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Abstract Background A proposed risk factor for cardiovascular disease is high occupational physical activity (OPA), which seems to increase blood pressure (BP), in contrast to leisure time physical activity. Increased BP may lead to hypertension that increase the risk of cardiovascular disease and premature death. Exposures to OPA differ across sex and also within occupational group. Thus, we aimed to investigate associations between OPA and LTPA and BP among men and women using compositional data analysis. Methods This population-based cross-sectional study, used data from the Copenhagen Aging and Midlife Biobank. OPA and LTPA were self-reported time spent in light physical activity (LPA) during work = standing or walking work; moderate-to-vigorous physical activity (MVPA) during work = heavy manual work; LPA during leisure = light physical activity during leisure; MVPA during leisure = biking or walking as commute to work + daily amount of MVPA during leisure, and sleep. Systolic and diastolic BP (SBP, DBP; mmHg) was measured during sitting rest. We used linear regression models to investigate the association between OPA and LTPA, expressed as isometric log-ratios, and BP. The models were used to predict the BP for reallocated physical activity (PA) compositions (i.e., theoretically ‘moving’ time from sitting to PA within each domain). Specifically, we predicted the BP for each reallocated PA compositions and calculated the difference in BP between the reallocated compositions and the mean composition. Results In total, 1,334 women and 2,983 men (mean age 55.1 and 52.5 years, respectively) were included in the analyses. About 50% of the women, and 66% of the men, had hypertension. The linear regressions based on the compositional data analysis, showed no association between OPA and LTPA and SBP among women or men. Among men, less time spent sitting and more time spent in LTPA, compared to the mean composition, was associated with a lower DBP (e.g., 60 min less sitting and 60 min more LTPA: -0.25, 95% CI: -0.05, -0.45 mmHg). Conclusion No association between OPA and LTPA and BP was observed across sexes, except between LTPA and DBP among men. This could be due to information bias and lack of precision in self-reported time use data of PA. Trial registration None.

Abstract Background Hypertension, type 2 diabetes, and cardiovascular disease affect the activities of daily living at varying degree. While the effects of aerobic exercise on functional capacity are well-documented, the extent of change for different types of exercise in these chronic conditions remains unexplored. Additionally, there is conflicting evidence regarding the role of exercise in reducing body weight. Methods We conducted systematic review with meta-analysis and trial sequential analysis and searched various databases from inception to July 2020. We included randomised clinical trials adding any form of trialist defined exercise to usual care versus usual care in people with either hypertension, type 2 diabetes, and/or cardiovascular disease irrespective of setting, publication status, year, and language. The outcomes assessed were i) functional capacity assessed through different scales separately i.e., Maximal Oxygen Uptake (VO2max), 6-min walk test (6MWT), 10-m walk test (10MWT), and ii) body weight. Results We included 950 studies out of which 444 trials randomising 20,098 participants reported on various functional outcomes (355 trials) and body weight (169 trials). The median follow-up was 3 months (Interquartile ranges (IQR): 2.25 to 6). Exercise added to the usual care, improved VO2max (Mean Difference (MD):2.72 ml/kg/min; 95% Confidence Interval (CI) 2.38 to 3.06; p

We formulate a data-independent latent space regularization constraint for general unsupervised autoencoders. The regularization relies on sampling the autoencoder Jacobian at Legendre nodes, which are the centers of the Gauss–Legendre quadrature. Revisiting this classic allows us to prove that regularized autoencoders ensure a one-to-one re-embedding of the initial data manifold into its latent representation. Demonstrations show that previously proposed regularization strategies, such as contractive autoencoding, cause topological defects even in simple examples, as do convolutional-based (variational) autoencoders. In contrast, topological preservation is ensured by standard multilayer perceptron neural networks when regularized using our approach. This observation extends from the classic FashionMNIST dataset to (low-resolution) MRI brain scans, suggesting that reliable low-dimensional representations of complex high-dimensional datasets can be achieved using this regularization technique.

Background: Concomitant type 2 diabetes (T2DM) and cardiovascular disease (CVD) is frequent with a poor prognosis with high risk of comorbidities. Strict risk factor control reduces the risk for complications – yet many people do not achieve treatment targets. The complexity and fragmentation of the healthcare system may, together with the vulnerability of these patients, be a reason. Objective: The purpose of this paper is to describe the protocol of a non-randomized interventional pilot study testing the feasibility and effect of a multidisciplinary, shared care clinic using personalized medicine and coordinated care in people living with concomitant T2D and CVD. Methods: Participants were included from the Holbaek area in Denmark. People suffered from T2DM and CVD and were dysregulated regarding to HbA1c, cholesterol, micro/macroalbuminuaria or blood pressure. Participants went through a thorough evaluation to identify their needs and resources and received consultations every three months for one year. Results: A total of 63 participants with T2DM and CVD were enrolled in the clinic. The participants had a mean age of 69 years and a BMI of 30.9 kg/m2. Almost 50 % had heart failure, 95 % dyslipidemia and 91 % hypertension. Around 54 % received GLP-1 agonists and 39 % received SGLT-2-inhibitors. Perspectives: To our knowledge, a similar study with a multidisciplinary, shared care, outpatient clinic treating people living with concomitant T2DM and CVD, has not been performed previously. This study will provide information about the feasibility and efficacy of a multidisciplinary clinic based on changes in cardiovascular risk factors and medication.

