A multicenter randomized controlled feasibility trial of a digital self-management intervention for adults with epilepsy.

OBJECTIVE: Self-management interventions may enhance health-related quality of life (HRQoL) in epilepsy. However, several barriers often impair their implementation in the real world. Digital interventions may help to overcome some of these barriers. Considering this, the Helpilepsy Plus Prototype was developed as a prototype smartphone-delivered self-care treatment program for adults with epilepsy. METHODS: The 12-week Helpilepsy Plus Prototype was evaluated through a randomized controlled feasibility trial with a waiting-list control (WLC) group. Outcome measurement at baseline and at 12 weeks assessed adherence to the prototype intervention and changes in epilepsy-related outcomes. The primary endpoint was patient autonomy measured with EASE, and secondary endpoints included HRQoL measured with QOLIE-31, health literacy measured with HLQ, anxiety, and depression symptoms measured with HADS. Semi-structured interviews were conducted with a heterogeneous sample of participants to assess user-friendliness and usefulness. The prototype program was delivered through the Neuroventis Platform (Neuroventis, BV, Overijse, Belgium), a certified medical device (under EU/MDD Class I, and EU/MDR grace period). RESULTS: Ninety-two patients were included (46 in the intervention group, 46 in WLC). Most participants (63%, 58/92 women, median age 30 years) had pharmacoresistant epilepsy (61%, 56/92). Only 22% of participants (10/46) in the intervention group completed at least half of all intervention sessions. No significant differences between the intervention group and WLC were observed. Although there was a larger proportion of patients in the intervention group with meaningful improvements in HRQoL compared to WLC (19/46 versus 11/46), the difference was not significant (p = 0.119). Qualitative feedback showed that participants would appreciate more personalization, such as adaptation of the content to their current epilepsy knowledge level, a more interactive interface, shorter text sections, and interaction through reminders and notifications. SIGNIFICANCE: Digital interventions should allow sufficient scope for personalization and interaction to increase patient engagement and enable benefits from self-care apps. Feedback loops allow the participatory development of tailored interventions. PLAIN LANGUAGE SUMMARY: In this study, we investigated the effectiveness of an app-based self-help intervention. Study participants were either randomly assigned to a group that had access to the app or a group that received access to the app after the end of the study. Although a larger proportion of participants in the intervention group showed a relevant improvement in quality of life, the difference between the two groups was not statistically significant. Less than one-fifth of participants in the intervention group attended at least half of all intervention sessions; patient feedback showed that patients required more personalization and interactive options.

Challenges to epilepsy management in Rwandan women living with epilepsy.

BACKGROUND AND PURPOSE: In Rwanda, epilepsy prevalence ranges between 29‰ and 49‰. Many women living with epilepsy (WwE) are of childbearing age. Epilepsy characteristics and management, contraception, pregnancy, puerperium and stigma in WwE presenting at the neurology clinic of Ndera, Rwanda, were investigated. METHODS: This prospective cross-sectional study investigated demographics, epilepsy characteristics, treatment, contraception, folic acid use, pregnancy, puerperium and stigma in WwE aged ≥18 years. Subgroups were analysed by status of any pregnancy and time of epilepsy diagnosis relative to pregnancy, with significant differences expected. RESULTS: During December 2020 and January 2021, a hundred WwE were enrolled (range 18-67 years). Fifty-two women had never been pregnant, 39 women had epilepsy onset before pregnancy and nine were diagnosed after pregnancy. No significant differences in age, marital status or occupation were observed. Contraception was used by 27%, of whom 50% were taking enzyme-inducing anti-epileptic medication. Valproate was used by 46% of WwE of reproductive age. Thirty-nine women with epilepsy onset before pregnancy reported 91 pregnancies, with 14% spontaneous abortions. None used folic acid before conception, and 59% only during pregnancy. Five of 78 newborns were preterm. No offspring had major congenital malformations. Nearly 25% of WwE were not compliant with their anti-epileptic medication schedule during pregnancy or breastfeeding. Internalized stigma was observed in more than 60%. Up to 25% had been discriminated against at school or work. CONCLUSION: A comprehensive strategy considering the reproductive health and societal challenges of WwE is needed to drive optimal epilepsy management, reproductive health outcomes and societal inclusion.

