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Category Archives: Back-up Power
Portable generators can be used for all kinds of outdoor events from camping to tailgating and for backup power in times of emergency. But like all gas powered equipment, there are potential hazards if you do not use them properly and follow safety guidelines. As with all our products, we recommend that you fully read […]Continue Reading »
In May, at the start of hurricane season, we wrote about National Hurricane Preparedness week and gave you 7 recommendations for each day of the week on how to prepare for a hurricane. This time of year, August through October, generally sees the most activity in the Atlantic, with September often experiencing the highest frequency […]Continue Reading »
Why Install a Standby Generator: Standby generators can provide home owners and business owners with peace of mind and confidence when the power goes out. Without back up power, outages can be costly. Here are the national average costs for power outages incurred by homeowners: Hotel stay per night: $150 Food loss: $200+ Basement flooding: […]Continue Reading »
Maybe you bought your portable generator to use for camping trips, tailgating, or big backyard parties or maybe you just wanted reliable backup power in case of an emergency. Whatever you plan to use your portable generator for, it's good practice to perform regular engine maintenance to ensure your generator is always ready to go […]Continue Reading »
Hurricane season is fast approaching. It takes just one storm to change your life. And while you can't control the weather, you can do your best to prepare for it and minimize its impact. The National Oceanic and Atmospheric Administration (NOAA) says those who live in areas prone to tropical storms – both coastline and […]Continue Reading »
Briggs & Stratton recently announced it is introducing a new premium brand of standby generators called Briggs & Stratton Fortress™. The line will be sold exclusively through our dealer network. The new Fortress product line will come with the industry's only six-year warranty* on parts, labor and travel. Plus, all air-cooled units (10kW – 20kW) […]Continue Reading »
If you've ever been in a blizzard, it's unlikely you'll forget the experience any time soon. With vicious winds, thick coats of ice, and frostbite-inducing temperatures, it can not only make travel unsafe, but even staying indoors can become dangerous if you aren't prepared. So before the storm strikes, knocking out your power and making […]Continue Reading »
We've talked about using an inverter generator for camping, tailgating, or other outdoor recreation more than once on this blog. It's great to be able to use a coffee maker while camping or charge your phone while in the stadium parking lot. You get all the convenience and still get to enjoy the outdoors. But […]Continue Reading »
Winter is one of the worst times for a power outage. When the temperatures drop and ice takes down power lines it doesn't just interrupt your life, it can put it in danger. Last winter was pretty volatile for a big section of the U.S.—just ask those in Boston, Syracuse and Nashville, to name a […]Continue Reading »
One of the things I love around this time of year is the number of people that choose to celebrate by displaying lights on their home for the world to see. Of course, there are those that go to the extreme, and, to no surprise, there is a reality show that pits families against each […]Continue Reading »


