Oral antiplatelet therapy in diabetes mellitus and the role of prasugrel: an overview

Diabetics have a prothrombotic state that includes increased platelet reactivity. This contributes to the less favorable clinical outcomes observed in diabetics experiencing acute coronary syndromes as well as stable coronary artery disease. Many diabetics are relatively resistant to or have insufficient response to several antithrombotic agents. In the setting of percutaneous coronary intervention, hyporesponsiveness to clopidogrel is particularly common among diabetics. Several strategies have been examined to further enhance the benefits of oral antiplatelet therapy in diabetics. These include increasing the dose of clopidogrel, triple antiplatelet therapy with cilostazol, and new agents such as prasugrel. The large TRITON TIMI 38 randomized trial compared clopidogrel to prasugrel in the setting of percutaneous coronary intervention for acute coronary syndromes. The diabetic subgroup (n = 3146) experienced considerable incremental benefit with a 4.8% reduction in cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke at 15-month follow-up with prasugrel treatment. Among diabetics on insulin this combined endpoint was reduced by 7.9% at 15 months. Major bleeding was not increased in the diabetic subgroup. This confirms the general hypothesis that more potent oral antiplatelet therapy can partially overcome the prothrombotic milieu and safely improve important clinical outcomes in diabetics

Repetitive arm functional tasks after stroke (RAFTAS): a pilot randomised controlled trial

Background Repetitive functional task practise (RFTP) is a promising treatment to improve upper limb recovery following stroke. We report the findings of a study to determine the feasibility of a multi-centre randomised controlled trial to evaluate this intervention. Methods A pilot randomised controlled trial was conducted. Patients with new reduced upper limb function were recruited within 14 days of acute stroke from three stroke units in North East England. Participants were randomised to receive a four week upper limb RFTP therapy programme consisting of goal setting, independent activity practise, and twice weekly therapy reviews in addition to usual post stroke rehabilitation, or usual post stroke rehabilitation. The recruitment rate; adherence to the RFTP therapy programme; usual post stroke rehabilitation received; attrition rate; data quality; success of outcome assessor blinding; adverse events; and the views of study participants and therapists about the intervention were recorded. Results Fifty five eligible patients were identified, 4-6% of patients screened at each site. Twenty four patients participated in the pilot study. Two of the three study sites met the recruitment target of 1-2 participants per month. The median number of face to face therapy sessions received was 6 [IQR 3-8]. The median number of daily repetitions of activities recorded was 80 [IQR 39-80]. Data about usual post stroke rehabilitation were available for 18/24 (75%). Outcome data were available for 22/24 (92%) at one month and 20/24 (83%) at three months. Outcome assessors were unblinded to participant group allocation for 11/22 (50%) at one month and 6/20 (30%) at three months. Four adverse events were considered serious as they resulted in hospitalisation. None were related to study treatment. Feedback from patients and local NHS therapists about the RFTP programme was mainly positive. Conclusions A multi-centre randomised controlled trial to evaluate an upper limb RFTP therapy programme provided early after stroke is feasible and acceptable to patients and therapists, but there are issues which needed to be addressed when designing a Phase III study. A Phase III study will need to monitor and report not only recruitment and attrition but also adherence to the intervention, usual post stroke rehabilitation received, and outcome assessor blinding

The stroke oxygen pilot study: a randomized control trial of the effects of routine oxygen supplementation early after acute stroke--effect on key outcomes at six months

Introduction: Post-stroke hypoxia is common, and may adversely affect outcome. We have recently shown that oxygen supplementation may improve early neurological recovery. Here, we report the six-month outcomes of this pilot study. Methods: Patients with a clinical diagnosis of acute stroke were randomized within 24 h of admission to oxygen supplementation at 2 or 3 L/min for 72 h or to control treatment (room air). Outcomes (see below) were assessed by postal questionnaire at 6 months. Analysis was by intention-to-treat, and statistical significance was set at p#0.05. Results: Out of 301 patients randomized two refused/withdrew consent and 289 (148 in the oxygen and 141 in the control group) were included in the analysis: males 44%, 51%; mean (SD) age 73 (12), 71 (12); median (IQR) National Institutes of Health Stroke Scale score 6 (3, 10), 5 (3, 10) for the two groups respectively. At six months 22 (15%) patients in the oxygen group and 20 (14%) in the control group had died; mean survival in both groups was 162 days (p= 0.99). Median (IQR) scores for the primary outcome, the modified Rankin Scale, were 3 (1, 5) and 3 (1, 4) for the oxygen and control groups respectively. The covariate-adjusted odds ratio was 1.04 (95% CI 0.67, 1.60), indicating that the odds of a lower (i.e. better) score were non-significantly higher in the oxygen group (p= 0.86). The mean differences in the ability to perform basic (Barthel Index) and extended activities of daily living (NEADL), and quality of life (EuroQol) were also non-significant. Conclusions: None of the key outcomes differed at 6 months between the groups. Although not statistically significant and generally of small magnitude, the effects were predominantly in favour of the oxygen group; a larger trial, powered to show differences in longer-term functional outcomes, is now on-going. Trial Registration: Controlled-Trials.com ISRCTN12362720; Eudract.ema.europa.eu 2004-001866-4

