Psychotropic medication use and cognition in institutionalized older adults with mild to moderate dementia

Background: Most studies examining psychotropic medication use on cognition in older persons with dementia include measures of global cognitive function. The present study examined the relationship between different types of psychotropic medication and specific cognitive functions in older people with dementia. Methods: Two hundred and six institutionalized older adults with dementia (180 women, mean age 85 years) were administered neuropsychological tests. Psychotropic medication use was extracted from their medical status and categorized as: sedatives, antidepressants and antipsychotics. Results: Analysis of covariance revealed that psychotropic consumers, and particularly those who used antipsychotics, performed worse on neuropsychological tests of executive/attentional functioning than non-consumers. There were no differences between consumers of other classes of psychotropic drugs and non-consumers. The number of psychotropic drugs used was inversely related to executive/attentional functioning. Conclusions: These findings show that in institutionalized older adults with dementia, specific impairment of cognitive function, i.e. executive/attentional impairments, are associated with antipsychotic medication use. Future longitudinal studies are recommended. © 2009 International Psychogeriatric Association

ESMO - Magnitude of Clinical Benefit Scale V.1.0 questions and answers

The ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a standardised, generic, validated tool to stratify the magnitude of clinical benefit that can be anticipated from anticancer therapies. The ESMO-MCBS is intended to both assist oncologists in explaining the likely benefits of a particular treatment to their patients as well as to aid public health decision makers' prioritise therapies for reimbursement. From its inception the ESMO-MCBS Working Group has invited questions and critiques to promote understanding and to address misunderstandings regarding the nuanced use of the scale, and to identify shortcomings in the scale to be addressed in future planned revisions and updates. The ESMO-MCBS V.1.0 has attracted many questions regarding its development, structure and potential applications. These questions, together with responses from the ESMO-MCBS Working Group, have been edited and collated, and are herein presented as a supplementary resource.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema

Brain oedema is a life-threatening complication of various neurological conditions. Understanding molecular mechanisms of brain volume regulation is critical for therapy development. Unique insight comes from monogenic diseases characterized by chronic brain oedema, of which megalencephalic leukoencephalopathy with subcortical cysts (MLC) is the prototype. Variants in MLC1 or GLIALCAM, encoding proteins involved in astrocyte volume regulation, are the main causes of MLC. In some patients, the genetic cause remains unknown. We performed genetic studies to identify novel gene variants in MLC patients, diagnosed by clinical and MRI features, without MLC1 or GLIALCAM variants. We determined subcellular localization of the related novel proteins in cells and in human brain tissue. We investigated functional consequences of the newly identified variants on volume regulation pathways using cell volume measurements, biochemical analysis and electrophysiology. We identified a novel homozygous variant in AQP4, encoding the water channel aquaporin-4, in two siblings, and two de novo heterozygous variants in GPRC5B, encoding the orphan G protein-coupled receptor GPRC5B, in three unrelated patients. The AQP4 variant disrupts membrane localization and thereby channel function. GPRC5B, like MLC1, GlialCAM and aquaporin-4, is expressed in astrocyte endfeet in human brain. Cell volume regulation is disrupted in GPRC5B patient-derived lymphoblasts. GPRC5B functionally interacts with ion channels involved in astrocyte volume regulation. In conclusion, we identify aquaporin-4 and GPRC5B as old and new players in genetic brain oedema. Our findings shed light on the protein complex involved in astrocyte volume regulation and identify GPRC5B as novel potentially druggable target for treating brain oedema

Embedding E-mail in primary schools: developing a tool for collective reflection

Reflection is an important aspect of learning in groups. In collective moments of reflection, learners can share and compare their ideas with others, and by doing so can reach an articulated and personal understanding of a learning task and domain. In the research presented here, e-mail is examined as a means for reflection in the context of group learning. In two design experiments, an e-mail tool is developed that seeks to (1) support collective reflection, and (2) overcome practical problems related to e-mail use in primary classrooms. Two prototypes of the tool are presented and tested in five primary classrooms. We conclude that e-mail supports collective reflection on a learning task after adding the following supportive measures to the regular e-mail program: (1) a fixed partnership, (2) fixed timing, (3) an exercise of individual freewriting, and (4) collective use of a paper worksheet

A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS)

The value of any new therapeutic strategy or treatment is determined by the magnitude of its clinical benefit balanced against its cost. Evidence for clinical benefit from new treatment options is derived from clinical research, in particular phase III randomised trials, which generate unbiased data regarding the efficacy, benefit and safety of new therapeutic approaches. To date, there is no standard tool for grading the magnitude of clinical benefit of cancer therapies, which may range from trivial (median progression-free survival advantage of only a few weeks) to substantial (improved longterm survival). Indeed, in the absence of a standardised approach for grading the magnitude of clinical benefit, conclusions and recommendations derived from studies are often hotly disputed and very modest incremental advances have often been presented, discussed and promoted as major advances or 'breakthroughs'. Recognising the importance of presenting clear and unbiased statements regarding the magnitude of the clinical benefit from new therapeutic approaches derived from high-quality clinical trials, the European Society for Medical Oncology (ESMO) has developed a validated and reproducible tool to assess the magnitude of clinical benefit for cancer medicines, the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). This tool uses a rational, structured and consistent approach to derive a relative ranking of the magnitude of clinically meaningful benefit that can be expected from a new anti-cancer treatment. The ESMO-MCBS is an important first step to the critical public policy issue of value in cancer care, helping to frame the appropriate use of limited public and personal resources to deliver cost-effective and affordable cancer care. The ESMO-MCBS will be a dynamic tool and its criteria will be revised on a regular basis. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved

A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).

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