The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer’s disease (AD).We searched 5 databases from their inception to January 2010.Five randomized...The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer’s disease (AD).We searched 5 databases from their inception to January 2010.Five randomized clinical trials of mood stabilizers to treat human patients suffering from AD were included.These trials assessed the effectiveness of mood stabilizers as an adjunct treatment to conventional anti-dementia drugs on behavioral and psychological symptoms, especially on agitation.Methodological quality was assessed using the Jadad score.The results suggested a significant effect in favor of placebo on the Mini-Mental Status Examination [n=270, weight mean difference (WMD), -0.89; 95% confidence intervals (CIs) -1.69 to -0.09, P=0.03] and on the Neuropsychiatric Inventory total (NPI total) (n=51, WMD, 3.71; 95% CIs 0.15 to 7.26, P=0.04).There were no significant differences in change scores on total Brief Psychiatric Rating Scale (BPRS total), NPI/BPRS agitation, Cohen-Mansfield Agitation Inventory total and Physical Self Maintenance Scale between mood stabilizers and placebo.Only one of these studies was free of methodological limittions (Jadad score=5).In conclusion, based on the existing evidence, mood stabilizers are ineffective or even harmful as a treatment for AD.展开更多
In this article, the present author, a research psychologist and measurement expert, evaluates the major clinical trials used to support the use of aripiprazole and the chemically almost identical cariprazine for trea...In this article, the present author, a research psychologist and measurement expert, evaluates the major clinical trials used to support the use of aripiprazole and the chemically almost identical cariprazine for treating bipolar disorder. The main problem with the trials is that they were conducted mainly with outpatients, who on average were only moderately manic in the mania studies and only moderately depressed in the depression studies. The effectiveness of aripiprazole and cariprazine in treating moderate mania, most likely hypomania, and moderate depression, was far from encouraging. Aripiprazole produced just 7% greater reduction of mania symptoms than did placebo treatment, and just 1% greater reduction of depression symptoms than did placebo treatment when administered, as is common practice, with an SSRI or SNRI antidepressant. Cariprazine proved to be not much better because at the high dosage level of 3.0 mg/day to 12.0 mg/day, cariprazine produced only 9% greater reduction of mania symptoms than did placebo treatment, and at the typical low dosage of 1.5 to 3.0 mg/day produced just 4% greater reduction of depression symptoms than did placebo treatment. Moreover, as the pharmaceutical industry has long suspected, there is a massive placebo effect associated with these two drugs, especially for depression. These findings imply that government regulatory authorities’ approval of aripiprazole and cariprazine as mood stabilizers for treating bipolar disorder is dubious. Nevertheless, the possibility remains that the purported mood-stabilizing mechanism of these two medicines is activated only with patients presently experiencing severe mania or severe depression, a possibility that requires an in-hospital clinical trial or, at the very least, a longitudinal analysis of bipolar patients’ treatment records. Furthermore, an appendix to the present article demonstrates that the measures used in the trials, the Young Mania Rating Scale and the Montgomery-Asberg Depression Rating Scale, are deficient and that a briefer combination measure focusing only on the core symptoms of bipolar disorder should be used.展开更多
In this paper we present a 2D/3D high order accurate finite volume scheme in the context of direct Arbitrary-Lagrangian-Eulerian algorithms for general hyperbolic systems of partial differential equations with non-con...In this paper we present a 2D/3D high order accurate finite volume scheme in the context of direct Arbitrary-Lagrangian-Eulerian algorithms for general hyperbolic systems of partial differential equations with non-conservative products and stiff source terms.This scheme is constructed with a single stencil polynomial reconstruction operator,a one-step space-time ADER integration which is suitably designed for dealing even with stiff sources,a nodal solver with relaxation to determine the mesh motion,a path-conservative integration technique for the treatment of non-conservative products and an a posteriori stabilization procedure derived from the so-called Multidimensional Optimal Order Detection(MOOD)paradigm.In this work we consider the seven equation Baer-Nunziato model of compressible multi-phase flows as a representative model involving non-conservative products as well as relaxation source terms which are allowed to become stiff.The new scheme is validated against a set of test cases on 2D/3D unstructured moving meshes on parallel machines and the high order of accuracy achieved by the method is demonstrated by performing a numerical convergence study.Classical Riemann problems and explosion problems with exact solutions are simulated in 2D and 3D.The overall numerical code is also profiled to provide an estimate of the computational cost required by each component of the whole algorithm.展开更多
基金supported by a grant from the Wuhan Bureau of Science and Technology, Hubei,China (No.200960-323132)
文摘The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer’s disease (AD).We searched 5 databases from their inception to January 2010.Five randomized clinical trials of mood stabilizers to treat human patients suffering from AD were included.These trials assessed the effectiveness of mood stabilizers as an adjunct treatment to conventional anti-dementia drugs on behavioral and psychological symptoms, especially on agitation.Methodological quality was assessed using the Jadad score.The results suggested a significant effect in favor of placebo on the Mini-Mental Status Examination [n=270, weight mean difference (WMD), -0.89; 95% confidence intervals (CIs) -1.69 to -0.09, P=0.03] and on the Neuropsychiatric Inventory total (NPI total) (n=51, WMD, 3.71; 95% CIs 0.15 to 7.26, P=0.04).There were no significant differences in change scores on total Brief Psychiatric Rating Scale (BPRS total), NPI/BPRS agitation, Cohen-Mansfield Agitation Inventory total and Physical Self Maintenance Scale between mood stabilizers and placebo.Only one of these studies was free of methodological limittions (Jadad score=5).In conclusion, based on the existing evidence, mood stabilizers are ineffective or even harmful as a treatment for AD.
