Treatment with higher dosages of heart failure medication is associated with improved outcome following cardiac resynchronization therapy

Background Cardiac resynchronization therapy (CRT) is associated with improved morbidity and mortality in patients with chronic heart failure (CHF) on optimal medical therapy. The impact of CHF medication optimization following CRT, however, has never been comprehensively evaluated. In the current study, we therefore investigated the effect of CHF medication dosage on morbidity and mortality in CHF patients after CRT implantation. Methods and results Chronic heart failure medication was assessed in 185 patients after CRT implantation. During an overall mean follow-up of 44.6 months, 83 patients experienced a primary endpoint (death, heart transplantation, assist device implantation, or hospitalization for CHF). Treatment with higher dosages of angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blockers (ARBs) (P = 0.001) and beta-blockers (P < 0.001) as well as with lower dosages of loop diuretics (P < 0.001) was associated with a reduced risk for the primary combined endpoint as well as for all-cause mortality. Echocardiographic super-responders to CRT were treated with higher average dosages of ACE-I/ARBs (68.1 vs. 52.4%, P < 0.01) and beta-blockers (59 vs. 42.2%, P < 0.01). During follow-up, the average dosage of loop diuretics was decreased by 20% in super-responders, but increased by 30% in non-super-responders (P < 0.03). Conclusion The use of higher dosages of neurohormonal blockers and lower dosages of diuretics is associated with reduced morbidity and mortality following CRT implantation. Our data imply a beneficial effect of increasing neurohormonal blockade whenever possible following CRT implantatio

Upgrading to resynchronization therapy after chronic right ventricular pacing improves left ventricular remodelling

Aims Chronic right ventricular (RV) pacing may impose ventricular dyssynchrony leading to LV remodelling and is associated with increased morbidity and mortality. Upgrading patients with chronic RV pacing to cardiac resynchronization therapy (CRT) may be considered to restore synchronicity and prevent these deleterious effects. Methods and results A total of 172 patients from two tertiary centres were analysed over a mean follow-up of 21.7 and 23.5 months after primary CRT implantation (n = 102) and CRT upgrade (n = 70), respectively. In the latter group, mean duration of RV pacing before CRT upgrade was 80.3 months, and ventricular stimulation was >95%. A significant improvement in left ventricular (LV) ejection fraction (10 and 11% absolute increase in primary CRT vs. upgrades, respectively), LV end-diastolic diameter index (−0.15 cm/m2 vs. −0.2 cm/m2), and LV end-systolic diameter (−6.0 vs. −7.0 mm) was observed in both groups, which did not differ between primary CRT recipients and CRT upgrades. Response to CRT upgrade was independent of the underlying rhythm, QRS duration, duration of prior RV pacing, or LV function and size at baseline. Of note, even seven of nine patients with RV pacing >12 years responded favourably to CRT. Conclusion The current study demonstrates that CRT reverses LV remodelling in heart failure patients with chronic RV pacing in a similar way as in primary CRT recipients, even after very long periods of RV pacing. Our data, therefore, may have important implications for the treatment of pacemaker-dependent patients with heart failure, and support the use of CRT in this settin

Rivaroxaban postmarketing risk of liver injury

BACKGROUND: Rivaroxaban is an oral direct factor Xa inhibitor that has been marketed worldwide since 2008 for the primary and secondary prevention and treatment of thromboembolic disorders. Although liver injury was observed in premarketing trials of rivaroxaban, there are no published postmarketing cases of liver injury associated with rivaroxaban. METHODS: Report of 14 cases of liver injury associated with rivaroxaban, including two with liver biopsy, and search queries in three large international pharmacovigilance databases for comparable cases. RESULTS: Formal causality assessment classified rivaroxaban as the "highly probable", "probable" and "possible" cause in 4, 7 and 3 patients, respectively. Search results from three large international pharmacovigilance databases revealed a considerable number of additional hepatic adverse events where rivaroxaban was reported as a suspected cause. CONCLUSIONS: We interpret the presented information as a relevant safety signal that should be followed by pharmacoepidemiological studies in order to reliably estimate absolute and relative risks of liver injury associated with rivaroxaban in support of rational risk-benefit assessment. Meanwhile, incident symptoms and signs of liver disease in patients treated with rivaroxaban should be considered as a potential adverse drug reaction, and if no other likely cause can be identified rivaroxaban should be stopped as soon as possible

The Newcomb-Benford Law in Its Relation to Some Common Distributions

An often reported, but nevertheless persistently striking observation, formalized as the Newcomb-Benford law (NBL), is that the frequencies with which the leading digits of numbers occur in a large variety of data are far away from being uniform. Most spectacular seems to be the fact that in many data the leading digit 1 occurs in nearly one third of all cases. Explanations for this uneven distribution of the leading digits were, among others, scale- and base-invariance. Little attention, however, found the interrelation between the distribution of the significant digits and the distribution of the observed variable. It is shown here by simulation that long right-tailed distributions of a random variable are compatible with the NBL, and that for distributions of the ratio of two random variables the fit generally improves. Distributions not putting most mass on small values of the random variable (e.g. symmetric distributions) fail to fit. Hence, the validity of the NBL needs the predominance of small values and, when thinking of real-world data, a majority of small entities. Analyses of data on stock prices, the areas and numbers of inhabitants of countries, and the starting page numbers of papers from a bibliography sustain this conclusion. In all, these findings may help to understand the mechanisms behind the NBL and the conditions needed for its validity. That this law is not only of scientific interest per se, but that, in addition, it has also substantial implications can be seen from those fields where it was suggested to be put into practice. These fields reach from the detection of irregularities in data (e.g. economic fraud) to optimizing the architecture of computers regarding number representation, storage, and round-off errors

