No effects of cerebellar transcranial direct current stimulation on force field and visuomotor reach adaptation in young and healthy subjects.

Previous studies have shown that cerebellar transcranial direct current stimulation (tDCS) leads to faster adaptation of arm reaching movements to visuomotor rotation and force field perturbations in healthy subjects. The first aim of the present study was to confirm a stimulation-dependent effect on motor adaptation. Second, we investigated whether tDCS effects differ depending on onset, that is, before or at the beginning of the adaptation phase. A total of 120 healthy and right-handed subjects (60 women, mean age 23.2 ± SD 2.7 yr, range 18-31 yr) were tested. Subjects moved a cursor with a manipulandum to one of eight targets presented on a vertically orientated screen. Three baseline blocks were followed by one adaptation block and three washout blocks. Sixty subjects did a force field adaptation task (FF), and 60 subjects did a visuomotor adaptation task (VM). Equal numbers of subjects received anodal, cathodal, or sham cerebellar tDCS beginning either in the third baseline block or at the start of the adaptation block. In FF and VM, tDCS and the onset of tDCS did not show a significant effect on motor adaptation (all P values >0.05). We were unable to support previous findings of modulatory cerebellar tDCS effects in reaching adaptation tasks in healthy subjects. Prior to possible application in patients with cerebellar disease, future experiments are needed to determine which tDCS and task parameters lead to robust tDCS effects. NEW & NOTEWORTHY Transcranial direct current stimulation (tDCS) is a promising tool to improve motor learning. We investigated whether cerebellar tDCS improves motor learning in force field and visuomotor tasks in healthy subjects and what influence the onset of stimulation has. We did not find stimulation effects of tDCS or an effect of onset of stimulation. A reevaluation of cerebellar tDCS in healthy subjects and at the end of the clinical potential in cerebellar patients is demanded.

Estimating summary statistics for electronic health record laboratory data for use in high-throughput phenotyping algorithms.

We study the question of how to represent or summarize raw laboratory data taken from an electronic health record (EHR) using parametric model selection to reduce or cope with biases induced through clinical care. It has been previously demonstrated that the health care process (Hripcsak and Albers, 2012, 2013), as defined by measurement context (Hripcsak and Albers, 2013; Albers et al., 2012) and measurement patterns (Albers and Hripcsak, 2010, 2012), can influence how EHR data are distributed statistically (Kohane and Weber, 2013; Pivovarov et al., 2014). We construct an algorithm, PopKLD, which is based on information criterion model selection (Burnham and Anderson, 2002; Claeskens and Hjort, 2008), is intended to reduce and cope with health care process biases and to produce an intuitively understandable continuous summary. The PopKLD algorithm can be automated and is designed to be applicable in high-throughput settings; for example, the output of the PopKLD algorithm can be used as input for phenotyping algorithms. Moreover, we develop the PopKLD-CAT algorithm that transforms the continuous PopKLD summary into a categorical summary useful for applications that require categorical data such as topic modeling. We evaluate our methodology in two ways. First, we apply the method to laboratory data collected in two different health care contexts, primary versus intensive care. We show that the PopKLD preserves known physiologic features in the data that are lost when summarizing the data using more common laboratory data summaries such as mean and standard deviation. Second, for three disease-laboratory measurement pairs, we perform a phenotyping task: we use the PopKLD and PopKLD-CAT algorithms to define high and low values of the laboratory variable that are used for defining a disease state. We then compare the relationship between the PopKLD-CAT summary disease predictions and the same predictions using empirically estimated mean and standard deviation to a gold standard generated by clinical review of patient records. We find that the PopKLD laboratory data summary is substantially better at predicting disease state. The PopKLD or PopKLD-CAT algorithms are not meant to be used as phenotyping algorithms, but we use the phenotyping task to show what information can be gained when using a more informative laboratory data summary. In the process of evaluation our method we show that the different clinical contexts and laboratory measurements necessitate different statistical summaries. Similarly, leveraging the principle of maximum entropy we argue that while some laboratory data only have sufficient information to estimate a mean and standard deviation, other laboratory data captured in an EHR contain substantially more information than can be captured in higher-parameter models.

Comparison of ultrasound guidance with palpation and direct visualisation for peripheral vein cannulation in adult patients: a systematic review and meta-analysis.

