| 1. |
- Andrén, Kerstin, 1980, et al.
(författare)
-
Adherence to anti-seizure medications in the Swedish Prospective Regional Epilepsy Database and Biobank for Individualized Clinical Treatment (PREDICT)
- 2023
-
Ingår i: Epilepsy and Behavior Reports. - 2589-9864. ; 24
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe the extent of, and risk factors for, non-adherence to anti-seizure medications (ASMs) in adult people with epilepsy (PWE) in Sweden. A cross-sectional multi-centre study was performed of PWEs in western Sweden, with data from medical records, and a questionnaire filled in by the participants including self-reports on how often ASM doses had been forgotten during the past year. Participants were categorized into adherent if they forgot at 0–1 occasion, and non-adherent if they forgot at 2–10 or >10 occasions. Demographic and clinical factors were compared by Chi2- or Fisher's test and a logistic regression model was used to find risk factors for non-adherence. In the cohort of 416 PWE aged median 43, IQR 29–62 years, 398 patients were prescribed ASM treatment at inclusion, and 39 % (n = 154) were in the non-adherent group. Significant factors in the multivariable analysis were: younger age, seizure freedom the past year, valproate treatment and experiencing side effects. The rate of self-reported non-adherence was high, illustrating a need for continuous focus on fundamental aspects of epilepsy care. The identified risk factors could enable quality improvement projects and patient education to be directed to those at risk of non-adherence.
|
|
| 2. |
- Banote, Rakesh Kumar, et al.
(författare)
-
Quantitative proteomic analysis to identify differentially expressed proteins in patients with epilepsy
- 2021
-
Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 174
-
Tidskriftsartikel (refereegranskat)abstract
- There is a great need for biomarkers in epilepsy, particularly markers of epileptogenesis. A first seizure will lead to epilepsy in 20-45 % of cases, but biomarkers that can identify these individuals are missing. The purpose of this study was to identify potential biomarkers of epilepsy/epileptogenesis in a cohort of adults with new-onset seizures, using quantitative proteomic analysis. Plasma was collected from 55 adults with new-onset seizures and sufficient follow-up to identify epilepsy. After a follow up period of two years, 63.6 % of the cohort had a diagnosis of epilepsy, whereas 36.4 % of patients only had a single seizure. Plasma proteins were extracted and labelled with tandem mass tags, then analyzed using mass spectrometry approach. Proteins that were up- or downregulated by >= 20 % and with a pvalue of <0.05 were considered as differentially expressed and were also annotated to their processes and pathways. Several proteins were differentially expressed in the epilepsy group compared to controls. A total of 1075 proteins were detected, out of which 41 proteins were found to be significantly dysregulated in epilepsy patients. Many of these have been identified in experimental studies of epilepogenesis. We report plasma proteome profiling in new-onset epilepsy in a pilot study with 55 individuals. The identified proteins could be involved in pathways associated with epileptogenesis. The results should be seen as hypothesisgenerating and targeted, confirmatory studies are needed.
|
|
| 3. |
- Eriksson, Hanna, et al.
(författare)
-
Brain injury markers in new-onset seizures in adults: A pilot study
- 2021
-
Ingår i: Seizure-European Journal of Epilepsy. - : Elsevier BV. - 1059-1311. ; 92, s. 62-67
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Biochemical markers of brain pathology could potentially contribute to diagnosis and prediction in epilepsy. We describe levels of five brain injury markers in adults with new-onset seizures, and assess group differences in patients with a single seizure, epilepsy, and poststroke epilepsy. Methods: In this prospective observational study, adults with new-onset seizures were recruited at Sahlgrenska University Hospital, Sweden, and concentrations of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), microtubule-associated protein tau (tau), S100 calcium-binding protein (S100B), and neuron-specific enolase (NSE) were measured. Participants were categorized as epilepsy, poststroke epilepsy (PSE), or single seizure (no additional seizures). Patients were followed until a diagnosis of epilepsy or PSE, or for at least two years in single seizure cases. Results: The cohort included 23 (37%) individuals with a single seizure, 24 (39%) with epilepsy, and 15 (24%) with PSE. The concentrations of S100B were higher in patients with epilepsy and PSE than in single seizures (p = 0.0023 and p = 0.0162, respectively). The concentrations of NfL were higher in patients with PSE than in single seizures (p=0.0027). After age-normalization, levels of S100B were higher in patients with epilepsy and levels of NfL were higher in patients with PSE (p = 0.0021 and p = 0.0180). Conclusion: Levels of S100B and NfL were higher in patients with epilepsy or PSE than patients with single seizures. Further studies are needed to investigate the biomarker potential of brain injury markers as predictors of epilepsy course or indicators of epileptogenesis.
