Moving Beyond Proof of Concept and Pilots to Mainstream: Discovery and Lessons from a Reference Framework and Implementation.

Blockchain technology is a radical innovation with the potential to disrupt and re-imagine more collaborative established business structures and processes. Significant advances, particularly in the payments space, include newer, faster, and less costly options for moving money. The underlying blockchain technology can be used for broader use cases spanning several verticals, including healthcare - although its adoption here is less than complete. Numerous proofs-of-concept and pilots have been executed and are increasing, although enterprise blockchain applications in healthcare at the production scale enabling transformative constituent processes are limited. In this article, the authors analyze the blockchain in healthcare literature for critical success factors and add practitioner views on crossing the chasm from proof-of-concept and pilots to a transformational scale. We explore 24 articles for key inflections for scale and highlight the need for a multifaceted execution framework to resolve the practical barriers to enabling reimagined network-based blockchain use cases for efficiencies, particularly in disparate health systems such as the U.S. In addition, we introduce the blockchain discovery framework to make this emerging technology meet the mainstream operations at scale systematically and in a stair-stepped and future-proofed manner, addressing practical stakeholder concerns. Finally, the authors present a reference case study discovered through the framework of one such healthcare administrative process for a scaled reimagined implementation. Healthcare executives and portfolio managers will benefit from these insights and help to increase the enterprise adoption of this inevitable technology of the future. Plan Language Summary: This article presents a practitioner's view of operating in emerging technology, exploring and advancing blockchain-based transformation in healthcare. Blockchain technology is maturing quickly, with financial technology (aka fintech) leading the way with efficient options for moving money, particularly in the public permissionless blockchain segment. The underlying technology allows for a broader set of capabilities, including provenance, data sharing, immutability, non-repudiation, and auditability, which provides for complete rethinking of existing business processes. These features can help to reimagine a more comprehensive set of use cases in many disciplines, including healthcare. However, enterprise adoption needs to catch up.

Illustration of Gut-Thyroid Axis in Alcohol Use Disorder: Interplay of Gut Dysfunction, Pro-Inflammatory Responses, and Thyroid Function.

(1) Background: Heavy and chronic alcohol drinking leads to altered gut dysfunction, coupled with a pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by heavy and chronic alcohol intake; however, the mechanism for altered gut-derived changes in thyroid function has not been studied thus far. This study investigates the role of alcohol-induced gut dysfunction and pro-inflammatory cytokine profile in the thyroid function of patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n = 44) were divided into Gr.1, patients with normal thyroid-stimulating hormone (TSH) levels (n = 28, 0.8 ≤ TSH ≤ 3 mIU/L); and Gr.2, patients with clinically elevated TSH levels (n = 16, TSH > 3 mIU/L). Demographics, drinking measures, comprehensive metabolic panels, and candidate thyroid markers (TSH, circulating triiodothyronine (T3), and free thyroxine (fT4)) were analyzed. Gut-dysfunction-associated markers (lipopolysaccharide (LPS), LPS-binding protein (LBP), and soluble LPS-induced pathogen-associated protein (sCD14)), and candidate pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-8, MCP-1, PAI-1) were also evaluated. (3) Results: Patients in both groups presented with a borderline overweight BMI category. Gr.2 reported numerically higher indices of chronic and heavy drinking patterns than Gr.1. The fT4 levels were elevated, while T3 was within normal limits in both groups. The gut dysfunction markers LBP and sCD14 were numerically elevated in Gr.2 vs. Gr.1, suggesting subtle ongoing changes. Candidate pro-inflammatory cytokines were significantly elevated in Gr.2, including IL-1 ß, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect on the gut-immune-thyroid response (r = 0.896, 36 p = 0.002) on TSH levels in a multivariate regression model with LBP, sCD14, and PAI-1 levels as upstream variables in the gut-thyroid pathway. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area = 0.774, 39 p < 0.001) and TNF-α (area = 0.708, p = 0.017), among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4, as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and a lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation by employing the gut-brain axis. These results also emphasize potential directions to carefully evaluate thyroid dysregulation in the overall medical management of AUD.

