Associations between Anticholinergic Burden and Adverse Health Outcomes in Parkinson Disease
Identifieur interne : 000153 ( Pmc/Curation ); précédent : 000152; suivant : 000154Associations between Anticholinergic Burden and Adverse Health Outcomes in Parkinson Disease
Auteurs : James A. G. Crispo [Canada, États-Unis] ; Allison W. Willis [États-Unis] ; Dylan P. Thibault [États-Unis] ; Yannick Fortin [Canada] ; Harlen D. Hays [États-Unis] ; Douglas S. Mcnair [États-Unis] ; Lise M. Bjerre [Canada] ; Dafna E. Kohen [Canada] ; Santiago Perez-Lloret [Argentine] ; Donald R. Mattison [Canada] ; Daniel Krewski [Canada]Source :
- PLoS ONE [ 1932-6203 ] ; 2016.
Abstract
Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population.
Using the Cerner Health Facts® database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits.
Many individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (≥4) were more likely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29–1.88) and delirium (AOR: 1.61, 95% CI: 1.08–2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10–1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01–1.33) within 30-days of discharge.
We found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD.
Url:
DOI: 10.1371/journal.pone.0150621
PubMed: 26939130
PubMed Central: 4777375
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Lamont Primary Health Care Research Centre, Department of Family Medicine, University of Ottawa, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>C. T. Lamont Primary Health Care Research Centre, Department of Family Medicine, University of Ottawa, Ottawa, Ontario</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Bruyère Research Institute, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Bruyère Research Institute, Ottawa, Ontario</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario</wicri:regionArea></affiliation></author><author><name sortKey="Kohen, Dafna E" sort="Kohen, Dafna E" uniqKey="Kohen D" first="Dafna E." last="Kohen">Dafna E. Kohen</name><affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario</wicri:regionArea></affiliation></author><author><name sortKey="Perez Lloret, Santiago" sort="Perez Lloret, Santiago" uniqKey="Perez Lloret S" first="Santiago" last="Perez-Lloret">Santiago Perez-Lloret</name><affiliation wicri:level="1"><nlm:aff id="aff010"><addr-line>Cardiology Research Institute, University of Buenos Aires, National Research Council (ININCA-UBA-CONICET), Buenos Aires, Argentina</addr-line></nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Cardiology Research Institute, University of Buenos Aires, National Research Council (ININCA-UBA-CONICET), Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Mattison, Donald R" sort="Mattison, Donald R" uniqKey="Mattison D" first="Donald R." last="Mattison">Donald R. 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G." last="Crispo">James A. G. Crispo</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Fulbright Canada Student, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Fulbright Canada Student, University of Pennsylvania, Philadelphia, Pennsylvania</wicri:regionArea></affiliation></author><author><name sortKey="Willis, Allison W" sort="Willis, Allison W" uniqKey="Willis A" first="Allison W." last="Willis">Allison W. Willis</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania</wicri:regionArea></affiliation></author><author><name sortKey="Thibault, Dylan P" sort="Thibault, Dylan P" uniqKey="Thibault D" first="Dylan P." last="Thibault">Dylan P. Thibault</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania</wicri:regionArea></affiliation></author><author><name sortKey="Fortin, Yannick" sort="Fortin, Yannick" uniqKey="Fortin Y" first="Yannick" last="Fortin">Yannick Fortin</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario</wicri:regionArea></affiliation></author><author><name sortKey="Hays, Harlen D" sort="Hays, Harlen D" uniqKey="Hays H" first="Harlen D." last="Hays">Harlen D. Hays</name><affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Cerner Corporation, Kansas City, Missouri, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cerner Corporation, Kansas City, Missouri</wicri:regionArea></affiliation></author><author><name sortKey="Mcnair, Douglas S" sort="Mcnair, Douglas S" uniqKey="Mcnair D" first="Douglas S." last="Mcnair">Douglas S. Mcnair</name><affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Cerner Corporation, Kansas City, Missouri, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Cerner Corporation, Kansas City, Missouri</wicri:regionArea></affiliation></author><author><name sortKey="Bjerre, Lise M" sort="Bjerre, Lise M" uniqKey="Bjerre L" first="Lise M." last="Bjerre">Lise M. Bjerre</name><affiliation wicri:level="1"><nlm:aff id="aff007"><addr-line>C. T. Lamont Primary Health Care Research Centre, Department of Family Medicine, University of Ottawa, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>C. T. Lamont