FLT3ITD drives context-specific changes in cell identity and variable interferon dependence during AML initiation.

Acute myeloid leukemia (AML) initiation requires multiple rate-limiting mutations to cooperatively reprogram progenitor cell identity. For example, FLT3 internal tandem duplication (FLT3ITD) mutations cooperate with a variety of different initiating mutations to reprogram myeloid progenitor fate. These initiating mutations often skew toward either pediatric or adult AML patient populations, though FLT3ITD itself occurs at similar frequencies in both age groups. This raises the question of whether FLT3ITD might induce distinct transcriptional programs and unmask distinct therapeutic vulnerabilities when paired with pediatric, as opposed to adult AML-initiating mutations. To explore this possibility, we compared AML evolution in mice that carried Flt3ITD/NUP98-HOXD13 (NHD13) or Flt3ITD/Runx1DEL mutation pairs, which are respectively most common in pediatric and adult AML. Single-cell analyses and epigenome profiling revealed distinct interactions between Flt3ITD and its cooperating mutations. Whereas Flt3ITD and Flt3ITD/Runx1DEL caused aberrant expansion of myeloid progenitors, Flt3ITD/NHD13 drove the emergence of a pre-AML population that did not resemble normal hematopoietic progenitors. Differences between Flt3ITD/Runx1DEL and Flt3ITD/NHD13 cooperative target gene expression extended to fully transformed AML as well. Flt3ITD/NHD13 cooperative target genes were enriched in human NUP98-translocated AML. Flt3ITD/NHD13 selectively hijacked type I interferon signaling to drive expansion of the pre-AML population. Blocking interferon signaling delayed AML initiation and extended survival. Thus, common AML driver mutations, such as FLT3ITD, can coopt different mechanisms of transformation in different genetic contexts. Furthermore, pediatric-biased NUP98 fusions convey actionable interferon dependence.

Poly(lactic-co-glycolic acid) Microparticles for the Delivery of Model Drug Compounds for Applications in Vascular Tissue Engineering.

Localized delivery of angiogenesis-promoting factors such as small molecules, nucleic acids, peptides, and proteins to promote the repair and regeneration of damaged tissues remains a challenge in vascular tissue engineering. Current delivery methods such as direct administration of therapeutics can fail to maintain the necessary sustained release profile and often rely on supraphysiologic doses to achieve the desired therapeutic effect. By implementing a microparticle delivery system, localized delivery can be coupled with sustained controlled release to mitigate the risks involved with the high dosages currently required from direct therapeutic administration. For this purpose, poly(lactic-co-glycolic acid) microparticles were fabricated via antisolvent microencapsulation and the loading, release, and delivery of model angiogenic molecules specifically a small molecule, nucleic acid, and protein, were assessed in vitro using microvascular fragments (MVF). The microencapsulation approach utilized enabled rapid spherical particle formation and encapsulation of model drugs of different sizes, all in one method. The addition of a fibrin scaffold, required for the culture of the MVFs, reduced the initial burst of model drugs, observed in release profiles from PLGA alone. Lastly, in vitro studies using MVFs demonstrated that higher concentrations of microparticles led to greater co-localization of the model therapeutic (miRNA) with MVFs, which is vital for targeted delivery methods. It was also found that the biodistribution of miRNA using the delivered microparticle system was enhanced compared to direct administration. Overall, poly(lactic-co-glycolic acid) microparticles, formulated and loaded with model therapeutic compounds in one step, resulted in improved biodistribution in a model of the vasculature leading to a future in translational revascularization.

Associations between PM2.5 and O3 exposures and new onset type 2 diabetes in regional and national samples in the United States.

