Search

Background Over half of the South African adults aged 45 years and older have hypertension but its effective management along the treatment cascade (awareness, treatment, and control) remains poorly understood. Methods We compared the prevalence of all stages of the hypertension treatment cascade in the rural HAALSI cohort of older adults at baseline and after four years of follow-up using household surveys and blood pressure data. Hypertension was a mean systolic blood pressure >140 mm Hg or diastolic pressure >90 mm Hg, or current use of anti-hypertension medication. Control was a mean blood pressure Results Prevalence along the treatment cascade increased from baseline (B) to follow-up (F): awareness (64.4% vs. 83.6%), treatment (49.7% vs. 73.9%), and control (22.8% vs. 41.3%). At both time points, women had higher levels of awareness (B: 70.5% vs. 56.3%; F: 88.1% vs. 76.7%), treatment (B: 55.9% vs. 41.55; F: 79.9% vs. 64.7%), and control (B: 26.5% vs. 17.9%; F: 44.8% vs. 35.7%). Prevalence along the cascade increased linearly with age for everyone. Predictors of awareness included being female, elderly, or visiting a primary health clinic three times in the previous 3 months, and the latter two also predicted hypertension control. Conclusions There were significant improvements in awareness, treatment, and control of hypertension from baseline to follow-up and women fared better at all stages, at both time points.

Fusarium wilt, caused by the soilborne fungus Fusarium oxysporum f. sp. cubense ( Foc), is considered one of the most destructive diseases of bananas in Brazil. In this study, a collection of 194 monosporic isolates from several banana-producing regions located in different climatic zones along a south-to-north transect in Brazil was formed to assess the genetic structure of the population of Foc. The isolates underwent pathogenicity tests, PCR diagnosis for the detection of tropical race 4, and screening of SIX homolog genes that produce putative effector proteins. The vegetative compatibility group (VCG) of 119 isolates was determined by pairing against 17 internationally known VCG-tester strains. A group of 158 isolates was selected for simple sequence repeat (SSR) genotyping. There was moderate diversity of Foc in Brazil. Eight VCGs were identified: 0120, 0122, 0124, 0125, 0128, 01215, 01220, and 01222, of which 78% of isolates belong to a single VCG, whereas 22% of isolates are assigned to multiple VCGs, belonging to complexes of VCGs. The distribution of VCGs is uneven and independent of the banana genotype. The isolates of a VCG shared a similar profile of SIX homologs, but there was no association with geographic region. Four SSR loci were polymorphic, and, on average, 7.5 alleles were detected per locus. Thirty-five multilocus genotypes (MLGs) were identified. There was no association between VCG and MLGs, and no genetic structure of the population of Foc in Brazil was detected.

Funding Acknowledgements Type of funding sources: None. Background Ultra-high-power short-duration (UHPSD) ablation with the novel QDOT™ catheter allows to maintain a target temperature by automatically adjusting flow and power during a 4-second application of 90 Watt. However, the optimal contact-force for a sufficient lesion generation is yet to be determined. Methods This study comprised 41 patients with symptomatic atrial fibrillation undergoing pulmonary vein isolation (PVI) with the QDot catheter using the UHPSD mode with 90 W for 4 seconds. All UHPSD applications for circumferential PVI were analyzed. Suboptimal UHPSD applications were defined as either an impedance drop of ≤5% or a cumulative temperature-limited energy ≤330 W. Results A total of 1904 UHPSD applications (46.4 applications per patient) were performed with an average contact force (aCF) of 12.3±6.4 g with a mean maximum temperature (maxTemp) of 48.4±3.8 °C and a mean impedance drop (ImpDrop) of 10±3.2%. An ImpDrop ≤5% occurred in 67 (3.5%) UHPSD applications which was associated with lower aCF (10.6±7 vs. 12.4±6.4 g; p=0.024) and a lower maxTemp (45.8±3.8 vs. 48.5±3.8 °C; p5%. A cumulative energy ≤330 W was observed in 39 (2%) UHPSD applications. Interestingly, low cumulative energy UHPSD applications (≤330 W) were characterized by a higher aCF (21±9.6 vs. 12.1±6.2 g; p21.1 g (10.2% vs 3.6%; p=0.004). Conclusion A low but also a high contact-force (21g) are associated with suboptimal UHPSD applications. Thus, UHPSD applications require a ’15-gram window’ of contact-force to achieve an optimal cumulative energy.

