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Type 2 diabetes is associated with an increased risk of heart failure. Left ventricular diastolic dysfunction and type 2 diabetes are frequently associated. Using echocardiography, we know that tissue Doppler imaging E/e’ ratio is a reliable predictor of left ventricular filling pressure. We performed a systematic review and meta-analysis to investigate the averaged E/e’ ratio value in patients with type 2 diabetes compared to non-diabetic controls. In the analysis we included cross-sectional studies providing the averaged E/e’ ratio. Subgroup/sensitivity analyses were conducted according to variables known to influence E/e’ ratio measurements. The analysis included 15 cross sectional studies with 877 type 2 diabetes patients and 1193 controls. The weighted mean difference showed higher values in diabetes (WMD 2.02; 95% CI 1.35, 2.70; p<0.001). The result was consistent in the subgroup/sensitivity analyses. Visual inspection of the funnel plot did not identify substantial asymmetry and the Egger test for funnel plot asymmetry showed a p value of 0.36. In conclusion, our assessment suggests that averaged E/e’ ratio is consistently increased in patients with type 2 diabetes compared to non-diabetic controls in the absence of cardiovascular diseases and complicated hypertension. This alteration may be a precocious diastolic alteration in the diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Objectives: Admission rates have increased in China, despite the fact that accessibility to primary care is improving. Hospital care could be cost-inefficient, and little is currently known about the appropriateness of admissions to tertiary hospitals in China. This study aims to measure the extent of inappropriate admissions in the cardiology and orthopedics departments of a tertiary hospital in Shanghai, to explore the factors associated with inappropriateness for each department, and to identify the causes of inappropriate admissions. Methods: The records of inpatients discharged on randomly sampled two days each week during March 2013 to February 2014 from the two departments were extracted. Two reviewers were recruited to assess the records according to the Chinese version of the Appropriateness Evaluation Protocol (C-AEP). Demographic, socio-economic, and other admissions-related variables were collected. Logistic regression analysis was adopted to determine the associated factors of inappropriateness. Results: 35.0% (N = 120) of the 343 admissions and 38.7% (N = 179) of the 463 admissions of the cardiology and orthopedics departments were not justified by the C-AEP, respectively. Age (OR = 0.717), self-pay (OR = 3.752), admission via outpatient sector (OR = 5.332), and readmission (OR = 2.501) were identified as factors affecting the appropriateness of admissions in the cardiology department. Age (OR = 0.930), self-pay (OR = 2.597), admission during 12:00–17:59 (OR = 3.211), and admission via outpatient sector (OR = 7.060) were determined to be associated with appropriateness of admission in the orthopedics department. The main reason for inappropriateness was premature admission for both departments. Conclusions: The magnitude of inappropriate admissions was considerable in the departments. To improve appropriateness, the results suggest that further interventions should be focused on both external and internal factors. [ABSTRACT FROM AUTHOR]

Myocardial perfusion abnormalities are the first sign of the ischemic cascade in the development of coronary artery disease (CAD). Thus, the early detection of myocardial perfusion abnormalities is significant for the prevention of CAD. Recently, a novel noninvasive method named Cardiodynamicsgram (CDG) has been proposed for early detection of CAD. This study aims to evaluate the predictive value of CDG in myocardial perfusion abnormalities for suspected ischemic heart disease. In the study, 86 suspected patients were enrolled. Standard 12-lead ECG and CDG were performed simultaneously before single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Diagnostic accuracy of CDG for myocardial perfusion abnormalities detection is assessed using SPECT MPI as the reference standard. Of these 86 suspected patients, 37 patients were positive in CDG, 49 patients were negative in CDG. Diagnostic accuracy of CDG at presentation for myocardial perfusion abnormalities was 84.9%, sensitivity 84.0%, and specificity 89.4%. Furthermore, of the 10 patients whose SPECT MPI results are reverse redistribution, 9 patients were positive in CDG. Underlying causes of false positive CDG findings included the factors that can change the stability of cardiac electrical conduction and measurement noise. Myocardial remodeling in patients with old myocardial infarction might be the major cause of false negative findings. Results show a good consistency between the CDG and SPECT MPI in evaluating myocardial perfusion abnormalities. It suggests that CDG might be used as a cost-effective tool for assessing the myocardial perfusion abnormalities in the clinic. [ABSTRACT FROM AUTHOR]

Background: Analysis of intracoronary thrombus type by optical coherence tomography (OCT) imaging is highly subjective. We aimed to compare a newly developed image analysis method to subjective visual classification of thrombus type identified by OCT. Methods: Thirty patients with acute ST elevation myocardial infarction were included. Thrombus type visually classified by two independent readers was compared with analysis using QCU-CMS software. Results: Repeatability of the computer-based measurements was good. By using a ROC, area under curve values for discrimination of white and red thrombi were 0.92 (95% confidence intervals (CI) 0.83–1.00) for median attenuation, 0.96 (95% CI 0.89–1.00) for mean backscatter and 0.96 (95% CI 0.89–1.00) for mean grayscale intensity. Median attenuation of 0.57 mm-1 (sensitivity 100%, specificity 71%), mean backscatter of 5.35 (sensitivity 92%, specificity 94%) and mean grayscale intensity of 120.1 (sensitivity 85%, specificity 100%) were identified as the best cut-off values to differentiate between red and white thrombi. Conclusions: Attenuation, backscatter and grayscale intensity of thrombi in OCT images differentiated red and white thrombi with high sensitivity and specificity. Measurement of these continuous parameters can be used as a less user-dependent method to characterize in vivo thrombi. The clinical significance of these findings needs to be tested in further studies. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the energy demand of one session of active video game (AVG) and its potential to reduce blood pressure (BP). Fourteen hypertensive (56.4±7.5 years) individuals performed sessions of AVG, a traditional sedentary video game sessions (SVG) and walking (WAL), as negative and positive controls, in a randomly determined order. Oxygen consumption and energy expenditure (EE) were measured during sessions. BP and cardiac autonomic modulation (CAM) were measured at rest and every 15 minutes of a 60-minute period of recovery from activities. A rating of enjoyment scale was also applied. AVG and WAL resulted in higher oxygen consumption (10.0±0.5 ml/kg/min and 16.6±3.1 ml/kg/min, respectively) and EE (3.5±0.2 kcal/min and 4.2±0.5 kcal/min) compared to 4.1±0.8 ml/kg/min and 1.4±0.1 kcal/min in SVG. A reduction in systolic and diastolic BP was evident following AVG sessions (-11.6±2.5 mmHg and -8.7±2.5 mmHg) and WAL (-10.8±2.8 mmHg and -8.6±2.3 mmHg) compared to pre-experiment value, and the same did not occur in SVG. All sessions promoted a feeling of enjoyment, with no difference between them. The parasympathetic activity was significantly lower at 30 and 45 minutes in post-WAL recovery (34.6±15.0 ms2 and 34.4±16.0 ms2) in the frequency domain (HF) in relation to both AVG (195.5±67.0 ms2 and 164.5±55.0 ms2) and the SVG (158.9±45.0 and 281.3±98.0 ms2). It is concluded that an AVG session promotes increased metabolic activity and is able to promote acute reduction of BP in hypertensive individuals similar to traditional walking exercise. [ABSTRACT FROM AUTHOR]

Background: A biphasic, U-shape relationship has been reported between body mass index (BMI) and clinical outcomes following percutaneous coronary intervention (PCI). However, the relationship between waist circumference (WC) and the cardiovascular risk following PCI has not been reported. Methods: A prospective cohort study was performed. A major adverse cardiac event (MACE) was defined as a composite of cardiac death (CD), nonfatal myocardial infarction (NFMI) and target vessel revascularization (TVR). Patients were evenly divided into 4 groups according to BMI (Q1BMI, Q2BMI, Q3BMI and Q4BMI) and WC (Q1WC, Q2WC, Q3WC and Q4WC). Results: A total of 1,421 patients were observed for 5 years. The risk of the composite events of CD and NFMI (CD/NFMI) was lower in the Q3WC and Q4WC groups than in the Q1WC group, whereas it was only marginally lower in the Q2BMI group than in the Q1BMI group (ANOVA, p = 0.062). The risk of MACE was highest in the Q1WC group and lowest in the Q3WC group; however, the risk of MACE did not differ among the 4 groups, according to BMI. Multivariate Cox-regression analyses showed that the risk of CD/NFMI gradually decreased with BMI (linear p = 0.030) and with WC (linear p = 0.015). The risks of TVR and MACEs that were driven by TVRs showed a distinguishing biphasic, U-shaped relationship with WC (nonlinear p = 0.009) but not with BMI (nonlinear p = 0.439). Landmark survival analysis showed that the incidences of CD and NFMI were higher in the lower BMI groups and lower WC groups than in the higher BMI groups and higher WC groups, respectively, until 1 year and did not differ afterward. In contrast, the incidence of MACE was highest in Q1WC and lowest in Q3WC (log-rank p = 0.003), whereas the incidence was not different among the groups according to BMI. Conclusions: Both BMI and WC were associated with a lower risk of early episodes of CD and NFMI after PCI. In the late period after PCI, WC demonstrated a biphasic, U-shaped association between cardiovascular outcomes and adiposity, whereas BMI did not. [ABSTRACT FROM AUTHOR]

