IntroductionThe aim is to perform an economic evaluation alongside a randomized controlled trial comparing guided self-help cognitive behavioral therapy-enhanced (CBT-E) for binge-eating disorder ... Show moreIntroductionThe aim is to perform an economic evaluation alongside a randomized controlled trial comparing guided self-help cognitive behavioral therapy-enhanced (CBT-E) for binge-eating disorder (BED) to a waiting list control condition. MethodsBED patients (N = 212) were randomly assigned to guided self-help CBT-E or the 3-month waiting list. Measurements took place at baseline and the end-of-treatment. The cost-effectiveness analysis was performed using the number of binge-eating episodes during the last 28 days as an outcome indicator according to the eating disorder examination. A cost-utility analysis was performed using the EuroQol-5D. ResultsThe difference in societal costs over the 3 months of the intervention between both conditions was euro679 (confidence interval [CI] 50-1330). The incremental costs associated with one incremental binge eating episode prevented in the guided self-help condition was approximately euro18 (CI 1-41). From a societal perspective there was a 96% likelihood that guided self-help CBT-E led to a greater number of binge-eating episodes prevented, but at higher costs. Each additional quality-adjusted life year (QALY) gained was associated with incremental costs of euro34,000 (CI 2494-154,530). With a 95% likelihood guided self-help CBT-E led to greater QALY gain at higher costs compared to waiting for treatment. Based on the National Institute for Health and Clinical Excellence willingness-to-pay threshold of euro35,000 per QALY, guided self-help CBT-E can be considered cost-effective with a likelihood of 95% from a societal perspective. DiscussionGuided self-help CBT-E is likely a cost-effective treatment for BED in the short-term (3-month course of treatment). Comparison to treatment-as-usual is recommended for future research, as it enables an economic evaluation with a longer time horizon. Public SignificanceOffering treatment remotely has several benefits for patients suffering from binge-eating disorders. Guided self-help CBT-E is an efficacious and likely cost-effective treatment, reducing binge eating and improving quality-of-life, albeit at higher societal costs. Show less
Kort, A.M. de; Kuiperij, H.B.; Marques, T.M.; Jäkel, L.; Berg, E. van den; Kersten, I.; ... ; Verbeek, M.M. 2023
Background: Owing to the gap between treatment supply and demand, there are long waiting periods for patients with binge eating disorder, and there is an urgent need to increase their access to... Show moreBackground: Owing to the gap between treatment supply and demand, there are long waiting periods for patients with binge eating disorder, and there is an urgent need to increase their access to specialized treatment. Guided self-help cognitive behavioral therapy-enhanced (CBT-E) may have great advantages for patients if its efficacy can be established.Objective: The aim of this study was to examine the efficacy of guided self-help CBT-E compared with that of a delayed-treatment control condition.Methods: A single-blind 2-arm randomized controlled trial was designed to evaluate guided self-help CBT-E according to an intention-to-treat analysis. A total of 180 patients were randomly assigned to guided self-help CBT-E (n=90, 50%) or the delayed-treatment control condition (n=90, 50%) for which guided self-help CBT-E was provided after the initial 12-week delay. The primary outcome was reduction in binges. The secondary outcome was full recovery at the end of treatment, as measured using the Eating Disorder Examination during the last 4 weeks of treatment. A linear mixed model analysis was performed to compare treatment outcomes at the end of treatment. A second linear mixed model analysis was performed to measure between and within-group effects for up to 24 weeks of follow-up. The Eating Disorder Examination-Questionnaire and clinical impairment assessment were conducted before and after treatment and during follow-up. In addition, dropout rates were assessed in both conditions.Results: During the last 4 weeks of treatment, objective binges reduced from an average of 19 (SD 16) to 3 (SD 5) binges, and 40% (36/90) showed full recovery in the guided self-help CBT-E group. Between-group effect size (Cohen d) was 1.0 for objective binges. At follow-up, after both groups received treatment, there was no longer a difference between the groups. Of the 180 participants, 142 (78.9%) completed treatment. The overall treatment dropout appeared to be associated with gender, level of education, and number of objective binges at baseline but not with treatment condition.Conclusions: This is the first study to investigate the efficacy of guided self-help CBT-E. Guided self-help CBT-E appeared to be an efficacious treatment. This study's findings underscore the international guidelines recommending this type of treatment for binge eating disorder. Show less