Impact of Hyperglycemia on Cardiovascular Events and Clinical Outcomes in Patients Hospitalized With COVID-19 Pneumonia.

OBJECTIVE: To study cardiovascular events and clinical outcomes in patients with elevated glycated hemoglobin (HbA1c) levels and/or admission hyperglycemia and those with type 2 diabetes hospitalized with SARS-CoV-2 pneumonia. METHODS: This was a multicenter retrospective study of 1645 patients hospitalized with SARS-CoV-2 pneumonia. Diagnosis of SARS-CoV-2 pneumonia required a positive reverse transcription-polymerase chain reaction result for SARS-CoV-2, presence of new or worsening pulmonary infiltrates on computed tomography scan or chest x-ray, and at least one of following: (1) new or increased cough, (2) temperature of >37.8 °C, or (3) dyspnea. Outcomes included in-hospital cardiovascular events, intensive care unit admission, and mortality. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for association of elevated HbA1c levels and/or admission hyperglycemia and type 2 diabetes for individual outcomes. RESULTS: Among 1645 adults hospitalized with SARS-CoV-2 pneumonia, 18 with type 1 diabetes were excluded from the analysis. Of 1627 adults, 634 (39%) had known diagnosis of type 2 diabetes, and among 993 patients with no diabetes, 107 (10.8%) patients were identified with elevated HbA1c levels and/or admission hyperglycemia. Patients with elevated HbA1c levels and/or admission hyperglycemia had increased odds of developing acute in-hospital cardiovascular events (OR, 1.73; 95% CI, 1.07-2.80), intensive care unit admissions (OR, 1.61; 95% CI, 1.10-2.34), and mortality (OR, 1.77; 95% CI, 1.02-3.07) compared to patients with type 2 diabetes and no diabetes. CONCLUSION: Patients with elevated HbA1c levels and/or admission hyperglycemia hospitalized with SARS-CoV-2 pneumonia have increased risk of developing acute in-hospital cardiovascular complications and overall poor clinical outcomes compared with patients with type 2 diabetes and no diabetes.

Exposure to volatile organic compounds - acrolein, 1,3-butadiene, and crotonaldehyde - is associated with vascular dysfunction.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Exposure to air pollution, specifically particulate matter of diameter ≤2.5 µm (PM2.5), is a well-established risk factor for CVD. However, the contribution of gaseous pollutant exposure to CVD risk is less clear. OBJECTIVE: To examine the vascular effects of exposure to individual volatile organic compounds (VOCs) and mixtures of VOCs. METHODS: We measured urinary metabolites of acrolein (CEMA and 3HPMA), 1,3-butadiene (DHBMA and MHBMA3), and crotonaldehyde (HPMMA) in 346 nonsmokers with varying levels of CVD risk. On the day of enrollment, we measured blood pressure (BP), reactive hyperemia index (RHI - a measure of endothelial function), and urinary levels of catecholamines and their metabolites. We used generalized linear models for evaluating the association between individual VOC metabolites and BP, RHI, and catecholamines, and we used Bayesian Kernel Machine Regression (BKMR) to assess exposure to VOC metabolite mixtures and BP. RESULTS: We found that the levels of 3HPMA were positively associated with systolic BP (0.98 mmHg per interquartile range (IQR) of 3HPMA; CI: 0.06, 1.91; P = 0.04). Stratified analysis revealed an increased association with systolic BP in Black participants despite lower levels of urinary 3HPMA. This association was independent of PM2.5 exposure and BP medications. BKMR analysis confirmed that 3HPMA was the major metabolite associated with higher BP in the presence of other metabolites. We also found that 3HPMA and DHBMA were associated with decreased endothelial function. For each IQR of 3HPMA or DHBMA, there was a -4.4% (CI: -7.2, -0.0; P = 0.03) and a -3.9% (CI: -9.4, -0.0; P = 0.04) difference in RHI, respectively. Although in the entire cohort the levels of several urinary VOC metabolites were weakly associated with urinary catecholamines and their metabolites, in Black participants, DHBMA levels showed strong associations with urinary norepinephrine and normetanephrine levels. DISCUSSION: Exposure to acrolein and 1,3-butadiene is associated with endothelial dysfunction and may contribute to elevated risk of hypertension in participants with increased sympathetic tone, particularly in Black individuals.