The estimation of the Sample Size Requirement (SSR) when using a binary composite endpoint (i.e. two or more outcomes combined in a unique primary endpoint) is not trivial. Besides information about the rate of events for each outcome, information about the strength of association between the outcomes is crucial, since it can determine an increase or decrease of the SSR. Specifically, the greater the strength of association between outcomes the higher the SSR. We present Bin-CE, a free tool to assist clinicians for computing the SSR for binary composite endpoints. In a first step, the user enters a set of candidate outcomes, the assumed rate of events for each outcome and the assumed effect of therapy on each outcome. Since the strength of the association between outcomes is usually unknown, a semi-parametric approach linking the a priori clinical knowledge of the potential degree of association between outcomes with the exact values of these parameters was programmed with Bin-CE. Bin-CE works with a recursive algorithm to choose the best combination of outcomes that minimizes the SSR. In addition, Bin-CE computes the sample size using different algorithms and shows different figures plotting the magnitude of the sample size reduction, and the effect of different combinations of outcomes on the rate of the primary endpoint. Finally, Bin-CE is programmed to perform sensitivity analyses. This manuscript presents the mathematic bases and introduces the reader to the use of Bin-CE using a real example. [ABSTRACT FROM AUTHOR]

Background: Achieving good medication adherence is a major challenge for patients with chronic conditions. Our study aimed to assess the Threshold for Unacceptable Risk of Non-adherence (TURN), defined as the threshold at which physicians consider the health risks incurred by patients due to medication non-adherence unacceptable, for the most commonly prescribed drugs in France. Methods: We conducted an online study using a crowdsourcing approach among French general practitioners and specialists from September 2016 to August 2017. Physicians assessed the TURN for various levels of missed doses by evaluating a series of randomly presented clinical vignettes, each presenting a given medication with a given therapeutic indication. For each “drug-indication group” (i.e., all drugs from the same pharmacological class with a similar therapeutic indication): 1) we described the distribution of physicians’ assessments, 2) we provided a summary estimate of the TURN, defined as the frequency of missed doses above which 75% of the physicians’ assessments were located; 3) we computed the number of pill boxes reimbursed in France in 2016 to put our results into context. Results: We collected a total of 5365 assessments from 544 physicians, each of whom evaluated a random sample among 528 distinct clinical vignettes. Estimates of the TURN varied widely across drug-indication groups, ranging from risk considered unacceptable with 1 daily dose missed per month (e.g., insulin for diabetes) to risk always considered acceptable (e.g., anti-dementia drugs). Drugs with an estimated TURN of over one missing daily dose per week represented 44.9% of the prescription volume of the medications assessed in our study. Conclusions: According to physicians, the impact of non-adherence may vary greatly. Patient-physician discussions on the variable consequences of non-adherence could lead to a paradigm shift by seeking to reach “optimal adherence” depending on drugs rather than unrealistic “perfect adherence” to all drugs. [ABSTRACT FROM AUTHOR]

Objective: Rheoencephalography is a simple and inexpensive technique for cerebral blood flow assessment, however, it is not used in clinical practice since its correlation to clinical conditions has not yet been extensively proved. The present study investigates the ability of Poincaré Plot descriptors from rheoencephalography signals to detect apneas in volunteers. Methods: A group of 16 subjects participated in the study. Rheoencephalography data from baseline and apnea periods were recorded and Poincaré Plot descriptors were extracted from the reconstructed attractors with different time lags (τ). Among the set of extracted features, those presenting significant differences between baseline and apnea recordings were used as inputs to four different classifiers to optimize the apnea detection. Results: Three features showed significant differences between apnea and baseline signals: the Poincaré Plot ratio (SDratio), its correlation (R) and the Complex Correlation Measure (CCM). Those differences were optimized for time lags smaller than those recommended in previous works for other biomedical signals, all of them being lower than the threshold established by the position of the inflection point in the CCM curves. The classifier showing the best performance was the classification tree, with 81% accuracy and an area under the curve of the receiver operating characteristic of 0.927. This performance was obtained using a single input parameter, either SDratio or R. Conclusions: Poincaré Plot features extracted from the attractors of rheoencephalographic signals were able to track cerebral blood flow changes provoked by breath holding. Even though further validation with independent datasets is needed, those results suggest that nonlinear analysis of rheoencephalography might be a useful approach to assess the correlation of cerebral impedance with clinical changes. [ABSTRACT FROM AUTHOR]

Introduction and aims: Patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are often managed conservatively. Clinical practice guidelines recommend treating these patients with the same pharmacological drugs as those who receive invasive treatment. We analyze the use of new antiplatelet drugs (NADs) and other recommended treatments in people discharged following an NSTE-ACS according to the treatment strategy used, comparing the medium-term prognosis between groups. Methods: Prospective observational multicenter registry study in 1717 patients discharged from hospital following an ACS; 1143 patients had experienced an NSTE-ACS. We analyzed groups receiving the following treatment: No cardiac catheterization (NO CATH): n = 134; 11.7%; Cardiac catheterization without revascularization (CATH-NO REVASC): n = 256; 22.4%; percutaneous coronary intervention (PCI): n = 629; 55.0%; and coronary artery bypass graft (CABG): n = 124; 10.8%. We assessed major adverse cardiovascular events (MACE), all-cause mortality, and hemorrhagic complications at one year. Results: NO CATH was the oldest, had the most comorbidities, and was at the highest risk for ischemic and hemorrhagic events. Few patients who were not revascularized with PCI received NADs (NO CATH: 3.7%; CATH-NO REVASC: 10.6%; PCI: 43.2%; CABG: 3.2%; p<0.001). Non-revascularized patients also received fewer beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), and statins (p<0.001). At one year, MACE incidence in NO CATH group was three times that of the other groups (30.1%, p<0.001), and all-cause mortality was also much higher (26.3%, p<0.001). There were no significant differences in hemorrhagic events. Belonging to NO CATH group was an independent predictor for MACE at one year in the multivariate analysis (HR 2.72, 95% CI 1.29–5.73; p = 0.008). Conclusions: Despite current invasive management of NSTE-ACS, patients not receiving catheterization are at very high risk for under treatment with recommended drugs, including NADs. Their medium-term prognosis is poor, with high mortality. Patients treated with PCI receive better pharmacological management, with high use of NADs. [ABSTRACT FROM AUTHOR]

Ischemia-induced left ventricular (LV) wall thickening compromises the hemodynamic effectiveness of cardiopulmonary resuscitation (CPR). However, accurate assessment of the severity of ischemia-induced LV wall thickening during CPR is challenging. We investigated, in a swine model, whether hemodynamic parameters, including end-tidal carbon dioxide (ETCO2) level, are linearly associated with the severity of ischemia-induced LV wall thickening during CPR of consistent quality. We retrospectively analyzed 96 datasets for ETCO2 level, arterial pressure, LV wall thickness, and the percent of measured end-diastolic volume (%EDV) relative to EDV at the onset of ventricular fibrillation from eight pigs. Animals underwent advanced cardiovascular life support based on resuscitation guidelines. During CPR, LV wall thickness progressively increased while %EDV progressively decreased. Systolic and diastolic arterial pressure and ETCO2 level were significantly correlated with LV wall thickness and %EDV. Linear mixed effect models revealed that, after adjustment for significant covariates, systolic and diastolic arterial pressure were not associated with LV wall thickness or %EDV. ETCO2 level had a significant linear relationship with %EDV (P = 0.004). However, it could explain only 28.2% of the total variance of %EDV in our model. In conclusion, none of the hemodynamic parameters examined in this study appeared to provide sufficient information on the severity of ischemia-induced LV wall thickening. [ABSTRACT FROM AUTHOR]

Introduction: The presence of late gadolinium enhancement (LGE) at the right ventricular insertion point (RVIP) on cardiac magnetic resonance (CMR) is generally believed to be nonspecific, but the clinical implication of this unique LGE pattern in patients with non-ischemic dilated cardiomyopathy (NICM) has not been elucidated. Objectives: We investigated the prognostic significance of RVIP-LGE in NICM patients. Methods: A total of 360 consecutive NICM patients referred for CMR (102 with no LGE, 50 with RVIP-LGE, 121 with left ventricular [LV]-LGE, and 87 with both an LV and RVIP-LGE) were studied. The primary endpoint was a composite of the all-cause death, hospitalization due to worsening of heart failure, and major arrhythmic events. Results: During a mean follow-up of 45.2 ± 36.5 months, 149 (41.4%) patients (22 [21.6%] no LGE vs. 16 [32.0%] RVIP-LGE vs. 62 [51.2%] LV-LGE vs. 49 [56.3%] both LV and RVIP-LGE, P < 0.0001) reached the primary endpoint. A Kaplan Meier curve demonstrated that RVIP-LGE patients had an intermediate trend of an event free survival rate for the composite endpoint (log-rank P < 0.0001). In a multivariable Cox regression model, LV-LGE (P = 0.008) and both LV and RVIP-LGE (P = 0.003) were significantly associated with a worse outcome, whereas RVIP-LGE was not (P = 0.101). In addition, RVIP-LGE patients (n = 32) had a more favorable outcome compared to LV-LGE patients (n = 32) even after matching the extent of the LGE (median 3.4% [interquartile range, 3.1–3.8], 8 [25.0%] RVIP-LGE vs. 20 [62.5%] LV-LGE, P = 0.002). Conclusions: LGE confined to the RVIP among NICM patients did not significantly increase the risk of adverse cardiac events, and also showed a better outcome than the same extent of LGE located in the LV. Identification of this unique LGE distribution may help refine the current risk stratification. [ABSTRACT FROM AUTHOR]

