Effect of Dendritic Side Groups on the Mobility of Modified Poly(epichlorohydrin) Copolymers.

The macromolecular dynamics of dendronized copolymer membranes (PECHs), obtained by chemical modification of poly(epichlorohydrin) with the dendron 3,4,5-tris[4-(n-dodecan-1-yloxy)benzyloxy] benzoate, was investigated. In response to a thermal treatment during membrane preparation, these copolymers show an ability to change their shape, achieve orientation, and slightly crystallize, which was also observed by CP-MAS NMR, XRD, and DSC. The phenomenon was deeply analyzed by dielectric thermal analysis. The dielectric spectra show the influence of several factors such as the number of dendritic side groups, the orientation, their self-assembling dendrons, and the molecular mobility. The dielectric spectra present a sub-Tg dielectric relaxation, labelled as γ, associated with the mobility of the benzyloxy substituent of the dendritic group. This mobility is not related to the percentage of these lateral chains but is somewhat hindered by the orientation of the dendritic groups. Unlike other less complex polymers, the crystallization was dismantled before the appearance of the glass transition (αTg). Only after that, clearing transition (αClear) can be observed. The PECHs were flexible and offered a high free volume, despite presenting a high degree of modifications. However, the molecular mobility is not independent in each phase and the self-assembling dendrons can be eventually fine-tuned according to the percentage of grafted groups.

Burden of disease of people with epilepsy during an optimized diagnostic trajectory: costs and quality of life.

BACKGROUND: Diagnosing epilepsy can be lengthy and stressful, potentially leading to increased use of healthcare resources and a reduction in quality of life. AIM: This study aims to determine cost and quality of life before and after an optimized diagnostic procedure for people suspected of having epilepsy from a societal perspective with a follow-up of 12 months. In addition, this study aims to differentiate between people diagnosed with epilepsy during the follow-up of the study and the people who are diagnosed as not having epilepsy or for whom diagnosis is still uncertain. METHODS: A questionnaire regarding the use of healthcare resources was used accompanied by the EQ-5D-3 L. Multiple imputations by chained equations with predictive mean matching was used to account for missing data. To investigate the uncertainty of the results, non-parametric bootstrapped (1000 times) was used. RESULTS: In total, 116 people were included in the study. Total average costs per patient made in the previous 3 months had decreased from €4594 before the optimized diagnostic trajectory to €2609 in the 12 months after the optimized diagnostic trajectory. Healthcare costs were the largest expense group (52-66%) and had decreased significantly from baseline measurement to 12 months after baseline (€2395 vs €1581). Productivity costs had decreased from €1367 to €442 per 3 months. Total annual costs were similar between people diagnosed with epilepsy during the follow-up of the study and the people who are diagnosed as not having epilepsy or for whom diagnosis is still uncertain. Quality of Life had significantly increased over the course of 12 months from 0.80 to 0.84 (Dutch tariff). DISCUSSION: This study indicates that an optimized diagnostic trajectory has positively influenced the use of healthcare resources and the quality of life in people with epilepsy. As chronic care patients make diverse costs, future research should identify the long-term costs after an optimized diagnostic trajectory for patients with epilepsy, possibly identifying patients who are at high risk of becoming high-cost users in the future for early intervention.

Effectiveness of a multicomponent self-management intervention for adults with epilepsy (ZMILE study): A randomized controlled trial.