Mobile App Use in Adults with Comorbid Type 2 Diabetes and Depression.

The purpose of this preliminary study was to determine smartphone usage, expressed level of interest, and intent to use mHealth apps among adults with comorbid type 2 diabetes (T2D) and depression. A convenience sample of adults (N=35) completed a Demographic and Mobile App Survey and the CESD-R-10. A majority reported using mobile apps (n=23, 65.7%) and felt comfortable or very comfortable using mobile apps (n=14, 46.7%). However, few respondents used a health app (n=6, 17.1%) or a diabetes-specific app for diabetes management (n=3, 8.6%). Adjusted, age and education were the two variables that independently impacted app use; those aged less than 55 years as well as those with a graduate degree were more likely to use apps. Being younger and having an advanced degree increased the odds of using a diabetes-specific app. The findings suggest that adults with T2D are amenable to using mHealth apps to manage diabetes.

Association between residential greenness and exposure to volatile organic compounds.

Residential proximity to vegetation and plants is associated with many health benefits, including reduced risk of cardiovascular disease, diabetes and mental stress. Although the mechanisms by which proximity to greenness affects health remain unclear, plants have been shown to remove particulate air pollution. However, the association between residential-area vegetation and exposure to volatile organic chemicals (VOCs) has not been investigated. We recruited a cohort of 213 non-smoking individuals and estimated peak, cumulative, and contemporaneous greenery using satellite-derived normalized difference vegetation index (NDVI) near their residence. We found that the urinary metabolites of exposure to VOCs - acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, propylene oxide were inversely associated (7-31% lower) with 0.1 higher peak NDVI values within 100 m radius of the participants' home. These associations were significant at radii ranging from 25 to 300 m. Strongest associations were observed within a 200 m radius, where VOC metabolites were 22% lower per 0.1 unit higher NDVI. Of the 18 measured urinary metabolites, 7 were positively associated with variation of greenness within a 200 m radius of homes. The percent of tree canopy and street trees around participants' residence were less strongly associated with metabolite levels. The associations between urinary VOC metabolites and residential NDVI values were stronger in winter than in summer, and in participants who were more educated, White, and those who lived close to areas of high traffic. These findings suggest high levels of residential greenness are associated with lower VOC exposure, particularly in winter.

Exposure to airborne fine particulate matter is associated with impaired endothelial function and biomarkers of oxidative stress and inflammation.

Epidemiological evidence suggests that exposure to air pollution is a leading risk factor for cardiovascular disease (CVD). However, there is little direct evidence linking exposure to vascular dysfunction. We conducted a cross-sectional study of 100 participants, recruited from the University of Louisville Clinics. Endothelial function was assessed by calculating the reactive hyperemia index (RHI). Oxidative stress was indexed by measuring urinary levels of isoprostanes (n = 91). Inflammatory biomarkers were measured in the plasma (n = 80). Daily average PM2.5 levels were obtained from regional monitoring stations. Adjusted associations between PM2.5 levels and measured outcomes were tested using generalized linear models. The average age of participants was 48 years (44% male, 62% white); 52% had a diagnosis of hypertension, and 44% had type-2 diabetes. A 12.4% decrease in RHI was associated with 10 µg/m3 increase in PM2.5 (95% CI: 21.0, -2.7). The F-2 isoprostane metabolite showed a positive association of 28.4% (95% CI: 2.7, 60.3) per 10 µg/m3 increase in PM2.5. Positive associations were observed with angiopoietin 1 (17.4%; 95% CI: 2.8, 33.8), vascular endothelial growth factor (10.4%; 95% CI: 0.6, 21.0), placental growth factor (31.7%; 95% CI: 12.2, 54.5), intracellular adhesion molecule-1 (24.6%; 95% CI: 1.6, 52.8), and matrix metalloproteinase-9 (30.3%; 95% CI: 8.0, 57.5) per 10 µg/m3 increase in PM2.5. Additionally, a 10 µg/m3 increase in PM2.5 was associated with 15.9% decrease in vascular cell adhesion molecule-1 (95% CI: 28.3, -1.3). These findings suggest that exposure to PM2.5 is associated with impaired vascular function, which may result from oxidative stress and inflammation, thereby leading to a pro-atherogenic state.