Methods of estimating the local false discovery rate (LFDR) have been applied to different types of datasets such as high-throughput biological data, diffusion tensor imaging (DTI), and genome-wide association (GWA) studies. We present a model for LFDR estimation that incorporates a covariate into each test. Incorporating the covariates may improve the performance of testing procedures, because it contains additional information based on the biological context of the corresponding test. This method provides different estimates depending on a tuning parameter. We estimate the optimal value of that parameter by choosing the one that minimizes the estimated LFDR resulting from the bias and variance in a bootstrap approach. This estimation method is called an adaptive reference class (ARC) method. In this study, we consider the performance of ARC method under certain assumptions on the prior probability of each hypothesis test as a function of the covariate. We prove that, under these assumptions, the ARC method has a mean squared error asymptotically no greater than that of the other method where the entire set of hypotheses is used and assuming a large covariate effect. In addition, we conduct a simulation study to evaluate the performance of estimator associated with the ARC method for a finite number of hypotheses. Here, we apply the proposed method to coronary artery disease (CAD) data taken from a GWA study and diffusion tensor imaging (DTI) data. [ABSTRACT FROM AUTHOR]

Introduction: International criteria for the interpretation of the athlete’s electrocardiogram (ECG) have been proposed. We aimed to evaluate the inter-observer agreement among observers with different levels of expertise. Methods: Consecutive ECGs of Swiss elite athletes (≥14 years), recorded during routine pre-participation screening between 2013 and 2016 at the Swiss Federal Institute of Sports were analysed. A medical student (A), a cardiology fellow (B) and an electrophysiologist (C) interpreted the ECG’s independently according to the most recent criteria. The frequencies and percentages for each observer were calculated. An inter-observer reliability analysis using Cohen Kappa (κ) statistics was used to determine consistency among observers. Results: A total of 287 ECGs (64.1% males) were analysed. Mean age of the athletes was 20.4±4.9 years. The prevalence of abnormal ECG findings was 1.4%. Both, normal and borderline findings in athletes showed moderate to good agreement between all observers. κ scores for abnormal findings resulted in excellent agreement (κ 0.855 in observer A vs C and B vs C to κ 1.000 in observer A vs B). Overall agreement ranged from moderate (κ 0.539; 0.419–0.685 95% CI) between observer B vs C to good agreement (κ 0.720; 0.681–0.821 95% CI) between observer A vs B. Conclusions: Our cohort of elite athletes had a low prevalence of abnormal ECGs. Agreement in abnormal ECG findings with the use of the recently published International recommendations for ECG interpretation in athletes among observers with different levels of expertise was excellent. ECG interpretation resulted in moderate to good overall agreement. [ABSTRACT FROM AUTHOR]

Circulatory shock is a life-threatening disease that accounts for around one-third of all admissions to intensive care units (ICU). It requires immediate treatment, which is why the development of tools for planning therapeutic interventions is required to deal with shock in the critical care environment. In this study, the ShockOmics European project original database is used to extract attributes capable of predicting mortality due to shock in the ICU. Missing data imputation techniques and machine learning models were used, followed by feature selection from different data subsets. Selected features were later used to build Bayesian Networks, revealing causal relationships between features and ICU outcome. The main result is a subset of predictive features that includes well-known indicators such as the SOFA and APACHE II scores, but also less commonly considered ones related to cardiovascular function assessed through echocardiograpy or shock treatment with pressors. Importantly, certain selected features are shown to be most predictive at certain time-steps. This means that, as shock progresses, different attributes could be prioritized. Clinical traits obtained at 24h. from ICU admission are shown to accurately predict cardiogenic and septic shock mortality, suggesting that relevant life-saving decisions could be made shortly after ICU admission. [ABSTRACT FROM AUTHOR]

Background: In patients with refractory heart failure (HF) peritoneal dialysis (PD) is associated with improved functional status and decrease in hospitalization. However, previous studies did not focus on right ventricular dysfunction as an important pathophysiologic component of cardiorenal syndrome. Methods: In a prospective cohort study PD was started in 40 patients with refractory right HF (with/without left HF). Refractoriness to conservative therapy was defined as persistent right heart congestion/ascites with intensified diuretic treatment and/or ≥2 hospitalizations within 6 months because of cardiac decompensation despite optimal medical treatment, and/or acute renal failure during intensified conservative treatment of cardiac decompensations. Results: Patient survival was 55.0% at 1 year, 35.0% at 2 years and 27.5% at 3 years. The number of hospitalization days declined after initiation of PD for both cardiac [13 (IQR 1–53) days before vs. 1 (IQR 0–12) days after start of PD, p<0.001] and unplanned reasons [12 (IQR 3–44) days before vs. 1 (IQR 0–33) days after start of PD, p = 0.007]. Using a combined endpoint including survival time of ≥1 year and either improvement in quality of life or decline in hospitalizations we found that patients with extended ascites, higher systolic pulmonary artery pressure, more marked impairment of right ventricular function and tricuspid valve insufficiency, higher residual renal function as well as those who could perform PD without assistance have benefited most from this therapy. Conclusions: Patients with more pronounced backward failure, less marked residual renal functional impairment and those not depending on assistance for therapy are likely to profit most from PD. [ABSTRACT FROM AUTHOR]

It is important to estimate the duration-distance relation in cycle commuting in the general population since this enables analyses of the potential for various public health outcomes. Therefore, the aim is to estimate this relation in the Swedish adult population of 2015. For that purpose, the first step was to establishit for adult male and female cycle commuters in Greater Stockholm, Sweden. Whether or not the slopes of these relations needed to be altered in order to make them representative of the general population was evaluated by comparing the levels of maximal oxygen uptake in samples of commuter cyclists and the population. The measure used was the maximal oxygen uptake divided by both the body weight and a cycle weight of 18.5 kg. The body weights in the population samples were adjusted to mirror relevant levels in 2015. Age adjustments for the duration–distance relations were calculated on the basis of the maximal oxygen uptake in the population samples aged 20–65 years. The duration-distance relations of the cycle commuters were downscaled by about 24–28% to mirror levels in the general population. The empirical formula for the distance (D, km) was based on duration (T, minutes) · speed (km/min) · a correction factor from cycle commuter to the general population · age adjustment (A, years). For the males in the general population the formula was: D = T · 20.76 km/h · 0.719 · (1.676–0.0147 · A). For females, the formula was: D = T · 16.14 km/h · 0.763 · (1.604–0.0129 · A). These formulas, combined with distributions of route distances between home and work in the population, enable realistic evaluations of the potential for different public health outcomes through cycle commuting. [ABSTRACT FROM AUTHOR]

Introduction: Definitive evidence of the effectiveness and cost-effectiveness of telemedicine home-interventions for the management of chronic diseases is still lacking. This study examines whether and how published reviews consider and discuss the influence on outcomes of different factors, including: setting, target, and intensity of intervention; patient engagement; the perspective of patients, caregivers and health professionals; the organizational model; patient education and support. Included reviews were also assessed in terms of economic and ethical issues. Methods: Two search algorithms were developed to scan PubMed for reviews published between 2000 and 2015, about ICT-based interventions for the management of hypertension, diabetes, heart failure, asthma, chronic obstructive pulmonary disease, or for the care of elderly patients. Based on our inclusion criteria, 25 reviews were selected for analysis. Results: None of the included reviews covered all the above-mentioned factors. They mostly considered target (44%) and intervention intensity (24%). Setting, ethical issues, patient engagement, and caregiver perspective were the most neglected factors (considered in 0–4% of the reviews). Only 4 reviews (16%) considered at least 4 of the 11 factors, the maximum number of factors considered in a review is 5. Conclusions: Factors that may be involved in ICT-based interventions, affecting their effectiveness or cost-effectiveness, are not enough studied in the literature. This research suggests to consider mostly the role of each one, comparing not only disease-related outcomes, but also patients and healthcare organizations outcomes, and patient engagement, in order to understand how interventions work. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the psychophysiological demand in different capoeira performances. Eleven experienced capoeira practitioners underwent the following procedures in different days: 1) anamnesis and anthropometric measurements; 2) aerobic performance assessment; 3 to 5) performances of 90 seconds in three capoeira styles (Angola, Benguela and São Bento), which were performed in randomized controlled cross-over design. The psychophysiological demand was assessed through the heart rate (HR), R-R interval (RRi), blood pressure (BP), blood lactate ([Lac]), blood glucose ([Gluc]), rating perceived effort (RPE), feeling scale (FS) and perceived activation (PA). Descriptive statistics with mean and standard deviation was performed. A two-way repeated measures ANOVA with Bonferroni post-hoc test was used. The Angola demand was between 56–71% maximal HR with [Lac]PEAK: 6.9±2.9 mM, RPEPEAK: 10.0±2.2 pts and FS: 2.7±1.7 pts, while in the Benguela participants reached 64–85% maximal HR with [Lac]PEAK: 9.5±3.0 mM, RPEPEAK: 11.0±2.8 pts and FS: 2.1±1.6 pts and for São Bento between 69–102% maximal HR with [Lac]PEAK: 15.7±2.6 mM, RPEPEAK: 15.5±4.1 pts and FS: -0.8±3.0 pts. Interaction time*performance occurred to [Lac] (F = 42.157; p<0.001), HR (F = 12.154; p<0.001), RRi (F = 4.774; p<0.001), parasympathetic modulation-rMSSD (F = 3.189; p<0.01), [Gluc] (F = 2.152; p<0.05), RPE (F = 5.855; p<0.01), FS (F = 2.448; p<0.05) and PA (F = 3.893; p<0.05). We concluded that São Bento rhythm resulted in a greater physiological demand according to the HR, [Lac] and cardiac autonomic indicators, with the Benguela rhythm being intermediate while the Angola rhythm presented a reduced demand. The [Gluc] increased after the São Bento rhythm when compared to the other rhythms. The perceptual demand presented increased in terms of RPE and PA variables and decreased in terms of FS when the São Bento performance was analyzed in comparison to the Angola and/or Benguela in capoeira. [ABSTRACT FROM AUTHOR]

