hudson et al.)

Background: High-risk medication dispenses to patients with a prior fall or hip fracture represent a potentially dangerous disease-drug interaction among older adults. The research team quantified the prevalence, identified risk factors, and generated patient and provider insights into high-risk medication dispenses in a large, community-based integrated health system using a commonly used quality measure., Methods: This was a mixed methods study with a convergent design combining a retrospective cohort study using electronic health record (EHR) data, individual interviews of primary care physicians, and a focus group of patient advisors., Results: Of 113,809 patients ≥ 65 years with a fall/fracture in 2009-2015, 35.4% had a potentially harmful medication dispensed after their fall/fracture. Most medications were prescribed by primary care providers. Older age, male gender, and race/ethnicity other than non-Hispanic White were associated with a reduced risk of high-risk medication dispenses. Patients with a pre-fall/fracture medication dispense were substantially more likely to have a post-fall/fracture medication dispense (hazard ratio [HR] = 13.26, 95% confidence interval [CI] = 12.91-13.61). Both patients and providers noted that providers may be unaware of patient falls due to inconsistent assessments and patient reluctance to disclose falls. Providers also noted the lack of a standard location to document falls and limited decision support alerts within the EHR., Conclusion: High-risk medication dispenses are common among older patients with a history of falls/fractures. Future interventions should explore improved assessment and documentation of falls, decision support, clinician training strategies, patient educational resources, building trusting patient-clinician relationships to facilitate long-term medication discontinuation among persistent medication users, and a focus on fall prevention., (Copyright © 2022 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

BACKGROUND: Therapy with angiotensinconverting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) requires laboratory monitoring to avoid hyperkalemia and acute kidney failure. OBJECTIVE: To assess the frequency of recommended annual serum potassium and creatinine monitoring and determine potential factors associated with care gaps among adults dispensed an ACEI or ARB. METHODS: This mixed-methods study integrated findings from a retrospective cohort study and individual patient interviews. Adults aged 21 years and over within Kaiser Permanente Southern California with at least 180 treatment days of an ACEI and/or ARB in 2015 were included. Patients invited for qualitative interviews included those who did and did not complete the recommended laboratory tests. We assessed the proportion of patients completing both recommended laboratory tests, factors associated with not receiving laboratory monitoring, and patients' insights into barriers and facilitators of recommended monitoring. RESULTS: Of 437,544 patients who received an ACEI or ARB, 9.0% did not receive both a serum potassium and creatinine laboratory test during treatment (defined as a care gap). Lower risk of a care gap was observed for patients with increasing age (rate ratio [RR] per 10-year increase = 0.78, 95% CI = 0.77-0.79); diabetes mellitus (RR = 0.62, 95% CI = 0.60-0.64); hypertension (RR = 0.71, 95% CI = 0.71-0.74); Charlson Comorbidity Index score of at least 2 (RR = 0.62, 95% CI = 0.60-0.64); those who changed medication classes (RR = 0.53, 95% CI = 0.51-0.56); and patients with a cardiologist (RR = 0.81, 95% CI = 0.73-0.90) or nephrologist (RR = 0.60, 95% CI = 0.52-0.69) as their prescribing provider. Twenty-five patients completed the qualitative interviews. Patients often lacked knowledge about the need for laboratory monitoring, cited logistical barriers to accessing the laboratory, and deemed the reminders they received through an outpatient safety program as a facilitator to completing tests. CONCLUSIONS: Given the large patient population on ACEI and ARB medications, monitoring and support strategies such as electronic clinical surveillance could be important in addressing care gaps and potentially reducing adverse drug effects. DISCLOSURES: This project was supported by grant number R01HS024437 from the Agency for Healthcare Research and Quality. The funder had no role in the design of the study; collection, analyses, or interpretation of the data, or decision to submit this manuscript for publication. Harrison, Reynolds, Hahn, Munoz-Plaza, Yi, Fischer, Luong, Sim, Brettler, Handler, and Mittman are employees of the Southern California Permanente Medical Group. Danworth was employed by the Southern California Permanente Medical Group at the time of this study. Singh was partially supported by the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIN13-413). Reynolds reports grants from Novartis, Amgen Inc., and Vital Strategies, Resolve to Save Lives, unrelated to this work. Yi reports grants from Novartis unrelated to this work. Kanter has nothing to disclose.

Purpose: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication., Methods: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician-adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD-9-CM code 995.1) meeting the inclusion criteria. The inter-rater reliability of physician teams, or kappa statistic, was also calculated., Results: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient-years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter-rater reliability was 0.65 (95% CI: 0.47, 0.82)., Conclusions: ICD-9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI., (© 2021 John Wiley & Sons Ltd.)