BACKGROUND: Peripheral vein cannulation is a routine and straightforward invasive procedure, although i.v. access can be difficult to obtain. To increase the success rate of inserting an i.v. catheter, many devices have been proposed, including ultrasonography. The objective of this study was to compare ultrasound guidance with the traditional approach of palpation and direct visualisation for peripehral vein cannulation. The primary outcome was successful peripheral i.v. cannulation. METHODS: Database search was performed on PubMed, Clinical Key, CINAHL, Cochrane Library of Clinical Trials, and Trip Database (from January 2000 to December 2017). Random-effect meta-analysis was performed to determine the pooled odds ratio for success in peripheral i.v. cannulation. RESULTS: After database review and eligibility screening, eight studies were included in the final analysis, with a total of 1660 patients. The success rate in the ultrasound group was 81% (n=855), and was 70% (n=805) in the control group, resulting in a pooled odds ratio for success upon ultrasound-guided peripheral i.v. cannulation of 2.49 (95% confidence interval 1.37-4.52, P=0.003). Furthermore, the ultrasound-guided technique reduced the number of punctures and time needed to achieve i.v. access, and increased the level of patient satisfaction, although it did not result in a decreased number of complications. CONCLUSIONS: Ultrasound guidance increases the success rate of peripheral i.v. cannulation, especially in patients with known or predicted difficult i.v. access.

Altered Cerebellar Activity in Visceral Pain-Related Fear Conditioning in Irritable Bowel Syndrome.

There is evidence to support a role of the cerebellum in emotional learning processes, which are demonstrably altered in patients with chronic pain. We tested if cerebellar activation is altered during visceral pain-related fear conditioning and extinction in irritable bowel syndrome (IBS). Cerebellar blood oxygenation level-dependent (BOLD) data from N = 17 IBS patients and N = 21 healthy controls, collected as part of a previous fMRI study, was reanalyzed utilizing an advanced normalizing method of the cerebellum. The differential fear conditioning paradigm consisted of acquisition, extinction, and reinstatement phases. During acquisition, two visual conditioned stimuli (CS) were presented either paired (CS+) or unpaired (CS-) with painful rectal distension as unconditioned stimulus (US). In the extinction phase, the CS+ and CS- were presented without US. For reinstatement, unpaired US presentations were followed by unpaired CS+ and CS- presentations. Group differences in cerebellar activation were analyzed for the contrasts CS+ > CS- and CS- > CS+. During acquisition, IBS patients revealed significantly enhanced cerebellar BOLD responses to pain-predictive (CS+) and safety (CS-) cues compared to controls (p < 0.05, family-wise error corrected). Increased activation was found in three main clusters, including the vermis (maximum in vermal lobule VI), intermediate cerebellum (maximum in lobule VIII), and the posterolateral cerebellar hemisphere (maximum in lobule VI). Areas overlapped for the contrasts CS+ > CS- and CS- > CS+. Group differences were most prominent in the contrast CS- > CS+. During extinction and reinstatement, no significant group differences were found. During visceral pain-related fear conditioning, IBS patients showed increased activations in circumscribed areas of the medial, intermediate, and lateral cerebellum. These areas are involved in autonomic, somatosensory, and cognitive functions and likely contribute to the different aspects of pain-related fear. The cerebellum contributes to altered pain-related fear learning in IBS.

Diffusion tensor imaging of the hippocampus predicts the risk of dementia; the RUN DMC study.

INTRODUCTION: Cerebral small vessel disease is one of the most important risk factors for dementia, and has been related to hippocampal atrophy, which is among the first observed changes on conventional MRI in patients with dementia. However, these volumetric changes might be preceded by loss of microstructural integrity of the hippocampus for which conventional MRI is not sensitive enough. Therefore, we investigated the relation between the hippocampal diffusion parameters and the risk of incident dementia, using diffusion tensor imaging, independent of hippocampal volume. METHODS: The RUNDMC study is a prospective study among 503 elderly with small vessel disease, without dementia, with 5 years follow-up in 2012 (99.6% response-rate). Cox regression analysis was performed to calculate hazard ratios for dementia, of fractional anisotropy and mean diffusivity within the hippocampus, adjusted for demographics, hippocampal volume, and white matter. This was repeated in participants without evident hippocampal volume loss, because in these participants the visible damage might not yet have already started, whereas damage might have started on a microstructural level. RESULTS: 43 participants developed dementia (8.6%), resulting in a 5.5-year cumulative risk of 11.1% (95%CI 7.7-14.6). Higher mean diffusivity was associated with an increased 5-year risk of dementia. In the subgroup of participants with the upper half hippocampal volume, higher hippocampal mean diffusivity, more than doubled the 5-year risk of dementia. CONCLUSION: This is the first prospective study showing a relation between a higher baseline hippocampal mean diffusivity and the risk of incident dementia in elderly with small vessel disease at 5-year follow-up, independent of hippocampal volume and white matter volume.

