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21. Hjalmarson A, Elmfeldt D, Herlitz J, et al. Effect on mortality of metoprolol in acute myocardial infarction: a double-blind randomised trial. Lancet. 1981; 2: 823827. Pedersen TR. Six-year follow-up of the Norwegian Multicenter Study on Timolol After Acute Myocardial Infarction. N Engl J Med. 1985; 313: 1055-1058. Gottlieb SS, McCarter RJ, Vogel RA. Effect of -blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med. 1998; 339: 489-497. Smith RS, Warren DJ. Effect of -blocking drugs on peripheral blood flow in intermittent claudication. J Cardiovasc Pharmacol. 1982; 4: 2-4. Hiatt WR, Stoll S, Nies AS. Effect of -adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease. Circulation. 1985; 72: 12261231. Radack K, Deck C. -Adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease: a meta-analysis of randomized controlled trials. Arch Intern Med. 1991; 151: 1769-1776. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001; 345: 494502.
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In this issue of Stroke, Zakarija and 12 co-authors1 describe 37 cases of thrombotic thrombocytopenic purpura TTP ; that occurred in the United States in the years 1998 to 2002 in association with clopidogrel Plavix ; therapy. This is of interest to those of us who as characterized by Donnan and Davis2 ; are "strokologists, " since it raises questions about our understanding of the CAPRIE study.3 In CAPRIE there were 25 cases of platelet counts 100 000 per mm3 in 9553 patients receiving clopidogrel 75 mg d, and 25 cases in 9546 patients receiving aspirin 325 mg d 2.6 cases per thousand with each treatment no cases of TTP were reported. We pose 2 questions: 1 ; Why did Zakarija et al find cases of TTP while the CAPRIE investigators did not? 2 ; Can we estimate the true risk of TTP during clopidogrel therapy? With regard to the first question, a possible explanation is that TTP occurs late in clopidogrel treatment, and was not seen in CAPRIE because treatment duration was too short. This explanation fails for 2 reasons: 1 ; Zakarija et al found that TTP occurred within the first 30 days in 87.5% of cases, and 2 ; mean treatment duration in CAPRIE was fairly long 1.63 years ; . Alternatively, we could conclude that very large numbers of instances of thrombocytopenia must occur before even a single instance of TTP will develop all 37 patients had thrombocytopenia ; , and that the CAPRIE cohort was too small to produce these numbers. This seems a more plausible explanation, and presumably underlies the pharmaceutical companies' postmarketing estimate of 4 cases per million patients, as cited by Zakarija et al. This brings us to the second question: do we accept the pharmaceutical companies' estimate of 4 cases per million patients, or can we examine the issue ourselves? Zakarija et al did not think that they could make an independent estimate; they commented: "An accurate estimate of incidence rate of clopidogrel-associated TTP cannot be determined from our data." We, however, see a way of using their data to make estimates of TTP occurrence; we present our methods and results below. Zakarija et al used 3 case-finding approaches. Thirteen of their cases were identified through the active querying of physicians performing plasma exchange, and of hematologists, in 8 urban areas. According to the New York Times World Almanac 2001, these 8 areas accounted for 40 million 14.8% ; of the 1998 US population of 270 million. On the assumptions of completeness of ascertainment in the 8 areas, and of uniformity of distribution of cases throughout the United States, the 5-year total for the United States should have been 13 0.148 approximately 88 cases. Obviously the assumptions can be questioned; nevertheless, if the second assumption is correct then the 37 13 24 cases identified through 2 passive reporting channels represent under-ascertainment compared with the active querying method. We have reviewed financial statements estimating the sales of Plavix by the manufacturers for the years 1998 to 2002. The approximate values for these years were $134 million, $485 million, $801 million, $1.1 billion, and $1.6 billion, respectively. On the estimate of $50 wholesale price for a month's supply, the number of "Plavix months" PMs ; of agent sold in 1998 would be $134 million $50 approximately 2.7 million. By similar calculation the values in millions for the subsequent years would be approximately 9.7, 16.0, 22.0, and 32.0. The total for 1998 to 2002 would be 82.4 million. If each patient took 1 month of treatment and then received no more clopidogrel the total number of patients treated would have been 82.4 million and the rate of TTP would have been 88 82.4 million or approximately 1.1 per million; the order of magnitude is similar to the pharmaceutical companies' estimate of 4 per million. The 4 per million rate from 88 TTP cases in 5 years would have required a total of 22 million patients: 88 per 22 million 4 per 1 million; in that circumstance the duration of treatment would have averaged 82.4 million 22 million ; 3.745 months. What about longer durations of treatment? The maximal treatment duration assumption would be that all patients begun on treatment at any time in the 5-year period remained on treatment as of December 31, 2002. Let us start in 1998 with the assumption that all 2.7 million PMs where consumed by firsttime users whose entry into treatment was distributed uniformly across the year. Therefore these first-time users averaged 6 PMs during the year; 2.7 million 6 450 000 new patients in 1998. In 1999 these 450 000 patients would have used 450 000 12 5.4 million PMs out of the 9.7 million PMs sold that year; 9.7 million 5.4 million 4.3 million PMs, which were consumed by 4.3 million 6 approximately 717 000 patients new to treatment