Objective: The role of uncontrolled blood pressure (BP) in COVID-19 severity among patients with hypertension is unclear. We evaluated the association between uncontrolled BP and the risk of hospitalization and/or mortality in patients with hypertension from a large US integrated healthcare system., Methods: We identified patients with hypertension and a positive RT-PCR test result or a diagnosis of COVID-19 between March 1 - September 1, 2020 from Kaiser Permanente Southern California. BP categories was defined using the most recent outpatient BP measurement during 12 months prior to COVID-19 infection. The primary outcome of interest was all-cause hospitalization or mortality within 30 days from COVID-19 infection., Results: Among 12,548 patients with hypertension and COVID-19 (mean age = 60 years, 47% male), 63% had uncontrolled BP (≥130/80 mm Hg) prior to COVID-19. Twenty-one percent were hospitalized or died within 30 days of COVID-19 infection. Uncontrolled BP was not associated with higher hospitalization or mortality (adjusted rate ratios for BP ≥ 160/100 mm Hg vs < 130/80 mm Hg = 1.00 [95% CI: 0.87, 1.14]; BP 140-159/90-99 mm Hg vs < 130/80 mm Hg = 1.02 [95% CI: 0.93, 1.11]). These findings were consistent across different age groups, treatment for antihypertensive medications, as well as atherosclerotic cardiovascular disease risk., Conclusion: Among patients with hypertension, uncontrolled BP prior to COVID-19 infection did not appear to be an important risk factor for 30-day mortality or hospitalization., (© 2021 The Authors.)

Background Direct oral anticoagulants (DOACs) are widely used in patients with nonvalvular atrial fibrillation for stroke prevention. However, long-term adherence to DOACs and clinical outcomes in real-world clinical practice is not well understood. This study evaluated long-term medication adherence patterns to DOAC therapy and clinical outcomes in a large US integrated health care system. Methods and Results We included adult patients with nonvalvular atrial fibrillation who newly initiated DOACs between 2012 and 2018 in Kaiser Permanente Southern California. Long-term (3.5 years) adherence trajectories to DOAC were investigated using monthly proportion of days covered and group-based trajectory models. Factors associated with long-term adherence trajectories were investigated. Multivariable Poisson regression analyses were used to investigate thromboembolism and major bleeding events associated with long-term adherence trajectories. Of 18 920 patients newly initiating DOACs, we identified 3 DOAC adherence trajectories: consistently adherent (85.2%), early discontinuation within 6 months (10.6%), and gradually declining adherence (4.2%). Predictors such as lower CHA 2 DS 2 -VASc (0-1 versus ≥5) and previous injurious falls were associated with both early discontinuation and gradually declining adherence trajectories. Early discontinuation of DOAC therapy was associated with a higher risk of thromboembolism (rate ratio, 1.40; 95% CI, 1.05-1.86) especially after 12 months from DOAC initiation but a lower risk of major bleed compared with consistent adherence (rate ratio, 0.48; 95% CI, 0.30-0.75), specifically during the first 12 months following DOAC initiation. A gradual decline in adherence to DOACs was not statistically significantly associated with thromboembolism outcomes compared with consistent adherence. Conclusions Although a large proportion of patients with nonvalvular atrial fibrillation were adherent to DOAC therapy over 3.5 years, early discontinuation of DOAC was associated a higher risk of thromboembolic events. Future tailored interventions for early discontinuers may improve clinical outcomes.

Background: High-risk medications pose serious safety risks to older adults, including increasing the risk of falls. Deprescribing potentially inappropriate medications (PIMs) in older adults who have experienced a fall is a key element of fall reduction strategies. However, continued use of PIMs in older adults is common, and clinicians may face substantial deprescribing barriers., Objective: Explore patient and clinician experiences with and perceptions of deprescribing PIMs in patients with a history of falls., Design: We led guided patient feedback sessions to explore deprescribing scenarios with patient stakeholders and conducted semi-structured interviews with primary care physicians (PCPs) to explore knowledge and awareness of fall risk guidelines, deprescribing experiences, and barriers and facilitators to deprescribing., Participants: PCPs from Kaiser Permanente Southern California (KPSC) and patient members of the KPSC Regional Patient Advisory Committee., Approach: We used maximum variation sampling to identify PCPs with patients who had a fall, then categorized the resulting PIM dispense distribution for those patients into high and low frequency. We analyzed the data using a hybrid deductive-inductive approach. Coders applied initial deductively derived codes to the data, simultaneously using an open-code inductive approach to capture emergent themes., Key Results: Physicians perceived deprescribing discussions as potentially contentious, even among patients with falls. Physicians reported varying comfort levels with deprescribing strategies: some felt that the conversations might be better suited to others (e.g., pharmacists), while others had well-planned negotiation strategies. Patients reported lack of clarity as to the reasons and goals of deprescribing and poor understanding of the seriousness of falls., Conclusions: Our study suggests that key barriers to deprescribing include PCP trepidation about raising a contentious topic and insufficient patient awareness of the potential seriousness of falls. Findings suggest the need for multifaceted, multilevel deprescribing approaches with clinician training strategies, patient educational resources, and a focus on building trusting patient-clinician relationships., (© 2021. Society of General Internal Medicine.)

