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The quality of drug products in the United States has been a matter of growing concern. Buyers and payers of pharmaceuticals have limited insight into measures of drug-product quality. Therefore, a quality-score system driven by data collection is proposed to differentiate between the qualities of drug products produced by different manufacturers. The quality scores derived using this proposed system would be based upon public regulatory data and independently-derived chemical data. A workflow for integrating the system into procurement decisions within health care organizations is also suggested. The implementation of such a quality-score system would benefit health care organizations by including the consideration of the quality of products while also considering price as a part of the drug procurement process. Such a system would also benefit the U.S. health care industry by bringing accountability and transparency into the drug supply chain and incentivizing manufacturers to place an increased emphasis on the quality and safety of their drug products., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objectives: This study evaluated the association of transthyretin (TTR) gene variant, in which isoleucine substitutes for valine at position 122 (V142I), with cardiac structure, function, and heart failure (HF) risk among middle-aged Black adults., Background: The valine-to-isoleucine substitution in the TTR protein is prevalent in Black individuals and causes cardiac amyloidosis., Methods: Jackson Heart Study participants without HF at baseline who had available data on the TTR V142I variant were included. The association of the TTR V142I variant with baseline echocardiographic parameters and repeated measures of high-sensitivity cardiac troponin-I (hs-cTnI) was assessed using adjusted linear regression models and linear mixed models, respectively. Adjusted Cox models, restricted mean survival time analysis, and Anderson-Gill models were constructed to determine the association of TTR V142I variant with the risk of incident HF, survival free of HF, and total HF hospitalizations., Results: A total of 119 of 2,960 participants (4%) were heterozygous carriers of the TTR V142I variant. The TTR V142I variant was not associated with measures of cardiac parameters at baseline but was associated with a greater increase in high-sensitivity troponin I (hs-TnI) levels over time. In adjusted Cox models, TTR V142I variant carriers had significantly higher risk of incident HF (HR: 1.80; 95% CI: 1.07-3.05; P = 0.03), lower survival free of HF (mean difference: 4.0 year; 95% CI: 0.6-6.2 years); P = 0.02), and higher risk of overall HF hospitalizations (HR: 2.12; 95% CI: 1.23-3.63; P = 0.007)., Conclusions: The TTR V142I variant in middle-aged Black adults is not associated with adverse cardiac remodeling but was associated with a significantly higher burden of chronic myocardial injury, and greater risk of incident HF and overall HF hospitalizations., Competing Interests: Funding Support and Author Disclosures The Jackson Heart Study was supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I and HHSN268201800012I) contracts from the National Heart, Lung, and Blood Institute and the National Institute for Minority Health and Health Disparities. Dr Hall has received support from the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant 1K08DK099415- 01A1, NIH/National Institute of General Medical Sciences grant P20GM104357, and NIH/National Institute of General Medical Sciences grant 5U54GM115428. This study was supported by research support from the Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, National Institute of Aging GEMSSTAR grant (1R03AG067960-01), and Applied Therapeutics to Dr Pandey. Disclosures: Dr Grodin is a consultant for Pfizer, Eidos Therapeutics, and Alynlam Pharmaceuticals; and has received research funding from the Texas Health Resources Clinical Scholars fund. Dr De Lemos has received financial support from Roche Diagnostics and Abbott Diagnostics; and is a consultant for Ortho Clinical Diagnostics, Quidel, and Regeneron. Dr Berry has received financial support from Roche Diagnostics, Abbott Diagnostics, and the National Institutes of Health; is a consultant for Abbott and the Cooper Institute. Dr Butler is a consultant for Abbott, Adrenomed, Arena Pharma, Array, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cardior, CVRx, Eli Lilly, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, Sequana Medical, V-Wave Limited, and Vifor. Dr Mentz has received financial support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Medtronic, Merck, Novartis, Roche, Sanofi, and Vifor. Dr Sanjiv Shah has received financial support from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and is a consultant for Abbott, Actelion, AstraZeneca, Amgen, Aria, Axon Therapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiora, CVRx, Cyclerion, Cytokinetics, Eisai, GlaxoSmithKline, Imara, Ionis, Ironwood, Keyto, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, Shifamed, Tenax, and United Therapeutics. Dr Amil Shah has received financial support from Novartis through Brigham and Women’s Hospital, and Philips Ultrasound through Brigham and Women’s Hospital, and personal fees from Philips Ultrasound Advisory Board outside the submitted work. Dr Pandey has served on the advisory board of Roche Diagnostics; and has received nonfinancial support from Pfizer and Merck. The