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Variations in the pharmacological management of patients treated with carotid endarterectomy: a survey of european vascular surgeons

Eur J Vasc Endovasc Surg (2009) 38, 402e407 Variations in the Pharmacological Management ofPatients Treated with Carotid Endarterectomy:A Survey of European Vascular Surgeons M. Hamish, M.S. Gohel, A. Shepherd, N.J. Howes, A.H. Dav Imperial Vascular Unit, Charing Cross Hospital, London W6 8RF, UK Submitted 19 December 2008; accepted 5 July 2009Available online 3 August 2009 Objectives: The peri-operative use of antiplatelet, anticoagulant and other drugs for patients undergoing carotid endarterectomy (CEA) is unclear and consensus is lacking. This study aimed to assess the current peri-operative practice of European vascular surgeons with respect to antiplatelet and other medications for patients undergoing CEA.
Methods: Members of the Vascular Society of Great Britain & Ireland and European Society forVascular Surgery were invited to complete an online survey in March 2008. Surgeons wereasked about their preferences for the peri-operative administration of antiplatelet, statinand other medications for patients undergoing carotid endarterectomy.
Results: Partial or complete responses were received from 399/650 (61.4%) surgeons witha collective annual throughput of >11500 CEA procedures. For symptomatic and asymptomaticpatients, 20/392 (5%) and 47/392 (12%) of surgeons would stop aspirin before surgery and 170/392 (43%) and 217/392 (55%) of surgeons would stop Clopidogrel prior to CEA. Of surgeons whowould stop Clopidogrel, 84/170 (49%) and 124/217 (57%) would do so >7 days before surgeryfor symptomatic and asymptomatic patients respectively. 12/393 (3%) surgeons would prescribeone 75 mg dose of Clopidogrel on the evening before surgery. Intra-operative Dextran was usedselectively by 40/395 (10%). Only 78/393 (20%) would delay surgery to commence a statin.
Intra-operatively, 348/394 (88%) used intravenous heparin, which was reversed routinely by47/348 (13%) and selectively by 60/348 (17%).
Conclusions: There appears to be broad consensus between vascular surgeons in the pharmacolog-ical management of patients undergoing carotid endarterectomy, although some variations do exist.
Further clinical studies may help clarify the optimum management strategy in this patient group.
ª 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Numerous large randomized studies including the North 1078-5884/$36 ª 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.ejvs.2009.07.001 (NASCET),the European Carotid Surgery Trial (ECST)and the Asymptomatic Carotid Surgery Trial (ACST)haveevaluated the effectiveness of carotid endarterectomy in Partial or completed questionnaires were received from 399 patients with significant internal carotid artery stenosis.
of the 650 (61.4%) Vascular Surgeons invited to participate.
These have demonstrated a significant reduction in the risk Published email addresses were inaccurate for 98/650 of death or disabling strokes for patients randomized to (15.1%) and 153/650 (23.5%) did not respond. A total of 284 surgery in comparison to those in the non-surgical arms.
responses were received after the initial invitation email and However, consensus is lacking on the peri-operative a further 115 responses were received after the reminder prescription of antiplatelet, cholesterol lowering or other email. The combined throughput of those who completed medications for patients requiring carotid endarterectomy the survey was >11,500 CEA procedures per annum. Of the (CEA). A recent meta-analysis reported that aspirin was 361 respondents that answered the specific question, 239 protective in most patients at increased risk of occlusive (66.2%) performed >20 CEA procedures per annum.
vascular events.Furthermore, large randomized clinical Procedures were routinely performed using general anaes- studies have demonstrated reductions in stroke and death thesia by 178/362 (49.1%) whereas 151/362 (41.7 %) used rates in patients treated with aspirin after local anaesthesia and 33/362 (9.1%) used both techniques.
These findings suggest that a period of pre-operativeadministration followed by post-operative administration of aspirin may have a protective effect in patientsundergoing CEA.
