Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines
Study Objective To compare efficacy and safety outcomes in nonintubated patients with severe alcohol withdrawal syndrome (AWS) who required a continuous infusion of a benzodiazepine or dexmedetomidine in addition to standard medical therapy for AWS. Design Retrospective cohort study. Setting Two hos...
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description | Study Objective
To compare efficacy and safety outcomes in nonintubated patients with severe alcohol withdrawal syndrome (AWS) who required a continuous infusion of a benzodiazepine or dexmedetomidine in addition to standard medical therapy for AWS.
Design
Retrospective cohort study.
Setting
Two hospitals within the same network that used different treatment strategies for AWS.
Patients
A total of 61 nonintubated adults who received a continuous infusion of either a benzodiazepine (BZD) (lorazepam or midazolam; 33 patients) or dexmedetomidine (DEX) (28 patients) for severe AWS between April 1, 2011, and October 31, 2012, as well as standard medical therapy for AWS.
Measurements and Main Results
The primary outcome was a composite end point including rates of respiratory distress requiring endotracheal intubation or occurrence of alcohol withdrawal seizures. No significant differences in the composite end point were noted between the BZD and DEX groups (9.1% and 7.1%, respectively, p>0.99) or its individual components of respiratory distress (9.1% and 7.1%, respectively, p>0.99) or alcohol withdrawal seizures (0% and 3.6%, respectively, p=0.46). The DEX group received a lower median total dose of lorazepam equivalents after initiation of the study drug (median [interquartile range] 105 [60–199.5] mg in the BZD group vs 3.5 [0–12] mg in the DEX group), but this did not translate into a reduced requirement for endotracheal intubation or decreased length of stay. DEX was associated with more adverse drug events including hypotension and bradycardia. Of concern, DEX may impair the ability to assess symptoms appropriately and administer BZDs in a symptom‐triggered fashion. Although the total cost of hospitalization was similar between groups, DEX was associated with a higher study drug cost per patient.
Conclusion
DEX demonstrated a BZD‐sparing effect in the treatment of AWS; however, this surrogate end point should be interpreted with caution. Although this study cannot disprove the possibility of a protective effect of DEX in preventing the requirement for endotracheal intubation in patients with AWS, an increased rate of adverse drug events and increased study drug costs were observed. If DEX is used in clinical practice, it should only be used as adjunctive therapy with BZDs that have a proven benefit in AWS. |
doi_str_mv | 10.1002/phar.1448 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1560097077</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1560097077</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4618-3f40ed6fb945f265d25b0db904fe632a79473284c06c73f1fc0e3769c48a9e1b3</originalsourceid><addsrcrecordid>eNp1kcFu1DAQhiMEotvCgRdAlrjAIa2dOHbCbRtKt6jatuyiHi0nmWhdEjvYTrfb1-IF8XaXHpA4WRp9882M_yh6R_AxwTg5GVbSHhNK8xfRhOQ8iwtC6MtoghPOY4xxfhAdOncXUMJo8jo6SGhe5JTkk-h3afpBWuWMRqZFZae0qmWHrkZfmx4cUhrNjVbaj5X00KBr6RVo79Ba-RVawD1YQNOuNivTodtQa6xcB8FioxsbDGhp4anxiS-N9kqPZnTxhW5Hp8LYBTTBeQ_uM_oCDz004E2vGqUBBbkbHToF_WgaJR9hCFX3JnrVys7B2_17FP34erYsZ_Hl1flFOb2Ma8pIHqctxdCwtipo1iYsa5Kswk1VYNoCSxPJC8rTJKc1ZjVPW9LWGFLOiprmsgBSpUfRx513sObXCM6LXrkauk5qCBcIkjGMC445D-iHf9A7M1odtttSjIVBOAvUpx1VW-OchVYMVvXSbgTBYpuk2CYptkkG9v3eOFbhT57Jv9EF4GQHrFUHm_-bxPVs-n2vjHcdynl4eO6Q9qcIC_JM3M7PBZ5lN8vk242Yp38Ajr67rQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1566673205</pqid></control><display><type>article</type><title>Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Crispo, Angela L. ; Daley, Mitchell J. ; Pepin, Jodie L. ; Harford, Paul H. ; Brown, Carlos V.R.</creator><creatorcontrib>Crispo, Angela L. ; Daley, Mitchell J. ; Pepin, Jodie L. ; Harford, Paul H. ; Brown, Carlos V.R.</creatorcontrib><description>Study Objective
To compare efficacy and safety outcomes in nonintubated patients with severe alcohol withdrawal syndrome (AWS) who required a continuous infusion of a benzodiazepine or dexmedetomidine in addition to standard medical therapy for AWS.
Design
Retrospective cohort study.
Setting
Two hospitals within the same network that used different treatment strategies for AWS.