Very high epilepsy prevalence in rural Southern Rwanda: The underestimated burden of epilepsy in sub-Saharan Africa.

OBJECTIVES: Up to 85% of people living with epilepsy (PwE) reside in low-and middle-income countries. In sub-Saharan Africa, the lifetime prevalence of epilepsy is 16 per 1000 persons. In Northern rural Rwanda, a 47.7 per 1000 prevalence has been reported. As variations in prevalence across geographical areas have been observed, we studied the prevalence in Southern rural Rwanda using the same robust methodology as applied in the North. METHODS: We conducted a three-stage, cross-sectional, door-to-door survey in two rural villages in Southern Rwanda from June 2022 to April 2023. First, trained enumerators administered the validated Limoges questionnaire for epilepsy screening. Second, neurologists examined the persons who had screened positively to confirm the epilepsy diagnosis. Third, cases with an inconclusive assessment were separately reexamined by two neurologists to reevaluate the diagnosis. RESULTS: Enumerators screened 1745 persons (54.4% female, mean age: 24 ± 19.3 years), of whom 304 (17.4%) screened positive. Epilepsy diagnosis was confirmed in 133 (52.6% female, mean age: 30 ± 18.2 years) and active epilepsy in 130 persons. Lifetime epilepsy prevalence was 76.2 per 1000 (95% CI: 64.2-89.7‰). The highest age-specific rate occurred in the 29-49 age group. No gender-specific differences were noted. In 22.6% of the PwE, only non-convulsive seizures occurred. The treatment gap was 92.2%, including a diagnosis gap of 79.4%. CONCLUSION: We demonstrated a very high epilepsy prevalence in Southern rural Rwanda, with over 20% of cases having only non-convulsive seizures, which are often underdiagnosed in rural Africa. In line with previous Rwandan reports, we reiterate the high burden of the disease in the country. Geographic variation in prevalence throughout Africa may result from differences in risk and aetiological factors. Case-control studies are underway to understand such differences and propose adapted health policies for epilepsy prevention.

Corrigendum: Long-Term Impact of Single Epilepsy Training on Knowledge, Attitude and Practices: Comparison of Trained and Untrained Rwandan Community Health Workers.

[This corrects the article DOI: 10.3389/ijph.2021.645598.].

Epilepsy-Related Direct Medical and Direct Non-Medical Cost in Adult Patients Living with Epilepsy at a Tertiary Neurology Center in Rwanda.

Objective: Up to one in four patients living with epilepsy (PwE) mentions financial constraints as a reason for loss to follow-up at the Ndera tertiary neuropsychiatry hospital. Therefore, we evaluated the annual direct medical cost (DMC) and direct non-medical cost (DnMC) of epilepsy and calculated costs assuming different follow-up frequency. Materials and Methods: DMC data were obtained from a descriptive retrospective study of medical records, pharmacy dispensation and hospital logs of PwE, following their initial consultation in 2018 and who adhered to the normal clinical practice of monthly consultations for one year. DnMC data were collected through structured interviews of PwE in a cross-sectional cohort in August 2020. DnMC included biomedical care costs (eg, transportation, hospitality) and non-biomedical costs (traditional healer visits). We report weighted means for total costs, health insurance costs, and out-of-pocket costs (OoP). Results: Mean annual total cost was 389.4 US$, of which 226.2 US$ was covered by the Rwandan Health Insurance co-payment for DMC and 163.2 US$ was OoP paid by patients. Mean weighted annual DMC (n = 55) was 248.9 US$. Mean weighted annual DMC for medical consultations and antiseizure medication accounted for 30.7 US$ and 161.7 US$, respectively. Based on structured interviews (n = 69), mean weighted annual DnMC for biomedical care was 73.0 US$. Mean DnMC for traditional healer care was 67.6 US$. Weighted annual total OoP was 163.2 US$ or 20% of the GDP per capita. OoP consisted of 14% DMC co-payment, 45% biomedical DnMC, and 41% traditional healer DnMC. Conclusion: Epilepsy-related costs at a tertiary center are an important economic burden for PwE and Rwandan Health Insurance. Biomedical and traditional healer DnMC constitute 86% of total OoP. Future prospective studies should evaluate outcomes and costs of reduced visit frequency, indirect costs, and costs of comorbidities.

Association of depression and epilepsy in Rwanda: A prospective longitudinal study.