Association Between Residential Greenness and Cardiovascular Disease Risk.

Background Exposure to green vegetation has been linked to positive health, but the pathophysiological processes affected by exposure to vegetation remain unclear. To study the relationship between greenness and cardiovascular disease, we examined the association between residential greenness and biomarkers of cardiovascular injury and disease risk in susceptible individuals. Methods and Results In this cross-sectional study of 408 individuals recruited from a preventive cardiology clinic, we measured biomarkers of cardiovascular injury and risk in participant blood and urine. We estimated greenness from satellite-derived normalized difference vegetation index ( NDVI ) in zones with radii of 250 m and 1 km surrounding the participants' residences. We used generalized estimating equations to examine associations between greenness and cardiovascular disease biomarkers. We adjusted for residential clustering, demographic, clinical, and environmental variables. In fully adjusted models, contemporaneous NDVI within 250 m of participant residence was inversely associated with urinary levels of epinephrine (-6.9%; 95% confidence interval, -11.5, -2.0/0.1 NDVI ) and F2-isoprostane (-9.0%; 95% confidence interval, -15.1, -2.5/0.1 NDVI ). We found stronger associations between NDVI and urinary epinephrine in women, those not on ß-blockers, and those who had not previously experienced a myocardial infarction. Of the 15 subtypes of circulating angiogenic cells examined, 11 were inversely associated (8.0-15.6% decrease/0.1 NDVI ), whereas 2 were positively associated (37.6-45.8% increase/0.1 NDVI ) with contemporaneous NDVI . Conclusions Independent of age, sex, race, smoking status, neighborhood deprivation, statin use, and roadway exposure, residential greenness is associated with lower levels of sympathetic activation, reduced oxidative stress, and higher angiogenic capacity.

Circulating angiogenic stem cells in type 2 diabetes are associated with glycemic control and endothelial dysfunction.

Circulating angiogenic cells (CACs) of various described phenotypes participate in the regeneration of the damaged endothelium, but the abundance of these cells is highly influenced by external cues including diabetes. It is not entirely clear which CAC populations are most reflective of endothelial function nor which are impacted by diabetes. To answer these questions, we enrolled a human cohort with variable CVD risk and determined relationships between stratified levels of CACs and indices of diabetes and vascular function. We also determined associations between CAC functional markers and diabetes and identified pro-angiogenic molecules which are impacted by diabetes. We found that subjects with low levels of CD34+/AC133+/CD31+/CD45dim cells (CAC-3) had a significantly higher incidence of diabetes (p = 0.004), higher HbA1c levels (p = 0.049) and higher CVD risk scores. Furthermore, there was an association between low CAC-3 levels and impaired vascular function (p = 0.023). These cells from diabetics had reduced levels of CXCR4 and VEGFR2, while diabetics had higher levels of certain cytokines and pro-angiogenic molecules. These results suggest that quantitative and functional defects of CD34+/AC133+/CD31+/CD45dim cells are associated with diabetes and vascular impairment and that this cell type may be a prognostic indicator of CVD and vascular dysfunction.

Diabetic Gastroparesis: Principles and Current Trends in Management.

