Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.
Identifieur interne : 002468 ( PubMed/Corpus ); précédent : 002467; suivant : 002469Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.
Auteurs : Ruth Keogh ; Chris Frost ; Gail Owen ; Rhian M. Daniel ; Doug R. Langbehn ; Blair Leavitt ; Alexandra Durr ; Raymund A C. Roos ; G Bernhard Landwehrmeyer ; Ralf Reilmann ; Beth Borowsky ; Julie Stout ; David Craufurd ; Sarah J. TabriziSource :
- PLoS currents [ 2157-3999 ] ; 2016.
Abstract
Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.
DOI: 10.1371/currents.hd.8060298fac1801b01ccea6acc00f97cb
PubMed: 26819833
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Tabrizi</name><affiliation><nlm:affiliation>Neurodegenerative Disease, UCL Institute of Neurology, London, UK.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:26819833</idno><idno type="pmid">26819833</idno><idno type="doi">10.1371/currents.hd.8060298fac1801b01ccea6acc00f97cb</idno><idno type="wicri:Area/PubMed/Corpus">002468</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002468</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.</title><author><name sortKey="Keogh, Ruth" sort="Keogh, Ruth" uniqKey="Keogh R" first="Ruth" last="Keogh">Ruth Keogh</name><affiliation><nlm:affiliation>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Frost, Chris" sort="Frost, Chris" uniqKey="Frost C" first="Chris" last="Frost">Chris Frost</name><affiliation><nlm:affiliation>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Owen, Gail" sort="Owen, Gail" uniqKey="Owen G" first="Gail" last="Owen">Gail Owen</name><affiliation><nlm:affiliation>UCL Institute of Neurology, University College London, Queen Square, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Daniel, Rhian M" sort="Daniel, Rhian M" uniqKey="Daniel R" first="Rhian M" last="Daniel">Rhian M. Daniel</name><affiliation><nlm:affiliation>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Langbehn, Doug R" sort="Langbehn, Doug R" uniqKey="Langbehn D" first="Doug R" last="Langbehn">Doug R. Langbehn</name><affiliation><nlm:affiliation>Psychiatry, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Leavitt, Blair" sort="Leavitt, Blair" uniqKey="Leavitt B" first="Blair" last="Leavitt">Blair Leavitt</name><affiliation><nlm:affiliation>Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name><affiliation><nlm:affiliation>Genetics, APHP- Groupe Hospitalier Pitié-Salpêtrière, Paris, France; INSERM U1127, CNRS UMR7225, UPMC University Paris VI UMR_S1127, Institut du Cerveau et de la Moelle, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Roos, Raymund A C" sort="Roos, Raymund A C" uniqKey="Roos R" first="Raymund A C" last="Roos">Raymund A C. Roos</name><affiliation><nlm:affiliation>Neurology, Leiden University Medical Centre, Leiden, Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Landwehrmeyer, G Bernhard" sort="Landwehrmeyer, G Bernhard" uniqKey="Landwehrmeyer G" first="G Bernhard" last="Landwehrmeyer">G Bernhard Landwehrmeyer</name><affiliation><nlm:affiliation>Neurology, Ulm University, Ulm, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Reilmann, Ralf" sort="Reilmann, Ralf" uniqKey="Reilmann R" first="Ralf" last="Reilmann">Ralf Reilmann</name><affiliation><nlm:affiliation>George-Huntington-Institute, Neurology, University of Münster, Münster, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Borowsky, Beth" sort="Borowsky, Beth" uniqKey="Borowsky B" first="Beth" last="Borowsky">Beth Borowsky</name><affiliation><nlm:affiliation>CHDI Management/CHDI Foundation, Princeton, NJ, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Stout, Julie" sort="Stout, Julie" uniqKey="Stout J" first="Julie" last="Stout">Julie Stout</name><affiliation><nlm:affiliation>School of Psychological Sciences, Monash University, VIC, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Craufurd, David" sort="Craufurd, David" uniqKey="Craufurd D" first="David" last="Craufurd">David Craufurd</name><affiliation><nlm:affiliation>Institute of Human Development, University of Manchester; Manchester Academic Health Science Centre; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J" last="Tabrizi">Sarah J. Tabrizi</name><affiliation><nlm:affiliation>Neurodegenerative Disease, UCL Institute of Neurology, London, UK.</nlm:affiliation></affiliation></author></analytic><series><title level="j">PLoS currents</title><idno type="eISSN">2157-3999</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"> Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">26819833</PMID><DateCreated><Year>2016</Year><Month>01</Month><Day>28</Day></DateCreated><DateCompleted><Year>2016</Year><Month>01</Month><Day>28</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>22</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2157-3999</ISSN><JournalIssue CitedMedium="Internet"><Volume>8</Volume><PubDate><Year>2016</Year><Month>Jan</Month><Day>11</Day></PubDate></JournalIssue><Title>PLoS currents</Title><ISOAbbreviation>PLoS Curr</ISOAbbreviation></Journal><ArticleTitle>Medication Use in Early-HD Participants in Track-HD: an Investigation of its Effects on Clinical Performance.