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Published on March 8, 2014
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Source: slideshare.net
European Heart Journal doi:10.1093/eurheartj/eht134 60 5 10 EHRA Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary† Hein Heidbuchel1*, Peter Verhamme1, Marco Alings2, Matthias Antz3, Werner Hacke4, Jonas Oldgren5, Peter Sinnaeve1, A. John Camm6, and Paulus Kirchhof7,8 65 70 15 1 Department of Cardiovascular Medicine, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium; 2Department of Cardiology, Amphia Ziekenhuis, Breda, ¨ Netherlands; 3Department of Cardiology, Klinikum Oldenburg, Oldenburg, Germany; 4Department of Neurology, Ruprecht Karls Universitat, Heidelberg, Germany; 5Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 6Clinical Cardiology, St George's University, London, UK; 7University of ¨ Birmingham Centre for Cardiovascular Sciences, Birmingham, UK; and 8Department of Cardiology and Angiology, University of Munster, Germany 20 25 30 New oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients will have to learn how to use these drugs effectively and safely in specific clinical situations. This text is an executive summary of a practical guide that the European Heart Rhythm Association (EHRA) has assembled to help physicians in the use of the different NOACs. The full text is being published in EP Europace. Practical answers have been formulated for 15 concrete clinical scenarios: (i) practical start-up and follow-up scheme for patients on NOACs; (ii) how to measure the anticoagulant effect of NOACs; (iii) drug –drug interactions and pharmacokinetics of NOACs; (iv) switching between anticoagulant regimens; (v) ensuring compliance of NOAC intake; (vi) how to deal with dosing errors; (vii) patients with chronic kidney disease; (viii) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?; (ix) management of bleeding complications; (x) patients undergoing a planned surgical intervention or ablation; (xi) patients undergoing an urgent surgical intervention; (xii) patients with AF and coronary artery disease; (xiii) cardioversion in a NOAC-treated patient; (xiv) patients presenting with acute stroke while on NOACs; (xv) NOACs vs. VKAs in AF patients with a malignancy. Since new information is becoming available at a rapid pace, an EHRA web site with the latest updated information accompanies the guide (www.NOACforAF.eu). It also contains links to the ESC AF Guidelines, a key message pocket booklet, print-ready files for a proposed universal NOAC anticoagulation card, and feedback possibilities. 75 80 85 ----------------------------------------------------------------------------------------------------------------------------------------------------------- 90 Whereas the 2010 ESC Guidelines (and the 2012 Update)1,2 mainly discuss the indications for anticoagulation in general (e.g. based on the CHA2DS2-VASc score) and of NOAC in particular, they guide less on how to deal with NOAC in specific clinical situations. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the practical use of the different NOACs, in a text that supplements the AF Guidelines as a guidance tool for safe, effective use of NOAC when prescribed.3 Please note that not 95 Keywords Atrial fibrillation † Anticoagulation † Stroke † Bleeding † Pharmacology 35 Introduction 40 45 New oral anticoagulants (NOACs) have emerged as an alternative for vitamin K antagonists (VKAs) for thrombo-embolic prevention in patients with non-valvular atrial fibrillation (AF). Although very promising in many regards (predictable effect without need for monitoring, fewer food and drug interactions, shorter plasma halflife, and an improved efficacy/safety ratio), the proper use of NOACs will require new approaches in many daily aspects. Full report in EP Europace 2013. 100 105 * Corresponding author: Tel: +32 16 34 42 48, Fax. +32 16 3442 40, Email: firstname.lastname@example.com 50 55 †Advisors: Azhar Ahmad, M.D. (Boehringer Ingelheim Pharma), Susanne Hess, M.D. (Bayer Healthcare Pharmaceuticals), Felix Munzel, Ph.D. (Daiichi Sankyo Europe), Markus ¨ Schwertfeger, M.D. (Daiichi Sankyo Europe), Martin van Eickels, M.D. (Bayer Healthcare Pharmaceuticals), Jean-Philippe Verbist, M.D. (Bristol Myers Squibb/Pfizer). Document reviewers: Coordinator: Antonio Raviele, Alliance to Fight Atrial Fibrillation (ALFA), Venice-Mestre, Italy. ´ Leandro Zimerman, M.D. (Hospital de Clınicas de Porto Alegre, Brasil), Chern-En Chiang, Ph.D. (Taipei Veterans General Hospital, Taiwan), Hans Diener, Ph.D. (University of Essen, Germany), Giuseppe Di Pasquale, Ph.D. (Ospedale Maggiore, Bologna, Italy), Stephan Hohnloser, Ph.D. (Klinikum der J.-W.-Goethe-Universitat, Frankfurt, Germany), Jean-Yves Le 110 ` Heuzey, Ph.D. (Hopital Europeen Georges Pompidou, Paris, France), Jose Lopez-Sendon, Ph.D. (Hospital Universitario La Paz. Madrid, Spain, Jonas Bjerring Olesen, Ph.D. (Copenhagen University Hospital Gentofte, Denmark), Frans H Rutten, Ph.D. (Julius Center UMC Utrecht, The Netherlands), Marco Valgimigli, Ph.D. (University Hospital of Ferrara, Italy), Freek W.A. Verheugt, Ph.D. (Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands), Michael Brainin, Ph.D. (Klinische Medizin Und Praeventionsmedizin, Danube University Krems, Austria), Kennedy Lees, Ph.D. (University of Glasgow, UK). Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: firstname.lastname@example.com
Page 2 of 13 115 120 125 130 135 140 145 150 155 160 165 170 all drugs discussed in this document may already be EMA approved for the non-valvular AF indication, and/or not available in the different constituent EU countries at the time of publication of this document. Since new information is becoming available at a rapid pace, an EHRA web site with the latest updated information accompanies this text (www.NOACforAF.eu, which links to www.escardio.org/ COMMUNITIES/EHRA, under 'Publications'). Any item that has been changed from the original printed version will be highlighted in the future. It also contains links to the ESC AF Guidelines, a key message pocket booklet, and print-ready files for a proposed universal NOAC anticoagulation card. Moreover, readers can address their suggestions for change or improvement on the web site. 1. Practical start-up and follow-up scheme for patients on new oral anticoagulants Before prescribing a NOAC to a patient with AF, a risk –benefit analysis should be made concerning anticoagulation in general and the choice of the specific anticoagulant on the basis of approved indications and on the preference of the patient after discussion of the different options.1 Concerning the choice of a given NOAC, it is also important to consider the clinical profile of the patient and co-medications, some of which may be contraindicated or pose unfavourable drug– drug interactions (see 'Drug –drug interactions and pharmacokinetics of new oral anticoagulants'). As for users of VKAs, it is equally important that those treated with NOACs carry details about their anticoagulant therapy to alert any (para-)medical participant in their care. We propose a uniform card to be completed and carried by each patient (Figure 1). It can be downloaded in digital form at www. NOACforAF.eu. The goal of the card is not only to list demographic and medication information, and to educate the patient, but mainly to structure a coordinated follow-up of the patient by different caregivers. The structure of initiation and follow-up is shown in Figure 2. A checklist for actions during the follow-up contacts is presented in the full document. Therapy with this new class of drugs requires vigilance, also because this is a fragile patient population and NOACs are drugs with potentially severe complications. Patients should return on a regular basis for on-going review of their treatment, preferably every 3 months. This review may be undertaken by general practitioners provided that they have good guidance on what to do and when. Nurse-coordinated AF clinics may be very helpful in this regard.4 Therefore, the card also lists the appropriate timing of laboratory testing, taking the patient profile into consideration. e.g. Renal function should be assessed more frequently in patients receiving dabigatran, or in potentially compromised patients such as the elderly, otherwise frail patients, or in those where an intercurring condition may affect renal function, since all NOACs require dose reductions depending on renal function (see 'Drug –drug interactions and pharmacokinetics of new oral anticoagulants' and 'Patients with chronic kidney disease'; see Table 1 of the ESC AF Guidelines Update2). Minor bleeding is a particular problem in patients treated with any anticoagulant. Most minor bleeding is temporary and is best H. Heidbuchel et al. classified as 'nuisance' in type. It is best dealt with by standard methods to control bleeding, but should not lead readily to discontinuation or dose adjustment of therapy. 175 2. How to measure the anticoagulant effect of new oral anticoagulants? New oral anticoagulants do not require routine monitoring of coagulation: neither the dose nor the dosing intervals should be altered in response to changes in laboratory coagulation parameters. However, the quantitative assessment of the drug exposure and the anticoagulant effect may be needed in emergency situations. When interpreting a coagulation assay in a patient treated with a NOAC, in contrast to VKA coagulation monitoring, it is paramount to know exactly when the NOAC was administered relative to the time of blood sampling. The time delay between intake and blood sampling should, therefore, be carefully recorded when biological monitoring is performed. A table with a complete overview of the effect on common coagulation assays by direct thrombin inhibitors (DTI) and FXa inhibitors is present in the full manuscript. The activated partial thromboplastin time (aPTT) may provide a qualitative assessment of the presence of dabigatran. If the aPTT level at trough (i.e. 12–24 h after ingestion) still exceeds two times the upper limit of normal, this may be associated with a higher risk of bleeding, and may warrant caution especially in patients with bleeding risk factors.5 The prothrombin time (PT) may provide a qualitative assessment of the presence of factor Xa inhibitors. Like the aPTT for dabigatran, these respective tests are not sensitive for the quantitative assessment of the NOAC effect! Quantitative tests for DTI and FXa inhibitors do exist (diluted thrombin-time and chromogenic assays, respectively), but they may not (yet) be routinely available in most hospitals. Moreover, there are no data on a cut-off of these specific tests below which elective or urgent surgery is 'safe', and therefore their use in this respect cannot be recommended at this time. Point of care tests to assess the international normalized ratio (INR) should not be used in patients on NOACs.6 3. Drug –drug interactions and pharmacokinetics of new oral anticoagulants Despite high expectations of less food interactions with the NOAC drugs, physicians will have to consider pharmacokinetic effects of accompanying drugs and of comorbidities when prescribing NOACs, especially when a combination of interfering factors is present. The absorption and metabolism of different NOACs is discussed in tables and figures in the full document. There is good rationale for reducing the dose of NOACs in patients with a high bleeding risk and/or when a higher plasma level of the drug can be anticipated.1,7,8 We have chosen an approach with three levels of alert for drug –drug interactions or other clinical factors that may affect NOAC plasma levels or effects (Table 1): 180 185 190 195 200 205 210 215 220 225
EHRA practical Guide for use of the new oral anticoagulants: executive summary Page 3 of 13 230 290 235 295 240 300 245 305 250 310 255 315 260 320 265 325 270 330 275 335 280 Figure 1 European Heart Rhythm Association proposal for a universal new oral anticoagulation card. A patient information card is crucial, both for the patient (instructions on correct intake; contact information in case of questions) as for health care workers (other care-takers are involved; renal function; follow-up schedule; concomitant medication, etc.). We present a generic and universal card that could serve all patients under new oral anticoagulant therapy. 285 340
Page 4 of 13 H. Heidbuchel et al. 400 345 405 350 410 355 415 360 420 365 425 370 430 375 Figure 2 Structured follow-up of patients on new oral anticoagulants. Structured follow-up of patients on new oral anticoagulants is mandatory to ensure safe and effective drug intake. The anticoagulation card, as proposed in Figure 1, is intended to document each planned visit, each relevant observation or examination, and any medication change, so that every person following up the patient is well-informed. Moreover, written communication between the different (para)medical players is required to inform them about the follow-up plan and execution. 435 380 440 385 390 395 (i) 'red' interactions preclude the use of a given NOAC in combination (i.e. 'contraindication' or 'discouragement' for use), (ii) 'orange' interactions refer to the recommendation to adapt the NOAC dose, since they result in changes of the plasma levels or effect of NOACs that could potentially have a clinical impact, and (iii) 'yellow' interactions with the recommendation to keep the original dose, unless two or more concomitant 'yellow' interactions are present. Two or more 'yellow' interactions need expert evaluation, and may lead to the decision of not prescribing the drug ('red') or of adapting its dose ('orange'). Unfortunately, for many potential interactions with drugs that are often used in AF patients no detailed information is available yet. These have been shaded in the Table. It is prudent to abstain from using NOACs in such circumstances until more information is available. Since food intake has an impact on the absorption and bioavailability of rivaroxaban (area under the curve plasma concentrations increase by 39%), rivaroxaban should be taken together with food. There is no relevant food interaction for the other NOAC and they may be taken with or without food. Also, concomitant use of proton-pump inhibitors (PPI) and H2-blockers does not constitute a contraindication for any NOAC. Apart from the pharmacokinetic interactions, it is clear that association of NOACs with other anticoagulants, platelet inhibitors (aspirin, clopidogrel, ticlodipine, prasugrel, ticagrelor, and others), and non-steroidal anti-inflammatory drugs (NSAID) increases the bleeding risk. There is data indicating that the bleeding risk in association with antiplatelet agents increases by at least 60% (similar as in association with VKAs).9 – 11 Therefore, such associations should be carefully balanced against the potential benefit in each clinical situation. Association of NOACs with (dual) antiplatelet drugs is extensively discussed in 'Patient with atrial fibrillation and coronary artery disease' below. 445 450 455