Lack of renewal effect in extinction of naturally acquired conditioned eyeblink responses, but possible dependency on physical context.

Context dependency of extinction is well known and has extensively been studied in fear conditioning, but has rarely been assessed in eyeblink conditioning. One way to demonstrate context dependency of extinction is the renewal effect. ABA paradigms are most commonly used to show the renewal effect of extinguished learned fear: if acquisition takes place in context A, and extinction takes place in context B (extinction phase), learned responses will recover in subsequent extinction trials presented in context A (renewal phase). The renewal effect of the visual threat eyeblink response (VTER), a conditioned eyeblink response, which is naturally acquired in early infancy, was examined in a total of 48 young and healthy participants with two experiments using an ABA paradigm. Twenty paired trials were performed in context A (baseline trials), followed by 50 extinction trials in context B (extinction phase) and 50 extinction trials in context A (renewal phase). In 24 participants, contexts A and B were two different rooms, and in the other 24 participants, two different background colors (orange and blue) and noises were used. To rule out spontaneous recovery, an AAA design was used for comparison. There were significant effects of extinction in both experiments. No significant renewal effects were observed. In experiment 2, however, extinction was significantly less using orange background during extinction compared to the blue background. The present findings suggest that extinction of conditioned eyeblinks depends on the physical context. Findings add to the animal literature that context can play a role in the acquisition of classically conditioned eyeblink responses. Future studies, however, need to be performed to confirm the present findings. Lack of renewal effect may be explained by the highly overlearned character of the VTER.

Unplanned Transfers from Hospital Wards to the Neurological Intensive Care Unit.

BACKGROUND: The aim of this study is to evaluate the characteristics of unplanned transfers of adult patients from hospital wards to a neurological intensive care unit (NICU). METHODS: We retrospectively reviewed consecutive unplanned transfers from hospital wards to the NICU at our institution over a 3-year period. In-hospital mortality rates were compared between patients readmitted to the NICU ("bounce-back transfers") and patients admitted to hospital wards from sources other than the NICU who were then transferred to the NICU ("incident transfers"). We also measured clinical characteristics of transfers, including source of admission and indication for transfer. RESULTS: A total of 446 unplanned transfers from hospital wards to the NICU occurred, of which 39% were bounce-back transfers. The in-hospital mortality rate associated with all unplanned transfers to the NICU was 17% and did not differ significantly between bounce-back transfers and incident transfers. Transfers to the NICU within 24 h of admission to a floor service accounted for 32% of all transfers and were significantly more common for incident transfers than bounce-back transfers (39 vs. 21%, p = .0002). Of patients admitted via the emergency department who had subsequent incident transfers to the NICU, 50% were transferred within 24 h of admission. CONCLUSIONS: Unplanned transfers to an NICU were common and were associated with a high in-hospital mortality rate. Quality improvement projects should target the triage process and transitions of care to the hospital wards in order to decrease unplanned transfers of high-risk patients to the NICU.

Extracorporeal membrane oxygenation use in patients with traumatic brain injury.

Venovenous extracorporeal membrane oxygenation (ECMO) is used for patients with severe, potentially reversible, respiratory failure unresponsive to conventional management. It is relatively contraindicated in patients with traumatic brain injury (TBI) due to bleeding complications and use of anticoagulation. We report two cases of TBI patients treated with ECMO.

Consensus paper: management of degenerative cerebellar disorders.

Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation.

Plasma proteome profiling identifies changes associated to AD but not to FTD.