BACKGROUND: Exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and ozone (O3) has been linked to numerous harmful health outcomes. While epidemiologic evidence has suggested a positive association with type 2 diabetes (T2D), there is heterogeneity in findings. We evaluated exposures to PM2.5 and O3 across three large samples in the US using a harmonized approach for exposure assignment and covariate adjustment. METHODS: Data were obtained from the Veterans Administration Diabetes Risk (VADR) cohort (electronic health records [EHRs]), the Reasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort (primary data collection), and the Geisinger health system (EHRs), and reflect the years 2003-2016 (REGARDS) and 2008-2016 (VADR and Geisinger). New onset T2D was ascertained using EHR information on medication orders, laboratory results, and T2D diagnoses (VADR and Geisinger) or report of T2D medication or diagnosis and/or elevated blood glucose levels (REGARDS). Exposure was assigned using pollutant annual averages from the Downscaler model. Models stratified by community type (higher density urban, lower density urban, suburban/small town, or rural census tracts) evaluated likelihood of new onset T2D in each study sample in single- and two-pollutant models of PM2.5 and O3. RESULTS: In two pollutant models, associations of PM2.5, and new onset T2D were null in the REGARDS cohort except for in suburban/small town community types in models that also adjusted for NSEE, with an odds ratio (95% CI) of 1.51 (1.01, 2.25) per 5 µg/m3 of PM2.5. Results in the Geisinger sample were null. VADR sample results evidenced nonlinear associations for both pollutants; the shape of the association was dependent on community type. CONCLUSIONS: Associations between PM2.5, O3 and new onset T2D differed across three large study samples in the US. None of the results from any of the three study populations found strong and clear positive associations.

Disparities in routine healthcare utilization disruptions during COVID-19 pandemic among veterans with type 2 diabetes.

BACKGROUND: While emerging studies suggest that the COVID-19 pandemic caused disruptions in routine healthcare utilization, the full impact of the pandemic on healthcare utilization among diverse group of patients with type 2 diabetes is unclear. The purpose of this study is to examine trends in healthcare utilization, including in-person and telehealth visits, among U.S. veterans with type 2 diabetes before, during and after the onset of the COVID-19 pandemic, by demographics, pre-pandemic glycemic control, and geographic region. METHODS: We longitudinally examined healthcare utilization in a large national cohort of veterans with new diabetes diagnoses between January 1, 2008 and December 31, 2018. The analytic sample was 733,006 veterans with recently-diagnosed diabetes, at least 1 encounter with veterans administration between March 2018-2020, and followed through March 2021. Monthly rates of glycohemoglobin (HbA1c) measurements, in-person and telehealth outpatient visits, and prescription fills for diabetes and hypertension medications were compared before and after March 2020 using interrupted time-series design. Log-linear regression model was used for statistical analysis. Secular trends were modeled with penalized cubic splines. RESULTS: In the initial 3 months after the pandemic onset, we observed large reductions in monthly rates of HbA1c measurements, from 130 (95%CI,110-140) to 50 (95%CI,30-80) per 1000 veterans, and in-person outpatient visits, from 1830 (95%CI,1640-2040) to 810 (95%CI,710-930) per 1000 veterans. However, monthly rates of telehealth visits doubled between March 2020-2021 from 330 (95%CI,310-350) to 770 (95%CI,720-820) per 1000 veterans. This pattern of increases in telehealth utilization varied by community type, with lowest increase in rural areas, and by race/ethnicity, with highest increase among non-hispanic Black veterans. Combined in-person and telehealth outpatient visits rebounded to pre-pandemic levels after 3 months. Despite notable changes in HbA1c measurements and visits during that initial window, we observed no changes in prescription fills rates. CONCLUSIONS: Healthcare utilization among veterans with diabetes was substantially disrupted at the onset of the pandemic, but rebounded after 3 months. There was disparity in uptake of telehealth visits by geography and race/ethnicity.

Addressing Financial Barriers to Health Care Among People Who are Low-Income and Insured in New York City, 2014-2017.

While health care-associated financial burdens among uninsured individuals are well described, few studies have systematically characterized the array of financial and logistical complications faced by insured individuals with low household incomes. In this mixed methods paper, we conducted 6 focus groups with a total of 55 residents and analyzed programmatic administrative records to characterize the specific financial and logistic barriers faced by residents living in public housing in East and Central Harlem, New York City (NYC). Participants included individuals who enrolled in a municipal community health worker (CHW) program designed to close equity gaps in health and social outcomes. Dedicated health advocates (HAs) were explicitly paired with CHWs to provide health insurance and health care navigational assistance. We describe the needs of 150 residents with reported financial barriers to care, as well as the navigational and advocacy strategies taken by HAs to address them. Finally, we outline state-level policy recommendations to help ameliorate the problems experienced by participants. The model of paired CHW-HAs may be helpful in addressing financial barriers for insured populations with low household income and reducing health disparities in other communities.