Objective: The objective of this formative study was to gather women’s perspectives in the design and communication modalities of a health kiosk set within a Planned Parenthood setting to promote patient education about the Human papillomavirus (HPV) and to motivate uptake of the HPV vaccine. Methods: Twenty-four women aged 18-35 participated in in-depth one-on-one interviews at a Planned Parenthood health center, which were analyzed in code-associated categories using NVivo11 Pro. Results: Most women showed receptivity to using an on-site health kiosk, as well as QR codes linked to text messages, to receive HPV-related health information outside of the clinic setting and reminders. Participants provided suggestions for kiosk design and communication modalities. Conclusions: Among low-income women we interviewed at Planned Parenthood, increasing HPV vaccination rates necessitates engaging digital health tools which incorporate both the preferences and needs of vulnerable populations. Innovation: Designing a point-of-service health kiosk that 1) draws on user preferences early in the design phase, 2) integrates multiple communication technologies, and 3) disseminates culturally grounded HPV vaccination decisions narratives that are tailored to vaccination awareness level is a promising approach in reducing barriers to HPV vaccine education and vaccine uptake among low-income women at safety-net clinics.

Abstract Background A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis. Methods The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for “site,” type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or

We present a variational approach aimed at enhancing the training of physics-informed neural networks (PINNs) and more general surrogate models for learning partial differential equations (PDE). In particular, we extend our formerly introduced notion of Sobolev cubatures to negative orders, enabling the approximation of negative order Sobolev norms. We mathematically prove the effect of negative order Sobolev cubatures in improving the condition number of discrete PDE learning problems, providing balancing scalars that mitigate numerical stiffness issues caused by loss imbalances. Additionally, we consider polynomial surrogate models ( PSMs ), which maintain the flexibility of PINN formulations while preserving the convexity structure of the PDE operators. The combination of negative order Sobolev cubatures and PSMs delivers well-conditioned discrete optimization problems, solvable via an exponentially fast convergent gradient descent for λ -convex losses. Our theoretical contributions are supported by numerical experiments, addressing linear and non-linear, forward and inverse PDE problems. These experiments show that the Sobolev cubature-based PSMs emerge as the superior state-of-the-art PINN technique.

BackgroundLeft ventricular hypertrophy (LVH) is the main marker of HMOD in children and young people (CYP). We aimed to assess the prevalence of LVH and its determinants in CYP with primary hypertension (PH).MethodsA meta-analysis of prevalence was performed. A literature search of articles reporting LVH in CYP with PH was conducted in Medline, Embase, and Cochrane databases. Studies with a primary focus on CYP (up to 21 years) with PH were included. Meta-regression was used to analyze factors explaining observed heterogeneity.ResultsThe search yielded a total of 2,200 articles, 153 of those underwent full-text review, and 47 reports were included. The reports evaluated 51 study cohorts including 5,622 individuals, 73% male subjects, and a mean age of 13.6 years. LVH was defined as left ventricle mass index (LVMI) ≥ 95th percentile in 22 (47%), fixed cut-off ≥38.6 g/m2.7 in eight (17%), sex-specific fixed cut-off values in six (13%), and miscellaneously in others. The overall prevalence of LVH was 30.5% (95% CI 27.2–33.9), while heterogeneity was high (I2 = 84%). Subgroup analysis including 1,393 individuals (76% male subjects, mean age 14.7 years) from pediatric hypertension specialty clinics and LVH defined as LVMI ≥95th percentile only (19 study cohorts from 18 studies), reported prevalence of LVH at 29.9% (95% CI 23.9 to 36.3), and high heterogeneity (I2 = 84%). Two studies involving patients identified through community screening (n = 1,234) reported lower LVH prevalence (21.5%). In the meta-regression, only body mass index (BMI) z-score was significantly associated with LVH prevalence (estimate 0.23, 95% CI 0.08–0.39, p = 0.004) and accounted for 41% of observed heterogeneity, but not age, male percentage, BMI, or waist circumference z-score. The predominant LVH phenotype was eccentric LVH in patients from specialty clinics (prevalence of 22% in seven studies with 779 participants) and one community screening study reported the predominance of concentric LVH (12%).ConclusionLeft ventricular hypertrophy is evident in at least one-fifth of children and young adults with PH and in nearly a third of those referred to specialty clinics with a predominant eccentric LVH pattern in the latter. Increased BMI is the most significant risk association for LVH in hypertensive youth.

Abstract A clinical audit of hospitals in Thailand was conducted to assess compliance with the national hypertension treatment guidelines and determine hypertension control rates across facilities of different sizes. Stratified random sampling was used to select sixteen hospitals of different sizes from four provinces. These included community (120 beds) hospitals. Among new cases, the audit determined whether (i) the recommended baseline laboratory assessment was completed, (ii) the initial choice of medication was appropriate based on the patient's cardiovascular risk, and (iii) patients received medication adjustments when indicated. The hypertension control rates at six months and at the last visit were recorded. Among the 1406 patients, about 75% had their baseline glucose and kidney function assessed. Nearly 30% (n = 425/1406) of patients were indicated for dual therapy but only 43% of them (n = 182/425) received this. During treatment, 28% (198/1406) required adjustments in medication but this was not done. The control of hypertension at six months after treatment initiation was 53% varying between 51% in community and 56% in large hospitals (p

Introduction: Smoking research demonstrates that parents can influence their adolescent’s tobacco smoking perceptions and behaviors, but little is known about the protective effects of different parenting practices on adolescent vaping. In this study we investigate how adolescent perceptions of parents’ knowledge of their activities and parental media mediation are associated with adolescents’ perceptions of vaping and adolescent vaping behaviors. Method: Six hundred thirty-nine youth (65.7% female, average age: 14.71 years old) recruited through 4-H clubs in nine states participated in a study evaluating a substance use intervention program. Because the evaluation design could influence participants, we used only baseline data. An online self-reported survey was administrated. Most youth self-identified as White (87.3%) and only handful youth indicated Asian (3.4%), African American (3.4%), American Indian (1.1%), and other or unreported (4.8%). Approximately 60% of youth lived in small town or rural areas in US. Results: Analyses revealed that parental knowledge was positively related with adolescent perceived harm of vaping and perceived prevalence of vaping, but was negatively related with perceived acceptability of vaping and social expectancy of vaping. In addition, youth who reported greater parental media mediation were more likely to perceive the harm of vaping and less likely to vape compared with youth with lower parental media mediation. Conclusion: These findings suggest that parental education about vaping, including those promoting conversations regarding vaping and vaping ads, may be important to the prevention of adolescent vaping.

Abstract Background The World Health Organization recommends consumption of a minimum of 400 g of fruits and vegetables per day for prevention of cardiovascular disease. Low fruit and vegetable intake is associated with an increased risk of stroke by 11% and ischemic heart disease by 31%. The present study aims to explore factors affecting the fruit and vegetable intake in Nepal and its association with history of self-reported major cardiovascular events (myocardial infarction and stroke). Method Data for this cross-sectional study were collected as part of the study “Community Based Management of Hypertension in Nepal” initiated in the Lekhnath Municipality in 2013. Demographic and nutrition information were collected using the WHO STEPwise approach to a surveillance tool. Descriptive statistics identified the frequency and percentage of fruit and vegetable intake. A Chi-square test examined the association between fruit and vegetable intake and history of self-reported cardiovascular events, socio-demographic and cardiovascular risk factors. Binary logistic regression analysis identified odds ratio with 95% confidence intervals between fruit and vegetable intake and history of self-reported cardiovascular events. Results The mean and median intake of fruits and vegetables were 3.3 ± 0.79 and 3 servings respectively. Of the 2815 respondents, 2% (59) reported having a history of major cardiovascular events. The adjusted odds of having a history of major cardiovascular events was 2.22 (95%CI, 1.06–4.66) for those who consumed

La hipertensión arterial es una causa modificable muy prevalente de enfermedades cardiovasculares, accidentes cerebrovasculares y muerte. Medir con exactitud la presión arterial es fundamental, dado que un error de medición de 5 mmHg puede ser motivo para clasificar incorrectamente como hipertensas a 84 millones de personas en todo el mundo. En la presente declaración de posición se resumen los procedimientos para optimizar el desempeño del observador al medir la presión arterial en el consultorio, con atención especial a los entornos de ingresos bajos o medianos, donde esta medición se ve complicada por limitaciones de recursos y tiempo, sobrecarga de trabajo y falta de suministro eléctrico. Es posible reducir al mínimo muchos errores de medición con una preparación adecuada de los pacientes y el uso de técnicas estandarizadas. Para simplificar la medición y prevenir errores del observador, deben usarse tensiómetros semiautomáticos o automáticos de manguito validados, en lugar del método por auscultación. Pueden ayudar también la distribución de tareas, la creación de un área específica de medición y el uso de aparatos semiautomáticos o de carga solar. Es fundamental garantizar la capacitación inicial y periódica de los integrantes del equipo de salud. Debe considerarse la implementación de programas de certificación de bajo costo y fácilmente accesibles con el objetivo de mejorar la medición de la presión arterial.