BACKGROUND: Frontotemporal dementia (FTD) is caused by frontotemporal lobar degeneration (FTLD), characterized mainly by inclusions of Tau (FTLD-Tau) or TAR DNA binding43 (FTLD-TDP) proteins. Plasma biomarkers are strongly needed for specific diagnosis and potential treatment monitoring of FTD. We aimed to identify specific FTD plasma biomarker profiles discriminating FTD from AD and controls, and between FTD pathological subtypes. In addition, we compared plasma results with results in post-mortem frontal cortex of FTD cases to understand the underlying process. METHODS: Plasma proteins (n = 1303) from pathologically and/or genetically confirmed FTD patients (n = 56; FTLD-Tau n = 16; age = 58.2 ± 6.2; 44% female, FTLD-TDP n = 40; age = 59.8 ± 7.9; 45% female), AD patients (n = 57; age = 65.5 ± 8.0; 39% female), and non-demented controls (n = 148; 61.3 ± 7.9; 41% female) were measured using an aptamer-based proteomic technology (SomaScan). In addition, exploratory analysis in post-mortem frontal brain cortex of FTD (n = 10; FTLD-Tau n = 5; age = 56.2 ± 6.9, 60% female, and FTLD-TDP n = 5; age = 64.0 ± 7.7, 60% female) and non-demented controls (n = 4; age = 61.3 ± 8.1; 75% female) were also performed. Differentially regulated plasma and tissue proteins were identified by global testing adjusting for demographic variables and multiple testing. Logistic lasso regression was used to identify plasma protein panels discriminating FTD from non-demented controls and AD, or FTLD-Tau from FTLD-TDP. Performance of the discriminatory plasma protein panels was based on predictions obtained from bootstrapping with 1000 resampled analysis. RESULTS: Overall plasma protein expression profiles differed between FTD, AD and controls (6 proteins; p = 0.005), but none of the plasma proteins was specifically associated to FTD. The overall tissue protein expression profile differed between FTD and controls (7-proteins; p = 0.003). There was no difference in overall plasma or tissue expression profile between FTD subtypes. Regression analysis revealed a panel of 12-plasma proteins discriminating FTD from AD with high accuracy (AUC: 0.99). No plasma protein panels discriminating FTD from controls or FTD pathological subtypes were identified. CONCLUSIONS: We identified a promising plasma protein panel as a minimally-invasive tool to aid in the differential diagnosis of FTD from AD, which was primarily associated to AD pathophysiology. The lack of plasma profiles specifically associated to FTD or its pathological subtypes might be explained by FTD heterogeneity, calling for FTD studies using large and well-characterize cohorts.

[Desmopressin for nocturia in the old: an inappropriate treatment due to the high risk of side-effects?]. / Desmopressine voor de behandeling van nycturie bij ouderen: ongewenst door hoog risico op bijwerkingen?

Desmopressin, a synthetic analog of the antidiuretic hormone, is used in the treatment of enuresis nocturna in children and increasingly also in adults. Nocturia in the elderly causes sleeping disorders and is associated with a higher risk of falling and increased mortality. Desmopressin leads to a significant decrement of nocturia and consequently, a better sleep quality and is for this reason increasingly prescribed in the old. Desmopressin causes borderline hyponatremia (130-135 mmol/l) in 15% and severe hyponatremia in 5% of all adult users. Factors that predispose to hyponatremia are a higher dose, age > 65 years, a low-normal serum sodium, a high 24-hour urine volume and co-medication (thiazide diuretics, tricyclic antidepressants, serotonin-reuptake-inhibitors, chlorpromazine, carbamazipine, loperamide, Non-Steroidal-Anti-Inflammatory-Drugs). Hyponatremia is associated with headache, nausea, vomiting, dizziness, and can cause somnolence, loss of consciousness and death. We present two cases where initiation of desmopressin led to hyponatremia, requiring hospitalization. In view of the high risk of desmopressin-associated hyponatremia in the older population, alternative treatment strategies for nocturia must be considered first. If desmopressin is prescribed, strict follow-up of serum sodium levels is necessary.

3D printed titanium prosthesis reconstruction following subtotal maxillectomy for myoepithelial carcinoma - a case report.

We present the case of a 43 year old male with a myoepithelial carcinoma of the hard palate who underwent a subtotal maxillectomy, resulting in a significant midfacial defect. The defect was successfully reconstructed with a titanium prosthesis using Additive Manufacturing (AM), better known as 3D printing; the process used to manufacture the prosthesis being Direct Metal Laser Sintering (DMLS). A maxillary denture was fitted onto the titanium DMLS frame post-operatively. This method of reconstruction of a large midfacial defect proved to be successful both functionally and cosmetically, and resulted in a good quality of life 3 years post-operatively.