Impact of land use and food environment on risk of type 2 diabetes: A national study of veterans, 2008-2018.

BACKGROUND: Large-scale longitudinal studies evaluating influences of the built environment on risk for type 2 diabetes (T2D) are scarce, and findings have been inconsistent. OBJECTIVE: To evaluate whether land use environment (LUE), a proxy of neighborhood walkability, is associated with T2D risk across different US community types, and to assess whether the association is modified by food environment. METHODS: The Veteran's Administration Diabetes Risk (VADR) study is a retrospective cohort of diabetes-free US veteran patients enrolled in VA primary care facilities nationwide from January 1, 2008, to December 31, 2016, and followed longitudinally through December 31, 2018. A total of 4,096,629 patients had baseline addresses available in electronic health records that were geocoded and assigned a census tract-level LUE score. LUE scores were divided into quartiles, where a higher score indicated higher neighborhood walkability levels. New diagnoses for T2D were identified using a published computable phenotype. Adjusted time-to-event analyses using piecewise exponential models were fit within four strata of community types (higher-density urban, lower-density urban, suburban/small town, and rural). We also evaluated effect modification by tract-level food environment measures within each stratum. RESULTS: In adjusted analyses, higher LUE had a protective effect on T2D risk in rural and suburban/small town communities (linear quartile trend test p-value <0.001). However, in lower density urban communities, higher LUE increased T2D risk (linear quartile trend test p-value <0.001) and no association was found in higher density urban communities (linear quartile trend test p-value = 0.317). Particularly strong protective effects were observed for veterans living in suburban/small towns with more supermarkets and more walkable spaces (p-interaction = 0.001). CONCLUSION: Among veterans, LUE may influence T2D risk, particularly in rural and suburban communities. Food environment may modify the association between LUE and T2D.

Synthesis and bioconjugation of alkanethiol-stabilized gold bipyramid nanoparticles.

Gold bipyramid (GBP) nanoparticles are promising for a range of biomedical applications, including biosensing and surface-enhanced Raman spectroscopy, due to their favorable optical properties and ease of chemical functionalization. Here we report improved synthesis methods, including preparation of gold seed particles with an increased shelf life of ∼1 month, and preparation of GBPs with significantly shortened synthesis time (< 1 h). We also report methods for the functionalization and bioconjugation of the GBPs, including functionalization with alkanethiol self-assembled monolayers (SAMs) and bioconjugation with proteins via carbodiimide cross-linking. Binding of specific antibodies to the nanoparticle-bound proteins was subsequently observed via localized surface plasmon resonance sensing. Rabbit IgG and goat anti-Rabbit IgG antibodies were used as a model system for antibody-antigen interactions. As-synthesized, SAM-functionalized, and bioconjugated bipyramids were characterized using scanning electron microscopy, UV-vis spectroscopy, zeta potential, and dynamic light scattering.

Feasibility and Outcomes of an Electronic Health Record Intervention to Improve Hypertension Management in Immigrant-serving Primary Care Practices.

BACKGROUND: South Asians experience a disproportionate burden of high blood pressure (BP) in the United States, arguably the most preventable risk factor for cardiovascular disease. OBJECTIVE: We report 12-month results of an electronic health record (EHR)-based intervention, as a component of a larger project, "Implementing Million Hearts for Provider and Community Transformation." The EHR intervention included launching hypertension patient registries and implementing culturally tailored alerts and order sets to improve hypertension control among patients treated in 14 New York City practices located in predominantly South Asian immigrant neighborhoods. DESIGN: Using a modified stepped-wedge quasi-experimental study design, practice-level EHR data were extracted, and individual-level data were obtained on a subset of patients insured by a Medicaid insurer via their data warehouse. The primary aggregate outcome was change in proportion of hypertensive patients with controlled BP; individual-level outcomes included average systolic BP (SBP) and diastolic BP (DBP) at last clinic visit. Qualitative interviews were conducted to assess intervention feasibility. MEASURES: Hypertension was defined as having at least 1 hypertension ICD-9/10 code. Well-controlled hypertension was defined as SBP<140 and DBP<90 mm Hg. RESULTS: Postintervention, we observed a significant improvement in hypertension control at the practice level, adjusting for age and sex patient composition (adjusted relative risk, 1.09; 95% confidence interval, 1.04-1.14). Among the subset of Medicaid patients, we observed a significant reduction in average SBP and DBP adjusting for time, age, and sex, by 1.71 and 1.13 mm Hg, respectively (P<0.05). Providers reported feeling supported and satisfied with EHR components. CONCLUSIONS: EHR initiatives in practices serving immigrants and minorities may enhance practice capabilities to improve hypertension control.

