Atherosclerosis quantification and cardiovascular risk: the ISCHEMIA trial.

BACKGROUND AND AIMS: The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)-derived atherosclerotic plaque analysis in ISCHEMIA. METHODS: Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2-4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. RESULTS: Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25-1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model's predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes. CONCLUSIONS: In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.

Survival After Invasive or Conservative Management of Stable Coronary Disease.

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. METHODS: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. RESULTS: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85-1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63-0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08-1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. CONCLUSIONS: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04894877.

Bias correction models for electronic health records data in the presence of non-random sampling.

Electronic health records (EHRs) contain rich clinical information for millions of patients and are increasingly used for public health research. However, non-random inclusion of subjects in EHRs can result in selection bias, with factors such as demographics, socioeconomic status, healthcare referral patterns, and underlying health status playing a role. While this issue has been well documented, little work has been done to develop or apply bias-correction methods, often due to the fact that most of these factors are unavailable in EHRs. To address this gap, we propose a series of Heckman type bias correction methods by incorporating social determinants of health selection covariates to model the EHR non-random sampling probability. Through simulations under various settings, we demonstrate the effectiveness of our proposed method in correcting biases in both the association coefficient and the outcome mean. Our method augments the utility of EHRs for public health inferences, as we show by estimating the prevalence of cardiovascular disease and its correlation with risk factors in the New York City network of EHRs.

Biomarkers and cardiovascular events in patients with stable coronary disease in the ISCHEMIA Trials.

IMPORTANCE: Biomarkers may improve prediction of cardiovascular events for patients with stable coronary artery disease (CAD), but their importance in addition to clinical tests of inducible ischemia and CAD severity is unknown. OBJECTIVES: To evaluate the prognostic value of multiple biomarkers in stable outpatients with obstructive CAD and moderate or severe inducible ischemia. DESIGN AND SETTING: The ISCHEMIA and ISCHEMIA CKD trials randomized 5,956 participants with CAD to invasive or conservative management from July 2012 to January 2018; 1,064 participated in the biorepository. MAIN OUTCOME MEASURES: Primary outcome was cardiovascular death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. Secondary outcome was cardiovascular death or MI. Improvements in prediction were assessed by cause-specific hazard ratios (HR) and area under the receiver operating characteristics curve (AUC) for an interquartile increase in each biomarker, controlling for other biomarkers, in a base clinical model of risk factors, left ventricular ejection fraction (LVEF) and ischemia severity. Secondary analyses were performed among patients in whom core-lab confirmed severity of CAD was ascertained by computed cardiac tomographic angiography (CCTA). EXPOSURES: Baseline levels of interleukin-6 (IL-6), high sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), lipoprotein a (Lp[a]), high sensitivity C-reactive protein (hsCRP), Cystatin C, soluble CD 40 ligand (sCD40L), myeloperoxidase (MPO), and matrix metalloproteinase 3 (MMP3). RESULTS: Among 757 biorepository participants, median (IQR) follow-up was 3 (2-5) years, age was 67 (61-72) years, and 144 (19%) were female; 508 had severity of CAD by CCTA available. In an adjusted multimarker model with hsTnT, GDF-15, NT-proBNP and sCD40L, the adjusted HR for the primary outcome per interquartile increase in each biomarker was 1.58 (95% CI 1.22, 2.205), 1.60 (95% CI 1.16, 2.20), 1.61 (95% 1.22, 2.14), and 1.46 (95% 1.12, 1.90), respectively. The adjusted multimarker model also improved prediction compared with the clinical model, increasing the AUC from 0.710 to 0.792 (P < .01) and 0.714 to 0.783 (P < .01) for the primary and secondary outcomes, respectively. Similar findings were observed after adjusting for core-lab confirmed atherosclerosis severity. CONCLUSIONS AND RELEVANCE: Among ISCHEMIA biorepository participants, biomarkers of myocyte injury/distension, inflammation, and platelet activity improved cardiovascular event prediction in addition to risk factors, LVEF, and assessments of ischemia and atherosclerosis severity. These biomarkers may improve risk stratification for patients with stable CAD.