EHRA practical Guide for use of the new oral anticoagulants: executive summary Page 5 of 13 Table 1 Effect on new oral anticoagulant plasma levels ('area under the curve, AUC') from drug –drug interactions and recommendations towards new oral anticoagulant dosing 515 460 520 465 525 470 530 475 535 480 540 485 545 490 550 495 555 500 560 505 565 510 570
Page 6 of 13 H. Heidbuchel et al. 630 575 635 580 640 585 645 590 650 595 655 600 660 605 665 610 670 615 675 620 625 Red, contraindicated/not recommended; orange, reduce dose (from 150 to 110 mg b.i.d. for dabigatran; from 20 to 15 mg q.d. for rivaroxaban; from 5 to 2.5 mg b.i.d. for apixaban); yellow, consider dose reduction if another 'yellow' factor is present; hatching, no data available; recommendation based on pharmacokinetic considerations. BCRP, breast cancer resistance protein; NSAID, non-steroidal anti-inflammatory drugs; H2B, H2-blockers; PPI, proton-pump inhibitors; P-gp, P-glycoprotein; NSAID, non-steroidal anti-inflammatory agent; GI, gastro-intestinal. a No EMA approval yet. Needs update after finalization of SmPC. b Pre-specified dose reduction has been tested in Phase 3 clinical trial (to be published). 680
EHRA practical Guide for use of the new oral anticoagulants: executive summary 685 690 695 700 705 710 4. Switching between anticoagulant regimens It is important to safeguard the continuation of anticoagulant therapy while minimizing the risk for bleeding when switching between different anticoagulant therapies. This requires insights into the pharmacokinetics and pharmacodynamics of different anticoagulation regimens, interpreted in the context of the individual patient. Practical switching scenarios have been described in the full document, for VKA or a parenteral anticoagulant to NOAC and vice versa. Especially for the circumstances where NOAC treatment should be switched to VKA, caution is required: due to the slow onset of action of VKAs, it may take 5–10 days before an INR in therapeutic range is obtained, with large individual variations. Therefore, the NOAC and the VKA should be administered concomitantly until the INR is in a range that is considered appropriate. Since NOACs may have an additional impact on the INR (especially the FXa inhibitors), influencing the measurement while on combined treatment during the overlap phase, it is important (i) that the INR be measured just before the next intake of the NOAC during concomitant administration, and (ii) be re-tested 24 h after the last dose of the NOAC (i.e. sole VKA therapy) to assure adequate anticoagulation. It is also recommended to closely monitor INR within the first month until stable values have been attained (i.e. three consecutive measurements should have yielded values between 2.0 and 3.0). 5. Ensuring compliance with new oral anticoagulant intake 715 720 725 730 735 The anticoagulant effect of NOACs fades rapidly 12– 24 h after the last intake. Therefore, strict therapy compliance by the patient is crucial for adequate protection. Physicians should develop ways to optimize compliance, which is known to be ≤80% for most drugs in daily practice. There is no scientific data yet on the actual compliance of NOACs in non-trial conditions, nor on how it can best be optimized. Nevertheless, all means to optimize compliance should be considered. These include: considerations on choosing a NOAC with once daily or twice daily intake; repeated patient education, as well of their family members; a clearly pre-specified follow-up schedule between general practitioner, cardiologist, or electrophysiologist (see 'Practical start-up and follow-up scheme for patients on new oral anticoagulants'); possibly technological aids like medication boxes or smartphone applications if their effectiveness could be proved; networked pharmacy database (as available in some countries). Finally, in NOAC patients in whom low compliance is suspected despite proper education and additional tools, conversion to VKAs could be considered. Moreover, some patients may themselves prefer INR monitoring to no monitoring. 6. How to deal with dosing errors? 740 Questions relating to dosing errors are very common in daily practice. Often, the patient calls the hospital, office or even a national poison centre. It is advisable to provide staff workers of these call Page 7 of 13 centres with clear instructions on how to advise patients in these circumstances. To prevent situations as described below, patients on NOACs should be urged to make use of well-labelled weekly pill containers, with separate spaces for each dose. In case of a missed dose, no double dose should be taken to make up for missed individual doses. The forgotten dose may, however, be taken until halfway the dosing interval (e.g. up to 12 h for a once daily dosing). If that is not possible anymore, the dose should be skipped and the next scheduled dose should be taken. In case a double dose has mistakenly been taken, one could opt to forgo the next planned dose. Sometimes, the patient is not sure about whether a dose has been taken or not. For NOACs with a BID dosing regimen, one could advise to not take another pill, but to just continue the planned dose regimen, i.e. starting with the next dose at the 12 h interval. For NOACs with a QD dosing regimen, one could advise to take another pill and then continue the planned dose regimen. In case of overdose, depending on the amount of suspected overdose, hospitalization for monitoring or urgent measures should be advised (see also 'What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?'). 7. Patients with chronic kidney disease Chronic kidney disease (CKD) constitutes a risk factor for both thrombo-embolic events and bleeding in AF patients.12,13 Recent findings suggest that a creatinine clearance of ,60 mL/min may even be an independent predictor of stroke and systemic embolism.14,15 Vitamin K antagonist therapy is associated with a significant reduction in the risk of stroke or thrombo-embolism in CKD patients but the risk of bleeding is also significantly increased. Thus, the net clinical effect of VKA treatment requires careful assessment in such patients.12,16 Many patients with mild-to-moderate CKD have been enrolled in the NOAC trials, with pre-specified dose reductions. In the context of NOAC treatment, CrCl is best assessed by the Cockroft method, as this was used in most NOAC trials. There are no outcome data for NOACs in patients with advanced chronic kidney disease (CrCL , 30 mL/min), and the current ESC Guidelines recommend against their use in such patients.2 Furthermore, there is very little data on patients on dialysis or close to dialysis (glomerular filtration rate ,15 mL/min, CKD stage V), neither from trials nor from clinical experience. In the absence of such experience, not any NOAC is approved for use in dialysis patients. New oral anticoagulants appear a reasonable choice for anticoagulant therapy in AF patients with mild or moderate CKD. A similar benefit–risk ratio of NOACs vs. VKAs was seen, and there are indications that the increase in the rate of bleeding by renal dysfunction was significantly less than with VKA.13,17 – 19 There are no comparative studies that the risks from CKD differ among the NOACs. Therefore, careful balancing of the clinical benefits and risks of each drug (and its dose adjustment) may justify its choice. For all drugs, however, a careful follow-up of renal function is required in CKD patients, since all are cleared more or less by the kidney. Renal function monitoring is especially relevant for dabigatran, which is predominantly cleared renally (see also 'Practical start-up and follow-up scheme for patients 745 750 755 760 765 770 775 780 785 790 795
Page 8 of 13 Table 2 H. Heidbuchel et al. Possible measures to take in case of bleeding 800 Direct thrombin inhibitors (dabigatran) FXa inhibitors (apixaban, edoxaban, rivaroxaban) Inquire last intake + dosing regimen Estimate normalization of haemostasis Normal renal function: 12–24 h CrCl 50–80 mL/min: 24– 36 h CrCl 30–50 mL/min: 36– 48 h CrCl ,30 mL/min: ≥48 h Maintain diuresis Local haemostatic measures Fluid replacement(colloids if needed) RBC substitution if necessary Platelet substitution (in case of thrombocytopenia ≤60 × 109/L or thrombopathy) Fresh frozen plasma as plasma expander (not as reversal agent) Tranexamic acid can be considered as adjuvans Desmopressin can be considered in special cases (coagulopathy or thrombopathy) Consider dialysis (preliminary evidence: 265% after 4h )53 Charcoal haemoperfusion not recommended (no data) Inquire last intake + dosing regimen Normalization of haemostasis: 12– 24 h All of the above Prothrombin complex concentrate (PCC) 25 U/kg (may be repeated once or twice) (but no clinical evidence) Activated PCC 50 IE/kg; max 200 IE/kg/day): no strong data about additional benefit over PCC. Can be considered before PCC if available Activated factor VII (rFVIIa; 90 mg/kg) no data about additional benefit + expensive (only animal evidence) All of the above Prothrombin complex concentrate (PCC) 25 U/kg (may be repeated once or twice) (but no clinical evidence) Activated PCC 50 IE/kg; max 200 IE/kg/day): no strong data about additional benefit over PCC. Can be considered before PCC if available. Activated factor VII (rFVIIa; 90 mg/kg) no data about additional benefit + expensive (only animal evidence) ............................................................................................................................................................................... Non-life-threatening bleeding 805 810 815 Local haemostatic measures Fluid replacement (colloids if needed) RBC substitution if necessary Platelet substitution (in case of thrombocytopenia ≤60 × 109/ L or thrombopathy) Fresh frozen plasma as plasma expander (not as reversal agent) Tranexamic acid can be considered as adjuvans Desmopressin can be considered in special cases (coagulopathy or thrombopathy) 860 865 870 ............................................................................................................................................................................... Life-threatening bleeding 820 875 880 825 RBC, red blood cells; CrCl, creatinine clearance; PCC, Prothrombin complex concentrate. 885 830 on new oral anticoagulants'). Acute illness often transiently affects renal function (infections, acute heart failure, etc.), and therefore should trigger re-evaluation. New oral anticoagulant therapy should be avoided and VKAs may be a more suitable alternative for now in AF patients on haemodialysis. management can be advocated in most cases. If a more aggressive normalization of plasma levels is deemed necessary, or rapid normalization is not expected (e.g. major renal insufficiency) the steps outlined in 'Management of bleeding complications' can be taken. 8. What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding? 9. Management of bleeding complications 890 835 840 845 850 855 Doses of NOACs beyond those recommended expose the patient to an increased risk of bleeding. In terms of management, it is important to distinguish between an overdose with and without bleeding complications. In case of bleeding complications, see 'Management of bleeding complications'. In the case of recent acute ingestion of an overdose, the use of activated charcoal to reduce absorption may be considered for any NOAC (with a standard dosing scheme for adults of 30 –50 g). In the case of an overdose suspicion, coagulation tests can help to determine its degree and possible bleeding risk (see 'How to measure the anticoagulant effect of new oral anticoagulants?'). There are currently no specific antidotes for the NOACs, although development for those is on-going. Given the relatively short plasma half-life of the NOAC drugs, in the absence of bleeding a 'wait-and-see' Given the absence of specific NOAC antidotes, strategies for the reversal of the anticoagulant effects are limited. Reversal of VKAs through the administration of vitamin K has a slow onset (i.e. at least 24 h), but administration of fresh frozen plasma or coagulation factors more rapidly restores coagulation. In the case of NOACs, however, the plasma abundance of the drug may block newly administered coagulation factors as well. On the other hand, studies have shown that the bleeding profile of NOACs, in particular that of intracranial and other life-threatening bleeding, is more favourable than that of warfarin. Nevertheless, as more patients will start using one of the NOACs, the number of bleeding related events is expected to increase. Currently, recommendations on bleeding management are not so much based on clinical experience, but rather reflect experts' opinions or laboratory endpoints. An overview of the possible measures is shown in Table 2, distinguishing non-life-threatening bleeding from life-threatening bleeding, and with slightly different options for dabigatran and 895 900 905 910
