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Find video protocols related to scientific articles indexed in Pubmed.
Epilepsy-related clinical characteristics and mortality: A systematic review and meta-analysis.
Neurology
PUBLISHED: 10-22-2014
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We systematically synthesized the epidemiologic literature on mortality in patients with epilepsy (PWE) by epilepsy-related clinical characteristics with an aggregate data meta-analysis.
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Clobazam is efficacious for patients across the spectrum of disease severity of Lennox-Gastaut syndrome: Post hoc analyses of clinical trial results by baseline seizure-frequency quartiles and VNS experience.
Epilepsy Behav
PUBLISHED: 08-01-2014
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Lennox-Gastaut syndrome (LGS) severity varies considerably, so the potential impact of differences in baseline severity on patient outcome following treatment is clinically informative. Here, two surrogate indicators of LGS severity (baseline seizure frequency and vagus nerve stimulation [VNS] use) were used in post hoc analyses of both short- and long-term clobazam trials (Phase III OV-1012 [CONTAIN] and open-label extension [OLE] OV-1004). In CONTAIN, 217 patients comprised the modified, intention-to-treat population. Each baseline seizure-frequency quartile had ~40 patients, and baseline weekly drop-seizure frequency ranges were as follows: <10 (Quartile 1), 10-30 (Quartile 2), 32-86 (Quartile 3), and 86-1077 (Quartile 4). Mean percentage decreases in average weekly drop and total seizures were similar for all quartiles. More than 50% of patients in all 4 quartiles demonstrated ?50% decreases in weekly drop- and total-seizure frequency. The percentage of patients achieving 100% reduction in drop seizures was 33% for clobazam-treated patients (vs. 7% for placebo) in Quartile 1. Five percent of clobazam-treated patients in Quartile 4 (most severe LGS) vs. 0% for placebo achieved 100% reduction in drop seizures. A total of 267 of 306 possible patients entered the OLE (61/68 from a Phase II study and 206/238 from Phase III CONTAIN). Each quartile had ~66 patients, and baseline weekly drop-seizure ranges were as follows: <10 (Quartile 1), 10-31 (Quartile 2), 32-110 (Quartile 3), and 111-1147 (Quartile 4). Median percentage decreases in average weekly drop and total seizures were similar between quartiles. Through 5years of therapy, >50% of patients in all 4 quartiles demonstrated ?50% decreases in weekly frequency for drop seizures. More than 12% of patients in Quartile 4 achieved 100% reduction in drop seizures from Month 3 through Year 5. For the VNS analyses in CONTAIN, the least-squares mean decreases in average weekly rate of drop seizures (mITT population) were 52% for VNS patients receiving clobazam vs. -22% for placebo (p<0.01). For non-VNS patients, these percentages were 53% for clobazam and 26% for placebo (p<0.01). Moreover, 50% and 54% of clobazam-treated patients in the VNS and non-VNS groups demonstrated ?50% decreases in average weekly drop- and total-seizure frequencies, and 11% and 14% in the two groups achieved drop-seizure freedom, respectively. Analyses using baseline seizure frequency and VNS use as surrogates for disease severity showed that clobazam treatment of patients with less severe or severe LGS was equally efficacious.
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Autoimmunity-related immunological serum markers and survival in a tertiary care cohort of adult patients with epilepsy.
Epilepsy Res.
PUBLISHED: 07-26-2014
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We evaluated mortality in relation to a panel of autoimmunity-related immunological serum markers in adult patients with epilepsy (PWE), seen in 1996-1997 at the Department of Neurology, Oulu University Hospital in Finland. Blood samples were drawn from 968 volunteers, and baseline measurements included serum immunoglobulins (IgG, IgA, and IgM), and the following antibodies: anticardiolipin, antinuclear, antimitochondrial, antigliadin (IgA and IgG classes), IgA tissue transglutaminase, and IgA endomysial. Hazard ratios (HR) for all-cause mortality in PWE with abnormal immunological markers relative to 413 patients with normal findings were evaluated with adjustment for confounders during a follow-up of nine years. Borderline statistically significant associations were found only for elevated IgA (HR 2.09, 95% CI 0.99-4.42) and for having two or more abnormal antibody titers (HR 1.58, 95% CI 0.98-2.56). The findings of this exploratory study suggested that elevated serum IgA might be associated with excess mortality in PWE.