INTRODUCTION: Depression is the most common psychiatric comorbidity for persons living with epilepsy. In Rwanda, the prevalence of epilepsy and depression are high, with 4,9% and 13.0% respectively. This prospective interventional study aimed to determine the prevalence and incidence of depression and the outcome of persons living with epilepsy (PwE) with depression attending the outpatient neurology department of a tertiary center. METHODS: Persons living with epilepsy enrolled between February and June 2018 in a screening cohort with a 12-month follow-up. At every 3-month study visit, PwE were screened for depression using the Patient Health Questionnaire (PHQ-9) questionnaire. Any positively screened subject was administered the Hamilton Depression Rating Scale (HDRS) to confirm the diagnosis and severity of depression. Subjects with moderate to severe depression (MSD), were started on treatment and were followed for another year. We describe the prevalence and incidence of depression, baseline characteristics, epilepsy and depression outcomes, and changes in PGI-C. RESULTS: Of 572 PwE enrolled, 46 were diagnosed with MSD in a twelve-month period, resulting in an incidence of MSD of 32.7/1000 patient-years. The prevalence of any depression and MSD was 14.2% and 4.7%, respectively. Longer epilepsy duration and seizure status at baseline were associated with MSD. Significant improvements in PGI-C and seizure frequency were observed after treatment optimization. CONCLUSION: The use of PHQ-9 and HDRS proved successful in identifying depression in PwE. Combined treatment of epilepsy and depression resulted in improved outcomes, warranting the implementation of depression screening every six months in daily neurology practice.

Effectiveness of community health workers on identification and mobilization of persons living with epilepsy in rural Rwanda using a validated screening tool.

INTRODUCTION: Engagement and training of community health workers (CHWs) have demonstrated their value in different conditions. Despite repeat epilepsy trainings of CHWs in Northern Rwanda, the treatment gap remained high. We hypothesized that effectiveness of CHWs on mobilization of patients living with epilepsy (PwE) could be improved using a validated tool for epilepsy screening. METHODS: CHWs associated with health centers (HCs) of Gataraga, Kimonyi and Karwasa attended a 1-day training on epilepsy and Limoges epilepsy screening questionnaire (Kinyarwanda version). Thereafter, CHWs screened households in their villages for persons with one or more positive answer. CHWs then accompanied positively screened persons to a consultation for clinical evaluation and diagnosis by neurologists, and demographic data were collected. CHW variables were collected retrospectively. RESULTS: A total of 1308 persons were screened positive by 281 CHWs. Clinical diagnosis of epilepsy was confirmed in 589 and in 93 additional unscreened PwE, presenting voluntarily at the consultation. Pre-intervention number of 48 PwE increased to 682 after, a 14.2-fold increase. The overall treatment gap amounted to 93.0%. The age distribution of male PwE preponderance at younger age inverted to females at older age. CHW characteristics showed non-significant differences within and across HCs. Logistic regression did not relate CHW age, gender, and experience to screening results. DISCUSSION: Equipping CHWs with a validated screening tool was effective in identifying and mobilizing PwE in a short time frame and offers opportunity for future scaling. Nonetheless, barriers to sustainability of care will need to be addressed before.

Long-Term Impact of Single Epilepsy Training on Knowledge, Attitude and Practices: Comparison of Trained and Untrained Rwandan Community Health Workers.

Objectives: To close the epilepsy treatment gap and reduce related stigma, eradication of misconceptions is importantIn 2014, Community Health Workers (CHWs) from Musanze (Northern Rwanda) were trained on different aspects of epilepsy. This study compared knowledge, attitude and practices (KAPs) towards epilepsy of trained CHWs 3 years after training, to untrained CHWs from Rwamagana (Eastern Rwanda). Methods: An epilepsy KAP questionnaire was administered to 96 trained and 103 untrained CHWs. Demographic and intergroup KAP differences were analysed by response frequencies. A multivariate analyses was performed based on desired and undesired response categories. Results: Epilepsy awareness was high in both groups, with better knowledge levels in trained CHWs. Negative attitudes were lowest in trained CHWs, yet 17% still reported misconceptions. Multivariate analysis demonstrated the impact of the training, irrespective of age, gender and educational level. Knowing someone with epilepsy significantly induced more desired attitudes. Conclusion: Despite demographic differences between trained and untrained CHWs, a single epilepsy training resulted in significant improvement of desired KAPs after 3 years. Nation-wide CHW training programs with focus on training-resistant items, e.g., attitudes, are recommended.