The vast majority of vascular surgeons surveyed would not In order to maintain low complication rates following stop aspirin prior to carotid endarterectomy for symptom- CEA, multiple components of the pre, intra and post- atic or asymptomatic patients (372/392 [94.8%] and 345/ operative care must be carefully managed. Tsurgical tech- 392 [88.0%] respectively) ). Of the 47 respondents nique and appropriate use hese factors include patient that would discontinue aspirin (including 20 who would do selection, assessment of cardiac risk factors, precise blood so for patients with symptomatic and asymptomatic carotid coagulation and other medications. The aim of this study surgery and 14/47 (29.8%) would stop aspirin for at least 7 was to evaluate the use of peri-operative antiplatelet, days. When asked about pre-operative Clopidogrel use, anticoagulant and other medications amongst European 170/392 (43.3%) and 217/392 (55.3%) of surgeons would stop Clopidogrel before surgery for symptomatic andasymptomatic patients respectively. Of surgeons who would stop Clopidogrel, 84/170 (49.4%) and 124/217 (57.1%) woulddo so >7 days before surgery for symptomatic and asymp- An email invitation to complete an online 16-part ques- tomatic patients respectively. For both aspirin and Clopi- tionnaire was sent to all listed members of the European dogrel, surgeons were more likely to stop antiplatelet Society of Vascular Surgery (ESVS) and the Vascular Society medications prior to surgery for asymptomatic rather that of Great Britain and Ireland (VSGBI). The societies were not involved in the design of the study. Questions relating to the pre, peri and post-operative pharmacological manage- A high proportion of respondents stated that they would ment of patients undergoing CEA were devised by the study continue Dipyridamole prior to surgery for symptomatic or authors Questions related to pre-operative asymptomatic disease; 247/250 (98.8%) and, 211/250 antiplatelet, anticoagulant and statin use; intra-operative (84.4%) respectively. A total of 285/392 (72.7%) and 389/ heparin, dextran, protamine and dexamethasone use and 392 (99.2%) of respondents would stop Warfarin prior to CEA post-operative antiplatelet use. The initial invitation email Interestingly, 12/393 (3.0%) of surgeons would was sent in March 2008 and a reminder email was sent in prescribe a pre-operative 75 mg dose of Clopidogrel, the June 2008. The questionnaire responses were anonymized day before surgery. CEA would be delayed by surgeons and only one response per email address was allowed by the to give statin medication by 18/393 (4.9%) for symptomatic online academic survey software (Bristol Online Surveys).
patients and 60/393 (15.2%) for asymptomatic patients.
All complete and partially completed responses wereincluded in the analysis and the number of completed responses received for each question is presented as thedenominator. Statistical analysis was performed using the Only 13/394 (3.2%) surgeons would give intra-operative Chi Square test (SPSS v16.0, Chic, IL, USA).
pooled platelets if the patient was on dual antiplatelet Numbers of respondents who would stop antiplatelet and anticoagulant medications prior to CEA therapy (aspirin and Clopidogrel or Dipyridamole). The TIA.Despite these studies, 5e12% of surveyed surgeons majority of surgeons would routinely give heparin prior to would stop aspirin and more than half would stop Clopidogrel arterial clamping (348/394 [88.3%]), but only 47/348 pre-operatively. Clearly, further clinical studies demon- (13.5%) would routinely reverse the heparin and 60/348 strating clear benefits are needed before dual antiplatelet (17.2%) would reverse it selectively. Regarding blood pres- therapy is widely adopted by surgeons performing CEA.
sure management during surgery, 245/394 (62.1%) would Interestingly, a small proportion of surgeons would delay aim to maintain normotension during CEA, although 97/394 carotid endarterectomy for a week or more in order to give (24.6%) would aim to keep patients hypertensive. Dextran statins. The use of statins has been suggested as a potential was routinely prescribed by 40/397 (10.0%) of respondents method of plaque stabilization prior to CEA, a hypothesis and selectively (based on transcranial Doppler readings) by supported by histological studies.Clinical studies have a further 27/397 (6.8%). Dexamethasone was used routinely also shown lower rates of adverse events in patients taking or selectively by a minority of respondents; 14/363 (3.8 %) statins prior to Interestingly, large studies have sug- gested that this benefit is greatest in symptomatic ratherthan asymptomatic In a retrospective study, McGirt et al. suggested that peri-operative statin use (atleast for one week before surgery and one month after) Among the surgeons who would discontinue antiplatelet may reduce the incidence of cerebrovascular events and drugs, 18/20 (90.0%) would restart aspirin and 131/189 mortality among patients undergoing A further study (69.3%) would restart Clopidogrel on first day post-opera- demonstrated that 4 weeks of treatment with atorvastatin resulted in significant local and systemic reductions ininflammatory mediators in patients undergoing carotid endarterectomy. These findings suggest that statins mayreduce atherosclerotic plaque inflammation and potentially This survey demonstrated that the majority of European delay or prevent plaque rupture.These observations are Vascular Surgeons who responded would continue aspirin, intriguing, but more definitive studies are needed before but most would stop other antiplatelet and anticoagulant broad recommendations can be agreed. A strategy of medications prior to carotid endarterectomy. Moreover, delaying CEA for the administration of statins may seem most respondents would use heparin intra-operatively, aim logical in asymptomatic patients, but may be detrimental in to maintain normal blood pressure during surgery and restart symptomatic patients. The increasingly widespread use of antiplatelet medications on the first post-operative day.