|
|
| 4. |
- Håkansson, Samuel, 1996, et al.
(författare)
-
Potential for improved retention rate by personalized antiseizure medication selection: A register-based analysis
- 2021
-
Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 62:9, s. 2123-2132
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The first antiseizure medication (ASM) is ineffective or intolerable in 50% of epilepsy cases. Selection between more than 25 available ASMs is guided by epilepsy factors, but also age and comorbidities. Randomized evidence for particular patient subgroups is seldom available. We asked whether register data could be used for retention rate calculations based on demographics, comorbidities, and ASM history, and quantified the potential improvement in retention rates of the first ASM in several large epilepsy cohorts. We also describe retention rates in patients with epilepsy after traumatic brain injury and dementia, patient groups with little available evidence. Methods We used medical, demographic, and drug prescription data from epilepsy cohorts from comprehensive Swedish registers, containing 6380 observations. By analyzing 381 840 prescriptions, we studied retention rates of first- and second-line ASMs for patients with epilepsy in multiple sclerosis (MS), brain infection, dementia, traumatic brain injury, or stroke. The rank of retention rates of ASMs was validated by comparison to published randomized control trials. We identified the optimal stratification for each brain disease, and quantified the potential improvement if all patients had received the optimal ASM. Results Using optimal stratification for each brain disease, the potential improvement in retention rate (percentage points) was MS, 20%; brain infection, 21%; dementia, 14%; trauma, 21%; and stroke, 14%. In epilepsy after trauma, levetiracetam had the highest retention rate at 80% (95% confidence interval [CI] = 65-89), exceeding that of the most commonly prescribed ASM, carbamazepine (p = .04). In epilepsy after dementia, lamotrigine (77%, 95% CI = 68-84) and levetiracetam (74%, 95% CI = 68-79) had higher retention rates than carbamazepine (p = .006 and p = .01, respectively). Significance We conclude that personalized ASM selection could improve retention rates and that national registers have potential as big data sources for personalized medicine in epilepsy.
