Racial and ethnic differences in uncontrolled diabetes mellitus among adults taking antidiabetic medication.

AIM: To examine whether racial and ethnic disparities in uncontrolled type 2 diabetes mellitus (T2DM) persist among those taking medication and after accounting for other demographic, socioeconomic, and health indicators. METHODS: Adults aged ≥20 years with T2DM using prescription diabetes medication were among participants assessed in a retrospective cohort study of the National Health and Nutrition Examination Survey 2007-2018. We estimated weighted sequential multivariable logistic regression models to predict odds of uncontrolled T2DM (HbA1c ≥ 8%) from racial and ethnic identity, adjusting for demographic, socioeconomic, and health indicators. RESULTS: Of 3649 individuals with T2DM who reported taking medication, 27.4% had uncontrolled T2DM (mean HgA1c 9.6%). Those with uncontrolled diabetes had a mean BMI of 33.8, age of 57.3, and most were non-Hispanic white (54%), followed by 17% non-Hispanic Black, and 20% Hispanic identity. In multivariable analyses, odds of uncontrolled T2DM among those with Black or Hispanic identities lessened, but persisted, after accounting for other indicators (Black OR 1.38, 97.5% CI: 1.04, 1.83; Hispanic OR 1.79, 97.5% CI 1.25, 2.57). CONCLUSIONS: Racial and ethnic disparities in T2DM control persisted among individuals taking medication. Future research might focus on developmental and epigenetic pathways of disparate T2DM control across racially and ethnically minoritized populations.

A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials.

Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)-thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. Funding: SPIRIT-SURROGATE/CONSORT-SURROGATE project is Medical Research Council Better Research Better Health (MR/V038400/1) funded.

Association of hospital spending with care patterns and mortality in patients hospitalized with community-acquired pneumonia.

BACKGROUND: Pneumonia is a leading cause of mortality and intensive therapy is costly. However, it is unclear whether more spending is associated with better patient outcomes or how hospitals could decrease costs. OBJECTIVES: This study investigates the association between hospital spending and 14-day inpatient mortality among community-acquired pneumonia inpatients. METHODS: This retrospective cohort study focused on adult pneumonia patients discharged between July 2010 and June 2015 from 260 US hospitals in the Premier database. Hospitals were divided into four pneumonia cost-of-care quartiles and average cost was calculated for each hospital. Odds of 14-day inpatient mortality and care practices were compared among high and low-cost hospitals. RESULTS: The study population comprised 534,038 patients with a mean age 69.5 (SD 16.3); 51.9% were female, 75% White, and 71.9% covered by Medicare. Hospitals were largely medium-sized (40.4%), located in the South (49.2%), and in urban areas (82.3%). The fully adjusted population-averaged cost was 14,486 US dollars (95% confidence interval [CI] 13,982-14,867). Hospital practices associated with cost included intensity of diagnostic work-up +$14 (95% CI +12 to +18; p < .0001) and de-escalation of antibiotic therapy, +$6836 (95% CI +2291 to +11,160; p = .004). There was no significant difference in odds of 14-day inpatient mortality between hospitals in the highest and lowest cost quartiles. CONCLUSIONS: Greater spending at the hospital level was not associated with lower mortality. Lower diagnostic costs were associated with lower cost of care, suggesting that judicious use of diagnostic testing might reduce costs without worsening patient outcomes.

Bringing Critical Race Praxis Into the Study of Electrophysiological Substrate of Sudden Cardiac Death: The ARIC Study.

