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BACKGROUND: The benefit of intravenous thrombolysis with alteplase before endovascular thrombectomy (EVT) for acute ischemic stroke due to large vessel occlusion remains debated. In this study, we analyzed the cost-effectiveness of EVT alone versus intravenous alteplase before EVT in patients directly admitted to EVT-capable stroke centers from the Dutch health care payer perspective. METHODS: A decision analysis was performed using a Markov model with 15-year simulated follow-up to estimate total costs, quality-adjusted life years, and an incremental cost-effectiveness ratio of intravenous alteplase before EVT compared with EVT alone. A hypothetical cohort of 10â 000 patients with large vessel occlusion aged 70 years was run in Monte Carlo simulation. Functional outcome of each treatment was derived from pooled results of 6 randomized controlled trials (RCTs). Uncertainty was assessed by probabilistic analyses, scenario analyses, and 1-way sensitivity analyses. RESULTS: Using functional outcomes obtained from 6 RCTs (intention-to-treat population), intravenous alteplase before EVT resulted in 0.05 quality-adjusted life years gained at an additional $2817 compared with EVT alone, resulting in the incremental cost-effectiveness ratio of $62â 287. Probabilistic analyses showed that intravenous alteplase before EVT had a probability of 45% and 54%, respectively, of being cost-effective at the $52â 500 and $84â 000 thresholds. Restricting functional outcomes from our post hoc modified as-treated analysis of 6 RCTs (scenario 1), European RCTs (scenario 2), or a Dutch RCT (scenario 3), intravenous alteplase before EVT was cost-effective in 64%, 81%, and 50% of simulations at the $52â 500 threshold, and 79%, 91%, and 67% of simulations at the $84â 000 threshold. CONCLUSIONS: Intravenous alteplase before EVT was not cost-effective in patients with large vessel occlusion in the Netherlands at the $52â 500 threshold but possibly cost-effective at the $84â 000 threshold. Variable functional outcomes at 3 months based on different trial populations affected the cost-effectiveness of intravenous alteplase before EVT.
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BACKGROUND: Endovascular treatment for anterior circulation ischaemic stroke is effective and safe within a 6 h window. MR CLEAN-LATE aimed to assess efficacy and safety of endovascular treatment for patients treated in the late window (6-24 h from symptom onset or last seen well) selected on the basis of the presence of collateral flow on CT angiography (CTA). METHODS: MR CLEAN-LATE was a multicentre, open-label, blinded-endpoint, randomised, controlled, phase 3 trial done in 18 stroke intervention centres in the Netherlands. Patients aged 18 years or older with ischaemic stroke, presenting in the late window with an anterior circulation large-vessel occlusion and collateral flow on CTA, and a neurological deficit score of at least 2 on the National Institutes of Health Stroke Scale were included. Patients who were eligible for late-window endovascular treatment were treated according to national guidelines (based on clinical and perfusion imaging criteria derived from the DAWN and DEFUSE-3 trials) and excluded from MR CLEAN-LATE enrolment. Patients were randomly assigned (1:1) to receive endovascular treatment or no endovascular treatment (control), in addition to best medical treatment. Randomisation was web based, with block sizes ranging from eight to 20, and stratified by centre. The primary outcome was the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included all-cause mortality at 90 days after randomisation and symptomatic intracranial haemorrhage. All randomly assigned patients who provided deferred consent or died before consent could be obtained comprised the modified intention-to-treat population, in which the primary and safety outcomes were assessed. Analyses were adjusted for predefined confounders. Treatment effect was estimated with ordinal logistic regression and reported as an adjusted common odds ratio (OR) with a 95% CI. This trial was registered with the ISRCTN, ISRCTN19922220. FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned, and 502 (94%) patients provided deferred consent or died before consent was obtained (255 in the endovascular treatment group and 247 in the control group; 261 [52%] females). The median mRS score at 90 days was lower in the endovascular treatment group than in the control group (3 [IQR 2-5] vs 4 [2-6]), and we observed a shift towards better outcomes on the mRS for the endovascular treatment group (adjusted common OR 1·67 [95% CI 1·20-2·32]). All-cause mortality did not differ significantly between groups (62 [24%] of 255 patients vs 74 [30%] of 247 patients; adjusted OR 0·72 [95% CI 0·44-1·18]). Symptomatic intracranial haemorrhage occurred more often in the endovascular treatment group than in the control group (17 [7%] vs four [2%]; adjusted OR 4·59 [95% CI 1·49-14·10]). INTERPRETATION: In this study, endovascular treatment was efficacious and safe for patients with ischaemic stroke caused by an anterior circulation large-vessel occlusion who presented 6-24 h from onset or last seen well, and who were selected on the basis of the presence of collateral flow on CTA. Selection of patients for endovascular treatment in the late window could be primarily based on the presence of collateral flow. FUNDING: Collaboration for New Treatments of Acute Stroke consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/tratamento farmacológico , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Angiografia por Tomografia Computadorizada , Países Baixos , Hemorragias Intracranianas/etiologia , AVC Isquêmico/complicações , Resultado do TratamentoRESUMO
OBJECTIVES: Model-based health economic evaluations of ischemic stroke are in need of cost- and utility estimates related to relevant outcome measures. This study aims to describe societal cost- and utility estimates per modified Rankin Scale (mRS)-score at different time points within 2 years post stroke. METHODS: Included patients had a stroke between 3 months and 2.5 years ago. mRS and EQ-5D-5L were scored during a telephone interview. Based on the interview date, records were categorized into a time point: 3 months (3M; 3-6 months), 1 year (Y1; 6-18 months), or 2 years (Y2; 18-30 months). Patients completed a questionnaire on healthcare utilization and productivity losses in the previous 3 months. Initial stroke hospitalization costs were assessed. Mean costs and utilities per mRS and time point were derived with multiple imputation nested in bootstrapping. Cost at 3 months post stroke were estimated separately for endovascular treatment (EVT)-/non-EVT-patients. RESULTS: 1106 patients were included from 18 Dutch centers. At each time point, higher mRS-scores were associated with increasing average costs and decreasing average utility. Mean societal costs at 3M ranged from 11 943 (mRS 1, no EVT) to 55 957 (mRS 5, no EVT). For Y1, mean costs in the previous 3 months ranged from 885 (mRS 0) to 23 215 (mRS 5), and from 1655 (mRS 0) to 22 904 (mRS 5) for Y2. Mean utilities ranged from 0.07 to 0.96, depending on mRS and time point. CONCLUSIONS: The mRS-score is a major determinant of costs and utilities at different post-stroke time points. Our estimates may be used to inform future model-based health economic evaluations.
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Qualidade de Vida , Acidente Vascular Cerebral , Humanos , Análise Custo-Benefício , Acidente Vascular Cerebral/terapia , Avaliação de Resultados em Cuidados de Saúde , Inquéritos e QuestionáriosRESUMO
PURPOSE: To determine the incidence and predictors of cerebral arterial air emboli (CAAE) on immediate post-endovascular treatment (EVT) dual-energy CT (DECT) in acute ischaemic stroke (AIS) patients, and describe their association with clinical outcomes. METHODS: EVT records from 2010 to 2019 were screened. Exclusion criteria included intracerebral haemorrhage on post-EVT DECT. In the affected middle cerebral artery (MCA)-territory, circular and linear (length ≥ 1.5*width) CAAE were counted. Clinical data were collected from prospective records. The modified Rankin Scale (mRS) at 90 days was the primary outcome. Multivariable linear, logistic, and ordinal regression were used to analyse the effect of (1) linear CAAE and (2) isolated circular CAAE. RESULTS: Out of 651 EVT-records, 402 patients were included. In 65 patients (16%), at least one linear CAAE was found in the affected MCA-territory. 17 patients (4%) showed isolated circular CAAE. Multivariable regression showed an association between both the presence and the number of linear CAAE and the mRS at 90 days (presence: adjusted (a)cOR 3.10, 95%CI 1.75-5.50; number: acOR 1.28, 95%CI 1.13-1.44), NIHSS at 24-48 h (presence: aß 4.15, 95%CI 1.87-6.43; number: aß 0.88, 95%CI 0.42-1.34), mortality at 90 days (presence: aOR 3.34, 95%CI 1.51-7.40; number: aOR 1.24, 95%CI 1.08-1.43) and stroke progression (presence: aOR 4.01, 95%CI 1.96-8.18; number: aOR 1.31, 95%CI 1.15-1.50). Isolated circular CAAE were not significantly associated with any outcome measure. CONCLUSION: CAAE were found frequently on post-EVT CT imaging. The presence and the number of linear CAAE, but not circular CAAE, are associated with unfavourable short- and long-term clinical outcomes.
