The value of time-to-onset in statistical signal detection of adverse drug reactions:a comparison with disproportionality analysis in spontaneous reports from the Netherlands

PURPOSE: In pharmacovigilance, the commonly used disproportionality analysis (DPA) in statistical signal detection is known to have its limitations. The aim of this study was to investigate the value of the time to onset (TTO) of ADRs in addition to DPA.METHODS: We performed a pilot study using individual case safety reports (ICSRs) for three drugs (Cervarix®, nitrofurantoin and simvastatin) from the Lareb spontaneous reporting database. TTO distributions for drug - ADR associations were compared to other ADRs for the same drug and to other drugs for the same ADR using two-sample Anderson-Darling testing. Statistically significant associations were considered true positive (TP) signals if the association was present in the official product information of the drug. Sensitivity and specificity for the TTO method were compared with the DPA method. As a measure of disproportionality, the reporting odds ratio (ROR) was used.RESULTS: In general, sensitivity was lower, and specificity was higher for the TTO method compared to DPA. The TTO method showed similar sensitivity for all three drugs, whereas specificity was lower for Cervarix®. Eight additional TP signals were found using the TTO method compared to DPA.CONCLUSIONS: Our study shows that statistical signal detection based on the TTO alone resulted in a limited number of additional signals compared to DPA. We therefore conclude that the TTO method is of limited value for full database statistical screening in our setting. Copyright © 2016 John Wiley &amp; Sons, Ltd.</p

Implementation of a postoperative handoff protocol

Background: Standardised handoff protocols have become necessary patient safety tools in the perioperative venue. In this study, the authors took a validated standardised perioperative handoff protocol and implemented it into their institution to improve the perioperative handoff communications from the cardiac operating theatres to the ICU.Methods: This was a prospective, unblinded cross-sectional study. During a 6-week pre-intervention phase, 30 perioperative handoffs were observed and data were collected. Then a new structured hand-off protocol was implemented for one month, which focused on training all participating healthcare providers. This was followed by a post-intervention audit consisting of 30 operating room theatre-to-ICU handoffs using the same methodology as the pre-intervention period.Results: Overall attendance significantly increased from 20 to 86.7%. The percentage of parallel conversations decreased from 100% pre-intervention to 60% post-intervention (p &lt; 0.0001). The mean number of interruptions of the anaesthesiology handoff report decreased from 3.37 to 0.77 (p &lt; 0.0001) and of the surgery report from 1.84 to 0.27 (p &lt; 0.0001). Information-sharing scores improved among all handoff attendees with the Overall Information Sharing Score (OISS) increasing from 51.47 to 88.24% (p &lt; 0.0001).Conclusions: The implementation of a perioperative handoff protocol resulted in a drastic improvement in attendance, decrease in the number of interruptions, and improved information sharing. Future research should focus on patient-specific outcomes.Keywords: handoffs, handover, ICU handoff, patient safety, perioperative handof

Connecting Wireless Sensor Networks to the Robot Operating System

AbstractRobot systems largely depend on embedded systems to operate. The interfaces of those embedded systems, e.g. motor controllers or laser scanners, are often vendor-specific and therefore require a component that translates from/to the Robot Operating System (ROS) Middleware interface. In this work we present an implementation and evaluation of a ROS Middleware client based on the Contiki operating systems, which is suitable for constrained embedded devices, like wireless sensor nodes. We show that in-buffer processing of ROS messages without relying on dynamic memory allocation is possible. That message contents can be accessed conveniently via well-known concepts of the C language (structs) with negligible processing overhead compared to a C++-based client. And that the message-passing middle- ware concept of ROS fits nicely in Contiki's event-based nature. Furthermore, in order for an environment enriched with wireless sensor network to help robots in navigating, understanding and manipulating environments a direct integration is mandatory

Variation in Modern Dutch D-Weakening: A Historical Perspective

Proceedings of the Twenty-First Annual Meeting of the Berkeley Linguistics Society: General Session and Parasession on Historical Issues in Sociolinguistics/Social Issues in Historical Linguistics (1995

Time to onset in statistical signal detection revisited:A follow-up study in long-term onset adverse drug reactions

