Development of Predictive Models to Inform a Novel Risk Categorization Framework for Antibiotic Resistance in Escherichia coli-Caused Uncomplicated Urinary Tract Infection.

BACKGROUND: In clinical practice, challenges in identifying patients with uncomplicated urinary tract infections (uUTIs) at risk of antibiotic nonsusceptibility may lead to inappropriate prescribing and contribute to antibiotic resistance. We developed predictive models to quantify risk of nonsusceptibility to 4 commonly prescribed antibiotic classes for uUTI, identify predictors of nonsusceptibility to each class, and construct a corresponding risk categorization framework for nonsusceptibility. METHODS: Eligible females aged ≥12 years with Escherichia coli-caused uUTI were identified from Optum's de-identified Electronic Health Record dataset (1 October 2015-29 February 2020). Four predictive models were developed to predict nonsusceptibility to each antibiotic class and a risk categorization framework was developed to classify patients' isolates as low, moderate, and high risk of nonsusceptibility to each antibiotic class. RESULTS: Predictive models were developed among 87 487 patients. Key predictors of having a nonsusceptible isolate to ≥3 antibiotic classes included number of previous UTI episodes, prior ß-lactam nonsusceptibility, prior fluoroquinolone treatment, Census Bureau region, and race. The risk categorization framework classified 8.1%, 14.4%, 17.4%, and 6.3% of patients as having isolates at high risk of nonsusceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, ß-lactams, and fluoroquinolones, respectively. Across classes, the proportion of patients categorized as having high-risk isolates was 3- to 12-fold higher among patients with nonsusceptible isolates versus susceptible isolates. CONCLUSIONS: Our predictive models highlight factors that increase risk of nonsusceptibility to antibiotics for uUTIs, while the risk categorization framework contextualizes risk of nonsusceptibility to these treatments. Our findings provide valuable insight to clinicians treating uUTIs and may help inform empiric prescribing in this population.

Risk Levels and Adverse Clinical Outcomes Among Patients With Nonvalvular Atrial Fibrillation Receiving Oral Anticoagulants.

Importance: The CHA2DS2-VASc score (calculated as congestive heart failure, hypertension, age 75 years and older, diabetes, stroke or TIA, vascular disease, age 65 to 74 years, and sex category) is the standard for assessing risk of stroke and systemic embolism and includes age and thromboembolic history. To our knowledge, no studies have comprehensively evaluated safety and effectiveness outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants according to independent, categorical risk strata. Objective: To evaluate the incidence of key adverse outcomes among patients with nonvalvular atrial fibrillation receiving oral anticoagulants by CHA2DS2-VASc risk score range, thromboembolic event history, and age group. Design, Setting, and Participants: This cohort study was a retrospective claims data analysis using combined data sets from 5 large health claims databases. Eligible participants were adult patients with nonvalvular atrial fibrillation who initiated oral anticoagulants. Data were analyzed between January 2012 and June 2019. Exposure: Initiation of oral anticoagulants. Main Outcomes and Measures: We observed clinical outcomes (including stroke or systemic embolism, major bleeding, and a composite outcome) on treatment through study end, censoring for discontinuation of oral anticoagulants, death, and insurance disenrollment. The population was stratified by CHA2DS2-VASc risk score; history of stroke, systemic embolism, or transient ischemic attack; and age groups. We calculated time to event, incidence rates, and cumulative incidence for outcomes. Results: We identified 1 141 097 patients with nonvalvular atrial fibrillation; the mean (SD) age was 75.0 (10.5) years, 608 127 patients (53.3%) were men, and over 1 million were placed in the 2 highest risk categories (high risk 1, 327 766 participants; high risk 2, 688 449 participants). Deyo-Charlson Comorbidity Index scores ranged progressively alongside CHA2DS2-VASc risk score strata (mean [SD] scores: low risk, 0.4 [1.0]; high risk 2, 4.1 [2.9]). The crude incidence of stroke and systemic embolism generally progressed alongside risk score strata (low risk, 0.25 events per 100 person-years [95% CI, 0.18-0.34 events]; high risk 2, 3.43 events per 100 person-years [95% CI, 3.06-4.20 events]); patients at the second-highest risk strata with thromboembolic event history had higher stroke incidence vs patients at the highest risk score strata without event history (2.06 events per 100 person-years [95% CI, 2.00-3.12 events] vs 1.18 events per 100 person-years [95% CI, 1.14-1.30 events]). Major bleeding and composite incidence also increased progressively alongside risk score strata (major bleeding: low risk, 0.68 events per 100 person-years [95% CI, 0.56-0.82 events]; high risk 2, 6.29 events per 100 person-years [95% CI, 6.21-6.62 events]; composite incidence: 1.22 events per 100 person-years [95% CI, 1.06-1.41 events]; high risk 2, 10.67 events per 100 person-years [95% CI, 10.26-11.48 events]). The 12-month cumulative incidence proportions for stroke and systemic embolism, major bleeding, and composite outcomes progressed alongside risk score strata (stroke or systemic embolism, 0.30%-1.85%; major bleeding, 0.55%-5.55%; composite, 1.05%-8.23%). Age subgroup analysis followed similar trends. Conclusions and Relevance: The observed incidence of stroke or systemic embolism and major bleeding events generally conformed to an expected increasing incidence by risk score, adding insight into the importance of specific risk score range, thromboembolic event history, and age group strata. These results can help inform clinical decision-making, research, and policy.