On the distance and reddening of the starburst galaxy IC10

We present deep and accurate optical photometry of the Local Group starburst galaxy IC10. The photometry is based on two sets of images collected with the Advanced Camera for Surveys and with the Wide Field Planetary Camera 2 on board the Hubble Space Telescope. We provide new estimates of the Red Giant Branch tip (TRGB) magnitude, m_{F814W}^{TRGB}=21.90+-0.03, and of the reddening, E(B-V)=0.78+-0.06, using field stars in the Small Magellanic Cloud (SMC) as a reference. Adopting the SMC and two globulars, Omega Centauri and 47 Tucanae, as references we estimate the distance modulus to IC10: independent calibrations give weighted average distances of mu=24.51+-0.08 (TRGB) and mu=24.56+-0.08 (RR Lyrae). We also provide a new theoretical calibration for the TRGB luminosity, and using these predictions we find a very similar distance to IC10 (mu~24.60+-0.15). These results suggest that IC10 is a likely member of the M31 subgroup.Comment: 4 pages, 4 figures, ApJ Letters accepte

The SOS Pilot Study: a RCT of routine oxygen supplementation early after acute stroke—effect on recovery of neurological function at one week

Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke

Mass-loss rates of Very Massive Stars

We discuss the basic physics of hot-star winds and we provide mass-loss rates for (very) massive stars. Whilst the emphasis is on theoretical concepts and line-force modelling, we also discuss the current state of observations and empirical modelling, and address the issue of wind clumping.Comment: 36 pages, 15 figures, Book Chapter in "Very Massive Stars in the Local Universe", Springer, Ed. Jorick S. Vin

The VLT-FLAMES Tarantula Survey XVIII. Classifications and radial velocities of the B-type stars

We present spectral classifications for 438 B-type stars observed as part of the VLT-FLAMES Tarantula Survey (VFTS) in the 30 Doradus region of the Large Magellanic Cloud. Radial velocities are provided for 307 apparently single stars, and for 99 targets with radial-velocity variations which are consistent with them being spectroscopic binaries. We investigate the spatial distribution of the radial velocities across the 30 Dor region, and use the results to identify candidate runaway stars. Excluding potential runaways and members of two older clusters in the survey region (SL 639 and Hodge 301), we determine a systemic velocity for 30 Dor of 271.6 ± 12.2 kms-1 from 273 presumed single stars. Employing a 3σ criterion we identify nine candidate runaway stars (2.9% of the single stars with radial-velocity estimates). The projected rotational velocities of the candidate runaways appear to be significantly different to those of the full B-type sample, with a strong preference for either large (≥345 kms-1) or small (≤65 kms-1) rotational velocities. Of the candidate runaways, VFTS 358 (classified B0.5: V) has the largest differential radial velocity (−106.9 ± 16.2 kms-1), and a preliminary atmospheric analysis finds a significantly enriched nitrogen abundance of 12 + log (N/H) ≳ 8.5. Combined with a large rotational velocity (ve sin i = 345 ± 22 kms-1), this is suggestive of past binary interaction for this star

A spectroscopic and proper motion search of Sloan Digital Sky Survey : red subdwarfs in binary systems

Red subdwarfs in binary systems are crucial for both model calibration and spectral classification. We search for red subdwarfs in binary systems from a sample of high proper motion objects with Sloan Digital Sky Survey spectroscopy. We present here discoveries from this search, as well as highlight several additional objects of interest. We find 30 red subdwarfs in wide binary systems including: two with spectral type of esdM5.5, 6 companions to white dwarfs and 3 carbon-enhanced red subdwarfs with normal red subdwarf companions. 15 red subdwarfs in our sample are partially resolved close binary systems. With this binary sample, we estimate the low limit of the red subdwarf binary fraction of similar to 10 per cent. We find that the binary fraction goes down with decreasing masses and metallicities of red subdwarfs. A spectroscopic esdK7 subdwarf + white dwarf binary candidate is also reported. 30 new M subdwarfs have spectral type of >= M6 in our sample. We also derive relationships between spectral types and absolute magnitudes in the optical and near-infrared for M and L subdwarfs, and we present an M subdwarf sample with measured U, V, W space velocities.Peer reviewe

Stroke risk associated with balloon based catheter ablation for atrial fibrillation: Rationale and design of the MACPAF Study

<p>Abstract</p> <p>Background</p> <p>Catheter ablation of the pulmonary veins has become accepted as a standard therapeutic approach for symptomatic paroxysmal atrial fibrillation (AF). However, there is some evidence for an ablation associated (silent) stroke risk, lowering the hope to limit the stroke risk by restoration of rhythm over rate control in AF. The purpose of the prospective randomized single-center study "Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation" (MACPAF) is to compare the efficacy and safety of two balloon based pulmonary vein ablation systems in patients with symptomatic paroxysmal AF.</p> <p>Methods/Design</p> <p>Patients are randomized 1:1 for the Arctic Front^®or the HD Mesh Ablator^®catheter for left atrial catheter ablation (LACA). The predefined endpoints will be assessed by brain magnetic resonance imaging (MRI), neuro(psycho)logical tests and a subcutaneously implanted reveal recorder for AF detection. According to statistics 108 patients will be enrolled.</p> <p>Discussion</p> <p>Findings from the MACPAF trial will help to balance the benefits and risks of LACA for symptomatic paroxysmal AF. Using serial brain MRIs might help to identify patients at risk for LACA-associated cerebral thromboembolism. Potential limitations of the study are the single-center design, the existence of a variety of LACA-catheters, the missing placebo-group and the impossibility to assess the primary endpoint in a blinded fashion.</p> <p>Trial registration</p> <p>clinicaltrials.gov NCT01061931</p