Early dyspnoea relief in acute heart failure: prevalence, association with mortality, and effect of rolofylline in the PROTECT Study

AIMS: Dyspnoea and pulmonary and/or peripheral congestion are the most frequent manifestations of acute heart failure (AHF) and are important targets for therapy. We have assessed changes in dyspnoea, their relationship with mortality, and the effects of the adenosine A1 receptor antagonist rolofylline on these endpoints in patients enrolled in the PROTECT trial. METHODS AND RESULTS: PROTECT was a prospective, double-blind, placebo-controlled study assessing the effect of rolofylline in patients hospitalized for AHF with dyspnoea, fluid overload, increased plasma natriuretic peptides, and mild-to-moderate renal dysfunction. Early dyspnoea relief, prospectively defined as moderately or markedly better dyspnoea at both 24 and 48 h after the start of study drug administration, occurred in 49.8% of the patients. Early dyspnoea relief was associated with greater weight loss and with reduced mortality at Days 14 and 30 [hazard ratio (HR) 0.28, 95% confidence interval (CI): 0.15, 0.50; and 0.35, 95% CI: 0.22, 0.55, respectively]. Rolofylline administration was associated with an increase in the proportion of patients showing early dyspnoea relief (HR 1.30; 95% CI: 1.08, 1.57) and with a numerically lower mortality at 14 and 30 days, largely driven by the mortality due to HF [at 30 days, HR (95% CI, P-value): 0.65 (0.38-1.10, P= 0.107)]. Rolofylline did not reduce episodes of in-hospital worsening HF or post-discharge re-admissions, nor did it improve survival at 60 or 180 days. CONCLUSION: The present analysis from PROTECT demonstrated that more weight loss was associated with early dyspnoea relief and reduced short-term mortality

Early prediction of cardiac resynchronization therapy response by non-invasive electrocardiogram markers