BACKGROUND: Sub-Saharan Africa is undergoing an epidemiologic transition from infectious diseases to cardiovascular diseases. From 2014 to 2019, sociodemographic surveillance was performed in a large cohort in rural South Africa. METHODS: Disease prevalence and incidence were calculated using inverse probability weights. Poisson regression was used to identify disease predictors. The percentage of individuals with controlled ( RESULTS: Compared with 2014 (n=5059), study participants in 2019 (n=4176) had similar rates of obesity (mean body mass index, 27.5±10.0 versus 27.0±6.5) but higher smoking (9.1% versus 11.5%) and diabetes (11.1% versus 13.9%). There was no significant increase in hypertension prevalence (58.4% versus 59.8%; age adjusted, 64.3% versus 63.3%), and there was a significant reduction in mean systolic blood pressure (138.0 versus 128.5 mm Hg; P CONCLUSIONS: The hypertension prevalence and incidence are plateauing in this aging cohort. There was a statistically and clinically significant decline in mean blood pressure and a substantial increase in individuals with controlled hypertension on medication. The prevalence of cardiometabolic risk factors did not decrease over time, suggesting that the blood pressure decrease is likely due to increased medication access and adherence, promoted by local health systems.

The genetic structure of the population of Sclerotinia sclerotiorum was analyzed using 238 individuals collected from different hosts. Individuals were characterized for microsatellite genotypes and mycelial compatibility groups (MCGs). A total of 22 MCGs and 64 multilocus lineages (MLLs) were identified. There was a close relationship between the MCGs and MLLs, but there was no association between MLLs and hosts or regions. At least 39 MCGs are present in Brazil, and 68.5% of the isolates were assigned to either MCG 1 or MCG 2. Eight new MCGs were found. Seven genetic groups were identified and associated with MCGs. Most genetic variation (70.0%) was because of differences among MCGs. High values of estimates of linkage disequilibrium among loci were more frequent in the total population (all MCGs). By contrast, there was evidence of random mating in subpopulations defined by MCGs 1 and 2. Additionally, there was evidence of outcrossing in the population of S. sclerotiorum in Brazil. The population was structured by MCGs; lineages originating from asexual reproduction or selfing prevail and are widely distributed in space, are persistent in time, and affect many hosts, but there is evidence of some degree of outcrossing, which may lead to a more genetically variable population in the future.

Begomoviruses have circular, single-stranded DNA genomes encapsidated into twinned quasi-icosahedral particles and are transmitted by whiteflies of the Bemisia tabaci sibling group. Begomoviruses infect cultivated and non-cultivated plants, causing great losses in economically important crops worldwide. To better understand the genetic diversity of begomoviruses infecting the non-cultivated host Cnidoscolus urens, leaf samples exhibiting virus-like symptoms were collected in different localities in the state of Alagoas, Brazil, during 2015 and 2016. Forty-two complete DNA-A sequences were cloned and sequenced by the Sanger method. Based on nucleotide sequence comparisons, the 42 new isolates were identified as the bipartite begomovirus cnidoscolus mosaic leaf deformation virus (CnMLDV). The CnMLDV isolates were clustered in two phylogenetic groups (clusters I and II) corresponding to their sampling areas, and the high value of Wright’s F fixation index observed for the DNA-A sequences suggests population structuring. At least seven independent intraspecies recombination events were predicted among CnMLDV isolates, with recombination breakpoints located in the common region (CR) and in the CP and Rep genes. Also, a high per site nucleotide diversity (π) was observed for CnMLDV isolates, with CP being significantly more variable than Rep. Despite the high genetic variability, strong negative or purifying selection was identified as the main selective force acting upon CP and Rep.

A previously healthy 39-year-old man presented in cardiogenic shock with evidence of multisystem inflammatory syndrome of adults 2 months after a mild case of coronavirus disease 2019. He was treated with intravenous immunoglobulin and pulse-dose corticosteroids with rapid resolution of his symptoms and normalization of biventricular function. (Level of Difficulty: Intermediate.), Central Illustration

