Hyperaldosteronism Screening and Findings From a Large Diverse Population With Resistant Hypertension Within an Integrated Health System.

INTRODUCTION: Hyperaldosteronism (HA) is a common cause of secondary hypertension and may contribute to resistant hypertension (RH). The authors sought to determine and characterize HA screening, positivity rates, and mineralocorticoid receptor antagonist (MRA) use among patients with RH. METHODS: A cross-sectional study was performed within Kaiser Permanente Southern California (7/1/2012-6/30/2017). Using contemporary criteria, RH was defined as blood pressure uncontrolled (≥ 130/80) on ≥ 3 medications or requiring ≥ 4 antihypertensive medications. The primary outcome was screening rate for HA defined as any aldosterone and plasma renin activity measurement. Secondary outcomes were HA screen positive rates and MRA use among all patients with RH. Multivariable logistic regression analysis was used to estimate odds ratio (with 95% confidence intervals) for factors associated with HA screening and for patients that screened positive. RESULTS: Among 102,480 patients identified as RH, 1977 (1.9%) were screened for HA and 727 (36.8%) screened positive for HA. MRA use was 6.5% among all patients with RH (22.5% among screened, 31.2% among screened positive). Black race, potassium < 4, bicarbonate > 29, chronic kidney disease, obstructive sleep apnea, and systolic blood pressure were associated with HA screening, but only Black race (1.55 [1.20-2.01]), potassium (1.82 [1.48-2.24]), bicarbonate levels (1.39 [1.10-1.75]), and diastolic blood pressure (1.15 [1.03-1.29]) were associated with positive screenings. CONCLUSION: The authors' findings demonstrate low screening rates for HA among patients with difficult-to-control hypertension yet a high positivity rate among those screened. Factors associated with screening did not always correlate with screening positive. Screening and targeted use of MRA may lead to improved blood pressure control and outcomes among patients with RH.

Identification of recurrent atrial fibrillation using natural language processing applied to electronic health records.

AIMS: This study aimed to develop and apply natural language processing (NLP) algorithms to identify recurrent atrial fibrillation (AF) episodes following rhythm control therapy initiation using electronic health records (EHRs). METHODS AND RESULTS: We included adults with new-onset AF who initiated rhythm control therapies (ablation, cardioversion, or antiarrhythmic medication) within two US integrated healthcare delivery systems. A code-based algorithm identified potential AF recurrence using diagnosis and procedure codes. An automated NLP algorithm was developed and validated to capture AF recurrence from electrocardiograms, cardiac monitor reports, and clinical notes. Compared with the reference standard cases confirmed by physicians' adjudication, the F-scores, sensitivity, and specificity were all above 0.90 for the NLP algorithms at both sites. We applied the NLP and code-based algorithms to patients with incident AF (n = 22 970) during the 12 months after initiating rhythm control therapy. Applying the NLP algorithms, the percentages of patients with AF recurrence for sites 1 and 2 were 60.7% and 69.9% (ablation), 64.5% and 73.7% (cardioversion), and 49.6% and 55.5% (antiarrhythmic medication), respectively. In comparison, the percentages of patients with code-identified AF recurrence for sites 1 and 2 were 20.2% and 23.7% for ablation, 25.6% and 28.4% for cardioversion, and 20.0% and 27.5% for antiarrhythmic medication, respectively. CONCLUSION: When compared with a code-based approach alone, this study's high-performing automated NLP method identified significantly more patients with recurrent AF. The NLP algorithms could enable efficient evaluation of treatment effectiveness of AF therapies in large populations and help develop tailored interventions.

Validation of ICD-10 hospital discharge diagnosis codes to identify incident and recurrent ischemic stroke from a US integrated healthcare system.

