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Background and Objectives: Late-onset epilepsy is a heterogenous entity associated with specific aetiologies and an elevated risk of premature mortality. Specific multimorbid-socioeconomic profiles and their unique prognostic trajectories have not been described. We sought to determine if specific clusters of late onset epilepsy exist, and whether they have unique hazards of premature mortality., Methods: We performed a retrospective observational cohort study linking primary and hospital-based UK electronic health records with vital statistics data (covering years 1998-2019) to identify all cases of incident late onset epilepsy (from people aged ≥65) and 1:10 age, sex, and GP practice-matched controls. We applied hierarchical agglomerative clustering using common aetiologies identified at baseline to define multimorbid-socioeconomic profiles, compare hazards of early mortality, and tabulating causes of death stratified by cluster., Results: From 1,032,129 people aged ≥65, we identified 1048 cases of late onset epilepsy who were matched to 10,259 controls. Median age at epilepsy diagnosis was 68 (interquartile range: 66-72) and 474 (45%) were female. The hazard of premature mortality related to late-onset epilepsy was higher than matched controls (hazard ratio [HR] 1.73; 95% confidence interval [95%CI] 1.51-1.99). Ten unique phenotypic clusters were identified, defined by 'healthy' males and females, ischaemic stroke, intracerebral haemorrhage (ICH), ICH and alcohol misuse, dementia and anxiety, anxiety, depression in males and females, and brain tumours. Cluster-specific hazards were often similar to that derived for late-onset epilepsy as a whole. Clusters that differed significantly from the base late-onset epilepsy hazard were 'dementia and anxiety' (HR 5.36; 95%CI 3.31-8.68), 'brain tumour' (HR 4.97; 95%CI 2.89-8.56), 'ICH and alcohol misuse' (HR 2.91; 95%CI 1.76-4.81), and 'ischaemic stroke' (HR 2.83; 95%CI 1.83-4.04). These cluster-specific risks were also elevated compared to those derived for tumours, dementia, ischaemic stroke, and ICH in the whole population. Seizure-related cause of death was uncommon and restricted to the ICH, ICH and alcohol misuse, and healthy female clusters., Significance: Late-onset epilepsy is an amalgam of unique phenotypic clusters that can be quantitatively defined. Late-onset epilepsy and cluster-specific comorbid profiles have complex effects on premature mortality above and beyond the base rates attributed to epilepsy and cluster-defining comorbidities alone., Competing Interests: Declaration of Competing Interest C.B. Josephson has received grant support from Epilepsy Canada and unrestricted educational grants from UCB Pharma Inc. and Eisai Inc. for work unrelated to this project. A. Gonzalez-Izquierdo reports no disclosures relevant to the manuscript. J.D.T. Engbers reports no disclosures relevant to the manuscript. S. Denaxas reports no disclosures relevant to the manuscript. G. Delgado-Garcia reports no disclosures relevant to the manuscript. T.T. Sajobi reports no disclosures relevant to the manuscript. M. Wang reports no disclosures relevant to the manuscript. M.R. Keezer has received unrestricted educational grants, as well as grants for investigator-initiated studies, from UCB Pharma Inc. and Eisai Inc. for work unrelated to this project. S. Wiebe has received unrestricted educational grants from UCB Pharma, Eisai and Sunovion for work unrelated to this project., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Importance: Both epilepsy and enzyme-inducing antiseizure medications (eiASMs) having varying reports of an association with increased risks for osteoporosis., Objective: To quantify and model the independent hazards for osteoporosis associated with incident epilepsy and eiASMS and non-eiASMs., Design, Setting, and Participants: This open cohort study covered the years 1998 to 2019, with a median (IQR) follow-up of 5 (1.7-11.1) years. Data were collected for 6275 patients enrolled in the Clinical Practice Research Datalink and from hospital electronic health records. No patients who met inclusion criteria (Clinical Practice Research Datalink-acceptable data, aged 18 years or older, follow-up after the Hospital Episode Statistics patient care linkage date of 1998, and free of osteoporosis at baseline) were excluded or declined., Exposure: Incident adult-onset epilepsy using a 5-year washout and receipt of 4 consecutive ASMs., Main Outcomes and Measures: The outcome was incident osteoporosis as determined through Cox proportional hazards or accelerated failure time models where appropriate. Incident epilepsy was treated as a time-varying covariate. Analyses controlled for age, sex, socioeconomic status, cancer, 1 or more years of corticosteroid use, body mass index, bariatric surgery, eating disorders, hyperthyroidism, inflammatory bowel disease, rheumatoid arthritis, smoking status, falls, fragility fractures, and osteoporosis screening tests. Subsequent analyses (1) excluded body mass index, which was missing in 30% of patients; (2) applied propensity score matching for receipt of an eiASM; (3) restricted analyses to only those with incident onset epilepsy; and (4) restricted analyses to patients who developed epilepsy at age 65 years or older. Analyses were performed between July 1 and October 31, 2022, and in February 2023 for revisions., Results: Of 8 095 441 adults identified, 6275 had incident adult-onset epilepsy (3220 female [51%] and 3055 male [49%]; incidence rate, 62 per 100 000 person-years) with a median (IQR) age of 56 (38-73) years. When controlling for osteoporosis risk factors, incident epilepsy was independently associated with a 41% faster time to incident osteoporosis (time ratio [TR], 0.59; 95% CI, 0.52-0.67; P < .001). Both eiASMs (TR, 0.91; 95% CI, 0.87-0.95; P < .001) and non-eiASMs (TR, 0.77; 95% CI, 0.76-0.78; P < .001) were also associated with significant increased risks independent of epilepsy, accounting for 9% and 23% faster times to development of osteoporosis, respectively. The independent associations among epilepsy, eiASMs, and non-eiASMs remained consistent in propensity score-matched analyses, cohorts restricted to adult-onset epilepsy, and cohorts restricted to late-onset epilepsy., Conclusions and Relevance: These findings suggest that epilepsy is independently associated with a clinically meaningful increase in the risk for osteoporosis, as are both eiASMs and non-eiASMs. Routine screening and prophylaxis should be considered in all people with epilepsy.

