Evaluating an Indigenous health curriculum for diabetes prevention: engaging the community through talking circles and knowledge translation of results.

Background: Kahnawà:ke is a Kanien'kehá:ka (Mohawk) community in Quebec, Canada. In 1997, the community-controlled Kateri Memorial Hospital Centre in partnership with the Kahnawake Education Center, and the Kahnawake Schools Diabetes Prevention Project (KSDPP) developed an elementary school diabetes prevention health education program, aimed to increase knowledge of Type 2 diabetes, healthy eating and active lifestyles. Long-term goals for KSDPP community and school interventions are to decrease obesity and diabetes. Objectives: To evaluate the Kateri Memorial Hospital Centre Health Education Program for Diabetes Prevention (HEP) and use key principles of knowledge translation to promote understanding of results to upgrade HEP content and improve delivery. Methods: A KSDPP community-based participatory research team used mixed methods for evaluation, combining a cross-sectional survey for 23 teachers with interviews of two elementary school principals and three culturally appropriate Indigenous talking circles with HEP authors, teachers and parents. Questionnaire results were presented as descriptive statistics. The thematic textual analysis identified emerging themes from talking circles and interviews. Results: Facilitators of HEP delivery were an acknowledgement of its importance; appreciation of prepared lesson plans for teachers; and KSDPP's strong community presence. Barriers included reduced administrative support and instructional time due to competing academic demands; the need for increased Kanien'kehá:ka cultural content; and outdated resource materials. Recommendations included increasing teacher training, Kanien'kehá:ka cultural content and administrative support. Conclusion: Community researchers undertook detailed knowledge translation activities of facilitators, barriers and recommendations with hospital and education centre administrators and Kahnawà:ke community to maximize uptake of findings before external dissemination of results.

Rate of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Use and the Number of COVID-19-Confirmed Cases and Deaths.

The novel coronavirus SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor as an entry point to the cell. Cardiovascular disease (CVD) is a risk factor for COVID-19 with poor outcomes. We tested the hypothesis that the rate of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use is associated with the rate of COVID-19-confirmed cases and deaths. We conducted a geospatial, ecological study using publicly available county-level data. The Medicare ACEI and ARB prescription rate was exposure. The COVID-19-confirmed case and death rates were outcomes. Spatial autoregression models were adjusted for the rate of births and deaths; Group Quarters population; percentage of female; percentage of Native American, Pacific Islander, Hispanic, and Black; percentage of children and older (>65 years) adults; percentage of uninsured; percentage of those living in poverty; percentage of those who are obese, smoking, admitting insufficient sleep, and those with at least some college degree; median household income; air quality index; CVD hospitalization rate in Medicare beneficiaries; and CVD death rate in a total county population. After adjustment for confounders, the ACEI use rate did not associate with COVID-19-confirmed case rate (direct county-own effect + 0.027%; 95% confidence interval [CI] -1.080 to 1.134; p = 0.962; indirect spillover effect + 0.26%; 95% CI -70.0 to 70.5; p = 0.994). Similarly, the ARB use rate was not associated with COVID-19-confirmed case rate (direct effect + 0.029%; 95% CI -0.803 to 0.862; p = 0.945; indirect effect + 0.19%; 95% CI -52.8 to 53.2; p = 0.994). In both unadjusted and adjusted Bayesian zero inflation Poisson analysis, neither ACEI nor ARB use rates were associated with COVID-19 death rates. In conclusion, ACEI and ARB use rates were not associated with COVID-19 infectivity and death rate in this ecological study.

Worsening Kidney Function Is the Major Mechanism of Heart Failure in Hypertension: The ALLHAT Study.