Purpose: To determine the relationship between the severity of diabetic retinopathy and the future risk of cerebrovascular accident (CVA), myocardial infarction (MI), congestive heart failure (CHF), and all-cause mortality in patients with type 2 diabetes mellitus., Design: Retrospective cohort study., Participants: Patients with type 2 diabetes who underwent diabetic retinopathy screening via fundus photography., Methods: The relationship between retinopathy status and the 5-year risk of first-time CVA, MI, CHF, and all-cause mortality was investigated using multivariate Cox proportional hazards regressions that controlled for age, gender, race or ethnicity, hemoglobin A1c, duration of diabetes, high-density lipoprotein level, low-density lipoprotein level, history of hypertension, systolic blood pressure, diastolic blood pressure, tobacco use, statin use, body mass index, urine microalbumin-to-creatinine ratio, and estimated glomerular filtration rate., Main Outcome Measures: Five-year risk of first-time CVA, MI, CHF, and all-cause mortality., Results: Seventy-seven thousand three hundred seventy-six patients were included in this study. The average age was 59.8 years with 53.6% male, 31.2% non-Hispanic White, and 41.4% Hispanic patients. Diabetic retinopathy was significantly associated with all outcomes on multivariate analysis. Compared with patients with no retinopathy, those with minimal nonproliferative diabetic retinopathy (NPDR) had a higher risk of CVA (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.18-1.46), MI (HR, 1.30; 95% CI, 1.15-1.46), CHF (HR, 1.29; 95% CI, 1.19-1.40), and death (HR, 1.15; 95% CI, 1.05-1.25). Similarly, patients with moderate to severe NPDR had a higher risk of each outcome (CVA: HR, 1.56; 95% CI, 1.29-1.89; MI: HR, 1.92; 95% CI, 1.57-2.34; CHF: HR, 1.90; 95% CI, 1.66-2.18, and death: HR, 1.55; 95% CI, 1.32-1.82), as did patients with proliferative diabetic retinopathy (CVA: HR, 2.53; 95% CI, 1.84-3.48; MI: HR, 1.89; 95% CI, 1.26-2.83; CHF: HR, 1.96; 95% CI, 1.47-2.59; and death: HR, 1.87; 95% CI, 1.36-2.56)., Conclusions: Diabetic retinopathy is significantly associated with future risk of CVA, MI, CHF, and death, with higher degrees of retinopathy appearing to carry a heightened risk for each outcome. Retinal information may provide valuable insights into patients' risk of future vascular disease and death., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: Although recent evidence suggests no increased risk of severe COVID-19 outcomes associated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) use, the relationship is less clear among patients with hypertension and diverse racial/ethnic groups. This study evaluates the risk of hospitalization and mortality among patients with hypertension and COVID-19 in a large US integrated healthcare system., Methods: Patients with hypertension and COVID-19 (between March 1- September 1, 2020) on ACEIs or ARBs were compared with patients on other frequently used antihypertensive medications., Results: Among 14,129 patients with hypertension and COVID-19 infection (mean age 60 years, 48% men, 58% Hispanic), 21% were admitted to the hospital within 30 days of COVID-19 infection. Of the hospitalized patients, 24% were admitted to intensive care units, 17% required mechanical ventilation, and 10% died within 30 days of COVID-19 infection. Exposure to ACEIs or ARBs prior to COVID-19 infection was not associated with an increased risk of hospitalization or all-cause mortality (rate ratios for ACEIs vs other antihypertensive medications ​= ​0.98, 95% CI: 0.88, 1.08; ARBs vs others ​= ​1.00, 95% CI: 0.90, 1.11) after applying inverse probability of treatment weights. These associations were consistent across racial/ethnic groups. Use of ACEIs or ARBs during hospitalization was associated with a lower risk of all-cause mortality (odds ratios for ACEIs or ARBs vs others ​= ​0.50, 95% CI: 0.34, 0.72)., Conclusion: Our study findings support continuation of ACEI or ARB use for patients with hypertension during the COVID-19 pandemic and after COVID-19 infection., Competing Interests: An reports grants from Novartis Pharma AG, Vital Strategies/Resolve to Save Lives, Merck & Co., and AstraZeneca Pharmaceuticals LP outside the submitted work. Wei and Luong report grants from Novartis Pharma AG and Vital Strategies/Resolve to Save Lives outside the submitted work. Zhou reports grants from AstraZeneca Pharmaceuticals LP. Gould, Mefford, Harrison, Creekmur, Lee, Sim, Brettler, Martin, and Ong‐Su have no financial disclosures. Reynolds reports grants from Novartis Pharma AG, Merck & Co., Amgen, and Vital Strategies/Resolve to Save Lives outside the submitted work., (© 2021 The Authors.)