Background and Objective: Frailty is an important aspect of biological aging, referring to the increased vulnerability of individuals with frailty to physical and psychological stressors. While older adults with epilepsy are an important and distinct clinical group, there are no data on frailty in this population. We hypothesize that frailty will correlate with the seizure frequency and especially the tolerability of antiseizure medications (ASMs) in older adults with epilepsy., Methods: We recruited individuals aged 60 years or older with active epilepsy from 4 Canadian hospital centers. We reported the seizure frequency in the 3 months preceding the interview, while ASM tolerability was quantified using the Liverpool Adverse Events Profile (LAEP). We applied 3 measures of frailty: grip strength as a measure of physical frailty, 1 self-reported score (Edmonton frail score [EFS]), and 1 scale completed by a healthcare professional (clinical frailty scale [CFS]). We also administered standardized questionnaires measuring levels of anxiety, depression, functional disability, and quality of life and obtained relevant clinical and demographic data., Results: Forty-three women and 43 men aged 60-93 years were recruited, 87% of whom had focal epilepsy, with an average frequency of 3.4 seizures per month. Multiple linear regression and zero-inflated negative binomial regression models showed that EFS and CFS scores were associated with decreased ASM tolerability, each point increase leading to 1.83 (95% CI: 0.67-4.30) and 2.49 (95% CI: 1.27-2.39) point increases on the LAEP scale, respectively. Neither the EFS and CFS scores nor grip strength were significantly associated with seizure frequency. The EFS was moderately correlated with depression, anxiety, quality of life, and functional disability, demonstrating the best construct validity among the 3 tested measures of frailty., Discussion: The EFS was significantly, both statistically and clinically, associated with ASM tolerability. It also showed multiple advantages in performance while assessing for frailty in older adults with epilepsy, when compared with the 2 other measures of frailty that we tested. Future studies must focus on what role the EFS during epilepsy diagnosis may play in ASM selection among older adults with epilepsy., (© 2022 American Academy of Neurology.)

Objective: We aimed to assess the reliability and validity of single-item global ratings (GR) of satisfaction with epilepsy surgery., Methods: We recruited 240 patients from four centers in Canada and Sweden who underwent epilepsy surgery ≥1 year earlier. Participants completed a validated questionnaire on satisfaction with epilepsy surgery (the ESSQ-19), plus a single-item GR of satisfaction with epilepsy surgery twice, 4-6 weeks apart. They also completed validated questionnaires on quality of life, depression, health state utilities, epilepsy severity and disability, medical treatment satisfaction and social desirability. Test-retest reliability of the GR was assessed with the intra-class correlation coefficient (ICC). Construct and criterion validity were examined with polyserial correlations between the GR measure of satisfaction and validated questionnaires and with the ESSQ-19 summary score. Non-parametric rank tests evaluated levels of satisfaction, and ROC analysis assessed the ability of GRs to distinguish among clinically different patient groups., Results: Median age and time since surgery were 42 years (IQR 32-54) and 5 years (IQR 2-8), respectively. The GR demonstrated good to excellent test-retest reliability (ICC = 0.76; 95% CI 0.67-0.84) and criterion validity (0.85; 95% CI 0.81-0.89), and moderate correlations in the expected direction with instruments assessing quality of life (0.59; 95% CI 0.51-0.63), health utilities (0.55; 95% CI 0.45-0.65), disability (-0.51; 95% CI -0.41, -0.61), depression (-0.48; 95% CI -0.38, -0.58), and epilepsy severity (-0.48; 95% CI -0.38, -0.58). As expected, correlations were lower for social desirability (0.40; 95% CI 0.28-0.52) and medical treatment satisfaction (0.33; 95% CI 0.21-0.45). The GR distinguished participants who were seizure-free (AUC 0.75; 95% CI 0.67-0.82), depressed (AUC 0.75; 95% CI 0.67-0.83), and self-rated as having more severe epilepsy (AUC 0.78; 95% CI 0.71-0.85) and being more disabled (AUC 0.82; 95% CI 0.74-0.90)., Significance: The GR of epilepsy surgery satisfaction showed good measurement properties, distinguished among clinically different patient groups, and appears well-suited for use in clinical practice and research., (© 2022 International League Against Epilepsy.)

Objective: The relationship between antiseizure medications (ASMs), which improve health outcomes by controlling seizures, and health-related quality of life (HRQOL) is poorly understood and may involve intermediate variables. We evaluated the potential mediators of the association between ASMs and HRQOL., Methods: Data are from an outpatient registry of adult patients with epilepsy seen at the Foothills Medical Center, Calgary, Alberta, Canada. Quality of life was measured using the 10-item Quality of Life in Epilepsy, and depression was measured using the Neurological Disorders Depression Inventory for Epilepsy. Propensity score matching was used to adjust for covariate imbalance between patients who received a single ASM (monotherapy) and those who received two or more ASMs (polytherapy) due to confounding. Mediation analysis was used to estimate the mediating effects of depression and ASM side effects on the association between patients' ASM polytherapy and HRQOL., Results: Of 778 patients included in this analysis, 274 (35.2%) were on two or more ASMs. Patient-reported depression and ASM side effects jointly mediated the association between ASMs and HRQOL; these mediators accounted for 42% of the total average effect of ASM polytherapy ( β  = -13.6, 95% confidence interval = -18.2 to -8.6) on HRQOL., Significance: These findings highlight the importance of managing depression and ASM side effects for improving health outcomes of patients requiring treatment with ASMs. Intervention programs aimed at improving HRQOL of patients with epilepsy need to target these potential mediators., (© 2021 International League Against Epilepsy.)

Importance: Enzyme-inducing antiseizure medications (eiASMs) have been hypothesized to be associated with long-term risks of cardiovascular disease., Objective: To quantify and model the putative hazard of cardiovascular disease secondary to eiASM use., Design, Setting, and Participants: This cohort study covered January 1990 to March 2019 (median [IQR] follow-up, 9 [4-15], years). The study linked primary care and hospital electronic health records at National Health Service hospitals in England. People aged 18 years or older diagnosed as having epilepsy after January 1, 1990, were included. All eligible patients were included with a waiver of consent. No patients were approached who withdrew consent. Analysis began January 2021 and ended August 2021., Exposures: Receipt of 4 consecutive eiASMs (carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide, or topiramate) following an adult-onset (age ≥18 years) epilepsy diagnosis or repeated exposure in a weighted cumulative exposure model., Main Outcomes and Measures: Three cohorts were isolated, 1 of which comprised all adults meeting a case definition for epilepsy diagnosed after 1990, 1 comprised incident cases diagnosed after 1998 (hospital linkage date), and 1 was limited to adults diagnosed with epilepsy at 65 years or older. Outcome was incident cardiovascular disease (ischemic heart disease or ischemic or hemorrhagic stroke). Hazard of incident cardiovascular disease was evaluated using adjusted propensity-matched survival analyses and weighted cumulative exposure models., Results: Of 10 916 166 adults, 50 888 (0.6%) were identified as having period-prevalent cases (median [IQR] age, 32 [19-50] years; 16 584 [53%] female), of whom 31 479 (62%) were diagnosed on or after 1990 and were free of cardiovascular disease at baseline. In a propensity-matched Cox proportional hazards model adjusted for age, sex, baseline socioeconomic status, and cardiovascular risk factors, the hazard ratio for incident cardiovascular disease was 1.21 (95% CI, 1.06-1.39) for those receiving eiASMs. The absolute difference in cumulative hazard diverges by more than 1% and greater after 10 years. For those with persistent exposure beyond 4 prescriptions, the median hazard ratio increased from amedian (IQR) of 1.54 (1.28-1.79) when taking a relative defined daily dose of an eiASM of 1 to 2.38 (1.52-3.56) with a relative defined daily dose of 2 throughout a maximum of 25 years' follow-up compared with those not receiving an eiASM. The hazard was elevated but attenuated when restricting analyses to incident cases or those diagnosed when older than 65 years., Conclusions and Relevance: The hazard of incident cardiovascular disease is higher in those receiving eiASMs. The association is dose dependent and the absolute difference in hazard seems to reach clinical significance by approximately 10 years from first exposure.