Decreased basal ganglia and thalamic iron in early psychotic spectrum disorders are associated with increased psychotic and schizotypal symptoms.

Iron deficits have been reported as a risk factor for psychotic spectrum disorders (PSD). However, examinations of brain iron in PSD remain limited. The current study employed quantitative MRI to examine iron content in several iron-rich subcortical structures in 49 young adult individuals with PSD (15 schizophrenia, 17 schizoaffective disorder, and 17 bipolar disorder with psychotic features) compared with 35 age-matched healthy controls (HC). A parametric approach based on a two-pool magnetization transfer model was applied to estimate longitudinal relaxation rate (R1), which reflects both iron and myelin, and macromolecular proton fraction (MPF), which is specific to myelin. To describe iron content, a synthetic effective transverse relaxation rate (R2*) was modeled using a linear fitting of R1 and MPF. PSD patients compared to HC showed significantly reduced R1 and synthetic R2* across examined regions including the pallidum, ventral diencephalon, thalamus, and putamen areas. This finding was primarily driven by decreases in the subgroup with schizophrenia, followed by schizoaffective disorder. No significant group differences were noted for MPF between PSD and HC while for regional volume, significant reductions in patients were only observed in bilateral caudate, suggesting that R1 and synthetic R2* reductions in schizophrenia and schizoaffective patients likely reflect iron deficits that either occur independently or precede structural and myelin changes. Subcortical R1 and synthetic R2* were also found to be inversely related to positive symptoms within the PSD group and to schizotypal traits across the whole sample. These findings that decreased iron in subcortical regions are associated with PSD risk and symptomatology suggest that brain iron deficiencies may play a role in PSD pathology and warrant further study.

Natural History of Patients With Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study.

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 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. RESULTS: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 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 1 year was not significantly correlated with change in angina (ρ=0.029). CONCLUSIONS: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02347215.

Outcomes of Participants With Diabetes in the ISCHEMIA Trials.

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: Of 5900 participants with complete baseline data, the median age was 64 years (interquartile range, 57-70), 24% were female, and the median estimated glomerular filtration was 80 mL·min-1·1.73-2 (interquartile range, 64-95). Among the 2553 (43%) of participants with diabetes, the median percent hemoglobin A1c was 7% (interquartile range, 7-8), and 30% were insulin-treated. Participants with diabetes had a 49% increased hazard of death or MI (hazard ratio, 1.49 [95% CI, 1.31-1.70]; P<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.

ISCHEMIA-EXTEND studies: Rationale and design.

BACKGROUND: The ISCHEMIA and the ISCHEMIA-CKD trials found no statistical difference in the primary clinical endpoint between initial invasive management and initial conservative management of patients with chronic coronary disease and moderate to severe ischemia on stress testing without or with advanced chronic kidney disease (CKD). In ISCHEMIA, there was numerically lower cardiovascular mortality but higher non-cardiovascular mortality with no significant difference in all-cause death with an initial invasive strategy when compared with a conservative strategy. However, an invasive strategy increased peri-procedural myocardial infarction (MI) but decreased spontaneous MI with continued separation of curves over time, which potentially may lead to reduced risk of cardiovascular and all-cause mortality. Thus, the long-term effect of invasive management strategy on mortality remains unclear. In ISCHEMIA-CKD, the treatment and cause-specific mortality rates were similar during follow-up. METHODS: Funded by the National Heart, Lung, and Blood Institute, the ISCHEMIA-EXTEND observational study is the long-term follow-up of surviving participants (projected median of 10 years) with chronic coronary disease from the ISCHEMIA trial. In the ISCHEMIA trial, 5,179 participants with moderate or severe stress-induced ischemia were randomized to initial invasive management with angiography, revascularization when feasible, and guideline-directed medical therapy (GDMT), or initial conservative management with GDMT alone and angiography reserved for failure of medical therapy. ISCHEMIA-CKD EXTEND is the long-term follow-up of surviving participants (projected median of 9 years) from the ISCHEMIA-CKD trial, a companion trial that included 777 patients with advanced CKD. Ascertainment of death will be conducted via direct participant contact, medical record review, and/or vital status registry search. The overarching objective of long-term follow-up is to assess whether there are between-group differences in long-term all-cause, cardiovascular, and non-cardiovascular mortality, and increase precision around the treatment effect estimates for risk of all-cause, cardiovascular, and non-cardiovascular mortality. We will conduct Bayesian survival modeling to take advantage of rich inferences using the posterior distribution of the treatment effect. CONCLUSIONS: The long-term effect of an initial invasive versus conservative strategy on all-cause, cardiovascular, and non-cardiovascular mortality will be assessed. The findings of ISCHEMIA-EXTEND and ISCHEMIA-CKD EXTEND will inform patients, practitioners, practice guidelines, and health policy.