|
|
| 5. |
- Larsson, David, 1986
(författare)
-
Acquired Epilepsy with a Focus on Stroke: Treatment and Prognosis
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The relationship between epilepsy and stroke is complicated. While stroke is a major cause of epilepsy after middle age, there is also evidence that the risk of stroke is increased in persons with epilepsy. The overall aim of this dissertation is to elaborate on the prognosis and treatment of epilepsy in older adults and its association to stroke. It is based on four studies which have been conducted using information from linked national registers, which offer unique opportunities to follow thousands of patients over a long period of time. The results from Papers I-II indicate that a significant proportion of all new-onset seizures after middle age will herald a subsequent stroke. Using incidence data and population statistics, we estimated the 10-year risk of stroke to be between 5-20%, depending on age group. In relative terms, the risk appears to be almost two-fold (odds ratio [OR] 1.77; 95% confidence interval [95%CI] 1.65-1.89) compared with age-matched controls from the general population – and highest during the first year after seizure onset (OR 2.21; 95 % CI 1.79–2.72). The studies described in Papers III-IV examined prognostic aspects of antiseizure medication (ASM) therapy in poststroke epilepsy. Paper III found the 5-year retention rate to be highest for lamotrigine (0.75, 95%CI 0.70–0.79) and levetiracetam (0.69, 95%CI 0.63–0.74), suggesting these drugs are well tolerated in this patient group. Paper IV used a similar methodology but investigated if mortality varied with different ASMs in monotherapy. Patients treated with lamotrigine had lower mortality (hazard ratio [HR] 0.72, 95%CI 0.60-0.86) than the reference group treated with carbamazepine, while patients treated with valproic acid had higher mortality (HR 1.40, 95%CI 1.23-1.59). Treatment with levetiracetam was associated with a reduced risk of cardiovascular death compared to carbamazepine (HR 0.77, 95%CI 0.60-0.99). In conclusion, this thesis supports a tailored management approach in adults with new-onset seizures late in life, particularly in those with a history of stroke. Persons with late-onset seizures have high vascular risk, potentially warranting screening and treatment for vascular risk factors. Moreover, the association between ASM selection and mortality raises concerns about clinically relevant drug-drug or drug-disease interactions that may modify vascular risk. Overall, lamotrigine and levetiracetam seem sensible initial treatment options in this patient group.
|
|
| 6. |
- Larsson, David, 1986, et al.
(författare)
-
Antiseizure medication selection and retention for adult onset focal epilepsy in a Swedish health service region: A population-based cohort study
- 2023
-
Ingår i: Epilepsia. - 0013-9580. ; 64:10, s. 2617-2624
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Historically, approximately half of those with newly diagnosed epilepsy have responded to and tolerated the first antiseizure medication (ASM), but there are few contemporary real-world data. Third-generation ASMs have improved tolerability and are increasingly used according to prescription data. We aimed to describe current ASM selection and retention in adult onset focal epilepsy in western Sweden. Methods: A multicenter retrospective cohort study was performed at five public neurology care providers in western Sweden (nearly complete coverage in the area). We reviewed 2607 medical charts and included patients diagnosed with nongeneralized epilepsy after January 1, 2020 who had a seizure onset after age 25 years (presumed focal onset) and were started on ASM monotherapy. Results: A total of 542 patients (median age at seizure onset = 68 years, interquartile range = 52-77) were included. Most patients received levetiracetam (62%) or lamotrigine (35%), with levetiracetam being more common among men and those with structural causes or short epilepsy duration. During follow-up (median = 471.5 days), 463 patients (85%) remained on the first ASM. Fifty-nine (18%) patients discontinued levetiracetam, and 18 (10%) ended treatment with lamotrigine (p =.010), most commonly because of side effects. In a multivariable Cox regression model, the discontinuation risk was higher for levetiracetam than lamotrigine (adjusted hazard ratio = 2.01, 95% confidence interval = 1.16-3.51). Significance: Levetiracetam and lamotrigine were the dominating first ASMs for adult onset focal epilepsy in our region, indicating good awareness of problems with enzyme induction or teratogenicity of older drugs. The most striking finding is the high retention rates, perhaps reflecting a shift toward an older epilepsy population, higher tolerability of newer ASMs, or suboptimal follow-up. The finding that treatment retention differed among patients receiving levetiracetam and lamotrigine aligns with the recent SANAD II results. It suggests lamotrigine may be underutilized in our region and that education efforts are needed to ensure it is considered the first choice more often.
|
|
| 7. |
- Larsson, David, 1986, et al.
