Faculty Bibliography

OBJECTIVE:To compare the image quality of an accelerated single-shot T2-weighted fat-suppressed (FS) MRI of the liver with deep learning-based image reconstruction (DL HASTE-FS) with conventional T2-weighted FS sequence (conventional T2 FS) at 1.5 T. METHODS:One hundred consecutive patients who underwent clinical MRI of the liver at 1.5 T including the conventional T2-weighted fat-suppressed sequence (T2 FS) and accelerated single-shot T2-weighted MRI of the liver with deep learning-based image reconstruction (DL HASTE-FS) were included. Images were reviewed independently by three blinded observers who used a 5-point confidence scale for multiple measures regarding the artifacts and image quality. Descriptive statistics and McNemar's test were used to compare image quality scores and percentage of lesions detected by each sequence, respectively. Intra-class correlation coefficient (ICC) was used to assess consistency in reader scores. RESULTS:Acquisition time for DL HASTE-FS was 51.23 +/ 10.1 s, significantly (p < 0.001) shorter than conventional T2-FS (178.9 ± 85.3 s). DL HASTE-FS received significantly higher scores than conventional T2-FS for strength and homogeneity of fat suppression; sharpness of liver margin; sharpness of intra-hepatic vessel margin; in-plane and through-plane respiratory motion; other ghosting artefacts; liver-fat contrast; and overall image quality (all, p < 0.0001). DL HASTE-FS also received higher scores for lesion conspicuity and sharpness of lesion margin (all, p < .001), without significant difference for liver lesion contrast (p > 0.05). CONCLUSIONS:Accelerated single-shot T2-weighted MRI of the liver with deep learning-based image reconstruction showed superior image quality compared to the conventional T2-weighted fat-suppressed sequence despite a 4-fold reduction in acquisition time. KEY POINTS/CONCLUSIONS:• Conventional fat-suppressed T2-weighted sequence (conventional T2 FS) can take unacceptably long to acquire and is the most commonly repeated sequence in liver MRI due to motion. • DL HASTE-FS demonstrated superior image quality, improved respiratory motion and other ghosting artefacts, and increased lesion conspicuity with comparable liver-to-lesion contrast compared to conventional T2FS sequence. • DL HASTE- FS has the potential to replace conventional T2 FS sequence in routine clinical MRI of the liver, reducing the scan time, and improving the image quality.

BACKGROUND:Among patients with diabetes and chronic coronary disease, it is unclear if invasive management improves outcomes when added to medical therapy. METHODS:The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trials (ie, ISCHEMIA and ISCHEMIA-Chronic Kidney Disease) randomized chronic coronary disease patients to an invasive (medical therapy + angiography and revascularization if feasible) or a conservative approach (medical therapy alone with revascularization if medical therapy failed). Cohorts were combined after no trial-specific effects were observed. Diabetes was defined by history, hemoglobin A1c ≥6.5%, or use of glucose-lowering medication. The primary outcome was all-cause death or myocardial infarction (MI). Heterogeneity of effect of invasive management on death or MI was evaluated using a Bayesian approach to protect against random high or low estimates of treatment effect for patients with versus without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease severity or left ventricular function). RESULTS:<0.001). At median 3.1-year follow-up the adjusted event-free survival was 0.54 (95% bootstrapped CI, 0.48-0.60) and 0.66 (95% bootstrapped CI, 0.61-0.71) for patients with diabetes versus without diabetes, respectively, with a 12% (95% bootstrapped CI, 4%-20%) absolute decrease in event-free survival among participants with diabetes. Female and male patients with insulin-treated diabetes had an adjusted event-free survival of 0.52 (95% bootstrapped CI, 0.42-0.56) and 0.49 (95% bootstrapped CI, 0.42-0.56), respectively. There was no difference in death or MI between strategies for patients with diabetes versus without diabetes, or for clinical (female sex or insulin use) or anatomic features (coronary artery disease severity or left ventricular function) of patients with diabetes. CONCLUSIONS:Despite higher risk for death or MI, chronic coronary disease patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in ISCHEMIA trial screen failures with INOCA) was an international cohort study conducted from 2014-2019 involving angina assessments (Seattle Angina Questionnaire [SAQ]) and stress echocardiograms 1-year apart. This was an ancillary study that included patients with history of angina who were not randomized in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease (CAD) status and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between changes in SAQ Angina Frequency score and change in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and compared CIAO participants with ISCHEMIA participants with obstructive CAD who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 vs. 26% of 865 ISCHEMIA participants with obstructive CAD, p<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [IQR 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (p=0.46) or ISCHEMIA stress echocardiography participants (p=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over one year was not significantly correlated with change in angina (rho=0.029). Conclusions:Improvement in ischemia and improvement in angina were common in INOCA, but not correlated. Our INOCA cohort had a similar degree of inducible wall motion abnormalities to concurrently enrolled ISCHEMIA participants with obstructive CAD. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02347215.