PURPOSE: This study validated incident and recurrent ischemic stroke identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) hospital discharge diagnosis codes. METHODS: Using electronic health records (EHR) of adults (≥18 years) receiving care from Kaiser Permanente Southern California with ICD-10 hospital discharge diagnosis codes of ischemic stroke (I63.x, G46.3, and G46.4) between October 2015 and September 2020, we identified 75 patients with both incident and recurrent stroke events (total 150 cases). Two neurologists independently evaluated validity of ICD-10 codes through chart reviews. RESULTS: The positive predictive value (PPV, 95% CI) for incident stroke was 93% (95% CI: 88%, 99%) and the PPV for recurrent stroke was 72% (95% CI: 62%, 82%). The PPV for recurrent stroke improved after applying a gap of 20 days (PPV of 75%; 95% CI: 63%, 87%) or removing hospital admissions related to stroke-related procedures (PPV of 78%; 95% CI: 68%, 88%). CONCLUSION: The ICD-10 hospital discharge diagnosis codes for ischemic stroke showed a high PPV for incident cases, while the PPV for recurrent cases were less optimal. Algorithms to improve the accuracy of ICD-10 codes for recurrent ischemic stroke may be necessary.

Incident Atrial Fibrillation and Risk of Dementia in a Diverse, Community-Based Population.

Background Atrial fibrillation (AF) is the most common, clinically relevant arrhythmia in adults and associated with ischemic stroke and premature death. However, data are conflicting on whether AF is independently associated with risk of dementia, particularly in diverse populations. Methods and Results We identified all adults from 2 large integrated health care delivery systems between 2010 and 2017 and performed a 1:1 match of incident AF: no AF by age at index date, sex, estimated glomerular filtration rate category, and study site. Subsequent dementia was identified through previously validated diagnosis codes. Fine-Gray subdistribution hazard models were used to examine the association of incident AF (versus no AF) with risk of incident dementia, adjusting for sociodemographics and comorbidity and accounting for competing risk of death. Subgroup analyses by age, sex, race, ethnicity, and chronic kidney disease status were also performed. Among 196 968 matched adults, mean (SD) age was 73.6 (11.3) years, with 44.8% women, and 72.3% White. Incidence rates (per 100 person-years) for dementia over a median follow-up of 3.3 (interquartile range, 1.7-5.4) years were 2.79 (95% CI, 2.72-2.85) and 2.04 (95% CI, 1.99-2.08) per 100 person-years in persons with versus without incident AF, respectively. In adjusted models, incident AF was associated with a significantly greater risk of diagnosed dementia (subdistribution hazard ratio [sHR], 1.13 [95% CI, 1.09-1.16]). With additional adjustment for interim stroke events, the association of incident AF with dementia remained statistically significant (sHR, 1.10 [95% CI, 1.07-1.15]). Associations were stronger for age <65 (sHR, 1.65 [95% CI, 1.29-2.12]) versus ≥65 (sHR, 1.07 [95% CI, 1.03-1.10]) years (interaction P<0.001); and those without (sHR, 1.20 [95% CI, 1.14-1.26]) versus with chronic kidney disease (sHR, 1.06 [95% CI, 1.01-1.11]; interaction P<0.001). No meaningful differences were seen by sex, race, or ethnicity. Conclusions In a large, diverse community-based cohort, incident AF was associated with a modestly increased risk of dementia that was more prominent in younger patients and those without chronic kidney disease but did not substantially vary across sex, race, or ethnicity. Further studies should delineate mechanisms underpinning these findings, which may inform use of AF therapies.

Incidence of Atherosclerotic Cardiovascular Disease in Young Adults at Low Short-Term But High Long-Term Risk.