Primary Health Care Research Centre, Department of Family Medicine, University of Ottawa, Ottawa, Ontario</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff008"><addr-line>Bruyère Research Institute, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Bruyère Research Institute, Ottawa, Ontario</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario</wicri:regionArea></affiliation></author><author><name sortKey="Kohen, Dafna E" sort="Kohen, Dafna E" uniqKey="Kohen D" first="Dafna E." last="Kohen">Dafna E. Kohen</name><affiliation wicri:level="1"><nlm:aff id="aff009"><addr-line>School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario</wicri:regionArea></affiliation></author><author><name sortKey="Perez Lloret, Santiago" sort="Perez Lloret, Santiago" uniqKey="Perez Lloret S" first="Santiago" last="Perez-Lloret">Santiago Perez-Lloret</name><affiliation wicri:level="1"><nlm:aff id="aff010"><addr-line>Cardiology Research Institute, University of Buenos Aires, National Research Council (ININCA-UBA-CONICET), Buenos Aires, Argentina</addr-line></nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Cardiology Research Institute, University of Buenos Aires, National Research Council (ININCA-UBA-CONICET), Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Mattison, Donald R" sort="Mattison, Donald R" uniqKey="Mattison D" first="Donald R." last="Mattison">Donald R. Mattison</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff011"><addr-line>Risk Sciences International, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Risk Sciences International, Ottawa, Ontario</wicri:regionArea></affiliation></author><author><name sortKey="Krewski, Daniel" sort="Krewski, Daniel" uniqKey="Krewski D" first="Daniel" last="Krewski">Daniel Krewski</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff011"><addr-line>Risk Sciences International, Ottawa, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Risk Sciences International, Ottawa, Ontario</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="sec001"><title>Background</title><p>Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population.</p></sec><sec id="sec002"><title>Methods</title><p>Using the Cerner Health Facts® database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits.</p></sec><sec id="sec003"><title>Results</title><p>Many individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (≥4) were more likely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29–1.88) and delirium (AOR: 1.61, 95% CI: 1.08–2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10–1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01–1.33) within 30-days of discharge.</p></sec><sec id="sec004"><title>Conclusions</title><p>We found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Gerretsen, P" uniqKey="Gerretsen P">P Gerretsen</name></author><author><name sortKey="Pollock, Bg" uniqKey="Pollock B">BG Pollock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sura, Sd" uniqKey="Sura S">SD Sura</name></author><author><name sortKey="Carnahan, Rm" uniqKey="Carnahan R">RM Carnahan</name></author><author><name sortKey="Chen, H" uniqKey="Chen H">H Chen</name></author><author><name sortKey="Aparasu, Rr" uniqKey="Aparasu R">RR Aparasu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tune, Le" uniqKey="Tune L">LE Tune</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aizenberg, D" uniqKey="Aizenberg D">D 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26939130</article-id><article-id pub-id-type="pmc">4777375</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0150621</article-id><article-id pub-id-type="publisher-id">PONE-D-15-53336</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Health Care</subject><subj-group><subject>Patients</subject><subj-group><subject>Inpatients</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Neuroscience</subject><subj-group><subject>Cognitive Science</subject><subj-group><subject>Cognitive Neuroscience</subject><subj-group><subject>Cognitive Neurology</subject><subj-group><subject>Cognitive Impairment</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Neuroscience</subject><subj-group><subject>Cognitive Neuroscience</subject><subj-group><subject>Cognitive Neurology</subject><subj-group><subject>Cognitive Impairment</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Neurology</subject><subj-group><subject>Cognitive Neurology</subject><subj-group><subject>Cognitive Impairment</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>People and Places</subject><subj-group><subject>Population Groupings</subject><subj-group><subject>Age Groups</subject><subj-group><subject>Elderly</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Neurology</subject><subj-group><subject>Neurodegenerative Diseases</subject><subj-group><subject>Movement Disorders</subject><subj-group><subject>Parkinson