High prevalence of epilepsy in Northern Rwanda: Exploring gender differences.

INTRODUCTION: In sub-Saharan Africa (SSA), the prevalence of lifetime epilepsy varies widely between subregions and is higher in rural compared to urban regions. Observed versus expected numbers of patients with epilepsy (PwE) in the northern province of Rwanda did not match the prevalence of 49‰ reported in 2005 in Rwanda. We report a confirmatory prevalence study focused on gender-specific observations. METHODS: A cross-sectional door-to-door approach was used in three rural villages. First, epilepsy screening using the Kinyarwanda version of the Limoges questionnaire was performed. Second, confirmation of epilepsy diagnosis was completed by trained physicians. RESULTS: In total, 2681 persons (56.14% female) were screened. Of 168 positively screened, 128 persons were diagnosed with epilepsy confirming the prevalence of lifetime epilepsy of 47.7‰ (CI 39.8-56.8). The diagnosis gap was 62.5% with 80 newly diagnosed. The overall female:male ratio was 1.61:1.00. A male preponderance below 9 years of age inverted to a female preponderance above 20 years of age. Female PwE had an older age at first seizure, reported different reasons for not seeking care, and differed from male PwE in possible etiology. For previously diagnosed PwE, the treatment gap was more than 77%. CONCLUSION: A high prevalence in rural areas was confirmed, with an observed female/male ratio among the highest of published door-to-door surveys in SSA. Gender differences in associated co-morbidities and age at first seizure warrant future research of underlying etiologies and possible survival bias. A better understanding and focus on gender-associated care-seeking patterns, education, and specific needs are recommended.

Letter to the Editor in response to Professor Josef Finsterer.

•Future actions to improve SUDEP reporting include training of healthcare professionals.•Future actions to improve SUDEP reporting include development of easy to use tools that ensure complete case reporting.

Mortality of all causes and sudden unexplained death in epilepsy (SUDEP) in a cohort of 235 persons living with epilepsy in Rwanda using WHO Verbal Autopsy Questionnaire.

INTRODUCTION: Mortality in persons living with epilepsy (PwE) is 1.6-9.3-fold higher than in the general population. Mortality from definite/probable Sudden Unexpected Death in EPilepsy (SUDEP) is estimated at 1.2 per 1000 person-years. We report mortality and SUDEP rate in a cohort of Rwandan PwE. METHODS: PwE presenting for a first visit at the Ndera epilepsy center between January and June 2016 were followed-up prospectively. For PwE who did not attend their follow-up visit, home visits were organized. Deaths were assessed using World Health Organization Verbal Autopsy Standards age-specific questionnaires. RESULTS: Of 235 PwE enrolled, home visits were organized for 81 (34.4%) PwE who did not return for their follow-up consultation. Seven fatalities (mortality 16.7/1000 patient-years [CI 6.7-34.3]) were recorded (aged 2-80 years). Four had an identified cause. Three were classified as probable SUDEP, resulting in a probable SUDEP rate of 7.1/1000 patient-years (CI 1.47-20.86). Probable SUDEP occurred in PwE (age: 2, 21, 34 years) showing no symptoms of illness while receiving antiepileptic treatment; in two cases, death occurred during sleep. CONCLUSION: Although autopsies were absent, the high mortality and probable SUDEP rates warrant future studies to establish causes of epilepsy-related deaths in Rwanda and sub-Saharan Africa.

Validity, Reliability, and Diagnostic Cut-off of the Kinyarwandan Version of the Hamilton Depression Rating Scale in Rwanda.