Melisse, B.; Dekker, J.; Berg, E. van den; Jonge, M. de; Furth, E.F. van; Peen, J.; Beurs, E. de 2023
Introduction: Cognitive behaviour therapy-enhanced (CBT-E) is an effective treatment for non-underweight patients with eating disorders. Its efficacy and effectiveness is investigated mostly among... Show moreIntroduction: Cognitive behaviour therapy-enhanced (CBT-E) is an effective treatment for non-underweight patients with eating disorders. Its efficacy and effectiveness is investigated mostly among transdiagnostic samples and remains unknown for binge eating disorder. The aim of present study was to assess several treatment outcome predictors and to compare effectiveness of CBT-E among adult outpatients with bulimia nervosa (N=370), binge eating disorder (N=113), and those with a restrictive food pattern diagnosed with other specified feeding and eating disorder (N=139).Method: Effectiveness of CBT-E was assessed in routine clinical practice in a specialised eating disorders centre. Eating disorder pathology was measured with the EDE-Q pre- and post-treatment, and at 20 weeks follow-up. Linear mixed model analyses with fixed effect were performed to compare treatment outcome among the eating disorder groups. Several predictors of treatment completion and outcome were examined with a regression analysis.Results: No predictors for drop-out were found, except the diagnosis of bulimia nervosa. Eating disorder pathology decreased among all groups with effect sizes between 1.43-1.70 on the EDE-Q total score. There were no differences in remission rates between the three groups at end of treatment or at follow-up. Eating disorder severity at baseline affected treatment response.Discussion: The results can be generalised to other specialised treatment centres. No subgroup of patients differentially benefited from CBT-E supporting the transdiagnostic perspective for the treatment of eating disorders. Longer-term follow-up data are necessary to measure persistence of treatment benefits. Show less
Kort, A.M. de; Kuiperij, H.B.; Marques, T.M.; Jäkel, L.; Berg, E. van den; Kersten, I.; ... ; Verbeek, M.M. 2023
ObjectiveVascular amyloid β (Aβ) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker... Show moreObjectiveVascular amyloid β (Aβ) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker of CAA. We studied the diagnostic potential of the peptides Aβ38, Aβ40, Aβ42, and Aβ43 in patients with sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD).MethodsAβ peptides were quantified by immunoassays in a discovery group (26 patients with sCAA and 40 controls), a validation group (40 patients with sCAA, 40 patients with AD, and 37 controls), and a group of 22 patients with D-CAA and 54 controls. To determine the diagnostic accuracy, the area under the curve (AUC) was calculated using a receiver operating characteristic curve with 95% confidence interval (CI).ResultsWe found decreased levels of all Aβ peptides in sCAA patients and D-CAA patients compared to controls. The difference was most prominent for Aβ42 (AUC of sCAA vs controls for discovery: 0.90, 95% CI = 0.82–0.99; for validation: 0.94, 95% CI = 0.89–0.99) and Aβ43 (AUC of sCAA vs controls for discovery: 0.95, 95% CI = 0.88–1.00; for validation: 0.91, 95% CI = 0.83–1.0). All Aβ peptides except Aβ43 were also decreased in sCAA compared to AD (CSF Aβ38: AUC = 0.82, 95% CI = 0.71–0.93; CSF Aβ40: AUC = 0.88, 95% CI = 0.80–0.96; CSF Aβ42: AUC = 0.79, 95% CI = 0.66–0.92). Show less
Berg, E. van den; Logman, P.S.W.M.; Veen, N. van 2023
Background and ObjectivesIt is important to identify at what age brain atrophy rates in genetic frontotemporal dementia (FTD) start to accelerate and deviate from normal aging effects to find the... Show moreBackground and ObjectivesIt is important to identify at what age brain atrophy rates in genetic frontotemporal dementia (FTD) start to accelerate and deviate from normal aging effects to find the optimal starting point for treatment. We investigated longitudinal brain atrophy rates in the presymptomatic stage of genetic FTD using normative brain volumetry software.MethodsPresymptomatic GRN, MAPT, and C9orf72 pathogenic variant carriers underwent longitudinal volumetric T1-weighted magnetic resonance imaging of the brain as part of a prospective cohort study. Images were automatically analyzed with Quantib (R) ND, which consisted of volume measurements (CSF and sum of gray and white matter) of lobes, cerebellum, and hippocampus. All volumes were compared with reference centile curves based on a large population-derived sample of nondemented individuals (n = 4,951). Mixed-effects models were fitted to analyze atrophy rates of the different gene groups as a function of age.ResultsThirty-four GRN, 8 MAPT, and 14 