EHRA practical Guide for use of the new oral anticoagulants: executive summary Table 3 Page 9 of 13 Last intake of drug before elective surgical intervention 970 915 975 920 980 925 Low risk, surgery with low risk of bleeding; high risk, surgery with high risk of bleeding. CrCl, creatinine clearance. a No EMA approval yet. Needs update after finalization of SmPC. b Many of these patients may be on the lower dose of dabigatran (i.e. 110 mg BID) or apixaban (i.e. 2.5 mg BID), or have to be on the lower dose of rivaroxaban (15 mg QD). 985 930 940 945 cataract or glaucoma) can be performed at trough concentration of the NOAC (i.e. 12 or 24 h after the last intake, depending on twice or once daily dosing), it may be more practical to have the intervention scheduled 18 –24 h after the last intake, and then restart 6 h later, i.e. with skipping one dose for BID NOAC. For procedures with a minor bleeding risk, it is recommended to discontinue NOACs 24 h before the elective procedure in patients with a normal kidney function, and for procedures that carry a risk for major bleeding to take the last NOAC 48 h before. We have provided a table with classification of surgical interventions according to bleeding risk in the full document. For dabigatran, a more graded pre-intervention termination depending on kidney function has been proposed, both for low- and high-risk interventions, as indicated in Table 3. Although the aPTT and PT may provide a semiquantitative assessment of dabigatran and FXa inhibitors, respectively (see 'How to measure the anticoagulant effect of new oral anticoagulants?'), a strategy that includes normalization of the aPTT or PT prior to elective/urgent interventions has not been validated. 10. Patients undergoing a planned surgical intervention or ablation 935 FXa inhibitors. Given their relatively short elimination half-lives, time is the most important antidote of the NOACs. This underscores the importance to inquire about the used dosing regimen, the exact time of last intake, factors influencing plasma concentrations (like P-gp therapy, chronic kidney disease, and others, see also Table 1), and other factors influencing haemostasis (like concomitant use of anti-platelet drugs). Based on scarce clinical data,20 – 22 the administration of PCC or aPCC can be considered in a patient with life-threatening bleeding if immediate haemostatic support is required (Table 2). Awaiting more data on the clinical effectiveness of these strategies, the choice may depend on their availability and the experience of the treatment centre. The place of recombinant-activated factor VIIa needs further evaluation.23 We recommend consultation among cardiologists, haemostasis experts and emergency physicians to develop a hospital-wide policy concerning bleeding management. Such policy should be communicated well, and be easily accessible (e.g. on an Intranet site or in pocket-sized leaflets). When to restart the new oral anticoagulants? 990 995 1000 1005 950 955 960 965 When to stop the new oral anticoagulants? About one-quarter of patients that are in need for anticoagulant therapy require temporary cessation within 2 years.24 Both patient characteristics (kidney function, age, history of bleeding complications, concomitant medication) and surgical factors should be taken into account on when to discontinue and restart the drug. Table 3 compiles this information for the different NOAC. Also other societies have formulated advice on temporary cessation of NOAC therapy.25 Again, we recommend the development of an institutional guideline and a hospital-wide policy concerning post-operative anticoagulation management in different surgical settings that is widely communicated and readily available. Although common interventions with no clinically important bleeding risk (like some dental procedures or interventions for For procedures with immediate and complete haemostasis, the NOAC can be resumed 6–8 h after the intervention. For many surgical interventions, however, resuming full dose anticoagulation within the first 48 –72 h after the procedure may carry a bleeding risk that could outweigh the risk of cardio-embolism. One also has to take into account the absence of a specific antidote in case bleeding should occur and/or re-intervention is needed. For procedures associated with immobilization, it is considered appropriate to initiate a reduced venous thromboprophylactic or intermediate dose of low molecular weight heparins (LMWH) 6 –8 h after surgery if haemostasis has been achieved, whereas therapeutic anticoagulation by restarting NOACs is deferred 48– 72 h after the invasive procedure. There are no data on the safety and efficacy of the post-operative use of a reduced dose of the NOACs (such as used for the prevention of VTE after hip/knee replacement) in patients with AF undergoing a surgical procedure. 1010 1015 1020 1025
Page 10 of 13 Special considerations concerning atrial fibrillation ablation procedures 1030 1035 For AF patients undergoing pulmonary vein isolation, there is some emerging information available on the use of dabigatran. There is no published data on the peri-interventional use of FXa inhibitors undergoing catheter ablation. With the limited available data,26 – 29 if a strategy of bridging and restarting of anticoagulation is chosen and appropriately executed, NOACs seem to allow such, whereas a too aggressively shortened peri-procedural cessation of NOACs and/or no bridging may be less safe when compared with continued VKA administration and ablation under an INR between 2.0 and 3.0, both concerning bleeding and cardioembolic complications. 1040 11. Patients undergoing an urgent surgical intervention 1045 1050 If an emergency intervention is required, the NOAC should be discontinued. Surgery or intervention should be deferred, if possible, until at least 12 h and ideally 24 h after the last dose. Evaluation of common coagulation tests (aPTT for DTI; sensitive PT for FXa inhibitors) or of specific coagulation test (dTT for DTI; chromogenic assays for FXa inhibitors) can be considered if there is concern about the pharmacokinetic waning of the anticoagulant effect (e.g. renal insufficiency and/or concomitant conditions). Nevertheless, such strategy has never been evaluated, and therefore cannot be recommended and should not be used routinely. 1055 12. Patient with atrial fibrillation and coronary artery disease 1060 1065 1070 1075 1080 The combination of AF and coronary heart disease not only is a common clinical setting, it is also a complex situation on how to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates.30 Unfortunately, there is not sufficient data available to optimally guide clinical practice in such settings. Moreover, new antiplatelet agents have entered the market for acute coronary syndromes (ACS), adding to uncertainty on how to use those in combination with VKAs or NOACs when both ACS and AF converge in a given patient. For the sake of clarity, we have opted to define three clinical scenarios with many different subscenarios, and proposed practical instructions for each: (i) ACS management in an AF patient on NOAC; (ii) management of the patient with a recent ACS (,1 year) who develops new-onset AF; and (iii) development of AF in a patient with a history of coronary heart disease, but without ACS within the last year, without an elective bare metal stent during the last month or a drug-eluting stent over the last 6 months ('stable coronary heart disease'). Given the complexity of these recommendations, we refer to the full document rather than to give an unnuanced summary here. The full document also contains three tables summarizing the recommendations for each of the scenarios. The type and level of anticoagulation as well as single vs. dual antiplatelet therapy in combination with NOAC, and its duration, need to be highly personalized based on atherothrombotic risk, cardioembolic risk, and bleeding risk.31 H. Heidbuchel et al. It is highly recommended to formally assess risk using validated tools such as the GRACE,32 CHA2DS2-VASc, and HAS-BLED scores.1,2 The document also lists key scientific data that form the basis of the guidance. Finally, we acknowledge that new data, which are highly needed, may change the management options. 13. Cardioversion in a new oral anticoagulant-treated patient Based on the ESC guidelines,1 in patients with AF of .48 h duration (or AF of unknown duration) undergoing cardioversion, oral anticoagulation should have been given for at least 3 weeks prior to cardioversion, or transoesophageal echocardiography should be performed to rule out left atrial thrombi. After cardioversion, continuous oral anticoagulation is mandatory for another 4 weeks. No prospective data are available concerning the safety of cardioversion under NOAC treatment. Observational data from the RE-LY, ROCKET-AF, and ARISTOTLE trials did not show any difference in the number of strokes or systemic embolisms, and that the stroke rate was comparable with that in prior trials with other forms of anticoagulation, with our without TEE guidance.33 – 35 Since there is no coagulation assay available for NOACs that provides information on effective anticoagulation over the past 3 weeks and because patient compliance may be variable, it is mandatory to explicitly ask the patient about adherence over the last weeks and to document the answer in the file. If compliance with NOAC intake can be reliably confirmed, cardioversion seems acceptably safe. However, a prior TEE should be considered if there is doubt about compliance. Good prospective registries or even randomized trials are needed on this topic to facilitate patient management in the future. 1085 1090 1095 1100 1105 1110 1115 14. Patients presenting with acute intracranial bleeding or ischaemic stroke while on new oral anticoagulants 1120 The acute phase Guidelines for the treatment of intracerebral haemorrhage under oral anticoagulants are limited to strategies for the reversal of VKAs.36 Data concerning NOACs are missing yet. By analogy to patients being treated with warfarin, the coagulation status of patients under NOAC who have acute or (apparently) on-going life-threatening bleeding such as intracranial haemorrhage should be corrected as rapidly as possible. Measures in this regard were discussed in 'Management of bleeding complications'. The efficacy and safety of such strategies for ICH needs to be further evaluated in clinical studies.37 For ischaemic stroke, according to current guidelines and official labelling, thrombolytic therapy with recombinant tissue plasminogen activator is not recommended in patients under therapy with anticoagulants. As plasma half-life of NOACs range between 8 and 17 h, thrombolytic therapy cannot be given within 48 h after the last administration of NOAC (corresponding to four plasma half-lives). This is an arbitrary recommendation, which has yet to be tested. In the case of uncertainty concerning last NOAC administration, a 1125 1130 1135 1140
EHRA practical Guide for use of the new oral anticoagulants: executive summary 1145 1150 prolonged aPTT (for dabigatran) or PT (for FXa inhibitors) indicates that the patient is anticoagulated and thrombolysis should not be administered. We believe that only in exceptional single cases in which reliable coagulation assessment (with specific tests, see 'How to measure the anticoagulant effect of new oral anticoagulants?') is within the normal reference range, the use of fibrinolytic agents can be considered. If NOACs have been administered within the last 48 h and/or appropriate coagulation tests are not available or abnormal, mechanical recanalization of occluded vessels maybe considered as an alternative treatment option. Again, no prospective data exist in this regard. Management of the post-acute phase 1155 1160 1165 1170 1175 1180 1185 1190 1195 According to the labelling of VKAs and also of the NOACs, a history of a spontaneous intracerebral bleed constitutes a contraindication against anticoagulation, unless the cause of the intracerebral bleed has been reversed. By analogy to the use of VKAs, the administration of NOACs may be restarted 10–14 days after intracerebral haemorrhage if cardioembolic risk is high and the risk of new intracerebral haemorrhage is estimated to be low. However, the same factors that are predictive for embolic stroke (age, hypertension, previous stroke, and others) are also predictive for haemorrhages. Non-pharmacological prevention strategies such as ablation or occlusion of the atrial appendage should be considered as potential substitutes.1,2 Continuation of NOACs after ischaemic stroke depends on the infarct size. Clinical study data regarding re-institution of anticoagulation are missing. Some advocate as a rule of thumb the 1-3-6-12 day rule, with re-institution of anticoagulation in patients with a transient ischaemic attack (TIA) after 1 day, with small, non-disabling infarct after 3 days, with a moderate stroke after 6 days, while large infarcts involving large parts of the arterial territory will be treated not before 2 (or even 3) weeks. If patient compliance and therapeutic effect of coagulation have been assured (i.e. the stroke must have occurred under adequate anticoagulation), alternative causes for ischaemic stroke should be investigated. After a TIA of cardioembolic origin, anticoagulation treatment with NOACs can be started as soon as possible. Bridging with LMWH is not required. Aspirin is no alternative option: in AF patients considered not suitable for VKA thrombo-embolic preventive treatment, the FXa inhibitor apixaban was shown to be superior to aspirin in stroke prevention.7 15. New oral anticoagulants vs. vitamin K antagonists in atrial fibrillation patients with a malignancy Patients with malignancies are at an increased risk for thromboembolic events. Many forms of cancer interact directly or indirectly with the coagulation system. Moreover, cancer therapy may induce bleeding through local wounds (surgery), tissue damage (irradiation), or systemic antiproliferative effects which will reduce platelet count and function (chemotherapy, some forms of irradiation).38 There is very little controlled data for antithrombotic Page 11 of 13 therapy in AF patients with malignancy. Active malignancy usually was an exclusion criterion in NOAC trials. Antithrombotic therapy in patients with AF and suffering a malignancy needs discussion between cardiologist and oncologist, taking into consideration the impact of the cancer on morbidity and mortality, the specific oncologic therapy used, and the anticipated effects of tumour and therapy on both thrombo-embolic risk and bleeding risk. When anticoagulant therapy needs to be initiated in a patient with malignancy, therapy with VKAs or heparins should be considered over NOACs, because of the clinical experience with these substances, the possibility of close monitoring (for VKAs and unfractionated heparin, UFH), and reversal options (for VKAs and UFH). In AF patients stably treated with a NOAC, who develop malignancies for which they need to receive moderately myelosuppressive therapies, continuation of NOACs may be defendable. When a potent myelosuppressive chemotherapy or radiation therapy is planned, temporary dose reduction or cessation of NOAC therapy should be considered, and/ or specific monitoring instituted, including repetitive full-blood counts (including platelets), regular monitoring of liver and renal function, and careful clinical examination for bleeding signs. Gastric protection with PPI or H2-blockers is not contraindicated and should even be considered in all patients treated with anticoagulants. 