Heartbeat classification is an important step in the early-stage detection of cardiac arrhythmia, which has been identified as a type of cardiovascular diseases (CVDs) affecting millions of people around the world. The current progress on heartbeat classification from ECG recordings is facing a challenge to achieve high classification sensitivity on disease heartbeats with a satisfied overall accuracy. Most of the work take individual heartbeats as independent data samples in processing. Furthermore, the use of a static feature set for classification of all types of heartbeats often causes distractions when identifying supraventricular (S) ectopic beats. In this work, a pyramid-like model is proposed to improve the performance of heartbeat classification. The model distinguishes the classification of normal and S beats and takes advantage of the neighbor-related information to assist identification of S bests. The proposed model was evaluated on the benchmark MIT-BIH-AR database and the St. Petersburg Institute of Cardiological Technics(INCART) database for generalization performance measurement. The results reported prove that the proposed pyramid-like model exhibits higher performance than the state-of-the-art rivals in the identification of disease heartbeats as well as maintains a reasonable overall classification accuracy. [ABSTRACT FROM AUTHOR]

Background: Rubella virus infection in early pregnancy lead to serious multi-organ birth defects known as congenital rubella syndrome (CRS). The incidence of CRS varies in different populations and the highest burden is found in developing countries in which rubella vaccination is not included in their national immunization programs. In Ethiopia, there is scarcity of data about congenital rubella syndrome. Therefore, the aim of this study was to determine the burden of CRS-related birth defects and its incidence in the pre-vaccine era in Amhara Regional State, Ethiopia. Materials and methods: A cross sectional study was conducted in Dessie, Felege-Hiwot and University of Gondar Referral Hospitals, from December 2015 to August 2017. After getting informed assent from each parent/guardian, blood was collected from infants < 1 year of age for laboratory determination of anti-rubella virus antibodies. Their socio-demographic data and clinical information compatible with congenital rubella syndrome were collected using WHO guideline. Results: During the study period, a total of 50 infants suspected for congenital rubella syndrome were included in the study. All infants suspected for CRS were tested against rubella specific IgM and IgG [for infants ≥ 6 months of age] antibodies using ELISA method. Of these, 9/50 (18%) and 4/14 (28.6%) of them were laboratory confirmed and potential CRS cases, respectively. In the present study, the most common laboratory confirmed defect was ocular manifestations 6 (66.7%) followed by heart related problems 5 (55.6%). In the present study, most of the laboratory confirmed cases (66.7%) were reported among 1–5 months of age infants. In addition, 5 (55.6%) of the infants with laboratory confirmed CRS cases were male and 6 (66.7%) of them were from urban settings. In this study, the incidence of CRS was 0.4 per 1000 live births. Conclusion: In this study, nearly one fifth of the infants had laboratory confirmed congenital rubella syndrome and most of them had multiple rubella associated congenital defects at a time. Most of these congenital anomalies were reported among infants ≥ 1 month of age. Based on our result, the incidence of the CRS was line with the global incidence of the CRS in the pre-vaccine era. Therefore, establishing strong rubella/CRS surveillance system as well as introducing the rubella containing vaccine in the national immunization program might be important to reduce the burden of rubella and CRS in the country. [ABSTRACT FROM AUTHOR]

This study investigated whether visual stimuli (FACES vs. CARS) combined with the presence of maternal scent can influence suck patterning in healthy infants. Fifteen healthy full-term infants (six months and younger) were exposed to their mother’s scent during a visual preference paradigm consisting of FACES vs. CARS stimuli while sucking on a custom research pacifier. Infants looked significantly longer to the FACES compared to CARS, p = .041. Repeated Measures ANOVA revealed a significant main effect for non-nutritive suck (NNS) bursts and visual stimuli (p = .001) with the largest differences evident between FACES and when the infant looked away from the visual stimuli (p = 0.008) as well as between FACES and CARS (p = 0.026). These preliminary findings suggest that infants have more suck attempts when looking at FACES in the presence of maternal scent thereby indicating potent links between visual preference and suck behavior. [ABSTRACT FROM AUTHOR]

The CXCL12-CXCR4 pathway has crucial roles in stem cell homing and maintenance, neuronal guidance, cancer progression, inflammation, remote-conditioning, cell migration and development. Recently, work in chick suggested that signalling via CXCR4 in neural crest cells (NCCs) has a role in the 22q11.2 deletion syndrome (22q11.2DS), a disorder where haploinsufficiency of the transcription factor TBX1 is responsible for the major structural defects. We tested this idea in mouse models. Our analysis of genes with altered expression in Tbx1 mutant mouse models showed down-regulation of Cxcl12 in pharyngeal surface ectoderm and rostral mesoderm, both tissues with the potential to signal to migrating NCCs. Conditional mutagenesis of Tbx1 in the pharyngeal surface ectoderm is associated with hypo/aplasia of the 4th pharyngeal arch artery (PAA) and interruption of the aortic arch type B (IAA-B), the cardiovascular defect most typical of 22q11.2DS. We therefore analysed constitutive mouse mutants of the ligand (CXCL12) and receptor (CXCR4) components of the pathway, in addition to ectodermal conditionals of Cxcl12 and NCC conditionals of Cxcr4. However, none of these typical 22q11.2DS features were detected in constitutively or conditionally mutant embryos. Instead, duplicated carotid arteries were observed, a phenotype recapitulated in Tie-2Cre (endothelial) conditional knock outs of Cxcr4. Previous studies have demonstrated genetic interaction between signalling pathways and Tbx1 haploinsufficiency e.g. FGF, WNT, SMAD-dependent. We therefore tested for possible epistasis between Tbx1 and the CXCL12 signalling axis by examining Tbx1 and Cxcl12 double heterozygotes as well as Tbx1/Cxcl12/Cxcr4 triple heterozygotes, but failed to identify any exacerbation of the Tbx1 haploinsufficient arch artery phenotype. We conclude that CXCL12 signalling via NCC/CXCR4 has no major role in the genesis of the Tbx1 loss of function phenotype. Instead, the pathway has a distinct effect on remodelling of head vessels and interventricular septation mediated via CXCL12 signalling from the pharyngeal surface ectoderm and second heart field to endothelial cells. [ABSTRACT FROM AUTHOR]

Most data sets consist of interlaced-distributed samples from multiple classes and since these samples always cannot be classified correctly by a linear hyperplane, so we name them nonlinearly separable data sets and corresponding classifiers are named nonlinear classifiers. Traditional nonlinear classifiers adopt kernel functions to generate kernel matrices and then get optimal classifier parameters with the solution of these matrices. But computing and storing kernel matrices brings high computational and space complexities. Since INMKMHKS adopts Nyström approximation technique and NysCK changes nonlinearly separable data to linearly ones so as to reduce the complexities, we combines ideas of them to develop an improved NysCK (INysCK). Moreover, we extend INysCK into multi-view applications and propose multi-view INysCK (MINysCK). Related experiments validate the effectiveness of them in terms of accuracy, convergence, Rademacher complexity, etc. [ABSTRACT FROM AUTHOR]

