Trends in Palliative Care Telephone Consultation Support for Health Care Professionals: A Dutch Nationwide Registry between 2004 and 2019.

Background: Regional palliative care consultation (PCC) teams aim to support health care professionals by telephone in providing quality palliative care (PC) in the Netherlands. Objectives: The study aims to assess trends in the number and characteristics of PC telephone consultations in the Netherlands between 2004 and 2019. Design: A retrospective observational study reviewed data from the Dutch national register for PC consultations by telephone (PRADO). To assess trends in the number of consultations, three time periods were defined: 2004-2008, 2009-2013, and 2014-2019. All analyses were conducted using STATA. Results: A total of 83,554 PC telephone consultations were analyzed. There was a slight decrease in the number of consultations since 2014, from 5811 (2014) to 4914 (2019). The Dutch PCC telephone helpdesk was mainly consulted by general practitioners, with pharmacological issues (65%) and pain (44%) being the main concerns. The data included 73,833 patients, of whom 63% were 65 years or older (18-109) and 51% were male. The proportion of noncancer patients increased during the selected time periods, 2004-2008 (11%), 2009-2013 (16%), and 2014-2019 (22%). The proportion of consultations requested for hospitalized patients was higher in 2014-2019 (7.9%) than in 2009-2013 (4.5%). Conclusion: Dutch PC telephone consultations have changed over time. More PC telephone consultations were held for hospitalized patients and noncancer diseases over the past years. These trends are in line with the shift toward more integrated PC in which different services collaborate.

Tau pathology in early Alzheimer's disease is linked to selective disruptions in neurophysiological network dynamics.

Understanding the role of Tau protein aggregation in the pathogenesis of Alzheimer's disease is critical for the development of new Tau-based therapeutic strategies to slow or prevent dementia. We tested the hypothesis that Tau pathology is associated with functional organization of widespread neurophysiological networks. We used electro-magnetoencephalography with [18F]AV-1451 PET scanning to quantify Tau-dependent network changes. Using a graph theoretical approach to brain connectivity, we quantified nodal measures of functional segregation, centrality, and the efficiency of information transfer and tested them against levels of [18F]AV-1451. Higher Tau burden in early Alzheimer's disease was associated with a shift away from the optimal small-world organization and a more fragmented network in the beta and gamma bands, whereby parieto-occipital areas were disconnected from the anterior parts of the network. Similarly, higher Tau burden was associated with decreases in both local and global efficiency, especially in the gamma band. The results support the translational development of neurophysiological "signatures" of Alzheimer's disease, to understand disease mechanisms in humans and facilitate experimental medicine studies.

Imaging Aß and tau in early stage Alzheimer's disease with [18F]AV45 and [18F]AV1451.

BACKGROUND: AD is a progressive neurodegenerative disorder that is associated with the accumulation of two different insoluble protein aggregates, Aß plaques and hyperphosphorylated tau. This study aimed to investigate the optimal acquisition and quantification of [18F]AV45 and [18F]AV1451 to image Aß and tau, respectively, in subjects with AD. Fifteen subjects with early stage AD underwent a T1-weighted structural MRI and two dynamic PET scans to image Aß (60 min, [18F]AV45) and tau (120 min, [18F]AV1451). Both dynamic BPND and static SUVR outcome measures were calculated and compared for 12 out of 15 subjects who completed 60 min of the Aß PET scan and at least 110 min of the tau PET scan. The SRTM and reference Logan graphical analysis were applied to the dynamic data to estimate regional BPND values and SUVR ratios from the static data. Optimal acquisition windows were explored for both the dynamic and static acquisitions. In addition, the spatial correlation between regional Aß and tau signals was explored. RESULTS: Both the SRTM and graphical analysis methods showed a good fit to the dynamic data for both Aß and tau dynamic PET scans. Mean regional BPND estimates became stable 30 min p.i. for [18F]AV45 and 80 min p.i. for [18F]AV1451. Time stability analysis of static SUVR data showed that the outcome measure starts to become stable for scan windows of 30-50 min p.i. for [18F]AV45 and 80-100 min p.i. for [18F]AV1451. The results from these time windows correlated well with the results from the full dynamic analysis for both tracers (R2 = 0.74 for [18F]AV45 and R2 = 0.88 for [18F]AV1451). There was a high correlation between amyloid uptake estimate using both dynamic analysis methods in thalamus and tau uptake in thalamus, hippocampus and amygdala. CONCLUSIONS: Short static PET scans at appropriate time windows provided SUVR values which were in reasonable agreement with BPND values calculated from dynamic scans using SRTM and reference Logan. These simplified methods may be appropriate for classification and intervention studies, although caution should be employed when considering interventional studies where blood flow and extraction could change.

