Efficiency and Safety of Prolonged Levosimendan Infusion in Patients with Acute Heart Failure

Background. Levosimendan is an inotropic drug with unique pharmacological advantages in patients with acute heart failure. Scope of this study is to determine whether longer infusion patterns without the hypotension-inducing loading dose could justify an effective and safe alternative approach. Methods. 70 patients admitted to the emergencies with decompensated chronic heart failure received intravenously levosimendan without a loading dose up to 72 hours. Clinical parameters, BNP (Brain Natriuretic Peptide) and signal-averaged-ECG data (SAECG) were recorded up to 72 hours. Results. The 48-hour group demonstrated a statistically significant BNP decrease (P < .001) after 48 hours, which also maintained after 72 hours. The 72-hour group demonstrated a bordeline decrease of BNP after 48 hours (P = .039), necessitating an additional 24-hour infusion to achieve significant reduction after 72 hours (P < .004). SAECG data demonstrated a statistically significant decrease after 72 hours (P < .04). Apart from two deaths due to advanced heart failure, no major complications were observed. Conclusion. Prolonged infusion of levosimendan without a loading dose is associated with an acceptable clinical and neurohumoral response

Rhenium fac-Tricarbonyl Bisimine Chalcogenide Complexes : Synthesis, Photophysical Studies, and Confocal and Time-Resolved Cell Microscopy

We describe the preparation, characterization, and imaging studies of rhenium carbonyl complexes with a pyta (4-(2-pyridyl)-1,2,3-triazole) or tapy (1-(2-pyridyl)-1,2,3-triazole)-based heteroaromatic N∧N ligand and thiolate or selenoate X ligand. The stability and photophysical properties of the selenolate complexes are compared with parent chloride complexes and previously described analogues with benzenethiolate ligands. Two complexes were imaged in A549 cells upon excitation at 405 nm. Colocalization studies suggest a lysosomal accumulation, while one parent chloride complex was described to localize at the Golgi apparatus. Preliminary fluorescence lifetime measurements and imaging demonstrate potential for application in time-resolved microscopy techniques due to the long and variable lifetimes observed in cellular environments, including an increase in lifetime between the solution and solid state many times larger than previously reported

Performance of the ESC 0/1-h and 0/3-h Algorithm for the Rapid Identification of Myocardial Infarction Without ST-Elevation in Patients With Diabetes

Patients with diabetes mellitus (DM) have elevated levels of high-sensitivity cardiac troponin (hs-cTn). We investigated the diagnostic performance of the European Society of Cardiology (ESC) algorithms to rule out or rule in acute myocardial infarction (AMI) without ST-elevation in patients with DM.; We prospectively enrolled 3,681 patients with suspected AMI and stratified those by the presence of DM. The ESC 0/1-h and 0/3-h algorithms were used to calculate negative and positive predictive values (NPV, PPV). In addition, alternative cutoffs were calculated and externally validated in 2,895 patients.; In total, 563 patients (15.3%) had DM, and 137 (24.3%) of these had AMI. When the ESC 0/1-h algorithm was used, the NPV was comparable in patients with and without DM (absolute difference [AD] -1.50 [95% CI -5.95, 2.96]). In contrast, the ESC 0/3-h algorithm resulted in a significantly lower NPV in patients with DM (AD -2.27 [95% CI -4.47, -0.07]). The diagnostic performance for rule-in of AMI (PPV) was comparable in both groups: 0/1-h (AD 6.59 [95% CI -19.53, 6.35]) and 0/3-h (AD 1.03 [95% CI -7.63, 9.7]). Alternative cutoffs increased the PPV in both algorithms significantly, while improvements in NPV were only subtle.; Application of the ESC 0/1-h algorithm revealed comparable safety to rule out AMI comparing patients with and without DM, while this was not observed with the ESC 0/3-h algorithm. Although alternative cutoffs might be helpful, patients with DM remain a high-risk population in whom identification of AMI is challenging and who require careful clinical evaluation

Heart failure therapy in diabetic patients-comparison with the recent ESC/EASD guideline

<p>Abstract</p> <p>Background</p> <p>To assess heart failure therapies in diabetic patients with preserved as compared to impaired systolic ventricular function.</p> <p>Methods</p> <p>3304 patients with heart failure from 9 different studies were included (mean age 63 ± 14 years); out of these, 711 subjects had preserved left ventricular ejection fraction (≥ 50%) and 994 patients in the whole cohort suffered from diabetes.</p> <p>Results</p> <p>The majority (>90%) of heart failure patients with reduced ejection fraction (SHF) and diabetes were treated with an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) or with beta-blockers. By contrast, patients with diabetes and preserved ejection fraction (HFNEF) were less likely to receive these substance classes (p < 0.001) and had a worse blood pressure control (p < 0.001). In comparison to patients without diabetes, the probability to receive these therapies was increased in diabetic HFNEF patients (p < 0.001), but not in diabetic SHF patients. Aldosterone receptor blockers were given more often to diabetic patients with reduced ejection fraction (p < 0.001), and the presence and severity of diabetes decreased the probability to receive this substance class, irrespective of renal function.</p> <p>Conclusions</p> <p>Diabetic patients with HFNEF received less heart failure medication and showed a poorer control of blood pressure as compared to diabetic patients with SHF. SHF patients with diabetes were less likely to receive aldosterone receptor blocker therapy, irrespective of renal function.</p