Introduction: In Rwanda, major depressive disorder affects 11.9% of the population and up to 35% of genocide survivors. Mental health services remain underutilized due to stigma and lack of awareness. Increasing the ability and capacity to diagnose and treat mental disorders is considered important to close this gap. We describe the translation, validity, and reliability assessment of the Hamilton Depression Rating Scale (HDRS) as a diagnostic tool for moderate to severe depression in Rwanda. Methods: The HDRS-21 was translated by a multi-group taskforce. We validated the translation against expert assessment in a comparative study on a sample of patients living with depression and of healthy volunteers. Psychometric properties, namely internal structure, reliability, and external validity were assessed using confirmatory factor analysis, three reliability calculations, and correlation analysis, respectively. Maximized Youden's index was used for determining diagnostic cut-off. Results: The translated version demonstrated a kappa of 0.93. We enrolled 105 healthy volunteers and 105 patients with confirmed mild to severe depression. In the confirmatory factor analysis, HDRS had good factor loadings of 0.32-0.80. Reliability coefficients above 0.92 indicated strong internal consistency. External validity was shown by good sensitivity (0.95) and specificity (0.94) to differentiate depression from absence of depression. At a cut-off point of 17 for the diagnosis of depression, sensitivity and specificity were both 0.95 relative to gold standard. Conclusion: The validated HDRS in Kinyarwanda with diagnostic cut-off provides mental healthcare staff with an accurate tool to diagnose moderate to severe depression, enabling closure of the diagnosis and treatment gap.

Validity, reliability and cut-offs of the Patient Health Questionnaire-9 as a screening tool for depression among patients living with epilepsy in Rwanda.

BACKGROUND: Patients with epilepsy (PwE) have an increased risk of active and lifetime depression. Two in 10 patients experience depression. Lack of trained psychiatric staff in low- and middle-income countries (LMIC) creates a need for screening tools that enable detection of depression in PwE. We describe the translation, validity and reliability assessment of the Patient Health Questionnaire-9 (PHQ-9) as a screening tool for depression among PwE in Rwanda. METHOD: PHQ-9 was translated to Kinyarwanda using translation-back translation and validated by a discussion group. For validation, PwE of ≥15 years of age were administered the PHQ-9 and Hamilton Depression Rating Scale (HDRS) by trained psychiatry staff at Visit 1. A random sample of 20% repeated PHQ-9 and HDRS after 14 days to assess temporal stability and intra-rater reliability. Internal structure, reliability and external validity were assessed using confirmatory factor analysis, reliability coefficients and HDRS-correlation, respectively. Maximal Youden's index was considered for cut-offs. RESULTS: Four hundred and thirty-four PwE, mean age 30.5 years (SD ±13.3), were included of whom 33.6%, 37.9%, 13.4%, and 15.1% had no, mild, moderate and severe depression, respectively. PHQ-9 performed well on a one-factor model (unidimensional model), with factor loadings of 0.63-0.86. Reliability coefficients above 0.80 indicated strong internal consistency. Good temporal stability was observed (0.79 [95% CI: 0.68-0.87]). A strong correlation (R = 0.66, p = 0.01) between PHQ-9 and HDRS summed scores demonstrated robust external validity. The optimal cut-off for the PHQ-9 was similar (≥5) for mild and moderate depression and ≥7 for severe depression. CONCLUSION: PHQ-9 validation in Kinyarwanda creates the capacity to screen PwE in Rwanda at scores of ≥5 for mild or moderate and ≥7 for severe depression. The availability of validated tools for screening and diagnosis for depression is a forward step for holistic care in a resource-limited environment.

Comparing healthcare cost associated with the use of enzyme-inducing and non-enzyme active antiepileptic drugs in elderly patients with epilepsy in the UK: a long-term retrospective, matched cohort study.