C9orf72 pathogenic variant carriers were included (mean age = 52.1, standard deviation = 7.2; 66% female). The mean follow-up duration of the study was 64 +/- 33 months (median = 52; range 13-108). GRN pathogenic variant carriers showed a faster decline than the reference centile curves for all brain areas, though relative volumes remained between the 5th and 75th percentiles between the ages of 45 and 70 years. In MAPT pathogenic variant carriers, frontal lobe volume was already at the 5th percentile at age 45 years and showed a further decline between the ages 50 and 60 years. Temporal lobe volume started in the 50th percentile at age 45 years but showed fastest decline over time compared with other brain structures. Frontal, temporal, parietal, and cerebellar volume already started below the 5th percentile compared with the reference centile curves at age 45 years for C9orf72 pathogenic variant carriers, but there was minimal decline over time until the age of 60 years.DiscussionWe provide evidence for longitudinal brain atrophy in the presymptomatic stage of genetic FTD. The affected brain areas and the age after which atrophy rates start to accelerate and diverge from normal aging slopes differed between gene groups. These results highlight the value of normative volumetry software for disease tracking and staging biomarkers in genetic FTD. These techniques could help in identifying the optimal time window for starting treatment and monitoring treatment response. Show less
Baas, M.; Schuwer, R.; Berg, E. van den; Huizinga, T.; Rijst, R. van der; Admiraal, W. 2022
The affordances of Open Educational Resources (OER) have resulted in various initiatives around the world, but most of them cease to exist once the initial project funding stops. Communities might... Show moreThe affordances of Open Educational Resources (OER) have resulted in various initiatives around the world, but most of them cease to exist once the initial project funding stops. Communities might be a means to create sustainable practices, yet, such communities can only function if their members perceive these communities as valuable. We applied the value creation framework of Wenger, Trayner, and De Laat to examine the value teachers ascribe to their engagement with an inter-institutional community on OER. In this community, 15 universities of applied sciences collaborated on sharing knowledge and resources across their institutional barriers. We collected data through user statistics, an online questionnaire, and semi-structured interviews. Major value creation occurred from teachers' personal needs, with dominant immediate and potential values. Findings on applied and realized values denote that it became easier for teachers to connect with peers, and to initiate collaboration projects across institutes. The framework we used is helpful to inform actions to further promote value creation in communities on OER. Recommendations relating to communities' aspirations, its relations with the wider organization, and adoption of OER are formulated to inform sustainable practices of inter-institutional communities. Show less
Melisse, B.; Berg, E. van den; Jonge, M. de; Blankers, M.; Furth, E. van; Dekker, J.; Beurs, E. de 2022
Background: Owing to the gap between treatment supply and demand, there are long waiting periods for patients with binge eating disorder, and there is an urgent need to increase their access to... Show moreBackground: Owing to the gap between treatment supply and demand, there are long waiting periods for patients with binge eating disorder, and there is an urgent need to increase their access to specialized treatment. Guided self-help cognitive behavioral therapy–enhanced (CBT-E) may have great advantages for patients if its efficacy can be established.Objective: The aim of this study is to examine the efficacy of guided self-help CBT-E compared with that of a delayed-treatment control condition.Methods: A single-blind 2-arm randomized controlled trial was designed to evaluate guided self-help CBT-E according to an intention-to-treat analysis. A total of 180 patients were randomly assigned to guided self-help CBT-E (n=90) or the delayed-treatment control condition (n=90) for which guided self-help CBT-E was provided after the initial 12-week delay. The primary outcome was reduction in binges. The secondary outcome was full recovery at the end of treatment, as measured using the Eating Disorder Examination during the last 4 weeks of treatment. A linear mixed model analysis was performed to compare treatment outcomes at the end of treatment. A second linear mixed model analysis was performed to measure between- and within-group effects for up to 24 weeks of follow-up. The Eating Disorder Examination–Questionnaire and clinical impairment assessment were conducted before and after treatment and during follow-up. In addition, dropout rates were assessed