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Introduction: The proportion of Canadians receiving anticoagulation medication is increasing. Falls in the elderly are the most common cause of minor head injury and an increasing proportion of these patients are prescribed anticoagulation. Emergency department (ED) guidelines advise performing a CT head scan for all anticoagulated head injured patients, but the risk of intracranial hemorrhage (ICH) after a minor head injury (patients who have a Glasgow comma score (GSC) of 15) is unclear. We conducted a systematic review and meta-analysis to determine the point incidence of ICH in anticoagulated ED patients presenting with a minor head injury. Methods: We systematically searched Pubmed, EMBASE, Cochrane database, DARE, google scholar and conference abstracts (May 2017). Experts were contacted. Meta-Analyses and Systematic Reviews of Observational Studies (MOOSE) guidelines were followed with two authors reviewing titles, four authors reviewing full text and four authors performing data extraction. We included all prospective studies recruiting consecutive anticoagulated ED patients presenting with a head injury. We obtained additional data from the authors of the included studies on the subset of GCS 15 patients. We performed a meta-analysis to estimate the point incidence of ICH among patients with a GCS score of 15 using a random effects model. Results: A total of five studies (and 4,080 GCS 15, anticoagulated patients) from the Netherlands, Italy, France, USA and UK were included in the analysis. One study contributed 2,871 patients. Direct oral anticoagulants were prescribed in only 60 (1.5%) patients. There was significant heterogeneity between studies with regards to mechanism of injury, CT scanning and follow up method (I2 =93%). The random effects pooled incidence of ICH was 8.9% (95% CI 5.0-13.8%). Conclusion: We found little data to reflect contemporary anticoagulant prescribing practice. Around 9% of warfarinized patients with a minor head injury develop ICH. Future studies should evaluate the safety of selective CT head scanning in this population.
Dextromethorphan hydrobromide and quinidine sulfate (DM/Q) 20mg/10mg is FDA approved to treat pseudobulbar affect (PBA), a neurological condition characterized by sudden, frequent, involuntary crying or laughing. Although the total dose of quinidine (20 mg) from twice daily DM/Q for PBA is well below the antiarrhythmic dose (600-1600 mg/day), clinicians may be reticent to use DM/Q due to concerns for cardiac safety.
DM/Q cardiac safety was evaluated in two thorough QTc (TQT) studies and by ECG monitoring in DM/Q phase 3 clinical trials. In the TQT studies, twice daily DM/Q 30mg/10mg (Study 08-AVR-126; N=50 enrolled) and supratherapeutic doses 30mg/30mg and 60mg/60mg (Study 05-AVR-119; N=36 enrolled) were studied in healthy volunteers. In phase 3 controlled clinical trials, the effects of DM/Q on Fridericia’s corrected QT intervals (QTcF) were assessed, as was the incidence of ECG outliers. Adverse events (AEs) were monitored in all clinical trials.
Overall, 47/50 participants completed TQT study 08-AVR-126 and 36/36 completed TQT study 05-AVR-119. Time-matched, placebo-corrected mean maximal changes in QTcF for DM/Q 30mg/10mg and 30mg/30mg occurred 3h post-dose (10.3 and 10.1ms, respectively) vs moxifloxacin (12.2 and 14.4ms at 1.5 and 1.0h). For the supratherapeutic DM/Q 60/60 mg dose, mean maximal QTcF change was 18.8ms. No participant had a QTcF >480 ms or QTc increase >60 ms. In PBA phase 3 controlled trials, mean changes in QTcF were similar for DM/Q containing Q 10 mg (0.4 to 3.5 ms; n=217) andplacebo (0.4 to 3.1 ms; n=183), but greater for DM/Q with Q 30 mg (2.9 to 7.6 ms; n=146). In an outlier analysis, a similar percentage of DM/Q-treated participants (3.9%) had a QTcF shift from <450 ms at baseline to ≥450 ms during treatment vs placebo (2.9%). No participant with PBA had a QTc change from baseline >60 ms or an absolute QTc interval >480 ms. No dose- or time-related trends in cardiac arrhythmias or other cardiac-related AEs were observed.