Objective: This study was undertaken to identify clusters of adult onset epilepsy with distinct comorbidities and risks of early and late death., Methods: This was a retrospective open cohort study that included all adults meeting a case definition for epilepsy after the Acceptable Mortality Recording date in the Health Improvement Network database for the years 2000-2012 inclusive. Unsupervised agglomerative hierarchical clustering was performed to identify unique clusters of patients based on their predicted risk of early (<4 years of epilepsy diagnosis) and late (≥4 years from diagnosis) mortality and patient-level clinical characteristics., Results: We identified 10 499 presumed incident cases of epilepsy from 11 194 182 patients. Four phenotypic clusters were identified in the early and late risk periods. Early clusters include older adults with cardiovascular disease and a high risk of death (median predicted risk = 20%, interquartile range [IQR] = 9%-31%), a group with moderate risk of death and cancer (median predicted risk = 6%, IQR = 2%-15%), a group with psychiatric disease/substance use and few somatic comorbidities (median predicted risk = 5%, IQR = 2%-9%), and one with a younger age at onset and few comorbidities (median predicted risk = 4%, IQR = 1%-11%). There was minimal movement of individuals between clusters for those surviving the early risk period. Age- and sex-standardized 3-year mortality ratios were more than sixfold higher than the general population for every cluster, even those primarily comprised of healthy younger adults., Significance: Adult onset epilepsy is marked by unique clusters of comorbid conditions and elevated risks of death that form discrete populations for targeted therapeutic interventions. These clusters remain relatively stable between the early and late mortality risk periods. Of particular interest are the clusters marked by young and otherwise healthy adults whose standardized mortality ratio is sixfold higher than general population despite few conventional risk factors for premature death., (© 2021 International League Against Epilepsy.)

Objective: The 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19) is a validated and reliable post hoc means of assessing patient satisfaction with epilepsy surgery. Prediction models building on these data can be used to counsel patients., Methods: The ESSQ-19 was derived and validated on 229 patients recruited from Canada and Sweden. We isolated 201 (88%) patients with complete clinical data for this analysis. These patients were adults (≥18 years old) who underwent epilepsy surgery 1 year or more prior to answering the questionnaire. We extracted each patient's ESSQ-19 score (scale is 0-100; 100 represents complete satisfaction) and relevant clinical variables that were standardized prior to the analysis. We used machine learning (linear kernel support vector regression [SVR]) to predict satisfaction and assessed performance using the R 2 calculated following threefold cross-validation. Model parameters were ranked to infer the importance of each clinical variable to overall satisfaction with epilepsy surgery., Results: Median age was 41 years (interquartile range [IQR] = 32-53), and 116 (57%) were female. Median ESSQ-19 global score was 68 (IQR = 59-75), and median time from surgery was 5.4 years (IQR = 2.0-8.9). Linear kernel SVR performed well following threefold cross-validation, with an R 2 of .44 (95% confidence interval = .36-.52). Increasing satisfaction was associated with postoperative self-perceived quality of life, seizure freedom, and reductions in antiseizure medications. Self-perceived epilepsy disability, age, and increasing frequency of seizures that impair awareness were associated with reduced satisfaction., Significance: Machine learning applied postoperatively to the ESSQ-19 can be used to predict surgical satisfaction. This algorithm, once externally validated, can be used in clinical settings by fixing immutable clinical characteristics and adjusting hypothesized postoperative variables, to counsel patients at an individual level on how satisfied they will be with differing surgical outcomes., (© 2021 International League Against Epilepsy.)

Objectives: Patient-reported outcome measures (PROMs) are used widely to elicit patient's self-appraisal of their health status and quality of life. One fundamental assumption when measuring PROMs is that all individuals interpret questions about their health status in a consistent manner. However, subgroups of patients with a similar health condition may respond differently to PROM questions (ie, differential item functioning [DIF]), leading to biased estimates of group differences on PROM scores. Understanding these differences can help inform the clinical interpretation of PROMs. This study examined whether DIF affects 10-item Quality of Life in Epilepsy (QOLIE10) scores reported by patients with epilepsy in outpatient clinics., Methods: Data were from the Calgary Comprehensive Epilepsy Program, a prospective registry of patients with epilepsy in Calgary, Alberta. Latent variable mixture models (LVMMs) based on standard two-parameter graded response models with increasing numbers of latent classes were applied to QOLIE10 item data. Model fit was assessed using the Bayesian Information Criterion (BIC) and latent class model entropy. Ordinal logistic regression was used to identify QOLIE10 items that exhibited DIF., Results: In this cohort of 1143 patients, 567 (49.6%) were female and the median age was 37.0 (interquartile range [IQR] 27.0) years. A two-class LVMM, which provided the best fit to the data, identified two subgroups of patients with different response patterns to QOLIE10 items, with class proportions of 0.62 and 0.38. The two subgroups differed with respect to antiseizure polytherapy, reported medication side effects, frequency of seizures, and psychiatric comorbidities. QOLIE10 items on the physical and psychological side effects of medication exhibited large DIF effects., Significance: Our study revealed two different response patterns to quality-of-life instruments, suggesting heterogeneity in how patients interpret some of the questions. Researchers and users of PROMs in epilepsy need to consider the differential interpretation of items for various instruments to ensure valid understanding and comparisons of PROM scores., (© 2021 International League Against Epilepsy.)