BACKGROUND: Young adults may have high long-term atherosclerotic cardiovascular disease (ASCVD) risk despite low short-term risk. OBJECTIVES: In this study, we sought to compare the performance of short-term and long-term ASCVD risk prediction tools in young adults and evaluate ASCVD incidence associated with predicted short-term and long-term risk. METHODS: We included adults aged 18 to 39 years, from 2008 to 2009 in a U.S. integrated health care system, and followed them through 2019. We calculated 10-year and 30-year ASCVD predicted risk and assessed ASCVD incidence. RESULTS: Among 414,260 young adults, 813 had an incident ASCVD event during a median of 4 years (maximum 11 years). Compared with 10-year predicted risk, 30-year predicted risk improved reclassification (net reclassification index: 16%) despite having similar discrimination (Harrell's C: 0.749 vs 0.726). Overall, 1.0% and 2.2% of young adults were categorized as having elevated 10-year (≥7.5%) and elevated 30-year (≥20%) predicted risk, respectively, and 1.6% as having low 10-year (<7.5%) but elevated 30-year predicted risk. The ASCVD incidence rate per 1,000 person-years was 2.60 (95% CI: 1.92-3.52) for those with elevated 10-year predicted risk, 1.87 (95% CI: 1.42-2.46) for those with low 10-year but elevated 30-year predicted risk, and 0.32 (95% CI: 0.30-0.35) for those with low 10-year and 30-year predicted risk. The age- and sex-adjusted incidence rate ratio was 3.04 (95% CI: 2.25-4.10) comparing those with low 10-year but elevated 30-year predicted risk and those with low 10-year and 30-year predicted risk. CONCLUSIONS: Long-term ASCVD risk prediction tools further discriminate a subgroup of young adults with elevated observed risk despite low estimated short-term risk.

Blood Pressure Control Among Black and White Adults Following a Quality Improvement Program in a Large Integrated Health System.

Importance: A higher percentage of non-Hispanic Black (hereinafter, Black) adults vs non-Hispanic White (hereinafter, White) adults with hypertension have uncontrolled blood pressure (BP) contributing to racial and ethnic disparities in cardiovascular disease. In 2010, Kaiser Permanente Southern California began implementing quality improvement (QI) strategies aimed at reducing this disparity. Objective: To examine the change in BP control between Black and White patients before and after the implementation of a QI program. Design, Setting, and Participants: A QI quasi-experimental, difference-in-difference analysis was conducted of Kaiser Permanente Southern California patients 18 years or older included in the population care management hypertension registry. The study was conducted from December 31, 2008, to December 31, 2019. Data analysis was performed from November 20, 2020, to November 7, 2022. Interventions: Quality improvement program implementation began in 2010. Main Outcomes and Measures: Blood pressure control (systolic BP <140 mm Hg and diastolic BP <90 mm Hg) was assessed using the last outpatient BP measurement in each calendar year. Changes in BP control between Black and White patients from before (2008-2009) to after (2016-2019) implementation of the QI program were examined using a difference-in-difference analysis. Blood pressure control disparities from 2008 through 2019 by age, sex, race and ethnicity, and factors associated with BP control were examined. Results: The number of patients with hypertension increased from 624 094 in 2008 (mean [SD] age, 61.8 [13.5] years; 330 551 [53.0%] female patients; 89 407 [14.3%] Black and 284 116 [45.5%] White patients) to 855 257 in 2019 (mean [SD] age, 64.5 [13.6] years; 444 422 [52.0%] female patients; 107 054 [12.5%] Black and 331 932 [38.8%] White patients). Blood pressure control increased an absolute 4.6% (95% CI, 4.3%-4.8%) among Black patients and 2.1% (95% CI, 2.0%-2.2%) among White patients from before to after the QI program implementation (difference-in-difference: 2.5%; 95% CI, 2.2%-2.8%). The largest reduction in BP control disparity between Black and White female patients was for those aged 50 to 64 years (difference-in-difference: 3.8%; 95% CI, 3.2%-4.4%) and for those aged 18 to 49 years between Black and White male patients (difference-in-difference: 4.2%; 95% CI, 3.0%-5.5%). The proportion of BP control among Black male patients aged 18 to 49 years was the lowest throughout 2008-2019 compared with male and female patients in other age and racial and ethnic groups. In 2019, uncontrolled BP was more common among Black vs White patients (prevalence ratio: 1.13; 95% CI, 1.12-1.14). Conclusions and Relevance: This QI program noted that disparities in BP control between Black and White patients were decreased but not eliminated following implementation of QI strategies aimed at reducing disparities in BP control. These findings suggest that more focused interventions may be needed to increase BP control among Black individuals.