Of 2552 DM/Q-treated patients and healthy participants across all controlled and open-label trials for any indication, 11 deaths due to any cardiovascular AE have been reported; none were attributable to DM/Q treatment and none occurred in placebo-controlled PBA clinical trials in any treatment group. Overall 16 patients had a QTcF that exceeded 500 ms at any ECG measurement.
The TQT studies demonstrated that DM/Q has the potential to prolong the QT interval in a dose-dependent manner, but that the risk for QTc prolongation and arrhythmias with Q 10 mg formulations is low. In clinical trials with PBA patients, the cardiac safety profile of DM/Q 20mg/10mg or 30/10 mg was indistinguishable from placebo.
Drug use during pregnancy and lactation remain underdeveloped areas of clinical pharmacology and drug research. Pregnancy risk factors together with an increased incidence of chronic diseases and a rise in the average maternal age predict medication use will continue to rise during gestation. Common exposure categories include over-the-counter (OTC) medication, psychiatric agents, gastrointestinal medications, herbals, vitamins, antibiotics, and topical products. Only a few medications have been tested specifically for safety and efficacy during human gestation. Profound physiologic changes occur during both normal and pathologic pregnancy that may dramatically alter drug clearance, efficacy, and safety. Under such circumstances, the danger of a drug to mothers, their fetuses, and nursing infants cannot be determined with any confidence until it has been widely used. It is important that women with medical disorders such as diabetes, hypertension, epilepsy, and inflammatory bowel disease continue necessary therapy while pregnant. Unfortunately, many physicians stop or delay medically important agents precisely because of the lack of information.
Precise measurements of surface elevation on the Greenland ice sheet have been made almost every year since 1991 by an airborne scanning laser altimeter operated by NASA/Wallops Flight Facility. Results show substantial thinning over large areas near the coast, with a general increase in thinning rates since 1997, in the drainage basins of thinning glaciers, and a recent thickening in the southeast associated with very high snowfall in this region during 2003. Here, we present first results from the comparison of the aircraft data with similar measurements from the laser altimeter aboard NASA’s Ice, Cloud and land Elevation Satellite (ICESat), which was launched in January 2003. These show very close agreement with results inferred solely from the aircraft measurements, indicating that accuracies are similar for both datasets. Broad spatial coverage by satellite, together with the baseline dataset of aircraft measurements, offers the prospects of routine surveys of ice-sheet elevation changes by ICESat and follow-on missions.
We describe the successful use of recombinant factor VIIa (rFVIIa) in the control of massive haemoptysis in a 17-year-old patient with a Fontan circulation. The patient was intubated and ventilated in the ICU with deteriorating gas exchange. Conventional methods to control the haemoptysis were ineffective, and rFVIIa was successfully administered as a rescue therapy. rFVIIa is a powerful pro-thrombotic agent, which is only licensed in haemophiliacs with acquired inhibitors to anticoagulation. It has been used off-license in the treatment of massive haemorrhage, although a Cochrane review did not show any significant benefit; however, it may have a role as a rescue therapy where alternatives options have been exhausted after careful risk–benefit analysis.
The shearing and ablation of “cold” ice that leads to the formation of ablation and end moraines and the characteristic form of the S.E. edge of the Barnes ice cap are discussed. Some evidence suggests the existence of considerable areas of dead glacier ice extending well beyond the current moraines and completely insulated from melting by glacial debris. This debris consists of old moraines whose relief has been inverted and subdued. An appendix by Mason E. Hale on the current moraine plant succession suggests that the last stable position of the S.E. edge of the ice cap occurred about 1860 and has been followed by retreat at an average rate of about 3 m. per year.
The analysis of multilayer networks is among the most active areas of network science, and there are several methods to detect dense “communities” of nodes in multilayer networks. One way to define a community is as a set of nodes that trap a diffusion-like dynamical process (usually a random walk) for a long time. In this view, communities are sets of nodes that create bottlenecks to the spreading of a dynamical process on a network. We analyze the local behavior of different random walks on multiplex networks (which are multilayer networks in which different layers correspond to different types of edges) and show that they have very different bottlenecks, which correspond to rather different notions of what it means for a set of nodes to be a good community. This has direct implications for the behavior of community-detection methods that are based on these random walks.
