Successfully Implementing Digital Health to Ensure Future Global Health Security During Pandemics: A Consensus Statement.

Importance: COVID-19 has highlighted widespread chronic underinvestment in digital health that hampered public health responses to the pandemic. Recognizing this, the Riyadh Declaration on Digital Health, formulated by an international interdisciplinary team of medical, academic, and industry experts at the Riyadh Global Digital Health Summit in August 2020, provided a set of digital health recommendations for the global health community to address the challenges of current and future pandemics. However, guidance is needed on how to implement these recommendations in practice. Objective: To develop guidance for stakeholders on how best to deploy digital health and data and support public health in an integrated manner to overcome the COVID-19 pandemic and future pandemics. Evidence Review: Themes were determined by first reviewing the literature and Riyadh Global Digital Health Summit conference proceedings, with experts independently contributing ideas. Then, 2 rounds of review were conducted until all experts agreed on the themes and main issues arising using a nominal group technique to reach consensus. Prioritization was based on how useful the consensus recommendation might be to a policy maker. Findings: A diverse stakeholder group of 13 leaders in the fields of public health, digital health, and health care were engaged to reach a consensus on how to implement digital health recommendations to address the challenges of current and future pandemics. Participants reached a consensus on high-priority issues identified within 5 themes: team, transparency and trust, technology, techquity (the strategic development and deployment of technology in health care and health to achieve health equity), and transformation. Each theme contains concrete points of consensus to guide the local, national, and international adoption of digital health to address challenges of current and future pandemics. Conclusions and Relevance: The consensus points described for these themes provide a roadmap for the implementation of digital health policy by all stakeholders, including governments. Implementation of these recommendations could have a significant impact by reducing fatalities and uniting countries on current and future battles against pandemics.

The Incremental Validity of Self-Report and Performance-Based Methods for Assessing Hostility to Predict Cardiovascular Disease in Physicians.

We evaluated the utility of an integrative, multimethod approach for assessing hostility-related constructs to predict premature cardiovascular disease (CVD) and premature coronary heart disease (CHD) using participants from the Johns Hopkins Precursors Study, which was designed to identify risk factors for heart disease. Participants were assessed at baseline while in medical school from 1946 to 1962 (M age = 24.6) and have been followed annually since then. Baseline assessment included individually administered Rorschach protocols (N = 416) scored for aggressive imagery (i.e., Aggressive Content, Aggressive Past) and self-reports of 3 possible anger responses to stress. Cox regression analyses predicting morbidity or mortality by age 55 revealed a significant interaction effect; high levels of Aggressive Content with high self-reported hostility predicted an increased rate of premature CVD and CHD, and incrementally predicted the rate of these events after controlling for the significant covariates of smoking (CVD and CHD) and cholesterol (CHD) that were also assessed at baseline. The hostility and anger measures, as well as other baseline covariates, were not predictors of CVD risk factors assessed at midlife during follow-up. Overall, this integrative model of hostility illustrates the potential value of multimethod assessment to areas of health psychology and preventive medicine.

Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND).

BACKGROUND: The presence of population structure in a sample may confound the search for important genetic loci associated with disease. Our four samples in the Family Investigation of Nephropathy and Diabetes (FIND), European Americans, Mexican Americans, African Americans, and American Indians are part of a genome- wide association study in which population structure might be particularly important. We therefore decided to study in detail one component of this, individual genetic ancestry (IGA). From SNPs present on the Affymetrix 6.0 Human SNP array, we identified 3 sets of ancestry informative markers (AIMs), each maximized for the information in one the three contrasts among ancestral populations: Europeans (HAPMAP, CEU), Africans (HAPMAP, YRI and LWK), and Native Americans (full heritage Pima Indians). We estimate IGA and present an algorithm for their standard errors, compare IGA to principal components, emphasize the importance of balancing information in the ancestry informative markers (AIMs), and test the association of IGA with diabetic nephropathy in the combined sample. RESULTS: A fixed parental allele maximum likelihood algorithm was applied to the FIND to estimate IGA in four samples: 869 American Indians; 1385 African Americans; 1451 Mexican Americans; and 826 European Americans. When the information in the AIMs is unbalanced, the estimates are incorrect with large error. Individual genetic admixture is highly correlated with principle components for capturing population structure. It takes ~700 SNPs to reduce the average standard error of individual admixture below 0.01. When the samples are combined, the resulting population structure creates associations between IGA and diabetic nephropathy. CONCLUSIONS: The identified set of AIMs, which include American Indian parental allele frequencies, may be particularly useful for estimating genetic admixture in populations from the Americas. Failure to balance information in maximum likelihood, poly-ancestry models creates biased estimates of individual admixture with large error. This also occurs when estimating IGA using the Bayesian clustering method as implemented in the program STRUCTURE. Odds ratios for the associations of IGA with disease are consistent with what is known about the incidence and prevalence of diabetic nephropathy in these populations.

Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

Interrelationship of Multiple Endothelial Dysfunction Biomarkers with Chronic Kidney Disease.

The interrelationship of multiple endothelial biomarkers and chronic kidney disease (CKD) has not been well studied. We measured asymmetric dimethylarginine (ADMA), L-arginine, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), von Willebrand factor (vWF), flow-mediated dilation (FMD), and nitroglycerin-induced dilation (NID) in 201 patients with CKD and 201 community-based controls without CKD. Multivariable analyses were used to examine the interrelationship of endothelial biomarkers with CKD. The multivariable-adjusted medians (interquartile ranges) were 0.54 (0.40, 0.75) in patients with CKD vs. 0.25 (0.22, 0.27) µmol /L in controls without CKD (p<0.0001 for group difference) for ADMA; 67.0 (49.6, 86.7) vs. 31.0 (27.7, 34.2) µmol/L (p<0.0001) for L-arginine; 230.0 (171.6, 278.6) vs. 223.9 (178.0, 270.6) ng/mL (p=0.55) for sICAM-1; 981.7 (782.6, 1216.8) vs. 633.2 (507.8, 764.3) ng/mL (p<0.0001) for sVCAM-1; 47.9 (35.0, 62.5) vs. 37.0 (28.9, 48.0) ng/mL (p=0.01) for sE-selectin; 1320 (1044, 1664) vs. 1083 (756, 1359) mU/mL (p=0.008) for vWF; 5.74 (3.29, 8.72) vs. 8.80 (6.50, 11.39)% (p=0.01) for FMD; and 15.2 (13.5, 16.9) vs. 19.1 (17.2, 21.0)% (p=0.0002) for NID, respectively. In addition, the severity of CKD was positively associated with ADMA, L-arginine, sVCAM-1, sE-selectin, and vWF and inversely associated with FMD and NID. Furthermore, FMD and NID were significantly and inversely correlated with ADMA, L-arginine, sVCAM-1, sE-selectin, and vWF. In conclusion, these data indicate that multiple dysfunctions of the endothelium were present among patients with CKD. Interventional studies are warranted to test the effects of treatment of endothelial dysfunction on CKD.

Access to Care, Treatment Ambivalence, Medication Nonadherence, and Long-Term Mortality Among Severely Hypertensive African Americans: A Prospective Cohort Study.

African Americans living in poor neighborhoods bear a high burden of illness and early mortality. Nonadherence may contribute to this burden. In a prospective cohort study of urban African Americans with poorly controlled hypertension, mortality was 47.6% over a median follow-up of 6.1 years. Patients with pill-taking nonadherence were more likely to die (hazard ratio, 1.80; 95% confidence interval [CI], 1.18-2.76) after adjustment for potential confounders. With regard to factors related to nonadherence, poor access to care such as difficulty paying for medications was associated with prescription refill nonadherence (odds ratio [OR], 4.12; 95% CI, 1.88-9.03). Pill-taking nonadherence was not associated with poor access to care; however, it was associated with factors related to treatment ambivalence including lower hypertension knowledge (OR, 2.97; 95% CI, 1.39-6.32), side effects (OR, 3.44; 95% CI, 1.47-8.03), forgetfulness (OR, 3.62; 95% CI, 1.78-7.34), and feeling that the medications do not help (OR, 2.78; 95% CI, 1.09-7.09). These data suggest that greater access to care is a necessary but insufficient remedy to the disparities experienced by urban African Americans with hypertension. To achieve its full promise, health reform must also address treatment ambivalence.

Effects of low-carbohydrate and low-fat diets: a randomized trial.

BACKGROUND: Low-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations. OBJECTIVE: To examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors. DESIGN: A randomized, parallel-group trial. (ClinicalTrials.gov: NCT00609271). SETTING: A large academic medical center. PARTICIPANTS: 148 men and women without clinical cardiovascular disease and diabetes. INTERVENTION: A low-carbohydrate (<40 g/d) or low-fat (<30% of daily energy intake from total fat [<7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial. MEASUREMENTS: Data on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months. RESULTS: Sixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, -3.5 kg [95% CI, -5.6 to -1.4 kg]; P = 0.002), fat mass (mean difference in change, -1.5% [CI, -2.6% to -0.4%]; P = 0.011), ratio of total-high-density lipoprotein (HDL) cholesterol (mean difference in change, -0.44 [CI, -0.71 to -0.16]; P = 0.002), and triglyceride level (mean difference in change, -0.16 mmol/L [-14.1 mg/dL] [CI, -0.31 to -0.01 mmol/L {-27.4 to -0.8 mg/dL}]; P = 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P < 0.001) than those on the low-fat diet. LIMITATION: Lack of clinical cardiovascular disease end points. CONCLUSION: The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors. PRIMARY FUNDING SOURCE: National Institutes of Health.