in both conditions.Results: During the last 4 weeks of treatment, objective binges reduced from an average of 19 (16) to 3 (5) binges, and 40% (36/90) showed full recovery in the guided self-help CBT-E group. Between-group effect size (Cohen d) was 1.0 for objective binges. At follow-up, after both groups received treatment, there was no longer a difference between groups. Of the 180 participants, 142 (78.9%) completed treatment. Overall treatment dropout appeared to be associated with gender, level of education, and number of objective binges at baseline but not with treatment condition.Conclusions: This is the first study to investigate the efficacy of guided self-help CBT-E. Guided self-help CBT-E appeared to be an efficacious treatment. This study’s findings underscore the international guidelines recommending this type of treatment for binge eating disorder. Show less
Melisse, B.; Dekker, J.; Berg, E. van den; Jonge, M. de; Furth, E.F. van; Peen, J.; Beurs, E. de 2022
Cognitive behaviour therapy-enhanced (CBT-E) is an effective treatment for non-underweight patients with eating disorders. Its efficacy and effectiveness is investigated mostly among... Show moreCognitive behaviour therapy-enhanced (CBT-E) is an effective treatment for non-underweight patients with eating disorders. Its efficacy and effectiveness is investigated mostly among transdiagnostic samples and remains unknown for binge eating disorder. The aim of the present study was to assess several treatment outcome predictors and to compare effectiveness of CBT-E among adult out-patients with bulimia nervosa (n=370), binge eating disorder (n=113), and those with a restrictive food pattern diagnosed with other specified feeding and eating disorders (n=139). Effectiveness of CBT-E was assessed in routine clinical practice in a specialised eating disorders centre. Eating disorder pathology was measured with the EDEQ pre- and post-treatment, and at 20 weeks follow-up. Linear mixed model analyses with fixed effect were performed to compare treatment outcome among the eating disorder groups. Several predictors of treatment completion and outcome were examined with a regression analysis. No predictors for drop-out were found, except the diagnosis of bulimia nervosa. Eating disorder pathology decreased among all groups with effect sizes between 1.43 and 1.70 on the EDE-Q total score. There were no differences in remission rates between the three groups at end of treatment or at follow-up. Eating disorder severity at baseline affected treatment response. The results can be generalised to other specialised treatment centres. No subgroup of patients differentially benefited from CBT-E supporting the transdiagnostic perspective for the treatment of eating disorders. Longer-term follow-up data are necessary to measure persistence of treatment benefits. Show less
Boon, B.D.C.; Bulk, M.; Jonker, A.J.; Morrema, T.H.J.; Berg, E. van den; Popovic, M.; ... ; Hoozemans, J.J.M. 2020
Alzheimer's disease (AD) is characterized by amyloid-beta (A beta) deposits, which come in myriad morphologies with varying clinical relevance. Previously, we observed an atypical A beta deposit,... Show moreAlzheimer's disease (AD) is characterized by amyloid-beta (A beta) deposits, which come in myriad morphologies with varying clinical relevance. Previously, we observed an atypical A beta deposit, referred to as the coarse-grained plaque. In this study, we evaluate the plaque's association with clinical disease and perform in-depth immunohistochemical and morphological characterization. The coarse-grained plaque, a relatively large (o approximate to 80 mu m) deposit, characterized as having multiple cores and A beta-devoid pores, was prominent in the neocortex. The plaque was semi-quantitatively scored in the middle frontal gyrus of A beta-positive cases (n = 74), including non-demented cases (n = 15), early-onset (EO)AD (n = 38), and late-onset (LO)AD cases (n = 21). The coarse-grained plaque was only observed in cases with clinical dementia and more frequently present in EOAD compared to LOAD. This plaque was associated with a homozygousAPOE epsilon 4 status and cerebral amyloid angiopathy (CAA). In-depth characterization was done by studying the coarse-grained plaque's neuritic component (pTau, APP, PrP (c)), A beta isoform composition (A beta(40), A beta(42), A beta(N3pE), pSer8A beta), its neuroinflammatory component (C4b, CD68, MHC-II, GFAP), and its vascular attribution (laminin, collagen IV, norrin). The plaque was compared to the classic cored plaque, cotton wool plaque, and CAA. Similar to CAA but different from classic cored plaques, the coarse-grained plaque was predominantly composed of A beta(40). Furthermore, the coarse-grained plaque was distinctly associated with both intense neuroinflammation and vascular (capillary) pathology. Confocal laser scanning microscopy (CLSM) and 3D analysis revealed for most coarse-grained plaques a particular A beta(40)shell structure and a direct relation with vessels. Based on its morphological and biochemical characteristics, we conclude that the coarse-grained plaque is a divergent A beta plaque-type associated with EOAD. Differences in A beta processing and aggregation, neuroinflammatory response, and vascular clearance may presumably underlie the difference between coarse-grained plaques and other A beta deposits. Disentangling specific A beta deposits between AD subgroups may be important in the search for disease-mechanistic-based therapies. Show less