[EN] Cardiac resynchronization therapy (CRT) is an effective treatment for those patients with severe heart failure. Regrettably, there are about one third of CRT "non-responders", i.e. patients who have undergone this form of device therapy but do not respond to it, which adversely affects the utility and cost-effectiveness of CRT. In this paper, we assess the ability of a novel surface ECG marker to predict CRT response. We performed a retrospective exploratory study of the ECG previous to CRT implantation in 43 consecutive patients with ischemic (17) or non-ischemic (26) cardiomyopathy. We extracted the QRST complexes (consisting of the QRS complex, the S-T segment, and the T wave) and obtained a measure of their energy by means of spectral analysis. This ECG marker showed statistically significant lower values for non-responder patients and, joint with the duration of QRS complexes (the current gold-standard to predict CRT response), the following performances: 86% accuracy, 88% sensitivity, and 80% specificity. In this manner, the proposed ECG marker may help clinicians to predict positive response to CRT in a non-invasive way, in order to minimize unsuccessful procedures.This work was supported by MINECO under grants MTM2013-43540-P and MTM2016-76647-P.Ortigosa, N.; Pérez-Roselló, V.; Donoso, V.; Osca Asensi, J.; Martínez-Dolz, L.; Fernández Rosell, C.; Galbis Verdu, A. (2018). Early prediction of cardiac resynchronization therapy response by non-invasive electrocardiogram markers. Medical & Biological Engineering & Computing. 56(4):611-621. https://doi.org/10.1007/s11517-017-1711-1S611621564Boggiatto P, Fernández C, Galbis A (2009) A group representation related to the stockwell transform. Indiana University Mathematics Journal 58(5):2277–2296Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G et al (2013) 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy. Europace 15:1070–1118Brown RA, Lauzon ML, Frayne R (2010) A general description of linear time-frequency transforms and formulation of a fast, invertible transform that samples the continuous s-transform spectrum nonredundantly. IEEE Trans Signal Process 58(1): 281–290Carità P, Corrado E, Pontone G, Curnis A, Bontempi L et al (2016) Non-responders to cardiac resynchronization therapy: insights from multimodality imaging and electrocardiography. A brief review. Int J Cardiol 225:402–407Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C et al (2001) Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 344:873–880Chang CC, Lin CJ (2011) LIBSVM: a library for support vector machines. ACM Trans Intell Syst Technol 2(3):27:1–27:27Chawla NV, Bowyer KW, Hall LO, Kegelmeyer WP (2002) SMOTE: synthetic minority over-sampling technique. J Artif Intell Res 16(1):321–357Cleland JGF, Abraham WT, Linde C, Gold MR, Young J et al (2013) An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resyn- chronization therapy on morbidity and mortality in patients with symptomatic heart failure. Eur Heart Journal 34(46):3547–3556Cleland JGF, Calvert MJ, Verboven Y, Freemantle N (2009) Effects of cardiac resynchronization therapy on long-term quality of life: an analysis from the Cardiac Resynchronisation-Heart Failure (CARE-HF) study. Am Heart J 157:457–466Cleland JGF, Freemantle N, Erdmann E, Gras D, Kappenberger L et al (2012) Long-term mortality with cardiac resynchronization therapy in the Cardiac Resynchronization-Heart Failure (CARE-HF) trial. Eur J Heart Fail 14:628–634Egoavil CA, Ho RT, Greenspon AJ, Pavri BB (2005) Cardiac resynchronization therapy in patients with right bundle branch block: analysis of pooled data from the MIRACLE and Contak CD trials. Heart Rhythm 2(6):611–615Engels EB, Mafi-Rad M, van Stipdonk AM, Vernooy K, Prinzen FW (2016) Why QRS duration should be replaced by better measures of electrical activation to improve patient selection for cardiac resynchronization therapy. J Cardiovasc Transl Res 9(4):257–265Engels EB, Végh EM, Van Deursen CJ, Vernooy K, Singh JP, Prinzen FW (2015) T-wave area predicts response to cardiac resynchronization therapy in patients with left bundle branch block. J Cardiovasc Electrophysiol 26(2):176–183Eschalier R, Ploux S, Ritter P, Haïssaguerre M, Ellenbogen K, Bordachar P (2015) Nonspecific intraventricular conduction delay: definitions, prognosis, and implications for cardiac resynchronization therapy. Heart Rhythm 12(5):1071–1079Goldenberg I, Kutyifa V, Klein HU, Cannom DS, Brown MW et al (2014) Survival with cardiac-resynchronization therapy in mild heart failure. N Engl J Med 370:1694–1701He H, Bai Y, Garcia EA, Li S (2008) ADASYN: adaptive synthetic sampling approach for imbalanced learning. In: International joint conference on neural networks, pp 1322–1328Jacobsson J, Borgguist R, Reitan C, Ghafoori E, Chatterjee NA et al (2016) Usefulness of the sum absolute QRST integral to predict outcomes in patients receiving cardiac resynchronization therapy. J Cardiovasc Electrophysiol 118(3):389–395McMurray JJ (2010) Clinical practice. Systolic heart failure. N Engl J Med 3623:228–238Meyer CR, Keiser HN (1977) Electrocardiogram baseline noise estimation and removal using cubic splines and state-space computation techniques. Comput Biomed Res 10:459–470Ortigosa N, Giménez VM (2014) Raw data extraction from electrocardiograms with portable document format. Comput Meth Programs Biomed 113(1):284–289Ortigosa N, Osca J, Jiménez R, Rodríguez Y, Fernández C, Galbis A (2016) Predictive analysis of cardiac resynchronization therapy response by means of the ECG. 2016 Comput Cardio 43:753–756. https://doi.org/10.22489/CinC.2016.218-415Ponikowski P, Voors AA, Anker S, Bueno H, Cleland JG, Coats AJ et al (2016) 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 18(8):891–975Rad MM, Wijntjens GW, Engels EB, Blaauw Y, Luermans JG et al (2016) Vectorcardiographic QRS area identifies delayed left ventricular lateral wall activation determined by electroanatomic mapping in candidates for cardiac resynchronization therapy. Heart Rhythm 13(1):217–225Shanks M, Delgado V, Bax JJ (2016) Cardiac resynchronization therapy in non-ischemic cardiomyopathy. Journal of Atrial Fibrillation 8(5):47–52Singh JP, Fan D, Heist EK, Alabiad CR, Taub C et al (2006) Left ventricular lead electrical delay predicts response to cardiac resynchronization therapy. Heart Rhythm 3(11):1285–1292Sohaib SM, Finegold JA, Nijjer SS, Hossain R, Linde C et al (2015) Opportunity to increase life span in narrow QRS cardiac resynchronization therapy recipients by deactivating ventricular pacing: evidence from randomized controlled trials. JACC Heart Fail 3:327–336Stockwell RG, Mansinha L, Lowe RP (1996) Localization of the complex spectrum: the S transform. IEEE Trans Signal Process 44(4):998–1001Tang ASL, Wells GA, Talajic M, Arnold MO, Sheldon R et al (2010) Cardiac-resynchronization therapy for mild-to-moderate heart failure. N Engl J Med 363:2385–2395Tereshchenko LG, Cheng A, Park J, Wold N, Meyer TE, Gold MR et al (2015) Novel measure of electrical dyssynchrony predicts response in cardiac resynchronization therapy: results from the SMART-AV trial. Heart Rhythm 12(2):2402–2410van Deursen CJ, Vernooy K, Dudink E, Bergfeldt L, Crijns HJ et al (2015) Vectorcardiographic QRS area as a novel predictor of response to cardiac resynchronization therapy. J Electrocardiol 48(1):45–52Wang TJ (2003) Natural history of asymptomatic left ventricular systolic dysfunction in the community. Circulation 108:977–982Woods B, Hawkins N, Mealing S, Sutton A, Abraham WT et al (2015) Individual patient data network meta-analysis of mortality effects of implantable cardiac devices. Heart 101:1800–1806Ypenburg C, van Bommel RJ, Borleffs CJ, Bleeker GB, Boersma E et al (2009) Long-term prognosis after cardiac resynchronization therapy is related to the extent of left ventricular reverse remodeling at midterm follow-up. 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Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb

The reshaping and decorrelation of similar activity patterns by neuronal networks can enhance their discriminability, storage, and retrieval. How can such networks learn to decorrelate new complex patterns, as they arise in the olfactory system? Using a computational network model for the dominant neural populations of the olfactory bulb we show that fundamental aspects of the adult neurogenesis observed in the olfactory bulb -- the persistent addition of new inhibitory granule cells to the network, their activity-dependent survival, and the reciprocal character of their synapses with the principal mitral cells -- are sufficient to restructure the network and to alter its encoding of odor stimuli adaptively so as to reduce the correlations between the bulbar representations of similar stimuli. The decorrelation is quite robust with respect to various types of perturbations of the reciprocity. The model parsimoniously captures the experimentally observed role of neurogenesis in perceptual learning and the enhanced response of young granule cells to novel stimuli. Moreover, it makes specific predictions for the type of odor enrichment that should be effective in enhancing the ability of animals to discriminate similar odor mixtures

Comparison of the effectiveness of three manual physical therapy techniques in a subgroup of patients with low back pain who satisfy a clinical prediction rule: Study protocol of a randomized clinical trial [NCT00257998]

BACKGROUND: Recently a clinical prediction rule (CPR) has been developed and validated that accurately identifies patients with low back pain (LBP) that are likely to benefit from a lumbo-pelvic thrust manipulation. The studies that developed and validated the rule used the identical manipulation procedure. However, recent evidence suggests that different manual therapy techniques may result similar outcomes. The purpose of this study is to investigate the effectiveness of three different manual therapy techniques in a subgroup of patient with low back pain that satisfy the CPR. METHODS/DESIGN: Consecutive patients with LBP referred to physical therapy clinics in one of four geographical locations who satisfy the CPR will be invited to participate in this randomized clinical trial. Subjects who agree to participate will undergo a standard evaluation and complete a number of patient self-report questionnaires including the Oswestry Disability Index (OSW), which will serve as the primary outcome measure. Following the baseline examination patients will be randomly assigned to receive the lumbopelvic manipulation used in the development of the CPR, an alternative lumbar manipulation technique, or non-thrust lumbar mobilization technique for the first 2 visits. Beginning on visit 3, all 3 groups will receive an identical standard exercise program for 3 visits (visits 3,4,5). Outcomes of interest will be captured by a therapist blind to group assignment at 1 week (3(rd )visit), 4 weeks (6(th )visit) and at a 6-month follow-up. The primary aim of the study will be tested with analysis of variance (ANOVA) using the change in OSW score from baseline to 4-weeks (OSW(Baseline )– OSW(4-weeks)) as the dependent variable. The independent variable will be treatment with three levels (lumbo-pelvic manipulation, alternative lumbar manipulation, lumbar mobilization). DISCUSSION: This trial will be the first to investigate the effectiveness of various manual therapy techniques for patients with LBP who satisfy a CPR

Should mechanical dyssynchrony be assessed in patients with implantable cardioverter-defibrillators?