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1371/currents.hd.8060298fac1801b01ccea6acc00f97cb</ELocationID><ELocationID EIdType="pii" ValidYN="Y">ecurrents.hd.8060298fac1801b01ccea6acc00f97cb</ELocationID><Abstract><AbstractText> Insufficient evidence exists to guide the long-term pharmacological management of Huntington's disease (HD) although most current interventions rely on symptomatic management. The effect of many frontline treatments on potential endpoints for HD clinical trials remains unknown. Our objective was to investigate how therapies widely used to manage HD affect the symptom for which they are prescribed and other endpoints using data from TRACK-HD. We used longitudinal models to estimate effects of medication use on performance on tests of motor, cognitive and neuropsychiatric function using data from 123 TRACK-HD stage 1/2 participants across four study visits. Adjustment for confounding by prior medication use, prior clinical performance, concomitant use of other medications, and baseline variables (sex, disease group, age, CAG, study site, education) enabled a closer-to-causal interpretation of the associations. Adjusting for baseline variables only, medication use was typically associated with worse clinical performance, reflecting greater medication use in more advanced patients. After additional adjustment for longitudinal confounders such "inverse" associations were generally eliminated and in the expected directions: participants taking neuroleptics tended to have better motor performance, improved affect and poorer cognitive performance, and those taking SSRI/SNRIs had less apathy, less affect and better total behaviour scores. However, we uncovered few statistically significant associations. Limitations include sample size and unmeasured confounding. In conclusion, adjustment for confounding by prior measurements largely eliminated associations between medication use and poorer clinical performance from simple analyses. However, there was little convincing evidence of causal effects of medication on clinical performance and larger cohorts or trials are needed.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Keogh</LastName><ForeName>Ruth</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Frost</LastName><ForeName>Chris</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Owen</LastName><ForeName>Gail</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>UCL Institute of Neurology, University College London, Queen Square, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Daniel</LastName><ForeName>Rhian M</ForeName><Initials>RM</Initials><AffiliationInfo><Affiliation>Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Langbehn</LastName><ForeName>Doug R</ForeName><Initials>DR</Initials><AffiliationInfo><Affiliation>Psychiatry, University of Iowa, Iowa City, Iowa, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leavitt</LastName><ForeName>Blair</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Durr</LastName><ForeName>Alexandra</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Genetics, APHP- Groupe Hospitalier Pitié-Salpêtrière, Paris, France; INSERM U1127, CNRS UMR7225, UPMC University Paris VI UMR_S1127, Institut du Cerveau et de la Moelle, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roos</LastName><ForeName>Raymund A C</ForeName><Initials>RA</Initials><AffiliationInfo><Affiliation>Neurology, Leiden University Medical Centre, Leiden, Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Landwehrmeyer</LastName><ForeName>G Bernhard</ForeName><Initials>GB</Initials><AffiliationInfo><Affiliation>Neurology, Ulm University, Ulm, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reilmann</LastName><ForeName>Ralf</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>George-Huntington-Institute, Neurology, University of Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Borowsky</LastName><ForeName>Beth</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>CHDI Management/CHDI Foundation, Princeton, NJ, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stout</LastName><ForeName>Julie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>School of Psychological Sciences, Monash University, VIC, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Craufurd</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Institute of Human Development, University of Manchester; Manchester Academic Health Science Centre; Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tabrizi</LastName><ForeName>Sarah J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Neurodegenerative Disease, UCL Institute of Neurology, London, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MR/L012936/1</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>01</Month><Day>11</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>PLoS Curr</MedlineTA><NlmUniqueID>101515638</NlmUniqueID><ISSNLinking>2157-3999</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Stat Med. 2002 Jun 30;21(12):1689-709</RefSource><PMID Version="1">12111906</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurol Neurosurg Psychiatry. 1997 Jul;63(1):35-9</RefSource><PMID Version="1">9221965</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lancet Neurol. 2013 Jul;12(7):637-49</RefSource><PMID Version="1">23664844</PMID></CommentsCorrections><CommentsCorrections 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