BACKGROUND: The objective of the ZMILE study was to compare the effectiveness of a multicomponent self-management intervention (MCI) with care as usual (CAU) in adult patients with epilepsy (PWE) over a six-month period. METHODS: Participants (PWE & relative) were randomized into intervention or CAU groups. Self-report questionnaires were used to measure disease-specific self-efficacy as the primary outcome measure and general self-efficacy, adherence, seizure severity, emotional functioning, quality of life, proactive coping, and side-effects of antiepileptic drugs (AED) as secondary outcome measures. Instruments used at baseline and during a six-month follow-up period were the following: disease-specific self-efficacy (Epilepsy Self-Efficacy Scale [ESES], General Self-Efficacy Scale [GSES]); adherence (Medication Adherence Scale [MARS] and Medication Event Monitoring System [MEMS]); seizure severity (National Hospital Seizure Severity Scale [NHS3]); emotional well-being (Hospital Anxiety and Depression Scale [HADS]); quality of life (Quality of Life in Epilepsy [QOLIE-31P]); proactive coping (Utrecht Proactive Coping Competence [UPCC]); and side-effects of antiepileptic drugs [SIDAED]. Multilevel analyses were performed, and baseline differences were corrected by inclusion of covariates in the analyses. RESULTS: In total, 102 PWE were included in the study, 52 of whom were in the intervention group. On the SIDAED and on three of the quality of life subscales QOLIE-31P, a significant difference was found (p<0.05) in the intervention group. Self-efficacy, however, showed no significant differences between the MCI and the CAU groups. None of the other outcome measures showed any significant difference between the two groups. SIGNIFICANCE: Although we found no statistically significant difference in the primary outcome measure, disease-specific self-efficacy, this MCI could prove promising, since we found improvement in some domains of quality of life in epilepsy scale and a decrease in AED side-effects in the MCI group compared with the CAU group.

A comparison of the responsiveness of EQ-5D-5L and the QOLIE-31P and mapping of QOLIE-31P to EQ-5D-5L in epilepsy.

OBJECTIVE: To investigate the responsiveness of and correlation between the EQ-5D-5L and the QOLIE-31P in patients with epilepsy, and develop a mapping function to predict EQ-5D-5L values based on the QOLIE-31P for use in economic evaluations. METHODS: The dataset was derived from two clinical trials, the ZMILE study in the Netherlands and the SMILE study in the UK. In both studies, patients' quality of life using the EQ-5D-5L and QOLIE-31P was measured at baseline and 12 months follow-up. Spearman's correlations, effect sizes (EF) and standardized response means (SRM) were calculated for both the EQ-5D-5L and QOLIE-31P domains and sub scores. Mapping functions were derived using ordinary least square (OLS) and censored least absolute deviations models. RESULTS: A total of 509 patients were included in this study. Low to moderately strong significant correlations were found between both instruments. The EQ-5D-5L showed high ceiling effects and small EFs and SRMs, whereas the QOLIE-31P did not show ceiling effects and also showed small to moderate EFs and SRMs. Results of the different mapping functions indicate that the highest adjusted R 2 we were able to regress was 0.265 using an OLS model with squared terms, leading to a mean absolute error of 0.103. CONCLUSIONS: Results presented in this study emphasize the shortcomings of the EQ-5D-5L in epilepsy and the importance of the development of condition-specific preference-based instruments which can be used within the QALY framework. In addition, the usefulness of the constructed mapping function in economic evaluations is questionable.

Process evaluation of a multi-component self-management intervention for adults with epilepsy (ZMILE study).

BACKGROUND: People with epilepsy need to monitor and manage their symptoms. They, as well as their relatives, have to deal with the psychological burden, reflected in a reduced quality of life. Support in self-management can be of importance. We have developed a multi-component self-management intervention for patients and their relatives (MCI). This eight-week group intervention is conducted by nurse practitioners and consists of six two-hour sessions. The main components are: 1) providing self-management education, 2) stimulating proactive coping and goal-setting and 3) facilitating peer and social support. This study is a process evaluation to establish the feasibility, fidelity and acceptability of the intervention by assessing performance according to protocol, attendance and adherence, and the opinion of patients, relatives and facilitators about the intervention. METHOD: Study population consists of 52 patients with epilepsy living in the community (e.g. at home), 37 relatives and six facilitators. In this prospective mixed methods study, data were gathered using questionnaires for patients and relatives, registration forms for facilitators and by carrying out semi-structured group interviews with patients, relatives and facilitators. RESULTS: Patients and relatives attended a mean of 5.2 sessions. Forty-seven (90%) patients and 32 (86.5%) relatives attended at least five sessions. The mean group size was 8.1 (SD=1.3; range 6-10). All elements of the intervention were offered to participants, except for one e-Health tool which was only available at the start of the study. Overall, the sessions were considered useful by patients, their relatives and facilitators. The participation of a relative (social support) and sharing ideas and feelings about having epilepsy with peers (peer support) were rated as important aspects. CONCLUSION: This process evaluation revealed that the MCI was largely performed according to protocol, attendance rate was high, and participants and facilitators had, on the whole, a favourable opinion about the MCI, and would recommend it to others with epilepsy and their relatives. Overall, the adherence of patients and relatives was high. The MCI is considered feasible according to patients, relatives and facilitators. Implementation is recommended if the intervention proves to be effective.