statins in high-risk populations is likely to mean that the Although a broad consensus was seen, it is worth noting that vast majority of patients requiring CEA will already be on some variation in the clinical practice of European Vascular Surgeons was demonstrated in this study, highlighting the The maintenance of hypertension (around 20% above scarcity of level 1 evidence or clinical guidelines in this area.
pre-operative systolic pressure) during CEA may be justified The decision to continue to stop antiplatelet and anti- by fears of ‘watershed’ stroke during carotid cross- coagulant drugs requires the clinician to evaluate the risks clampingand evidence from patients undergoing awake and benefits for each individual patient and balance the risks CEA where neurological deficits may be reversed by of bleeding and thrombosis. In a study that investigated the elevation of arterial pressure.However, most clinicians use of 75 mg of Clopidogrel in addition to 150 mg of aspirin, would agree that absolute values or targets should be a significant reduction in peri-operative emboli was seen viewed as guidelines only and adapted to individual without any increase in bleeding complications or blood patients,particularly as augmentation of arterial pressure transfusion.A recent systematic review found that the risk may be associated with increased risks, including a higher of peri-operative stroke among those receiving antiplatelet incidence of myocardial infarctionand intracerebral agents was significantly reduced in comparison with the risk haemorrhage.Dextran is thought to prevent platelet for those not receiving antiplatelet therapy, but that the adherence to the endarterectomy site, although its role in risks of peri-operative death in the two groups were not CEA remains unclear. There is evidence to suggest that significantly Another study suggested that dextran 40 may reduce the incidence of post-operative a single 75-mg dose of Clopidogrel, taken the evening before emboli and stroke (assessed using transcranial carotid endarterectomy, may reduce post-operative embo- Corticosteroids (dexamethasone 24e40 mg/day in divided lisation, a marker of thrombo-embolic Moreover, doses) may reduce vasogenic cerebral oedema, but their a recent meta-analysis suggested that the use of Dipyr- routine use in treatment of ischaemic strokes is idamole in combination with aspirin may be the best choice for secondary prevention of vascular events after stroke or patients treated with CEA are scarce, although a recent Time to restarting antiplatelet and anticoagulant medications randomized trial did suggest that dexamethasone may be medications, which is an increasingly common clinical effective in reducing the incidence of temporary cranial scenario. In conclusion, there appears to be broad consensus between vascular surgeons in the use of anti- We recognize that survey studies are often limited by platelet and statins for patients undergoing carotid endar- poor response rates. The response rate in this study was terectomy, although some variations do exist. Only by only 61%, although this compares favourably with other establishing evidence-based guidelines can we achieve similar Moreover, it is likely that a large number greater consistency of treatment for this patient group.
of surgeons (not members of ESVS or VSGBI) were notincluded and heterogeneity in clinical practice acrossEurope may limit the generalisability of this study. Another limitation of this study was the lack of questions on themanagement stop the following medications prior to CEA: c. Clopidogrel one dose pre-operatively only d. Clopidogrel 48 h pre-operativelye. Clopidogrel 7 days pre-operatively If a patient is not taking a statin would you delay endarterectomy in order to start one? If you do not routinely stop antiplatelet medication, would you routinely give patients additional platelets? c. Yes but only if the patient is on Clopidogrel d. Yes but only if the patient is taking aspirin and Clopidogrele. Yes if the patient is taking aspirin and Dipyridamole Intra operatively, how best describes the patients’ systolic blood pressure before d. Selectively based on clinical assessmente. No Answer Peri-operatively do you give dexamethasone? d. Selectively based on clinical assessmente. No Answer medication prior to surgery, when do you restart it? On average how many carotid endarterectomy What type of anaesthesia do you use for the majority of your carotid endarterectomy procedures? Which antiplatelet medications do you routinely prescribe for patients requiring carotid endarterectomy? 8 Payne DA, Jones CI, Hayes PD, Naylor AR, Goodal AHI. Thera- peutic benefit of low-dose Clopidogrel in patients undergoingcarotid surgery is linked to variability in the platelet adenosine 1 North American Symptomatic Carotid Endarterectomy Trial diphosphate response and patients’ weight. Stroke 2007;38: Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J 9 Verro P, Gorelick PB, Nguyen D. Aspirin plus dipyridamole versus aspirin for prevention of vascular events after stroke or TIA: 2 Rothwell PM, Gutnikov SA, Warlow CPfor the European Carotid Surgery Trialists’ Collaboration. Reanalysis of the final results of 10 Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, the European Carotid Surgery Trial. Stroke 2003;34:514e23.