Abstract Background Treatment with beta-blockers is currently recommended after myocardial infarction (MI). The evidence relies on trials conducted decades ago before implementation of revascularization and contemporary medical therapy or in trials enrolling patients with heart failure or reduced left ventricular ejection fraction (LVEF ≤ 40%). Accordingly, the impact of beta-blockers on mortality and morbidity following acute MI in patients without reduced LVEF or heart failure is unclear. Methods/design The Danish trial of beta-blocker treatment after myocardial infarction without reduced ejection fraction (DANBLOCK) is a prospective, randomized, controlled, open-label, non-blinded endpoint clinical trial designed to evaluate the efficacy of beta-blocker treatment in post-MI patients in the absence of reduced LVEF or heart failure. We will randomize 3570 patients will be randomized within 14 days of index MI to beta-blocker or control for a minimum of 2 years. The primary endpoint is a composite of all-cause mortality, recurrent MI, acute decompensated heart failure, unstable angina pectoris, or stroke. The primary composite endpoint will be assessed through locally reported and adjudicated endpoints supplemented by linkage to the Danish national registers. A number of secondary endpoints will be investigated including patient reported outcomes and cardiovascular mortality. Data from similar ongoing trials in Norway and Sweden will be pooled to perform an individual patient data meta-analysis. Discussion DANBLOCK is a randomized clinical trial investigating the effect of long-term beta-blocker therapy after myocardial infarction in patients without heart failure and reduced LVEF. Results from the trial will add important scientific evidence to inform future clinical guidelines. Trial registration Clinicaltrials.gov, NCT03778554 . Registered on 19 December 2018. European Clinical Trials Database, 2018-002699-42 , registered on 28 September 2018.

La Comisión Lancet de Hipertensión determinó que una medida clave para responder a la carga mundial que representa la hipertensión arterial era mejorar la calidad de las mediciones de la presión arterial, mediante la utilización de dispositivos cuya exactitud haya sido validada. En la actualidad existen 3000 dispositivos comercializados, pero muchos no tienen datos publicados sobre pruebas de exactitud conformes a las normas científicas establecidas. La falta de regulación o su ineficiencia, que permiten la autorización de dispositivos para uso comercial sin una validación oficial, posibilitan este problema. Además, han surgido tecnologías nuevas de medición de la presión arterial (por ejemplo, los sensores sin brazalete) sobre las cuales no existe unanimidad en la comunidad científica con respecto a las normas de exactitud de la medición. En conjunto, estos aspectos contribuyen a la disponibilidad generalizada de tensiómetros de consultorio o domiciliarios que ofrecen una exactitud limitada o incierta, que llevan a diagnósticos, manejo y farmacoterapia inapropiados de la hipertensión a escala mundial. Los problemas más importantes relacionados con la exactitud de los dispositivos de medición de la presión arterial se pueden resolver mediante el requisito regulatorio de una validación independiente obligatoria de los dispositivos, en consonancia con la norma ISO universalmente aceptada. Esta es una recomendación básica y constituye una necesidad internacional acuciante. Otras recomendaciones clave son la elaboración de normas de validación específicas para las tecnologías nuevas de medición de la presión arterial y la publicación en línea de listas de los dispositivos nuevos exactos que están a la disposición de los usuarios y los profesionales de salud. Las recomendaciones están en consonancia con las políticas de la Organización Mundial de la Salud sobre los dispositivos médicos y la atención universal de la salud. El cumplimiento de las recomendaciones aumentará la disponibilidad mundial de dispositivos de medición de la presión arterial que sean exactos y tendrá como efecto un mejor diagnóstico y tratamiento, reduciendo así la carga mundial de la hipertensión.

Hypertension and heart failure are important contributors to global morbidity and mortality. Despite therapeutic lifestyle and pharmacological measures, a significant proportion of people with hypertension do not reach treatment targets. Patients with resistant or poorly controlled hypertension are at significantly increased risk of cardiovascular events, including heart failure. Since dysfunction of the sympathetic nervous system appears to play a key role in the development and progression of both hypertension and heart failure, these patients may benefit from treatment modalities aimed at reducing sympathetic function. The purpose of this paper is to provide an overview of baroreflex activation therapy as a potential treatment strategy in patients with resistant hypertension or heart failure.

Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high‐risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high‐risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24‐hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0–170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8–7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m2 (95% CI, 36.6–45.6). In 96 patients with available 3‐month follow‐up data, mean 24‐hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4–23.8; P

We present novel approximates of variational losses, being applicable for the training of physics-informed neural networks (PINNs). The formulations reflect classic Sobolev space theory for partial differential equations (PDEs) and their weak formulations. The loss approximates rest on polynomial differentiation realised by an extension of classic Gauss–Legendre cubatures , we term Sobolev cubatures , and serve as a replacement of automatic differentiation . We prove the training time complexity of the resulting Sobolev -PINNs with polynomial differentiation to be less than required by PINNs relying on automatic differentiation. On top of one-to-two order of magnitude speed-up the Sobolev-PINNs are demonstrated to achieve closer solution approximations for prominent forward and inverse, linear and non-linear PDE problems compared to established PINNs.

Background and Objectives: The opioid epidemic has permeated all strata of society over the last two decades, especially within the adolescent student athletic environment, a group particularly at risk and presenting their own challenges for science and practice. This paper (a) describes the development of a web-based intervention called the Student Athlete Wellness Portal that models effective opioid misuse resistance strategies and (b) details the findings of a single-group design to test its effectiveness. Materials and Methods: Formative research included 35 student athletes residing in the United States, ages 14 to 21, who had been injured in their school-based sport. They participated in in-depth qualitative interviews to explore narratives relating to their injuries and pain management plans. Inductive analyses of interview transcripts revealed themes of the challenges of being a student athlete, manageable vs. unmanageable pain, and ways to stay healthy. These themes were translated into prevention messages for the portal, which was then tested in a single-group design. Results: Users of the portal (n = 102) showed significant decreases in their willingness to misuse opioids and increases in their perceptions of opioid risks. Conclusions: This manuscript illuminates the processes involved in translating basic research knowledge into intervention scripts and reveals the promising effects of a technology-based wellness portal.

Abstract Background Hypertension, type 2 diabetes mellitus and cardiovascular disease are among the leading causes of mortality globally. Exercise is one of the commonly recommended interventions/preventions for hypertension, type 2 diabetes mellitus and cardiovascular disease. However, the previous reviews have shown conflicting evidence on the effects of exercise. Our objective is to assess the beneficial and harmful effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease. Methods This protocol for a systematic review was undertaken using the recommendations of The Cochrane Collaboration, the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the eight-step assessment procedure suggested by Jakobsen et al. We plan to include all relevant randomised clinical trials and cluster-randomised trials assessing the effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded on Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP) and BIOSIS. We will systematically assess the risks of random errors using Trial Sequential Analysis as well as risks of bias of all included trials. We will create a ‘Summary of Findings’ table in which we will present our primary and secondary outcomes, and we will assess the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Discussion The present systematic review will have the potential to aid patients, clinicians and decision-makers recommending exercise and thereby, benefit patients with hypertension, type 2 diabetes mellitus and/or cardiovascular disease. Systematic review registration PROSPERO CRD42019142313

Abstract Background Heart failure is a highly prevalent disease with a global prevalence of 37 million, and the prevalence is increasing. Patients with heart failure are at an increased risk of death and morbidity. Traditionally, patients with heart failure have been treated with a beta-blocker in addition to an inhibitor of the renin-angiotensin-aldosterone system. However, new drugs are currently being added to the recommended guideline therapy. The latest drug to be added combines inhibition of the renin-angiotensin-aldosterone system pathway with inhibiting the neprilysin enzyme and is therefore classified as an ARNI. Our objective is to identify the beneficial and harmful effects of ARNIs in the treatment of patient with heart failure. Methods This protocol for a systematic review was undertaken using the recommendations of the Cochrane, the Preferred Report Items of Systematic reviews with Meta-Analysis Protocols, and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials assessing the use of ARNIs in the treatment of patients with heart failure. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded on Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP), and BIOSIS to identify relevant trials. We will also search for grey literature and unpublished trials. Extracted data will be analysed using Review Manager 5, STATA 5, and Trial Sequential Analysis. Our primary outcomes will be all-cause mortality and serious adverse events. We will create a ‘Summary of Findings’ table in which we will present our primary and secondary outcomes, and we will assess the quality of evidence using the GRADE assessment. Discussion The present systematic review will have the potential to aid clinicians in decision-making and thereby, benefit patients with heart failure. Systematic review registration PROSPERO CRD42019129336