PET Tau and Amyloid-ß Burden in Mild Alzheimer's Disease: Divergent Relationship with Age, Cognition, and Cerebrospinal Fluid Biomarkers.

BACKGROUND: Combining PET amyloid-ß (Aß) and tau imaging may be critical for tracking disease progression in Alzheimer's disease (AD). OBJECTIVE: We sought to characterize the relationship between Aß and tau ligands as well as with other measures of pathology. METHODS: We conducted a multi-center observational study in early AD (MMSE >20) participants aged 50 to 85 y. The schedule included cognitive assessments (ADAS-Cog) and CSF measurement of Aß and tau at baseline and 6 months; PET-CT imaging with Aß ([18F]AV45) and tau ([18F]AV1451) ligands at baseline. RESULTS: 22 participants took part in the study with 20 completing its 6-month duration and 12 having both tau and amyloid PET. The PET biomarker analysis revealed a strong negative correlation between age and tau in multiple regions. Entorhinal cortex tau and age interacted significantly in terms of cognitive change over 6 months which may have been to older participants deteriorating faster despite lower levels of cortical tau. Cortical Aß associated with entorhinal cortex tau while CSF tau/Aß ratio correlated strongly with cortical tau but not Aß. CONCLUSION: The negative relationship between age and cortical tau whereby younger patients with mild AD had relatively greater tau burden is potentially important. It suggests that younger-age onset AD may be primarily driven by tau pathology while AD developing later may depend on a multitude of pathological mechanisms. These data also suggest that PET-tau performs better than PET-amyloid in predicting the best validated AD diagnostic marker- the CSF total tau/Aß ratio.

Insight on automated lesion delineation methods for PET data.

BACKGROUND: Defining tumour volume for treatment response and radiotherapy planning is challenging and prone to inter- and intra-observer variability. Various automated tumour delineation methods have been proposed in the literature, each having abilities and limitations. Therefore, there is a need to provide clinicians with practical information on delineation method selection. METHODS: Six different automated positron emission tomography (PET) delineation methods were evaluated and compared using National Electrical Manufacturer Association image quality (NEMA IQ) phantom data and three in-house synthetic phantoms with clinically relevant lesion shapes including spheres with necrotic core and irregular shapes. The impact of different contrast ratios, emission counts, realisations and reconstruction algorithms on delineation performance was also studied using similarity index (SI) and percentage volume error (%VE) as performance measures. RESULTS: With the NEMA IQ phantom, contrast thresholding (CT) performed best on average for all sphere sizes and parameter settings (SI = 0.83; %VE = 5.65% ± 24.34%). Adaptive thresholding at 40% (AT40) was the next best method and required no prior parameter tuning (SI = 0.78; %VE = 23.22% ± 70.83%). When using SUV harmonisation filtering prior to delineation (EQ.PET), AT40 remains the best method without prior parameter tuning (SI = 0.81; %VE = 11.39% ± 85.28%). For necrotic core spheres and irregular shapes of the synthetic phantoms, CT remained the best performing method (SI = 0.83; %VE = 26.31% ± 38.26% and SI = 0.62; %VE = 24.52% ± 46.89%, respectively). The second best method was fuzzy locally adaptive Bayesian (FLAB) (SI = 0.83; %VE = 29.51% ± 81.79%) for necrotic core sphere and AT40 (SI = 0.58; %VE = 25.11% ± 32.41%) for irregular shapes. When using EQ.PET prior to delineation, AT40 was the best performing method without prior parameter tuning for both necrotic core (SI = 0.83; %VE = 27.98% ± 59.58%) and complex shapes phantoms (SI = 0.61; %VE = 14.83% ± 49.39%). CONCLUSIONS: CT and AT40/AT50 are recommended for all lesion sizes and contrasts. Overall, considering background uptake information improves PET delineation accuracy. Applying EQ.PET prior to delineation improves accuracy and reduces coefficient of variation (CV) across different reconstructions and acquisitions.