An economic evaluation of a multicomponent self-management intervention for adults with epilepsy (ZMILE study).

OBJECTIVE: The objective of this (trial-based) economic evaluation was, from a societal perspective, to compare the cost-effectiveness of a multicomponent self-management intervention (MCI) with care as usual (CAU) in adult patients with epilepsy over a 12-month period. METHODS: In a randomized-controlled trial, participants were randomized into intervention or CAU group. Adherence, self-efficacy (Epilepsy Self-Efficacy Scale [ESES]), quality-adjusted life years (QALYs), healthcare costs, production losses, and patient and family costs were assessed at baseline and during the 12-month study period. Incremental cost-effectiveness ratios (ICERs) (i.e., cost per increased adherence, self-efficacy, or QALY), and cost-effectiveness acceptability curves were calculated. RESULTS: In total, 102 patients were included in the study, of whom 52 were in the intervention group. Adherence rates over 6 months were 63.7% for the CAU group and 75.9% for the intervention group. Adherence, ESES, and quality of life did not differ significantly between groups. An ICER of €54 per point increase in ESES score at 6 months and €1,105 per point increase at 12-month follow-up was found. The intervention resulted in an ICER of €88 per percentage of adherence increase at 6 months. ICERs of €8,272 and €15,144 per QALY gained were found at 6- and 12-month follow-up, respectively. SIGNIFICANCE: Although no statistically significant difference was found after baseline adjustments, cost-effectiveness estimates for MCI appear promising. As rules of inference are arbitrary, it has been argued that decisions should be based only on the net benefits, irrespective of whether differences are statistically significant. Hence, the MCI may be a cost-effective addition to the current standard care for adults with epilepsy.

Long-term clinical outcomes and economic evaluation of the ketogenic diet versus care as usual in children and adolescents with intractable epilepsy.

OBJECTIVE: To examine long-term retention rate, clinical outcomes, cost-utility and cost-effectiveness of the Ketogenic Diet (KD) compared with care as usual (CAU) in children and adolescents with intractable epilepsy from a societal perspective. METHODS: Participants were randomized into a KD or CAU group. Seizure frequency, quality adjusted life years (QALYs), side-effects, seizure severity, health care costs, production losses, patient and family costs were assessed at baseline and during 16-months of follow-up. Incremental cost-effectiveness ratios (ICERs) (i.e. cost per QALY and cost per responder) and cost-effectiveness acceptability curves are presented. RESULTS: 48 children were included in the analyses of this study (26 from KD group). In total, 58% of the KD group completed the follow-up of 16 months; 11 dropped-out for various reasons. At 16 months, 35% of the KD participants had a seizure reduction≥50% from baseline, compared with 18% of the CAU participants. Mean costs per patient in the CAU group were €53,367 (extrapolated) compared to €61,019 per patient in the KD group, resulting in an ICER of €46,564 per responder. Cost per QALY rose well above any acceptable ceiling ratio. At 4-months' follow-up, the KD group showed significantly more gastro-intestinal problems compared to the CAU group. At 16 months, the KD group reported fewer problems compared to CAU. Furthermore, 46.2% of the KD group reported a decrease in severity of their worst seizure compared to 32% of the CAU group. CONCLUSION: The KD group resulted in more responders and showed greater improvement on seizure severity. Furthermore, the KD did not lead to worsening of side-effects other than gastro-intestinal problems (only at 4 months' follow-up). However, as only a minimal difference in QALYs was found between the KD group and the CAU group, the resulting cost per QALY ratios were inconclusive.