views expressed in this paper are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The opioid crisis significantly affects residents of rural communities who already experience poor health outcomes based on social determinants. Therefore, this project evaluated the reported availability and accessibility of opioid use disorder (OUD) treatment resources in rural Utah county pharmacies through a multistep process intended to estimate the distance (miles) to registered (waivered) OUD care providers and community pharmacies and, thus, the ability to fill prescriptions for OUD treatment medications., Methods: First, the United States Department of Agriculture Economic Research Service dichotomous classification scheme was used to identify nonmetropolitan counties. Second, online resources were used to identify the volume of waivered treatment providers and community pharmacies by county. Third, the driving distances to both resources were estimated according to ZIP Code and county. Finally, the immediate availability of filling a prescription for OUD treatment medications was determined by surveying community pharmacists in rural Utah counties., Results: Nineteen of the 29 Utah counties were identified as rural and included in the study. Pharmacists in 50 of the 75 viable pharmacies completed surveys (66.7% usable response rate). OUD treatment medications were immediately available for dispensing in 90% (45 of 50) of the responding pharmacies. Two of the 19 counties (10.5%) lacked a pharmacy, and 6 of the 19 counties (31.6%) lacked a registered OUD treatment provider. Driving distances ranged from 1 mile to 71 miles to the nearest pharmacy and from 1 mile to 96 miles to the nearest waivered treatment provider., Conclusion: OUD treatment medications were readily available in some but not all rural Utah pharmacies. However, geographic barriers may prevent reasonable access to treatment providers and pharmacies for residents of smaller, remote communities., (Copyright © 2021 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Hypertensive diseases in pregnancy have been associated with altered cardiac structure and function, yet these associations have not been systematically investigated in larger populations including African Americans. We evaluated the relationships between hypertensive diseases in pregnancy with cardiac structure and function later in life in the Genetic Epidemiology Network of Arteriopathy (GENOA) study., Methods: We investigated 1013 African American women sibships with echocardiographic measurements from the GENOA study (Phase II, 2000-05; Jackson, MS). Women were classified as self-reported nulliparous (n = 61), a history of normotensive pregnancies (n = 780), a history of a hypertensive pregnancies (n = 152), or a history of preeclampsia (n = 20). We compared adjusted associations among these 4 groups with echocardiographic measurements of cardiac structure and function using generalized estimating equations, accounting for familial clustering., Results: Among 1013 women with echocardiographic data (mean age 62 ± 9.5 years), women with a history of hypertensive pregnancy had lower left ventricular ejection fraction (LVEF) (P = 0.043) compared to nulliparous women and higher left atrial systolic dimension (LASD) compared to women with a history of normotensive pregnancies (P = 0.010), After adjusting for cardiovascular risk factors. There were no statistically significant differences in other echocardiographic parameters among these groups., Conclusions: A history of hypertension in pregnancy is associated with lower LVEF later in life, compared to nulliparous women and higher LASD compared to women with a history of normotensive pregnancies. However, given the multiple comparisons considered, this finding should be interpreted cautiously and requires further study., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Prescription drug shortages can disrupt essential patient care and drive up drug prices., Objective: To evaluate some predictors of shortages within a large cohort of generic drugs in the United States and to determine the association between drug shortages and changes in generic drug prices., Methods: This was a retrospective cohort study. Outpatient prescription claims from commercial health plans between 2008 and 2014 were analyzed. Seven years of data were divided into fourteen 6-month periods; the first period was designated as the baseline period. The first model estimated the probability of experiencing a drug shortage using drug-specific competition levels, market sizes, formulations (e.g., capsules), and drug prices as predictors. The second model estimated the percentage change in drug prices from baseline on the basis of drug shortage duration., Results: From 1.3 billion prescription claims, a cohort of 1114 generic drugs was identified. Low-priced generic drugs were at a higher risk for drug shortages compared with medium- and high-priced generic drugs, with odds ratios of 0.60 (95% confidence interval [CI] 0.44-0.82) and 0.72 (95% CI 0.52-0.99), respectively. Compared with periods of no shortage, drug shortages lasting less than 6 months, 6 to 12 months, 12 to 18 months, and at least 18 months had corresponding price increases of 6.0% (95% CI 4.7-7.4), 10.9% (95% CI 8.5-13.4), 14.2% (95% CI 10.6-17.9), and 14.0% (95% CI 9.1-19.2), respectively., Conclusions: Study findings may not be generalizable to drugs that became generic after 2008 or those commonly used in an inpatient