Improving neurocognitive outcomes following treatment for brain metastases have become increasingly important. We propose that a brief telephone-based neurocognitive assessment may improve follow-up cognitive assessments in this palliative population. Aim: To prospectively assess the feasibility and reliability of a telephone based brief neurocognitive assessment compared to the same tests delivered face-to-face. Methods: Brain metastases patients to be treated with whole brain radiotherapy (WBRT) were assessed using a brief validated neurocognitive battery at baseline, at 1 month and 3 months following WBRT (in person and over the phone). The primary outcome was feasibility and inter-procedural (in person versus telephone) reliability. The secondary objective was to evaluate the change in neurocognitive function before and after WBRT. Results: Out of 39 patients enrolled, 82% of patients completed the baseline in-person and telephone neurocognitive assessments. However, at 1 month, only 41% of enrolled patients completed the in-person and telephone cognitive assessments and at 3 months, only 10% of patients completed them. Results pertaining to reliability and change in neurocognitive function will be updated. Conclusion: The pre-defined definition of feasibility (at least 80% completion for face to face and telephone neurocognitive assessments) was met at baseline. However, a large proportion of participants did not complete either telephone or in person neurocognitive follow-up at 1 month and at 3 months post-WBRT. Attrition remained a challenge for neurocognitive testing in this population even when a telephone-based brief assessment was used.
Individuals with primary brain tumors experience a range of physical, cognitive and psychosocial sequelae which impact their independence, safety and quality of life. These impairments may be addressed through rehabilitation intervention. Despite acknowledgement that timely rehabilitation services over the course of the disease process is of benefit, few outpatient neuro-oncology treatment teams include a rehabilitation professional. Purpose: The aims are: (1) to describe a rehabilitation consultation model of care integrated into outpatient neuro-oncology treatment for individuals with primary brain tumors; and (2) to describe the characteristics of individuals referred for rehabilitation services. Methods: This retrospective descriptive study examined data from 200 individuals that received rehabilitation consultation from January 2015 to March 2016 at Princess Margaret Hospital, Pencer Brain Tumor Centre. Information on patient demographics, referral characteristics, and number of patient care visits was collected. Descriptive statistics were calculated. Preliminary Results: Of all patients, (n=195), the most common diagnosis is glioblastoma, 39% (n=76), and 50% are 50-69 years of age (M=55, SD=15.0). The most common reason for initial referral was decline in physical functioning, strength and balance (41%). In 77% of cases, patients were seen immediately at the time of referral. In total, 540 consultations were completed (face-to-face=230, telephone=310) with 2.78 on average (SD=4.0) per patient. Conclusion: Given the range of symptoms that individuals with primary brain tumors experience coupled with changes in functional status as the disease progresses, integrated and timely rehabilitation consultation is feasible.
In the 1998-99 flight, BOOMERanG has produced maps of ∼4% of the sky at high Galactic latitudes, at frequencies of 90, 150, 240 and 410 GHz, with resolution ≳ 10'. The faint structure of the Cosmic Microwave Background at horizon and sub-horizon scales is evident in these maps. These maps compare well to the maps recently obtained at lower frequencies by the WMAP experiment. Here we compare the amplitude and morphology of the structures observed in the two sets of maps. We also outline the polarization sensitive version of BOOMERanG, which was flown early this year to measure the linear polarization of the microwave sky at 150, 240 and 350 GHz.