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Estudos Prospectivos , Trombectomia/métodos , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Artéria Cerebral Média/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To describe the incidence, risk factors, and prognostic relevance of intracranial haemorrhage (ICH) immediately after endovascular treatment (EVT) for ischaemic stroke in the anterior circulation. METHODS: EVT records from 2010 to 2019 were screened. Included patients underwent DECT within 3h post-EVT. Virtual native reconstructions were evaluated for ICH according to the Heidelberg criteria and grouped into Heidelberg classes (HCs): [HC1] haemorrhagic infarction (HI)1, HI2 and parenchymal haematoma (PH)1; [HC2] PH2; [HC3] i.a. intraventricular and subarachnoid haemorrhage. If ICH corresponding to multiple HCs was observed, we assumed that the (largest) parenchymal ICH would have the greatest prognostic impact. Hence, a single HC was attributed by the following order of severity: HC2, HC1, HC3. The primary outcome was the modified Rankin Scale (mRS) at 90 days. The effect of asymptomatic ICH (aICH) and symptomatic ICH (sICH) of (1) HC1 or HC2 and (2) HC3 on patient outcomes was evaluated with multivariable regression after multiple imputation. RESULTS: Out of 651 records, 498 patients were included. Eighty-one (16%) patients showed ICH on post-EVT DECT, of which 19 were classified as HC1 (21% symptomatic), 6 as HC2 (100% symptomatic), and 56 as HC3 (14% symptomatic). ICH development was mainly associated with unfavourable procedural characteristics. Both aICH and sICH of HC1 or HC2 were associated with the mRS (aICH: adjusted [a]cOR 4.92, 95%CI [1.48-16.35]; sICH: acOR 12.97, 95%CI [2.39-70.26]) and mortality (aICH: aOR 10.08, 95%CI [2.48-40.88]; sICH: aOR 9.92, 95%CI [1.48-66.31]). Likewise, sICH of HC3 was associated with the mRS and mortality (acOR 19.91, 95%CI [4.03-98.35], and aOR 13.23, 95%CI [2.27-77.18], respectively). aICH of HC3 was not significantly associated with the mRS or mortality (acOR 0.87, 95%CI [0.48-1.57], and cOR 0.84, 95%CI [0.32-2.20], respectively). CONCLUSIONS: Immediate post-EVT ICH is a frequent finding. Except for aICH of HC3, any ICH is associated with poor long-term clinical outcomes.
