Anglo-amerikanische Case-Management-Konzepte treffen aufgrund weitreichender Managementprobleme in der klinischen Versorgung vor allem chronisch kranker Patienten und einem zugleich wachsenden ...ökonomischen Druck bei Gesundheitspolitikern und Leistungsanbietern auch in Deutschland immer häufiger auf Interesse. Basierend auf einer umfassenden Literaturstudie sowie einer theoretischen Analyse und konzeptionellen Klärung wird die historische Entwicklung und aktuelle Anwendung der Methode in der klinischen Versorgung der USA nachgezeichnet. Dabei wird deutlich, wie sehr das Case Management durch die zunehmende Ökonomisierung in der Gefahr steht, seinen innovativen Charakter zu verlieren und auf die Funktion der Zugangs- und Ausgabenkontrolle reduziert zu werden. Angesichts dieser Erkenntnisse werden die Perspektiven für die Übertragung von Case Management auf das bundesdeutsche Gesundheitssystem abschließend kritisch beleuchtet. Due to dramatic problems in the management and delivery of health care services especially for people with chronic disease and increasing economic constraints German policy makers and service providers are particularly interested in Anglo-American case management concepts. Based upon literature survey, theoretical and conceptual review the historical development and comtemporary use of clinical case management in the USA will be described. This paper shows how much the innovative case management approach is affected by the economic restmction of the US health care system and therefore is in danger to be reduced to gatekeeping and cost containment roles. Perspectives for the implementation of Anglo-American case management concepts into the German health care system will be discussed critically.PUBLICATION ABSTRACT
Physostigmine and nefiracetam were tested alone and in combination in 104 rabbits with a mean age of 28 months conditioned in the 750
ms delay eyeblink classical conditioning procedure. In Experiment ...1, five doses of physostigmine (0.0005–0.2
mg/kg) enhanced conditioning. In Experiment 2, combinations of 10
mg/kg nefiracetam and 0.01, 0.1 and 0.2
mg/kg physostigmine improved the rate and magnitude of learning over rabbits treated with vehicle or 10
mg/kg nefiracetam alone. Brain AChE levels were significantly lower than vehicle for all doses of physostigmine and physostigmine plus nefiracetam. Control rabbits tested in the explicitly unpaired condition demonstrated that physostigmine alone and nefiracetam plus physostigmine had no non-associative effects. Physostigmine had a dramatic cognition-enhancing effect in older rabbits, and when nefiracetam was combined with physostigmine at a low dose, the ameliorating effect of physostigmine on learning was improved indicating that drug combinations for cognition enhancement may have therapeutic efficacy.
The familial early-onset form of Alzheimer's disease has been linked to mutations in genes encoding the amyloid precursor protein (APP), presenilin 1 (PS1) or presenilin 2. Transgenic mouse models ...expressing a single or a combination of these gene mutations develop Alzheimer-like amyloidogenic neuropathology. Here we investigate behavioral changes in the doubly transgenic mouse line carrying a c-DNA copy of the Swedish mutation of the human APP gene together with a mutation of the human PS1 gene (APP + PS1). The transgenic APP + PS1 mice show at about 12 months of age a peak level of compact plaques in cortical brain areas. To investigate changes in learning, 14 APP + PS1 and 17 wild-type mice were tested on eyeblink classical conditioning, a form of associative learning that has been shown to be impaired in patients with Alzheimer's disease. The mice were trained either on the 500 ms trace (for which the hippocampus and cerebellum are essential) or 500 ms delay (for which the cerebellum is essential) conditioning procedure. In addition, the startle response, prepulse inhibition and rotarod were assessed in the 12 month-old mice. Results showed that the APP + PS1 mice exhibited normal performance on delay and trace conditioning when compared to wild-type littermates across a training period of 15 daily sessions. Since both groups exhibited a training-dependent increase in short-latency/startle responses, we compared both groups on percentage of conditioned responses adjusted for short-latency responses. Consistent with findings on the unadjusted percentage of conditioned responses, no group differences were evident in the residualized percentage of conditioned responses. Both groups exhibited a comparable level of startle responses and prepulse inhibition across a range of stimulus intensities. However, the APP + PS1 mice showed an impaired performance on the rotarod, suggesting a deficit in motor coordination in the APP + PS1 mice. The normal performance of the APP + PSI mice on eyeblink conditioning suggests that no severe dysfunction of the medial temporal lobe and cerebellar structures are present in 12 month old APP + PS1 mice.