Effectiveness and Safety of Dabigatran in Atrial Fibrillation Patients with Severe Obesity: a Real-World Retrospective Cohort Study.

BACKGROUND: Direct oral anticoagulants such as dabigatran are the preferred anticoagulant in treating atrial fibrillation (AF) patients due to their effectiveness and safety. Whether this applies to severely obese patients needs to be determined. OBJECTIVE: To compare the effectiveness and safety of dabigatran with warfarin among AF patients with severe obesity. DESIGN: Retrospective cohort study. PARTICIPANTS: AF patients with a BMI >40kg/m2 or a weight >120kg receiving dabigatran or warfarin between 10/01/2010 and 12/31/2019 in a large integrated health system and followed through 08/01/2020. INTERVENTIONS: Not applicable. MAIN MEASURES: Primary effectiveness outcome was composite thromboembolism including transient ischemic attack, ischemic stroke, or systemic embolism. Primary safety outcome was composite bleeding including gastrointestinal bleeding, intracranial bleeding, or other bleeding. Secondary outcomes included the individual outcomes and all-cause mortality. Propensity score matching (PSM) was performed to create a 1:1 matched cohort and Cox proportional hazards model was used to estimate the hazard ratio (HR) of each outcome for dabigatran users compared to warfarin users. KEY RESULTS: A total of 6848 patients receiving either dabigatran or warfarin were identified. In a 1:1 matched cohort, dabigatran users had a HR of 0.71 (95% confidence interval (CI): 0.56-0.91) for composite thromboembolism, a HR of 1.24 (95%CI: 1.07-1.42) for composite bleeding, and a HR of 0.57 (95% CI: 0.45-0.71) for all-cause mortality when compared to warfarin users. CONCLUSIONS: Among AF patients with a BMI >40kg/m2 or a weight >120kg in a real-world clinical setting, dabigatran was effective in reducing the risk of thromboembolism and mortality but was associated with an increased risk of bleeding when compared to warfarin. Dabigatran may be a reasonable option for AF patients with severe obesity.

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.

Cardiovascular and kidney outcomes of spironolactone or eplerenone in combination with ACEI/ARBs in patients with diabetic kidney disease.

BACKGROUND: Mineralocorticoid receptor antagonist (MRA) when combined with either angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may provide additional benefits of cardiovascular and kidney disease risk reduction in patients with diabetic kidney disease (DKD) and hypertension. We evaluated the effectiveness of combination therapy (MRAs, either spironolactone or eplerenone, plus ACEI/ARB) compared with monotherapy (ACEI/ARB only) in patients with DKD and hypertension. METHODS: Retrospective cohort study was performed in patients (age ≥ 18 years) with hypertension, diabetes, and albuminuria between 2008 and 2018 within an integrated health system. MRA with ACEI/ARB compared to ACEI/ARB alone was evaluated on composite of cardiovascular events, progression to end-stage kidney disease, or all-cause mortality. Hyperkalemia was compared as a safety outcome. RESULTS: We identified 1282 patients who received MRAs with ACEI/ARBs and 5484 patients who received ACEI/ARBs alone. Median exposure time for combination therapy was 126 days. The rates per 100 person-years of cardiovascular, kidney, or all-cause mortality outcomes were 12.2 and 9.2 for combination therapy and monotherapy, respectively (hazard ratios = 1.24, 95% Confidence Interval (CI):0.94, 1.63). Patients receiving combination therapy had greater reduction in urine albumin-to-creatinine ratio compared with monotherapy (Mean reduction: 823 and 585 mg/g; p < 0.001, respectively). Hyperkalemia was more frequent in combination therapy versus monotherapy (22.3 vs. 10.9 per 100 person-years for combination and monotherapy, respectively; hazard ratios = 1.78, 95%CI: 1.42, 2.24). CONCLUSIONS: Among patients with DKD and hypertension, the short-term use of MRAs, either spironolactone or eplerenone, in combination with ACEI/ARBs, was not associated with lower risk of cardiovascular or kidney outcomes compared with ACEI/ARB monotherapy. The risk of hyperkalemia and the short duration of combination therapy may suggest a real-world clinical challenge for MRA with ACEI/ARB combination therapy.