Background Previous reports suggest that the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may upregulate angiotensin-converting enzyme 2 receptors and increase severe acute respiratory syndrome coronavirus 2 infectivity. We evaluated the association between ACEI or ARB use and coronavirus disease 2019 (COVID-19) infection among patients with hypertension. Methods and Results We identified patients with hypertension as of March 1, 2020 (index date) from Kaiser Permanente Southern California. Patients who received ACEIs, ARBs, calcium channel blockers, beta blockers, thiazide diuretics (TD), or no therapy were identified using outpatient pharmacy data covering the index date. Outcome of interest was a positive reverse transcription polymerase chain reaction test for COVID-19 between March 1 and May 6, 2020. Patient sociodemographic and clinical characteristics were identified within 1 year preindex date. Among 824 650 patients with hypertension, 16 898 (2.0%) were tested for COVID-19. Of those tested, 1794 (10.6%) had a positive result. Overall, exposure to ACEIs or ARBs was not statistically significantly associated with COVID-19 infection after propensity score adjustment (odds ratio [OR], 1.06; 95% CI, 0.90-1.25) for ACEIs versus calcium channel blockers/beta blockers/TD; OR, 1.10; 95% CI, 0.91-1.31 for ARBs versus calcium channel blockers/beta blockers/TD). The associations between ACEI use and COVID-19 infection varied in different age groups ( P -interaction=0.03). ACEI use was associated with lower odds of COVID-19 among those aged ≥85 years (OR, 0.30; 95% CI, 0.12-0.77). Use of no antihypertensive medication was significantly associated with increased odds of COVID-19 infection compared with calcium channel blockers/beta blockers/TD (OR, 1.32; 95% CI, 1.11-1.56). Conclusions Neither ACEI nor ARB use was associated with increased likelihood of COVID-19 infection. Decreased odds of COVID-19 infection among adults ≥85 years using ACEIs warrants further investigation.

Purpose: The purpose of this study was to characterize the differences in myopic progression in children by race/ethnicity and age., Methods: Patients enrolled in Kaiser Permanente Southern California between 2011 and 2016 and between the ages of 4 and 11 years old with a documented refraction between -6 and -1 diopters (Ds) were included in this retrospective cohort study. Patients with a history of amblyopia, strabismus, retinopathy of prematurity, or prior ocular surgery were excluded from analyses. Patients' race/ethnicity and language information were used to create the following groups for analysis: white, Black, Hispanic, South Asian, East/Southeast Asian, Other Asian, and other/unknown. A growth curve analysis using linear mixed-effects modeling was used to trace longitudinal progression of spherical equivalents over time, modeled by race/ethnicity. Analyses adjusted for potential confounders, including body mass index (BMI), screen time, and physical activity., Results: There were 11,595 patients who met the inclusion criteria. Patients were 53% girls, 55% Latino, 15% white, 9% black, 9% East/Southeast Asian, and 2% South Asian. Mean age (standard deviation [SD]) at the time of initial refraction was 8.9 years (1.6 years). Patients had an average (SD) of 3.4 (1.5) refractions, including the baseline measurement, during the study period. A three-way interaction model that assessed the effects of age at baseline, time since baseline, and race/ethnicity found that children of East/Southeast Asian descent showed significantly faster myopia progression across time (P < 0.001). East/Southeast Asian patients who presented with myopia between 6 to < 8 years progressed similarly to white patients in the same age group and significantly faster compared with white patients in other age groups., Conclusions: Myopia progression differed significantly between East/Southeast Asian and white patients depending on the patients' age.

Background: Disparities in bladder cancer survival by race/ethnicity and gender are likely related to differences in diagnosis. We assessed disparities in stage at diagnosis and potential contributing factors within a large, integrated delivery system., Patients and Methods: We conducted a retrospective cohort study of 7244 patients with bladder cancer age ≥ 21 years diagnosed from January 2001 to June 2015 within Kaiser Permanente Southern California. Bivariate analyses compared stage at diagnosis - as well as comorbidities, health plan membership length, and health care utilization prior to diagnosis - by race/ethnicity, gender, and age. Multivariable generalized linear mixed models with urologist as a random effect were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for diagnosis of muscle-invasive bladder cancer (MIBC) versus non-muscle-invasive bladder cancer., Results: In multivariable analyses, stage at diagnosis varied significantly by race/ethnicity (P < .001). Non-Hispanic black patients had significantly higher odds of being diagnosed with MIBC than non-Hispanic white patients (OR, 1.33; 95% CI, 1.05-1.67), whereas Asian patients had significantly lower odds (OR, 0.67; 95% CI, 0.49-0.91). Women were significantly more likely to be diagnosed with MIBC than men (OR, 1.40; 95% CI, 1.22-1.61). Non-Hispanic black women had the highest proportion (39%) of MIBC diagnoses. Among Hispanic and Asian patients, a greater proportion of diagnoses occurred at younger ages., Conclusions: Health care coverage within an equal-access system did not eliminate disparities in stage at diagnosis by race/ethnicity or gender. Studies are needed to identify etiologic factors and aspects of care delivery (eg, patient-physician interactions) that may affect the diagnostic process to inform efforts to improve health equity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To characterize the visual outcomes and the treatment course of patients with exudative age-related macular degeneration (AMD) based on ocular hypotensive use., Design: A matched retrospective cohort study of patients enrolled in Kaiser Permanente Southern California health plan was conducted. Patients taking ocular hypotensives were identified using pharmacy dispensing data and were matched to controls to compare visual acuity, number of anti-VEGF injections, and conversation to secondary anti-VEGF agents in the first year of treatment. Subgroup analysis was performed based on the number of ocular hypotensive agents (0, 1, 2 or 3+ agents) and drug class (aqueous suppressants and prostaglandin analogs)., Results: A total of 234 patients patients were examined. Baseline and final visual acuity did not significantly differ between drop users and controls, including on subgroup analysis. The average number of anti-VEGF injections did not differ between drop users and controls (6.1 vs 6.2, p=0.97), nor did the percentage of patients who were switched to a second-line anti-VEGF agent (23.9% vs 17.9%, p=0.26). Subgroup analysis did not reveal significant differences in the number of anti-VEGF injections and the percentage of patients switched to secondary agents, with patients receiving 6 ±1 injections across regardless of the number or class of ocular hypotensive agents used., Conclusion: Patients with concurrent glaucoma and exudative AMD have similar visual outcomes and treatment courses compared to those not taking ocular hypotensives. Although aqueous suppressants have been suggested to prolong anti-VEGF residence time, patients using these agents did not demonstrate visual benefit or a reduced injection burden in this series., Competing Interests: Dr Fong has received grant support outside the submitted work from Allergan, Regeneron, and Santen. Ms Luong has received grant support outside the submitted work from Allergan and Santen. The authors report no other conflicts of interest in this work., (© 2020 Modjtahedi et al.)

