Diagnostic errors in paediatric cardiac intensive care

AbstractIntroductionDiagnostic errors cause significant patient harm and increase costs. Data characterising such errors in the paediatric cardiac intensive care population are limited. We sought to understand the perceived frequency and types of diagnostic errors in the paediatric cardiac ICU.MethodsPaediatric cardiac ICU practitioners including attending and trainee physicians, nurse practitioners, physician assistants, and registered nurses at three North American tertiary cardiac centres were surveyed between October 2014 and January 2015.ResultsThe response rate was 46% (N=200). Most respondents (81%) perceived that diagnostic errors harm patients more than five times per year. More than half (65%) reported that errors permanently harm patients, and up to 18% perceived that diagnostic errors contributed to death or severe permanent harm more than five times per year. Medication side effects and psychiatric conditions were thought to be most commonly misdiagnosed. Physician groups also ranked pulmonary overcirculation and viral illness to be commonly misdiagnosed as bacterial illness. Inadequate care coordination, data assessment, and high clinician workload were cited as contributory factors. Delayed diagnostic studies and interventions related to the severity of the patient’s condition were thought to be the most commonly reported process breakdowns. All surveyed groups ranked improving teamwork and feedback pathways as strategies to explore for preventing future diagnostic errors.ConclusionsPaediatric cardiac intensive care practitioners perceive that diagnostic errors causing permanent harm are common and associated more with systematic and process breakdowns than with cognitive limitations.</jats:sec

Epidemiologic Questions from Anthrax Outbreak, Hunter Valley, Australia

Anthrax was introduced into Australia in 1847 near Sydney, New South Wales, and spread along stock routes throughout New South Wales and southern Queensland. Anthrax was considered endemic to the Hunter Valley, New South Wales, during the 1890s. The last recorded anthrax-related stock losses there occurred on 3 properties in the Upper Hunter Valley in 1939. During the past 4 decades, anthrax has become uncommon in Australia. However, our experience is a timely reminder that veterinary public health authorities should be on high alert for possible anthrax when unexpected livestock deaths follow flooding in areas where anthrax has historically occurred

Deterministic delivery of externally cold and precisely positioned single molecular ions

We present the preparation and deterministic delivery of a selectable number of externally cold molecular ions. A laser cooled ensemble of Mg^+ ions subsequently confined in several linear Paul traps inter-connected via a quadrupole guide serves as a cold bath for a single or up to a few hundred molecular ions. Sympathetic cooling embeds the molecular ions in the crystalline structure. MgH^+ ions, that serve as a model system for a large variety of other possible molecular ions, are cooled down close to the Doppler limit and are positioned with an accuracy of one micrometer. After the production process, severely compromising the vacuum conditions, the molecular ion is efficiently transfered into nearly background-free environment. The transfer of a molecular ion between different traps as well as the control of the molecular ions in the traps is demonstrated. Schemes, optimized for the transfer of a specific number of ions, are realized and their efficiencies are evaluated. This versatile source applicable for broad charge-to-mass ratios of externally cold and precisely positioned molecular ions can serve as a container-free target preparation device well suited for diffraction or spectroscopic measurements on individual molecular ions at high repetition rates (kHz).Comment: 11 pages, 8 figure

A comprehensive study of GRB 070125, a most energetic gamma ray burst

We present a comprehensive multiwavelength analysis of the bright, long duration gamma-ray burst GRB 070125, comprised of observations in $\gamma$-ray, X-ray, optical, millimeter and centimeter wavebands. Simultaneous fits to the optical and X-ray light curves favor a break on day 3.78, which we interpret as the jet break from a collimated outflow. Independent fits to optical and X-ray bands give similar results in the optical bands but shift the jet break to around day 10 in the X-ray light curve. We show that for the physical parameters derived for GRB 070125, inverse Compton scattering effects are important throughout the afterglow evolution. While inverse Compton scattering does not affect radio and optical bands, it may be a promising candidate to delay the jet break in the X-ray band. Radio light curves show rapid flux variations, which are interpreted as due to interstellar scintillation, and are used to derive an upper limit of $2.4 \times 10^{17}$ cm on the radius of the fireball in the lateral expansion phase of the jet. Radio light curves and spectra suggest a high synchrotron self absorption frequency indicative of the afterglow shock wave moving in a dense medium. Our broadband modeling favors a constant density profile for the circumburst medium over a wind-like profile ($R^{-2}$). However, keeping in mind the uncertainty of the parameters, it is difficult to unambiguously distinguish between the two density profiles. Our broadband fits suggest that \event is a burst with high radiative efficiency ($> 60$).Comment: 50 pages, 33 figures, sty file included, Appeared in 20 Aug 2008 edition of Astrophysical Journa