setting. The lowest priced drugs are at a substantially elevated risk of experiencing a drug shortage. Periods of drug shortages were associated with modest increases in drug prices., (Copyright © 2018 ISPOR--The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular false tendons (LVFTs) are chord-like structures that traverse the LV cavity and are generally considered to be benign. However, they have been associated with arrhythmias, LV hypertrophy and LV dilation in some small studies. We hypothesize that LVFTs are associated with LV structural and functional changes assessed by echocardiography., Methods: We retrospectively evaluated echocardiographic and clinical parameters of 126 patients identified as having LVFTs within the past 2 years and compared them to 85 age-matched controls without LVFTs., Results: There were no significant differences in age (52 ± 18 versus 54 ± 18 years, P = 0.37), sex (55% versus 59% men, P = 0.49), race (36% versus 23% white, P = 0.07), systolic blood pressure (131 ± 22 versus 132 ± 23mmHg, P = 0.76) or body mass index (BMI, 31 ± 8 versus 29 ± 10kg/m 2 , P = 0.07) between controls and patients with LVFTs, respectively. Patients with LVFTs had more prevalent heart failure (43% versus 21%, P = 0.001). Patients with LVFTs had more LV dilation, were 2.5 times more likely to have moderate-to-severe mitral regurgitation, had more severe diastolic dysfunction and reduced LV systolic function (18% lower) compared with controls (all P < 0.05). After adjustment for covariates, basal and middle LVFT locations were associated with reduced LV systolic function (P < 0.01), and middle LVFTs were associated with LV dilation (P < 0.01)., Conclusions: Our findings suggest that LVFTs may not be benign variants, and basal and middle LVFTs may have more deleterious effects. Further prospective studies should be performed to determine their pathophysiological significance and whether they play a causal role in LV dysfunction., (Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Digital vascular tone and function, as measured by peripheral arterial tonometry (PAT), are associated with cardiovascular risk and events in non-Hispanic whites. There are limited data on relations between PAT and cardiovascular risk in African-Americans. PAT was performed on a subset of Jackson Heart Study participants using a fingertip tonometry device. Resting digital vascular tone was assessed as baseline pulse amplitude. Hyperemic vascular response to 5 minutes of ischemia was expressed as the PAT ratio (hyperemic/baseline amplitude ratio). Peripheral augmentation index (AI), a measure of relative wave reflection, also was estimated. The association of baseline pulse amplitude (PA), PAT ratio, and AI to risk factors was assessed using stepwise multivariable models. The study sample consisted of 837 participants from the Jackson Heart Study (mean age, 54 ± 11 years; 61% women). In stepwise multivariable regression models, baseline pulse amplitude was related to male sex, body mass index, and diastolic blood pressure (BP), accounting for 16% of the total variability of the baseline pulse amplitude. Age, male sex, systolic BP, diastolic BP, antihypertensive medication, and prevalent cardiovascular disease contributed to 11% of the total variability of the PAT ratio. Risk factors (primarily age, sex, and heart rate) explained 47% of the total variability of the AI. We confirmed in our cohort of African-Americans, a significant relation between digital vascular tone and function measured by PAT and multiple traditional cardiovascular risk factors. Further studies are warranted to investigate the utility of these measurements in predicting clinical outcomes in African-Americans., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Peripheral vascular endothelial dysfunction assessed by digital peripheral arterial tonometry (PAT) has been associated with risk for adverse cardiovascular events. We examined the relations of peripheral microvascular dysfunction and left ventricular mass in a community-based cohort of African Americans. We examined participants of the Jackson Heart Study who had PAT and cardiac magnetic resonance imaging evaluations between 2007 and 2013. Consistent with pertinent literature, left ventricular mass index (LVMI) was adjusted for body size by indexing to height 2.7 . Pearson's correlation and general linear regression analyses were used to relate reactive hyperemia index, baseline pulse amplitude (BPA), and augmentation index (markers of microvascular vasodilator function, baseline vascular pulsatility, and relative wave reflection, respectively) to LVMI after adjusting for traditional cardiovascular risk factors. A total of 440 participants (mean age 59 ± 10 years, 60% women) were included. Age- and sex-adjusted Pearson's correlation analysis suggested that natural log transformed LVMI was negatively correlated with reactive hyperemia index (coefficient: -0.114; P = .02) and positively correlated with BPA (coefficient: 0.272; P < .001). In multivariable analyses, higher log e LVMI was associated with higher BPA (β: 0.210; P = .03) after accounting for age, sex, body mass index, diabetes, hypertension, ratio of total cholesterol and high-density lipoprotein cholesterol, smoking, and history of cardiovascular disease. In a community-based sample of African Americans, higher baseline pulsatility measured by PAT was associated with higher LVMI by cardiac magnetic resonance imaging after adjusting for traditional