This article is a comprehensive review of diabetic gastroparesis, defined as delayed or disordered gastric emptying, including basic principles and current trends in management. This review includes sections on anatomy and physiology, diagnosis and differential diagnosis as well as management and current guidelines for treatment of diabetic gastroparesis. Diabetic gastroparesis (DGp) is a component of autonomic neuropathy resulting from long-standing poorly controlled type 1 and type 2 diabetes. The diagnostic workup of DGp first excludes obstruction and other causes including medications that may mimic delayed/disordered gastric emptying. Targeting nutrition, hydration, symptomatic relief and glycemic control are mainstays of treatment for DGp. Additionally, optimal treatment of DGp includes good glycemic management, often involving customizing insulin delivery using basal-bolus insulin and technology, including sensor-augmented pumps and continuous glucose monitoring systems. Prokinetic medications may be helpful in DGp symptoms, although only limited number of medications is currently available in the USA. Selected medication-refractory patients with DGp may benefit from gastric neuromodulation, and some from surgical interventions including pyloric therapies that can also be done endoscopically. As is true of any of the diabetic complications, prevention of DGp by early and optimal glycemic control is more cost-effective.Funding: Hansa Medcell, India.

Residential Proximity to Major Roadways Is Associated With Increased Levels of AC133+ Circulating Angiogenic Cells.

OBJECTIVES: Previous studies have shown that residential proximity to a roadway is associated with increased cardiovascular disease risk. Yet, the nature of this association remains unclear, and its effect on individual cardiovascular disease risk factors has not been assessed. The objective of this study was to determine whether residential proximity to roadways influences systemic inflammation and the levels of circulating angiogenic cells. APPROACH AND RESULTS: In a cross-sectional study, cardiovascular disease risk factors, blood levels of C-reactive protein, and 15 antigenically defined circulating angiogenic cell populations were measured in participants (n=316) with moderate-to-high cardiovascular disease risk. Attributes of roadways surrounding residential locations were assessed using geographic information systems. Associations between road proximity and cardiovascular indices were analyzed using generalized linear models. Close proximity (<50 m) to a major roadway was associated with lower income and higher rates of smoking but not C-reactive protein levels. After adjustment for potential confounders, the levels of circulating angiogenic cells in peripheral blood were significantly elevated in people living in close proximity to a major roadway (CD31(+)/AC133(+), AC133(+), CD34(+)/AC133(+), and CD34(+)/45(dim)/AC133(+) cells) and positively associated with road segment distance (CD31(+)/AC133(+), AC133(+), and CD34(+)/AC133(+) cells), traffic intensity (CD31(+)/AC133(+) and AC133(+) cells), and distance-weighted traffic intensity (CD31(+)/34(+)/45(+)/AC133(+) cells). CONCLUSIONS: Living close to a major roadway is associated with elevated levels of circulating cells positive for the early stem marker AC133(+). This may reflect an increased need for vascular repair. Levels of these cells in peripheral blood may be a sensitive index of cardiovascular injury because of residential proximity to roadways.

Diet self-management and readiness to change in underserved adults with type 2 diabetes.

AIM: Dietary assessment in diabetes may be enhanced by considering patient-centered perspectives and barriers to change within IDF guidelines. Consideration of readiness to change (RTC) diet in underserved samples may guide future interventions in high risk populations. This study assesses the utility of a rapid assessment of RTC diet in a medically underserved sample. METHOD: Participants were 253 Black (43.7%) and White (55.1%) American adults with type 2 diabetes [M age=57.93 (11.52); 60.5% female; 19% below the US poverty threshold]. Participants were recruited at medical clinics and completed validated self-report measures assessing diabetes knowledge, self-efficacy and dietary behaviors and barriers by RTC. RESULTS: Stage-based comparisons identified significant differences in diabetes and dietary domains: participants in the Action stage endorsed fewer behavioral dietary barriers (p<.001), more frequent dietary problem-solving (p<.001), and greater diabetes self-efficacy (p<.001) than participants in the Contemplation and Preparation stages. Women were more likely to be in the Preparation stage and beyond (p<.05). CONCLUSIONS: Findings highlight the clinical utility of a brief measure of RTC in understanding patient perspectives toward dietary behaviors in a medically underserved sample. The impact of gender on RTC diet warrants further exploration.

Self-Reported Physical Activity in Medically Underserved Adults With Type 2 Diabetes in Clinical and Community Settings.