Disease</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Geriatrics</subject></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Health Care</subject><subj-group><subject>Health Care Facilities</subject><subj-group><subject>Hospitals</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject><subj-group><subject>Research Design</subject><subj-group><subject>Clinical Research Design</subject><subj-group><subject>Adverse Events</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Health Care</subject><subj-group><subject>Patients</subject><subj-group><subject>Outpatients</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Associations between Anticholinergic Burden and Adverse Health Outcomes in Parkinson Disease</article-title><alt-title alt-title-type="running-head">Anticholinergic Burden and Adverse Outcomes in Parkinson Disease</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Crispo</surname><given-names>James A. G.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib><contrib contrib-type="author"><name><surname>Willis</surname><given-names>Allison W.</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref><xref ref-type="aff" rid="aff004"><sup>4</sup></xref><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Thibault</surname><given-names>Dylan P.</given-names></name><xref ref-type="aff" rid="aff003"><sup>3</sup></xref><xref ref-type="aff" rid="aff004"><sup>4</sup></xref><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fortin</surname><given-names>Yannick</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hays</surname><given-names>Harlen D.</given-names></name><xref ref-type="aff" rid="aff006"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>McNair</surname><given-names>Douglas S.</given-names></name><xref ref-type="aff" rid="aff006"><sup>6</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bjerre</surname><given-names>Lise M.</given-names></name><xref ref-type="aff" rid="aff007"><sup>7</sup></xref><xref ref-type="aff" rid="aff008"><sup>8</sup></xref><xref ref-type="aff" rid="aff009"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kohen</surname><given-names>Dafna E.</given-names></name><xref ref-type="aff" rid="aff009"><sup>9</sup></xref></contrib><contrib contrib-type="author"><name><surname>Perez-Lloret</surname><given-names>Santiago</given-names></name><xref ref-type="aff" rid="aff010"><sup>10</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mattison</surname><given-names>Donald R.</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff011"><sup>11</sup></xref></contrib><contrib contrib-type="author"><name><surname>Krewski</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff011"><sup>11</sup></xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Fulbright Canada Student, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America</addr-line></aff><aff id="aff005"><label>5</label><addr-line>Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America</addr-line></aff><aff id="aff006"><label>6</label><addr-line>Cerner Corporation, Kansas City, Missouri, United States of America</addr-line></aff><aff id="aff007"><label>7</label><addr-line>C. T. Lamont Primary Health Care Research Centre, Department of Family Medicine, University of Ottawa, Ottawa, Ontario, Canada</addr-line></aff><aff id="aff008"><label>8</label><addr-line>Bruyère Research Institute, Ottawa, Ontario, Canada</addr-line></aff><aff id="aff009"><label>9</label><addr-line>School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada</addr-line></aff><aff id="aff010"><label>10</label><addr-line>Cardiology Research Institute, University of Buenos Aires, National Research Council (ININCA-UBA-CONICET), Buenos Aires, Argentina</addr-line></aff><aff id="aff011"><label>11</label><addr-line>Risk Sciences International, Ottawa, Ontario, Canada</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Marengoni</surname><given-names>Alessandra</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Brescia, ITALY</addr-line></aff><author-notes><fn fn-type="conflict" id="coi001"><p><bold>Competing Interests: </bold>Mr. Crispo, Dr. Willis, Mr. Thibault, Mr. Fortin, Dr. Bjerre, and Dr. Kohen report no disclosures. Dr. McNair and Mr. Hays are employed by the Cerner Corporation. Dr. Perez-Lloret served as a consultant for Aguettant Laboratories in 2014. Drs. Mattison and Krewski serve as Chief Medical Officer and Chief Risk Scientist of Risk Sciences International, a Canadian company formed in partnership with the University of Ottawa in 2006 (<ext-link ext-link-type="uri" xlink:href="http://www.risksciences.com">www.risksciences.com</ext-link>) that conducts risk assessment work for public and private sector clients in Canada and internationally. To date, RSI has not conducted work on the subject of the present research paper. Dr. Krewski holds a Natural Sciences and Engineering Council of Canada (NSERC) Industrial Research Chair in Risk Science, through a peer-reviewed university-industry partnerships program administered by NSERC. None of the industrial partners in this program are from the pharmaceutical industry. Commercial affiliation with the Cerner Corporation and Risk Sciences International does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.