(författare)
-
Association Between Antiseizure Drug Monotherapy and Mortality for Patients With Poststroke Epilepsy
- 2022
-
Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 79:2, s. 169-175
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE There is little evidence to guide the choice of antiseizure medication (ASM) for patients with poststroke epilepsy. Theoretical concerns about detrimental effects of ASMs on survival exist. Enzyme-inducing drugs could interfere with secondary stroke prevention. The US Food and Drug Administration recently issued a safety announcement about the potential proarrhythmic properties of lamotrigine. OBJECTIVE To investigate whether mortality varies with specific ASMs among patients with poststroke epilepsy. DESIGN, SETTING, AND PARTICIPANTS A cohort study was conducted using individual-level data from linked registers on all adults in Sweden with acute stroke from July 1, 2005, to December 31, 2010, and subsequent onset of epilepsy before December 31, 2014. A total of 2577 patients receiving continuous ASM monotherapy were eligible for the study. Data were analyzed between May 27, 2019, and April 8, 2021. EXPOSURES The dispensed ASM (Anatomical Therapeutic Chemical code N03A) determined exposure status, and the first dispensation date marked the start of treatment. MAIN OUTCOMES AND MEASURES The primary outcome, all-cause death, was analyzed using Cox proportional hazards regression with carbamazepine as the reference. Cardiovascular death (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I0-I99 as the underlying cause) was assessed using Fine-Gray competing risk regression models. RESULTS A total of 2577 patients (1400 men [54%]; median age, 78 years [IQR, 69-85 years]) were included. The adjusted hazard ratio of all-cause death compared with carbamazepine was 0.72 (95% CI, 0.60-0.86) for lamotrigine, 0.96 (95% CI, 0.80-1.15) for levetiracetam, 1.40 (95% CI, 1.23-1.59) for valproic acid, 1.16 (95% CI, 0.88-1.51) for phenytoin, and 1.16 (95% CI, 0.81-1.66) for oxcarbazepine. The adjusted hazard ratio of cardiovascular death compared with carbamazepine was 0.76 (95% CI, 0.61-0.95) for lamotrigine, 0.77 (95% CI, 0.60-0.99) for levetiracetam, 1.40 (95% CI, 1.19-1.64) for valproic acid, 1.02 (95% CI, 0.71-1.47) for phenytoin, and 0.71 (95% CI, 0.42-1.18) for oxcarbazepine. CONCLUSIONS AND RELEVANCE This cohort study's findings suggest differences in survival between patients treated with different ASMs for poststroke epilepsy. Patients receiving lamotrigine monotherapy had significantly lower mortality compared with those receiving carbamazepine. The opposite applied to patients prescribed valproic acid, who had a higher risk of cardiovascular and all-cause death. Levetiracetam was associated with a reduced risk of cardiovascular death compared with carbamazepine, but there was no significant difference in overall mortality.
|
|
| 8. |
- Larsson, David, 1986, et al.
(författare)
-
Risk of stroke after new-onset seizures
- 2020
-
Ingår i: Seizure-European Journal of Epilepsy. - : Elsevier BV. - 1059-1311 .- 1532-2688. ; 83, s. 76-82
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Observational cohort studies have reported a potentially increased risk of stroke in patients with epileptic seizures. Whether late-onset seizures merit primary stroke prophylaxis is not known, and more information on stroke risk is needed for the planning of RCTs. We performed a case-control study based on Swedish national registers to quantify the risk of stroke after epileptic seizures. Methods: Cases <= 100 years of age with a first-ever stroke 2001-2009 were identified through the Swedish Stroke Register, and stroke-free controls (matched for age and sex) were obtained from the Population Register. The National Patient Register provided information on diagnostic codes for seizures, epilepsy and comorbidities. 123 105 stroke cases and 250 506 controls were included. Results: Epileptic seizures prior to index stroke date were detected in 1559 (1.27 %) cases and 1806 (0.72 %) controls, yielding an odds ratio (95 % confidence interval) for stroke of 1.77 (1.65-1.89). ORs were similar in men and women, but higher below the age of 75. An onset of seizures in the year preceding stroke date resulted in a higher risk for stroke (OR = 2.21, 95 % CI =1.79-2.72) compared to when more than 5 years had passed since the first seizure (OR = 1.57, 95 % CI = 1.43-1.72). Conclusion: A history of epileptic seizures was associated with an increased risk of subsequent stroke. The risk seems to be particularly high in the first year following seizure diagnosis, which supports the notion that unexplained late-onset seizures may merit swift assessment of vascular risk profile. The nature of stroke prevention requires further study.
|
|
| 9. |
- Onerup, Aron, 1983, et al.
