Low-dose sodium valproate in the treatment of idiopathic generalized epilepsies.

OBJECTIVE: Most patients with idiopathic generalized epilepsies (IGEs) have good seizure control when on antiepileptic drugs. To analyze prospectively the response to low-dose sodium valproate (VPA) treatment (<1000 mg/day) together with plasma VPA levels in a cohort of patients with IGE. METHODS: Patients with IGE were selected and followed for almost 2 years. In patients on VPA with no seizures in the last year, VPA dose was lowered to <1000 mg/day. Newly diagnosed patients with IGE started treatment on VPA directly on this low dose. RESULTS: Fifty-four patients were included, with juvenile myoclonic epilepsy (JME) in 23 (42.6%), juvenile absence epilepsy (JAE) in 17 (31.5%), and generalized tonic-clonic seizures only (GTCS only) in 14 (25.9%). VPA at low dose was administered to 38 (70%) patients. Mean plasma VPA level was 44.21 mg/l (18-78; SD 15.18). Seizure relapse during the 2-year follow-up was observed in 8 (21%). A reduction in adverse events was observed (P < 0.048). The only factor related to efficacy of VPA at low dose was syndromic diagnosis. Low-dose VPA controlled 92.9% (13) of patients with GTCS only, 78.3% (18) of those with JME, and 29.5% (5) of those with JAE. CONCLUSIONS: Low-dose VPA was a highly effective treatment for the majority of those with JME and GTCS only. The seizures in JAE tended to be more resistant to treatment, usually requiring higher doses of VPA or polytherapy.

Efficacy of intravenous lacosamide as an add-on treatment in refractory status epilepticus: a multicentric prospective study.

OBJECTIVE: Treatment of status epilepticus (SE) has not changed in the last few decades, benzodiazepines plus phenytoin or valproate being the most common treatment. Once this first and second line treatment has failed SE is considered refractory (RSE). This study aimed to assess the efficacy and tolerability of intravenous (iv) lacosamide (LCM) in RSE. METHOD: Patients with RSE who were treated with ivLCM in six Spanish centers were prospectively included. Efficacy was defined as cessation of seizures after starting ivLCM, with no need for any further antiepileptic drug. All patients had been unsuccessfully treated following the standard protocol (benzodiazepines plus phenytoin or valproate) before ivLCM was added. RESULTS: Thirty-four patients were included, 52.9% men, with mean age of 60.15 years. In 58.9% of patients the etiology was symptomatic, and the most common type of SE was focal convulsive (82.4%). Mean initial bolus dose of LCM was 323.53mg. ivLCM was effective in more than half of patients (64.7%), with termination of SE before 12h in 50% of them. ivLCM was used as a fourth or later option in 76.5% of patients. No serious adverse events attributable to LCM were reported. CONCLUSIONS: LCM might be a fast, effective and safe add-on treatment in RSE.

Commutability and traceability: their repercussions on analytical bias and inaccuracy.

The commutability of calibrators and accuracy control materials affects the traceable link between patient sample results and standards. We sought to identify the repercussions of commutability on various aspects of laboratory practice (calibration, control of bias and accuracy assessment) and to discover the solutions that can reduce the problems produced by non-commutability with presently available resources. Ten serum constituents, ten comparison procedures and 37 analytical procedures were studied. The information concerning accuracy and bias provided from materials found to be commutable in previous works was challenged with native serum results for each routine and reference method compared, using Passing-Bablok regression and decision limits derived from biological variation. We found that: (1) Use of commutable control materials did not assure reliable information on the bias (systematic component of analytical error) of analytical procedures, and (2) Results from native serum and commutable controls were very highly concordant, indicating that these materials provide a good indication of the inaccuracy (total analytical error) of results. We suggest that the performance of individual laboratories would be better evaluated by occasional use of native sera with values assigned by reference methods in EQAS schemes. Moreover, our findings support the idea that manufacturers should assign values to calibrators using reference methods and native sera to reduce matrix effects and promote traceability.

Commutability between stabilized materials and fresh human serum to improve laboratory performance.

With the recent advances in laboratory technology, many quality-related problems have been improved. However, the issue of commutability, a factor that greatly affects daily decisions concerning patient status, still remains to be solved. This paper determines the commutability between 27 stabilized materials (controls and calibrators) and clinical specimens for five serum quantities, using carrier-bound reagent chemistry and conventional wet methods. Our aim was to pinpoint the specific problems related to non-commutable calibrators and controls in our setting, and minimize their effect in daily practice. We found major difficulties in selecting appropriate accuracy controls in carrier-bound reagent techniques, and in finding materials commutable for several analytes simultaneously. Several suggestions for reducing problems related to non-commutability, such as procedures for assigning values to multicalibrators, are proposed. We explain the apparent incongruencies observed in daily quality surveillance, when data from different control materials (internal quality control and external quality assessment) are evaluated. The conclusions emphasize the need for a combined effort (manufacturers, organizers of external quality assessment schemes and individual laboratories) to find the cause of, and eliminate, the negative repercussions on laboratory performance produced by non-commutability.

Procedure for studying commutability validated by biological variation.

In the field of laboratory medicine, the two quantitative approaches designed to identify the stabilized materials that produce results that are commutable with results from patients' samples were found to differ. In commutability evaluations, the responses of each material and each method studied are specific, thus, it is vital to standardise the procedure used for determining this characteristic. We incorporated statistical components from the two described methods that seemed to be consistent, and added a new element based on biological variation, to validate the criterion of acceptability that determines whether or not a material is commutable. The three methods for studying commutability (using the confidence interval [alpha = 0.05], the +/- 2s(yx) formula, and the limit based on biological variation as acceptability criteria) were applied to creatinine results from 31 stabilised materials and serum samples analysed with seven instruments, when compared against a reference method for creatinine analysis. Over the wide range of concentrations studied, the confidence interval limit and the biological variation limit coincided in the identification of commutable materials, whereas the +/- 2s(yx) was excessively permissive at normal and low concentration levels. We therefore recommend the use of Passing-Bablok regression with its confidence interval (alpha = 0.05) in studies concerning commutability. Using this method, commutability is simple to calculate with available software and, as validated by biological variation, results are reliable.