Background Sub-Saharan Africa is undergoing an epidemiologic transition dominated by a widespread epidemic of hypertension (HTN). Since 2014, we began studying a cohort of 5,059 individuals in rural South Africa, to describe the evolution of HTN among older adults, and understand the impact of targeted interventions by local health systems. Purpose Characterize the updated prevalence and incidence of HTN in a prospective cohort between baseline (2014) and follow-up (2019), and describe changes in blood pressure (BP) treatment. Methods HTN was defined as systolic blood pressure (SBP) ≥140 mm Hg, diastolic blood pressure (DBP) ≥90 mm Hg, or self-reported medication use. Prevalence and incidence rates were calculated using inverse-probability weights to account for mortality and attrition. Poisson regression was used to identify predictors of disease incidence. We calculated the percentage of individuals with controlled versus uncontrolled HTN (with 140/90 mm Hg as cutoff), self-reported medication use, and compared these values between 2014 and 2019. Results Compared to 2014 (n=5,059), study participants in 2019 (n=4,176) were expectedly older (mean age 61.7±13.1 vs 66.0±13.0 years) but had similar sex distribution (53.6% vs 53.5% females) and weighted rates of obesity (mean BMI 27.5±10.0 vs 27.0±6.5), with higher rates of smoking (9.1% vs 11.8%) and diabetes (11.1% vs 13.7%). The HTN prevalence did not increase over time (58.4% vs 59.8%), and there was a significant reduction in mean SBP (138.0 vs 128.5 mm Hg, p Conclusions The prevalence of HTN did not increase in this aging cohort; in fact there was a clinically and statistically significant decline in mean BP and a substantial increase in the proportion of hypertensive patients with controlled HTN taking medications between 2014 and 2019. The prevalence of obesity, smoking and other risk factors did not decrease over time, suggesting that the mean BP decrease in this cohort is likely due to increased access and adherence to medications, promoted by local health systems. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute on Aging (P01 AG041710), and Department of Science and Innovation, the University of the Witwatersrand, South Africa.

This Viewpoint summarizes the complexity of the existing terminology used for dual antiplatelet therapy (DAPT) and the need to standardize the terminology for use in clinical cardiology and scientific research.

Fusarium wilt, caused by the soilborne fungus

Introducción. Actualmente el carcinoma de células basales y escamosas es tratado principalmente por medio de cirugía. En búsqueda de tratamientos que no invasivos se ha desarrollado el tratamiento tópico con 188Re que ha mostrado resultados terapéuticos satisfactorios. Sin embargo, en la actualidad solo se cuenta con descripciones bidimensionales de la distribución de dosis absorbida en la región blanco, lo que limita la información referente a la dosis absorbida (D)al tejido sano circundante. Por lo que el objetivo del presente trabajo es determinar con la técnica Monte Carlo la distribución tridimensional de la D en el tratamiento tópico con 188Re de carcinoma de células escamosas y basales. Metodología. El escenario de la simulación constó de una crema que contiene 188Re distribuido uniformemente, una lámina de plástico mylar, y un maniquí tipo voxel representando a la piel con un volumen de 2X2X0.1 cm3 y un tamaño de voxel de 100 µm por lado. Se analizaron las superficies de isodosis, así como las curvas en los cortes sagitales y transversales para describir la distribución de dosis. Resultados y Conclusión. El Índice de Homogeneidad revela la forma en que la homogeneidad disminuye a medida que aumenta la profundidad. Se reportan tablas con el tiempo de irradiación necesario para impartir una dosis de 50 Gy en un rango de 250-750 µm de profundidad. Con la configuración terapéutica descrita en este trabajo, que es la que se usa en la práctica clínica, se encontró que es posible dar un tratamiento para una profundidad de 250-650µm sin rebasar los límites de dosis absorbida recomendados para la epidermis; los cuales se rebasan si se alcanza la dosis prescrita a una profundidad 750 µm.

Introduction Recent attention on the possible use of hydroxychloroquine and chloroquine to treat COVID-19 disease has potentially triggered a number of overdoses from hydroxychloroquine. Toxicity from hydroxychloroquine manifests with cardiac conduction abnormalities, seizure activity, and muscle weakness. Recognizing this toxidrome and unique management of this toxicity is important in the COVID-19 pandemic. Case Report A 27-year-old man with a history of rheumatoid arthritis presented to the emergency department 7 hours after an intentional overdose of hydroxychloroquine. Initial presentation demonstrated proximal muscle weakness. The patient was found to have a QRS complex of 134 ms and QTc of 710 ms. He was treated with early orotracheal intubation and intravenous diazepam boluses. Due to difficulties formulating continuous diazepam infusions, we opted to utilize an intermitted intravenous bolus strategy that achieved similar effects that a continuous infusion would. The patient recovered without residual side effects. Discussion Hydroxychloroquine toxicity is rare but projected to increase in frequency given its selection as a potential modality to treat COVID-19 disease. It is important for clinicians to recognize the unique effects of hydroxychloroquine poisoning and initiate appropriate emergency maneuvers to improve the outcomes in these patients.