Effectiveness and Safety of Apixaban Versus Warfarin in Obese Patients with Nonvalvular Atrial Fibrillation Enrolled in Medicare and Veteran Affairs.

Real-world studies have evaluated the use of anticoagulants in obese patients with nonvalvular atrial fibrillation (NVAF), but they have been limited by sample size or the use of diagnosis codes on claims to define obesity. This retrospective study used body weight data of ≥100 kg or a body mass index of ≥30 kg/m2 to identify elderly (aged ≥65 years) NVAF patients with obesity in dually enrolled Veterans Affairs and fee-for-service Medicare patients. It evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients that initiated apixaban versus warfarin. Stabilized inverse probability treatment weighting was used to balance the baseline characteristics between patients prescribed apixaban and warfarin in obese patients. Cox models were used to evaluate the relative risk of stroke/SE and MB. Overall, 35.9% (n = 26,522) of the NVAF population were obese, of which 13,604 apixaban and 12,918 warfarin patients were included. After inverse probability treatment weighting, patient characteristics were balanced. The mean age was 75 years, the mean CHA2DS2-VASc score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65-74, Female) was 3.8, the mean HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) Score was ∼2.6, and >98% of patients were males. Obese apixaban patients were associated with a similar risk of stroke/SE (hazard ratio: 0.82; 95% confidence interval: 0.66 to 1.03) and a significantly lower risk of MB (hazard ratio: 0.62; 95% confidence interval: 0.54 to 0.70) versus warfarin. No significant interaction was observed between treatment and obesity status (nonobese, obese/nonmorbid, obese/morbid) for stroke/SE (interaction p = 0.602) or MB (interaction p = 0.385). In obese patients with NVAF, apixaban was associated with a similar risk of stroke/SE and a significantly lower risk of MB versus warfarin.

Prevalence and incidence of patients with paroxysmal supraventricular tachycardia in the United States.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) encompasses a range of heart rhythm disorders leading to rapid heart rates. By virtue of its episodic nature, diagnosing PSVT is difficult and estimating incidence and prevalence on a population level is challenging. The objective of this study was to estimate the incidence and prevalence of PSVT in the United States (US) in contemporary practice. METHODS AND RESULTS: An observational retrospective longitudinal study using claims, enrollment, and demographic data from the IBM MarketScan® Commercial Research database (age < 65) and the Medicare Limited Data Set (age ≥ 65) from 2008 to 2016. Patients with a PSVT diagnosis code (ICD-9: 427.0; ICD-10: I47.1) on ≥2 outpatient, ≥1 emergency room, or ≥1 inpatient visit were considered as having PSVT. Patients with atrial fibrillation/atrial flutter (AF/AFL) were excluded from the initial analysis given the potential for misclassification. Incidence was estimated by assessing diagnoses made during year 5 of continuous enrollment. Finally, a sensitivity analysis was performed by including patients with both PSVT and AF/AFL diagnoses. Period prevalence and incidence rate were estimated to be 332.9 (323.2-342.9) and 57.8 (52.8-63.3) per 100 000 individuals, respectively, when excluding patients with AF/AFL. Projected to the 2018 US Census, prevalence and incidence are 1.26 million (1.21-1.30 million) and 188,981 (172,891-206,943), respectively. Including patients with AF/AFL, the prevalence may increase to 479.7 (467.9-491.8) with an incidence of 93.4 (86.9-100.5) per 100 000 individuals or a prevalence of 2.06 million (2.01-2.12 million). CONCLUSIONS: Approximately 1 in 300 people in the US had PSVT with the highest rates in older and female patients.