In recognition of its special interdisciplinary character, IAU Commission 14 is linked directly to the Executive Committee. The Commission’s role is to inform the astronomical community of new developments in the diverse fields of research which involve atoms and molecules. Conversely it endeavors to sensitize the research community active in those fields to the specific needs of astronomy, especially concerning basic data and modeling tools. More generally, Commission 14 tries to foster long term relations and collaborations between the two communities and, when necessary, to alert funding authorities to the specific needs of ground and space based astronomy for specific atomic and molecular data. This report is one of the main contributions of Commission 14 to the information of the astronomical community. Several meetings concerned, at least in part, with the need and availability of atomic and molecular data for astrophysics were also sponsored or co-sponsored. In the last triennium, Commission 14 cosponsored IAU Symposium 194 “Astrochemistry: From Molecular Cloud to Planetary Systems” held in Sogwipo (Korea) from Aug. 23 to 27, 1999 and organized by Commission 34. A Joint Discussion: JD1 on “Atomic and Molecular Data for Astrophysics, New Developments, Case Studies and Future Needs” has been planned for the XXIVth IAU General Assembly in Manchester (Aug. 7-19, 2000) and cosponsored by Commissions 15, 16, 29, 34, 36, 40 and 44. Several other Joint Discussions to be held at the Manchester General Assembly are co-sponsored by this commission.
A geological disposal facility (GDF) will include fissile materials that could, under certain conditions, lead to criticality. Demonstration of criticality safety therefore forms an important part of a GDF's safety case.
Containment provided by the waste package will contribute to criticality safety during package transport and the GDF operational phase. The GDF multiple-barrier system will ensure that criticality is prevented for some time after facility closure. However, on longer post-closure timescales, conditions in the GDF will evolve and it is necessary to demonstrate: an understanding of the conditions under which criticality could occur; the likelihood of such conditions occurring; and the consequences of criticality should it occur.
Work has addressed disposal of all of the UK's higher-activity wastes in three illustrative geologies. This paper, however, focuses on presenting results to support safe disposal of spent fuel, plutonium and highlyenriched uranium in higher-strength rock.
The results support a safety case assertion that post-closure criticality is of low likelihood and, if it was to occur, the consequences would be tolerable.
1.1.1. In October 1980 the Council of the Faculty of Actuaries set up a Working Party with the following brief:—
(1) To investigate the criteria by which the solvency of life assurance companies should be assessed and to determine the amount of the solvency margin which should be required in practice by supervisory authorities. The existing requirements of the E.E.C. Life Establishment Directive should be considered with a view to recommending any desirable alterations thereto to be made when those requirements are reviewed in due course by the E.E.C. Commission. In carrying out its work the Working Party should co-operate with Working Parties or Committees of other actuarial bodies.
(2) To report the result of their investigations to Council.
A large measles outbreak occurred in South Wales in 2012/2013. The outbreak has been attributed to low take-up of measles-mumps-rubella (MMR) immunization in the early 2000s. To understand better the factors that led to this outbreak we present the findings of a case-control study carried out in the outbreak area in 2001 to investigate parents' decision on whether to accept MMR. Parents who decided not to take-up MMR at the time were more likely to be older and better educated, more likely to report being influenced by newspapers [adjusted odds ratio (aOR) 3·07, 95% confidence interval (CI) 1·62–5·80], television (aOR 3·30, 95% CI 1·70–6·43), the internet (aOR 7·23, 3·26–16·06) and vaccine pressure groups (aOR 5·20, 95% CI 2·22–12·16), and less likely to be influenced by a health visitor (aOR 0·30, 95% CI 0·16–0·57). In this area of Wales, daily English-language regional newspapers, UK news programmes and the internet appeared to have a powerful negative influence. We consider the relevance of these findings to the epidemiology of the outbreak and the subsequent public health response.
We present the results of an all sky survey for binary systems among the massive stars that we made with the HST Fine Guidance Sensors. The sample of 225 stars is comprised mainly of Galactic O- and B-type stars and Luminous Blue Variables, plus a few luminous stars in the LMC. The FGS TRANS mode observations are sensitive to detection of companions with an angular separation of 0.01–1 arcsec and brighter than △m = 5 mag. The FGS observations resolved 52 binary and 6 triple star systems and detected partially resolved binaries in 7 additional targets, yielding a companion detection frequency of 29%. We also gathered literature results on the numbers of close spectroscopic binaries and wider astrometric binaries among the sample. These results confirm the high multiplicity fraction. The period distribution is essentially flat in increments of log P, although there remains an observational gap in detections for periods of years and decades.