Dilatation tracheoscopy for laryngeal and tracheal stenosis in patients with Wegener’s granulomatosis

Wegener’s granulomatosis (WG) frequently involves the subglottis and trachea and may compromise the upper airway. The objective of this study is to evaluate retrospectively the effect of treatment of subglottic stenosis (SGS) and tracheal stenosis (TS) by dilatation tracheoscopy (DT) in patients with WG. We performed a cohort study on all patients who underwent DT between February 2001 and September 2005 in our institution. From this cohort we identified a total of nine WG patients. In all patients, clinical, serological and histopathological data had been prospectively collected by a standardized protocol from the time point of diagnosis. In the nine patients that were identified with SGS or TS due to WG (eight women and one man), a total of 22 DT’s were performed. Two patients needed a tracheostoma (one temporarily). The mean follow-up after the first DT was 25.4 ± 14.1 months. Two patients did not experience a recurrence of SGS or TS. Six patients required a second DT without recurrence of local disease. The remaining patient underwent 8 DT's in a 4-year period. DT can offer a simple and repeatable solution to SGS and TS due to WG. Seven of the nine patients required more than one dilatation and some patients experience a functional restriction. One patient has a definitive tracheostoma

Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies: A European Case-Malformed Control Study.

The prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy. The objective of this study was to investigate whether first-trimester use of beta-blockers increases the risk of specific congenital anomalies in offspring. A population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies. The signals from the literature (congenital heart defects, oral clefts, neural tube defects and hypospadias) were not confirmed. Our exploratory analysis revealed that multi-cystic renal dysplasia had significantly increased odds of occurring after maternal exposure to combined alpha- and beta-blockers (adjusted odds ratio 3.8; 95% confidence interval 1.3-11.0). Beta-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm or refute our findings

Optimal resource allocation for multi-queue systems with a shared server pool

We study optimal allocation of servers for a system with multiple service facilities and with a shared pool of servers. Each service facility poses a constraint on the maximum expected sojourn time of a job. A central decision maker can dynamically allocate servers to each facility, where adding more servers results in faster processing speeds but against higher utilization costs. The objective is to dynamically allocate the servers over the different facilities such that the sojourn-time constraints are met at minimal costs. This situation occurs frequently in practice, e.g., in Grid systems for real-time image processing (iris scans, fingerprints). We model this problem as a Markov decision process and derive structural properties of the relative value function. These properties, which are hard to derive for multi-dimensional systems, give a full characterization of the optimal policy. We demonstrate the effectiveness of these policies by extensive numerical experiments

Recent investigations of the 0-5 geomagnetic field recorded by lava flows

Sherpa Romeo green journal (pre or post print only)We present a synthesis of paleomagnetic directional data collected from 873 lava flows at 17 different locations under the collaborative Time Averaged geomagnetic Field Initiative (TAFI). The data range from 05 Ma in age, and provide new high quality data with improved spatial coverage. Data quality at each site is measured using k, the best estimate of the Fisherian precision parameter, and its influence on inclination anomaly and VGP dispersion is evaluated by systematically excluding data with successively higher values of k. When combined with regional compilations from NW USA, SW USA, Japan, New Zealand, Hawaii, Mexico, S. Pacific and the Indian Ocean, a data set of 2283 pairs of declination and inclination data, with k>100, and VGP latitudes greater than 45 is obtained. This is a more than 7fold increase over similar quality data in the existing Global Paleomagnetic Database (GPMDB). The new data set spans 78 S to 53 N, and has sufficient temporal and spatial sampling to allow characterization of latitudinal variations in the timeaveraged field (TAF) and paleosecular variation (PSV) for the Brunhes and Matuyama epochs, and for the 0–5 Myr interval combined. PSV, as measured by dispersion of virtual geomagnetic poles, shows less latitudinal variation than predicted by current statistical PSV models. Variation of inclination anomaly with latitude is assessed using 2parameter zonal TAF models – these have axial quadrupole contributions of 2% – 4% of the axial dipole term, and axial octupole contributions of 3% – 5%. Approximately 2% of the octupole signature is likely the result of bias incurred by averaging unit vectors. The new data set provides significant improvement over previous compilations, and can contribute to a new generation of global paleomagnetic field models.Ye

Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial

Item does not contain fulltextBACKGROUND: Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. METHODS: We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. FINDINGS: Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2.05, 95% CI 1.18-3.56; p=0.0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay. INTERPRETATION: Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice. FUNDING: The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health

Patch: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect.</p> <p>Methods/Design</p> <p>The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included.</p> <p>Discussion</p> <p>To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.</p> <p>Trial registration</p> <p>The Netherlands National Trial Register (NTR1303)</p

Statistical analysis plan for the PlAtelet Transfusion in Cerebral Haemorrhage (PATCH) trial:a multicentre randomised controlled trial

Use of antiplatelet therapy shortly before stroke due to spontaneous primary intracerebral haemorrhage (ICH) is associated with higher case fatality in comparison to ICH without prior antithrombotic drug use. The PlAtelet Transfusion in Cerebral Haemorrhage (PATCH) trial aimed to assess the effect of platelet transfusion in patients presenting with ICH while using antiplatelet therapy. The main hypothesis of PATCH was that platelet transfusion would reduce death or dependence by reducing ICH growth. PATCH was a multicentre prospective, randomised, open, blinded endpoint (PROBE) parallel group trial, conducted at 60 hospitals in The Netherlands, Scotland and France. Forty-one sites enrolled 190 patients with spontaneous supratentorial ICH aged ≥18 years, who had used antiplatelet therapy for ≥7 days preceding ICH, if Glasgow Coma Scale was ≥8. Participants were randomised (1:1, with a secure web-based system using permuted blocks, stratified by study centre and type of antiplatelet therapy pre-ICH) to receive either platelet transfusion within 6 hours of symptom onset and 90 minutes of diagnostic brain imaging, or standard care without platelet transfusion. The primary outcome was modified Rankin Scale (mRS) score assessed blind to treatment allocation at 3 months after ICH. Planned secondary outcomes included ICH growth on brain imaging performed approximately 24 hours after randomisation, survival at 3 months, disability at 3 months scored using the Amsterdam Medical Centre linear disability score, heterogeneity of treatment effect on mRS and ICH growth according to presence of the computed tomography angiography spot sign, causes of poor outcome, and cost-effectiveness. Safety outcomes were transfusion reactions, thromboembolic complications, and serious adverse events occurring during hospitalisation. This statistical analysis plan was written without knowledge of the unblinded data. The trial was registered with the Netherlands Trial Register on 29 April 2008 ( NTR1303

New developments in the treatment of hypertension: are some antihypertensives more equal than others?

In 2002, a major topic of discussion in the field of clinical hypertension was the efficacy of the various types of antihypertensive agents. The results of three large endpoint studies have recently been published and it was hoped that these would provide some answers. What could be concluded from their findings is that angiotensin II receptor (A II) antagonists can now also be allowed as initial treatment for uncomplicated essential hypertension. Thiazide diuretics remain the treatment of choice in patients with uncomplicated essential hypertension because of low costs. Recent trials suggest however, that agents that interfere in the renin-angiotensin system, such as ACE inhibitors and A II antagonists, may be superior in preventing end-organ damage. We therefore propose that subgroups of patients should be defined, in which specific agents should be preferentially used because of proven efficacy