Beta-Blocking Agents and Electroconvulsive Therapy

In this review we want to summarize the results of the placebo-controlled randomized clinical trials with betablocking adrenergic agents during electroconvulsive therapy (ECT), and review the effect on seizure duration and cardiovascular variables. We sea

A double blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients

Antidepressant effects of mirtazapine and imipramine were compared in a randomized, double blind, fixed blood-level study with in-patients in a single centre. Patients with a DSM-III-R diagnosis of major depression and a Hamilton (17-item) score of ≤ 18 were selected. After a drug-free and a placebo-washout period of 7 days in total, 107 patients still fulfilling the HRSD criterion of ≤ 18, started on active treatment. The dose was adjusted to a predefined fixed blood level to avoid suboptimal dosing of imipramine. Concomitant psychotropic medication was administered only in a few cases because of intolerable anxiety or intolerable psychotic symptoms. Eight patients dropped out and two were excluded from analyses because of non-compliance; 97 completed the study. According to the main response criterion (50% or more reduction on the HRSD score) 11/51 (21.6%) patients responded on mirtazapine and 23/46 (50%) on imipramine after 4 weeks' treatment on the predefined blood level. Such a dramatic difference in efficacy between antidepressants has not often been reported before. The selection of (severely ill) in-patients, including those with suicidal or psychotic features, may have significance in this respect. Optimization of treatment with the reference drug imipramine through blood level control, exclusion of non-compliance for both drugs, exclusion of most concomitant medication and a low drop-out rate may also have contributed. It is concluded that imipramine is superior to mirtazapine in the patient population studied

Automated entire thrombus density measurements for robust and comprehensive thrombus characterization in patients with acute ischemic stroke

Background and Purpose: In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method: In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described usingmedians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between themedian of entire thrombusmeasurements and commonly applied manualmeasurements using 3 regions of interest were determined using linear regression. Results: Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions: Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, d

Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN): Design and statistical analysis plan of the extended follow-up study

Background: MR CLEAN was the first randomized trial to demonstrate the short-term clinical effectiveness of endovascular treatment in patients with acute ischemic stroke caused by large vessel occlusion in the anterior circulation. Several other trials confirmed that endovascular treatment improves clinical outcome at three months. However, limited data are available on long-term clinical outcome. We aimed to estimate the effect of endovascular treatment on functional outcome at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed to assess the effect of endovascular treatment on major vascular events and mortality during two years of follow-up. Methods: MR CLEAN is a multicenter clinical trial with randomized treatment allocation, open-label treatment, and blinded endpoint evaluation. Patients included were 18 years or older with acute ischemic stroke caused by a proven anterior proximal artery occlusion who could be treated within six hours after stroke onset. The intervention contrast was endovascular treatment and usual care versus no endovascular treatment and usual care. The current study extended the follow-up duration from three months to two years. The primary outcome is the score on the modified Rankin scale at two years. Secondary outcomes include all-cause mortality and the occurrence of major vascular events within two years of follow-up. Discussion: The results of our study provide information on the long-term clinical effectiveness of endovascular treatment, which may have implications for individual treatment decisions and estimates of cost-effectiveness. Trial registration:NTR1804. Registered on 7 May 2009; ISRCTN10888758. Registered on 24 July 2012 (main MR CLEAN trial); NTR5073. Registered on 26 February 2015 (extended follow-up study)

Big data in the public sector: Uncertainties and readiness

Big data is being implemented with success in the private sector and science. Yet the public sector seems to be falling behind, despite the potential value of big data for government. Government organizations do recognize the opportunities of big data but seem uncertain about whether they are ready for the introduction of big data, and if they are adequately equipped to use big data. This paper addresses those uncertainties. It presents an assessment framework for evaluating public organizations’ big data readiness. Doing so demystifies the concept of big data, as it is expressed in terms of specific and measureable organizational characteristics. The framework was tested by applying it to organizations in the Dutch public sector. The results suggest that organizations may be technically capable of using big data, but they will not significantly gain from these activities if the applications do not fit their organizations and main statutory tasks. The framework proved helpful in pointing out areas where public sector organizations could improve, providing guidance on how government can become more big data ready in the future.Organisation and GovernancePolicy Analysi

Low-dose esmolol bolus reduces seizure duration during electroconvulsive therapy: a double-blind, placebo-controlled study

We have measured the effect of a bolus dose of esmolol 80 mg i.v. on heart rate, and systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures during electroconvulsive therapy (ECT). We also assessed seizure duration using both the cuff method and two-lead EEG. We studied 20 patients in a double-blind, placebo-controlled, within-patient blocked randomized study. No patient was receiving psychotherapeutic drugs or had cardiovascular disease. Esmolol significantly reduced heart rate, SAP and MAP before the stimulus, and also significantly reduced the increases in these variables during the convulsion, compared with placebo. However, seizure duration was also significantly reduced, possibly making ECT less effective. The reduction in seizure duration was 5.83 s when monitored clinically and 9.9 s when measured by the EEG. Because of the reduction in seizure duration, routine administration of esmolol is not advisable because it may interfere with the efficacy of ECT, but administration of esmolol during ECT could be useful to reduce tachycardia and hypertension in high-risk patients

Malignant transformation of Slp65-deficient pre-B cells involves disruption of the Arf-Mdm2-p53 tumor suppressor pathway

The adapter protein Slp65 is a key component of the precursor-B (pre-B) cell receptor. Slp65-deficient mice spontaneously develop pre-B cell leukemia, but the mechanism by which Slp65-/- pre-B cells become malignant is unknown. Loss of Btk, a Tec-family kinase that cooperates with Slp65 as a tumor suppressor, synergizes with deregulation of the c-Myc oncogene during lymphoma formation. Here, we report that the presence of the immunoglobulin heavy chain transgene VH81X prevented tumor development in Btk -/-Slp65-/- mice. This finding paralleled the reported effect of a human immunoglobulin heavy chain transgene on lymphoma development in Eμ-myc mice, expressing transgenic c-Myc. Because activation of c-Myc strongly selects for spontaneous inactivation of the p19Arf-Mdm2-p53 tumor suppressor pathway, we investigated whether disruption of this pathway is a common alteration in Slp65-/- pre-B cell tumors. We found that combined loss of Slp65 and p53 in mice transformed pre-B cells very efficiently. Aberrations in p19Arf, Mdm2, or p53 expression were found in all Slp65-/-(n = 17)andBtk-/-Slp65-/-(n = 32) pre-B cell leukemias analyzed. In addition, 9 of 10 p53-/-Slp65 -/- pre-B cell leukemias manifested significant Mdm2 protein expression. These data indicate that malignant transformation of Slp65 -/- pre-B cells involves disruption of the p19Arf-Mdm2-p53 tumor suppressor pathway