Predictors of outcome in the ISCHEMIA-CKD trial: Anatomy versus ischemia.

BACKGROUND: The ISCHEMIA-CKD (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease) trial found no advantage to an invasive strategy compared to conservative management in reducing all-cause death or myocardial infarction (D/MI). However, the prognostic influence of angiographic coronary artery disease (CAD) burden and ischemia severity remains unknown in this population. We compared the relative impact of CAD extent and severity of myocardial ischemia on D/MI in patients with advanced chronic kidney disease (CKD). METHODS: Participants randomized to invasive management with available data on coronary angiography and stress testing were included. Extent of CAD was defined by the number of major epicardial vessels with ≥50% diameter stenosis by quantitative coronary angiography. Ischemia severity was assessed by site investigators as moderate or severe using trial definitions. The primary endpoint was D/MI. RESULTS: Of the 388 participants, 307 (79.1%) had complete coronary angiography and stress testing data. D/MI occurred in 104/307 participants (33.9%). Extent of CAD was associated with an increased risk of D/MI (P < .001), while ischemia severity was not (P = .249). These relationships persisted following multivariable adjustment. Using 0-vessel disease (VD) as reference, the adjusted hazard ratio (HR) for 1VD was 1.86, 95% confidence interval (CI) 0.94 to 3.68, P = .073; 2VD: HR 2.13, 95% CI 1.10 to 4.12, P = .025; 3VD: HR 4.00, 95% CI 2.06 to 7.76, P < .001. Using moderate ischemia as the reference, the HR for severe ischemia was 0.84, 95% CI 0.54 to 1.30, P = .427. CONCLUSION: Among ISCHEMIA-CKD participants randomized to the invasive strategy, extent of CAD predicted D/MI whereas severity of ischemia did not.

Comparison of Prostate Imaging and Reporting Data System V2.0 and V2.1 for Evaluation of Transition Zone Lesions: A 5-Reader 202-Patient Analysis.

OBJECTIVE: The aim of the study was to compare the distribution of Prostate Imaging and Reporting Data System (PI-RADS) scores, interreader agreement, and diagnostic performance of PI-RADS v2.0 and v2.1 for transition zone (TZ) lesions. METHODS: The study included 202 lesions in 202 patients who underwent 3T prostate magnetic resonance imaging showing a TZ lesion that was later biopsied with magnetic resonance imaging/ultrasound fusion. Five abdominal imaging faculty reviewed T2-weighted imaging and high b value/apparent diffusion coefficient images in 2 sessions. Cases were randomized using a crossover design whereby half in the first session were reviewed using v2.0 and the other half using v2.1, and vice versa for the 2nd session. Readers provided T2-weighted imaging and DWI scores, from which PI-RADS scores were derived. RESULTS: Interreader agreement for all PI-RADS scores had κ of 0.37 (v2.0) and 0.26 (v2.1). For 4 readers, the percentage of lesions retrospectively scored PI-RADS 1 increased greater than 5% and PI-RADS 2 score decreased greater than 5% from v2.0 to v2.1. For 2 readers, the percentage scored PI-RADS 3 decreased greater than 5% and, for 2 readers, increased greater than 5%. The percentage of PI-RADS 4 and 5 lesions changed less than 5% for all readers. For the 4 readers with increased frequency of PI-RADS 1 using v2.1, 4% to 16% were Gleason score ≥3 + 4 tumor. Frequency of Gleason score ≥3 + 4 in PI-RADS 3 lesions increased for 2 readers and decreased for 1 reader. Sensitivity of PI-RADS of 3 or greater for Gleason score ≥3 + 4 ranged 76% to 90% (v2.0) and 69% to 96% (v2.1). Specificity ranged 32% to 64% (v2.0) and 25% to 72% (v2.1). Positive predictive value ranged 43% to 55% (v2.0) and 41% to 58% (v2.1). Negative predictive value ranged 82% to 87% (v2.0) and 81% to 91% (v2.1). CONCLUSIONS: Poor interreader agreement and lack of improvement in diagnostic performance indicate an ongoing need to refine evaluation of TZ lesions.