Objective: To use clinically informed machine learning to derive prediction models for early and late premature death in epilepsy., Methods: This was a population-based primary care observational cohort study. All patients meeting a case definition for incident epilepsy in the Health Improvement Network database for inclusive years 2000-2012 were included. A modified Delphi process identified 30 potential risk factors. Outcome was early (within 4 years of epilepsy diagnosis) and late (4 years or more from diagnosis) mortality. We used regularized logistic regression, support vector machines, Gaussian naive Bayes, and random forest classifiers to predict outcomes. We assessed model calibration, discrimination, and generalizability using the Brier score, mean area under the receiver operating characteristic curve (AUC) derived from stratified fivefold cross-validation, plotted calibration curves, and extracted measures of association where possible., Results: We identified 10 499 presumed incident cases from 11 194 182 patients. All models performed comparably well following stratified fivefold cross-validation, with AUCs ranging from 0.73 to 0.81 and from 0.71 to 0.79 for early and late death, respectively. In addition to comorbid disease, social habits (alcoholism odds ratio [OR] for early death = 1.54, 95% confidence interval [CI] = 1.12-2.11 and OR for late death = 2.62, 95% CI = 1.66-4.16) and treatment patterns (OR for early death when no antiseizure medication [ASM] was prescribed at baseline = 1.33, 95% CI = 1.07-1.64 and OR for late death after receipt of enzyme-inducing ASM at baseline = 1.32, 95% CI = 1.04-1.66) were significantly associated with increased risk of premature death. Baseline ASM polytherapy (OR = 0.55, 95% CI = 0.36-0.85) was associated with reduced risk of early death., Significance: Clinically informed models using routine electronic medical records can be used to predict early and late mortality in epilepsy, with moderate to high accuracy and evidence of generalizability. Medical, social, and treatment-related risk factors, such as delayed ASM prescription and baseline prescription of enzyme-inducing ASMs, were important predictors., (© 2020 International League Against Epilepsy.)

Objective: No validated tools exist to assess satisfaction with epilepsy surgery. We aimed to develop and validate a new measure of patient satisfaction with epilepsy surgery, the 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19)., Methods: An initial 31-item measure was developed based on literature review, patient focus groups, thematic analysis, and Delphi panels. The questionnaire was administered twice, 4-6 weeks apart, to 229 adults (≥18 years old) who underwent epilepsy surgery ≥1 year earlier, at three centers in Canada and one in Sweden. Participants also completed seven validated questionnaires to assess construct validity. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) assessed the factorial structure of the questionnaire. Cronbach alpha and intraclass correlation coefficients (ICCs) assessed the internal consistency and test-retest reliability of the ESSQ-19. Spearman and polyserial correlations assessed construct validity., Results: Median age of participants and time since surgery were 42 years (interquartile range [IQR] = 32-54) and 5 years (IQR = 2-8.75), respectively. EFA and CFA yielded 18 items that segregated into four domains (mean score [SD]), namely, seizure control (76.4 [25]), psychosocial functioning (67.3 [26]), surgical complications (84 [22]), and recovery from surgery (73 [24]), one global satisfaction item, and a summary global score (74 [21]). The domain and summary scores demonstrated good to excellent internal reliability (Cronbach ⍺ range = .84-.95) and test-retest reliability (ICC range = 0.71-0.85). Construct validity was supported by predicted correlations with other instruments., Significance: The ESSQ-19 is a new, valid, and reliable measure of patient satisfaction with epilepsy surgery that can be used in clinical and research settings., (© 2020 International League Against Epilepsy.)

Objective: To apply unsupervised machine learning to patient-reported outcomes to identify clusters of epilepsy patients exhibiting unique psychosocial characteristics., Methods: Consecutive outpatients seen at the Calgary Comprehensive Epilepsy Program outpatient clinics with complete patient-reported outcome measures on quality of life, health state valuation, depression, and epilepsy severity and disability were studied. Data were acquired at each patient's first clinic visit. We used k-means++ to segregate the population into three unique clusters. We then used multinomial regression to determine factors that were statistically associated with patient assignment to each cluster., Results: We identified 462 consecutive patients with complete patient-reported outcome measure (PROM) data. Post hoc analysis of each cluster revealed one reporting elevated measures of psychosocial health on all five PROMs ("high psychosocial health" cluster), one with intermediate measures ("intermediate" cluster), and one with poor overall measures of psychosocial health ("poor psychosocial health" cluster). Failing to achieve at least 1 year of seizure freedom (relative risk [RR] = 4.34, 95% confidence interval [CI] = 2.13-9.09) predicted placement in the "intermediate" cluster relative to the "high" cluster. In addition, failing to achieve seizure freedom, social determinants of health, including the need for partially or completely subsidized income support (RR = 6.10, 95% CI = 2.79-13.31, P < .001) and inability to drive (RR = 4.03, 95% CI = 1.6-10.00, P = .003), and a history of a psychiatric disorder (RR = 3.16, 95% CI = 1.46-6.85, P = .003) were associated with the "poor" cluster relative to the "high" cluster., Significance: Seizure-related factors appear to drive placement in the "intermediate" cluster, with social determinants driving placement in the "poor" cluster, suggesting a threshold effect. Precision intervention based on cluster assignment, with an initial emphasis on improving social support and careful titration of medications for those reporting the worst psychosocial health, could help optimize health for patients with epilepsy., (© 2020 International League Against Epilepsy.)