Limited real-world data are available regarding the comparative safety of non-vitamin K antagonist oral anticoagulants (NOACs). The objective of this retrospective claims observational cohort study was to compare the risk of bleeding among non-valvular atrial fibrillation (NVAF) patients prescribed apixaban, dabigatran, or rivaroxaban. NVAF patients aged ≥18 years with a 1-year baseline period were included if they were new initiators of NOACs or switched from warfarin to a NOAC. Cox proportional hazards modelling was used to estimate the adjusted hazard ratios of any bleeding, clinically relevant non-major (CRNM) bleeding, and major inpatient bleeding within 6 months of treatment initiation for rivaroxaban and dabigatran compared to apixaban. Among 60,227 eligible patients, 8,785 were prescribed apixaban, 20,963 dabigatran, and 30,529 rivaroxaban. Compared to dabigatran or rivaroxaban patients, apixaban patients were more likely to have greater proportions of baseline comorbidities and higher CHA2DS2-VASc and HAS-BLED scores. After adjusting for baseline clinical and demographic characteristics, patients prescribed rivaroxaban were more likely to experience any bleeding (HR: 1.35, 95% confidence interval [CI]: 1.26–1.45), CRNM bleeding (HR: 1.38, 95% CI: 1.27–1.49), and major inpatient bleeding (HR: 1.43, 95% CI: 1.17–1.74), compared to patients prescribed apixaban. Dabigatran patients had similar bleeding risks as apixaban patients. In conclusion, NVAF patients treated with rivaroxaban appeared to have an increased risk of any bleeding, CRNM bleeding, and major inpatient bleeding, compared to apixaban patients. There was no significant difference in any bleeding, CRNM bleeding, or inpatient major bleeding risks between patients treated with dabigatran and apixaban. [ABSTRACT FROM AUTHOR]

Introduction: Projected temperature rise in the upcoming years due to climate change has increased interest in studying the effects of heat stress in dairy cows. Environmental indices are commonly used for detecting heat stress, but have been used mainly in studies focused on the productivity-related effects of heat stress. The welfare approach involves identifying physiological and behavioural measurements so as to start heat stress mitigation protocols before the appearance of impending severe health or production issues. Therefore, there is growing interest in studying the effects of heat stress on welfare. This systematic review seeks to summarise the animal-based responses to heat stress (physiological and behavioural, excluding productivity) that have been used in scientific literature. Methods: Using systematic review guidelines set by PRISMA, research articles were identified, screened and summarised based on inclusion criteria for physiology and behaviour, excluding productivity, for animal-based resilience indicators. 129 published articles were reviewed to determine which animal-based indicators for heat stress were most frequently used in dairy cows. Results: The articles considered report at least 212 different animal-based indicators that can be aggregated into body temperature, feeding, physiological response, resting, drinking, grazing and pasture-related behaviour, reactions to heat management and others. The most common physiological animal-based indicators are rectal temperature, respiration rate and dry matter intake, while the most common behavioural indicators are time spent lying, standing and feeding. Conclusion: Although body temperature and respiration rate are the animal-based indicators most frequently used to assess heat stress in dairy cattle, when choosing an animal-based indicator for detecting heat stress using scientific literature to establish thresholds, characteristics that influence the scale of the response and the definition of heat stress must be taken into account, e.g. breed, lactation stage, milk yield, system type, climate region, bedding type, diet and cooling management strategies. [ABSTRACT FROM AUTHOR]

Stress is proven to have detrimental effects on physical and mental health. Due to different tasks and study designs, the direct consequences of acute stress have been found to be wide-reaching: while some studies report prosocial effects, others report increases in antisocial behavior, still others report no effect. To control for specific effects of different stressors and to consider the role of social anxiety in stress-related social behavior, we investigated the effects of social versus physical stress on behavior in male participants possessing different levels of social anxiety. In a randomized, controlled two by two design we investigated the impact of social and physical stress on behavior in healthy young men. We found significant influences on various subjective increases in stress by physical and social stress, but no interaction effect. Cortisol was significantly increased by physical stress, and the heart rate was modulated by physical and social stress as well as their combination. Social anxiety modulated the subjective stress response but not the cortisol or heart rate response. With respect to behavior, our results show that social and physical stress interacted to modulate trust, trustworthiness, and sharing. While social stress and physical stress alone reduced prosocial behavior, a combination of the two stressor modalities could restore prosociality. Social stress alone reduced nonsocial risk behavior regardless of physical stress. Social anxiety was associated with higher subjective stress responses and higher levels of trust. As a consequence, future studies will need to investigate further various stressors and clarify their effects on social behavior in health and social anxiety disorders. [ABSTRACT FROM AUTHOR]

Background: The challenge of addressing unhealthy lifestyle choice is of global concern. Motivational Interviewing has been widely implemented to help people change their behaviour, but it is unclear for whom it is most beneficial. This overview aims to appraise and synthesise the review evidence for the effectiveness of Motivational Interviewing on health behaviour of adults in health and social care settings. Methods: A systematic review of reviews. Methods were pre-specified and documented in a protocol (PROSPERO–CRD42016049278). We systematically searched 7 electronic databases: CDSR; DARE; PROSPERO; MEDLINE; CINAHL; AMED and PsycINFO from 2000 to May 2018. Two reviewers applied pre-defined selection criteria, extracted data using TIDIER guidelines and assessed methodological quality using the ROBIS tool. We used GRADE criteria to rate the strength of the evidence for reviews including meta-analyses. Findings: Searches identified 5222 records. One hundred and four reviews, including 39 meta-analyses met the inclusion criteria. Most meta-analysis evidence was graded as low or very low (128/155). Moderate quality evidence for mainly short term (<6 months) statistically significant small beneficial effects of Motivational Interviewing were found in 11 of 155 (7%) of meta-analysis comparisons. These outcomes include reducing binge drinking, frequency and quantity of alcohol consumption, substance abuse in people with dependency or addiction, and increasing physical activity participation. Conclusions: We have created a comprehensive map of reviews relating to Motivational Interviewing to signpost stakeholders to the best available evidence. More high quality research is needed to be confident about the effectiveness of Motivational Interviewing. We identified a large volume of low quality evidence and many areas of overlapping research. To avoid research waste, it is vital for researchers to be aware of existing research, and the implications arising from that research. In the case of Motivational Interviewing issues relating to monitoring and reporting fidelity of interventions need to be addressed. [ABSTRACT FROM AUTHOR]

While stress is a widely utilized concept, no direct methods facilitating its measurement are currently available. In our previous work we proposed stress entropic load (SEL) as a potential new marker of stress response in the human body. However, at that time no method for SEL measurement existed. In this pilot study we devised and then tested methodology for SEL measurement. Healthy male participants were monitored by indirect calorimetry and thermography while resting and subsequently while under prolonged mental effort. The acquired data was then used to calculate the temporal development of SEL for each participant. Our results show that SEL production increased significantly in participants subjected to prolonged mental effort. Furthermore, we observed that the calculated development of SEL over time may be used to accurately determine the time point at which participants started performing stressful tasks. [ABSTRACT FROM AUTHOR]

Background: Permanent pacemaker implantation (PPI) following TAVR is a frequent post interventional complication and its management remains controversial. Objective: We sought to elucidate the electrophysiological, procedural, and clinical baseline parameters that are associated with and perhaps predict the need for PPI after TAVR in a heterogeneous-valve-type real-world cohort. Methods: Overall, 494 patients receiving TAVR at our center from April 2009 to August 2015 were screened. ECG analyses and clinical parameters were collected prospectively. Results: Overall, 401 patients in this all-comers real-world TAVR cohort with a PPI rate of 16% were included. The mean age was 82 years, and the mean duration to PPI was 5.5 days. A large proportion of Edwards SAPIEN valves (81%), DirectFlow, CoreValve, and Portico were implanted. The main indications for PPI were atrioventricular (AV) block III, AV-block Mobitz type II, bradycardic atrial fibrillation and persistent sinus bradycardia. Between groups with and without PPI, significant differences were noted in the prevalence of post TAVR balloon dilatation, resting heart rate, QRS interval, PR interval with a cut-off of >178 ms, left anterior fascicular block and RBBB in univariate analyses. In the subsequent multiple regression analysis, post TAVR balloon dilatation and a PR interval with a cut-off of >178 ms were significant predictors of PPI. Conclusion: This real-world cohort differs from others in its size and heterogeneous valve selection, and indicates for the first time that patients with post balloon dilatation or prolonged PR interval are at a higher risk for pacemaker dependency after TAVR. [ABSTRACT FROM AUTHOR]

Student engagement during classes includes behavioural, cognitive and emotional components, and is a pre-requisite for successful active learning environments. A novel approach to measuring student engagement was developed, involving triangulation of real-time student-self report, observation by trained observers and heart rate measurement. The self-report instrument was evaluated in four separate cohorts (n = 123) at Monash University and the University of North Carolina. The six item self-report demonstrated good reliability (Cronbach’s alpha values ranged from 0.7–0.81). The self-report showed predictive validity in that small group activities were rated as significantly more engaging than didactic lecturing. Additionally, there was significant inter-instructor variability and within-class variability, indicating good discrimination between classroom activities. This self-report may prove useful to academic teaching staff in evaluating and refining their active learning activities. Independent observation was not found to correlate with student self-report, due in part to students who were pretending to engage being rated as engaged by an observer. Strikingly, students reported that they were pretending to engage for 23% of class time, even for highly regarded instructors. Individual participants were rated as engaged for 42 of the 46 intervals for which they reported that they had “pretended to engage”, indicating that the two observers were unable to detect disengagement during periods in which students pretended to engage. Instructors should be aware that student cues such as eye contact and nodding may indicate pretending to engage. One particular self-report item; “I tried a new approach or way of thinking about the content”, correlated positively with heart rates, and a controlled study reproduced this finding during two activities that required students to try a new approach to understanding a concept. Agreement with this item also correlated with superior performance on two in-class written assessment tasks (n = 101, p<0.01). Further use of this tool and related educational research may be useful to identify in-class activities that are engaging and likely to lead to improved student attainment of learning outcomes. [ABSTRACT FROM AUTHOR]