Buhrmann, A.; Brands, A.M.A.; Grond, J. van der; Schilder, C.; Mast, R.C. van der; Ottenheim, N.R.; ... ; Berg, E. van den 2020
The cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter... Show moreThe cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter volume (GMV), white matter hyperintensities (WMHs), lacunar infarcts (LIs) and microbleeds (MBs)) and measures of cognitive, psychological (i.e. symptoms of depression and apathy) and general daily functioning in a population of community-dwelling older persons with mild cognitive deficits, but without dementia. In 194 participants of the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden, the association between cerebellar GMV, WMHs, LIs and MBs and measures of cognitive, psychological and general daily functioning was analysed with linear regression analysis, adjusted for age, sex, education and cerebral volume. Cerebellar GMV was associated with the overall cognition score (standardised beta 0.20 [95% CI, 0.06-0.33]). Specifically, posterior cerebellar GMV was associated with executive function (standardised beta 0.18 [95% CI, 0.03-0.16]). No relation was found between vascular pathology and cognition. Also, no consistent associations were found on the cerebellar GMV and vascular pathology measures and psychological and general daily functioning. In this population of community-dwelling elderly, less posterior cerebellar GMV but not vascular pathology was associated with worse cognitive function, specifically with poorer executive function. No relation was found between cerebellar pathology and psychological and general daily functioning. Show less
Heuvel, D. van den; Berg, E. van den; Montagne, B. 2020
Background: Binge eating disorder is characterized by recurrent episodes of binge eating accompanied by a sense of lack of control. Of the different treatments available, Cognitive Behavioral... Show moreBackground: Binge eating disorder is characterized by recurrent episodes of binge eating accompanied by a sense of lack of control. Of the different treatments available, Cognitive Behavioral Therapy-Enhanced and guided self-help treatment are recommended. As online treatment offers several additional advantages, we have developed a CBT-Enhanced online guided self-help intervention. The aim of this study is to determine whether this intervention reduces eating disorder pathology and increases the amount of binge free days in adults classified with binge eating disorder or other specified feeding or eating disorder- binge eating disorder, compared to an untreated waiting list condition. The experimental condition is hypothesized to be superior to the waiting list condition.Methods: The efficacy of an online guided self-help intervention for binge eating disorder will be assessed by conducting a randomized controlled trial. The trial will target adult individuals classified with binge eating disorder or other specified feeding or eating disorder- binge eating disorder with a body mass index between 19.5 and 40, referred to an eating disorder treatment center. Dual arm allotment will be performed in a 1:1 ratio stratified for BMI above or below 30. Randomization will be blinded to the online intervention (n = 90), or to the control waiting list condition (n = 90). Assessors will be blinded and assessments will be administered at baseline, week 5, at end-of-treatment, and at 12 and 24 weeks follow-up. Primary outcome will be eating disorder pathology, operationalized as number of days on which binge eating occurred between the two conditions during the period of the intervention. Secondary outcome measures will be differences in other eating disorder pathology, clinical impairment and in quality of life, while therapeutic alliance, demographic characteristics and followed treatment module will serve as effect moderators. Several types of costs will be assessed.Discussion: This paper presents an online guided self-help Cognitive Behavioral Therapy- Enhanced study protocol for individuals classified with binge eating disorder or other specified feeding or eating disorder. Efficacy will be examined through a Randomized Controlled Trial. Show less
Poos, J.M.; Jiskoot, L.C.; Leijdesdorff, S.M.J.; Seelaar, H.; Panman, J.L.; Ende, E.L. van der; ... ; Berg, E. van den 2020