Fusarium wilt, caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense (Foc), is considered one of the most destructive diseases of bananas. Paradoxically, knowledge of the genetics of the pathogen population in the Americas is very limited. In this study, a collection of 178 monosporic isolates from several banana producing regions, located in different climatic zones along a South to North transect in Brazil, was formed to assess the genetic structure of the population of Foc. The isolates underwent pathogenicity tests, PCR diagnosis for the detection of Tropical race 4 and screening to SIX homologs. The VCG of 119 isolates was determined by pairing against 17 testers. A group of 158 isolates was selected for microsatellite genotyping. There was moderate diversity of Foc in Brazil. Eight VCGs were identified: 0120, 0122, 0124, 0125, 0128, 01215, 01220, and 01222, of which 78% of isolates belong to a single VCG, while 22% of isolates belong to complexes of VCGs. The distribution of VCGs is uneven and independent of the banana genotype. VCGs were correlated with homologs of the SIX genes and varied according to geographic regions. Four SSR loci were polymorphic and on average 7.5 alleles were detected per locus. Thirty-five multilocus genotypes (MLGs) were identified. There was no association between VCG and MLGs and no genetic structure of the population of Foc in Brazil was detected.

BACKGROUND: Frailty is associated with significant morbidity and mortality in older adults. Whether frailty predicts adverse outcomes after percutaneous left atrial appendage closure (LAAC) remains uncertain. OBJECTIVE: The purpose of this study was to examine the association between frailty and clinical outcomes after percutaneous LAAC. METHODS: We identified patients 65 years and older in Medicare fee-for-service claims who underwent LAAC between October 1, 2016, and December 31, 2019. Patients were identified as frail on the basis of the Hospital Frailty Risk Score (HFRS), a validated frailty measure centered on health resource utilization, with the cohort stratified into low (15) risk groups. RESULTS: Of the 21,787 patients who underwent LAAC, 10,740 (49.3%) were considered frail (HFRS >5), including 3441 (15.8%) in the high-risk group. The mortality rate (up to 1095 days) were 16.1% in the low-risk group, 26.7% in the intermediate-risk group, and 41.1% in the high-risk group (P < .001). After adjusting for age, sex, and comorbidities, HFRS >15 (compared with HFRS

Background: Sub-Saharan Africa is undergoing an epidemiological transition fueled by the interaction between infectious and cardiovascular diseases. Our cross-sectional study aimed to characterize the spectrum of abnormalities suggesting end-organ damage on ECG and transthoracic echocardiograms (TTE) among older adults with cardiovascular diseases in rural South Africa. Methods: The prevalence of ECG and TTE abnormalities was estimated; χ 2 analyses and multivariable logistic regressions were performed to test their association with sex, hypertension, and other selected comorbidities. Results: Overall, 729 ECGs and 155 TTEs were completed, with 74 participants completing both. ECG evaluation showed high rates of left ventricular hypertrophy (LVH, 36.5%) and T wave abnormalities (13.6%). TTE evaluation showed high rates of concentric LVH (31.6%), with moderate-severe (56.8%) diastolic dysfunction. Participants with hypertension showed more cardiac remodeling on ECG by LVH (45.4% versus 22.1%, P P P P P =0.001). Male participants (n=326, 40.2%) were more likely than females (n=484, 59.8%) to show ECG abnormalities like LVH (45% versus 30.8%, P P P Conclusions: Our findings suggest that cardiovascular diseases are widespread in rural South Africa, with a larger burden of hypertensive heart disease than previously appreciated, and define the severity of end-organ damage that is already underway. Local health systems must adapt to face the growing burden of hypertension, as suboptimal rates of hypertension diagnosis and treatment may dramatically increase the heart failure burden.

SGLT-2 inhibitors remain vastly underused in clinical practice despite their broad cardiorenal benefits.

Since the implementation of the Hospital Readmissions Reduction Program (HRRP), readmissions have declined for Medicare patients with conditions targeted by the policy (acute myocardial infarction, heart failure, and pneumonia). To understand whether HRRP implementation was associated with a readmission decline for patients across all insurance types (Medicare, Medicaid, and private), we conducted a difference-in-differences analysis using information from the Nationwide Readmissions Database. We compared how quarterly readmissions for target conditions changed before (2010–12) and after (2012–14) HRRP implementation, using nontarget conditions as the control. Our results demonstrate that readmissions declined at a significantly faster rate after HRRP implementation not just for Medicare patients but also for those with Medicaid, both in the aggregate and for individual target conditions. However, composite Medicaid readmission rates remained higher than those for Medicare. Throughout the study period privately insured patients had the lowest aggregate readmission rates, which declined at a similar rate compared to nontarget conditions. The HRRP was associated with nationwide readmission reductions beyond the Medicare patients originally targeted by the policy. Further research is needed to understand the specific mechanisms by which hospitals have achieved reductions in readmissions.