Background: Timely follow-up of abnormal laboratory results is important for high-quality care. We sought to identify risk factors, facilitators, and barriers to timely follow-up of an abnormal estimated glomerular filtration rate (eGFR) for the diagnosis of chronic kidney disease., Study Design: Mixed-methods study: retrospective electronic health record (EHR) analyses, physician interviews., Setting & Participants: Large integrated health care delivery system. Quantitative analyses included 244,540 patients 21 years or older with incident abnormal eGFRs from January 1, 2010, to December 31, 2015, ordered by 7,164 providers. Qualitative analyses included 15 physician interviews., Exposures: Patient-, physician-, and system-level factors., Outcome: Timely follow-up of incident abnormal eGFRs, defined as repeat eGFR obtained within 60 to 150 days, follow-up testing before 60 days that indicated normal kidney function, or diagnosis before 60 days of chronic kidney disease or kidney cancer., Analytical Approach: Multivariable robust Poisson regression models accounting for clustering within provider were used to estimate risk ratios (RRs) and 95% CIs for lack of timely follow-up. Team coding was used to identify themes from physician interviews., Results: 58% of patients lacked timely follow-up of their incident abnormal eGFRs (ie, had a care gap). An abnormal creatinine result flag in the EHR was associated with better follow-up (RR for care gap, 0.65; 95% CI, 0.64-0.66). Patient online portal use and physician panel size were weakly associated with follow-up. Patients seen by providers behind on managing their EHR message box were at higher risk for care gaps. Physician interviews identified system-level (eg, panel size and assistance in managing laboratory results) and provider-level (eg, proficiency using EHR tools) factors that influence laboratory result management., Limitations: Unable to capture intentional delays in follow-up testing., Conclusions: Timely follow-up of abnormal results remains challenging in an EHR-based integrated health care delivery system. Strategies improving provider EHR message box management and leveraging health information technology (eg, flagging abnormal eGFR results), making organizational/staffing changes (eg, increasing the role of nurses in managing laboratory results), and boosting patient engagement through better patient portals may improve test follow-up., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine treatment variability, disparities, and quality among newly diagnosed nonmuscle invasive bladder cancer (NMIBC) patients, and to identify factors associated with treatment use in a large, diverse integrated delivery system., Methods: Retrospective cohort study of 5386 NMIBC patients diagnosed between January 2001 and June 2015 within Kaiser Permanente Southern California. Electronic health data were used to identify treatment outcomes and patient, provider, and tumor characteristics. Outcomes were use of (1) postoperative intravesical chemotherapy, (2) induction Bacille Calmette-Guérin (BCG) immunotherapy, and (3) any intravesical therapy. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using generalized linear mixed models with a binary outcome and urologist as a random effect., Results: From 2001 to 2015, 41% of newly diagnosed NMIBC patients were treated with intravesical therapy. Postoperative chemotherapy use increased significantly over this period (OR per-year = 1.16, 95% CI: 1.07-1.25). BCG use was strongly associated with tumor characteristics: patients with high-grade or carcinoma in situ tumors were more likely to receive BCG (OR = 10.10, 95% CI: 8.39-12.16). Few treatment differences were found by sex or race/ethnicity, but were observed by age. Wide treatment variability across urologists was observed, with some urologists never using intravesical therapy as part of initial treatment while others almost always used it. Differences across urologists accounted for more variability in postoperative chemotherapy (intraclass correlation coefficient = 0.52) than BCG immunotherapy (intraclass correlation coefficient = 0.11) use., Conclusion: Substantial variability in initial treatment of NMIBC was observed across urologists, accounting for tumor, patient, and provider characteristics. Results suggest a considerable opportunity for quality improvement programs to reduce unwanted treatment variability and improve care for patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Most patients with diabetes have little or no retinopathy on initial examination. Tracking the long-term outcomes of these patients may increase our understanding of how to best provide follow-up treatment., Objective: To assess how many patients with minimal or no retinopathy require retinal intervention within 2 years of retinal evaluation., Design, Setting, and Participants: This retrospective cohort study assessed patients who underwent screening for diabetic retinopathy within a telemedicine program at Kaiser Permanente Southern California and had minimal or no retinopathy on fundus photographs., Exposure: Retinal interventions performed within 2 years of photographs., Main Outcomes and Measures: Patients with minimal or no retinopathy on initial screening photographs taken in 2012 had their medical records searched for Current Procedural Terminology codes for intravitreal injections, retinal lasers, or pars plana vitrectomy. The medical records of patients identified as having received these interventions within 2 years of retinal evaluation were then manually reviewed for further characterization., Results: Diabetic retinopathy screening photographs were taken for 116 134 patients (mean [SD] age, 58 [12.8] years; 54 582 [47.0%] female; 46 453 [40.0%] Latino). Of these patients, 79 445, including 69 634 patients without retinopathy and 9811 patients with minimal retinopathy, had 2 years of follow-up. Eleven patients without baseline retinopathy required treatment of diabetic retinopathy in the following 2 years (1 of 12 660 or 0.000079 patients per year), and 11 patients with minimal retinopathy required intervention during the same period (1 of 1784 or 0.000561 patients per year). In addition, retinal interventions were performed for conditions not directly related to diabetic eye disease in 44 patients without baseline retinopathy (1 of 3165 or 0.000316 patients per year) and 5 patients with minimal retinopathy at baseline (1 of 3924 or 0.000255 patients per year)., Conclusions and Relevance: These findings suggest that it is rare for patients with minimal or no baseline retinopathy to require retinal interventions in the 2 years after retinal evaluation. It appears that extending the recommended follow-up interval for low-risk patients may be reasonable as long as this does not lead to worse follow-up in later years, because most are unlikely to have vision-threatening disease that necessitates treatment.

