Correction: Nguyen et al. The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem Cells. Cells 2022, 11, 635

In the original publication [...

Multiply robust estimation for causal survival analysis with treatment noncompliance

Comparative effectiveness research with randomized trials or observational studies frequently addresses a time-to-event outcome and can require unique considerations in the presence of treatment noncompliance. Motivated by the challenges in addressing noncompliance in the ADAPTABLE pragmatic trial, we develop a multiply robust estimator to estimate the principal survival causal effects under the principal ignorability and monotonicity assumption. The multiply robust estimator involves several working models including that for the treatment assignment, the compliance strata, censoring, and time to event of interest. We demonstrate that the proposed estimator is consistent even if one, and sometimes two, of the working models are incorrectly specified. We further contribute sensitivity analysis strategies for investigating the robustness of the multiply robust estimator under violation of two identification assumptions specific to noncompliance. We implement the multiply robust method in the ADAPTABLE trial to evaluate the effect of low- versus high-dose aspirin assignment on patients' death and hospitalization from cardiovascular diseases, and further obtain the causal effect estimates when the identification assumptions fail to hold. We find that, comparing to low-dose assignment, assignment to the high-dose leads to differential effects among always high-dose takers, compliers, and always low-dose takers. Such treatment effect heterogeneity contributes to the null intention-to-treatment effect, and suggests that policy makers should design personalized strategies based on potential compliance patterns to maximize treatment benefits to the entire study population

Identification of Heart Failure Events in Medicare Claims: The Atherosclerosis Risk in Communities (ARIC) Study

We examined the accuracy of CMS Medicare HF diagnostic codes in the identification of acute decompensated and chronic stable HF (ADHF and CSHF)

Diabetes and Prediabetes and Risk of Hospitalization: The Atherosclerosis Risk in Communities (ARIC) Study

To examine the magnitude and types of hospitalizations among persons with prediabetes, undiagnosed diabetes, and diagnosed diabetes

Peripheral Artery Disease Prevalence and Incidence Estimated From Both Outpatient and Inpatient Settings Among Medicare Fee‐for‐Service Beneficiaries in the Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND: Outpatient ascertainment of peripheral artery disease (PAD) is rarely considered in the measurement of PAD clinical burden; therefore, the clinical burden of PAD likely has been underestimated while contributing to a decreased awareness of PAD in comparison to other circulatory system disorders. METHODS AND RESULTS: The purpose of this study was to estimate the age-standardized annual period prevalence and incidence of PAD in the outpatient and inpatient settings using data from the Atherosclerosis Risk in Communities (ARIC) study linked with Centers for Medicare and Medicaid Services claims. The majority (>70%) of all PAD encounters occurred in the outpatient setting. The weighted mean age-standardized prevalence and incidence of outpatient PAD was 11.8% (95% CI 11.5-12.1) and 22.4 per 1000 person-years (95% CI 20.8-24.0), respectively. Black patients had higher weighted mean age-standardized prevalence (15.6%; 95% CI 14.6-16.4) compared with white patients (11.4%; 95% CI 11.1-11.7). Black women had the highest weighted mean age-standardized prevalence (16.9%; 95% CI 16.0-17.8). Black patients also had a higher incidence rate of PAD (31.3 per 1000 person-years; 95% CI 27.3-35.4) compared with white patients (25.4 per 1000 person-years; 95% CI 23.5-27.3). PAD prevalence and incidence did not differ by sex alone. CONCLUSIONS: This study provides comprehensive estimates of PAD in the inpatient and outpatient settings where the majority of PAD burden was found. PAD is an important circulatory system disorder similar in prevalence to stroke and coronary heart disease

Iterative Outlier Removal: A Method for Identifying Outliers in Laboratory Recalibration Studies

Extreme values that arise for any reason, including through non-laboratory measurement procedure-related processes (inadequate mixing, evaporation, mislabeling), lead to outliers and inflate errors in recalibration studies. We present an approach termed iterative outlier removal (IOR) for identifying such outliers

Validity of hospital discharge diagnosis codes for stroke: The atherosclerosis risk in communities study