</p></fn><fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: JAGC AWW LMB DEK DRM DK. Performed the experiments: JAGC DPT YF. Analyzed the data: JAGC AWW DPT YF HDH DSM LMB DEK SPL DRM DK. Wrote the paper: JAGC AWW. Edited the manuscript: JAGC AWW DPT YF HDH DSM LMB DEK SPL DRM DK.</p></fn><corresp id="cor001">* E-mail: <email>jcris021@uottawa.ca</email></corresp></author-notes><pub-date pub-type="epub"><day>3</day><month>3</month><year>2016</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>11</volume><issue>3</issue><elocation-id>e0150621</elocation-id><history><date date-type="received"><day>9</day><month>12</month><year>2015</year></date><date date-type="accepted"><day>17</day><month>2</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 Crispo et al</copyright-statement><copyright-year>2016</copyright-year><copyright-holder>Crispo et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:type="simple" xlink:href="pone.0150621.pdf"></self-uri><abstract><sec id="sec001"><title>Background</title><p>Elderly adults should avoid medications with anticholinergic effects since they may increase the risk of adverse events, including falls, delirium, and cognitive impairment. However, data on anticholinergic burden are limited in subpopulations, such as individuals with Parkinson disease (PD). The objective of this study was to determine whether anticholinergic burden was associated with adverse outcomes in a PD inpatient population.</p></sec><sec id="sec002"><title>Methods</title><p>Using the Cerner Health Facts® database, we retrospectively examined anticholinergic medication use, diagnoses, and hospital revisits within a cohort of 16,302 PD inpatients admitted to a Cerner hospital between 2000 and 2011. Anticholinergic burden was computed using the Anticholinergic Risk Scale (ARS). Primary outcomes were associations between ARS score and diagnosis of fracture and delirium. Secondary outcomes included associations between ARS score and 30-day hospital revisits.</p></sec><sec id="sec003"><title>Results</title><p>Many individuals (57.8%) were prescribed non-PD medications with moderate to very strong anticholinergic potential. Individuals with the greatest ARS score (≥4) were more likely to be diagnosed with fractures (adjusted odds ratio (AOR): 1.56, 95% CI: 1.29–1.88) and delirium (AOR: 1.61, 95% CI: 1.08–2.40) relative to those with no anticholinergic burden. Similarly, inpatients with the greatest ARS score were more likely to visit the emergency department (adjusted hazard ratio (AHR): 1.32, 95% CI: 1.10–1.58) and be readmitted (AHR: 1.16, 95% CI: 1.01–1.33) within 30-days of discharge.</p></sec><sec id="sec004"><title>Conclusions</title><p>We found a positive association between increased anticholinergic burden and adverse outcomes among individuals with PD. Additional pharmacovigilance studies are needed to better understand risks associated with anticholinergic medication use in PD.</p></sec></abstract><funding-group><funding-statement>This study was supported by the Canadian Institutes of Health Research (DRA 201210—PA: Drug Safety and Effectiveness; <ext-link ext-link-type="uri" xlink:href="http://www.cihr-irsc.gc.ca">www.cihr-irsc.gc.ca</ext-link>), Fulbright Canada (<ext-link ext-link-type="uri" xlink:href="http://www.fulbright.ca">www.fulbright.ca</ext-link>), the McLaughlin Centre for Population Health Risk Assessment (<ext-link ext-link-type="uri" xlink:href="http://www.mclaughlincentre.ca">www.mclaughlincentre.ca</ext-link>), the Cerner Corporation (<ext-link ext-link-type="uri" xlink:href="http://www.cerner.com">http://www.cerner.com</ext-link>), and Risk Sciences International (<ext-link ext-link-type="uri" xlink:href="http://www.risksciences.com">www.risksciences.com</ext-link>). The Cerner Corporation and Risk Sciences International are commercial companies. The funders provided support in the form of salaries for authors [JAGC, YF, HDH, DSM, and DRM], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.</funding-statement></funding-group><counts><fig-count count="0"></fig-count><table-count count="4"></table-count><page-count count="15"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are available from the uO Research repository at the University of Ottawa: <ext-link ext-link-type="uri" xlink:href="http://hdl.handle.net/10393/34297">http://hdl.handle.net/10393/34297</ext-link>.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are available from the uO Research repository at the University of Ottawa: <ext-link ext-link-type="uri" xlink:href="http://hdl.handle.net/10393/34297">http://hdl.handle.net/10393/34297</ext-link>.</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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