Analysis of glyphosate, AMPA, Glufosinate and MPPA with ION chromatography tandem mass spectrometry using A membrane suppressor in the ammonium form application to surface water of low to moderate salinity.

This paper describes a simple and reliable method for the sensitive and selective determination of the pesticides Glyphosate and Glufosinate and their main metabolites aminomethylphosphonic acid (AMPA) and 3-[hydroxy(methyl)phosphinoyl]propionic acid (MPPA) in surface water. The developed method is based on ion chromatography hyphenated to electrospray tandem mass spectrometry and does not require derivatization. A membrane suppressor, regenerated at pH 9, has been used in this work to strongly improve the peak shape of AMPA, which suffered from huge tailing due to the interaction of this compound with acidic membrane suppressors. With this modified suppressor the sensitivity for AMPA improved about 100 times. Moreover, addition of 40% methanol to the hydroxy eluent improved MS sensitivity for all compounds by 1.3-2.8 times. The separation is performed on a strong anion exchange column. Glyphosate and AMPA are detected in the negative ion ESI mode, whereas Glufosinate and MPPA show much better sensitivity in the positive ion ESI mode. Surface water samples were spiked with the labelled parent compounds. Sample preparation comprised a filtering step over coupled solid phase extraction Ba, Ag and Na cartridges to remove chloride and sulphate ions. The performance characteristics of the method were determined with real surface water samples. Samples containing 12.6 g L-1 chloride were also used in the validation process and showed no problem. Nitrate is not removed from the samples and may give ion-suppression for Glyphosate. Linearity of the method was established over at least three orders of magnitude in the measuring range 10-2000 ng L-1 for surface water. The reliability of the results was ensured by the application of the criteria from the Dutch Technical Agreement (NTA 8379) concerning "identification", "indication", and "absence" of substances. The limit of quantitation with regard to identification was 10 ng L-1 for all compounds and the limits of detection with regard to indication were 6.5-9.6 ng L-1. The recovery (94-104%) and reproducibility variance (5.5-6.2%) were excellent. The suitability of the developed method was demonstrated by the analysis of 172 surface water samples of low to moderate salinity from different parts of The Netherlands. AMPA was identified in 99% of the samples and always exceeded the maximum allowable concentration of 100 ng L-1. The maximal concentration found in surface water was 9900 ng L-1. Glyphosate was identified in 82% of the samples and in only 6% Glyphosate exceeded the maximum allowable concentration of 100 ng L-1. MPPA was identified in about 75% of the samples whereas Glufosinate was rarely detected and never exceeded the limit of quantitation.

Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group.

The analysis of spontaneous EEG activity and evoked potentialsis a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). Thepast few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury,opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of bothconsolidated and investigational electrophysiological techniquesfor the prognostic and diagnostic assessment of DoC.We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats.The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation.

Rationale for adjuvant fatty acid therapy to prevent radiotherapy failure and tumor recurrence during early laryngeal squamous cell carcinoma.

Information from a preceding lipid study contributed to the pathobiological assessment of laryngeal squamous cell carcinoma (LSCC). Lipid-driven signaling pathways are responsible for laryngeal carcinogenesis and immunodeficiency. The construction of fatty acid (FA) profiles for LSCC allowed the identification of FA role players. The integration of lipid and clinicomolecular information encountered in the literature, in turn, allowed the identification of biological prognostic markers to distinguish between early (less aggressive) and advanced (more aggressive) LSCCs. High arachidonic acid (AA) and cyclooxygenase (COX-2) activities are criteria for less aggressive growth, whilst low AA and COX-2 activities occur during more aggressive growth. Excessive tobacco use and environmental smoke or human papillomavirus (HPV) infection and alcohol abuse can, respectively, elicit cumulative oxidative stress and an oxidative burst or interfere with signaling pathways during essential fatty acid (EFA) metabolism, all factors and events which may cause LSCC. Research revealed that enhanced COX-2 activity and Bcl-2 expression prevent apoptosis and, hence, LSCCs become resistant to radiotherapy. It was also observed that recurrent laryngeal cancers become more aggressive after radiotherapy failure. It is predicted that manipulation of AA activity and consequently a cascade of downstream factors that include COX-2 and Bcl-2 expression responsible for LSCC may have therapeutic potential to improve radiotherapy outcome during early LSCC. Adjuvant FA therapy to improve early LSCC management by counteracting radiotherapy failure and unwanted complications for further management is proposed. FA therapeutic strategies before and during radiotherapeutic courses need to be evaluated.