Purpose: To evaluate the relationship between preoperative vision and surgeon volume with visual outcomes after cataract surgery., Design: Retrospective cohort study., Participants: Patients aged ≥18 years old enrolled in the Kaiser Permanente Southern California Health Plan who underwent cataract surgery by nontrainee surgeons., Methods: Patients who underwent cataract surgery between January 1, 2013 and December 31, 2015, were included. A multivariate analysis using Generalized Additive Mixed Models was performed to determine the relationship between surgeon volume and postoperative visual acuity after controlling for patient age, preoperative visual acuity, history of diabetes, and history of diabetic retinopathy. Modeling was done for the relationship between preoperative vision and visual outcomes while controlling for surgeon volume, patient age, history of diabetes, and history of diabetic retinopathy., Main Outcome Measure: Absolute letter change and percentage of patients to achieve ≥5 Early Treatment Diabetic Retinopathy Study (ETDRS) letter gain postoperatively., Results: There were 103 920 cataract surgeries performed by 136 surgeons included in this analysis. Patients whose surgeons performed <91.0 surgeries/year (95% confidence interval [CI], 61.1-139; P < 0.05) gained fewer letters postoperatively than the overall average, whereas those whose surgeons performed >91 but <227 surgeries/year (95% CI, 169-∞; P < 0.05) gained more letters than average. Although statistically significant, the difference between the lowest and highest performing surgeons was approximately 1.25 letters. Surgeons who performed <110 surgeries/year (95% CI, 81.7-149; P < 0.05) had fewer patients who gained ≥5 letters. Surgeons who performed >110 but <293 surgeries/year (95% CI, 232-∞; P < 0.05) were approximately 15% more likely to have patients who gained ≥5 letters. Patients with preoperative vision <74.7 letters (95% CI, 74.7-74.8; P < 0.05) and <75.8 letters (95% CI, 75.8-75.9; P < 0.05) gained more letters and were more likely to gain ≥5 letters postoperatively, respectively., Conclusions: Patients whose vision is approximately 20/32 or worse are more likely to have significant visual gains after cataract surgery. Although statistically significant differences exist in postoperative vision based on surgeon volume, these do not appear to be clinically meaningful. Overall, visual outcomes are functionally comparable across a wide range of surgeon volumes., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to characterize International Classification of Diseases (ICD-9) coding patterns used by ophthalmologists in clinical practice for hydroxychloroquine (HCQ) retinal toxicity., Design: This is a retrospective cohort study., Subjects: Patients enrolled in the Kaiser Permanente Southern California health plan who were dispensed HCQ between 2001 and 2014 were included in this study., Methods: Patients' medical records were electronically searched for the following ICD-9 codes that can be used to characterize retinopathy or maculopathy: toxic maculopathy, non-exudative age-related macular degeneration (AMD), drusen (degenerative), and/or (other) background retinopathy. The charts of patients with these codes were then manually reviewed to determine which of these patients had been diagnosed by their ophthalmologists with HCQ retinopathy., Main Outcome Measures: ICD-9 codes used to indicate HCQ toxicity., Results: A total of 23,362 patients were dispensed HCQ between 2001 and 2014. Of whom, 678 (2.9%) patients received at least one of the aforementioned ICD-9 codes with 53 having confirmed HCQ toxicity on chart review. Forty-three patients who were taking HCQ received a diagnosis code for toxic maculopathy, and of whom, 35 (81.4%) had HCQ toxicity. Of the patients with confirmed HCQ toxicity, 32.1% received a code other than toxic maculopathy to connote the presence of disease., Conclusion: Although toxic maculopathy is the most commonly used ICD-9 code to identify patients with HCQ toxicity, a significant number of patients with toxicity received other codes in their medical records. Additionally, almost one-fifth of the patients who were coded as having toxic maculopathy were ultimately not diagnosed with HCQ toxicity. This study underscores the often imprecise nature of ICD coding, especially in conditions without a specific associated code. The limitations of using coding information should also be considered when conducting research that utilizes electronic databases. Future investigations should determine how to improve database searches and methods to create more uniform coding standards among ophthalmologists, especially for rare conditions such as HCQ toxicity., Competing Interests: Disclosure DS Fong has the following disclosure outside of the submitted manuscript: grants from Allergan, ThromboGenics, and Nightstar. The authors report no other conflicts of interest in this work.