(författare)
-
Effect of Short-Term Homebased Pre- and Postoperative Exercise on Recovery after Colorectal Cancer Surgery (PHYSSURG-C): A Randomized Clinical Trial.
- 2022
-
Ingår i: Annals of surgery. - 1528-1140. ; 275:3, s. 448-455
-
Tidskriftsartikel (refereegranskat)abstract
- To determine the effect of a short-term, unsupervised exercise intervention before and after colorectal cancer surgery on self-assessed physical recovery.Preoperative exercise interventions could help improve recovery after colorectal cancer surgery and is currently recommended.A randomized, parallel, open-label trial in six university or regional hospitals in Sweden. Inclusion criteria were age ≥20years and planned elective colorectal cancer surgery. Participants were randomised to either a physical activity intervention with aerobic activity and inspiratory muscle training two weeks pre- and four weeks postoperatively or usual care. The primary outcome measure was self-assessed physical recovery four weeks postoperatively. Analyses were performed according to intention to treat. Outcome assessors were masked regarding the intervention while both participants and physiotherapists were informed due to the nature of the intervention.Between Jan 22, 2015, and May 28, 2020, 761 participants were recruited and assigned to either intervention (I) (n = 379) or control (C) (n = 382). After exclusions 668 participants (I = 317, C = 351) were included in the primary analysis. There was no effect from the intervention on the primary outcome measure (adjusted odds ratio (OR) 0.84, 95% confidence interval (CI) 0.62 - 1.15) with 13% and 15% of participants feeling fully physically recovered in I and C respectively. There were no reported adverse events.There was no effect from a physical activity intervention before and after colorectal cancer surgery on short-term self-assessed physical recovery. The results from this study call for reconsiderations regarding current recommendations for preoperative physical activity interventions.
|
|
| 10. |
- Polychronidis, Konstantinos, et al.
(författare)
-
Second antiseizure medication monotherapy in patients with adult-onset epilepsy: A register-based analysis
- 2024
-
Ingår i: EPILEPSY & BEHAVIOR. - 1525-5050 .- 1525-5069. ; 155
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Revision of therapy is fundamental in epilepsy care, since only half of patients achieve seizure freedom and tolerate the first antiseizure medication (ASM). We studied the selection and retention of second antiseizure medication monotherapy in adults who discontinued treatment with one of the three most frequently prescribed first ASMs, and the impact of age or brain comorbidities. Methods: Using Swedish national registers, we conducted a population-based, retrospective cohort study from 2007 to 2019 on patients age >= 30 at the epilepsy diagnosis that had switched to a second monotherapy after the three most common initial monotherapies (n = 7369). Retention rates (RR) were estimated via Kaplan-Meier. Discontinuation of the second monotherapy was defined as 12-month prescription gap or initiation of a third ASM. Analyses were stratified by sex, age, and presence of stroke or dementia. Results: The three most commonly prescribed second ASMs were carbamazepine, levetiracetam, and lamotrigine. The 1-year retention rate was 63-76% in all patients. For groups with stroke or dementia, the maximal 1-year RRs were 77% and 87%, respectively. After five years, retention rates ranged from 12% to 39%. There were no major differences between ASMs, apart from in patients discontinuing carbamazepine, where lamotrigine had a superior retention compared to levetiracetam as second monotherapy. Significance: The three most often prescribed second ASMs seem to be suitable treatment options according to present guidelines. The second ASMs' retention rates were initially high in all studied patient groups but dropped to approximately the expected proportion of second monotherapy responders over the next five years. This suggests that therapy revision could be expedited.
|
|
