Stomach Cancer Prediction Model (SCoPM): An approach to risk stratification in a diverse U.S. population.

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.

Association of endoscopic biopsy sampling methods with detection of precursor lesions of gastric cancer.

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.

Machine learning versus regression for prediction of sporadic pancreatic cancer.

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.

Derivation and External Validation of Machine Learning-Based Model for Detection of Pancreatic Cancer.

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.

Factors Affecting Compliance with Diabetic Retinopathy Screening: A Qualitative Study Comparing English and Spanish Speakers.

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.

Changes in the Incidence of Retinal Vascular Occlusions After COVID-19 Diagnosis.

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.

Potentially Harmful Medication Dispenses After a Fall or Hip Fracture: A Mixed Methods Study of a Commonly Used Quality Measure.

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.

Laboratory monitoring to reduce adverse drug-related events: a mixed methods study.

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.

Risk of hospitalization and mortality associated with uncontrolled blood pressure in patients with hypertension and COVID-19.

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.

Long-Term Medication Adherence Trajectories to Direct Oral Anticoagulants and Clinical Outcomes in Patients With Atrial Fibrillation.

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 CHA2DS2-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.

Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin-converting enzyme inhibitor therapy.

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.

COVID-19 morbidity and mortality associated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers use among 14,129 patients with hypertension from a US integrated healthcare system.

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 â€‹= â€‹0.98, 95% CI: 0.88, 1.08; ARBs vs others â€‹= â€‹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 â€‹= â€‹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.

Patient and Physician Perspectives of Deprescribing Potentially Inappropriate Medications in Older Adults with a History of Falls: a Qualitative Study.

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.

Severity of Diabetic Retinopathy and the Risk of Future Cerebrovascular Disease, Cardiovascular Disease, and All-Cause Mortality.

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.

Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers Use and COVID-19 Infection Among 824 650 Patients With Hypertension From a US Integrated Healthcare System.

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.

Racial and Ethnic Differences in Myopia Progression in a Large, Diverse Cohort of Pediatric Patients.

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.

Treatment Course of Patients with Exudative Age-Related Macular Degeneration Using Ocular Hypotensives.

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.

Disparities in Stage at Diagnosis in an Equal-access Integrated Delivery System: A Retrospective Cohort Study of 7244 Patients With Bladder Cancer.

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.

Follow-up of Abnormal Estimated GFR Results Within a Large Integrated Health Care Delivery System: A Mixed-Methods Study.

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.

Care Quality and Variability in the Use of Intravesical Therapy for Initial Treatment of Nonmuscle Invasive Bladder Cancer Within a Large, Diverse Integrated Delivery System.

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.