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Efficacy of lacosamide by focal seizure subtype.
Epilepsy Res.
PUBLISHED: 05-30-2014
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The purpose of this post hoc exploratory analysis was to determine the effects of the antiepileptic drug, lacosamide, on focal (partial-onset) seizure subtypes. Patient data from the three lacosamide pivotal trials were grouped and pooled by focal seizure subtype at Baseline: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized partial seizures (SGPS). Both efficacy outcomes (median percent change from Baseline to Maintenance Phase in seizure frequency per 28 days and the proportion of patients experiencing at least a 50% reduction in seizures) were evaluated by lacosamide dose (200, 400, or 600 mg/day) compared to placebo for each seizure subtype. An additional analysis was performed to determine whether a shift from more severe focal seizure subtypes to less severe occurred upon treatment with lacosamide. In patients with CPS or SGPS at Baseline, lacosamide 400 mg/day (maximum recommended daily dose) and 600 mg/day reduced the frequency of CPS and SGPS compared to placebo. Likewise, a proportion of patients with CPS and SGPS at Baseline experienced at least a 50% reduction in the frequency of CPS and SGPS (?50% responder rate) in the lacosamide 400 and 600 mg/day groups compared with placebo. For both outcomes, numerically greatest responses were observed in the lacosamide 600 mg/day group among patients with SGPS at Baseline. In patients with SPS at Baseline, no difference between placebo and lacosamide was observed for either efficacy outcome. An additional exploratory analysis suggests that in patients with SPS at Baseline, CPS and SGPS may have been shifted to less severe SPS upon treatment with lacosamide. The results of these exploratory analyses revealed reductions in CPS and SGPS frequency with adjunctive lacosamide. Reduction in CPS and SGPS may confound assessment of SPS since the CPS or SGPS may possibly change to SPS by effective treatment.
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Withdrawal-related adverse events from clinical trials of clobazam in Lennox-Gastaut syndrome.
Epilepsy Behav
PUBLISHED: 03-21-2014
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To assess withdrawal-related adverse event (AE) rates following abrupt clobazam discontinuation in Phase I trials and gradual clobazam tapering (2-3 weeks) following discontinuation from III trials met the criteria for potential/III trials, we evaluated AE data from four multiple-dosage Phase I trials (duration: 8-34 days). Therapeutic (20 and 40 mg/day) and supratherapeutic clobazam dosages (120 and 160 mg/day) were administered. Adverse events (AEs) were also assessed for patients with Lennox-Gastaut syndrome enrolled in Phase II (OV-1002) and Phase III (OV-1012) studies (duration ?15 weeks) and in the open-label extension (OLE) trial OV-1004 (?5 years). Potential withdrawal-related AEs were identified by preferred terms, provided that the AEs occurred ?1 day following and ?30 days after the last clobazam doses, or were deemed withdrawal symptoms by investigators. Clinical Institute Withdrawal Assessment for Benzodiazepines (CIWA-B) scale was used to evaluate withdrawal intensity in three of the four Phase I trials. A total of 207 participants in Phase I trials received steady-state clobazam dosages of 20-160 mg/day, 182 received clobazam dosages of ?40 mg/day, and 94 received clobazam dosages of ?120 mg/day. Abrupt clobazam discontinuation led to 193 withdrawal-related AEs for 68 Phase I participants. Nearly 50% of AEs occurred after discontinuation of clobazam dosages of ?120 mg/day. Adverse events were mild or moderate and included headache (14% of Phase I participants), insomnia (12.6%), tremor (10.1%), and anxiety (8.7%). The CIWA-B scores varied (range: 0-59). Most scores were <30, indicating possible mild benzodiazepine withdrawal. III trials met the criteria for potential/III patients received clobazam dosages of ?40 mg/day, and those in the OLE trial received clobazam dosages of ?80 mg/day. Eighty-seven patients discontinued clobazam and were gradually tapered. No withdrawal-related AEs or incidences of status epilepticus were reported. Withdrawal-related AEs observed in Phase I studies following abrupt clobazam discontinuation at therapeutic and supratherapeutic dosages were generally mild. No withdrawal-related AEs occurred when dosages were tapered over 3 weeks, after short- or long-term clobazam use (?5 years).