risk factors., (Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Background: Low-normal potassium is a risk factor for diabetes and may account for some of the racial disparity in diabetes risk. Aldosterone affects serum potassium and is associated with insulin resistance., Objectives: We sought to confirm the association between potassium and incident diabetes in an African-American cohort, and to determine the effect of aldosterone on this association., Design: We studied participants from the Jackson Heart Study, an African-American adult cohort, who were without diabetes at baseline. With the use of logistic regression, we characterized the associations of serum, dietary, and urinary potassium with incident diabetes. In addition, we evaluated aldosterone as a potential effect modifier of these associations., Results: Of 2157 participants, 398 developed diabetes over 8 y. In a minimally adjusted model, serum potassium was a significant predictor of incident diabetes (OR: 0.83; 95% CI: 0.74, 0.92 per SD increment in serum potassium). In multivariable models, we found a significant interaction between serum potassium and aldosterone (P = 0.046). In stratified multivariable models, in those with normal aldosterone (<9 ng/dL, n = 1163), participants in the highest 2 potassium quartiles had significantly lower odds of incident diabetes than did those in the lowest potassium quartile [OR (95% CI): 0.61 (0.39, 0.97) and 0.54 (0.33, 0.90), respectively]. Among those with high-normal aldosterone (≥9 ng/dL, n = 202), we found no significant association between serum potassium and incident diabetes. In these stratified models, serum aldosterone was not a significant predictor of incident diabetes. We found no statistically significant associations between dietary or urinary potassium and incident diabetes., Conclusions: In this African-American cohort, we found that aldosterone may modify the association between serum potassium and incident diabetes. In participants with normal aldosterone, high-normal serum potassium was associated with a lower risk of diabetes than was low-normal serum potassium. Additional studies are warranted to determine whether serum potassium is a modifiable risk factor that could be a target for diabetes prevention. This trial was registered at clinicaltrials.gov as NCT00415415., (© 2017 American Society for Nutrition.)

Objectives: In an entirely African-American cohort, we compared clinical characteristics, cardiac structure and function, and all-cause mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF) in relation to patients with heart failure with reduced ejection fraction (HFrEF) and those without HF., Background: African Americans are at increased risk for HF. Nevertheless, there are limited phenotypic and prognostic data in African Americans with HFpEF compared with those with HFrEF and those without HF., Methods: Middle-aged African Americans from the Jackson, Mississippi, cohort of the ARIC (Atherosclerosis Risk In Communities) study (n = 2,445) underwent echocardiography between 1993 and 1995. HF prevalence was available in 1,962 patients for whom left ventricular ejection fraction (LVEF) could be quantified. Participants with HF were categorized as having HFpEF (LVEF ≥50%), HFrEF (LVEF <50%), or no HF, with comparisons made between groups., Results: HF was identified in 116 (5.9%) participants (HFpEF n = 85 [73%]; HFrEF n = 31 [27%]). Compared with those without HF, those with HFpEF were older, were more likely to be female, and had more frequent comorbidities and concentric hypertrophy. In relation to HFrEF, those with HFpEF were more likely to be female but less likely to have coronary heart disease, diabetes mellitus, chronic kidney disease, left atrial enlargement, and eccentric hypertrophy. Over a median 13.7 years of follow-up, risk of death differed between groups, with age- and sex-adjusted hazard ratios of 1.51 (95% confidence interval: 1.01 to 2.25) for HFpEF versus those without HF and 2.50 (95% confidence interval: 1.37 to 4.58) for HFrEF versus HFpEF., Conclusions: In this cohort of middle-aged African Americans, HFpEF was the most common form of HF and was associated with a substantially better prognosis than HFrEF but worse than those without HF.

Background: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans., Objective: To identify novel genetic variants associated with resting heart rate in African Americans., Methods: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8))., Results: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans., Conclusions: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin., (Copyright © 2013 Heart Rhythm Society. All rights reserved.)

An interesting case of a young patient presenting with Austrian's Triad: pneumococcal pneumonia, pneumococcal meningitis, and pneumococcal endocarditis. On echocardiogram the patient was noted to have a noncoronary sinus of Valsalva aneurysm and vegetations on the aortic cusps resulting in disruption of valvular integrity and severe aortic insufficiency. Color Doppler also revealed rupture of the aneurysm into the right atrium. The patient was taken to surgery where the noncoronary cusp was noted to be completely replaced with vegetative lesions. The aortic valve was replaced with a No. 21 Carpentier-Edwards bioprosthetic valve (Edwards Lifesciences, Irvine, CA), and the noncoronary sinus of Valsalva was repaired with concomitant closure of the fistula using glutaraldehyde autologous pericardium.