Importance: Patients with epilepsy are at an elevated risk of premature mortality. Interventions to reduce this risk are crucial., Objective: To determine if the level of care (non-neurologist, neurologist, or comprehensive epilepsy program) is negatively associated with the risk of premature mortality., Design, Setting, and Participants: In this retrospective open cohort study, all adult patients 18 years or older who met the administrative case definition for incident epilepsy in linked databases (Alberta Health Services administrative health data and the Comprehensive Calgary Epilepsy Programme Registry [CEP]) inclusive of the years 2002 to 2016 were followed up until death or loss to follow-up. The final analyses were performed on May 1, 2019., Exposures: Evaluation by a non-neurologist, neurologist, or epileptologist., Main Outcomes and Measures: The outcome was all-cause mortality. We used extended Cox models treating exposure to a neurologist or the CEP as time-varying covariates. Age, sex, socioeconomic deprivation, disease severity, and comorbid burden at index date were modeled as fixed-time coefficients., Results: A total 23 653 incident cases were identified (annual incidence of 89 per 100 000); the mean age (SD) at index date was 50.8 (19.1) years and 12 158 (50.3%) were women. A total of 14 099 (60%) were not exposed to specialist neurological care, 9554 (40%) received care by a neurologist, and 2054 (9%) received care in the CEP. In total, 4098 deaths (71%) occurred in the nonspecialist setting, 1481 (26%) for those seen by a neurologist, and 176 (3%) for those receiving CEP care. The standardized mortality rate was 7.2% for the entire cohort, 9.4% for those receiving nonspecialist care, 5.6% for those seen by a neurologist, and 2.8% for those seen in the CEP. The hazard ratio (HR) of mortality was lower in those receiving neurologist (HR, 0.85; 95% CI, 0.77-0.93) and CEP (HR, 0.49; 95% CI, 0.38-0.62) care. In multivariable modeling, specialist care, the age at index, and disease severity were retained in the final model of the association between specialist care and mortality., Conclusions and Relevance: Exposure to specialist care is associated with incremental reductions in the hazard of premature mortality. Those referred to a comprehensive epilepsy program received the greatest benefit.

Importance: Levetiracetam is a commonly used antiepileptic drug, yet psychiatric adverse effects are common and may lead to treatment discontinuation., Objective: To derive prediction models to estimate the risk of psychiatric adverse effects from levetiracetam use., Design, Setting, and Participants: Retrospective open cohort study. All patients meeting the case definition for epilepsy after the Acceptable Mortality Reporting date in The Health Improvement Network (THIN) database based in the United Kingdom (inclusive January 1, 2000, to May 31, 2012) who received a first-ever prescription for levetiracetam were included. Of 11 194 182 patients registered in THIN, this study identified 7400 presumed incident cases (66.1 cases per 100 000 persons) over a maximum of 12 years' follow-up. The index date was when patients received their first prescription code for levetiracetam, and follow-up lasted 2 years or until an event, loss to follow-up, or censoring. The analyses were performed on April 22, 2018., Exposure: A presumed first-ever prescription for levetiracetam., Main Outcomes and Measures: The outcome of interest was a Read code for any psychiatric sign, symptom, or disorder as reached through consensus by 2 authors. This study used regression techniques to derive 2 prediction models, one for the overall population and one for those without a history of a psychiatric sign, symptom, or disorder during the study period., Results: Among 1173 patients with epilepsy receiving levetiracetam, the overall median age was 39 (interquartile range, 25-56) years, and 590 (50.3%) were female. A total of 14.1% (165 of 1173) experienced a psychiatric symptom or disorder within 2 years of index prescription. The odds of reporting a psychiatric symptom were significantly elevated for women (odds ratio [OR], 1.41; 95% CI, 0.99-2.01; P = .05) and those with a preexposure history of higher social deprivation (OR, 1.15; 95% CI, 1.01-1.31; P = .03), depression (OR, 2.20; 95% CI, 1.49-3.24; P < .001), anxiety (OR, 1.74; 95% CI, 1.11-2.72; P = .02), or recreational drug use (OR, 2.02; 95% CI, 1.20-3.37; P = .008). The model performed well after stratified k = 5-fold cross-validation (area under the curve [AUC], 0.68; 95% CI, 0.58-0.79). There was a gradient in risk, with probabilities increasing from 8% for 0 risk factors to 11% to 17% for 1, 17% to 31% for 2, 30% to 42% for 3, and 49% when all risk factors were present. For those free of a preexposure psychiatric code, a second model performed comparably well after k = 5-fold cross-validation (AUC, 0.72; 95% CI, 0.54-0.90). Specificity was maximized using threshold cutoffs of 0.10 (full model) and 0.14 (second model); a score below these thresholds indicates safety of prescription., Conclusions and Relevance: This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam. These algorithms can be used to guide prescription in clinical practice.

Patient satisfaction with therapeutic interventions is an important outcome of care. Although generic measures of patient satisfaction exist, there is no validated scale for measuring patient satisfaction with epilepsy surgery. We aimed to systematically obtain patient-identified factors related to satisfaction with epilepsy surgery as a means of informing clinicians about the ways that patients evaluate outcomes of their treatment and as a conceptual basis for the future development of epilepsy surgery patient satisfaction scales. Focus group discussions with epilepsy surgery patients (n=9) were conducted to identify themes relevant to patient satisfaction with epilepsy surgery and to draft initial items of importance. Consensus methodology (Delphi technique) was used to obtain expert opinion (n=13) to refine the items. Member-checking with focus group participants was performed to ensure the identified items were relevant, clear, and inclusive. A list of 31 items embodied 12 themes related to patient-reported satisfaction with epilepsy surgery. These included adverse effects, medical care or rehabilitation, seizure control, post-operative recovery, anti-seizure medication, independence, seizure worry, ability to drive, social relationships, self-confidence, improved cognitive function, and improved physical health. This study used a systematic approach to identify factors that are important to patients when assessing satisfaction with epilepsy surgery. This knowledge can assist clinicians caring for these patients and is also a critical step towards the validation of a formal scale to assess satisfaction with epilepsy surgery.