A systematic review of economic evaluations of treatments for patients with epilepsy.

The increasing number of treatment options and the high costs associated with epilepsy have fostered the development of economic evaluations in epilepsy. It is important to examine the availability and quality of these economic evaluations and to identify potential research gaps. As well as looking at both pharmacologic (antiepileptic drugs [AEDs]) and nonpharmacologic (e.g., epilepsy surgery, ketogenic diet, vagus nerve stimulation) therapies, this review examines the methodologic quality of the full economic evaluations included. Literature search was performed in MEDLINE, EMBASE, NHS Economic Evaluation Database (NHS EED), Econlit, Web of Science, and CEA Registry. In addition, Cochrane Reviews, Cochrane DARE and Cochrane Health Technology Assessment Databases were used. To identify relevant studies, predefined clinical search strategies were combined with a search filter designed to identify health economic studies. Specific search strategies were devised for the following topics: (1) AEDs, (2) patients with cognitive deficits, (3) elderly patients, (4) epilepsy surgery, (5) ketogenic diet, (6) vagus nerve stimulation, and (7) treatment of (non)convulsive status epilepticus. A total of 40 publications were included in this review, 29 (73%) of which were articles about pharmacologic interventions. Mean quality score of all articles on the Consensus Health Economic Criteria (CHEC)-extended was 81.8%, the lowest quality score being 21.05%, whereas five studies had a score of 100%. Looking at the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), the average quality score was 77.0%, the lowest being 22.7%, and four studies rated as 100%. There was a substantial difference in methodology in all included articles, which hampered the attempt to combine information meaningfully. Overall, the methodologic quality was acceptable; however, some studies performed significantly worse than others. The heterogeneity between the studies stresses the need to define a reference case (e.g., how should an economic evaluation within epilepsy be performed) and to derive consensus on what constitutes "standard optimal care."

Model-based economic evaluations in smoking cessation and their transferability to new contexts: a systematic review.

AIMS: To identify different types of models used in economic evaluations of smoking cessation, analyse the quality of the included models examining their attributes and ascertain their transferability to a new context. METHODS: A systematic review of the literature on the economic evaluation of smoking cessation interventions published between 1996 and April 2015, identified via Medline, EMBASE, National Health Service (NHS) Economic Evaluation Database (NHS EED), Health Technology Assessment (HTA). The checklist-based quality of the included studies and transferability scores was based on the European Network of Health Economic Evaluation Databases (EURONHEED) criteria. Studies that were not in smoking cessation, not original research, not a model-based economic evaluation, that did not consider adult population and not from a high-income country were excluded. FINDINGS: Among the 64 economic evaluations included in the review, the state-transition Markov model was the most frequently used method (n = 30/64), with quality adjusted life years (QALY) being the most frequently used outcome measure in a life-time horizon. A small number of the included studies (13 of 64) were eligible for EURONHEED transferability checklist. The overall transferability scores ranged from 0.50 to 0.97, with an average score of 0.75. The average score per section was 0.69 (range = 0.35-0.92). The relative transferability of the studies could not be established due to a limitation present in the EURONHEED method. CONCLUSION: All existing economic evaluations in smoking cessation lack in one or more key study attributes necessary to be fully transferable to a new context.

Are people with epilepsy using eHealth-tools?