Liquid Chromatography Separation and Mass Spectrometry Detection of Silver-Lipoate Ag29(LA)12 Nanoclusters: Evidence of Isomerism in the Solution Phase.

Evidence for the existence of condensed-phase isomers of silver-lipoate clusters, Ag29(LA)12, where LA = (R)-α lipoic acid, was obtained by reversed-phase ion-pair liquid chromatography with in-line UV-vis and electrospray ionization (ESI)-MS detection. All components of a raw mixture were separated according to surface chemistry and increasing size via reversed-phase gradient HPLC methods and identified by their corresponding m/z ratio by ESI in the negative ionization mode. Aqueous and methanol mobile-phase mixtures, each containing 400 mM hexafluoroisopropanol (HFIP)-15 mM triethylamine (TEA), were employed to facilitate the interaction between the clusters and stationary phase via formation of ion-pairs. TEA-HFIP (triethylammonium-hexafluoroisopropoxide) had been shown to provide superior chromatographic peak shape and mass spectral signal compared with alternative modifiers such as TEAA (triethylammonium-acetate) for analysis of oligonucleotide samples. Liquid chromatographic separation prior to mass spectrometry detection facilitated sample analysis by production of simplified mass spectra for each eluting cluster species and provided insight into the existence of at least two major solution-phase isomers of Ag29(LA)12. UV-vis detection in-line with ESI analysis provided independent confirmation of the existence of the isomers and their similar electronic structure as judged from their identical optical spectra in the 300-500 nm range. [Diastereomerism provides a possible interpretation for the near-equal abundance of the two forms, based on a structurally defined nonaqueous homologue.].

Protocol for project IMPACT (improving millions hearts for provider and community transformation): a quasi-experimental evaluation of an integrated electronic health record and community health worker intervention study to improve hypertension management among South Asian patients.

BACKGROUND: The Million Hearts® initiative aims to prevent heart disease and stroke in the United States by mobilizing public and private sectors around a core set of objectives, with particular attention on improving blood pressure control. South Asians in particular have disproportionately high rates of hypertension and face numerous cultural, linguistic, and social barriers to accessing healthcare. Interventions utilizing Health information technology (HIT) and community health worker (CHW)-led patient coaching have each been demonstrated to be effective at advancing Million Hearts® goals, yet few studies have investigated the potential impact of integrating these strategies into a clinical-community linkage initiative. Building upon this initiative, we present the protocol and preliminary results of a research study, Project IMPACT, designed to fill this gap in knowledge. METHODS: Project IMPACT is a stepped wedge quasi-experimental study designed to test the feasibility, adoption, and impact of integrating CHW-led health coaching with electronic health record (EHR)-based interventions to improve hypertension control among South Asian patients in New York City primary care practices. EHR intervention components include the training and implementation of hypertension-specific registry reports, alerts, and order sets. Fidelity to the EHR intervention is assessed by collecting the type, frequency, and utilization of intervention components for each practice. CHW intervention components consist of health coaching sessions on hypertension and related risk factors for uncontrolled hypertensive patients. The outcome, hypertension control (<140 mmHg systolic blood pressure (BP) and <90 mmHg diastolic BP), is collected at the aggregate- and individual-level for all 16 clinical practices enrolled. DISCUSSION: Project IMPACT builds upon the evidence base of the effectiveness of CHW and Million Hearts® initiatives and proposes a unique integration of provider-based EHR and community-based CHW interventions. The project informs the effectiveness of these interventions in team-based care approaches, thereby, helping to develop relevant sustainability strategies for improving hypertension control among targeted racial/ethnic minority populations at small primary care practices. TRIAL REGISTRATION: This study protocol has been approved and is made available on Clinicaltrials.gov by NCT03159533 as of May 17, 2017.