Patients
A total of 61 nonintubated adults who received a continuous infusion of either a benzodiazepine (BZD) (lorazepam or midazolam; 33 patients) or dexmedetomidine (DEX) (28 patients) for severe AWS between April 1, 2011, and October 31, 2012, as well as standard medical therapy for AWS.
Measurements and Main Results
The primary outcome was a composite end point including rates of respiratory distress requiring endotracheal intubation or occurrence of alcohol withdrawal seizures. No significant differences in the composite end point were noted between the BZD and DEX groups (9.1% and 7.1%, respectively, p>0.99) or its individual components of respiratory distress (9.1% and 7.1%, respectively, p>0.99) or alcohol withdrawal seizures (0% and 3.6%, respectively, p=0.46). The DEX group received a lower median total dose of lorazepam equivalents after initiation of the study drug (median [interquartile range] 105 [60–199.5] mg in the BZD group vs 3.5 [0–12] mg in the DEX group), but this did not translate into a reduced requirement for endotracheal intubation or decreased length of stay. DEX was associated with more adverse drug events including hypotension and bradycardia. Of concern, DEX may impair the ability to assess symptoms appropriately and administer BZDs in a symptom‐triggered fashion. Although the total cost of hospitalization was similar between groups, DEX was associated with a higher study drug cost per patient.
Conclusion
DEX demonstrated a BZD‐sparing effect in the treatment of AWS; however, this surrogate end point should be interpreted with caution. Although this study cannot disprove the possibility of a protective effect of DEX in preventing the requirement for endotracheal intubation in patients with AWS, an increased rate of adverse drug events and increased study drug costs were observed. If DEX is used in clinical practice, it should only be used as adjunctive therapy with BZDs that have a proven benefit in AWS.</description><identifier>ISSN: 0277-0008</identifier><identifier>EISSN: 1875-9114</identifier><identifier>DOI: 10.1002/phar.1448</identifier><identifier>PMID: 24898418</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Alcohol ; alcohol withdrawal syndrome ; benzodiazepines ; Benzodiazepines - adverse effects ; Benzodiazepines - therapeutic use ; Cohort Studies ; critical care ; dexmedetomidine ; Dexmedetomidine - adverse effects ; Dexmedetomidine - therapeutic use ; Ethanol - adverse effects ; Female ; Humans ; Hypnotics and Sedatives - adverse effects ; Hypnotics and Sedatives - therapeutic use ; Infusions, Intravenous ; Intubation ; lorazepam ; Lorazepam - adverse effects ; Lorazepam - therapeutic use ; Male ; Medical treatment ; midazolam ; Midazolam - adverse effects ; Midazolam - therapeutic use ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Substance Withdrawal Syndrome - drug therapy ; Treatment Outcome</subject><ispartof>Pharmacotherapy, 2014-09, Vol.34 (9), p.910-917</ispartof><rights>2014 Pharmacotherapy Publications, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4618-3f40ed6fb945f265d25b0db904fe632a79473284c06c73f1fc0e3769c48a9e1b3</citedby><cites>FETCH-LOGICAL-c4618-3f40ed6fb945f265d25b0db904fe632a79473284c06c73f1fc0e3769c48a9e1b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fphar.1448$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fphar.1448$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24898418$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Crispo, Angela L.</creatorcontrib><creatorcontrib>Daley, Mitchell J.</creatorcontrib><creatorcontrib>Pepin, Jodie L.</creatorcontrib><creatorcontrib>Harford, Paul H.</creatorcontrib><creatorcontrib>Brown, Carlos V.R.</creatorcontrib><title>Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines</title><title>Pharmacotherapy</title><addtitle>Pharmacotherapy</addtitle><description>Study Objective
To compare efficacy and safety outcomes in nonintubated patients with severe alcohol withdrawal syndrome (AWS) who required a continuous infusion of a benzodiazepine or dexmedetomidine in addition to standard medical therapy for AWS.
Design
Retrospective cohort study.
Setting
Two hospitals within the same network that used different treatment strategies for AWS.
Patients
A total of 61 nonintubated adults who received a continuous infusion of either a benzodiazepine (BZD) (lorazepam or midazolam; 33 patients) or dexmedetomidine (DEX) (28 patients) for severe AWS between April 1, 2011, and October 31, 2012, as well as standard medical therapy for AWS.
