Discrepancies between physicians' prescriptions and patients' use of antiepileptic drugs.

OBJECTIVES: The purpose of this study was to investigate whether prescribed antiepileptic drugs (AEDs) were consistent with what patients actually used, and to explore challenges in treatment and reasons for possible discrepancies according to patients' view of their medication. MATERIAL AND METHODS: Anonymized data were collected from a questionnaire distributed to in- and outpatients and their physicians at the National Center for Epilepsy, Norway. They were asked to report AEDs and dosages currently used. Additionally, 20 patients were interviewed regarding AED treatment. This information was analyzed qualitatively. RESULTS: Answers from 174 patients and their physicians were analyzed. The patients' mean age was 43 years (21-83 years), 85 (49%) were women, and 56% used AED polytherapy (2-5 AEDs). For 56 patients (32%), there was a discrepancy regarding either dosage (n = 70) or prescribed drug (n = 32) (12%). There were discrepancies for all top 10 used drugs, with a similar distribution of patients stating lower or higher doses. Based upon interviews of 20 patients, concerns and challenges in AED treatment were addressed. Polytherapy and adverse effects which reduced the patients' quality of life were the most important obstacles for adherence to the treatment. CONCLUSIONS: This study revealed that 32% of the patients had one or more discrepancies between what the physician had prescribed and what the patients actually used, in either the type or the dosages of AEDs. Polytherapy, adverse effects, and poor adherence were common challenges. Improved communication and information about AEDs may improve adherence and thus treatment outcome.

Withdrawal of antiepileptic drugs during presurgical video-EEG monitoring: an observational study for evaluation of current practice at a referral center for epilepsy.

OBJECTIVES: Withdrawal of antiepileptic drugs (AEDs) before and during video-EEG-monitoring is commonly implemented to reduce time needed to register a sufficient number of seizures during presurgical evaluation. There are, however, few guidelines regarding withdrawal rate and observation time. MATERIAL AND METHODS: We performed an observational study including sixty patients admitted to the national Norwegian epilepsy centre and registered tapering of AEDs and their effect on seizure rate and possible complications. RESULTS: The mean daily seizure rate before admission to the EMU was 0.4 (range 0.02-4) increasing to 1.1 (range 0-8) at the EMU. 29 patients (48%) followed a slow tapering rate whereas 31 (52%) had an intermediate tapering rate. There was no significant difference between the patients with a daily seizure rate during LTM of more or <0.7 seizures per day, an increase of seizure frequency from habitual to during LTM of more or <3.3 or 6.9 with regard to rate of tapering (slow vs intermediate) etiology or AED monotherapy vs polytherapy. Twenty-six patients (43%) had a sufficient number of seizures registered within 3 days to conclude regarding the presurgical evaluation. Two patients received escape treatment while 25 patients did have 24 h-seizure-clusters. There was no serious event. CONCLUSIONS: Less than 50% of the patients got a sufficient number of seizures for a conclusive result within 3 days. An increase in the registration period could increase the number of successful registrations.

There is no 1954 in that core! Interpreting sedimentation rates and contaminant trends in marine sediment cores.

Marine sediment preserves a useful archive for contaminants and other properties that associate with particles. However, biomixing of sediments can smear the record on a scale of years to thousands of years, depending on sedimentation rate and on the depth and vigour of mixing within a particular sediment. Where such mixing occurs, dates can no longer be associated with discrete sediment depths. Nevertheless, much can still be learned from biomixed profiles, provided that mixing is accounted for. With no modelling at all, it is possible to calculate an inventory of a contaminant at a site and a maximum possible sedimentation rate, and to determine whether the contaminant has increased or decreased over time. Radiodating the core with (210)Pb permits the estimation of sedimentation and mixing rates, which can be combined with the surface contaminant concentration to estimate an approximate flux of the contaminant. Numerical models that incorporate sedimentation and mixing rates (determined using (210)Pb and other transient signals with known deposition histories) can provide the basis to propose plausible histories for contaminant fluxes.

Biogeochemical cycling in the Strait of Georgia.