Accelerated single-shot T2-weighted fat-suppressed (FS) MRI of the liver with deep learning-based image reconstruction: qualitative and quantitative comparison of image quality with conventional T2-weighted FS sequence.

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: • 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.

Residential Racial Isolation and Spatial Patterning of Type 2 Diabetes Mellitus in Durham, North Carolina.

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.

Assessing Geographic Variation in Strabismus Diagnosis among Children Enrolled in Medicaid.

PURPOSE: To determine how strabismus diagnosis varies within a given community and across communities among children with Medicaid health insurance. DESIGN: Retrospective cohort analysis. PARTICIPANTS: Children aged ≤10 years enrolled in Medicaid in Michigan or North Carolina during 2009. METHODS: Children who met the study inclusion criteria were identified from the Medicaid Analytic Extract database, which includes claims data for all children enrolled in Medicaid throughout the United States. Residential location was determined by the last known 5-digit ZIP code for each child, which was linked to the centroid of a ZIP Code Tabulation Area (ZCTA) for geo-referencing and spatial analyses. International Classification of Diseases, 9th Revision, Clinical Modification billing codes were used to identify children diagnosed with strabismus (code 378.xx). Bayesian hierarchical intrinsic conditional autoregressive spatial probit models were used to determine the risk of a child receiving a strabismus diagnosis in communities throughout Michigan and North Carolina. Maps display communities (ZCTAs) where the 95% credible intervals for the spatial random effects estimates do not cross zero, allowing for identification of locations with increased and decreased strabismus diagnosis risk relative to other communities in the states. MAIN OUTCOME MEASURES: Likelihood of receiving a diagnosis of strabismus. RESULTS: In 2009, among 519 212 eligible children in Michigan, 7535 (1.5%) received ≥1 strabismus diagnosis, and in North Carolina, 5827 of 523 886 eligible children (1.1%) were diagnosed with strabismus. In both states, the proportion receiving a strabismus diagnosis among black (0.9% in Michigan; 0.7% in North Carolina) and Hispanic (1.1% in Michigan; 0.8% in North Carolina) children was lower than the proportion for white children (1.8% in Michigan; 1.6% in North Carolina). Children living in poorer communities in both states were less likely to be diagnosed with strabismus independent of their race/ethnicity. CONCLUSIONS: A child's likelihood of being diagnosed with strabismus is associated with characteristics of the residential community where he or she resides. The findings of this study highlight the importance of ensuring that children who live in less affluent communities have access to the necessary services and eye care professionals to properly diagnose and treat them for this condition.

Implications of construction method and spatial scale on measures of the built environment.