BACKGROUND: In elderly patients (≥65 years of age) with epilepsy who take medications for comorbid conditions, some antiepileptic drugs (AEDs) may alter the metabolism of other treatments and increase the risk of adverse consequences and healthcare utilisation. This analysis compares healthcare costs associated with enzyme-inducing AEDs (EIAEDs) and non-enzyme active AEDs (nEAAEDs) use in elderly patients with epilepsy. METHODS: This retrospective matched cohort study used the Clinical Practice Research Datalink (CPRD) of UK primary care medical records, linked to the Hospital Episode Statistics (HES) database. Selected patients with epilepsy were ≥ 65 years and prescribed an EIAED or nEAAED between 2001 and 2010 (index) after ≥1 year without AEDs (baseline) and followed until the first occurrence of the following: end of HES data coverage, end of GP registration, or death; practice's up-to-standard status or addition of an AED belonging to another cohort or discontinuation of the last AED of that cohort. Propensity score matching reduced confounding factor effects between cohorts. Key outcomes included time to cohort treatment failure, time to index AED treatment failure, and direct healthcare costs in 2014 Pound Sterling (£) values. RESULTS: Overall, 1425 elderly patients were included: 964 with EIAEDs and 461 with nEAAEDs. At baseline, the EIAED cohort was older (mean age, 76.2 vs. 75.1 years) and a higher proportion were male. Baseline direct healthcare costs were similar. After matching (n = 210 each), and over the entire follow-up period, median monthly direct healthcare costs were higher for patients taking EIAEDs than nEAAEDs (£403 vs. £317; p = 0.0150, Mann-Whitney U). Costs were higher for patients remaining in the EIAED cohort after 3 follow-up years. The median time to cohort treatment failure for the EIAED cohort was 1110 days vs. 1175 days for the nEAAED cohort. CONCLUSION: Newly treated elderly patients with epilepsy were more likely to be prescribed EIAEDs than nEAAEDs. In matched cohorts, elderly patients with epilepsy treated with EIAEDs had higher average total direct and epilepsy-related healthcare costs than nEAAED-treated patients; this difference was greater than previously reported in the overall adult population. Changing treatment practices could improve patient care and reduce costs.

Changes in drug load during lacosamide combination therapy: A noninterventional, observational study in German and Austrian clinical practice.

INTRODUCTION: Effects of antiepileptic drug (AED) load changes in patients with focal seizures have not been well evaluated. METHODS: SP1065 (NCT01673282) was a noninterventional, prospective, observational study conducted in a clinical practice setting. Patients (aged ≥18 years) with focal seizures were enrolled within 7 days of being prescribed adjunctive lacosamide. Observation period was ~6 months. Drug load was assessed using percentage change in ratio of actual prescribed dose and World Health Organization defined daily dose (DDD) for concomitant AEDs and all AEDs (including lacosamide). Subgroups were defined for patients with at least one concomitant sodium channel-blocking AED (SCB [+]) and those without (SCB [-]). RESULTS: A total of 311 patients were assessed for safety, 302 for measurement of drug load, and 240 for effectiveness. Ratio of AED dose to DDD decreased for concomitant AEDs (-9.6%) and increased for all AEDs (including lacosamide; 15.5%). Median reduction in focal seizure frequency per 28 days was 100% (range: -100, 2275.8). 70.4% and 61.7% of patients had a ≥50% or ≥75% reduction in seizure frequency, respectively; 50.8% became seizure-free. In the SCB (+) subgroup (n = 149), ratio of AED dose to DDD decreased for concomitant AEDs (-15.0%) and increased for all AEDs (10.7%). In the SCB (-) subgroup (n = 153), ratio of AED dose to DDD decreased for concomitant AEDs (-4.4%) and increased for all AEDs (20.2%). Fifty-seven patients (18.3%) reported ADRs, most commonly dose >400 mg/d (7.1%). Seventeen patients (5.5%) had ADRs leading to discontinuation. SIGNIFICANCE: Addition of lacosamide resulted in reduction of concomitant AED drug load regardless of whether concomitant AEDs were SCB (+) or SCB (-). These results indicate that addition of lacosamide in patients with focal seizures could allow clinicians to withdraw or reduce the dose of less well-tolerated or less effective AEDs.

Safety and tolerability of adjunctive lacosamide in a pediatric population with focal seizures - An open-label trial.

PURPOSE: To evaluate safety and tolerability of adjunctive lacosamide in children with focal seizures. METHODS: Patients were eligible for this open-label, fixed-titration trial (SP0847; NCT00938431) if aged 1 month-17 years with focal seizures taking 1-3 antiepileptic drugs. Findings from Cohort 1, aged 5-11 years, who received lacosamide ≤8 mg/kg/day, informed dosing for age-based cohorts 2-5, who then received ≤12 mg/kg/day (≤600 mg/day). Oral lacosamide was initiated at 2 mg/kg/day (1 mg/kg bid) and uptitrated by 2 mg/kg/day/week to the maximum cohort-defined dose (maximum trial duration: 13 weeks). Patients who did not achieve the maximum cohort-defined dose were discontinued. RESULTS: Forty-seven patients (aged 6 months-≤17 years) enrolled (≥1 month-<4 years: n = 15; ≥4-<12 years: n = 23; ≥12-≤17 years: n = 9). 24/47 (51.1%) patients completed the trial at the maximum cohort-defined dose and 40/47 (85.1%) continued lacosamide in the extension trial. Treatment-emergent adverse events (TEAEs) were reported by 42/47 (89.4%) patients. The most common TEAEs (≥10% of patients) were vomiting (21.3%), diarrhea (14.9%), somnolence (12.8%), irritability, dizziness, and pyrexia (10.6% each). Twenty (42.6%) patients discontinued due to TEAEs, most commonly vomiting (8.5%), gait disturbance, dizziness, and somnolence (6.4% each). Six (12.8%) patients reported serious TEAEs, most commonly status epilepticus (3/47; 6.4%). CONCLUSION: This fixed-titration trial supports the safety of adjunctive lacosamide in children (aged 6 months-≤17 years) with focal seizures. The TEAE profile was generally consistent with that observed in trials in adults, and no new safety concerns were identified.