Predictors of Human Papillomavirus Vaccine Completion Among Female and Male Vaccine Initiators in Family Planning Centers.

OBJECTIVES: We estimated human papillomavirus (HPV) vaccine series completion and examined predictors of completion among adolescents and young adults in a large family planning network. METHODS: Our retrospective cohort study of vaccine completion within 12 months and time to completion used electronic health record data from 119 Planned Parenthood health centers in 11 US states for 9648 patients who initiated HPV vaccination between January 2011 and January 2013. RESULTS: Among vaccine initiators, 29% completed the series within 12 months. Patients who were male, younger than 22 years, or non-Hispanic Black or who had public insurance were less likely to complete within 12 months and completed more slowly than their counterparts. Gender appeared to modify the effect of public versus private insurance on completion (adjusted hazard ratio = 0.76 for women and 0.95 for men; relative excess risk due to interaction = 0.41; 95% confidence interval = 0.09, 0.73). CONCLUSIONS: Completion was low yet similar to previous studies conducted in safety net settings.

Avatrombopag treatment response in patients with immune thrombocytopenia: the REAL-AVA 1.0 study.

Background: Thrombopoietin-receptor agonists (TPO-RAs) are used to treat immune thrombocytopenia (ITP), a disorder characterized by prolonged low platelet counts (PCs) that pose a risk of serious bleeding episodes. Avatrombopag (AVA) is the most recently approved TPO-RA for the treatment of chronic ITP. A high proportion of patients responded to AVA in clinical trials, and treatment was well-tolerated; however, limited real-world effectiveness data have been reported to date. Objectives: To describe demographic and clinical characteristics, treatment patterns, and outcomes following the initiation of AVA in patients with ITP in the United States. Design: This is a retrospective study using administrative claims data from the Komodo Healthcare Map (1 February 2017 to 28 February 2022) linked with PC laboratory data. Methods: Patients with ⩾1 diagnosis of ITP, ⩾1 paid prescription for AVA (index date), and ⩾1 month of pharmacy coverage after AVA initiation were selected. Baseline characteristics and follow-up steroid, immunosuppressant, and rescue medication use were described. The percentage of patients achieving clinically meaningful PC thresholds (⩾30 × 109/l) were assessed among patients with ⩾1 PC following AVA initiation and prior to AVA discontinuation/switch (effectiveness subgroup). Results: A total of 205 patients met eligibility criteria and 49% reported TPO-RA use in the prior 6 months. Approximately 70% and 93% of patients did not require use of steroid or immunoglobulin rescue medication during follow-up, respectively. Among patients with concomitant steroid (n = 75) or immunosuppressant (n = 7) use at AVA initiation, 35% and 57% discontinued those treatments, respectively. Of the 21 patients in the effectiveness subgroup, 81% achieved clinically meaningful PC thresholds. Conclusion: A high proportion of evaluable patients with ITP in this real-world study achieved clinically meaningful PCs, without requiring rescue medication during AVA treatment, with many able to discontinue baseline concomitant steroid or immunosuppressant utilization. Despite limited availability of PC data, these results are consistent with results from the AVA pivotal clinical trials.

Integrating Community Health Workers into Community-Based Primary Care Practice Settings to Improve Blood Pressure Control Among South Asian Immigrants in New York City: Results from a Randomized Control Trial.