BACKGROUND: Research surrounding the built environment (BE) and health has resulted in inconsistent findings. Experts have identified the need to examine methodological choices, such as development and testing of BE indices at varying spatial scales. We sought to examine the impact of construction method and spatial scale on seven measures of the BE using data collected at two time points. METHODS: The Children's Environmental Health Initiative conducted parcel-level assessments of 57 BE variables in Durham, NC (parcel N = 30,319). Based on a priori defined variable groupings, we constructed seven mutually exclusive BE domains (housing damage, property disorder, territoriality, vacancy, public nuisances, crime, and tenancy). Domain-based indices were developed according to four different index construction methods that differentially account for number of parcels and parcel area. Indices were constructed at the census block level and two alternative spatial scales that better depict the larger neighborhood context experienced by local residents: the primary adjacency community and secondary adjacency community. Spearman's rank correlation was used to assess if indices and relationships among indices were preserved across methods. RESULTS: Territoriality, public nuisances, and tenancy were weakly to moderately preserved across methods at the block level while all other indices were well preserved. Except for the relationships between public nuisances and crime or tenancy, and crime and housing damage or territoriality, relationships among indices were poorly preserved across methods. The number of indices affected by construction method increased as spatial scale increased, while the impact of construction method on relationships among indices varied according to spatial scale. CONCLUSIONS: We found that the impact of construction method on BE measures was index and spatial scale specific. Operationalizing and developing BE measures using alternative methods at varying spatial scales before connecting to health outcomes allows researchers to better understand how methodological decisions may affect associations between health outcomes and BE measures. To ensure that associations between the BE and health outcomes are not artifacts of methodological decisions, researchers would be well-advised to conduct sensitivity analysis using different construction methods. This approach may lead to more robust results regarding the BE and health outcomes.

Racial residential segregation and preterm birth: built environment as a mediator.

BACKGROUND: Racial residential segregation has been associated with preterm birth. Few studies have examined mediating pathways, in part because, with binary outcomes, indirect effects estimated from multiplicative models generally lack causal interpretation. We develop a method to estimate additive-scale natural direct and indirect effects from logistic regression. We then evaluate whether segregation operates through poor-quality built environment to affect preterm birth. METHODS: To estimate natural direct and indirect effects, we derive risk differences from logistic regression coefficients. Birth records (2000-2008) for Durham, North Carolina, were linked to neighborhood-level measures of racial isolation and a composite construct of poor-quality built environment. We decomposed the total effect of racial isolation on preterm birth into direct and indirect effects. RESULTS: The adjusted total effect of an interquartile increase in racial isolation on preterm birth was an extra 27 preterm events per 1000 births (risk difference = 0.027 [95% confidence interval = 0.007 to 0.047]). With poor-quality built environment held at the level it would take under isolation at the 25th percentile, the direct effect of an interquartile increase in isolation was 0.022 (-0.001 to 0.042). Poor-quality built environment accounted for 35% (11% to 65%) of the total effect. CONCLUSION: Our methodology facilitates the estimation of additive-scale natural effects with binary outcomes. In this study, the total effect of racial segregation on preterm birth was partially mediated by poor-quality built environment.

Model-based estimation of individual-level social determinants of health and its applications in All of Us.

OBJECTIVES: We introduce a widely applicable model-based approach for estimating individual-level Social Determinants of Health (SDoH) and evaluate its effectiveness using the All of Us Research Program. MATERIALS AND METHODS: Our approach utilizes aggregated SDoH datasets to estimate individual-level SDoH, demonstrated with examples of no high school diploma (NOHSDP) and no health insurance (UNINSUR) variables. Models are estimated using American Community Survey data and applied to derive individual-level estimates for All of Us participants. We assess concordance between model-based SDoH estimates and self-reported SDoHs in All of Us and examine associations with undiagnosed hypertension and diabetes. RESULTS: Compared to self-reported SDoHs, the area under the curve for NOHSDP is 0.727 (95% CI, 0.724-0.730) and for UNINSUR is 0.730 (95% CI, 0.727-0.733) among the 329 074 All of Us participants, both significantly higher than aggregated SDoHs. The association between model-based NOHSDP and undiagnosed hypertension is concordant with those estimated using self-reported NOHSDP, with a correlation coefficient of 0.649. Similarly, the association between model-based NOHSDP and undiagnosed diabetes is concordant with those estimated using self-reported NOHSDP, with a correlation coefficient of 0.900. DISCUSSION AND CONCLUSION: The model-based SDoH estimation method offers a scalable and easily standardized approach for estimating individual-level SDoHs. Using the All of Us dataset, we demonstrate reasonable concordance between model-based SDoH estimates and self-reported SDoHs, along with consistent associations with health outcomes. Our findings also underscore the critical role of geographic contexts in SDoH estimation and in evaluating the association between SDoHs and health outcomes.