An ambispective cohort study on treatment outcomes of patients with epilepsy in a tertiary epilepsy center in Rwanda and recommendations for improved epilepsy care.

OBJECTIVE: Because outcome data inform and drive healthcare decisions and improvement of patient care, this study aimed to gain a deep understanding of sociodemographic profiles and treatment outcomes of newly presenting and recently diagnosed persons living with epilepsy (PwE) at a tertiary epilepsy center in Rwanda. METHODS: In June 2016 (T1), as a first stage of this single-center cohort study, an ambispective chart review was conducted on baseline sociodemographic and disease characteristics of PwE using a structured questionnaire. Missing data were obtained by phone interview. In 2017, follow-up data were collected by phone interview on treatment outcomes after 15-months (T2). RESULTS: Of 406 PwE screened, 235 were included at T1 and outcomes on 166 PwE were obtained at T2. More than 70% were <20 years of age, with a male preponderance. A high number of patients were aged ≥20 years, were single (67.4%), unemployed (41.5%), and had no formal education or primary level education (53.9%), possibly reflecting stigma. A mean delay in diagnosis since first seizure increased with age at first seizure, amounting to 3 years for patients aged ≥20 years. At T2, 69.6% of 166 patients who could be contacted reported no seizures in the previous month. Valproate monotherapy was the most frequently prescribed treatment. At T2, 47% had discontinued treatment, which was often not recommended by a physician, despite medical insurance coverage in >90% of patients. Only 19% reported an adverse event. Marked and partial improvement in quality of life (QoL) was reported by, respectively, 50.9% and 32.7% of patients. SIGNIFICANCE: Encouraging results on improved seizure control and QoL were observed at follow-up. The treatment gap remains high due to loss to follow-up and treatment discontinuation. In this article, we discuss needs and recommendations for improving patient care, requiring concerted efforts of stakeholders at all levels of the healthcare system.

The challenges of assessing effectiveness of lacosamide using electronic medical record databases.

PURPOSE: Electronic health record (EHR) databases are a potential source for conducting research to generate real world evidence on patient outcomes. The objective of the study was to evaluate the feasibility of using EHR data to assess seizure outcomes in patients treated with lacosamide (LCM) monotherapy. METHODS: This was a retrospective cohort study conducted using the Optum clinical EHR database. The study sample comprised patients ≥17 years of age with epilepsy or seizures and treated with LCM monotherapy between 1 January 2009 and 31 December 2013. Structured and unstructured data from prescribed medication and abstracted physician note records were used to identify patients with epilepsy treated with LCM monotherapy and measure seizure frequency outcomes. The index date was the first date of LCM monotherapy, with a 6-month baseline period. Patients were observed for up to 12 months beginning on the index date (follow-up period). The EHR data were not sufficient to compute days supply and explicit duration of LCM and other antiepileptic drug (AED) therapies; therefore, LCM monotherapy was estimated from prescription dates of AEDs. Outcomes were change in seizures per month or change in seizure frequency category from baseline to follow-up. Descriptive statistics were used to describe baseline characteristics and study outcomes. RESULTS: A total of 10,988 patients with at least one LCM prescription were identified during the study period, 470 of whom met all the selection criteria and were included in the study sample. Although many patients had abstracted physician note records that referred to their seizures, only 3.2% of the patients had seizure frequency information that could be used to quantify the number of seizures per month in both the baseline and follow-up periods; thus, this information could not be used to assess the effectiveness of LCM monotherapy on seizure outcomes. CONCLUSION: Lacosamide monotherapy effectiveness was not estimated because the EHR prescription record data did not have sufficient information on days supply. Additionally, most patients' records did not contain adequate information to allow for evaluation of quantitative changes in seizure frequency based on the number of seizures per month. More studies are needed to validate these study findings.