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PURPOSE: While levetiracetam (LEV) usage is a known risk factor for psychosis in epilepsy, the modulating effect of certain patient and treatment characteristics on the risk of psychosis has yet to be fully elucidated. METHODS: In our tertiary epilepsy center, 84 patients with psychotic symptoms during LEV usage and 100 controls without psychotic symptoms during LEV usage were selected. Patient records were reviewed including demographics, medical history, antiepileptic drug use, and cognitive abilities. Univariate comparisons were performed, and variables with pâ¯<â¯0.1 were selected for binary logistic regression analysis. RESULTS: The total incidence of psychosis during LEV therapy in our population was 3.7%. The timing of psychotic symptoms was classified as postictal in 20 (19.8%), interictal in 14 (15.4%), postepilepsy surgery in 1 (1.1%), and unknown in 18 cases (19.8%). In 31 cases (34.1%), psychotic symptoms were classified as an antiepileptic drug-induced psychotic disorder (AIPD) as a result of LEV. In 7 cases (7.7%), AIPD occurred as a result of a different antiepileptic drug. A significant association was found between the experience of psychotic symptoms and status epilepticus (pâ¯=â¯0.002), a history of psychotic symptoms (pâ¯<â¯0.000), a history of psychiatric illness other than psychosis (pâ¯=â¯0.010), and concomitant phenytoin (PHT) usage (pâ¯=â¯0.044). Cotherapy with lamotrigine (LTG) was protective (pâ¯=â¯0.042). A separate analysis of controls and exclusively the 31 cases with LEV-induced AIPD yielded comparable results; a significant association was confirmed with status epilepticus (pâ¯=â¯0.021) and history of psychotic symptoms (pâ¯=â¯0.018), as well as with female gender (pâ¯=â¯0.047) and intellectual disability (pâ¯=â¯0.043). CONCLUSION: Our retrospective study found that psychotic symptoms during LEV therapy were significantly associated with status epilepticus, a history of psychotic symptoms, a history of psychiatric illness other than psychosis, and concomitant PHT usage, whereas concomitant LTG usage was protective. Psychotic symptoms specifically as an adverse drug reaction to LEV were significantly associated with female gender, intellectual disability, status epilepticus, and a history of psychotic symptoms.
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Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Levetiracetam/efeitos adversos , Psicoses Induzidas por Substâncias/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Levetiracetam/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Psicoses Induzidas por Substâncias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
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 co-twin 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 (χ2 = 5.6, df = 2, p = 0.06). Analyses of CAPE subscales revealed a significant interaction between CT and genetic liability (χ2 = 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.
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Maus-Tratos Infantis/psicologia , Predisposição Genética para Doença/psicologia , Transtornos Psicóticos/genética , Transtornos Psicóticos/psicologia , Adulto , Criança , Emoções , Feminino , Humanos , Masculino , Fatores de Risco , Inquéritos e Questionários , Avaliação de SintomasRESUMO
BACKGROUND AND PURPOSE: Endovascular treatment (EVT) is the preferred treatment option in eligible acute ischemic stroke (AIS) patients with a large vessel occlusion of the anterior circulation. Several comorbidities have been identified that can affect clinical outcomes. Various studies have investigated the association between anemia and clinical outcome and found conflicting. RESULTS: . The aim is to investigate the association between pre-EVT anemia and clinical outcomes at different time points post-EVT, primarily focusing on the National Institutes of Health Stroke Scale (NIHSS) at 24-48 hours. METHODS: We prospectively included 560 AIS patients who received EVT in the Maastricht University Medical Center+. Hemoglobin levels (Hb; g/dL) were determined on admission. Hb levels were also categorized into two groups: anemia (male: Hb ≤12.9 g/dL; female: Hb ≤11.9 g/dL) and no anemia. Multiple imputation was used to handle missing data. Multivariable regression was used to investigate the association between anemia or Hb levels and clinical outcomes. RESULTS: Anemia was present in 26% of the patients. Multivariable regression did not show a significant association between anemia or Hb levels and NIHSS at 24-48 hours (adjusted ß [aß]anemia: 1.44, 95% confidence interval [CI]: -0.47 to 3.36; aßHb: -0.37, 95% CI: -0.88 to 0.13). However, multivariable regression showed significant associations with modified Rankin Scale (adjusted common odds ratio [acOR]anemia: 1.66, 95% CI: 1.12 to 2.48; acORHb: 0.83, 95% CI: 0.75 to 0.93) and poor functional outcome at 90 days (adjusted OR [aOR]anemia: 2.09, 95% CI: 1.21 to 3.63; aORHb: 0.80, 95% CI: 0.69 to 0.92). CONCLUSION: Anemia was not independently associated with early neurological deficit (NIHSS) post-AIS, suggesting it is more suitable as a general frailty marker.