Comparison of intra- and inter-reader agreement of abbreviated versus comprehensive MRCP for pancreatic cyst surveillance.

OBJECTIVE: To retrospectively compare inter- and intra-reader agreement of abbreviated MRCP (aMRCP) with comprehensive MRI (cMRCP) protocol for detection of worrisome features, high-risk stigmata, and concomitant pancreatic cancer in pancreatic cyst surveillance. METHODS: 151 patients (104 women, mean age: 69[10] years) with baseline and follow-up contrast-enhanced MRIs were included. This comprised 138 patients under cyst surveillance with 5-year follow-up showing no pancreatic ductal adenocarcinoma (PDAC), 6 with pancreatic cystic lesion-derived malignancy, and 7 with concomitant PDAC. The aMRCP protocol used four sequences (axial and coronal Half-Fourier Single-shot Turbo-spin-Echo, axial T1 fat-saturated pre-contrast, and 3D-MRCP), while cMRCP included all standard sequences, including post-contrast. Three blinded abdominal radiologists assessed baseline cyst characteristics, worrisome features, high-risk stigmata, and PDAC signs using both aMRCP and cMRCP, with a 2-week washout period. Intra- and inter-reader agreement were calculated using Fleiss' multi-rater kappa and Intra-class Correlation Coefficient (ICC). 95% confidence intervals (CI) were calculated. RESULTS: Cyst size, growth, and abrupt main pancreatic duct transition had strong intra- and inter-reader agreement. Intra-reader agreement was ICC = 0.93-0.99 for cyst size, ICC = 0.71-1.00 for cyst growth, and kappa = 0.83-1.00 for abrupt duct transition. Inter-reader agreement for cyst size was ICC = 0.86 (aMRCP) and ICC = 0.83 (cMRCP), and for abrupt duct transition was kappa = 0.84 (aMRCP) and kappa = 0.69 (cMRCP). Thickened cyst wall, mural nodule and cyst-duct communication demonstrated varying intra-reader agreements and poor inter-reader agreements. CONCLUSION: aMRCP showed high intra- and inter-reader agreement for most pancreatic cyst parameters that highly rely on T2-weighted sequences.

Trends in Racial and Ethnic Disparities in Early Glycemic Control Among Veterans Receiving Care in the Veterans Health Administration, 2008-2019.

OBJECTIVE: Racial and ethnic disparities in glycemic control among non-Hispanic Black (NHB) and non-Hispanic White (NHW) veterans with type 2 diabetes (T2D) have been reported. This study examined trends in early glycemic control by race and ethnicity to understand how disparities soon after T2D diagnosis have changed between 2008 and 2019 among cohorts of U.S. veterans with newly diagnosed T2D. RESEARCH DESIGN AND METHODS: We estimated the annual percentage of early glycemic control (average A1C <7%) in the first 5 years after diagnosis among 837,023 veterans (95% male) with newly diagnosed T2D in primary care. We compared early glycemic control by racial and ethnic group among cohorts defined by diagnosis year (2008-2010, 2011-2013, 2014-2016, and 2017-2018) using mixed-effects models with random intercepts. We estimated odds ratios of early glycemic control comparing racial and ethnic groups with NHW, adjusting for age, sex, and years since diagnosis. RESULTS: The average annual percentage of veterans who achieved early glycemic control during follow-up was 73%, 72%, 72%, and 76% across the four cohorts, respectively. All racial and ethnic groups were less likely to achieve early glycemic control compared with NHW veterans in the 2008-2010 cohort. In later cohorts, NHB and Hispanic veterans were more likely to achieve early glycemic control; however, Hispanic veterans were also more likely to have an A1C ≥9% within 5 years in all cohorts. Early glycemic control disparities for non-Hispanic Asian, Native Hawaiian/Pacific Islander, and American Indian/Alaska Native veterans persisted in cohorts until the 2017-2018 cohort. CONCLUSIONS: Overall early glycemic control trends among veterans with newly diagnosed T2D have been stable since 2008, but trends differed by racial and ethnic groups and disparities in very poor glycemic control were still observed. Efforts should continue to minimize disparities among racial and ethnic groups.

