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- Kivipelto, M, et al.
(author)
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Future of clinical trials
- 2011
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In: INTERNATIONAL PSYCHOGERIATRICS. - 1041-6102. ; 23, s. S1-S2
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Conference paper (other academic/artistic)
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- Mecocci, P, et al.
(author)
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Cognitive Impairment Is the Major Risk Factor for Development of Geriatric Syndromes during Hospitalization : Results from the GIFA Study
- 2005
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In: Dementia and Geriatric Cognitive Disorders. - Basel : Karger. - 1420-8008 .- 1421-9824. ; 20:4, s. 262-269
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Journal article (peer-reviewed)abstract
- Objective: To detect the main factors associated with the occurrence of specific geriatric syndromes (namely pressure sores, fecal incontinence, urinary incontinence and falls) in elderly patients during hospitalization. Design: Observational prospective study. Setting: Eighty-one community and university hospitals throughout Italy. Participants: 13,729 patients aged 65 years and more, consecutively admitted to medical or geriatric acute wards during 20 months in the period between 1991 and 1998. Measurements: Occurrence of pressure sores, fecal incontinence, urinary incontinence and falls during the stay in hospital. Results: Pressure sores were already present in 3% of hospitalized subjects, fecal incontinence in 7.3%, while urinary incontinence, evaluated on a subgroup of total population (4,268 subjects), had a prevalence of 22.3%. During hospitalization (mean stay of 15 days), 74 subjects developed new pressure sores, 55 became fecal and 35 urinary incontinent, and 279 subjects had at least one episode of fall. In multivariate analyses, cognitive impairment, advanced age (85+ years), length of stay (more than 3 weeks) and severe disability were the main independent predictors of development of the four geriatric syndromes, with cognitive impairment as the most significant risk factor for all the four outcomes (OR 4.9, 95% CI 2.4–9.9 for pressure sores; OR 6.3, 95% CI 3.0–13.0 for fecal incontinence; OR 5.3, 95% CI 2.3–12.0 for urinary incontinence; OR 1.6, 95% CI 1.2–2.3 for falls). Conclusion: Very old people have a significant increased risk of several geriatric syndromes during the stay in hospital, particularly if it is long and they are cognitively impaired. A standardized comprehensive geriatric evaluation at admission could be helpful in detecting all subjects at risk and preventing the development of hospital-acquired geriatric syndromes.
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- Schneider, L. S., et al.
(author)
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Clinical trials and late-stage drug development for Alzheimer's disease : an appraisal from 1984 to 2014
- 2014
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 275:3, s. 251-283
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Journal article (peer-reviewed)abstract
- The modern era of drug development for Alzheimer's disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer's disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here, we review the development of treatments for Alzheimer's disease during the past 30years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer's disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild-to-moderate Alzheimer's disease criteria, recently extending to early or prodromal Alzheimer disease or mild cognitive impairment due to Alzheimer's disease', for drugs considered to be disease modifying. The duration of trials has remained at 6-12months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities of daily living, global change and severity ratings have persisted as the primary clinically relevant outcomes. Regulatory guidance and oversight have evolved to allow for enrichment of early-stage Alzheimer's disease trial samples using biomarkers and phase-specific outcomes. In conclusion, validated drug targets for Alzheimer's disease remain to be developed. Only drugs that affect an aspect of cholinergic function have shown consistent, but modest, clinical effects in late-phase trials. There is opportunity for substantial improvements in drug discovery and clinical development methods.
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