For managing overactive bladder (OAB), mirabegron, a β3 adrenergic receptor agonist, is typically used as second-line pharmacotherapy after antimuscarinics. Therefore, patients initiating treatment with mirabegron and antimuscarinics may differ, potentially impacting associated clinical outcomes. When using observational data to evaluate real-world safety and effectiveness of OAB treatments, residual bias due to unmeasured confounding and/or confounding by indication are important considerations. Falsification analysis, in which clinically irrelevant endpoints are tested as a reference, can be used to assess residual bias. The objective in this study was to compare baseline cardiovascular risk among OAB patients by treatment, and assess the presence of residual bias via falsification analysis of OAB patients treated with mirabegron or antimuscarinics, to determine whether clinically relevant comparisons across groups would be feasible. Linked electronic health record and claims data (Optum/Humedica) for OAB patients in the United States from 2011–2015 were available, with index defined as first date of OAB treatment during this period. Unadjusted characteristics were compared across groups at index and propensity-matching conducted. Falsification endpoints (hepatitis C, shingles, community-acquired pneumonia) were compared between groups using odds ratios (ORs) and 95% confidence intervals (CI). The study identified 10,311 antimuscarinic- and 408 mirabegron-treated patients. Mirabegron patients were predominantly older males, with more comorbidities. The analytic sample included 1,188 antimuscarinic patients propensity-matched to 396 mirabegron patients; after matching, no significant baseline differences remained. Estimates of falsification ORs were 0.7 (CI:0.3–1.7) for shingles, 1.5 (CI:0.3–8.2) for hepatitis C, 0.8 (CI:0.4–1.8) and 0.9 (CI:0.6–1.4) for pneumonia. While propensity matching successfully balanced observed covariates, wide CIs prevented definitive conclusions regarding residual bias. Accordingly, further observational comparisons by treatment group were not pursued. In real-world analysis, bias-detection methods could not confirm that differences in cardiovascular risk in patients receiving mirabegron versus antimuscarinics were fully adjusted for, precluding clinically relevant comparisons across treatment groups. [ABSTRACT FROM AUTHOR]

Neurological dysfunction has been reported in Gulf War Illness (GWI), including abnormal cerebral blood flow (CBF) responses to physostigmine challenge. However, it is unclear whether the CBF response to normal physiological challenges and regulation is similarly dysfunctional. The goal of the present study was to evaluate the CBF velocity response to orthostatic stress (i.e., sit-to-stand maneuver) and increased fractional concentration of carbon dioxide. 23 cases of GWI (GWI+) and 9 controls (GWI) volunteered for this study. Primary variables of interest included an index of dynamic autoregulation and cerebrovascular reactivity. Dynamic autoregulation was significantly lower in GWI+ than GWI- both for autoregulatory index (2.99±1.5 vs 4.50±1.5, p = 0.017). In addition, we observed greater decreases in CBF velocity both at the nadir after standing (-18.5±6.0 vs -9.8±4.9%, p = 0.001) and during steady state standing (-5.7±7.1 vs -1.8±3.2%, p = 0.042). In contrast, cerebrovascular reactivity was not different between groups. In our sample of Veterans with GWI, dynamic autoregulation was impaired and consistent with greater cerebral hypoperfusion when standing. This reduced CBF may contribute to cognitive difficulties in these Veterans when upright. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) due to left heart failure (HF) is the most common form of PH. However, treatment is unclear because there are conflicting results about safety and efficacy of PH-targeted therapies. Objectives: To assess the effects of PH-targeted therapy on exercise capacity in HF patients. Methods: MEDLINE, EMBASE and the Cochrane Library were searched from January 1990 to July 2017 for randomized controlled trials comparing PH-targeted therapies to conventional therapy in HF. The primary outcome was to assess the effects on exercise capacity. Secondary outcomes included mortality, hospitalisation, NT-proBNP levels, echocardiographic and hemodynamics parameters and discontinuation rate. Results: 22 studies were included (n = 5448), including 3, 8 and 11 studies with low, high and unknown risk of bias, respectively. PH-targeted therapies were associated with an improvement of exercise capacity (standardized mean difference 0.29;95%CI:0.08–0.50, p = 0.006). Pre-specified subgroup analyses found that this improvement was predominantly observed in studies evaluating phosphodiesterase-5 inhibitors and prostanoids and in patients with reduced ejection fraction. Moreover, systolic pulmonary artery pressure measured by echocardiography was improved (mean difference: -7.5mmHg; [95%CI]: -14.9,-0.1, p = 0.05), which was also entirely driven by studies evaluating phosphodiesterase-5 inhibitors. However, PH-targeted therapies were associated with an increased treatment discontinuation rates and a potential increase in mortality compared to standard treatment. Conclusions: In conclusion, PH-targeted therapies and especially phosphodiesterase-5 inhibitors may improve exercise capacity in patients with HF. However, an increase in adverse outcomes was likely. Moreover, most studies were at high or unknown risk of bias, precluding confident conclusions about the effects of PH-targeted therapies. [ABSTRACT FROM AUTHOR]

Background: A multidisciplinary approach has been recommended for the management of patients with infective endocarditis. We evaluated the impact of multidisciplinary case conferences on morbidity, mortality, and quality of care for these patients. Methods: We conducted a quasi-experimental study of consecutive patients admitted for infective endocarditis before (2013/10/1–2015/10/12, n = 97) and after (2015/10/13–2017/11/30, n = 80) implementation of case conferences to discuss medical and surgical management. These occurred as face-to-face discussions or electronically (for non-complex patients), and included physicians from cardiac surgery, cardiology, critical care, infectious diseases and neurology. We assessed process-of-care and clinical outcomes, with the primary outcome being complications up to 90 days after hospital discharge. Results: A case conference was held for 80/80 (100%) of patients in the post-intervention group. After the intervention, more patients received inpatient cardiology assessment (81.3% [post-intervention] vs. 63.9% [pre-intervention], p = 0.01), and more patients with definite infective endocarditis underwent cardiac surgery treatment (44.6% vs. 21.7%, p = 0.007). All pre-intervention and post-intervention patients received guideline-concordant antimicrobial therapy. There was no difference in rates of complications (40.0% vs. 51.5%, p = 0.13) or mortality up to 90 days after hospital discharge (26.3% vs. 17.5%, p = 0.20). In multivariable analyses, the intervention was not associated with differences in mortality (odds ratio 1.87, 95% confidence interval 0.88–3.99) or a composite measure of complications and mortality (odds ratio 0.86, 95% confidence interval 0.46–1.58). Conclusion: We successfully implemented a standardized multidisciplinary case conference protocol for patients with infective endocarditis. This intervention had no detectable effect on complications or mortality. [ABSTRACT FROM AUTHOR]

Competitive runners will occasionally undergo exercise in a laboratory setting to obtain predictive and prescriptive information regarding their performance. The present research aimed to assess whether the physiological demands of lab-based treadmill running (TM) can simulate that of over-ground (OG) running using a commonly used protocol. Fifteen healthy volunteers with a weekly mileage of ≥ 20 km over the past 6 months and treadmill experience participated in this cross-sectional study. Two stepwise incremental tests until volitional exhaustion was performed in a fixed order within one week in an Outpatient Clinic research laboratory and outdoor athletic track. Running velocity (IATspeed), heart rate (IATHR) and lactate concentration at the individual anaerobic threshold (IATbLa) were primary endpoints. Additionally, distance covered (DIST), maximal heart rate (HRmax), maximal blood lactate concentration (bLamax) and rate of perceived exertion (RPE) at IATspeed were analyzed. IATspeed, DIST and HRmax were not statistically significantly different between conditions, whereas bLamax and RPE at IATspeed showed statistical significance (p < 0.05). Apart from RPE at IATspeed, IATspeed, DIST, HRmax and bLamax strongly correlate between conditions (r = 0.815–0.988). High reliability between conditions provides strong evidence to suggest that running on a treadmill are physiologically comparable to that of OG and that training recommendations and be made with assurance. [ABSTRACT FROM AUTHOR]