Aims: Atrial fibrillation (AF) is associated with increased cardiovascular risk and the incidence increases with age, hypertension and left ventricular hypertrophy (LVH). Reducing in-treatment systolic blood pressure (SBP) prevents new-onset AF but has previously not been studied in patients with isolated systolic hypertension (ISH). We aimed to investigate the effect on preventing new-onset AF by decreased in-treatment SBP in patients with ISH compared to patients with non-ISH. Methods and results: Double-blind, randomized, parallel-group study of 1320 patients with ISH and electrocardiographic (ECG) LVH, included among the 9193 patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Annual ECGs were Minnesota coded centrally, and new-onset AF was evaluated in 1248 ISH patients and compared with 7583 non-ISH patients during mean 4.8 ± 0.9 years follow-up. Cox regression analyses were used to assess the effect of reduced in-treatment SBP. New-onset AF occurred in 61 (4.9%) ISH patients and 292 (3.9%) non-ISH patients. In multivariate analysis lower in-treatment SBP was associated with 17% risk reduction (p = 0.008) for new-onset AF in ISH patients and 9% risk reduction (p = 0.006) in non-ISH patients per 10 mmHg decrease in in-treatment SBP, independent of treatment modality, baseline risk factors, baseline SBP and in-treatment heart rate and ECG-LVH. There was a significant interaction (p = 0.041) in favor of SBP reduction and AF prevention in ISH vs. non-ISH patients. Conclusion: Our data suggest that the effect of in-treatment SBP reduction in preventing new-onset AF is stronger in ISH compared to non-ISH patients with hypertension and ECG-LVH. However, the principal findings were the same in ISH and non-ISH patients.

Introduction Atrial fibrillation is the most common heart arrhythmia with a prevalence of approximately 2% in the western world. Atrial fibrillation is associated with an increased risk of death and morbidity. In many patients, a rate control strategy is recommended. The optimal heart rate target is disputed despite the results of the the RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient vs strict rate control II (RACE II) trial.Our primary objective will be to investigate the effect of lenient rate control strategy (

Current guidelines recommend angiotensin receptor blocker neprilysin inhibitors (ARNI) (sacubitril/valsartan) as a replacement for angiotensin-converting-enzymeinhibitor (ACE-I) in heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy. The effects of ARNIs have not previously been assessed in a systematic review. We searched for relevant trials until October 2019 in CENTRAL, MEDLINE, Embase, LILACS, BIOSIS, CNKI, VIP, WanFang and CBM. Our primary outcomes were all-cause mortality and serious adverse events. We systematically assessed the risks of random errors and systematic errors. PROSPERO registration: CRD42019129336. 48 trials randomising 19 086 participants were included. The ARNI assessed in all trials was sacubitril/valsartan. ACE-I or ARB were used as control interventions. Trials randomising HFrEF participants (27 trials) and heart failure with preserved ejection fraction (HFpEF) participants (four trials) were analysed separately. In HFrEF participants, meta-analyses and Trial Sequential Analyses showed evidence of a beneficial effect of sacubitril/valsartan when assessing all-cause mortality (risk ratio (RR), 0.86; 95% CI, 0.79 to 0.94) and serious adverse events (RR, 0.89; 95% CI, 0.86 to 0.93); and the results did not differ between the guideline recommended target population and HFrEF participants in general. We found no evidence of an effect of sacubitril/valsartan in HFpEF participants. Sacubitril/valsartan compared with either ACE-I or ARB seems to have a beneficial effect in patients with HFrEF. Our results indicate that sacubitril/valsartan might be beneficial in a wider population of patients with heart failure than the guideline recommended target population. Sacubitril/valsartan does not seem to show evidence of a difference compared with valsartan in patients with HFpEF.

Introduction: Home BP monitoring is recommended to guide clinical decisions on hypertension and is used worldwide. People make their own decisions when purchasing BP measurement devices, which are often made online. One potential barrier to accurate home BP monitoring is that patients may purchase an unvalidated device (one that has not been proven accurate according to an internationally sanctioned protocol). This study aimed to evaluate the number, type, percentage validated and cost of home BP devices available online. Methods: A systematic search of online businesses selling BP devices that may be used for home BP monitoring was conducted. Multinational companies make international deliveries, so searches were restricted to BP devices available for one nation (Australia) as an example of device availability through the globally connected online marketplace. Validation status of BP devices was determined according to established protocols. Results: 59 online businesses, selling 972 unique BP devices were identified. These included 278 upper-arm cuff devices (18.3% validated), 162 wrist-cuff devices (8.0% validated) and 532 wrist-band wearables (0% validated). Most BP devices (92.4%) were stocked by international ‘e-commerce’ businesses (e.g. eBay, Amazon), but only 5.5% of these were validated. Validated cuff BP devices were more expensive than non-validated devices: median (interquartile range) of 101.14 (75.00 to 151.50; versus 67.37 (30.40 to 112.83) AUD, p < 0.0001. Conclusion: Non-validated BP devices dominate the online marketplace and are sold at lower cost than validated devices. The widespread use of non-validated BP devices is a barrier to accurate home BP monitoring and must be urgently addressed.