INTRODUCTION: Self-management for people with epilepsy (PWE) should lead to shared decision-making and thus to adherence to the treatment plan. eHealth is an important way of supporting PWE in their self-management. METHOD: In this survey, we used a mixed method to explore the following: 1) which factors were monitored by PWE and how (using pen and paper or eHealth-tools), 2) how many PWE own a computer or smartphone, and 3) how do they perceive the use of eHealth. A consecutive series of 1000 PWE attending the outpatient clinic of a tertiary epilepsy center were asked to fill in a questionnaire. RESULTS: In comparison with the general population, fewer PWE owned a computer or smartphone. They were, however, more likely to self-monitor their health than other patients suffering from a chronic condition. Although PWE did not use eHealth-tools often, they perceived it as a user-friendly tool, promoting health behavior as well as adherence. On the other hand, problems with privacy and the perception that not everyone is able to use eHealth were considered as disadvantages by PWE. Promoting self-care was perceived as both an advantage and a disadvantage. It was seen as an advantage when PWE mentioned the option of eHealth-tools in order to gain insight into one's epilepsy. At the same time, it was seen as a disadvantage because it confronts PWE with their disease, which causes emotional stress. CONCLUSION: The high level of self-monitoring combined with a low usage of eHealth-tools seems to indicate that there is a need for a more tailored approach to stimulate the use of eHealth-tools by PWE. Further research should focus on this aspect, e.g., what PWE need in order to make more use of eHealth-tools in their self-care.

From clinically relevant outcome measures to quality of life in epilepsy: A time trade-off study.

OBJECTIVES: A proposed method for bridging the gap between clinically relevant epilepsy outcome measures and quality-adjusted life years is to derive utility scores for epilepsy health states. The aim of this study is to develop such a utility-function and to investigate the impact of the epilepsy outcome measures on utility. METHODS: Health states, based on clinically important epilepsy attributes (e.g. seizure frequency, seizure severity, side-effects), were valued by a sample of the Dutch population (N=525) based on the time trade-off method. In addition to standard demographics, every participant was asked to rate 10 or 11 different health state scenarios. A multilevel regression analysis was performed to account for the nested structure of the data. RESULTS: Results show that the best health state (no seizures and no side-effects) is estimated at 0.89 and the worst state (seizures type 5 twice a day plus severe side-effects) at 0.22 (scale: 0-1). An increase in seizure frequency, occurrence of side-effects, and seizure severity were all significantly associated with lower utility values. Furthermore, seizure severity has the largest impact on quality of life compared with seizure frequency and side-effects. CONCLUSIONS: This study provides a utility-function for transforming clinically relevant epilepsy outcome measures into utility estimates. We advise using our utility-function in economic evaluations, when quality of life is not directly measured in a study and hence, no health state utilities are available, or when there is convincing empirical evidence of the insensitivity of a generic quality-of-life-instrument within epilepsy.

Cognitive and behavioral impact of the ketogenic diet in children and adolescents with refractory epilepsy: A randomized controlled trial.

PURPOSE: The ketogenic diet (KD) is increasingly used for the treatment of refractory epilepsy in childhood because of the beneficial effect on seizure reduction. The aim of the current study was to objectively assess cognition and aspects of behavior during the first 4months of a randomized controlled study in children and adolescents. METHODS: Participants from a tertiary epilepsy center were randomized to a KD group (intervention) or a care-as-usual (CAU) group (control). Follow-up assessments on cognition and behavior were performed approximately 4months after initiation of the KD with a combination of parent report questionnaires and individually administered psychological tests for the children. RESULTS: A total of 50 patients were enrolled in this study, 28 patients from the KD group and 22 patients from the CAU group. The KD group showed lower levels of anxious and mood-disturbed behavior and was rated as more productive. Cognitive test results showed an improvement of activation in the KD group. CONCLUSIONS: This study showed a positive impact of the KD on behavioral and cognitive functioning in children and adolescents with refractory epilepsy. More specifically, an activated mood and cognitive activation were observed in patients treated with the KD.

An economic evaluation of the ketogenic diet versus care as usual in children and adolescents with intractable epilepsy: An interim analysis.