1200 1205 1210 1215 1220 Funding This article and its related educational material (slide set, web site, booklet, etc.) were produced by and under the sole responsibility of 1225 EHRA, the European Heart Rhythm Association, and funded by unrestricted and unconditional educational grants from BoehringerIngelheim, Bayer, Daiichi-Sankyo and the Pfizer/BMS Alliance. The EHRA writing committee collaborated with medical experts from the different companies to assure data accuracy and completeness. 1230 Conflict of interest: H.H. received research funding through the University of Leuven from Siemens Medical Solutions. J.C. received grants for clinical research from: Bristol-Myers Squibb, Daiichi Sankyo, Sanofi-Aventis, and Servier. W.H. received grants for clinical research from Boehringer Ingelheim Pharmaceuticals. P.V. received research funding through the University of Leuven from BoehringerIngelheim, Bayer Health-Care, Daiichi-Sankyo and ThromboGenics. H.H. is holder of the AstraZeneca Chair in Cardiac Electrophysiology, University of Leuven. H.H. is Coordinating Clinical Investigator for the Biotronik-sponsored EuroEco study on health-economics of remote device monitoring. H.H. is a member of the scientific advisory board of Biosense Webster, Inc., St Jude Medical, Inc., Siemens Medical Solutions, Boehringer-Ingelheim, Bayer and Sanofi-Aventis, and receives unconditional research grants through the University of Leuven from St Jude Medical, Medtronic, Biotronik and Boston Scientific, Inc. M.A. has received travel support from Bristol-Myers Squibb and Boston Scientific; advisory board fees from Bayer, Boehringer Ingelheim, Bristol-Meyer-Squib/Pfizer, Merck Sharp and Dohme, and Sanofi-Aventis; lecture fees from Bayer, Boehringer Ingelheim, Merck Sharp and Dohme, and AstraZeneca; and fees for development of educational presentations from Boehringer Ingelheim. M.A. received speaker honoraria from Bayer HealthCare, Biosense Webster, Boehringer-Ingelheim and Sanofi-Aventis as well as consulting honoraria from Bayer HealthCare, Biosense Webster, Bristol-Myers Squibb, and Pioneer Medical Devices. J.C. Served as an advisor, speaker, and/or consultant for Actelion Pharmaceuticals, ARYx 1235 1240 1245 1250
Page 12 of 13 1255 1260 1265 1270 1275 1280 1285 1290 1295 1300 1305 1310 Therapeutics, Bristol-Myers Squibb, Cardiome Pharma, CV Therapeutics, Daiichi Sankyo, Menarini Group, Merck, Novartis Pharmaceuticals, Pfizer, Sanofi-Aventis, Servier, and Xention. He served as a member of the data and safety monitoring board for Bristol-Myers Squibb, Novartis Pharmaceuticals and Servier. He served as an expert witness for Johnson & Johnson, Sanofi-Aventis and Servier. W.H. served as an advisor, speaker, and/or consultant for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Micrus Endovascular, and PhotoThera. He received grants for clinical research from Boehringer Ingelheim Pharmaceuticals. P.K. received consulting fees and honoraria from 3M Medica, MEDA Pharma, AstraZeneca, Bayer Healthcare, Biosense Webster, Boehringer Ingelheim, Daiichi-Sankyo, German Cardiac Society, MEDA Pharma, Medtronic, Merck, MSD, Otsuka Pharma, Pfizer/BMS, sanofi, Servier, Siemens, TAKEDA, and support for research from 3M Medica/MEDA Pharma, Cardiovascular Therapeutics, Medtronic, OMRON, SANOFI, St Jude Medical, German Federal Ministry for Education and Research (BMBF), Fondation Leducq, German Research Foundation (DFG), and the European Union (EU). J.O. reports institutional research grant from BoehringerIngelheim; and has received consulting and speaker fees from Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Pfizer. P.S. has received research funding through the University of Leuven from Astra-Zeneca and GSK, and has received speaker and/or consulting honoraria from Boehringer-Ingelheim, Bayer Healthcare, DaiichiSankyo, Pfizer, Sanofi-Aventis, Bristol-Meyer-Squib, and Abbott. 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EHRA practical Guide for use of the new oral anticoagulants: executive summary 1370 1375 1380 1385 1390 1395 1400 1405 1410 23. Warkentin TE, Margetts P, Connolly SJ, Lamy A, Ricci C, Eikelboom JW. Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. Blood 2012;119:2172 –2174. 24. Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, Themeles E, Heidbuchel H, Avezum A, Reilly P, Connolly SJ, Yusuf S, Ezekowitz M. Periprocedural bleeding and thromboembolic events with dabigatran compared to warfarin: results from the RE-LY randomized trial. Circulation 2012;126:343–348. 25. Sie P, Samama CM, Godier A, Rosencher N, Steib A, Llau JV, Van der Linden P, Pernod G, Lecompte T, Gouin-Thibault I, Albaladejo P. Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Haemostasis and the French Study Group on Thrombosis and Haemostasis. Arch Cardiovasc Dis 2011;104:669–676. 26. Lakkireddy D, Reddy YM, Di Biase L, Vanga SR, Santangeli P, Swarup V, Pimentel R, Mansour MC, D'Avila A, Sanchez JE, Burkhardt JD, Chalhoub F, Mohanty P, Coffey J, Shaik N, Monir G, Reddy VY, Ruskin J, Natale A. Feasibility and safety of dabigatran vs. warfarin for periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation: results from a multicenter prospective registry. J Am Coll Cardiol 2012;59:1168 – 1174. 27. Kaseno K, Naito S, Nakamura K, Sakamoto T, Sasaki T, Tsukada N, Hayano M, Nishiuchi S, Fuke E, Miki Y, Yamashita E, Kumagai K, Oshima S, Tada H. Efficacy and safety of periprocedural dabigatran in patients undergoing catheter ablation of atrial fibrillation. Circ J 2012;76:2337 – 2342. 28. Snipelisky D, Kauffman C, Prussak K, Johns G, Venkatachalam K, Kusumoto F. A comparison of bleeding complications post-ablation between warfarin and dabigatran. J Interv Card Electrophysiol 2012;35:29–33. 29. Winkle RA, Mead RH, Engel G, Kong MH, Patrawala RA. The use of dabigatran immediately after atrial fibrillation ablation. J Cardiovasc Electrophysiol 2012;23: 264 –268. 30. Lopes RD, Pieper KS, Horton JR, Al-Khatib SM, Newby LK, Mehta RH, Van de Werf F, Armstrong PW, Mahaffey KW, Harrington RA, Ohman EM, White HD, Wallentin L, Granger CB. Short- and long-term outcomes following atrial fibrillation in patients with acute coronary syndromes with or without ST-segment elevation. Heart 2008;94:867–873. 31. De Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H, Bachmann F, Baigent C, Huber K, Jespersen J, Kristensen SD, Lip GY, Morais J, Rasmussen LH, Siegbahn A, Verheugt FW, Weitz JI. New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC Working Group on Thrombosis-Task Force on Anticoagulants in Heart Disease position paper. J Am Coll Cardiol 2012;59:1413 –1425. 32. Fox KA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, Van de Werf F, Avezum A, Goodman SG, Flather MD, Anderson FA Jr, Granger CB. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). Br Med J 2006;333:1091. 33. Nagarakanti R, Ezekowitz MD, Oldgren J, Yang S, Chernick M, Aikens TH, Flaker G, Brugada J, Kamensky G, Parekh A, Reilly PA, Yusuf S, Connolly SJ. Dabigatran vs. warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion. Circulation 2011;123:131 –136. 34. Flaker G, Lopes R, Al-Khatib S, Hermosillo A, Thomas L, Zhu J, Ruzyllo W, Mohan P, Granger C. Apixaban and warfarin are associated with a low risk of stroke following cardioversion for AF: results from the ARISTOTLE Trial. Eur Heart J 2012;33(Abstract Supplement):686. 35. Piccini JP, Stevens S. Outcomes following cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET-AF trial. Circulation 2012;126:(Abstract Supplement, Abstract A19281). 36. Morgenstern LB, Hemphill JC III, Anderson C, Becker K, Broderick JP, Connolly ES Jr, Greenberg SM, Huang JN, MacDonald RL, Messe SR, Mitchell PH, Selim M, Tamargo RJ. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. Page 13 of 13 the American Heart Association/American Stroke Association. Stroke 2010;41: 2108 –2129. Zhou W, Schwarting S, Illanes S, Liesz A, Middelhoff M, Zorn M, Bendszus M, Heiland S, van Ryn J, Veltkamp R. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke 2011;42:3594 – 3599. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012;33:1500 – 1510. Stangier J, Rathgen K, Stahle H, Reseski K, Kornicke T, Roth W. Coadministration of dabigatran etexilate and atorvastatin: assessment of potential impact on pharmacokinetics and pharmacodynamics. Am J Cardiovasc Drugs 2009;9:59 –68. Mendell J, Noveck R, Zahir H, Lee F, Petrushin V, Rubets I, Zhang G, Shi M, Chen S. The effect of quinidine and verapamil, P glycoprotein/CYP3A4/5 inhibitors, on edoxaban pharmacokinetics and pharmacodynamics. Basic Clin Pharmacol Toxicol 2010;107:2848 (Abstract). Kubitza D, Mueck W, Becka M. No interaction between rivaroxaban—a novel, oral direct factor Xa inhibitor—and atorvastatin. Pathophysiol Haemost Thromb 2008;36:A40 (Abstract P062). Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol 2013; doi 10.1111/bcp.12075. Published ahead of print. Stangier J, Stahle H, Rathgen K, Roth W, Reseski K, Kornicke T. Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, with coadministration of digoxin. J Clin Pharmacol 2011; doi: 10.1177/ 0091270010393342. Published online ahead of print. Kubitza D, Becka M, Zuehlsdorf M, Mueck W. No interaction between the novel, oral direct factor Xa inhibitor BAY 59 –7939 and digoxin. J Clin Pharmacol 2006; 46:702 (Abstract 11). Liesenfeld KH, Lehr T, Dansirikul C, Reilly PA, Connolly SJ, Ezekowitz MD, Yusuf S, Wallentin L, Haertter S, Staab A. Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial. J Thromb Haemost 2011;9:2168 –2175. Gnoth MJ, Buetehorn U, Muenster U, Schwarz T, Sandmann S. In vitro and in vivo P-glycoprotein transport characteristics of rivaroxaban. J Pharmacol Exp Ther 2011;338:372 –380. Hartter S, Koenen-Bergmann M, Sharma A, Nehmiz G, Lemke U, Timmer W, Reilly PA. Decrease in the oral bioavailability of dabigatran etexilate after co-medication with rifampicin. Br J Clin Pharmacol 2012;74:490 – 500. Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008;36:386 –399. Stangier J, Stahle H, Rathgen K, Fuhr R. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet 2008;47:47–59. Kubitza D, Becka M, Zuehlsdorf M, Mueck W. Effect of food, an antacid, and the H2 antagonist ranitidine on the absorption of BAY 59 –7939 (rivaroxaban), an oral, direct factor Xa inhibitor, in healthy subjects. J Clin Pharmacol 2006;46: 549 –558. Moore KT, Plotnikov AN, Thyssen A, Vaccaro N, Ariyawansa J, Burton PB. Effect of multiple doses of omeprazole on the pharmacokinetics, pharmacodynamics, and safety of a single dose of rivaroxaban. J Cardiovasc Pharmacol 2011;58: 581 –588. Yasaka M, Inoue H, Kawai Y, Yamaguchi T, Uchiya
Internal Medicine
using turningpoint
Internal Medicine
Internal Medicine
Calcification Inhibitors in CKD and Dialysis Patients
Eur Heart J. 2013 Jul;34 ... EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary.
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EHRA Practical Guide on the Use of New Oral Anticoagulants in Patients With Non-valvular Atrial Fibrillation Executive Summary. ... Eur Heart J. 2013;34 ...
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new oral anticoagulants in patients with non-valvular atrial fibrillation ... EHRA Practical Guide on the use of new oral ... Eur Heart J, 2013 ...
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Updated European Heart Rhythm Association Practical Guide ... use of new oral anticoagulants in patients ... executive summary. Eur Heart J 2013; ...
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DOI: http://dx.doi.org/10.1093/eurheartj/eht134 eht134 First published online: 26 April 2013 New oral anticoagulants (NOACs) are an alternative for vitamin ...
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... with non-valvular atrial fibrillation ... Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial ...
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EHRA practical guide on the use of new oral ... with non-valvular atrial fibrillation. Executive ... org/EHRA 1. Camm et al, Eur Heart J ...
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EHRA Practical Guide on the Use of New Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: Executive Summary. ... Eur Heart J 2013; ...
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... P. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J ...
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... et al. EHRA practical guide on the use of new oral ... executive summary. Eur Heart J. 2013; ... oral anticoagulants in patients with atrial ...
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1/2 PRICE SHAKE HAPPY HOUR Enjoy 1/2 price shakes and malts every day from 3-5 pm and 8 pm-close. SOCIALIZE WITH US y Big Boy on Facebook, Instagram and Twitter #tsYourBigBoy Not valid with an other coupons or dscourts. No cash value. Tax sodsional where applicable. Price and participaton nay vary by location All trademarks and engistered trademksered to withi Boy Retaurants itornational LLC products are tie property of BigBoy Restaurats normatnal LLC©2017 BigBoyAnsturnhten ition tuc