Purpose: The purpose of this study was to characterize a pilot program using e-health to monitor glaucoma suspects in a large integrated health system., Methods: A retrospective chart review of patients enrolled in the first 2 years of a new glaucoma suspect telemedicine monitoring program was conducted. Patients were enrolled in the program after being diagnosed as glaucoma suspects in the regular clinic setting and were eligible for the program if they had better than 20/40 vision, intraocular pressure (IOP) <25 mmHg, a normal baseline visual field, and an optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) without clear evidence of glaucomatous optic nerve damage. Patients were followed annually thereafter with measurements of vision, IOP, and OCT RNFL, which were reviewed at a centralized telemedicine reading center. Patients were retained within the program unless there was evidence of disease progression, in which case they were referred to an ophthalmologist for further evaluation. The first 100 patients received a survey assessing their satisfaction with the program after their first visit. The number of patients who adhered to follow-up recommendations, who were referred to an ophthalmologist for additional evaluation, and who began on IOP-lowering medications was evaluated., Results: A total of 225 patients were enrolled in this program. Of eligible patients, 97.3% attended their 1-year follow-up visit and 92.5% attended their 2-year follow-up visit. Over the course of 2 years, five patients were referred for further clinic evaluation due to concern for progressive RNFL loss, of which two were started on IOP-lowering medications. No patients were referred to the clinic for vision loss or elevated IOP. In all, 87% of patients said that they would be extremely or quite likely to recommend the program to a friend. More than 80% of patients said that the program was extremely or very helpful, convenient, and professional., Conclusion: This novel telemedicine program for monitoring low-risk glaucoma suspects achieved high patient retention. Significant disease progression was rare with a few patients requiring referrals back to the clinic setting or initiation of IOP-lowering therapy. Telemedicine is a promising method to follow patients who are glaucoma suspects., Competing Interests: Disclosure DS Fong has the following disclosure outside of the submitted manuscript: grants from Allergan, ThromboGenics, and Nightstar. PP Lee has the following disclosures outside the submitted work: consultant for Alcon and equity owner in Pfizer, GSK, Merck, and Medco Health Solutions. C Mattox has the following disclosures outside of the submitted manuscript: grants and personal fees from Alcon and Allergan and personal fees from Aerie Pharmaceuticals, New World Medical, and Novartis. The authors report no other conflicts of interest in this work.

Purpose: To assess health care utilization and vision outcomes over 2 years in patients receiving bevacizumab treatment in clinical practice for diabetic macular edema., Methods: Patients with newly diagnosed diabetic macular edema who received an intravitreal bevacizumab injection within 12 months of initial diagnosis were identified from Kaiser Permanente's 350,000 patients with diabetes mellitus treated between 2008 and 2013. Snellen best-corrected visual acuity (BCVA), number of intravitreal injections, and patient characteristics were abstracted from the electronic record. The main outcome measure was change in BCVA., Results: Three hundred and nine patients met the inclusion criteria and had 2 years of follow-up after their first bevacizumab injection. These patients had a mean of 3.1 injections (range, 1-17) during the 2-year follow-up. Mean BCVA improvement was 5.4 letters at 12 months and 5.3 letters at 24 months. Only 29.8% of patients demonstrated ≥3 lines of vision improvement from baseline, whereas 12.3% had ≥3 lines of vision loss from baseline at 24 months., Conclusion: This is the largest U.S. clinical practice-based study of bevacizumab use in diabetic macular edema. Consistent with national studies, the frequency of injection was low. Average BCVA improvement was lower than in anti-vascular endothelial growth factor trials. Significant BCVA improvement was achieved in approximately 30% of patients with newly diagnosed diabetic macular edema.

