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.

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.

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.

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.

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.

Two-year outcomes of a pilot glaucoma suspect telemedicine monitoring program.

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.

TREATMENT PATTERNS AND 2-YEAR VISION OUTCOMES WITH BEVACIZUMAB IN DIABETIC MACULAR EDEMA: An Analysis From a Large U.S. Integrated Health Care System.

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.