Background: Several randomized control trials have established that drugs can decrease the heart failure (HF) rehospitalization in patients with HF. However, limited studies have investigated the duration of medicine use to decrease the rehospitalization period in the real world. Hence, this study aims to investigate whether the evidence-based medicine decreases the HF rehospitalization in different treatment intervals in the clinical practice. Method: We examined patients admitted with acute HF from the National Health Insurance Research Database in Taiwan. In addition, the major adverse cardiovascular events (MACE) were the composite endpoints of the in-hospital mortality and rehospitalization after 1 year. Furthermore, we analyzed the medicine use to decrease 14 days and 1, 6, and 12 months' HF rehospitalization. Results: Overall, we examined 11,012 patients. The use of the renin–angiotensin system (RAS) blockers [hazard ratio (HR), 0.58; P < 0.01], β-blocker (HR, 0.67; P < 0.01), spironolactone (HR, 0.63; P < 0.01), and digitalis (HR, 0.67; P < 0.01) associated with the lower in-hospital mortality rate. The Cox regression analysis revealed that RAS blocker (HR, 0.86; P < 0.01) and β-blocker (HR, 0.71; P < 0.01) were independent predictors for MACE. Although RAS blockers declined rehospitalization to 6 months, β-blocker decreased the rehospitalization rate after 1 month use and the benefit persisted till 12 months. Furthermore, digitalis only lowered rehospitalization to 14 days. Conclusion: This study suggests that the use of evidence-based medicine is associated with lower MACE for patients with HF, and these drugs could play vital roles in different periods to decrease the rehospitalization in the clinical setting. [ABSTRACT FROM AUTHOR]

Fibrates are used in patients with dyslipidemia and high cardiovascular risk. However, information regarding drug response to fibrate has been highly limited. We investigated treatment results and factors associated with triglyceride reduction after fenofibrate therapy using large-scale real-world data. Patients with one or more cardiovascular risk factors, at low-density lipoprotein-cholesterol goal but with triglyceride level ≥150 mg/dL, and undergoing treatment with fenofibrate 135–160 mg for the first time were included in this retrospective observational study. The outcome variable was the percentage changes of TG levels. The achievement rate of triglyceride <150 mg/dL was additionally analyzed. Factors associated with treatment results were also analyzed. Among 2546 patients who were initially screened, 1113 patients were enrolled (median age: 61 years; male: 71%). After median follow-up of 4 months, the median change in triglyceride was -60%, and 49% of the patients reached triglyceride <150 mg/dL. After adjusting for confounding variables, female sex, non-diabetic status, coronary artery disease, lower baseline triglyceride, and no statin use were identified to be independently associated with achievement of triglyceride <150 mg/dL. Among them, female sex, non-diabetic status, and coronary artery disease were also related to median or greater percentage reduction of triglyceride. In conclusion, only half of the study patients reached triglyceride levels <150 mg/dL after real-world fenofibrate therapy. This study indicates that more attention is needed on some subgroups to obtain optimal triglyceride levels when treating with fenofibrate. [ABSTRACT FROM AUTHOR]

Background: Acute medical units (AMUs) receive the majority of acute medical patients presenting to hospital as an emergency in the United Kingdom (UK) and in other international settings. They have emerged as a result of local service innovation in the context of a limited evidence base. As such, the AMU model is not well characterised in terms of its boundaries, patient populations and components of care. This makes service optimisation and development through strategic resource planning, quality improvement and research challenging. Aim: This study aims to evaluate a national set of AMUs with the intent of characterising the AMU model. Methods: Twenty-nine AMUs in Scotland were identified. Data were collected by semi-structured interviews with multidisciplinary healthcare professionals working in each AMU. A draft report was produced for each unit and verified by a unit representative. The unit reports were then analysed to develop a conceptual framework of key components of AMUs and a service definition of the boundaries of acute medical care. Results: Acute medical care in Scotland can be described as being delivered in “acute medical services” rather than geographically distinct AMUs. Twelve key components of AMU care were identified: care areas, functions, populations, patient flow, support services, communication, nurse care, allied healthcare professional care, non-consultant medical care, consultant care, patient assessment and specialty care. Discussion: This empirically derived characterisation of the AMU model is likely to be of utility to practitioners, managers, policy makers and researchers: it is relevant on an operational level, will aid quality improvement and is a foundation to needed further research into how best to deliver care in AMUs. This is important given the central role AMUs play in the journey of the majority of patients presenting to hospital acutely in Scotland, the UK and internationally. [ABSTRACT FROM AUTHOR]

Background: Arrhythmias in children are often paroxysmal, complicating the ability to capture the abnormal rhythm on routine ECG during an outpatient visit. The Alivecor Kardia Mobile (KM) device is a wireless mobile health (mHealth) device that generates a single lead ECG tracing with a FDA-approved algorithm for detection of atrial fibrillation in adults. Objective: The goal of this study is to assess the accuracy of interval measurements on KM tracings by directly comparing to standard 12-lead ECGs in pediatric patients. Methods: This single center, prospective study enrolled pediatric outpatients, age <18 years presenting for cardiology clinic visits, into 3 groups based on age: 0–5 years, 6–10 years, and 11–18 years. Patients were excluded if 12-lead ECG was not ordered during the visit. Each enrolled subject underwent standard 12-lead ECG followed by 30-second KM tracing. ECG parameters were batch read by 2 blinded pediatric electrophysiologists. Results: Thirty patients were recruited with 10 patients/group. Structural heart disease and/or conduction abnormality was present in 20 patients (67%). Majority of tracings (27/30, 90%) were of diagnostic quality on first attempt. Overall, the ΔPR was 15.2±10.8ms (r = 0.86), ΔQRS was 9.6±8ms (r = 0.86), and ΔQTc was 15.6±12.7ms (r = 0.83). There were 9 patients with ΔQTc measurements >20ms with 4/9 (44%) having a conduction disorder and 2/9 (22%) having marked sinus arrhythmia. Bland-Altman method of agreement demonstrated strong agreement for QRSd and QTc. The AF algorithm reported 4/30 (13%) false positive "possible AF" diagnoses (rhythm over-read on KM demonstrated n = 3 marked sinus arrhythmia, n = 1 sinus rhythm with aberrated PACs) resulting in a specificity of 87%. Conclusion: The Alivecor Kardia device produces accurate single lead ECG tracings in both healthy children and children with cardiac disease or rhythm abnormalities across the pediatric spectrum. This mHealth application provides an accurate, non-invasive, real-time approach for ambulatory ECG monitoring in children and adolescents. [ABSTRACT FROM AUTHOR]

Epilepsy is often associated with modifications in autonomic nervous system, which usually precede the onset of seizures of several minutes. Thus, there is a great interest in identifying these modifications enough time in advance to prevent a dangerous effect and to intervene. In addition, these changes can be a risk factor for epileptic patients and can increase the possibility of death. Notably autonomic changes associated to seizures are highly depended of seizure type, localization and lateralization. The aim of this study was to develop a patient-specific approach to predict seizures using electrocardiogram (ECG) features. Specifically, from the RR series, both time and frequency variables and features obtained by the recurrence quantification analysis were used. The algorithm was applied in a dataset of 15 patients with 38 different types of seizures. A feature selection step, was used to identify those features that were more significant in discriminating preictal and interictal phases. A preictal interval of 15 minutes was selected. A support vector machine (SVM) classifier was then built to classify preictal and interictal phases. First, a classifier was set up to classify preictal and interictal segments of each patient and an average sensibility of 89.06% was obtained, with a number of false positive per hour (FP/h) of 0.41. Then, in those patients who had at least 3 seizures, a double-cross-validation approach was used to predict unseen seizures on the basis of a training on previous ones. The results were quite variable according to seizure type, achieving the best performance in patients with more stereotypical seizure. The results of the proposed approach show that it is feasible to predict seizure in advance, considering patient-specific, and possible seizure specific, characteristics. [ABSTRACT FROM AUTHOR]

Objectives: Heart transplant (HTx) recipients have a high heart rate (HR), because of graft denervation and are frequently started on β-blockade (BB). We assessed whether BB and HR post HTx are associated with a specific urinary proteomic signature. Methods: In 336 HTx patients (mean age, 56.8 years; 22.3% women), we analyzed cross-sectional data obtained 7.3 years (median) after HTx. We recorded medication use, measured HR during right heart catheterization, and applied capillary electrophoresis coupled with mass spectrometry to determine the multidimensional urinary classifiers HF1 and HF2 (known to be associated with left ventricular dysfunction), ACSP75 (acute coronary syndrome) and CKD273 (renal dysfunction) and 48 sequenced urinary peptides revealing the parental proteins. Results: In adjusted analyses, HF1, HF2 and CKD273 (p ≤ 0.024) were higher in BB users than non-users with a similar trend for ACSP75 (p = 0.06). Patients started on BB within 1 year after HTx and non-users had similar HF1 and HF2 levels (p ≥ 0.098), whereas starting BB later was associated with higher HF1 and HF2 compared with non-users (p ≤ 0.014). There were no differences in the urinary biomarkers (p ≥ 0.27) according to HR. BB use was associated with higher urinary levels of collagen II and III fragments and non-use with higher levels of collagen I fragments. Conclusions: BB use, but not HR, is associated with a urinary proteomic signature that is usually associated with worse outcome, because unhealthier conditions probably lead to initiation of BB. Starting BB early after HTx surgery might be beneficial. [ABSTRACT FROM AUTHOR]