HEE-GER: a systematic review of German economic evaluations of health care published 1990–2004

BACKGROUND: Studies published in non-English languages are systematically missing in systematic reviews of growth and quality of economic evaluations of health care. The aims of this study were: to characterize German evaluations, published in English or German-language, in terms of various key parameters; to investigate methods to derive quality-of-life weights in cost-utility studies; and to examine changes in study characteristics over the years. METHODS: We conducted a country-specific systematic review of the German and English-language literature of German economic evaluations (assessment of or application to the German health care system) published 1990–2004. Generic and specialized health economic databases were searched. Two independent reviewers verified fulfillment of inclusion criteria and extracted study characteristics. RESULTS: The fulltexts of 730 articles were reviewed of which 283 fulfilled all entry criteria. 32% of included studies were published in German-language. 51% of studies evaluated pharmaceuticals and 63% were cost-effectiveness analyses. Economic appraisals concentrate on few disease categories and important health areas are strongly underrepresented. Declaration of sponsorship was associated with article language (49% English articles vs. 29% German articles, p < 0.001). The methodology used to obtain quality-of-life weights in published cost-utility studies was very diverse, poorly reported and most studies did not use German patients' or community health state valuations. CONCLUSION: Many of the German-language evaluations included in our study are likely to be missing in international reviews and may be systematically different from English-language reviews from Germany. Lack of transparency and adherence to recommended reporting practices constitute a serious problem in German economic evaluations

First outline and baseline data of a randomized, controlled multicenter trial to evaluate the health economic impact of home telemonitoring in chronic heart failure — CardioBBEAT

Background: Evidence that home telemonitoring for patients with chronic heart failure (CHF) offers clinical benefit over usual care is controversial as is evidence of a health economic advantage. Methods: Between January 2010 and June 2013, patients with a confirmed diagnosis of CHF were enrolled and randomly assigned to 2 study groups comprising usual care with and without an interactive bi-directional remote monitoring system (Motiva$^{®}$). The primary endpoint in CardioBBEAT is the Incremental Cost-Effectiveness Ratio (ICER) established by the groups' difference in total cost and in the combined clinical endpoint "days alive and not in hospital nor inpatient care per potential days in study" within the follow-up of 12 months. Results: A total of 621 predominantly male patients were enrolled, whereof 302 patients were assigned to the intervention group and 319 to the control group. Ischemic cardiomyopathy was the leading cause of heart failure. Despite randomization, subjects of the control group were more often in NYHA functional class III-IV, and exhibited peripheral edema and renal dysfunction more often. Additionally, the control and intervention groups differed in heart rhythm disorders. No differences existed regarding risk factor profile, comorbidities, echocardiographic parameters, especially left ventricular and diastolic diameter and ejection fraction, as well as functional test results, medication and quality of life. While the observed baseline differences may well be a play of chance, they are of clinical relevance. Therefore, the statistical analysis plan was extended to include adjusted analyses with respect to the baseline imbalances. Conclusions: CardioBBEAT provides prospective outcome data on both, clinical and health economic impact of home telemonitoring in CHF. The study differs by the use of a high evidence level randomized controlled trial (RCT) design along with actual cost data obtained from health insurance companies. Its results are conducive to informed political and economic decision-making with regard to home telemonitoring solutions as an option for health care. Overall, it contributes to developing advanced health economic evaluation instruments to be deployed within the specific context of the German Health Care System

Multidecadal variability in Atlas cedar growth in northwest Africa during the last 850 years: implications for dieback and conservation of an endangered species

Widespread forest dieback is a phenomenon of global concern that requires an improved understanding of the relationship between tree growth and climate to support conservation efforts. One priority for conservation is the Atlas cedar (Cedrus atlantica), an endangered species exhibiting dieback throughout its North African range. In this study, we evaluate the long-term context for recent dieback and develop a projection of future C. atlantica growth by exploring the periodic variability of its growth through time. First, we present a new C. atlantica tree- ring chronology (1150–2013 CE) from the Middle Atlas mountains, Morocco. We then compare the new chronology to existing C. atlantica chronologies in Morocco and use principal components analysis (PCA) to isolate the common periodic signal from the seven longest available records (PCA7, 1271–1984 CE) in the Middle and High Atlas portions of the C. atlantica range. PCA7 captures 55.7% of the variance and contains significant multidecadal ( ̃95yr, ̃57yr, ̃21yr) periodic components, revealed through spectral and wavelet analyses. Parallel analyses of historical climate data (1901–2016 CE) suggests that the multidecadal growth signal ori- ginates primarily in growing season (spring and summer) precipitation variability, compounded by slow- changing components of summer and winter temperatures. Finally, we model the long-term growth patterns between 1271–1984 CE using a small number (three to four) of harmonic components, illustrating that sup- pressed growth since the 1970s – a factor implicated in the dieback of this species – is consistent with recurrent climatically-driven growth declines. Forward projection of this model suggests two climatically-favourable periods for growth in the 21st century that may enhance current conservation actions for the long-term survival of the C. atlantica in the Middle and High Atlas mountains