BACKGROUND AND PURPOSE: Characterizing International Classification of Disease 9th Revision, Clinical Modification (ICD-9-CM) code validity is essential given widespread use of hospital discharge databases in research. Using the Atherosclerosis Risk in Communities (ARIC) Study, we estimated the accuracy of ICD-9-CM stroke codes. METHODS: Hospitalizations with ICD-9-CM codes 430 to 438 or stroke keywords in the discharge summary were abstracted for ARIC cohort members (1987-2010). A computer algorithm and physician reviewer classified definite and probable ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Using ARIC classification as a gold standard, we calculated the positive predictive value (PPV) and sensitivity of ICD-9-CM codes grouped according to the American Heart Association/American Stroke Association (AHA/ASA) 2013 categories and an alternative code grouping for comparison. RESULTS: Thirty-three percent of 4260 hospitalizations were validated as strokes (1251 ischemic, 120 intracerebral hemorrhage, 46 subarachnoid hemorrhage). The AHA/ASA code groups had PPV 76% and 68% sensitivity compared with PPV 72% and 83% sensitivity for the alternative code groups. The PPV of the AHA/ASA code group for ischemic stroke was slightly higher among blacks, individuals <65 years, and at teaching hospitals. Sensitivity was higher among older individuals and increased over time. The PPV of the AHA/ASA code group for intracerebral hemorrhage was higher among blacks, women, and younger individuals. PPV and sensitivity varied across study sites. CONCLUSIONS: A new AHA/ASA discharge code grouping to identify stroke had similar PPV and lower sensitivity compared with an alternative code grouping. Accuracy varied by patient characteristics and study sites

Temporal Trends in Hospitalization for Acute Decompensated Heart Failure in the United States, 1998–2011

Estimates of the numbers and rates of acute decompensated heart failure (ADHF) hospitalization are central to understanding health-care utilization and efforts to improve patient care. We comprehensively estimated the frequency, rate, and trends of ADHF hospitalization in the United States. Based on Atherosclerosis Risk in Communities (ARIC) Study surveillance adjudicating 12,450 eligible hospitalizations during 2005–2010, we developed prediction models for ADHF separately for 3 International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 428 discharge diagnosis groups: 428 primary, 428 nonprimary, or 428 absent. We applied the models to data from the National Inpatient Sample (11.5 million hospitalizations of persons aged ≥55 years with eligible ICD-9-CM codes), an all-payer, 20% probability sample of US community hospitals. The average estimated number of ADHF hospitalizations per year was 1.76 million (428 primary, 0.80 million; 428 nonprimary, 0.83 million; 428 absent, 0.13 million). During 1998–2004, the rate of ADHF hospitalization increased by 2.0%/year (95% confidence interval (CI): 1.8, 2.5) versus a 1.4%/year (95% CI: 0.8, 2.1) increase in code 428 primary hospitalizations (P < 0.001). In contrast, during 2005–2011, numbers of ADHF hospitalizations were stable (−0.5%/year; 95% CI: −1.4, 0.3), while the numbers of 428-primary hospitalizations decreased by −1.5%/year (95% CI: −2.2, −0.8) (P for contrast = 0.03). In conclusion, the estimated number of hospitalizations with ADHF is approximately 2 times higher than the number of hospitalizations with ICD-9-CM code 428 in the primary position. The trend increased more steeply prior to 2005 and was relatively flat after 2005

Obstructive Sleep Apnea and 15-Year Cognitive Decline: The Atherosclerosis Risk in Communities (ARIC) Study

Prospective data evaluating abnormal sleep quality and quantity with cognitive decline are limited because most studies used subjective data and/or had short follow-up. We hypothesized that, over 15 y of follow-up, participants with objectively measured obstructive sleep apnea (OSA) and other indices of poor sleep quantity and quality would experience greater decline in cognitive functioning than participants with normal sleep patterns

Midlife Alcohol Consumption and the Risk of Stroke in the Atherosclerosis Risk in Communities Study

Alcohol consumption is common in the US and may confer beneficial cardiovascular effects at light-to-moderate doses. The alcohol-stroke relationship remains debated. We estimated the relationship between mid-life, self-reported alcohol consumption and ischemic stroke (IS) and intracerebral hemorrhage (ICH) in a biracial cohort