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Some New Medical Points in Neurology

Warfarin Use Associates with Increased Risk for Stroke in Hemodialysis Patients with Atrial Fibrillation

Use of warfarin, clopidogrel, or aspirin associates with mortality among patients with ESRD, but the risk-benefit ratio may depend on underlying comorbidities. Here, we investigated the association between these medications and new stroke, mortality, and hospitalization in a retrospective cohort analysis of 1671 incident hemodialysis patients with preexisting atrial fibrillation. We followed patient outcomes from the time of initiation of dialysis for an average of 1.6 yr. Compared with nonuse, warfarin use associated with a significantly increased risk for new stroke (hazard ratio 1.93; 95% confidence interval 1.29 to 2.90); clopidogrel or aspirin use did not associate with increased risk for new stroke. Analysis using international normalized ratio (INR) suggested a dose-response relationship between the degree of anticoagulation and new stroke in patients on warfarin (P = 0.02 for trend). Warfarin users who received no INR monitoring in the first 90 d of dialysis had the highest risk for stroke compared with nonusers (hazard ratio 2.79; 95% confidence interval 1.65 to 4.70). Warfarin use did not associate with statistically significant increases in all-cause mortality or hospitalization. In conclusion, warfarin use among patients with both ESRD and atrial fibrillation associates with an increased risk for stroke. The risk is greatest in warfarin users who do not receive in-facility INR monitoring.

Rational polytherapy

Monotherapy has been considered the gold standard for drug treatment of epilepsy. However, there is renewed interest in polytherapy because of the advent of new drugs with fewer drug interactions and novel mechanisms of action, and the realization that most patients with refractory epilepsy are eventually treated with drug combinations. Careful consideration must be given to drug additions and conversions; it may be less risky to add a drug than to convert from one monotherapy to another in patients with frequent or severe seizures. Rational choice of drug combinations is, at present, based more on avoidance of pharmacodynamic or pharmacokinetic side effects than on evidence for supra-additive efficacy. There are indications that combinations of two sodium-channel blocking agents are less effective than combinations of drugs with different primary mechanisms of action, and some human studies suggest that lamotrigine and valproate may be synergistic for efficacy. However, more animal and human research is needed, with attention to the effects of various combinations on both toxicity and seizure control.

Use of a new antiepileptic drug or an old one as first drug for treatment of absence epilepsy

Treatment of absence epilepsy requires understanding the efficacy and side effects of several drugs, one of which first became available more than 50 years ago. Methods for drug development and procedures for evaluating their safety and efficacy over that time have changed dramatically. Observational studies of the efficacy of ethosuximide, a drug developed in the 1950s, reported complete seizure control in 40-60% of patients. Valproic acid, a drug with a broad spectrum of effect, showed robust efficacy as well for control of absence seizures. Because side effects limit use in some patients, newer drugs were evaluated in patients with absence seizures. Of drugs becoming available in the last 15 years, lamotrigine has some effect in absence seizures. Although older and newer drugs presently are used without the rigorous underpinnings of the highest quality of evidence, our analysis found that ethosuximide, valproate, and lamotrigine are effective in the treatment of absence seizures, with ethosuximide quite possibly being the first drug of choice.

The first line of therapy in a girl with juvenile myoclonic epilepsy: should it be valproate or a new agent?

Juvenile myoclonic epilepsy is a common idiopathic generalized epileptic syndrome that includes generalized myoclonic seizures and commonly generalized tonic-clonic and generalized absence seizures. Before the emergence of the newer antiepileptic drugs (AEDs) in the 1990s, valproate was the usual first-line treatment in both men and women. However, the frequent adverse effect of weight gain and the risk of teratogenicity have resulted in a search for alternative first-line therapies in women. Four new AEDs- lamotrigine, topiramate, levetiracetam, and zonisamide-have been used as monotherapy or adjunctive therapy for juvenile myoclonic epilepsy in small patient series. Because they are not associated with weight gain and because they may have less risk of teratogenicity than valproate, they have been proposed as alternative first-line agents in women who have childbearing potential. However, the new AEDs may not be effective for all the seizure types of juvenile myoclonic epilepsy, and valproate appeared overall more effective in a large comparative trial in idiopathic generalized epilepsy. In addition, valproate is often effective at lower doses that have less teratogenicity, and an extended-release preparation may be less likely to produce weight gain. The current review presents evidence and arguments supporting the use of a new AED and those supporting the use of valproate as the first-line treatment in a girl with newly diagnosed juvenile myoclonic epilepsy. The review then concludes with a compromise approach.


September 13, 2009 - Posted by | 1

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