OBJECTIVES: To gain insight into the cost-effectiveness of the ketogenic (KD) diet compared with care as usual (CAU) in children and adolescents with intractable epilepsy, we conducted an economic evaluation from a societal perspective, alongside a randomized controlled trial. METHODS: Participants from a tertiary epilepsy center were randomized into KD (intervention) group or CAU (control) group. Seizure frequency, quality adjusted life years (QALYs), health care costs, production losses of parents and patient, and family costs were assessed at baseline and during a 4-month study period and compared between the intervention and control groups. The incremental cost-effectiveness ratios (ICERs) (i.e., cost per QALY and cost per responder), and cost-effectiveness acceptability curves (CEACs) were calculated and presented. RESULTS: In total, 48 children were included in the analyses of this study (26 KD group). At 4 months, 50% of the participants in the KD group had a seizure reduction ≥50% from baseline, compared with 18.2 of the participants in the CAU group. The mean costs per patient in the CAU group were €15,245 compared to €20,986 per patient in the KD group, resulting in an ICER of €18,044 per responder. We failed, however, to measure any benefits in terms of QALYs and therefore, the cost per QALY rise high above any acceptable ceiling ratio. It might be that the quality of life instruments used in this study were not sufficiently sensitive to detect changes, or it might be that being a clinical responder is not sufficient to improve a patient's quality of life. Univariate and multivariate sensitivity analyses and nonparametric bootstrapping were performed and demonstrated the robustness of our results. SIGNIFICANCE: The results show that the KD reduces seizure frequency. The study did not find any improvements in quality of life and, therefore, unfavorable cost per QALY ratio's resulted.

Is exposure in vivo cost-effective for chronic low back pain? A trial-based economic evaluation.

BACKGROUND: Back pain is one of the most expensive health complaints. Comparing the economic aspects of back pain interventions may therefore contribute to a more efficient use of available resources. This study reports on a long-term cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) of two treatments as viewed from a societal perspective: 1) exposure in vivo treatment (EXP), a recently developed cognitive behavioral treatment for patients with chronic low back pain who have elevated pain-related fear and 2) the more commonly used graded activity (GA) treatment. METHODS: Sixty-two patients with non-specific chronic low back pain received either EXP or GA. Primary data were collected at four participating treatment centers in the Netherlands. Primary outcomes were self-reported disability (for the CEA) and quality-adjusted life years (for the CUA). Program costs, health care utilization, patient and family costs, and production losses were measured by analyzing therapy records and cost diaries. Data was gathered before, during, and after treatment, and at 6 and 12 months after treatment. Non-parametric bootstrap analyses were used to quantify the uncertainty concerning the cost-effectiveness ratio. In addition, cost-effectiveness planes and cost-effectiveness acceptability curves were performed. RESULTS: EXP showed a tendency to reduce disability, increase quality adjusted life years and decrease costs compared to GA. The incremental cost-effectiveness ratios of both the CEA and CUA are in favor of EXP. CONCLUSIONS: Based on these results, implementing EXP for this group of patients seems to be the best decision. TRIAL REGISTRATION: ISRCTN88087718.

The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A prospective study with 2-year follow-up.

The present study assessed the long-term (i.e., 24months) efficacy of the ketogenic diet (KD) as an add-on therapy in children with refractory epilepsy, with focus on seizure frequency, seizure severity, and tolerability. Most patients were treated with the MCT-diet. At one and two years, 33% and 23%, respectively, of the 48 included patients were still on the KD. After three months, one year, and two years of treatment, 16.7% of the patients were responders. The highest responder rate (i.e., 22.9%) was seen at six and nine months of treatment. Of the fifteen patients with seizure clusters during baseline, 60% were responders after three months when looking at cluster reduction and most of them were not responders for the total seizure frequency. From three months of treatment onwards, most of the patients had a relevant decrease in seizure severity which was mainly related to the most severe seizure type. Gastrointestinal dysfunction was often reported, especially in the first six weeks of treatment. Growth deceleration was present in 30% of the patients, and weight reduction in 15%. Improved arousal was mentioned in 30% of patients. No patients developed ECG abnormalities or kidney stones. Increase in lipid profile was rare. The KD is an effective therapy for children with therapy-resistant epilepsy. Effectiveness is reflected in the reduction of seizure frequency as well as in the reduction of seizure severity. After 6months of treatment, it is obvious which patients are responders and tolerate the treatment well. Most of these patients will continue to benefit from the KD for a longer time. Long-term use of the diet was well tolerated.

