Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease
Identifieur interne : 000105 ( Pmc/Checkpoint ); précédent : 000104; suivant : 000106Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease
Auteurs : Thuy Vu [États-Unis] ; John Nutt [États-Unis] ; Nicholas Holford [Nouvelle-Zélande]Source :
- British Journal of Clinical Pharmacology [ 0306-5251 ] ; 2012.
Abstract
To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables.
Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outcome events were obtained from 800 patients who initially had early Parkinson's disease. Parametric hazard models were used to describe the time to the events of interest.
Time course of disease status (severity) was an important predictor of clinical outcome events. There was an increased hazard ratio for death 1.4 (95% CI 1.31, 149), disability 2.75 (95% CI 2.30, 3.28), cognitive impairment 4.35 (95% CI 1.94, 9.74), and depressive state 1.43 (95% CI 1.26, 1.63) with each 10 unit increase of UPDRS. Age at study entry increased the hazard with hazard ratios of 49.1 (95% CI 8.7, 278) for death, 4.76 (95% CI 1.10, 20.6) for disability and 90.0 (95% CI 63.3–128) for cognitive impairment at age 60 years. Selegiline treatment had independent effects as a predictor of death at 8 year follow-up with a hazard ratio of 2.54 (95% CI 1.51, 4.25) but had beneficial effects on disability with a hazard ratio of 0.363 (95% CI 0.132, 0.533) and depression with a hazard ratio of 0.372 (95% CI 0.12, 0.552).
Our findings show that the time course of disease status based on UPDRS is a much better predictor of future clinical events than any baseline disease characteristic. Continued selegiline treatment appears to increase the hazard of death.
Url:
DOI: 10.1111/j.1365-2125.2012.04208.x
PubMed: 22300470
PubMed Central: 3630748
Affiliations:
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<author><name sortKey="Vu, Thuy C" sort="Vu, Thuy C" uniqKey="Vu T" first="Thuy" last="Vu">Thuy Vu</name>
<affiliation wicri:level="2"><nlm:aff id="au1">Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA</nlm:aff>
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<wicri:cityArea>Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks</wicri:cityArea>
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<author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John" last="Nutt">John Nutt</name>
<affiliation wicri:level="2"><nlm:aff id="au2">Department of Neurology, Oregon Health and Science University, Portland, OR, USA</nlm:aff>
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<author><name sortKey="Holford, Nicholas H G" sort="Holford, Nicholas H G" uniqKey="Holford N" first="Nicholas" last="Holford">Nicholas Holford</name>
<affiliation wicri:level="1"><nlm:aff id="au3">Department of Pharmacology and Clinical Pharmacology, University of Auckland, New Zealand</nlm:aff>
<country xml:lang="fr">Nouvelle-Zélande</country>
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<author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John" last="Nutt">John Nutt</name>
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<series><title level="j">British Journal of Clinical Pharmacology</title>
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<front><div type="abstract" xml:lang="en"><sec><title>AIM</title>
<p>To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables.</p>
</sec>
<sec><title>METHODS</title>
<p>Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outcome events were obtained from 800 patients who initially had early Parkinson's disease. Parametric hazard models were used to describe the time to the events of interest.</p>
</sec>
<sec><title>RESULTS</title>
<p>Time course of disease status (severity) was an important predictor of clinical outcome events. There was an increased hazard ratio for death 1.4 (95% CI 1.31, 149), disability 2.75 (95% CI 2.30, 3.28), cognitive impairment 4.35 (95% CI 1.94, 9.74), and depressive state 1.43 (95% CI 1.26, 1.63) with each 10 unit increase of UPDRS. Age at study entry increased the hazard with hazard ratios of 49.1 (95% CI 8.7, 278) for death, 4.76 (95% CI 1.10, 20.6) for disability and 90.0 (95% CI 63.3–128) for cognitive impairment at age 60 years. Selegiline treatment had independent effects as a predictor of death at 8 year follow-up with a hazard ratio of 2.54 (95% CI 1.51, 4.25) but had beneficial effects on disability with a hazard ratio of 0.363 (95% CI 0.132, 0.533) and depression with a hazard ratio of 0.372 (95% CI 0.12, 0.552).</p>
</sec>
<sec><title>CONCLUSIONS</title>
<p>Our findings show that the time course of disease status based on UPDRS is a much better predictor of future clinical events than any baseline disease characteristic. Continued selegiline treatment appears to increase the hazard of death.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Clin Pharmacol</journal-id>