Measurements and Main Results
The primary outcome was a composite end point including rates of respiratory distress requiring endotracheal intubation or occurrence of alcohol withdrawal seizures. No significant differences in the composite end point were noted between the BZD and DEX groups (9.1% and 7.1%, respectively, p>0.99) or its individual components of respiratory distress (9.1% and 7.1%, respectively, p>0.99) or alcohol withdrawal seizures (0% and 3.6%, respectively, p=0.46). The DEX group received a lower median total dose of lorazepam equivalents after initiation of the study drug (median [interquartile range] 105 [60–199.5] mg in the BZD group vs 3.5 [0–12] mg in the DEX group), but this did not translate into a reduced requirement for endotracheal intubation or decreased length of stay. DEX was associated with more adverse drug events including hypotension and bradycardia. Of concern, DEX may impair the ability to assess symptoms appropriately and administer BZDs in a symptom‐triggered fashion. Although the total cost of hospitalization was similar between groups, DEX was associated with a higher study drug cost per patient.
Conclusion
DEX demonstrated a BZD‐sparing effect in the treatment of AWS; however, this surrogate end point should be interpreted with caution. Although this study cannot disprove the possibility of a protective effect of DEX in preventing the requirement for endotracheal intubation in patients with AWS, an increased rate of adverse drug events and increased study drug costs were observed. If DEX is used in clinical practice, it should only be used as adjunctive therapy with BZDs that have a proven benefit in AWS.</description><subject>Adult</subject><subject>Aged</subject><subject>Alcohol</subject><subject>alcohol withdrawal syndrome</subject><subject>benzodiazepines</subject><subject>Benzodiazepines - adverse effects</subject><subject>Benzodiazepines - therapeutic use</subject><subject>Cohort Studies</subject><subject>critical care</subject><subject>dexmedetomidine</subject><subject>Dexmedetomidine - adverse effects</subject><subject>Dexmedetomidine - therapeutic use</subject><subject>Ethanol - adverse effects</subject><subject>Female</subject><subject>Humans</subject><subject>Hypnotics and Sedatives - adverse effects</subject><subject>Hypnotics and Sedatives - therapeutic use</subject><subject>Infusions, Intravenous</subject><subject>Intubation</subject><subject>lorazepam</subject><subject>Lorazepam - adverse effects</subject><subject>Lorazepam - therapeutic use</subject><subject>Male</subject><subject>Medical treatment</subject><subject>midazolam</subject><subject>Midazolam - adverse effects</subject><subject>Midazolam - therapeutic use</subject><subject>Middle Aged</subject><subject>Retrospective Studies</subject><subject>Severity of Illness Index</subject><subject>Substance Withdrawal Syndrome - drug therapy</subject><subject>Treatment Outcome</subject><issn>0277-0008</issn><issn>1875-9114</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFu1DAQhiMEotvCgRdAlrjAIa2dOHbCbRtKt6jatuyiHi0nmWhdEjvYTrfb1-IF8XaXHpA4WRp9882M_yh6R_AxwTg5GVbSHhNK8xfRhOQ8iwtC6MtoghPOY4xxfhAdOncXUMJo8jo6SGhe5JTkk-h3afpBWuWMRqZFZae0qmWHrkZfmx4cUhrNjVbaj5X00KBr6RVo79Ba-RVawD1YQNOuNivTodtQa6xcB8FioxsbDGhp4anxiS-N9kqPZnTxhW5Hp8LYBTTBeQ_uM_oCDz004E2vGqUBBbkbHToF_WgaJR9hCFX3JnrVys7B2_17FP34erYsZ_Hl1flFOb2Ma8pIHqctxdCwtipo1iYsa5Kswk1VYNoCSxPJC8rTJKc1ZjVPW9LWGFLOiprmsgBSpUfRx513sObXCM6LXrkauk5qCBcIkjGMC445D-iHf9A7M1odtttSjIVBOAvUpx1VW-OchVYMVvXSbgTBYpuk2CYptkkG9v3eOFbhT57Jv9EF4GQHrFUHm_-bxPVs-n2vjHcdynl4eO6Q9qcIC_JM3M7PBZ5lN8vk242Yp38Ajr67rQ</recordid><startdate>201409</startdate><enddate>201409</enddate><creator>Crispo, Angela L.</creator><creator>Daley, Mitchell J.</creator><creator>Pepin, Jodie L.</creator><creator>Harford, Paul H.</creator><creator>Brown, Carlos V.R.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201409</creationdate><title>Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines</title><author>Crispo, Angela L. ; Daley, Mitchell J. ; Pepin, Jodie L. ; Harford, Paul H. ; Brown, Carlos V.R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4618-3f40ed6fb945f265d25b0db904fe632a79473284c06c73f1fc0e3769c48a9e1b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Alcohol</topic><topic>alcohol withdrawal syndrome</topic><topic>benzodiazepines</topic><topic>Benzodiazepines - adverse effects</topic><topic>Benzodiazepines - therapeutic use</topic><topic>Cohort Studies</topic><topic>critical care</topic><topic>dexmedetomidine</topic><topic>Dexmedetomidine - adverse effects</topic><topic>Dexmedetomidine - therapeutic use</topic><topic>Ethanol - adverse effects</topic><topic>Female</topic><topic>Humans</topic><topic>Hypnotics and Sedatives - adverse effects</topic><topic>Hypnotics and Sedatives - therapeutic use</topic><topic>Infusions, Intravenous</topic><topic>Intubation</topic><topic>lorazepam</topic><topic>Lorazepam - adverse effects</topic><topic>Lorazepam - therapeutic use</topic><topic>Male</topic><topic>Medical treatment</topic><topic>midazolam</topic><topic>Midazolam - adverse effects</topic><topic>Midazolam - therapeutic use</topic><topic>Middle Aged</topic><topic>Retrospective Studies</topic><topic>Severity of Illness Index</topic><topic>Substance Withdrawal Syndrome - drug therapy</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Crispo, Angela L.