in 1999. Application of the algorithm to the next 3 years leads to the estimation of 333 000 new patients in 2000, 667 000 new patients in 2001, and 999 000 new patients in 2002. From this algorithm the total of new patients and therefore of all patients treated ; for 1998 through 2002 is 3.166 million; 88 TTP cases in 3.166 million patients would give a rate of approximately 27.8 per million, an order of magnitude greater than the pharmaceutical companies' estimate. The range of our estimates--1.1 to 27.8 per million--reflects the assumptions we made. For instance, the estimate of $65 rather than $50 per would result in the range of 1.4 to 36.2 per million. ; It should be possible to replace some of these assumptions with data. The manufacturers can make a valuable contribution by publishing the actual net numbers of Plavix tablets sold for the years 1998 to 2002; this would obviate the need to use price estimates. Data giving ratios of new prescriptions to refills should be solicited from major retail pharmacy. The fda should not allow this drug to continue to be on the market. The drug may also be beneficial for patients who do not respond to neuroleptic drugs and lopressor. Lopid hyperPists since they joined an Special Association. Many of them could continue doing their daily activities but without increasing their lymphoedema because of given advice. The majority of the patients treated with lymphatic Drainage, physical exercise and contention measures could diminish either lymphoedema range or complication, except in two cases CONClUSIONS Reviewing these results we conclude that it is good for patients suffering from lymphoedema to be associated with other patients suffering same problem in order to access more easily to medical consulting, therapies and other information such as psychological coping skills. The Patients Associations must cooperate with hospitals and PRM services in order to alleviate the burden of patients disability and lotrimin, because lopid drug. Steven H. Yale, MD, Department of Internal Medicine, Marshfield Clinic, and Clinical Research Center, Marshfield Clinic Research Foundation, 1000 N. Oak Avenue, Marshfield, Wisconsin 54449. Loren A. Rolak, MD, Department of Neurology, Marshfield Clinic, 1000 N. Oak Avenue, Marshfield, Wisconsin 54449. What is lopid medicationLopid and alcoholGemfibrozil lopix drugThis issue of Entre Nous has been specially funded by the International Planned Parenthood Federation European Network in order to address one of the most important public health problems facing women in Europe today. No. 59 - 2005 and nordette. PROTECTED HEALTH INFORMATION A. Use and Disclosure of Protected Health Information PHI, for instance, llpid 900. Yao T. Wang Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan and ocuflox. Ordering clopidogrel from our online pharmacy is easy, save your money, high security, private and fast. If the proposed settlement were to become effective, the march agreement provided for a reimbursement of up to $40 million by the companies to apotex relating to apotex’ s existing inventory and for provisions in relation to supply arrangements for its clopidogrel bisulfate product and oxybutynin. Division of Microbiology, Calgary Laboratory Services, #9, 3535 Research Rd NW, Calgary, Alberta, Canada T2L 2K8; 2Departments of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada; 3Departments of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada; 4Service de Bacteriologie-Virologie, Hopital de Bicetre, Assistance Publique Hopitaux de Paris, Faculte de Medecine Paris-Sud, University Paris XI, 94275 Le K.-Bicetre, France; 5Department of Medicine, University of Calgary, Calgary, Alberta, Canada; 6Department of Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada. Many patients presenting for emergency coronary revascularisation have had failed coronary stenting procedures. These patients have usually received aspirin and clopidogrel. Haemorrhage during the subsequent emergency surgery is a major problem. The combination of platelet transfusions and aprotinin therapy has been used to decrease blood loss. Patients who have received clopidogrel within 7 days of the proposed date of surgery should, where possible, have their surgery postponed. If the surgery is a genuine emergency, platelets should be made available for transfusion, and use of aprotonin should be considered. Delaying for 24 hours after the last dose of clopidogrel will improve the response to platelet transfusion and prednisolone and lopid. The drugs usually prescribed to treat Attention Deficit Hyperactivity Disorder ADHD ; -- a class of drugs known as stimulants -- are generally effective and safe. Most children and teens 60% to 80% ; who take them become less hyperactive and impulsive, better able to focus, and less disruptive at home or school. Diagnosis of the condition can be difficult, however, and many children and teens taking stimulants either do not have ADHD or have only mild symptoms. They may not need medication. Be sure to get a careful diagnosis and a second opinion if you have doubts. Adults with ADHD also appear to benefit from taking stimulants. But far fewer studies have examined the effectiveness of the medicines in this population. Our analysis found no evidence that any one stimulant drug is more effective than any other. Each raises different safety issues, however, and you should discuss these with your doctor. Dosing convenience taking one pill a day instead of two or more ; and the period of time that a stimulant pill is active in your body are critical elements of ADHD treatment. Taking into account the evidence for effectiveness, safety, dosing convenience, duration of action, and cost, we have chosen the following as Consumer Report Best Buy Drugs to treat ADHD.
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