<journal-id journal-id-type="iso-abbrev">Br J Clin Pharmacol</journal-id>
<journal-id journal-id-type="publisher-id">bcp</journal-id>
<journal-title-group><journal-title>British Journal of Clinical Pharmacology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0306-5251</issn>
<issn pub-type="epub">1365-2125</issn>
<publisher><publisher-name>Blackwell Publishing Ltd</publisher-name>
<publisher-loc>Oxford, UK</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22300470</article-id>
<article-id pub-id-type="pmc">3630748</article-id>
<article-id pub-id-type="doi">10.1111/j.1365-2125.2012.04208.x</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Treatment of Parkinson's disease</subject>
</subj-group>
</article-categories>
<title-group><article-title>Disease progress and response to treatment as predictors of survival, disability, cognitive impairment and depression in Parkinson's disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Vu</surname>
<given-names>Thuy C.</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nutt</surname>
<given-names>John G.</given-names>
</name>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Holford</surname>
<given-names>Nicholas H. G.</given-names>
</name>
<xref ref-type="aff" rid="au3">3</xref>
</contrib>
</contrib-group>
<aff id="au1"><label>1</label>
Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA</aff>
<aff id="au2"><label>2</label>
Department of Neurology, Oregon Health and Science University, Portland, OR, USA</aff>
<aff id="au3"><label>3</label>
Department of Pharmacology and Clinical Pharmacology, University of Auckland, New Zealand</aff>
<author-notes><corresp id="cor1">Professor Nick Holford MBChB FRACP, Department Pharmacology & Clinical Pharmacology, University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand. Tel.: +64 (9) 923 6730. Fax: +64 (9) 373 7090. E-mail: <email>n.holford@auckland.ac.nz</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><month>8</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>10</day>
<month>7</month>
<year>2012</year>
</pub-date>
<volume>74</volume>
<issue>2</issue>
<fpage>284</fpage>
<lpage>295</lpage>
<history><date date-type="received"><day>21</day>
<month>1</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>25</day>
<month>1</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2012 The British Pharmacological Society</copyright-statement>
<copyright-year>2012</copyright-year>
</permissions>
<abstract><sec><title>AIM</title>
<p>To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables.</p>
</sec>
<sec><title>METHODS</title>
<p>Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outcome events were obtained from 800 patients who initially had early Parkinson's disease. Parametric hazard models were used to describe the time to the events of interest.</p>
</sec>
<sec><title>RESULTS</title>
<p>Time course of disease status (severity) was an important predictor of clinical outcome events. There was an increased hazard ratio for death 1.4 (95% CI 1.31, 149), disability 2.75 (95% CI 2.30, 3.28), cognitive impairment 4.35 (95% CI 1.94, 9.74), and depressive state 1.43 (95% CI 1.26, 1.63) with each 10 unit increase of UPDRS. Age at study entry increased the hazard with hazard ratios of 49.1 (95% CI 8.7, 278) for death, 4.76 (95% CI 1.10, 20.6) for disability and 90.0 (95% CI 63.3–128) for cognitive impairment at age 60 years. Selegiline treatment had independent effects as a predictor of death at 8 year follow-up with a hazard ratio of 2.54 (95% CI 1.51, 4.25) but had beneficial effects on disability with a hazard ratio of 0.363 (95% CI 0.132, 0.533) and depression with a hazard ratio of 0.372 (95% CI 0.12, 0.552).</p>
</sec>
<sec><title>CONCLUSIONS</title>
<p>Our findings show that the time course of disease status based on UPDRS is a much better predictor of future clinical events than any baseline disease characteristic. Continued selegiline treatment appears to increase the hazard of death.</p>
</sec>
</abstract>
<kwd-group><kwd>disease progress</kwd>
<kwd>levodopa</kwd>
<kwd>Parkinson's disease</kwd>
<kwd>selegiline</kwd>
<kwd>time-dependent covariate</kwd>
<kwd>time to event</kwd>
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<affiliations><list><country><li>Nouvelle-Zélande</li>
<li>États-Unis</li>
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<region><li>Californie</li>
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<name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John" last="Nutt">John Nutt</name>
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<country name="Nouvelle-Zélande"><noRegion><name sortKey="Holford, Nicholas H G" sort="Holford, Nicholas H G" uniqKey="Holford N" first="Nicholas" last="Holford">Nicholas Holford</name>
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