文摘In this article, the present author, a research psychologist and measurement expert, evaluates the major clinical trials used to support the use of aripiprazole and the chemically almost identical cariprazine for treating bipolar disorder. The main problem with the trials is that they were conducted mainly with outpatients, who on average were only moderately manic in the mania studies and only moderately depressed in the depression studies. The effectiveness of aripiprazole and cariprazine in treating moderate mania, most likely hypomania, and moderate depression, was far from encouraging. Aripiprazole produced just 7% greater reduction of mania symptoms than did placebo treatment, and just 1% greater reduction of depression symptoms than did placebo treatment when administered, as is common practice, with an SSRI or SNRI antidepressant. Cariprazine proved to be not much better because at the high dosage level of 3.0 mg/day to 12.0 mg/day, cariprazine produced only 9% greater reduction of mania symptoms than did placebo treatment, and at the typical low dosage of 1.5 to 3.0 mg/day produced just 4% greater reduction of depression symptoms than did placebo treatment. Moreover, as the pharmaceutical industry has long suspected, there is a massive placebo effect associated with these two drugs, especially for depression. These findings imply that government regulatory authorities’ approval of aripiprazole and cariprazine as mood stabilizers for treating bipolar disorder is dubious. Nevertheless, the possibility remains that the purported mood-stabilizing mechanism of these two medicines is activated only with patients presently experiencing severe mania or severe depression, a possibility that requires an in-hospital clinical trial or, at the very least, a longitudinal analysis of bipolar patients’ treatment records. Furthermore, an appendix to the present article demonstrates that the measures used in the trials, the Young Mania Rating Scale and the Montgomery-Asberg Depression Rating Scale, are deficient and that a briefer combination measure focusing only on the core symptoms of bipolar disorder should be used.
基金W.B.has been financed by the European Research Council(ERC)under the European Union’s Seventh Framework Programme(FP7/2007-2013)with the research project STiMulUs,ERC Grant agreement no.278267R.L.has been partially funded by the ANR under the JCJC project“ALE INC(ubator)3D”JS01-012-01the“International Centre for Mathematics and Computer Science in Toulouse”(CIMI)partially supported by ANR-11-LABX-0040-CIMI within the program ANR-11-IDEX-0002-02.The authors would like to acknowledge PRACE for awarding access to the SuperMUC supercomputer based in Munich,Germany at the Leibniz Rechenzentrum(LRZ).Parts of thematerial contained in this work have been elaborated,gathered and tested while W.B.visited the Mathematical Institute of Toulouse for three months and R.L.visited the Dipartimento di Ingegneria Civile Ambientale e Meccanica in Trento for three months.
文摘In this paper we present a 2D/3D high order accurate finite volume scheme in the context of direct Arbitrary-Lagrangian-Eulerian algorithms for general hyperbolic systems of partial differential equations with non-conservative products and stiff source terms.This scheme is constructed with a single stencil polynomial reconstruction operator,a one-step space-time ADER integration which is suitably designed for dealing even with stiff sources,a nodal solver with relaxation to determine the mesh motion,a path-conservative integration technique for the treatment of non-conservative products and an a posteriori stabilization procedure derived from the so-called Multidimensional Optimal Order Detection(MOOD)paradigm.In this work we consider the seven equation Baer-Nunziato model of compressible multi-phase flows as a representative model involving non-conservative products as well as relaxation source terms which are allowed to become stiff.The new scheme is validated against a set of test cases on 2D/3D unstructured moving meshes on parallel machines and the high order of accuracy achieved by the method is demonstrated by performing a numerical convergence study.Classical Riemann problems and explosion problems with exact solutions are simulated in 2D and 3D.The overall numerical code is also profiled to provide an estimate of the computational cost required by each component of the whole algorithm.