PURPOSE: In a previous study, we developed a signal detection method using the time to onset (TTO) of adverse drug reactions (ADRs). The aim of the current study was to investigate this method in a subset of ADRs with a longer TTO and to compare its performance with disproportionality analysis. METHODS: Using The Netherlands's spontaneous reporting database, TTO distributions for drug-ADR associations with a median TTO of 7 days or more were compared with other drugs with the same ADR using the two-sample Anderson-Darling (AD) test. Presence in the Summary of Product Characteristics (SPC) was used as the gold standard for identification of a true ADR. Twelve combinations with different values for the number of reports and median TTO were tested. Performance in terms of sensitivity and positive predictive value (PPV) was compared with disproportionality analysis. A sensitivity analysis was performed to compare the results with those from the previous study. RESULTS: A total of 38 017 case reports, containing 32 478 unique drug-ADR associations. Sensitivity was lower for the TTO method (range 0.08-0.34) compared with disproportionality analysis (range 0.60-0.87), whereas PPV was similar for both methods (range 0.93-1.0). The results from the sensitivity analysis were similar to the original analysis. CONCLUSIONS: Because of its low sensitivity, the developed TTO method cannot replace disproportionality analysis as a signal detection tool. It may be useful in combination with other methods

Visualizing Geophylogenies - Internal and External Labeling with Phylogenetic Tree Constraints

A geophylogeny is a phylogenetic tree where each leaf (biological taxon) has an associated geographic location (site). To clearly visualize a geophylogeny, the tree is typically represented as a crossing-free drawing next to a map. The correspondence between the taxa and the sites is either shown with matching labels on the map (internal labeling) or with leaders that connect each site to the corresponding leaf of the tree (external labeling). In both cases, a good order of the leaves is paramount for understanding the association between sites and taxa. We define several quality measures for internal labeling and give an efficient algorithm for optimizing them. In contrast, minimizing the number of leader crossings in an external labeling is NP-hard. We show nonetheless that optimal solutions can be found in a matter of seconds on realistic instances using integer linear programming. Finally, we provide several efficient heuristic algorithms and experimentally show them to be near optimal on real-world and synthetic instances

Eccentricity of radiative discs in close binary-star systems

Discs in binaries have a complex behavior because of the perturbations of the companion star. Planet formation in binary-star systems both depend on the companion star parameters and on the properties of the circumstellar disc. An eccentric disc may increase the impact velocity of planetesimals and therefore jeopardize the accumulation process. We model the evolution of discs in close binaries including the effects of self-gravity and adopting different prescriptions to model the disc's radiative properties. We focus on the dynamical properties and evolutionary tracks of the discs. We use the hydrodynamical code FARGO and we include in the energy equation heating and cooling effects. Radiative discs have a lower disc eccentricity compared to locally isothermal discs with same temperature profile. As a consequence, we do not observe the formation of an internal elliptical low density region as in locally isothermal disc models. However, the disc eccentricity depends on the disc mass through the opacities. Akin to locally isothermal disc models, self-gravity forces the disc's longitude of pericenter to librate about a fixed orientation with respect to the binary apsidal line ($\pi$). The disc's radiative properties play an important role in the evolution of discs in binaries. A radiative disc has an overall shape and internal structure that are significantly different compared to a locally isothermal disc with same temperature profile. This is an important finding both for describing the evolutionary track of the disc during its progressive mass loss, and for planet formation since the internal structure of the disc is relevant for planetesimals growth in binary systems. The non-symmetrical distribution of mass in these discs causes large eccentricities for planetesimals that may affect their growth.Comment: accepted for publication in A&A (abstract truncated to comply with astro-ph rules

Magnetic bright points in the quiet Sun

We present a visual determination of the number of bright points (BPs) existing in the quiet Sun, which are structures though to trace intense kG magnetic concentrations. The measurement is based on a 0.1 arcsec angular resolution G-band movie obtained with the Swedish Solar Telescope at the solar disk center. We find 0.97 BPs/Mm^2, which is a factor three larger than any previous estimate. It corresponds to 1.2 BPs per solar granule. Depending on the details of the segmentation, the BPs cover between 0.9% and 2.2% of the solar surface. Assuming their field strength to be 1.5 kG, the detected BPs contribute to the solar magnetic flux with an unsigned flux density between 13 G and 33 G. If network and inter-network regions are counted separately, they contain 2.2 BPs/Mm^2 and 0.85 BPs/Mm^2, respectively.Comment: Accepted for publication in ApJL. 2 figs