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.

Comparison of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Bioprosthetic Heart Valves.

There are limited data regarding direct oral anticoagulants (DOACs) for stroke prevention in patients with bioprosthetic heart valves (BHVs) and atrial fibrillation (AF). The objectives of this study were to evaluate the ambulatory utilization of DOACs and to compare the effectiveness and safety of DOACs versus warfarin in patients with AF and BHVs. We conducted a retrospective cohort study at a large integrated health care delivery system in California. Patients with BHVs and AF treated with warfarin, dabigatran, rivaroxaban, or apixaban between September 12, 2011 and June 18, 2020 were identified. Inverse probability of treatment-weighted comparative effectiveness and safety of DOACs compared with warfarin were determined. Use of DOACs gradually increased since 2011, with a significant upward in trend after a stay-at-home order related to COVID-19. Among 2,672 adults with BHVs and AF who met the inclusion criteria, 439 were exposed to a DOAC and 2233 were exposed to warfarin. For the primary effectiveness outcome of ischemic stroke, systemic embolism and transient ischemic attack, no significant association was observed between use of DOACs compared with warfarin (HR 1.19, 95% CI 0.96 to 1.48, p = 0.11). Use of DOACs was associated with lower risk of the primary safety outcome of intracranial hemorrhage, gastrointestinal bleeding, and other bleed (HR 0.69, 95% CI 0.56 to 0.85, p < 0.001). Results were consistent across multiple subgroups in the sensitivity analyses. These findings support the use of DOACs for AF in patients with BHVs.

GABA-producing Lactobacillus plantarum inhibits metastatic properties and induces apoptosis of 5-FU-resistant colorectal cancer cells via GABAB receptor signaling.

5-Fluorouracil (5-FU) is an essential drug in systemic chemotherapy treatments for colorectal cancer (CRC). Despite the development of several treatment strategies over the past decades, the patient benefits of 5-FU-based therapies have been compromised by the development of chemoresistance. Differences in treatment responses among CRC patients may be due to genetic and epigenetic factors unique to individuals. Therefore, important factors for realizing personalized medicine are to accurately understand the causes and mechanisms of drug resistance to 5-FU-based therapies and to identify and validate prognostic biomarkers. Gut microbes that interact directly with the host contribute to human health and cancer control. Lactobacillus plantarum, in particular, has the potential to be a therapeutic agent by producing bioactive compounds that may benefit the host. Here, we investigated the gamma-aminobutyric acid (GABA) and GABAB receptor (GABABR)-dependent signaling pathway as a treatment option for 5-FU-resistant HT-29 cells. GABA-producing L. plantarum activates anti-proliferative, anti-migration, and anti-invasion effects against 5-FU-resistant HT-29 cells. The inhibitory effects of GABA-producing L. plantarum are mediated via GABABR. Activated GABABR induces apoptosis through the inhibition of cAMP-dependent signaling pathways and cellular inhibitor of apoptosis protein 2 (cIAP2) expression. Thus, the GABAergic system has potential in 5-FU-resistant HT-29 cells as a predictive biomarker. In addition, GABA-producing L. plantarum is promising as an adjuvant treatment for 5-FU-resistant CRC, and its intervention in neurobiological signaling imply new possibilities for chemoprevention and the treatment of colon cancer-related diseases.

Prevalence and incidence of microvascular and macrovascular complications over 15 years among patients with incident type 2 diabetes.