Objective: To explore the effects of baroreflex activation therapy (BAT) on hypertension in patients with treatment resistant or refractory hypertension. Methods: This investigator-initiated randomized, double-blind, 1:1 parallel-design clinical trial will include 100 patients with refractory hypertension from 6 tertiary referral hypertension centers in the Nordic countries. A Barostim Neo System will be implanted and after 1 month patients will be randomized to either BAT for 16 months or continuous pharmacotherapy (BAT off) for 8 months followed by BAT for 8 months. A second randomization will take place after 16 months to BAT or BAT off for 3 months. Eligible patients have a daytime systolic ambulatory blood pressure (ABPM) of ≥145 mm Hg, and/or a daytime diastolic ABPM of ≥95 mm Hg after witnessed drug intake (including ≥3 antihypertensive drugs, preferably including a diuretic). Results: The primary end point is the reduction in 24-hour systolic ABPM by BAT at 8 months, as compared to pharmacotherapy. Secondary and tertiary endpoints are effects of BAT on home and office blood pressures, measures of indices of cardiac and vascular structure and function during follow-up, and safety. Conclusions: This academic initiative will increase the understanding of mechanisms and role of BAT in the refractory hypertension.

Patients with diabetes are prone to develop a distinct primary myocardial condition, diabetic cardiomyopathy, placing them at an increased risk for heart failure [1-3]. This occurs independently of hypertension, coronary artery disease, and other established causes of heart failure. Pertinent findings include increased mass, concentric changes, and diastolic dysfunction of the left ventricle [4,5]. Such adverse remodeling is common among patients with diabetes and appears to be strongly associated with its duration, suggesting a role for persistent metabolic stress [6-8]. However, which exact components of the diabetic syndrome determine these cardiac alterations is not clear. Moreover, most studies have investigated patients with type 2 diabetes, and it is uncertain whether patients with type 1 diabetes experience similar myocardial changes. Continue reading the full text in the PDF version.

Summary: Background: The greatest risk factor for cardiovascular disease is hypertension, which can be alleviated via diet, exercise, and adherence to medication. Yet, blood pressure control in Nepal is inadequate, which is partly hindered by a lack of evidence-based, low-cost, scalable, and cost-effective cardiovascular disease prevention programmes. The the community-based management of hypertension in Nepal (COBIN) study was a 12-month community-based hypertension management programme of blood pressure monitoring and lifestyle counselling intervention undertaken by female community health volunteers (FCHVs) in Nepal, against usual care, which showed success in reducing blood pressure. Here we aimed to retrospectively quantify the budget impact and cost-effectiveness of the scale-up of the programme. Methods: In this retrospective analysis, we collected participant-level data from the COBIN study; programme delivery cost data from programme administrators from the COBIN study group; and popualtion and other data from WHO, the World Bank, and the Nepalese Government. We estimated costs per participant and total costs of a national scale-up of the COBIN programme focusing on two scenarios: scenario A, delivery of the intervention to only people aged 25–65 years with hypertension; and scenario B, delivery of the intervention to all adults aged 25–65 years regardless of hypertension status. Effectiveness was based on in-trial blood pressure reductions converted to cardiovascular disease disability-adjusted life-years (DALYs) averted. The primary cost-effectiveness measure was incremental cost per averted cardiovascular disease DALY (calculated using the incremental cost-effectiveness ratio [ICER]) from a health system perspective, including programme delivery and incremental medication costs. We did univariate sensitivity analyses of scenario B to assess the effect of uncertainty in key parameter values in our calculations. Findings: From a health system perspective, the first-year budget impact was US$7·1 million in scenario A and $10·8 million in scenario B. With each subsequent year, the costs decreased by approximately 50%. In the base-case cost-effectiveness analysis, from the health system perspective, scenario A resulted in an ICER of $582 per DALY averted and scenario B resulted in an ICER of $411 per DALY averted. The ICER was most sensitive to uncertainty in the number of total avertable cardiovascular disease DALYs in the eligible population. Interpretation: The programme is projected to be highly cost-effective in both scenarios compared with the WHO thresholds for cost-effectiveness for Nepal. For policy makers intending to meet the UN Sustainable Development Goal of reducing premature mortality from non-communicible diseases, this intervention should be considered. Funding: Duke-NUS Medical School, Singapore.