Purpose: To evaluate the prevalence and risk factors for pediatric myopia in a contemporary American cohort., Methods: A cross-sectional study of pediatric patients enrolled in the Kaiser Permanente Southern California health plan was done. Eligible patients were 5- to 19-years old between January 1, 2008, through December 31, 2013, and received an ophthalmologic or optometric refraction. Electronic medical records were reviewed for demographic data, refraction results, and exercise data. Prevalence and relative risks of myopia (defined as ≤-1.0 diopter) were characterized. Age, sex, race/ethnicity, median neighborhood income, and minutes of exercise per day were examined as risk factors., Results: There were 60,789 patients who met the inclusion criteria, of which 41.9% had myopia. Myopia was more common in older children (14.8% in 5- to 7-year olds, 59.0% in 17- to 19-year olds). Asian/Pacific Islander patients (OR 1.64, CI 1.58-1.70) had an increased rate of myopia compared to White patients as did African Americans to a lesser extent (OR 1.08, CI 1.03-1.13). Median neighborhood household income of $25,000-40,000 was associated with lower rates of myopia (OR 0.90, CI 0.83-0.97) compared to median neighborhood household incomes less than $25,000. Having at least 60 min of daily exercise was associated with lower prevalence of myopia (OR 0.87, CI 0.85-0.89)., Discussion: Myopia was common in this large and diverse Southern Californian pediatric cohort. The prevalence of myopia increases with age. Asian children are at highest risk for myopia. Exercise is associated with a lower rate of myopia and represents an important potentially modifiable risk factor that may be a target for future public health efforts., Competing Interests: Disclosure Donald S Fong has received grants from Allergan, ThromboGenics, Regeneron, and Nightstar. The other authors report no conflicts of interest in this work.

Purpose: To describe the effect of routine use of topical nonsteroidal anti-inflammatory drugs (NSAIDs) on the incidence of postoperative macular edema (PME) after cataract surgery. The role of diabetic retinopathy on the relationship between NSAID use and PME was further analyzed., Design: Retrospective matched cohort study., Methods: Patients undergoing cataract surgery between January 2007 and June 2014 were included in this study. A total of 108 093 Kaiser Permanente Southern California patients underwent cataract surgery and 89 731 met inclusion criteria. Cataract surgery patients who had a perioperative prescription of topical NSAIDs filled in addition to topical steroids were compared to those taking topical steroids only. The main outcome measure was the diagnosis of macular edema within 90 days of cataract surgery., Results: A prescription for an NSAID was filled by 56.4% of patients. The prevalence of PME was 1.3% among those prescribed and 1.7% among those not prescribed NSAIDs. The number needed to treat was 320 patients to prevent 1 case of PME. A matched cohort analysis was performed to account for confounders. NSAID use was associated with a lower incidence of PME in patients without diabetes [relative risk (RR) 0.68, 95% confidence interval (CI) 0.58-0.72] and diabetics without retinopathy (RR 0.51, 95% CI 0.32-0.82). NSAID use was not associated with a change in the incidence of PME among patients with diabetic retinopathy (RR 1.06, 95% 0.81-1.38)., Conclusion: Topical NSAIDs were associated with a modest reduction of PME incidence in patients undergoing cataract surgery; however, this relationship was not seen among those with diabetic retinopathy. The risk for PME is low and the number of patients benefiting from treatment is small., (Copyright © 2017 Elsevier Inc. All rights reserved.)

HIV is able to outpace the innate immune response, including that mediated by interferon (IFN), to establish a productive infection. Primary macrophages, however, may be protected from HIV infection by treatment with type I IFN before virus exposure. The ability of HIV to modulate the type I IFN-mediated innate immune response when it encounters a cell that has already been exposed to IFN remains poorly defined. The optimal pretreatment time (12 h) and the most potent HIV-inhibitors (e.g., IFN-α2 and -ω) were identified to investigate the ability of HIV to modulate an established type I IFN response. Gene expression at the level of the entire transcriptome was then compared between primary macrophages treated with type I IFNs, as opposed to treated with IFNs and then infected with HIV. Although HIV was not able to establish a robust infection, the virus was able to downregulate a number of IFN-stimulated genes (ISGs) with a fold change greater than 1.5 (i.e., AXL, IFI27, IFI44, IFI44L, ISG15, OAS1, OAS3, and XAF1). The downregulation of OAS1 by the presence of HIV was confirmed by real-time quantitative polymerase chain reaction. In conclusion, even though HIV replication is significantly inhibited by IFN pretreatment, the virus is able to downregulate the transcription of known antiviral ISGs (e.g., IFI44, ISG15, and OAS1).