Trends in health care resource use and expenditures in patients with newly diagnosed paroxysmal supraventricular tachycardia in the United States.

BACKGROUND: Few data are available on the temporal patterns of health resource utilization (HRU) and expenditures around paroxysmal supraventricular tachycardia (PSVT) diagnosis. This study assessed the longitudinal trends in HRU and expenditures in the 3 years preceding and subsequent to PSVT diagnosis. METHODS: Adult patients (age 18-65 years) with newly diagnosed PSVT were identified using administrative claims from the IBM MarketScan Research Database between January 1, 2008 and December 31, 2016 and propensity-score matched (1:1) with non-PSVT controls. RESULTS: Among the 12,305 PSVT patients compared with matched controls, PSVT was associated with statistically significant higher annual rates of emergency department visits, physician office visits, inpatient hospitalizations, and diagnostic testing. HRU increased in the years preceding PSVT diagnosis, reaching its peak in the year following PSVT diagnosis. Over the 6-year follow-up period, PSVT was associated with higher mean annual per patient expenditures ($12,665) compared to matched controls ($6,004; P < .001). Upon diagnosis of PSVT, the mean expenditures per PSVT patient doubled from $11,714 in the year immediately preceding index diagnosis to $23,335 in the first postdiagnosis year. Inpatient services, diagnostic testing, and ablation procedures were the principle drivers of higher mean expenditures in the first year post-PSVT diagnosis versus the year prior to PSVT diagnosis. CONCLUSIONS: PSVT presents a substantial economic burden to health care systems. The annual expenditure per PSVT patient is within the range previously reported for atrial fibrillation. The increased HRU and expenditures in the year following diagnosis, which do not return to baseline, suggest a potential gap in non-interventional, long-term PSVT management.

Healthcare Resource Use and Expenditures in Patients Newly Diagnosed With Paroxysmal Supraventricular Tachycardia.

Information on paroxysmal supraventricular tachycardia (PSVT) patient characteristics and the associated economic burden of the disease is limited. Therefore, we sought to characterize newly diagnosed PSVT patients and quantify their healthcare resource use and expenditures. We used enrollment, demographic, and claims data from IBM MarketScan Research Database and Medicare Limited Data Set (LDS) to identify patients newly diagnosed with PSVT (ICD-9: 427.0; ICD-10: I47.1) from 10/1/2012 to 9/30/2016. Patients were required to be observable 1-year before and after index diagnosis. Patients were stratified by age (<65 years and ≥65 years), and propensity-matched to patients without PSVT. Expenditures and healthcare resource use were analyzed 1 year before and 1-year following index diagnosis. Among 49,316 patients <65 years and 23,954 patients ≥65 years, most were female (64% and 63%, respectively). Compared with matched controls, all PSVT patients had significantly more emergency department visits pre- and postdiagnosis, and more hospitalizations following diagnosis. Mean annual per patient expenditures paid by insurers were significantly higher in the year post-PSVT diagnosis, tripling for patients <65 years ($9,028 to $29,867) and nearly doubling for patients ≥65 years ($10,867 to $20,143). Spending for PSVT services accounted for 43% and 33% of the increase in expenditures in these patient-groups, respectively. Few patients had an ablation within 1 year of diagnosis, although ablations were more frequent in patients age <65 years (13% vs 3%). In conclusion, PSVT imposes a substantial economic burden, with increases in expenditures following initial diagnosis in both younger (<65 years) and older (≥65 years) patients who are not accounted for by cardiac ablation spending alone.