Objective: To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population. Methods: We tested cross-sectional associations between electrocardiographic and echocardiographic LVH, defining LVH according to the Sokolow-Lyon voltage combination, Cornell voltage-duration product, or left ventricular mass index (LVMI). Differences between standardized LVMI and Sokolow-Lyon voltage combination or Cornell voltage-duration product (absolute value/cut-off value for LVH) were used as outcome variables in order to identify explanatory variables associated with diagnostic discrepancies between ECG and echocardiography. Results: Of the 1382 subjects included, 77% did not display any signs of LVH, 6% had LVH defined by ECG only, 13% had LVH defined by echocardiography only, and 5% had LVH on both ECG and echocardiography. Older subjects and those with higher blood pressure and RWT were more likely to have a relatively greater LVMI on echocardiography than that predicted on ECG (odds ratio: 1.65 per 10 years (95% confidence interval (CI): 1.27-2.15), p = .0002, odds ratio: 1.17 per 10 mmHg (95% CI: 1.09-1.25), p

Protein sequence space is vast; nature uses only an infinitesimal fraction of possible sequences to sustain life. Are there solutions to biological problems other than those provided by nature? Can we create artificial proteins that sustain life? To investigate these questions, we have created combinatorial collections, or libraries, of novel sequences with no homology to those found in living organisms. Previously designed libraries contained numerous functional proteins. However, they often formed dynamic, rather than well-ordered structures, which complicated structural and mechanistic characterization. To address this challenge, we describe the development of new libraries based on the de novo protein S-824, a 4-helix bundle with a very stable 3-dimensional structure. Distinct from previous libraries, we targeted variability to a specific region of the protein, seeking to create potential functional sites. By characterizing variant proteins from this library, we demonstrate that the S-824 scaffold tolerates diverse amino acid substitutions in a putative cavity, including buried polar residues suitable for catalysis. We designed and created a DNA library encoding 1.7 × 106 unique protein sequences. This new library of stable de novo α-helical proteins is well suited for screens and selections for a range of functional activities in vitro and in vivo.

Background: The recommendation for carotid–femoral pulse wave velocity (cfPWV) is to use a calliper to measure the aortic length as a straight line. In adults, it has been shown that tape follows the body contours potentially making the distance longer – ultimately a higher cfPWV – interpreted as a higher aortic stiffness. Our objective was to investigate to what extent a tape measurement is influenced by abdominal obesity in children and adolescents. Methods: In a cross-sectional design, 100 obese patients with age 10–18 years were compared to 50 healthy control individuals. CfPWV was measured by applanation tonometry. The aortic length was determined with tape and a calliper (distance-tape and distance-calliper). The bias of the tape measurements was calculated as distance-tape minus distance-calliper. Results: The bias of the tape measurements (mean ± SD) was significant in both the obese (Δ 14.6 ± 11.2 mm, P < 0.0001) and the control group (Δ 5.7 ± 5.8 mm, P < 0.0001), and showed a linear relationship with waist-height ratio in the obese group (obese: β = 96.9, CI: 75.3–118.5, P < 0.0001). Likewise, cfPWV was significantly higher when tape was used for the distance measurements in both groups (P values

Background: The methodology of the gold standard for measuring aortic stiffness, carotid–femoral pulse wave velocity (cfPWV), has been revised in respect to the choice of distance measure. In order to clarify whether increased aortic stiffness is present in obese children and adolescents we investigated cfPWV with the previous (cfPWV-subtracted) and a newly revised methodology (cfPWV-direct). Methods: In a cross-sectional design, 104 obese patients with age 10–18 years newly referred to the Children’s Obesity Clinic were compared to 50 healthy control individuals. CfPWV was measured non-invasively using the SphygmoCor device, while all distance measures were made with a calliper. Results: Opposite to the direct distance, the subtracted distance differed across study groups in relation to height (P < 0.006). CfPWV-subtracted was significantly higher for the obese (4.5 m/s CI: 4.4–4.6 vs. 4.3 m/s CI: 4.2–4.5, P = 0.03), whereas cfPWV-direct was significantly lower (4.8 m/s CI: 4.7–4.9 vs. 5.1 m/s CI: 4.9–5.3, P = 0.008). In multiple regression, being obese did not significantly influence cfPWV-subtracted (β = 0.126, CI: −0.04–0.29, NS) whereas it significantly reduced cfPWV-direct (β = −0.34, CI: −0.53–0.15, P < 0.001), when adjusting for age, gender, mean arterial blood pressure and heart rate. Both groups had normal values of cfPWV-subtracted in respect to a European reference material. Conclusion: The distance measure of cfPWV-direct was associated similarly to height across study groups. Adjusted for main confounders, cfPWV-subtracted was equal whereas cfPWV-direct was reduced in obese compared to normal weighted children and adolescents.