Background Race is an established risk factor for sudden cardiac death (SCD). We sought to determine whether the association of electrophysiological substrate with SCD varies between black and white individuals. Methods and Results Participants from the ARIC (Atherosclerosis Risk in Communities) study with analyzable ECGs (n=14 408; age, 54±6 years; 74% white) were included. Electrophysiological substrate was characterized by ECG metrics. Two competing outcomes were adjudicated: SCD and non-SCD. Interaction of ECG metrics with race was studied in Cox proportional hazards and Fine-Gray competing risk models, adjusted for prevalent cardiovascular disease, risk factors, and incident nonfatal cardiovascular disease. At the baseline visit, adjusted for age, sex, and study center, blacks had larger spatial ventricular gradient magnitude (0.30 mV; 95% CI, 0.25-0.34 mV), sum absolute QRST integral (18.4 mV*ms; 95% CI, 13.7-23.0 mV*ms), and Cornell voltage (0.30 mV; 95% CI, 0.25-0.35 mV) than whites. Over a median follow-up of 24.4 years, SCD incidence was higher in blacks (2.86 per 1000 person-years; 95% CI, 2.50-3.28 per 1000 person-years) than whites (1.37 per 1000 person-years; 95% CI, 1.22-1.53 per 1000 person-years). Blacks with hypertension had the highest rate of SCD: 4.26 (95% CI, 3.66-4.96) per 1000 person-years. Race did not modify an association of ECG variables with SCD, except QRS-T angle. Spatial QRS-T angle was associated with SCD in whites (hazard ratio, 1.38; 95% CI, 1.25-1.53) and hypertension-free blacks (hazard ratio, 1.52; 95% CI, 1.09-2.12), but not in blacks with hypertension (hazard ratio, 1.15; 95% CI, 0.99-1.32) (P-interaction=0.004). Conclusions Race did not modify associations of electrophysiological substrate with SCD and non-SCD. Electrophysiological substrate does not explain racial disparities in SCD rate.

Quantitative Assessment of Vectorcardiographic Loop Morphology.

Vectorcardiography (VCG), developed 100years ago, characterizes clinically important electrophysiological properties of the heart. In this study, VCG QRS loop roundness, planarity, thickness, rotational angle, and dihedral angle were measured in 81 healthy control subjects (39.0±14.2y; 51.8% male; 94% white), and 8 patients with infarct-cardiomyopathy and sustained monomorphic ventricular tachycardia (VT) (68.0±7.8y, 37.5% male). The angle between two consecutive QRS vectors was defined as the rotational angle, while dihedral angle quantified planar alteration over the QRS loop. In VT subjects, planarity index decreased (0.63±0.22 vs. 0.88±0.10; P=0.014), and dihedral angle was significantly more variable (variance of dihedral angle, median (IQR): 897(575-1450) vs. 542(343-773); P=0.029; rMSSD: 47.7±12.7 vs. 35.1±13.1; P=0.027). Abnormal electrophysiological substrate in VT patients is characterized by the appearance of QRS loop folding, likely due to local conduction block. The presence of fragmented QRS complexes on the 12-lead ECG had low sensitivity (31%) for detecting QRS loop folding on the VCG.

Assessment of Joint Interactions between Respiration and Baroreflex Activity using Joint Symbolic Dynamics in Heart Failure Patients.

In this paper we employed a novel approach based on joint symbolic dynamics (JSD) to study interaction between respiratory phase and baroreflex activity. Electrocardiogram (ECG) and blood pressure recordings from six participants with history of heart failure were included in this study. First, the ECG R-peaks and systolic blood pressure indices were detected using parabolic fitting. Second, the respiratory signal was derived from Frank orthogonal ECG leads using QRS slopes and R-wave angles. Third, time series of R-R intervals and systolic blood pressure (SBP) were extracted, and respiratory phases were obtained using the Hilbert transform. Subsequently, each series was transformed into binary symbol vectors based on their successive changes and words of length '2' were formed. Baroreflex patterns were studied using word combinations representing baroreflex activity for specific changes in respiratory phases. Baroreflex activity was significantly higher for alternating low-high/high-low heart rate and SBP during inspiration as compared to continuous increase or decrease in heart rate and SBP ([Formula: see text], wRP=11: 39.1±9.3% vs. [Formula: see text], wRP=11: 6.4±3.9%, p<0.0001).