We sought to examine the risk of psychiatric symptoms associated with a first prescription for specific antiepileptic drugs (AEDs) used in monotherapy in a general cohort of patients with epilepsy. We used The Health Improvement Network database (comprising the years 2000-2012) to identify incident patients with epilepsy. The index date was that on which they met the case definition for epilepsy, and analyses only included patients who remained on monotherapy or received no AED therapy following diagnosis to avoid confounding by polytherapy. Psychiatric symptoms were defined using mental health clinical or treatment (medical or therapeutic) code. We analyzed the AED of interest as a time-varying covariate in multivariate Cox proportional hazard regression models controlling for confounding factors. We identified 9595 patients with incident epilepsy, 7400 of whom (77%) received a first-recorded AED prescription. Prescriptions for newer generation AEDs (lamotrigine and levetiracetam) steadily increased (constituting over 30% of all AED prescriptions by 2012) while valproate use significantly declined in females (~40% in 2002 to just over 20% by 2012). A total of 2190 patients were first exposed to carbamazepine (29.3%) and 222 to lamotrigine (3%), both of which were associated with a lower hazard of any coded psychiatric symptom or disorder in multivariate analyses (hazard ratio [HR]: 0.84, 95% confidence interval [95% CI]: 0.73-0.97; p = 0.02 and HR: 0.83, 95% CI: 0.70-0.99; p = 0.03, respectively, for carbamazepine and lamotrigine). Carbamazepine was also associated with a lower hazard for depression (HR: 0.81; 95% CI: 0.69-0.96; p = 0.013) and anxiety (HR: 0.77; 95% CI: 0.63-0.95; p = 0.013) in secondary analyses. This study provides evidence that carbamazepine and lamotrigine are associated with lower hazards for psychiatric symptoms following a diagnosis of epilepsy. These estimates can be used in clinical settings, and the precision should improve with more contemporary data that include larger proportions of newer generation AEDs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: It is unclear whether anxiety and depression impact health-related quality of life (HRQoL) equally across neurological diseases. This study examines the association between anxiety or depression and HRQoL in select neurological disorders., Methods: HRQoL was measured using the Short Form Health Survey (SF-12) in neurological patients: epilepsy (n = 279), migraine (n = 268), multiple sclerosis (MS) (n = 222), stroke (n = 204), and Parkinson's disease (PD) (n = 224). Depression and anxiety symptoms were assessed using the Patient Health Questionnaire (PHQ-9) and Hospital Anxiety and Depression Scale (HADS-A), respectively. Multiple linear regression was used to evaluate variables associated with the SF-12 mental health component (MCS) and physical health component scores (PCS). Pratt index was used to estimate the relative importance of anxiety and depression on HRQoL., Results: Anxiety and depression had the largest contribution to PCS in stroke and to MCS in epilepsy. Overall, anxiety and depression had a larger contribution to MCS as compared to PCS, except in stroke patients. Different patterns were seen across neurological diseases, with mental health variables strongly affecting MCS in all conditions, with also a sizable contribution to PCS in migraine, MS, and stroke., Conclusions: Anxiety and depression have varying impacts on HRQoL across neurological diseases. It is important for clinicians to be aware of how these patterns differ in each condition., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Preliminary evidence suggests that serotonin reuptake inhibitor (SRI) use may increase postictal respiratory drive and prevent death. We sought to determine whether SRIs are associated with improved all-cause and possible seizure-specific mortality in patients with epilepsy., Methods: Patients with epilepsy and a random 10:1 sample without epilepsy were extracted from The ClinicAl research using LInked Bespoke studies and Electronic health Records (CALIBER) resource. The hazard ratio (HR) of all-cause and possible seizure-specific mortality, treating SRI use as a time-varying covariate, was determined using the date of a second SRI prescription as exposure and in discrete 6-month periods over the entire duration of follow-up. We used Cox regression and competing risk models with Firth correction to calculate the HR. We controlled for age, sex, depression, comorbidity, (Charlson comorbidity index) and socioeconomic status (Index of Multiple Deprivation)., Results: We identified 2,718,952 eligible patients in CALIBER, of whom 16,379 (0.60%) had epilepsy. Median age and follow-up were 44 (interquartile range [IQR] 29-61]) and 6.4 years (IQR 2.4-10.4 years), respectively, and 53% were female. A total of 2,178 patients (13%) had at least two SRI prescriptions. Hazard of all-cause mortality was significantly elevated following a second prescription for an SRI (HR 1.64 95% confidence interval [95% CI] 1.44-1.86; p < 0.001). The HR was similar in 163,778 age, sex, and general practitioner (GP) practice-matched controls without epilepsy. Exposure to an SRI was not associated with seizure-related death (HR 1.08, 95% CI 0.59-1.97; 0.796)., Significance: There is no evidence in this large population-based cohort that SRIs protect against all-cause mortality or seizure-specific mortality. Rather, SRI use was associated with increased mortality, irrespective of epilepsy, which is probably due to various factors associated with the use of antidepressants. Larger studies with systematically collected clinical data are needed to shed further light on these findings., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Objective: Diagnosis of epilepsy is known to impact health-related quality of life (HRQOL) of children with new-onset epilepsy and can also influence their conceptualization and valuation of HRQOL construct, also known as response shift. This study investigates the presence of response shift in a cohort of children with new-onset epilepsy., Methods: Data are from the HEalth-Related QUality of Life in children with Epilepsy Study, a prospective cohort study of 373 children with new-onset epilepsy. Hypotheses about the presence of reconceptualization, reprioritization, and recalibration response shift were tested in the Quality of Life in Childhood Epilepsy (QOLCE-55) Questionnaire, a parent-reported, disease-specific HRQOL measure, using Oort's structural equation model between baseline and 1-year follow-up. Model fit was assessed using log-likelihood ratio test, root mean square error of approximation, and comparative fit index., Results: Small positive uniform recalibration response shift effects were observed on physical, emotional, and social functioning domains of the QOLCE-55, but negligibly small negative nonuniform recalibration response shift effect was observed on social functioning domain. There was no significant change in overall QOLCE-55 scores over time after adjusting for response shift effects., Significance: Parents of children with new-onset epilepsy are likely to positively recalibrate (upward bias) their assessments of their children's HRQOL over a 1-year period after diagnosis. This study highlights the potential benefits of response shift as a desired consequence in parents' perception of changes in HRQOL of children with new-onset epilepsy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The diagnosis of epilepsy in children is known to impact the trajectory of their health-related quality of life (HRQOL) over time. However, there is limited knowledge about variations in longitudinal trajectories across multiple domains of HRQOL. This study aims to characterize the heterogeneity in HRQOL trajectories across multiple HRQOL domains and to evaluate predictors of differences among the identified trajectory groups in children with new-onset epilepsy. Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study (HERQULES), a prospective multi-center study of 373 children newly diagnosed with new-onset epilepsy who were followed up over 2years. Child HRQOL and family factors were reported by parents, and clinical characteristics were reported by neurologists. Group-based multi-trajectory modeling was adopted to characterize longitudinal trajectories of HRQOL as measured by the individual domains of cognitive, emotional, physical, and social functioning in the 55-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Multinomial logistic regression was used to assess potential factors that explain differences among the identified latent trajectory groups. Three distinct HRQOL trajectory subgroups were identified in children with new-onset epilepsy based on HRQOL scores: "High" (44.7%), "Intermediate" (37.0%), and "Low" (18.3%). While most trajectory groups exhibited increasing scores over time on physical and social domains, both flat and declining trajectories were noted on emotional and cognitive domains. Less severe epilepsy, an absence of cognitive and behavioral problems, lower parental depression scores, better family functioning, and fewer family demands were associated with a "Higher" or "Intermediate" HRQOL trajectory. The course of HRQOL over time in children with new-onset epilepsy appears to follow one of three different trajectories. Addressing the clinical and psychosocial determinants identified for each pattern can help clinicians provide more targeted care to these children and their families., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Importance: A bidirectional relationship exists between epilepsy and depression. However, any putative biological gradient between depression severity and the risk of epilepsy, and the degree to which depression mediates the influence of independent risk factors for epilepsy, has yet to be examined., Objective: To determine the effect of depression on the risk of epilepsy and seizure outcomes., Design, Setting, and Participants: An observational study of a population-based primary care cohort (all patients free of prevalent depression and epilepsy at 18-90 years of age who were active after the Acceptable Mortality Reporting date in The Health Improvement Network database) and a prospectively collected tertiary care cohort (all patients whose data were prospectively collected from the Calgary Comprehensive Epilepsy Programme). The analyses were performed on March 16, 2016., Main Outcome and Measures: The hazard of developing epilepsy after incident depression and vice versa was calculated. In addition, a mediation analysis of the effect of depression on risk factors for epilepsy and the odds of seizure freedom stratified by the presence of depression were performed., Results: We identified 10 595 709 patients in The Health Improvement Network of whom 229 164 (2.2%) developed depression and 97 177 (0.9%) developed epilepsy. The median age was 44 years (interquartile range, 32-58 years) for those with depression and 56 years (interquartile range, 43-71 years) for those with epilepsy. Significantly more patients with depression (144 373 [63%] were women, and 84 791 [37%] were men; P < .001) or epilepsy (54 419 [56%] were women, and 42 758 [44%] were men; P < .001) were female. Incident epilepsy was associated with an increased hazard of developing depression (hazard ratio [HR], 2.04 [95% CI, 1.97-2.09]; P < .001), and incident depression was associated with an increased hazard of developing epilepsy (HR, 2.55 [95% CI, 2.49-2.60]; P < .001) There was an incremental hazard according to depression treatment type with lowest risk for those receiving counselling alone (HR, 1.84 [95% CI, 1.30-2.59]; P < .001), an intermediate risk for those receiving antidepressants alone (HR, 3.43 [95% CI, 3.37-3.47]; P < .001), and the highest risk for those receiving both (HR, 9.85 [95% CI, 5.74-16.90]; P < .001). Furthermore, depression mediated the relationship between sex, social deprivation, and Charlson Comorbidity Index with incident epilepsy, accounting for 4.6%, 7.1%, and 20.6% of the total effects of these explanatory variables, respectively. In the Comprehensive Epilepsy Programme, the odds of failing to achieve 1-year seizure freedom were significantly higher for those with depression or treated depression., Conclusions and Relevance: Common underlying pathophysiological mechanisms may explain the risk of developing epilepsy following incident depression. Treated depression is associated with worse epilepsy outcomes, suggesting that this may be a surrogate for more severe depression and that severity of depression is associated with severity of epilepsy.