INTRODUCTION: Type 2 diabetes (T2D) is a common condition that, if left untreated or poorly managed, can lead to adverse microvascular and macrovascular complications. We estimated the prevalence and incidence of microvascular and macrovascular complications among patients newly diagnosed with T2D within a US integrated healthcare system. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study among patients newly diagnosed with T2D between 2003 and 2014. We evaluated 13 complications, including chronic kidney disease (CKD), cardiovascular disease (CVD), and all-cause mortality through 2018. Multivariable Cox proportional hazards models were used to study factors associated with complications. RESULTS: We identified 135 199 patients with incident T2D. The mean age was 58 years, and 48% were women. The prevalence of CKD was the highest of the complications at the time of T2D diagnosis (prevalence=12.3%, 95% CI 12.2% to 12.5%), while the prevalence of CVD was among the lowest at 3.3% (95% CI 3.2% to 3.3%). The median time to incidence of a T2D complication ranged from 3.0 to 5.2 years. High incidence rates (95% CI) of T2D complications included peripheral neuropathy (26.9, 95% CI 26.5 to 27.3 per 1000 person-years (PY)), CKD (21.2, 95% CI 20.9 to 21.6 per 1000 PY), and CVD (11.9, 95% CI 11.7 to 12.2 per 1000 PY). The trend of 5-year incidence rates of T2D complications by diagnosis year decreased over time (p value<0.001). Older age, non-Hispanic white race/ethnicity, sex, higher A1C, smoking, and hypertension were associated with increased CKD and CVD incidence. CONCLUSION: Though incidence rates of T2D complications were lower in more recent years (2010-2014), a significant proportion of patients had complications at T2D diagnosis. Earlier preventive therapies as well as managing modifiable factors may help delay the development and progression of T2D complications.

Treatment Patterns and Blood Pressure Control With Initiation of Combination Versus Monotherapy Antihypertensive Regimens.

Many patients with hypertension require 2 or more drug classes to achieve their blood pressure (BP) goal. We compared antihypertensive medication treatment patterns and BP control between patients who initiated combination therapy versus monotherapy. We identified adults with hypertension enrolled in a US integrated healthcare system who initiated antihypertensive medication between 2008 and 2014. Patient demographics, clinical characteristics, antihypertensive medication, and BP were extracted from electronic health records. Antihypertensive medication patterns and multivariable adjusted prevalence ratios (PRs) of achieving the 2017 American College of Cardiology/American Heart Association guideline-recommended BP <130/80 mm Hg were evaluated for 2 years following treatment initiation. Of 135 971 patients, 43% initiated antihypertensive combination therapy (35% ACE [angiotensin converting enzyme] inhibitor (ACEI)-thiazide diuretics; 8% with other combinations) and 57% initiated monotherapy (22% ACEIs; 16% thiazide diuretics; 11% ß blockers; 8% calcium channel blockers). After multivariable adjustment including premedication BP levels, patients who initiated ACEI-thiazide diuretic combination therapy were more likely to achieve BP <130/80 mm Hg compared with their counterparts who initiated monotherapy with ACEI (PR, 1.10 [95% CI, 1.08-1.12]), thiazide diuretic (PR, 1.21 [95% CI, 1.18-1.24]), ß blocker (PR, 1.17 [95% CI, 1.14-1.20]), or calcium channel blocker (PR, 1.25 [95% CI, 1.22-1.29]). Compared with initiating monotherapy, patients initiating ACEI-thiazide diuretic combination therapy were more likely to achieve BP goals.

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.

Recurrent Atherosclerotic Cardiovascular Event Rates Differ Among Patients Meeting the Very High Risk Definition According to Age, Sex, Race/Ethnicity, and Socioeconomic Status.