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last.fm. If you are already use last.fm then simply enable this feature at the preferences screen and enter your last.fm account data. From now on each song that that is playing at the SoundBridge is scrobbled automatically as long as RokuControl is running at your Android phone.
Scrobbling works with any music server, like UPnP and DAAP servers but not with Internet radio. The app has to check the song that is playing at the SoundBridge regularly to get noticed when the song changes. So turning on this feature may drain the phone's accumulator somewhat faster.


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To please the luxury car lovers, Honda Motors has unveiled all new 2014 Civic Coupe and Si Coupe at SEMA show in Las Vegas. New Civic expected to be announced by the end of Nov. 2013 at Los Angeles Auto Show how how ever no confirmation about pricing.
The all new 2014 Honda Civic Coupe is powered by a 2.4-liter four cylinder engine capable of producing maximum power of 205 hp @ 7000 rpm and maximum torque of 174 lb-ft of torque @ 4400 rpm. It also offers you aggressively styled grille, hood, front fenders and headlights, new wheel designs, side mirrors and taillight lenses, as well as sportier front and rear bumpers. While 2014 Civic Si Coupe will feature Si-exclusive details like a decklid spoiler, distinctive front and rear air diffusers and larger and newly designed 18-inch (+1 inch) wheels and tires.
At last I would like to say that 2014 Honda Civic Coupe coming to rock the world market. What you think? For more updates please stay tuned….