Cost-effectiveness of the ketogenic diet and vagus nerve stimulation for the treatment of children with intractable epilepsy.

PURPOSE: The objective of this study was to estimate the expected cost-utility and cost-effectiveness of the ketogenic diet (KD), vague nerve stimulation (VNS) and care as usual (CAU), using a decision analytic model with a 5-year time horizon. METHODS: A Markov decision analytical model was constructed to estimate the incremental costs, quality-adjusted life years (QALYs) and successfully treated patient (i.e. 50% or more seizure reduction) of the treatment strategies KD, VNS and CAU, from a health care perspective. The base case considered children with intractable epilepsy (i.e. two or more antiepileptic drugs had failed) aged between 1 and 18 years. Data were derived from literature and expert meetings. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Our results suggest that KD is more effective and less costly, and thus cost-effective compared with VNS, after 12 months. However, compared to CAU, neither KD nor VNS are cost-effective options, they are both more effective but also more expensive (€346,899 and €641,068 per QALY, respectively). At 5 years, VNS is cost-effective compared with KD and CAU (€11,378 and €68,489 per QALY, respectively) and has a 51% probability of being cost-effective at a ceiling ratio of €80,000 per QALY. CONCLUSIONS: Our results suggest that on average the benefits of KD and VNS fail to outweigh the costs of the therapies. However, these treatment options should not be ignored in the treatment for intractable epilepsy in individual or specific groups of patients. There is a great need for high quality comparative studies with large patient samples which allow for subgroup analyses, long-term follow-up periods and outcome measures that measure effects beyond seizure frequency (e.g. quality of life). When this new evidence becomes available, reassessment of the cost-effectiveness of KD and VNS in children with intractable epilepsy should be carried out.

Side-effects of antiepileptic drugs: the economic burden.

PURPOSE: Antiepileptic drugs are a potentially effective treatment for epilepsy. Side-effects are, however, common and the negative consequences necessitate treatment ranging from minor interventions to very expensive hospitalization. This analysis has been conducted to provide insight into the costs of side-effects due to antiepileptic drugs in The Netherlands from a societal perspective. METHOD: Resources allocated to care (grouped according to health, patient and family and other) for five different categories of side-effect were measured using a questionnaire. Standard cost prices were derived from the Dutch costing manual. Chronic epilepsy patients were invited to complete the questionnaire if they had experienced side-effects during the previous 12 months. RESULTS: Based on data from 203 patients, the total societal costs of common side-effects in 2012 are estimated to be € 20,751 CI:15,049-27,196 (US$26,675 CI:19,345-34,960) per patient per year. These consist of: health care costs (mean € 4458; US$5731), patient and family costs (i.e. informal care, mean € 10,526; US$13,531) and other costs (i.e. productivity losses, mean € 5761; US$7406). Examining the different categories of side-effects separately, ranging from the most to the least expensive category, the cost estimates per patient per year were as follows: other (mean € 13,228; US$17,005), behavioral (mean € 9689; US$12,455), general health (mean € 7454; US$9582), cognitive (mean € 7285; US$9365) and cosmetic side-effects (mean € 2845; US$3657). Subgroup analyses showed significant differences in costs between patients using monotherapy and those using polytherapy when looking at cognitive and cosmetic side-effects. CONCLUSION: These estimates should be considered in the overall assessment of the economic impact of a pharmacotherapy.

Cost effectiveness of medication adherence-enhancing interventions: a systematic review of trial-based economic evaluations.