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Long-term mortality risk by cause of death in newly diagnosed patients with epilepsy in Finland: a nationwide register-based study.
Eur. J. Epidemiol.
PUBLISHED: 09-02-2013
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To estimate long-term mortality by cause of death in a nationwide, register-based cohort of newly diagnosed patients with epilepsy (PWE). All noninstitutionalized Finnish PWE aged 10-74 years (n = 10,818) eligible for reimbursement for antiepileptic medication for the first time between 1990 and 1994 were identified in the database of Social Insurance Institution of Finland. Mortality was compared against a population-based reference cohort (n = 43,894). Hazard ratios (HR) and their 95 % confidence intervals (95 % CI) during a follow-up of 18 years were estimated using proportional hazards modeling. Potential years of life lost (PYLL) and excess fraction of causes of death attributable to epilepsy were estimated. PWE contributed 137,610 person-years of observation and there were 3,558 deaths. Mortality remained elevated up to 18 years post-diagnosis (HR 3.21, 95 % CI 3.07-3.35). Ischemic heart disease mortality in PWE was two-fold (HR 2.31, 95 % CI 2.09-2.54), and remained constantly elevated during entire follow-up in both men and women. Most premature mortality in terms of PYLL was attributable to brain cancer (17 %), other cancers (15 %), ischemic heart disease (11 %), as well as cerebrovascular diseases (10 %). The percentage of deaths in PWE statistically attributable to epilepsy was 3.9 % for accidents, 3.4 % for alcohol-related diseases, and 1.6 % for suicides. PWE had substantial excess mortality from non-communicable diseases, which did not disappear by 18 years. Diseases of the circulatory system and cancers, especially brain cancer, were the most important causes of death almost regardless of the mortality indicator.
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Perceived benefits of sharing health data between people with epilepsy on an online platform.
Epilepsy Behav
PUBLISHED: 06-20-2011
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An epilepsy community was developed on PatientsLikeMe.com to share data between patients to improve their outcomes by finding other patients like them. In a 14-day response period, 221 patients with epilepsy (mean age: 40 years, SD: 12, range: 17-72, 66% female) completed a survey about benefits they perceived. Prior to using the site, a third of respondents (30%) did not know anyone else with epilepsy with whom they could talk; of these, 63% now had at least one other patient with whom they could connect. Perceived benefits included: finding another patient experiencing the same symptoms (59%), gaining a better understanding of seizures (58%), and learning more about symptoms or treatments (55%). Number of benefits was associated with number of relationships with other patients, F(4,216)=8.173, P<0.001). Patients with epilepsy reported an array of perceived benefits similar to those reported by populations with other diseases. Controlled sharing of health data may have the potential to improve disease self-management of people with epilepsy.
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Evaluation of Heart Rate Variation Analysis during Rest and Tilting in Patients with Temporal Lobe Epilepsy.