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With Victor on tour. Getting ready for JFL 2017!
On March 21st 1995 the story of the MozART group began!
Thank you China! At the Forbidden City 2014
Singapore - the Esplanade concert hall again and always a pleasure!
Meeting our fans in South Korea.
We like the Bullet Train in China very much.
At the Forbidden City Concert Hall in Beijing.
Relaxing after the show...
Ohridsko Leto Festival 2014
Royal Concertgebouw Amsterdam 2014
made in osostudio
design by openform


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Choose to extend your visit to us with a break at Ravenglass Station. We have three self catering properties available to hire. Each property sleeps up to six persons for a week. All three properties are ideally situated overlooking the line, bringing new meaning to the term 'railway sleeper'. Free travel on the railway is included for all self catering guests too!
We are now taking bookings for 2018! More information on our self-catering holiday accommodation can be found below:
Elmira is one of the two Pullman Coaches located at Ravenglass Station available for self-catering accommodati...Read More
Hilton Cottage is the third of the Railway's self catering properties and is situated at the end of platform 1...Read More
Maid of Kent is the second of the two Pullman Coaches located at Ravenglass Station available for self-caterin...Read More


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Pregnancy and Substance Use
It is generally known, and widely accepted, that the use of drugs (including alcohol) during pregnancy can lead to a number of possible health and social complications for both mother and child. That being said, simply quitting using your substance of choice the moment you find out you are expecting is often very difficult. It is also often too late, since a large number of pregnancies are unplanned and the fact that many women do not know they are pregnant for weeks or even months into their pregnancy.
If you or someone you know is expecting a baby and is struggling with substance use concerns please scroll down for some specific local programs and resources. For a listing of general substance use supports in Halton please visit our Find Help page.
Halton FASD Collaborative
A team of dedicated professionals and parents who represent 31 Halton-based service agencies whose mission is "To respond to the unique needs of children, youth, adults (birth to 24 years) and their families affected by FASD in Halton Region ensuring that FASD can be identified early and that residents of Halton who are living with the effects of FASD and their families/caregivers receive the support they need to live satisfying lives"
Hope Place Centres
Offers specific information and supports for pregnant and parenting mothers. Over the past several years, many women have been helped by the caring and competent Case Managers in the Baby's Best Beginnings program.
Opioid Outreach and Treatment Services
Brings together a team of dedicated clinicians from four different agencies (ADAPT, PAARC, Hope Place and Salvation Army) also offer programs specifically to pregnant/ parenting woman.
Other Resources
Rethink Your Drinking is a great resource for information about drinking and pregnancy but also alcohol use in general.
The Government of Canada also has a Fetal Alcohol Spectrum Disorder (FASD) Initiative which seeks to prevent FASD and improve outcomes for those who are already affected, including their families and communities.
Motherisk is another great website for resources and information related to alcohol, nicotine and substance use during pregnancy.


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Subject Headings
Well researched and nicely written, this book is a good reminder that 'nothing is set in stone." - in other words, that marriage was, is and may be in the future, a changing, evolving and developing construct blown hither and yon by political exigencies, personal dilemmas and sometimes religious fervour.
Shortlisted for the 2010 Governor General's Award for nonfiction.
There are no age suitabilities for this title yet.
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Jimmy Kimmel Parodies United With Spoof Ad That Feels A Little Too RealisticBy Mustafa Gatollari
If you've been on the Internet in the past two days, then you know how badly United Airlines screwed up when they forcibly dragged a passenger off its flight after seating him when they were already overbooked.
Because this is the Internet we're talking about here, people began decrying the airline and roasting it to high hell for the way it treated its passengers. What's even more disgusting, is the fact that the company's CEO blamed the victim, Dr. David Yao, in a statement to United Staff, and didn't even apologize for the way they handled the situation.
The way United handled the mess and it's subsequent response to the fiasco is taking a toll on the airline's stock - they've already lost $800 million in market value.


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The Arts Markets are organised by Artists in Business, a community arts and business support initiative.
We deliver art community projects and work in schools and community centres to deliver great visual arts projects. We also deliver seminars and workshops for start up arts businesses. We hold arts markets and hand made events to support designer-makers.


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Know more about this business than we do? Cool! Please submit any corrections or missing details you may have.Help us make it right
Be the first NOLA.com user to add photos or videos of Dupuy's Plumbing & Heating
I've used this service several times and the service provided was very professional and good. Highly recommend.
Dupuy's Plumbing & Heating can be found at Metairie Rd 2575. The following is offered: Plumbing. The entry is present with us since Sep 9, 2010 and was last updated on Nov 14, 2013. In Metairie there are 38 other Plumbing. An overview can be found here.
Dupuy's Plumbing & Heating is located at 2575 Metairie Rd, Metairie, LA. This business specializes in Heating Ventilation & Air Conditioning and Plumbing.


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And as most Korean rappers cite American influence, their style inevitably reflects this, with a lot of their lyrics either being in English or using English words.
But a few are resisting the temptation, writing rhymes exclusively in Korean.
"If hip-hop music starts from wanting to express oneself as he or she is, I thought it was only natural that a Korean would rap in the Korean language," MC Meta of Garion told The Korea Herald.
Garion, a pioneer of Korea's underground hip-hop scene, is one of the few hip hop groups who refuse to even use "Yo," or "What's up?" -- two of the most well-worn phrases among Korean rappers -- in their lyrics.
|Garion (Garion's official webpage)
The duo once had said that the simple reason they rap only in Korean is because listeners can understand the lyrics better and they find Korean lyrics more attractive.
English proficiency is a sign of high status in Korea, even more so in the 1990s when fewer people were fluent speakers.
This held true in music as well. K-pop acts often separately credited "rappers" and "English rappers." For example, first generation boyband Shinhwa credited its member Jun Jin for "rap" and credited Eric Mun for "English rap" on its album cover.
There were times when most music fans would consider Korean rap less glamorous.
"That perception spread like the plague across the country," said rapper Kim Ji-hwan, who also raps only in Korean under the stage name PK Heman.
"But there were times when rapping in English was frowned upon. I think it's a matter of trend, just like the standard of being 'hip' keeps changing over time. And I think the controversy has all been settled. Rappers today care more about style or fashion these days."
|PK Heman (PK Heman)
"English phrases can have multiple meanings depending on the situation, which allows for a more diverse content within a single beat or a segment," he said. "Rhyming, for sure, is one of the biggest challenges in Korean-language rapping."
With hip-hop being a cultural product that originates in the West, it is easy to consider Korean hip-hop as playing second. But Garion said that Korean hip-hop has its own identity and values.
"The popularity of shows like 'Show Me the Money' in itself demonstrates Korean hip-hop's identity," he said. "But I do think that we Korean rappers have the potential to express more things through music."
There have been movements to commemorate Hangeul, the Korean writing system, by blending music and poetry that uses exclusively Korean language.
Such was the hip-hop-poetry concert called "Hip-hop Shidae (Hip-hop era)" held last year and broadcast on KBS, to celebrate Hangeul Day, in which local rappers, including Garion, DinDin and Kisum rapped verses written by poets. Hangeul Day, a day celebrating its creation by King Sejong, falls on Oct. 9 each year.
|A scene from last year's hip-hop-poetry concert "Hip-hop Sidae," which was broadcast on KBS to celebrate Hangeul Day. (KBS)
He said he plans to hold a concert in High1 Resort in Jeongseon-gun, Gangwon Province for teenagers, which would consist mostly of Korean-only rap. This would be part of his ongoing effort to promote Korean-language hip-hop, and the unique value it upholds.
Through such events, Kim and others rappers seek to promote rapping in Korean, which he described was "more beautiful than half-baked English rap."
"Korean language tends to express things in a more direct way, which means Korean rap delivers less substance in same volume compared to English. In this context, I'd say that the quality of Korean rappers' lyrics are quite high."
By Hong Dam-young (firstname.lastname@example.com)


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For bookings, appearances and commissions, contact Desiree's publisher.
"After spending a lot of time, doing lots of things, I'm finally where I'm supposed to be, doing what I'm supposed to do."
Desiree Reynolds was brought up in Clapham, London to Jamaican parents. She told her Mum, at about 8 years old, that she was going to write a book and has been writing ever since. The early works continue to be hidden in a drawer. She started her writing career as a freelance journalist for the Jamaica Gleaner and the Village Voice. She left school as quickly as she could and went to South Thames and Westminster College. Having completed two degrees, she has been a shop assistant, youth worker and an editor. She has gone on to write film scripts, poetry and short stories. She continues to work as a journalist, writing book and film reviews.
Desiree is a broadcaster, creative writing workshop facilitator, DJ and mentor. She has had several short stories published in various publications, including A Generation Defining Itself, Hair: A Journey into the Afro and Asian Experience, Moss Side Stories, The Suitcase Book of Love Poems and Tangled Roots. Desiree is inspired by internal landscapes and collective memory. Seduce is her first novel. She is currently working on a collection of short stories, based on growing up in South London and a novel about the collapse of the plantation system in the Caribbean.
Her first novel, Seduce, is out now from Peepal Tree Press.


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Sunny sky brings relief to waterlogged PatnaJuly 17th, 2008 - 9:12 pm ICT by IANS
Patna, July 17 (IANS) After five cloudy days, a clear sky Thursday brought relief to hundreds of people in the flooded residential areas of Patna where seven people have died in rain-related accidents. The sun appeared, bringing the smiles back on some faces in the Bihar capital, where most roads still remain under two to three feet of water.
The district authorities deployed half a dozen boats to facilitate the movement of people in marooned localities.
"Some boats have been deployed in the low-lying Kankarbagh and Rajendra Nagar neighbourhoods to help people," an official of the district administration said.
But the relief is likely to be temporary as the meteorological office has predicted heavy to very heavy showers again.
The Patna Municipal Corporation (PMC) has failed to drain the water from homes and roads.
Thanks to the flooding, cycle rickshaw pullers are a happy lot as they remain much sought after for transport. They have been charging double their regular rates.
Waterlogging has affected over a dozen residential areas. All schools here have been closed since Tuesday after heavy rains and waterlogging began to affect normal life.
Seven people have died in rain-related accidents - two after slipping into overflowing ditches and five of electrocution - in the last four days.
The state legislative assembly compound and the state's only international sports arena, Moinul Haque Stadium, have been waterlogged for the last few days.
Waterlogging has even affected Patliputra Colony, known as a VIP residential area where the political and business top brass live.
Bihar Urban Development Minister Bhola Singh and Patna Municipal Corporation Commissioner Mihir Kumar Singh blamed nature for the situation.
Residents have staged protests against the failure of government agencies to drain out water.
Tags: bhola, clear sky, cloudy days, cycle rickshaw, development minister, district administration, district authorities, dozen boats, electrocution, heavy rains, international sports arena, legislative assembly, meteorological office, mihir, neighbourhoods, patna, residential areas, rickshaw pullers, sunny sky, top brass


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Our 2nd Birthday Gift to you!!
This week we have a Quick Page for you. You can download it by clicking on the image below. It will take you to our MyMemories store and you can download it free from there. If you do not have an account at MyMemories, it is easy and fast to make one and totallly free.