BACKGROUND: In light of the pressure to reduce unnecessary healthcare expenditure in the current economic climate, a systematic review that assesses evidence of cost effectiveness of adherence-enhancing interventions would be timely. OBJECTIVE: Our objective was to examine the cost effectiveness of adherence-enhancing interventions compared with care as usual in randomised controlled trials, and to assess the methodological quality of economic evaluations. METHODS: MEDLINE, PsycInfo, EconLit and the Centre for Reviews and Dissemination databases were searched for randomised controlled trials reporting full economic evaluations of adherence-enhancing interventions (published up to June 2013). Information was collected on study characteristics, cost effectiveness of treatment alternatives, and methodological quality. RESULTS: A total of 14 randomised controlled trials were included. The quality of economic evaluations and the risk of bias varied considerably between trials. Four studies showed incremental cost-effectiveness ratios (ICERs) below the willingness-to-pay threshold. Few studies seemed to evaluate interventions that successfully changed adherence. CONCLUSIONS: Only 14 randomised controlled trials examined the cost effectiveness of adherence interventions. Despite that some studies showe favourable ICERs, the overall quality of studies was modest and the economic perspectives applied were frequently narrow. To demonstrate that adherence interventions can be cost effective, we recommend that proven-effective adherence programmes are subjected to comprehensive economic evaluations.

The ketogenic diet as a treatment option in adults with chronic refractory epilepsy: efficacy and tolerability in clinical practice.

The ketogenic diet (KD) is a high-fat, low-protein, low-carbohydrate diet that is used as a treatment for patients with difficult-to-control epilepsy. The present study assesses the efficacy and tolerability of the KD as an add-on therapy in adults with chronic refractory epilepsy. 15 adults were treated with the classical diet or MCT diet. During a follow-up period of 1 year we assessed seizure frequency, seizure severity, tolerability, cognitive performance, mood and quality of life (QOL). We found a significant reduction in seizures among the patients who followed the diet at least 1 year (n=5). Of these 5 patients, 2 had a reduction between 50 and 90%. Analyzing the study months separately, we found a seizure reduction of ≥50% in 26.6% of the patients during at least 1 month of treatment. Common side-effects were gastrointestinal disorders, loss of weight and fatigue. There was a considerable, non-significant improvement found in mood and QOL scores. Improvements were independent of reduction in seizure frequency, indicating that the effects of the KD reach further than seizure control.

Research into the (Cost-) effectiveness of the ketogenic diet among children and adolescents with intractable epilepsy: design of a randomized controlled trial.

BACKGROUND: Epilepsy is a neurological disorder, characterized by recurrent unprovoked seizures which have a high impact on the individual as well as on society as a whole. In addition to the economic burden, epilepsy imposes a substantial burden on the patients and their surroundings. Patients with uncontrolled epilepsy depend heavily on informal care and on health care professionals. About 30% of patients suffer from drug-resistant epilepsy. The ketogenic diet can be a treatment of last resort, especially for children. The beneficial effect of the ketogenic diet has been proven, but information is lacking about its cost-effectiveness. In the current study we will evaluate the (cost-) effectiveness of the ketogenic diet in children and adolescents with intractable epilepsy. METHODS/DESIGN: In a RCT we will compare the ketogenic diet with usual care. Embedded in this RCT will be a trial-based and model-based economic evaluation, looking from a societal perspective at the cost-effectiveness and cost-utility of the ketogenic diet versus usual care. Fifty children and adolescents (aged 1-18) with intractable epilepsy will be screened for eligibility before randomization into the intervention or the usual care group. The primary outcome measure is the proportion of children with a 50% or more reduction in seizure frequency. Secondary outcomes include seizure severity, side effects/complaints, neurocognitive, socio-emotional functioning, and quality of life. Costs and productivity losses will be assessed continuously by a prospective diary and a retrospective questionnaire. Measurements will take place during consults at baseline, at 6 weeks and at 4 months after the baseline period, and 3, 6, 9 and 12 months follow-up after the 4 months consult. DISCUSSION: The proposed research project will be the first study to provide data about the cost-effectiveness of the ketogenic diet for children and adolescents with intractable epilepsy, in comparison with usual care. It is anticipated that positive results in (cost-) effectiveness of the proposed intervention will contribute to the improvement of treatment for epilepsy in children and adolescents and will lead to a smaller burden to society.