Addressing Information Biases Within Electronic Health Record Data to Improve the Examination of Epidemiologic Associations With Diabetes Prevalence Among Young Adults: Cross-Sectional Study.

Background: Electronic health records (EHRs) are increasingly used for epidemiologic research to advance public health practice. However, key variables are susceptible to missing data or misclassification within EHRs, including demographic information or disease status, which could affect the estimation of disease prevalence or risk factor associations. Objective: In this paper, we applied methods from the literature on missing data and causal inference to assess whether we could mitigate information biases when estimating measures of association between potential risk factors and diabetes among a patient population of New York City young adults. Methods: We estimated the odds ratio (OR) for diabetes by race or ethnicity and asthma status using EHR data from NYU Langone Health. Methods from the missing data and causal inference literature were then applied to assess the ability to control for misclassification of health outcomes in the EHR data. We compared EHR-based associations with associations observed from 2 national health surveys, the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health and Nutrition Examination Survey, representing traditional public health surveillance systems. Results: Observed EHR-based associations between race or ethnicity and diabetes were comparable to health survey-based estimates, but the association between asthma and diabetes was significantly overestimated (OREHR 3.01, 95% CI 2.86-3.18 vs ORBRFSS 1.23, 95% CI 1.09-1.40). Missing data and causal inference methods reduced information biases in these estimates, yielding relative differences from traditional estimates below 50% (ORMissingData 1.79, 95% CI 1.67-1.92 and ORCausal 1.42, 95% CI 1.34-1.51). Conclusions: Findings suggest that without bias adjustment, EHR analyses may yield biased measures of association, driven in part by subgroup differences in health care use. However, applying missing data or causal inference frameworks can help control for and, importantly, characterize residual information biases in these estimates.

Demographic and geographic distribution of diabetes and pre-diabetes risk in rural settings: results from a cross-sectional, countywide rural health survey in Sullivan County, New York.

OBJECTIVE: To perform a detailed characterisation of diabetes burden and pre-diabetes risk in a rural county with previously documented poor health outcomes in order to understand the local within-county distribution of diabetes in rural areas of America. DESIGN, SETTING, AND PARTICIPANTS: In 2021, we prospectively mailed health surveys to all households in Sullivan County, a rural county with the second-worst health outcomes of all counties in New York State. Our survey included questions on demographics, medical history and the American Diabetes Association's Pre-diabetes Risk Test. PRIMARY OUTCOME AND METHODS: Our primary outcome was an assessment of diabetes burden within this rural county. To help mitigate non-response bias in our survey, raking adjustments were performed across strata of age, sex, race/ethnicity and health insurance. We analysed diabetes prevalence by demographic characteristics and used geospatial analysis to assess for clustering of diagnosed diabetes cases. RESULTS: After applying raking procedures for the 4725 survey responses, our adjusted diagnosed diabetes prevalence for Sullivan County was 12.9% compared with the 2019 Behavioural Risk Factor Surveillance System (BRFSS) estimate of 8.6%. In this rural area, diagnosed diabetes prevalence was notably higher among non-Hispanic Black (21%) and Hispanic (15%) residents compared with non-Hispanic White (12%) residents. 53% of respondents without a known history of pre-diabetes or diabetes scored as high risk for pre-diabetes. Nearest neighbour analyses revealed that hotspots of diagnosed diabetes were primarily located in the more densely populated areas of this rural county. CONCLUSIONS: Our mailed health survey to all residents in Sullivan County demonstrated higher diabetes prevalence compared with modelled BRFSS estimates that were based on small telephone samples. Our results suggest the need for better diabetes surveillance in rural communities, which may benefit from interventions specifically tailored for improving glycaemic control among rural residents.