Clinical decision rules (CDRs) have been empirically demonstrated to improve patient satisfaction and enhance cost-effective care. The use of CDRs has not yet been robustly explored for epilepsy. We performed a systematic review of MEDLINE (from 1946) and Embase (from 1947) using Medical Subject Headings and keywords related to CDRs and epilepsy. We included original research of any language deriving, validating, or implementing a CDR using standardized definitions. Study quality was determined using a modified version of previously published criteria. A bivariate model was used to meta-analyze studies undergoing sequential derivation and validation studies. Of 2445 unique articles, 5 were determined to be relevant to this review. Three were derivation studies (three diagnostic and one therapeutic), one validation study, and one combined derivation and validation study. No implementation studies were identified. Study quality varied but was primarily of a moderate level. Two CDRs were validated and, thus, able to be meta-analyzed. Although initial measures of accuracy were high (sensitivity ~80% or above), they tended to diminish significantly in the validation studies. The pooled estimates of sensitivity and specificity both exhibited wide 95% confidence and prediction intervals that may limit their utility in routine practice. Despite the advances in therapeutic and diagnostic interventions for epilepsy, few CDRs have been developed to guide their use. Future CDRs should address common clinical scenarios such as efficient use of diagnostic tools and optimal clinical treatment decisions. Given their potential for advancing efficient, evidence-based, patient-centered healthcare, CDR development should be a priority in epilepsy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To determine whether postictal cognitive and behavioral impairment (PCBI) is independently associated with specific aspects of a patient's psychosocial health in those with epilepsy and nonepileptic events., Methods: We used the University of Calgary's Comprehensive Epilepsy Clinic prospective cohort database to identify patients reporting PCBI. The cohort was stratified into those diagnosed with epilepsy or nonepileptic events at first clinic visit. Univariate comparisons and stepwise multiple logistic regression with backward elimination method were used to identify factors associated with PCBI for individuals with epilepsy and those with nonepileptic events. We then determined if PCBI was independently associated with depression and the use of social assistance when controlling for known risk factors., Results: We identified 1,776 patients, of whom 1,510 (85%) had epilepsy and 235 had nonepileptic events (13%). PCBI was independently associated with depression in those with epilepsy (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.06-2.83; p = 0.03) and with the need for social assistance in those with nonepileptic events (OR 4.81; 95% CI 2.02-11.42; p < 0.001)., Conclusions: PCBI appears to be significantly associated with differing psychosocial outcomes depending on the patient's initial diagnosis. Although additional research is necessary to examine causality, our results suggest that depression and employment concerns appear to be particularly important factors for patients with PCBI and epilepsy and nonepileptic attacks, respectively., (© 2016 American Academy of Neurology.)