Cardiac Dysfunction and Arrhythmia

Limits to modern contraceptive use among young women in developing countries: a systematic review of qualitative research

<p>Abstract</p> <p>Background</p> <p>Improving the reproductive health of young women in developing countries requires access to safe and effective methods of fertility control, but most rely on traditional rather than modern contraceptives such as condoms or oral/injectable hormonal methods. We conducted a systematic review of qualitative research to examine the limits to modern contraceptive use identified by young women in developing countries. Focusing on qualitative research allows the assessment of complex processes often missed in quantitative analyses.</p> <p>Methods</p> <p>Literature searches of 23 databases, including Medline, Embase and POPLINE^®, were conducted. Literature from 1970–2006 concerning the 11–24 years age group was included. Studies were critically appraised and meta-ethnography was used to synthesise the data.</p> <p>Results</p> <p>Of the 12 studies which met the inclusion criteria, seven met the quality criteria and are included in the synthesis (six from sub-Saharan Africa; one from South-East Asia). Sample sizes ranged from 16 to 149 young women (age range 13–19 years). Four of the studies were urban based, one was rural, one semi-rural, and one mixed (predominantly rural). Use of hormonal methods was limited by lack of knowledge, obstacles to access and concern over side effects, especially fear of infertility. Although often more accessible, and sometimes more attractive than hormonal methods, condom use was limited by association with disease and promiscuity, together with greater male control. As a result young women often relied on traditional methods or abortion. Although the review was limited to five countries and conditions are not homogenous for all young women in all developing countries, the overarching themes were common across different settings and contexts, supporting the potential transferability of interventions to improve reproductive health.</p> <p>Conclusion</p> <p>Increasing modern contraceptive method use requires community-wide, multifaceted interventions and the combined provision of information, life skills, support and access to youth-friendly services. Interventions should aim to counter negative perceptions of modern contraceptive methods and the dual role of condoms for contraception and STI prevention should be exploited, despite the challenges involved.</p

Quantum Process Tomography of a Universal Entangling Gate Implemented with Josephson Phase Qubits

Quantum logic gates must perform properly when operating on their standard input basis states, as well as when operating on complex superpositions of these states. Experiments using superconducting qubits have validated the truth table for particular implementations of e.g. the controlled-NOT gate [1,2], but have not fully characterized gate operation for arbitrary superpositions of input states. Here we demonstrate the use of quantum process tomography (QPT) [3,4] to fully characterize the performance of a universal entangling gate between two superconducting quantum bits. Process tomography permits complete gate analysis, but requires precise preparation of arbitrary input states, control over the subsequent qubit interaction, and simultaneous single-shot measurement of the output states. We use QPT to measure the fidelity of the entangling gate and to quantify the decoherence mechanisms affecting the gate performance. In addition to demonstrating a promising fidelity, our entangling gate has a on/off ratio of 300, a level of adjustable coupling that will become a requirement for future high-fidelity devices. This is the first solid-state demonstration of QPT in a two-qubit system, as solid-state process tomography has previously only been demonstrated with single qubits [5,6]

Association between perceived built environmental attributes and physical activity among adults in South Africa

Background: To investigate the association between perceived environmental attributes and leisure-time and transport-related physical activity. Methods: This was a cross-sectional survey involving 671 South Africans aged ?35 years from urban and rural settings. International Physical Activity Questionnaire and Neighbourhood Walkability Scale were used to collect data. Multivariable logistic regressions were used to investigate the associations. Results: Significant urban vs. rural differences were apparent in the distribution of most attributes of neighborhood environment. After adjusting for gender, age, setting and relevant interaction terms, proximity to local stores was significantly associated with leisure-time physical activity (OR: 4.26; 95% CI, 1.00-18.08); while proximity to transit stops (2.44; 1.48-4.02), pleasant scenery (1.93; 1.07-3.46), sidewalks (2.36; 1.25-4.44), shade from trees (2.14; 1.19-3.85), traffic (2.17; 91.21-3.91) and well-lit streets (2.01; 1.04-3.89) were significantly associated with walking for leisure. Four-way intersections (4.54; 1.54-13.43), pleasant scenery (3.84; 1.35-10.99), traffic (0.28; 0.09-0.89), sidewalks (3.75; 1.06-13.27) and crosswalks were associated with transport related physical activity. Proximity to transit stops (2.12; 1.17-3.84) and well maintained sidewalks (2.69; 2.20-10.02) were significantly associated with total physical activity. Significant interactions by setting were apparent in some of the associations. Conclusion: Some, but not all attributes of a neighborhood environment were significantly associated in expected directions with the three physical activity domains in this mixed urban and rural population. This study highlights the need for policy strategies aimed at improving or maintaining these perceived environmental attributes to promote physical activity.IS