BACKGROUND: Blood pressure (BP) control is suboptimal in minority communities, including Asian populations. We evaluate the feasibility, adoption, and effectiveness of an integrated CHW-led health coaching and practice-level intervention to improve hypertension control among South Asian patients in New York City, Project IMPACT (Integrating Million Hearts for Provider and Community Transformation). The primary outcome was BP control, and secondary outcomes were systolic BP and diastolic BP at 6-month follow-up. METHODS: A randomized-controlled trial took place within community-based primary care practices that primarily serve South Asian patients in New York City between 2017 and 2019. A total of 303 South Asian patients aged 18-85 with diagnosed hypertension and uncontrolled BP (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg) within the previous 6 months at 14 clinic sites consented to participate. After completing 1 education session, individuals were randomized into treatment (n=159) or control (n=144) groups. Treatment participants received 4 additional group education sessions and individualized health coaching over a 6-month period. A mixed effect generalized linear model with a logit link function was used to assess intervention effectiveness for controlled hypertension (Yes/No), adjusting for practice level random effect, age, sex, baseline systolic BP, and days between BP measurements. RESULTS: Among the total enrolled population, mean age was 56.8±11.2 years, and 54.1% were women. At 6 months among individuals with follow-up BP data (treatment, n=154; control, n=137), 68.2% of the treatment group and 41.6% of the control group had controlled BP (P<0.001). In final adjusted analysis, treatment group participants had 3.7 [95% CI, 2.1-6.5] times the odds of achieving BP control at follow-up compared with the control group. CONCLUSIONS: A CHW-led health coaching intervention was effective in achieving BP control among South Asian Americans in New York City primary care practices. Findings can guide translation and dissemination of this model across other communities experiencing hypertension disparities. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03159533.

Mediation of an association between neighborhood socioeconomic environment and type 2 diabetes through the leisure-time physical activity environment in an analysis of three independent samples.

INTRODUCTION: Inequitable access to leisure-time physical activity (LTPA) resources may explain geographic disparities in type 2 diabetes (T2D). We evaluated whether the neighborhood socioeconomic environment (NSEE) affects T2D through the LTPA environment. RESEARCH DESIGN AND METHODS: We conducted analyses in three study samples: the national Veterans Administration Diabetes Risk (VADR) cohort comprising electronic health records (EHR) of 4.1 million T2D-free veterans, the national prospective cohort REasons for Geographic and Racial Differences in Stroke (REGARDS) (11 208 T2D free), and a case-control study of Geisinger EHR in Pennsylvania (15 888 T2D cases). New-onset T2D was defined using diagnoses, laboratory and medication data. We harmonized neighborhood-level variables, including exposure, confounders, and effect modifiers. We measured NSEE with a summary index of six census tract indicators. The LTPA environment was measured by physical activity (PA) facility (gyms and other commercial facilities) density within street network buffers and population-weighted distance to parks. We estimated natural direct and indirect effects for each mediator stratified by community type. RESULTS: The magnitudes of the indirect effects were generally small, and the direction of the indirect effects differed by community type and study sample. The most consistent findings were for mediation via PA facility density in rural communities, where we observed positive indirect effects (differences in T2D incidence rates (95% CI) comparing the highest versus lowest quartiles of NSEE, multiplied by 100) of 1.53 (0.25, 3.05) in REGARDS and 0.0066 (0.0038, 0.0099) in VADR. No mediation was evident in Geisinger. CONCLUSIONS: PA facility density and distance to parks did not substantially mediate the relation between NSEE and T2D. Our heterogeneous results suggest that approaches to reduce T2D through changes to the LTPA environment require local tailoring.

Age and sex differences in the association between neighborhood socioeconomic environment and incident diabetes: Results from the diabetes location, environmental attributes and disparities (LEAD) network.

Objective: Worse neighborhood socioeconomic environment (NSEE) may contribute to an increased risk of type 2 diabetes (T2D). We examined whether the relationship between NSEE and T2D differs by sex and age in three study populations. Research design and methods: We conducted a harmonized analysis using data from three independent longitudinal study samples in the US: 1) the Veteran Administration Diabetes Risk (VADR) cohort, 2) the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, and 3) a case-control study of Geisinger electronic health records in Pennsylvania. We measured NSEE with a z-score sum of six census tract indicators within strata of community type (higher density urban, lower density urban, suburban/small town, and rural). Community type-stratified models evaluated the likelihood of new diagnoses of T2D in each study sample using restricted cubic splines and quartiles of NSEE. Results: Across study samples, worse NSEE was associated with higher risk of T2D. We observed significant effect modification by sex and age, though evidence of effect modification varied by site and community type. Largely, stronger associations between worse NSEE and diabetes risk were found among women relative to men and among those less than age 45 in the VADR cohort. Similar modification by age group results were observed in the Geisinger sample in small town/suburban communities only and similar modification by sex was observed in REGARDS in lower density urban communities. Conclusions: The impact of NSEE on T2D risk may differ for males and females and by age group within different community types.