Objective: Elderly onset epilepsy represents a distinct subpopulation that has received considerable attention due to the unique features of the disease in this age group. Research into this particular patient group has been limited by a lack of a standardized definition and understanding of the attributes associated with elderly onset epilepsy., Methods: We used a prospective cohort database to examine differences in patients stratified according to age of onset. Linear support vector machine learning incorporating all significant variables was used to predict age of onset according to prespecified thresholds. Sensitivity and specificity were calculated and plotted in receiver-operating characteristic (ROC) space. Feature coefficients achieving an absolute value of 0.25 or greater were graphed by age of onset to define how they vary with time., Results: We identified 2,449 patients, of whom 149 (6%) had an age of seizure onset of 65 or older. Fourteen clinical variables had an absolute predictive value of at least 0.25 at some point over the age of epilepsy-onset spectrum. Area under the curve in ROC space was maximized between ages of onset of 65 and 70. Features identified through machine learning were frequently threshold specific and were similar, but not identical, to those revealed through simple univariable and multivariable comparisons., Significance: This study provides an empirical, clinically informed definition of "elderly onset epilepsy." If validated, an age threshold of 65-70 years can be used for future studies of elderly onset epilepsy and permits targeted interventions according to the patient's age of onset., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Background: Epilepsy severity has been recognized as a significant predictor of health-related quality of life in patients with epilepsy. However, clinical markers of epilepsy severity such as seizure frequency often fail to capture important aspects of the disease. This study investigates the factors associated with patient-reported severity of epilepsy, assessed by the Global Assessment of Severity of Epilepsy (GASE) scale in adults with epilepsy., Methods: Data from a cohort of 250 patients consecutively enrolled in the Neurological Diseases and Depression Study (NEEDS) were used to assess the determinants of epilepsy severity as measured by the GASE scale. Multiple linear regression analyses were used to examine the mediation effect of clinical and sociodemographic characteristics on patients' ratings on the GASE scale., Results: The mean age of the study participants was 39.8 (SD=14.9) years, of which 44.4% were male. About 66.8% of the participants reported "not at all severe" or "a little severe" epilepsy, while 0.4% reported "extremely severe" epilepsy. One-year seizure freedom, number of antiseizure medications, medication side effects, depression, anxiety, and seizure-related disability were identified as significant determinants of patients' ratings of epilepsy severity. Seizure-related disability mediated the effects of 1-year seizure freedom, number of antiseizure medications, and medication side effects on epilepsy severity., Conclusion: Overall, patients with epilepsy who reported higher GASE scores were less likely to achieve 1-year seizure freedom and more likely to be on more antiseizure medications, experience more side effects from medication, endorse more depression and anxiety symptoms, and have increased self-reported seizure-related disability. The identified determinants of global, self-rated epilepsy severity can aid the design of appropriate interventions and support services for patients with severe epilepsy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Seizure-related disability is an important contributor to health-related quality of life in persons with epilepsy. Yet, there is little information on patient-centered reports of seizure-related disability, as most studies focus on specific constructs of health-related disability, rather than epilepsy. We investigated how patients rate their own disability and how these ratings correlate with various clinical and sociodemographic characteristics., Methods: In a prospective cohort of 250 adults with epilepsy consecutively enrolled in the Neurological Disease and Depression Study (NEEDs), we obtained a broad range of clinical and patient-reported measures, including patients' ratings of seizure-related disability and epilepsy severity using self-completed, single-item, 7-point response global assessment scales. Spearman's correlation, multiple linear regression, and mediation analyses were used to examine the association between seizure-related disability scores and clinical and demographic characteristics of persons with epilepsy., Results: The mean age and duration of epilepsy was 39.8 and 16.7 years, respectively. About 29.5% of the patients reported their seizures as "not at all disabling," whereas 5.8% of the patients reported them as "extremely disabling." Age, seizure freedom at 1 year, anxiety, and epilepsy severity were identified as statistically significant predictors of disability scores. The indirect effects of age and seizure freedom, attributable to mediation through epilepsy severity, accounted for 25.0% and 30.3% of the total effects of these determinants on seizure-related disability, respectively., Significance: Measuring seizure-related disability has heuristic value and it has important correlates and mediators that can be targeted for intervention in practice. Addressing modifiable factors associated with disability (e.g., seizure freedom and anxiety) could have a significant impact on decreasing the burden of disability in people with epilepsy., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Objectives Health-related quality of life ( HRQOL) is an important indicator of well-being in patients with epilepsy. When assessing changes in HRQOL over time, some of the changes observed may be due to the patients' change in the internal standards, value, or meaning that they attribute to the HRQOL domain being measured, rather than actual change, a phenomenon known as response shift. Response shifts are increasingly recognized as an important explanation for the seemingly paradoxical or counterintuitive HRQOL results often observed in chronic conditions. We investigated the presence of changing values (reprioritization response shift) in data from a surgical randomized controlled trial of patients with temporal lobe epilepsy ( TLE). Methods Eighty patients with TLE, who were randomized to surgical and medical treatment, provided data on the epilepsy-specific 31-item Quality of life in Epilepsy (QOLIE-31) questionnaire at baseline and 1 year after randomization. Reprioritization response shift among the seven QOLIE-31 domains was assessed using changes in the relative importance weights derived from logistic regression and discriminant analysis. Results The relative importance analysis showed a statistically significant increase over time in the importance of social function, but a significant decrease in the relative importance of seizure worry. There were no significant changes in the relative importance of the remaining five domains in distinguishing between surgical and medical group over time. Significance Patients that receive surgical treatment are more likely to experience a decrease in the valuation of seizure worry and an increase in the value of social function as compared to patients who are medically treated. Changes in expectation about seizure freedom and social function may confound the assessment of longitudinal change on these outcomes, and highlight the importance of assessing response shift and the limitations of assessing HRQOL at a single point in time or without a control group. A PowerPoint slide summarizing this article is available for download in the Supporting Information section . [ABSTRACT FROM AUTHOR]

Objective Methods Results Significance Health state utilities are required to obtain quality adjusted life years, a common metric that informs clinical decision‐making at individual, group, and health policy levels. Health state utilities are different from health‐related quality of life, and their distribution across patients with epilepsy, as well as the factors that impact them, have not been studied in depth. We aimed to describe the distribution of health state utilities in people with epilepsy and the impact of different combinations of clinical and demographic factors on health state evaluation.We performed a retrospective analysis of patients' data prospectively collected in the Calgary Comprehensive Epilepsy Program registry. Patient‐reported health state utilities were measured using the 5‐level EuroQol 5‐Dimension scale (EQ‐5D‐5L) completed at their initial assessment. EQ‐5D‐5L index scores were derived via the time trade‐off approach based on Canadian norms, and their distribution across different health states and patient characteristics was obtained. The Tobit regression model was used to evaluate the determinants of EQ‐5D‐5L index scores.Of 1446 patients included in this analysis, 724 (50.5%) were female. The median (interquartile range) Canada‐normed EQ‐5D‐5L index score was .87 (.71–.91). Patients with significantly lower health utilities were more likely to be female (p = .008), to be older (p = .034), to be unmarried (p = .013), to have failed to achieve 1‐year seizure freedom (p < .001), to have no postsecondary education (p = .028), to be depressed (p < .001), to have antiseizure medication side effects (p = .001), to be unemployed (p < .001), and to be unable to drive (p < .001). A look‐up table of health utilities based on combinations of clinical–demographic characteristics was produced.Health utility estimates for combinations of different health states in people with epilepsy attending specialty clinics are now available. These can help guide clinical decision‐making in routine clinical practice, economic evaluations of treatment interventions, and health care policies. [ABSTRACT FROM AUTHOR]