[Orthostatic hypotension in elderly patients]. / Orthostatische hypotensie bij de oudere patiënt.

- Orthostatic hypotension is a condition in which there is insufficient recovery of the blood pressure drop which occurs after getting up, which causes a temporary reduction of cerebral perfusion. This increases the risk of falls resulting in injuries.- Orthostatic hypotension is most common in the elderly. The cause is usually multifactorial (including reduced circulating volume, reduced peripheral resistance and limited heart rate increase). Orthostatic hypotension caused by autonomic dysfunction is called neurogenic orthostatic hypotension.- The most important groups of drugs that may elicit orthostatic hypotension are: diuretics (but only if they lead to hypovolaemia), antidepressants (mainly tricyclic antidepressants), sympatholytics (alpha-blockers as well as beta-blockers) and vasodilators (for example, nitrates).- Treatment of the elderly with orthostatic hypotension starts with lifestyle advice (getting up slowly) and possible medication adjustments.

Influence of Induced Blood Pressure Variability on the Assessment of Cerebral Autoregulation in Patients after Cardiac Arrest.

OBJECTIVE: To determine if increasing variability of blood pressure influences determination of cerebral autoregulation. METHODS: A prospective observational study was performed at the ICU of a university hospital in the Netherlands. 13 comatose patients after cardiac arrest underwent baseline and intervention (tilting of bed) measurements. Mean flow velocity (MFV) in the middle cerebral artery and mean arterial pressure (MAP) were measured. Coefficient of variation (CV) was used as a standardized measure of dispersion in the time domain. In the frequency domain, coherence, gain, and phase were calculated in the very low and low frequency bands. RESULTS: The CV of MAP was significantly higher during intervention compared to baseline. On individual level, coherence in the VLF band changed in 5 of 21 measurements from unreliable to reliable and in 6 of 21 measurements from reliable to unreliable. In the LF band 1 of 21 measurements changed from unreliable to reliable and 3 of 21 measurements from reliable to unreliable. Gain in the VLF and LF band was lower during intervention compared to baseline. CONCLUSIONS: For the ICU setting, more attention should be paid to the exact experimental protocol, since changes in experimental settings strongly influence results of estimation of cerebral autoregulation.

Seizures in the critically ill.

Critically ill patients with seizures are either admitted to the intensive care unit because of uncontrolled seizures requiring aggressive treatment or are admitted for other reasons and develop seizures secondarily. These patients may have multiorgan failure and severe metabolic and electrolyte disarrangements, and may require complex medication regimens and interventions. Seizures can be seen as a result of an acute systemic illness, a primary neurologic pathology, or a medication side-effect and can present in a wide array of symptoms from convulsive activity, subtle twitching, to lethargy. In this population, untreated isolated seizures can quickly escalate to generalized convulsive status epilepticus or, more frequently, nonconvulsive status epileptics, which is associated with a high morbidity and mortality. Status epilepticus (SE) arises from a failure of inhibitory mechanisms and an enhancement of excitatory pathways causing permanent neuronal injury and other systemic sequelae. Carrying a high 30-day mortality rate, SE can be very difficult to treat in this complex setting, and a portion of these patients will become refractory, requiring narcotics and anesthetic medications. The most significant factor in successfully treating status epilepticus is initiating antiepileptic drugs as soon as possible, thus attentiveness and recognition of this disease are critical.

[Dementia: growing disaster or declining epidemic?] / Dementie: groeiende ramp of afnemende epidemie?

- There is currently a lot of uncertainty about the future prevalence of dementia. Not only increasing age, but also educational level and lifestyle of the population appear to play a role.- There is little scientific and societal attention for the great uncertainty around average incidence and prevalence estimates for dementia.- When estimating the prognosis of people with dementia, the average disease course is often used as a basis, while this is not at all representative of the individual course of most patients.- The beneficial findings of recent lifestyle intervention studies ask for more targeted prevention strategies for risk groups. There is no standard preventative strategy which works equally well for everyone.- Given the large influence of dementia-related publications on the expectations of people regarding their ageing, it is important to present measures of dispersion alongside all study results.