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Thursday, 22 February 2018
Leisurely 5 miles / 8.1 km
Start: 11.00 Wandsworth Town station (Zone 2, Waterloo 10.37, Vauxhall 10.41, Clapham Junction 10.47).
Finish: Victoria station (Zone 1, Circle, District and Victoria Lines).
An easy five mile walk discovering more about the Thames, historic streets and buildings, with a cafe stop along the way. Should finish by 15.00.
Wandsworth Town Railway Station
Victoria Station
This is a linear walk
This is one of hundreds of Ramblers group walks for all ages and abilities every week - all led by our experienced walk leaders.
You're welcome to join us on any of our walks to see if the Ramblers is for you. Then, once you've enjoyed the views, fun, exhilaration and good company, it's just a case of becoming a member.
Do make sure you're fit enough and have the right footwear and clothing for the walk you want to do, though. You can contact the group or leader if in doubt.


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April 18, 2016
An agreement to freeze oil production has fallen apart, after top oil producers left a summit in Doha, Qatar saying more time was needed to work out a deal. Following the gathering, attended by OPEC members and non-members, oil prices tumbled.
Iran elected not to attend, and that non-participation reportedly helped to thwart any potential deal. Industry observers believed the agreement would help boost, or at the very least, stabilize world oil prices, which have fallen by as much as 70% since mid-2014.
Oil industry analysts say the lack of an agreement will likely be viewed "as a disappointment to the market." Oil prices were expected to rise in the near term if a production agreement would have been reached.


text: Stephan Freissmann studied General and Comparative Literary Studies, Sociology, and Visual Arts and Media Studies at Konstanz University (Germany) and at York University, Toronto (Canada). He is currently a Ph.D. candidate at the Justus-Liebig-University Gießen (Germany), working on a dissertation that deals with the representation, transformation, and construction of cognition in contemporary English and American fiction. Among his other research interests are North American postmodern writing and the interaction of narration with culture and knowledge. His article on identity formation in Richard Powers� Galatea 2.2 is forthcoming in 2008.


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Know more about this business than we do? Cool! Please submit any corrections or missing details you may have.Help us make it right
Be the first NOLA.com user to add photos or videos of Luna Mini Storage
Luna Mini Storage can be found at Highway 557 2347. The following is offered: Storage. The entry is present with us since Sep 8, 2010 and was last updated on Nov 12, 2013. In West Monroe there are 13 other Storage. An overview can be found here.


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Upcoming Events
Events List Navigation
February 2016March 2016+ Export Listed Events
The Bluesbeaters
Come celebrate the Valentine weekend starting this Friday with the romantic sounds of THE LEGENDARY Bluesbeaters. Find out more »
Jackson Station
Jackson Station has come in to play a Special Valentine's day show. Show starts at 8:00. Come in for dinner and stick around for a great night of dancing and fun. Find out more »
Familiar Spirit Band
Dance Dance Dance. One of the best bands in the tri-state area. Find out more »
The Breeze Band
THEY'RE BACK!!!!!!!!! Find out more »
The Vendetta's
They made their debut at The Bullfrog Bar on Halloween night and just rocked the place. So glad to have them back for some shows in 2016 starting with this friday show. Find out more »


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We believe that success is linked to three vital ingredients: faith, vision, and customer focus.
Innovation, Faith and Customer Focus
Our Crew
Our talented team has provided a well designed, easy to use, and affordable software to take your fitness business to the next level. Reliability is important to us. We've optimized our infrastructure to be fault tolerant and always available. What sets us apart is our unparalleled accessibility to our customers. Chalkbucket recognizes that each business owner has different priorities, so we will collaborate for the ideal solution. We'll be there for you every step of the way. When you need us, we are here!
Our Passion
Chalkbucket Labs was founded in 2012 by health and fitness enthusiasts. We've lived the grind of running a fitness business and know how the mix of good operations and member focus is a recipe for success. Keeping members information secure is important to maintaining a good reputation and member retention. With over 15 years experience in cyber security software and fitness industry experience we offer a unique advantage that will ensure success. Our goal is to simplify your day-to-day management and offer a way to engage with your members in one easy to use platform. That's Chalkbucket!
Our Partners
Partnerships is one of the most efficient and practical ways to build the best fitness business platform that's attainable for customers around the world. We work with technology leaders, industry organizations, and vendors that enable us to make Chalkbucket the first choice when fitness business owners need automate billing and scheduling, engage with their members and track all business activity.
One Solution. One Software Experience. One Place
A software platform with all the tools you need to simplify your operations and reduce costs so you can focus on your members.


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Shawcross Bligh provides high quality, professional and enthusiastic tutors. Every student learns in a different way and has different experiences, so our tutors tailor their lessons to the individual. Our tutors cover South West London, including Richmond, Putney and Chiswick.
Shawcross Bligh cares about making a difference to their students' education, so our tutors are carefully selected for their knowledge and passion. They use their expertise carefully, to support their students and help them fulfil their potential.
Our tutors help your child achieve their potential
Discover a fulfilling and rewarding experience


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Legal & General UK Mortgage Lender
The original forerunner of Legal and General was founded in 1836, by six lawyers, in a London coffee shop, under the name New Law Life Assurance Society. Originally, it only marketed life assurance policies to the legal profession, but when it started to offer policies to the general public it changed its name to the Legal and General Life Assurance Society. Nowadays, the company markets a full range of financial services.
Mortgage Products
Legal and General doesnt market mortgages in its own right.
However, it does provide mortgage life insurance policies. These include Mortgage Level Term Assurance policies for terms of between one and forty years and Mortgage Decreasing Term Assurance policies for terms of between five and forty years, depending on the age of the borrower when the mortgage is first taken on. The company also offers terminal illness cover and house moving day insurance.
Although Legal and General does not offer its own mortgages it is one of the most trusted names when it comes to providing the back up services for the true mortgage providers. One of the options includes a property ISA which allows investors to put in regular amounts to a fund that will then be invested across a range of commercial properties.
There are also a range of options in terms of investments such as pension schemes and life insurance that can be used to supplement any type of mortgage.
Website: www.legalandgeneral.com


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The Guardian
March 14, 2016
Damian Carrington and Michael Slezack
February smashed a century of global temperature records by "stunning" margin, according to data released by Nasa.
The unprecedented leap led scientists, usually wary of highlighting a single month's temperature, to label the new record a "shocker" and warn of a "climate emergency".
The Nasa data shows the average global surface temperature in February was 1.35C warmer than the average temperature for the month between 1951-1980, a far bigger margin than ever seen before. The previous record, set just one month earlier in January, was 1.15C above the long-term average for that month.
"Nasa dropped a bombshell of a climate report," said Jeff Masters and Bob Henson, who analysed the data on the Weather Underground website. "February dispensed with the one-month-old record by a full 0.21C – an extraordinary margin to beat a monthly world temperature record by."
"This result is a true shocker, and yet another reminder of the incessant long-term rise in global temperature resulting from human-produced greenhouse gases," said Masters and Henson. "We are now hurtling at a frightening pace toward the globally agreed maximum of 2C warming over pre-industrial levels."
The UN climate summit in Paris in December confirmed 2C as the danger limit for global warming which should not be passed. But it also agreed agreed to "pursue efforts" to limit warming to 1.5C, a target now looking highly optimistic.
Climate change is usually assessed over years and decades, and 2015 shattered the record set in 2014 for the hottest year seen, in data stretching back to 1850. The UK Met Office also expects 2016 to set a new record, meaning the global temperature record will have been broken for three years in a row.
One of the world's three key temperature records is kept by Nasa's Goddard Institute for Space Studies (Giss) and its director Prof Gavin Schmidt reacted to the February Giss temperature measurements with a simple "wow". He tweeted:
"We are in a kind of climate emergency now," said Prof Stefan Rahmstorf, from the Potsdam Institute of Climate Impact Research in Germany. He told Fairfax Media: "This is really quite stunning ... it's completely unprecedented."
"This is a very worrying result," said Bob Ward, policy director at the Grantham Research Institute on Climate Change at the London School of Economics, noting that each of the last five months globally have been hotter than any month preceding them.
"These results suggest that we may be even closer than we realised to breaching the [2C] limit. We have used up all of our room for manoeuvre. If we delay any longer strong cuts in greenhouse gas emissions, it looks like global mean surface temperature is likely to exceed the level beyond which the impacts of climate change are likely to be very dangerous."
A major El Niño event, the biggest since 1998, is boosting global temperatures, but scientists are agreed that global warming driven by humanity's greenhouse gas emissions is by far the largest factor in the astonishing run of temperature records.
Prof Adam Scaife, at the UK Met Office, said the very low levels of Arctic ice were also helping to raise temperatures: "There has been record low ice in the Arctic for two months running and that releases a lot of heat." He said the Met Office had forecast a record-breaking 2016 in December: "It is not as if you can't see these things coming."
Read more here.