BACKGROUND: This study assessed physical activity (PA) in community dwelling adults with Type 2 diabetes, using multiple instruments reflecting internationally normed PA and diabetes-specific self-care behaviors. METHODS: Two hundred and fifty-three Black (44.8%) and White (55.2%) Americans [mean age = 57.93; 39.5% male] recruited at low-income clinic and community health settings. Participants completed validated PA self-report measures developed for international comparisons (International Physical Activity Questionnaire Short Form), characterization of diabetes self-care (Summary of Diabetes Self-Care Activities Measure; SDSCA) and exercise-related domains including provider recommendations and PA behaviors and barriers (Personal Diabetes Questionnaire; PDQ). RESULTS: Self-reported PA and PA correlates differed by instrument. BMI was negatively correlated with PA level assessed by the PDQ in both genders, and assessed with SDSCA activity items in females. PA levels were low, comparable to previous research with community and diabetes samples. Pain was the most frequently reported barrier; females reported more frequent PA barriers overall. CONCLUSIONS: When using self-report PA measures for PA evaluation of adults with diabetes in clinical settings, it is critical to consider population and setting in selecting appropriate tools. PA barriers may be an important consideration when interpreting PA levels and developing interventions. Recommendations for incorporating these measures in clinical and research settings are discussed.

Sex hormone-binding globulin and the risk for metabolic syndrome in children of South Asian Indian origin.

OBJECTIVE: To determine whether the plasma level of sex hormone-binding globulin (SHBG) identifies South Asian Indian children at risk for metabolic syndrome. METHODS: Adults and their children aged 5 to 9 years were recruited at the annual health fair at the Hindu temple serving the South Asian Indian community in Louisville, Kentucky. Anthropometric data were collected in adults and children, and blood pressure, lipid, and glucose levels were measured in adults. SHBG levels were measured in children using a fingerstick blood sample. In adults, metabolic syndrome was diagnosed according to the International Diabetes Federation criteria. Twelve months later, follow-up anthropometric data were obtained for a portion of the children. RESULTS: The study included 30 sets of parents and 30 children. The prevalence of metabolic syndrome among 310 adults attending the health fair was 42% in men and 39% in women. Children with 1 parent with metabolic syndrome had 24% lower SHBG levels that increased to 55% if both parents had metabolic syndrome. SHBG levels were inversely related to waist circumference and to body mass index percentile. Both SHBG and waist circumference predicted weight gain over 1 year in children. CONCLUSIONS Low SHBG levels were found in South Asian Indian children whose parents had attributes of metabolic syndrome. The dose dependency of SHBG is consistent with inheritance of a genetic trait, and if the results are applicable to other racial/ethnic groups, SHBG may be a useful marker to identify at-risk children for early intervention.

Diabetes-related molecular signatures in infrared spectra of human saliva.

BACKGROUND: There is an ongoing need for improvements in non-invasive, point-of-care tools for the diagnosis and prognosis of diabetes mellitus. Ideally, such technologies would allow for community screening. METHODS: In this study, we employed infrared spectroscopy as a novel diagnostic tool in the prediction of diabetic status by analyzing the molecular and sub-molecular spectral signatures of saliva collected from subjects with diabetes (n = 39) and healthy controls (n = 22). RESULTS: Spectral analysis revealed differences in several major metabolic components - lipid, proteins, glucose, thiocyanate and carboxylate - that clearly demarcate healthy and diseased saliva. The overall accuracy for the diagnosis of diabetes based on infrared spectroscopy was 100% on the training set and 88.2% on the validation set. Therefore, we have established that infrared spectroscopy can be used to generate complex biochemical profiles in saliva and identify several potential diabetes-associated spectral features. CONCLUSIONS: Infrared spectroscopy may represent an appropriate tool with which to identify novel diseases mechanisms, risk factors for diabetic complications and markers of therapeutic efficacy. Further study into the potential utility of infrared spectroscopy as diagnostic and prognostic tool for diabetes is warranted.