</creatorcontrib><creatorcontrib>Daley, Mitchell J.</creatorcontrib><creatorcontrib>Pepin, Jodie L.</creatorcontrib><creatorcontrib>Harford, Paul H.</creatorcontrib><creatorcontrib>Brown, Carlos V.R.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Pharmacotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Crispo, Angela L.</au><au>Daley, Mitchell J.</au><au>Pepin, Jodie L.</au><au>Harford, Paul H.</au><au>Brown, Carlos V.R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines</atitle><jtitle>Pharmacotherapy</jtitle><addtitle>Pharmacotherapy</addtitle><date>2014-09</date><risdate>2014</risdate><volume>34</volume><issue>9</issue><spage>910</spage><epage>917</epage><pages>910-917</pages><issn>0277-0008</issn><eissn>1875-9114</eissn><abstract>Study Objective
To compare efficacy and safety outcomes in nonintubated patients with severe alcohol withdrawal syndrome (AWS) who required a continuous infusion of a benzodiazepine or dexmedetomidine in addition to standard medical therapy for AWS.
Design
Retrospective cohort study.
Setting
Two hospitals within the same network that used different treatment strategies for AWS.
Patients
A total of 61 nonintubated adults who received a continuous infusion of either a benzodiazepine (BZD) (lorazepam or midazolam; 33 patients) or dexmedetomidine (DEX) (28 patients) for severe AWS between April 1, 2011, and October 31, 2012, as well as standard medical therapy for AWS.
Measurements and Main Results
The primary outcome was a composite end point including rates of respiratory distress requiring endotracheal intubation or occurrence of alcohol withdrawal seizures. No significant differences in the composite end point were noted between the BZD and DEX groups (9.1% and 7.1%, respectively, p>0.99) or its individual components of respiratory distress (9.1% and 7.1%, respectively, p>0.99) or alcohol withdrawal seizures (0% and 3.6%, respectively, p=0.46). The DEX group received a lower median total dose of lorazepam equivalents after initiation of the study drug (median [interquartile range] 105 [60–199.5] mg in the BZD group vs 3.5 [0–12] mg in the DEX group), but this did not translate into a reduced requirement for endotracheal intubation or decreased length of stay. DEX was associated with more adverse drug events including hypotension and bradycardia. Of concern, DEX may impair the ability to assess symptoms appropriately and administer BZDs in a symptom‐triggered fashion. Although the total cost of hospitalization was similar between groups, DEX was associated with a higher study drug cost per patient.
Conclusion
DEX demonstrated a BZD‐sparing effect in the treatment of AWS; however, this surrogate end point should be interpreted with caution. Although this study cannot disprove the possibility of a protective effect of DEX in preventing the requirement for endotracheal intubation in patients with AWS, an increased rate of adverse drug events and increased study drug costs were observed. If DEX is used in clinical practice, it should only be used as adjunctive therapy with BZDs that have a proven benefit in AWS.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>24898418</pmid><doi>10.1002/phar.1448</doi><tpages>8</tpages></addata></record> |
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source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
subjects | Adult Aged Alcohol alcohol withdrawal syndrome benzodiazepines Benzodiazepines - adverse effects Benzodiazepines - therapeutic use Cohort Studies critical care dexmedetomidine Dexmedetomidine - adverse effects Dexmedetomidine - therapeutic use Ethanol - adverse effects Female Humans Hypnotics and Sedatives - adverse effects Hypnotics and Sedatives - therapeutic use Infusions, Intravenous Intubation lorazepam Lorazepam - adverse effects Lorazepam - therapeutic use Male Medical treatment midazolam Midazolam - adverse effects Midazolam - therapeutic use Middle Aged Retrospective Studies Severity of Illness Index Substance Withdrawal Syndrome - drug therapy Treatment Outcome |
title | Comparison of Clinical Outcomes in Nonintubated Patients with Severe Alcohol Withdrawal Syndrome Treated with Continuous-Infusion Sedatives: Dexmedetomidine versus Benzodiazepines |
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