Neurol Res Int
PUBLISHED: 03-15-2011
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Objective. To evaluate spectral heart rate (HR) variation using short-term ECG recordings at rest and during the tilt table test. Methods. The values of spectral components of total power (TP), high-frequency power (HF), low-frequency power (LF) and LF: HF ratio were measured at rest and during the head-up tilt in patients with temporal lobe epilepsy (TLE) and their control subjects. Results. Compared to the control subjects, patients with TLE had lower HF (P < 0.05) and LF?:?HF ratio (P < 0.05) at rest and lower TP (P < 0.001), HF (P < 0.05), and LF (P < 0.05) during the head-up tilt. Upon changing from supine to standing position TP (P < 0.05) and LF (P < 0.05) were attenuated in patients with TLE compared to the control subjects. Conclusion. These results suggest that spectral analysis of HR variation from ECG recordings of short duration may add value to assessment of autonomic nervous system function using autonomic cardiac tests in patients with TLE.
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A pooled analysis of lacosamide clinical trial data grouped by mechanism of action of concomitant antiepileptic drugs.
CNS Drugs
PUBLISHED: 11-25-2010
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Lacosamide, a new antiepileptic drug (AED) with a different pharmacological action that enhances sodium channel slow inactivation, is approved for the adjunctive treatment of partial-onset seizures in adults. Previous analyses of pooled phase II/III trials have demonstrated that lacosamide provides additional efficacy when added to a broad range of AEDs.
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Examining the clinical utility of lacosamide: pooled analyses of three phase II/III clinical trials.
CNS Drugs
PUBLISHED: 11-25-2010
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Lacosamide is an antiepileptic drug (AED) approved for the adjunctive treatment of partial-onset seizures in adults. Completed phase II/III clinical trials of lacosamide provide a valuable opportunity to evaluate clinically relevant aspects of the resulting large patient pool.
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Heart rate dynamics in temporal lobe epilepsy-A long-term follow-up study.
Epilepsy Res.
PUBLISHED: 03-07-2010
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The aim of the present study was to prospectively evaluate long-term changes in interictal heart rate variability (HRV) in patients with temporal lobe epilepsy (TLE). A 24-h ECG was recorded at baseline and after a mean follow-up of 6.1 years in 18 patients with refractory TLE and 18 patients with well-controlled TLE. After the follow-up, the Poincaré components SD(1) (p=0.039) and SD(2) (p=0.001) were decreased in patients with refractory TLE compared to baseline, whereas in patients with well-controlled TLE no changes (p>0.05) in HR variability were observed. The reduction in HRV seems to be progressive in patients with chronic refractory TLE with recurrent seizures.
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Antiepileptic drugs and quality of life in the elderly: results from a randomized double-blind trial of carbamazepine and lamotrigine in patients with onset of epilepsy in old age.
Epilepsy Behav
PUBLISHED: 02-09-2010
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During an international double-blind trial evaluating the efficacy and tolerability of lamotrigine and carbamazepine in patients aged >or=65 with newly diagnosed epilepsy, the comparative effects of the drugs on health-related quality of life were investigated based on screening and 12-, 28-, and 40-week data, using the modified Side Effect and Life Satisfaction (SEALS) Inventory and the Liverpool Adverse Event Profile. Of 167 patients, 29 discontinued before first follow-up, and data were incomplete for 13. In 125 eligible subjects (62 taking carbamazepine, 63 taking lamotrigine), comparable baseline data did not change significantly during medication, within or across treatments. A borderline difference in the SEALS Dysphoria subscores favored lamotrigine. No difference between completers and noncompleters was identified. Twelve-week data for noncompleters were comparable across treatments. Changes in the inventories up to 40 weeks correlated moderately. Neither lamotrigine nor carbamazepine seems likely to cause significant changes in health-related quality of life measures after 40 weeks at therapeutic doses.
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Epilepsy in the northern Finland birth cohort 1966 with special reference to fertility.