OBJECTIVES: The authors aimed to quantify the extent to which the effect of antihypertensive drugs on incident heart failure (HF) is mediated by their effect on kidney function. BACKGROUND: The authors hypothesized that the dynamic change in kidney function is the mechanism behind differences in the rate of incident HF in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) participants randomized to lisinopril and chlorthalidone, in comparison with those randomized to amlodipine and doxazosin. METHODS: Causal mediation analysis of ALLHAT data (1994 to 2002) included participants with available baseline and 24- to 48-month estimated glomerular filtration rate (eGFR) (N = 27,918; mean age 66 ± 7.4 years; 32.4% Black, 56.3% men). Change in eGFR was the mediator. Incident symptomatic HF was the primary outcome. Hospitalized/fatal HF was the secondary outcome. Linear regression (for mediator) and logistic regression (for outcome) analyses were adjusted for demographics, cardiovascular disease, and risk factors. RESULTS: There were 1,769 incident HF events, including 1,359 hospitalized/fatal HF events. In fully adjusted causal mediation analysis, the relative change in eGFR mediated 18% of the effect of chlorthalidone, and 33% of lisinopril on incident symptomatic HF, and 25% of the effect of chlorthalidone, and 41% of lisinopril on hospitalized/fatal HF. In participants with diabetes, the relative change in eGFR mediated nearly 50% of the effect of lisinopril on incident symptomatic HF, whereas in diabetes-free participants, only 17%. CONCLUSIONS: On the risk difference scale, change in eGFR accounts for up to 50% of the mechanism by which antihypertensive medications affect HF. (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]; NCT00000542).

Electrophysiological ventricular substrate of stroke: a prospective cohort study in the Atherosclerosis Risk in Communities (ARIC) study.

OBJECTIVES: The goal of the study was to determine an association of cardiac ventricular substrate with thrombotic stroke (TS), cardioembolic stroke (ES) and intracerebral haemorrhage (ICH). DESIGN: Prospective cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) study in 1987-1989 enrolled adults (45-64 years), selected as a probability sample from four US communities (Minneapolis, Minnesota; Washington, Maryland; Forsyth, North Carolina; Jackson, Mississippi). Visit 2 was in 1990-1992, visit 3 in 1993-1995, visit 4 in 1996-1998 and visit 5 in 2011-2013. PARTICIPANTS: ARIC participants with analysable ECGs and no history of stroke were included (n=14 479; age 54±6 y; 55% female; 24% black). Ventricular substrate was characterised by cardiac memory, spatial QRS-T angle (QRS-Ta), sum absolute QRST integral (SAIQRST), spatial ventricular gradient magnitude (SVGmag), premature ventricular contractions (PVCs) and tachycardia-dependent intermittent bundle branch block (TD-IBBB) on 12-lead ECG at visits 1-5. OUTCOME: Adjudicated TS included a first definite or probable thrombotic cerebral infarction, ES-a first definite or probable non-carotid cardioembolic brain infarction. Definite ICH was included if it was the only stroke event. RESULTS: Over a median 24.5 years follow-up, there were 899 TS, 400 ES and 120 ICH events. Cox proportional hazard risk models were adjusted for demographics, cardiovascular disease, risk factors, atrial fibrillation, atrial substrate and left ventricular hypertrophy. After adjustment, PVCs (HR 1.72; 95% CI 1.02 to 2.92), QRS-Ta (HR 1.15; 95% CI 1.03 to 1.28), SAIQRST (HR 1.20; 95% CI 1.07 to 1.34) and time-updated SVGmag (HR 1.19; 95% CI 1.08 to 1.32) associated with ES. Similarly, PVCs (HR 1.53; 95% CI 1.03 to 2.26), QRS-Ta (HR 1.08; 95% CI 1.01 to 1.16), SAIQRST (HR 1.07; 95% CI 1.01 to 1.14) and time-updated SVGmag (HR 1.11; 95% CI 1.04 to 1.19) associated with TS. TD-IBBB (HR 3.28; 95% CI 1.03 to 10.46) and time-updated SVGmag (HR 1.23; 95% CI 1.03 to 1.47) were associated with ICH. CONCLUSIONS: PVC burden (reflected by cardiac memory) is associated with ischaemic stroke. Transient cardiac memory (likely through TD-IBBB) precedes ICH.

The Association Between the Rate of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Use and the Number of Covid-19 Confirmed Cases and Deaths in the United States: Geospatial Study.