Joining the dots: Conditional pass and programmatic assessment enhances recognition of problems with professionalism and factors hampering student progress

<p>Abstract</p> <p>Background</p> <p>Programmatic assessment that looks across a whole year may contribute to better decisions compared with those made from isolated assessments alone. The aim of this study is to describe and evaluate a programmatic system to handle student assessment results that is aligned not only with learning and remediation, but also with defensibility. The key components are standards based assessments, use of "Conditional Pass", and regular progress meetings.</p> <p>Methods</p> <p>The new assessment system is described. The evaluation is based on years 4-6 of a 6-year medical course. The types of concerns staff had about students were clustered into themes alongside any interventions and outcomes for the students concerned. The likelihoods of passing the year according to type of problem were compared before and after phasing in of the new assessment system.</p> <p>Results</p> <p>The new system was phased in over four years. In the fourth year of implementation 701 students had 3539 assessment results, of which 4.1% were Conditional Pass. More in-depth analysis for 1516 results available from 447 students revealed the odds ratio (95% confidence intervals) for failure was highest for students with problems identified in more than one part of the course (18.8 (7.7-46.2) p < 0.0001) or with problems with professionalism (17.2 (9.1-33.3) p < 0.0001). The odds ratio for failure was lowest for problems with assignments (0.7 (0.1-5.2) NS). Compared with the previous system, more students failed the year under the new system on the basis of performance during the year (20 or 4.5% compared with four or 1.1% under the previous system (p < 0.01)).</p> <p>Conclusions</p> <p>The new system detects more students in difficulty and has resulted in less "failure to fail". The requirement to state conditions required to pass has contributed to a paper trail that should improve defensibility. Most importantly it has helped detect and act on some of the more difficult areas to assess such as professionalism.</p

A trial assessing N-3 as treatment for injury-induced cachexia (ATLANTIC trial): does a moderate dose fish oil intervention improve outcomes in older adults recovering from hip fracture?

<p>Abstract</p> <p>Background</p> <p>Proximal femoral fractures are associated with increased morbidity and mortality. Pre-existing malnutrition and weight loss amongst this patient group is of primary concern, with conventional nutrition support being largely ineffective. The inflammatory response post proximal femoral fracture surgery and the subsequent risk of cachexia may explain the inability of conventional high energy high protein management to produce an anabolic response amongst these patients. Omega-3 fatty acids derived from fish oils have been extensively studied for their anti-inflammatory benefits. Due to their anti-inflammatory properties, the benefit of fish oil combined with individualized nutrition support amongst proximal femoral fracture patients post surgery is an attractive potential therapeutic strategy. The aim of the ATLANTIC trial is to assess the potential benefits of an anti-inflammatory dose of fish oil within the context of a 12 week individualised nutrition program, commencing seven days post proximal femoral fracture surgery.</p> <p>Methods/Design</p> <p>This randomized controlled, double blinded trial, will recruit 150 community dwelling elderly patients aged ≥65 years, within seven days of surgery for proximal femoral fracture. Participants will be randomly allocated to receive either a 12 week individualized nutrition support program complemented with 20 ml/day anti-inflammatory dose fish oil (~3.6 g eicosapentaenoic acid, ~2.4 g docosahexanoic acid; intervention), or, a 12 week individualized nutrition support program complemented with 20 ml/day low dose fish oil (~0.36 g eicosapentaenoic acid, ~0.24 g docosahexanoic acid; control).</p> <p>Discussion</p> <p>The ATLANTIC trial is the first of its kind to provide fish oil combined with individualized nutrition therapy as an intervention to address the inflammatory response experienced post proximal femoral fracture surgery amongst elderly patients. The final outcomes of this trial will assist clinicians in the development of effective and alternative treatment methods post proximal femoral fracture surgery which may ultimately result in a reduction in systemic inflammation, loss of weight and lean muscle and improvements in nutritional status, mobility, independence and quality of life among elderly patients.</p> <p>Trial Registration</p> <p>ACTRN12609000241235</p