The papers in this special issue present the results of a five-year project to study sedimentary biogeochemical processes in the Strait of Georgia, with special emphasis on the near-field of a large municipal outfall. Included in this special issue are overviews of the sedimentology, benthic biology, status of siliceous sponge reefs and distribution of organic carbon in the water column. Other papers address the cycling of contaminants (PCBs, PBDEs) and redox metals in the sediment, a method to map the extent of the influence of municipal effluent from staining on benthic bivalves, and the relationships among geochemical conditions and benthic abundance and diversity. The latter set of papers addresses the role of municipal effluent as a pathway of organic carbon and other contaminants into the Strait of Georgia and the effect of the effluent on benthic geochemistry and biology.

Responses of subtidal benthos of the Strait of Georgia, British Columbia, Canada to ambient sediment conditions and natural and anthropogenic depositions.

Patterns in infaunal biota in the Strait of Georgia are explored relative to water depth, substrate type, organic content of sediments and sedimentation characteristics. The analyses are based on geographically-diverse grab and core data collected over a 19-year period. Infaunal abundance and biomass were not predictable by sediment particle size, organic content or water depth. While organic flux was a reasonable predictor of biotic factors, quality of organic material, relative proportions of organic and inorganic input and source of inputs were also important in this regard. Areas with high accumulation of sediment and high organic flux rates from terrestrial (riverine) sources supported the highest macro-infaunal abundance and biomass found to date in the Strait of Georgia, and were dominated by bivalves. Polychaetes dominated in low organic deposition conditions, and where anthropogenic organic deposition was high. However, biota were severely impoverished in sediments with high organic content from marine deposition, due to low fluxes and poor quality of organic material. Taxa number was related to percent total nitrogen and to the ratio of organic/inorganic flux, both in background conditions and where there was labile organic enrichment. Faunal communities from the Fraser River delta, which experiences considerable bottom-transported riverine material, were very different in composition from those that proliferate in habitats with high deposition and organic flux from the water column.

Water column organic carbon in a Pacific marginal sea (Strait of Georgia, Canada).

Marginal seas provide a globally important interface between land and interior ocean where organic carbon is metabolized, buried or exported. The trophic status of these seas varies seasonally, depending on river flow, primary production, the proportion of dissolved to particulate organic carbon and other factors. In the Strait of Georgia, about 80% of the organic carbon in the water column is dissolved. Organic carbon enters at the surface, with river discharge and primary production, particularly during spring and summer. The amount of organic carbon passing through the Strait (approximately 16x10(8) kg C yr(-1)) is almost twice the standing inventory (approximately 9.4x10(8) kg C). The organic carbon that is oxidized within the Strait (approximately 5.6x10(8) kg yr(-1)) presumably supports microbial food webs or participates in chemical or photochemical reactions, while that which is exported (7.2x10(8) kg yr(-1)) represents a local source of organic carbon to the open ocean.

Sediment redox tracers in Strait of Georgia sediments--can they inform us of the loadings of organic carbon from municipal wastewater?

Organic carbon composition and redox element (Mn, Cd, U, Re, Mo, SigmaS, AVS) distributions are examined in seven 210Pb-dated box cores collected from the Strait of Georgia, British Columbia to evaluate the potential for redox elements to reveal impacts of anthropogenic loadings of labile organic carbon to sediments. In particular, the cores have been collected widely including regions far from local anthropogenic inputs and from locations within the zone of influence of two municipal outfalls where sediments are exposed to enhanced organic loadings from outfalls. We find a wide natural range in organic carbon forcing within the basin sediments generally reflected as Mn enrichments near the surface in cores exhibiting slow organic oxidation and sulphide, Cd, Mo, U and Re enrichments in cores exhibiting higher organic oxidation rates. Concentration profiles for redox elements or organic carbon are misleading by themselves, as they are influenced strongly by sediment porosity and sedimentation rate, and the organic matter remaining in sediment cores is predominantly recalcitrant. Fluxes of redox elements together with rates of organic metabolism estimated from sedimentation rates provide a better picture of the organic forcing. One core, GVRD-3, collected within the zone of influence of the Iona municipal outfall (0.5 km away), exhibits the highest organic carbon oxidation rates, enhanced Ag fluxes in the sediment surface mixed layer and altered delta15N composition, all of which implicate outfall particulates. Cd is also elevated in the GVRD-3 surface sediments, but evidence points to contamination and not redox forcing supporting this observation. Uranium also shows enrichment at sites near the outfalls, possibly in response to enhanced microbial metabolism. Predominantly these cores exhibit a wide natural range of organic carbon fluxes and organic carbon oxidation rates, supported by fluxes of marine and terrigenous organic carbon, within which it is difficult to identify any significant impact from municipal outfall organic carbon.