Health care cost associated with the use of enzyme-inducing and non-enzyme-active antiepileptic drugs in the UK: a long-term retrospective matched cohort study.

BACKGROUND: Some antiepileptic drugs (AEDs) induce expression of hepatic enzymes. This can contribute to comorbidities via interference with metabolic pathways and concomitant drug metabolization, thereby increasing the likelihood of health care interventions. Using medical records, we compared the direct health care cost in patients initiating epilepsy therapy with enzyme-inducing AEDs (EIAEDs) vs non-enzyme-active AEDs (nEAAEDs) over up to 12 years. METHODS: Patients with untreated epilepsy were indexed in the UK Clinical Practice Research Datalink and Hospital Episode Statistics database when prescribed a new EIAED or nEAAED between January 2001 and December 2010. Propensity score matching reduced confounding factors between cohorts. Patients were followed until cohort treatment failure or data cut-off. The primary outcome was the median standardized monthly direct health care cost during follow-up in 2014 £GBP, calculated using published reference costs and compared using a Mann-Whitney U test. RESULTS: The unmatched EIAED cohort (n = 2752) was older (54 vs 46 years), more likely to be male, had more comorbidities, and higher health care resource use/cost during the 1-year pre-index period (median £3014 vs £2516) than the nEAAED cohort (n = 2,137). The most common index EIAED and nEAAED were carbamazepine (63.3%) and lamotrigine (58.0%), respectively. After matching, cohorts had similar features (n = 951 each). Over up to 12 years of follow-up, the median standardized monthly direct health care cost was £229 for the EIAED and £188 for the nEAAED cohorts (p = 0.0091). The median cost was higher for the EIAED cohort in every year of follow-up. In the two cohorts, 25.1% and 20.1% of total mean cost during follow-up was epilepsy-related, with approximately 4.6% and 3.0% for AED acquisition, respectively. The median time to cohort treatment failure was shorter in the matched EIAED cohort (468 vs 1194 days). CONCLUSIONS: Patients in the UK who initiated epilepsy therapy with an EIAED appeared to be at higher risk of complications associated with enzyme induction. In long-term matched cohort analyses, the median total direct health care cost associated with EIAED therapy was higher than with nEAAEDs. Changing current treatment practices could potentially improve patient outcomes and reduce costs.

Randomized double-blind comparison of cognitive and EEG effects of lacosamide and carbamazepine.

Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. This study evaluated cognitive and EEG effects of lacosamide (LCM) compared with carbamazepine immediate-release (CBZ-IR). A randomized, double-blind, double-dummy, two-period crossover, fixed-dose study in healthy subjects compared neuropsychological and EEG effects of LCM (150mg, b.i.d.) and CBZ-IR (200mg, t.i.d.). Testing was conducted at screening, predrug baseline, the end of each treatment period (3-week titration; 3-week maintenance), and the end of each washout period (4weeks after treatment). A composite Z-score was derived for the primary outcome variable (computerized cognitive tests and traditional neuropsychological measures) and separately for the EEG measures. Other variables included individual computer, neuropsychological, and EEG scores and adverse events (AEs). Subjects included 60 healthy adults (57% female; mean age: 34.4years [SD: 10.5]); 44 completed both treatments; 41 were per protocol subjects. Carbamazepine immediate-release had worse scores compared with LCM for the primary composite neuropsychological outcome (mean difference=0.33 [SD: 1.36], p=0.011) and for the composite EEG score (mean difference=0.92 [SD: 1.77], p=0.003). Secondary analyses across the individual variables revealed that CBZ-IR was statistically worse than LCM on 36% (4/11) of the neuropsychological tests (computerized and noncomputerized) and 0% of the four EEG measures; none favored CBZ-IR. Drug-related AEs occurred more with CBZ-IR (49%) than LCM (22%). Lacosamide had fewer untoward neuropsychological and EEG effects and fewer AEs and AE-related discontinuations than CBZ-IR in healthy subjects. Lacosamide exhibits a favorable cognitive profile.