Relating protein pharmacology by ligand chemistry

The identification of protein function based on biological information is an area of intense research. Here we consider a complementary technique that quantitatively groups and relates proteins based on the chemical similarity of their ligands. We began with 65,000 ligands annotated into sets for hundreds of drug targets. The similarity score between each set was calculated using ligand topology. A statistical model was developed to rank the significance of the resulting similarity scores, which are expressed as a minimum spanning tree to map the sets together. Although these maps are connected solely by chemical similarity, biologically sensible clusters nevertheless emerged. Links among unexpected targets also emerged, among them that methadone, emetine and loperamide (Imodium) may antagonize muscarinic M3, α2 adrenergic and neurokinin NK2 receptors, respectively. These predictions were subsequently confirmed experimentally. Relating receptors by ligand chemistry organizes biology to reveal unexpected relationships that may be assayed using the ligands themselves

Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety

&lt;p&gt;Background: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment.&lt;/p&gt; &lt;p&gt;Methods: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit.&lt;/p&gt; &lt;p&gt;Results: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome.&lt;/p&gt; &lt;p&gt;Conclusions: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation.&lt;/p&gt

Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors

Tolvaptan is a selective vasopressin V2 receptor antagonist, approved in several countries for the treatment of hyponatremia and autosomal dominant polycystic kidney disease (ADPKD). No liver injury has been observed with tolvaptan treatment in healthy subjects and in non-ADPKD indications, but ADPKD clinical trials showed evidence of drug-induced liver injury (DILI). Although all DILI events resolved, additional monitoring in tolvaptan-treated ADPKD patients is required. In vitro assays identified alterations in bile acid disposition and inhibition of mitochondrial respiration as potential mechanisms underlying tolvaptan hepatotoxicity. This report details the application of DILIsym software to determine whether these mechanisms could account for the liver safety profile of tolvaptan observed in ADPKD clinical trials. DILIsym simulations included physiologically based pharmacokinetic estimates of hepatic exposure for tolvaptan and2 metabolites, and their effects on hepatocyte bile acid transporters and mitochondrial respiration. The frequency of predicted alanine aminotransferase (ALT) elevations, following simulated 90/30 mg split daily dosing, was 7.9% compared with clinical observations of 4.4% in ADPKD trials. Toxicity was multifactorial as inhibition of bile acid transporters and mitochondrial respiration contributed to the simulated DILI. Furthermore, simulation analysis identified both pre-treatment risk factors and on-treatment biomarkers predictive of simulated DILI. The simulations demonstrated that in vivo hepatic exposure to tolvaptan and the DM-4103 metabolite, combined with these 2 mechanisms of toxicity, were sufficient to account for the initiation of tolvaptan-mediated DILI. Identification of putative risk-factors and potential novel biomarkers provided insight for the development of mechanism-based tolvaptan risk-mitigation strategies

Pion emission from the T2K replica target: method, results and application

The T2K long-baseline neutrino oscillation experiment in Japan needs precise predictions of the initial neutrino flux. The highest precision can be reached based on detailed measurements of hadron emission from the same target as used by T2K exposed to a proton beam of the same kinetic energy of 30 GeV. The corresponding data were recorded in 2007-2010 by the NA61/SHINE experiment at the CERN SPS using a replica of the T2K graphite target. In this paper details of the experiment, data taking, data analysis method and results from the 2007 pilot run are presented. Furthermore, the application of the NA61/SHINE measurements to the predictions of the T2K initial neutrino flux is described and discussed.Comment: updated version as published by NIM

Measurement of Production Properties of Positively Charged Kaons in Proton-Carbon Interactions at 31 GeV/c

Spectra of positively charged kaons in p+C interactions at 31 GeV/c were measured with the NA61/SHINE spectrometer at the CERN SPS. The analysis is based on the full set of data collected in 2007 with a graphite target with a thickness of 4% of a nuclear interaction length. Interaction cross sections and charged pion spectra were already measured using the same set of data. These new measurements in combination with the published ones are required to improve predictions of the neutrino flux for the T2K long baseline neutrino oscillation experiment in Japan. In particular, the knowledge of kaon production is crucial for precisely predicting the intrinsic electron neutrino component and the high energy tail of the T2K beam. The results are presented as a function of laboratory momentum in 2 intervals of the laboratory polar angle covering the range from 20 up to 240 mrad. The kaon spectra are compared with predictions of several hadron production models. Using the published pion results and the new kaon data, the K+/\pi+ ratios are computed.Comment: 10 pages, 11 figure