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Implementing frailty into clinical practice: a cautionary tale.

ABSTRACT: Little is known about the contribution of frailty in improving patient-level prediction beyond readily available clinical information. The objective of this study is to compare the predictive ability of 129 combinations of seven frailty markers (cognition, energy, mobility, mood, nutrition, physical activity, and strength) and quantify their contribution to predictive accuracy beyond age, sex, and number of chronic diseases.Two cohorts from the Established Populations for Epidemiologic Studies of the Elderly were used. The model with the best predictive fit in predicting 6-year incidence of disability was determined using the Akaike Information Criterion. Predictive accuracy was measured by the C statistic.Incident disability was 23% in one cohort and 20% in the other cohort. The "best model" in each cohort was found to be a model including between five and seven frailty markers including cognition, mobility, nutrition, physical activity, and strength. Predictive accuracy of the 129 models ranged from 0.73 to 0.77 across both cohorts. Adding frailty markers to age, sex, and chronic disease increased predictive accuracy by up to 3% in both cohorts (p < .001). The contribution of frailty increased up to 9% in the oldest age group.Adding frailty markers provided a modest increase in patient-level prediction of disability. Such a modest increase may still be worthwhile because while age, sex, and the number of chronic diseases are not modifiable, frailty may be. Further studies examining the contribution of frailty in improving prediction are needed before adopting frailty as a prognostic tool.

SUBMITTER: Sourial N

PROVIDER: S-EPMC3806754 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Implementing frailty into clinical practice: a cautionary tale.

Sourial Nadia N Bergman Howard H Karunananthan Sathya S Wolfson Christina C Payette Hélène H Gutierrez-Robledo Luis Miguel LM Béland François F Fletcher John D JD Guralnik Jack J

The journals of gerontology. Series A, Biological sciences and medical sciences 20130502 12

<h4>Background</h4>Little is known about the contribution of frailty in improving patient-level prediction beyond readily available clinical information. The objective of this study is to compare the predictive ability of 129 combinations of seven frailty markers (cognition, energy, mobility, mood, nutrition, physical activity, and strength) and quantify their contribution to predictive accuracy beyond age, sex, and number of chronic diseases.<h4>Methods</h4>Two cohorts from the Established Popu ...[more]

PMID: 23640761

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Project description:FURIN is a pro-protein convertase previously shown to be important for placental syncytialisation (Zhou et al. [1]), a process of cell fusion whereby placental cytotrophoblast cells fuse to form a multinucleated syncytium. This finding has been broadly accepted however, we have evidence suggesting the contrary. Spontaneously syncytialising term primary human trophoblast cells and BeWo choriocarcinoma cells were treated with either FURIN siRNA or negative control siRNA or the protease inhibitor, DEC-RVKR-CMK, or vehicle. Cells were then left to either spontaneously syncytialise (primary trophoblasts) or were induced to syncytialise with forskolin (BeWo). Effects on syncytialisation were measured by determining human chorionic gonadotrophin secretion and E-cadherin protein levels. We showed that FURIN is not important for syncytialisation in either cell type. However, in primary trophoblasts another protease also inhibited by DEC-RVKR-CMK, may be involved. Our results directly contrast with those published by Zhou et al. Zhou et al. however, used first trimester villous explants to study syncytialisation, and we used term primary trophoblasts. Therefore, we suggest that FURIN may be involved in syncytialisation of first trimester trophoblasts, but not term trophoblasts. What is more concerning is that our results using BeWo cells do not agree with their results, even though for the most part, we used the same experimental design. It is unclear why these experiments yielded different results, however we wanted to draw attention to simple differences in measuring syncytialisation or flaws in method reporting (including omission of cell line source and passage numbers, siRNA concentration and protein molecular weights) and choice of immunoblot loading controls, that could impact on experimental outcomes. Our study shows that careful reporting of methods by authors and thorough scrutiny by referees are vital. Furthermore, a universal benchmark for measuring syncytialisation is required so that various studies of syncytialisation can be validated.

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Implementing frailty into clinical practice: a cautionary tale.

Publications

Implementing frailty into clinical practice: a cautionary tale.

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