Quantification of intracranial aneurysm morphodynamics from ECG-gated CT angiography.

RATIONALE AND OBJECTIVES: Aneurysm morphodynamics is potentially relevant for assessing aneurysm rupture risk. A method is proposed for automated quantification and visualization of intracranial aneurysm morphodynamics from electrocardiogram (ECG)-gated computed tomography angiography (CTA) data. MATERIALS AND METHODS: A prospective study was performed in 19 aneurysms from 14 patients with diagnostic workup for recently discovered aneurysms (n = 15) or follow-up of untreated known aneurysms (n = 4). The study was approved by the Institutional Review Board of the hospital and written informed consent was obtained from each patient. An image postprocessing method was developed for quantifying aneurysm volume changes and visualizing local displacement of the aneurysmal wall over a heart cycle using multiphase ECG-gated (four-dimensional) CTA. Percentage volume changes over the heart cycle were determined for aneurysms, surrounding arteries, and the skull. RESULTS: Pulsation of the aneurysm and its surrounding vasculature during the heart cycle could be assessed from ECG-gated CTA data. The percentage aneurysmal volume change ranged from 3% to 18%. CONCLUSION: ECG-gated CTA can be used to study morphodynamics of intracranial aneurysms. The proposed image analysis method is capable of quantifying the volume changes and visualizing local displacement of the vascular structures over the cardiac cycle.

Intracranial aneurysm segmentation in 3D CT angiography: method and quantitative validation with and without prior noise filtering.

Intracranial aneurysm volume and shape are important factors for predicting rupture risk, for pre-surgical planning and for follow-up studies. To obtain these parameters, manual segmentation can be employed; however, this is a tedious procedure, which is prone to inter- and intra-observer variability. Therefore there is a need for an automated method, which is accurate, reproducible and reliable. This study aims to develop and validate an automated method for segmenting intracranial aneurysms in Computed Tomography Angiography (CTA) data. Also, it is investigated whether prior smoothing improves segmentation robustness and accuracy. The proposed segmentation method is implemented in the level set framework, more specifically Geodesic Active Surfaces, in which a surface is evolved to capture the aneurysmal wall via an energy minimization approach. The energy term is composed of three different image features, namely; intensity, gradient magnitude and intensity variance. The method requires minimal user interaction, i.e. a single seed point inside the aneurysm needs to be placed, based on which image intensity statistics of the aneurysm are derived and used in defining the energy term. The method has been evaluated on 15 aneurysms in 11 CTA data sets by comparing the results to manual segmentations performed by two expert radiologists. Evaluation measures were Similarity Index, Average Surface Distance and Volume Difference. The results show that the automated aneurysm segmentation method is reproducible, and performs in the range of inter-observer variability in terms of accuracy. Smoothing by nonlinear diffusion with appropriate parameter settings prior to segmentation, slightly improves segmentation accuracy.

Withdrawal of statins and risk of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the risk of SAH. METHODS: We conducted a population-based case-control study within the PHARMO database. A case was defined as a person hospitalized for SAH (ICD-9-CM code 430) in the period January 1, 1998 to December 31, 2006. Ten randomly chosen controls were matched to each case on age, gender, and calendar date. RESULTS: During the study period 1004 incident cases of SAH were identified. Current use of statins did not significantly decrease the risk of SAH (OR=0.77, 95% CI 0.55 to 1.07). The odds ratio for recent withdrawal compared to nonusers was 1.62 (95% CI 0.96 to 2.73). Compared to current use, recent withdrawal was associated with an increased risk of SAH (OR=2.34, 95% CI 1.35 to 4.05). Interaction analysis showed that the effect of statin withdrawal was highest in patients who had also recently stopped antihypertensive drugs (OR=6.77, 95% CI 2.10 to 21.8). CONCLUSIONS: Current use of statins seems to lower the risk of SAH, although the reduction was not significant in new users. Statin withdrawal increased the risk of SAH by a factor 2, even more in patients who had also recently stopped their antihypertensive treatment.