Neighborhood Socioeconomic Environment and Risk of Type 2 Diabetes: Associations and Mediation Through Food Environment Pathways in Three Independent Study Samples.

OBJECTIVE: We examined whether relative availability of fast-food restaurants and supermarkets mediates the association between worse neighborhood socioeconomic conditions and risk of developing type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: As part of the Diabetes Location, Environmental Attributes, and Disparities Network, three academic institutions used harmonized environmental data sources and analytic methods in three distinct study samples: 1) the Veterans Administration Diabetes Risk (VADR) cohort, a national administrative cohort of 4.1 million diabetes-free veterans developed using electronic health records (EHRs); 2) Reasons for Geographic and Racial Differences in Stroke (REGARDS), a longitudinal, epidemiologic cohort with Stroke Belt region oversampling (N = 11,208); and 3) Geisinger/Johns Hopkins University (G/JHU), an EHR-based, nested case-control study of 15,888 patients with new-onset T2D and of matched control participants in Pennsylvania. A census tract-level measure of neighborhood socioeconomic environment (NSEE) was developed as a community type-specific z-score sum. Baseline food-environment mediators included percentages of 1) fast-food restaurants and 2) food retail establishments that are supermarkets. Natural direct and indirect mediating effects were modeled; results were stratified across four community types: higher-density urban, lower-density urban, suburban/small town, and rural. RESULTS: Across studies, worse NSEE was associated with higher T2D risk. In VADR, relative availability of fast-food restaurants and supermarkets was positively and negatively associated with T2D, respectively, whereas associations in REGARDS and G/JHU geographies were mixed. Mediation results suggested that little to none of the NSEE-diabetes associations were mediated through food-environment pathways. CONCLUSIONS: Worse neighborhood socioeconomic conditions were associated with higher T2D risk, yet associations are likely not mediated through food-environment pathways.

[Deep sweet syndrome as a cause or fever of unknown origin. A case report and literature review]. / Síndrome de Sweet subcutáneo como causa de fiebre de origen desconocido. Informe de un caso y revisión de la literatura.

Sweet syndrome is the prototype of neutrophilic dermatosis, which typically presents an intense inflammatory infiltrate of neutrophils in the epidermis and/or dermis, apparently due to a hypersensitivity reaction. This is a case of a 31 year-old woman with fever of more than three weeks duration and erythematous nudosities on her arms and legs. The histological study of a skin lesion showed a lobular inflammatory infiltrate of lymphocytes and neutrophils, with excellent response to prednisone. Therefore, it was concluded as subcutaneous sweet syndrome.

Longitudinal Analysis of Neighborhood Food Environment and Diabetes Risk in the Veterans Administration Diabetes Risk Cohort.

Importance: Diabetes causes substantial morbidity and mortality among adults in the US, yet its incidence varies across the country, suggesting that neighborhood factors are associated with geographical disparities in diabetes. Objective: To examine the association between neighborhood food environment and risk of incident type 2 diabetes across different community types (high-density urban, low-density urban, suburban, and rural). Design, Setting, and Participants: This is a national cohort study of 4 100 650 US veterans without type 2 diabetes. Participants entered the cohort between 2008 and 2016 and were followed up through 2018. The median (IQR) duration of follow-up was 5.5 (2.6-9.8) person-years. Data were obtained from Veterans Affairs electronic health records. Incident type 2 diabetes was defined as 2 encounters with type 2 diabetes International Classification of Diseases, Ninth Revision or Tenth Revision codes, a prescription for diabetes medication other than metformin or acarbose alone, or 1 encounter with type 2 diabetes International Classification of Diseases Ninth Revision or Tenth Revision codes and 2 instances of elevated hemoglobin A1c (≥6.5%). Data analysis was performed from October 2020 to March 2021. Exposures: Five-year mean counts of fast-food restaurants and supermarkets relative to other food outlets at baseline were used to generate neighborhood food environment measures. The association between food environment and time to incident diabetes was examined using piecewise exponential models with 2-year interval of person-time and county-level random effects stratifying by community types. Results: The mean (SD) age of cohort participants was 59.4 (17.2) years. Most of the participants were non-Hispanic White (2 783 756 participants [76.3%]) and male (3 779 555 participants [92.2%]). The relative density of fast-food restaurants was positively associated with a modestly increased risk of type 2 diabetes in all community types. The adjusted hazard ratio (aHR) was 1.01 (95% CI, 1.00-1.02) in high-density urban communities, 1.01 (95% CI, 1.01-1.01) in low-density urban communities, 1.02 (95% CI, 1.01-1.03) in suburban communities, and 1.01 (95% CI, 1.01-1.02) in rural communities. The relative density of supermarkets was associated with lower type 2 diabetes risk only in suburban (aHR, 0.97; 95% CI, 0.96-0.99) and rural (aHR, 0.99; 95% CI, 0.98-0.99) communities. Conclusions and Relevance: These findings suggest that neighborhood food environment measures are associated with type 2 diabetes among US veterans in multiple community types and that food environments are potential avenues for action to address the burden of diabetes. Tailored interventions targeting the availability of supermarkets may be associated with reduced diabetes risk, particularly in suburban and rural communities, whereas restrictions on fast-food restaurants may help in all community types.