After 12 years of rigorous cardiovascular outcome trials (CVOTs), sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) emerged as new therapeutic options for patients with type 2 diabetes mellitus to reduce the risk of heart disease. SGLT2i additionally cause a reduction in heart failure and renal events in patients both with and without diabetes. This article reviews the major CVOTs that support the use of these agents, describes the mechanisms of action that lead to their broad cardiorenal benefits, explains current guidelines, and offers practical clinical advice to initiate and monitor treatment with these agents.

The genetic structure of the population of

Cardiovascular clinicians are increasingly expected not only to optimise their patients’ health outcomes, but also to control costs and ensure the judicious use of healthcare resources. Clinicians must therefore have a rigorous understanding of cost-effectiveness in order to determine whether the increased effectiveness or safety of novel therapies justifies their higher costs, compared with usual care. These economic considerations are becoming increasingly salient as newly approved cardiovascular drugs enter the market at eye-wateringly high costs.1 Terms like cost-effectiveness , affordability and budget impact are sometimes erroneously used interchangeably, yet they can have profoundly different implications for patients, providers and payors. In this paper, we offer a foundational understanding of cost-effectiveness analysis (CEA) through three case studies of novel cardiovascular medications: tafamidis, proprotein convertase/subtilisin type 9 inhibitors (PCSK9i) and direct oral anticoagulants (DOACs). By helping readers confidently and correctly interpret CEAs, we hope to ensure that novel and effective cardiovascular therapies reach the patients most likely to benefit from them. The cost-effectiveness of a novel therapy is estimated by comparing the cost and benefit of a new therapy with the best available alternative (often the pre-existing standard of care), to generate a ratio known as the incremental cost-effectiveness ratio (ICER) (figure 1).2 If the ICER is equal to or lower than the society’s willingness-to-pay threshold, the new therapy is considered cost-effective in the population studied, that is, the health benefits are assumed to justify the additional costs. If the ICER exceeds the threshold, the therapy is not considered cost-effective. Willingness-to-pay levels vary among countries based on their economic development and political priorities. A consensus statement among US cardiovascular professional societies suggested that therapies with ICERs below $50 000/ quality-adjusted life-year (QALY) …

Sweepoviruses are begomoviruses (genus Begomovirus, family Geminiviridae) with ssDNA genomes infecting sweet potato and other species of the family Convolvulaceae. Deltasatellites (genus Deltasatellite, family Tolecusatellitidae) are small-size non-coding DNA satellites associated with begomoviruses. In this study, the genetic diversity of deltasatellites associated with sweepoviruses infecting Ipomoea indica plants was analyzed by further sampling the populations where the deltasatellite sweet potato leaf curl deltasatellite 1 (SPLCD1) was initially found, expanding the search to other geographical areas in southern continental Spain and the Canary Islands. The sweepoviruses present in the samples coinfected with deltasatellites were also fully characterized by sequencing in order to define the range of viruses that could act as helper viruses in nature. Additionally, experiments were performed to assess the ability of a number of geminivirids (the monopartite tomato leaf deformation virus and the bipartite NW begomovirus Sida golden yellow vein virus, the bipartite OW begomovirus tomato leaf curl New Delhi virus, and the curtovirus beet curly top virus) to transreplicate SPLCD1 in their natural plant hosts or the experimental host Nicotiana benthamiana. The results show that SPLCD1 can be transreplicated by all the geminivirids assayed in N. benthamiana and by tomato leaf curl New Delhi virus in zucchini. The presence of SPLCD1 did not affect the symptomatology caused by the helper viruses, and its effect on viral DNA accumulation depended on the helper virus–host plant combination.