Background The risk for atherosclerotic cardiovascular disease (ASCVD) events may differ by sociodemographic factors among patients meeting the definition of very high risk according to the 2018 American Heart Association/American College of Cardiology cholesterol guideline, leading to treatment disparities. We estimated the risk for recurrent ASCVD events among adults meeting the definition of very high risk by age, sex, race/ethnicity, and socioeconomic status in a US integrated healthcare system. Methods and Results The study cohort included Kaiser Permanente Southern California members aged ≥21 years with a history of clinical ASCVD on September 30, 2009. Very high risk for recurrent ASCVD was defined by a history of ≥2 major ASCVD events or a history of 1 major event along with ≥2 high-risk conditions. Patients were followed through 2015 for a first recurrent ASCVD event. Of 77 101 patients with ASCVD, 50.8% met the definition for very high risk. Among patients meeting the definition of very high risk, recurrent ASCVD rates were higher in older (>75 years) versus younger patients (21-40 years) (sex-adjusted hazard ratio [HR] [95% CI] 1.85; 1.23-2.79), non-Hispanic Black patients versus non-Hispanic White patients (age-, sex-adjusted HR, 1.32; 1.23-1.41), those who lived in neighborhoods with lower (<$35k) versus higher annual household income (≥$80k) (HR, 1.20; 1.11-1.30), or with lower (≥31.2%) versus higher education levels (<8.8% high school or lower) (HR, 1.26; 1.19-1.34). Conclusions Disparities in the risk for recurrent ASCVD events were present across sociodemographic factors among very high risk patients. The addition of sociodemographic factors to current definitions of very high risk could reduce health disparities.

Apparent treatment-resistant hypertension: characteristics and prevalence in a real-world environment of an integrated health system.

OBJECTIVES: We compared the prevalence of apparent treatment-resistant hypertension (aTRH) according to the seventh report of the Joint National Committee (JNC 7) and the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline in an integrated healthcare delivery system. METHODS: We identified individuals aged at least 18 years with hypertension from Kaiser Permanente Southern California between 1 July 2014 and 30 June 2015. aTRH was defined as either blood pressure (BP) above goal (≥140/90 mmHg per JNC7, and ≥130/80 mmHg per 2017 ACC/AHA for most adults with hypertension) while taking at least 3 classes of antihypertensive medication or taking at least four classes regardless of BP level. A secondary analysis was conducted requiring use of a diuretic for the definition of aTRH. Patient clinical characteristics and antihypertensive medication use were described using electronic health records. RESULTS: We included 469 509 patients with treated hypertension [mean (SD) age 65 years (12), 46% white, 26% Hispanic, 13% black, and 12% Asian]. The prevalence of aTRH was 16.9 and 21.8% according to the JNC 7 and the 2017 ACC/AHA guidelines, respectively [Δ = 4.9% (95% CI: 4.7--5.1%)]. By requiring a diuretic to be considered as aTRH, the prevalence of aTRH decreased to 13.4 and 17.2% according to the JNC 7 and the 2017 ACC/AHA guidelines, respectively. Among patients with aTRH, 1.9% received a long-acting thiazide-like diuretic, and 5.6% received a mineralocorticoid receptor blocker. CONCLUSION: The prevalence of aTRH increased using the more stringent BP goals of the 2017 ACC/AHA guideline. The use of recommended therapy for aTRH was suboptimal suggesting a potential area for improvement.

Economic Evaluation of Anticyclic Citrullinated Peptide Positivity in Rheumatoid Arthritis.