Epilepsy Behav
PUBLISHED: 04-21-2009
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The aim of the study was to evaluate both the prevalence of epilepsy and the reproductive history of subjects with epilepsy in a population-based cohort study. The Northern Finland Birth Cohort 1966 (NFBC 1966) comprises 12,058 subjects with 39 years of follow-up. Of these subjects, 222 were identified as having epilepsy on the basis of information obtained from mailed questionnaires, hospital discharge registers, and records for reimbursed antiepileptic medications. The information on reproductive outcome was also updated. Both men and women with epilepsy did not differ from the reference group with respect to number of children. However, subjects with active epilepsy during adulthood had fewer children than those who achieved remission before adulthood. Subjects with epilepsy who achieved remission before adulthood did not differ from control subjects with respect to number of children.
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Cardiac function and antiepileptic drug treatment in the elderly: a comparison between lamotrigine and sustained-release carbamazepine.
Epilepsia
PUBLISHED: 03-23-2009
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To investigate the comparative effects of carbamazepine (CBZ) and lamotrigine (LTG) on electrocardiography (ECG) parameters in elderly patients with newly diagnosed epilepsy.
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Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study.
Epilepsy Behav
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In an ongoing open-label extension (OV-1004), patients with Lennox-Gastaut syndrome who had completed 1 of 2 randomized controlled trials (OV-1002 [Phase II] or OV-1012 [Phase III]) are receiving clobazam at dosages ?2.0 mg/kg/day (?80 mg/day). Of 306 eligible patients from OV-1002 or OV-1012, 267 entered the open-label extension. As of the interim date, July 1, 2010, 213 patients (79.8%) had remained in the trial, and 189 had received clobazam for ?12 months, 128 for ?18 months, and 94 for ?24 months. Median percentage decreases in average weekly rates of drop seizures were 71.1% and 91.6% at Months 3 and 24. Mean modal and mean maximum daily dosages were 0.94 mg/kg and 1.22 mg/kg for those who had received clobazam for ?1 year. The 4 most common adverse events were upper respiratory tract infection (18.4%), fall (14.2%), pneumonia (13.9%), and somnolence (12.7%). Clobazams adverse event profile was consistent with its profile in controlled trials.
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Mortality by clinical characteristics in a tertiary care cohort of adult patients with chronic epilepsy.
Epilepsia
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The authors evaluated the contribution of various clinical characteristics to mortality risk and underlying causes of death among all adult patients with epilepsy seen at the Department of Neurology, Oulu University Hospital in Finland during 1996 and 1997. Hazard ratios (HRs) for mortality in 1998-2006 relative to a population-based reference cohort were estimated using Cox modeling, with adjustment for age and gender. The HR for total mortality was 2.66 (95% confidence interval [CI] 2.09-3.39). Infectious etiology of epilepsy (HR 5.77, 95% CI 2.52-13.2) and a seizure frequency of ?1 per month (HR 4.42, 95% CI 3.00-6.52) related to high risks of death. Cancer (21%), ischemic heart disease (15%), and accidents (12%) caused most of the potential years of life lost. Despite recent advances in treatment of epilepsy and improved seizure control, chronic epilepsy still carries a substantially increased risk of death.
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High concentration of immunoglobulin A is associated with temporal lobe epilepsy.
Epilepsy Res.
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Dysfunction of immunoglobulins (Igs) has been detected in association with antiepileptic drugs (AEDs) and in newly diagnosed epilepsy patients. The aim of this study was to evaluate the effect of clinical features and the current or past use of AEDs on serum Ig concentrations in a well-examined group of patients with refractory epilepsy.
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Safety and tolerability of adjunctive lacosamide intravenous loading dose in lacosamide-naive patients with partial-onset seizures.
Epilepsia
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To examine the safety and tolerability of rapidly initiating adjunctive lacosamide via a single intravenous loading dose followed by twice-daily oral lacosamide in lacosamide-naive adults with partial-onset seizures.
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Long-term safety and efficacy in patients with uncontrolled partial-onset seizures treated with adjunctive lacosamide: results from a Phase III open-label extension trial.
Epilepsia
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To evaluate the long-term (up to 5 years exposure) safety and efficacy of lacosamide as adjunctive therapy in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs) in open-label extension trial SP756 (NCT00522275).
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.