CONTEXT Elevated β-secretase (β-site amyloid precursor protein–cleaving enzyme 1 BACE1) activity has been found in the brains of patients with sporadic Alzheimer disease (AD) compared with controls. ...Now we are particularly interested in whether BACE1 can be identified in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI), a population at high risk for AD. The possible presence of BACE1 in the CSF of patients with AD and MCI has so far gone unreported. OBJECTIVE To examine whether BACE1 can be identified in the CSF of patients with MCI. DESIGN We evaluated CSF BACE1 levels using 2 sandwich enzyme-linked immunosorbent assays, BACE1 enzymatic activities by means of synthetic fluorescence substrate, and total amyloid-β peptide levels using a sandwich enzyme-linked immunosorbent assay. SETTING Two independent research centers. PARTICIPANTS Eighty patients with sporadic AD, 59 patients with MCI, and 69 controls. MAIN OUTCOME MEASURES BACE1 levels and enzymatic activities and amyloid-β peptide levels. RESULTS Increased CSF levels of BACE1 protein were associated with increased risk ratios (RRs) for patients with MCI compared with controls (RR, 2.08; 95% confidence interval CI, 1.58-2.58) and patients with AD (RR, 1.65; 95% CI, 1.19-2.03). Similarly, patients with MCI showed increased levels of BACE1 activity compared with controls (RR, 2.17; 95% CI, 1.66-2.71) and patients with AD (RR, 3.71; 95% CI, 2.74-4.36). For total amyloid-β peptide and tau, increased CSF levels were associated with a higher risk of MCI compared with controls. The BACE1 activity was significantly correlated with BACE1 protein level (ρ = 0.23; P<.001) and amyloid-β peptide level (ρ = 0.39; P<.001), with amyloid-β peptide correlated with BACE1 protein level (ρ = 0.30; P<.001). CONCLUSION Significant elevation of BACE1 levels and activity in CSF is an indicator of MCI, which could be an early stage of AD.Arch Gen Psychiatry. 2007;64:718-726-->
Background: Although convolutional neural networks (CNN) achieve high diagnostic accuracy for detecting Alzheimer's disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not ...yet applied in clinical routine. One important reason for this is a lack of model comprehensibility. Recently developed visualization methods for deriving CNN relevance maps may help to fill this gap. We investigated whether models with higher accuracy also rely more on discriminative brain regions predefined by prior knowledge. Methods: We trained a CNN for the detection of AD in N=663 T1-weighted MRI scans of patients with dementia and amnestic mild cognitive impairment (MCI) and verified the accuracy of the models via cross-validation and in three independent samples including N=1655 cases. We evaluated the association of relevance scores and hippocampus volume to validate the clinical utility of this approach. To improve model comprehensibility, we implemented an interactive visualization of 3D CNN relevance maps. Results: Across three independent datasets, group separation showed high accuracy for AD dementia vs. controls (AUC\(\geq\)0.92) and moderate accuracy for MCI vs. controls (AUC\(\approx\)0.75). Relevance maps indicated that hippocampal atrophy was considered as the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearson's r\(\approx\)-0.86, p<0.001). Conclusion: The relevance maps highlighted atrophy in regions that we had hypothesized a priori. This strengthens the comprehensibility of the CNN models, which were trained in a purely data-driven manner based on the scans and diagnosis labels.
The purpose of this article is to examine the current state of home care services for people living with HIV/AIDS and other seriously ill patients in Germany. It is based on a research project ...promoted by the Federal Ministry for Labor that aimed to investigate the possibilities and problems related to home care of the critically ill and thus establish basic scientific principles that could be used to close a health care gap that has long been of concern. The article will initially offer a brief explanation of the causes underlying the current problems in the field of home care for seriously ill patients. The authors then present the implications for nursing qualification that will have to be addressed to develop a patient-oriented, priority-level home nursing care program for people with HIV/AIDS in Germany.
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