Towards a standard typology of endogenous landslide seismic sources

The objective of this work is to propose a standard classification of seismic signals generated by gravitational processes and detected at close distances (&lt;1&thinsp;km). We review the studies where seismic instruments have been installed on unstable slopes and discuss the choice of the seismic instruments and the network geometries. Seismic observations acquired at 13 unstable slopes are analyzed in order to construct the proposed typology. The selected slopes are affected by various landslide types (slide, fall, topple and flow) triggered in various material (from unconsolidated soils to consolidated rocks). We investigate high-frequency bands (&gt;1&thinsp;Hz) where most of the seismic energy is recorded at the 1&thinsp;km sensor to source distances. Several signal properties (duration, spectral content and spectrogram shape) are used to describe the sources. We observe that similar gravitational processes generate similar signals at different slopes. Three main classes can be differentiated mainly from the length of the signals, the number of peaks and the duration of the autocorrelation. The classes are the “slopequake” class, which corresponds to sources potentially occurring within the landslide body; the “rockfall” class, which corresponds to signals generated by rock block impacts; and the “granular flow” class, which corresponds to signals generated by wet or dry debris/rock flows. Subclasses are further proposed to differentiate specific signal properties (frequency content, resonance, precursory signal). The signal properties of each class and subclass are described and several signals of the same class recorded at different slopes are presented. Their potential origins are discussed. The typology aims to serve as a standard for further comparisons of the endogenous microseismicity recorded on landslides.</p

An integrated approach to control soil-transmitted helminthiasis, schistosomiasis, intestinal protozoa infection, and diarrhea : protocol for a cluster randomized trial

Background: The global strategy to control helminthiases (schistosomiasis and soil-transmitted helminthiasis) emphasizes preventive chemotherapy. However, in the absence of access to clean water, improved sanitation, and adequate hygiene, reinfection after treatment can occur rapidly. Integrated approaches might be necessary to sustain the benefits of preventive chemotherapy and make progress toward interruption of helminthiases transmission. Objective: The aim of this study was to assess and quantify the effect of an integrated control package that consists of preventive chemotherapy, community-led total sanitation, and health education on soil-transmitted helminthiasis, schistosomiasis, intestinal protozoa infection, and diarrhea in rural Côte d’Ivoire. Methods: In a first step, a community health education program was developed that includes an animated cartoon to promote improved hygiene and health targeting school-aged children, coupled with a health education theater for the entire community. In a second step, a cluster randomized trial was implemented in 56 communities of south-central Côte d’Ivoire with 4 intervention arms: (1) preventive chemotherapy; (2) preventive chemotherapy plus community-led total sanitation; (3) preventive chemotherapy plus health education; and (4) all 3 interventions combined. Before implementation of the aforementioned interventions, a baseline parasitologic, anthropometric, and hygiene-related knowledge, attitudes, practices, and beliefs survey was conducted. These surveys were repeated 18 and 39 months after the baseline cross-sectional survey to determine the effect of different interventions on helminth and intestinal protozoa infection, nutritional indicators, and knowledge, attitudes, practices, and beliefs. Monitoring of diarrhea was done over a 24-month period at 2-week intervals, starting right after the baseline survey. Results: Key results from this cluster randomized trial will shed light on the effect of integrated approaches consisting of preventive chemotherapy, community-led total sanitation, and health education against infections with soil-transmitted helminths, schistosomes, an intestinal protozoa and prevention of diarrhea in a rural part of Côte d’Ivoire. Conclusions: The research provided new insights into the acceptability, strengths, and limitations of an integrated community-based control package targeting helminthiases, intestinal protozoa infections, and diarrhea in rural communities of Côte d’Ivoire. In the longer term, the study will allow determining the effect of the integrated control approach on infection patterns with parasitic worms and intestinal protozoa, diarrheal incidence, anthropometric measures, and hygiene-related knowledge, attitudes, practices, and beliefs

Toward an Open-Access Global Database for Mapping, Control, and Surveillance of Neglected Tropical Diseases

There is growing interest in the scientific community, health ministries, and other organizations to control and eventually eliminate neglected tropical diseases (NTDs). Control efforts require reliable maps of NTD distribution estimated from appropriate models and survey data on the number of infected people among those examined at a given location. This kind of data is often available in the literature as part of epidemiological studies. However, an open-access database compiling location-specific survey data does not yet exist. We address this problem through a systematic literature review, along with contacting ministries of health, and research institutions to obtain disease data, including details on diagnostic techniques, demographic characteristics of the surveyed individuals, and geographical coordinates. All data were entered into a database which is freely accessible via the Internet (http://www.gntd.org). In contrast to similar efforts of the Global Atlas of Helminth Infections (GAHI) project, the survey data are not only displayed in form of maps but all information can be browsed, based on different search criteria, and downloaded as Excel files for further analyses. At the beginning of 2011, the database included over 12,000 survey locations for schistosomiasis across Africa, and it is continuously updated to cover other NTDs globally