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BACKGROUND: The MR CLEAN-LATE trial provided evidence for the safety and efficacy of endovascular treatment for acute ischaemic stroke within the late window (after 6-24 h) in patients who were preselected based on the presence of collateral flow on CT angiography. We aimed to evaluate clinical outcomes 2 years after randomisation. METHODS: MR CLEAN-LATE was a phase 3, multicentre, open-label, blinded-endpoint, randomised controlled trial conducted at 18 stroke intervention centres in the Netherlands. If endovascular treatment could be initiated within 6-24 h of symptom onset or last seen well, patients (aged 18 years or older) with an acute ischaemic stroke due to a large vessel occlusion in the anterior circulation and at least some collateral flow in the affected middle cerebral artery territory on CT angiography were randomly assigned (1:1) to either endovascular treatment with best medical treatment (endovascular treatment group) or best medical treatment alone (control group). Web-based randomisation, stratified by centre, was performed with the use of permuted blocks (block size eight to 20). The researchers who collected clinical outcomes and analysed the results were masked to treatment allocation; treating physicians, local investigators, and patients were aware of the received treatment. The primary outcome of MR CLEAN-LATE was the modified Rankin Scale (mRS) score at 90 days after randomisation. For this 2-year prespecified analysis, the primary outcome was mRS score at 2 years (minus 3 months to plus 6 months). Primary and safety analyses were performed based on the modified intention-to-treat principle, and included patients who provided (deferred) consent or died before consent could be obtained. Missing data were handled with multiple imputation by chained equations. The trial is completed and is registered at ISRCTN, ISRCTN19922220. FINDINGS: Between Feb 2, 2018, and Jan 27, 2022, 535 patients were randomly assigned in the MR CLEAN-LATE trial, of whom 502 (94%) gave deferred consent and comprised the modified intention-to-treat population (255 in the endovascular treatment group and 247 in the control group). 261 (52%) patients were female and 241 (48%) were male. Data for mRS score at 2 years were available for 226 (89%) patients in the endovascular treatment group and for 202 (82%) patients in the control group. The median mRS score at 2 years was 4 (IQR 2-6) in the endovascular treatment group and 6 (2-6) in the control group. The endovascular treatment group demonstrated a shift towards better functional outcomes on the mRS (adjusted common odds ratio 1·41 [95% CI 1·00-1·99]; p=0·049). All-cause mortality at 2 years was 34% (87 of 255) in the endovascular treatment group and 41% (101 of 247) in the control group (adjusted hazard ratio 0·81 [95% CI 0·60-1·08]; p=0·15). Major vascular events (ie, transient ischaemic attack, ischaemic stroke, haemorrhagic stroke, and cardiac events) were reported between 90 days and 2 years in 23 patients in the endovascular treatment group and 13 patients in the control group. INTERPRETATION: Our results show that the effectiveness of late-window (after 6-24 h) endovascular treatment in improving clinical outcomes is sustained for up to 2 years in a population preselected based on the presence of collateral flow on CT angiography. This finding might be important for prompting further evaluations of cost-effectiveness, health-care policy development, and clinical decision making. FUNDING: The Dutch Organization for Health Research and Health Innovation (ZonMW), Collaboration for New Treatments of Acute Stroke Consortium, Dutch Heart Foundation, Stryker, Medtronic, Cerenovus, Health Holland Top Sector Life Sciences & Health, and the Netherlands Brain Foundation.