BACKGROUND:Patients with chronic kidney disease (CKD) and coronary artery disease frequently undergo preemptive revascularization before kidney transplant listing. OBJECTIVES/OBJECTIVE:In this post-hoc analysis from ISCHEMIA-CKD, we compared outcomes of patients not listed versus those listed according to management strategy. METHODS:In ISCHEMIA-CKD (n=777), 194 patients (25%) with chronic coronary syndromes and at least moderate ischemia were listed for transplant. The primary (all-cause mortality or nonfatal myocardial infarction [MI]) and secondary (death, nonfatal MI, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke) outcomes were analyzed using Cox multivariable modeling. Heterogeneity of randomized treatment effect between listed versus not listed groups was assessed. RESULTS:Compared with those not listed, listed patients were younger (60 versus 65 years), less likely of Asian race (15% versus 29%), more likely on dialysis (83% versus 44%), had fewer anginal symptoms, and more likely to have coronary angiography and coronary revascularization irrespective of treatment assignment. Among patients assigned to an invasive strategy versus conservative strategy, the adjusted hazard ratios (aHR) (95% confidence interval [CI]) for the primary outcome were 0.91 (0.54-1.54) and 1.03 (0.78-1.37) for those listed and not listed, respectively (pinteraction=0.68). Adjusted HR for secondary outcomes were 0.89 (0.55-1.46) in listed and 1.17 (0.89-1.53) in those not listed (pinteraction=0.35). CONCLUSIONS:In ISCHEMIA-CKD, an invasive strategy in kidney transplant candidates did not improve outcomes compared with conservative management. These data do not support routine coronary angiography or revascularization in patients with advanced CKD and chronic coronary syndromes listed for transplant.

Purpose : Ophthalmology clinics with minimal statistical analytics capabilities may struggle to implement a quality monitoring system to evaluate patient outcomes. We performed a quality improvement study by designing a quality monitoring system for a low-resource ophthalmology clinic that would use small samples to estimate outcomes for larger patient populations. Methods : We evaluated the proportion of primary open-angle glaucoma (POAG) patients who were treated successfully according to American Academy of Ophthalmology Preferred Practice Patterns (PPPs). We analyzed 100 patients seen in the clinic over 3 months in 2019 as the input for our Bayesian analysis. We also created a standardized note template for use by clinicians in the electronic medical record (EMR) for POAG patient visits to facilitate monitoring of treatment successes without requiring clinical expertise. We evaluated adherence to clinician template use in POAG patient notes on the weekly day of glaucoma patient visits over 9 weeks in 2020. Results : Using Bayesian analysis based on our initial data, we created tables that allow for quality monitoring of future 3 month intervals using parameters from smaller samples. Using a small sample of 30 patients, we were able to determine that there was a 100% probability that the clinic as a whole was not achieving the pre-defined target percentage of 80% of POAG patients successfully treated, as defined by the PPPs. Regarding adherence to use of the note template for POAG patients, the median proportion of patients for which the template was used on a single clinic day was 27%, with a maximum of 53% and a minimum of 11%. Conclusions : Based on the input parameters of the number of patients in the sample, the number of treatment successes in that sample, and the target proportion of successfully treated patients, a small sample Bayesian analysis can be used for quality monitoring of patient outcomes for larger patient populations in low-resource clinical settings. Future work includes creation of an open-access database of tables derived from Bayesian analysis for use as a reference by other low-resource clinics in quality monitoring efforts

