BackgroundThe effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population.MethodsA Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs.ResultsEVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: −65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs.ConclusionOne-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs.

BackgroundNeither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive.ObjectiveA meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met).Data sourcesPubMed, Embase, PsychInfo.Study eligibility criteriaAll observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome.Study appraisal and synthesis methodsA meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions".ResultsFor case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05–2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16–0.08).LimitationA substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects.ConclusionThe interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing.

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Background: Endovascular treatment (EVT) for acute ischemic stroke (AIS) is performed in intervention centers that provide the full range of neuro(endo)vascular care (level 1) and centers that only perform EVT for AIS (level 2). We compared outcomes between these center types and assessed whether differences in outcomes could be explained by center volume (CV). Patients and methods: We analyzed patients included in the MR CLEAN Registry (2014–2018), a registry of all EVT-treated patients in the Netherlands. Our primary outcome was the shift on the modified Rankin scale (mRS) after 90 days (ordinal regression). Secondary outcomes were the NIHSS 24–48 h post-EVT, door-to-groin time (DTGT), procedure time (linear regression), and recanalization (binary logistic regression). We compared outcomes between level 1 and 2 centers using multilevel regression models, with center as random intercept. We adjusted for relevant baseline factors, and in case of observed differences, we additionally adjusted for CV. Results: Of the 5144 patients 62% were treated in level 1 centers. We observed no significant differences between center types in mRS (adjusted(a)cOR: 0.79, 95% CI: 0.40 to 1.54), NIHSS (aβ: 0.31, 95% CI: −0.52 to 1.14), procedure duration (aβ: 0.88, 95% CI: −5.21 to 6.97), or DTGT (aβ: 4.24, 95% CI: −7.09 to 15.57). The probability for recanalization was higher in level 1 centers compared to level 2 centers (aOR 1.60, 95% CI: 1.10 to 2.33), and this difference probably depended on CV. Conclusions: We found no significant differences, that were independent of CV, in the outcomes of EVT for AIS between level 1 and level 2 intervention centers.

Purpose Whilst childhood trauma (CT) is a known risk factor across the spectrum of psychosis expression, little is known about possible interplay with genetic liability. Methods The TwinssCan Study collected data in general population twins, focussing on expression of psychosis at the level of subthreshold psychotic experiences. A multilevel mixed-effects linear regression analysis was performed including 745 subjects to assess the interaction between genetic liability and CT. The Symptom Checklist-90 (SCL-90-R) score of the cotwin was used as an indirect measure of genetic liability to psychopathology, while the Childhood Trauma Questionnaire Short-Form (CTQ-SF) was used to assess CT in the domains of physical, emotional and sexual abuse, as well as physical and emotional neglect. The Community Assessment of Psychic Experience (CAPE) questionnaire was used to phenotypically characterize psychosis expression. Results In the model using the CAPE total score, the interaction between CT and genetic liability was close to statistical significance (χ 2 = 5.6, df = 2, p = 0.06). Analyses of CAPE subscales revealed a significant interaction between CT and genetic liability (χ 2 = 8.8, df = 2, p = 0.012) for the CAPE-negative symptoms subscale, but not for the other two subscales (i.e. positive and depressive). Conclusion The results suggest that the impact of CT on subthreshold expression of psychosis, particularly in the negative subdomain, may be larger in the co-presence of significant genetic liability for psychopathology.

Background: The clinical and economic benefit of endovascular treatment (EVT) in addition to best medical management in patients with stroke with mild preexisting symptoms/disability is not well studied. We aimed to investigate cost-effectiveness of EVT in patients with large vessel occlusion and mild prestroke symptoms/disability, defined as a modified Rankin Scale score of 1 or 2. Methods: Data are from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials), which pooled patient-level data from 7 large, randomized EVT trials. We used a decision model consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes from a health care and a societal perspective. Incremental cost-effectiveness ratio and net monetary benefits were calculated, and a probabilistic sensitivity analysis was performed. Results: EVT in addition to best medical management resulted in lifetime cost savings of $2821 (health care perspective) or $5378 (societal perspective) and an increment of 1.27 quality-adjusted life years compared with best medical management alone, indicating dominance of additional EVT as a treatment strategy. The net monetary benefits were higher for EVT in addition to best medical management compared with best medical management alone both at the higher (100 000$/quality-adjusted life years) and lower (50 000$/quality-adjusted life years) willingness to pay thresholds. Probabilistic sensitivity analysis showed decreased costs and an increase in quality-adjusted life years for additional EVT compared with best medical management only. Conclusions: From a health-economic standpoint, EVT in addition to best medical management should be the preferred strategy in patients with acute ischemic stroke with large vessel occlusion and mild prestroke symptoms/disability.

Objective: To determine the association between early post-endovascular treatment (EVT) contrast extravasation (CE) on dual-energy CT (DECT) and stroke outcomes. Methods: EVT records in 2010–2019 were screened. Exclusion criteria included the occurrence of immediate post-procedural intracranial haemorrhage (ICH). Hyperdense areas on iodine overlay maps were scored according to the Alberta Stroke Programme Early CT Score (ASPECTS), thus forming a CE-ASPECTS. Maximum parenchymal iodine concentration and maximum iodine concentration relative to the torcula were recorded. Follow-up imaging was reviewed for ICH. The primary outcome measure was the modified Rankin Scale (mRS) at 90 days. Results: Out of 651 records, 402 patients were included. CE was found in 318 patients (79%). Thirty-five patients developed ICH on follow-up imaging. Fourteen ICHs were symptomatic. Stroke progression occurred in 59 patients. Multivariable regression showed a significant association between decreasing CE-ASPECTS and the mRS at 90 days (adjusted (a)cOR: 1.10, 95% CI: 1.03–1.18), NIHSS at 24–48 h (aβ: 0.57, 95% CI: 0.29–0.84), stroke progression (aOR: 1.14, 95% CI: 1.03–1.26) and ICH (aOR: 1.21, 95% CI: 1.06–1.39), but not symptomatic ICH (aOR 1.19, 95% CI: 0.95–1.38). Iodine concentration was significantly associated with the mRS (acOR: 1.18, 95% CI: 1.06–1.32), NIHSS (aβ: 0.68, 95% CI: 0.30–1.06), ICH (aOR: 1.37, 95% CI: 1.04–1.81) and symptomatic ICH (aOR: 1.19, 95% CI: 1.02–1.38), but not stroke progression (aOR: 0.99, 95% CI: 0.86–1.15). Results of the analyses with relative iodine concentration were similar and did not improve prediction. Conclusions: CE-ASPECTS and iodine concentration are both associated with short- and long-term stroke outcomes. CE-ASPECTS is likely a better predictor for stroke progression.