Joined by geochemistry, divided by history: PCBs and PBDEs in Strait of Georgia sediments.

Polychlorinated biphenyls (PCBs) are relict contaminants, while polybrominated diphenyl ethers (PBDEs) are in increasing use. Using sediment cores collected in the Strait of Georgia, we demonstrate that the surface sediment concentration of PCBs is largely determined by environmental processes, such as sediment accumulation and mixing rates, while that of PBDEs is strongly influenced by proximity to source. The Iona Island wastewater outfall appears to be a primary pathway for PBDEs. As well, Vancouver Harbour is highly contaminated with both classes of chemical. BDE-209, the main component of deca-BDE, is the dominant PBDE congener. Environmental debromination is not evident. Currently, the ranges of the surface concentration of PCBs and PBDEs are similar to one another, but that will change in the future, as the concentration of PBDEs continues to rise. The experience with PCBs suggests that if PBDEs were banned today, it would take decades for inorganic sediment to bury them.

CT appearances of unilateral cleft palate 20 years after bone graft surgery.

PURPOSE: To describe CT appearances in patients with unilateral cleft lip and palate (CLP) 20 years after bone graft surgery. MATERIAL AND METHODS: Eighteen consecutive patients with unilateral CLP were examined. All patients had been treated with primary closure, both in infancy and early childhood, supplemented with bone grafting at the age of around 10 years. The CT examination of the upper jaw included a dental CT program. The CT appearances of the cleft side were compared with those of the untreated non-cleft side. RESULTS: Abnormal CT appearances included skew nasal aperture (n=17), nasal septal deviation (n=17), low floor of nasal aperture (n=15) at or towards the cleft side, and deviation of anterior nasal spine towards the non-cleft side (n=18). The posterior part of the bone cleft was visible in all patients, and the dental arch was V-shaped in 8. CONCLUSION: Although adherence to the present treatment protocol is considered to give satisfactory functional and cosmetic results, certain abnormalities persist. A knowledge of these is a prerequisite for a complete and final evaluation of the surgical and orthodontic regimen.

Progress report on new antiepileptic drugs: a summary of the Sixth Eilat Conference (EILAT VI).

The Sixth Eilat Conference on New Antiepileptic Drugs (AEDs) took place in Taormina, Sicily, Italy from 7th to 11th April, 2002. Basic scientists, clinical pharmacologists and neurologists from 27 countries attended the conference, whose main themes included dose-response relationships with conventional and recent AEDs, teratogenic effects of conventional and recent AEDs, update on clinical implications of AED metabolism, prevention of epileptogesis, and seizure aggravation by AEDs. According to tradition, the central part of the conference was devoted to a review of AEDs in development, as well to updates on AEDs, which have been marketed in recent years. This article summarizes the information presented on drugs in preclinical and clinical development, including carabersat (SB-204269), CGX-1007 (Conantokin-G), pregabalin, retigabine (D-23129), safinamide, SPD421 (DP-VPA), SPM 927, talampanel and valrocemide (TV 1901). Updates on fosphenytoin, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin, zonisamide, new formulations of valproic acid, and the antiepileptic vagal stimulator device are also presented.

Recurrent conventional cemento-ossifying fibroma of the mandible.

Cemento-ossifying fibromas are slow growing, benign lesions. Recurrence is considered rare. A mandibular periapical radiolucent lesion in a 30-year-old female was diagnosed histologically as a cemento-ossifying fibroma and excised. A recurrence was found 2 years and 6 months postoperatively. CT demonstrated that the recurrent lesion was larger than indicated by conventional radiography.

Ortho cubic super-high resolution computed tomography: a new radiographic technique with application to the temporomandibular joint.