Background: The efficacy of an aggressive multiple risk factor intervention approach - optimal medical therapy (OMT) - to reduce major adverse cardiovascular events in patients with CKD has not been tested.
Objective(s): to examine OMT goal attainment in patients with CKD on dialysis (CKD-D) and non-dialysis CKD (CKD-ND) in the ISCHEMIA-CKD trial.
Method(s): OMT was recommended to all participants in ISCHEMIA-CKD. Longitudinal trajectories of individual OMT components (smoking cessation, systolic blood pressure (SBP) <140 mmHg, low density lipoprotein (LDL) cholesterol <70 mg/dL, high-intensity statin use, and aspirin use) were modeled over study follow-up. Covariateadjusted percentage point difference in each OMT goal achieved at 24 months between CKD-D and CKD-ND groups (% difference [95% credible interval (CrI)]) was estimated.
Result(s): There were 415 CKD-D and 362 CKD-ND patients at baseline. CKD-D were younger (61 v 67 yrs, p<0.001) and less often diabetic (53% v 62%, p=0.023). CKD-D patients were 7.9 % (0.7%, 14.8%) more likely than CKD-ND to attain the SBP goal at 24 months (Figure). CKD-D patients were 22.7% (-33.3%, -11.4%) less likely to receive high-intensity statins. There was a steady and similar increase in proportional achievement of OMT during follow up.
Conclusion(s): OMT improved over time in advanced CKD-ND and CKD-D. CKD-D achieved the SBP goal more than CKD-ND, yet CKD-D were less likely to be treated with high-intensity statin. Future studies should explore systemic and patient-related barriers to attainment of OMT in this high-risk cohort.(Figure Presented)

BACKGROUND:Few studies examine relationships between built environment (BE) and type 2 diabetes mellitus (T2DM) using spatial models, investigate BE domains apart from food environment or physical activity resources or conduct sensitivity analysis of methodological choices made in measuring BE. We examine geographic heterogeneity of T2DM, describe how heterogeneity in T2DM relates to BE and estimate associations of T2DM with BE. METHODS:Individual-level electronic health records (n=41 203) from the Duke Medicine Enterprise Data Warehouse (2007-2011) were linked to BE based on census block. Data on housing damage, property disorder, territoriality, vacancy and public nuisances were used to estimate BE based on four different construction methods (CMs). We used race-stratified aspatial and spatial Bayesian models to assess geographic heterogeneity in T2DM and associations of T2DM with BE. RESULTS:Among whites, a 1 SD increase in poor quality BE was associated with a 1.03 (95% credible interval 1.01 to 1.06) and 1.06 (95 % credible interval 1.02 to 1.11) increased risk of T2DM for poor quality BE CM1 and CM2, respectively. Among blacks/African Americans, associations between T2DM and BE overlapped with the null for all CMs. The addition of BE to white models reduced residual geographic heterogeneity in T2DM by 4%-15%, depending on CM. In black/African-American models, BE did not affect residual heterogeneity. CONCLUSION/CONCLUSIONS:Associations of T2DM with BE were sensitive to CM and geographic heterogeneity in T2DM differed by race/ethnicity. Findings underscore the need to consider multiple methods of estimating BE and consider differences in relationships by race/ethnicity.

Neighborhood characteristics such as racial segregation may be associated with type 2 diabetes mellitus, but studies have not examined these relationships using spatial models appropriate for geographically patterned health outcomes. We constructed a local, spatial index of racial isolation (RI) for black residents in a defined area, measuring the extent to which they are exposed only to one another, to estimate associations of diabetes with RI and examine how RI relates to spatial patterning in diabetes. We obtained electronic health records from 2007-2011 from the Duke Medicine Enterprise Data Warehouse. Patient data were linked to RI based on census block of residence. We used aspatial and spatial Bayesian models to assess spatial variation in diabetes and relationships with RI. Compared with spatial models with patient age and sex, residual geographic heterogeneity in diabetes in spatial models that also included RI was 29% and 24% lower for non-Hispanic white and black residents, respectively. A 0.20-unit increase in RI was associated with an increased risk of diabetes for white (risk ratio = 1.24, 95% credible interval: 1.17, 1.31) and black (risk ratio = 1.07, 95% credible interval: 1.05, 1.10) residents. Improved understanding of neighborhood characteristics associated with diabetes can inform development of policy interventions.

Globally, the majority of childhood deaths in the post-neonatal period are caused by infections that can be effectively treated or prevented with inexpensive interventions delivered through even very basic health facilities. To understand the role of inadequate health systems on childhood mortality in Kenya, we assemble a large, retrospective cohort of children (born 1996-2013) and describe the health systems context of each child using health facility survey data representative of the province at the time of a child's birth. We examine the relationship between survival beyond 59 months of age and geographic distribution of health facilities, quality of services, and cost of services. We find significant geographic heterogeneity in survival that can be partially explained by differences in distribution of health facilities and user fees. Higher per capita density of health facilities resulted in a 25% reduction in the risk of death (HRR = 0.73, 95% CI:0.58 to 0.91) and accounted for 30% of the between-province heterogeneity in survival. User fees for sick-child visits increased risk by 30% (HRR = 1.30, 95% CI:1.11 to 1.53). These results implicate health systems constraints in child mortality, quantify the contribution of specific domains of health services, and suggest priority areas for improvement to accelerate reductions in child mortality.