Begomoviruses have circular, single-stranded DNA genomes encapsidated into twinned quasi-icosahedral particles and are transmitted by whiteflies of the Bemisia tabaci sibling group. Begomoviruses infect cultivated and non-cultivated plants, causing great losses in economically important crops worldwide. To better understand the genetic diversity of begomoviruses infecting the non-cultivated host Cnidoscolus urens, leaf samples exhibiting virus-like symptoms were collected in different localities in the state of Alagoas, Brazil, during 2015 and 2016. Forty-two complete DNA-A sequences were cloned and sequenced by the Sanger method. Based on nucleotide sequence comparisons, the 42 new isolates were identified as the bipartite begomovirus cnidoscolus mosaic leaf deformation virus (CnMLDV). The CnMLDV isolates were clustered in two phylogenetic groups (clusters I and II) corresponding to their sampling areas, and the high value of Wright's F fixation index observed for the DNA-A sequences suggests population structuring. At least seven independent intraspecies recombination events were predicted among CnMLDV isolates, with recombination breakpoints located in the common region (CR) and in the CP and Rep genes. Also, a high per site nucleotide diversity (π) was observed for CnMLDV isolates, with CP being significantly more variable than Rep. Despite the high genetic variability, strong negative or purifying selection was identified as the main selective force acting upon CP and Rep.

This study aims to assess ozonized mineral oil ointment application as an antiplaque therapy for dogs. Domestic healthy dogs received dental scaling and polishing under general anesthesia. Under standard feeding and homecare during 7 days, 20 dogs were randomly placed into 2 different groups for dental treatment. The control group (CG) was given a single placebo application and the ozone group (O3G) received daily ozonized ointment application. The average age (CG = 4.4; O3G = 5.7 years old), body weight (CG = 15.7; O3G = 15.3 kg) and the gingivitis index obtained on the first day (D0) allowed initial homogeneity between the groups. The dental plaque index, including clinical and computerized analysis on the seventh day, was obtained from the buccal aspect of specific dental locations. Both analyses revealed significant statistical association between daily application of ozone and antiplaque effect. There was no evidence of toxicity during the study. These results suggest that ozone therapy may be an efficient adjuvant to conventional periodontal treatment in decreasing initial dental plaque formation.

Background The African continent is undergoing an epidemiologic transition from infectious to cardiovascular (CV) diseases. National health systems face a critical shortage of population-level data to target the growing burden of hypertension (HTN). Very little is known on the impact of HTN on the rural population in many African countries, where over 85% of the rural population will migrate to cities and shape the modern CV disease spectrum of Africa in the next decade. Purpose To characterize the prevalence of HTN and HTN-related EKG and TTE abnormalities in a rural cohort in South Africa (n=5,059). Methods Between 2014 and 2015, 804 EKGs and 158 TTEs were performed on participants aged 40 or older randomly sampled from a longitudinal cohort residing in the Agincourt sub-district of rural South Africa. EKGs and TTEs were interpreted by two blinded physicians, and clinically meaningful variables defined using the Minnesota code (EKG) and European Association of Cardiovascular Imaging guidelines (TTE). Chi-square tests were conducted to define the association of EKG/TTE abnormalities with HTN, and stratify by gender. Results Over 55% of the sample (n=810) met blood pressure criteria for HTN, with a high prevalence of obesity (29%). On EKG, 36.5% participants had left ventricular hypertrophy (LVH), 13.6% T wave abnormalities, 7.5% Q wave abnormalities and 18.8% prolonged QT interval. Males (n=291) had more LVH (45% vs 30.8%, p Conclusions The rural population in South Africa is already affected by a high burden of HTN and high obesity levels. Within this cohort, patients with HTN have significantly more EKG and TTE abnormalities that predict adverse CV outcomes. EKG and TTE evaluation can be used to identify high-risk groups that national health systems should prioritize with frequent monitoring and more aggressive medical treatment. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Brigham and Women's Hospital

Background Anthracycline (ANT) therapy has dramatically improved clinical outcomes for patients with breast cancer, but it causes cardiotoxicity (CTX) in a dose-dependent manner. Current cardiac biomarkers (troponin, brain natriuretic peptide) and 2D echocardiography only detect CTX in advanced and often irreversible stages. Metabolomic analysis may allow early diagnosis of CTX, and prompt initiation of cardio protective therapies. Purpose To diagnose early CTX via speckle tracking echocardiography (STE), and to characterize the metabolomic fingerprint of patients affected by ANT-mediated CTX. Methods In 2019, patients with breast cancer and normal baseline ejection fraction (EF) were enrolled and longitudinally monitored through clinical assessment, blood sample collection and echocardiography, before initiation of ANT therapy and at 180, 270 and 360 mg/m2 of ANT. CTX, defined as >15% reduction in Global Longitudinal Strain (GLS), was monitored at each ANT dose increment. Unsupervised Principal Component Analysis, supervised Partial Least Square and Partial Least-Square Discriminant Analyses were used to compare the metabolomic profiles of patients who did and did not develop CTX during the study period. Results In the study sample (n=33), no patient developed clinical heart failure, but 8 patients (25%) developed CTX by GLS criteria. Patients with CTX had a significant decrease in GLS compared to patients without CTX at 270 mg/m2 (GLS 20.5 vs 17.9, p=0.01) and 360 mg/m2 ANT (GLS 21.6 vs 17.7, p Conclusions For the first time in a human population of breast cancer patients, we show that early ANT-induced CTX (diagnosed via asymptomatic GLS reduction) is associated with a unique metabolomic profile, which affects molecular pathways of energy production. Notably, CTX damage upregulates similar metabolites to those previously identified in clinical heart failure and in mouse CTX models. Our results suggest that a metabolomic fingerprint can be leveraged to create prediction models to identify patients at higher risk of developing cardiovascular complications from ANT therapy. This, in turn, will allow to personalize both chemotherapy and cardioprotective treatments. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): University of Cagliari