Nilsson J. Pravastatin treatment increases collagen content and 3 Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, decreases lipid content, inflammation, metalloproteinases, and et alMRC Asymptomatic Carotid Surgery Trial (ACST) Collabo- cell death in human carotid plaques: implications for plaque rative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent 11 Kennedy J, Quan H, Buchan AH. Statins are associated with neurological symptoms: randomised controlled trial. Lancet better outcomes after carotid endarterectomy in symptomatic 4 Antithrombotic Trialists’ Collaboration Collaborative meta- 12 Poldermans D, Bax JJ, Kertai MD, Krenning B, Westerhout CM, analysis of randomized trials of antiplatelet therapy for Schinkel AFL, et al. Statins are associated with a reduced prevention of death, myocardial infarction and stroke in high- incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery. Circulation 2003;107: 5 CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 13 McGirt M, Perler B, Brooke B, Woodworth G, Coon A, Jain S, patients with acute ischaemic stroke. Lancet 1997;349:1641e9.
et al. 3-Hydroxy-3-methylglutaryl coenzyme A reductase 6 Payne DA, Jones CI, Hayes PD. Beneficial effects of Clopidogrel inhibitors reduce the risk of perioperative stroke and mortality combined with aspirin in reducing cerebral emboli in patients after carotid endarterectomy. J Vasc Surg 2005;42:829 undergoing carotid endarterectomy. Circulation 2004;109: 14 Martin-Ventura JL, Blanco-Colio LM, Gomez-Hernandez A, Munoz- Garcia B, Vega M, Serrano J, et al. Intensive treatment 7 Engelter S, Lyrer P. Antiplatelet therapy for preventing stroke and with atorvastatin reduces inflammation in mononuclear cells other vascular events after carotid endarterectomy. Cochrane and human atherosclerotic lesions in one month. Stroke 2005; Database Syst Rev 2003;(Issue 3). doi:10.1002/14651858. Art.
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carotid endarterectomy: the role of transcranial Doppler ultra- 16 Stoneham MD, Warner O. Blood pressure manipulation during awake carotid surgery to reverse neurological deficit after 21 Norris JW, Hachinski V. High doses steroid treatment in cerebral carotid cross-clamping. Br J Anaesth 2001;87:641e4.
17 Stoneham MD, Thompson JP. Arterial pressure management and 22 Regina G, Angiletta D, Impedovo G, De Robertis G, Fiorella M, carotid endarterectomy. Br J Anaesth 2009;102(4):442e52.
Carratu’ MR. Dexamethasone minimizes the risk of cranial nerve 18 Riles TS, Kopelman I, Imparato AM. Myocardial infarction injury during CEA. J Vasc Surg 2009 Jan;49:99e102.
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23 Girn H, Dellagrammaticas D, Laughlan K, Gough M. Carotid endarterectomy: technical practices of surgeons participating 19 Russell DA, Gough MJ. Intracerebral haemorrhage following carotid in the GALA trial. Eur J Vasc Endovasc Surg 2008;36(4): endarterectomy. Eur J Vasc Endovasc Surg 2004;28:115e23.


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GINA SONG UNC Eshelman School of Pharmacy ♦ (919)966-1622 ♦ EDUCATION  University of North Carolina , Chapel Hill, NC  Present Eshelman School of Pharmacy Division of Pharmacotherapy and Experimental Therapeutics Ph.D. student  University of Minnesota , Minneapolis, MN  May 2005 – May 2008  Ewha Women’s University, Seoul, Republ

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