Improving global health education: development of a Global Health Competency Model.

Although global health is a recommended content area for the future of education in public health, no standardized global health competency model existed for master-level public health students. Without such a competency model, academic institutions are challenged to ensure that students are able to demonstrate the knowledge, skills, and attitudes (KSAs) needed for successful performance in today's global health workforce. The Association of Schools of Public Health (ASPH) sought to address this need by facilitating the development of a global health competency model through a multistage modified-Delphi process. Practitioners and academic global health experts provided leadership and guidance throughout the competency development process. The resulting product, the Global Health Competency Model 1.1, includes seven domains and 36 competencies. The Global Health Competency Model 1.1 provides a platform for engaging educators, students, and global health employers in discussion of the KSAs needed to improve human health on a global scale.

Open-source collaboration for Global Health: Science and Practice.

USAID and the Schools of Public Health at JHU and GWU welcome you to the inaugural issue of GHSP-an open-access, peer-reviewed journal for the global health community, particularly program implementers, to contribute to and benefit from a dialogue based on science and practical programmatic experience.

Body mass index and risk of incident hypertension over the life course: the Johns Hopkins Precursors Study.

BACKGROUND: The obesity-hypertension link over the life course has not been well characterized, although the prevalence of obesity and hypertension is increasing in the United States. METHODS AND RESULTS: We studied the association of body mass index (BMI) in young adulthood, into middle age, and through late life with risk of developing hypertension in 1132 white men of The Johns Hopkins Precursors Study, a prospective cohort study. Over a median follow-up period of 46 years, 508 men developed hypertension. Obesity (BMI ≥30 kg/m(2)) in young adulthood was strongly associated with incident hypertension (hazard ratio, 4.17; 95% confidence interval, 2.34-7.42). Overweight (BMI 25 to <30 kg/m(2)) also signaled increased risk (hazard ratio, 1.58; 95% confidence interval, 1.28-1.96). Men of normal weight at age 25 years who became overweight or obese at age 45 years were at increased risk compared with men of normal weight at both times (hazard ratio, 1.57; 95% confidence interval, 1.20-2.07), but not men who were overweight or obese at age 25 years who returned to normal weight at age 45 years (hazard ratio, 0.91; 95% confidence interval, 0.43-1.92). After adjustment for time-dependent number of cigarettes smoked, cups of coffee taken, alcohol intake, physical activity, parental premature hypertension, and baseline BMI, the rate of change in BMI over the life course increased the risk of incident hypertension in a dose-response fashion, with the highest risk among men with the greatest increase in BMI (hazard ratio, 2.52; 95% confidence interval, 1.82-3.49). CONCLUSIONS: Our findings underscore the importance of higher weight and weight gain in increasing the risk of hypertension from young adulthood through middle age and into late life.

Genetic association and gene-gene interaction analyses in African American dialysis patients with nondiabetic nephropathy.

BACKGROUND: African Americans have increased susceptibility to nondiabetic nephropathy relative to European Americans. STUDY DESIGN: Follow-up of a pooled genome-wide association study (GWAS) in African American dialysis patients with nondiabetic nephropathy; novel gene-gene interaction analyses. SETTING & PARTICIPANTS: Wake Forest sample: 962 African American nondiabetic nephropathy cases, 931 non-nephropathy controls. Replication sample: 668 Family Investigation of Nephropathy and Diabetes (FIND) African American nondiabetic nephropathy cases, 804 non-nephropathy controls. PREDICTORS: Individual genotyping of top 1,420 pooled GWAS-associated single-nucleotide polymorphisms (SNPs) and 54 SNPs in 6 nephropathy susceptibility genes. OUTCOMES: APOL1 genetic association and additional candidate susceptibility loci interacting with or independently from APOL1. RESULTS: The strongest GWAS associations included 2 noncoding APOL1 SNPs, rs2239785 (OR, 0.33; dominant; P = 5.9 × 10(-24)) and rs136148 (OR, 0.54; additive; P = 1.1 × 10(-7)) with replication in FIND (P = 5.0 × 10(-21) and 1.9 × 10(-05), respectively). rs2239785 remained associated significantly after controlling for the APOL1 G1 and G2 coding variants. Additional top hits included a CFH SNP (OR from meta-analysis in the 3,367 African American cases and controls, 0.81; additive; P = 6.8 × 10(-4)). The 1,420 SNPs were tested for interaction with APOL1 G1 and G2 variants. Several interactive SNPs were detected; the most significant was rs16854341 in the podocin gene (NPHS2; P = 0.0001). LIMITATIONS: Nonpooled GWASs have not been performed in African American patients with nondiabetic nephropathy. CONCLUSIONS: This follow-up of a pooled GWAS provides additional and independent evidence that APOL1 variants contribute to nondiabetic nephropathy in African Americans and identified additional associated and interactive nondiabetic nephropathy susceptibility genes.