BACKGROUND: The novel coronavirus SARS-Cov2 uses the angiotensin-converting enzyme 2 (ACE2) receptor as an entry point to the cell. Cardiovascular disease (CVD) is a risk factor for the novel coronavirus disease (Covid-19) with poor outcomes. We hypothesized that the rate of ACE inhibitor (ACEI) and angiotensin receptor blocker (ARB) use is associated with the rate of Covid-19 confirmed cases and deaths. METHODS: We conducted a geospatial study using publicly available county-level data. The Medicare ACEI and ARB prescription rate was exposure. The Covid-19 confirmed case and death rates were outcomes. Spatial autoregression models were adjusted for the percentage of Black residents, children, residents with at least some college degree, median household income, air quality index, CVD hospitalization rate in Medicare beneficiaries, and CVD death rate in a total county population. FINDINGS: After adjustment for confounders, the ACEI use rate did not associate with Covid-19 confirmed case rate (direct county-own effect +0.11 %; 95%CI -0.31 to 0.53; P=0.600, and indirect spillover effect -0.53 %; 95%CI -3.89 to 2.84; P=0.760). The ARB use rate was associated with increased Covid-19 confirmed case rate (direct county-owned effect +0.12 %; 95%CI 0.05-0.19; P=0.002, and indirect spillover effect -0.33 %; 95%CI -2.11 to 1.44; P=0.714). Sensitivity analysis indicated an absence of significant reverse causality bias for analyses with Covid-19 confirmed case rate, but not death rate outcome. INTERPRETATION: Our results highlight the safety of ACEI use for patients with clinical indications for ACEI use. However, an increase in ARB use by 1% was associated with a 0.12 % increase in Covid-19 confirmed cases. The use of ARB, due to known ACE2 upregulation, may facilitate SARS-CoV-2 entry into target cells and increase infectivity. Cluster-randomized controlled trial is warranted to answer the question of whether the replacement of ARB by ACEI may reduce the Covid-19 confirmed case rate.

Bringing Critical Race Praxis Into the Study of Electrophysiological Substrate of Sudden Cardiac Death: The ARIC Study.

Background Race is an established risk factor for sudden cardiac death (SCD). We sought to determine whether the association of electrophysiological substrate with SCD varies between black and white individuals. Methods and Results Participants from the ARIC (Atherosclerosis Risk in Communities) study with analyzable ECGs (n=14 408; age, 54±6 years; 74% white) were included. Electrophysiological substrate was characterized by ECG metrics. Two competing outcomes were adjudicated: SCD and non-SCD. Interaction of ECG metrics with race was studied in Cox proportional hazards and Fine-Gray competing risk models, adjusted for prevalent cardiovascular disease, risk factors, and incident nonfatal cardiovascular disease. At the baseline visit, adjusted for age, sex, and study center, blacks had larger spatial ventricular gradient magnitude (0.30 mV; 95% CI, 0.25-0.34 mV), sum absolute QRST integral (18.4 mV*ms; 95% CI, 13.7-23.0 mV*ms), and Cornell voltage (0.30 mV; 95% CI, 0.25-0.35 mV) than whites. Over a median follow-up of 24.4 years, SCD incidence was higher in blacks (2.86 per 1000 person-years; 95% CI, 2.50-3.28 per 1000 person-years) than whites (1.37 per 1000 person-years; 95% CI, 1.22-1.53 per 1000 person-years). Blacks with hypertension had the highest rate of SCD: 4.26 (95% CI, 3.66-4.96) per 1000 person-years. Race did not modify an association of ECG variables with SCD, except QRS-T angle. Spatial QRS-T angle was associated with SCD in whites (hazard ratio, 1.38; 95% CI, 1.25-1.53) and hypertension-free blacks (hazard ratio, 1.52; 95% CI, 1.09-2.12), but not in blacks with hypertension (hazard ratio, 1.15; 95% CI, 0.99-1.32) (P-interaction=0.004). Conclusions Race did not modify associations of electrophysiological substrate with SCD and non-SCD. Electrophysiological substrate does not explain racial disparities in SCD rate.

Response of murine bone marrow-derived mesenchymal stromal cells to dry-etched porous silicon scaffolds.

Porous silicon shows great promise as a bio-interface material due to its large surface to volume ratio, its stability in aqueous solutions and to the ability to precisely regulate its pore characteristics. In the current study, porous silicon scaffolds were fabricated from single crystalline silicon wafers by a novel xenon difluoride dry etching technique. This simplified dry etch fabrication process allows selective formation of porous silicon using a standard photoresist as mask material and eliminates the post-formation drying step typically required for the wet etching techniques, thereby reducing the risk of damaging the newly formed porous silicon. The porous silicon scaffolds supported the growth of primary cultures of bone marrow derived mesenchymal stromal cells (MSC) plated at high density for up to 21 days in culture with no significant loss of viability, assessed using Alamar Blue. Scanning electron micrographs confirmed a dense lawn of cells at 9 days of culture and the presence of MSC within the pores of the porous silicon scaffolds.