Comparing competing geospatial measures to capture the relationship between the neighborhood food environment and diet.

PURPOSE: To examine how the choice of neighborhood food environment definition impacts the association with diet. METHODS: Using food frequency questionnaire data from the Reasons for Geographic and Racial Differences in Stroke study at baseline (2003-2007), we calculated participants' dietary inflammation score (DIS) (n = 20,331); higher scores indicate greater pro-inflammatory exposure. We characterized availability of supermarkets and fast food restaurants using several geospatial measures, including density (i.e., counts/km2) and relative measures (i.e., percentage of all food stores or restaurants); and various buffer distances, including administrative units (census tract) and empirically derived buffers ("classic" network, "sausage" network) tailored to community type (higher density urban, lower density urban, suburban/small town, rural). Using generalized estimating equations, we estimated the association between each geospatial measure and DIS, controlling for individual- and neighborhood-level sociodemographics. RESULTS: The choice of buffer-based measure did not change the direction or magnitude of associations with DIS. Effect estimates derived from administrative units were smaller than those derived from tailored empirically derived buffer measures. Substantively, a 10% increase in the percentage of fast food restaurants using a "classic" network buffer was associated with a 6.3 (SE = 1.17) point higher DIS (P< .001). The relationship between the percentage of supermarkets and DIS, however, was null. We observed high correlation coefficients between buffer-based density measures of supermarkets and fast food restaurants (r = 0.73-0.83), which made it difficult to estimate independent associations by food outlet type. CONCLUSIONS: Researchers should tailor buffer-based measures to community type in future studies, and carefully consider the theoretical and statistical implications for choosing relative (vs. absolute) measures.

US veterans administration diabetes risk (VADR) national cohort: cohort profile.

PURPOSE: The veterans administration diabetes risk (VADR) cohort facilitates studies on temporal and geographic patterns of pre-diabetes and diabetes, as well as targeted studies of their predictors. The cohort provides an infrastructure for examination of novel individual and community-level risk factors for diabetes and their consequences among veterans. This cohort also establishes a baseline against which to assess the impact of national or regional strategies to prevent diabetes in veterans. PARTICIPANTS: The VADR cohort includes all 6 082 018 veterans in the USA enrolled in the veteran administration (VA) for primary care who were diabetes-free as of 1 January 2008 and who had at least two diabetes-free visits to a VA primary care service at least 30 days apart within any 5-year period since 1 January 2003, or veterans subsequently enrolled and were diabetes-free at cohort entry through 31 December 2016. Cohort subjects were followed from the date of cohort entry until censure defined as date of incident diabetes, loss to follow-up of 2 years, death or until 31 December 2018. FINDINGS TO DATE: The incidence rate of type 2 diabetes in this cohort of over 6 million veterans followed for a median of 5.5 years (over 35 million person-years (PY)) was 26 per 1000 PY. During the study period, 8.5% of the cohort were lost to follow-up and 17.7% died. Many demographic, comorbidity and other clinical variables were more prevalent among patients with incident diabetes. FUTURE PLANS: This cohort will be used to study community-level risk factors for diabetes, such as attributes of the food environment and neighbourhood socioeconomic status via geospatial linkage to residence address information.