Background: Silent atrial fibrillation (AF) episodes are common but the role of anticoagulation treatment is under debate. Methods: Consecutive patients with dual-chamber pacemakers for sinus node disease or AV block/bundle branch block were retrospectively enrolled and the development of silent AF, any anticoagulation and the incidence of ischaemic stroke and dementia were recorded. Results: In total 411 patients without and 267 with known AF at implant were included. During a median follow-up of 38 months, 30% (125/411) of patients without known AF at implant were diagnosed with silent AF, 62% of those had or were prescribed anticoagulation. Heart failure (p = 0.03) and age >75 years (p = 0.0002) were risk markers for incident silent AF. In patients with known AF at implant, 80% (216/267) were on anticoagulation at implant. The annual stroke incidence was 2.1% in patients with known AF at implant, as compared to 1.9% in patients who developed silent AF during follow-up, and 1.4% in patients without AF. Vascular dementia developed in 11.2% and 6.2% respectively in patients with known AF versus no AF (p = 0.048) as well as in 5.6% of those with silent AF (p = 0.09) Conclusion: The stroke risk in our study population with an incident silent AF diagnosis may have been significantly decreased by the high proportion of anticoagulation treatment. This could imply that without this treatment the stroke risk might have been high enough to justify anticoagulation. Development of vascular dementia was twice as common among patients with known AF as compared to those witht silent AF or no AF. More data is needed to inform the optimal treatment for these patients. [ABSTRACT FROM AUTHOR]

Background: CKD is associated with several comorbidities, cardiovascular disease being the most significant. Aerobic training has a beneficial effect on cardiovascular health in healthy and some well-defined non-healthy populations. However, the effect of aerobic training on glomerular filtration rate in patients with CKD stages 3–4 is unclear. Objective: To review the effects of aerobic exercise training on kidney and cardiovascular function in patients with chronic kidney disease (CKD) stages 3–4. Methods: A random-effects meta-analysis was performed to analyse published randomized controlled trials through February 2018 on the effect of aerobic training on estimated glomerular filtration rate, blood pressure and exercise tolerance in patients with CKD stages 3–4. Web of Science, PubMed and Embase databases were searched for eligible studies. Results: 11 randomized controlled trials were selected including 362 participants in total. Favourable effects were observed on estimated glomerular filtration rate (+2.16 ml/min per 1.73m2; [0.18; 4.13]) and exercise tolerance (+2.39 ml/kg/min; [0.99; 3.79]) following an on average 35-week aerobic training program when compared to standard care. No difference in change in blood pressure was found. Conclusions: There is a small beneficial effect of aerobic training on estimated glomerular filtration rate and exercise tolerance, but not on blood pressure, in patients with CKD stages 3–4. However, data are limited and pooled findings were rated as of low to moderate quality. [ABSTRACT FROM AUTHOR]

The study aimed at evaluating the effects of combined aerobic and resistance exercise training on cardiac morphometry and function, oxidative stress and inflammatory parameters in diabetic ovariectomized rats. For this, female Wistar rats (10 weeks-old) were divided into 4 groups (n = 8): euglycemic (E), diabetic (streptozotocin, 50 mg/kg, iv) (D), diabetic ovariectomized (DO) and trained diabetic ovariectomized (TDO). The combined exercise training was performed on a treadmill and in a ladder adapted to rats (8 weeks, at 40–60% of maximal capacity). The left ventricle (LV) morphometry and function were evaluated by echocardiography. Oxidative stress and inflammatory markers were measured on ventricles tissue. The sedentary diabetic animals (D and DO) showed impaired systolic and diastolic functions, as well as increased cardiac overload, evaluated by myocardial performance index (MPI- D: 0.32 ± 0.05; DO: 0.39 ± 0.13 vs. E: 0.25 ± 0.07), in relation to E group. Systolic and MPI dysfunctions were exacerbated in DO when compared to D group. The DO group presented higher protein oxidation and TNF-α/IL-10 ratio than D groups. Glutathione redox ratio (GSH/GSSG) and IL-10 were decreased in both D and DO groups when compared to E group. Exercise training improved exercise capacity, systolic and diastolic functions and MPI (0.18±0.11). The TDO group showed reduced protein oxidation and TNF-α/IL-10 ratio and increased GSH/GSSG and IL-10 in relation to the DO group. These results showed that combined exercise training was able to attenuate the cardiac dysfunctions, probably by reducing inflammation and oxidative stress in an experimental model of diabetes and menopause. [ABSTRACT FROM AUTHOR]

Background: In Bangladesh, female paramedics known as Family Welfare Visitors (FWVs), conduct normal deliveries in first-level primary care facilities, or Union Health and Family Welfare Centres (UH&FWC). Utilization of partographs allow for early identification of abnormal labour and referral for advanced care to Emergency Obstetric Care (EmOC) facilities. A systematic assessment of the quality of partograph utilization in clinical-decision making will contribute to understanding the use of the tool by health workers. Methods: In 2013, the USAID supported MaMoni HSS project, led in country by Save the Children, trained FWVs on the use of partographs in five UH&FWCs in Habiganj district. As part of the follow-up after training, intrapartum case record forms, accompanying partographs, and referral registers for all obstetric cases managed in these five facilities from July 2013 to June 2014 were reviewed. Partographs were reviewed to identify abnormal labour cases based on pre-defined indications. All referred cases were ascertained from the case records in the referral registers. Five health workers were interviewed to assess their knowledge, attitude and experience in partograph use and to explore the challenges for referral decision making associated with the tool. Results: A total of 1,198 deliveries were managed at the study sites, of which 663 presented with cervical dilatation of 8 cm or less. Partographs were initiated in 98% of these cases. Indication of abnormal labour was found in 71 partographs (11%) and among them, only 1 was referred to a higher-level facility. Foetal heart rate and cervical dilatation were appropriately recorded in 61% and 70% of the partographs, respectively. Interviews with health workers revealed poor interpretation of referral indications from the partographs. Limited accessibility to the nearest EmOC facility, inadequate time for referral, and non-compliance to referral by clients were identified by the interviewed health workers as the key barriers for referral decision making. Conclusions: Supporting the health workers at first-level primary care facilities to better interpret and act on partograph data in a timely manner, and strengthening the referral systems are needed to ensure that women in labour receive the prompt quality care they and their babies require to survive. [ABSTRACT FROM AUTHOR]

Predicting ecological responses to climate change requires an understanding of the mechanisms that influence species’ tolerances to temperature. Based on the idea that air and water breathing animals are differentially suited to life in either medium due to differences in their respiratory morphology, we examined the possibility that the thermal tolerances of co-existing intertidal pulmonate and patellogastropod limpets may differ in different breathing media. We tested this by determining each species’ median lethal temperature (LT50) and cardiac Arrhenius breakpoint temperature (ABT) as measures of upper thermal tolerance limits, in air and water. Although all these species can survive in air and water, we hypothesised that the pulmonate limpets, Siphonaria capensis and S. serrata, would have higher thermal limits than the patellogastropod limpets, Cellana capensis and Scutellastra granularis, in air and vice versa in water. The results did not support our hypotheses, since C. capensis had similar thermal tolerance limits to the pulmonate limpets in air and the pulmonate limpets had thermal tolerance limits similar to or higher than S. granularis in water. Thus, considering pulmonate and patellid limpets as groups, we found no differences in their collective upper thermal tolerance limits in either medium. We conclude that differences between these two limpet groups in their respiratory morphology do not influence thermal tolerance, but that tolerances are species-specific. [ABSTRACT FROM AUTHOR]

Introduction: The single nucleotide polymorphism (SNP) rs2106261 in the transcription factor gene ZFHX3 (16q22), a major regulator of inflammation, has been reported linking to atrial fibrillation (AF) by genome-wide association studies. Inflammation is known to be a strong predictor of atrial fibrillation recurrence after ablation, so we examined the association of the ZFHX3 SNP rs2106261 to inflammation marker expression and recurrence after AF ablation. Methods: We genotyped ZFHX3 SNP rs2106261 and compared the minor (T) allele frequency between 362 paroxysmal AF (PAF) patients underwent pulmonary vein isolation (PVI) and 627 non-AF controls. We also analyzed associations between ZFHX3 SNP rs2106261 genotype and recurrence rate after pulmonary vein isolation and the inflammation markers. Results: The minor (T) allele frequency of the ZFHX3 SNP rs2106261 was significantly higher in AF patients than non-AF controls (odds ratio 1.52, p = 2.2×10−5). Multivariable analysis revealed that the minor allele (T) decreased AF recurrence rate after pulmonary vein isolation (hazard ratio 0.53, p = 0.04). Further, neutrophil/lymphocyte (N/L) ratio, C-reactive protein (CRP), and interleukin-6 (IL-6) expression levels were lower in PAF patients with the ZFHX3 SNP rs2106261 minor allele (TT+TC) than in CC patients (N/L ratio: CC 2.22 ± 0.08, TT+TC 1.98 ± 0.06, p = 0.018; CRP: CC 0.103 ± 0.009 mg/dl, TT+TC 0.076 ±0.007 mg/dl, p = 0.016; IL-6: CC 60.3 ± 3.0 pg/ml, TT+TC 52.8 ± 2.3 pg/ml, p = 0.04). Conclusions: The ZFHX3 SNP rs2106261 minor allele is associated with lower AF recurrence rate after pulmonary vein isolation. Low baseline inflammation conferred by this allele may reduce AF recurrence risk. [ABSTRACT FROM AUTHOR]