OBJECTIVE: The purpose of this study was to present a newly developed ortho cubic super-high resolution computerized radiographic technique (Ortho-CT) and its application to the temporomandibular joint. METHOD AND PATIENTS: A prototype was assembled on a Scanora (Soredex Findent Co) with the use of a 4-inch image intensifier instead of film. Data were collected from a single 360 degrees scan and a cylinder 32 mm in height and 38 mm in diameter. Images were reconstructed with a software program on a personal computer. Imaging data consisted of 240 (height) x 280 (diameter) cubic voxels, each with a dimension of 0.136 mm. With this small voxel size, the image resolution was high and was the same in any direction. Three patients with temporomandibular joint disease (trauma, pain and dysfunction, fibroosseous ankylosis) were evaluated with Ortho-CT, and the images were compared to routine radiographic films. CONCLUSION: Preliminary clinical experience with Ortho-CT demonstrates subjectively superior image quality compared to panoramic and conventional tomographic images. The images were similar to conventional computed tomography, but this new radiographic technique is less expensive, takes less space, and gives a lesser patient dose.

Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V).

The Fifth Eilat Conference on New Antiepileptic Drugs (AEDs) took place at the Dan Hotel, Eilat, Israel, 25-29 June 2000. Basic scientists, clinical pharmacologists and neurologists from 20 countries attended the conference, whose main themes included recognition of unexpected adverse effects, new indications of AEDs, and patient-tailored AED therapy. According to tradition, the central part of the conference was devoted to a review of AEDs in development, as well to updates on AEDs that have been marketed in recent years. This article summarizes the information presented on drugs in preclinical and clinical development, including AWD 131-138, DP-valproate, harkoseride, LY300164, NPS 1776, NW 1015, pregabalin, remacemide, retigabine, rufinamide and valrocemide. The potential value of an innovative strategy, porcine embryonic GABAergic cell transplants, is also discussed. Finally, updates on felbamate, fosphenytoin, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin, zonisamide, and the antiepileptic vagal stimulator device are presented.

Gabapentin versus vigabatrin as first add-on for patients with partial seizures that failed to respond to monotherapy: a randomized, double-blind, dose titration study. GREAT Study Investigators Group. Gabapentin in Refractory Epilepsy Add-on Treatment.

PURPOSE: Our objective was to compare the efficacy and safety of gabapentin and vigabatrin as first-line add-on treatment in patients with partial epilepsy. METHODS: This was a multicenter, double-blind, randomized dose titration study. After baseline assessment and randomization, the dose could be increased if seizures persisted and reduced if side effects occurred. Health-related quality of life was assessed at baseline and at the end of the study. By a protocol amendment post hoc, all randomized patients were offered a standardized perimetry examination at the end of the study. Improvement rate was the proportion of patients with a reduction of seizure frequency of at least 50% during an 8-week period without any adverse events causing withdrawal. RESULTS: One hundred two patients were randomized and analyzed on an intent-to-treat basis. The improvement rate was 48% in the gabapentin group and 56% in the vigabatrin group. The improvement rate, when per protocol criteria were fulfilled, was 57% in the gabapentin group and 59% in the vigabatrin group. The proportion of seizure-free patients was 31% in the gabapentin group and 39% in the vigabatrin group. There was no difference in quality-of-life scores between the groups. Perimetry after termination of the study on 64 patients showed abnormal results in 3 of 32 patients in the vigabatrin group. CONCLUSION: Approximately one third of the patients in both groups became seizure-free. Although no major differences were seen in terms of the improvement rate between the groups, equivalence between the two drugs was not found.

[Topiramate--a new antiepileptic agents]. / Topiramat--et nytt antiepileptikum.

BACKGROUND: Topiramate is a novel antiepileptic drug that was licensed in Norway in 1997 as adjunctive treatment for patients with partial seizures. Metaanalysis of randomized controlled studies suggest that topiramate may be the most potent of the new antiepileptic drugs and have a favourable pharmacokinetic profile. At the National Center for Epilepsy we have used topiramate since 1990. We present our clinical experience with the drug. MATERIAL AND METHODS: We have, retrospectively, assessed 114 adult patients, mainly with intractable partial seizures, who received topiramate as add-on treatment. Average follow-up was 2.3 years. RESULTS: Four patients (3.5%) became seizure free. The overall seizure frequency was reduced by > 50% in 56 patients (49%). Adverse effects were observed in 82 patients (72%); in 54 patients (47%) the drug had to be withdrawn due to unacceptable side effects and/or lack of clinical effect. The most frequent side effects were weight loss, fatigue, behavioural and cognitive problems. INTERPRETATION: Our results corroborate an impression of topiramate being an effective drug used as adjuntive therapy in patients with refractory epilepsy. Side effects can be a problem, but a low starting dose, a slow dose escalation, and topiramate used alone may reduce this problem.