Background: Statistical testing in phase III clinical trials is subject to chance errors, which can lead to false conclusions with substantial clinical and economic consequences for patients and society. Methods: We collected summary data for the primary endpoints of overall survival (OS) and progression-related survival (PRS) (eg, time to other type of event) for industry-sponsored, randomized, phase III superiority oncology trials from 2008 through 2017. Using an empirical Bayes methodology, we estimated the number of false-positive and false-negative errors in these trials and the errors under alternative P value thresholds and/or sample sizes. Results: We analyzed 187 OS and 216 PRS endpoints from 362 trials. Among 56 OS endpoints that achieved statistical significance, the true efficacy of experimental therapies failed to reach the projected effect size in 33 cases (58.4% false-positives). Among 131 OS endpoints that did not achieve statistical significance, the true efficacy of experimental therapies reached the projected effect size in 1 case (0.9% false-negatives). For PRS endpoints, there were 34 (24.5%) false-positives and 3 (4.2%) false-negatives. Applying an alternative P value threshold and/or sample size could reduce false-positive errors and slightly increase false-negative errors. Conclusions: Current statistical approaches detect almost all truly effective oncologic therapies studied in phase III trials, but they generate many false-positives. Adjusting testing procedures in phase III trials is numerically favorable but practically infeasible. The root of the problem is the large number of ineffective therapies being studied in phase III trials. Innovative strategies are needed to efficiently identify which new therapies merit phase III testing.

Background High‐sensitivity troponin assays (hs‐Tn) detect lower serum concentrations than prior‐generation assays and help guide acute coronary syndrome (ACS) evaluation in emergency departments. Outpatient hs‐Tn utilization is not well described. Hypothesis Outpatient providers use hs‐TnT to triage patients with suspected ACS. Methods We compared the volume of outpatient prior‐generation troponin tests in the pre‐hsTn implementation period (January 2015‐March 2018) with outpatient hs‐TnT volume in the post‐implementation period (April 2018‐January 2020). Triage patterns were compared between patients with hs‐TnT≥99th vs 99th percentile were more likely to be sent to the ED (RR, 3.36; 95% CI, 1.22‐9.25; P = .002). Among patients sent home (n = 66), those with hs‐TnT > 99th percentile had more adverse events by 6 months (3.3% vs 22.2% RR, 6.67; 95% CI, 1.04‐42.9; P = .026). Conclusions In this healthcare system, outpatient troponin utilization significantly declined since hs‐TnT implementation. Some providers use hs‐TnT to triage patients with suspected ACS to the ED; others test asymptomatic patients and some send patients home despite high hs‐TnT values.

This study describes SARS-CoV-2 PCR test positivity among health care workers before, during, and after implementation of a policy requiring universal masking of all health care workers and patients in a large health care system in Massachusetts.

Several key evolutionary events marked the evolution of geminiviruses, culminating with the emergence of bipartite genomes represented by viruses classified in the genusBegomovirus. This genus represents the most abundant group of multipartite viruses, contributing significantly to the observed abundance of multipartite species in the virosphere. Although aspects related to virus-host interactions and evolutionary dynamics have been extensively studied, the bipartite nature of these viruses has been little explored in evolutionary studies. We performed a parallel evolutionary analysis of the DNA-A and DNA-B components of New World begomoviruses. A total of 239 full-length DNA-B sequences obtained in this study, combined with 292 DNA-A and 76 DNA-B sequences retrieved from GenBank, were analyzed. The results indicate that the DNA-A and DNA-B respond differentially to evolutionary processes, with the DNA-B being more permissive to variation and more prone to recombination than the DNA-A. Although a clear geographic segregation was observed for both components, differences in the genetic structure between DNA-A and DNA-B were also observed, with cognate components belonging to distinct genetic clusters. DNA-B coding regions evolve under the same selection pressures than DNA-A coding regions. Together, our results indicate an interplay between reassortment and recombination acting at different levels across distinct subpopulations and components.