BACKGROUND: Anticyclic citrullinated peptide (anti-CCP) positivity may be a strong predictor of joint erosion and a potential biomarker for guiding treatment decisions for rheumatoid arthritis (RA). However, limited studies are currently available on the effect of anti-CCP positivity on health care utilization and/or medical costs of RA patients. OBJECTIVE: To investigate short-term and long-term direct health care expenditures associated with anti-CCP positivity in newly diagnosed RA patients. METHODS: A retrospective cohort study was conducted in adult RA patients within a U.S. integrated health care delivery system (January 1, 2007-June 30, 2015). Patients were required to have 2 RA diagnoses and treatment with a conventional or biologic disease-modifying antirheumatic drug (DMARD) within 12 months. The first RA diagnosis date was labeled as the index date, and patients were followed until they left the health plan, died, or reached the end of the study period. Patient demographics, anti-CCP results, comorbid conditions, and health care resource utilization during baseline (12 months before the index date) and follow-up periods were collected. Nationally recognized direct medical costs were assigned to health care utilization to calculate health care costs in 2015 U.S. dollars. The baseline differences between anti-CCP positivity and negativity and differences in censoring during follow-up were addressed using propensity scores. The mean differences in costs were estimated using recycled prediction methods. RESULTS: 2,448 newly diagnosed RA patients were identified and followed for a median of 3.7 years (range = 1-8 years). At baseline, 65.8% of patients were anti-CCP positive. Anti-CCP-positive patients had fewer comorbid conditions at baseline. During the first 12 months of follow-up, median (interquartile range) total health care expenditures for anti-CCP-positive and anti-CCP-negative patients were $6,200 ($3,563-$13,260) and $7,022 ($3,885-$12,995), respectively. After adjusting for baseline differences, total incremental mean cost associated with anti-CCP positivity during the first 12 months was estimated to be $2,163 per patient (P = 0.001). The annual incremental costs in anti-CCP-positive patients became progressively larger over time, from $2,163 during the first year to $5,062 during the fourth year. Anti-CCP positivity was associated with higher prescription, laboratory testing, and rheumatologist utilization. A higher percentage of anti-CCP-positive patients received 1 or more biologic DMARDs (11.6% for anti-CCP-positive vs. 5.7% for anti-CCP negative; P < 0.001) compared with anti-CCP-negative patients during the 12-month follow-up, which resulted in $2,499 in incremental prescription costs (P < 0.001). Total additional burden associated with anti-CCP positivity during the first 4 years was estimated to be $14,089 per patient. CONCLUSIONS: In newly diagnosed RA patients, higher economic burden associated with anti-CCP positivity was mainly driven by prescription costs. DISCLOSURES: This research and manuscript were funded by Bristol-Myers Squibb (BMS). Alemao and Connolly are employees and shareholders of BMS and participated in the design of the study, interpretation of the data, review/revision of the manuscript, and approval of the final version of the manuscript. An and Cheetham received a grant from BMS for this research. At the time of this study, An was employed by Western University of Health Sciences, and Cheetham was employed by Kaiser Permanente Southern California. Bider-Canfield, Kang, and Lin have nothing to disclose. Some study results were presented as a poster at the American College of Rheumatology Annual Meeting; November 5, 2017; San Diego, CA, and at the International Society for Pharmacoeconomics and Outcomes Research Meeting; May 19, 2018; Baltimore, MD.

Economic evaluation of patient-centered care among long-term cancer survivors.

OBJECTIVES: To evaluate the economic outcomes associated with patient perceptions of patient-centered medical home (PCMH) characteristics among long-term cancer survivors in the United States. STUDY DESIGN: A retrospective analysis of the 2008 to 2012 Medical Expenditure Panel Survey. METHODS: A nationally representative sample of adult long-term cancer survivors (≥3 years since diagnosis) was categorized into either patient-centered care (PCC) or non-PCC groups based on responses to PCMH model hallmark attributes of "comprehensive care," "whole-person orientation," and "accessible care." The positive perception of all 3 attributes was defined as PCC. The patient perceptions, as well as patient characteristics, were measured at year 1 (baseline), with a propensity score model to balance baseline characteristics. Adjusted total healthcare utilization and healthcare expenditures in 2014 US$ at year 2 (follow-up) were compared between the PCC and non-PCC groups. RESULTS: A total of 4288 long-term cancer survivors were identified, with a mean (SD) age of 65.2 (13.8) years. The PCC group was associated with a reduction in mean adjusted healthcare expenditures at follow-up (savings of $1596 per cancer survivor; P = .020). These findings are driven by lower odds of hospitalization (odds ratio, 0.81; 95% CI, 0.66-0.99; P = .035) and lower hospitalization-related healthcare expenditures (PCC: $3323; 95% CI, $2727-$3918; non-PCC: $4912; 95% CI, $4039-$5785; P = .002) associated with PCC among the population who were 65 years and older. The whole-person orientation attribute had a major impact on reduced healthcare expenditures. CONCLUSIONS: The positive patient perception of PCMH characteristics was associated with reduced healthcare expenditures in adult long-term cancer survivors.