Despite all efforts to control the COVID-19 spread, the SARS-CoV-2 reached South America within three months after its first detection in China, and Brazil became one of the hotspots of COVID-19 in the world. Several SARS-CoV-2 lineages have been identified and some local clusters have been described in this early pandemic phase in Western countries. Here we investigated the genetic diversity of SARS-CoV-2 during the early phase (late February to late April) of the epidemic in Brazil. Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. This SARS-CoV-2 Brazilian lineage was probably established during February 2020 and rapidly spread through the country, reaching different Brazilian regions by the middle of March 2020. Our study also supports occasional exportations of this Brazilian B.1.1 lineage to neighboring South American countries and to more distant countries before the implementation of international air travels restrictions in Brazil.

Among the nanomaterials, rare sesquioxides (lanthanide oxides such as Lu

Introduction: High sensitivity troponin T (hs-TnT) are more sensitive than prior assays to evaluate patients for acute coronary syndrome. To date, hs-TnT utilization in the outpatient setting is not well described. Methods: We identified outpatient hs-TnT tests ordered at a large medical center in the first 9 months of implementation (April-December 2018). Charts were reviewed by physicians to identify patient characteristics, specialty of ordering provider, reason for ordering hs-TnT, and clinical action taken. Using unadjusted two-sample t-tests, we compared the proportion of patients referred to the ED between patients with hs-TnT levels ≥99 th % sex-specific cutoffs (≥15 ng/dL men, ≥10 ng/dL women) versus those with either undetectable hs-TnT or detectable th % (control group). Results: About 100 hs-TnT outpatient tests were ordered. Patients had mean age of 66 years, 53% were male; 30% had coronary artery disease, and 12% had left ventricular ejection fraction ≤40%. Most orders were placed by cardiologists (n=58) followed by primary care physicians (n=30). The top chief complaints were dyspnea (n=38) and chest pain (n=33). Of all hs-TnT samples, 27% were undetectable, while mean detectable hs-TnT level was 38.8 ng/L, of which 57% were ≥99 th %. About 25% of patients had chronic cardiovascular conditions (like heart failure) but were asymptomatic at the time of the test. Among symptomatic patients (n=75), 31% were sent home, 28% to stress test, and 16% to the ED. Patients with hs-TnT ≥99 th % were 4.6 times more likely (95% CI 1.1-19.5, p=0.04) to be referred to the ED, compared to control. Conclusions: This is the first study describing outpatient utilization of the novel hs-TnT assay in the U.S. Despite the lack of consensus on diagnosing cardiac ischemia in outpatient clinics, providers are ordering hs-TnT in this setting - and hs-TnT values seem to influence their decision to triage patients to the ED. Our results highlight the need to standardize the implementation of hs-TnT for outpatient evaluation of cardiac ischemia. Providers are also collecting hs-TnT among asymptomatic patients with heart disease unrelated to ischemia. This suggests that novel uses of hs-TnT may emerge to monitor and prognosticate chronic cardiovascular conditions. Figure. Patient Triage based on Elevation in Outpatient hs-TnT Level

BACKGROUND AND AIM: Permanent Atrial Fibrillation (pAF) is associated with increased risk of embolic complications. The relationship between pAF and pulmonary embolism (PE) has not been extensively investigated in elderly patients. Here, we aim at verifying whether pAF is associated to an increased risk of PE in a cohort of elderly patients with and without Deep Vein Thrombosis (DVT). METHODS: 235 patients older than 65 years with PE with or without pAF were retrospectively enrolled and stratified by the absence or presence of DVT. The diagnosis of PE was performed by computed tomography angiography (CTA). Right echocardiographic parameters were monitored. The severity of PE was evaluated by CTA quantization (PE score = 1, involvement of main branches of pulmonary artery) and by dimer-D (> 3000 µg/L). RESULTS: DVT was identified only in 51 cases of PE (21.7%). pAF prevalence was higher in PE without than in those with DVT (64.9% vs. 35.1%, p 3000 µg/L). CONCLUSIONS: We conclude that in elderly patients with PE, the prevalence of pFA was doubled, in the absence of DVT, and it is associated with a more severe PE in the absence than in the presence of DVT. Thus, in the absence of DVT, pFA should be considered as cause of PE.